Diagnostic Modalities, Management Considerations, and Outcomes of Insulinoma: A Case Series from a Tertiary Care Centre.

Introduction: Insulinomas are rare, usually sporadic, and typically benign pancreatic neuroendocrine tumours. Pre-operative localization is challenging and evidence on comparative analysis of anatomic and scintigraphic modalities for pre-operative tumour localization is limited, even in contemporary series. Methods: The current study was designed to study the clinical features and management challenges of insulinomas managed at a tertiary care centre. Clinical features, diagnosis, imaging techniques, surgical procedures, and outcomes details were collated. Pre-operative imaging techniques (CT/MRI, nuclear scintigraphy) were compared with intraoperative and histopathological findings to assess their accuracy of localization. Results: Thirty-seven patients (15 females [42%]; median age 36 years [IQR 28-49]) were included in the study. In four patients (10.8%), the tumour occurred in the setting of multiple endocrine neoplasia type 1 (MEN 1) while the remaining were sporadic. The sensitivity of pre-operative localization was 61.5% (multiphasic CT), 66.6% (multiphasic MRI), 100% (68Ga Exendin-4 PET-CT), and 91.6% (EUS). Three patients with normal multiphasic CT had localization on 68Ga Exendin-4 PET-CT. The positive predictive value (PPV) of both Exendin-PET-CT and EUS was similar at 91.6% and 91.6%, respectively. All patients (except one with nesidioblastosis), who underwent enucleation or partial pancreatic resection, were cured. Conclusion: 68Ga Exendin-4 PET-CT based is a non-invasive imaging modality that has high sensitivity and PPV and can be used as a first-line imaging modality. The overall prognosis of these tumours is good with high cure rates attained following surgical resection.

Clinico-Epidemiologic Profile of Non-Syndromic Congenital Ichthyosis - A Retrospective Chart Review of 107 Patients.

Background: Congenital ichthyoses are a rare Mendelian group of disorders affecting the integument with a heterogeneous clinical presentation amongst which scaling is a constant feature. There is scanty epidemiologic data regarding the clinical profile and histologic patterns of inherited ichthyosis from resource-poor countries. Aims and Objectives: The study was aimed at assessing the clinic-epidemiologic characteristics associated with the different forms of non-syndromic congenital ichthyosis. Materials and Methods: This was a retrospective chart review of ichthyosis patients that presented between July 2016 and Jun 2020. Details including demographic profile, clinical characteristics along with any relevant investigations done were included. Results: During the study period of 4 years, 107 patients with congenital non-syndromic ichthyosis were seen. The most frequent diagnosis was of common ichthyoses, followed by autosomal recessive congenital ichthyosis, epidermolytic ichthyosis and erythrokeratoderma, in decreasing order. Conclusion: Important clinical findings like erythema and the type of scales as well as histological differences including an absent or reduced granular layer in ichthyosis vulgaris can help differentiate among the clinical phenotypes of inherited non-syndromic ichthyosis especially in resource-poor settings. Also, there is a high prevalence of vitamin D deficiency and hence a need for screening for the same in all patients of congenital ichthyosis including the milder phenotypes.

Comparative Evaluation of Bioavailability, Efficacy and Safety of MICROCORE NESC® with Calcium Carbonate and Calcium Citrate Malate in Osteopenic and Osteoporotic Patients: A Randomized Clinical Trial.

Introduction: Osteoporosis is a skeletal disease characterized by loss of bone mass, reduced bone strength and increased bone fragility predisposing to fractures. This study was planned to evaluate the efficacy, safety and relative bioavailability of Microcore NESC® (Natural Egg Shell Calcium) in osteopenia and osteoporotic patients. Methods: This was a randomized, open label, parallel group interventional clinical trial which included 60 study participants with osteopenia and osteoporosis who were randomized into three groups (20 each). Group 1-Microcore NESC®, Group 2-Shelcal and Group 3-CCM with 12 weeks treatment period. The participants were evaluated for relative oral bioavailability, bone mineral density (BMD), serum osteocalcin, change in VAS pain scale and quality of life-Questionnaires. Results: There was significant improvement in the BMD T scores-post-treatment with MICROCORE NESC® and Shelcal. Higher percentage of improvement in calcium absorption as depicted by an increase in serum calcium levels (10.23%) in the MICROCORE NESC®-treated group when compared to Shelcal (7.7%) and CCM (7.2%). The relative bioavailability of MICROCORE NESC® with respect to Shelcal was 93%. Discussion: MICROCORE NESC®, has shown a better oral relative bio availability of calcium (93%), better improvement of BMD T score compared to Shelcal and CCM. The general health status has improved to very good/excellent in 83% of patients in MICROCORE NESC®-treated group. Thus, MICROCORE NESC® can be considered a better and safe calcium supplement, as there are very few side effects observed without any clinically significant abnormalities in lab parameters.

