Αρχειοθήκη ιστολογίου

Τετάρτη 29 Ιουνίου 2022

Comparison of transfusion reactions in children and adults: A systematic review and meta‐analysis

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Abstract

Background

There are no international standards or normalizations for diagnosing and treating complications from blood transfusions. We comprehensively compared the incidence of adverse blood transfusions in children and adults.

Methods

Available literature on blood transfusion adverse reactions in children and adults prior to November 27, 2021 was collected from several electronic databases. This meta-analysis was performed using Revman 5.2 and Stata 15.1.

Results

The incidence of transfusion reactions is higher in children than in adults. Children transfused with red blood cells and platelets exhibited a higher incidence of transfusion reaction than that of adults. Moreover, the incidence of allergic and febrile non-hemolytic transfusion reactions was significantly higher in children than in adults. The incidence of some rare transfusion reactions was also significantly higher in children than in adults.

Conclusion

The incidence of transfusion reactions in children and adults is varied. Guidelines for children are necessary.

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Safety and value of pre‐transplant antibiotic allergy delabeling in a quaternary transplant center

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Abstract

Background

Self-reported antibiotic allergies, also known as antibiotic allergy labels, are common and may lead to worse patient outcomes. Within immunocompromised patients, antibiotic allergy labels can lead to inappropriate use of antimicrobials and may limit options for prophylactic and therapeutic options in the post-transplant period. While antibiotic allergy delabeling is considered an important aspect of antibiotic stewardship protocols, evidence and awareness of its application in transplant recipients is limited.

Methods

We describe our experience with an antibiotic allergy delabeling intervention in the pre-transplant evaluation period and its impact on post-transplant antimicrobial utilization. This was a retrospective analysis of patients with an antibiotic allergy label who underwent evaluation for solid organ or stem cell transplantation between 2015–2020. Patients included in this analysis were those who completed pre-transplant antibiotic allergy delabeling through our Drug Allergy Clinic and were retained in care for six months after transplant.

Results

Twenty-six of 27 patients underwent pre-transplant antibiotic allergy delabeling and safely received the delabeled antibiotic post-transplant. There were no reported side effects to the delabeled antibiotic within 6 months post-transplant. Specific examination of sulfonamide (sulfa)-antibiotic delabeling showed cost savings of $254 to $2,910 per patient in the post-transplant period compared to the use of alternative antibiotics for prophylaxis protocol.

Conclusion

Antibiotic allergy delabeling prior to transplant is safe, is of high value, and should be considered in the pre-transplant evaluation period. More resources are needed for the development of delabeling guidelines and support for broad implementation of pre-transplant antibiotic allergy delabeling programs.

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Evaluation of soft tissue and labial plate of bone stability with immediate implant in direct contact versus gap with socket shield: A randomized clinical trial with 1 year follow‐up

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Abstract

Objective

In the anterior region, the resorption of the buccal plate of bone after tooth extraction leads to contraction of the overlying soft tissues, resulting in an esthetic problem. In the socket shield technique, the buccal root section of the tooth is maintained, to preserve the buccal bone for immediate implant placement. The aim of this randomized clinical trial was to investigate the effect of leaving a gap or not between implant and retained root fragment on bone dimensions and soft tissue esthetics.

Methods

This was a two armed parallel group randomized clinical trial with allocation ratio 1:1. Patients were eligible in case they needed immediate implant replacing teeth in esthetic zone with sufficient buccal bone support. CBCT was performed immediately after the intervention and 12 months later.

Results

Forty six patients (26 females and 20 males) were enrolled in the study with 23 of them placed in contact with shield and 23 were placed palatal leaving a gap to graft with a xenograft. After 12 months, excellent soft tissue stability was reported (mean pink esthetic score at placement group A: 12.00 ± 1.60 after 12 months 12.90 ± 1.69, group B 12.62 ± 2.07 and after 12 months 12.38 ± 2.20) Using both surgical techniques. Radiographic crestal bone level changes mean for group A was −0.26 ± 0.52 and for group B -0.34 ± 0.31. There was a strong positive correlation between clinical and radiographic bone width values which was statistically significant (r = 0.782, p < 0.001). Width and thickness of keratinized gingiva showed no significant difference between values measured in both groups. Nonsignificant difference between studied groups according to the labial plate of bone clinical and radiographic changes after i mmediate implantation.

