Visceral Adiposity Index in Type 2 Diabetes Mellitus (DM) and Its Correlation With Microvascular Complications.

Background Obesity, specifically abdominal obesity, is a major risk factor for diabetes. A strong association has been marked between diabetes and obesity. Many abdominal obesity indices have been established, including waist circumference (WC), BMI, and a new tool, the visceral adiposity index (VAI). However, very limited research highlights the association of these anthropometric parameters and VAI to the various microvascular complications of diabetes mellitus (DM). The objective of this study is to investigate the association of VAI with microvascular complications such as retinopathy, nephropathy, and neuropathy in type 2 DM (T2DM) patients. Methodology Data from Acharya Vinoba Bhave Rural Hospital (AVBRH) was analyzed in this case-control study with a sample size of 250 patients consisting of 125 cases and 125 controls. The cases and controls were age- and gender-matched. BMI and WC were measured in these patients, and the VAI was calculated. These anthropometric parameters were then analyzed to estimate their correlation with the microvascular complications of T2DM. Results The mean age of cases in this study was 58.37 ± 12.08 years and that of controls was 57.61 ± 14.51 years. Anthropometric parameters, namely, BMI, WC, and VAI were raised in cases as compared with controls, and they showed significant statistical relation with diabetes (for BMI, P = 0.003; for WC, P = 0.001 for males and P = 0.002 for females; and for VAI, P = 0.005). A significant correlation was noted in the high-density lipoprotein (HDL) cholesterol (P = 0.017 for males and P = 0.0004 for females) and triglyceride (TG) levels (P < 0.0001) between cases and controls. On distributing the male and female cases in quartiles, it was observed that with increasing quartiles, VAI increased significantly and was associated with an increased risk of microvascular complications such as retinopathy, nephropathy, and neuropathy. When the anthropometric parameters and VAI were compared with the total microvascular complications and the receiver operating characteristic curve studied, VAI had the maximum AUC (AUC for VAI was 0.826, WC was 0.813, and BMI was 0.806). Univariate analysis of the various microvascular complications showed that WC, BMI, HDL, TGs, and glycated hemoglobin (HbA1c) were all significantly correlated to the microvascular complications in T2DM patients. Conclusions As the VAI was significantly raised in T2DM patients and also seen to be significantly associated with microvascular complications, it could be used as a screening tool for T2DM patients.

Riluzole and Edavarone: The Hope Against Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is one of the most frequent motor neuron illnesses. Motor neuron illnesses are various disorders that include upper and lower motor neuron abnormalities. Amyotrophic lateral sclerosis accounts for roughly 80% of motor neuron disorders. ALS is a fatal motor neuron disease that involves the loss of motor neurons in the spinal cord and brain, resulting in gliosis and muscle weakening and wasting in the upper, lower, and respiratory muscles, reducing life expectancy to 2-5 years from the onset of symptoms. Up until now, oral riluzole, a glutamatergic neurotransmitter inhibitor, has been used to manage ALS, the only drug for the management of ALS that has been approved by the United States (US) Food and Drug Administration (FDA). In recent studies, edaravone has been used through intravenous mode to halt the progression of ALS. We conducted a systematic search on PubMed; we selected Google Scholar, PubMed, websites regarding ALS, WebMD, Researchgate, als.org, consultant360, and the relevant articles for the review. It shows us riluzole and edaravone's efficacy for managing A.L.S. and how it can increase the life span of the patients.

A Case of Gastric Diverticulum Presenting As Upper Gastrointestinal Bleeding in Rural Central India.

Gastric diverticula (GD) are the least prevalent type of gastrointestinal diverticula and are extremely uncommon anatomical anomalies in general. Although the majority of GD cases are asymptomatic and are identified by chance during normal diagnostic testing, they can manifest with a variety of symptoms. In some instances they can lead to life-threatening problems, necessitating surgical intervention. The majority of gastric diverticula go unnoticed. Upper abdomen pain, nausea, emesis, and dyspepsia are the most prevalent symptoms. Patients with GD can present with dramatic symptoms such as major bleeding or perforation on rare occasions. We report a rare case of a 60-year-old male, who presented with a complaint of haematemesis, and upon doing endoscopy and contrast-enhanced computed tomography of the abdomen was diagnosed with GD. The patient was managed successfully with proton pump inhibitor infusion and somatostatin analogs and was discharged in stable condition. Here, we highlight a rare but potentially life-threatening cause of hematemesis which is often missed by treating clinicians, especially in rural and remote areas, and therefore, requires more awareness and clinical vigilance.

