Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174: 09/18/17

Δευτέρα 18 Σεπτεμβρίου 2017

JCM, Vol. 6, Pages 87: Technical Advances in the Measurement of Residual Disease in Acute Myeloid Leukemia

JCM, Vol. 6, Pages 87: Technical Advances in the Measurement of Residual Disease in Acute Myeloid Leukemia

Journal of Clinical Medicine doi: 10.3390/jcm6090087

Authors: Gregory Roloff Catherine Lai Christopher Hourigan Laura Dillon

Outcomes for those diagnosed with acute myeloid leukemia (AML) remain poor. It has been widely established that persistent residual leukemic burden, often referred to as measurable or minimal residual disease (MRD), after induction therapy or at the time of hematopoietic stem cell transplant (HSCT) is highly predictive for adverse clinical outcomes and can be used to identify patients likely to experience clinically evident relapse. As a result of inherent genetic and molecular heterogeneity in AML, there is no uniform method or protocol for MRD measurement to encompass all cases. Several techniques focusing on identifying recurrent molecular and cytogenetic aberrations or leukemia-associated immunophenotypes have been described, each with their own strengths and weaknesses. Modern technologies enabling the digital quantification and tracking of individual DNA or RNA molecules, next-generation sequencing (NGS) platforms, and high-resolution imaging capabilities are among several new avenues under development to supplement or replace the current standard of flow cytometry. In this review, we outline emerging modalities positioned to enhance MRD detection and discuss factors surrounding their integration into clinical practice.

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JCM, Vol. 6, Pages 88: Can Diet Help Non-Obese Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD)?

JCM, Vol. 6, Pages 88: Can Diet Help Non-Obese Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD)?

Journal of Clinical Medicine doi: 10.3390/jcm6090088

Authors: Hamid Merchant

Subjects diagnosed with non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis are usually obese or overweight. NAFLD has also been reported in many non-obese healthy subjects as an incidental finding during imaging. Subjects with early-stage NAFLD who are otherwise healthy are often left unmanaged in current clinical practice; it is not clear if an early intervention in those individuals would be of any benefit in preventing NAFLD progression to more serious conditions. Since many of these subjects are non-alcoholic and have a normal body mass index (BMI), an intensive lifestyle change program is not usually recommended. This report presents an otherwise healthy non-alcoholic subject with incidental NAFLD having a normal BMI and a waist circumference below 90 cm who successfully reversed his condition by undertaking a lifestyle intervention. The case report is expected to encourage large cohort studies to substantiate the benefits of dietary interventions in alleviating hepatic steatosis among non-obese individuals.

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Platelet-released growth factors inhibit proliferation of primary keratinocytes in vitro

Publication date: Available online 18 September 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Andreas Bayer, Mersedeh Tohidnezhad, Rouven Berndt, Sebastian Lippross, Peter Behrendt, Tim Klüter, Thomas Pufe, Holger Jahr, Jochen Cremer, Franziska Rademacher, Maren Simanski, Regine Gläser, Jürgen Harder
Autologous thrombocyte concentrate lysates as platelet-released growth factors (PRGF) or Vivostat Platelet Rich Fibrin (PRF^®) represent important tools in modern wound therapy, especially in the treatment of chronic, hard-to-heal or infected wounds.Nevertheless, underlying cellular and molecular mechanisms of the beneficial clinical effects of a local wound therapy with autologous thrombocyte concentrate lysates are poorly understood. Recently, we have demonstrated that PRGF induces antimicrobial peptides in primary keratinocytes and accelerates keratinocytes' differentiation. In the present study we analyzed the influence of PRGF on primary human keratinocytes' proliferation.Using the molecular proliferation marker Ki-67 we observed a concentration- and time dependent inhibition of Ki-67 gene expression in PRGF treated primary keratinocytes. These effects were independent from the EGFR- and the IL-6-R pathway. Inhibition of primary keratinocytes' proliferation by PRGF treatment was confirmed in colorimetric cell proliferation assays.Together, these data indicate that the clinically observed positive effects of autologous thrombocytes concentrates in the treatment of chronic, hard-to-heal wounds are not based on an increased keratinocytes proliferation.

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Debates in Allergy Medicine: Allergy skin testing cannot be replaced by molecular diagnosis in the near future

Percutaneous skin prick tests (SPT) have been considered the preferred method for confirming IgE-mediated sensitization. This reliable and minimally invasive technique correlates with in vivo challenges, has g...

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Debates in allergy medicine: Molecular allergy diagnosis with ISAC will replace screenings by skin prick test in the future

In today's clinical practice patients' skin is used as screening organ for diagnosing type 1 allergy. According to European guidelines skin prick testing with a panel of 18 allergen extracts is recommended, in...

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Debates in Allergy Medicine: Allergy skin testing cannot be replaced by molecular diagnosis in the near future

Percutaneous skin prick tests (SPT) have been considered the preferred method for confirming IgE-mediated sensitization. This reliable and minimally invasive technique correlates with in vivo challenges, has g...

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Debates in allergy medicine: Molecular allergy diagnosis with ISAC will replace screenings by skin prick test in the future

In today's clinical practice patients' skin is used as screening organ for diagnosing type 1 allergy. According to European guidelines skin prick testing with a panel of 18 allergen extracts is recommended, in...

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New method of dental imaging uses squid ink for a painless, non-invasive check-up

According to engineers at the University of California San Diego, people who are getting checked at their dentists' offices for gum disease need not worry anymore about pain and discomfort. Why? Because squid ink is the answer to their problems.

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Influence of obesity on experimental periodontitis in rats: histopathological, histometric and immunohistochemical study

Abstract

Objectives

This study assessed the influence of obesity on the progression of ligature-induced periodontitis in rats.

Materials and methods

Forty-eight adult Wistar rats were randomly divided into two groups: the HL group (n = 24) was fed high-fat animal food to induce obesity, and the NL group (n = 24) was fed normolipidic animal food. Obesity was induced within a period of 120 days, and the induction of experimental periodontitis (EP) was subsequently performed for 30 days. The animals were euthanized after 7, 15, and 30 days, and the jaws were removed for histopathological, histometric, and immunohistochemical analyses. Tartrate-resistant acid phosphatase (TRAP), receptor activator of nuclear factor kappa beta ligand (RANKL), and osteoprotegerin (OPG) were analyzed via immunolabeling.

Results

Histological findings indicated that the inflammation was more extensive and lasted longer in the HL⁄EP; however, advanced destruction also occurred in the NL/EP. Greater bone loss was verified in the HL/EP group (2.28 ± 0.35) in the period of 7 days than in the NL/EP group (1.2 ± 0.29). High immunolabeling was identified in the HL/EP group in the initial periods for RANKL and TRAP, whereas the NL⁄EP group presented with moderate immunolabeling for both factors. The HL/EP and NL/EP groups showed low immunolabeling for OPG.

Conclusions

Obesity induced by a high-fat diet influenced alveolar bone metabolism when associated with experimental periodontitis and caused a more severe local inflammatory response and alveolar bone loss.

Clinical relevance

Obesity is related to greater alveolar bone loss and an accentuated local inflammatory response, which may be reflected in the clinical severity of periodontitis and dental loss.

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Peripheral T-cell lymphomas:focusing on novel agents in relapsed and refractory disease

Publication date: Available online 17 September 2017
Source:Cancer Treatment Reviews
Author(s): Alessandro Broccoli, Lisa Argnani, Pier Luigi Zinzani
Patients with relapsed or refractory peripheral T-cell lymphoma display a dismal prognosis and their therapy represents an unmet medical need, as the best treatment strategy is yet to be determined. Exciting data on novel targeted agents are now emerging from recently concluded and ongoing clinical trials in patients with relapsed and refractory PTCL. Four recently approved compounds are used as single agents: pralatrexate, a novel antifolate agent; romidepsin and belinostat, both histone deacetylase (HDAC) inhibitors; brentuximab vedotin, an anti-CD30 drug-conjugated monoclonal antibody. Several other molecules have demonstrated their activity in the same context: gemcitabine, bendamustine, lenalidomide, duvelisib, copanlisib, alisertib, mogamulizumab, selinexor and ARGX-110. Robust preclinical observations strongly support chemo-free combinations, which are expected to enhance the quality and duration of responses in pretreated patients and in those who are unable to receive a stem cell transplantation.

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Influence of obesity on experimental periodontitis in rats: histopathological, histometric and immunohistochemical study

Abstract

Objectives

This study assessed the influence of obesity on the progression of ligature-induced periodontitis in rats.

Materials and methods

Results

Conclusions

Obesity induced by a high-fat diet influenced alveolar bone metabolism when associated with experimental periodontitis and caused a more severe local inflammatory response and alveolar bone loss.

Clinical relevance

Obesity is related to greater alveolar bone loss and an accentuated local inflammatory response, which may be reflected in the clinical severity of periodontitis and dental loss.

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Trends in active surveillance for very low-risk prostate cancer: do guidelines influence modern practice?

