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Background Epiretinal membrane (ERM) is a disease that affects the vitreoretinal interface and causes metamorphopsia, anorthopia, and decreased visual acuity. In this study, ERM patients who underwent internal limiting membrane (ILM) peeling were classified as those with glaucoma (Group G) and a control group (Group C). Changes in ganglion cell complex (GCC) thickness were compared between these groups to investigate whether such changes had an effect on progression of glaucoma from structural change. Methods This was a retrospective, observational study that included 27 eyes of 27 patients. Group C included 22 eyes, and Group G included 5 eyes. Patients underwent ILM peeling, and cataract surgery was combined with vitrectomy for 16 phakic eyes; 2 phakic eyes and 9 aphakic eyes were treated only with vitrectomy. GCC thickness was measured preoperatively and at 2 weeks and 1, 3, and 6 months postoperatively, and these values and the rates of thinning were compared between the two groups. Results The mean age of patients was 66.7±12.8 years (range 30-84 years). There was no significant difference between groups in the thickness of the GCC or its rate of thinning after ILM peeling. Conclusions The present results suggest that this procedure does not cause structural exacerbation of glaucoma in glaucoma patients. Although further studies of the functional effects of ILM peeling are required, the present results suggest that there is no significant difference between the two groups.

Social anxiety disorder (SAD) is associated with fear of negative evaluation and heightened performance monitoring. The best-established treatments help only a subset of patients, and there are no well-established predictors of treatment response. The current study investigated whether individual differences in processing errors might predict response to gaze-contingent music reward therapy (GC-MRT). At baseline, healthy control subjects (HC; n = 20) and adults with SAD (n = 29), ages 19–43 years, completed the Flanker Task while electroencephalography (EEG) data were recorded. SAD participants then received up to 12 sessions over 8 weeks of GC-MRT, designed to train participants’ attention away from threatening and toward neutral faces. Clinical assessments were completed 9- (post-treatment) and 20-weeks (follow-up) after initiating the treatment. At baseline, compared to HC, SAD performed the task more accurately and exhibited increased error-related negativity (ERN) and delta power to error commission. After controlling for age and baseline symptoms, more negative ERN and increased frontal midline theta (FMT) predicted reduced self-reported social anxiety symptoms at post-treatment, and FMT also predicted clinician-rated and self-reported symptom reduction at the follow-up assessment. Hypervigilance to error is characteristic of SAD and warrants further research as a predictor of treatment response for GC-MRT.

After a percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD), in-stent neoatherosclerosis may pose a risk of in-stent restenosis (ISR). To clarify whether non-fasting hypertriglyceridemia contributes to ISR, we examined the relationship between non-fasting hypertriglyceridemia (i.e., triglyceride (TG) level ≥ 200 mg/dL) and ISR after stenting with a bare metal stent (BMS) post-primary PCI in patients with CAD by means of a single-site retrospective analysis. A total of 1,039 patients with CAD were enrolled, and 86 patients (112 lesions) were evaluated for BMS-ISR 3-6 months post-primary PCI. The percentage of patients with non-fasting hypertriglyceridemia was significantly higher in the ISR (+) group than in the ISR (-) group (P < 0.009). The follow-up period and number of patients in the ISR (+) group were significantly smaller than those in the ISR (-) group (P < 0.001). There were no significant between-group differences in the other baseline patient characteristics before the primary PCI or at the time of the follow-up coronary angiography. However, at the follow-up period, the ISR (+) group had significantly lower diastolic blood pressure and high-density lipoprotein cholesterol levels (P = 0.015) and significantly higher TG levels (P = 0.012) than the ISR (-) group. A multiple logistic regression analysis demonstrated that non-fasting hypertriglyceridemia and a follow-up period of ≥ 6 months were independent risk factors for ISR after primary PCI in patients with BMS implantation for stenotic CAD (P = 0.006), with an adjusted odds ratio of 8.232 (1.201-56.410) and 0.006 (95% confidence interval < 0.001-0.045), respectively. Non-fasting hypertriglyceridemia may be an additional independent risk factor for BMS-ISR after primary PCI in patients with CAD.

BACKGROUND Data regarding the clinical features, outcomes and prognostic factors in patients presenting with acute total/subtotal occlusion of the unprotected left main coronary artery (LMCA) remain limited.Methods and Results:From a multi-center registry, 134 patients due to acute total/subtotal occlusion of the unprotected LMCA were reviewed. Emergency room (ER) status classification was defined according to the presence of cardiogenic shock and cardiopulmonary arrest (CPA) in the ER (class 1=no cardiogenic shock; class 2= cardiogenic shock but not CPA; and class 3=CPA). In-hospital mortality and cerebral performance category (CPC) as the endpoints were evaluated. One-half (67/134) of the enrolled patients presented with total occlusion of the unprotected LMCA. Regarding ER status classification, class 1, 2, and 3 were observed in 30.6%, 45.5%, and 23.9% of the patients, respectively. In-hospital mortality occurred in 73 (54.5%) patients; of the remaining patients, 52 (85.3%) could be discharged with a CPC 1 or 2. ER status classification (odds ratio 4.4 [95% confidence interval: 2.33-10.67]; P

To characterize the issues regarding work and employment specific to allogeneic hematopoietic cell transplantation (allo-HCT) survivors, we conducted a nationwide cross-sectional questionnaire survey. We targeted allo-HCT survivors employed at diagnosis, aged 20–64 at survey, and survived ≥2 years without relapse. The questionnaire included the timing of and reasons for resignation (termination of employment contract), and patient-related, HCT-related, work-related, and HCT center-related factors. A total of 1048 eligible participants were included in the analysis (response rate, 60%). The median time after allo-HCT was 5 years (range, 2–30) at the time of survey. After diagnosis, 41% of participants resigned from work throughout the course of treatment. The most frequent timing of the first resignation was “after discharge post-HCT” (46%), followed by “from diagnosis to initial treatment” (27%). Factors significantly associated with resignation included female gender, older age, and part-time employment. Favorable factors included the presence of occupational health staff at the workplace, employment of ≥10 years, and self-employed/freelance. After resignation, the overall incidence of return to work with some accommodations was 76% at 5 years after HCT, but it was 52% without any accommodation. Overall, the rate of resignation was 41%, and the most frequent timing of resignation was after discharge post-HCT, accounting for approximately half of the resignations (46%). Workplace accommodations increased the rate of return to work from 52% to 76%. Early detection of employment-related concerns and support throughout the treatment process are necessary for patients receiving allo-HCT.

