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Malnutrition negatively affects the quality of life of patients with dysphagia. Despite the need for nutritional status assessment in patients with dysphagia, standard, effective nutritional assessments are not yet available, and the identification of optimal nutritional assessment items for patients with dysphagia is inadequate. We conducted a scoping review of the use of nutritional assessment items in adult patients with oropharyngeal and esophageal dysphagia. The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched to identify articles published in English within the last 30 years. Twenty-two studies met the inclusion criteria. Seven nutritional assessment categories were identified: body mass index (BMI), nutritional screening tool, anthropometric measurements, body composition, dietary assessment, blood biomarkers, and other. BMI and albumin were more commonly assessed in adults. The Global Leadership Initiative on Malnutrition (GLIM), defining new diagnostic criteria for malnutrition, includes the categories of BMI, nutritional screening tool, anthropometric measurements, body composition, and dietary assessment as its required components, but not the blood biomarkers and the “other” categories. We recommend assessing nutritional status, including GLIM criteria, in adult patients with dysphagia. This would standardize nutritional assessments in patients with dysphagia and allow future global comparisons of the prevalence and outcomes of malnutrition, as well as of appropriate interventions.

Only 2 cases of human adenovirus type 14 (HAdV-14) have been reported in Japan since 1980. We report a 7-year-old girl with acute encephalopathy associated with HAdV-14 infection genetically similar to strains from the United States. The patient had not had contact with international travelers. HAdV-14 surveillance should be strengthened in Japan.

To evaluate the efficacy of subcutaneous injection of triamcinolone acetonide (SCTA) in treating upper eyelid retraction and swelling in patients with thyroid eye disease (TED). This case series included consecutive patients (aged 16-69 years, monitored from June 2012 to December 2015) with TED-related eyelid symptom and without an enlarged extraocular muscle on magnetic resonance imaging (MRI). SCTA (0.5 mL, 40 mg/mL) was administered to target the orbital fat around the levator palpebrae superioris (LPS) muscle. Patients who did not exhibit improvement after the first trial received an additional injection. Follow-up was conducted for 12 months with 3-month intervals. Eyelid retraction, eyelid swelling, and eyelid lag were evaluated at each follow-up visit. In total, 116 eyelids of 102 patients were analyzed. SCTA led to significant improvement in 93% of eyes (108/116), disappearance of eyelid symptoms (74%, 87%, and 73% in retraction, swelling, and lag, respectively), and improvement of scores (from 1.64 to 0.12, 1.32 to 0.26, and 1.72 to 0.30, respectively). Improvement in eyelid symptoms was observed in eight eyes; however, additional steroid therapy was required in these cases due to the emergence of other extraocular muscle inflammation. Additional injection was required in 39.8% of patients. The clinical activity score was lower in the single SCTA group than in the multiple SCTA group (1.5 vs 0.9; p < 0.01). However, the levels of thyroid-stimulating hormone receptor antibody and MRI findings were not significantly different between the two groups. No elevation in intraocular pressure was observed. Eight female patients experienced menstrual disorder. SCTA effectively reduced LPS muscle enlargement and fat tissue swelling in patients with TED. A single SCTA was sufficient in almost 60% of the patients; nevertheless, follow-up is necessary to detect early signs of orbital inflammation even in eyelid-symptom-improved patients.

Clostridium perfringens bacteremia is rare but often fatal. In particular, once bacteremia with massive intravascular hemolysis (MIH) occurs, the mortality rate is extremely high. However, because of its rarity, the detailed pathophysiology of this fulminant form of bacteremia is unclear. To elucidate the detailed pathogenesis of MIH, we retrospectively reviewed the data of all patients with C. perfringens bacteremia from two university hospitals from 2000 to 2014. The medical records and laboratory data of 60 patients with bacteremia, including 6 patients with MIH and 54 patients without MIH, were analyzed. Patients with MIH had higher rates of intense pain at onset, impaired consciousness, shock at presentation, hematuria, metabolic acidosis, and gas formation than patients without MIH. The antibiotic susceptibility of the clinical isolates was not significantly different between the two groups. All patients with MIH, although treated with appropriate antimicrobial agents, died within 26 h of admission due to rapidly progressive acute lung injury or acute respiratory distress syndrome, and the median time from arrival at the hospital to death was only 4 h and 20 min. When clinicians observe intravascular hemolysis in blood samples from patients with characteristic symptoms of MIH, they should prepare for a severe disease outcome. The underlying pathophysiology of fulminant cases must be investigated.

