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A 69-year-old woman who had undergone renal transplantation and was receiving sulfamethoxazole/trimethoprim (ST) developed pulmonary nocardiosis. To our knowledge, this is the first report of the identification of Nocardia elegans using nanopore sequencing, supported by 16S rDNA capillary sequencing findings. Chest computed tomography performed after ST initiation revealed significant improvement of the pulmonary shadows compared to previous findings. We herein report the value of nanopore sequencing for rapid identification of rare pathogens, such as Nocardia elegans. Furthermore, our findings suggest that Nocardia may infect even patients receiving ST, which is currently the most effective prophylactic drug.

Aim After the hepatitis A virus (HAV) outbreak among men who have sex with men (MSM) around 2018, the importance of HAV vaccination was emphasized, especially for MSM-living with human immunodeficiency virus (MSM-LWHIV). Aimmugen® is licensed and distributed exclusively in Japan. While administration of three doses is recommended, 85% of recipients in the general population were reported to acquire seroprotection after the second dose. In this study, we evaluated the efficacy of two or three vaccine doses along with predictors associated with the response to Aimmugen® in MSM-LWHIV. Methods We retrospectively examined anti-HA-IgG titers of MSM-LWHIV vaccinated with Aimmugen® in our hospital. Patients' data were collected from medical records. Results Between January 2018 and October 2019, 141 subjects whose median age was 46 years old, were examined. All the subjects were on antiretroviral therapy (ART) and the median CD4 count was 615/μL. The acquisition rate of protectable anti-HA-IgG titers after the second and third dose was 71.1% and 98.6%, respectively. In 114 subjects whose anti-HA-IgG titers were tested after the second-dose, factors significantly associated with better response were prolonged ART duration and higher CD4 count. The titers of anti-HA-IgG after the third dose were higher in those who became seropositive after the second-dose than those who did not. Conclusions Three-dose of Aimmugen® for MSM-LWHIV was effective while two-dose was less effective compared to non-HIV-infected people. People-LWHIV with shorter duration of ART and lesser CD4 cell count achieved lower titers of anti-HA-IgG and might require an additional vaccination. This article is protected by copyright. All rights reserved.

Organized hematoma (OH) is benign tumor in the maxillary sinus. The standard treatment for OH is complete surgical resection, however massive bleeding can occur during the procedure, albeit rarely. Some reports have suggested preoperative embolization is useful for reducing the volume of intraoperative bleeding. We report 3 cases of OH in the maxillary performed preoperative embolization. We identified the feeding arteries by angiography or IVR-CT, and we embolized them using Gelatin sponge particles. The embolized artery was the maxillary artery or both the maxillary and the facial artery. There were no major complications as a result of embolization. The mean fluoroscopy time was 35.8 minutes, and the mean fluoroscopy dose was 329.3 mGy. Tumor resection was performed the next day after arterial embolization. The mean bleeding volume for surgery was 383.3 ml, and the mean operative time was 194 minutes. No recurrence was observed in any of the cases over a 4-year follow-up period. We considered that it is possible that preoperative artery embolization is useful for decreasing intraoperative bleeding volume. Although the methods and usefulness of embolization await future reports, it is a technique that should be considered preoperatively because of its potential to prevent massive bleeding.

Introduction Tuberculin skin test (TST) has been used to diagnose tuberculosis (TB) and latent tuberculosis infection (LTBI). However, in Bacillus Calmette-Guerin (BCG) vaccinated patients, TST tends to produce false-positive results. According to the previous vaccination schedule, Japanese people were mandated to receive up to three doses of BCG-vaccine. The vaccination schedule was changed in 2003 and as per the new schedule, only infants are administered a dose of BCG vaccine. Our hypothesis is that this change can lead to a reduction in the cross-reaction to TST. Methods We evaluated the TST results obtained from 1097 recruits from six defense camps and 667 recruits from an air base. These TST data were divided into two groups according to the date of birth: a new group and an old group according to the BCG immunization schedule. We then analyzed positive and negative reaction of TST and erythema sizes. Results We confirmed that the change in BCG-vaccination schedule significantly decreased TST false-positive reaction (Pmeta = 1.4 × 10−18; risk ratio = 0.83; 95% confidence interval: 0.80–0.87) and erythema size (Pmeta = 1.1 × 10−4; mean difference = 6.6 mm; 95% confidence interval: 3.2 mm–9.9 mm). Conclusions We showed the reduction in BCG cross-reaction to TST, in the new BCG vaccination schedule group, compared to the old group, we also have extracted information on the improvement in the specificity of TST for LTBI and TB diagnosis, which resulted from BCG schedule change.

The utility of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) for gastric subepithelial lesions (SELs) has been reported. In this study, we examined the optimal number of needle punctures during EUS-FNB for gastric SELs without rapid on-site evaluation (ROSE). The factors that allowed for a single needle puncture to arrive at the correct diagnosis were also analyzed. We conducted a retrospective study of all patients who underwent EUS-FNB to evaluate gastric SELs between April 2015 and September 2020; 51 patients with 57 gastric SELs were enrolled. The optimal number of needle punctures was determined when additional needle passes did not increase diagnostic sensitivity by more than 10%. Factors allowing for only a single needle puncture to arrive at the correct diagnosis were identified by univariate and multivariate logistic regression analyses. EUS-FNB resulted in a definitive final diagnosis in 48 of 57 lesions (84%). Lesions in the gastric body (odds ratio [OR] 6.15, 95% confidence interval [CI] 1.75–21.6; P