Background Infective endocarditis (IE) in patients with adult congenital heart disease (ACHD) remains a diagnostic challenge due to difficulties in detecting endocardial lesions by echocardiography. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has shown good diagnostic performance in prosthetic valve IE. This study aimed to assess its additional diagnostic value in ACHD-associated IE and to characterize its advantages.Methods and Results:Overall, 22 patients with ACHD and clinical suspicion of IE were retrospectively studied. 18F-FDG PET/CT was performed in addition to conventional assessment based on the modified Duke criteria. The final IE diagnosis was determined by an expert team during a 3-month clinical course, resulting in 18 patients diagnosed with IE. Seven patients (39%) were diagnosed with definite IE only by initial echocardiography. An 18F-FDG PET/CT assessment revealed endocardial involvement in the other 9 patients, resulting in the diagnosis of definite IE in 16 in total (88%). Right-sided endocardial lesions were more common (n=12, 67%) but rarely identified by echocardiography, whereas 18F-FDG PET/CT revealed right-sided lesions in 9 patients. A negative 18F-FDG PET/CT (n=7, 39%) assessment was associated with a native valve IE (71% vs. 0%). In 4 patients who were identified with not-IE, neither echocardiography nor 18F-FDG PET/CT detected any suspicious cardiac involvement. Conclusions In the diagnosis of ACHD-associated IE, characterized by right-sided IE, 18F-FDG PET/CT assessment should be useful.

Background Undifferentiated carcinoma (UC) of the pancreas has been considered a highly aggressive malignancy. However, only a few studies have systematically described the clinical course of UC patients. The aim of this study was to clarify the prognosis and construct a prognostic model for patients with unresectable UC. Methods This study was conducted at 17 institutions in Japan, and a total of 55 patients were analyzed. Results The median overall survival (OS) of patients with unresectable UC was 3.95 months. In the multivariate Cox proportional hazards (CPH) model, age ≥65 years, Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, and C-reactive protein (CRP) >10 mg/L were independent prognostic factors for OS (age ≥65 years: hazard ratio [HR], 2.732; 95% confidence interval [CI], 1.353–5.515; ECOG PS ≥ 2: HR, 7.866; 95% CI, 1.981–31.241; CRP >10 mg/L: HR, 1.956; 95% CI, 1.013–3.775). Based on the β coefficients from the CPH model, the prognostic scores were defined as follows: age ≥65 years (3 points), ECOG PS ≥ 2 (6 points), and CRP >10 ml/L (2 points). The final prognostic model was the sum of the points. The derived prognostic model stratified patients into high-risk (score ≥4) and low-risk (score 0–3) groups, with significant differences in OS (1.45 vs. 8.19 months, respectively; p Conclusions The prognostic model stratified patients into high-risk and low-risk groups. These findings suggest that this model can serve as a tool for patient information and decision-making with regard to the therapeutic strategy for UC.

This study investigated the impact of the severity and treatment of Parkinson’s disease (PD) on the swallowing ability and oral environment of patients. Swallowing dysfunction increases the aspiration risk and may lead to poor oral health among patients with PD. We investigated the influences of PD progression and drug treatment on the swallowing ability and oral environment using simple noninvasive screening measurements. We recruited 87 patients with PD (mean age, 71.9 ± 8.0 years; mean Hoehn and Yahr score, 2.9 ± 0.9). The PD condition was assessed in each patient using the unified Parkinson’s disease rating scale (UPDRS) part III, diet type and oropharyngeal function using the swallowing disturbances questionnaire (SDQ), maximum bite force (MBF), tongue pressure (TP), and oral bacterial count (OBC). Levodopa equivalent daily dose (LEDD) was also calculated for 56 participants. Based on an SDQ score of ≥11, 29.5% of patients were dysphagic, but almost all were still on a regular diet. The SDQ score was positively correlated with disease duration (rho = 0.228, p = 0.047 ) and UPDRS part III score (rho = 0.307, p = 0.007 ) but was negatively correlated with OBC (rho = −0.289, p = 0.012 ). OBC was significantly higher among patients with an SDQ score of p = 0.01 ), and the SDQ score was lower in patients with higher OBC requiring professional oral care ( p = 0.03 ). However, OBC was also negatively correlated with LEDD (rho = −0.411, p = 0.004 ). These results indicated low self-awareness of dysphagia among the participants and an association between dysphagia and PD progression. Moreover, the oral environment could have deteriorated with swallowing dysfunction. Patients and clinicians should be aware that higher LEDD can increase xerostomia and associated deficits in oral health.

Objectives This study sought to determine the predictors of anatomical-functional discordance between quantitative coronary angiography (QCA) derived diameter stenosis (QCA-DS) and diastolic pressure ratio during wave-free period (dPRWFP ). Background The discrepancy between angiographical stenosis and physiological significance is frequently experienced in clinical practice. Although the anatomical-functional discordance between angiography and fractional flow reserve (FFR) has been intensively investigated, that of resting index including dPRWFP remains to be elucidated. Methods In a total of 647 angiographically intermediate lesions with QCA-DS between 30 and 70% in 502 patients, predictors of having QCA-DS >50% and dPRWFP > 0.89 (QCA-dPRWFP mismatch), and those of having QCA-DS ≤50% and dPRWFP ≤ 0.89 (QCA-dPRWFP reverse mismatch) were determined. FFR ≤0.80 was defined as positive FFR and the predictors of QCA-FFR discordance were determined as well. Results QCA-dPRWFP mismatch and reverse mismatch were observed in 27.5 and 17.6% of cases, respectively. The predictors of mismatch were non-left anterior descending artery (LAD) lesion, large minimal lumen diameter, low baseline heart rate, and high coronary flow reserve (CFR), while those of reverse mismatch were LAD lesion, non-culprit lesion of acute coronary syndrome, long lesion length, low left ventricular ejection fraction, and low CFR and index of microcirculatory resistance. Age, sex, and the culprit vessel of prior myocardial infarction were not significant determinants of QCA-dPRWFP discordance unlike QCA-FFR discordance derived from the same cohort. Conclusions Anatomical-functional discordance between angiography and dPRWFP was not uncommon. Predictors differed between QCA-dPRWFP discordance and QCA-FFR discordance.

Limited information is available regarding the impact of body weight loss (BWL) in patients with advanced gastric cancer (AGC) who receive second-line chemotherapy. We retrospectively reviewed data for consecutive AGC patients who received second-line treatment with taxane-based chemotherapy at our institution between January 2014 and September 2018. We calculated variables, including percent BWL per month during chemotherapy (%BWL/m), and analyzed the correlations between BWL and other clinicopathological parameters with survival. Forty-four AGC patients were registered (median age, 67.5 years; females

Since sexual function and testosterone levels after image-guided proton therapy (IGPT) have not yet been examined in detail, we prospectively evaluated changes before and after IGPT. Among patients treated with IGPT with or without combined androgen blockade (CAB) therapy between February 2013 and September 2014, patients who agreed to participate in the study and were followed up for >3 years after IGPT were evaluated. Serum testosterone levels were regularly measured together with prostate-specific antigen (PSA) levels before and after IGPT. The Erection Hardness Score (EHS) and the sexual domain summary, function subscale and bother subscale of the sexual domain in the Expanded Prostate Cancer Index Composite (EPIC) were assessed. There were 38 low-risk, 46 intermediate-risk and 43 high- or very-high-risk patients (NCCN classification). Although serum testosterone levels in low-risk patients did not decrease after IGPT, reductions were observed in the average EHS and the sexual domain summary score of the EPIC. In intermediate-, high- and very-high-risk patients, testosterone and PSA levels both increased following the termination of CAB after IGPT, and the average EHS increased. The sexual domain summary score gradually increased, but not above minimally important differences. In intermediate-risk patients, the function subscale increased from 4.4 to 14.8 (P < 0.05) 12 months after IGPT and reached a plateau after 60 months. The results of the present study would suggest the potential of IGPT, and further prospective studies to directly compare IGPT with other modalities are warranted.

