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An 11-year-old girl presented with pain in the sinus tarsi and a foot deformity after spraining her left foot. She had flat foot due to spasticity of the peroneal tendon, which was difficult to correct manually. An imaging study revealed an accessory anterolateral talar facet (AALTF) and bone marrow oedema at the lateral aspect of the posterior talocalcaneal joint. We diagnosed peroneal spastic flat foot with possible involvement of sinus tarsi syndrome and AALTF. When conservative therapy failed, we applied a cast with the foot in full plantar flexion and an inverted position. After 4 weeks, the patient had a normal range of motion in the foot, the pain had resolved completely and the peroneal spasticity had disappeared. Orthopaedic treatment with a cast may be worth attempting before surgery in such cases.

A select group of patients with hepatocellular carcinomas (HCC) benefit from surgical, radiologic, and systemic therapies that include a combination of anti-angiogenic and immune-checkpoint inhibitors. However, because HCC is generally asymptomatic in its early stages, this not only leads to late diagnosis, but also to therapy resistance. The nucleoside analogue 6-thio-dG (THIO) is a first-in-class telomerase-mediated telomere-targeting anticancer agent. In telomerase expressing cancer cells, THIO is converted into the corresponding 5′-triphosphate, which is efficiently incorporated into telomeres by telomerase, activating telomere damage responses and apoptotic pathways. Here, we show how THIO is effective in controlling tumor growth and, when combined with immune checkpoint inhibitors, is even more effective in a T-cell-dependent manner. We also show telomere stress induced by THIO increases both innate sensing and adaptive antitumor immunity in HCC. Importantly, the extracellular high-mobility group box 1 protein acts as a prototypical endogenous DAMP (Damage Associated Molecular Pattern) in eliciting adaptive immunity by THIO. These results provide a strong rationale for combining telomere-targeted therapy with immunotherapy.

Objective The 2018 Tokyo Guidelines (TG18) were published to facilitate the decision-making processes (DMP), including the diagnosis and operation of acute cholecystitis (AC). However, only a few guidelines consider older adults. This study evaluated the DMP based on the TG18, focusing on older patients with AC. Methods This was a single-armed, single-center retrospective study. The primary outcome measure was the "undiagnosable" AC rate, and the secondary outcome measure was the degree of concordance of "unfit for surgery" decisions. Patients Two hundred and nine patients with AC. Results Sixty (28.7%) of 209 patients with AC were "undiagnosable" on admission based on the TG18 criteria. The numbers and rate of "undiagnosable" AC in patients ≤59, 60-79, and ≥80 years old were 4 (10.0%), 20 (24.4%), and 36 (41.4%), respectively (P0.001). The multiple logistic regression analysis following the univariate analysis revealed that age73 years old was the most significant risk factor for undiagnosable AC (P=0.006, odds ratio [OR]: 3.06, 95% confidence interval [CI]: 1.38-6.81). Female sex (P=0.033, OR: 2.09, 95% CI: 1.06-4.09) and severe AC (P=0.049, OR: 2.97, 95% CI: 1.01-8.76) were also significant risk factors for undiagnosable AC. The number of cases unfit for surgery based on the Charlson Comorbidity Index and American Society of Anesthesiologists physical status was 90 (43.1%) and 75 (35.9%), respectively. The κ value between these 2 indicators revealed a minimal concordance of 0.33 (95% CI: 0.20-0.47). Conclusion The DMP based on the TG18 potentially harbors a misjudgment risk, especially in older patients with AC (UMIN000047715).

Hiatal hernia is a common condition in elderly patients, but the additional presence of prolapse of the pancreas is extremely rare. We herein report an 89-year-old woman who presented with liver function disorders and abdominal pain. Her laboratory tests revealed cholestasis, and imaging examinations showed stenosis of the common bile duct pulled toward the hernia sac. She was diagnosed with a common bile duct stricture due to pancreatic herniation and underwent laparoscopic surgery. Our review of the literature identified three types of pancreatic herniations: asymptomatic, bile duct complication, and acute pancreatitis. Pancreatic head herniation tends to induce bile duct complications.

