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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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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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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DETECTION OF SARS‐COV‐2 RNA AND ANTIBODIES IN BREAST MILK OF INFECTED MOTHERS

alexandrossfakianakis shared this article with you from Inoreader DETECTION OF SARS‐COV‐2 RNA AND ANTIBODIES IN BREAST MILK OF INFECTED MOTHERS via Journal of Medical Virology Abstract The SARS-CoV-2 outbreak in December 2019 brought many challenges to be addressed. One concerns the possible transmission of the virus and protective antibodies against SARS-CoV-2 to newborns through breastfeeding. The aim of this study was the detection of SARS-CoV-2 RNA and antibodies in the milk of SARS-CoV-2 positive mothers. Milk and blood samples were collected from twelve women with SARS-CoV-2 positive nasopharyngeal swabs. Viral RNA was investigated by RT-PCR, and the presence of IgA, IgM, and IgG anti-SARS-CoV-2 was evaluated in both breast milk and maternal blood. All milk samples showed negative results for SARS-CoV-2 RNA. Eight women (66%) had a detectable level of anti -SARS-CoV-2 IgA in their milk. Of this group, only one sample presented simultaneously serum antiviral IgM and IgG while other three samples showed only anti-SARS-CoV-2 IgG. The remaining four mothers with anti-SARS-CoV-2 IgA in their breast milk had no serum antibodies again st SARS-CoV-2. Finally, four mothers (34%) did not have any anti-SARS-CoV-2 antibodies in breast milk and serum, except one mother who had antiviral IgG and IgA in serum. Our results suggest that breastfeeding of SARS-CoV-2 infected mothers is safe and should be encouraged as breast milk transmits maternal antiviral antibodies which protect the infant while its immune system is immature. This article is protected by copyright. All rights reserved. View on Web

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Comparison of the accuracy between conventional and various digital implant impressions for an implant‐supported mandibular complete arch fixed prosthesis: an in vitro study

alexandrossfakianakis shared this article with you from Inoreader Comparison of the accuracy between conventional and various digital implant impressions for an implant‐supported mandibular complete arch fixed prosthesis: an in vitro study via Journal of Prosthodontics Abstract Purpose This in vitro study compared the accuracy between conventional and different intraoral scanner impression methods and stereophotogrammetry term of 3D deviation for a complete mandibular edentulous arch with 5 placed implants. Materials and methods An edentulous mandibular model was prepared with three straight and two 17° angled screw-retained abutments screwed on implants. Different impression techniques were compared: 1 conventional impression, CO (Open-tray splint impression coping, Polyether), 3 groups of intraoral scanners, TS (Trios 4), IT (iTero Element 2), and PS (Primescan), and 1 Stereophotogrammetry, PIC (Precise Implants Capture). An extraoral scanner (E4 scanner) was used to digitize the reference model as a control group. Scan body positions were compared with 3D deviation by using a 3D analysis software program (Geomagic ControlX 2020.1.1) with the best fit alignment technique. The accuracy of the scan bodies' position of each impression technique between each group area was analyzed using one-way ANOVA followed by Scheffé's comparison test for trueness and precision. (α = 0.05) Results Statistical 3D deviations of the whole scan body were found among the CO, TS, PS, IT, and PIC groups for both trueness (p < 0.05) and precision (p < 0.05). PIC showed the least 3D deviation of trueness (48.74 ± 1.80 μm) and precision (5.46 ± 1.10 μm), followed by TS, PS, IT, and CO. CO had the highest 3D deviation of trueness (141 ± 5.58 μm) and precision (40.4 ± 1.3.39 μm), which was significantly different from PIC, TS, and PS. Conclusion For completed-arch digital implant impressions, a stereophotogrammetry has shown better accuracy than other digital and conventional impression techniques, especially in terms of precision. The highest 3D deviation was found in the conventional splint open tray impression technique. This article is protected by copyright. All rights reserved 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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Heritable cancer predisposition testing in pediatric cancer patients excluding retinoblastoma in a middle‐income country

alexandrossfakianakis shared this article with you from Inoreader Heritable cancer predisposition testing in pediatric cancer patients excluding retinoblastoma in a middle‐income country via Pediatric Blood & Cancer Abstract Resource-limited settings often have financial barriers to genetic testing for heritable cancer. This retrospective study investigated the pattern of heritable cancer predisposition testing in a middle-income country over the period 2014–2021, excluding retinoblastoma. After establishing a specific fund in 2019, rate of tests increased from 1.1% to 10.9% of new diagnoses. Most common testing was for constitutional mismatch repair deficiency (CMMRD), rhabdoid predisposition syndrome, TP53 (tumor protein 53) mutation, and hereditary cancer panel. Of 33 patients, 13 (39%) tested positive, 12 (36%) negative, and eight (24%) had variants of unknown significance. Positivity rate was 43% for a clinical phenotype and 44% for a tumor type indication. 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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Opsoclonus‐myoclonus syndrome associated with neuroblastoma: Insights into antitumor immunity

alexandrossfakianakis shared this article with you from Inoreader Opsoclonus‐myoclonus syndrome associated with neuroblastoma: Insights into antitumor immunity via Pediatric Blood & Cancer Abstract Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder. Half of these cases occur in children with neuroblastoma. Neuroblastoma patients with OMS usually have better oncological outcomes than those without OMS even after stratification by tumor stage and age, indicating that factors mediating OMS may also inhibit tumor cell proliferation. Although the mechanisms underlying OMS remain undefined, the cytokines and lymphocytes alterations in the cerebrospinal fluid support the concept that it is a pattern of neuroinflammation due to an autoimmune effect. The presence of lymphoid follicles consisting of follicular dendritic cells, CD20+ B lymphocytes, CD3+ T lymphocytes, and CD68+ macrophages in the tumor microenvironment in OMS-associated neuroblastoma support the autoimmune nature of this disorder. This review focuses on the clinical and genetic features of OMS-associated neuroblastoma, and we update readers on immune features of neurobl astoma with or without OMS to gain insights into antitumor immunity as it relates to tumor biology and prognosis. View on Web

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