Japan is a well-qualified country in promoting scientific advancement, but female scientists are too few in academic medicine positions. The government of Japan announced that the share of women in leadership positions accounted to at least 30% by 2020 in all fields in society. The number of female students also increased, but it was not much higher than other Organisation for Economic Co-operation and Development (OECD) countries. Women students always have higher passing frequencies in national examination for medical practitioners in Japan. The potential gap between physician gender and academic advancement is mentioned in any medical fields. Women physicians in academic medicine position are still few. For women physicians, medical and familial situations are inversely affected by the coronavirus disease 2019. We propose the recommendations to support women physicians' right in academic medicine, accordingly to patients' benefit. Women may be stepping up and leading efforts without titles or positions in ways that are significant and meaningful for their group or organization.

Infectious diseases are posing threats to the world. Although several types of antibiotics and antivirals have been created to treat the diseases, emerging/re-emerging infectious diseases, as well as those caused by pathogens with multidrug resistance, remain to be significant challenges. As a new therapeutic approach, "host-directed therapy" that enhances immune responses of host cells has been proposed. Nevertheless, the agents used in this strategy often lead to a side effect of hyperinflammation, posing a challenge in developing safe and effective drugs. In this review, I suggest boosting a novel CD4⁺ T lymphocyte population called "memory-phenotype (MP) cells" as a target of the host-directed therapy. MP cells are homeostatically generated from peripheral naïve precursors via recognition of self rather than foreign antigens and are maintained via rapid proliferation in steady state. Surprisingly, MP cells possess innate immune function; they can respond to an inflammatory cytokine IL-12 in the absence of antigen recognition to produce IFN-γ, thereby contributing to host defense against Toxoplasma and Mycobacterium. In this article, I summarize our current understanding of the mechanisms of generation, maintenance, differentiation, and innate effector function of MP CD4⁺ T lymphocytes and further discuss how we can target these cells as a new therapeutic strategy to infectious and autoimmune/inflammatory diseases.

The deposition of amyloid β (Aβ) peptides as senile plaques and tau as neurofibrillary changes causes the hallmark neuropathological lesions of Alzheimer's disease (AD), which are implicated in its pathogenesis and deemed as the prime target for disease-modifying therapies (DMTs). Aβ is produced by sequential proteolytic cleavage by β- and γ-secretases. γ-Secretase, harboring presenilins (PS) as the catalytic center, forms the C-terminus of Aβ that determines its propensity to aggregate; missense mutations in PS genes cause familial AD by altering the preferred γ-secretase cleavage sites to increase the production of pathogenic Aβ42 species. Numerous DMTs for AD have been tested in clinical trials, some of which met the clinical endpoints, whereas others, especially those conducted in dementia stages, have failed, underscoring the needs for early intervention. Notably, positive outcomes of recent trials for anti-Aβ antibody drugs have depended largely on molecular imaging and fluid biomarkers, underscoring the needs of markers that surrogate the clinical and pathophysiological progression of AD. Longitudinal observational studies as represented by the AD Neuroimaging Initiative (ADNI) in North America, as well as the Japanese ADNI (J-ADNI), have contributed greatly toward the goal of very early treatment at the prodromal and preclinical AD stages by delineating the early natural course of AD and facilitating the development of biomarkers. It has been demonstrated that the clinical and biomarker profiles of prodromal AD in J-ADNI were remarkably similar to those in the North American ADNI, supporting the harmonization of global clinical trials. These clinical studies in Japan, accelerated by the development and implementation of biomarkers, will pave the way toward the development of AD therapies targeting its very early stages.

Today, approximately one in every two people in Japan is diagnosed with cancer at least once in their lifetime, making cancer control a matter of national concern. However, advances in diagnosis and treatment have made it possible to cure 70%-80% of cancers. Early-stage malignancies can now be resolved in nearly all cases, with the current challenge lying in how to fully cure the patient in a manner that conserves the affected organ and its function. Minimally invasive, function-preserving surgery for early-stage tumors will likely further evolve with the introduction of robotics and individualized surgery. Meanwhile, cancers that are difficult to control-advanced or intractable forms-require a multidisciplinary approach combining diverse therapeutic strategies. The future of treatment for advanced cancer promises to bring innovations such as individualized treatment planning based on cancer genome analysis, precise determination of treatment responsiveness using gene mutations as indicators, and early diagnosis of metastasis/recurrence through liquid biopsy. This paper provides an overview of the current state and future prospects of multidisciplinary cancer care, with a focus on the author's field of expertise-upper gastrointestinal (GI) cancers.

