Theoretical insight into physical characteristics of lead-free perovskites Rb2TlSbX6 (X = Cl, Br, I) for optoelectronic devices.

CONTEXT: Novel optoelectronic and thermoelectric properties with broad compositional range, non-toxic nature and structural stability make halide-based double perovskites fascinating for flexible optoelectronic devices. In this work, the structural electronic, optical and transport properties of Rb2TlSbX6 (X = Cl, Br, I) were studied using density functional theory for optoelectronic devices. The elastic analysis demonstrates ductile nature, mechanical stability, anisotropic behaviour and feasibility for flexible optoelectronic devices. The band structure study using Tran-Blaha-modified Becke-Johnson (TB-mBJ) potential shows that all studied materials have direct bandgap. In addition, the bandgap of Rb2TlSbCl6 is more appropriate for optoelectronic devices. The small loss and maximum absorption in visible regions make these materials prime candidates for optoelectronic devices. The transport features indicate that all the studied double perovskites reflect p-type semiconducting behaviour as highlighted by positive Seebeck coefficient values. Furthermore, the high power factor values of Rb2TlSbX6 (X = Cl, Br, I) double perovskites make them suitable for thermoelectric device applications at high temperatures. Based on electronic optical and thermoelectric properties Rb2TlSbCl6 is the best candidate for flexible optoelectronic devices. METHODS: In this paper, structural optimization of Rb2TlSbX6 (X = Cl, Br, I) double perovskites was conducted utilizing the Wien2k software based on first principle calculations with Perdew-Burke-Ernzerhof's generalized-gradient approximation (PBE-sol approximation). The TB-mBJ potential was employed to compute the accurate band gap of studied materials. The thermoelectric properties are evaluated with BoltzTraP code, showing a predominance of P-type charge carriers in all studied perovskites. This methodological strategy verifies the material's remarkable stability and optical properties and offers a solid framework for examining its potential in optoelectronic devices.

MXene: A Roadmap to Sustainable Energy Management, Synthesis Routes, Stabilization, and Economic Assessment.

MXenes with their wide range of tunability and good surface chemistry provide unique and distinctive characteristics offering potential employment in various aspects of energy management applications. These high-performance materials have attracted considerable attention in recent decades due to their outstanding characteristics. In the literature, most of the work is related to specific methods for the preparation of MXenes. In this Review, we present a detailed discussion on the synthesis of MXenes through different etching routes involving acids, such as hydrochloric acid, hydrofluoric acid, and lithium fluoride, and non-acidic alkaline solution, electrochemical, and molten salt methods. Furthermore, a concise overview of the different structural, optical, electronic, and magnetic properties of MXenes is provided corresponding to their role in supporting high thermal, chemical, mechanical, environmental, and electrochemical stability. Additionally, the role of MXenes in maintaining the thermal management performance of photovoltaic thermal systems (PV/T), wearable light heaters, solar water desalination, batteries, and supercapacitors is also briefly discussed. A techno-economic and life cycle analysis of MXenes is provided to analyze their sustainability, scalability, and commercialization to facilitate a comprehensive array of energy management systems. Lastly, the technology readiness level of MXenes is defined, and future recommendations for MXenes are provided for their further utilization in niche applications. The present work strives to link the chemistry of MXenes to process economics for energy management applications.

The surgical technique and protocol for dynamic sentinel node biopsy for penile cancer at a Southeast Asian regional hospital.

