Polygenic Risk Scores for Prediction of Subclinical Coronary Artery Disease in Persons Living with HIV: The Swiss HIV Cohort Study

alexandrossfakianakis shared this article with you from Inoreader Polygenic Risk Scores for Prediction of Subclinical Coronary Artery Disease in Persons Living with HIV: The Swiss HIV Cohort Study via Clinical Infectious Diseases Advance Access Abstract Background In people living with HIV (PLWH), individual polygenic risk scores (PRSs) are associated with coronary artery disease (CAD) events. Whether PRSs are associated with subclinical CAD is unknown. Methods In Swiss HIV Cohort Study participants of European descent, we defined subclinical CAD as presence of soft, mixed, or high risk plaque (SMHRP) on coronary CT angiography, or as participants in the top tertile of the study population's coronary artery calcium (CAC) score, using non-contrast CT. We obtained uni-/multivariable odds ratios (OR) for subclinical CAD endpoints based on non-genetic risk factors, and validated genome-wide PRSs built from single nucleotide polymorphisms (SNPs) associated with CAD, carotid intima-media thickness (IMT), or longevity in the general population. Results We included 345 genotyped participants (median age 53 years, 89% male, 96% suppressed HIV RNA); 172 and 127 participants had SMHRP and CAC, respectively. CAD-associated PRS and IMT-associated PRS were associated with SMHRP and CAC (all p < 0.01), but longevity-PRS was not. Participants with unfavorable CAD-PRS (top quintile) had adjusted SMHRP-OR = 2.58 (95% confidence interval [CI], 1.18-5.67), and CAC-OR = 3.95 (95% CI, 1.45-10.77), vs. bottom quintile. Unfavorable non-genetic risk (top vs. bottom quintile) was associated with adjusted SMHRP-OR = 24.01 (95% CI, 9.75-59.11), and CAC-OR = 65.07 (95% CI, 18.48-229.15). Ar ea under the ROC curve increased when we added CAD-PRS to non-genetic risk factors (SMHRP: 0.75, 0.78, respectively; CAC: 0.80, 0.83, respectively). Conclusions In Swiss PLWH, subclinical CAD is independently associated with an individual CAD-associated PRS. Combining non-genetic and genetic cardiovascular risk factors provided the most powerful subclinical CAD prediction. View on Web

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Validity of the Central Sensitization Inventory compared with traditional measures of disease severity in fibromyalgia

alexandrossfakianakis shared this article with you from Inoreader Validity of the Central Sensitization Inventory compared with traditional measures of disease severity in fibromyalgia via Pain Practice Abstract Objective The goal of the present study was to explore additional evidence of convergent and discriminant validity of the Central Sensitization Inventory (CSI) in a large sample of subjects with fibromyalgia (FM). Methods Patients were consecutively enrolled for a cross-sectional assessment comprehensive of three FM-specific measures (the revised Fibromyalgia Impact Questionnaire [FIQR], the modified Fibromyalgia Assessment Status [modFAS], and the Polysymptomatic Distress Scale [PDS]) and of CSI. To test the convergent validity, the Spearman's rho was used to measure the degree of correlation between the variables CSI and the FM-specific measures. To assess discriminant validity, CSI scores were grouped according to FIQR disease severity states, and differences between these groups studied with the Kruskal-Wallis test. Interpretative cut-offs were established with the interquartile reconciliation approach. Results The study included 562 FM patients, 199 (35.4%) were classified as having central sensitization syndrome (CSI ≥40). CSI was largely correlated with modFAS (rho = 0.580; p <0.0001), FIQR (rho = 0.542; p <0.0001), and PDS (rho = 0.518; p <0.0001). The differences between the CSI scores in accordance with the FIQR were significant (p <0.000001). CSI cut-offs proposed for FM: 21 between remission and mild severity, 30 between mild and moderate severity, 37 between moderate and severe disease, and 51 between severe and very severe disease. Conclusion The current study successfully showed additional evidence of the convergent and discriminant validity of the CSI in FM patients. View on Web

