Characteristics of Fatal Cases of Pandemic Influenza A (H1N1) from September 2009 to January 2010 in Saurashtra Region, India

Background: India reported first case of 2009 pandemic influenza A (H1N1) virus infection in May, 2009 and Saurashtra region in August, 2009. We describe the characteristics of fatal cases of 2009 influenza A (H1N1) infection reported in Saurashtra region. Methods: From September, 2009 to January, 2010, we observed 71 fatal cases that were infected with 2009 influenza A (H1N1) virus and admitted in different hospitals in Rajkot city. Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm infection; the clinico-epidemiological features were observed and documented. Results: Median age of the deceased (71) was 29 years, and 57.7% were females. Median time observed was 5 days from onset of illness to diagnosis of influenza A (H1N1), and 57.7% were referred from general practitioner (OR=0.42, CI=0.24-0.74). Median hospital stay reported was 3 days. All admitted patients received oseltamivir, but only 16.9% received it within 2 days of onset of illness. The most common symptoms were cough (97.2%), fever (93%), sore throat and shortness of breath. Co-morbid conditions were present in almost half of the patients who ultimately died, the most common of which was pregnancy (OR=0.15, CI=0.04-0.52). Radiological pneumonia was reported in 98% patients. Conclusion: Residing in urban area, delayed referral from general practitioner, presence of co-existing condition, especially pregnancy was responsible for mortality among influenza A (H1N1) infected positive

Concordance of Cross-Sectional Imaging and Adrenal Venous Sampling Results for Patients with Surgically Treated Primary Hyperaldosteronism​

Background Adrenal venous sampling (AVS) is used to distinguish unilateral from bilateral aldosterone hypersecretion as a cause of primary hyperaldosteronism (PHA). This distinction is critical because unilateral disease is treated, and often cured, by adrenalectomy, whereas bilateral hypersecretion should be managed medically. Methods We performed a retrospective cohort review of adult patients undergoing index adrenalectomy for PHA at the University of Nebraska Medical Center from July of 2013 to June of 2022. Clinical and pathologic variables were assessed including patient age at surgery, sex, race or ethnicity, body mass index, systolic and diastolic blood pressure, number and type of antihypertensive medications pre- and post-operatively, potassium level and supplementation, PAC, PRA, ARR, imaging findings, adrenal venous sampling results and concordance of imaging findings with AVS and surgical outcomes. Statistical analysis was performed with Mann Whitney U and chi-squared Fisher’s exact using STATA version 17. Results In our cohort, 21 patients were identified who underwent adrenalectomy for primary hyperaldosteronism. Of these, 2 patients did not have any imaging findings and 19 were image localized. For patients with image localization AVS was concordant in 9, discordant in 4, and nondiagnostic in 6. For both patients without image localization the AVS was lateralizing. The overall discordance between imaging results and AVS was 40%. The only significant difference between patients with concordant and discordant results was the aldosterone level with concordant patients having a mean of 58ng/dL compared with discordant patients 23ng/dL (p = 0.0022). There was a significant reduction in antihypertensive medications in the entire cohort from a mean of 3.2 medications to 1.2 medications (p \u3c 0.001). Conclusions and Future Directions In this cohort, 40% of patients with selective AVS had discordant imaging and AVS results. Preoperative plasma aldosterone concentration was positively associated with concordance, with higher PAC more likely to have imaging and AVS concordance. Overall, hypertension was significantly improved following adrenalectomy for PHA with a median decrease of 2 antihypertensives. Our results support the recommendation to perform AVS on all candidates for adrenalectomy for PHA. Further study is warranted to identify factors associated with discordance.https://digitalcommons.unmc.edu/surp2022/1008/thumbnail.jp