Lymph node status is a key prognostic factor in penile cancer. The European Association of Urology (EAU) recommends intermediate-risk (pT1a, Grade 2) or high-risk (pT1b or greater) penile cancer patients with clinically non-palpable inguinal lymph node (cN0) to undergo either an invasive bilateral modified inguinal lymph node dissection (ILND) or dynamic sentinel node biopsy (DSNB). DSNB has been reported to have acceptable false negative rates, and lower rates of long-term morbidity compared to ILND. We developed a protocol for DSNB at a regional hospital in Singapore that was adopted from St James's University Hospital, Leeds Teaching Hospitals Trust. Four patients with cN0 penile cancer underwent DSNB between November 2021 and October 2022 according to this protocol. Our surgical technique and protocol are described. The patients' oncological characteristics and their outcomes were evaluated. In this small case series, there was no complication attributable to the performance of DSNB, and there was no groin that was documented to be false negative over a median follow up of 15.5 months (range, 12 to 22 months). Using our protocol, 5 of 8 groins (62.5%) were able to avoid ILND in the cN0 setting. We recommend the adoption of DSNB for the surgical staging of inguinal lymph nodes for patients with intermediate to high-risk penile cancer and non-palpable inguinal nodes due to its significantly lower risks of long-term morbidity compared to ILND. Appropriate specialist training and a multi-disciplinary team is vital to ensure the success of the procedure.

Assessing the arrhythmogenic propensity of fibrotic substrate using digital twins to inform a mechanisms-based atrial fibrillation ablation strategy.

Atrial fibrillation (AF), the most common heart rhythm disorder, may cause stroke and heart failure. For patients with persistent AF with fibrosis proliferation, the standard AF treatment-pulmonary vein isolation-has poor outcomes, necessitating redo procedures, owing to insufficient understanding of what constitutes good targets in fibrotic substrates. Here we present a prospective clinical and personalized digital twin study that characterizes the arrhythmogenic properties of persistent AF substrates and uncovers locations possessing rotor-attracting capabilities. Among these, a portion needs to be ablated to render the substrate not inducible for rotors, but the rest (37%) lose rotor-attracting capabilities when another location is ablated. Leveraging digital twin mechanistic insights, we suggest ablation targets that eliminate arrhythmia propensity with minimum lesions while also minimizing the risk of iatrogenic tachycardia and AF recurrence. Our findings provide further evidence regarding the appropriate substrate ablation targets in persistent AF, opening the door for effective strategies to mitigate patients' AF burden.

Application of Hydrothermal Synthesized Titanium Dioxide-Doped Multiwalled Carbon Nanotubes on Filtration Properties-Response Surface Methodology Study.

The success of any drilling activity mainly depends on the characteristics of the drilling fluid. Therefore, a high-performance drilling fluid is substantial for any drilling operation. During overbalance drilling operations, the drilling mud invades the permeable formations and causes the loss of circulation, which is responsible for nonproductive time events. Hence, the filtration characteristics of the drilling mud are an imperative property. The purpose of this study is to evaluate the filtration characteristics of water-based mud systems in the presence of polyanionic cellulose (PAC) and multiwalled carbon nanotubes (MWCNTs)/TiO2 nanoparticles. The nanoparticles were synthesized by using the hydrothermal technique. For the first time, a composite of MWCNTs and TiO2 has been utilized as a fluid loss control additive in the petroleum sector, marking a significant development in the field. The filtration properties of water-based mud were assessed at two concentrations (0.35 g and 3.5 g). Furthermore, based on the two levels (concentrations) and two factors (particles), the novel application of the central composite response surface design of experiment (CCD) was implemented. The results showed that the predicted model from CCD was in good agreement with the filter press experimental result with R 2 = 0.8446. Furthermore, based on the ANOVA analysis, the concentration of MWCNTs/TiO2 nanoparticles was the most significant parameter with p-value < 0.05. In addition, 10 out of 13 experimental points fall under the ±10% error window, thus indicating a higher accuracy of the regression model. The 2D interactive plots further show that the concentration of PAC is insignificant and has no considerable influence on fluid loss control, which was also validated by p-value > 0.05. The performance of MWCNTs/TiO2 nanoparticles is superior to PAC because these nanodimension particles plug the pore-spacing and block the permeation channels on the filter paper. However, the PAC, because of its long molecular chain, entangles around the pore spaces and plugs the microsize pores, which eventually reduces the filtration loss volume up to some extent. By observing the synergistic interaction between MWCNTs/TiO2 nanoparticles and PAC, this study develops valuable insights that assist in improving the performance of drilling fluid and minimizes the wellbore instability issues in the oil and gas sector.