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Virologic failure following low-level viremia and viral blips during antiretroviral therapy: results from a European multicenter cohort

alexandrossfakianakis shared this article with you from Inoreader Virologic failure following low-level viremia and viral blips during antiretroviral therapy: results from a European multicenter cohort via Clinical Infectious Diseases Advance Access Abstract Background It is unclear whether low-level viremia (LLV), defined as repeatedly detectable viral load (VL) of <200 copies/mL, and/or transient viremic episodes (blips) during antiretroviral therapy (ART), predict future virologic failure. We investigated the association between LLV, blips, and virologic failure (VF) in a multi-center European cohort. Methods People with HIV-1 who started ART 2005 or later were identified from the EuResist Integrate d Database. We analyzed the incidence of VF (≥200 copies/mL) depending on viremia exposure, starting 12 months after ART initiation (grouped as suppression [≤50 copies/mL], blips [isolated VL of 51–999 copies/mL], and LLV [repeated VLs of 51–199 copies/mL]) using Cox proportional hazard models adjusted for age, sex, injecting drug use, pre-ART VL, CD4 count, HIV-1 subtype, type of ART, and treatment experience. We queried the database for drug resistance mutations (DRM) related to episodes of LLV and VF and compared those with baseline resistance data. Results During 81,837 person-years of follow-up, we observed 1,424 events of VF in 22,523 participants. Both blips (adjusted subhazard ratio [aHR], 1.7; 95% confidence interval [CI], 1.3−2.2) and LLV (aHR, 2.2; 95% CI, 1.6−3.0) were associated with VF, compared with virologic suppression. These associations remained statistically significant in sub-analyses restricted to people with VL <200 copies/mL and those starting ART 2014 or later. Among people with LLV and genotype data available within 90 days following LLV, 49/140 (35%) had at least one DRM. Conclusions Both blips and LLV during ART are associated with increased risk of subsequent VF. View on Web

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Antagonistic, synergistic, and additive antibacterial interaction between ciprofloxacin and amoxicillin against Staphylococcus aureus

alexandrossfakianakis shared this article with you from Inoreader Antagonistic, synergistic, and additive antibacterial interaction between ciprofloxacin and amoxicillin against Staphylococcus aureus via Fundamental & Clinical Pharmacology Abstract The aim of this in vitro study was to evaluate the interaction between ciprofloxacin and amoxicillin against beta-lactamase-producing Staphylococcus aureus (S. aureus). Concentration-dependent curves for each individual drug were carried out to obtain the mean inhibitory concentration in the agar well diffusion assay. Then, different ratios of the ciprofloxacin-amoxicillin combination (0.5:0.5, 0.8:0.2, 0.2:0.8, 0.9:0.1, 0.1:0.9, 0.95:0.05 and 0.05:0.95) were assessed. Data were analyzed using the isobolographic analysis and interaction index. The isobolographic evaluation show that the 0.9:0.1 and 0.95:0.05 ratios of the ciprofloxacin-amoxicillin combination produced a synergistic antimicrobial interaction, the 0.8:0.2, 0.2:0.8, 0.1:0.9, and 0.05:0.95 proportions showed an additive antibacterial effect, and the 0.5:0.5 proportion induced antagonistic antimicrobial effects. The interaction index showed similar outcomes to the isobolographic analysis. In conclu sion, the data of this study mainly show antimicrobial additive results of the ciprofloxacin-amoxicillin combination against beta-lactamase-producing S. aureus. View on Web

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The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review

