Valvular heart disease in Antiphospholipid antibody syndrome: Isolated Tricuspid stenosis

Antiphospholipid antibody syndrome (APLS) is a rare disorder characterized by a hypercoagulable state. Manifestations include arterial or venous thrombosis, recurrent fetal wastage, coronary artery disease, valvular heart disease, dilated cardiomyopathy, pulmonary artery hypertension, and intracardiac thrombus. Most commonly mitral valve is affected followed by aortic and then tricuspid valve. In this report, a rare case of spontaneous aortic thrombosis with tricuspid stenosis uncomplicated by other valve lesions is presented with clinical and echocardiographic studies and computed tomographic images.     

Heparin in haemorrhagic infarction in cerebral venous sinus thrombosis

Morbidity and mortality in puerperal cerebral venous thrombosis (CVT) can be reduced by arresting the progression of thrombosis using heparin. However, conventional dose of heparin requires monitoring of coagulation parameters and carries a risk of haemorrhage. The present study involved 56 patients of puerperal CVT with CT evidence of haemorrhagic infarction. Twenty nine of these patients received low dose heparin till 30th post-partum day or symptomatic relief. Their clinical features and severity were similar to 27 patients who did not receive heparin. The mortality and morbidity at discharge was significantly less (P < 0.001) in heparin treated group. There were no haemorrhagic complications. Low dose heparin is safe and effective in cerebral venous thrombosis, even with haemorrhagic infarction.     

Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors.

The diagnosis of thyroid tumors is critical for clinical management; however, tumors with follicular architecture often present problems. We evaluated the diagnostic use of the protein expression of four genes that were found to be upregulated in papillary thyroid carcinoma compared to normal thyroid (LGALS3, FN1, CITED1 and KRT19), and of the mesothelial cell surface protein recognized by monoclonal antibody HBME1 in thyroid tumors. Tissues from 85 carcinomas (67 papillary, six follicular, eight Hürthle cell and four anaplastic) and 21 adenomas were evaluated by immunohistochemistry for the expression of these gene protein products, for example, galectin-3 (GAL3), fibronectin-1 (FN1), CITED1, cytokeratin-19 (CK19) and HBME1. Non-neoplastic thyroids (29 adenomatous and 14 thyrotoxic hyperplasia, and 59 normal) were also studied. The expression of all five proteins was significantly associated with malignancy, and highly specific (> or = 90%) for carcinoma compared to adenoma. GAL3, FN1 and/or HBME1 expression was seen in 100% of carcinomas (85/85) and in 24% of adenomas (5/21). Coexpression of multiple proteins was seen in 95% of carcinomas and only 5% of adenomas (P<0.0001). Coexpression of FN1 and GAL3 (FN1+ GAL3+, 70/85) or FN1 and HBME1 (FN1+ HBME1+, 53/85) was restricted to carcinomas, while their concurrent absence (FN1- GAL3- or FN1- HBME1-, 18/21 adenoma) was highly specific (96%) for benign lesions. Among non-neoplastic thyroids, adenomatous hyperplasia frequently expressed GAL3 (n=16), CK19 (n=9) and CITED1 (n=7), but the expression was predominantly focal in contrast to the diffuse expression in carcinomas. An immunohistochemical panel consisting of GAL3, FN1 and HBME1 may be useful in the diagnosis of follicular cell-derived thyroid tumors.     

Thirty-day mortality of patients with hip fracture during COVID-19 pandemic and pre-pandemic periods: A systematic review and meta-analysis

BACKGROUNDTimely intervention in hip fracture is essential to decrease the risks of perioperative morbidity and mortality. However, limitations of the resources, risk of disease transmission and redirection of medical attention to a more severe infective health problem during coronavirus disease 2019 (COVID-19) pandemic period have affected the quality of care even in a surgical emergency.AIMTo compare the 30-d mortality rate and complications of hip fracture patients treated during COVID-19 pandemic and pre-pandemic times.METHODSThe search of electronic databases on 1^st August 2020 revealed 45 studies related to mortality of hip fracture during the COVID-19 pandemic and pre-pandemic times. After careful screening, eight studies were eligible for quantitative and qualitative analysis of data.RESULTSThe pooled data of eight studies (n = 1586) revealed no significant difference in 30-d mortality rate between the hip fracture patients treated during the pandemic and pre-pandemic periods [9.63% vs 6.33%; odds ratio (OR), 0.62; 95%CI, 0.33, 1.17; P = 0.14]. Even the 30-d mortality rate was not different between COVID-19 non-infected patients who were treated during the pandemic time, and all hip fracture patients treated during the pre-pandemic period (OR, 1.03; 95%CI, 0.61, 1.75; P = 0.91). A significant difference in mortality rate was observed between COVID-19 positive and COVID-19 negative patients (OR, 6.99; 95%CI, 3.45, 14.16; P < 0.00001). There was no difference in the duration of hospital stay (OR, -1.52, 95%CI, -3.85, 0.81; P = 0.20), overall complications (OR, 1.62; P = 0.15) and incidence of pulmonary complications (OR, 1.46; P = 0.38) in these two-time frames. Nevertheless, the preoperative morbidity was more severe, and there was less use of general anesthesia during the pandemic time.CONCLUSIONThere was no difference in 30-d mortality rate between hip fracture patients treated during the pandemic and pre-pandemic periods. However, the mortality risk was higher in COVID-19 positive patients compared to COVID-19 negative patients. There was no difference in time to surgery, complications and hospitalization time between these two time periods.     