Agreement of Gallbladder Reporting and Data System for Gallbladder Wall Thickening at Ultrasonography: A Multireader Validation Study.

Objective: This article aims to evaluate the intrareader and interreader agreement of ultrasound (US) gallbladder reporting and data system (GB-RADS) and validate the risk of malignancy in each GB-RADS category. Materials and methods: This retrospective study comprised consecutive patients with nonacute gallbladder wall thickening who underwent US evaluation between January 2019 and December 2022. Three radiologists independently read the static US images and cine-loops for GB-RADS findings and assigned GB-RADS categories. The intraobserver (static images) and interobserver (static images and cine-loops) agreement was calculated using kappa statistics and Krippendorff's alpha. Another radiologist assigned a consensus GB-RADS category. The percentage of malignancy in each GB-RADS category was calculated. Results: Static US images of 414 patients (median age, 56 years; 288 women, benign = 45.6% and malignant = 54.4%) and cine-loops of 50 patients were read. There was weak to moderate intrareader agreement for most GB-RADS findings and moderate intrareader agreement for the GB-RADS category for all readers. On static images, the interreader agreement was acceptable for GB-RADS categories. On cine-loops, the interreader agreement for GB-RADS findings and categories was better than static images. The percentage of malignancy was 1.2%, 37%, 71.1%, and 89.1% in GB-RADS 2, 3, 4, and 5 categories. Conclusion: GB-RADS has moderate intrareader for GB-RADS categories. As originally proposed, the risk of malignancy is negligible in GB-RADS 2 category and highest in GB-RADS 5 category. However, the discriminatory performance of GB-RADS 3 and 4 categories is low. Larger multicenter studies with more readers must assess the reader agreement and validate the GB-RADS systems for wider clinical utilization.

Mapping three-dimensional intratumor proteomic heterogeneity in uterine serous carcinoma by multiregion microsampling.

BACKGROUND: Although uterine serous carcinoma (USC) represents a small proportion of all uterine cancer cases, patients with this aggressive subtype typically have high rates of chemotherapy resistance and disease recurrence that collectively result in a disproportionately high death rate. The goal of this study was to provide a deeper view of the tumor microenvironment of this poorly characterized uterine cancer variant through multi-region microsampling and quantitative proteomics. METHODS: Tumor epithelium, tumor-involved stroma, and whole "bulk" tissue were harvested by laser microdissection (LMD) from spatially resolved levels from nine USC patient tumor specimens and underwent proteomic analysis by mass spectrometry and reverse phase protein arrays, as well as transcriptomic analysis by RNA-sequencing for one patient's tumor. RESULTS: LMD enriched cell subpopulations demonstrated varying degrees of relatedness, indicating substantial intratumor heterogeneity emphasizing the necessity for enrichment of cellular subpopulations prior to molecular analysis. Known prognostic biomarkers were quantified with stable levels in both LMD enriched tumor and stroma, which were shown to be highly variable in bulk tissue. These USC data were further used in a comparative analysis with a data generated from another serous gynecologic malignancy, high grade serous ovarian carcinoma, and have been added to our publicly available data analysis tool, the Heterogeneity Analysis Portal ( https://lmdomics.org/ ). CONCLUSIONS: Here we identified extensive three-dimensional heterogeneity within the USC tumor microenvironment, with disease-relevant biomarkers present in both the tumor and the stroma. These data underscore the critical need for upfront enrichment of cellular subpopulations from tissue specimens for spatial proteogenomic analysis.

Sonographic "Cervix Sign": A New Ancillary Sign of Gallbladder Neck Malignancy.

