Chronic obstructive pulmonary disease, asthma, and mechanical ventilation are risk factors for dyspnea in patients with long COVID: A Japanese nationwide cohort study.

BACKGROUND: Patients often experience multiple prolonged symptoms following acute coronavirus disease 2019 (COVID-19) recovery, defined as long coronavirus disease (COVID). Patients with long COVID may experience dyspnea during acute and post-acute phases. Therefore, this study aimed to identify specific risk factors for dyspnea in patients with long COVID. METHODS: Hospitalized patients with COVID-19, aged ≥18 years, were enrolled in this multicenter cohort study conducted at 26 medical institutions across Japan. Clinical data during hospitalization and patient-reported outcomes after discharge at the 3, 6, and 12-month follow-ups were retrieved from medical records and paper-based or smartphone application-based questionnaires, respectively. RESULTS: Generalized linear mixed model (GLMM) analysis of prolonged dyspnea at each time point during follow-up showed that this symptom was associated with chronic obstructive pulmonary disease (COPD) (odds ratio [OR], 2.74; 95% confidence interval [CI], 1.31-5.74), asthma (OR, 2.21; 95%CI, 1.17-4.16), and ventilator management (OR, 3.10; 95%CI, 1.65-5.83). In addition, patients with COPD (44.4%) and ventilator management (25.0%) were more frequently associated with delayed dyspnea onset. The generalized estimating equations analysis results with multiple imputed datasets, conducted as a sensitivity analysis, confirmed the adjusted GLMM analysis results. CONCLUSIONS: Prolonged dyspnea was associated with COPD, asthma, and severe infection that required mechanical ventilation in the Japanese population with long COVID. Further investigation is needed to clarify its mechanism and develop prophylactic and therapeutic strategies for dyspnea in patients with long COVID.

Multifocal motor neuropathy in Japan: A nationwide survey on prevalence, clinical profiles, and treatment.

INTRODUCTION/AIMS: Multifocal motor neuropathy (MMN) is a rare disease for which epidemiological and clinical data are limited. We conducted a nationwide survey to determine disease prevalence, incidence, clinical profile, and current treatment status in Japan. METHODS: A nationwide survey was conducted in 2021 using an established epidemiological method. Questionnaires were sent to all neurology and pediatric neurology departments in Japan. An initial questionnaire was administered to determine the number of patients with and incidence of MMN. A second questionnaire was administered to collect detailed clinical information. The European Federation of Neurological Societies/Peripheral Nerve Society 2010 guidelines were used as diagnostic criteria. RESULTS: The estimated number of patients with MMN was 507. The estimated prevalence was 0.40 per 100,000 individuals. Detailed clinical profiles were available for 120 patients. The male-to-female ratio was 2.3:1 and the median onset age was 42 years. The median disease duration at diagnosis was 25 months. Most patients presented with upper limb-dominant muscle weakness. Motor nerve conduction blocks were found in 62% of patients and positive anti-GM1 IgM antibody results in 54%. A total of 117 (98%) patients received immunoglobulin therapy, and 91% of them showed improvement. At the time of the last visit (median, 82 months from treatment initiation), 89 (74%) patients were receiving maintenance immunoglobulin therapy. A slight progression of neurological deficits was observed during follow-up. DISCUSSION: Most patients with MMN in Japan received induction and maintenance immunoglobulin therapies, which appear to suppress long-term disease progression.