Candida Tropicalis Endocarditis: A case report and literature review.

Fungi rarely cause infective endocarditis but when they do, they are often associated with poor outcomes. Candida tropicalis accounts for only 10% of Candida endocarditis cases. A case of a 30-year-old male with a history of intravenous drug abuse was reported to the emergency department in August, 2021 with right-sided leg pain and fever for 3 days. A trans-thoracic echocardiogram showed a vegetation on the aortic valve and a computed tomography angiogram showed complete nonopacification of the right-sided common iliac artery and the superficial femoral artery just distal to its branching of the right profunda femoris artery. An emergent right iliofemoral embolectomy was done. Candida tropicalis was isolated from tissue and blood cultures. The patient was successfully treated with aortic valve replacement and intravenous caspofungin. The other reported cases of Candida tropicalis were reviewed and findings were compared with those reported in patients with Candida albicans and Candida parapsilosis endocarditis.

Core outcome sets for trials of interventions to prevent and to treat multimorbidity in adults in low and middle-income countries: the COSMOS study.

INTRODUCTION: The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for the study of multimorbidity in LMICs do not presently exist. These are required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at preventing and treating multimorbidity in adults in LMICs. METHODS: To generate a comprehensive list of relevant prevention and treatment outcomes, we conducted a systematic review and qualitative interviews with people with multimorbidity and their caregivers living in LMICs. We then used a modified two-round Delphi process to identify outcomes most important to four stakeholder groups (people with multimorbidity/caregivers, multimorbidity researchers, healthcare professionals and policymakers) with representation from 33 countries. Consensus meetings were used to reach agreement on the two final COS. REGISTRATION: https://www.comet-initiative.org/Studies/Details/1580. RESULTS: The systematic review and qualitative interviews identified 24 outcomes for prevention and 49 for treatment of multimorbidity. An additional 12 prevention and 6 treatment outcomes were added from Delphi round 1. Delphi round 2 surveys were completed by 95 of 132 round 1 participants (72.0%) for prevention and 95 of 133 (71.4%) participants for treatment outcomes. Consensus meetings agreed four outcomes for the prevention COS: (1) adverse events, (2) development of new comorbidity, (3) health risk behaviour and (4) quality of life; and four for the treatment COS: (1) adherence to treatment, (2) adverse events, (3) out-of-pocket expenditure and (4) quality of life. CONCLUSION: Following established guidelines, we developed two COS for trials of interventions for multimorbidity prevention and treatment, specific to adults in LMIC contexts. We recommend their inclusion in future trials to meaningfully advance the field of multimorbidity research in LMICs. PROSPERO REGISTRATION NUMBER: CRD42020197293.

Fluvoxamine maleate alleviates amyloid-beta load and neuroinflammation in 5XFAD mice to ameliorate Alzheimer disease pathology.