UTILIZATION OF UNSERVICEABLE STRAWBERRIES FOR PRODUCTION OF ELLAGIC ACID AND ITS ENHANCEMENT BY ASPERGILLUS NIGER

Objective: Use of Aspergillus Niger (616) for the fabrication of ellagic acid from unserviceable strawberry as a substrate which is readily and chiefly available from Agro-industries and farm waste.Methods: The ellagic acid content was determined by HPLC method which shows a higher concentration of ellagic acid (143.085+1.669 ppm) after fermentation of 96 h at 35 °C. DPPH assay was carried out for antioxidant activity of ellagic acid.Results: Results designated that ellagic acid has higher antioxidant activity as compared with ascorbic acid.Conclusion: Existing study exposes that this agro waste and farm waste can be used at commercially for the production of ellagic acid which has enormous medicinal properties.Keywords: Ellagic acid, Raw strawberry, DPPH assay, Aspergillus Niger, Fermentation, and HPL

SARS-COV-ATE risk assessment model for arterial thromboembolism in COVID-19

Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications conferring an extremely poor prognosis. COVID-19 infection is known to be an independent risk factor for acute ischemic stroke and myocardial infarction (MI). We developed a risk assessment model (RAM) to stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). This multicenter, retrospective study included adult COVID-19 patients admitted between 3/1/2020 and 9/5/2021. Among 3531 patients from the training cohort, 15.5% developed acute in-hospital ATE, including stroke, MI, and other ATE, compared to 13.4% in the validation cohort. The 16-item final score was named SARS-COV-ATE (Sex: male = 1, Age [40-59 = 2, \u3e 60 = 4], Race: non-African American = 1, Smoking = 1 and Systolic blood pressure elevation = 1, Creatinine elevation = 1; Over the range: leukocytes/lactate dehydrogenase/interleukin-6, B-type natriuretic peptide = 1, Vascular disease (cardiovascular/cerebrovascular = 1), Aspartate aminotransferase = 1, Troponin-I [\u3e 0.04 ng/mL = 1, troponin-I \u3e 0.09 ng/mL = 3], Electrolytes derangement [magnesium/potassium = 1]). RAM had a good discrimination (training AUC 0.777, 0.756-0.797; validation AUC 0.766, 0.741-0.790). The validation cohort was stratified as low-risk (score 0-8), intermediate-risk (score 9-13), and high-risk groups (score ≥ 14), with the incidence of ATE 2.4%, 12.8%, and 33.8%, respectively. Our novel prediction model based on 16 standardized, commonly available parameters showed good performance in identifying COVID-19 patients at risk for ATE on admission

Data of atrial arrhythmias in hospitalized COVID-19 and influenza patients

Atrial arrhythmias (AA) are common in hospitalized COVID-19 patients with limited data on their association with COVID-19 infection, clinical and imaging outcomes. In the related research article using retrospective research data from one quaternary care and five community hospitals, patients aged 18 years and above with positive SARS-CoV-2 polymerase chain reaction test were included. 6927 patients met the inclusion criteria. The data in this article provides demographics, home medications, in-hospital events and COVID-19 treatments, multivariable generalized linear regression regression models using a log link with a Poisson distribution (multi-parameter regression [MPR]) to determine predictors of new-onset AA and mortality in COVID-19 patients, computerized tomography chest scan findings, echocardiographic findings, and International Classification of Diseases-Tenth Revision codes. The clinical outcomes were compared to a propensity-matched cohort of influenza patients. For influenza, data is reported on baseline demographics, comorbid conditions, and in-hospital events. Generalized linear regression models were built for COVID-19 patients using demographic characteristics, comorbid conditions, and presenting labs which were significantly different between the groups, and hypoxia in the emergency room. Statistical analysis was performed using R programming language (version 4, ggplot2 package). Multivariable generalized linear regression model showed that, relative to normal sinus rhythm, history of AA (adjusted relative risk [RR]: 1.38; 95% CI: 1.11-1.71; p = 0.003) and newly-detected AA (adjusted RR: 2.02 95% CI: 1.68-2.43; p \u3c 0.001) were independently associated with higher in-hospital mortality. Age in increments of 10 years, male sex, White race, prior history of coronary artery disease, congestive heart failure, end-stage renal disease, presenting leukocytosis, hypermagnesemia, and hypomagnesemia were found to be independent predictors of new-onset AA in the MPR model. The dataset reported is related to the research article entitled Incidence, Mortality, and Imaging Outcomes of Atrial Arrhythmias in COVID-19 [Jehangir et al. Incidence, Mortality, and Imaging Outcomes of Atrial Arrhythmias in COVID-19, American Journal of Cardiology] [1]