Prognosis prediction of PDAC via detection of O-glycan altered extracellular vesicles in perioperative sera.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy due to the difficulty in diagnosis and poor prognosis because of the high recurrence rate, necessitating reliable biomarkers to improve the diagnosis and prognosis. However, the existing markers have limitations. We previously identified extracellular vesicles (EVs) recognized by O-glycan-binding lectins (Amaranthus caudatus agglutinin [ACA]) as a novel diagnostic biomarker for PDAC using an EV-counting system (ExoCounter). This retrospective study analyzed changes in ACA-positive EVs in perioperative PDAC serum and its association with prognosis using ExoCounter. Absolute EV levels in the pre- and postoperative sera of 44 patients who underwent curative pancreatectomy for PDAC were quantified using ExoCounter. The carbohydrate antigen 19-9 levels declined in most samples postoperatively, and presented no correlation with poor prognosis. In contrast, ACA-positive EVs increased in serum at 7 days postoperatively in 27 of 44 patients (61.4%). We therefore divided participants with ACA-positive EVs before and after surgery into elevation and decline groups. The overall survival (OS) and recurrence-free survival (RFS) of patients with higher ACA-positive EVs were significantly shorter than those with lower ACA-positive EVs (26.1 months vs. not reached, P = 0.018; 11.9 vs. 38.6 months, P = 0.013). Multivariable analysis revealed that ACA-positive EV elevation in postoperative serum was an independent prognostic factor for poor OS (hazard ratio [HR] = 3.891, P = 0.023) and RFS (HR = 2.650, P = 0.024). The detection of ACA-positive EVs in perioperative serum may be used to predict the prognosis of PDAC in the early postoperative period.

Distinctive clinical features of radiological pleuroparenchymal fibroelastosis with nontuberculous mycobacterial pulmonary disease: A multicenter retrospective cohort study.

OBJECTIVES: To compare the characteristics and prognosis of patients with nontuberculous mycobacterial (NTM) pulmonary disease (PD) with pleuroparenchymal fibroelastosis (PPFE) with those of patients with nodular/bronchiectatic (NB) and fibrocavitary (FC) NTM-PD. METHODS: This multicenter, retrospective, observational study enrolled 32 patients with NTM-PPFE (median age: 70.5 years, 15 females) from six institutions in Japan from January 2003 to December 2018. Their clinical characteristics, and response to therapy were compared with age- and sex-matched cohorts of patients with non-cavitary NB and cavitary NB/FC NTM-PD. RESULTS: Patients with NTM-PPFE had a lower body mass index and a higher standard NTM-PD therapy initiation rate than patients with other NTM-PD types. Sputum culture conversion rates were comparable between groups; however, patients with NTM-PPFE had a higher incidence of treatment-related adverse events, including optic neuropathy associated with high-dose ethambutol therapy, lower percent predicted forced vital capacity values, higher serum Krebs von den Lungen 6 (KL-6) levels, and poorer treatment outcomes than the other groups. Cox regression revealed that NTM-PPFE was an independent risk factor for death/pneumothorax (adjusted hazard ratio: 35.3, 95% confidence interval: 3.90-4692). CONCLUSIONS: NTM-PPFE is a unique NTM-PD phenotype with a poorer prognosis than the NB and FC phenotypes.

Advanced esophagogastric junction mixed neuroendocrine-non-neuroendocrine neoplasm with long-term recurrence-free survival.

BACKGROUND: Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare malignant gastrointestinal tumor. The prognosis of patients with MiNEN is poor because of the high frequency of recurrence and metastases. We report a case of esophagogastric junction MiNEN (EGJ-MiNEN) with a long-term recurrence-free survival of 5.5 years. CASE PRESENTATION: A 58-year-old male patient underwent thoracoscopic esophagectomy for esophagogastric junction adenocarcinoma. The patient's postoperative course was uneventful. R0 resection was achieved, and the pathological diagnosis of the surgical specimen was pT3N2M0 Stage IIIA (according to the Japanese Classification of Gastric Cancer, 4th edition). Based on the pathology results, the patient was treated with postoperative adjuvant therapy with oral S-1. The patient maintained recurrence-free survival for 5.5 years postoperatively. However, 6 years postoperatively, the patient visited our department with cachexia. Computed tomography (CT) revealed a large amount of ascites and pleural effusion. He rapidly developed a poor circulatory and respiratory status and died 16 days after admission. An autopsy revealed severe bloody ascites and pleural effusion, as well as numerous nodules on the pleura and mesentery. Immunohistochemistry of the nodules revealed positivity for chromogranin A, Synaptophysin A, neural cell adhesion molecule (NCAM or CD56), and insulinoma-associated protein 1 (INSM1). The specimen showed a mixture of adenocarcinoma and neuroendocrine cell carcinoma and was diagnosed as MiNEN. Retrospective immunostaining of the surgical specimen showed similar results, and we diagnosed the patient with recurrence of EGJ-MiNEN. CONCLUSION: MiNEN has a poor prognosis; however, in some cases, long-term recurrence-free survival is achieved with radical resection and adjuvant chemotherapy.