Background: The differentiation of benign and malignant gallbladder wall thickening is challenging. The purpose of this study is to evaluate a new sonographic sign, "cervix sign" for differentiation of benign and malignant gallbladder neck thickening. Methods: This retrospective study comprised consecutive patients with gallbladder neck thickening who underwent sonography between August 2019 and December 2021. The presence of "cervix sign" was assessed by two radiologists independently. Results: Sixty-five patients had gallbladder neck thickening (28 malignant and 37 benign). The sonographic "cervix sign" was present in 18 (64%) patients with malignant thickening and in only one (2.7%) patient with benign thickening (P = 0.0001). The mean wall thickness was greater, and symmetric wall thickening and liver metastases were more common in malignant thickening with "cervix sign" (without reaching statistical significance). There was substantial agreement (kappa = 0.78) between the two observers for the cervix sign. Conclusion: Sonographic "cervix sign" is a useful ancillary feature of gallbladder neck cancer.

2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure.

Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

A versatile 16-pole ion trap setup for investigating photophysics of biomolecular ions.

A linear 16-pole ion trap-based experimental setup has been designed, implemented, and characterized to investigate the photophysics of biomolecules in the gas phase. Electrospray ionization is employed to generate the ions in the gas phase at atmospheric pressure. The voltage configuration on the ion funnel, the ion optic device in the first vacuum interface, is used to control the energy of the ions. A home-built quadrupole mass-filter is utilized for the mass-selection of the ions of interest. A 16-pole ion trap designed and built in-house is implemented for ion trapping. The instrument's versatility and capability are showcased by demonstrating the fragmentation patterns of protonated and deprotonated tryptophan, as well as describing the photodetachment decay of deprotonated indole.

2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure.

Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Outcomes of percutaneous left atrial appendage occlusion device implantation in atrial fibrillation patients based on underlying stroke risk.

AIMS: To determine outcomes in atrial fibrillation patients undergoing percutaneous left atrial appendage occlusion (LAAO) based on the underlying stroke risk (defined by the CHA2DS2-VASc score). METHODS AND RESULTS: Data were extracted from the National Inpatient Sample for calendar years 2016-20. Left atrial appendage occlusion implantations were identified on the basis of the International Classification of Diseases, 10th Revision, Clinical Modification code of 02L73DK. The study sample was stratified on the basis of the CHA2DS2-VASc score into three groups (scores of 3, 4, and ≥5). The outcomes assessed in our study included complications and resource utilization. A total of 73 795 LAAO device implantations were studied. Approximately 63% of LAAO device implantations occurred in patients with CHA2DS2-VASc scores of 4 and ≥5. The crude prevalence of pericardial effusion requiring intervention was higher with increased CHA2DS2-VASc score (1.4% in patients with a score of ≥5 vs. 1.1% in patients with a score of 4 vs. 0.8% in patients with a score of 3, P < 0.01). In the multivariable model adjusted for potential confounders, CHA2DS2-VASc scores of 4 and ≥5 were found to be independently associated with overall complications [adjusted odds ratio (aOR) 1.26, 95% confidence interval (CI) 1.18-1.35, and aOR 1.88, 95% CI 1.73-2.04, respectively] and prolonged length of stay (aOR 1.18, 95% CI 1.11-1.25, and aOR 1.54, 95% CI 1.44-1.66, respectively). CONCLUSION: A higher CHA2DS2-VASc score was associated with an increased risk of peri-procedural complications and resource utilization after LAAO. These findings highlight the importance of patient selection for the LAAO procedure and need validation in future studies.

Association of CT Findings With Perineural Invasion in Gallbladder Cancer: Preliminary Assessment.

Perineural invasion (PNI) indicates a worse prognosis for patients with gallbladder cancer (GBC). This preliminary retrospective study included 19 patients with GBC who under-went contrast-enhanced CT in the 4 weeks before undergoing surgical resection. GBC showed PNI on pathologic assessment in eight of 19 patients. On CT, wall thickening morphology had sensitivity of 75.0% and specificity of 81.8% for PNI; soft-tissue stranding around the celiac plexus had sensitivity of 62.5% and specificity of 100.0% for PNI.

Patient-reported tolerability of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk stage III-IV melanoma in phase III trial E1609.

