Oral contraceptive pills induced hemichorea in an adolescent female with polycystic ovarian disease

Chorea is a neurological adverse effect of oral contraceptive pills (OCPs). The onset of chorea following OCPs usage varies widely from few weeks to several years. We report a rare case of chorea which developed within a week of starting OCPs in an adolescent girl with polycystic ovarian disease.KEY WORDS: Chorea, oral contraceptive pills, polycystic ovarian disease     

Influence of Bleeding Risk on Outcomes of Radial and Femoral Access for Percutaneous Coronary Intervention: An Analysis From the GLOBAL LEADERS Trial

BackgroundRadial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding.MethodsPatients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days.ResultsIn the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; P_interaction = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; P_interaction = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant.ConclusionsOur findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because this was not a primary analysis, it should be considered hypothesis generating.     

Haploidentical Hematopoietic Stem Cell Transplantation in Leukemia’s: Experience from a Cancer Center in India

There has been a surge in haploidentical hematopoietic stem cell transplantation (HSCT) in India recently. However, there is a paucity of data on haploidentical HSCT from India. The report is an analysis of data of haploidentical HSCT performed at our center. Analysis of patients with acute leukemia or chronic myeloid leukemia who underwent haploidentical HSCT during 2014–2019 was performed. The graft versus host disease (GVHD) prophylaxis was post-transplant Cyclophosphamide with Mycophenolate-mofetil and Cyclosporine. All patients were transfused peripheral blood stem cells from donors. Overall survival (OS) was calculated using the Kaplan–Meier method. Twenty-one patients underwent haploidentical HSCT. Fourteen-patients were males. The median age of patients was 15 years. Fludarabine with total body irradiation was the most common conditioning regimen (n = 15, 71.4%). The median duration for neutrophil and platelet engraftment was 14 days. Cumulative incidence of acute and chronic GVHD was 19%, and 38% respectively. The median follow-up was 26 months and the two-year OS was 38%. Twelve (57%) patients died during the study period, 8 patients (38%) died from transplant-related mortality (TRM), and 4 from disease relapse. Sepsis was the cause of death in six of the eight TRM. Nine out of 21 patients (42.8%) are leukemia-free on follow-up. Haploidentical HSCT is a promising modality of treatment in patients who have no suitable matched donors. Though the TRM remains high, good disease control was achieved in 42.8% of patients. Multi-drug resistant bacterial infection remains a challenge in performing haploidentical HSCT in developing countries.     

Structural Signaling Regulates Inflammation-Induced Enhanced Restitution and Increased Mib-1 and Bax-Indexes After Superficial Injury in Isolated Guinea Pig Gastric Mucosa

Several growth factors and cytokines are involved in regulation of the immediate repair of gastrointestinal mucosa, a process also called restitution. Few data exist on the effect of inflammation on this process using an explant model, where the folded basal lamina is included. The aim of the present study was to investigate the effect of simulated inflammation on restitution and on concomitant proliferation and apoptosis in isolated guinea pig gastric mucosa. Paired gastric mucosae were mounted in Ussing chambers (37 degrees C) and a superficial injury was induced (1.25 M NaCl/5 min) followed by a 4-hr restitution (pH 7.3-7.5). During perfusion, simulated inflammation was induced (with 0.5 or 5.0 ng/ml IL-1beta or with activated polymorphonuclear [PMN] cells). The PI (proliferative index) and AI (apoptotic index) are expressed as the number of Mib-1- or Bax-immunopositive cells per 300 foveolar cells, respectively. The mean recovery of electrophysiological resistance of tissues (R) after injury and exposure to serosal IL-1beta during restitution was 95.2 +/- 5.3% (mean +/- SD), whereas the value for control tissues was 89.6 +/- 6.9% (P = 0.016; N = 9). The mean recovery of R in tissues exposured to activated serosal PMN cells during restitution was 97.6 +/- 2.7%, whereas the value for unexposed control tissues was 93.8 +/- 2.9 (P = 0.004; N = 9). The enhancing effect of PMN cells was partially eliminated by serosal anti-ICAM, whereas serosal cytochalasin D abolished the process completely. The PI of tissues exposed to serosal PMN cells was 34.6 +/- 17.3, whereas the value for unexposed controls was 24.7 +/- 15.5 (P = 0.04; N = 5). The corresponding AI values were 17.0 +/- 2.8 and 12.0 +/- 5.7, respectively (NS; N = 4). Simulated inflammation either with serosal IL-1beta or with activated PMN cells enhances restitution and proliferation, whereas their effect on AI is only suggestive. Exogenous serosal anti-ICAM modulates restitution, whereas cytochalasin D abolishes it completely, suggesting that the structural signaling system including focal adhesions and cytoskeleton plays a significant role in the regulation of restitution.     

Bortezomib down-regulates the cell-surface expression of HLA class I and enhances natural killer cell-mediated lysis of myeloma

Human leukocyte antigen class I molecules expressed by tumor cells play a central role in the regulation of natural killer (NK) cell-mediated immune responses. The proteasome inhibitor bortezomib has demonstrated significant activity in multiple myeloma (MM). We hypothesized that treatment of MM with bortezomib results in the reduction of cell-surface expression of class I and thereby sensitizes MM to NK cell-mediated lysis. Here we report that bortezomib down-regulates class I in a time- and dose-dependent fashion on all MM cell lines and patient MM cells tested. Downregulation of class I can also be induced in vivo after a single dose of 1.0 mg/m(2) bortezomib. Bortezomib significantly enhances the sensitivity of patient myeloma to allogeneic and autologous NK cell-mediated lysis. Further, the level of decrease in class I expression correlates with increased susceptibility to lysis by NK cells. Clinically relevant bortezomib concentrations do not affect NK-cell function. Our findings have clear therapeutic implications for MM and other NK cell-sensitive malignancies in the context of both allogeneic and autologous adoptively transferred NK cells.     

Genetic basis of congenital generalized lipodystrophy

Congenital generalized lipodystrophy (CGL) is an autosomal recessive disorder characterized by extreme lack of body fat and severe insulin resistance since birth. Recently, mutations have been reported in 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2) and Berardinelli-Seip congenital lipodystrophy 2 (BSCL2 or Seipin) genes in affected subjects from pedigrees linked to chromosomes 9q34 and 11q13, respectively. The AGPAT2 catalyses the acylation of the lysophosphatidic acid at the sn-2 position to form phosphatidic acid, a key intermediate in the biosynthesis of triacylglycerol and glycerophospholipids. High expression of AGPAT2 mRNA in adipose tissue compared to other isoforms suggests that the mutations might affect the adipose tissue the most. The function of BSCL2 remains unknown. Several CGL pedigrees reveal no mutation in either of the above genes and are not linked to these loci, suggesting additional genetic loci for CGL. Thus, several distinct mechanisms can lead to extreme lack of adipose tissue in humans and cause CGL.     

Low,fixed dose defibrotide in management of hepatic veno-occlusive disease post stem cell transplantation

Objective/background

Hepatic veno-occlusive disease (VOD) is well recognized potentially serious regimen-related toxicity seen after stem cell transplantation. Severe VOD is associated with poor long-term outcomes with very high mortality. Besides supportive care, only defibrotide has been found to be effective in the management of VOD. The recommended dose of defibrotide is 25 mg/kg/d but there has been no classical dose finding study done for this drug. A higher dose of defibrotide is associated with increased risk of bleeding and this drug is prohibitively expensive. We report our experience of using fixed low dose of defibrotide in patients with VOD.