Diverse Etiologies Research Articles

New evidence of vascular defects in neurodegenerative diseases revealed by single cell RNA sequencing.

Neurodegenerative diseases (NDs) involve the progressive loss of neuronal structure or function in the brain and spinal cord. Despite their diverse etiologies, NDs manifest similar pathologies. Emerging research identifies vascular defects as a previously neglected hallmark of NDs. The development and popularization of single-cell RNA sequencing (scRNA-seq) technologies have significantly advanced our understanding of brain vascular cell types and their molecular characteristics, including gene expression changes at the single-cell level in NDs. These unprecedented insights deepen our understanding of the pathogenic mechanisms underlying NDs. However, the occurrence and role of vascular defects in disease progression remain largely unexplored. In this paper, we systematically summarize recent advances in the structure and organization of the central nervous system vasculature in mice, healthy individuals, and patients with NDs, focussing primarily on disease-specific alterations in vascular cell types or subtypes. Combining scRNA-seq with pathology evidence, we propose that vascular defects, characterized by disruptions in cell types and structural integrity, may serve as common early features of NDs. Finally, we discuss several pathways through which vascular defects in NDs lead to neuronal degeneration. A deeper understanding of the causes and contributions of vascular defects to NDs aids in elucidating the pathogenic mechanisms and developing meaningful therapeutic interventions.

A Pharmaceutical Study on Panchanan Rasa

Rasa Shastra is a specialized branch of Indian system of traditional medicine which mainly deals with the use of metals, minerals and herbs along-with the application of varied principles of Alchemy. Panchanan Rasa a chief reference from Rasa Ratna Sammuchya 14/09 was taken for Hridya Roga. It is a herbo-mineral preparation made finally with the use Kharal Yantra so called Kharaliye Rasayan, & is given after proper Mardan only in powder form with vehicle indicated for administering it. In recent scenario Hridya Roga is becoming a major concern disease every 1 in 10 person is suffering from sudden/chronic heart/artery disease with varied etiology & also patients are not able to afford such costly intervention to manage it, so effort is made to do pre-clinical study on the formulation & get some data to go for further clinical study in future.

Middle Ear Malformations

Middle ear malformations (MEMs) represent a diverse group of congenital anomalies with significant implications for auditory function. These malformations, which occur in approximately 0.5 to 3% of conductive hearing loss cases, can arise from various genetic and environmental factors. They often manifest unilaterally and may occur in isolation or as part of a syndromic condition. MEMs are closely associated with abnormalities of the external ear and less frequently with inner ear anomalies.Embryologically, the middle ear develops from the first and second pharyngeal arches, with interactions between the ectoderm and endoderm contributing to the formation of essential structures such as the tympanic membrane, ossicles and Eustachian tube. Disruptions in these developmental processes can lead to a spectrum of MEMs, ranging from minor defects to severe malformations affecting multiple middle ear components.Clinical management of MEMs requires a multidisciplinary approach, involving otolaryngologists, pediatricians, and audiologists. Early intervention with appropriate hearing aids, including conventional hearing aids and bone conduction devices, is essential to mitigate the impact of conductive hearing loss on speech and language development, particularly in children.Surgical planning involves comprehensive preoperative assessment, including high-resolution computed tomography imaging to evaluate middle ear anatomy, the facial nerve course, and vascular anomalies. Traditional surgical approaches such as stapesplasty and tympanoplasty remain mainstays for correcting specific middle ear defects, while advances in technology have expanded the role of active middle ear implants in treating special cases.In conclusion, MEMs represent a heterogeneous group of congenital anomalies with diverse etiologies and clinical implications. A thorough understanding of their embryological basis, genetic underpinnings, and surgical management strategies is crucial for optimizing outcomes in affected individuals.

Influence of Cataract Causing Mutations on αA-Crystallin: A Computational Approach.