Background The association between the development of checkpoint inhibitor pneumonitis (CIP) with tumor response and survival has remained unclear so far. The aim of the present study was to evaluate the association between CIP and the clinical efficacy of anti‐programmed cell death‐1 antibody in patients with advanced non‐small cell lung cancer (NSCLC). Methods Between January 2016 and August 2019, 203 advanced NSCLC patients were administered with nivolumab or pembrolizumab. Comparisons were made between patients with and without CIP. We evaluated the time‐to‐treatment failure (TTF), progression‐free survival (PFS), and overall survival (OS). Results CIP was observed in 28 (14%) patients. CIP was associated with a longer PFS (18.9 months [95% confidence interval, CI: 8.7 months–not reached] vs. 3.9 months [95% CI: 3.4–5.1 months, p, This study aimed to evaluate the association between checkpoint inhibitor pneumonitis (CIP) and the clinical efficacy of anti‐programmed cell death‐1 monotherapy in patients with advanced non‐small cell lung cancer (NSCLC). CIP was associated with a longer PFS (18.9 months vs. 3.9 months, p

Background and Objective Patients with position-dependent obstructive sleep apnea have a > 2-fold higher apnea-hypopnea index when sleeping in a supine position compared with a non-supine position. We investigated the effect of body pillow use on sleeping body position and sleep architecture in healthy young adults. Methods In experiment 1, we evaluated the body pressure distribution with or without body pillow use in 8 healthy young adults [age, 36.5 ± 13.0 years; body mass index (BMI); 20.6 ± 1.2 kg/m2]. In experiment 2, we performed a randomized-crossover intervention study to evaluate the effects of body pillow use on sleeping position and sleep architecture in 10 healthy young adults (age, 24.3 ± 7.8 years; BMI, 21.4 ± 1.7 kg/m2). Sleep architecture was characterized by polysomnography, and body positions were monitored using a sensor. Subjective sleep quality was evaluated with the Oguri-Shirakawa-Azumi sleep inventory, middle age and aged version. Results In experiment 1, body pillow use significantly reduced mean body pressure on the shoulder, hip, and whole body. In experiment 2, mean time spent in the supine, lateral, and prone body positions did not differ significantly between the 2 trials. Body pillow use, however, significantly extended the sustained time spent in the lateral body position compared with the control trial. Subjective sleep quality and sleep architecture did not differ significantly between the 2 trials, but body pillow use decreased the number of short (30 s) slow-wave sleep episodes. Conclusions Sleeping with a body pillow effectively extends sustained time in a lateral sleeping position and prevents segmentation of slow-wave sleep episodes.

Hospital-acquired severe acute respiratory virus coronavirus 2 (SARS-CoV-2) infection is a healthcare challenge. We hypothesized that polymerase chain reaction testing of symptomatic triaged outpatients and all inpatients before hospitalization in Shinjuku, a coronavirus disease 2019 (COVID-19) epicenter in Tokyo, using the Tokyo Women's Medical University (TMWU) model would be feasible and efficient at preventing COVID-19. This retrospective study enrolled 2981 patients from March to May 2020. The prevalence of SARS-CoV-2 infection was 1.81% (95% credible interval [CI]: 0.95–3.47%) in triaged symptomatic outpatients, 0.04% (95% CI: 0.0002–0.2%) in scheduled asymptomatic inpatients, 3.78% (95% CI: 1.82–7.26%) in emergency inpatients, and 2.4% (95% CI: 1.49–3.82%) in symptomatic patients. There were no cases of hospital-acquired SARS-CoV-2 infection. This shows that the TWMU model could prevent hospital-acquired SARS-CoV-2 infection and is feasible and effective in reducing the impact of SARS-CoV-2 infection in the hospitals.

Residents with limited experience of thoracic surgery have difficulty performing video-assisted thoracoscopic surgery (VATS) lobectomy. However, they can learn early in a stepwise training method to safely manage the pulmonary veins (PVs), which are relatively strong vessels. In this study, we investigated whether the time required to manage the PVs could serve as an indicator of technical skill acquisition in VATS lobectomy. To evaluate the acquisition of residents’ technical skills, we retrospectively assessed the PV management time of 5 residents at our institution who had performed more than 15 VATS lobectomies over an 8-year period (2012–2019). Their PV management time was determined from surgical video. We analyzed whether PV management time was affected by patient characteristics, operative factors, and experience of lobectomy. The 5 residents performed a total of 103 VATS lobectomies during the study period. Median PV management time was 9.6 min. The most frequently resected lobe was the right upper lobe (56.3%). Median PV management time for right middle lobe was 5.2 min, which was shorter than that for other lobes. We categorized the lobectomies according to whether PV management time was ≤10 min or > 10 min. Univariate analysis identified that shorter PV management time (≤10 min) was significantly associated with more right middle lobectomies performed (7.3% vs 0%, p = 0.02) and more lobectomies performed (14 vs 8, p = 0.01). Longer PV management time (>10 min) was significantly associated with lower lobectomies performed (18% vs 35%, p

Introduction Influenza remains a clinically heavy burden worldwide. The objective of this study was to clarify clinical manifestations of severely ill patients infected with influenza. Methods The clinical data for patients who were severely ill with influenza, and required hospitalization were gathered and analyzed between November 2014 and August 2019 (5 influenza seasons) using an internet-surveillance system. Results A total of 924 patients were enrolled and analyzed. The median age was 78 years (IQR, 67–84), and the patients in the 2015–2016 season were significantly younger than those in other seasons. Pneumonia was the most common disease indicated as a cause for hospitalization, followed by a poor general condition and exacerbation of underlying respiratory diseases. Antiviral drugs were administered in 97.0% of the patients with peramivir being the most-frequently use antiviral. In-hospital death was recorded for 44 patients (4.8%). Multivariate analysis indicated that nursing home resident (OR: 6.554) and obesity (OR: 24.343) were independent predictors of in-hospital mortality. Conclusions Complications of influenza infection remain a heavy burden especially among the elderly. Continuous nationwide surveillance will be required to grasp the actual situation of influenza epidemics. (UMIN000015989).

We herein report a case of diffuse alveolar hemorrhage (DAH) associated with dilated cardiomyopathy (DCM) and sleep apnea syndrome (SAS) in a 47-year-old man. The patient exhibited recurring dyspnea and bloody sputum. Chest radiography showed bilateral diffuse infiltrative opacities without pleural effusion. A bronchoscopic analysis of bronchoalveolar lavage fluid revealed hemosiderin-laden macrophages. Based on these findings, he was diagnosed with DAH. Laboratory and pathological findings ruled out the possibility of collagen diseases and vasculitis. Overnight polysomnography revealed concomitant severe obstructive SAS. Treatment with continuous positive-pressure ventilation and pharmacological therapy for DCM prevented recurrence of DAH.

