Lack of women physician representation in the Japanese Society of Hospital General Medicine.

Background: The increasing number of women physicians is in contrast to their underrepresentation in academic positions and professional associations. This study aimed to evaluate the status of women physicians in the Japanese Society of Hospital General Medicine (JHGM) based on society membership, board membership, and annual meeting authorship. Methods: A cross-sectional analysis was conducted. Information on women physicians, society and board membership, and annual meeting authorship was collected. Data from the Japanese Primary Care Association (JPCA) served as the control. The gender of authors with accepted abstracts in the JHGM and JPCA annual meetings was determined by name or Internet search. Results: In the JHGM, 14.2% of members were women physicians, compared to 19.1% in the JPCA (p < 0.001). None of the 21 JHGM board members were women, compared to 20.5% in the JPCA (p < 0.001). The average number of years of experience was significantly higher for the JHGM board members than for the JPCA board members (37.0 vs. 28.1 years, p < 0.001). Women first authors in the 2022-2023 JHGM meeting comprised 17.9%, significantly lower than the 28.4% in the 2023 JPCA meeting (p = 0.002). Similar patterns were seen for women last authors (6.0% in the JHGM vs. 18.8% in the JPCA, p < 0.001) and women chairpersons (17.9% in the JHGM vs. 40.3% in the JPCA, p = 0.036). Conclusions: The JHGM has low women representation in society and board membership, and annual meeting authorship. Strategies are needed to enhance diversity and inclusion by increasing women's participation and leadership in the JHGM.

An Unusual Case of Sarcoidosis with a Prolonged Fever and Progressive Arthropathy.

A 70-year-old man had developed a high fever and arthralgia in his right elbow 6 months prior. Loxoprofen improved the symptoms temporarily, but arthropathy developed in other joints. Long-term recurrent arthropathy and the fever caused activity reduction and progressive debilitation. We performed fluorine-18 fluorodeoxyglucose-positron emission tomography and detected a positive accumulation in multiple joints and lymph nodes. A lymph node biopsy revealed epithelioid cell granulomas, which, along with elevated angiotensin-converting enzyme levels, led to the diagnosis of sarcoid arthropathy. After prednisolone administration, the fever and arthralgia resolved, and his activities of daily living improved. Clinicians should be aware of this type of sarcoid arthropathy.

Lifestyle Factors Associated With Erosive Esophagitis in Japanese Individuals With and Without Obesity Undergoing Health Checkups.

BACKGROUND: Several lifestyle factors have been reported to be associated with erosive esophagitis (EE). Many studies examined the associated factors for EE independent of obesity. However, lifestyle factors associated with EE might differ depending on sex or the presence of obesity. This study thus aimed to investigate the lifestyle risk factors for EE stratified by obesity and sex. METHODS: A cross-sectional survey was conducted among Japanese people who underwent an annual health checkup at the Oita Health Checkup Center between 2019 and 2021. Multivariate analysis was performed to determine the factors associated with EE in participants stratified by sex and the presence of obesity. RESULTS: EE was diagnosed in 676 of 5240 participants (12.9%) who were analyzed, and occurred most often in males (601 cases). The percentage of obesity based on body mass index was significantly higher among EE than non-EE participants (50.3% and 26.5%, P < .001). In obese males, eating just before bedtime (OR = 1.34, 95% CI 1.01-1.78) and hiatal hernia (OR = 3.42, 95% CI 2.57-4.54) were significantly associated with EE in multivariate analysis. In non-obese males, current smoking (OR = 1.48, 95% CI 1.07-2.04), alcohol consumption of 40 to 60 g/day (OR = 1.60, 95% CI 1.11-2.30), and hiatal hernia (OR = 3.63, 95% CI 2.79-4.73) were significantly associated with EE. CONCLUSIONS: We found that factors associated with EE were different between obese and non-obese males. In obese males, avoiding going to bed within 2 h after dinner might contribute to preventing the occurrence of EE. In non-obese males, prevention of obesity, quitting smoking, and avoiding heavy alcohol consumption might be important for preventing the development of EE.

A Case of Tumor-Induced Osteomalacia Detected by Venous Sampling.