The αA-crystallin protein plays a vital role in maintaining the refractive index and transparency of the eye lens. Significant clinical studies have emerged as the αA-crystallin is prone to aggregation, resulting in the formation of cataracts with varied etiologies due to mutations. This work aims to comprehend the structural and functional role of cataract-causing mutations in αA-crystallin, particularly at N-Terminal and α-Crystallin Domains, using in-silico approaches including molecular dynamics simulation. About 19 mutants of αA-crystallin along with native structure were simulated for 100 ns and the post-simulations analyses reveal pronounced dynamics of αA-crystallin due to the enhanced structure flexibility as its native compactness was lost and is witnessed mainly by the mutants R12L, R21L, R21Q, R54L, R65Q, R116C and R116H. It is observed that αA-crystallin discloses the NTD motions as the dominant one and the same was endorsed by the linear variation between Rg and the center-of-mass of αA-crystallin. Interestingly, such enhanced dynamics of αA-crystallin mutants associated with the structure flexibility is internally modulated by the dynamic exchange of secondary structure elements β-sheets and coils (R2 = 0.619) during simulation. Besides, the observed pronounced dynamics of dimer interface region (β3-L6-β4 segment) of ACD along with CTD dynamics also gains importance. Particularly, the highly dynamic mutants are also characterized by enhanced non-covalent and hydrophobic interactions which renders detrimental effects towards its stability, and favours possible protein unfolding mechanisms. Overall, this study highlights the mutation-mediated structural distortions in αA-crystallin and demands the need for further potential development of inhibitors against cataract formation.

Trichomonad Disease in Wild Turkeys (Meleagris gallopavo): Pathology and Molecular Characterization of Histomonas, Tetratrichomonas, Tritrichomonas, and Simplicimonas spp.

The Wild Turkey (Meleagris gallopavo) is a geographically widespread, popular game bird and conservation icon in North America. Following successful reestablishment in parts of the US and Canada, regional declines have fueled population health concerns; therefore, understanding mortality causes and spatiotemporal patterns of disease is important to uncover potential ongoing and future health risks. Histomonosis, caused by the trichomonad Histomonas meleagridis, is a well-established and potentially fatal disease in Wild Turkeys; however, its prevalence and potential population health impacts remain poorly understood. Moreover, molecular tools recently have allowed for the detection of additional trichomonads that similarly can cause fatal disease in Wild Turkeys. We describe and compare disease due to H. meleagridis with that of Tetratrichomonas gallinarum, Tritrichomonas sp., and Simplicimonas sp. in Wild Turkeys in the southeastern US. Among 857 Wild Turkeys evaluated postmortem from 2002 to 2023, 34 (4.0%) were diagnosed with trichomonad disease, often assumed to be histomonosis prior to molecular testing. However, among 25 debilitating to fatal trichomonad disease cases for which etiologies were confirmed by PCR from 2015 to 2023, H. meleagridis was detected in 16/25 (64.0%), T. gallinarum in 6/25 (24.0%), Tritrichomonas sp. in 2/25 (8.0%) and Simplicimonas sp. in 1/25 (4.0%). These turkeys had similar clinical manifestations, and although lesion patterns varied to some extent, liver and/or intestinal tract was most commonly affected. Coinfections were common among all turkeys with trichomonad disease from 2015 to 2023 (21/25, 84.0%) and included viruses (lymphoproliferative disease virus, avian poxvirus), bacteria (Streptococcus gallolyticus, Listeria monocytogenes, Escherichia coli), and other protozoa (Sarcocystis sp., Haemoproteus sp.). Our results highlight the importance of molecular diagnostic testing in determining etiologies of trichomonad disease in Wild Turkeys. Further evaluation of the epidemiology and pathogenesis of trichomonad disease and its varied etiologies in Wild Turkeys and other birds is warranted to better understand risk factors and potential health impacts.

Blueberry Muffin Baby Syndrome in a Patient with Congenital Leukemia: Clinical Case

Background. Blueberry muffin baby syndrome in newborns is characterized by diffuse nodular skin lesions and it is difficult for diagnosis due to diverse etiology. Etiological factors include congenital infections, intrauterine hemolytic disease, multifocal vascular abnormalities, and neoplastic conditions. Congenital neonatal leukemia is rare disease and it is usually revealed during the first month of life. Clinical case description. This clinical case presents a patient with congenital acute myeloid leukemia and severe skin manifestations. Treatment has included risk-adapted chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation from a haploidentical donor (father). Conclusion. The significance of multidisciplinary approach in management of patients with congenital leukemias consist of timely determination of the disease variant, prognostic risk group, and initiation of programmed treatment.

