Safe administration of sotrovimab to a COVID-19 patient with acute phase type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) and poor glycemic control are risk factors for severe coronavirus disease 2019 (COVID-19). Sotrovimab can treat mild-to-moderate COVID-19 in patients at a high risk of progression to severe COVID-19. However, its safety and efficacy in T1DM patients remain to be elucidated. We report the case of a 12-yr-old patient who was treated with sotrovimab for COVID-19 immediately after treatment for diabetic ketoacidosis (DKA) due to new-onset T1DM. He presented with nausea and sore throat and was diagnosed with severe DKA and COVID-19. A productive cough and sputum developed after admission. On the 3rd day of admission, the DKA resolved, and sotrovimab was administered to prevent exacerbation of COVID-19. Although the blood glucose levels increased after the administration of sotrobimab, there was no recurrence of DKA. Hyperglycemia may be a sotrovimab-related adverse event in T1DM patients. Nevertheless, the benefits of sotrovimab treatment may far outweigh the potential risks. Thus, sotrovimab was considered safe for patients with T1DM immediately after treatment of severe DKA.

Heads or tails: exaggerated morphologies in relation to the use of large bamboo internodes in two lizard beetles, Doubledaya ruficollis and Oxylanguria acutipennis (Coleoptera: Erotylidae: Languriinae).

The cavities of bamboos (Poaceae) are used by various animals. Most of the animals access these cavities either by existing cracks or by excavating bamboos with soft walls or small, thin-walled bamboos. Only a few animals excavate into the cavities of large and thick- and hard-walled internodes of mature bamboos. We studied two lizard beetle species (Coleoptera: Erotylidae: Languriinae), Doubledaya ruficollis and Oxylanguria acutipennis, that excavate into large internode cavities of recently dead mature bamboos and have morphological modifications. We observed that females of D. ruficollis used their mandibles to bore oviposition holes on Schizostachyum sp. (mean wall thickness = 3.00 mm) and O. acutipennis did so on Dendrocalamus sp. (3.37 mm) bamboos. Previous studies suggested that the markedly asymmetrical mandibles and needle-like ovipositors of females in the genus Doubledaya are adaptive traits for excavating hard-walled bamboos for oviposition. Therefore, we measured their mandibular lengths and ovipositor lengths. D. ruficollis females had greater asymmetry in the mandibles and shorter and less-sclerotized ovipositors than females of congeners using small bamboos. In contrast, O. acutipennis females had slightly asymmetrical mandibles and elongated, well-sclerotized ovipositors. Oviposition holes of D. ruficollis were cone-shaped (evenly tapering), whereas those of O. acutipennis were funnel-shaped (tube-like at the internal apex). This suggests that D. ruficollis females excavate oviposition holes using the mandibles only, and O. acutipennis females use both the mandibles and ovipositors. These differences suggest different oviposition-associated morphological specialization for using large bamboos: the extremely asymmetrical mandibles in D. ruficollis and elongated, needle-like ovipositors in O. acutipennis.

Umbilical resection during laparoscopic surgery for urachal remnants.

INTRODUCTION: Because urachal remnants are rare, no standard therapeutic guidelines have been established for this lesion. In recent years, laparoscopic surgery (LS) has been performed by many surgeons and urologists to treat urachal remnants. The prevention of postoperative umbilical infection and late malignant transformation are major issues in the treatment of urachal remnants. Adequate resection of the urachal epithelial tissue is required, and therefore, umbilical resection (UR) is performed. We retrospectively assessed the feasibility of this modality for urachal remnants by examining cases we have experienced as well as 210 Japanese surgical cases found through literature review. METHODS: From January 1998 to March 2016, we experienced 14 operative cases of urachal remnants who underwent LS at Shimane Prefectural Central Hospital. We examined the types of urachal remnants and patients' ages, symptoms, surgical methods, and pathological findings. RESULTS: We performed UR in 6 of these 14 LS patients to achieve appropriate resection of the urachal epithelial tissue. The main indication for UR was a long history of preoperative therapies for umbilical infection. The average observation period after the operation was 3.95 years, and no patients developed recurrent umbilical infection or cancer. No patients complained about the aesthetic outcome after umbilicoplasty. CONCLUSION: We recommend that UR with LS be performed for urachal remnants to prevent any recurrent umbilical infection or malignant transformation in the future.

Worsening of Acute Cholangitis Caused by a Bile Duct Stone After Hospitalization: A Case Series.