Abstract

As recommended by current NCCN guidelines, patients with very low-risk prostate cancer may be treated with active surveillance (AS), but this may be underutilized. Using the National Cancer Database (NCDB), we identified men (2010–2013) with biopsy-proven, very low-risk prostate cancer that met AS criteria as suggested by Epstein (stage ≤ T1c; Gleason score (GS) ≤ 6; PSA < 10; and ≤2 [or <33%] positive biopsy cores) and aged ≤76, and low comorbidity index (Charlson-Deyo score = 0). For those patients meeting this criteria, we performed generalized estimation equation (GEE) method with incorporation of correlation in patients clustered within facility to determine the likelihood of undergoing AS. Among the 448 773 patients in the NCDB with low-risk prostate cancer, 40 839 patients met the inclusion criteria. AS was utilized in 5798 patients (14.2%), while within the very low-risk patients receiving treatment, up to 52.2% received radical prostatectomy. In univariate analyses, AS utilization was associated with older age, uninsured status (compared to private insurance), farther distance from facility, academic/research institutions and particularly in the New England region (all P < 0.01). After adjustments of other predictors in multivariate analysis, patients preferentially received AS if they were older (all OR's > 1 compared to younger groups), uninsured (vs. any insurance type, OR's > 1); or treated at academic/research center (OR > 1). The overall use of AS increased from 11.6% (2010) to 27.3% (2013). We found a low, but rising rate of AS in a nationally representative group of very low-risk prostate cancer patients. Disparities in the use of AS may be targeted to improve adherence to national guidelines.

This article demonstrates one of the largest series examining the role of active surveillance in patients with very low-risk prostate cancer. Our results in disparities and trends in recommendations for active surveillance reveal an important aspect of cancer care in the management of this disease entity.

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Expression of Concern to: Therapeutic potential of human embryonic stem cell transplantation in patients with cerebral palsy

The Editor-in-Chief of the Journal of Translational Medicine is issuing an editorial expression of concern to alert readers that concerns have been raised regarding the ethics of this study [1] and the potential...

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Impact of perioperative nutritional status on the outcome of abdominal surgery in a sub-Saharan Africa setting

Malnutrition is a clinical condition of multifactorial etiologies and it is associated with several adverse outcomes. In high-income countries, malnutrition has been described as a determinant of delayed wound...

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Intestinal parasitic infections and risk factors: a cross-sectional survey of some school children in a suburb in Accra, Ghana

This study aimed to determine the prevalence and establish some risk factors associated with the acquisition of gastrointestinal parasitic infections in school children in Accra, Ghana.

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“I think it is right”: a qualitative exploration of the acceptability and desired future use of oral swab and finger-prick HIV self-tests by lay users in KwaZulu-Natal, South Africa

The uptake of HIV testing has increased in sub-Saharan Africa over the past three decades. However, the proportion of people aware of their HIV status remains lower than required to change the pandemic. HIV se...

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Dubin–Johnson syndrome and intrahepatic cholestasis of pregnancy in a Sri Lankan family: a case report

Dubin–Johnson syndrome and intrahepatic cholestasis of pregnancy are rare chronic liver disorders. Dubin–Johnson syndrome may manifest as conjugated hyperbilirubinemia, darkly pigmented liver, presence of abno...

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Burnout is associated with changes in error and feedback processing

Publication date: Available online 18 September 2017
Source:Biological Psychology
Author(s): Patrick D. Gajewski, Sylvia Boden, Gabriele Freude, Guy G. Potter, Michael Falkenstein
Burnout is a pattern of complaints in individuals with emotionally demanding jobs that is often seen as a precursor of depression. One often reported symptom of burnout is cognitive decline. To analyze cognitive control and to differentiate between subclinical burnout and mild-to-moderate depression a double-blinded study was conducted that investigates changes in the processing of performance errors and feedback in a task switching paradigm. Fifty-one of 76 employees from emotionally demanding jobs showed a sufficient number of errors to be included in the analysis. The sample was subdivided into groups with low (EE-) and high (EE+) emotional exhaustion and no (DE-) and mild-to-moderate depression (DE+). The behavioral data did not significantly differ between the groups. In contrast, in the EE+ group, the error negativity (Ne/ERN) was enhanced while the error positivity (Pe) did not differ between the groups. After negative feedback the feedback-related negativity (FRN) was enhanced, while the subsequent positivity (FRP) was reduced in EE+ relative to EE-. None of these effects were observed in the DE+ vs. DE-. These results suggest an upregulation of error and negative feedback processing, while the later processing of negative feedback was attenuated in employees with subclinical burnout but not in mild-to-moderate depression.

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When Theory and Biology Differ: The Relationship Between Reward Prediction Errors and Expectancy

Publication date: Available online 18 September 2017
Source:Biological Psychology
Author(s): Chad C. Williams, Cameron D. Hassall, Robert Trska, Clay B. Holroyd, Olave E. Krigolson
Comparisons between expectations and outcomes are critical for learning. Termed prediction errors, the violations of expectancy that occur when outcomes differ from expectations are used to modify value and shape behaviour. In the present study, we examined how a wide range of expectancy violations impacted neural signals associated with feedback processing. Participants performed a time estimation task in which they had to guess the duration of one second while their electroencephalogram was recorded. In a key manipulation, we varied task difficulty across the experiment to create a range of different feedback expectancies − reward feedback was either very expected, expected, 50/50, unexpected, or very unexpected. As predicted, the amplitude of the reward positivity, a component of the human event-related brain potential associated with feedback processing, scaled inversely with expectancy (e.g., unexpected feedback yielded a larger reward positivity than expected feedback). Interestingly, the scaling of the reward positivity to outcome expectancy was not linear as would be predicted by some theoretical models. Specifically, we found that the amplitude of the reward positivity was about equivalent for very expected and expected feedback, and for very unexpected and unexpected feedback. As such, our results demonstrate a sigmoidal relationship between reward expectancy and the amplitude of the reward positivity, with interesting implications for theories of reinforcement learning.

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Extracellular Vesicles released by Mesenchymal-like Prostate Carcinoma Cells modulate EMT state of recipient Epithelial-like carcinoma cells through regulation of AR signaling

Extracellular vesicles released from cancer cells may play an important role in cancer progression by shuttling oncogenic information into recipient cells. However, our knowledge is still fragmentary and there remain numerous questions regarding the mechanisms at play and the functional consequences of these interactions. We have recently established a mesenchymal-like prostate cancer cell line (22Rv1/CR-1; Mes-PCa). In this study, we assessed the effects of the extracellular vesicles released by these cells on recipient androgen-dependent epithelial VCaP prostate cancer cells.

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Extracellular Vesicles released by Mesenchymal-like Prostate Carcinoma Cells modulate EMT state of recipient Epithelial-like carcinoma cells through regulation of AR signaling

Etiology, diagnosis, and demographic analysis of maxillofacial trauma in elderly persons: A 10-year investigation

The aim of this study was to investigate etiologies and diagnoses of maxillofacial trauma in emergency services in Brazil over a period of 10 years. Additionally, associations among sex, age, accident location, and dependent variables were analyzed. Understanding the epidemiology of trauma and the physiology of aging is important in maintaining health and bettering service for the elderly population.

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Surgical treatment of synkinesiss between smiling and eyelid closure

Synkinetics movements are common among patients with incomplete recovery from facial palsy, with reported rates ranging from 9.1% to almost 100%.The authors propose the separation of the neural stimulus of the orbicularis oculi from that of the zygomatic muscular complex to treat eyelid closure/smiling synkinesiss. This technique, associated with an anastomosis between the masseteric nerve and a central branch of the facial nerve, as well as with the use of a cross-facial nerve graft, resolves most of the spasms of the midface musculature, leading to a more relaxed tone when the mimic muscle is at rest and enhancing muscle excursion during voluntary and spontaneous smiling.

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Tongue movement during articulation in magnetic resonance imaging: Findings in 20 healthy volunteers and a patient with anterior floor of the mouth squamous cell carcinoma

Combined ablative and reconstructive oral maxillofacial surgery involves a multitude of anatomical and functional structures for speech and swallowing. Although there are a few methods to objectively examine swallowing function, this is not true for speech. We describe the development of an objective visualization and measurement tool for magnetic resonance imaging (MRI) to evaluate speech and its first application in a patient.

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Nipple sparing mastectomy and microsurgical breast reconstruction: an approach for success

Surgical management of breast cancer has evolved to allow for nipple sparing mastectomy (NSM) in oncologically eligible patients. Successful reconstruction requires complication-free execution and overall aesthetic harmony of the reconstructed and unaffected breasts. Few articles have described technical considerations and challenges encountered while performing NSM reconstruction with autologous tissue. Herein, we report our algorithm for success.

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LDT classification and therapeutic strategy of congenital body wall defects

We shared the repairing methods, which were used in our 5 cases of congenital malformations, at "The Third World Congress for Plastic Surgeons of Chinese Descent" in 2012. The title of this conference paper was "Clinical Experiences on Repairing of Huge Body Wall Defects".

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Reply to “Transungual fibrokeratoma”

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Kimura's disease in the oral cavity: A rare manifestation of immunoglobulin G4-related disease

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Autoimmune diseases involving skin and intestinal mucosa are more frequent in adolescents and young adults suffering from atopic dermatitis

Abstract

Evidence has emerged about the relationship between atopic dermatitis (AD) and autoimmune diseases, but the underlying mechanism of this association is complex and still unclear. Recent epidemiological data from the published work suggest a positive correlation. The aim of this review is to analyze the frequency of co-occurrence of AD and autoimmune diseases. Our systematic review included 22 articles from PubMed describing the reciprocal association between AD and autoimmune diseases. Although not all the studies achieved statistically significant results, patients suffering from autoimmune diseases involving skin and intestinal mucosa, such as vitiligo, alopecia areata, celiac disease and inflammatory bowel diseases, showed a higher risk to have AD as comorbidity. In contrast, patients with rheumatological autoimmune disorders did not show a significant correlation with AD. By analyzing the occurrence of autoimmune disorders in patients with AD, we confirmed a positive correlation between AD and autoimmune diseases involving skin and intestinal mucosa, but also with systemic lupus erythematosus, while the association between AD and type 1 diabetes, autoimmune thyroiditis and rheumatoid arthritis showed conflicting results. Further investigations are need to explain the mechanism underlying the observed comorbidity between AD and autoimmune diseases and to develop targeted prevention strategies and treatment.