Conclusion

Within the limitations of this study, the present data seem to support that the clinical outcome of the socket shield technique with immediate implant placement placed in contact or leaving a gap gave excellent esthetic results.

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Inflammatory and oxidative stress markers in intracerebral hemorrhage: Relevance as prognostic markers for quantification of the edema volume

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Inflammatory and oxidative stress markers in intracerebral hemorrhage: Relevance as prognostic markers for quantification of the edema volume

The complex formation of post-ICH brain edema.


Abstract

We aimed to analyze the inflammatory and oxidative stress (OS) markers after intracerebral hemorrhage (ICH) and their temporal changes, interaction effects, and prognostic values as biomarkers for the prediction of the edema volume. Our prospective, longitudinal study included a cohort group of 73 conservatively treated patients with ICH, without hematoma expansion or intraventricular bleeding, which were initialized with the same treatment and provided with the same in-hospital care during the disease course. Study procedures included multilevel comprehensive analyses of clinical and neuroimaging data, aligned with the exploration of 19 inflammatory and five OS markers. White blood cells (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophilia, and lymphopenia peaked 3 days post-ICH, and they showed much stronger correlations with clinical and neuroimaging variables, when compared to the admission values. An intricate interplay among inflammatory (WBC , CRP, neutrophils, neutrophil-to-lymphocyte ratio [NLR], interleukin (IL)-6, and IL-10) and OS mechanisms (catalase activity and advanced oxidation protein products [AOPP]) was detected operating 3-days post-ICH, being assessed as relevant for prediction of the edema. The overall results suggested complex pathology of formation of post-ICH edema, via: (A) Not additive, but statistically significant synergistic interactions between CRP-ESR, neutrophils-CRP, and neutrophils-IL-6 as drivers for the edema formation; (B) Significant antagonistic effect of high protein oxidation on the CRP-edema dependence, suggesting a mechanism of potential OS-CRP negative feedback loop and redox inactivation of CRP. The final multiple regression model separated the third-day variables NLR, CRP × AOPP, and WBC, as significant prognostic biomarkers for the prediction of the edema volume, with NLR being associated with the highest effect size. Our developed mathematical equation with 3D modeling for prediction and quantification of the edema volume might be beneficial for taking timely adequate strategies for prevention of delayed neurological deteriorations.

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Differences in levothyroxine action on thyroid autoimmunity and hypothalamic–pituitary–thyroid axis activity between metformin‐ and myo‐inositol‐treated women with autoimmune subclinical hypothyroidism

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Differences in levothyroxine action on thyroid autoimmunity and hypothalamic–pituitary–thyroid axis activity between metformin- and myo-inositol-treated women with autoimmune subclinical hypothyroidism

The impact of levothyroxine on thyroid antibody titers, thyrotropin, free thyroxine and free triiodothyronine is more pronounced in women with autoimmune subclinical hypothyroidism receiving metformin than myo-inositol.


Abstract

What is known and objective

Insulin resistance impairs the impact of levothyroxine on thyroid autoimmunity and hypothalamic–pituitary–thyroid axis activity. Both metformin and myo-inositol were found to improve insulin sensitivity and to reduce thyrotropin levels in individuals with hypothyroidism. The aim of the present study was to compare the effect of levothyroxine on thyroid autoimmunity and hypothalamic–pituitary–thyroid axis activity between women receiving metformin and myo-inositol.

Methods

The study included two groups of women with autoimmune hypothyroidism, treated for at least 6 months with either metformin (group A; n = 25) or myo-inositol (group B; n = 25). Both groups were matched for age, insulin sensitivity, hormone levels and antibody titers. For the following 6 months, all women received levothyroxine. Plasma levels of glucose, insulin, thyrotropin, free thyroid hormones, prolactin, 25-hydroxyvitamin D and high-sensitivity C-reactive protein (hsCRP), as well as titers of thyroid peroxidase and thyroglobulin antibodies were assessed at the beginning and at the end of the study.

