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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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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An in vitro trial on the effect of arch form on connector size requirements in long span anterior zirconia fixed dental prostheses

alexandrossfakianakis shared this article with you from Inoreader An in vitro trial on the effect of arch form on connector size requirements in long span anterior zirconia fixed dental prostheses via Journal of Prosthodontics Abstract Purpose To test the fracture resistance of maxillary canine to canine fixed partial denture with four missing incisors, with increasing anterior-cantilevers of the pontics and varying connector sizes. Material and Methods Two 3D-printed titanium alloy (Ti6Al4V) models mimicking a maxillary canine to canine fixed partial denture (FPD) with four pontics replacing the incisors were used as master models. Zirconia FPDs were digitally designed and milled with two different connector sizes (9 and 12 mm2) each with three different anterior cantilevers (7, 10, and 13 mm) accounting for 6 test groups. Seven samples were milled for each group generating a total of 42 samples. The Zi FPDs were cemented on the titanium model using resin modified glass ionomer cement and the model fixated to a variable angle vice. A sinusoidal cyclic wave form load from 50N to 280N was applied using a universal testing machine at a frequency of 30 cycles per second and a total of 5 million cycles. Results The results of Fisher's exact tests showed that the difference in the proportion of fractured versus non fractured fixed partial dentures was not statistically significant when comparing the 9 with the 12 mm2 connector size (p = 1.00), as well as when comparing the six test groups (p = 0.2338); on the other hand, it proved to be statistically significant when comparing the 7 mm cantilever with the 10 and 13 mm cantilevers combined (p = 0.0407) indicating that a 7 mm anterior spread of the pontics showed a significantly greater proportion of fixed partial dentures that fractured. Conclusions Fracture susceptibility was not a function of cantilever length in this testing configuration for anterior FPDs. Retainer crown thickness seems to be a more important parameter than connector size thickness. Based on the results, a smaller connector size (9 mm2) can be used to improve the esthetics of pontics in long span anterior FPDs. 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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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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Imaging of pediatric liver tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

alexandrossfakianakis shared this article with you from Inoreader Imaging of pediatric liver tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper via Pediatric Blood & Cancer Abstract Primary hepatic malignancies are relatively rare in the pediatric population, accounting for approximately 1%–2% of all pediatric tumors. Hepatoblastoma and hepatocellular carcinoma are the most common primary liver malignancies in children under the age of 5 years and over the age of 10 years, respectively. This paper provides consensus-based imaging recommendations for evaluation of patients with primary hepatic malignancies at diagnosis and follow-up during and after therapy. 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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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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