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Lipofuscin deposition causes the pigmentation of apocrine hidrocystoma

Abstract

Apocrine hidrocystoma (AHC) is a benign cystic lesion arising from apocrine glands and frequently presents as a blue hae with a whitish gloss. It has been reported that the amount of lipofuscin and the degree of its oxidation determines the pigmentation of AHC. However, little is known about the correlation between clinical color and lipofuscin granules. In this study, we histopathologically investigated three cases of AHC and statistically analyzed the quantitative correlation between the clinical color tone and the amount of cytoplasmic lipofuscin deposits. The color tone was quantified as the mean gray value using Image J software. Statistical analysis showed a negative correlative tendency (P = 0.09) between the color tone and the amount of lipofuscin. Our study suggests that the color tone of AHC is associated with the amount of lipofuscin.

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Dermoscopy of linear dermatosis along Blaschko's line in childhood: Lichen striatus versus inflammatory linear verrucous epidermal nevus

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Accelerating Vaccine Development During the 2013-2016 West African Ebola Virus Disease Outbreak.

Accelerating Vaccine Development During the 2013-2016 West African Ebola Virus Disease Outbreak.

Curr Top Microbiol Immunol. 2017 Sep 17;:

Authors: Higgs ES, Dubey SA, Coller BAG, Simon JK, Bollinger L, Sorenson RA, Wilson B, Nason MC, Hensley LE

Abstract
The Ebola virus disease outbreak that began in Western Africa in December 2013 was unprecedented in both scope and spread, and the global response was slower and less coherent than was optimal given the scale and pace of the epidemic. Past experience with limited localized outbreaks, lack of licensed medical countermeasures, reluctance by first responders to direct scarce resources to clinical research, community resistance to outside interventions, and lack of local infrastructure were among the factors delaying clinical research during the outbreak. Despite these hurdles, the global health community succeeded in accelerating Ebola virus vaccine development, in a 5-month interval initiating phase I trials in humans in September 2014 and initiating phase II/III trails in February 2015. Each of the three Ebola virus disease-affected countries, Sierra Leone, Guinea, and Liberia, conducted a phase II/III Ebola virus vaccine trial. Only one of these trials evaluating recombinant vesicular stomatitis virus expressing Ebola virus glycoprotein demonstrated vaccine efficacy using an innovative mobile ring vaccination trial design based on a ring vaccination strategy responsible for eradicating smallpox that reached areas of new outbreaks. Thoughtful and intensive community engagement in each country enabled the critical community partnership and acceptance of the phase II/III in each country. Due to the delayed clinical trial initiation, relative to the epidemiologic peak of the outbreak in the three countries, vaccine interventions may or may not have played a major role in bringing the epidemic under control. Having demonstrated that clinical trials can be performed during a large outbreak, the global research community can now build on the experience to implement trials more rapidly and efficiently in future outbreaks. Incorporating clinical research needs into planning for future health emergencies and understanding what kind of trial designs is needed for reliable results in an epidemic of limited duration should improve global response to future infectious disease outbreaks.

PMID: 28918539 [PubMed - as supplied by publisher]

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Temporal distribution of alcohol related facial fractures

Alcohol intoxication as a common concomitant factor in facial fractures is well reported. However, less has been described on its temporal pattern of presentations. Studies have found such pattern to be dependent on factors such as seasonal climate variations, timing of social, leisure and sporting activities, and road traffic conditions.

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Evaluation of KGF, EGF, VEGF, bcl-2, IL-6 and ki67 expression in oral epithelium adjacent to bisphosphonate-related osteonecrosis and florid osseous dysplasia: a comparative immunohistochemical study

Bisphosphonates are associated with impairment of epithelial proliferation and it is suggested that this feature can play a role in the pathogenesis of bisphosphonate-related osteonecrosis of the jaws (ON). Objective: to compare the expression of proliferative markers and apoptosis-associated proteins in the oral mucosa adjacent to bone sequestrum associated with ON and florid osseous dysplasia (OD). Study design: oral mucosal samples derived from surgical procedures performed for treatment of ON and OD (10 cases each) were retrieved.

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Etiology, diagnosis, and demographic analysis of maxillofacial trauma in elderly persons: A 10-year investigation

The aim of this study was to investigate etiologies and diagnoses of maxillofacial trauma in emergency services in Brazil over a period of 10 years. Additionally, associations among sex, age, accident location, and dependent variables were analyzed. Understanding the epidemiology of trauma and the physiology of aging is important in maintaining health and bettering service for the elderly population.

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Tongue movement during articulation in magnetic resonance imaging: Findings in 20 healthy volunteers and a patient with anterior floor of the mouth squamous cell carcinoma

Combined ablative and reconstructive oral maxillofacial surgery involves a multitude of anatomical and functional structures for speech and swallowing. Although there are a few methods to objectively examine swallowing function, this is not true for speech. We describe the development of an objective visualization and measurement tool for magnetic resonance imaging (MRI) to evaluate speech and its first application in a patient.

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Surgical treatment of synkinesiss between smiling and eyelid closure

Synkinetics movements are common among patients with incomplete recovery from facial palsy, with reported rates ranging from 9.1% to almost 100%.The authors propose the separation of the neural stimulus of the orbicularis oculi from that of the zygomatic muscular complex to treat eyelid closure/smiling synkinesiss. This technique, associated with an anastomosis between the masseteric nerve and a central branch of the facial nerve, as well as with the use of a cross-facial nerve graft, resolves most of the spasms of the midface musculature, leading to a more relaxed tone when the mimic muscle is at rest and enhancing muscle excursion during voluntary and spontaneous smiling.

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Autonomous Bone Reposition around Anatomical Landmark for Robot-Assisted Orthognathic Surgery

The purpose of this study was to develop a new method for enabling a robot to assist a surgeon in repositioning a bone segment to accurately transfer a preoperative virtual plan into the intraoperative phase in orthognathic surgery. We developed a robot system consisting of an arm with six degrees of freedom, a robot motion-controller, and a PC. An end-effector at the end of the robot arm transferred the movements of the robot arm to the patient's jawbone. The registration between the robot and CT image spaces was performed completely preoperatively, and the intraoperative registration could be finished using only position changes of the tracking tools at the robot end-effector and the patient's splint.

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Marital status as a predictor of survival in patients with human papilloma virus-positive oropharyngeal cancer

Determine whether marital status is a significant predictor of survival in human papillomavirus-positive oropharyngeal cancer.

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Comparison of radiation doses imparted during 128-multislice CT-scanners and cone beam computed tomography for intra- and perioperative cochlear implant assessment

To examine radiation-doses imparted during multislice (MSCT) and cone-beam computed-tomography (CBCT) for perioperative examination of cochlear-implant insertion.

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The folded postauricular flap: A novel approach to reconstruction of large full thickness defects of the conchal bowl

Extensive subtotal full-thickness auriculectomy defects pose a challenge for the reconstructive surgeon. The posterior island flap (PIF), based on the posterior auricular artery, has been described as a reconstructive option for auricular defects, with reports describing a "pull-through" or "revolving door" technique to reconstruct subtotal partial thickness and full thickness auricular defects. These techniques may result in posterior "pinning" of the auricle. This patient is an 87-year-old male who presented after Mohs excision of squamous cell carcinoma of the conchal bowl, which resulted in a 4x4cm subtotal auriculectomy defect.

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Marital status as a predictor of survival in patients with human papilloma virus-positive oropharyngeal cancer

Determine whether marital status is a significant predictor of survival in human papillomavirus-positive oropharyngeal cancer.

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Comparison of radiation doses imparted during 128-multislice CT-scanners and cone beam computed tomography for intra- and perioperative cochlear implant assessment

To examine radiation-doses imparted during multislice (MSCT) and cone-beam computed-tomography (CBCT) for perioperative examination of cochlear-implant insertion.

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The folded postauricular flap: A novel approach to reconstruction of large full thickness defects of the conchal bowl

Extensive subtotal full-thickness auriculectomy defects pose a challenge for the reconstructive surgeon. The posterior island flap (PIF), based on the posterior auricular artery, has been described as a reconstructive option for auricular defects, with reports describing a "pull-through" or "revolving door" technique to reconstruct subtotal partial thickness and full thickness auricular defects. These techniques may result in posterior "pinning" of the auricle. This patient is an 87-year-old male who presented after Mohs excision of squamous cell carcinoma of the conchal bowl, which resulted in a 4x4cm subtotal auriculectomy defect.

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Serous retinal detachment after panretinal photocoagulation for proliferative diabetic retinopathy: a case report

Proliferative diabetic retinopathy is a major cause of visual impairment in working-age adults worldwide. Panretinal photocoagulation is a cornerstone in its management; however, it may include a range of side...

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Measuring the preference towards patient-centred communication with the Chinese-revised Patient-Practitioner Orientation Scale: a cross-sectional study among physicians and patients in clinical settings in Shanghai, China

Objectives

To adapt the Patient–Practitioner Orientation Scale (PPOS), to a Chinese context, and explore the preference towards patient-centred communication among physicians and patients with the Chinese-revised Patient–Practitioner Orientation Scale (CR-PPOS).

Design

A cross-sectional questionnaire-based study.

Setting

Clinical settings from eight medical units, including four community hospitals and four general hospitals, in Shanghai, China.

Participants

1018 participants, including 187 physicians and 831 patients, completed this study in two successive stages.

Outcome measurements

Psychometric properties of the CR-PPOS and participants' score on the CR-PPOS.

Results

Compared with the original PPOS, the 11-item CR-PPOS obtained better psychometric indices. Physicians and patients scored differently on both the total CR-PPOS and its two subscales. Compared with physicians, the scores of patients were more influenced by their personal characteristics, such as age and education.