Changes in serum levels of liver-related parameters, uric acid, and hemoglobin in patients with type 2 diabetes mellitus under treatment with tofogliflozin-a post-hoc analysis of the UTOPIA study.

Aims/Introduction: The aim of the study was to evaluate the effects of tofogliflozin, a selective sodium-glucose cotransporter 2 inhibitor, on circulating levels of hepatic enzymes, uric acid and hemoglobin levels in patients with type 2 diabetes mellitus (T2DM). Materials and methods: We evaluated longitudinal changes in circulating aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), uric acid, and hemoglobin levels in tofogliflozin (n = 169) and conventional treatment groups (n = 170) using data obtained from the UTOPIA trial, a randomized prospective study conducted to evaluate the efficacy of tofogliflozin in preventing atherosclerosis. Results: Within 104 weeks, tofogliflozin treatment, but not conventional treatment, significantly reduced AST, ALT, and γ-GTP levels. This reduction was significantly greater in the tofogliflozin group than in the conventional group. Stratified analysis showed that, in patients with obesity (defined as body mass index (BMI) ≥ 25.0 kg/m2), significant differences were observed in AST, ALT, and γ-GTP changes from baseline to 104 weeks between treatment groups. However, in patients without obesity, there were no significant differences in AST and γ-GTP changes from baseline to 104 weeks between treatment groups. Multivariable regression analysis showed that changes in BMI and HbA1c levels were independently associated with changes in AST, ALT, and γ-GTP levels. The reduction of uric acid and the increase of hemoglobin from baseline to 104 weeks were significantly greater in the tofogliflozin group than in the conventional group. Conclusions: The beneficial effects of tofogliflozin on circulating levels of hepatic enzymes, uric acid, and Hb lasted for 2 years in patients with T2DM. Clinical trial registration: UMIN000017607 (https://www.umin.ac.jp/icdr/index.html). Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00693-x.

Safety and effectiveness of tofogliflozin in Japanese people with type 2 diabetes: A multicenter prospective observational study in routine clinical practice.

AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors effectively and safely reduce fasting and postprandial hyperglycemia while promoting weight loss. However, their unique mechanism of action contributes to concerns regarding their safety. We therefore carried out a large-scale, non-commercial, investigator-initiated study on the safety and effectiveness of the SGLT2 inhibitor tofogliflozin. MATERIALS AND METHODS: This multicenter, open-label, uncontrolled, prospective observational study was carried out at hospitals and clinics across Japan in participants aged ≥20 years who were SGLT2 inhibitor-naïve and had an established diagnosis of type 2 diabetes. The primary endpoint was adverse drug reactions (ADRs) of special interest. Secondary endpoints included all other ADRs and adverse events, glycated hemoglobin (HbA1c), and weight loss. RESULTS: The study, carried out from June 2014 through February 2020, enrolled 11,480 participants from 1,103 medical institutions; 6,967 participants completed the 104-week follow up. The most common ADRs of special interest were urinary and genital tract infections (1.53%), followed by volume depletion (1.25%). Hypoglycemia occurred in 27 participants (0.24%), adverse events in 1,054 (9.18%) and ADRs in 645 (5.62%). HbA1c decreased by 0.85% (95% confidence interval 0.82%-0.88%) and bodyweight decreased by 3.05 kg (95% confidence interval 2.94-3.17 kg). The HbA1c target was achieved by 51.70% of participants for target HbA1c <7.0%, 85.3% for <8.0% and 5.4% for <6.0% at week 104. CONCLUSIONS: Tofogliflozin was associated with only mild or moderate ADRs characteristic of SGLT2 inhibitors, with no unpredictable, new, serious, or high-incidence adverse events or ADRs. This independent study confirmed the safety and effectiveness of tofogliflozin in adult type 2 diabetes patients.