The essential role of the miRNA-208a/TARBP2/Sox6 axis in myosin expression in the end stage human heart failure

Abstract Despite diverse aetiologies, failing human hearts (HF) of various origins (coronary artery disease (CAD), dilated cardiomyopathy (DCM), restrictive cardiomyopathy, and hypertrophic cardiomyopathy (HCM)) exhibit impaired contractility and share alterations in MYH6, MYH7, and MYH7B gene expression. Here, we explore the miRNA-208a/TARBP2/Sox6 axis in regulating myosin expression within left ventricles of explanted human hearts. Methods Samples of left ventricles were obtained from explanted hearts of patients with terminal HF (NYHA III-IV) and reduced left ventricle ejection fraction (LVEF <25%) due to CAD (n=10), DCM (n=10), HCM (n=6), and controls (n=5). We analysed the expression of cardiac myosin heavy chains (MYH6, MYH7, MYH7B), cardiac damage markers (ANP, BNP), and heart-related MyoMiRs using quantitative real-time PCR. Results Pre-transplant data for the 31 subjects (25 male, 3 female) included: age 54.4±8.2y, BP 112±18/67±11 mmHg, HR 79±16 min-1, LVEF 27±14%, LVEDD 8.8±15.8mm, RVEDD 32.8±5.1mm, QRS 0.140±0.05s, QT 0.42±0.04s, NT-proBNP 5551±4259 ng/l. In all diseased groups, MYH6 mRNA was downregulated, while MYH7 and MHRT ncRNA were upregulated. We observed strong positive correlations between MYH7, MYH7B, and MHRT transcription, suggesting coordinated expression. The miRNA-208a/miRNA-208b ratio shifted heavily towards miRNA-208b in controls, with a similar effect for miRNA-499 and MYH7B. A strong negative correlation existed between miRNA-499 and MYH7B expression across HF samples. TARBP2 expression decreased slightly in all pathological groups, while Sox6 mRNA increased. Conclusion Elevated Sox6 expression may contribute to MYH6 downregulation and MYH7/MYH7B upregulation. Altered TARBP2 expression could promote cardiomyopathy via Sox6-mediated repression of cardiac slow-twitch myofiber proteins. Changes in miRNA-208a processing leading to Sox6 upregulation may inhibit Sox6-dependent myosin transcript expression.

Embolic myocardial infarction. Clinical characteristics, etiology, and prognosis

Abstract Introduction A small proportion of acute myocardial infarctions (AMI) are of embolic origin. There is limited information about the actual causes of these AMIs, the population they affect, and their prognosis. Purpose The purpose of this study is to describe the clinical characteristics of embolic myocardial infarction (EMB-AMI) and compare them with atherosclerotic myocardial infarction (ATH-AMI). Methods Retrospective observational study of patients admitted for AMI at our centre (2010-2022). Clinical characteristics, ethology, and prognosis are described, and the EMB-AMI cohort is compared with the ATH-AMI cohort. Results Out of 6046 AMIs, 75 (1.2%) were EMB-AMI. Cardiovascular risk factors were similarly distributed in both groups, except for a higher rate of smokers, males, and older age in the ATH-AMI group (figure 1). Additionally, EMB-AMIs more frequently presented as ST-elevation myocardial infarctions. Hospital mortality for EMB-AMI and ATH-AMI was 10.7% vs. 6.2% (p=0.177), and the rate of mechanical complications was higher in the EMB-AMI group (6.7% vs. 1.8%, p=0.009). Of the EMB-AMIs, 8 (10.7%) had other systemic emboli during admission, including a 5.3% of strokes (vs. 1.4% in the ATH-AMI group, p=0.021). In EMB-AMIs, coronary embolism was multivessel in 8 (10.7%) patients, 46 (61.3%) had distal vessel involvement, and 66 (88.0%) had initial TIMI 0 flow. Thrombectomy was performed in 51 (68%) patients, with 82% of them being successful. However, final TIMI was 0-1 in 36 (48%) patients and 3 in 32 (42.7%) patients. Angioplasty was performed in 12 (16.0%) patients. In 52 (67.5%) EMB-AMI patients, atrial fibrillation (AF) was diagnosed at some point during follow-up, and in 43 (57.3%), embolism was exclusively attributed to AF. Nine (12.0%) embolisms were attributed to prosthetic thrombosis, although thrombosis was confirmed by imaging in only one third of cases. Six (8%) embolisms were attributed to endocarditis, and 5 (6.7%) to patent foramen ovale. Rest of embolism causes detected are outlined in figure 2. During a mean follow-up of 44.8 months, 11 patients experienced new embolic events in the EMB-AMI cohort: 7 strokes, 2 probable coronary embolisms, and 2 systemic embolisms. Twenty-seven (36.0%) patients died during follow-up (38.4% of whom from cardiac causes), and 18 (24.0%) were admitted for heart failure. Conclusions EMB-AMI exhibits specific clinical characteristics distinct from ATH-AMI, with varied etiologies, with atrial fibrillation being the most common cause. These AMIs are associated with a higher incidence of complications, including mechanical complications of myocardial infarction and recurrence of embolic events.Characteristics and outcomesEmbolic source