Conclusions

The CR-PPOS is a better instrument in a Chinese context than the original translated version. The divergence in the extent to which patient-centred communication is preferred among Chinese physicians and patients should be noted. Adapting physicians' communication strategy to patients' preferences based on their personal characteristics can be a viable approach towards improving clinical efficiency.

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Exercise for patients with major depression: a systematic review with meta-analysis and trial sequential analysis

Objectives

To assess the benefits and harms of exercise in patients with depression.

Design

Systematic review

Data sources

Bibliographical databases were searched until 20 June 2017.

Eligibility criteria and outcomes

Eligible trials were randomised clinical trials assessing the effect of exercise in participants diagnosed with depression. Primary outcomes were depression severity, lack of remission and serious adverse events (eg, suicide) assessed at the end of the intervention. Secondary outcomes were quality of life and adverse events such as injuries, as well as assessment of depression severity and lack of remission during follow-up after the intervention.

Results

Thirty-five trials enrolling 2498 participants were included. The effect of exercise versus control on depression severity was –0.66 standardised mean difference (SMD) (95% CI –0.86 to –0.46; p<0.001; grading of recommendations assessment, development and evaluation (GRADE): very low quality). Restricting this analysis to the four trials that seemed less affected of bias, the effect vanished into –0.11 SMD (–0.41 to 0.18; p=0.45; GRADE: low quality). Exercise decreased the relative risk of no remission to 0.78 (0.68 to 0.90; p<0.001; GRADE: very low quality). Restricting this analysis to the two trials that seemed less affected of bias, the effect vanished into 0.95 (0.74 to 1.23; p=0.78). Trial sequential analysis excluded random error when all trials were analysed, but not if focusing on trials less affected of bias. Subgroup analyses found that trial size and intervention duration were inversely associated with effect size for both depression severity and lack of remission. There was no significant effect of exercise on secondary outcomes.

Conclusions

Trials with less risk of bias suggested no antidepressant effects of exercise and there were no significant effects of exercise on quality of life, depression severity or lack of remission during follow-up. Data for serious adverse events and adverse events were scarce not allowing conclusions for these outcomes.

Systematic review registration

The protocol was published in the journal Systematic Reviews: 2015; 4:40.

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How novice, skilled and advanced clinical researchers include variables in a case report form for clinical research: a qualitative study

Objectives

Despite varying degrees in research training, most academic clinicians are expected to conduct clinical research. The objective of this research was to understand how clinical researchers of different skill levels include variables in a case report form for their clinical research.

Setting

The setting for this research was a major academic institution in Beijing, China.

Participants

The target population was clinical researchers with three levels of experience, namely, limited clinical research experience, clinicians with rich clinical research experience and clinical research experts.

Methods

Using a qualitative approach, we conducted 13 individual interviews (face to face) and one group interview (n=4) with clinical researchers from June to September 2016. Based on maximum variation sampling to identify researchers with three levels of research experience: eight clinicians with limited clinical research experience, five clinicians with rich clinical research experience and four clinical research experts. These 17 researchers had diverse hospital-based medical specialties and or specialisation in clinical research.

Results

Our analysis yields a typology of three processes developing a case report form that varies according to research experience level. Novice clinician researchers often have an incomplete protocol or none at all, and conduct data collection and publication based on a general framework. Experienced clinician researchers include variables in the case report form based on previous experience with attention to including domains or items at risk for omission and by eliminating unnecessary variables. Expert researchers consider comprehensively in advance data collection and implementation needs and plan accordingly.

Conclusion

These results illustrate increasing levels of sophistication in research planning that increase sophistication in selection for variables in the case report form. These findings suggest that novice and intermediate-level researchers could benefit by emulating the comprehensive planning procedures such as those used by expert clinical researchers.

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Integrated management of atrial fibrillation including tailoring of anticoagulation in primary care: study design of the ALL-IN cluster randomised trial

Introduction

In our ageing society, we are at the merge of an expected epidemic of atrial fibrillation (AF). AF management requires an integrated approach, including rate or rhythm control, stroke prevention with anticoagulation and treatment of comorbidities such as heart failure or type 2 diabetes. As such, primary care seems to be the logical healthcare setting for the chronic management of patients with AF. However, primary care has not yet played a dominant role in AF management, which has been in fact more fragmented between different healthcare providers. This fragmentation might have contributed to high healthcare costs. To demonstrate the feasibility of managing AF in primary care, studies are needed that evaluate the safety and (cost-)effectiveness of integrated AF management in primary care.

Methods and analysis

The ALL-IN trial is a multicentre, pragmatic, cluster randomised, non-inferiority trial performed in primary care practices in a suburban region in the Netherlands. We aim to include a minimum of 1000 patients with AF aged 65 years or more from around 18 to 30 practices. Duration of the study is 2 years. Practices will be randomised to either the intervention arm (providing integrated AF management, involving a trained practice nurse and collaboration with secondary care) or the control arm (care as usual). The primary endpoint is all-cause mortality. Secondary endpoints are cardiovascular mortality, (non)-cardiovascular hospitalisation, major adverse cardiac events, stroke, major bleeding, clinically relevant non-major bleeding, quality of life and cost-effectiveness.

Ethics and dissemination

The protocol was approved by the Medical Ethical Committee of the Isala Hospital Zwolle, the Netherlands. Patients in the intervention arm will be asked informed consent for participating in the intervention. Results are expected in 2019 and will be disseminated through both national and international journals and conferences.

Trial registration number

This trial is registered at the Netherlands Trial Register (NTR5532).

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A pragmatic group sequential, placebo-controlled, randomised trial to determine the effectiveness of glyceryl trinitrate for retained placenta (GOT-IT): a study protocol

Introduction

A retained placenta is diagnosed when the placenta is not delivered following delivery of the baby. It is a major cause of postpartum haemorrhage and treated by the operative procedure of manual removal of placenta (MROP).

Methods and analysis

The aim of this pragmatic, randomised, placebo-controlled, double-blind UK-wide trial, with an internal pilot and nested qualitative research to adjust strategies to refine delivery of the main trial, is to determine whether sublingual glyceryl trinitrate (GTN) is (or is not) clinically and cost-effective for (medical) management of retained placenta. The primary clinical outcome is need for MROP, defined as the placenta remaining undelivered 15 min poststudy treatment and/or being required within 15 min of treatment due to safety concerns. The primary safety outcome is measured blood loss between administration of treatment and transfer to the postnatal ward or other clinical area. The primary patient-sided outcome is satisfaction with treatment and a side effect profile. The primary economic outcome is net incremental costs (or cost savings) to the National Health Service of using GTN versus standard practice. Secondary outcomes are being measured over a range of clinical and economic domains. The primary outcomes will be analysed using linear models appropriate to the distribution of each outcome. Health service costs will be compared with multiple trial outcomes in a cost-consequence analysis of GTN versus standard practice.

Ethics and dissemination

Ethical approval has been obtained from the North-East Newcastle & North Tyneside 2 Research Ethics Committee (13/NE/0339). Dissemination plans for the trial include the Health Technology Assessment Monograph, presentation at international scientific meetings and publication in high-impact, peer-reviewed journals.

Trial registration number

ISCRTN88609453; Pre-results.

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Controlling Nutritional Status (CONUT) score as a predictor of all-cause mortality in elderly hypertensive patients: a prospective follow-up study

Objectives

The aim of this study was to elucidate the impact of nutritional status on survival per Controlling Nutritional Status (CONUT) score and Geriatric Nutritional Risk Index (GNRI) in patients with hypertension over 80 years of age.

Design

Prospective follow-up study.

Participants

A total of 336 hypertensive patients over 80 years old were included in this study.

Outcome measures

All-cause deaths were recorded as Kaplan-Meier curves to evaluate the association between CONUT and all-cause mortality at follow-up. Cox regression models were used to investigate the prognostic value of CONUT and GNRI for all-cause mortality in the 90-day period after admission.

Results

Hypertensive patients with higher CONUT scores exhibited higher mortality within 90 days after admission (1.49%, 6.74%, 15.38%, respectively, ²=30.92, p=0.000). Surviving patients had higher body mass index (24.25±3.05 vs 24.25±3.05, p=0.012), haemoglobin (123.78±17.05 vs 115.07±20.42, p=0.040) and albumin levels, as well as lower fasting blood glucose (6.90±2.48 vs 8.24±3.51, p=0.010). Higher GRNI score (99.42±6.55 vs 95.69±7.77, p=0.002) and lower CONUT (3.13±1.98 vs 5.14±2.32) both indicated better nutritional status. Kaplan-Meier curves indicated that survival rates were significantly worse in the high-CONUT group compared with the low-CONUT group (¹ =13.372, p=0.001). Cox regression indicated an increase in HR with increasing CONUT risk (from normal to moderate to severe). HRs (95% CI) for 3-month mortality was 1.458 (95% CI 1.102 to 1.911). In both respiratory tract infection and 'other reason' groups, only CONUT was a sufficiently predictor for all-cause mortality (HR=1.284, 95% CI 1.013 to 1.740, p=0.020 and HR=1.841, 95% CI 1.117 to 4.518, p=0.011). Receiver operating characteristic showed that CONUT higher than 3.0 was found to predict all-cause mortality with a sensitivity of 77.8% and a specificity of 64.7% (area under the curve=0.778, p<0.001).

Conclusion

Nutritional status assessed via CONUT is an accurate predictor of all-cause mortality 90 days postadmission. Evaluation of nutritional status may provide additional prognostic information in hypertensive patients.