Tumor-induced osteomalacia (TIO) can cause osteomalacia due to excessive production of fibroblast growth factor 23 (FGF23) by the tumor. Since TIO is a very rare disease, it is often misdiagnosed as intervertebral disc herniation, spondyloarthritis, or osteoporosis. We report a 65-year-old man who developed generalized arthralgia and difficulty walking two years ago and was diagnosed with multiple fractures throughout his body. He was initially diagnosed with osteoporosis and was treated with calcitriol. However, he was referred to our hospital since his symptoms did not improve. We diagnosed tumor-induced osteomalacia based on low serum phosphorus, high bone-type alkaline phosphatase, high FGF23 levels, and the presence of two tumors. The responsible tumor was identified using FGF23 levels in venous sampling. As the location of the tumor made surgical resection difficult, we selected treatment with burosumab, a human monoclonal antibody against FGF23, leading to improvement in the hypophosphatemia and pain, such that he was able to walk with a cane. In cases of osteoporosis with hypophosphatemia, general physicians should keep TIO in mind, and attempt to identify the responsible tumor lesion.

Metabolic changes in the plasma of mild Alzheimer's disease patients treated with Hachimijiogan.

Background: Alzheimer's disease (AD), the most prevalent form of dementia, is a debilitating, progressive neurodegeneration. Amino acids play a wide variety of physiological and pathophysiological roles in the nervous system, and their levels and disorders related to their synthesis have been related to cognitive impairment, the core feature of AD. Our previous multicenter trial showed that hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), has an adjuvant effect for Acetylcholine estelase inhibitors (AChEIs) and that it delays the deterioration of the cognitive dysfunction of female patients with mild AD. However, there are aspects of the molecular mechanism(s) by which HJG improves cognitive dysfunction that remain unclear. Objectives: To elucidate through metabolomic analysis the mechanism(s) of HJG for mild AD based on changes in plasma metabolites. Methods: Sixty-seven patients with mild AD were randomly assigned to either an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI (HJG:33, Control:34). Blood samples were collected before, 3 months, and 6 months after the first drug administration. Comprehensive metabolomic analyses of plasma samples were done by optimized LC-MS/MS and GC-MS/MS methods. The web-based software MetaboAnalyst 5.0 was used for partial least square-discriminant analysis (PLS-DA) to visualize and compare the dynamics of changes in the concentrations of the identified metabolites. Results: The VIP (Variable Importance in Projection) score of the PLS-DA analysis of female participants revealed a significantly higher increase in plasma metabolite levels after HJG administration for 6 months than was seen in the control group. In univariate analysis, the aspartic acid level of female participants showed a significantly higher increase from baseline after HJG administration for 6 months when compared with the control group. Conclusion: Aspartic acid was a major contributor to the difference between the female HJG and control group participants of this study. Several metabolites were shown to be related to the mechanism of HJG effectiveness for mild AD.

Positive Rate and Utility of Blood Culture among Nursing and Healthcare-associated Pneumonia Inpatients: A Cross-sectional Study.

Objective Although blood cultures to identify the presence of bacteremia are recommended for nursing- and healthcare-associated pneumonia (NHCAP), the incidence of true bacteremia and the relationship between true bacteremia and the outcome remain unclear. Physicians can therefore sometimes be confused regarding whether or not blood cultures should be obtained for NHCAP patients. This study assessed the incidence of true bacteremia and the relationship between true bacteremia and the outcome of NHCAP in a Japanese hospital setting. Methods We retrospectively analyzed NHCAP patients hospitalized between April 2016 and March 2021. The primary outcome was the incidence of true bacteremia in blood cultures. The incidence of true bacteremia was also examined according to quick Sequential Organ Failure Assessment (qSOFA) and A-DROP scores. In addition, we compared the incidence of true bacteremia between survivors and non-survivors. Results In total, 205 patients were included in this study. Blood cultures were obtained from 150 of the 205 patients (73.2%). Positive blood cultures were detected in 26 patients (17.3%), of which only 8 cases (5.3%; 95% confidence interval, 2.3-10.2%) were considered true bacteremia. Trend analyses for the incidence of true bacteremia according to qSOFA and A-DROP scores did not show any statistically significant results (p=0.49 for qSOFA; p=0.14 for A-DROP). The proportion of true bacteremia cases did not differ significantly between survivors and non-survivors. Conclusions The incidence of true bacteremia among NHCAP patients was very low. A strategy for determining indications for obtaining blood cultures from NHCAP patients needs to be established.