RISK FACTORS OF ARTERIAL THROMBOEMBOLISM IN HOSPITALIZED COVID-19 PATIENTS: A MULTICENTER COHORT STUDY

Background: Endothelial cell dysfunction from infection by SARS-CoV-2 and inflammatory cytokines leading to hyperinflammatory and hypercoagulable state is thought to be the mechanism of arterial thromboembolism (ATE) in COVID-19 patients. COVID-19 infection is known to be an independent risk factor for acute stroke and myocardial infarction (MI). However, data on the risk factors of ATE in hospitalized COVID-19 patients is limited. Methods: This retrospective, multicenter cohort study included adult patients admitted to one quaternary care and three community hospitals with PCR-proven SARS-CoV-2 infection between 3/1/2020 and 12/31/2020. The composite outcome was in-hospital ATE events, including acute ischemic stroke, MI, and other ATE identified by ICD-10 codes. Student t-test was conducted for continuous variables and the Chi-square test for categorical variables. Multivariate logistic regression using forward selection was conducted. All statistical tests were 2-sided with an α level of 0.05. All data was analyzed using R version 4.0.4. Results: The cohort included 3531 patients with 371 (10.5%) patients who developed acute ATE. There were 398 ATE events: 270 patients had MI, 43 had stroke, 85 had other ATE, 12 had MI + stroke, 13 had MI + other ATE, and 2 had stroke + other ATE. The model suggested that initial systolic blood pressure (BP) \u3c90 mmHg and \u3e160 mmHg; elevated initial biomarkers including B-type natriuretic peptide (\u3e100 pg/mL), troponin-I (\u3e0.03 ng/mL), lactate dehydrogenase (\u3e192 U/L), creatine phosphokinase (male \u3e280 U/L and female \u3e155 U/L), C-reactive protein (\u3e0.5 mg/dL), leukocytes (\u3e11 K/uL), lactate (\u3e2.2 mmol/L), and aspartate aminotransferase (\u3e41 U/L); presenting hypoalbuminemia (\u3c3.5 g/dL) and hypomagnesemia (\u3c1.8 mg/dL); age \u3e60; male sex; and history of cerebrovascular accident (CVA), coronary artery disease (CAD), hyperthyroidism, and cigarette smoking were associated with an increased risk of ATE (all p\u3c0.05). Conclusion: Hypo or hypertension on admission, elevated inflammatory and cardiac markers, hypoalbuminemia, hypomagnesemia, smoking, and comorbidities including CAD and CVA are associated with ATE in hospitalized COVID-19 patients

Venous thromboembolism in COVID-19 patients and prediction model: a multicenter cohort study

