High prevalence of metallo-beta-lactamase-producing acinetobacter baumannii in a teaching hospital in Tabriz, Iran

Metallo-beta-lactamase (MBL)-producing Acinetobacter baumannii has become a growing therapeutic concern worldwide. The aims of this study were to evaluate the antimicrobial susceptibility of A. baumannii isolates and to determine the prevalence of MBL genes among carbapenem non-susceptible isolates. During a period of 16 months (March 2008-June 2009), 100 isolates of A. baumannii were collected from different clinical specimens of inpatients admitted to the largest teaching hospital in the northwest of Iran. All isolates were tested for antimicrobial susceptibility by Kirby-Bauer disk diffusion method. Carbapenem non-susceptible isolates were further screened for production of MBL by Etest and were then subjected to PCR for detection of MBL genes of types bla(IMP) and bla(VIM). Among 63 carbapenem (imipenem and meropenem) non-susceptible isolates of A. baumannii, 31 (49%) were found to be MBL producers. Of 31 MBL-producing isolates, 19 (61%) carried the bla(IMP) gene and 9 (29%) carried the bla(VIM) gene. All MBL-producing isolates were multidrug resistant. This is the first report of IMP and VIM types among MBL-producing A. baumannii in Iran.     

Efficacy,safety, and quality of life of generic and innovator ibrutinib in Indian CLL patients

To report the efficacy, safety, and quality of life (QoL) on generic and innovator ibrutinib in Indian CLL patients. This was a single centre, prospective study of treatment-naive (TN), and relapsed/refractory (R/R) CLL patients receiving ibrutinib in India. The choice of innovator or generic ibrutinib was as per patient discretion. Response and adverse events were recorded as per the 2018 iwCLL guidelines and CTCAEv4.0. QoL was assessed using the EORTC QLQ-C30 and CLL17 questionnaires. A total of 32 CLL patients (TN, n = 7 and R/R, n = 25) received ibrutinib from 2016–2019. The median age was 60 years (37–84). All TN patients attained partial response without any grade 3/4 adverse events (AE). Ibrutinib was less tolerated in the R/R setting, with 52% patients developing grade 3/4 AE and required dose reduction. Eleven patients (44%) died during follow-up. Grade 3–5 infections were seen in 44% of R/R CLL patients. Generic ibrutinib (n = 8) was comparable to innovator ibrutinib (n = 17) in terms of efficacy, safety, and QoL. Ibrutinib is less well tolerated in Indian R/R CLL patients. Infections are a common cause of morbidity and mortality. This study affirms the safety and efficacy of generic ibrutinib.Electronic supplementary materialThe online version of this article (10.1007/s12288-020-01378-6) contains supplementary material, which is available to authorized users.     

Serum adiponectin and coronary heart disease risk in older Black and White Americans

CONTEXT: Adiponectin may influence the risk of coronary heart disease (CHD) independently of traditional cardiovascular risk factors. OBJECTIVE: Because body composition and adiponectin levels vary by race, we examined the relationship of adiponectin with prevalent and incident CHD in a cohort of older Black and White adults. DESIGN AND SETTING: We conducted a cross-sectional and prospective cohort study at two U.S. clinical centers. PARTICIPANTS: Participants included 3075 well-functioning adults between ages 70 and 79 yr enrolled in the Health, Aging, and Body Composition study. MAIN OUTCOME MEASURES: Prevalent CHD was defined as history of myocardial infarction, coronary artery bypass graft, percutaneous coronary transluminal angioplasty, angina, or major electrocardiogram abnormalities. After excluding those with prevalent CHD, incident CHD was defined as hospitalized myocardial infarction or CHD death. RESULTS: At baseline, 602 participants (19.6%) had CHD. During 6 yr of follow-up, 262 (10.6%) incident CHD events occurred. Whites had higher median adiponectin than Blacks (12 vs. 8 microg/ml, P < 0.001). Race modified the effect of adiponectin (P for interaction was 0.002 for prevalent CHD, and P = 0.02 for incident CHD). Among Whites, an inverse association of adiponectin with CHD was explained by high-density lipoprotein and glucose. Among Blacks, a doubling of adiponectin was associated with a 40% higher risk of both prevalent CHD (odds ratio, 1.41; 95% confidence interval, 1.11-1.78) and incident CHD (hazards ratio, 1.37; 95% confidence interval, 1.01-1.87) after adjusting for explanatory variables. CONCLUSION: High circulating concentrations of adiponectin were associated with higher risk of CHD in older Blacks, even accounting for traditional CHD risk factors.     