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Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) versus alteplase (rt-PA) as fibrinolytic therapy for acute ST-segment elevation myocardial infarction (China TNK STEMI): protocol for a randomised, controlled, non-inferiority trial

Aim

To evaluate the efficacy and safety of recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) in lowering major adverse cardiovascular and cerebrovascular events (MACCEs) in Chinese acute ST-segment elevation myocardial infarction (STEMI) patients.

Methods and analysis

The study is designed as a multicentre, randomised, controlled non-inferiority phase IV trial with balanced randomisation (1:1) in patients with STEMI. The planned sample size is 6200 participants (or 3100 per arm). Participants with STEMI will be randomised to receive either rhTNK-tPA or alteplase (rt-PA), with stratification by research centre, age and the time from symptom onset to randomisation. All patients will receive concomitant antiplatelet and anticoagulant therapy before fibrinolytic therapy. The participants assigned to the intervention group will receive an intravenous bolus of 16 mg rhTNK-tPA, while those assigned to the control group will receive an intravenous bolus of 8 mg rt-PA followed by 42 mg infusion over 90 mins. Other medications can also be administered at the discretion of the cardiologists in charge. All participants will be followed up for the primary study endpoint, the occurrence of MACCEs within 30 days after fibrinolytic therapy, which is defined as all-cause mortality, non-fatal re-infarction, non-fatal stroke, percutaneous coronary intervention (PCI) due to thrombolysis failure, and PCI due to reocclusion. Both intention-to-treat and per-protocol analyses will be done for the primary analyses.

Ethics and dissemination

The study procedures and informed consent form were approved by all participating hospitals. The results will be disseminated in peer review journals and academic conferences. This multicentre randomised controlled trial will provide high-quality data about the efficacy and safety of rhTNK-tPA and, once approved, its easier use should help improve the application of reperfusion therapy and hence the treatment outcomes of STEMI patients.

Trial registration number

NCT02835534.

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Adherence and dosing interval of subcutaneous antitumour necrosis factor biologics among patients with inflammatory arthritis: analysis from a Canadian administrative database

Objectives

Subcutaneous tumour necrosis factor alpha TNFαinhibitors (SC-TNFis) such as golimumab (GLM), adalimumab (ADA), etanercept (ETA) and certolizumab pegol (CZP) have been used for many years for the treatment of inflammatory arthritis. Non-adherence to therapy is an important modifiable factor that may compromise patient outcomes. The aim of this analysis was to compare adherence and dosing interval of SC-TNFis in the treatment of people with inflammatory arthritis.

Design

We used the IMS Brogan database combining both Canadian private and public drug plan databases of Ontario and Quebec. Target drugs included SC-TNFis for inflammatory arthritis. The index period was from 1 January 2010 to 30 June 2012 and patients were followed for 24 months through 30 June 2014. Inclusion criteria were adult patients newly prescribed a SC-TNFis with at least three prescriptions and retained on therapy at 24 months.

Dosing regimens as per the product monographs were used to compare actual versus expected drug utilisation. The mean possession ratio was used as a marker for adherence. Patients who scored >80% were considered adherent. The average days between units was estimated by taking the total days on therapy and divided by the number of units the patient received.

Results

4035 patients were included: 683 (16.9%), 1400 (34.7%), 1765 (43.7%) and 187 (4.6%) were treated with GLM, ADA, ETA and CZP, respectively. The proportion of adherent patients in the GLM cohort (n=595/683, 87%, p<0.0001) was greater compared with ADA (n=1044/1400, 75%), ETA (n=1285/1765, 73%) and CZP-treated patients (132/187, 71%). In addition, the number of patients receiving biological drug at a shorter dosing interval was similar between cohorts, and was 5%, 6%, 12% and 4% in GLM (≤26 days), ADA (≤12 days), ETA (≤6 days) and CZP-treated patients (≤12 days), respectively.

Conclusions

In this real-life administrative database, GLM had better adherence compared with other SC-TNFis.

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Interdisciplinary model of care (RADICALS) for early detection and management of chronic obstructive pulmonary disease (COPD) in Australian primary care: study protocol for a cluster randomised controlled trial

Introduction

Up to half of all smokers develop clinically significant chronic obstructive pulmonary disease (COPD). Gaps exist in the implementation and uptake of evidence-based guidelines for managing COPD in primary care. We describe the methodology of a cluster randomised controlled trial (cRCT) evaluating the efficacy and cost-effectiveness of an interdisciplinary model of care aimed at reducing the burden of smoking and COPD in Australian primary care settings.

Methods and analysis

A cRCT is being undertaken to evaluate an interdisciplinary model of care (RADICALS — Review of Airway Dysfunction and Interdisciplinary Community-based care of Adult Long-term Smokers). General practice clinics across Melbourne, Australia, are identified and randomised to the intervention group (RADICALS) or usual care. Patients who are current or ex-smokers, of at least 10 pack years, including those with an existing diagnosis of COPD, are being recruited to identify 280 participants with a spirometry-confirmed diagnosis of COPD. Handheld lung function devices are being used to facilitate case-finding. RADICALS includes individualised smoking cessation support, home-based pulmonary rehabilitation and home medicines review. Patients at control group sites receive usual care and Quitline referral, as appropriate. Follow-ups occur at 6 and 12 months from baseline to assess changes in quality of life, abstinence rates, health resource utilisation, symptom severity and lung function. The primary outcome is change in St George's Respiratory Questionnaire score of patients with COPD at 6 months from baseline.

Ethics and dissemination

This project has been approved by the Monash University Human Research Ethics Committee and La Trobe University Human Ethics Committee (CF14/1018 – 2014000433). Results of the study will be disseminated in peer-reviewed journals and research conferences. If the intervention is successful, the RADICALS programme could potentially be integrated into general practices across Australia and sustained over time.

Trial registration number

ACTRN12614001155684; Pre-results.

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Trend analysis of mortality rates and causes of death in children under 5 years old in Beijing, China from 1992 to 2015 and forecast of mortality into the future: an entire population-based epidemiological study

Objectives

To analyse trends in mortality and causes of death among children aged under 5 years in Beijing, China between 1992 and 2015 and to forecast under-5 mortality rates (U5MRs) for the period 2016–2020.

Methods

An entire population-based epidemiological study was conducted. Data collection was based on the Child Death Reporting Card of the Beijing Under-5 Mortality Rate Surveillance Network. Trends in mortality and leading causes of death were analysed using the ² test and SPSS 19.0 software. An autoregressive integrated moving average (ARIMA) model was fitted to forecast U5MRs between 2016 and 2020 using the EViews 8.0 software.

Results

Mortality in neonates, infants and children aged under 5 years decreased by 84.06%, 80.04% and 80.17% from 1992 to 2015, respectively. However, the U5MR increased by 7.20% from 2013 to 2015. Birth asphyxia, congenital heart disease, preterm/low birth weight and other congenital abnormalities comprised the top five causes of death. The greatest, most rapid reduction was that of pneumonia by 92.26%, with an annual average rate of reduction of 10.53%. The distribution of causes of death differed among children of different ages. Accidental asphyxia and sepsis were among the top five causes of death in children aged 28 days to 1 year and accident was among the top five causes in children aged 1–4 years. The U5MRs in Beijing are projected to be 2.88, 2.87, 2.90, 2.97 and 3.09 for the period 2016–2020, based on the predictive model.

Conclusion

Beijing has made considerable progress in reducing U5MRs from 1992 to 2015. However, U5MRs could show a slight upward trend from 2016 to 2020. Future considerations for child healthcare include the management of birth asphyxia, congenital heart disease, preterm/low birth weight and other congenital abnormalities. Specific preventative measures should be implemented for children of various age groups.

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Diagnostic validity of early-onset obsessive-compulsive disorder in the Danish Psychiatric Central Register: findings from a cohort sample

Objectives

Employing national registers for research purposes depends on a high diagnostic validity. The aim of the present study was to examine the diagnostic validity of recorded diagnoses of early-onset obsessive-compulsive disorder (OCD) in the Danish Psychiatric Central Register (DPCR).

Design

Review of patient journals selected randomly through the DPCR.

Method

One hundred cases of OCD were randomly selected from DPCR. Using a predefined coding scheme based on the Children's Yale Brown Obsessive Compulsive Scale (CYBOCS), experienced research nurse or child and adolescent psychiatrists assessed each journal to determine the presence/absence of OCD diagnostic criteria. The detailed assessments were reviewed by two senior child and adolescent psychiatrists to determine if diagnostic criteria were met.

Primary outcome measurements

Positive predictive value (PPV) was used as the primary outcome measurement.

Results

A total of 3462 children/adolescents received an OCD diagnosis as the main diagnosis between 1 January 1995 and 31 December 2015. The average age at diagnosis was 13.21±2.89 years. The most frequent registered OCD subcode was the combined diagnosis DF42.2. Of the 100 cases we examined, 35 had at least one registered comorbidity. For OCD, the PPV was good (PPV 0.85). Excluding journals with insufficient information, the PPV was 0.96. For the subcode F42.2 the PPV was 0.77. The inter-rater reliability was 0.94. The presence of the CYBOCS in the journal significantly increased the PPV for the OCD diagnosis altogether and for the subcode DF42.2.

Conclusion

The validity and reliability of International Classification of Disease 10th revision codes for OCD in the DPCR is generally high. The subcodes for predominant obsessions/predominant compulsions are less certain and should be used with caution. The results apply for both children and adolescents and for both older and more recent cases. Altogether, the study suggests that there is a high validity of the OCD diagnosis in the Danish National Registers.

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Comparison of anthropometric indices for predicting the risk of metabolic syndrome and its components in Chinese adults: a prospective, longitudinal study

Objectives

Our study aimed to distinguish the ability of anthropometric indices to assess the risk of metabolic syndrome (MetS).

Design

Prospective cohort study.

Setting

Shenyang, China.