Validity test of small cell lung cancer (SCLC) graded prognostic assessment and proposal of a new index for patients with brain metastases from SCLC.

Background and purpose: We performed a validity test of a recently-reported, small cell lung cancer (SCLC) graded prognostic assessment (GPA) system for SCLC patients with brain metastases (BMs). Thereafter, we created a new prognostic index, the SCLC Grade, for such patients. Materials and methods: We studied 508 SCLC patients selected from among nearly 7000 consecutive patients undergoing gamma knife SRS for BMs since 1998. Results: In the SCLC GPA, there were no median survival time (MST) differences among pairs of the neighboring subgroups. Therefore, the 508 patients were randomly divided into the two series, i.e., a test (340 patients) and a validity (168) series. In the test series, five factors were identified by univariable analyses as favoring longer survival (rounded lower 95 % CI of the HR was at least 1.3): Sex, Karnofsky Performance Status, tumor numbers, primary tumor status and extracerebral metastases. This new index is the sum of scores (0 and 1) of these five factors: SCLC-Grade 4-6 (score of 4, 5 or 6), 2-3 (2 or 3), and 0-1 (0 or 1). This new system showed highly statistically significant MST differences among subclasses. Next, this SCLC-Grade was applied to the verification series. Consistent results were obtained, i.e., there were highly statistically significant MST differences among subclasses. Conclusions: Our validity test results for the SCLC GPA demonstrated this system to not precisely reflect the outcomes of SCLC patients with BMs. Our results suggest the herein-proposed SCLC-Grade to have superior prognostic value.

Intraoperative surgical complications of open surgery for congenital diaphragmatic hernia: a multicenter, observational study in Japan.

PURPOSE: This study aimed to clarify surgical complications associated with open surgery for congenital diaphragmatic hernia (CDH). METHODS: We performed an exploratory data analysis of the clinical characteristics of surgical complications of neonates with CDH who underwent laparotomy or thoracotomy between 2006 and 2021. Data of these patients were obtained from the database of the Japanese CDH Study Group. RESULTS: Among 1,111 neonates with left or right CDH, 852 underwent open surgery (laparotomy or thoracotomy). Of these 852 neonates, 51 had the following surgical complications: organ injury (n = 48; 6% of open surgeries); circulatory failure caused by changes in the organ location (n = 2); and skin burns (n = 1). Injured organs included the spleen (n = 30; 62% of organ injuries), liver (n = 7), lungs (n = 4), intestine (n = 4), adrenal gland (n = 2), and thoracic wall (n = 2). Fourteen of the patients who experienced organ injury required a blood transfusion (2% of open surgeries). The adjusted odds ratio of splenic injury for patients with non-direct closure of the diaphragm was 2.2 (95% confidence interval, 1.1-4.9). CONCLUSION: Of the patients who underwent open surgery for CDH, 2% experienced organ injury that required a blood transfusion. Non-direct closure of the diaphragmatic defect was a risk factor for splenic injury.

Histopathological growth pattern and vessel co-option in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) exhibits different blood imaging features and prognosis depending on histology. To clarity histopathological growth patterns (HGPs) and vascularization processes of iCCA, we collected 145 surgical specimens and histologically classified them into large bile duct (LBD) (20 cases), small bile duct (SBD) (54), cholangiolocarcinoma (CLC) (35), combined SBD-CLC (cSBD-CLC) (26), and ductal plate malformation (DPM) (10) (sub)types. According to the invasive pattern at the interface between tumor and adjacent background liver, HGPs were classified into desmoplastic, pushing, and replacing HGPs. Desmoplastic HGP predominated in LBD type (55.5%), while replacing HGP was common in CLC (82.9%) and cSBD-CLC (84.6%) subtypes. Desmoplastic HGP reflected angiogenesis, while replacing HGP showed vessel co-option in addition to angiogenesis. By evaluating microvessel density (MVD) using vascular markers, ELTD1 identified vessel co-option and angiogenesis, and ELTD1-positive MVD at invasive margin in replacing HGP was significantly higher than those in desmoplastic and pushing HGPs. REDD1, an angiogenesis-related marker, demonstrated preferably higher MVD in the tumor center than in other areas. iCCA (sub)types and HGPs were closely related to vessel co-option and immune-related factors (lymphatic vessels, lymphocytes, and neutrophils). In conclusion, HGPs and vascular mechanisms characterize iCCA (sub)types and vessel co-option linked to the immune microenvironment.