The role of mutant UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase 3 in regulating serum intact fibroblast growth factor 23 and matrix extracellular phosphoglycoprotein in heritable tumoral calcinosis

CONTEXT: Familial tumoral calcinosis (TC) results from disruptions in phosphate metabolism and is characterized by high serum phosphate with normal or elevated 1,25 dihydroxyvitamin vitamin D concentrations and ectopic and vascular calcifications. Recessive loss-of-function mutations in UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) and fibroblast growth factor-23 (FGF23) result in TC. OBJECTIVE: The objective of the study was to determine the relationship between GALNT3 and FGF23 in familial TC. DESIGN, SETTING, AND PATIENTS: We assessed the major biochemical defects and potential genes involved in patients with TC. Intervention: Combination therapy consisted of the phosphate binder Sevelamer and the carbonic anhydrase inhibitor acetazolamide. RESULTS: We report a patient homozygous for a GALNT3 exon 1 deletion, which is predicted to truncate the encoded protein. This patient had high serum FGF23 concentrations when assessed with a C-terminal FGF23 ELISA but low-normal FGF23 levels when tested with an ELISA for intact FGF23 concentrations. Matrix extracellular phosphoglycoprotein has been identified as a possible regulator of phosphate homeostasis. Serum matrix extracellular phosphoglycoprotein levels, however, were normal in the family with GALNT3-TC and a kindred with TC carrying the FGF23 S71G mutation. The tumoral masses of the patient with GALNT3-TC completely resolved after combination therapy. CONCLUSIONS: Our findings demonstrate that GALNT3 inactivation in patients with TC leads to inadequate production of biologically active FGF23 as the most likely cause of the hyperphosphatemic phenotype. Furthermore, combination therapy may be effective for reducing the tumoral burden associated with familial TC.     

Morphometric evaluation of endometrial blood vessels

Five hundred endometrial specimens were studied to document the changes in blood vessels in various phases of menstrual cycle, menstrual disturbances and in unexplained infertility. Sixty-three cases were taken as control and 437 cases as study group which included cases of dysfunctional uterine bleeding (DUB), endometrial polyps, fibroids, adenomyosis, infertility and atrophic endometrium. Using light microscopy, the vascular morphology was studied. The blood vessels were concentrated more in basal layer in the proliferative phase and in functional layer in the secretory phase. Cases of complex hyperplasia and pill endometrium had significantly higher vessel concentration. Congestion and dilatation of blood vessels were significantly higher in cases of DUB. The present study showed a positive correlation between endometrial angiogenesis and menstrual disorders. The alteration in blood vessel morphology has significant role in prognosis and in various anti-angiogenic therapies.     

Hypereosinophilia in Acute Lymphoblastic Leukemia: Two Cases with Review of Literature

Eosinophilia is rare in acute leukemia at presentation. Discrete reports and case studies in recent years have created significant interest in the field of “Acute leukemia with eosinophilia”. We herein present two cases of eosinophilia in association with acute lymphoblastic leukemia with brief review of literature in this field. First case is about 21-year-old female who presented with mediastinal mass along with leukocytosis and hypereosinophilia. On evaluation, she was found to have T cell acute lymphoblastic leukemia. After ruling out benign causes of eosinophilia, she was treated with modified BFM-90 protocol. Her eosinophilia resolved after 4 weeks of induction therapy. Second case is about 32-year-old male who was diagnosed as a case of mixed phenotype leukemia (B cell/myeloid type) along with severe eosinophilia. His hypereosinophilia finally resolved by week 16 of modified BFM-90 protocol. Diagnosing ALL is challenging when eosinophilia is the initial presentation. These two cases emphasize on the importance of considering ALL amongst one of the etiological causes of eosinophilia as delay in diagnosis endangers patient’s life at risk. Also eosinophilia per se is an independent poor risk factor, hence prompt diagnosis and early treatment is the key in all such cases.