Participants

A total of 379 residents aged between 40 and 65 were enrolled. 253 of them were free of MetS and had been followed up for 4.5 years.

Methods

At baseline, all the participants underwent a thorough medical examination. A variety of anthropometric parameters were measured and calculated, including waist circumference (WC), body mass index (BMI), a body shape index (ABSI), abdominal volume index (AVI), body adiposity index, body roundness index, conicity index, waist-to-hip ratio and visceral adiposity index (VAI). After 4.5 year follow-up, we re-examined whether participants were suffering from MetS. A receiver operating characteristic (ROC) curve was applied to examine the potential of the above indices to identify the status and risk of MetS.

Outcomes

Occurrence of MetS.

Results

At baseline, 33.2% participants suffered from MetS. All of the anthropometric indices showed clinical significance, and VAI was superior to the other indices as it was found to have the largest area under the ROC curve. After a 4.5 year follow-up, 37.8% of men and 23.9% of women developed MetS. ROC curve analysis suggested that baseline BMI was the strongest predictor of MetS for men (0.77 (0.68–0.85)), and AVI was the strongest for women (0.72 (0.64–0.79)). However, no significant difference was observed between WC and both indices. In contrast, the baseline ABSI did not predict MetS in both genders.

Conclusions

The present study indicated that these different indices derived from anthropometric parameters have different discriminatory abilities for MetS. Although WC did not have the largest area under the ROC curve for diagnosing and predicting MetS, it may remain a better index of MetS status and risk because of its simplicity and wide use.

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Comparative effectiveness of injectable penicillin versus a combination of penicillin and gentamicin in children with pneumonia characterised by indrawing in Kenya: protocol for an observational study

Introduction

WHO treatment guidelines are widely recommended for guiding treatment for millions of children with pneumonia every year across multiple low-income and middle-income countries. Guidelines are based on synthesis of available evidence that provides moderate certainty in evidence of effects for forms of pneumonia that can result in hospitalisation. However, trials have included fewer children from Africa than other settings, and it is suggested that African children with pneumonia have higher mortality. Thus, despite improving access to recommended treatments and deployment with high coverage of childhood vaccines, pneumonia remains one of the top causes of mortality for children in Kenya. Establishing whether there are benefits of alternative treatment regimens to help reduce mortality would require pragmatic clinical trials. However, these remain relatively expensive and time consuming. This protocol describes an approach to using secondary analysis of a new, large observational dataset as a potentially cheaper and quicker way to examine the comparative effectiveness of penicillin versus penicillin plus gentamicin in treatment of indrawing pneumonia. Addressing this question is important, as although it is now recommended that this form of pneumonia is treated with oral medication as an outpatient, it remains associated with non-trivial mortality that may be higher outside trial populations.

Methods and analysis

We will use a large observational dataset that captures data on all admissions to 13 Kenyan county hospitals. These data represent the findings of clinicians in practice and, because the system was developed for large observational research, pose challenges of non-random treatment allocation and missing data. To overcome these challenges, this analysis will use a rigorous approach to study design, propensity score methods and multiple imputation to minimise bias.

Ethics and dissemination

The primary data are held by hospitals participating in the Kenyan Clinical Information Network project with de-identifed data shared with the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme for agreed analyses. The use of data for the analysis described received ethical clearance from the KEMRI scientific and ethical review committee. The findings of this analysis will be published.

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A cross-sectional study in a tertiary care hospital in China: noise or silence in the operating room

Objectives

This study aims to provide a comprehensive description of noise levels in operating rooms (ORs) in a tertiary care hospital in China. Additionally, the study aims to examine the deviation in noise levels from international and internal standards as well as the differences in noise levels by category of surgery and day of the week.

Methods

We monitored noise levels in 23 ORs in a tertiary care hospital in China between August 2015 and March 2016. Dosimeters were used to determine noise levels. The noise data collected in the dosimeter were downloaded to an IBM computer for subsequent analysis. One-way analysis of variance and Student's t-test were used to examine the differences in noise levels.

Results

The noise level in the ORs ranged between 59.2 and 72.3 dB(A), with 100% of the measurements exceeding the recommended hospital noise standards. There was substantial similarity in noise levels from Monday to Friday (F=1.404, p=0.234), with a range between 63.7 and 64.5 dB(A). The difference in noise levels by category of surgery was significant (F=3.381, p<0.001). The results of the post hoc analysis suggested that ophthalmic surgery had significantly higher noise levels than otolaryngological surgery or general surgery.

Conclusions

Ophthalmic surgery had significantly higher noise levels than otolaryngological or general surgeries. High noise levels were identified in all evaluated ORs during weekdays, and these levels consistently exceeded the currently accepted standards. These findings warrant further investigation to determine the harmful effects of noise on both patients and staff in ORs.

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Does improving sleep lead to better mental health? A protocol for a meta-analytic review of randomised controlled trials

Introduction

Sleep and mental health go hand-in-hand, with many, if not all, mental health problems being associated with problems sleeping. Although sleep has been traditionally conceptualised as a secondary consequence of mental health problems, contemporary views prescribe a more influential, causal role of sleep in the formation and maintenance of mental health problems. One way to evaluate this assertion is to examine the extent to which interventions that improve sleep also improve mental health.

Method and analysis

Randomised controlled trials (RCTs) describing the effects of interventions designed to improve sleep on mental health will be identified via a systematic search of four bibliographic databases (in addition to a search for unpublished literature). Hedges' g and associated 95% CIs will be computed from means and SDs where possible. Following this, meta-analysis will be used to synthesise the effect sizes from the primary studies and investigate the impact of variables that could potentially moderate the effects. The Jadad scale for reporting RCTs will be used to assess study quality and publication bias will be assessed via visual inspection of a funnel plot and Egger's test alongside Orwin's fail-safe n. Finally, mediation analysis will be used to investigate the extent to which changes in outcomes relating to mental health can be attributed to changes in sleep quality.

Ethics and dissemination

This study requires no ethical approval. The findings will be submitted for publication in a peer-reviewed journal and promoted to relevant stakeholders.

PROSPERO registration number

CRD42017055450.

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Development of core outcome sets for effectiveness trials of interventions to prevent and/or treat delirium (Del-COrS): study protocol

Introduction

Delirium is a common, serious and potentially preventable condition with devastating impact on the quality of life prompting a proliferation of interventional trials. Core outcome sets aim to standardise outcome reporting by identifying outcomes perceived fundamental for measurement in trials of a specific interest area. Our aim is to develop international consensus on two core outcome sets for trials of interventions to prevent and/or treat delirium, irrespective of study population. We aim to identify additional core outcomes specific to the critically ill, acutely hospitalised patients, palliative care and older adults.

Methods and analysis

We will conduct a systematic review of published and ongoing delirium trials (1980 onwards) and one-on-one interviews of patients who have experienced delirium and family members. These data will inform Delphi round 1 of a two-stage consensus process. In round 2, we will provide participants their own response, summarised group responses and those of patient/family participants for rescoring. We will randomise participants to receive feedback as proportion scoring the outcome as critical or as group mean responses. We will hold a consensus meeting using nominal group technique to finalise outcomes for inclusion. We will repeat the Delphi process and consensus meeting to select measures for each core outcome. We will recruit 240 Delphi participants giving us 80% power to detect a 1.0–1.5 point (9-point scale) difference by feedback method between rounds. We will analyse differences for subsequent scores, magnitude of opinion change, items retained and level of agreement.

Ethics and dissemination

We are obtaining research ethics approvals according to local governance. Participation will be voluntary and data deidentified. Support from three international delirium organisations will be instrumental in dissemination and core outcome set uptake. We will disseminate through peer-reviewed open access publications and present at conferences selected to reach a wide range of knowledge users.

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Disability acquisition and mental health: effect modification by demographic and socioeconomic characteristics using data from an Australian longitudinal study

Objectives

There is evidence of a causal relationship between disability acquisition and poor mental health, but the substantial heterogeneity in the magnitude of the effect is poorly understood and may be aetiologically informative. This study aimed to identify demographic and socioeconomic factors that modify the effect of disability acquisition on mental health.

Design and setting

The Household, Income and Labour Dynamics in Australia Survey is a nationally representative longitudinal survey of Australian households that has been conducted annually since 2001. Four waves of data were included in this analysis, from 2011 to 2014.

Participants

Individuals who acquired a disability (n=387) were compared with those who remained disability-free in all four waves (n=7936).

Primary outcome measure

Mental health was measured using the mental health subscale of the Short Form 36 (SF-36) general health questionnaire, which measures symptoms of depression, anxiety and psychological well-being.

Methods

Linear regression models were fitted to estimate the effect of disability acquisition on mental health, testing for effect modification by key demographic and socioeconomic characteristics. To maximise causal inference, we used a propensity score approach with inverse probability of treatment weighting to control for confounding and multiple imputation using chained equations to assess the impact of missing data.

Results

On average, disability acquisition was associated with a 5-point decline in mental health score (estimated mean difference: –5.1, 95% CI –7.2 to –3.0). There was strong evidence that income and relationship status modified the effect, with more detrimental effects in the lowest (–12.5, 95% CI –18.5 to –6.5) compared with highest income quintile (–1.1, 95% CI –4.9 to 2.7) and for people not in a relationship (–8.8, 95% CI –12.9 to –4.8) compared with those who were (–3.7, 95% CI –6.1 to –1.4).

Conclusions

Our results suggest that the detrimental effect of disability acquisition on mental health is substantially greater for socioeconomic disadvantaged individuals.

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Gender differences in longevity in free-living older adults who eat-with-others: a prospective study in Taiwan

Objectives

Social activities such as 'eating-with-others' can positively affect the ageing process. We investigated the gender-specific association between eating arrangements and risk of all-cause mortality among free-living older adults.