Background The deterioration of renal function is a strong prognostic predictor in patients with coronary artery disease. Although percutaneous coronary intervention (PCI) has sometimes resulted in improved renal function (IRF) in acute coronary syndrome (ACS) patients, its clinical implications have not been fully elucidated. This study aimed to investigate the prevalence and predictors of IRF after PCI and its relationship with long-term renal outcomes. Methods In this retrospective observational cohort study, we examined data from 177 ACS patients with non-dialysis advanced renal dysfunction (estimated glomerular filtration rate [eGFR] Results IRF was observed in 66 (37.3%) patients. ST-elevation myocardial infarction and shock during PCI were independent predictors of IRF. Patients were followed up for a median of 695 days. Kaplan-Meier analyses demonstrated that patients with IRF had the lower incidence of initiation of permanent dialysis than those without IRF (Log-rank P = 0.015). Conclusions IRF was relatively common in non-dialysis patients with ACS and advanced renal dysfunction who underwent PCI. ST-elevation myocardial infarction and shock, which may be indicative of hemodynamic instability during PCI, were independent predictors of IRF. Further, IRF was associated with favorable renal outcomes. Hemodynamic stabilization may be important for improving the short-term and long-term renal outcomes of high-risk patients.

Aim As an emergency measure during the coronavirus disease pandemic, the monitoring interval for clozapine use was temporarily extended beyond the regulatory requirement in Japan, which is the safest monitoring interval worldwide. In this study, we aimed to explore the effect of this measure on patients undergoing clozapine treatment. Methods This retrospective chart review study included patients with treatment‐resistant schizophrenia (TRS) who were undergoing clozapine treatment at four psychiatric institutions in Japan. Demographic characteristics and clinical information of these patients were collected on April 27, 2020, when Japanese psychiatrists were virtually allowed to prescribe clozapine beyond the regulatory requirement. Furthermore, information of adverse events related to the emergency measure was collected and analyzed. Results Of the 41 patients with TRS included in this study, 19 patients underwent extended hematological monitoring during clozapine treatment. No psychiatric or hematological adverse events were observed in the patients during the extended monitoring interval. Conclusion This study suggested that there were few adverse events of clozapine‐treated patients related to emergency measures in Japan. However, hematological monitoring intervals during clozapine treatment have been emergently extended worldwide; hence, it is necessary to verify the results of these measures., This retrospective chart review study explored patients with treatment‐resistant schizophrenia who were undergoing clozapine treatment on the expanded hematological monitoring during the coronavirus disease pandemic in April 2020 at four psychiatric institutions in Japan. This study suggested that there were few adverse events of clozapine‐treated patients related to emergency measures in Japan.

Purpose: Neoadjuvant chemotherapy (NAC) has been shown to eradicate axillary lymph node metastasis in approximately 40% of patients. Sentinel lymph node biopsy (SLNB) could be an alternative surgical approach for these patients to avoid morbidity from axillary lymph node dissection (ALND). However, high false-negative rates of SLNB for initially node-positive patients were reported in previous trials. The aim of this study was to evaluate clinicopathological factors and imaging characteristics by MRI and ultrasound (US) as predictors of axillary pathologic complete response (ypN0) after NAC, which enable to identify candidates for SLNB in patients with clinically node-positive disease. Patients and methods: We identified 153 patients with clinically node-positive breast cancer who received NAC from May 2009 to December 2019. Clinicopathological data including age, clinical T/N status, nuclear grade, hormone receptor (HR) and HER2 status were collected. All patients underwent MRI and US before and after NAC. Patients were judged to be node-positive when they have cytologically-proven nodal disease by fine-needle aspiration (FNA) or suspicious lymph nodes by diagnostic imaging. Lymph nodes with cortical thickness (>3.5mm), loss of fatty hilum or round shape (short-axis/long-axis ratio > 0.5) were defined as suspicious lymph nodes. All imaging data were evaluated at baseline and after NAC. To develop a predictive model for ypN0, the association between ypN0 status and clinicopathological and imaging characteristics were assessed by multivariate logistic regression analysis. The area under the receiver operating characteristic (ROC) curve was used to evaluate discrimination by the model. Results: The median age was 55.0 (range: 22-79) years and the mean tumor size was 3.86 ± 2.04 cm. Pretherapeutic lymph node status was assessed by FNA in 88 (57.5%) patients. Of 153 patients, 80 (52.3%) patients had luminal, 39 (25.5%) had HER2-positive, and 34 (22.2%) had triple negative disease. Sequential anthracycline and taxane were administered for 138 (90.2%) patients, and 37 (94.9%) patients with HER2-positive-disease received concomitant anti-HER2 agents preoperatively. Overall, 62 (40.5%) patients achieved ypN0. Independent predictors of ypN0 status were breast complete response by MRI (odds ratio [OR]: 9.01, p Conclusions: Our predictive model based on imaging characteristics by MRI and US could help to identify good candidates for omission of ALND after NAC in patients with initially node-positive breast cancer. Citation Format: Akiko Matsumoto, Miki Yamada, Daisuke Tsukahara, Yasuko Umemoto, Hiromitsu Jinno. Predicting axillary pathologic response to neoadjuvant chemotherapy for node-positive breast cancer: Clinical predictive model by using MRI and ultrasound [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-29.

Study design Acute experimental study. Objectives To investigate the acute response of markers of lipid metabolism and interleukin (IL)-6 to dopamine infusion in people with a cervical spinal cord injury (CSCI). Setting Laboratory of Wakayama Medical University, Japan. Methods Ten participants, four with CSCI and six AB individuals, underwent 50 min of dopamine infusion. Blood samples were collected prior to, immediately after and 1 h following cessation of dopamine infusion for the determination of circulating catecholamine, lipid, ketone body and IL-6 concentrations. Results The adrenaline concentration following dopamine infusion was increased by 59 ± 7% in CSCI (p = 0.038, Cohen's d effect size (ES): 1.47), while this was not changed in AB (p = 0.223). Triglycerides and acetoacetic acid concentration were increased in both groups, immediately after and 1 h post-infusion (triglycerides p ≤ 0.042, ES CSCI: 1.00, ES AB: 1.12; acetoacetic acid p ≤ 0.030; ES CSCI: 1.72, ES AB: 1.31). 3-Hydroxybutyric acid concentration was increased in CSCI only (48 ± 15%, p = 0.039, ES: 1.44; AB p = 0.115). Dopamine infusion did not affect plasma IL-6 concentration in either group (p ≥ 0.368). Conclusions Dopamine infusion induced a sustained increase in triglyceride and ketone body concentrations in persons with CSCI. In contrast, cytokine concentrations were not affected by dopamine infusion. These findings suggest that circulating catecholamines can stimulate metabolism in people with CSCI despite the presence of autonomic dysfunction.