Introduction: Alzheimer pathology (AD) is characterized by the deposition of amyloid beta (Aß) and chronic neuroinflammation, with the NLRP3 inflammasome playing a significant role. This study demonstrated that the OCD drug fluvoxamine maleate (FXN) can potently ameliorate AD pathology in 5XFAD mice by promoting autophagy-mediated clearance of Aß and inhibiting the NLRP3 inflammasome. Methods: We used mice primary astrocytes to establish the mechanism of action of FXN against NLRP3 inflammasome by using various techniques like ELISA, Western blotting, confocal microscopy, Immunofluorescence, etc. The anti-AD activity of FXN was validated in transgenic 5XFAD mice following two months of treatment. This was followed by behavior analysis, examination of inflammatory and autophagy proteins and immunohistochemistry analysis for Aß load in the hippocampi. Results: Our data showed that FXN, at a low concentration of 78 nM, induces autophagy to inhibit NF-κB and the NLRP3 inflammasome, apart from directly inhibiting NLRP3 inflammasome in primary astrocytes. FXN activated the PRKAA2 pathway through CAMKK2 signaling, leading to autophagy induction. It inhibited the ATP-mediated NLRP3 inflammasome activation by promoting the autophagic degradation of NF-κB, resulting in the downregulation of pro-IL-1ß and NLRP3. The anti-NLRP3 inflammasome effect of FXN was reversed when autophagy was inhibited by either genetic knockdown of the PRKAA2 pathway or pharmacological inhibition with bafilomycin A1. Furthermore, FXN treatment led to improved AD pathology in 5XFAD mice, resulting in significant improvements in various behavioral parameters such as working memory and neuromuscular coordination, making their behavior more similar to that of wild-type animals. FXN improved behavior in 5XFAD mice by clearing the Aß deposits from the hippocampi and significantly reducing multiple inflammatory proteins, including NF-κB, GFAP, IBA1, IL-1ß, TNF-α, and IL-6, which are associated with NF-κB and NLRP3 inflammasome in the brain. Moreover, these changes were accompanied by increased expression of autophagic proteins. Discussion: Our data suggest that FXN ameliorates AD pathology, by simultaneously targeting two key pathological features: Aß deposits and neuroinflammation. As an already approved drug, FXN holds potential as a candidate for human studies against AD.

Integrative network pharmacology, molecular docking, and dynamic simulation analysis of a polyherbal formulation for potential therapeutic impact on prostate cancer.

Background: Prostate cancer (PCa) remains a significant health concern globally, prompting a continual search for novel therapeutic strategies. In this study, we employed a comprehensive approach combining network pharmacology, molecular docking and dynamic simulation to explore the potential impact of a polyherbal formulation on PCa. Methods: Utilizing comprehensive network pharmacology approaches, we elucidated the complex interactions between the bioactive compounds within the polyherbal formulation and key targets associated with PCa progression, highlighting their multitarget mechanisms through integrated protein‒protein interaction and KEGG pathway analyses. Molecular docking simulation studies were performed to predict the binding affinities and modes of interaction between the identified bioactive compounds and their respective protein targets. Results: Complex connections comprising 486 nodes and 845 edges were found by the compound-target network analysis. Significant interactions were observed, and the average node degree was 4.23. KEGG research revealed that PCa and the PI3K-Akt signalling pathway are implicated in modulating prostate cancer. The Quercetin docking investigations revealed that the binding energies for AR and PIK3R1 were -9 and -9.5 kcal/mol, respectively. Based on the results of the MD simulations, it appears that tiny molecules and proteins have formed stable complexes with low fluctuations. Conclusion: In conclusion, this comprehensive method emphasises the value of network pharmacology in conjunction with molecular docking and dynamic simulation in revealing the anti-PCa therapeutic potential of polyherbal formulations, opening up new possibilities for the creation of efficient anti-cancer medicines.

Large Scale Genomic Investigation of Pediatric Cholestasis Reveals a Novel Hepatorenal Ciliopathy Caused by PSKH1 Mutations.

PURPOSE: Pediatric cholestasis is the phenotypic expression of clinically and genetically heterogeneous disorders of bile acid synthesis and flow. Although a growing number of monogenic causes of pediatric cholestasis have been identified, the majority of cases remain undiagnosed molecularly. METHODS: In a cohort of 299 pediatric participants (279 families) with intrahepatic cholestasis, we performed exome sequencing as a first-tier diagnostic test. RESULTS: A likely causal variant was identified in 135 families (48.56%). These comprise 135 families that harbor variants spanning 37 genes with established or tentative links to cholestasis. In addition, we propose a novel candidate gene (PSKH1) (HGNC:9529) in 4 families. PSKH1 was particularly compelling because of strong linkage in three consanguineous families who shared a novel hepatorenal ciliopathy phenotype. Two of the four families shared a founder homozygous variant while the third had a different homozygous variant in PSKH1. PSKH1 encodes a putative protein serine kinase of unknown function. Patient fibroblasts displayed abnormal cilia that are long and show abnormal transport. A homozygous Pskh1 mutant mouse faithfully recapitulated the human phenotype and displayed abnormally long cilia. The phenotype could be rationalized by the loss of catalytic activity observed for each recombinant PSKH1 variant using in vitro kinase assays. CONCLUSION: Our results support the use of genomics in the workup of pediatric cholestasis and reveal PSKH1-related hepatorenal ciliopathy as a novel candidate monogenic form.