alexandrossfakianakis shared this article with you from Inoreader The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review via Journal of Oral Rehabilitation Abstract Background Temporomandibular disorders (TMD) are diagnosed based on symptom presentation and, like other functional pain disorders, often lack definitive pathology. There is a strong association between elevated stress levels and the severity of TMD-related pain, which suggests that alterations in autonomic tone may contribute to this pain condition. Objectives This narrative review examines the association between altered autonomic function and pain in TMD. Methods Relevant articles were identified by searching PubMed and through the reference list of those studies. Results TMD sufferers report an increased incidence of orthostatic hypotension. As in other chronic musculoskeletal pain conditions, TMD is associated with increased sympathetic tone, diminished baroreceptor reflex sensitivity and decreased parasympathetic tone. It remains to be determined whether ongoing pain drives these autonomic changes and/or is exacerbated by them. To examine whether increased sympathetic tone contributes to TMD-related pain through β2 adrenergic receptor activation, clinical trials with the beta blocker propranolol have been undertaken. Although evidence from small studies suggested propranolol reduced TMD-related pain, a larger clinical trial did not find a significant effect of propranolol treatment. This is consistent with human experimental pain studies that were unable to demonstrate an effect of β2 adrenergic receptor activation or inhibition on masticatory muscle pain. In preclinical models of temporomandibular joint arthritis, β2 adrenergic receptor activation appears to contribute to inflammation and nociception, whereas in masticatory muscle, α1 adrenergic receptor activation has been found to induce mechanical sensitization. Some agents used to treat TMD, such as botulinum neurotoxin A, antidepressants and α2 adrenergic receptor agonists, may interact with the autonomic nervous system as part of their analgesic mechanism. Conclusion Even if dysautonomia turns out to be a consequence rather than a causative factor of painful TMD, the study of its role has opened up a greater understanding of the pathogenesis of this condition. View on Web

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Imaging of pediatric cardiac tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

alexandrossfakianakis shared this article with you from Inoreader Imaging of pediatric cardiac tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper via Pediatric Blood & Cancer Abstract Cardiac tumors in children are rare and the majority are benign. The most common cardiac tumor in children is rhabdomyoma, usually associated with tuberous sclerosis complex. Other benign cardiac masses include fibromas, myxomas, hemangiomas, and teratomas. Primary malignant cardiac tumors are exceedingly rare, with the most common pathology being soft tissue sarcomas. This paper provides consensus-based imaging recommendations for the evaluation of patients with cardiac tumors at diagnosis and follow-up, including during and after therapy. View on Web

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HSPA9 frameshift and loss‐of‐function mutations in a patient manifesting syndromic sideroblastic anemia and congenital anomalies

alexandrossfakianakis shared this article with you from Inoreader HSPA9 frameshift and loss‐of‐function mutations in a patient manifesting syndromic sideroblastic anemia and congenital anomalies via Pediatric Blood & Cancer View on Web

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Failure modes and effects analysis of pediatric I‐131 MIBG therapy: Program design and potential pitfalls

alexandrossfakianakis shared this article with you from Inoreader Failure modes and effects analysis of pediatric I‐131 MIBG therapy: Program design and potential pitfalls via Pediatric Blood & Cancer Abstract Background There is growing interest among pediatric institutions for implementing iodine-131 (I-131) meta-iodobenzylguanidine (MIBG) therapy for treating children with high-risk neuroblastoma. Due to regulations on the medical use of radioactive material (RAM), and the complexity and safety risks associated with the procedure, a multidisciplinary team involving radiation therapy/safety experts is required. Here, we describe methods for implementing pediatric I-131 MIBG therapy and evaluate our program's robustness via failure modes and effects analysis (FMEA). Methods We formed a multidisciplinary team, involving pediatric oncology, radiation oncology, and radiation safety staff. To evaluate the robustness of the therapy workflow and quantitatively assess potential safety risks, an FMEA was performed. Failure modes were scored (1–10) for their risk of occurrence (O), severity (S), and being undetected (D). Risk priority number (RPN) was calculated from a product of these scores and used to identify high-risk failure modes. Results A total of 176 failure modes were identified and scored. The majority (94%) of failure modes scored low (RPN <100). The highest risk failure modes were related to training and to drug-infusion procedures, with the highest S scores being (a) caregivers did not understand radiation safety training (O = 5.5, S = 7, D = 5.5, RPN = 212); (b) infusion training of staff was inadequate (O = 5, S = 8, D = 5, RPN = 200); and (c) air in intravenous lines/not monitoring for air in lines (O = 4.5, S = 8, D = 5, RPN = 180). Conclusion Through use of FMEA methodology, we successfully identified multiple potential points of failure that have allowed us to proactively mitigate risks when implementing a pediatric MIBG program. View on Web