Supplemental digital content is available in the text., Objective The combination of gemcitabine plus nab-paclitaxel (GnP) has not been studied in Japanese patients with resectable pancreatic cancer (PC). This study aimed to assess the tolerability of adjuvant GnP in Japanese patients with resected PC. Methods This was a Phase I, open-label, multicenter, single-arm study of patients with resected PC in Japan. Patients received 125 mg/m2 of nab-paclitaxel and 1000 mg/m2 of gemcitabine on days 1, 8, and 15 of a 28-day cycle for a total of 6 cycles. The primary end point was tolerability, defined as the absence of specific grade 3 or higher treatment-related adverse events by the end of cycle 2. Secondary end points included safety, disease-free survival, and overall survival. Results Forty-one patients were enrolled between June 2016 and February 2017 (median age, 68 years; 51% male; stage II, 95%). Gemcitabine plus nab-paclitaxel met the tolerability criteria in 39 of the 40 patients included in the tolerability analysis set (97.5%). The most common treatment-related adverse events were leukopenia, neutropenia, alopecia, and peripheral sensory neuropathy. After a follow-up of 30.1 months, median disease-free survival was 17.0 months and median overall survival was not reached. Conclusions These results show that adjuvant GnP is tolerable in Japanese patients with resected PC. Clinical Trial Registration No.: JapicCTI-163179

Purpose Breast ultrasound has been widely used as an essential examination for diagnosing breast cancer. However, standardized diagnostic criteria are as yet lacking. This study aimed to develop a simple diagnostic flowchart for beginners learning breast ultrasonography. The diagnostic flowchart was developed based on the recall criteria widely used in Japan. Methods We conducted a multicenter study to examine recall criteria usefulness in the diagnostic phase of breast disease. Women with ultrasound-visible breast masses who underwent B-mode breast ultrasound examination were recruited from 22 hospitals in Japan between September 2009 and January 2010. B-mode images were evaluated by members of the centralized image interpretation committee. We developed the new diagnostic flowchart based on the results. The usefulness of the diagnostic flowchart was assessed by employing datasets from the current study and another study which we conducted (BC-04 study). Results We evaluated 1045 solid masses (malignant: 495, benign: 550). Multivariate analysis showed that shape, margin, echogenic halo, interruption of the mammary gland interface, and depth width ratio were significant findings for distinguishing between benign and malignant masses. We modified the recall criteria and developed our novel diagnostic flowchart using these findings. The sensitivity and specificity of the new flowchart (current study: 0.97, 0.45; BC-04 study dataset: 0.95, 0.45) were similar to those of experts (current study: 0.96, 0.54; BC-04 study dataset: 0.98, 0.38). Conclusion We developed a simple diagnostic flowchart for breast ultrasound. This flowchart is anticipated to be applicable to educating beginners learning breast ultrasound.

[Purpose] To determine the effects of lower limb ergometer exercise on the spasticity and joint range of motion of the lower extremity and gait function in patients with cerebral palsy and spastic paralysis. [Participants and Methods] This study included 8 participants with cerebral palsy and spastic paralysis (GMFCS levels I to IV) who received care at the outpatient clinic. After a 5-min rest, the lower limb ergometer exercises were performed for 10 min. We measured the participants’ arterial blood pressure, pulse rate, passive range of knee joint extension, muscle tone using the Modified Ashworth scale (MAS) and Modified Tardieu scale (MTS), and 10-m walk test (10MWT). Measurements were collected three times (at baseline before exercise, immediately at the end of exercise, and 5 min after exercise during recovery). [Results] The 10-min lower limb ergometer exercise significantly improved the knee joint extension, MAS and MTS scores, and reduced lower extremity spasticity. Furthermore, it significantly increased the range of knee joint extension and decreased the 10MWT score. [Conclusion] The results showed that the 10-minute lower limb ergometer exercise is beneficial in reducing the spasticity of the lower limb muscles and in increasing the range of motion of knee extension in paraplegic patients with cerebral palsy, suggesting that its implementation in young children could prevent spasticity and enhance motor function.

Purpose This study aimed to analyze technical and clinical factors related to oncological outcomes in patients with localized prostate cancer (PC) who were treated with whole-gland high-intensity focused ultrasound (HIFU). Materials and Methods From 2007–2014, patients diagnosed with localized PC who underwent whole-gland HIFU were consecutively included retrospectively. Biochemical failure was defined according to the Phoenix ASTRO guidelines. The relationship between oncological outcomes and technical and clinical factors was evaluated. Results The study cohort included 428 patients. The median age was 67 years, and the median prostate-specific antigen level was 7.61 ng/mL. Patient risk classifications were low (n = 102), intermediate (n = 240), and high (n = 86). Biochemical disease-free survival rates of patients with HIFU for localized PC in the total, low-, intermediate-, and high-risk groups according to D’Amico risk groups over a median follow-up period of 5 years (range 9-144) were 68.4%, 80.4%, 65.6%, and 61.6%, respectively. In multivariate logistic regression analyses to predict biochemical failure of the treatment, neoadjuvant hormonal therapy (NHT) in the high-risk group (OR 0.225, p = 0.015), and compression method in the low- (OR 0.178, p = 0.030), intermediate- (OR0.291, p

Objectives To evaluate acute changes in serum brain-derived neurotrophic factor (BDNF) concentration following combined endurance exercise and heat stress through head-out water immersion (HOI). Setting Observational study with crossover design. Methods Ten healthy young male participants performed HOI at 40 °C (40 °C HOI) or continuous cycling at 60% of maximal oxygen uptake while immersed in 40 °C (40 °C HOI-ex) or 23 °C water (23 °C HOI-ex) for 15 min. Serum BDNF, cortisol and lactate concentrations, and core temperature (Tcore) were measured pre, immediately post, and 15 and 30 min post-immersion. Results BDNF concentration increased immediately and 15 min after 40 °C HOI-ex, but not after 40 °C or 23 °C HOI-ex. No changes in Tcore concentration were observed during 23 °C HOI-ex (Pre; 37.3 °C ± 0.3 °C, Post; 37.8 °C ± 0.2 °C, Post 15; 37.4 °C ± 0.3 °C, Post 30; 37.2 °C ± 0.2 °C). Tcore increased significantly post, post 15, and post 30 min of 40 °C HOI (Pre; 37.1 °C ± 0.4 °C, Post; 38.8 °C ± 0.5 °C, Post 15; 37.9 °C ± 0.4 °C, Post 30; 37.9 °C ± 0.2 °C) and 40 °C HOI-ex (Pre; 37.2 °C ± 0.2 °C, Post; 40.2 °C ± 0.7 °C, Post 15; 38.9 °C ± 0.5 °C, Post 30; 38.3 °C ± 0.5 °C). Tcore was higher in 40 °C HOI-ex compared with 40 °C HOI and 23 °C HOI-ex immediately post and post 15 min. Plasma lactate and cortisol were significantly higher in 40 °C HOI-ex compared with 40 °C HOI and 23 °C HOI-ex after immersion (p = 0.001). Conclusion While 15 min HOI alone or thermoneutral exercise do not increase BDNF concentration, both combined may form a time-efficient strategy to acutely elevate BDNF.