Treatment of Posttraumatic Zygomatic Coronoid Ankylosis. Systematic Review.

Facial trauma is mostly associated with traffic accidents, fights, and sports accidents. The mandible, midface, and temporomandibular joint are usually the region's most frequently affected. Coronoid process fractures are rare, representing ∼2% of facial fractures in the literature, usually being the result of direct trauma to the zygomatic region. Due to the anatomical relationship of the coronoid process, it may be associated with other facial fractures, such as fractures of the zygomatic bone. Zygomatic-coronoid ankylosis is a rare clinical entity with variable etiology. It is most commonly associated with trauma (13%-100%), local or systemic infection (0%-53%), or systemic diseases, such as ankylosing spondylitis, rheumatoid arthritis, or psoriasis. The aim of this research is to evaluate the different treatments for ankylosis from the coronoid process to the zygoma after trauma, allowing to determine the treatment to obtain the best results. A systematic review was carried out following PRISMA "preferred reports for systematic reviews and meta-analyses" search matrix, based on a PICO question; was used PubMed, Embase, Sciencedirect, Cochrane, Google Scholar, and manual search in high-impact journals between 1946 and 2023 publications in English or Spanish, including randomized and nonrandomized clinical trials, prospective and retrospective cohort studies, case-control studies, series, and case reports. A total of 1993 articles were obtained from the 4 databases. After corroborating duplicate articles, 847 articles were excluded. Another 1112 articles were excluded in the title evaluation, and an additional 1093 after the abstract review; a total of 19 articles eligible for full-text evaluation were established and 1 article was added as a result of the manual search. After the full-text review, it was decided to include 16 articles in the study that met the objectives of the systematic review. After evaluating the different treatments described in the literature, the authors can determine that coronoidectomy through an intraoral approach is the most appropriate treatment for zygomatic coronoid ankylosis, accompanied by postoperative physiotherapy to achieve greater oral opening without recurrences.

Real-world evidence for patient phenotypes in heart failure with preserved ejection fraction