Objective: Hypertensive disorders of pregnancy (HDP) are thought to be a multifactorial genetic disease. Myosin light chain phosphorylation, which is involved in the regulation of vascular smooth m...

This study aimed to examine the incidence of hypertensive disorders of pregnancy (HDP) among Japanese women with oocyte donation pregnancy (ODP) aged 40 years or older and estimate whether the women with ODP were more likely to develop HDP than those with autologous oocyte pregnancy (AOP) and spontaneous pregnancy (SP). In our study (N = 1361), the proportions of women who developed HDP were 20.5%, 12.8%, and 7.6% for ODP, AOP, and SP, respectively. After adjustment of covariables, the women with ODP were more likely to develop HDP than those with AOP or SP.

Background Implant treatment using guided surgery is becoming widespread in clinical dental practice. Furthermore, the development of digital technology has enabled the use of intraoral scanners (IOSs) to fabricate surgical guide plates. The objective of this study was to compare the accuracy of guided surgery using the silicone impression method with a three-dimensional (3D) scanner and the digital impression method with IOS for one side of the mandibular free end. In addition, we compared the accuracy of tooth-supported vs tooth/mucosa-supported surgical guide plates. Results The accuracy of the tooth-supported surgical guide plate using the new IOS method instead of the method of obtaining impressions with conventional silicone resulted in better measurements of 3D deviation at the crest, 3D deviation at the apex, and angular deviation. In terms of the accuracy of the tooth/mucosa-supported surgical guide plate, there were no significant differences in all measurements. The surgical guide plate using an IOS and the tooth/mucosa-supported surgical guide plate may enable more accurate guided surgery. Conclusion Tooth/mucosa-supported guided surgery involving preparation with an IOS may result in more accurate implant surgery.

Acute heart failure (AHF) has become a global public health burden largely because of the associated high morbidity, mortality, and cost. The treatment options for AHF have remained relatively unchanged over the past decades. Historically, clinical congestion alone has been considered the main target for treatment of acute decompensation in patients with AHF; however, this is an oversimplification of the complex pathophysiology. Within the similar clinical presentation of congestion, significant differences in pathophysiological mechanisms exist between the fluid accumulation and redistribution. Tissue hypoperfusion is another vital characteristic of AHF and should be promptly treated with appropriate interventions. In addition, recent clinical trials of novel therapeutic strategies have shown that heart failure management is ‘time sensitive’ and suggested that treatment selection based on individual aetiologies, triggers, and risk factor profiles could lead to better outcomes. In this review, we aim to describe the specifics of the ‘time‐sensitive’ approach by the clinical phenotypes, for example, pulmonary/systemic congestion and tissue hypoperfusion, wherein patients are classified based on pathophysiological conditions. This mechanistic classification, in parallel with the comprehensive risk assessment, has become a cornerstone in the management of patients with AHF and thus supports effective decision making by clinicians. We will also highlight how therapeutic modalities should be individualized according to each clinical phenotype.

Obstructive sleep apnea (OSA) is induced by a sleep-related collapse of the upper airway in association with multiple factors. The severity of OSA is determined by the apnea-hypopnea index (AHI). Although obesity and sex differences are common factors in OSA, the level of the AHI varies to the same degree according to the age and sex and degree of obesity. However, only a few studies have evaluated AHI over 100/h, those reports did not describe why they set the AHI cutoff at 100/h. The purpose of this study was to elucidate the pathogenesis of “very” severe OSA, defined as having an AHI > 100/h. AHI > 100/h was set as very severe OSA (VS-OSA) in this study. As controls, moderate to severe OSA patients, matched with VS-OSA for age, sex, and body mass index (BMI), were enrolled. The findings of polysomnography and cephalography between VS-OSA and controls were compared. Eleven patients in the VS-OSA group (mean AHI 110.2/h) and 22 patients in the control group (mean AHI 41.6/h) were compared (mean age 50.2 vs 50.6, male:female 5:6 vs 10:12, mean BMI 35.4 kg/m2 vs 34.5 kg/m2). There were no significant differences in the clinical characteristics. In the polysomnographic parameters, the VS-OSA group showed apnea predominance, the mean percutaneous oxygen saturation (SO2) was significantly lower in all sleep stages, and the minimum SO2 was significantly lower (49.0% vs 77.5%, p = 0.002). A similar apnea duration and rather shorter hypopnea duration were shown. The time of apnea-to-arousal was significantly earlier (− 0.1 s vs 0.9 s, p = 0.003). Lung-to-finger circulation time showed no differences. The cephalometric findings showed no significant differences. VS-OSA patients were more likely to have apnea predominance, desaturation when sleeping despite a similar apnea duration, and rather shorter hypopnea duration, and arousals were evoked significantly earlier.

The novel coronavirus infection that began at the end of 2019 (coronavirus disease 2019: COVID-19) epidemic has become a pandemic and is now pandemic in the world At present, the most recent data available, the cumulative number of patients and deaths worldwide is over 20 9 million and 750,000, respectively The cumulative number of patients in Japan is 52,600, with more than 1,000 deaths After the so-called first wave in April-May of this year, the number of patients is now on the rise again across the country At the beginning of the epidemic, it was a completely unknown infectious disease, but physicians in the field are gradually gaining experience and knowledge Report of a Roundtable Discussion on the COVID-19 epidemic over the past 7 months and how physicians should approach this disease in the future

Clear cell carcinoma (CCC) is a malignant neoplasm of epithelial origin classified in the 2017 World Health Organization (WHO) classification as a low-grade salivary gland tumor consisting of glycogen-rich clear cytoplasm. We report a case of a 34-year-old woman presented in our department following the complaint of a mass in her right retromolar area. The tumor measured 10-mm in diameter and was elastic and hard mass. Spontaneous pain or tenderness and desensitization of the tongue were not observed. Marginal resection of the mandible was performed under general anesthesia. The lesion was located in the minor salivary gland that is mainly composed of mucus glands and had a relatively clearly defined circular shape. However, there was no film fabrication in the surrounding resions. Additionally, atypical cells comprising a clear cytoplasm and irregularly shaped pyknotic nuclei were growing in sheet form or island form, and markedly hyalinized fascicles were observed between the alveolar walls of the atypical cells. Immunohistochemical stains revealed these tumor cells to be positive for epithelial cell markers but negative for myoepithelial ones. Considering the above findings, the tumor was diagnosed as CCC. The patient is currently free from disease 37 months after surgery.