Importance of Second-Look Surgery in a Newborn Presenting With Early Malrotation.

Intestinal malrotation refers to the abnormal positioning of the intestines due to a deviation from normal developmental stages. Volvulus is seen in 60%-70% of neonates diagnosed with intestinal malrotation. We are reporting a case of s six-day-old male who presented with multiple episodes of bilious vomiting and constipation and had malrotation of intestines with midgut volvulus. After a contrast upper GI study, the patient was taken for exploratory laparotomy, and extensive patches of an early stage of bowel ischemia were observed; resection was avoided at this stage. In the second-look surgery, all the gangrenous bowel loops were resected, and anastomosis was done.

A Case Report of Hemophagocytic Lymphohistiocytosis (HLH) - An Unusual Complication of Dengue Infection.

Hemophagocytic lymphohistiocytosis (HLH) is an autoimmune phenomenon characterized by reactive hyperactivity of cytotoxic T cells and histiocytes, leading to hypercytokinemic injury to cells and organ system, which leads to multiorgan dysfunction and ultimate failure. Epstein-Barr virus (EBV) is most commonly associated with secondary HLH with high mortality, but increasing evidence suggests the association of the dengue virus. When associated with dengue infection, it carries a grave prognosis and correlates with the disease severity. Furthermore, it overlaps with dengue sepsis, so it can often be misdiagnosed as sepsis. Typically the patients have hyperferritinemia, hypertriglyceridemia, transaminitis, and marrow features suggestive of hemophagocytosis. The treatment is usually systemic corticosteroids, intravenous immunoglobulin, and chemotherapy with etoposide. We present a case of a 25-year-old male patient who had a dengue infection and further developed HLH with pulmonary infiltrates. Clinical suspicion alerted us to look for other evidence of HLH on the fourth day of admission, and appropriate investigations were done. Diagnosis of HLH was confirmed by HLH-2004, HScore criteria, and bone marrow aspirate examination. Treatment was given in the form of corticosteroids and chemotherapy along with other supportive measures. The patient responded to the line of management.

Yamaguchi Syndrome: A Hidden Masquerader of Ischemic Heart Disease.

Yamaguchi syndrome, also known as apical (Ap) hypertrophic cardiomyopathy (HCM), is a variant of cardiomyopathy that affects the apical region of the left ventricle. ApHCM is frequently misdiagnosed or missed because its symptoms are extremely similar to those of acute coronary syndrome. As clinicians are unfamiliar with this disease, diagnosis can be missed or delayed; as a result, this condition is frequently discovered by chance. ApHCM has a favorable long-term prognosis once properly diagnosed. We report a case of a 50-year-old male who was diagnosed with Yamaguchi syndrome incidentally.

Association of Metabolic-Associated Fatty Liver Disease With Various Anthropometric Parameters in Pre-diabetes in Comparison With Diabetes and Control: A Single Tertiary Care Center Study.

Introduction Individuals with pre-diabetes and metabolic-associated fatty liver disease (MAFLD) have an increased risk of developing diabetes mellitus (type-2) when compared with individuals with pre-diabetes without MAFLD. Patients with any of the components of metabolic syndrome should be screened for the risk of MAFLD, as all its components are well correlated with the degree of liver fat content. In this research article, we have highlighted the association of MAFLD with various anthropometric parameters in pre-diabetes as compared to diabetes and normal individual. Methods In this cross-sectional study a total of 356 patients more than 18 years of age who meet the criteria for diabetes and pre-diabetes according to WHO, were enrolled. Anthropometric indices like body mass index (BMI), waist-hip ratio, waist to height ratio, and neck circumference were recorded. Patients underwent ultrasonography of liver and blood investigations like lipid profile, and liver function tests. Results The prevalence of MAFLD observed in this study was 44.1% in diabetics and 22% in pre-diabetics, compared to 9.2% in healthy controls. The ROC analyses showed that MAFLD predict pre-diabetes using the waist-hip ratio was higher in women compared to men (0.750 and 0.693 respectively). In men, the waist-hip ratio was followed by 0.648 for Neck Circumference, 0.646 for BMI, and 0.635 for waist-to-height ratio respectively, whereas the ROC analyses in women showed that other than waist-hip ratio, no other anthropometric index that had consistently higher AUC value. Conclusion Though there was an association between high BMI, waist-hip ratio, waist to height ratio, and neck circumference with MAFLD in pre-diabetes, it was not strongly associated as in the diabetic group.

Communicating Hydrocephalus as a Consequence of Chronic Kidney Disease on Maintenance Hemodialysis: An Uncommon Complication of a Common Disease.