PURPOSE: Trial E1609 demonstrated superior overall survival with ipilimumab 3 mg/kg (ipi3) compared to high-dose interferon (HDI) for patients with resected high-risk melanoma. To inform treatment tolerability, we compared health-related quality of life (HRQoL), gastrointestinal (GI), and treatment-specific physical and cognitive/emotional symptoms. We also compared treatment-specific concerns between all arms. METHODS: We assessed HRQoL using the Functional Assessment of Cancer Therapy-General, physical and cognitive/emotional concerns using the FACT-Biologic Response Modifier subscale, and GI symptoms with the Functional Assessment of Chronic Illness Therapy-Diarrhea subscale pre-treatment and every 3 months. The primary outcome was the difference in HRQoL at 3 months between ipi3/ipi10 vs. HDI. RESULTS: 549 patients (n = 158 ipi3; n = 191 ipi10; n = 200 HDI) were analyzed. 3-month completion was 58.7%. Compared to HDI, ipilimumab patients reported better HRQoL (ipi3 = 87.5 ± 14.6 vs. HDI = 74.7 ± 15.4, p < .001; ipi10 = 84.9 ± 16.5 vs. HDI, p < .001) and fewer physical (ipi3 = 22.3 ± 4.6 vs. HDI = 17.1 ± 5.4, p < .001; ipi10 = 21.8 ± 5.0 vs. HDI p < .001) and cognitive/emotional (ipi3 = 18.6 ± 4.4 vs. HDI = 15.0 ± 5.3, p < .001; ipi10 = 17.7 ± 4.8 vs. HDI p < .001) concerns, but worse GI symptoms (ipi3 = 40.8 ± 5.0 vs. HDI = 42.2 ± 2.9, p = .011; ipi10 = 39.5 ± 7.0 vs. HDI, p < .001). Fewer ipilimumab patients reported worsening treatment-specific concerns (e.g., 52% of ipi3 and 58% of ipi10 reported worsening fatigue vs. 82% HDI, p's < .001). CONCLUSION: PROs demonstrated less toxicity of ipi3 compared to HDI and ipi10. Priorities for symptom management among patients receiving ipilimumab include GI toxicities, fatigue, weakness, appetite loss, arthralgia, and depression. TRIAL REGISTRATION: NCT01274338, January 11, 2011 (first posted date) https://clinicaltrials.gov/ct2/show/NCT01274338?term=NCT01274338&draw=2&rank=1 .

Incidence and implications of atrial fibrillation in patients hospitalized for COVID compared to non-COVID pneumonia: A multicenter cohort study.

Background: Atrial fibrillation (AF) has been reported to occur with coronavirus disease 2019 (COVID-19), but whether it is related to myocarditis or lung injury is unclear. Objectives: The purpose of this study was to compare incident AF in patients with pneumonia/adult respiratory distress syndrome (ARDS) with and without COVID. Methods: This retrospective multicenter cohort study from 17 hospitals (March 2020 to December 2021) utilizing the University of California COVID Research Data Set (CORDS) included patients aged ≥18 years with primary diagnosis of pneumonia or ARDS during hospitalization. Patients with a history of AF were excluded. All subjects had documented COVID test results. Cohorts were compared using the χ2 test for categorical variables and the Wilcoxon rank test for continuous variables. Multivariable logistic regression models were used to investigate the association between COVID and development of new AF. Results: Of the 39,415 subjects, 12.2% had COVID. The COVID+ cohort consisted predominantly of younger males with more comorbidities. Incident AF was lower in the COVID+ group than in the non-COVID group (523 [10.85%] vs 4899 [14.16%]; odds ratio [OR] 0.74; P <.001), which remained significant after adjustment for demographics and comorbidities (OR 0.71; P <.001). Patients had normal cardiac troponin levels. AF was related to intensive care unit care, pressor support, and mechanical ventilation, and was associated with higher mortality (26.2% vs 10.21%; P <.001) and longer hospitalization (22.5 vs 15.1 days; P <.001) in the COVID+ group compared to the controls. Conclusion: Incident AF is lower in COVID+ compared to non-COVID pneumonia/ARDS patients and seems to be related to severity of illness rather cardiac injury. AF was associated with higher mortality and prolonged hospitalization.

Noninvasive Stereotactic Radiation for Refractory Ventricular Tachycardia After Failure of Cardiac Sympathetic Denervation.