Disseminated nontuberculous mycobacterial infection in a patient with idiopathic CD4 lymphocytopenia and IFN-γ neutralizing antibodies: a case report.

BACKGROUND: Disseminated nontuberculous mycobacterial (NTM) infection usually occurs in immunodeficient patients, such as those with human immunodeficiency virus infection and idiopathic CD4 lymphopenia. However, disseminated NTM diseases have also been reported in immunocompetent patients. Autoantibodies to interferon-gamma (IFN-γ) are known to be involved in disseminated NTM disease, although anti-IFN-γ antibodies are mainly seen in immunocompetent patients rather than those with immunodeficiency. Here, we report a rare case of disseminated NTM patient with idiopathic CD4 lymphopenia and anti-IFN-γ antibodies. CASE PRESENTATION: A 64-year-old Asian male presented with fever, back pain, anorexia and weight loss. Physical examination revealed subcutaneous masses in the forehead, sternoclavicular joint, and right inguinal region. Computed tomography showed multiple osteosclerotic changes with soft structures and osteolytic changes. Both blood and sputum cultures were positive for Mycobacterium intracellulare, confirming the presence of disseminated NTM infection. Histopathological evaluation of the subcutaneous mass in the right inguinal region showed numerous granulomas consisting of epithelioid cells with Langhans-type giant cells. He was diagnosed with idiopathic CD4 lymphocytopenia. Interestingly, he also had anti-IFN-γ autoantibodies with suppression of IFN-γ-dependent signal transducer and activator of transcription 1 (STAT1) phosphorylation. Two-drug combination therapy with clarithromycin and ethambutol was started for the NTM infection, which resulted in a favorable disease course. CONCLUSIONS: In patients with disseminated NTM infection, idiopathic CD4 lymphocytopenia and anti-IFN-γ autoantibody-positive immunodeficiency can be coexisted. It is necessary to clarify the pathogenesis and clinical course of CD4 lymphocytopenic conditions and IFN-γ neutralizing antibody-positive in the disseminated NTM disease.

An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer's disease.

Background: Alzheimer's disease (AD) is a progressive neurodegeneration and is the most prevalent form of dementia. Intervention at an early stage is imperative. Although three acetylcholinesterase inhibitors (AChEIs) are currently approved for the treatment of mild AD, they are not sufficiently effective. Novel treatments for mild AD are of utmost importance. Objective: To assess the effectiveness of hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), in the treatment of mild AD. Methods: This exploratory, open-label, randomized, multicenter trial enrolled patients with mild AD whose score on the Mini Mental State Examination (MMSE) was over 21points. All participants had been taking the same dosage of AChEI for more than 3 months. The participants were randomly assigned to an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI. The primary outcome was the change from baseline to 6 months post treatment initiation on the Alzheimer's Disease Assessment Scale-cognitive component- Japanese version(ADAS-Jcog). The secondary outcomes were change from baseline of the Instrumental Activity of Daily Life (IADL), Apathy scale, and Neuropsychiatric Inventory (NPI) -Q score. Results: Among the 77 enrollees, the data of 69(34 HJG and 35 control)were available for analysis. The difference in the change of ADAS-Jcog from baseline to 6 months of the HJG and control groups was 1.29 (90% Confidence interval (CI), -0.74 to 3.32 p = 0.293). In the subgroup analysis, the differences in the change from baseline to 3 and 6 months for women were 3.70 (90% CI ,0.50 to 6.91, p = 0.059) and 2.90 (90% CI,0.09 to 5.71, p = 0.090), respectively. For patients over 65 years, the difference at 3 months was 2.35 (90%CI, 0.01 to 4.68 p = 0.099). No significant differences were found between the HJG and control groups in IADL score, Apathy scale, or NPI-Q score. Conclusion: Although not conclusive, our data indicate that HJG has an adjuvant effect for acetylcholinesterase inhibitors and that it delays the deterioration of the cognitive dysfunction of mild Altzheimer's disease patients. Clinical Trial Registration: http://clinicaltrials.gov Japan Registry of clinical trials, identifier jRCTs 071190018.

Cognitive Function and Olfactory Impairment in Community-Dwelling Older Adults Attending a Salon.