Trends of Nanobiosensors in Modern Agriculture Systems.

Sustainable agriculture and the provision of food for all become dependent on the availability of efficient diagnostic techniques for the prompt identification of plant diseases. Current scientific findings suggest that nanotechnology can positively affect the agrifood industry by reducing the adverse effects of agricultural practices on human health and the environment, increasing food security and productivity, and fostering social and economic justice. Nanomaterials' unique physical and chemical characteristics have made it possible to employ them as cutting-edge, effective diagnostic instruments for various plant infections and other significant disease biomarkers. By creating diagnostic instruments and methods, nanobiosensors significantly contribute to the revolution of farming. In real time, nanobiosensors can detect infections, metabolites, pesticides, nutrient levels, soil moisture, and temperature. This helps with precision farming techniques and maximises resource use. To better address agricultural concerns, we have included the most recent research on the concept, types, applications, commercial aspects, and future scope of nanobiosensors in this review.

A Case Report on the Use of a Novel Technique for Intra-operative Nasojejunal Tube Placement in a Patient Undergoing Ivor-Lewis Esophagectomy.

Esophagectomy is an important cornerstone in the management of esophageal cancer. Post-operative feeding options in Ivor-Lewis esophagectomy include nasojejunal tube (NJT), feeding jejunostomy, and direct oral feeding. NJT is traditionally placed endoscopically or under fluoroscopic guidance. In this case report we present an alternate technique for NJT placement. A 55-year-old male presented to our clinic with dysphagia. On esophagogastroduodenoscopy, a gastroesophageal junction (GOJ) tumor was noted. A diagnosis of moderately differentiated adenocarcinoma was made on biopsy. The patient received eight cycles of epirubicin, cisplatin, and capecitabine (ECX), following which an Ivor-Lewis esophagectomy was carried out. This case report highlights the technical aspects and potential pitfalls of placing NJT in patients undergoing Ivor-Lewis esophagectomy without the use of endoscopy or fluoroscopic guidance. Direct oral feeding after Ivor-Lewis esophagectomy may lead to suboptimal caloric provision while feeding jejunostomy is associated with complications such as dermatitis, wound infection, and intestinal obstruction. On the other hand, endoscopic or fluoroscopic insertion of NJT can expose the anastomosis to potentially harmful mechanical forces. NJT can be easily placed using our technique in patients undergoing hybrid Ivor-Lewis esophagectomy. The safety of this technique can be investigated by further studies.

Unveiling the enigma: A challenging case of protein C deficiency concealed by fever and epistaxis.

Protein C deficiency is a rare genetic disorder caused by mutations in the protein C, inactivator of coagulation factors Va and VIIA gene, affecting approximately 1 in 200-500 individuals. It leads to a hypercoagulable state, increasing the risk of blood clots. Symptoms vary with age, ranging from life-threatening purpura fulminans in neonates to venous thromboembolism, particularly deep vein thrombosis, in adults. A recent case involved a 21-year-old South Asian male presenting with persistent fever, weight loss, epistaxis, abdominal tenderness, and acute pain in the right thigh and leg, raising suspicion of deep vein thrombosis. Tests confirmed deep vein thrombosis in multiple leg veins and a pulmonary embolism. The patient was diagnosed with protein C deficiency and received anticoagulant therapy, thrombolysis, and an inferior vena cava filter. Complications of protein C deficiency include deep vein thrombosis, pulmonary embolism, stroke, and ischemic colitis. Diagnosis involves immunoassays and genetic analysis. Treatment includes heparin followed by anticoagulation therapy with warfarin. In severe cases, an inferior vena cava filter may be implanted. The described case required extensive treatment due to multiple deep vein thrombosis and a pulmonary embolism, with lifelong anticoagulant therapy. Early diagnosis and appropriate management are crucial in young patients with a history of venous thromboembolism to prevent and manage complications associated with protein C deficiency.