STUDY OBJECTIVES: Sleep is an important recovery period for athletes. Women, including athletes, have reported sleep disturbances around menses. Thus, the aim of this study was to assess the changes in objective sleep parameters in the nights during menses and in the midfollicular phase of the menstrual cycle of young female athletes. METHODS: Female collegiate athletes with regular menstrual cycles were recruited. The participants underwent home electroencephalogram monitoring during the first and second nights after the onset of menses (M1 and M2, respectively) and during one night between the 7th and the 10th night after menses onset (midfollicular phase). RESULTS: Data from 45 athletes were analyzed. The total sleep time was significantly reduced, and sleep onset latency was significantly prolonged in M2 compared with those in the night during the midfollicular phase. Sleep efficiency was significantly reduced in M1 compared with that in the night during the midfollicular phase. Changes in the percentage of deep sleep across menstrual cycles differed among the participants with and without menstrual symptoms or concerns for sanitary products; moreover, such participants spent a lower percentage of time in deep sleep in M1 compared with the other nights. CONCLUSIONS: Collegiate female athletes with regular menstrual cycles are likely to have trouble falling asleep, tend to sleep less, and when concerned about sanitary products, have less deep sleep during menses. Even in young female athletes with regular menstrual cycles, sleep can be disturbed during menses. Interventions to restore or improve sleep should be considered. CITATION: Koikawa N, Takami Y, Kawasaki Y, et al. Changes in the objective measures of sleep between the initial nights of menses and the nights during the midfollicular phase of the menstrual cycle in collegiate female athletes. J Clin Sleep Med. 2020;16(10):1745–1751.

Background: Sleep disordered breathing (SDB) is prevalent and associated with increased mortality in patients both with and without cardiovascular disease (CVD). Many portable monitoring devices, including peripheral arterial tonometry (PAT)-based devices, have been developed. Although previous studies have demonstrated that the apnea-hypopnea index (AHI) determined by PAT devices (pAHI) is strongly correlated with AHI determined by polysomnography (AHI-PSG), no data have been reported from a Japanese patient population or patients with CVD. In this study we compared the parameters determined by PAT-based devices with those determined by polysomnography in Japanese patients with CVD. Methods and Results: We enrolled 120 patients undergoing overnight polysomnography at 6 Japanese centers. A PAT-based device was used simultaneously with polysomnography. Polysomnography recordings were scored centrally by a technician in a blinded manner. PAT-based device recordings were scored using an automatic algorithm. There was a strong correlation between pAHI and AHI-PSG (r=0.896; P

BACKGROUND Portable monitoring devices have been developed for in-home screening and to aid in the diagnosis of sleep disordered breathing (SDB) while increasing accessibility and reducing costs. Although there are many different devices available in the market, most have not undergone rigorous validation. Therefore, although such devices are promising, more research on their clinical utility is necessary. The purpose of this study was to assess the clinical utility of a type 4 home sleep apnea test (HSAT) as an in-home screening for SDB. METHODS We investigated consecutive subjects who underwent in-laboratory overnight polysomnography following in-home screening using HSAT. We evaluated the correlation between apnea-hypopnea index (AHI) by in-laboratory overnight polysomnography and by HSAT and evaluated the sensitivity and specificity for AHI ≥5 and AHI ≥30 by the receiver operating characteristic (ROC) analysis. RESULTS Finally, data of 387 participants (86.8% men, mean age 55.3±13.3 years and body mass index 25.1±4.1 kg/m2) were assessed. In all patients, AHI by HSAT correlated significantly with AHI by polysomnography (r=0.670, P

Preeclampsia (PE) is a leading cause of maternal morbidity and mortality. Nicotinamide has beneficial effects on PE. In this study, we evaluated the effect of nicotinamide on placental development using a PE mouse model. To generate the PE model, a recombinant adenovirus to overproduce soluble fms-like tyrosine kinase 1 (sFlt-1) was administered to mice (Jcl:ICR) at 8.5 day post-coitum (dpc). Plasma and placenta samples were harvested at 12.5 dpc. Fetal and placental weight was significantly decreased at 12.5 dpc in PE mice. Plasma and placental acylcarnitine levels were significantly higher in PE mice than those in control mice. Glycolysis was accelerated and glucose metabolic flow was altered with hypoxia, leading to ATP shortage in the labyrinth of PE mice. In PE mice, ATP production was diminished, and fatty acid oxidation was accelerated in the placenta, consequently, blood carnitine and acylcarnitine levels were increased. The mitochondrial morphology in BeWo cells was impaired under hypoxia. Nicotinamide treatment reversed fetal growth restriction, placental development, and altered metabolic flow in the early stage in PE. In addition, nicotinamide normalized impaired mitochondrial morphology. Hence, targeting this metabolic alteration in the placenta using nicotinamide may serve as a potential therapeutic approach for PE treatment.