Introduction: Bacillus Calmette-Guérin instillation is an established therapy for the treatment of carcinoma in situ of the upper urinary tract. Case Presentation: A 72-year-old woman underwent radical cystectomy with cutaneous ureterostomy for invasive bladder cancer with carcinoma in situ of both ureters. For the treatment of upper urinary tract carcinoma in situ, an infusion of 40 mg bacillus Calmette-Guérin through each ureterostomy was performed once weekly for 5 times. Urine cytology of the left upper urinary tract became negative, with a recurrence-free survival of 4 months. On the other hand, the right upper urinary tract became temporarily negative but turned positive after 3 months. Conclusion: Bacillus Calmette-Guérin perfusion therapy via cutaneous ureterostomy is considered as one of the useful therapies for carcinoma in situ of the upper urinary tract. Furthermore, there are several factors to be discussed, including the treatment duration, dosage and secondary therapeutic options.

BACKGROUND Fistula formation is a severe adverse event related to antiangiogenetic agents such as bevacizumab and inferior mesenteric arteriovenous fistula (IMAVF) is a result of acquired factor, especially colon surgery. However, IMAVF occurs very rarely and there are few reports in patients during chemotherapy. We report a case of a patient who developed IMAVF during treatment with bevacizumab in metastatic colorectal cancer (mCRC) after colon surgery. CASE SUMMARY An 81-year-old man was diagnosed with descending colon cancer and underwent left hemicolectomy without any complications. He was definitely diagnosed with high-risk stage 2 and received tegafur-uracil plus leucovorin as adjuvant chemotherapy. Three years and 6 mo after the operation, the cancer relapsed with peritoneal dissemination. The patient underwent CyberKnife radiosurgery targeting the recurrent tumor and received chemotherapy with S-1 plus bevacizumab. At 1 year after chemotherapy, he complained of severe diarrhea, which is suspected drug-induced colitis. As diarrhea worsened despite the termination of treatment, he underwent colonoscopy and computed tomography (CT) scans that revealed edematous change from sigmoid to rectosigmoid colon. CT scans also revealed an aneurysm adjacent to the inferior mesenteric vein and multidetector CT angiography showed the IMAVF. Elective angiography confirmed the diagnosis of an IMAVF and it was successfully treated by arterial embolization. The patient resumed chemotherapy with only S-1 6 mo after embolization. CONCLUSION Clinicians should keep in mind the probability of severe diarrhea arose from IMAVF in mCRC patients treated with bevacizumab.

The aim of the present study was to evaluate the renal outcomes, including the time course of renal function, after elective PCI in patients with advanced renal dysfunction and to assess the predictors of renal dysfunction progression. This is a subanalysis of a previous observational multicenter study that investigated long-term clinical outcomes in patients with advanced renal dysfunction (eGFR

Aim The objective of the current study was to identify risk factors that affect the onset of dependence and chronic psychosis due to cannabis use. Methods We examined clinical genetic factors, psychiatric disorders prior to cannabis use, starting age of cannabis use, duration and frequency of cannabis use, types of cannabis products used, combined use of other psychoactive substances, and the psychiatric diagnosis of 71 patients with cannabis‐related psychiatric disorders who underwent treatment at nine mental health hospitals in Japan. Information was collected from cross‐sectional interview surveys conducted by each patient's attending psychiatrist. Results For the diagnosis of dependence syndrome due to the use of cannabis, we found associations with the number of years of cannabis use and the use of cannabis products with a high Δ9‐tetrahydrocannabinol (THC) content. However, we found no association between diagnosis of residual and late‐onset psychotic disorders and clinical genetic factors, presence of preceding psychiatric disorders, duration and frequency of cannabis use, starting age of cannabis use, or combined use of other psychoactive substances; an association was found only for the absence of use of cannabis products other than dried cannabis. Conclusion The onset of cannabis dependence was related to long‐term cannabis use and the use of cannabis products with a high THC content. However, chronic psychosis was not associated with total THC intake or psychiatric vulnerability. Thus, unknown factors appear to be involved in the onset of chronic psychosis., The onset of cannabis dependence was related to long‐term cannabis use and the use of cannabis products with a high THC content. However, chronic psychosis was not associated with total THC intake or psychiatric vulnerability.

Sarcopenia, a syndrome characterized by the loss of skeletal muscle mass, has attracted attention in the field of oncology, as it reflects poor nutritional status. The present study aimed to determine the risk factors for postoperative inguinal hernia (PIH) development after robot-assisted laparoscopic radical prostatectomy (RARP) for prostate cancer, and discuss whether sarcopenia could be used as a sensitive predictor of PIH. We reviewed the medical records of 147 patients who underwent RARP at our institution. The psoas muscle volume (PMV), as an indicator of sarcopenia, was quantified from computed tomography images using a 3-dimensional image analysis system. Multivariate cox regression analyses were performed to identify independent predictors of PIH, including pre- and peri-operative factors. The mean PMV was 393 cm3, and the correlation coefficient between PMV and body mass index was 0.37 (p

Background The latest guidelines recommend early intervention in adult atrial septal defect (ASD) patients with signs of right ventricular (RV) enlargement. However, the criteria of RV enlargement for optimal intervention remain unclear. We investigated the preoperative determinants for normalizing the RV volume after transcatheter closure of ASD in adults.Methods and Results:We retrospectively analyzed 52 ASD patients who underwent transcatheter closure. Cardiac magnetic resonance imaging (CMR) measured RV volume before and 1 year after the closure. The patients were divided into normalized (postoperative RV end-systolic volume index [RVESVI] Conclusions Preoperative RVESVI is an independent predictor for normalization of RV volume at 1 year after transcatheter closure of ASD in adults. Early intervention before RVESVI reaches 75 mL/m2may confer optimal timing for normalizing RV volume.

