4D flow MRI left atrial kinetic energy in hypertrophic cardiomyopathy is associated with mitral regurgitation and left ventricular outflow tract obstruction

To noninvasively assess left atrial (LA) kinetic energy (KE) in hypertrophic cardiomyopathy (HCM) patients using 4D flow MRI and evaluate coupling associations with mitral regurgitation (MR) and left ventricular outflow tract (LVOT) obstruction. Twenty-nine retrospectively identified patients with HCM underwent 4D flow MRI. MRI-estimated peak LVOT pressure gradient (?P_MRI) was used to classify patients into non-obstructive and obstructive HCM. Time-resolved volumetric LA kinetic energy (KE_LA) was computed throughout systole. Average systolic (KE_LA-avg) and peak systolic (KE_LA-peak) KE_LA were compared between non-obstructive and obstructive HCM groups, and associations to MR severity and LVOT ?P_MRI were tested.The study included 15 patients with non-obstructive HCM (58.6 [45.9, 65.2] years, 7 females) and 14 patients with obstructive HCM (51.9 [47.6, 62.6] years, 6 females). Obstructive HCM patients demonstrated significantly elevated instantaneous KE_LA over all systolic time-points compared to non-obstructive HCM (P?<?0.05). Obstructive HCM patients also demonstrated higher KE_LA-avg (14.8 [10.6, 20.4] J/m³ vs. 33.4 [23.9, 61.3] J/m³, P?<?0.001) and KE_LA-peak (22.1 [15.9, 28.7] J/m³ vs. 57.2 [44.5, 121.4] J/m³, P?<?0.001) than non-obstructive HCM. MR severity was significantly correlated with KE_LA-avg (rho?=?0.81, P?<?0.001) and KE_LA-peak (rho?=?0.79, P?<?0.001). LVOT ?P_MRI was strongly correlated with KE_LA metrics in obstructive HCM (KE_LA-avg: rho?=?0.86, P?<?0.001; KE_LA-peak: rho?=?0.85, P?<?0.001).In HCM patients, left atrial kinetic energy, by 4D flow MRI, is associated with MR severity and the degree of LVOT obstruction.

     

Prevalence of coeliac disease in healthy blood donors: a study from north India

BackgroundBlood donor screening can help predict prevalence of coeliac disease in population.MethodsBetween December 2010 and June 2011, healthy blood donors were screened using anti-tissue glutaminase antibodies. Those positive underwent duodenoscopy. Their age, gender, body mass index and haemoglobin and histological changes were recorded.ResultsOf the 1610 blood donors screened, 1581 (98.2%) were males. The mean age of donors was 31.51 ± 9.66 years and the mean body mass index was 22.12 ± 4.24 kg/m². Nine (0.56%) men were seropositive. Endoscopic features included reduced fold height (9), scalloping (8), grooving (7) and mosaic mucosal pattern (3). Eight had Marsh IIIa changes whilst one had IIIb change. The prevalence of coeliac disease was 1:179 (0.56%, 95% confidence interval 1/366–1/91, 0.27–1.1%). None of the 9 patients had any symptoms. Their mean haemoglobin and body-mass index was similar to rest of the cohort.ConclusionThe prevalence of coeliac disease amongst apparently healthy blood donors was 1:179 (0.56%).     

Congenital thrombotic thrombocytopenic purpura: Upshaw–Schulman syndrome: a cause of neonatal death and review of literature

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder in children characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. The classic Moschcowitz Pentads of TTP include hemolytic anemia, with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decrease renal function and fever. We report a newborn who was diagnosed with congenital TTP. The newborn was admitted at age of 40 h, in our hospital, in view of respiratory distress with impending respiratory failure and red colored urine. On examination, the newborn was febrile, tachypneic, had deep icterus, pallor and no hepatosplenomegaly. Family history was significant with one unexplained neonatal death at age of 24 with symptoms of red colored urine. Examination of peripheral smear was diagnostic with the presence of fragmented RBCS, giant but fewer platelets consistent with a diagnosis of MAHA. The diagnosis of TTP was confirmed with low ADAMTS activity and gene analysis showed c 2203 G > T-p.Glu735X (domain TSP1-2) mutation in exon 18 of ADAMTS 13 gene. The newborn had rapid deterioration, with respiratory distress and refractory shock leading to death. Post-mortem bone marrow done showed marrow hyperplasia.     

Bacteriological profile and clinical predictors of ESBL neonatal sepsis

Study objective: Bacteriologic profile and risk factors for ESBL sepsis in newborns admitted to a Level III NICU.