Regarding the comparison between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) for stage III/IV ovarian, tubal and peritoneal cancers, EORTC55971 and CHORUS studies demonstrated noninferiority of NACT. Previously, we reported reduced invasiveness of NACT in JCOG0602. This is a final analysis including the primary endpoint of overall survival (OS).Patients were randomised to PDS (PDS followed by 8x paclitaxel and carboplatin, i.e. TC regimen) or NACT (4x TC, interval debulking surgery [IDS], 4x TC). The primary endpoint was OS. The noninferiority hazard ratio (HR) margin for NACT compared with PDS was 1·161. The planned sample size was 300.Between 2006 and 2011, 301 patients were randomised, 149 to PDS and 152 to NACT. The median OS was 49·0 and 44·3 months in the PDS and NACT. HR for NACT was 1·052 [90·8% confidence interval (CI) 0·835-1·326], and one-sided noninferiority p-value was 0·24. Median progression-free survival was 15·1 and 16·4 months in the PDS and NACT (HR: 0·96 [95%CI 0·75-1·23]). In the PDS arm, 147/149 underwent PDS and 49/147 underwent IDS. In the NACT arm 130/152 underwent IDS. Complete resection was achieved in 12% (17/147) of PDS and 31% (45/147) of PDS ± IDS in the PDS arm and in 64% (83/130) of IDS in the NACT arm. Optimal surgery (residual tumour1 cm) was achieved in 37% (55/147), 63% (92/147), and 82% (107/130 respectively. In the NACT, PS 2/3, serum albumin ≤2·5, CA125 2000 an institution with low study activity was advantageous, whereas clear/mucinous histology was disadvantageous for OS.The noninferiority of NACT was not confirmed. NACT may not always be a substitute for PDS. However, as our study had smaller numbers, the noninferiority of the previous studies cannot be denied.Ministry of Health, Labour and Welfare, Japan and the National Cancer Center, Japan.UMIN000000523.

Objective: Additional risk factors for preterm delivery in pregnant women with cervical shortening are not fully understood; however, mid-trimester cervical shortening is accepted as a risk factor for preterm delivery. This study aimed to identify risk factors associated with subsequent preterm delivery among patients with short cervix detected after late mid-trimester. Materials and methods: This was a retrospective study of medical data from a single perinatal tertiary facility. We identified 134 asymptomatic women with singleton pregnancies where cervical shortening (≤25 mm) was detected during routine universal screening at 22–33 weeks. Statistical analyses were conducted to identify causal relationships between the incidence of preterm delivery and known risk factors for preterm delivery. Results: Incidence of preterm delivery was 27.6% (37/134) and preterm premature rupture of membrane was preceded in 46.0% (17/37) of the women with preterm delivery. Using logistic regression analysis, we identified uterine contractions [aOR 4.25, 95% confidence intervals (CI):1.68–12.1] and increased C-reactive protein (CRP) and increased white blood cell (WBC) in blood test (CRP: aOR 3.45, 95% CI:1.50–9.71; WBC: aOR 1.28, 95% CI: 1.08–1.55) as risk factors which significantly increased the risk of preterm delivery among women diagnosed with short cervix. Preterm delivery occurred in 91% of women positive for both uterine contractions and CRP >0.5 mg/dl. Conclusions: Uterine contraction and elevated CRP were additional risk factors for preterm delivery among women with short cervix. These results might be clinically useful to evaluate subsequent risk for preterm delivery in asymptomatic pregnant women presenting with short cervix in mid-pregnancy. Keywords: Preterm labor, Cervical length, Inflammation, Pregnancy

Relationship between metabolic syndrome and hypercapnia among obese patients with sleep apnea

In human sepsis, little is known about the relationships between complement activation and the clinical characteristics of sepsis, including disseminated intravascular coagulation (DIC), interventions, and prognosis.Adult patients with sepsis admitted from November 2016 to December 2018 were included. We used the plasma levels of soluble C5b-9 (SC5b-9) as a marker of complement activation. We compared the clinical characteristics and complement components between patients with and without DIC. We also compared the clinical characteristics and each DIC parameter across quartile groups for the SC5b-9 value.Forty-nine sepsis patients were eligible. Thirty-four patients developed DIC, and eight patients died. The median (interquartile range) SC5b-9 value was 342 (261-501) ng/mL. Compared with patients without DIC, patients with DIC showed lower C3 levels (mean, 95.7 vs. 70.4 mg/dL, P 0.01) and higher SC5b-9 levels (median, 287 vs. 400 ng/mL, P = 0.01). Patients were stratified by SC5b-9 quartile (ng/mL: low:260, moderate: 260-342, high: 343-501, highest:501). The mean Sequential Organ Failure Assessment score varied across these groups (P = 0.02). In the high and highest groups, many more patients received vasopressors and developed DIC. In the highest group, the coagulation parameters were severe, and thrombocytopenia was prolonged. In-hospital mortality tended to be high (33%) in the highest group.The degree of complement activation is related to DIC, severity, intensive interventions, and mortality. Further studies are needed to confirm the usefulness of SC5b-9 for stratifying sepsis patients.

Hypercalcemia of malignancy frequently manifests as paraneoplastic syndrome in patients with solid tumors. A 71-year-old man was diagnosed with stage IIIB lung squamous cell carcinoma. Laboratory examination revealed high serum calcium concentration with elevated serum parathyroid hormone-related protein (PTHrP) and 1,25-dihydroxyvitamin D3 levels. As the patient did not respond to the initial treatment with calcitonin, extracellular fluid infusion, and chemotherapy, systemic prednisolone was administered additionally. Thus, the levels of serum calcium normalized and PTHrP and 1,25-dihydroxyvitamin D3 decreased simultaneously. To our knowledge, this is the first case report on the successful treatment of hypercalcemia of malignancy caused by PTHrP and 1,25-dihydroxyvitamin D3 cosecretion in a patient with lung cancer.

Spindle cell lipomas and pleomorphic lipomas are uncommon and distinct variants of benign lipomas. Although spindle cell lipomas and pleomorphic lipomas were originally considered different entities, the recent WHO classification defines them as spindle cell/pleomorphic lipoma (SCL/PL). This is because of their similar clinical features and the existence of intermediate histopathological features between them. A 77-year-old male presented to our clinic with a painless swelling on the left inferior border of the mandible. Computed tomography revealed a clearly defined mass in the subcutaneous lesion. With a histopathological diagnosis of myxolipoma, demonstrated by biopsy, excisional surgery was performed under general anesthesia. The histopathology revealed SCL/PL with the presence of spindle cells and mature adipocytes. No tumor recurrence had been noted at two year after surgery.