Results and discussion

At baseline there were not differences between the study groups. Although levothyroxine reduced thyrotropin levels, increased free thyroid hormone levels and decreased antibody titers in both study groups, these effects were more pronounced in group A than group B. Only in group A, levothyroxine increased 25-hydroxyvitamin D, decreased hsCRP and improved insulin sensitivity. The impact of levothyroxine on thyrotropin and free thyroid hormones correlated with treatment-induced changes in insulin sensitivity, antibody titers, 25-hydroxyvitamin D and hsCRP.

What is new and conclusion

The present study suggests that the impact of levothyroxine on thyroid autoimmunity and hypothalamic–pituitary–thyroid axis activity is stronger in women receiving metformin than in women treated with myo-inositol.

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Τρίτη 28 Ιουνίου 2022

A Phase I Study of Apolizumab, an Anti-HLA-DR ß-chain Monoclonal Antibody, in Patients With Solid Tumor Malignancies

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imageBackground: Human leukocyte antigen (HLA)-DR, a member of the major histocompatibility complex class II antigen family, is a target for antibody-based therapeutics. Apolizumab (Hu1D10, Remitogen), a humanized IgG1 monoclonal anti-HLA-DR ß-chain antibody targets the antigen, 1D10, expressed on a wide variety of hematologic and solid tumor malignancies. In this Phase 1 trial, the maximum tolerated dose and dose-limiting toxicity of weekly apolizumab in patients with advanced solid tumor malignancies were determined. Patients and Methods: Eligible patients with refractory solid tumors were initially screened for ID10 Ag on their tumor. Patients whose tumors expressed 1D10 were administered apolizumab 0.5, 1.0, 1.5, or 3.0 mg/kg intravenously over 90 minutes weekly for 4 consecutive weeks, followed by a 4-week break, and assessment of response. Patients whose disease had not progressed were offered additional treatment. Results: Tumors from 75 patients were screened for 1D10 Ag of which 17 patients were positive and underwent treatment. The first 3 dose levels were well-tolerated. Dose-limiting toxicities of grade 3 infusion-related hypersensitivity reactions and grade 3 headache and hypertension occurred in 2 patients, respectively, at apolizumab 3.0 mg/kg. Four patients, 1 each with breast carcinoma, melanoma, renal cell carcinoma, and sarcoma had stable disease for a median of 15 weeks (range: 12 to 19 wk). Conclusion: Apolizumab can be administered safely at a maximum tolerated dose of 1.5 mg/kg for 4 consecutive weeks. Adverse events and limited clinical data in both hematologic and solid tumor malignancies resulted in discontinuation of clinical development of apolizumab. HLA-DR remains an interesting immunotherapeutic target.
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Effect of Somatosensory Interaction Transcutaneous Electrical Acupoint Stimulation on Cancer-related Fatigue and Immunity: A Randomized Controlled Trial

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imageBackground: This study was intended to evaluate the clinical effect of somatosensory interaction transcutaneous electrical acupoint stimulation (SI-TEAS) on cancer-related fatigue (CRF) and its safety. Methods: The study protocol had been registered in China Clinical Trial Registration Center with registration number: ChiCTR2100045655. CRF patients were equally divided into SI-TEAS Group, Acupressure Group and Sham Acupressure Group to receive SI-TEAS, acupressure and sham acupressure treatments 5 times a week. The fatigue levels of patients in the 3 groups were measured by the Piper Fatigue Scale during the baseline period and after 4 and 8 weeks (of treatment). The cell immunity of these patients was determined by detecting the T-lymphocyte subsets and NK cells. Result: Of the 300 participants, 279 have gone through the independent rehabilitation intervention study, including 94 in the SI-TEAS Group, 92 in the Acupressure Group, and 93 in the Sham Acupressure Group. Intergroup comparisons of fatigue degree and cell immunity, namely SI-TEAS Group versus Acupressure Group, Acupressure Group versus Sham Acupressure Group, and SI-TEAS Group versus Sham Acupressure Group, showed that group changes observed during the baseline period and different time points after Week 4 and 8 were statistically different (P
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An Exploratory Study of Neoadjuvant Cetuximab Followed by Cetuximab and Chemoradiotherapy in Women With Newly Diagnosed Locally Advanced Cervical Cancer