Setting

A representative sample from the Elderly Nutrition and Health Survey in Taiwan during 1999–2000.

Participants

Some 1894 participants (955 men and 939 women) who aged ≥65 and completed eating arrangement question as well as confirmed survivorship information.

Primary and secondary outcome measures

Eating arrangements, health condition and 24-hour dietary recall information were collected at baseline. We classified eating arrangements as the daily frequency of eating-with-others (0–3). Survivorship was determined by the National Death Registry until the end of 2008. Cox proportional-hazards regression was used to assess the association between eating-with-others and mortality risk.

Results

Overall, 63.1% of men and 56.4% of women ate with others three times a day. Both men and women who ate with others were more likely to have higher meat and vegetable intakes and greater dietary quality than those who ate alone. The HRs (95% CI) for all-cause mortality when eating-with-others two and three times per day were 0.42 (0.28 to 0.61), 0.67 (0.52 to 0.88) in men and 0.68 (0.42 to 1.11), 0.86 (0.64 to 1.16) in women, compared with those who ate alone. Multivariable HRs (95% CI) adjusted for sociodemographic, nutritional and 'activities of daily living' covariates were 0.43 (0.25 to 0.73), 0.63 (0.41 to 0.98) in men and 0.68 (0.35 to 1.30), 0.69 (0.39 to 1.21) in women. With further adjustment for financial status, HR was reduced by 54% in men who ate with others two times a day. Pathway analysis shows this to be dependent on improved dietary quality by eating-with-others.

Conclusions

Eating-with-others is an independent survival factor in older men. Providing a social environment which encourages eating-with-others may benefit survival of older people, especially for men.

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Economic volatility in childhood and subsequent adolescent mental health problems: a longitudinal population-based study of adolescents

Objective

The aim of the current paper was to investigate the association between the patterns of duration, timing and sequencing of exposure to low family income during childhood, and symptoms of mental health problems in adolescence.

Setting

Survey administered to a large population-based sample of Norwegian adolescents.

Participants

Survey data from 9154 participants of 16–19 years age (53% participation rate; 52.7% girls) were linked to registry-based information about childhood family income from tax return data.

Outcome measures

Mental health outcomes were symptoms of emotional, conduct, hyperactivity, peer problems and general mental health problems measured with the Strengths and Difficulties Questionnaire, symptoms of depression measured with Short Mood and Feelings Questionnaire and symptoms of attention-deficit/hyperactivity disorder (ADHD) measured with the Adult ADHD Self-Report Scale.

Results

Latent class analysis and the BCH approach in Mplus were used to examine associations between patterns of poverty exposure and mental health outcomes. Four latent classes of poverty exposure emerged from the analysis. Participants moving into poverty (2.3%), out of poverty (3.5%) or those chronically poor (3.1%) had more symptoms of mental health problems (Cohen's d=16-.50) than those with no poverty exposure (91.1%). This pattern was, however, not found for symptoms of ADHD. The pattern of results was confirmed in robustness checks using observed data.

Conclusions

Exposure to poverty in childhood was found to be associated with most mental health problems in adolescence. There was no strong suggestion of any timing or sequencing effects in the patterns of associations.

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Assessing the extent of drug interactions among patients with multimorbidity in primary and secondary care in the West Midlands (UK): a study protocol for the Mixed Methods Multimorbidity Study (MiMMS)

Introduction

The numbers of patients with three or more chronic conditions (multimorbidity) are increasing, and will rise to 2.9 million by 2018 in the UK alone. Currently in the UK, conditions are mainly managed using over 250 sets of single-condition guidance, which has the potential to generate conflicting recommendations for lifestyle and concurrent medication for individual patients with more than one condition. To address some of these issues, we are developing a new computer-based tool to help manage these patients more effectively. For this tool to be applicable and relevant to current practice, we must first better understand how existing patients with multimorbidity are being managed, particularly relating to concerns over prescribing and potential polypharmacy.

Methods and analysis

Up to four secondary care centres, two community pharmacies and between four and eight primary care centres in the West Midlands will be recruited. Interviewees will be purposively sampled from these sites, up to a maximum of 30. In this mixed methods study, we will perform a dual framework analysis on the qualitative data; the first analysis will use the Theoretical Domains Framework to assess barriers and enablers for healthcare professionals around the management of multimorbid patients; the second analysis will use Normalisation Process Theory to understand how interventions are currently being successfully implemented in both settings. We will also extract quantitative anonymised patient data from primary care to determine the extent of polypharmacy currently present for patients with multimorbidity in the West Midlands.

Discussion

We aim to combine these data so that we can build a useful, fully implementable tool which addresses the barriers most amenable to change within both primary and secondary care contexts.

Ethics and dissemination

Favourable ethical approval has been granted by The University of Birmingham Research Ethics Committee (ERN_16–0074) on 17 May 2016. Our work will be disseminated through peer-reviewed literature, trade journals and conferences. We will also use the dedicated web page hosted by the University to serve as a central point of contact and as a repository of our findings. We aim to produce a minimum of three articles from this work to contribute to the international scientific literature.

Protocol registration number

NIHR Clinical Research Network Portfolio Registration CPMS ID 30613.

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Glioblastoma multiforme

Glioblastoma multiforme: A highly malignant, rapidly growing type of brain tumor that arises from glial cells in the brain. Early symptoms may include sleepiness, headache, and vomiting. Also called a grade IV astrocytoma. Treatment can involve surgery and radiation treatment.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

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Evaluating the sinus and Nasal Quality of Life Survey in the pediatric cystic fibrosis patient population

The Sinus and Nasal Quality of Life Survey (SN-5) is a validated quality of life (QOL) questionnaire for chronic rhinosinusitis in patients age 2–12. Its utility in the cystic fibrosis (CF) has been studied, but not yet validated. The purpose of this study is to determine the effectiveness of the SN-5 for evaluation of sinonasal symptoms in the pediatric CF population.

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The use of CT-scan in foreign body aspiration in children: A 6 years' experience

A foreign body aspiration is a risky situation, common in pediatric emergency. The "gold standard" to rule out a foreign body or proceed to its extraction, is rigid bronchoscopy (RB) under general anesthesia. However, RB is an intrusive exam with possible complications. Depending on authors, RB in emergency is a procedure at risk of complications in 4–17% of cases. Advances in radiology allow CT-scanners of fast acquisition and high definition, which could be used as an alternative to RB.

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Evaluating the sinus and Nasal Quality of Life Survey in the pediatric cystic fibrosis patient population

The Sinus and Nasal Quality of Life Survey (SN-5) is a validated quality of life (QOL) questionnaire for chronic rhinosinusitis in patients age 2–12. Its utility in the cystic fibrosis (CF) has been studied, but not yet validated. The purpose of this study is to determine the effectiveness of the SN-5 for evaluation of sinonasal symptoms in the pediatric CF population.

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The use of CT-scan in foreign body aspiration in children: A 6 years' experience

A foreign body aspiration is a risky situation, common in pediatric emergency. The "gold standard" to rule out a foreign body or proceed to its extraction, is rigid bronchoscopy (RB) under general anesthesia. However, RB is an intrusive exam with possible complications. Depending on authors, RB in emergency is a procedure at risk of complications in 4–17% of cases. Advances in radiology allow CT-scanners of fast acquisition and high definition, which could be used as an alternative to RB.

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DNA damage response inhibitors: mechanisms and potential applications in cancer therapy

Maintenance of genomic integrity is a pre-requisite for a safe and long life, preventing diseases associated with genomic instability such as cancer. DNA is constantly damaged by a large variety of endogenous and exogenous influences. Examples of endogenous lesions are incomplete DNA replication due to stalled replication forks and reactive oxygen species (ROS), and exogenous influences are exemplified by damaging physical or chemical agents such as UV light, ionizing radiation (IR) and DNA-damaging chemotherapeutics.

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Cancers, Vol. 9, Pages 126: The Impact of DNA Repair Pathways in Cancer Biology and Therapy

Cancers, Vol. 9, Pages 126: The Impact of DNA Repair Pathways in Cancer Biology and Therapy

Cancers doi: 10.3390/cancers9090126

Authors: Anatoly Nikolaev Eddy Yang

Genomic instability is one of the key hallmarks of cancer progression [1].[...]

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DNA damage response inhibitors: mechanisms and potential applications in cancer therapy

Treatment outcomes of sialendoscopy for submandibular gland sialolithiasis: The minor axis of the sialolith is a regulative factor for the removal of sialoliths in the hilum of the submandibular gland using sialendoscopy alone

To assess the general guidelines for the removal of sialoliths for submandibular gland sialolithiasis using sialendoscopy alone.

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Treatment outcomes of sialendoscopy for submandibular gland sialolithiasis: The minor axis of the sialolith is a regulative factor for the removal of sialoliths in the hilum of the submandibular gland using sialendoscopy alone

To assess the general guidelines for the removal of sialoliths for submandibular gland sialolithiasis using sialendoscopy alone.

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Sutureless Perceval aortic valve implantation compared with conventional Mitroflow valve replacement

Abstract

Background

Patients at a high operative risk for conventional aortic valve replacement (AVR) may be offered sutureless valve implantation. Sutureless valves resemble conventional valves but incorporate an anchoring mechanism and features to circumvent paravalvular leaks without requiring annular sutures. Haematological and echocardiographic parameters in sutureless Perceval and conventional Mitroflow valves were compared retrospectively using risk-matched controls.

Methods

Perceval and Mitroflow valve patients were matched for pre-operative risk status using logistic Euroscore risk stratification. Haematological and echocardiographic data was collected retrospectively. Independent t tests and Mann-Whitney tests were used to compare variables between groups, with a binomial logistic regression model to determine independent variables.