Cervical intraepithelial neoplasia (CIN), a precursor lesion to cervical cancer, is caused by high-risk human papillomavirus (HPV), high-grade CIN lesions (CIN2-3) are precancerous and require treatment. No globally approved therapy is available for CIN2-3 treatment. This study is a placebo-controlled randomized clinical trial of GLBL101c treatment for CIN2 in 40 patients with HPV16-positive CIN2 who were 1:1 randomized to receive GLBL101c (1 g/daily) or placebo for 5 days at 1, 2, 4, and 8 weeks. No differences were noted between the GLBL101c and placebo groups for patient background and adverse events. Moreover, no statistically significant difference was noted between the two groups at the primary endpoint, pathological regression after 16 weeks of the first oral dose, however, only in the GLBL101c group, two patients had complete regression (CR, regression to normal within 16 weeks). IFNγ production was significantly correlated with the number of spots identified by the interferon gamma enzyme-linked immunospot (IFNγ-ELISPOT) assay using cervical lymphocytes (CxLs) or peripheral blood mononuclear cells. In the two cases of CR, E7-specific Th1 immune responses were observed at week 16. Therefore, we concluded as a novel Lactobacillus-based vaccine with stronger immunogenicity than GLBL101c should be developed.

STUDY OBJECTIVES: Postarousal hypersynchrony (PAH) is an atypical arousal pattern in children’s electroencephalography. PAH is an abrupt shift to slower frequencies in arousal-related responses, appearing as slow-wave clusters. In contrast, the prevalence of PAH in healthy young adults is still unknown. Here, we examined the prevalence and characteristics of PAH in healthy young participants. METHODS: Thirty healthy young participants underwent 1 night of polysomnography (13 females, 22.8 ± 2.0 years [mean ± standard deviation]). We examined the prevalence of PAH as a function of sleep stage, sleep cycle, and time course (the first or the second half). The correlation between PAH and sleep variables was examined. The percent of total sleep time in the N3 stage (%N3) was compared for each sleep cycle and time course. RESULTS: Twenty-eight out of 30 participants exhibited PAH (4.6 ± 4.8 times per night). PAH increased significantly during the first sleep cycle and the first half-sleep period. It was observed only in nonrapid eye movement and not in rapid eye movement sleep. The number of PAHs correlated with the number of arousals and arousal indices. The %N3 increased in the first half-sleep and the first sleep cycle. CONCLUSIONS: PAH was relatively common in healthy young participants. Since PAH occurred in a state with a high prevalence of %N3, the first sleep cycle, or the first half-sleep, we suggest that PAH may be affected by the sleep homeostasis process. Since PAH occurred only in non-rapid eye movement sleep and correlated with arousal increment, it may have the function of suppressing non-rapid eye movement sleep’s cortical arousal. CITATION: Suzuki Y, Kawana F, Satoh M, Abe T. The abrupt shift to slower frequencies after arousal from sleep in healthy young adults. J Clin Sleep Med. 2021;17(12):2373–2381.

STUDY OBJECTIVES: Patients with sleep-disordered breathing have cyclic variation of heart rate (CVHR) in response to respiratory events. However, limited data are available regarding the utility of CVHR as a screening tool for sleep-disordered breathing in patients with mixed heart failure (HF) and those without HF. METHODS: We enrolled consecutive patients with and without HF who underwent full polysomnographies with simultaneous Holter electrocardiogram monitoring. We determined the temporal position of the individual dips comprising the CVHR score using time-domain methods. RESULTS: The data of 101 patients, including 70 with and 31 without HF, were analyzed. The CVHR score was significantly correlated with the apnea-hypopnea index (r = .667, P < .001) and limits of agreement between the apnea-hypopnea index and CVHR score were −21.8 to 35.2. The receiver operating characteristic analysis demonstrated that the CVHR score (best cut-off of 23.5 events/h) identified severe sleep-disordered breathing with a sensitivity of 83.3%, specificity of 79.5%, and the area under the curve of 0.856. In addition, there was no interaction between the presence or absence of HF and the apnea-hypopnea index–CVHR score relationship (P = .323). CONCLUSIONS: The CVHR score, determined by Holter electrocardiogram monitoring, is a useful tool for evaluating sleep-disordered breathing even in patients with mixed HF and patients without HF. CITATION: Yatsu S, Kasai T, Naito R, et al. Utility of cyclic variation of heart rate score as a screening tool for sleep-disordered breathing in patients with heart failure. J Clin Sleep Med. 2021;17(11):2187–2196.

The health benefits of physical activity have been widely recognized, yet there is limited information on associations between accelerometer-related parameters and established patient-reported health status. This study investigated the association between the waist-worn accelerometer measurements, cardiopulmonary exercise testing (CPX), and results of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in heart failure (HF) patients hospitalized for acute decompensation. A total of 31 patients were enrolled and wore a validated three-axis accelerometer for 2 weeks and completed the short version of the KCCQ after removing the device. Daily step counts, exercise time (metabolic equivalents × hours), and %sedentary time (sedentary time/device-equipped time) were measured. Among the measured parameters, the best correlation was observed between %sedentary time and the KCCQ overall and clinical summary scores (r = −0.65 and −0.65, each p &lt, 0.001). All of the individual domains of the KCCQ (physical limitation, symptom frequency, and quality of life), with the exception of the social limitation domain, showed moderate correlations with %sedentary time. Finally, oxygen consumption assessed by CPX demonstrated only weak associations with the accelerometer-measured parameters. An accelerometer could complement the KCCQ results in accurately assessing the physical activity in HF patients immediately after hospitalization, albeit its correlation with CPX was at most moderate.

Spitz nevus is an important differential diagnosis of malignant melanoma, especially in young adults. This case provides a significant information about unusual dermoscopic features of adult Spitz nevus, which may reflect changes over the years.