Catecholamine modulatory effects of nepicastat (RS-25560-197), a novel,potent and selective inhibitor of dopamine-β-hydroxylase

1. Inhibitory modulation of sympathetic nerve function may have a favourable impact on the progression of congestive heart failure. Nepicastat is a novel inhibitor of dopamine-β-hydroxylase, the enzyme which catalyses the conversion of dopamine to noradrenaline in sympathetic nerves. The in vitro pharmacology and in vivo catecholamine modulatory effects of nepicastat were investigated in the present study.
2. Nepicastat produced concentration-dependent inhibition of bovine (IC₅₀=8.5±0.8 nM) and human (IC₅₀=9.0±0.8  nM)dopamine-β-hydroxylase. The corresponding R-enantiomer (RS-25560-198) was approximately 2–3 fold less potent than nepicastat. Nepicastat had negligible affinity (>10 μM) for twelve other enzymes and thirteen neurotransmitter receptors.
3. Administration of nepicastat to spontaneously hypertensive rats (SHRs) (three consecutive doses of either 3, 10, 30 or 100 mg kg⁻¹, p.o.; 12 h apart) or beagle dogs (0.05, 0.5, 1.5 or 5 mg kg⁻¹, p.o.; b.i.d., for 5 days) produced dose-dependent decreases in noradrenaline content, increases in dopamine content and increases in dopamine/noradrenaline ratio in the artery (mesenteric or renal), left ventricle and cerebral cortex. At the highest dose studied, the decreases in tissue noradrenaline were 47%, 35% and 42% (in SHRs) and 88%, 91% and 96% (in dogs) in the artery, left ventricle and cerebral cortex, respectively. When tested at 30 mg kg⁻¹, p.o., in SHRs, nepicastat produced significantly greater changes in noradrenaline and dopamine content, as compared to the R-enantiomer (RS-25560-198), in the mesenteric artery and left ventricle.
4. Administration of nepicastat (2 mg kg⁻¹, b.i.d, p.o.) to beagle dogs for 15 days produced significant decreases in plasma concentrations of noradrenaline and increases in plasma concentrations of dopamine and dopamine/noradrenaline ratio. The peak reduction (52%) in plasma concentration of noradrenaline and the peak increase (646%) in plasma concentration of dopamine were observed on day-6 and day-7 of dosing, respectively.
5. The findings of this study suggest that nepicastat is a potent, selective and orally active inhibitor of dopamine-β-hydroxylase which produces gradual modulation of the sympathetic nervous system by inhibiting the biosynthesis of noradrenaline. This drug may, therefore, be of value in the treatment of cardiovascular disorders associated with over-activation of the sympathetic nervous system, such as congestive heart failure.

     

Forced swimming stress induced alterations in ingestive behavior in rats.

The effects of forced swimming stress (15 minutes per day) on body weight, food intake, blood sugar, water intake, and urine output were studied in adult male Wistar rats on the first, seventh, fourteenth and 21st days in different subgroups. There was a significant initial decrease in the body weight up to 14 days followed by a regain in the body weight, which was sustained until 21 days. Though there was no change in the food intake initially for 7 days, after 14 days a significant increase in the food intake was observed. A significant hypoglycemia was observed throughout the entire period of stress. More significant fall in the blood sugar level was observed in the initial period of exposure of stress (1-7 days). There was a significant reduction in the water intake in the stressed animals. Urine output decreased significantly up to 7 days of stress, though it got marginally increased later. Thus, repeated stress may produce a reduction in body weight only initially, which is accompanied with an initial decrease in food and water intake also. The peak response to stress was seen after 7 days of stress exposure. There was a gradual recovery back to normal in the body weight, food intake, and water intake and urine output when stress period was prolonged to 14-21 days. This is suggestive of the adaptation of the organism to repeated exposure of similar kind of stress.     

Linear Stability Analysis and Gas Kinetic Scheme (GKS) Simulations of Instabilities in Compressible Plane Poiseuille Flow

The fundamental nature of flow instability in wall bounded flows changes with Mach number. The objectives of this study are two-fold, (i) compute the instability modes in high Mach number Poiseuille flows using linear stability analysis (LSA) and, (ii) perform direct numerical simulations (DNS) of the instability development using a solver based on gas kinetic method (GKM) for the purpose of code validation by comparison against LSA results. The LSA and DNS are performed for the case of Poiseuille flow over a range of Mach numbers – from moderately supersonic to hypersonic speeds. First, LSA is employed to identify the most unstable mode over the range of Mach numbers. We then perform two sets of GKM-DNS to corroborate the LSA results over the Mach number range. In the first set of simulations, the background field is initially perturbed with the most unstable mode identified by LSA and the evolution is monitored. It is shown that GKM-DNS accurately captures the exponential growth in kinetic energy for all Mach numbers. The second set of GKM-DNS simulations is performed by superposing the background pressure field with random initial perturbations. After an initial transient period, the modes predicted by LSA dominate the DNS flow field evolution. The wave-vector and mode shapes of the dominant instability are well replicated by GKM-DNS at each Mach number. These insights in the linear regime of high speed Poiseuille flow and validation of GKM are important for understanding and simulating wall bounded flows.     

Prosthetic mitral valve thrombosis,malfunction, and paroxysmal mitral regurgitation

Intermittent dysfunction of mechanical mitral valve prosthesis is an uncommon condition. It carries serious clinical implications if unrecognized. Here, we present a case of a 28‐year‐old female with a history of rheumatic multivalvular disease, for which she had undergone double valve replacement and tricuspid annuloplasty. Six months later, she presented with heart failure. Clinical examination revealed intermittent loss of closing clicks followed by a pansystolic murmur at the apex, suggestive of mitral prosthetic valve dysfunction. We highlight the echocardiographic findings of paroxysmal mitral valvular regurgitation secondary to prosthetic valve malfunction secondary to prosthetic valve thrombosis.