Abstract Background Heart failure (HF) with preserved ejection fraction (HFpEF) presents a high mortality risk due to its heterogeneous and multifactorial nature, coupled with limited treatment options. The incompletely understood pathophysiology is influenced by various comorbidities, resulting in different clinical phenotypes. Identifying these could be crucial for tailored HFpEF treatments. While previous studies focused on small, well-characterized patient populations, electronic health records (EHRs) offer the potential to unveil HFpEF phenotypes in larger real-world patient groups. Purpose We aimed to establish a sizable, unselected HFpEF patient population using real-world data. Employing cluster analysis, we intended to uncover distinct groups with varied disease aetiology and medical needs based on comorbidity profiles and prognoses. Methods From EHRs of n = 1,610,101 HF patients, we identified an HFpEF cohort of n = 32,009 patients, by applying thresholds for the LVEF and data availability, and by excluding confounding conditions. Clustering by the relative frequency of common comorbidities aimed to reveal patient populations with unique prognoses, comorbidity profiles, and clinical and demographic characteristics. Results Six clusters of different sizes, comorbidity prevalence, clinical presentation, and all-cause mortality were identified. About 50% of patients (n = 15,445) were predominantly hypertensive, with varying extents of coronary heart disease and diabetes mellitus (DM), and a 5-year mortality of about 30%. Around 22% (n = 7,089) exhibited a cardiometabolic comorbidity profile, with an increased prevalence of obesity and sleep apnea, but also DM and hypertension, and a 5-year mortality of 22.5%. Over 15% of patients (n = 5,298) had a 5-year mortality rate of 45.0%, marked by highest rates of anaemia and chronic kidney disease (CKD) but also DM, elevated N-terminal prohormone of brain natriuretic peptide levels, and a reduced estimated glomerular filtration rate. Conclusion Despite the favourable prognosis, a significant proportion of patients represent a cardiometabolic HFpEF phenotype with notable unmet medical needs regarding cohort size and multimorbidity. Patients simultaneously suffering from CKD, anaemia, and the highest mortality rates may represent a previously underrecognized phenotype. Our study demonstrates that distinct medical needs can be identified in a large, unselected real-world HFpEF cohort. In contrast to clinical trials, this approach enabled access to a broader patient population, revealing novel phenotypes to be targeted by precision medicine in the future.

Diffuse alveolar hemorrhage: a retrospective study from a tertiary care center.

Diffuse alveolar hemorrhage (DAH) is characterized by a syndrome of alveolar bleeding, a fall in hemoglobin, and respiratory failure. It can occur because of various immunologic and non-immunologic conditions. The etiology of DAH is important, as treatment varies with the etiology. This retrospective observational study evaluates the diverse etiologies, time to diagnosis from symptom onset, management strategies, and outcome of DAH in a span of 12 months at our tertiary care center. A total of 8 patients were identified with 8 different etiologies. 6/8 (75%) patients had immunologic causes, and 2/8 (25%) had non-immunologic causes of DAH. 6/8 (75%) patients were females, the mean time to DAH diagnosis was 4.25 months from symptom onset, 6/8 (75%) patients improved, and 2/8 (25%) died due to complications. It is necessary to differentiate between the etiologies of DAH and establish an early diagnosis to plan management and improve outcomes.

Latent class analysis-derived classification improves the cancer-specific death stratification of lymphomas: A large retrospective cohort study.

Lymphomas have diverse etiologies, treatment approaches, and prognoses. Accurate survival estimation is challenging for lymphoma patients due to their heightened susceptibility to non-lymphoma-related mortality. To overcome this challenge, we propose a novel lymphoma classification system that utilizes latent class analysis (LCA) and incorporates demographic and clinicopathological factors as indicators. We conducted LCA using data from 221,812 primary lymphoma patients in the Surveillance, Epidemiology, and End Results (SEER) database and identified four distinct LCA-derived classes. The LCA-derived classification efficiently stratified patients, thereby adjusting the bias induced by competing risk events such as non-lymphoma-related death. This remains effective even in cases of limited availability of cause-of-death information, leading to an enhancement in the accuracy of lymphoma prognosis assessment. Additionally, we validated the LCA-derived classification model in an external cohort and observed its improved prognostic stratification of molecular subtypes. We further explored the molecular characteristics of the LCA subgroups and identified potential driver genes specific to each subgroup. In conclusion, our study introduces a novel LCA-based lymphoma classification system that provides improved prognostic prediction by accounting for competing risk events. The proposed classification system enhances the clinical relevance of molecular subtypes and offers insights into potential therapeutic targets.

Cerebral Venous Thrombosis in a Term Child: A Case Report

Thrombosis of cerebral venous sinuses is a rare condition but can be associated with serious clinical consequences. Pathogenesis of thrombosis of cerebral venous sinus is still not clear. As there is diverse etiology but presentation is subtle, it often leads to delay in the diagnosis. We are reporting the case of a term male neonate born by LSCS (indication obstructed labour with meconium stained amniotic fluid) with diagnosis of severe birth asphyxia, Hypoxic Ischemic Encephalopathy- stage II, probable sepsis, shock and Germinal Matrix Haemorrhage. The magnetic resonance imaging (MRI) of brain and magnetic resonance (MR) venogram done at 2 weeks of age showed superior saggital sinus thrombosis. Baby received anticoagulation therapy and extensive workup was done. Early neuroimaging in all the babies who has neonatal seizures will improve the identification and will warrant early treatment.