External Validation and Update of the Risk Prediction Model for Denosumab-Induced Hypocalcemia Developed From a Hospital-Based Administrative Database.

PURPOSE: Denosumab is used to treat patients with bone metastasis from solid tumors, but sometimes causes severe hypocalcemia, so careful clinical management is important. This study aims to externally validate our previously developed risk prediction model for denosumab-induced hypocalcemia by using data from two facilities with different characteristics in Japan and to develop an updated model with improved performance and generalizability. METHODS: In the external validation, retrospective data of Kameda General Hospital (KGH) and Miyagi Cancer Center (MCC) between June 2013 and June 2022 were used and receiver operating characteristic (ROC)-AUC was mainly evaluated. A scoring-based updated model was developed using the same data set from a hospital-based administrative database as previously employed. Selection of variables related to prediction of hypocalcemia was based on the results of external validation. RESULTS: For the external validation, data from 235 KGH patients and 224 MCC patients were collected. ROC-AUC values in the original model were 0.879 and 0.774, respectively. The updated model consisting of clinical laboratory tests (calcium, albumin, and alkaline phosphatase) afforded similar ROC-AUC values in the two facilities (KGH, 0.837; MCC, 0.856). CONCLUSION: We developed an updated risk prediction model for denosumab-induced hypocalcemia with small interfacility differences. Our results indicate the importance of using data from plural facilities with different characteristics in the external validation of generalized prediction models and may be generally relevant to the clinical application of risk prediction models. Our findings are expected to contribute to improved management of bone metastasis treatment.

Risk factors for chronic kidney disease progression over 20 years for primary prevention in Japanese individuals at a preventive medicine research center: Focus on the influence of plasma glucose levels.

AIMS/INTRODUCTION: Chronic kidney disease (CKD) is a very important issue globally because of the risk of its progressing to end-stage renal disease. We aimed to identify factors contributing to long-term estimated glomerular filtration rate (eGFR) decline to determine an early diagnosis and prevent CKD progression. MATERIALS AND METHODS: From January 2003 to December 2006, 5,507 individuals underwent health checkups at our hospital's Preventive Medicine Research Center. We ultimately enrolled 2,175 individuals. The eGFR was ≥60 mL/min/1.73 m2 at the start of observation period, which was 20 years. The event onset time was the day that the eGFR became <30 mL/min during the 20-year period. Baseline risk factors - in particular, the effect of plasma glucose levels on the eGFR - were extracted and evaluated by using Fine and Gray analysis. RESULTS: During the 20-year observation, the hazard ratio (HR) of CKD progression was examined. A fasting plasma glucose (FPG) level ≥105 mg/dL was significantly associated with the risk of CKD progressing to an eGFR <30 mL/min. This trend was similar in the slope of eGFR. An FPG ≥105 mg/dL or an glycated hemoglobin level ≥6.5% was useful for intervening in CKD progression. Multivariate analysis showed that independent risk factors were an FPG level ≥105 mg/dL (HR 1.9; P < 0.001), age ≥60 years (HR 3.86; P < 0.001), obesity (HR 1.61; P < 0.01) and urinary protein (HR 1.55; P < 0.01). CONCLUSIONS: For early intervention against a reduction in the eGFR, detecting mild increases in FPG ≥105 mg/dL in patients with CKD with or without diabetes is useful.

Systemic Candida abscess after hypofractionated radiotherapy with temozolomide for glioblastoma in an older patient: illustrative case.