Hirotomo Saitsu, Noboru Mizushima, Naomichi Matsumoto and colleagues report the identification of de novo mutations in WDR45 that cause static encephalopathy of childhood with neurodegeneration in adulthood. WDR45 encodes a homolog of the yeast autophagy protein Atg18. Static encephalopathy of childhood with neurodegeneration in adulthood (SENDA) is a recently established subtype of neurodegeneration with brain iron accumulation (NBIA) 1 , 2 , 3 . By exome sequencing, we found de novo heterozygous mutations in WDR45 at Xp11.23 in two individuals with SENDA, and three additional WDR45 mutations were identified in three other subjects by Sanger sequencing. Using lymphoblastoid cell lines (LCLs) derived from the subjects, aberrant splicing was confirmed in two, and protein expression was observed to be severely impaired in all five. WDR45 encodes WD-repeat domain 45 (WDR45). WDR45 (also known as WIPI4) is one of the four mammalian homologs of yeast Atg18, which has an important role in autophagy 4 , 5 . Lower autophagic activity and accumulation of aberrant early autophagic structures were demonstrated in the LCLs of the affected subjects. These findings provide direct evidence that an autophagy defect is indeed associated with a neurodegenerative disorder in humans.

Oseltamivir has been shown to prolong the atrial conduction time and effective refractory period, and to suppress the onset of burst pacing-induced atrial fibrillation in vitro . To better predict its potential clinical benefit as an anti-atrial fibrillatory drug, we performed translational studies by assessing in vivo anti-atrial fibrillatory effect along with in vivo and in vitro electropharmacological analyses. Oseltamivir in intravenous doses of 3 (n = 6) and 30 mg/kg (n = 7) was administered in conscious state to the persistent atrial fibrillation model dogs to confirm its anti-atrial fibrillatory action. The model was prepared by tachypacing to the atria of chronic atrioventricular block dogs for > 6 weeks. Next, oseltamivir in doses of 0.3, 3 and 30 mg/kg was intravenously administered to the halothane-anesthetized intact dogs to analyze its in vivo electrophysiological actions (n = 4). Finally, its in vitro effects of 10–1,000 μM on I K,ACh , I Kur , I Kr , I Na and I CaL were analyzed by using cell lines stably expressing Kir3.1/3.4, K V 1.5, hERG, Na V 1.5 or Ca V 1.2, respectively (n = 3 for I K,ACh and I Kr or n = 6 for I Kr , I Na and I CaL ). Oseltamivir in doses of 3 and 30 mg/kg terminated the atrial fibrillation in 1 out of 6 and in 6 out of 7 atrial fibrillation model dogs, respectively without inducing any lethal ventricular arrhythmia. Its 3 and 30 mg/kg delayed inter-atrial conduction in a frequency-dependent manner, whereas they prolonged atrial effective refractory period in a reverse frequency-dependent manner in the intact dogs. The current assay indicated that IC 50 values for I K,ACh and I Kr were 160 and 231 μM, respectively, but 1,000 µM inhibited I Na , I CaL and I Kur by 22, 19 and 13%, respectively. The extent of I Na blockade was enhanced at faster beating rate and more depolarized resting membrane potential. Oseltamivir effectively terminated the persistent atrial fibrillation, which may be largely due to the prolongation of the atrial effective refractory period and inter-atrial conduction time induced by I K,ACh and I Kr inhibitions along with I Na suppression. Thus, oseltamivir can exert a powerful anti-atrial fibrillatory action through its ideal multi-channel blocking property; and oseltamivir would become a promising seed compound for developing efficacious and safe anti-atrial fibrillatory drugs.

BackgroundColposcopy, which is a standard modality for diagnosing cervical intraepithelial neoplasia (CIN), can have limited accuracy owing to poor visibility. Flexible magnifying endoscopy with narrow band imaging (ME-NBI) has excellent diagnostic accuracy for early gastrointestinal neoplasms and is expected to be highly useful for CIN diagnosis. This study aimed to determine the characteristic findings and evaluate the diagnostic ability of ME-NBI for lesions ≥ CIN 3.MethodsA well-designed prospective diagnostic case series conducted at multiple tertiary-care centers. A total of 24 patients who underwent cervical conization with a preoperative diagnosis of high-grade squamous cell intraepithelial lesions (HSILs) or lesions ≥ CIN 3 were enrolled. Prior to conization, still images and video of ME-NBI were captured to investigate the cervical lesions. The images were reviewed based on histological examination of the resected specimens.ResultsThe NBI-ME images revealed the following abnormal findings: (1) light white epithelium (l-WE), (2) heavy white epithelium (h-WE), and (3) atypical intra-epithelial papillary capillary loop (IPCL). Pathological examination of the resected specimens confirmed cervical lesions ≥ CIN 3 in 21 patients. The ME-NBI findings were classified into four groups: l-WE, l-WE with atypical IPCL, h-WE, and h-WE with atypical IPCL, at rates of 0, 23.8, 9.5, and 66.7%, respectively. Additionally, all 3 patients with micro-invasive carcinoma showed a strong irregularity of IPCLs.ConclusionThe lesions ≥ CIN 3 demonstrated characteristic ME-NBI findings of h-WE alone, or l-/h-WE with atypical micro-vessels. This study indicates that ME-NBI may have novel value for CIN diagnosis.