Infectious Neuropathies.

This review explores diverse infectious etiologies of peripheral nervous system (PNS) dysfunction, spanning sensory and motor neurons, nerves, and associated structures. Progress in viral and bacterial infections reveals multifaceted mechanisms underlying neuropathies, including viral neurotoxicity and immune-mediated responses. Latest diagnostic advances facilitate early PNS complication detection, with ongoing research offering promising treatment avenues. Emerging pathogens like severe acute respiratory syndrome coronavirus 2, Zika virus, and EV-D68 highlight the evolving infectious neuropathy paradigm. Recognizing characteristic patterns and integrating clinical factors are pivotal for precise diagnosis and tailored intervention. Challenges persist in assessment and management due to varied pathogenic mechanisms. Advancements in understanding pathogenesis have improved targeted therapies, yet gaps remain in effective treatments. Ongoing research is crucial for optimizing approaches and improving patient outcomes.

The contribution of the sphingosine 1-phosphate signaling pathway to chronic kidney diseases: recent findings and new perspectives.

Chronic kidney disease (CKD) is a multifactorial condition with diverse etiologies, such as diabetes mellitus, hypertension, and genetic disorders, often culminating in end-stage renal disease (ESRD). A hallmark of CKD progression is kidney fibrosis, characterized by the excessive accumulation of extracellular matrix components, for which there is currently no effective anti-fibrotic therapy. Recent literature highlights the critical role of sphingosine 1-phosphate (S1P) signaling in CKD pathogenesis and renal fibrosis. This review provides an in-depth analysis of the latest findings on S1P metabolism and signaling in renal fibrosis and in specific CKDs, including diabetic nephropathy (DN), lupus nephritis (LN), focal segmental glomerulosclerosis (FSGS), Fabry disease (FD), and IgA nephropathy (IgAN). Emerging studies underscore the therapeutic potential of modulating S1P signaling with receptor modulators and inhibitors, such as fingolimod (FTY720) and more selective agents like ozanimod and cenerimod. Additionally, the current knowledge about the effects of established kidney protective therapies such as glucocorticoids and SGLT2 and ACE inhibitors on S1P signaling will be summarized. Furthermore, the review highlights the potential role of S1P as a biomarker for disease progression in CKD models, particularly in Fabry disease and diabetic nephropathy. Advanced technologies, including spatial transcriptomics, are further refining our understanding of S1P's role within specific kidney compartments. Collectively, these insights emphasize the need for continued research into S1P signaling pathways as promising targets for CKD treatment strategies.