Methods: This was a retrospective observational study that enrolled newborns admitted to NICU with perinatal risk factors or clinical signs of sepsis and positive blood culture from January 2013 to August 2014. Blood cultures were done by BACTEC and ESBL production was evaluated from double-disc synergy method. Maternal, perinatal and neonatal risk factors were recorded from the case records and computerized information base. Mothers received cephalosporins for PPROM but its use was restricted in newborns for both probable and culture-positive sepsis.

Results: Among the infants with sepsis 24% had early-onset sepsis. The incidence of ESBL of early-onset Gram-negative sepsis (EOGNS) was 44.7% (n?=?17 of 38) and it was 65% in late-onset Gram-negative sepsis (n?=?84 of 129). The predominant ESBL-producing microbe responsible for neonatal sepsis was Klebsiella sp. Among newborns with EOGNS, the risk factors for the production of ESBL were preterm PROM (p?=?0.004) and maternal exposure to antibiotics (p?=?0.05).

Conclusion: ESBL Gram-negative sepsis is a substantial problem in neonatal infections. Maternal exposure to cephalosporins and maternal PPROM are important risk factors for ESBL Gram-negative EOS.     

Post-operative morbidity results in decreased long-term survival after resection for hilar cholangiocarcinoma

Background

The purpose of the present study was to demonstrate that post-operative morbidity (PM) associated with resections of hilar cholangiocarcinoma (HCCA) is associated with short- and long-term patient survival.

Methods

Between 1998 and 2008, 51 patients with a median age of 64 years underwent resection for HCCA at a single institution. Associations between survival and clinicopathologic factors, including peri- and post-operative variables, were studied using univariate and multivariate models.

Results

Seventy-six per cent of patients underwent major hepatectomy with resection of the extrahepatic bile ducts. The 30- and 90-day operative mortality was 10% and 12%. The overall incidence of PM was 69%, with 68% of all PM as major (Clavien grades III–V). No difference in operative blood loss or peri-operative transfusion rates was observed for patients with major vs. minor or no PM. Patients with major PM received adjuvant chemotherapy less frequently than patients with minor or no complications 29% vs. 52%, P= 0.15. The 1-, 3- and 5-year overall (OS) and disease-specific survival (DSS) rates for all patients were 65%, 36%, 29% and 77%, 46%, 35%, respectively. Using univariate and multivariate analysis, margin status (27% R1), nodal metastasis (35% N1) and major PM were associated with OS and DSS, P < 0.01. Major PM was an independent factor associated with decreased OS and DSS [hazard ratio (HR) = 3.6 and 2.8, respectively, P < 0.05]. The median DSS for patients with major PM was 14 months compared with 40 months for patients who experienced minor or no PM, P < 0.01.

Conclusion

Extensive operations for HCCA can produce substantial post-operative morbidity. In addition to causing early mortality, major post-operative complications are associated with decreased long-term cancer-specific survival after resection of HCCA.     

Synthesis, characterization and pharmacological evaluation of (E)-N′-(substituted-benzylidene)isonicotinohydrazide derivatives as potent anticonvulsant agents

A series of (E)-N′-(substituted-benzylidene)isonicotinohydrazide derivatives were synthesized by coupling it with different substituted aldehydes, acetophenone, and benzophenones in presence of absolute ethanol along with catalytic amount of glacial acetic acid. All the synthesized compound were confirmed and characterized by using various spectral technique like IR, ¹H NMR, ¹³C NMR, and mass spectroscopy studies. Anticonvulsant evaluations of all the synthesized compounds were done using various seizures models like maximal electroshock-induced seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) at a dose of 30, 100, and 300?mg/kg body weight and anticonvulsant activity was noted at 0.5?h and 4?h time intervals after the drug administration. Compound 1a (E)-N′-2-benzylidene isonicotinohydrazide, 1g (E)-N′-2-ethoxybenzylidene isonicotinohydrazide, 1k (E)-N′-3-flourobenzylidene isonicotinohydrazide and 3a (E)-N′-diphenylmethylene isonicotinohydrazide showed protection in MES model, which indicates that these compounds have the ability to prevent the spread of seizure at 300?mg/kg dose and showed protection at 0.5?h duration. Compound 3a was also found to be active in scPTZ screen at a dose of 300?mg/kg. In neurotoxicity screen, all the synthesized compounds were found non-toxic except compounds 1n, 2a, and 3b. Further compounds 1a, 1g, 1k, and 3a were also evaluated in the minimal clonic seizure model and exhibited potent anticonvulsant activity with lower neurotoxicity. Among all synthesized derivatives, analogue 3a was found to exhibit protection in MES and scPTZ seizure models. This study proved that isonicotinoyl hydrazides synthesized by condensing isoniazid with various aldehydes and ketones displayed moderate to potent anticonvulsant activity.