Validation of the 2022 American College of Rheumatology/EULAR classification criteria for Takayasu arteritis.

OBJECTIVES: The present study validates the 2022 ACR/European Alliance of Associations for Rheumatology (EULAR) classification criteria for Takayasu's arteritis (TAK), compared with the 1990 ACR TAK classification criteria. METHODS: The fulfilment of 2022 ACR/EULAR and 1990 ACR TAK criteria from four referral centres was assessed for TAK compared with extracranial giant cell arteritis (EC-GCA) and other controls. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio of a positive test (LR+) or negative test (LR-), and area under receiver operating characteristics curve (AUC) were calculated. RESULTS: Among 504 patients with TAK (404 females) and 222 controls (151 females, 144 patients with EC-GCA), the 2022 ACR/EULAR criteria had better sensitivity (95.83% vs 82.94%) and NPV, but poorer specificity (63.51% vs 90.54%), PPV, LR+, LR- and AUC at the pre-determined cut-offs than the 1990 ACR criteria. The 2022 ACR/EULAR criteria had greater specificity (76.06% vs 57.62%) and AUC (0.845 vs 0.771), with similar sensitivity (93% vs 96.53%) in males as in females. The 2022 ACR/EULAR criteria performed similarly with only EC-GCA as controls (sensitivity 95.83%, specificity 60.42%, AUC 0.781). Sensitivity remained similar, whereas specificity was higher for 40-60 years vs <40 years. Cut-offs of ≥6 (sensitivity 91.87%, specificity 82.88%) and ≥7 (sensitivity 86.71%, specificity 86.49%), or removing the point for female sex (sensitivity 92.64%, specificity 81.08%) greatly improved the balance between sensitivity and specificity. CONCLUSION: The poor specificity of the 2022 ACR/EULAR TAK criteria in real-life settings was improved by increasing the cut-off to 6 or 7, or removing the point for female sex.

Stroke Characteristics as Predictors of New-onset Seizure in Patients with Acute Ischemic Stroke.

INTRODUCTION: The current guidelines on diagnosis and management of new-onset seizures in stroke are not well defined, especially in the Indian setting. Our study aims at providing insight into the hospital prevalence risk of new-onset seizures following ischemic stroke and to correlate seizure risk with the characteristics of stroke and other clinical parameters. METHODS: A total of 127 patients were analyzed for the study where we assessed the clinical severity and the imaging severity of stroke using the National Institute of Health Stroke Scale (NIHSS) score and Alberta Stroke Program Early CT (ASPECT) score, respectively. Seizure-related variables including semiology, timing, and details of antiepileptic drugs (AEDs) were assessed under the domain of early and late poststroke seizures (PSSs). All patients were followed for 6 months for the seizure recurrence and change in Barthel index. In statistical analysis, quantitative variables were compared using the independent t-test/Mann-Whitney U test, and qualitative variables were correlated using Chi-square test/Fisher's exact test. Univariate and multivariate logistic regression was used to find out the significant risk factors of acute symptomatic seizure. RESULTS: The mean age of the study population was 59.72 years (±14.77), with a male predominance (60.63%). About 78.74% of the cases had an NIHSS score more than or equal to 6.24% had posterior circulation strokes and the rest had anterior circulation strokes. A cortical location of infarct was observed in 62.2% of cases and a subcortical location in 61.4% of cases. The prevalence of early PSSs observed in our study was 10.6%. Of those, 80% had generalized seizures, 13.3% had focal seizures, and 6.67% had focal seizures with secondary generalizations. No patient in the study group had late-onset seizures. Total leukocyte count, serum protein levels, serum uric acid levels, and erythrocyte sedimentation rate (ESR) values were associated with early seizures (p<0.05). Patients with early seizures were found to have a longer hospital stay (8 vs 6 days with p<0.05). In the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) etiological classification, an acute stroke of undetermined etiology was found to have a significant association with the occurrence of early seizure in both univariate and multivariate analysis [p = 0.030; odds ratio (OR) 4.735 (1.160-22.576)]. There was no difference in change in the Barthel index among the two groups. CONCLUSION: There was no recurrence of seizures in those who defaulted for AED and one patient had a seizure even on AED. Prophylactic AEDs in stroke patients based on stroke characteristics could not be ascertained, but the sample size was small. Knowing the fact that antiepileptics cause sedation and increase the chance of aspiration, continuing AEDs in patients who develop acute symptomatic seizures should be judged judiciously.

Sclerosing mesenteritis as a cause of porto-mesenteric vascular obstruction.

A woman in her 20s presented with haematemesis, post-prandial abdominal pain, weight loss and anaemia. Imaging revealed a non-enhancing mass in the retroperitoneal space along the mesenteric plane, encasing the porto-mesenteric vasculature. Endoscopy showed oesophageal varices. She was diagnosed with sclerosing mesenteritis, causing extrinsic compression of the portal vein and superior mesenteric artery. She underwent endoscopic variceal ligation and received prednisolone and tamoxifen. After 3 months, her post-prandial pain improved, and she did not have further bleeding episodes.

Bilateral Optic Neuritis and Facial Palsy Following COVID-19 Infection.