While many etiologies of hydrocephalus for different age groups have been studied in detail, chronic kidney disease remains rare. We report a case of a 42-year-old male who was a known case of chronic kidney disease on maintenance hemodialysis since seven years. He was brought to the emergency department with a history of altered sensorium and irrelevant talk since the last 4-5 hours and was found to be a case of communicating hydrocephalus with periventricular ooze, as revealed by a computed tomography (CT) of the brain. A ventriculoperitoneal shunt surgery was performed, and the patient ultimately recovered and was discharged.

Seronegative Autoimmune Basal Ganglia Encephalitis Presenting as Acute Parkinsonism and Refractory Faciobrachial Seizures: A Case Report.

Autoimmune basal ganglia encephalitis (BGE) typically presents with acute onset parkinsonism and on imaging is associated with lesions in the basal ganglia. It is associated with chorea and other movement disorders. Seizures are still rare. Various autoantibodies are associated with the development of basal ganglia encephalitis. These autoantibodies are against dopamine D2 receptor (D2R) and N-methyl-D-aspartate receptor (NMDAR). Another paraneoplastic antibody known as anti-recoverin antibodies (Abs) is also associated with basal ganglia encephalitis. We report a case of a 45-year-old male who presented in this hospital with a history of cognitive dysfunction and slowness of activities for eight days and faciobrachial seizures. Magnetic resonance imaging (MRI) of the brain revealed lesions in the putamen and caudate nucleus. Infection and antibody screening were negative. The seizures were refractory to conventional antiepileptics. The patient responded to intravenous immunoglobulin (IVIG) therapy.

Myopericarditis - A catastrophic complication of dengue fever.

Dengue is a mosquito-borne viral fever seen commonly in the urban areas of tropical and sub-tropical countries. The spectrum of this disease varies from a simple fever which can be managed with anti-pyretics to dengue shock syndrome, which requires urgent intensive care admission. Dengue shock syndrome can be a life-threatening condition. Dengue fever can progress to dengue shock and later to dengue shock syndrome if not managed with promptness. Apart from the spectrum of progression known to us, dengue fever can have a varied set of atypical presentations. These atypical presentations can be neurological, cardiac, or even gastro-intestinal. Cardiac complications, although rare, have been reported, such as various atrioventricular arrhythmias, myocarditis, pericarditis, and even myopericarditis. Here, we report a case of a 65-year-old male who presented to us with severe dyspnea and fever. Examination and investigations revealed dengue fever with myopericarditis.

Single-cell analysis of patient-derived PDAC organoids reveals cell state heterogeneity and a conserved developmental hierarchy.

Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer mortality by 2030. Bulk transcriptomic analyses have distinguished 'classical' from 'basal-like' tumors with more aggressive clinical behavior. We derive PDAC organoids from 18 primary tumors and two matched liver metastases, and show that 'classical' and 'basal-like' cells coexist in individual organoids. By single-cell transcriptome analysis of PDAC organoids and primary PDAC, we identify distinct tumor cell states shared across patients, including a cycling progenitor cell state and a differentiated secretory state. Cell states are connected by a differentiation hierarchy, with 'classical' cells concentrated at the endpoint. In an imaging-based drug screen, expression of 'classical' subtype genes correlates with better drug response. Our results thus uncover a functional hierarchy of PDAC cell states linked to transcriptional tumor subtypes, and support the use of PDAC organoids as a clinically relevant model for in vitro studies of tumor heterogeneity.

Atrial Tachycardia Masquerading As Inappropriate Sinus Tachycardia (IST) After COVID-19 Infection: A Matter of Concern?

COVID-19 Infection has wrecked havoc all over the world; the spectrum of this disease ranges from asymptomatic mild cases to severe cases such as acute respiratory distress syndrome (ARDS). Not only the acute infection but post COVID sequelae are also a cause of concern. Post-COVID states or Long COVID are the sequences of complications following the active infection. As post COVID sequelae are unpredictable it is absolutely the need of the hour to educate physicians and make them aware of all possibilities. We report one such case of a post COVID recovered young lady, who presented with drug-refractory recurrent palpitations. She was initially suspected to have inappropriate sinus tachycardia. But electrophysiological study confirmed the diagnosis of atrial tachycardia which was successfully ablated. The patient now has completed six months of follow-up and is off any medication.

Lack of evidence for a role of genetic variation in TMEM230 in the risk for Parkinson's disease in the Caucasian population.