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Examining multi‐level immune response to determine prevalence of COVID‐19 in pediatric tonsillectomy

alexandrossfakianakis shared this article with you from Inoreader Examining multi‐level immune response to determine prevalence of COVID‐19 in pediatric tonsillectomy via The Laryngoscope Objective To determine the prevalence of COVID-19 in a cohort of children undergoing tonsillectomy through assessment of B cell immune responses to SARS-CoV-2 in both peripheral blood and tonsil tissue. Methods In this cohort study at a tertiary pediatric hospital (Children's National Hospital) in Washington, DC, we recruited 100 children undergoing tonsillectomy from late September 2020 to January 2021. Serum, peripheral blood cells, and tonsil tissue were collected and examined for immune reactivity to SARS-CoV-2. Parent-reported clinical histories were compared to antibody and B-cell responses. Results Among 100 children undergoing tonsillectomy, 19% had evidence of immune responses to SARS-CoV-2 (CoV2+), indicating prior COVID-19. In all seropositive participants, we detected SARS-CoV-2 specific B cells in both peripheral blood mononuclear cells and tonsils, providing evidence for tissue-specific immunity in these children. Of the 19, 63% reported no known history of COVID-19, and an additional 3 were asymptomatic or unaware of an acute infection when detected on pre-surgery screen. Hispanic children represented 74% of CoV2+ subjects compared to 37% of the full cohort. 100% of CoV2+ children lived in a zip code with poverty level >10%. Conclusions Nearly one-fifth of children undergoing tonsillectomy at an urban U.S. hospital had evidence of prior COVID-19 during the early pandemic, with the majority unaware of prior infection. Our results underscore the ethnic and socio-economic disparities of COVID-19. We found concordant evidence of humoral immune responses in children in both blood and tonsil tissue, providing evidence of local immune responses in the upper respiratory tract. Level of Evidence 3 Laryngoscope, 2022 View on Web

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Cricopharyngeus Muscle Dysfunction and Hypopharyngeal Diverticula (e.g., Zenker): A Multicenter Study

alexandrossfakianakis shared this article with you from Inoreader Cricopharyngeus Muscle Dysfunction and Hypopharyngeal Diverticula (e.g., Zenker): A Multicenter Study via The Laryngoscope This serves as the seminal work from the prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeal Hypertonicity Surgery (POUCHS) Collaborative. Of the 250 persons enrolled, 85% had a Zenker diverticula (ZD), 9% had evidence of cricopharyngeus muscle dysfunction (CPMD) without diverticula and 4% had a Killian Jamieson diverticula (KJD). Patients with isolated CPMD appear to be more symptomatic than persons with ZD or KJD. Objective To describe demographics and imaging and compare findings and symptoms at presentation in a large cohort of persons with cricopharyngeus muscle dysfunction (CPMD) with and without hypopharyngeal diverticula. Methodology Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeal Hypertonicity (POUCH) Collaborative. Patient survey, comorbidities, radiography, laryngoscopy findings, and patient-reported outcome measures (e.g., Eating Assessment Tool [EAT-10]) data were abstracted from a REDCap database and summarized using means, medians, percentages, and frequencies. Diagnostic categories were compared using analysis of variance. Results A total of 250 persons were included. The mean age (standard deviation [SD]) of the cohort was 69.0 (11.2). Forty-two percent identified as female. Zenker diverticula (ZD) was diagnosed in 85.2%, 9.2% with CPMD without diverticula, 4.4% with a Killian Jamieson diverticula (KJD), and 1.2% traction-type diverticula. There were no differences between diagnostic categories in regard to age, gender, and duration of symptoms (p = 0.25, 0.19, 0.45). The mean (SD) EAT-10 score for each group was 17.1 (10.1) for ZD, 20.2 (9.3) for CPMD, and 10.3 (9.4) for KJD. Patients with isolated CPMD had significantly greater EAT-10 scores compared to the other diagnostic groups (p = 0.03). Conclusion ZD is the most common, followed by CPMD without diverticula, KJD, and traction-type. Patients with isolated obstructing CPMD may be more symptomatic than persons with ZD or KJD. Level of Evidence Level 4 Laryngoscope, 2022 View on Web

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