BACKGROUND: Hypofractionated radiotherapy with temozolomide is recommended for older patients with glioblastoma. Nevertheless, a potential complication of treatment is opportunistic infections with immunosuppression. OBSERVATIONS: An 86-year-old man presented with hemiparesis, prompting an investigation that revealed a right frontotemporal glioblastoma, isocitrate dehydrogenase wildtype. After the diagnostic biopsy, hypofractionated radiotherapy with temozolomide was administered. Lymphocytopenia was observed before the start of chemoradiotherapy and gradually worsened until 2 months later, possibly as a side effect of the treatment. One month after the completion of the initial treatment, the patient developed septic shock, leading to death within 2 days. Postmortem examination with autopsy revealed evidence of an invasive Candida infection possibly originating from the urinary catheter. LESSONS: Immunodeficiency, which is a side effect of radiation therapy with temozolomide, can cause rare and potentially fatal invasive Candida infections, especially in older and frail patients with newly diagnosed glioblastoma, even with short-term hypofractionated chemoradiotherapy. https://thejns.org/doi/10.3171/CASE24175.

Definitive chemoradiotherapy with paclitaxel for locally advanced esophageal squamous cell carcinoma in older patients (PARADISE-1): a phase I trial.

BACKGROUND: In older patients, esophageal squamous cell carcinoma (ESCC) is difficult to treat using standard therapies, including surgery and cisplatin-based chemoradiotherapy. Paclitaxel (PTX) has radiosensitizing activity. We conducted a phase I trial of PTX combined with radiotherapy to establish a standard therapy for locally advanced ESCC in older patients. METHODS: Enrollment was conducted at six centers in Japan from April 2016 to September 2019. The participants were aged ≥ 70 years, had locally advanced ESCC, and were intolerant to surgery or unwilling. A fixed 60-Gy radiation dose was administered in 30 fractions. PTX dosing levels started at 30 mg/m2 weekly for 6 weeks. Depending on the number of DLTs, the dose was set to be increased by 10 mg/m2 or switched to biweekly. A geriatric assessment was performed before treatment using the Geriatric-8 screening tool. The primary endpoint was dose-limiting toxicity (DLT). RESULTS: We enrolled 24 patients (6 per group); DLT was observed in one (grade 4 hypokalemia), one (grade 3 aspiration), two (grade 3 radiodermatitis, grade 3 esophageal hemorrhage), and two (grade 3 anorexia, grade 5 pneumonitis) patients in the weekly PTX 30, 40, 50, and 60 mg/m2 groups, respectively. All adverse events, except death in the 60 mg/m2 group, showed reversible improvement, and the safety profile was considered acceptable. The 2-year survival and complete response rates were 40.0% and 54.2%, respectively. There was a significant difference in survival between favorable and unfavorable Geriatric-8 scores. CONCLUSIONS: The recommended PTX dose with concomitant radiation was determined to be 50 mg/m2 weekly. Phase II trials at this dose are underway.

Comparison between asymptotic and re-randomisation tests under non-proportional hazards in a randomised controlled trial using the minimisation method.

BACKGROUND: Pocock-Simon's minimisation method has been widely used to balance treatment assignments across prognostic factors in randomised controlled trials (RCTs). Previous studies focusing on the survival outcomes have demonstrated that the conservativeness of asymptotic tests without adjusting for stratification factors, as well as the inflated type I error rate of adjusted asymptotic tests conducted in a small sample of patients, can be relaxed using re-randomisation tests. Although several RCTs using minimisation have suggested the presence of non-proportional hazards (non-PH) effects, the application of re-randomisation tests has been limited to the log-rank test and Cox PH models, which may result in diminished statistical power when confronted with non-PH scenarios. To address this issue, we proposed two re-randomisation tests based on a maximum combination of weighted log-rank tests (MaxCombo test) and the difference in restricted mean survival time (dRMST) up to a fixed time point τ , both of which can be extended to adjust for randomisation stratification factors. METHODS: We compared the performance of asymptotic and re-randomisation tests using the MaxCombo test, dRMST, log-rank test, and Cox PH models, assuming various non-PH situations for RCTs using minimisation, with total sample sizes of 50, 100, and 500 at a 1:1 allocation ratio. We mainly considered null, and alternative scenarios featuring delayed, crossing, and diminishing treatment effects. RESULTS: Across all examined null scenarios, re-randomisation tests maintained the type I error rates at the nominal level. Conversely, unadjusted asymptotic tests indicated excessive conservatism, while adjusted asymptotic tests in both the Cox PH models and dRMST indicated inflated type I error rates for total sample sizes of 50. The stratified MaxCombo-based re-randomisation test consistently exhibited robust power across all examined scenarios. CONCLUSIONS: The re-randomisation test is a useful alternative in non-PH situations for RCTs with minimisation using the stratified MaxCombo test, suggesting its robust power in various scenarios.