BACKGROUND: Patients with COVID-19 infection are commonly reported to have an increased risk of venous thrombosis. The choice of anti-thrombotic agents and doses are currently being studied in randomized controlled trials and retrospective studies. There exists a need for individualized risk stratification of venous thromboembolism (VTE) to assist clinicians in decision-making on anticoagulation. We sought to identify the risk factors of VTE in COVID-19 patients, which could help physicians in the prevention, early identification, and management of VTE in hospitalized COVID-19 patients and improve clinical outcomes in these patients. METHOD: This is a multicenter, retrospective database of four main health systems in Southeast Michigan, United States. We compiled comprehensive data for adult COVID-19 patients who were admitted between 1st March 2020 and 31st December 2020. Four models, including the random forest, multiple logistic regression, multilinear regression, and decision trees, were built on the primary outcome of in-hospital acute deep vein thrombosis (DVT) and pulmonary embolism (PE) and tested for performance. The study also reported hospital length of stay (LOS) and intensive care unit (ICU) LOS in the VTE and the non-VTE patients. Four models were assessed using the area under the receiver operating characteristic curve and confusion matrix. RESULTS: The cohort included 3531 admissions, 3526 had discharge diagnoses, and 6.68% of patients developed acute VTE (N = 236). VTE group had a longer hospital and ICU LOS than the non-VTE group (hospital LOS 12.2 days vs. 8.8 days, p \u3c 0.001; ICU LOS 3.8 days vs. 1.9 days, p \u3c 0.001). 9.8% of patients in the VTE group required more advanced oxygen support, compared to 2.7% of patients in the non-VTE group (p \u3c 0.001). Among all four models, the random forest model had the best performance. The model suggested that blood pressure, electrolytes, renal function, hepatic enzymes, and inflammatory markers were predictors for in-hospital VTE in COVID-19 patients. CONCLUSIONS: Patients with COVID-19 have a high risk for VTE, and patients who developed VTE had a prolonged hospital and ICU stay. This random forest prediction model for VTE in COVID-19 patients identifies predictors which could aid physicians in making a clinical judgment on empirical dosages of anticoagulation

Miscellaneous Rheumatic Diseases [73-83]: 73. Is There a Delay in Specialist Referral of Hot Swollen Joint?

Background: Patients with acute, hot, swollen joints commonly present to general practitioners, emergency departments and/or acute admitting teams rather than directly to rheumatology. It is imperative to consider septic arthritis in the differential diagnosis of these patients. The British Society of Rheumatology (BSR) has produced guidelines for the management of this condition, which include recommendations for early specialist referral and joint aspiration of all patients with suspected septic arthritis. We examined whether the initial management of patients with acute hot swollen joint(s) at University College London Hospital (UCLH) follows BSR guidelines. Methods: For the period Feb to Nov 2009, appropriate patients were identified by searching the UCLH database using the diagnostic terms, "pyogenic arthritis”, "septic arthritis” and "gout”; and from all joint aspirate requests sent to microbiology. Medical notes were obtained and any patients who had elective arthroscopies or chronic (> 6 weeks) symptoms were excluded. Data were collected on the time taken from the onset of symptoms to specialist (orthopaedic/rheumatology) referral and joint aspiration, collection of blood cultures and antibiotic treatment with or without microbiology advice. Results: Twenty patients were identified with hot swollen (18 monoarticular, 3 prosthetic) joint(s) of < 2 weeks duration. Of whom, 3/20 (15%) were admitted directly to rheumatology, 7/20 (35%) to the acute admissions unit, 3/20 (15%) to orthopaedic, 4/20 (20%) to a medical team and 1/20 (5%) to general surgery. In 19 (95%) cases, specialist (rheumatology/orthopaedic) advice was sought. Of 14 cases not seen directly by specialists 9 (64%) were referred at 24-48 h and 5 (36%) at 48-192 h. All 20 patients had joint aspiration. In 9/20 (45%) of cases, joint aspiration was performed in less than 6 h, 3/20 (15%) cases at 6-24h and 6/20 (30%) cases at 24-192 h and was not recorded in two patients. Of these, crystals were identified in two and one was culture positive. Blood cultures were received for only 6/20 (30%) of cases and only clearly documented to have been taken prior to antibiotic therapy and none were positive. Of 14/20 (70%) started on antibiotic treatment empirically, only 6 (42%) were preceded by joint aspiration. In the 6 patients not treated with antibiotics due to low index of suspicion of septic arthritis, synovial fluid and blood cultures were negative. Microbiology advice was sought in 10/20 (50%) of cases by the admitting teams but the timing of this advice is unclear. Conclusions: Despite the provision of 24 h rheumatology and orthopaedic cover at UCLH, we found a significant delay in acute medical firms seeking specialist advice on the management of patients with acute, hot swollen joints with subsequent deviation from BSR guidelines. Consequently, we plan to increase awareness of these guidelines amongst medical firms at UCLH. Disclosure statement: All authors have declared no conflicts of interes

HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes