People devoid of COVID-19 may exhibit mental health problems, such as anxiety disorders, depression, panic attack, insomnia, emotional disorder, and suicidal actions. Healthcare workers (HCWs) may also exhibit these problems. Physicians should be careful an "at-risk" population. Physicians revealed higher levels of resilience than the popular workers. Humans with stronger resilience have lower feeling of anxiety and depression. We investigated the risk to physicians from an infected environment to infected patients during the pandemic. The social and psychological support of all HCWs, particularly physicians, is significant in the fight against this pandemic. Physicians working with patients with COVID-19 should set enough time to relax, sleep, and spend time with family. Resilience in physicians facing COVID-19 can induce post-traumatic growth in the future.

Background: Postoperative pain is a major cause of delayed recovery following inguinal hernia repair. Transcutaneous electrical nerve stimulation (TENS) is a simple, low-cost method of noninvasive analgesia. This study aimed to assess the efficacy and safety of TENS for pain management following inguinal hernia repair.

Methods: We searched nine electronic databases and trial registries to identify randomized controlled trials (RCTs). The primary outcomes were postoperative pain and the use of rescue analgesics. The Risk of Bias 2 tool was used to evaluate the risk of bias in the included trials. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Subgroup analyses were conducted based on the anesthesia type or TENS dose and frequency. This study is registered with PROSPERO (CRD42022353932).

Results: Eleven RCTs, with a total of 559 patients, were included. The overall risk of bias was concerning due to the lack of information about concealment or published protocols. TENS may reduce pain on postoperative day (POD) 0 (standardized mean difference [SMD], −2.14; 95% confidence interval [CI], −3.54 to −0.73; moderate certainty of the evidence), POD 1 (SMD, −1.22; 95% CI, −1.92 to −0.52; moderate certainty of the evidence), and POD 2 (SMD, −0.97; 95% CI, −2.04 to 0.10; low certainty of the evidence). According to the subgroup analyses, postoperative pain was reduced, particularly with local anesthesia or repetitive and frequent TENS (P < 0.05). TENS may result in little-to-no difference in rescue analgesic use (risk ratio, 0.75; 95% CI, 0.47-1.18; low certainty of the evidence). No serious adverse events occurred (moderate certainty of the evidence).

Conclusions: TENS may reduce pain in patients who have undergone inguinal hernia repair. Further trials are warranted to confirm our findings.

Sarcopenia is a condition characterized by age-related muscle loss and dysfunction. Over the past decade, several working groups have developed diagnostic criteria for sarcopenia, including muscle mass, grip strength, and gait speed measurements. However, there is debate over which muscle mass indicator is the most appropriate. Some groups used appendicular lean mass divided by height squared, whereas others used appendicular lean mass divided by body mass index. In addition, the association between muscle mass and long-term health outcomes is inconsistent. As a result, some experts question the necessity of using muscle mass as a diagnostic criterion for sarcopenia. This review summarizes the measurement methods and muscle mass indicators of previous studies, highlighting issues with past muscle mass assessments.

Cardiomyocytes undergo cell division during the fetal period but do not divide after birth; thus, they grow into adult heart cells by enlarging their size. Therefore, heart failure occurs when a certain number of cardiomyocytes are lost owing to myocardial infarction, myocarditis, sarcoidosis, etc.

Through scientific efforts, we have developed methods to safely and efficiently generate induced pluripotent stem (iPS) cells from peripheral blood T cells, generate ventricle-specific cardiomyocytes from iPS cells, and remove residual iPS cells and non-cardiomyocytes using the "metabolic selection method" and purify the cardiomyocytes from iPS cell derivatives. We have also developed the technology to mass-produce and efficiently engraft cardiomyocytes by generating cardiomyocyte spheroids and have developed devices suitable for cell transplantation.

We have confirmed the safety and efficacy of these techniques by performing preclinical studies (oncogenesis, arrhythmogenicity, etc.) using immunodeficient mice, rats, pigs, and monkeys. Based on these technologies, we have successfully regenerated human ventricular muscle-specific cardiomyocytes with purity greater than 99%. We have also confirmed that the regenerated myocardium transplanted into immunodeficient mice maintained autonomic beating for more than a year without tumor formation.

We are planning to conduct clinical trials to transplant iPS cell-derived cardiomyocytes into patients with heart failure associated with ischemic heart disease, which will, in the near future, enable clinical applications using HLA-deficient iPS cells and iPS cells generated from the patient's own lymphocytes to generate regenerative cardiomyocytes without rejection. It would also help establish personalized medicine for heart failure and usher in the long-awaited treatment for intractable severe heart failure using ventricular muscle supplementation.

Introduction: Following recently increased public awareness, the number of medical malpractice litigation cases in Japan has increased in all fields of health care. A pathological autopsy is important for medical practice but has not yet been subject to much litigation.

Methods: This study presents a review of all civil lawsuits involving pathological autopsies identified in a Japanese database of lawsuits (Westlaw.com). The basic characteristics of cases, the main issues in each case, results, and reasons for the results given by the court were examined.

Results: Over 500 cases were examined, among which four autopsy-related negligence lawsuits were retained for analysis. Judgments in these cases were delivered between February 2000 and February 2017. Two judgments were regarding the same case, which was discussed in two different civil procedures (monetary damages and request to return the specimens of patients to relatives). This included three factual cases, which were all civil. Each case was brought by close relatives, and all defendants were hospitals. The main issues were informed consent and the accuracy of autopsy results in two and one cases, respectively. The issues related to informed consent were the need for informed consent to take a specimen and the scope of informed consent.

Conclusions: This study describes the basic characteristics of malpractice lawsuits related to autopsies. Lawsuits related to pathological autopsies seem to be relatively rare in Japan.

Introduction: As the characteristics of coronavirus disease 2019 (COVID-19) vary across regions and countries, the relationship between regional characteristics, such as the distribution of physicians and hospital beds, and COVID-19 mortality was assessed in the 47 prefectures of Japan.

Methods: This ecological study was based on the number of patients with COVID-19 by prefecture during the seventh wave of COVID-19 in Japan (June-October 2022). COVID-19 mortality was indexed as the number of COVID-19 deaths divided by the number of new COVID-19 cases. Data on regional factors, such as population size, number of physicians, and hospital beds by prefecture, were obtained from government statistics. Correlations between regional characteristics and COVID-19 mortality index were analyzed by dividing the 47 prefectures into two groups at the median level of population size (more populated group [MPG] ≥ 1.6 million and less populated group [LPG] < 1.6 million).

Results: The COVID-19 mortality index (mean 12.7, minimum-maximum: 4.7-25.7) was correlated negatively with the number of physicians per hospital bed (r = −0.386, p = 0.007) and positively with the number of long-term care facilities per 10,000 population (r = 0.397, p = 0.006) and aging rate (the proportion of population aged ≥ 65 years) (r = 0.471, p = 0.001). The two groups varied with respect to the number of physicians (28.7 physicians in the LPG vs. 26.1 physicians in the MPG, p = 0.038) and hospital beds (156 beds in the LPG vs. 119 beds in the MPG, p < 0.001) per 10,000 population. In the multiple regression analysis, the COVID-19 mortality index was correlated negatively with the number of physicians per hospital bed (β = −0.543, p = 0.024) and positively with the aging rate (β = 0.434, p = 0.032) in the LPG, with nonsignificant correlations in the MPG.

Conclusions: The data may suggest a need of improvement in the distribution of physicians and hospital beds in the healthcare system in regions with smaller and older populations to reduce the rate of COVID-19.

Introduction: Chronic kidney disease (CKD) significantly affects activities of daily living (ADLs) before and after the initiation of dialysis, particularly in elderly individuals. However, the impact of admission functional status on dialysis patients' outcome is not fully understood. This study aimed to investigate the effect of the number of ADL disabilities usually measured for all patients hospitalized in Japan on in-hospital outcome for dialysis patients.

Methods: Using an inpatient administrative claims database, we included 104,557 admissions of patients undergoing chronic dialysis aged 65 years and above from 2012 to 2014. The primary outcome was in-hospital all-cause mortality (evaluated using logistic regression models), and the secondary outcomes were length of stay and care cost.

Results: The mean age of the participants was 74.0 ± 6.2 years, the mean body mass index (BMI) was 21.8 ± 3.9, 31% needed assistance for one or more of five basic ADLs (feeding, transferring, going to toilet, dressing, and bathing) at admission, and 3.5% (n = 3,701) died after hospitalization. After adjusting for confounding factors, the odds ratios (ORs) (95% confidence intervals) of death for 1, 2, 3, 4, and 5 ADL disabilities were 1.43 (1.19-1.70), 2.04 (1.71-2.45), 2.58 (2.19-3.04), 3.74 (3.35-4.17), and 6.83 (6.29-7.41) versus a complete independence, respectively. The increasing number of ADL disabilities was also associated with greater length of stay and costs. Risk stratification by age, admission functional status, and BMI showed an 18-mortality risk matrix with a maximal risk of a 15.5-higher OR for lean patients aged ≥75 years with severe ADL disability compared with that for patients aged <75 years with middle BMI and no ADL disability on admission.

Conclusions: Admission functional status decline significantly increases in-hospital mortality, length of stay, and costs. Routine assessment of functional status can facilitate the risk prediction of dialysis patients.

Introduction: In Japan, the clinical information on post-COVID-19 syndrome, including nursing care requirements, is limited. The present study investigated the incidence of acute and post-COVID-19 symptoms, including nursing care requirements, when different SARS-CoV2 strains were prevalent and vaccination statuses changed to mass vaccination programs in Japan.

Methods: Electronic health records of 122,045 patients diagnosed with COVID-19 between January 1, 2020, and June 30, 2022, were obtained from the Tokushukai Group Medical Database. Patient data was divided into three observation periods. Using the International Statistical Classification of Diseases and Related Health Problems 10 codes, typical symptoms of acute (within two weeks after diagnosis) and post-COVID-19 (2-12 weeks after diagnosis) were extracted. Moreover, the nursing care requirements of patients who visited the hospital before and after the COVID-19 diagnosis were examined.

Results: Original and alpha strains were prevalent in Period 1, wherein most of the population was unvaccinated. The delta strain was prevalent in Period 2, wherein approximately 70% of the population was vaccinated. The omicron strain was prevalent in Period 3, wherein approximately 70% of the population completed the two vaccination doses. Headache, malaise/fatigue, depression, and disuse syndrome were detected in acute and post-COVID-19. The incidence of depression and disuse syndrome in post-COVID-19 increased with age, with the highest incidence in the 60-85-year group. Moreover, increased high-level nursing care requirements were observed after COVID-19 in the 60-85-year-age group.

Conclusions: A lower incidence of acute and post-COVID-19 symptoms in Japan is linked to increased population vaccination coverage. However, differences in viral strains may be involved. Moreover, a reduction in long-term quality of life exists in older adult patients after COVID-19. These data provide fundamental information for preventing and treating post-COVID-19 syndrome in Japan.

Introduction: Hepatitis B virus (HBV) DNA and cytomegalovirus (CMV) DNA can be detected in patient genomes. However, it remains unknown whether viral DNA can be integrated into host genomic DNA and detected in fingernails.

Methods: Nails from patients with chronic HBV infection were investigated. A total of 60 patients (male/female = 20/40, age range from 2 years to 59 years, median 15 years) were included in this study. The viral DNA levels of herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), varicella-zoster virus (VZV), Epstein‒Barr virus (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV-6), human herpes virus 7 (HHV-7), and HBV in nails were measured with real-time PCR. Viral DNA integration into host genomic DNA was analyzed by capture-based next-generation sequencing (NGS). Moreover, virus/host chimeric sequences, which were detected by capture-based NGS, were confirmed by Sanger sequencing.

Results: Of the 60 patients, 37 (62%) were positive for nail HBV DNA. All 60 patients were negative for nail HSV-1, HSV-2, VZV, CMV, EBV, or HHV-6 DNA. However, three patients were positive for nail HHV-7 DNA. All three nail HHV-7-positive patients were also positive for nail HBV DNA. The three nail samples that were positive for both HBV and HHV-7 DNA were used for viral integration analysis by capture-based NGS. One of the three nail samples showed HBV/host chimeric sequences. In addition, all three nail samples showed HHV-7/host chimeric sequences. However, these viral integration breakpoints were not confirmed by Sanger sequencing.

Conclusions: Viral integrations were detected in nails by capture-based NGS. However, Sanger sequencing did not confirm any virus/host chimeric sequences. This study could not show reliable evidence of viral integration in nails.

Introduction: Many countries have reported persistent and concomitant symptoms of coronavirus disease 2019 (COVID-19). This study aimed to identify persistent COVID-19 and concomitant symptoms in discharged patients and identify the risk factors for such symptoms.

Methods: This study enrolled patients with COVID-19 who were admitted to the University of Fukui Hospital, Japan, and discharged between April 3, 2020, and August 19, 2021. Persistent and concomitant symptoms were confirmed based on medical examinations approximately 2 weeks after discharge. Patient characteristics and symptoms were collected from the patients' medical records by a technical assistant.

Results: This study included 120 patients (60 men and 60 women; mean age, 53.5 ± 17.0 years). Persistent COVID-19 symptoms were observed in 62 patients (51.7%). The most common persistent symptom was weakened physical function, manifesting as physical weakness (48.4%) and muscle weakness (29.0%). Binary logistic regression analysis revealed that cough with expectoration within the acute phase of COVID-19 was a risk factor predisposing patients to COVID-19 sequelae (odds ratio: 2.94, 95% confidence interval: 1.300 - 6.630, p = 0.009).

Conclusions: The study findings suggest that productive cough in the acute phase is associated with subsequent physical and muscle weaknesses in the subacute phase.

Introduction: There remains to be lacking real-world evidence for the treatment of rosacea with a topical sulfur preparation (TSP) or topical metronidazole preparation (TMP) among Japanese patients. Therefore, in this study, we examined the effects of TSP and TMP on rosacea in Japanese patients in real-world clinical settings.

Methods: This retrospective observational analysis reviewed the medical records of 47 Japanese patients who were treated with TSP or TMP for more than 8 weeks in our clinic. Disease severity was evaluated using the Investigator Global Assessment (IGA) and the visual analog scale (VAS) for itching, burning sensation, flushing, and hypersensitivity before and 8 weeks after the initiation of the intervention.

Results: In total, 10 erythematotelangiectatic rosacea (ETR) and 12 papulopustular rosacea (PPR) patients treated with TSP and 12 ETR and 13 PPR patients treated with TMP were analyzed. IGA and VAS scores for itching, burning sensation, flushing, and hypersensitivity were noted to significantly improve in the ETR and PPR patient groups treated with TSP and both groups treated with TMP, except for the VAS score for itching in the TSP-treated ETR group. No significant differences were observed in terms of the improvement rates of IGA, VAS scores, or the prevalence of adverse events between the TSP- and TMP-treated groups.

Conclusions: As per our findings, TSP and TMP have similarly favorable effects on both ETR and PPR in Japanese patients in real-world settings.

Introduction: We investigated the association between history of vaccination for coronavirus disease 2019 (COVID-19) and symptoms at its diagnosis.

Methods: We retrospectively analyzed 2566 consecutive individuals suspected of having COVID-19 and visited a designated clinic between January and September 2022 (1733 were diagnosed with COVID-19, and 816 tested negative for COVID-19) in Japan. The individuals were divided by vaccination history for COVID-19.

Results: In the COVID-19-free individuals, the vaccination was not significantly associated with any symptoms. Contrarily, those with COVID-19 demonstrated an inverse relationship between the vaccination and body temperature; the adjusted mean value was higher by 0.01°C, 0.04°C, 0.09°C, 0.27°C, and 0.34°C and 0.48°C in individuals vaccinated 2-4, 4-6, 6-8, 8-10, and >10 months before and those unvaccinated, respectively, than in those vaccinated within 2 months (P = 0.96, 0.41, 0.081, 0.006, 0.004, and <0.001). Furthermore, among the affected population, individuals vaccinated long before or never vaccinated more frequently complained of fatigue and headache; the adjusted odds ratios of those vaccinated >10 months before and those unvaccinated compared with those vaccinated within 2 months were 2.53 and 2.45 for fatigue and 2.53 and 2.17 for headache (all P < 0.05). Contrarily, the prevalence of rhinorrhea, sore throat, and cough was higher in recently vaccinated individuals (adjusted odds ratios of those vaccinated within 2 months versus those unvaccinated, 2.40, 2.46, and 2.46; all P < 0.05).

Conclusions: Symptoms at the COVID-19 diagnosis differed with the vaccination history. Information on vaccination history would be worth using when suspecting COVID-19 based on symptoms.

Introduction: In Japan, approximately 97 million individuals have received their primary two doses of coronavirus disease 2019 (COVID-19) vaccine at the end of 2022. In this study, we aim to examine the effectiveness of the primary vaccines and compare its efficacy to booster vaccine shots in terms of preventing COVID-19 exacerbations during the Omicron-predominant period in Japan.

Methods: For this analysis, we have collected all the confirmed COVID-19-positive cases from different medical institutions in Okayama City and have also utilized the information from the public Vaccination Record System. Taking the number of vaccinations into consideration, we then conducted a population-based study to assess the effectiveness of the two primary vaccine doses in preventing COVID-19 exacerbations during the Omicron waves. Our primary and secondary outcomes were COVID-19 exacerbations with respiratory failure (i.e., oxygen saturation on room air ≤ 93%, requiring supplemental oxygen), intensive care unit admission and/or mechanical ventilator requirement, or death, in accordance with the Japanese COVID-19 guidelines, and pneumonia during the course of COVID-19 infection, respectively.

Results: In total, 95,329 COVID-19-positive individuals, aged 5 years and above, were included in this analysis (study period from January 1 to September 10, 2022). As per our findings, the effectiveness of the primary two doses against COVID-19 exacerbations compared with those who had never been vaccinated was 55.5% (95% confidential interval [CI]: 32.6-71.7), whereas it was higher after the third dose (76.9%; 95% CI: 66.7-84.0) and the fourth dose (75.7%; 95% CI: 58.8-85.7). Effectiveness was sustained for ≥ 5 months after the third vaccination, and preventive effectiveness was observed in individuals aged ≥ 65 years.

Conclusions: As per the results of this study, we can conclude that the efficacy of the primary two doses of SARS-CoV-2 vaccine can be further strengthened in terms of preventing COVID-19 exacerbations by administering third and fourth booster vaccine shots. The additional bivalent vaccine is anticipated to further increase its efficacy against the Omicron strain, suggesting that individuals who have not received their booster shots yet should consider getting them to prevent COVID-19 exacerbations.

Introduction: A critical value (or panic value) is a laboratory test result that significantly deviates from the normal value and represents a potentially life-threatening condition requiring immediate action. Although notification of critical values by critical value list (CVL) is a well-established method, their contribution to mortality prediction is unclear.

Methods: A total of 335,430 clinical laboratory results from 92,673 patients from July 2018 to December 2019 were used. Data in the first 12 months were divided into two datasets at a ratio of 70:30, and a 7-day mortality prediction model by machine learning (eXtreme Gradient Boosting [XGB] decision tree) was created using stratified random undersampling data of the 70% dataset. Mortality predictions by the CVL and XGB model were validated using the remaining 30% of the data, as well as different 6-month datasets from July to December 2019.

Results: The true results which were the sum of correct predictions by the XGB model and CVL using the remaining 30% data were 61,535 and 61,024 tests, and the false results which were the sum of incorrect predictions were 5,492 and 6,003, respectively. Furthermore, the true results with the different datasets were 105,956 and 102,061 tests, and the false results were 6,052 and 9,947, respectively. The XGB model was significantly better than CVL (p < 0.001) in both datasets.

The receiver operating characteristic-area under the curve values for the 30% and validation data by XGB were 0.9807 and 0.9646, respectively, which were significantly higher than those by CVL (0.7549 and 0.7172, respectively).

Conclusions: Mortality prediction within 7 days by machine learning using numeric laboratory results was significantly better than that by conventional CVL. The results indicate that machine learning enables timely notification to healthcare providers and may be safer than prediction by conventional CVL.

Introduction: The gold standard for evaluating kidney function is kidney inulin clearance (Cin). However, this procedure is difficult to perform in patients with neuromuscular disabilities and/or bladder dysfunction. We aimed to develop a simpler method for determining the estimated glomerular filtration rate (eGFR) using equations and values for three biomarkers: serum creatinine (sCr), serum cystatin C (cysC), and serum beta-2 microglobulin (β2MG). This study evaluated three eGFR equations in patients with severe motor and intellectual disabilities (SMID).

Methods: We evaluated the equations using data of 18 adult SMID patients with a clinical need for creatinine clearance (Ccr). We compared the results of each equation with Ccr-based eGFR instead of Cin using mean error (ME), root mean square error (RMSE), and P30.

Results: Based on eGFR, the ME values of Cr, cysC, β2MG, and Ccr were 74.5, 2.3, and 6.5 mL/min/1.73 m², RMSE values, 92.3, 25.7, and 33.4 mL/min/1.73 m²; and P30, 16.7%, 77.8%, and 72.2%, respectively.

Conclusions: eGFR-Cr cannot be used to reliably assess kidney function in adult SMID patients. It is better to use eGFR-cysC to evaluate kidney function in this patient population.

Introduction: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is superior to enalapril for chronic heart failure (CHF) with reduced ejection fraction (EF). However, its efficacy and safety in older Japanese patients in clinical practice are poorly understood. We aimed to investigate the efficacy and safety of ARNI compared with angiotensin receptor blocker (ARB) in older patients with CHF in real-world clinical practice. In addition, nutritional status and body composition were investigated as essential indicators of efficacy.

Methods: This retrospective single-center observational study enrolled 55 consecutive older patients (aged ≥75 years) with CHF who received ARNI (n = 27) or ARB (n = 28) therapy between October 2020 and March 2021. Blood samples were collected before (baseline) and 4, 12, and 24 weeks after ARNI or ARB therapy initiation. Furthermore, echocardiography was performed before (baseline) and 24 weeks after ARNI or ARB therapy initiation. The efficacy endpoints were changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, left ventricular EF, nutritional status, and body composition changes. The controlling nutritional status (CONUT) score and geriatric nutritional risk index were investigated as nutritional status indices. The safety endpoints were symptomatic hypotension, renal function exacerbation, and hyperkalemia in patients who continued ARNI or ARB therapy for >24 weeks without additional nonpharmacological treatment.

Results: There were no significant changes in NT-proBNP levels and estimated glomerular filtration rates; however, there was a significant CONUT score improvement in the ARNI group (least-squares mean difference, −1.0; 95% confidence interval, −1.4 to −0.3; p = 0.04). The initial ARNI dose could not be uptitrated in five patients (19%) due to hypotension.

Conclusions: ARNI exhibited significant improvement in the nutritional status in older patients with CHF compared with ARB. However, the ARNI dose should be adjusted according to the patient's blood pressure.

Introduction: Remote antenatal checkups were conducted on the northernmost island of Japan to reduce the burden of hospital visits among pregnant women. This study aims to investigate the effectiveness and safety of remote antenatal checkups for pregnant women living on a remote island.

Methods: This observational study included singleton pregnancies on Rebun Island between October 2020 and September 2022. General surgeons conducted medical interviews and performed fetal sonography using an obstetrician videoconference system at the main central hospital. The primary outcomes were the degrees of physical, mental, and economic burdens of hospital visits and the levels of anxiety and satisfaction with remote antenatal checkups as assessed using a questionnaire survey. Moreover, we investigated the incidence of adverse perinatal events, including maternal death, fetal death, neonatal death, severe neonatal neurological disorders, and other obstetric complications.

Results: This study included 16 out of 22 pregnant women from Rebun Island who visited the central hospital. No adverse perinatal events occurred as a result of the remote antenatal checkups. One pregnant woman had gestational diabetes, whereas the others had no obstetric complications. The participants underwent a median of two remote antenatal checkups. According to a questionnaire survey, 90.0%, 80.0%, and 70.0% of the pregnant women perceived improvements in their physical, mental, and economic burdens, respectively. Although 70.0% of the participants experienced anxiety regarding remote antenatal checkups before the introduction, all were satisfied after delivery.

Conclusions: Remote antenatal checkups effectively reduced the burden of hospital visits for pregnant women, who reported high levels of satisfaction. Furthermore, antenatal checkups were safely conducted on remote islands.

Introduction: Due to the increase in the number of early-stage breast cancer patients, there is growing interest in minimally invasive local therapies for breast cancer. Radiofrequency ablation (RFA) therapy is one of the most promising minimally invasive treatments. The Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (RAFAELO) study, a multicenter collaborative study that aims to validate the efficacy and safety of RFA and to standardize its use for early-stage breast cancer, was conducted under the Advanced Medical Care B system in 2013. This study enrolled the expected number of patients in November 2017; moreover, it is currently in the follow-up period. Some patients with early-stage breast cancer who are eligible for RFA could not receive the RFA treatment, as it is still not covered by insurance. Therefore, the Patients Offer Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (PO-RAFAELO) study under the Patient-proposed Health Services (PPHS) was proposed and approved in March 2019.

Methods: The PPHS is a system that allows patients to receive prompt access to advanced medical care at a medical facility close to them, starting with their request. This system is considered a part of the specific and special medical coverage. The PO-RAFAELO study is the only study in the surgical field utilizing the PPHS, aiming to help in achieving regulatory approval and insurance coverage of RFA for breast cancer.

Results: As of January 2023, 120 patients have undergone RFA using the PPHS and no grade 3 or higher early adverse events have occurred.

Conclusions: A certain number of patients with early-stage breast cancer prefer nonsurgical treatment, and it is important to provide information regarding the availability of RFA for early-stage breast cancer under the PPHS.

Trial registration: registered with Japan Registry of Clinical Trial on March 06, 2019 (Trial ID: jRCTs032180187).

Vaccination is a crucial and evidence-based measure against novel coronavirus disease 2019 (COVID-19) implemented worldwide, including in Japan, where more than 67% of the population has received more than three doses of vaccination as of February 2023. Although some common adverse reactions of the vaccine, such as fever and arm pain, have been reported, serious adverse reactions resulting in death, such as myocarditis and Guillain-Barré syndrome, are rare. However, the biased reporting of the adverse reactions of the COVID-19 vaccine in the Japanese media has recently become more frequent, which is similar to the past biased reporting on the human papillomavirus (HPV) vaccine. Previously, the media's biased reporting on the HPV vaccine caused public mistrust in vaccines, leading to a drop in vaccination rates in Japan. Thus, overlooking the sensational reporting of the media on the current COVID-19 vaccine may potentially influence people's health behavior and awareness in the long run. Actually, experts worldwide agree that the COVID-19 vaccine is safe, and the media reports are inconsistent with the observations. Thus, it is necessary to urge the media to release accurate information to prevent tragedies caused by biased reporting. Moreover, it is essential to correct misinformation in reporting, disseminate accurate information from media outlets, such as Internet news and video-sharing sites, and promote awareness among people to support the vaccination rate against COVID-19.

As an economic activity, any medical practice involves greenhouse gas (GHG) emissions. In Japan, healthcare accounts for approximately 5% of GHG emissions estimated based on economic costs. In the medical sector, pharmaceuticals account for a large proportion of these emissions. GHG produced during drug manufacturing is generally estimated in three scopes. Scope 1 encompasses direct emissions from equipment and business activities owned by the company; Scope 2 encompasses indirect emissions from the production of energy used in the company's activities; and Scope 3 encompasses GHG emissions outside the scope of the company's ownership or control but related to its supply chain (i.e., material procurement, logistics, sales, and disposal). Japanese pharmaceutical companies, similar to companies in other countries, strive to build a sustainable industry. Their efforts have been objectively evaluated, and several companies have been certified by organizations, such as the Carbon Disclosure Project. Regarding biotechnology and the healthcare and pharmaceuticals sectors, 6 of the 14 highest-ranking companies in the world are located in Japan, compared to one or two companies in other nations. Each pharmaceutical company has generally set high emissions goals, although these goals do not necessarily match due to operational differences between companies. Typical strategies to reduce GHG emissions include consolidation of plant facilities, use of renewable energy and eco-cars, simplified packaging of drugs, and shortening of the supply chain. If consumers ignore such companies' efforts, it could put the brakes on environmental conservation activities in the pharmaceutical sector. Stakeholders, including healthcare providers, could further encourage movement toward environmentally friendly pharmaceuticals by market mechanism through proactively prescribing drugs with less environmental burden. Any clinicians can recognize corporate efforts to protect the environment and contribute to developing environmentally friendly medicine for sustainable growth.

The International Committee of Medical Journal Editors (ICMJE) recommendations are used by medical journals worldwide to guide editors and authors regarding "best practices" related to the intersection between research and publishing. In this opinion paper, we bring two discussion points to the attention of readers and users of the ICMJE recommendations. The first pertains to journals' use of the old conflicts of interest form, replaced in 2021 with a new disclosure form. The second relates to inconsistent or outdated policies in journals' instructions for authors mismatching the current ICMJE recommendations. The ICMJE does not monitor how journals use or apply the ICMJE recommendations. Thus, the editors must be mindful of updates and changes relevant to the authors. Furthermore, authors should carefully examine journals before submission to ensure that journals use updated forms and policies and should be mindful of submitting to non-ICMJE-recommendations-conforming journals despite claiming to follow them.

Clinical practice guidelines (CPGs) consist of clinical questions (CQs) and corresponding recommendations. Considering the estimation of body of evidence, patients' opinions, and medical economics, recommendations can vary depending on the votes of the committee members of CPGs. Taking this into consideration, concerns have already been raised on how financial conflict of interest (COI) potentially influences recommendations. In this study, we developed the third edition of guideline for the management of hyperuricemia and gout. This CPG was composed of seven CQs and recommendations. The direction and strength of the recommendations were determined by votes. There are three CQs. Individual questions asked whether uric acid-lowering-agents (ULAs) could be applied to hyperuricemic patients with chronic kidney disease (CKD) (CQ A), hypertension (CQ B), or heart failure (CQ C) to prevent organ damage. We examined whether the absence (18 members) or presence (8 members) of COIs of committee members could influence the votes. In total, 26 committee members with and without COI have equally determined the direction and strength of recommendations. In CQ A, members without financial COIs and those with financial COI selected conditional recommendation for the use of ULAs in patients with CKD (without COI, 17/18; with COI, 7/8). In CQ B, members without financial COIs and those with financial COI selected conditional recommendation against the use of ULAs in hypertensive patients (without COI, 14/18; with COI, 5/8). In CQ C, members without financial COIs and those with financial COIs have selected conditional recommendation against the use of ULAs in patients suffering from heart failure (without COI, 15/18; with COI, 4/8).

We found that members with financial COIs have determined their recommendations in the same direction and strength as those without financial COIs.

Platinum-based combination chemotherapy has been a frontline therapeutic strategy for advanced ovarian cancer. Although patients with ovarian high-grade serous carcinoma (HGSC) respond well to the combination therapy, those with relatively rare histologic subtypes, such as mucinous or clear cell carcinoma of the ovary (OCCC), show resistance to platinum-based chemotherapy. Even with the recently developed maintenance therapies using molecular targeted inhibitors for ovarian cancers, such as bevacizumab or poly (ADP-ribose) polymerase (PARP) inhibitors, the prognosis of non-HGSC ovarian cancers is unsatisfactory. To overcome the limitations in the treatment of rare ovarian cancers, the Japanese Gynecologic Oncology Group (JGOG) has launched a comprehensive project utilizing publicly available genomic databases, including a national clinico-genomic database maintained by the Center for Cancer Genomics and Advanced Therapeutics (C-CAT). JGOG, a leading group in Japan that conducts clinical trials for the treatment of gynecological malignancies, also established a nationwide network through the long-standing efforts of all participants. Currently, JGOG is engaged in a phase II international clinical trial (CYH33-G201: jRCT2031210216), targeting OCCC with PIK3CA hotspot mutations. The CYH33-G201 trial is sponsor-initiated, and JGOG, in collaboration with pharmaceutical companies, is actively recruiting participants. To expand the functions of the nationwide network that JGOG had already established, we held explanatory meetings for this clinical trial in nine different areas throughout Japan to promote the penetration of the CYH33-G201 trial. Through C-CAT database analysis, we estimated that approximately 40% of the patients with OCCC harbored at least 1 of the 17 PIK3CA hotspot mutations designated in the CYH33-G201 trial. JGOG will continue the challenge of establishing novel treatment strategies for rare refractory cancers that will benefit patients suffering from gynecological malignancies, especially those who do not receive satisfactory standard treatment and care.

The internal carotid artery (ICA) typically runs posterolaterally to the external carotid artery (ECA) at the level of the common carotid artery (CCA) bifurcation in the neck. The "twisted ICA" is an anatomical variation, wherein the ICA is medial to the ECA. Several studies on the twisted ICA have discussed its anatomical definition, incidence, clinical features, and surgical results in patients with luminal stenosis. Computed tomography angiography (CTA) -based analyses of surgically treated cohorts documented a twist angle, reaching up to 95°. Carotid endarterectomy (CEA) was successfully performed for these patients. This study reports a case of a significantly twisted ICA with severe luminal stenosis that was successfully treated with CEA. An 81-year-old male was incidentally diagnosed with asymptomatic right ICA stenosis based on magnetic resonance (MR) angiography. Three-dimensional (3D) -CTA showed that the ICA revealed 74% stenosis of the ICA, based on the North American Symptomatic Carotid Endarterectomy Trial criteria. The 3D-CTA showed the ICA medial to the ipsilateral ECA at the level of the CCA bifurcation in the neck. It extended proximally to the pharynx, and the twist angle was 102°. Black-blood MR of the carotid plaque exhibited a high intensity on T1-weighted imaging, indicating vulnerability. Intraoperatively, the position of the ICA was corrected using multiple hooks instead of a surgical retractor. He showed no permanent deficits, such as an ipsilateral cerebral infarction, although transient postoperative hoarseness was observed. This case report documented a significantly twisted ICA with luminal stenosis, successfully treated via CEA, by correcting the carotid position using multiple hooks with gentle manipulation.