Introduction: Length of stay (LOS) is a major concern while optimizing medical resources and costs. Hence, factors influencing LOS should be investigated. In Japan, breast cancer surgery generally involves several days of hospitalization for observation, despite few complications. We hypothesized that the day of surgery (weekday; Monday-Friday) affects LOS.

Methods: Using a Japanese nationwide database, we retrospectively identified 146,610 patients who underwent partial mastectomy for stage 0-III breast cancer from July 2010 to March 2017. We conducted multivariable linear and logistic regression analyses adjusting for background characteristics (such as comorbidities and hospital characteristics) with a generalized estimating equation for within-hospital clustering to compare postoperative and total LOS, total hospitalization costs, and postoperative complications between the groups for whom the surgery was performed on different days of the week.

Results: In total, whereas the median postoperative LOS was 4 days (interquartile range, 3-6 days), the median total LOS was 6 days (5-8 days). The median total hospitalization cost was 6,189 US dollars (5,609-6,668 US dollars), and postoperative complications occurred in 3.3% of cases. Despite no significant difference in postoperative complications, Monday-Wednesday surgeries showed significantly shorter postoperative LOS than Friday surgeries (−0.11 days [95% confidence interval, −0.14 to −0.07] on Monday with reference to Friday). Nevertheless, Monday surgeries showed significantly increased total LOS (0.69 days [0.64-0.74]) and hospitalization costs (93 US dollars [71-116]) in comparison with Friday surgeries.

Conclusions: The operative day of the week was associated with increased LOS and cost, with no difference in postoperative complications after partial mastectomy. Surgeries on Monday involved longer preoperative hospital stays and higher total hospitalization costs than those on other weekdays.

Introduction: Fibrates are recommended not to be used for the treatment of hypertriglyceridemia in patients with chronic kidney disease (CKD) based on clinical practice guidelines. The major reason for the negative suggestion is the elevation of serum creatinine and rhabdomyolysis by fibrates. This may cause clinical inertia for the treatment of hypertriglyceridemia using fibrate in patients with CKD, who are associated with an increasing risk of cardiovascular disease.

Methods: We retrospectively studied the change of serum creatinine via the treatment of pemafibrate.

Results: A total of 39 patients with CKD were treated with 0.2 mg of pemafibrate. Serum triglyceride was decreased in 23 fibrate-naïve patients from 380 [308, 455] mg/dL to 180 [152, 215] mg/dL via treatment with pemafibrate (p = 0.00003). Serum creatinine and eGFR were not changed from 1.22 ± 0.29 mg/dL to 1.21 ± 0.28 mg/dL (p = 0.70) and from 45.7 ± 10.9 mL/min/1.73 m² to 46.2 ± 12.0 mL/min/1.73 m² (p = 0.67) via treatment with pemafibrate, respectively. In 16 patients, with a change of treatment from fenofibrate or bezafibrate to pemafibrate, serum creatinine was significantly decreased from 1.32 ± 0.36 mg/dL to 1.17 ± 0.24 mg/dL (p = 0.003). eGFR was significantly increased from 45.2 ± 9.9 mL/min/1.73 m² to 50.1 ± 8.6 mL/min/1.73 m² (p = 0.001).

Conclusions: These results suggest that treatment with pemafibrate does not affect the serum creatinine level and is suitable for use in patients with CKD for the treatment of hypertriglyceridemia.

Introduction: Febrile episodes in patients with cancer and chemotherapy-induced neutropenia can be life-threatening and generally require prompt administration of broad-spectrum antimicrobials. However, little evidence exists for treating patients with solid tumors and febrile neutropenia (FN) with oral antimicrobials.

Methods: In this prospective study, we aimed to determine the efficacy and safety of sitafloxacin (STFX) for treating FN in lung cancer patients. In this prospective study, low-risk FN patients with lung cancer received STFX. The primary endpoint was response rate, defined as 5 sequential days of absence of fever without adverse events. The study was registered as UMIN000010911.

Results: As a result, STFX was administered to 26 patients, all of whom survived during its administration. Of the 26, 14 completed primary endpoint (53.85%). The low response rate was attributed to occurrence of fevers of unknown cause rather than failure of FN treatment. Only two patients received antibacterial agents other than STFX. If response rate omitted absence of fever and been defined only as recovery from FN without changing microbial agents or serious complications, the response rate would have been 91.67%. Adverse events occurred in eight patients, none of which were serious.

Conclusions: In conclusion, STFX might be used to treat low-risk FN in patients with lung cancer; however, a more detailed study will be required in future.

Introduction: Fetal growth restriction (FGR) is a clinical condition wherein a fetus fails to achieve the expected growth potential. Although FGR is the leading cause of perinatal morbidity and mortality, there is a lack of knowledge about the long-term developmental outcomes of children who had FGR in Japan. Here, we sought to clarify the features of neurodevelopmental outcomes in preterm-born children with severe FGR (sFGR) and identify associated clinical factors.

Methods: The clinical data of 26 preterm sFGR cases and 26 preterm appropriate for gestational age (AGA) cases with a similar gestational age distribution were reviewed retrospectively. Developmental quotient (DQ) scores assessed during the 1- and 2-year corrected ages using the Kyoto Scale of Psychological Development were analyzed.

Results: sFGR was diagnosed at 26 (18-34) weeks of gestation, and the gestational age at delivery was 31 (25-36) weeks. The overall DQ scores of children in the sFGR group were significantly lower than those in the AGA group (80 vs. 90.5, P = 0.0127). Of the three areas that comprise the DQ (Postural-Motor, Cognitive-Adaptive, and Language-Social), the sFGR group only showed significantly lower DQ scores (72.5 vs. 88, P = 0.0255) in the Language-Social area. Both fetal body weight and fetal body weight Z score at birth significantly correlated with the DQ scores (r = 0.4912, P = 0.0108, and r = 0.5621, P = 0.0028), whereas neither the duration of fetal growth arrest nor the gestational age at birth correlated with the DQ scores (r = 0.3598, P = 0.0842, and r = 0.3522, P = 0.0776).

Conclusions: Our results indicate that preterm-born children with sFGR have greater neurodevelopmental impairment than preterm-born children without FGR, specifically in terms of the DQ scores for the Language-Social area. It is imperative to encourage continuous long-term follow-up and appropriate interventions after birth.

Introduction: In recent years, there has been an increase in noninvasive prenatal testing (NIPT), where maternal blood samples are used to extract fetal cell-free DNA. Despite this being offered in several facilities in urban areas, NIPT remains to be scarcely unavailable in rural areas. Moreover, there is lacking information with regard to how pregnant women in rural areas perceive NIPT. Thus, in this study, we conducted a survey among pregnant women who came to our clinic for NIPT and examined their views on NIPT and genetic counseling.

Methods: A questionnaire survey was administered to pregnant women who requested NIPT and underwent genetic counseling at our hospital between November 2016 and February 2020. The questionnaire was administered twice, once after completing the genetic counseling and once after explaining the NIPT results. The number of genetic counseling and NIPT sessions and positive test results, as well as anxiety about the test and evaluation of genetic counseling and NIPT, were assessed.

Results: In total, 115 patients received genetic counseling, of which 109 underwent NIPT. The test results were found to be positive in six patients. As per our findings, 103 patients (93%) indicated they needed genetic counseling for NIPT, whereas 99 (93%) were satisfied with the counseling they received from a genetic medicine specialist. On the other hand, 82 patients (77%) requested for more testing facilities.

Conclusions: The enhancement of genetic counseling systems is essential to expand the environment in which NIPT is performed. Therefore, we need to consider the need to make the NIPT testing environment more conducive and inform clients of the importance of genetic counseling in NIPT.

The coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of research, practice, social contribution, and education in social medicine and public health, which relate to the core mission of universities. Early-career researchers and professionals play an important role in these domains, but little is known about the challenges and issues they encountered or recognized during this pandemic. Therefore, we summarized the opinions of 37 participants (30 early-career researchers and seven senior researchers) on this issue from discussions at the Social Medicine Young Retreat, 2019, of the Japanese Medical Science Federation. The retreat was initially planned to be held during March 5-6, 2020 in Yamanashi but was changed to be held virtually on March 5, 2021. Early-career researchers participated in group discussions on how social medicine should transform itself to serve the public during the COVID-19 pandemic. Afterward, each group provided opinions on challenges and issues in social medicine. For example, participants perceived difficulties in implementing research in a timely way and the lack of multidisciplinary collaboration. They recognized challenges in continuing practice because of the limited evidence on COVID-19. On social contribution, they described difficulties in communicating risk as professionals. They also noted issues arising from online teaching and learning. One group suggested that the essence of social medicine did not need to be changed, but methodologies should be updated to tackle multiple existing challenges. These opinions may not cover all issues but could help establish a better relationship between medicine and society in a bottom-up manner. The continuous promotion of interdisciplinary collaboration in social medicine (and basic and clinical medicine) would provide ideas to solve these issues at scale. Organizational support is warranted to ensure sustainability and scalability of these actions.