Cases of optic neuritis have been reported following the novel coronavirus disease 2019 (COVID-19), with most being unilateral and associated with demyelinating illness. We report a case of a 22-year-old woman who presented with sudden onset painless diminution of vision in both eyes six weeks following COVID-19 infection. She also had a history of left lower motor neuron (LMN) facial palsy immediately following COVID-19 disease that recovered fully on steroids. Ocular examination and ancillary and laboratory investigations pointed to bilateral atypical optic neuritis. The patient responded well to the standard optic neuritis treatment protocol. We diagnosed her as a case of left LMN facial palsy and parainfectious bilateral optic neuritis following COVID-19. Parainfectious bilateral optic neuritis and facial nerve palsy associated with COVID-19 can occur following COVID-19 disease. Ours is the first case to report the occurrence of both in a patient.

Expanded dengue syndrome with small-medium-vessel vasculitis: A case report.

Expanded dengue syndrome (EDS) is a well-described entity in the literature (after 2009), with various new atypical presentations being identified each year. We report a case of 38-year-old man who presented to the emergency department with high-grade, intermittent fever for 7 days along with myalgia and headache. He had multiple painless palpable purpura over both lower limbs and breathlessness from the 4th day of fever. On admission, purpura progressed in the severity and dry impending gangrene of the toes of both feet developed. Blood cultures turned out to be sterile, and other infectious markers (malaria, scrub typhus, and chikungunya) were negative except for dengue serology (enzyme-linked immunosorbent assay-immunoglobulin M [ELISA-IgM]). Skin biopsy confirmed to be cutaneous small-vessel vasculitis. The respiratory distress was due to myocarditis (supported by raised NT-pro-BNP levels) and pulmonary edema. He also had possibly hemolytic anemia due to microangiopathy. Although there are many EDS cases of dengue myocarditis reported till date, dengue resulting in widespread endothelial activation and extensive vasculitis (small vessel due to purpura and medium vessel due to gangrene) is a rare phenomenon.

Immune-mediated Coombs negative intravascular haemolysis in systemic lupus erythematosus (SLE).

A 27-year-old woman presented with a history of excessive hair loss, loss of appetite, loss of weight, amenorrhoea and loss of axillary and pubic hair for 6 months followed by fever and vomiting for 5 months and abdominal pain for 1 month. During the course of her illness, the patient developed intravascular haemolysis as evidenced by a drop in haemoglobin, indirect hyperbilirubinaemia, raised lactate dehydrogenase (LDH) and haemoglobinuria. Examination revealed severe pallor, mild icterus, elevated jugular venous pressure, generalised lymphadenopathy and hyperpigmentation. Investigations revealed severe anaemia, indirect hyperbilirubinaemia, raised LDH and negative Coombs test. Antinuclear antibody and anti-dsDNA, anti-Sm and anti-SS-A/Ro antibodies were positive and complement C3 was low. The patient was diagnosed to have systemic lupus erythematosus and immune-mediated intravascular haemolysis and was treated with prednisolone and hydroxychloroquine. Haemolysis resolved following steroid therapy, and during follow-up, there were no further episodes of haemolysis.

Cocktail treatment of antibiotic, steroid, and analgesic in a tubercular case; the urgency to set up antimicrobial stewardship practices in the community.

Tuberculosis is a well-known entity in India with many implemented policies to ensure the cost-effective early management. Missed, delayed, and complicated presentations do occur, requiring expensive tertiary level of health care. Among many contributing factors, lack of antibiotic stewardship is at the top. We report a case of 65-year-old man who presented with on and off fever for six months, receiving cocktail treatments of antibiotics, analgesics, and steroids from a local dispensary. Our initial investigations revealed microcytic anemia with high erythrocyte sedimentation rate, leukocytosis, and bilateral pleural effusion on chest X-ray. Contrast enhanced computer tomography of chest and abdomen suggested disseminated tuberculosis including bilateral empyema. Frank pus was drained on thoracocentesis, which was negative for Gram stain, Ziehl-Neelsen stain, and bacterial culture, but positive CB-NAAT for tubercular bacilli with no resistance to rifampicin. Mantoux test and stool occult blood were positive. This case highlights an unusual presentation of tuberculosis and the ongoing lacunae in the society with importance to the primary care providers in the effective management of tuberculosis focusing on antimicrobial stewardship.

Clinical candidate and genistein analogue AXP107-11 has chemoenhancing functions in pancreatic adenocarcinoma through G protein-coupled estrogen receptor signaling.

Despite advances in cancer therapeutics, pancreatic cancer remains difficult to treat and often develops resistance to chemotherapies. We have evaluated a bioavailable genistein analogue, AXP107-11 which has completed phase Ib clinical trial, as an approach to sensitize tumor cells to chemotherapy. Using organotypic cultures of 14 patient-derived xenografts (PDX) of pancreatic ductal adenocarcinoma, we found that addition of AXP107-11 indeed sensitized 57% of cases to gemcitabine treatment. Results were validated using PDX models in vivo. Further, RNA-Seq from responsive and unresponsive tumors proposed a 41-gene treatment-predictive signature. Functional and molecular assays were performed in cell lines and demonstrated that the effect was synergistic. Transcriptome analysis indicated activation of G-protein-coupled estrogen receptor (GPER1) as the main underlying mechanism of action, which was corroborated using GPER1-selective agonists and antagonists. GPER1 expression in pancreatic tumors was indicative of survival, and our study proposes that activation of GPER1 may constitute a new avenue for pancreatic cancer therapeutics.