7745 Hirsutism in young girls, Beyond PCOS

Abstract Disclosure: I. Mishra: None. A. Baliarsinha: None. Hirsutism is excessive terminal hair that appears in a male pattern in women.Though obesity,insulin resistance and PCOS are common cause of hirsutism in young girls,suspicion of other etiologies must be made on a background of overlapping features.We describe 3 cases of young females presenting with hirsutism with varied etiologies. Case 1.16 year 11months old female presented with oligomenorrhea -3years,excessive hair growth over face -2 years.On examination,BMI was 25.2 kg/m2,Grade 2 acanthosis,A3P5B5,modified FG- 16/36,clitoral length-1.3cm and clitoral index - 70 mm2.Biochemical evaluation revealed normal thyroid function tests,s.prolactin- 23.65 ng/ml,ONDST- 1.2 mcg/dl,LH - 1.49 IU/ml,FSH- 7.44IU/ml,serum testosterone- 70ng/dl,17OHP- 7.03 ng/ml,DHEAS- 553mcg/dl and post synacthen 17OHP- 36.89 ng/ml respectively. USG abdomen & pelvis was normal.HOMA-IR was 4.1. Diagnosis was LOCAH Case 2.19 year old female presented with hair growth in androgen dependent areas-5years, regular predictable menstrual cycles and was treated as a case of PCOS for 5 years with no changes in hair growth pattern.She was off therapy since 1 year prior presenting to us.On examination,BMI was 24 kg/m2,acanthosis absent,A3P5B5,modified FG- 18/36, clitoral length- 6 mm,clitoral index - 25mm2.Biochemical evaluation revealed normal thyroid function tests,s.prolactin- 22.9 ng/ml,ONDST- 0.508 mcg/dl,LH - 5.98 IU/ml,FSH- 5.29 IU/ml, serum testosterone- 23.4 ng/dl,17OHP- 1.01 ng/ml and DHEAS- 298 mcg/dl respectivelyUSG Abdomen & pelvis;RO - 5.7cc,LO - 5.6 cc with B/L PCOM.Review TVS was normal.In view of discordant results DHT and luteal phase serum progesterone were done which were 80.5 pg/ml and 2.1ng/ml respectively.HOMA IR was 1.9.Diagnosis was IDIOPATHIC HIRSUTISM. Case 3.12 year old female child presented with excessive hair growth over face,chest,back and abdomen- 1yr,hoarseness of voice - 1 yr,onset of breast enlargement apprx 8 to 9yrs with non-attainment of menarche.On examination BMI was 30 kg/m2,Grade 3 acanthosis, A3P5B3,modified FG- 15/36,clitoral length- 2.8 cm & clitoral index - 120 mm2. Biochemical evaluation revealed normal thyroid function tests,LH - 15.3 IU/ml,FSH- 6 IU/ml,s.prolactin- 11.2 ng/ml,ONDST- 0.38 mcg/dl,DHEAS- 161 mcg/dl,serum testosterone- 140 ng/dl,17OHP- 3.9 ng/ml and post synacthen 17OHP- 4.10 ng/ml respectively.USG abdomen-s/o PCOS with normal adrenals. In view of discordant results short DAST was done which was Testosterone(ng/dl)baseline-125;4hr-91.1, DHEAS (mcg/dl) baseline-180;4hr-188 cortisol (mcg/dl) baseline-7.04;4hr-0.95.HOMA-IR was 5.4. Diagnosis was PCOS(OVARIAN THECOSIS).Varied presentations of hyperandrogenic disorders occurs in young females.A need to revise the diagnosis must be made if no response is obtained with initial drug regimes. Presentation: 6/3/2024

Autoimmune and infectious encephalitis: development of a discriminative tool for early diagnosis and initiation of therapy.

Encephalitis originates from diverse autoimmune and infectious etiologies. Diagnostic challenges arise due to the spectrum of presentation and the frequent absence of specific biomarkers. This study aimed to comprehensively characterize and differentiate autoimmune encephalitis (AE) from infectious encephalitis (IE) in adults, and disentangle clinical, paraclinical, and therapeutic differences. A cohort study spanning 10years was conducted across three Austrian tertiary care hospitals. Inclusion criteria comprised adults with probable or definite encephalitis. Demographics, clinical features, technical findings, treatment modalities, and outcomes were collected from the electronic patient files. A follow-up was performed via telephone interviews and clinical visits. Of 149 patients, 17% had AE, 73% IE, and 10% encephalitis of unknown etiology. Significant differences between AE and IE included the prevalence of acute symptomatic seizures (AE: 85% vs. IE: 20%, p < 0.001), fever (8% vs. 72%, p < 0.001), headache (15% vs. 61%, p < 0.001), and focal neurological deficits (56% vs. 23%, p = 0.004), respectively. Paraclinical differences comprised lower CSF pleocytosis in AE compared to IE (median 6 cells/µl vs. 125 cells/µl, p < 0.001). Epileptic discharges on EEG and MRI lesions were more prevalent in AE than IE (50% vs. 14%, p < 0.001; 50% vs. 28%, p = 0.037). The modified Rankin Scale scores at discharge and last follow-up (median duration 2304days, IQR 1433-3274) indicated favorable outcomes in both groups. This comprehensive analysis provides insights into the epidemiology, clinical, paraclinical, and therapeutic aspects and the outcomes of AE and IE in adults. We developed a diagnostic tool that facilitates early differentiation between AE and IE, aiding in timely therapeutic decision-making.