Management of patients with concurrent clonal plasma cell and myeloid disorders: A single center descriptive case series.

Both clonal plasma cell and myeloid disorders occur more frequently with age. Patients with concurrent clonal plasma cell and myeloid disorders (CPCMD) can present clinical and therapeutic challenges. In this single-institution cohort of patients with CPCMD (n = 18), we abstracted clinically relevant themes. A majority of patients (12/18) were treated with clone-directed therapies and three received treatment targeting both clones. Treatment of clones with targetable genetic lesions or those causing end-organ complications should be prioritized. Simultaneous treatment of both clones can be safe but is best done in a stepwise manner. Further study of patients with dual clonal processes is warranted.

Comparison of polymeric clip and endoloop in laparoscopic appendectomy: A systematic review and meta-analysis.

BACKGROUND: Appendicitis is a common surgical emergency with diverse clinical presentations, making its diagnosis challenging. Laparoscopic appendectomy has become the standard treatment, with various methods for appendiceal stump closure, including polymeric clips and endoloops. This study aims to compare the efficacy and safety of polymeric clips compared with endoloops in laparoscopic appendectomy. METHODS: A systematic review and meta-analysis were conducted followingPreferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Medline, Scopus, and Embase were searched for studies up to March 25, 2024. RESULTS: In total, 13 studies, including 6 randomized controlled trials, were analyzed. Polymeric clipping demonstrated significantly shorter surgical time compared with the endoloop (standardized mean difference 0.37, 95% confidence interval 0.22-0.53, P < .00001), with no difference in hospital stay or overall complications. However, the endoloop was associated with a greater incidence of intra-abdominal abscess (risk ratio 3.53, 95% confidence interval 1.56-8.00, P = .003). Other outcomes, including time from instrument application to appendiceal cutting, ileus, and surgical-site infection, showed no significant differences between the 2 techniques. CONCLUSION: Polymeric clipping appears to be superior to endoloop in terms of shorter surgical time and lower risk of intra-abdominal abscess formation in laparoscopic appendectomy for uncomplicated appendicitis. However, both techniques have similar outcomes regarding hospital stay and overall complications. Further research addressing study limitations and exploring patient-centered outcomes is warranted to guide clinical practice.

Impact of COVID-19 on the Mental Health of Elderly Patients at Midnapore Medical College, West Bengal.

Background Depression, anxiety, and stress are leading causes of disability worldwide and major contributors to suicide. The burden of these disorders among the Indian geriatric population is often described as a silent epidemic. The sudden emergence of the COVID-19 pandemic has only intensified this public health problem. Finding out factors associated with poor mental health is critical to improving overall healthcare for high-risk patients, especially in underserved and inaccessible communities. Aim This study was conducted to measure the prevalence rates of depression, anxiety, and stress and their sociodemographic correlates among the Indian geriatric patient population. This study also aimed to assess the coping strategies employed and difficulties faced by the population during the COVID-19 pandemic. Methods A cross-sectional survey was conducted using a pre-designed and pre-tested questionnaire. A total of 107 participants were recruited through convenience sampling. Depression, anxiety, and stress were measured using the Bangla version of the Depression, Anxiety, and Stress Scale (DASS-21 BV), a 21-item self-reported questionnaire.  Results Of the sampled group, 43.9%, 32.7%, and 34.6% were moderately to extremely severely depressed, anxious, and stressed, respectively. Factors associated with worse mental health were increasing age, female gender, living separately from their spouses, unemployment, retirement, or any occupation that did not require one to leave their house. Of the sample population, 80.3% had experienced a loss of income due to the pandemic. The most frequently used coping strategy was to solve problems they faced daily, closely followed by praying and participating in religious activities. Conclusion Depression, anxiety, and stress showed a higher prevalence than previously described, before the pandemic. This could be due to the effects of the COVID-19 pandemic. Our study also demonstrated some of the factors associated with and the most commonly used ways to tackle poor mental health. Adequate educational awareness programmes that are accessible in different regional languages, strengthening mental health infrastructure, and community mental health services will significantly improve outcomes, especially among high-risk populations.