This report shows a case with a rare small-sized lung adenocarcinoma that rapidly progressed from a nonsolid nodule (NSN) to a solid nodule (SON) over a period of just 1 year after a very long-term observation from its first detection. In 2007, the patient was an asymptomatic 52-year-old man at the time of the first detection via chest low-dose computed tomography (CT) screening as part of a periodic medical checkup at our hospital. It revealed an abnormal shadow in another location of the lung field, necessitating a more thorough examination. Then, he visited our outpatient clinic for the first time and a workup examination was performed using thin-section CT (TSCT) images, which incidentally detected a small NSN with a maximum diameter of 1.2 cm in the mid-zone of the left upper lung field. Since it did not disappear in the periodic subsequent workup examinations, the patient was informed of the suspicious early lung adenocarcinoma each time; however, the patient desired to continue watchful waiting. The radiographical properties of the NSN remained almost unchanged until 2019, but in 2020, the inside of the nodule showed a skip-like change to a SON. Finally, because of the unexpectedly fast transition, consent for lobectomy could be obtained. Surgery was then performed, 13 years after its first detection, at an age of 65 years. The pathological findings revealed a 1.2 cm, pT1bN0M0, pStage IA2-adenocarcinoma, which was 90% of the acinar subtype with positive vascular permeation. Management of a NSN, that does not resolve and/or change, must continue watchful waiting, and at the very least continue follow-up with TSCT observation to ensure the safe and appropriate timing of excision using imaging as a marker of transition.

A urinary tract stone is a common urologic problem in Asia. In recent years, the incidence of urinary tract stones has increased but tends to be neglected by people with a lack of knowledge and low socioeconomic status. The occurrence of a bladder stone weighing more than 100 grams is unusual. We report the case of a 46-year-old Indonesian male patient who presented with complaints of lower abdominal pain, urinary pain, frequency, urgency, and hematuria. The patient also had severe anemia due to chronic hematuria. The patient then received open cystolithotomy because the ultrasonographic and X-ray findings of the kidney, ureter, and bladder revealed a giant bladder stone. This bladder stone measured 62 × 59 mm and weighed 301 grams. Gender, age, living in a tropical country, and lack of knowledge contributed to the patient's neglect of symptoms.

Orbital intravascular lymphoma is rare and typically of B-cell lineage. In this study, we report a patient who developed orbital lesions of intravascular natural killer/T-cell lymphoma (IVNKL), an extremely rare lymphoma. An 88-year-old man presented with rapidly progressive right vision loss and double vision. A neurological examination revealed that he had decreased visual acuity and severe oculomotor impairment in the right eye. Magnetic resonance imaging showed right-dominant, nonmass lesions in both orbits. No lesions were found in the lymph nodes, skin, or brain. The patient received immunosuppressive and antifungal therapy, but his clinical condition rapidly deteriorated, and he died of multiple organ failure. Autopsy revealed natural killer/T-cell lymphoma proliferation within the lumina of small blood vessels in multiple organs, including the ocular adnexa of the right orbit. These findings show that he was ultimately diagnosed with IVNKL. IVNKL could initially cause ocular symptoms due to the involvement of the ocular adnexa. Ocular involvements have not been described previously. Even if patients initially present with only ocular symptoms, IVNKL should be considered.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is characterized by bilateral synovitis and marked pitting edema of the hands and/or feet. Despite the unknown etiology of RS3PE, several reports have described the putative association of this disease with malignant tumors. We herein report the findings of a 76-year-old man with RS3PE syndrome who developed hepatocellular carcinoma 3 years after achieving clinical remission of RS3PE using corticosteroid treatment; high vascular endothelial growth factor and tumor necrosis factor-alpha levels were considered to have contributed to carcinogenesis in this patient. The sequence of clinical events in this case strongly suggests that careful follow-up, even after clinical remission, is necessary for patients with RS3PE syndrome whose malignancy is not confirmed at diagnosis.