Duchene muscular dystrophy (DMD) is a progressive muscle wasting disease, caused by mutations in the dystrophin (DMD) on the X chromosome. One-third of patients are estimated to have de novo mutations. To provide in-depth genetic counseling, the comprehensive identification of mutations is mandatory. However, many DMD patients did not undergo genetic diagnosis because detailed genetic diagnosis was not available or their mutational types were difficult to identify. Here we report the genetic testing of a sporadic DMD boy, who died >20 years previously. Dried umbilical cord preserved for 38 years was the only available source of genomic DNA. Although the genomic DNA was severely degraded, multiplex ligation-dependent probe amplification analysis was performed but no gross mutations found. Sanger sequencing was attempted but not conclusive. Next-generation sequencing (NGS) was performed by controlling the tagmentation during library preparation. A nonsense mutation in DMD (p.Arg2095*) was clearly identified in the proband. Consequently, the identical mutation was detected as an 11% mosaic mutation from his healthy mother. Finally, the proband's sister was diagnosed as a non-carrier of the mutation. Thus using NGS we have identified a pathogenic DMD mutation from degraded DNA and low-level somatic mosaicism, which would have been overlooked using Sanger sequencing.

ObjectiveThis study aimed to evaluate the efficacy of paclitaxel and carboplatin in patients with completely or optimally resected uterine carcinosarcoma.Materials and MethodsWe conducted a single-arm multicenter prospective phase II trial at 20 Japanese medical facilities. Eligible patients had histologically confirmed uterine carcinosarcoma without prior chemotherapy or radiotherapy. Patients received 6 courses of 175 mg/m2 paclitaxel over 3 hours, followed by a 30-minute intravenous administration of carboplatin at an area under the serum concentration-time curve of 6.ResultsA total of 51 patients were enrolled in this study, 48 of whom underwent complete resection and 3 of whom underwent optimal resection. At 2 years, the progression-free survival and overall survival rates were 78.2% (95% confidence interval [CI], 64.1%–87.3%) and 87.9% (95% CI, 75.1%–94.4%), respectively. At 4 years, these rates were 67.9% (95% CI, 53.0%–79.0%) and 76.0% (95% CI, 60.5%–86.1%), respectively. Although 15 patients showed disease recurrence during the follow-up period (median, 47.8 months; range, 2.1–72.8 months), a total of 40 (78.4%) patients completed the 6 courses of treatment that had been planned.ConclusionsThe combination of paclitaxel and carboplatin was a feasible and effective postoperative adjuvant therapy for patients with completely or optimally resected uterine carcinosarcoma.

The Na + /Ca 2+ exchanger (NCX) is a plasma membrane transporter that is involved in regulating intracellular Ca 2+ concentrations in various tissues. The physiological roles by which NCX influences gastrointestinal motility are incompletely understood, although its role in the heart, brain, and kidney has been widely investigated. In this study, we focused on the functions of the NCX isoforms, NCX1 and NCX2, in the motility of the ileum in the gastrointestinal tract. We investigated the response to electric field stimulation (EFS) in the longitudinal smooth muscle of the ileum obtained from wild-type mice (WT), NCX1-heterozygote knockout mice (NCX1 HET), NCX2 HET and smooth muscle-specific NCX1.3 transgenic mice (NCX1.3 Tg). EFS induced a phasic contraction that persisted during EFS and a tonic contraction that occurred after the end of EFS. We found that the amplitudes of the phasic and tonic contractions were significantly smaller in NCX2 HET, but not in NCX1 HET, compared to WT. Moreover, the magnitudes of acetylcholine (ACh)- and substance P (SP)-induced contractions of NCX2 HET, but not of NCX1 HET, were smaller compared to WT. In contrast, the amplitudes of the phasic and tonic contractions were greater in NCX1.3 Tg compared to WT. Similar to EFS, the magnitude of ACh-induced contraction was greater in NCX1.3 Tg than in WT. Taken together, our findings indicated that NCX1 and NCX2 play important roles in ileal motility and suggest that NCX1 and NCX2 regulate the motility in the ileum by controlling the sensitivity of smooth muscles to ACh and SP.