Immune-related adverse events (irAEs) mimicking rheumatic diseases are observed in 1.5%-22% of patients receiving cancer therapy with immune checkpoint inhibitors (ICIs). Relapsing polychondritis (RP) is a rare autoimmune disease mainly involving auricle, nose, and airway cartilage inflammation. However, knowledge regarding RP as an irAE is scarce. Pembrolizumab, a type of ICI that regulates the programmed cell death protein-1 (PD-1), is used in patients whose cancer cannot be cured with surgery or radiation therapy. We report the first case of pembrolizumab-induced RP with isolated auricular lesions resolved without immunosuppressants. A 49-year-old man with lower lip cancer underwent surgical resection followed by reconstruction. Histopathological investigation confirmed the diagnosis of squamous cell carcinoma. Since multiple metastases 6 months post-surgery rendered the carcinoma inoperative, pembrolizumab was initiated, improving lymph node involvement. However, 4 months later, the patient developed rapidly progressive swelling and pain in both auricles. While no pathogen was detected, C-reactive protein levels were elevated (11.21 mg/dL). Computed tomography (CT) showed swelling of the bilateral auricles; the biopsy of the right auricle revealed cartilage destruction by infiltration of surrounding granulation tissue. Since these characteristic findings were not observed before pembrolizumab was initiated, we clinically diagnosed the patient with RP induced by pembrolizumab.

The swelling of the auricles resolved spontaneously 1 month after pembrolizumab discontinuation. ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) -positron emission tomography/CT revealed no ¹⁸F-FDG uptake in reduced auricular lesions. On re-administration of pembrolizumab to maintain antitumor immunity, both auricles swelled again, and pembrolizumab was switched to paclitaxel, considering the risk of tracheobronchial chondritis. Although no recurrence of auricular chondritis was observed, the patient died from cancer progression 8 months after paclitaxel administration. RP can occur as a rheumatic irAE in patients receiving anti-PD-1 therapy, and a literature review with retrospective analysis indicates that PD-1 inhibition-induced RP is unusual and atypical.

We encountered a pediatric case of cubitus varus deformity with a sheared olecranon fracture in an 8-year-old boy who underwent corrective osteotomy without relevant medical history. The patient fell, resulting in a sheared olecranon fracture. He underwent a closed reduction and casting. As the displacement slightly increased within a week, we followed him without secondary reduction to expect remodeling. No remodeling occurred; corrective osteotomy was performed one-year post-injury for a marked cubitus varus deformity. At 2.5 years after corrective osteotomy, little difference existed in the carrying angle (CA) and varus angulation (VA) of the proximal ulna than that of the contralateral side, without pain or limited range of motion.

The acceptable displacement range for pediatric forearm fractures is <1 cm shortening and 15° angular deformation in patients under 10 years old, and 10° angular deformation in older children. Here, the deformity of the ulna in the coronal plane did not remodel. Proximal forearm deformity can be accurately evaluated in flexion contracture elbows by measuring VA. Ulnar osteotomies are commonly performed on Monteggia fractures to reduce the radial head, and the osteotomy site is at the center of the deformity of the diaphysis. Corrective osteotomy for cubitus varus deformity after supracondylar humerus fracture improves function and cosmetic appearance, with good clinical results. In addition, it could prevent cubitus varus deformity from causing posterolateral rotatory instability.

The coronal-plane deformity of the proximal ulnar was not expected to remodel. We recommended early accurate reduction and consideration of additional internal fixation for preventing re-displacement. Corrective osteotomy for cubitus varus deformity of the proximal ulna was an effective treatment.

Direct oral anticoagulants (DOACs) are considered to cause a few hemorrhagic complications, including hemorrhagic infarction; these are administered in the acute phase of cerebral infarction for secondary prevention of cerebral embolism. Hemorrhagic infarction with cerebral herniation requires urgent decompressive craniectomy and can become fatal. Perioperative management is challenging because patients are often on antithrombotic therapy. In this study, we report on a case of a 61-year-old man with left-sided hemiparesis and impaired consciousness; he suffered from a hemorrhagic infarction with cerebral herniation during oral DOAC treatment after endovascular recanalization for the middle cerebral artery occlusion. As the patient was on apixaban for <3 h, performing decompressive craniectomy was considered difficult to stop hemostasis. We then opted to perform a small craniotomy to remove the hematoma, control the intracranial pressure (ICP), and administer fresh frozen plasma. We waited for the effect of apixaban to diminish before performing decompressive craniectomy. Gradually, his level of consciousness was noted to improve. Hemorrhagic cerebral infarction while on DOAC medications can be safely treated with small craniotomy and ICP monitoring followed by decompressive craniectomy. Thus, this case highlights the value of staged surgery under ICP monitoring in the absence of an immediate administration of DOAC antagonists.