The optimal management of patients with appendiceal endometriosis has not been determined because of the difficulty of establishing a preoperative diagnosis. There are no reports of preoperative hormone therapy for a patient with appendiceal endometriosis. We report a patient who underwent resection of appendiceal endometriosis after hormone therapy. A 40-year-old woman with history of recurrent pelvic abscesses presented to the emergency department with lower abdominal pain. The recurrent pelvic abscesses were synchronised with her menstrual cycle. CT scan demonstrated a 25 mm contrast-enhanced luminal structure adjacent to the cecum, which was thought to be a mucocele of the appendix. Considering the recurrent symptoms during menstruation, endometriosis was suspected. Treatment with a gonadotropin-releasing hormone agonist was started for appendiceal endometriosis, which alleviated the symptoms. After 3 months, elective laparoscopic appendectomy was performed. Preoperative hormonal therapy is an option for patients with appendiceal endometriosis, especially when there is concern for dense adhesions.

Home-care manipulation robot requires exploring and performing the navigation task safely to reach the grasping target and ensure human safety in the home environment. An indoor home environment has complex obstacles such as chairs, tables, and sports equipment, which make it difficult for robots that rely on 2D laser rangefinders to detect. On the other hand, the conventional approaches overcome the problem by using 3D LiDAR, RGB-D camera, or fusing sensor data. The convolutional neural network has shown promising results in dealing with unseen obstacles in navigation by predicting the unseen obstacle from 2D grid maps to perform collision avoidance using 2D laser rangefinders only. Thus, this paper investigated the predicted grid map from the obstacle prediction network result for improving indoor navigation performance using only 2D LiDAR measurement. This work was evaluated by combining the configuration of the various local planners, type of static obstacles, raw map, and predicted map. Our investigation demonstrated that using the predicted grid map enabled all the local planners to achieve a better collision-free path by using the 2D laser rangefinders only rather than the RGB-D camera with 2D laser rangefinders with a raw map. This advanced investigation considers that the predicted map is potentially helpful for future work in the learning-based local navigation system.

Objective We examined whether home blood pressure (BP)-based behavioural guidance had an additional anti-albuminuric effect on school workers with the simple diagnostic provision of microalbuminuria. Methods Of 169 school staff diagnosed with microalbuminuria (30-299.9 mg/gCr) in the annual 2019 health check-up, 91 agreed to receive home-BP-based guidance. Guidance comprised, for subjects with ≥ 135/85 mmHg, 5 days mean of home BP measurements, or encouraging medical consultation and lifestyle guidance; lifestyle guidance for subjects with BP 125-134/80-84 mmHg; and adequate lifestyle guidance for subjects BP125/80 mmHg, if necessary. The main outcome was a change in the frequency of microalbuminuria the following year. Subjects with menstruation were excluded from analysis. Finally, there were 48 and 43 participants in guided and the non-guided groups, respectively. Results The guided and non-guided groups demonstrated similar baseline clinical data. Their prescription rates for hypertension (39.6 vs. 41.9 %) and diabetes (18.8 vs. 30.2 %) were similar. One year later, microalbuminuria was present in 31.2% and 30.2% of the guided and non-guided groups (n.s.), respectively, suggesting a ~70% risk reduction of microalbuminuria in both groups. Sensitivity analysis, excluding patients treated for hypertension or diabetes at baseline, demonstrated essentially similar results. In conclusion, the risk reduction of microalbuminuria was nearly 70% for both the home-BP-based guidance and non-guidance groups. Conclusion These data suggest that home BP-based guidance did not increase anti-albuminuric effects on simple diagnostic provision of microalbuminuria in school workers.