A 23-year-old man was admitted to our hospital with a huge pelvic tumor. MRI showed a tumor mixed with a solid component and polycystic cyst with maximum diameter of about 20 cm. Percutaneous tumor needle biopsy was performed and diagnosis was Ewing sarcoma. At that time, operation is extremely difficult, so the neoadjuvant chemotherapy with ifosfamide, etoposide, Adriamycin, and vincristine were administered. After 6 courses, MRI showed tumor reduction to maximum diameter of 10 cm. We planned tumor resection with total cystectomy for radical resection, but we also tried to preserve bladder considering the young age and quality of life. Although the bladder was partially resected, tumor resection was succeeded without removing surrounding organs. Histopathological examination revealed viable cells remained, but more than 95% was disappeared and the surgical margins were negative. Here we report a case of extra skeletal Ewing sarcoma in the retroperitoneum that was treated with chemotherapy and surgery without scarifying surrounding organs.

Background Spontaneous coronary artery dissection (SCAD) has recently been recognized as a cause of acute coronary syndrome (ACS), especially in young women. However, the characteristics, optimal treatment, and prognosis of patients who experience SCAD have not been fully described. Methods Data were retrospectively collected from a multicenter registry. Among 187 young women less than 60 years of age who underwent percutaneous coronary intervention, 19 (10.2%) with SCAD were identified through coronary angiography. Clinical characteristics and outcomes were investigated. Results Those with SCAD less frequently exhibited coronary risk factors, such as diabetes, dyslipidemia, and smoking, than those without SCAD. Intense emotional and/or physical stress was more frequently observed as a prominent precipitating factor in cases of SCAD. All 19 SCAD patients presented with ACS, 7 of whom were treated using stents, and the other 12 treated without stents. During a median follow-up of 960 days (interquartile range, 686-1504 days), two recurrent coronary artery dissections occurred within 7 days, both of which occurred in a vessel other than that in which primary dissection occurred. There were no deaths or recurrent dissection after 1 week. Conclusion SCAD was not uncommon among young Japanese women requiring percutaneous coronary intervention. Patients with SCAD exhibited fewer coronary risk factors and more precipitating factors than those without SCAD, and long-term clinical outcomes after an early period appeared to be favorable.

Using conditional survival (CS) analysis, we investigated whether the duration of survival without biochemical recurrence (BCR) of prostate cancer after laparoscopic radical prostatectomies (LRP) affected the BCR rate. We also investigated the impact of well-known risk factors for BCR.Between 2002 and 2014, 627 consecutive patients underwent LRPs at our institution. Prostate-specific antigen (PSA) concentrations above 0.2 ng/mL were defined as BCR. Conditional BCR-free survival rates were determined through Kaplan-Meier analysis. Assessment of potential BCR risk factors was performed using a Cox proportional hazard analysis.The 10-year BCR-free rates after LRP increased to 82.4%, 84.5%, 86.6%, 90.1%, and 94.7% in patients surviving 1, 2, 3, 5, and 7.5 years without BCR, respectively. Multivariate analyses of age, PSA concentrations, neoadjuvant therapy, and pathological findings were performed for all patients. In all patients, positive surgical margins (PSM) and Gleason Grade Groups (GG) ≥ 4 were independent risk factors for BCR (p 0.001, hazard ratio [HR] = 2.45; and p 0.001, HR = 2.83, respectively,). Similarly, PSM and GG ≥ 4 were significant risk factors in patients surviving 1-5 years without BCR. No clear risk factors were observed in patients surviving 5 years without BCR after LRPs.The BCR-free rate increased with time after LRP. It is recommended that patients with PSM, GG ≥ 4, or with both factors are strictly monitored for 5 years postoperatively. CS analysis is particularly useful for predicting the postoperative course of patients.

Warm ischemia and reperfusion injury (IRI) is a prognostic factor in donation after cardiac death donor transplantation. However, a reliable method to predict IRI before transplantation has not been established. The aim of this study was to identify predictive markers of hepatic IRI by simultaneous measurement of endogenous molecules using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). Rats were subjected to hepatic warm ischemia (70%) for 30 or 90 minutes and subsequent reperfusion. The livers were collected at the end of ischemia and 1 hour, 6 hours, and 24 hours after reperfusion. The liver tissue sections were applied to IMS (m/z 200-2000). Candidate molecules were identified by tandem mass spectrometry. Imaging mass spectrometry (IMS) revealed a significant increase in the taurine conjugates of dihydroxycholanoic acid (TDHCA) during ischemia and a tendency to return to the basal level after reperfusion. Notably, high-resolution measurements revealed focal accumulation of TDHCA in the intrahepatic bile duct with ischemic time. In conclusion, IMS is a useful method to detect minute changes provoked by ischemia, which are barely detectable in assays involving homogenization. Accordingly, focal accumulation of TDHCA during ischemia may be a candidate marker for predicting later IRI.

Nivolumab is part of the standard therapy for mRCC. Although deep and long-lasting responses are seen in some patients, the benefit of treatment is limited to some patients and the majority of patients will experience disease progression. PD-L1 is still under evaluation as a predictive biomarker and there is an urgent need to establish biomarkers for the treatment of nivolumab. Here, we investigate C-reactive protein (CRP) at 1 month after treatment of nivolumab as a target to predict the response of patients with metastatic renal cell carcinoma (mRCC) to nivolumab.After approval of the study by our institutional review board, 64 patients with mRCC who underwent nivolumab treatment at Kanagawa Cancer Center and Yokohama City University Hospital were enrolled. The patient characteristics, blood examination data at start of nivolumab treatment and 1 month after treatment, response to treatment and progression-free survival (PFS) were evaluated. Tumour responses were assessed according to both the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and the immune RECIST (iRECIST) criteria. Moreover, in 12 patients who agreed to an additional blood examination, several serum inflammatory factors were investigated and their correlation with CRP level was examined.The median follow-up was 8.3 months (range 0.2-29.8 months). The median PFS period was 4.5 months and the median immune-PFS (iPFS) period was 5.3 months. RECIST 1.1 criteria underestimated the benefits of nivolumab in four (6.4%) cases. Multivariate analyses showed that an Eastern Cooperative Oncology Group performance status (≥ 2) at start of treatment and CRP level at 1 month after treatment (≥ 1.5 mg/dL) were independent risk factors for a poor iPFS of nivolumab. The CRP level at baseline was not an independent prognostic factor for iPFS. When compared with the responder group (iCR + iPR + iSD), the non-responder group (iPD) had a significantly higher CRP levels at 1 month after treatment (p 0.001). In the responder group, there was significant decrease in the CRP level after nivolumab treatment when compared with the baseline (p = 0.002), whereas there was a significant increase in the non-responder group (p = 0.019). Even patients with high baseline CRP (≥ 1.5 mg/dL) obtained good iPFS if CRP was decreased ( 1.5 mg/dL) 1 month after treatment. In addition, the classification of Glasgow prognostic score (GPS), which is a cumulative prognostic score based on CRP and albumin, was a significant predictor for iPFS. A strong correlation (|r| 0.7) with CRP level at 1 month after treatment was seen for sCD163, IL-34, MMP-1, MMP-2, osteopontin, sTNF-R1 and sTNF-R2. Of these, MMP-1 and MMP-2 were not correlated at baseline.Our results indicated that the CRP level at 1 month after treatment with nivolumab appears to be a promising predictive biomarker for response to nivolumab treatment in patients with mRCC. It is clinically useful to be able to predict the effect within a short period. Further prospective trials are needed to prove these preliminary findings.