Profile of juvenile systemic lupus erythematosus patients with a special reference to monogenic lupus and lupus nephritis: a cross-sectional study.

To study the clinical, laboratory profile and outcome of juvenile Systemic Lupus Erythematosus (jSLE) patients at a tertiary care centre in South India. A retrospective review of the medical records of all jSLE patients visiting the Pediatric Immunology and Rheumatology Unit, Aster CMI Hospital, India from February 2017 to December 2023 was performed. The clinical characteristics, treatment and outcomes were recorded and tabulated. Seventy patients diagnosed with jSLE were included in the study. The female-to-male ratio was 4.4:1. Mean age at onset and delay in diagnosis were 120.1 (+/- 56.8) and 11.7 (+/- 22.7) months respectively. The median follow-up period was 13 months (range 4, 29 months). Nine patients presented with early onset SLE (< 5 years). Most common manifestations were constitutional symptoms (n = 56), followed by haematologic (n = 55), and mucocutaneous(n = 50) involvement. Immunological workup showed SLE-specific antibody positivity in 38 patients, hypocomplementemia in 40 patients, and anti-phospholipid antibody positivity in 13 patients. Mortality was observed in five patients with LN while there was no mortality in the non-nephritis group (p 0.004). C1q deficiency was the most common cause of monogenic lupus seen in 5/9 patients; protein kinase C delta (PRKCD) defect and chronic granulomatous disease (CYBB mutation) were seen in one patient each. We describe a large cohort of jSLE from Southern India. Lupus nephritis was noted in 35.7% of our cohort and had a direct correlation with mortality. 10% of patients had monogenic lupus. Serious infections were more frequent in patients with monogenic lupus.

A PHASE 1 FIRST-IN-HUMAN STUDY OF THE MCL-1 INHIBITOR AZD5991 IN PATIENTS WITH RELAPSED/REFRACTORY HEMATOLOGIC MALIGNANCIES.

BACKGROUND: AZD5991, a human MCL-1 inhibitor, was assessed for safety, tolerability, pharmacokinetics (PK), and antitumor activity as monotherapy and in combination with venetoclax in patients with relapsed or refractory (R/R) hematologic malignancies. METHODS: In the monotherapy cohort (n=61), patients with hematologic malignancies received AZD5991 intravenously in escalating doses either once or twice weekly, following intrapatient dose escalation, on a 3-week cycle. In the combination cohort (n=17), patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) received escalating doses of AZD5991 and venetoclax on either a 3-week or 4-week cycle. Primary objectives were safety and maximum tolerated dose; secondary objectives included plasma PK and antitumor activity. RESULTS: The most common (≥30%) adverse events (AEs) were diarrhea (59.0%), nausea (55.1%), and vomiting (47.4%). Four deaths occurred due to AEs: cardiac arrest, sepsis, tumor lysis syndrome (TLS), and acute respiratory failure; only TLS was related to AZD5991. Dose-limiting toxicities occurred in 5 patients. Three patients with MDS achieved an objective response: 1 marrow complete remission (mCR) without hematologic improvement, 1 partial remission with AZD5991 monotherapy, and 1 mCR with AZD5991+venetoclax. Asymptomatic elevations of troponin I or T were observed in 8 (10.3%) patients. Post hoc retrospective analysis revealed elevated troponin T in 14/31 patients before any AZD5991 dose and in 54/65 patients after any AZD5991 dose at or after cycle 1. There were no associations between elevated troponin and cardiovascular risk factors. CONCLUSIONS: Treatment with AZD5991 was associated with high incidence of laboratory troponin elevation and a low overall response rate.