Results

The use of sutureless Perceval aortic valves results in lower red cell distribution width (RDW) p = 0.001 and lower white cell (WBC) counts p = 0.034 but also resulted in a post-operative drop in platelet counts in two thirds of patients p = 0.038. A platelet level below 80 × 10⁹/L on post-operative day 2 lengthened hospital stay in Perceval patients by 4.7 days, p = 0.050. Perceval implantation lead to lower crossclamp times p = 0.001 and bypass times p = 0.001 and reduced patient-prosthesis mismatch (p = 0.055).

Conclusions

Perceval stentless valves offer a promising alternative to conventional aortic valve replacement, with lower bypass and cross-clamp times, and an increase in indexed effective orifice area. The lower improved implantation time was associated with a lower post-operative RDW and WBC levels, indicating a muted systemic inflammatory response. The lower post-operative platelet counts delayed discharge but did not otherwise affect clinical outcome.

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Personal use of hair dyes and risk of leukemia: a systematic literature review and meta-analysis

Abstract

The objective of this study was to examine the association between personal use of hair dyes and the risk of leukemia. We conducted a systematic literature review of epidemiology studies reporting leukemia-specific cancer risks among hair dye users, and estimated the meta-relative risk (meta-RR) and corresponding 95% confidence interval (95% CI) of leukemia, comparing hair dye users to nonusers. When data from all 20 studies that met the inclusion criteria were combined, ever use of hair dye was associated with a nonstatistically significant increased risk of leukemia, meta-RR = 1.09 (95% CI: 0.97–1.22). When restricted to studies that adjusted for smoking, ever use of hair dye was not associated with leukemia, meta-RR = 0.99 (95% CI: 0.76–1.29). A statistically significant increased risk of leukemia was associated with permanent hair dye use (meta-RR = 1.19 [95% CI: 1.07–1.33]), dark hair dye use (meta-RR = 1.29 [95% CI: 1.11–1.50]), hair dye use among males (meta-RR = 1.42 [95% CI: 1.01–2.00]), hair dye use pre-1980 (meta-RR = 1.49 [95% CI: 1.21–1.83]), and hair dye use for ≥15 years (meta-RR = 1.35 [95% CI: 1.13–1.62]). Overall, findings suggest that ever use of hair dye is not a significant risk factor for leukemia. Certain hair dye use characteristics were associated with a statistically significant increased risk, but further research is required to determine whether these associations truly reflect a risk of leukemia due to methodological limitations in the underlying studies.

The purpose of this study was to synthesize and examine the evidence on the relative risk of leukemia among hair dye users under various exposure scenarios. Findings suggest that personal hair dye use is not a significant risk factor for leukemia when data from all studies were combined. Upon stratification, permanent hair dye use, dark hair dye use, hair dye use pre-1980, hair dye use among males, and hair dye use for ≥15 years were associated with a statistically significant increased risk of leukemia. Further research is required to determine whether these associations truly reflect a risk of leukemia due to methodological limitations in the underlying studies.

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Relationship of tumor PD-L1 (CD274) expression with lower mortality in lung high-grade neuroendocrine tumor

Abstract

Programmed death-ligand 1 (PD-L1) promotes immunosuppression by binding to PD-1 on T lymphocytes. Although tumor PD-L1 expression is a potential predictive marker of clinical response to anti-PD-1/PD-L1 therapy, little is known about its association with clinicopathological features, including prognosis, in high-grade neuroendocrine tumors (HGNETs), including small-cell lung carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC), of the lung. We immunohistochemically examined the membranous of expression of PD-L1 in 115 consecutive surgical cases of lung HGNET (74 SCLC cases and 41 LCNEC cases). We examined the prognostic association of tumor PD-L1 positivity using the log-rank test as well as Cox proportional hazards regression models to calculate the hazard ratio (HR) for mortality. Programmed death-ligand 1 immunostaining (at least 5% tumor cells) was observed in 25 (21%) of the 115 HGNET cases. In a univariable analysis, PD-L1 positivity was associated with lower lung cancer-specific (univariable HR = 0.23; 95% confidence interval [CI] = 0.056–0.64; P = 0.0028) and overall (univariable HR = 0.28; 95% CI = 0.11–0.60; P = 0.0005) mortality. Additionally, in a multivariable analysis, PD-L1 positivity was independently associated with lower lung cancer-specific (multivariable HR = 0.24; 95% CI = 0.058–0.67; P = 0.0039) and overall (multivariable HR = 0.29; 95% CI = 0.11–0.61; P = 0.0006) mortality. Our study demonstrated the prevalence of PD-L1 positivity in lung HGNET cases, and the independent association of tumor PD-L1 positivity with lower mortality in lung HGNET cases. Further studies are needed to confirm our findings.

High-grade neuroendocrine tumor (HGNET) (small cell lung carcinoma and large cell neuroendocrine carcinoma) is the most aggressive histological subtype of lung cancer, and immunotherapies, including anti-PD-1/Programmed death-ligand 1 (PD-L1) therapy, are emerging and promising. The prevalence of PD-L1 positivity in lung HGNET is shown. PD-L1 positivity is associated with lower mortality in lung HGNET.

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Clinical predictive factors of long-term survival after curative resection of pancreatic cancer: a retrospective study

Abstract

Pancreatic ductal adenocarcinoma (PDAC) continues to have the poorest prognosis of all gastrointestinal malignancies, even after the tumor has been completely resected. However, only a proportion of patients achieve 5-year survival after resection. The factors predictive of achieving 5-year survival remain unclear. The aim of this study was to investigate the pre- and postoperative clinicopathological characteristics of PDAC patients with a >5-year survival after curative resection. We retrospectively reviewed patients who underwent pancreatectomy for PDAC between January 1995 and December 2011. Logistic regression analysis was performed to determine the predictive factors for 5-year survival. One hundred and fifty-one patients were enrolled, including 38 patients with 5-year survival (actual 5-year survival rate, 25.2%). The independent preoperative factors predictive of achieving 5-year survival included serum albumin levels (odds ratio [OR]: 5.06, 95.0% confidence interval [CI]: 1.49–17.19; P = 0.009) and neoadjuvant chemoradiotherapy (OR: 3.02, 95.0% CI: 1.00–9.08; P = 0.049). Venous infiltration (OR: 2.99, 95.0% CI: 1.09–8.25; P = 0.034), liver recurrence (OR: 0.17, 95.0% CI: 0.04–0.69; P = 0.013), and perioperative portal vein infusion chemotherapy (OR: 3.06, 95.0% CI: 1.09–8.25; P = 0.028) were found to be independent postoperative predictive factors for achieving 5-year survival. Serum albumin levels could be a biomarker for predicting the prognosis of PDAC patients after curative resection. Liver recurrence and perioperative portal vein infusion chemotherapy were independent postoperative factors, suggesting that perioperative portal vein infusion chemotherapy could be promising for improving the survival rate of PDAC patients after curative resection.

Relationship between neoadjuvant chemoradiotherapy (NACRT) and (A) postoperative disease-free survival (DFS) and (B) postoperative overall survival (OS) and relationship between perioperative adjuvant portal vein infusion (PVI) chemotherapy and (C) postoperative DFS and (D) postoperative OS.

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JCM, Vol. 6, Pages 86: Gut Microbiota-Dependent Trimethylamine-N-oxide and Serum Biomarkers in Patients with T2DM and Advanced CKD

JCM, Vol. 6, Pages 86: Gut Microbiota-Dependent Trimethylamine-N-oxide and Serum Biomarkers in Patients with T2DM and Advanced CKD

Journal of Clinical Medicine doi: 10.3390/jcm6090086

Authors: Mohammed Al-Obaide Ruchi Singh Palika Datta Kathy Rewers-Felkins Maria Salguero Ibtisam Al-Obaidi Kameswara Kottapalli Tetyana Vasylyeva

Trimethylamine-N-oxide (TMAO) is a product of dietary, gut microbiome, and tissues metabolism. Elevated blood TMAO levels are associated with heart attack, stroke and chronic kidney disease (CKD). The purpose of our study was to investigate the gut microbiota associated with trimethylamine (TMA) production, the precursor of TMAO, and the serum levels of TMAO and inflammatory biomarkers associated with type 2 diabetes mellitus (T2DM) and CKD. Twenty adults with T2DM and advanced CKD and 20 healthy adults participated in the study. Analyses included anthropometric and metabolic parameters, characterization of TMA producing gut microbiota, and concentrations of TMAO, lipopolysaccharides (LPS) endotoxin, zonulin (Zo) gut permeability marker, and serum inflammatory and endothelial dysfunction biomarkers. Diversity of the gut microbiota was identified by amplification of V3–V4 regions of the 16S ribosomal RNA genes and DNA sequencing. TMAO was quantified by Mass Spectrometry and serum biomarkers by ELISA. The significance of measurements justified by statistical analysis. The gut microbiome in T2DM-CKD patients exhibited a higher incidence of TMA-producing bacteria than control, p < 0.05. The serum levels of TMAO in T2DM-CKD patients were significantly higher than controls, p < 0.05. TMAO showed a positive correlation with Zo and LPS, inflammatory and endothelial dysfunction biomarkers. A positive correlation was observed between Zo and LPS in T2DM-CKD subjects. An increased abundance of TMA-producing bacteria in the gut microbiota of T2DM-CKD patients together with excessive TMAO and increased gut permeability might impact their risk for cardiovascular disease through elevation of chronic inflammation and endothelial dysfunction.

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Αρχειοθήκη ιστολογίου

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Δευτέρα 18 Σεπτεμβρίου 2017

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Αναζήτηση αυτού του ιστολογίου

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