Relationship Between Patient-reported Outcome Measures and Accelerometer-measured Physical Activity and Sleep in Patients With Postherpetic Neuralgia.

OBJECTIVE: Available treatment for chronic neuropathic pain is still limited, and the positive effects are modest. Thus, clinicians aim to improve activity and quality of life despite pain. The objective monitoring of activity is attracting attention in chronic pain assessments. Therefore, we objectively evaluated daytime activity and sleep in patients with postherpetic neuralgia (PHN), using actigraphy to determine risk factors for decreased activity. METHODS: Participants with PHN wore an actigraph (a wristwatch-like accelerometer) on the nondominant hand. The actigraph measured day-time activity and sleep, which were compared with participant-reported subjective pain and sleep assessments. RESULTS: Fifty-four individuals with PHN who visited our outpatient clinic completed questionnaires and a week of actigraph monitoring. Subjective scores of pain intensity, neuropathic pain, disability in daily life, pain-catastrophizing thoughts, and insomnia were all well correlated. However, the actigraph-monitored activity levels, using 2 equations, and sleep quality were not associated with any pain or sleep-related subjective scores. CONCLUSION: The discrepancy between the subjective and objective scores in this study may be due to (1) features of PHN, an archetype of peripheral neuropathic pain affecting no motor nerves, (2) actigraph measurement limitations regarding the sedentary life of the elderly, or (3) activity misperception, a new proposition explaining the discrepancy between subjective and objective measures of activity, similar to the sleep state misperception. In patients with PHN, high pain intensity may be reported in those with highly maintained activity, in which treatment must be selected cautiously to prevent interruption of their physical abilities.

Social impact of brain fog and analysis of risk factors: Long COVID in Japanese population.

OBJECTIVE: To reveal the clinical features and assess risk factors linked to brain fog and its societal implications, including labor productivity, providing valuable insights for the future care of individuals who have experienced coronavirus disease 2019 (COVID-19). METHODS: We analyzed a comprehensive cohort dataset comprising 1,009 patients with COVID-19 admitted to Japanese hospitals. To assess brain fog, we analyzed patients who responded to a questionnaire indicating symptoms such as memory impairment and poor concentration. RESULTS: The prevalence of brain fog symptoms decreased 3 months posthospitalization but remained stable up to 12 months. Neurological symptoms such as taste and smell disorders and numbness at hospitalization correlated with a higher frequency of identifying brain fog as a long COVID manifestation. Our findings indicated that advanced age, female sex, a high body mass index, oxygen required during hospitalization, chronic obstructive pulmonary disease, asthma, and elevated C-reactive protein and elevated D-dimer levels were risk factors in patients exhibiting brain fog. Additionally, we demonstrated the negative impact of brain fog on labor productivity by presenteeism scores. INTERPRETATIONS: This study clarified the clinical characteristics of patients experiencing brain fog as a long COVID manifestation, specifically emphasizing neurological symptoms during hospitalization and their correlation with brain fog. Additionally, the study identified associated risk factors for its onset and revealed that the emergence of brain fog was linked to a decline in labor productivity.

Primary hepatobiliary mucoepidermoid carcinoma: a case report and review of literature.