Comparing skin and serum testing to direct challenge outcomes in children with beta-lactam allergies.

BACKGROUND: There is a scarcity of prospective studies investigating the relative roles of skin prick and intradermal testing, serum-specific Immunoglobulin E, and extended oral challenges in diagnosing children with reported beta-lactam allergies. OBJECTIVE: To determine the sensitivity and specificity of skin testing and serum-specific Immunoglobulin E in children with beta-lactam allergies, with immediate and non-immediate historic reactions. METHODS: Four hundred children with parent-reported beta-lactam allergies were recruited into an open-label prospective study. Detailed allergy histories were collected. Those with medically observed and documented histories of anaphylaxis, requiring epinephrine, or SCARs were excluded. In total, 380 children underwent all testing modalities and a direct provocation test. Each child was followed up for a minimum of three years. RESULTS: True allergy in children was uncommon, 8·3% reacted to the direct provocation challenge or the 5-day extended oral provocation challenge. Children reporting cephalosporin allergy or a reaction within one year were more likely to react to direct provocation testing. The sensitivity, specificity, and positive predictive value of skin testing was 12·5%, 98·8% and 20·0% for direct challenge outcomes, 4·76%, 99·0% and 25·0% for extended challenge outcomes, and 6·9%, 99·0% and 40·0% for both challenges combined. Follow-up investigations revealed that 5·7% of children had a mild repeat reaction and 2·7% continued to avoid the culprit despite successful delabeling. The relabeling rate for children readmitted to hospital was 15% with the relabeing being unfounded. CONCLUSION: Genuine beta-lactam allergies were rare, with over 90% of children effectively delabeled. Skin and serum-specific Immunoglobulin E testing did not aid the diagnosis of beta-lactam antibiotic allergy in children, regardless of medical history. Extended oral challenges proved valuable in confirming allergies and boosted parental confidence.

Evaluation of clinico-radiological outcome of conservative treatment in patients with partial-thickness rotator cuff tears.

Objective: While some patients may require surgical treatment a lot of patients do recover on conservative treatment alone while the optimal treatment being unclear. The purpose of this study was to treat the PT-RCTs conservatively for a period of 6 months and to determine its clinical outcome, radiological outcome on MRI and the baseline clinical factors predictive of that outcome. Methodology: All patients with a partial tear of supraspinatus and/or infraspinatus on their 1st MRI and aged 18-80 years were eligible and 47 patients (22 males, 25 females) were enrolled. Patients were evaluated using a standardised format including clinical history, imaging, and ASES(American Shoulder and Elbow Surgeons) score. Patients underwent a course of physical therapy for a period of minimum of 6 months which was augmented with the use of analgesics and/or anti-inflammatory drugs, multivitamins and supplements which were patient specific. Patients were followed up at 3 months and 6 months, ASES score was calculated, and a follow-up MRI was done at 6 months to determine if their tear had healed, remained the same, or progressed. A patient that had a better ASES score at 6 months was tagged as "clinically improved". Radiologically, patients were considered treated "successfully" if the tear size was reduced or remained the same while some "failed" that had an increased size of tear. Result: Non-operatively treated patients demonstrated a mean ASES score of 63.45 ± 16.24 at the end of 6 months. Overall, 35 patients (74.5 %) had the same size, seven patients (14.9 %) demonstrated tear progression and 5 (10.6 %) patients showed a decrease in size of their tear on MRI done at 6 months. In the end, 30 (63.8 %) patients improved clinically and 40 (85.1 %) patients improved radiologically. Statistical analysis also showed that patients with their non-dominant side involved and with an atraumatic onset of their injury were more likely to improve clinically. Conclusion: Conservative treatment of PT-RCTs may lead to a successful clinical outcome but it may or may not reveal itself radiologically. ASES score is an effective tool to evaluate and manage various conditions of the shoulder and not just the rotator cuff. The baseline factors such as onset (traumatic versus atraumatic) and shoulder involved (dominant versus non-dominant) can predict the outcome of conservative treatment.