Peripheral blood immunophenotypic diversity in patients with rheumatoid arthritis and its impact on therapeutic responsiveness

ObjectiveConsidering the diverse aetiologies and immunodysregulatory statuses observed in each patient with rheumatoid arthritis (RA), stratification based on peripheral blood immunophenotyping holds the potential to enhance therapeutic responses to molecular...

Impact of Etiology on Efficacy Outcomes with Atezolizumab Plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Retrospective Analysis in Asia-Pacific.

Atezolizumab-bevacizumab is a standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). Given the diversity in HCC etiology and its potential impact on the tumor microenvironment, understanding how different liver disease etiologies affect treatment efficacy is important. We assessed the influence of liver disease etiology on the efficacy of atezolizumab-bevacizumab and evaluated changes in liver function during treatment with atezolizumab-bevacizumab. This study included 390 patients with uHCC treated with first-line atezolizumab-bevacizumab from Asan Medical Center, South Korea, and National Cancer Centre Singapore, Singapore from July 2016 to March 2023. Patients were classified to viral, metabolic dysfunction-associated liver disease (MASLD) and nonviral/non-MASLD groups. Albumin-bilirubin (ALBI) scores were recorded at baseline and every two cycles up to cycle six and at the time of disease progression. The majority of patients presented with viral etiologies (74.1%), and 17.2% had MASLD. Across etiological groups (viral versus MASLD versus nonviral/non-MASLD) no significant differences in objective response rate (23.2% versus 29.9% versus 23.5%, respectively; p = 0.515), progression-free survival (median 5.4 versus 7.7 versus 6.0 months; p = 0.320), and overall survival (18.1 versus 18.9 versus 14.4 months; p = 0.400) were observed. Among the patients with disease progression, ALBI scores at the time of progression were significantly higher than at baseline. Subsequent therapy was administered significantly less often to patients with ALBI grade 3 at disease progression compared with those with ALBI grades 1 or 2 (48.4% versus 78.8%, p = 0.002) CONCLUSIONS: Atezolizumab-bevacizumab demonstrates consistent efficacy regardless of HCC etiology, supporting its use as a first-line treatment across diverse patient populations. Liver function assessments remain crucial for managing therapy and predicting outcomes.

Can CONUT and PNI Scores Predict Necrotizing Pancreatitis in Acute Pancreatitis Patients Presenting to the Emergency Department?

Background and Objectives: Acute pancreatitis, characterized by pancreatic inflammation, poses significant morbidity and mortality worldwide, with varied etiologies including gallstones, alcohol, and certain medications. Necrotizing pancreatitis represents a severe form of parenchymal damage with considerable impact on patient quality of life. Early identification of necrotizing pancreatitis is crucial for timely intervention and improved outcomes. The aim of this study was to investigate the usability of CONUT and PNI scores as prognostic indicators. Materials and Methods: We conducted a retrospective observational study involving patients presenting to the emergency department with acute pancreatitis between January 2020 and October 2023. The Controlling Nutritional Status (CONUT) score and Prognostic Nutrition Index (PNI) were calculated from serum biomarkers to assess nutritional status. Patients were categorized into necrotizing and nonnecrotizing pancreatitis groups, and the utility of CONUT and PNI scores in predicting necrotizing pancreatitis was evaluated. Results: A total of 339 patients were included, with 8.26% diagnosed with necrotizing pancreatitis. CONUT and PNI scores significantly differed between necrotizing and nonnecrotizing groups, with higher CONUT scores and lower PNI scores observed in the necrotizing group. Receiver operating characteristic (ROC) curve analysis revealed significant predictive value of CONUT and PNI scores for necrotizing pancreatitis, with cutoff values of >5 and ≤34, respectively. Conclusions: CONUT and PNI scores demonstrate promise in predicting necrotizing pancreatitis in patients admitted to the emergency department with acute pancreatitis. Additionally, these scores may serve as prognostic indicators for mortality in acute pancreatitis patients. Early identification using CONUT and PNI scores could facilitate timely intervention, potentially reducing mortality and morbidity in this patient population.