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imageObjectives: This study explored the feasibility of cetuximab with chemoradiation in women with cervical carcinoma and evaluated fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) to assess early response to cetuximab (NCT00292955). Patients and Methods: Eligible patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IVB invasive carcinoma of the uterine cervix were treated on 1 of 3 dose levels (DL). DL1 consisted of neoadjuvant cetuximab, then concurrent radiotherapy with cetuximab 250 mg/m2/cisplatin 40 mg/m2, followed by weekly cetuximab. DL2 consisted of radiotherapy with cetuximab 200 mg/m2 and cisplatin 30 mg/m2. DL3 consisted of radiotherapy with cetuximab 250 mg/m2 and cisplatin 30 mg/m2. Patients underwent 18F-FDG-PET/CT before treatment, after neoadjuvant cetuximab, and at the end of treatment. Results: Of the 21 patients enrolled, 9, 3, and 9 were treated in DL1, DL2, and DL3, respectively. DL1 required dose reductions due to gastrointestinal toxicities. DL2 and 3 were tolerated with 1 dose-limiting toxicity (grade 4 renal failure) at DL3. Following 3 weekly treatments of neoadjuvant cetuximab in DL1, 7 patients had maximum standardized uptake value changes on 18F-FDG-PET/CT consistent with response to cetuximab. Of the 12 patients with locally advanced disease, eleven evaluable patients had no evidence of disease on 18F-FDG-PET/CT at treatment end. Five-year progression-free survival and overall survival rates for all patients were 57.5% and 58.5%, respectively. Conclusions: Cetuximab with cisplatin 30 mg/m2 and radiotherapy was tolerated. 18F-FDG-PET/CT demonstrated early evidence of response to neoadjuvant cetuximab. With advances in precision oncology and the recent approval of pembrolizumab in metastatic cervical cancer, dual-target inhibition with an epidermal growth factor receptor inhibitor may be a promising treatment in the future.
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Blood T-cell profiling in metastatic melanoma patients as a marker for response to immune checkpoint inhibitors combined with radiotherapy

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Publication date: Available online 27 June 2022

Source: Radiotherapy and Oncology

Author(s): Gishan Ratnayake, Simone Reinwald, Jack Edwards, Nicholas Wong, Di Yu, Rachel Ward, Robin Smith, Andrew Haydon, Pei Au, Menno C. van Zelm, Sashendra Senthi

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Early treatment of high-risk hospitalized COVID-19 patients with a combination of interferon beta-1b and remdesivir: a phase 2 open-label randomized controlled trial

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Abstract
Background
Early antiviral therapy was effective in the treatment of COVID-19. We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients.
Methods
We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200mg loa ding on day 1 followed by 100mg daily on day 2 to 5 (combination-group), or to remdesivir only of similar regimen (control-group) (1:1). The primary end-point was the time to complete alleviation of symptoms (NEWS2 = 0).
Results
Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom-onset was 3 days. The median age was 65 years and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary-endpoint, the combination-group was significantly quicker to NEWS2 = 0 (4 versus 6.5 days; hazard-ratio [HR],6.59; 95% confidence-interval [CI],6.1-7.09; p < 0.0001) when compared to the control-group. For the secondary endpoints, the combination-group was quicker to negative NPS VL (6 versus 8 days; HR,8.16; 95% CI,7.79-8.52; p < 0.0001) and develop seropositive IgG (8 versus 10 days; HR,10.78; 95% CI,9.98-11.58; p < 0.0001). All adverse events resolved upo n follow-up. Combination group (HR,4.1 95%CI,1.9-8.6, p < 0.0001), was the most significant independent factor associated with NEWS2 = 0 on day 4.
Conclusions
Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, shorten viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients.
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