Ao contrário de tecnologias da informação e comunicação (TICs) de gerações anteriores, cuja implantação em grande parte era mais restrita ao ambiente corporativo, a tríade de tecnologias formada por internet das coisas (internet of things – IoT), computação em nuvem e na borda, e inteligência artificial (IA) é aplicável às mais variadas áreas da atividade humana. Se o Brasil perdeu oportunidades em décadas anteriores no setor de eletroeletrônicos, existem notícias alvissareiras que permitem um maior otimismo no que diz respeito à IoT. Em primeiro lugar, o país possui um sistema setorial de inovação com capacidade para gerar e implementar as tecnologias necessárias. O Brasil desenvolveu também um plano de IoT bem elaborado e com uma boa governança de acompanhamento. Finalmente, várias iniciativas de classe mundial já são realidade. Este texto traz uma caracterização da IoT no Brasil composta de análise bibliométrica; apresentação do Plano Nacional de IoT e sua inserção na Estratégia Brasileira para a Transformação Digital (E-Digital); uma revisão de trabalhos sobre IoT e agronegócio; um detalhamento das políticas setoriais relacionadas à oferta de tecnologias para a IoT; e uma comparação internacional e casos de sucesso de implementação da tecnologia no Brasil.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co‐primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We report 5-year results from the phase III KEYNOTE-042 study (ClinicalTrials.gov identifier: NCT02220894 ). Eligible patients with locally advanced/metastatic non–small-cell lung cancer (NSCLC) without EGFR/ALK alterations and with programmed death ligand-1 (PD-L1) tumor proportion score (TPS) ≥ 1% received pembrolizumab 200 mg once every 3 weeks for 35 cycles or chemotherapy (carboplatin + paclitaxel or pemetrexed) for 4-6 cycles with optional maintenance pemetrexed. Primary end points were overall survival (OS) in PD-L1 TPS ≥ 50%, ≥ 20%, and ≥ 1% groups. Patients who completed 35 cycles of pembrolizumab with ≥ stable disease could begin second-course pembrolizumab upon progression. One thousand two hundred seventy‐four patients were randomly assigned (pembrolizumab, n = 637; chemotherapy, n = 637). Median follow-up time was 61.1 (range, 50.0-76.3) months. OS outcomes favored pembrolizumab ( v chemotherapy) regardless of PD-L1 TPS (hazard ratio [95% CI] for TPS ≥ 50%, 0.68 [0.57 to 0.81]; TPS ≥ 20%, 0.75 [0.64 to 0.87]; TPS ≥ 1%, 0.79 [0.70 to 0.89]), with estimated 5-year OS rates with pembrolizumab of 21.9%, 19.4%, and 16.6%, respectively. No new toxicities were identified. Objective response rate was 84.3% among 102 patients who completed 35 cycles of pembrolizumab and 15.2% among 33 patients who received second-course pembrolizumab. First-line pembrolizumab monotherapy continued to show durable clinical benefit versus chemotherapy after 5 years of follow-up in PD-L1–positive, locally advanced/metastatic NSCLC without EGFR/ALK alterations and remains a standard of care.

Background Anger has been suggested as a risk factor for stroke. Perceived social support (PSS) may relieve anger, thus reducing the risk of stroke; however, evidence supporting this is limited. We aimed to examine whether PSS modifies the risk of stroke associated with anger expression. Methods A cohort study was conducted among 1,806 community residents aged 40-74 years who received a cardiovascular risk survey including anger expression in 1997. A Cox proportional hazards model was applied to the participants with low and high PSS to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the risks of total stroke and its subtypes based on total anger expression after adjusting for known stroke risk factors. Results The median follow-up duration was 18.8 years, with 51 incident strokes. Among the participants with low PSS, anger expression had a positive association with the total stroke risk: The multivariable HR per SD increment of total anger expression was 1.43 (95% CI, 1.13-1.82). In contrast, no association was identified among those with high PSS. The corresponding HR was 0.83 (95% CI, 0.49-1.40), with a significant interaction between low and high PSS (p = 0.037). Similar associations regarding the risk of ischemic stroke were found. Conclusions We found an increased risk of stroke associated with anger expression among the participants with low PSS, but not among those with high PSS. Our results suggest that PSS might mitigate the risk of stroke associated with anger.