Acute cholangitis is a fatal condition if inadequately treated. It is possible to underestimate the severity of the condition because bacterial cultures are not immediately available. We evaluated the clinical features of patients with cholangitis due to bile duct stones who were diagnosed with severe bacteremia at the time of hospitalization, but not at the time of the initial visit. We conducted a retrospective analysis of cases of endoscopic retrograde cholangiopancreatography performed between January 2007 and October 2011 in patients with bile duct stones complicated by cholangitis. The severity of cholangitis was assessed based on the 2005 Japanese Evidence-Based Practice Guidelines for the Management of Acute Cholangitis and Cholecystitis (JG05). Of 130 cases, 23 were diagnosed as severe cholangitis, including 11 of bacterial cause. However, based on the JG05, two cases were classified as "mild" at initial assessment and nine cases as "moderate". A history of endoscopic sphincterotomy (EST) was identified in the two cases classified as "mild" cholangitis. Obstruction by a bile duct stone, possibly due to reflux from the duodenum, can lead to rapid progression to sepsis in a short time. For patients with a history of EST, early biliary drainage is necessary to prevent rapid progression of bacterial cholangitis.

Allopatric color forms of Scaphidium morimotoi Löbl, 1982 (Coleoptera, Staphylinidae, Scaphidiinae) endemic to the Amami Islands, the Ryukyus, Japan.

The shining fungus beetle, Scaphidium amamiense Hoshina & Morimoto, 1999 is synonymized with S. morimotoi Löbl, 1982, based on a review of morphological characters and molecular analysis. This species is endemic to the Amami Islands, the Ryukyus, Japan. An almost completely melanic form (morimotoi in strict) is known only on the island Yoro-shima, where the ordinary form with reddish fasciae on the elytra (previously called amamiense) is absent. The present study suggests that the melanic form on the small island has been fixed by random genetic drift.

Paclitaxel-based chemotherapy for advanced pancreatic cancer after gemcitabine-based therapy failure: a case series of 5 patients.

BACKGROUND/OBJECTIVES: Gemcitabine (GEM) is a gold-standard chemotherapy agent for advanced pancreatic cancer. Because of the malignant character of the disease, nearly all patients show disease progression despite treatment with GEM-based chemotherapy; therefore, second-line chemotherapy may be beneficial for these patients. We report a retrospective analysis of 5 patients with advanced pancreatic cancer, treated with a paclitaxel-containing regimen as second-, third- or fourth-line chemotherapy after various therapies, such as a GEM-based regimen, S-1 regimen, and chemoradiation. We retrospectively analyzed the efficacy and adverse events, and evaluated the paclitaxel-containing regimens. A review of the literature is also discussed. RESULTS: The median overall survival from the start of salvage therapy was 10.7 months. The disease control rate of the paclitaxel-containing regimen according to RECIST criteria was 60%, including complete response in 0 patients, partial response in 3, and stable disease in 2. Two patients had malignant ascites at the start of this salvage therapy, and in both of them the ascites and clinical complaints improved. Grade 3 and 4 hematological adverse events were observed in 2 patients and 1 patient, respectively. CONCLUSION: Salvage paclitaxel-based therapy could be beneficial to advanced pancreatic cancer patients who maintain good performance status after several chemotherapy failures.

A case of retroperitoneal mucinous cystadenoma treated successfully by laparoscopic excision.

A case of retroperitoneal mucinous cystadenoma treated laparoscopically is reported. A 26-year-old woman, who complained of abdominal fullness, was referred to us after a large intra-abdominal mass was discovered at her local hospital. Ultrasound and computed tomography showed a fluid-filled mass, 9 cm in diameter, in the left retroperitoneal space. Laparoscopic surgery was performed. We found a smooth and thin-walled cystic tumor that displaced the descending colon to the right and arose from the retroperitoneum, loosely adhering to the psoas muscle. We successfully extirpated the tumor laparoscopically. The surgical specimen consisted of a multilocular, red to yellowish-gray, cystic mass with a smooth, glistening external surface, and inner lining. The mass was filled with thin, yellowish fluid. The histologic diagnosis was benign mucinous cystadenoma. The postoperative course was uneventful, and the patient remains free of recurrence 15 months after surgery. Retroperitoneal mucinous cystadenoma is a rare entity, and the treatment of choice is surgical excision. Laparoscopic extirpation should be considered for the treatment of selected retroperitoneal cystic lesions.

Gene-specific requirement of a nuclear protein, IkappaB-zeta, for promoter association of inflammatory transcription regulators.