Hepatobiliary mucoepidermoid carcinoma is a rare malignant tumor comprising mucous, intermediate, and epidermoid cells. Herein, we presented a case of primary liver mucoepidermoid carcinoma preoperatively misdiagnosed as conventional intrahepatic cholangiocarcinoma. A 67-year-old male was admitted to our hospital. Preoperative laboratory tests showed increased aspartate transaminase, alanine transaminase, and carbohydrate antigen 19-9. Abdominal Computer Tomography revealed a 4.8 × 4.9 cm liver mass in segment VI. A preliminary diagnosis of intrahepatic cholangiocarcinoma was made, with undergoing partial hepatectomy. However, on histopathology, the tumor comprised a mixture of epidermoid, mucous, and intermediate cells with diffuse infiltrating at the tumor margin. On special stains, mucous and intermedia cells were positive for mucicarmine and Alcian blue, whereas epidermoid cells were positive for Keratin 5/6 and p63. Intermediate cells are also positive for p63. All tumor cells were positive for Keratin 7. The Ki-67 index was 35%. The final diagnosis was primary hepatic mucoepidermoid carcinoma. Although rare, hepatic mucoepidermoid carcinoma should be considered in the intrahepatic cholangiocarcinoma differential diagnosis. We reviewed previous studies and found that hepatobiliary mucoepidermoid carcinoma is more likely to originate from the biliary tract adjacent to the tumor.

A phase II trial evaluating the efficacy and safety of repeated high dose medroxyprogesterone acetate (MPA) therapy for patients with recurrent early-stage endometrial cancer or atypical endometrial hyperplasia: Japanese Gynecologic Oncology Group study (JGOG2051/KGOG2031, REMPA trial).

BACKGROUND: Fertility preserving therapy using medroxyprogesterone acetate (MPA) is an important option for young patients with endometrial cancer or atypical endometrial hyperplasia (AEH). However, the effectiveness and feasibility of repeated MPA therapy for patients with intrauterine recurrence following initial MPA therapy is controversial. Only a few single-institution retrospective studies have been conducted on repeated MPA therapy, therefore, multicenter prospective studies for repeated MPA therapy are highly needed. The aim of this study is to assess whether repeated MPA therapy is effective and feasible for patients with intrauterine recurrence following initial MPA therapy. METHODS: This is a prospective, single-arm, a multicenter phase II trial on repeated MPA therapy for intrauterine recurrence following fertility-preserving therapy for AEH or stage IA (the International Federation of Gynecology and Obstetrics [FIGO] 2008) non-myoinvasive endometrioid carcinoma grade 1. Patients are treated with oral MPA (500-600 mg/day). Pathologically assessment via dilation and curettage will be performed every 2 months until complete response. The major inclusion criteria are 1) intrauterine recurrence of AEH or stage IA (FIGO 2008) endometrioid carcinoma grade 1 without myometrial invasion or extrauterine spread confirmed by imaging tests after complete remission with the previous MPA therapy. 2) The number of recurrences should be up to twice. 3) histologically diagnosed as AEH or endometrioid carcinoma grade 1, 4) 20-42 years of age, and 5) strong desire and consent for fertility-sparing treatment. The primary endpoint is 2-year recurrence-free survival rate. A total of 115 patients will be enrolled from multiple institutions in Japan and Korea within 4 years and followed up for 2 years. TRIAL REGISTRATION: Japan Registry of Clinical Trials Identifier: jRCTs031200256.

Underweight in young Japanese women over time: a longitudinal retrospective study of the change in body mass index from ages 6 to 20 years.

BACKGROUND: The high prevalence of underweight in young women has become a serious health problem in Japan. When and how young women reach a low body mass index (BMI) has not been clarified. AIM: To clarify the characteristics of BMI standard deviation scores (BMI SDS) trajectory of young Japanese women with underweight. SUBJECTS AND METHODS: A total of 601 Japanese female university students aged 20 years were classified into underweight and healthy weight groups. Their school health check-up data were available from the ages of 6 to 20 years. We evaluated the estimated mean values of BMI SDS at each age and differences in BMI SDS (ΔBMI SDS) from 6 years to each age using a mixed-effects model and compared between the two groups at each age. RESULTS: In the underweight group, the BMI SDS at every age (-1.67 to -0.91) and the ΔBMI SDS after 16 years of age (-0.76 to -0.38) were significantly lower than those in the healthy weight group (-0.41 to -0.13, -0.07 to 0.04), respectively. CONCLUSION: Young Japanese women with underweight have at least two characteristics of BMI SDS trajectory: being constitutionally underweight and shifting their weight status from baseline towards underweight in their late teens.