INTRODUCTION: Bone is a unique tissue that undergoes frequent remodeling. An imbalance between bone formation and resorption results in osteoporosis. Glucocorticoids (GCs) are widely used clinically as anti-inflammatory and immunomodulatory. However, their prolonged use may induce osteoporosis. Currently, evidences revealed that also the alveolar processes are subject to osteoporosis. Bisphosphonates, such as Alendronate, Risedronate and Zoledronate, are recommended by several international guidelines as the first-line therapy for the prevention and treatment of generalized glucocorticoids induced osteoporosis (GIOP). OBJECTIVES: To evaluate the effect of bisphosphonates (Risedronate) on the alveolar bone of rats with glucocorticoids induced osteoporosis. MATERIALS AND METHODS: Thirty female albino rats were divided into 3 equal groups (10 rats each) as follows: Group I: control group. Group II: glucocorticoids group (Dexamethasone 0.6mg/kg twice/week subcutaneously). Group III: Risedronate treated group; rats were given Dexamethasone (0.6mg/kg twice/week subcutaneously) and Risedronate (1mg/kg/day orally). After 12 weeks, rats were euthanized, and the mandibular alveolar bone was evaluated histologically by light microscope and ultra-structurally by scanning electron microscopy and energy dispersive X-ray (EDX) microanalysis. RESULTS: Group II showed deterioration of the alveolar bone in comparison to the control group I. The alveolar bone structure in Group III rats, treated by bisphosphonates (Risedronate), showed remarkable improvement both histologically and ultrastructurally in comparison to group II. Moreover, EDX analysis revealed a significant decrease of calcium levels in group II in comparison to group I. However, in group III calcium levels were restored to normal levels comparable to the control group I. CONCLUSIONS: Glucocorticoids intake induces loss of the alveolar bone; which, could be counterbalanced by bisphosphonates.

INTRODUCTION: Depression is one of the most prevalent psychological disorders. It affects all body systems including endocrinal,neurological and immune system. Additionally, it is thought to affect bone homeostasis. Antidepressants are the most commonly prescribeddrugs. They are classified into tricyclic and tetra cyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs) and selectiveserotonin-reuptake inhibitors (SSRIs). Fluoxetine, which is a selective serotonin-reuptake inhibitor, is used for the treatment of depression byselectively acting on serotonin (5-HT). Fluoxetine plays a major role in bone apposition and in maintaining the bone homeostasis.OBJECTIVES: To investigate the effect of selective serotonin-reuptake inhibitor (fluoxetine) on the structure of alveolar bone in rats withinduced depression.MATERIALS AND METHODS: Thirty adult male rats were divided as follows: Group I: (control group) which consists of 10 rats, Group II: (depression group) 10 rats were exposed to chronic unpredictable stress (CUS) to induce depression, Group III: (fluoxetine group) 10 ratswere exposed to chronic unpredictable stress (CUS) to induce depression and at the same time they were orally supplied with 10 mg/kg/day offluoxetine. After 3 months, the mandibles were dissected out and prepared for histological analysis using light microscope, scanning electronmicroscope (SEM) and energy dispersive x-ray microanalysis (EDX).RESULTS: In the control group, the alveolar bone surface showed a regular and smooth outline. In the depression group, there was a significantdisturbance in the bone architecture. The bone surface showed an irregular outline with multiple osteoclasts lying in How ship's lacunae. Deeplystained incremental lines were also evident. In the fluoxetine group, the bone surface restored its regular outline with multiple osteoblasts andosteocytes. The bone showed incremental lines indicating bone formation.CONCLUSIONS: Depression can lead to bone loss and osteoporosis. Fluoxetine is an effective drug in enhancing the bone condition andrestoring the normal architecture of the alveolar bone.

Background and Objective This study evaluated the effects of a mattress with better body pressure dispersal in comparison to a control mattress on sleep quality. Methods In this randomized crossover study, 10 healthy young men slept in an experimental sleep room on either a functional mattress made from polyurethane, with a special four-layer three-dimensional structure, or a control mattress made from solid polyester wadding, which is a mattress commercially available in Japan. Polysomnography recordings were used to characterize sleep architecture, and the length of slow wave sleep (SWS) episodes and delta power density were calculated from the electroencephalography data and subjective sleep quality was evaluated by questionnaire they answered after waking. Results There were no significant differences in sleep latency, the total duration of each sleep stages, total sleep time, or sleep efficiency. Although the difference was subtle, delta power density significantly increased with the functional mattress. There was no difference in the total duration of SWS, but there were significantly fewer SWS episodes with the functional mattress (10.3 ± 1.8) than with the control mattress (16.9 ± 1.2) and longer SWS episode duration (10.9 ± 1.7 min) with the functional mattress than with the control mattress (5.6 ± 0.5 min). Conclusions It was suggested that the functional mattress lengthened SWS episode duration, and its fragmentation was effective in evaluating the sleep quality of healthy young individuals.

Background Anti-programmed cell death 1 antibody is a standard therapy for advanced non-small cell lung cancer (NSCLC). However, immune-related adverse events (irAEs), such as skin reactions, are frequently observed. Although skin reactions are associated with clinical efficacy in melanoma, this association in advanced NSCLC and predictors of irAEs remain unclear. Accordingly, this study identified potential correlations of skin reactions with clinical efficacy and clinical predictors of development of skin reactions. Subjects, Materials, and Methods We retrospectively surveyed patients with advanced NSCLC who received nivolumab or pembrolizumab monotherapy at Sendai Kousei Hospital (n = 155) during January 2016 to April 2018. Treatment efficacy was evaluated in patients with and without skin reactions, and associated predictive markers were determined. A 6-week landmark analysis was conducted to assess the clinical benefit of early skin reactions. Results Skin reactions were observed in 51 patients with a median time to onset of 6.4 weeks. The overall response rate (ORR) was significantly higher in patients with skin reactions (57% vs. 19%, p < .001). Median progression-free survival (PFS) durations of 12.9 and 3.5 months and overall survival durations of not reached and 11.4 months were observed in patients with and without skin reactions, respectively. In the 6-week landmark analysis, the ORR was significantly higher in patients with skin reactions, and skin reactions were significantly associated with increased PFS. A multivariate analysis identified pre-existing rheumatoid factor (RF) as an independent predictor of skin reactions. Conclusion Skin reactions appeared beneficial in patients treated with nivolumab/pembrolizumab for advanced NSCLC and could be predicted by pre-existing RF. Further large-scale validations studies are warranted.