Expression of many inflammatory genes is induced through activation of the transcription factor NF-kappaB. In contrast to the advanced understanding of cytoplasmic control of NF-kappaB activation, its regulation in the nucleus has not been fully understood despite its importance in selective gene expression. We previously identified an inducible nuclear protein, IkappaB-zeta, and demonstrated that this molecule is indispensable for the expression of a group of NF-kappaB-regulated genes. In this study, we established a unique gene induction system, in which IkappaB-zeta is expressed independently of inflammatory stimuli, to specifically investigate the molecular basis underlying IkappaB-zeta-mediated gene activation. We show that in the presence of IkappaB-zeta other primary response genes are dispensable for the expression of the target secondary response genes. ChIP analyses revealed that IkappaB-zeta is required for stimulus-induced recruitment of NF-kappaB onto the target promoter in a gene-specific manner. Surprisingly, IkappaB-zeta is also necessary for the gene-selective promoter recruitment of another inflammatory transcription factor, C/EBPbeta, and the chromatin remodeling factor Brg1. We propose a new gene regulatory mechanism underlying the selective expression of inflammatory genes.

Large mucinous cystadenoma of the pancreas during pregnancy: report of a case.

A 33-year-old woman, gravida 2, para 1, was diagnosed to have a benign mucinous cystic neoplasm of the pancreas 5 months before delivery. The tumor measured 12 cm in diameter at the time of diagnosis. The antenatal course was uneventful, and a vaginal delivery produced a normal infant. By 2 months after delivery, the tumor reached 18 cm. At surgery, a huge cyst was found to originate from the pancreas, and a distal pancreatectomy with splenectomy was performed. The cystic mass was multilocular 18 x 17 x 12 cm, 2450 g, and red to yellowish-gray. The histologic diagnosis was benign mucinous cystadenoma. The postoperative course was uneventful, and the patient remains free of recurrence at 7 months after surgery. To our knowledge, this is only the fifth reported case of pancreatic mucinous cystadenoma in association with pregnancy. This is the first reported case of a successful resection of such a tumor after delivery.

Crucial roles of binding sites for NF-kappaB and C/EBPs in IkappaB-zeta-mediated transcriptional activation.

IkappaB-zeta [inhibitor of NF-kappaB (nuclear factor kappaB) zeta] is a nuclear protein that is induced upon stimulation of TLRs (Toll-like receptors) and IL (interleukin)-1 receptor. IkappaB-zeta harbours C-terminal ankyrin repeats that interact with NF-kappaB. Our recent studies have shown that, upon stimulation, IkappaB-zeta is essential for the induction of a subset of inflammatory genes, represented by IL-6, whereas it inhibits the expression of TNF (tumour necrosis factor)-alpha. In the present study, we investigated mechanisms that determine the different functions of IkappaB-zeta. We found that co-expression of IkappaB-zeta and the NF-kappaB subunits synergistically activates transcription of the hBD-2 (human beta-defensin 2) and NGAL (neutrophil gelatinase-associated lipocalin) genes, whereas it inhibits transcription of E-selectin. Reporter analyses indicated that, in addition to an NF-kappaB-binding site, a flanking C/EBP (CCAAT/enhancer-binding protein)-binding site in the promoters is essential for the IkappaB-zeta-mediated transcriptional activation. Using an artificial promoter consisting of the NF-kappaB- and C/EBP-binding sites, transcriptional activation was observed upon co-transfection with IkappaB-zeta and NF-kappaB, indicating that these sequences are minimal elements that confer the IkappaB-zeta-mediated transcriptional activation. Chromatin immunoprecipitation assays and knockdown experiments showed that both IkappaB-zeta and the NF-kappaB subunits were recruited to the NGAL promoter and were essential for the transcriptional activation of the hBD-2 and NGAL promoters on stimulation with IL-1beta. The activation of the NGAL promoter by transfection of IkappaB-zeta and NF-kappaB was suppressed in C/EBPbeta-depleted cells. Thus IkappaB-zeta acts as an essential transcriptional activator by forming a complex with NF-kappaB on promoters harbouring the NF-kappaB- and C/EBP-binding sites, upon stimulation of TLRs or IL-1 receptor.

Successful conservative treatment of a bicycle-handlebar hernia: report of a case.

Handlebar hernia is a rare type of blunt traumatic abdominal wall hernia (TAWH). It involves a disruption of the abdominal wall muscles, with bowel loop herniation through the defect in the abdominal wall. We report a case of bicycle-handlebar hernia in a 9-year-old boy who had all layers of his abdominal wall disrupted after falling from his bicycle. He was brought to our hospital with lower abdominal pain and bulging. A physical examination revealed left lower quadrant bulging in a standing posture, and a palpable fascial defect, 3 cm in diameter. Computed tomography showed a disruption of the abdominal rectal muscle layer, but his skin and intra-abdominal organs were completely intact. The patient was treated conservatively with abdominal wall compression using a cotton cloth corset. Within 3 weeks, his abdominal wall hernia had healed without the need for any surgical intervention.

Induction of the nuclear IkappaB protein IkappaB-zeta upon stimulation of B cell antigen receptor.