Mutations in TMEM230 have recently been associated to Parkinson's disease (PD). To further understand the role of this gene in the Caucasian population, we interrogated our large repository of next generation sequencing data from unrelated PD cases and controls, as well as multiplex families with autosomal dominant PD. We identified 2 heterozygous missense variants in 2 unrelated PD cases and not in our control database (p.Y106H and p.I162V), and a heterozygous missense variant in 2 PD cases from the same family (p.A163T). However, data presented herein is not sufficient to support the role of any of these variants in PD pathology. A series of unified sequence kernel association tests also failed to show a cumulative effect of rare variation in this gene on the risk of PD in the general Caucasian population. Further evaluation of genetic data from different populations is needed to understand the genetic role of TMEM230 in PD etiology.

PLA2G6 Mutations Related to Distinct Phenotypes: A New Case with Early-onset Parkinsonism.

BACKGROUND: PLA2G6-associated neurodegeneration (PLAN) is a recessive neurodegenerative disorder characterized by three distinct phenotypes: infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (atypical NAD), and PLA2G6-related dystonia-parkinsonism. METHODS: A consanguineous index case from Turkey was diagnosed with early-onset Parkinsonism at the Istanbul Faculty of Medicine. She and her unaffected brother were subjected to whole-genome sequencing. RESULTS: In this report, we describe a 33-year-old index case with parental consanguinity and early-onset Parkinsonism. Whole-genome sequencing of this individual revealed that a homozygous p.R747W mutation in PLA2G6 segregates with the disease in this family. DISCUSSION: This result supports the importance of prioritizing this gene in mutational analysis of autosomal recessive Parkinsonism, and confirms the clinical heterogeneity of PLAN.

A novel homozygous DJ1 mutation causes parkinsonism and ALS in a Turkish family.

OBJECTIVE: DJ1 mutations (PARK7) are among the monogenic causes of early-onset autosomal recessive parkinsonism. Here, we report clinical and genetic findings in a family with Turkish origin carrying a new DJ1 mutation and presenting with early-onset levodopa responsive parkinsonism and signs of amyotrophic lateral sclerosis (ALS). METHODS: The family consisted of 12 members including 10 offsprings of whom three were affected. All family members underwent detailed clinical examination. DNA samples from the index case, his unaffected sister, and his parents were subjected to whole genome sequencing analysis. RESULTS: The index case 38-year-old man developed left hand tremor at the age of 24 years. He had progressive asymmetrical parkinsonism, depression and developed signs of ALS within 4 years. His two affected sisters had young-onset asymmetrical tremor-dominant parkinsonism with signs of ALS. A new homozygous p.Q45X mutation in exon 3 in DJ1 was found in all three patients. Their unaffected parents and one clinically healthy sibling were found to be heterozygous for this mutation. CONCLUSIONS: This is the second report of DJ1 mutations associated with parkinsonism and ALS. This is relevant for genetic counseling as well as for understanding the pathogenesis of the broad spectrum of parkinsonism-ALS disease complex.

MicroRNAs distinguish cytogenetic subgroups in pediatric AML and contribute to complex regulatory networks in AML-relevant pathways.

BACKGROUND: The role of microRNAs (miRNAs), important post-transcriptional regulators, in the pathogenesis of acute myeloid leukemia (AML) is just emerging and has been mainly studied in adults. First studies in children investigate single selected miRNAs, however, a comprehensive overview of miRNA expression and function in children and young adults is missing so far. METHODOLOGY/PRINCIPAL FINDINGS: We here globally identified differentially expressed miRNAs between AML subtypes in a survey of 102 children and adolescent. Pediatric samples with core-binding factor AML and promyelocytic leukemia could be distinguished from each other and from MLL-rearranged AML subtypes by differentially expressed miRNAs including miR-126, -146a, -181a/b, -100, and miR-125b. Subsequently, we established a newly devised immunoprecipitation assay followed by rapid microarray detection for the isolation of Argonaute proteins, the hallmark of miRNA targeting complexes, from cell line models resembling core-binding factor and promyelocytic leukemia. Applying this method, we were able to identify Ago-associated miRNAs and their targeted mRNAs. CONCLUSIONS/SIGNIFICANCE: miRNAs as well as their mRNA-targets showed binding preferences for the different Argonaute proteins in a cell context-dependent manner. Bioinformatically-derived pathway analysis suggested a concerted action of all four Argonaute complexes in the regulation of AML-relevant pathways. For the first time, to our knowledge, a complete AML data set resulting from carefully devised biochemical isolation experiments and analysis of Ago-associated miRNAs and their target-mRNAs is now available.