Background Restless legs syndrome (RLS) is a neurological disorder characterized by leg restlessness and dysesthesia. Although the relationship between RLS and heart failure (HF) has been reported, the prevalence and clinical significance of RLS in patients with HF remain to be elucidated. Methods and Results We enrolled consecutive patients with HF who were admitted to our institutions. RLS was diagnosed using the International Restless Legs Syndrome Study Group criteria. Subjective sleepiness, sleep quality, and quality of life (QoL) were assessed using the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and 8-item Short Form (SF-8), respectively. Among the 133 patients, 18 (13.6%) had RLS and were younger than those without RLS (62.4±13.4 vs 70.0±12.2, P = .017). The RLS group had significantly disrupted sleep quality and QoL, with greater PSQI score (8.0±3.2 vs 5.9±3.3, P = .015) and lower SF-8 physical component summary (PCS) score (35.6±6.5 vs 40.7±9.5, P = .031), despite similar ESS and SF-8 mental component summary scores. In the multivariable regression analysis, RLS was associated with greater PSQI (β=0.211; P = .014) and lower PCS score (β=−0.177; P = .045). Conclusion In the patients with HF, RLS was prevalent, and sleep quality and QoL may be disrupted by RLS.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2014. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January 2014 and April 2015 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1534 strains (335 Staphylococcus aureus, 264 Streptococcus pneumoniae, 29 Streptococcus pyogenes, 281 Haemophilus influenzae, 164 Moraxella catarrhalis, 207 Klebsiella pneumoniae, and 254 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 43.6%, and those of penicillin-susceptible S. pneumoniae was 100%. Among H. influenzae, 8.2% of them were found to be β-lactamase-producing ampicillin-resistant strains, and 49.1% to be β-lactamase-non-producing ampicillin-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 9.2% and 0.4%, respectively.

INTRODUCTION: Ozone (O3) gas is a molecule consisting of three atoms of oxygen in a dynamically unstable structure due to the presence of mesomeric states. Ozone therapy has been utilized and heavily studied for more than a century. Its effects on bone are proven and consistent. It enhance osteoblastic activity and new bone formation. Diabetes mellitus (DM) is a chronic metabolic disease that potentially affect bone metabolism, structure, and mineral density. OBJECTIVES: to evaluate histologically the possible effect of ozone therapy on bone healing after tooth extraction in rabbits with alloxan induced diabetes mellitus. MATERIALS AND METHODS Thirty adult male New Zealand rabbits weighing 1500-2500 grams (approximately six months of age) will be divided into 3 equal groups: group I;(control group), group II; (diabetic group): diabetes was induced by a single intravenous injection of alloxan in a dose of 100 mg/kg and group III:(Ozone group) rabbits was treated as in diabetic group then they was treated with ozone therapy which will be applied topically in the form of gel inside the tooth socket. Rabbits were sacrificed after six weeks. Each sample were dissected and prepared for histological evaluation. RESULTS: in diabetic group the socket showed empty central region surrounded by disorganization bony trabeculae. The bony trabeculae surrounded less vascular spaces and more fibrous tissue.in diabetic group treated with ozone therapy the socket showed complete filling of the socket with newly formed bone.The socket with newly formed bone surrounding highly vascular bone marrow. CONCLUSIONS: Ozone gel application accelerates socket healing and enhances bone formation in diabetes mellitus

Purpose: Monitoring response and resistance to 5-azacitidine (AZA) is essential when treating patients with myelodysplastic syndrome (MDS). To quantify methylated DNA not only in the promoter region but also in the gene body, we established a single-molecule methylation assay (SMMA). Patients and methods: We first investigated the methylation extent (expressed as methylation index [MI]) by SMMA among 28 MDS and 6 post-MDS acute myeloid leukemia patients. We then analyzed the MI in 13 AZA-treated patients. Results: Whole-blood DNA from all 34 patients had low MI values compared with healthy volunteers (P

Background Primary pulmonary leiomyosarcoma is a rare malignant tumor. We herein report a case of primary pulmonary leiomyosarcoma that was completely resected by surgery after neoadjuvant chemotherapy. Case presentation A 60-year-old man presented with cough. Chest computed tomography showed an 11-cm mass in the right upper lobe of the lung that had invaded the superior vena cava. Endobronchial ultrasound-guided transbronchial needle aspiration revealed leiomyosarcoma of the lung. We considered complete resection of the tumor to be very difficult because of the tumor invasion into the right atrium inflow of the superior vena cava, so we performed chemotherapy using doxorubicin for five cycles. After chemotherapy, the tumor size decreased to 5.6 cm, and we performed right upper lobectomy with combined resection of the superior vena cava. The tumor was completely resected by surgery. The patient is alive without recurrence 17 months postoperatively. Conclusions We encountered a case of primary pulmonary leiomyosarcoma that was successfully treated by surgery after neoadjuvant chemotherapy. Doxorubicin monotherapy was effective in this case. Surgery combined with neoadjuvant chemotherapy should be considered for such cases, as a long-term survival can be achieved by complete resection of primary pulmonary leiomyosarcoma.

The push and slide method is a method of endoscopic bronchial occlusion using an endobronchial Watanabe spigot that facilitates occlusion of the target bronchus rapidly and accurately using a guidewire. We herein report the case of a man who was diagnosed with empyema forming bronchopulmonary fistulae that was successfully treated by endoscopic bronchial occlusion. Because of the multiple fistulae, balloon occlusion was not a favorable therapeutic approach. Instead, the push and slide method was used in order to detect the fistulae. Endoscopic occlusion, particularly that using the push and slide method, may be a valid treatment option for empyema with multiple bronchopulmonary fistulae.