The nuclear IkappaB protein IkappaB-zeta is barely detectable in resting cells and is induced in macrophages and fibroblasts following stimulation of innate immunity via Toll-like receptors. The induced IkappaB-zeta associates with nuclear factor (NF)-kappaB in the nucleus and plays crucial roles in its transcriptional regulation. Here, we examined the induction of IkappaB-zeta in B lymphocytes, one of the major players in adaptive immunity. Upon crosslinking of the surface immunoglobulin complex, IkappaB-zeta mRNA was robustly induced in murine B-lymphoma cell line A20 cells. While the crosslinking activated NF-kappaB and induced its target gene, IkappaB-alpha, co-crosslinking of Fcgamma receptor IIB to the surface immunoglobulin complex inhibited NF-kappaB activation and the induction of IkappaB-zeta and IkappaB-alpha, suggesting critical roles for NF-kappaB in the induction. These results indicate that IkappaB-zeta is also induced by stimulation of B cell antigen receptor, suggesting that IkappaB-zeta is involved in the regulation of adaptive immune responses.

A missense mutation of the Toll-like receptor 3 gene in a patient with influenza-associated encephalopathy.

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and mediate the activation of NF-kappaB and the production of proinflammatory cytokines, which is critical for the innate immune system. TLR3 recognizes both double-stranded RNA and the influenza A virus. Since influenza-associated encephalopathy is frequent in Japan and East Asia and its pathological mechanism remains unknown, we analyzed several genes including TLRs and the retinoic acid inducible gene I, which could be involved in the recognition of the RNA virus. In one of three patients with influenza-associated encephalopathy, we detected a novel missense mutation (F303S) in just the TLR3 gene. This was confirmed as a loss-of-function mutant in a dose-dependent manner by NF-kappaB and IFN-beta reporter assays using wild-type and mutant TLR3-transfected HEK293 cells. Our results imply that a mutation of the TLR3 gene could be one of the factors responsible for influenza-associated encephalopathy.

Stimulus-specific induction of a novel nuclear factor-kappaB regulator, IkappaB-zeta, via Toll/Interleukin-1 receptor is mediated by mRNA stabilization.

We have recently identified an inducible nuclear factor-kappaB (NF-kappaB) regulator, IkappaB-zeta, which is induced by microbial ligands for Toll-like receptors such as lipopolysaccharide and the proinflammatory cytokine interleukin (IL)-1beta but not by tumor necrosis factor (TNF)-alpha. In the present study, we examined mechanisms for stimulus-specific induction of IkappaB-zeta. The analysis of the IkappaB-zeta promoter revealed an essential role for an NF-kappaB binding sequence in transcriptional activation. The activation, however, did not account for the Toll-like receptor/IL-1 receptor-specific induction of IkappaB-zeta, because the promoter analysis and nuclear run-on analysis indicated that its transcription was similarly induced by TNF-alpha. To examine post-transcriptional regulation, we analyzed the decay of IkappaB-zeta mRNA, and we found that it was specifically stabilized by lipopolysaccharide or IL-1beta but not by TNF-alpha. Furthermore, we found that costimulation with TNF-alpha and another proinflammatory cytokine, IL-17, elicited the IkappaB-zeta induction. Stimulation with IL-17 alone did not induce IkappaB-zeta but stabilized its mRNA. Therefore, IkappaB-zeta induction requires both NF-kappaB activation and stimulus-specific stabilization of its mRNA. Because IkappaB-zeta is essential for expression of a subset of NF-kappaB target genes, the stimulus-specific induction of IkappaB-zeta may be of great significance in regulation of inflammatory reactions.

[A case of recurrent early gastric cancer with peritonitis carcinomatosa successfully treated with TS-1].

A 62-year-old man with carcinomatous ascites more than 5 years after early gastric cancer operation was admitted to our hospital because of suspected pancreatic cancer, and was diagnosed with a relapse of the gastric cancer. TS-1 was administered at a dose of 120 mg/day. At the end of 1 course a partial response of a decrease of tumor markers and ascites and improvement of QOL was achieved, and the patient was followed in the outpatient clinic. The current case suggests that TS-1 may have a potent therapeutic efficacy in cases of gastric cancer relapse with carcinomatous ascites.

[A case of advanced gastric cancer successfully treated with TS-1].

A patient with advanced gastric cancer complicated with liver and lymph node metastases was successfully treated with a novel oral anticancer drug, TS-1, TS-1 was administered at a dose of 100 mg/day. One course consisted of consecutive administration of TS-1 for 28 days and withdrawal for 14 days. At the end of 3 courses a partial response of the liver metastases was achieved. Although the patient has had complications with ascites collection due to hypoalbuminemia, he has been well without regrowth of any metastases for over 8 months.