Clinical impact of complete atrioventricular block in patients with ST‐segment elevation myocardial infarction

Complete atrioventricular block (CAVB) is a common complication of ST‐segment elevation myocardial infarction (STEMI). Although STEMI patients complicated with CAVB had a higher mortality in the thrombolytic era, little is known about the impact of CAVB on STEMI patients who underwent primary percutaneous coronary intervention (PCI). The study aimed at evaluating the clinical impact of CAVB on STEMI patients in the primary PCI era. We consecutively enrolled 1295 STEMI patients undergoing primary PCI within 24 hours from onset. Patients were divided into two groups according to the infarct location: anterior STEMI (n = 640) and nonanterior STEMI (n = 655). The outcomes were all‐cause death and major adverse cardiocerebrovascular events (MACCE) with a median follow‐up period of 3.8 (1.7–6.6) years. Eighty‐one patients (6.3%) developed CAVB. The incidence of CAVB was lower in anterior STEMI patients than in nonanterior STEMI (1.7% vs 10.7%, p < .05). Anterior STEMI patients with CAVB had a higher incidence of all‐cause deaths (82% vs 20%, p < .05) and MACCE (82% vs 25%, p < .05) than those without CAVB. Although higher incidence of all‐cause deaths was found more in nonanterior STEMI patients with CAVB compared with those without CAVB (30% vs 18%, p < .05), there was no significant difference in the incidence of MACCE (24% vs 19%). Multivariate analysis showed that CAVB was an independent predictor for all‐cause mortality and MACCE in anterior STEMI patients, but not in nonanterior STEMI. CAVB is rare in anterior STEMI patients, but remains a poor prognostic complication even in the primary PCI era.     

NLRP3 Inflammasome Inhibitor OLT1177 Suppresses Onset of Inflammation in Mice with Dextran Sulfate Sodium-Induced Colitis

Digestive Diseases and Sciences - NLRP3 inflammasomes have been reported to have a key role in the initiation and perpetuation of inflammatory bowel diseases (IBD). Here we investigated the effects...     

Evolution of bacterial steroid biosynthesis and its impact on eukaryogenesis

Steroids are components of the eukaryotic cellular membrane and have indispensable roles in the process of eukaryotic endocytosis by regulating membrane fluidity and permeability. In particular, steroids may have been a structural prerequisite for the acquisition of mitochondria via endocytosis during eukaryogenesis. While eukaryotes are inferred to have evolved from an archaeal lineage, there is little similarity between the eukaryotic and archaeal cellular membranes. As such, the evolution of eukaryotic cellular membranes has limited our understanding of eukaryogenesis. Despite evolving from archaea, the eukaryotic cellular membrane is essentially a fatty acid bacterial-type membrane, which implies a substantial bacterial contribution to the evolution of the eukaryotic cellular membrane. Here, we address the evolution of steroid biosynthesis in eukaryotes by combining ancestral sequence reconstruction and comprehensive phylogenetic analyses of steroid biosynthesis genes. Contrary to the traditional assumption that eukaryotic steroid biosynthesis evolved within eukaryotes, most steroid biosynthesis genes are inferred to be derived from bacteria. In particular, aerobic deltaproteobacteria (myxobacteria) seem to have mediated the transfer of key genes for steroid biosynthesis to eukaryotes. Analyses of resurrected steroid biosynthesis enzymes suggest that the steroid biosynthesis pathway in early eukaryotes may have been similar to the pathway seen in modern plants and algae. These resurrected proteins also experimentally demonstrate that molecular oxygen was required to establish the modern eukaryotic cellular membrane during eukaryogenesis. Our study provides unique insight into relationships between early eukaryotes and other bacteria in addition to the well-known endosymbiosis with alphaproteobacteria.

The emergence of modern eukaryotic cells from their archaeal ancestor requires multiple evolutionary steps, most notably the acquisition of mitochondria, nucleus, endomembrane system, and bacterial-like cellular membranes. The acquisition of mitochondria by early eukaryotes before the last eukaryotic common ancestor (LECA) would have been a key step to exploit new resources within an aerobic environment (1). Similarly, the transformation of the eukaryotic cellular membrane system from an archaeal-type to bacterial-type membrane would have also been crucial to develop the dynamic cellular membrane system observed in modern eukaryotes (2). Such a dynamic membrane may have been the prerequisite for a pre-LECA cell to perform endocytosis and, hence, later acquire organelles such as mitochondria and chloroplasts. While the tetraether monolayer membrane in archaea is more rigid and is advantageous to harsh environments, such as high temperature and low pH conditions, the diester bilayer membrane found in bacteria and eukaryotes has been suggested to be adaptable to more general environments (3). Recent phylogenomic analyses of archaea and eukaryotes suggest that eukaryotes evolved from within the archaeal domain (4, 5). However, there is little similarity between the archaeal and the bacterial/eukaryotic cellular membranes. Both the stereochemistry of lipid molecules (i.e., phospholipids) and their lipid composition (e.g., fatty acid chain versus isoprenoid chain and the presence of sphingolipids and steroids) are fundamentally different between the two types of membranes. As such, the evolutionary history of the eukaryotic cellular membrane is a major gap in our understanding of eukaryogenesis (6).Here, we focus on the evolution of the steroid component of the eukaryotic cellular membrane. Steroids have indispensable roles in the process of eukaryotic endocytosis because they are embedded in the cellular membrane and are known to regulate membrane fluidity and permeability (7–9). Thus, steroids may also have been integral for the endocytic process to acquire mitochondria during eukaryogenesis. Steroids would also function as hormones to control various cellular processes, including differentiation, morphogenesis, and homeostasis to enable multicellularity (10). In addition to the vital biochemical role in modern eukaryotes, steroids also have a geobiological importance. They can serve as unique biological markers (biomarkers) for eukaryotes in the geological record and thus provide clues to trace the evolutionary history of eukaryotes on a geological time scale. Membrane-bound steroids are modified in a unique manner within each eukaryotic taxon. For instance, cholesterol is a major component of cellular membrane in metazoans, whereas stigmasterol is a major component in plants (11, 12). These taxon-specific modifications can be used as taxonomic markers in the geological record (13–15). No analogous steroid biosynthesis pathway has been observed in archaea and thus steroid biosynthesis is generally inferred to have evolved de novo within eukaryotes (16). Despite this inference, some bacteria are known to produce hopanoids that are structurally similar to steroids (17). Indeed, several genes that are involved in hopanoid and steroid biosynthesis are suggested to have been horizontally transferred from bacteria to eukaryotes (18, 19). These recent observations suggest a more complex evolutionary history of steroid biosynthesis in eukaryotes. Ancestral sequence reconstruction (ASR) enables us to experimentally analyze resurrected enzymes (20, 21) and thus infer evolutionary histories of steroid biosynthesis and their impacts on eukaryogenesis.     