Recent studies have suggested that speech perception outcomes after cochlear implantation (CI) in prelingually deafened adults have improved with advances in CI technology and speech processing strategies. However, the outcomes vary from case to case. Communication mode has been reported in many studies as the factor that related to the post CI outcomes. This study aimed at investigating the post CI outcomes and the progress during 2 years for each communication mode.The subjects were 17 prelingually deafened adults undergoing CI at our hospital between April 2013 and March 2019. We investigated preoperative factors affecting post CI outcomes. Also we analyzed post CI outcomes for each communication mode and compared preoperative factors for each communication mode.Communication mode and preoperative discrimination score were the factor affecting on postoperative discrimination score. The speech perception score after CI improved significantly in the oral and lip-reading group and total communication group. The speech perception scores in postlingually deafened adults improved significantly during the first six months and became to plateau after CI. On the other hand, the scores of prelingually deafened adults tended to improve gradually after six months postoperatively. Furthermore, the degree of improvement and progress differed by each communication mode.The communication mode is important factors in predicting outcomes in prelingually deafened adults after CI. Long-term auditory training is important for prelingually deafened adults who use visual information as their preoperative method of communication.

Adult T-cell leukemia/lymphoma (ATLL) is a mature peripheral T-cell neoplasm caused by human T-cell leukemia virus type I (HTLV-1) infection. Besides the oncogenic property, HTLV-1 causes HTLV-1-associated myelopathy/tropical spastic paraparesis and certain inflammatory diseases via a complex host immune response to latent virus infection. Cardiac involvement of ATLL is rare, with the majority of cases being disclosed in postmortem autopsy in patients with advanced subtypes. We herein report the case of a 64-year-old female patient with indolent chronic ATLL with severe mitral regurgitation. Although the condition of ATLL was stable, dyspnea on exertion gradually progressed over the course of three years and echocardiography revealed marked thickening of the mitral valve. Finally, the patient experienced hemodynamic collapse with atrial fibrillation and underwent surgical valve replacement. The removed mitral valve was grossly edematous and swollen. A histological examination revealed a granulomatous reaction mimicking the active phase of rheumatic valvulitis, with the infiltration of ATLL cells that were immunohistochemically positive for CD3, CD4, FoxP3, HLA-DRα, and CCR4. The postoperative course was uneventful, with the exception that Sjögren's syndrome was noted. The history of rheumatic fever was unclear, and such unique valvular pathology was presumably related to autoimmune mechanisms associated with HTLV-1 infection. LEARNING OBJECTIVE: We report a case of chronic adult T-cell leukemia/lymphoma (ATLL) with isolated valvular infiltration with a unique histology of granulomatous reaction. Human T-cell leukemia virus type I infection may accelerate autoimmune reactions and cardiac inflammation, irrespective of indolent clinical subtype. Among ATLL cases, possible progression of valvular insufficiency and heart failure in patients with cardiac symptoms should be carefully evaluated.

The Asian Precipitation Experiment (AsiaPEX) was initiated in 2019 to understand terrestrial precipitation over diverse hydroclimatological conditions for improved predictions, disaster reduction, and sustainable development across Asia under the framework of the Global Hydroclimatology Panel (GHP)/Global Energy and Water Exchanges (GEWEX). AsiaPEX is the successor to GEWEX Asian Monsoon Experiment (GAME; 1995–2005) and Monsoon Asian Hydro-Atmosphere Scientific Research and Prediction Initiative (MAHASRI; 2006–16). While retaining the key objectives of the aforementioned projects, the scientific targets of AsiaPEX focus on land–atmosphere coupling and improvements to the predictability of the Asian hydroclimatological system. AsiaPEX was designed for both fine-scale hydroclimatological processes occurring at the land surface and the integrated Asian hydroclimatological system characterized by multiscale interactions. We adopt six approaches including observation, process studies, scale interactions, high-resolution hydrological modeling, field campaigns, and climate projection, which bridge gaps in research activities conducted in different regions. Collaboration with mesoscale and global modeling researchers is one of the core methods in AsiaPEX. We review these strategies based on the literature and our initial outcomes. These include the estimation and validation of high-resolution satellite precipitation, investigations of extreme rainfall mechanisms, field campaigns over the Maritime Continent and Tibetan Plateau, areas of significant impact on the entire AsiaPEX region, process studies on diurnal- to interdecadal-scale interactions, and evaluation of the predictabilities of climate models for long-term variabilities. We will conduct integrated observational and modeling initiative, the Asian Monsoon Year (AMY)-II around 2025–28, whose strategies are the subregional observation platforms and integrated global analysis.