Serial changes of electrocardiograms (ECG) could be used to assess their clinical features in atrial septal defects (ASD) after transcatheter closure together with other clinical parameters. We retrospectively studied 100 ASD patients who underwent transcatheter closure. Complications of persistent atrial fibrillation occurred in five ASD patients, and they were excluded. We divided the other 95 patients according to PQ intervals before closure (normal

Recently, the effectiveness of anti-programmed death 1 (PD-1) antibody therapy in the treatment of renal cell carcinoma (RCC) has been established. Nevertheless, efficacy has been reported to be limited to only 10–30% of patients. To develop more effective immunotherapy for RCC, we analyzed the immunological characteristics in RCC tissues by immunohistochemistry (IHC). We prepared a tissue microarray that consisted of tumor tissue sections (1 mm in diameter) from 83 RCC patients in Kanagawa Cancer Center between 2006 and 2015. IHC analysis was performed with antibodies specific to immune-related (CD8 and Foxp3) and immune checkpoint (programmed death ligand 1 (PD-L1) and 2 (PD-L2), B7-H4 and galectin-9) molecules. The numbers and proportions of positively stained tumor cells or immune cells were determined in each section. From multivariate analysis of all 83 patients, higher galectin-9 expression was detected as a factor associated with worse overall survival (OS) (P = 0.029) and that higher stage and higher B7-H4 expression were associated with worse progression-free survival (PFS) (P

Although there are several case reports of progressive multifocal leukoencephalopathy (PML) in multiple myeloma (MM), there are few reports of cases associated with pomalidomide. Here, we report the case of a 69-year-old female who had received 41 cycles of pomalidomide and dexamethasone treatment for relapsed/refractory IgG-κ MM presented with right-hand weakness; she was diagnosed as pomalidomide-associated PML. Fluid-attenuated inversion recovery (FLAIR) on admission showed high signals in the bilateral front-parietal lobe white matter, with multiple punctate lesions in the vicinity of the main lesions. These punctate pattern findings on FLAIR were similar to that of natalizumab-associated PML. Susceptibility weighted imaging (SWI) showed hypointense rims within the cortex at unaffected sites, in the initial stages. Subsequently, the clinical manifestations deteriorated, and the FLAIR images showed new hyperintense white matter lesions at the sites where cortical SWI hypointense rims were detected on the initial MRI examination. Our patient's serial MRI findings suggest that cortical SWI hypointense rims appear prior to the visible demyelinating white matter lesions in patients with PML.

The present study aimed to clarify the current status, therapeutic strategy, and 1-year outcome in acute limb ischemia (ALI) patients in Japan. The EnDOvascular treatment (Edo) registry database includes 324 patients from 10 institutes who were registered between November 2011 and October 2013. A total of 70 ALI patients (mean age 74.0 years) from the Edo registry database were enrolled in this study. Of the 70 included patients, 72.9% were male and 35.7% had embolism. Of patients, 38.6%, 42.9%, and 18.6% underwent EVT, surgery, and hybrid thrombectomy, respectively, in primary revascularization strategy. Limb ischemia was categorized into four classes at initial evaluation: SVS/ISCVS class I (n = 13, 18.6%), SVS/ISCVS class IIa (n = 36, 51.4%), SVS/ISCVS class IIb (n = 21, 30%), and SVS/ISCVS class III (n = 0, 0%). Three patients with SVS/ISCVS class IIb limb ischemia developed myonephropathic metabolic syndrome. No catheter-directed thrombolysis was employed as a primary revascularization strategy. The 1-year rates of all-cause death, major amputation, and a composite of perioperative death or major adverse limb event were 28.6%, 5.7%, and 40.0%, respectively. Lower age, male sex, dyslipidemia, high estimated glomerular filtration rate, high albumin level, and low C-reactive protein level were independent positive predictors of all-cause death. In this registry, SVS/ISCVS class IIa ALI was predominant. Approximately 40% of primary revascularization strategy was surgery and EVT, followed by hybrid therapy. All-cause death and major amputation rates at 1 year were less than 30% and 6%, respectively.

Various methods of rehabilitation for dysphagia have been suggested through the experience of treating stroke patients. Although most of these patients recover their swallowing function in a short period, dysphagia in Parkinson's disease (PD) and Parkinson-related disorder (PRD) degenerates with disease progression. Muscle rigidity and bradykinesia are recognized as causes of swallowing dysfunction, and it is difficult to easily apply the strategies for stroke to the rehabilitation of dysphagia in PD patients. Disease severity, weight loss, drooling, and dementia are important clinical predictors. Silent aspiration is a pathognomonic sign that may lead to aspiration pneumonia. Severe PD patients need routine video fluoroscopy or video endoscopy to adjust their food and liquid consistency. Patients with PRD experience rapid progression of swallowing dysfunction. Nutrition combined with nasogastric tube feeding or percutaneous endoscopic gastrostomy feeding should be considered owing to the increased risk of aspiration and difficulty administrating oral nutrition.

Background Detection of atrial fibrillation (AF) out of electrocardiograph (ECG) on sinus rhythm (SR) using artificial intelligence (AI) algorithm has been widely studied within recent couple of years. Generally, it is believed that a huge number of ECGs are necessary for developing an AI-enabled ECG to be adequate to correspond to a lot of minor variations of ECGs. For example, structural heart diseases have typical ECG characteristics, but they could be a noise for the purpose of detecting the small signs of electrocardiographic signature of AF. We hypothesized that when patients with structural heart diseases are excluded, AI-enabled ECG for identifying patients with AF can be developed with a small number of ECGs. Methods We developed an AI-enabled ECG using a convolutional neural network to detect the electrocardiographic signature of AF present during normal sinus rhythm (NSR) using a digital, standard 10-second, 12-lead ECGs. We included all patients who newly visited the Cardiovascular Institute with at least one NSR ECG between Feb 1, 2010, and March 31, 2018. We classified patients with at least one ECG with a rhythm of AF as positive for AF (AF label) and others as negative for AF (SR label). We allocated ECGs to the training, internal validation, and testing datasets in a 7:1:2 ratio. We calculated the area under the curve (AUC) of the receiver operating characteristic curve for the internal validation dataset to select a probability threshold, which we applied to the testing dataset. We evaluated model performance on the testing dataset by calculating the AUC and the sensitivity, specificity, F1 score, and accuracy with two-sided 95% confidence intervals (CIs). Results We totally included 19170 patients with 12-lead ECG. After excluding patients with structural heart diseases, 12825 patients with NSR ECGs at the initial visit were identified (1262 were clinically diagnosed as AF anytime during the time course and 11563 were never diagnosed as AF). Of 11563 non-AF patients, 1818 patients who were followed over 1095 days were selected for the analysis with the SR label, to secure the robustness for maintaining SR. Of 1262 AF patients, 251 patients were selected for the analysis with the AF label, of whom a NSR ECG within 31 days before or after the index AF ECG (the first AF ECG during the time course) could be obtained. In the patients with AF label, the NSR ECG of which the date was the nearest to the index AF ECG was selected for the analysis. The AI-enabled ECG showed an AUC of 0.88 (0.84–0.92) with sensitivity 81% (72–88), specificity 80% (77–83), F1 score 50% (43–57), and overall accuracy 80% (78–83). Conclusion An AI-enabled ECG acquired during NSR allowed identification of patients with AF in a small population without structural heart diseases. Funding Acknowledgement Type of funding sources: None.