Severe exacerbation of hepatitis after short‐term corticosteroid therapy in a patient with “latent” chronic hepatitis B

Abstract: We present a case of severe exacerbation of hepatitis after short‐term corticosteroid therapy for chronic inflammatory demyelinating polyneuropathy (CIPD) with “latent” chronic hepatitis B showing no HBV‐related antigens and antibodies. After corticosteroid pulse therapy for CIPD, the patient had severe exacerbation of hepatitis twice. Although she did not show any hepatitis B virus (HBV)‐related antigens or antibodies, sequences of HBV were detected in serum and liver by a nested polymerase chain reaction. A sequence analysis of HBV at the second exacerbation showed that the G‐to‐A point mutation at nucleotide 1896 that converted codon 28 from tryptophan (TGG) to a stop codon (TAG) in the precore region resulted in amino acid change, which has been frequently observed in fulminant hepatitis and severe hepatitis in Japan.     

Laparoscopic total gastrectomy for advanced gastric cancer in a patient with situs inversus totalis

Situs inversus totalis (SIT) is a rare congenital anomaly. Generally, laparoscopic surgery is difficult to perform in patients with SIT because of both the potential challenges associated with unexpected vascular anomalies and the lack of standardized strategy for handling such cases. This is the first report of laparoscopic total gastrectomy with lymph node dissection for advanced gastric cancer in a patient with SIT. A 79‐year‐old man with SIT was diagnosed with advanced gastric cancer. We performed laparoscopic total gastrectomy with modified D2 lymph node dissection (D2 without splenectomy) and esophagojejunal anastomosis using an overlap method involving retrocolic Roux‐en‐Y reconstruction. The total operating time was 232 min, and blood loss was 110 mL. There were no postoperative complications. In summary, laparoscopic total gastrectomy for gastric cancer can be performed safely, even in a patient with SIT.     

Mid‐term results of bariatric surgery in morbidly obese Japanese patients with slow progressive autoimmune diabetes

Introduction

Bariatric surgery is recognized as an effective treatment for type 2 diabetes mellitus, but data on its efficacy for type 1 diabetes mellitus, especially slowly progressive insulin‐dependent diabetes mellitus, are limited.

Methods

We investigated five Japanese patients with slowly progressive insulin‐dependent diabetes mellitus who underwent bariatric surgery at our center.

Results

Five morbidly obese glutamic acid decarboxylase antibody‐positive diabetic patients underwent two different types of bariatric surgery. The mean titer of anti‐glutamic acid decarboxylase antibody was 4.6 U/mL, and the mean preoperative bodyweight and BMI were 113 kg and 39.6 kg/m², respectively. The mean hemoglobin A1c was 8.4%. The mean fasting serum C‐peptide was 5.0 ng/mL. Laparoscopic sleeve gastrectomy was performed in two patients, while laparoscopic sleeve gastrectomy with duodenojejunal bypass was performed in three patients. At one year after surgery, the mean bodyweight and BMI significantly dropped, and the mean percentage of excess weight loss was 96.4%. The mean hemoglobin A1c was 5.7%. This favorable trend was maintained at mid‐term.

Conclusion

Bariatric surgery for morbidly obese patients with anti‐glutamic acid decarboxylase antibody–positive type 1 diabetes mellitus, especially slow progressive autoimmune diabetes, seemed effective in achieving mid‐term glycemic control. Longer follow‐up with a larger number of patients, as well as validation with more advanced patients with slowly progressive insulin‐dependent diabetes mellitus, will be needed.

     

First case of a bloodstream infection caused by the genus Brachybacterium

An 83-year-old previously self-sufficient man was referred to our hospital for a fever, severe tenderness over the lumbar spine, and elevated C-reactive protein levels. Computed tomography revealed fluid collection in the intervertebral space of L3/4. Gram-positive, short rod-shaped bacteria were isolated from two sets of blood cultures. A 16S rRNA sequence analysis of an isolate showed a similarity of 98.1% to the nearest type strain Brachybacterium squillarum JCM 16464^T. Biochemical characteristics of the presently isolated strain differed from those of the most closely related species of the genus Brachybacterium. The patient was successfully discharged on day 73 of admission with antimicrobial therapies and showed no recurrence during outpatient visits. Brachybacterium spp. have mainly been isolated from the environment, and human Brachybacterium infections have rarely been documented to date. To our knowledge, this is the first clinical isolation of Brachybacterium sp. as a causative pathogen of bloodstream infection.