Stereotactic body radiation therapy is a novel treatment option for refractory ventricular tachycardia. We present a case of ventricular tachycardia, with epicardial origin located in large inferior infarct scar, that recurred despite treatment with multiple antiarrhythmic drugs, catheter ablation, and cardiac sympathetic denervation. Stereotactic body radiation therapy safely and effectively terminated the arrhythmia. (Level of Difficulty: Advanced.).

Catheter Ablation for Atrial Fibrillation in Adult Congenital Heart Disease: An International Multicenter Registry Study.

BACKGROUND: Data on atrial fibrillation (AF) ablation and outcomes are limited in patients with congenital heart disease (CHD). We aimed to investigate the characteristics of patients with CHD presenting for AF ablation and their outcomes. METHODS: A multicenter, retrospective analysis was performed of patients with CHD undergoing AF ablation between 2004 and 2020 at 13 participating centers. The severity of CHD was classified using 2014 Pediatric and Congenital Electrophysiology Society/Heart Rhythm Society guidelines. Clinical data were collected. One-year complete procedural success was defined as freedom from atrial tachycardia or AF in the absence of antiarrhythmic drugs or including previously failed antiarrhythmic drugs (partial success). RESULTS: Of 240 patients, 127 (53.4%) had persistent AF, 62.5% were male, and mean age was 55.2±13.3 years. CHD complexity categories included 147 (61.3%) simple, 68 (28.3%) intermediate, and 25 (10.4%) severe. The most common CHD type was atrial septal defect (n=78). More complex CHD conditions included transposition of the great arteries (n=14), anomalous pulmonary veins (n=13), tetralogy of Fallot (n=8), cor triatriatum (n=7), single ventricle physiology (n=2), among others. The majority (71.3%) of patients had trialed at least one antiarrhythmic drug. Forty-six patients (22.1%) had reduced systemic ventricular ejection fraction <50%, and mean left atrial diameter was 44.1±8.2 mm. Pulmonary vein isolation was performed in 227 patients (94.6%); additional ablation included left atrial linear ablations (40%), complex fractionated atrial electrogram (19.2%), and cavotricuspid isthmus ablation (40.8%). One-year complete and partial success rates were 45.0% and 20.5%, respectively, with no significant difference in the rate of complete success between complexity groups. Overall, 38 patients (15.8%) required more than one ablation procedure. There were 3 (1.3%) major and 13 (5.4%) minor procedural complications. CONCLUSIONS: AF ablation in CHD was safe and resulted in AF control in a majority of patients, regardless of complexity. Future work should address the most appropriate ablation targets in this challenging population.

DRESS syndrome due to first-line antitubercular therapy - A diagnostic imbroglio!

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome after the use of first-line antitubercular drugs (ATDs) is rare and literature regarding DRESS syndrome due to ATDs is scarce in children. We report a young boy with tuberculosis who developed DRESS syndrome after exposure to isoniazid. A 9-year-old boy, diagnosed clinically as pulmonary tuberculosis, presented with fever, fast breathing, maculopapular rash, and one episode of gross hematuria. He had been on 4-drug ATD therapy (isoniazid, rifampicin, ethambutol, and pyrazinamide) for the past 4 weeks. In view of multiorgan involvement and absence of a microbiological diagnosis of tuberculosis, vasculitis was considered and he was treated with steroids. As the child recovered, both corticosteroids and ATD therapy were stopped. At 6 months of follow-up, he was presented with pneumonia. Microbiological diagnosis of tuberculosis was made and 4-drug ATD therapy was reinitiated. After 15 days, he again developed a high-grade fever and rash. On evaluation, isoniazid-induced DRESS syndrome was diagnosed. Subsequently, he received a modified regimen of ethambutol, pyrazinamide, levofloxacin, and linezolid. DRESS syndrome did not recur on these ATDs and the child became asymptomatic. Linezolid was stopped after 3 months of therapy and ethambutol, pyrazinamide, and levofloxacin are being continued. Currently, he has completed 15 months of modified ATD therapy. As a high index of suspicion is required for early diagnosis and management that are crucial to reducing morbidity and mortality, DRESS syndrome should be among the differentials in children with unexplained febrile illnesses.