The purpose of this study was to experimentally assess the effect of a one touch clamp and rack smart pump on the time needed for patient mobilisation and the clinical staff`s perceived burden associated with these procedures when compared with the traditional type infusion system. Participants were randomly assigned to one of three groups: Multi-layer rack group (MULTI), One-touch pole clamp group (ONE), and a Control group (CON). In CON, traditional type pumps were replaced from pole stands to pole stands. In MULTI, the smart pumps were replaced from multi-layer rack to multi-layer rack, and in ONE the smart pumps were replaced from pole stands to multi-layer rack. In each group, the subject round-transported the simulated patient and re-replaced the pumps. The time of both pump replacements and the transport time were significantly shorter in MULTI and ONE compared with CON (p

INTRODUCTION AND OBJECTIVE:Late marriage is a serious social issue in Japan. We reported an increasing trend in the age of men with azoospermia in accordance with late marriage (AUA annual meeting ...

INTRODUCTION AND OBJECTIVE:In cryptorchid boys, germ cell development failure occurs during infancy. Thus, the establishment of serum markers for predicting infertility is warranted. Serum inhibin ...

Branchial cleft cysts in the parapharyngeal space are rare. Various surgical approaches into the parapharygeal space have been reported. Due to its difficult access and close proximity to blood vessels and cranial nerves, any surgical complication would adversely affect the quality of life or could be life-threatening. Surgeons need to be mindful of their operating skills and limitations while undertaking a surgical procedure. Here, we describe the case of a young woman who suffered from repeated infection of a parapharyngeal branchial cleft cyst. She eventually underwent a combined transoral and endoscopic marsupialization surgery uneventfully and infection control was obtained. Therefore, this surgical technique could be an alternative approach for the extirpation of parapharyngeal cysts. It ensures the clearance of infection, minimizes complications, and requires no incisions on the neck. In addition, the endoscopic component of this approach aids visualization and confirmation of the diagnosis prior to the definitive surgery.

Background The effects of pharmacological blood-pressure-lowering on cardiovascular outcomes in individuals aged 70 years and older, particularly when blood pressure is not substantially increased, is uncertain. We compared the effects of blood-pressure-lowering treatment on the risk of major cardiovascular events in groups of patients stratified by age and blood pressure at baseline. Methods We did a meta-analysis using individual participant-level data from randomised controlled trials of pharmacological blood-pressure-lowering versus placebo or other classes of blood-pressure-lowering medications, or between more versus less intensive treatment strategies, which had at least 1000 persons-years of follow-up in each treatment group. Participants with previous history of heart failure were excluded. Data were obtained from the Blood Pressure Lowering Treatment Triallists' Collaboration. We pooled the data and categorised participants into baseline age groups (Findings We included data from 358 707 participants from 51 randomised clinical trials. The age of participants at randomisation ranged from 21 years to 105 years (median 65 years [IQR 59–75]), with 42 960 (12·0%) participants younger than 55 years, 128 437 (35·8%) aged 55–64 years, 128 506 (35·8%) 65–74 years, 54 016 (15·1%) 75–84 years, and 4788 (1·3%) 85 years and older. The hazard ratios for the risk of major cardiovascular events per 5 mm Hg reduction in systolic blood pressure for each age group were 0·82 (95% CI 0·76–0·88) in individuals younger than 55 years, 0·91 (0·88–0·95) in those aged 55–64 years, 0·91 (0·88–0·95) in those aged 65–74 years, 0·91 (0·87–0·96) in those aged 75–84 years, and 0·99 (0·87–1·12) in those aged 85 years and older (adjusted pinteraction=0·050). Similar patterns of proportional risk reductions were observed for a 3 mm Hg reduction in diastolic blood pressure. Absolute risk reductions for major cardiovascular events varied by age and were larger in older groups (adjusted pinteraction=0·024). We did not find evidence for any clinically meaningful heterogeneity of relative treatment effects across different baseline blood pressure categories in any age group. Interpretation Pharmacological blood pressure reduction is effective into old age, with no evidence that relative risk reductions for prevention of major cardiovascular events vary by systolic or diastolic blood pressure levels at randomisation, down to less than 120/70 mm Hg. Pharmacological blood pressure reduction should, therefore, be considered an important treatment option regardless of age, with the removal of age-related blood-pressure thresholds from international guidelines. Funding British Heart Foundation, National Institute of Health Research Oxford Biomedical Research Centre, Oxford Martin School.

Patient: Male, 52-year-old Final Diagnosis: Renal cell carcinoma Symptoms: Cough Medication:— Clinical Procedure: — Specialty: Urology Objective: Unusual clinical course Background: The efficacy and safety of re-challenge with immune checkpoint inhibitors after immune-related adverse events have not been established. We report a case of successful re-administration of nivolumab in metastatic renal cell carcinoma after discontinuation due to immune-related adverse events. Case Report: Laparoscopic nephrectomy was performed on a 52-year-old man diagnosed with renal cell carcinoma pT1b-N0M0. After surgery, left adrenal and lung metastases appeared. Nivolumab was administered as a sixth-line therapy, and he achieved a partial response, but interstitial pneumonia occurred. He was diagnosed with grade 2 immune-related adverse events, and nivolumab treatment was discontinued. Interstitial pneumonia was well controlled by steroids. He maintained a partial response for a long time, and the lung metastases disappeared 7 months after discontinuation. However, bilateral lung metastases reappeared 10 months after the discontinuation. We decided to re-administer nivolumab, while carefully monitoring the patient and fully explaining the risk of recurrence of immune-related adverse events. After 5 cycles of re-administration, computed tomography revealed a reduction in metastases without re-activation of interstitial pneumonia. He experienced a grade 1 fever the day after re-administration, but continued nivolumab therapy without other adverse events. After 7 cycles of re-administration, the lung metastases increased, and nivolumab treatment was terminated. Two months later, a grade 2 interstitial pneumonia recurred, but improved rapidly with oral steroids. Conclusions: For patients who have discontinued immune checkpoint inhibitors due to immune-related adverse events, re-challenge of immune checkpoint inhibitors may be an option after explaining the risk of relapse of immune-related adverse events.