BACKGROUND: Early detection, treatment, and care are important for the prevention of dementia. Though olfactory impairment has been reported to be associated with mild cognitive impairment (MCI), there are few reports involving community-dwelling older adults with no difficulty in daily life in Japan. OBJECTIVE: This study aimed to identify the frequency of MCI in community-dwelling elderly people attending community salons in a city with a high aging population, and to determine the usefulness of a pocket olfactory discrimination test. METHODS: We recruited 268 independent older adults attending community salons. The Japanese version of the MCI Screen was used to evaluate cognitive function, defining MCI as <49.8 out of 100 scores of the memory performance index (MPI). The Japanese version of the University of Pennsylvania Smell Identification Test (UPSIT-J) was used for olfactory discrimination and the number of correct answers out of 4 questions was noted. RESULTS: Of the salon participants, 138 (51.5%) were classified as having MCI. As the number of correct answers on the olfactory test decreased, the percentage of participants with MCI increased. The MPI score of the low UPSIT score group was significantly lower than that of the high UPSIT score group. CONCLUSIONS: This study revealed that approximately half of the elderly local residents living without daily problems were suspected of having MCI. The UPSIT-J-4 is a simple olfactory identification test, and can be used at any time and any place. It is useful for screening cognitive function via olfactory identification in a salon-like setting.

Helicobacter pylori genomes reveal Paleolithic human migration to the east end of Asia.

A virulence bacterium, Helicobacter pylori, evolved parallel to its host human, therefore, can work as a marker for tracing the human migration. We found H. pylori strains indigenous in the southernmost islands of Japanese Archipelago, Okinawa, and defined them as hspOkinawa and hpRyukyu. Genome data of the strains revealed that hspOkinawa diverged from other East Asian strains about 20,000 years ago, and that hpRyukyu diverged about 45,000 years ago. The closest strains of hpRyukyu were found from Afghanistan, Punjab, and Nepal, which suggest this strain originated in the central Asia and traveled across the Eurasian continent during Paleolithic era. The divergence date of hpRyukyu corresponds with human fossil records in Okinawa. Although it is controversial from human DNA analyses whether descendants of the Paleolithic migrants remain in the modern Japanese population, this study reveals that the bacterium of Paleolithic origin remains in the stomachs of current Japanese.

Esophageal achalasia: An unusual reason for lung abscess.

Our case serves as a reminder that clinicians should pay attention to the presence of esophageal diseases in patients with lung abscesses. The esophagus should be evaluated during pulmonary CT imaging.

Bacteremia caused by Enterobacter asburiae misidentified biochemically as Cronobacter sakazakii and accurately identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: a case report.

BACKGROUND: Biochemical analyses of causative bacteria do not always result in clear identification, and new technologies aimed at improving diagnostic accuracy continue to be developed. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry is a rapid and accurate technique for bacterial identification. Misidentification of Cronobacter sakazakii is related to clinical and industrial problems. Here, we encountered a case of rare bacteremia in which the causative organism Enterobacter asburiae was biochemically misidentified as C. sakazakii before being correctly identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. CASE PRESENTATION: An 87-year-old Asian man with no diabetes or active disease developed bacteremia and was admitted to our hospital. While the route of infection could not be determined despite various examinations, the clinical course was good following antibiotic therapy. Biochemical analyses identified the causative organism as C. sakazakii, but colonies on the blood agar medium showed a grayish coloration, differing from the yellowish coloration of typical Cronobacter colonies. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was therefore performed, identifying the bacterium as E. asburiae on three independent analyses. This result was confirmed by multilocus sequence analysis using five housekeeping genes. CONCLUSIONS: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry may reduce misidentification of bacteria as C. sakazakii and improve the reporting rate of E. asburiae. This technique should be considered when biochemical bacterial misidentification is suspected.

Plasma Exchange Did Not Reduce Viral Load in a Recovered Case of Severe Fever with Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV). There is no specific treatment for SFTS, although several reports have indicated that plasma exchange (PE) can be an effective therapy for severe SFTS. However, whether or not PE can reduce the viral load is unclear. We herein report a woman with SFTS who had her SFTSV viral load measured just before and after PE. While the patient recovered, there was no significant difference in the SFTSV viral load after PE. Our results confirmed that PE itself does not reduce the SFTSV viral load.

A case of community-onset Acinetobacter pneumonia in a healthy person.

A 56-year-old woman with fever, sore throat and productive cough was referred to our hospital, where mild community-acquired pneumonia was diagnosed. Sputum smears revealed Gram-negative coccobacilli. Treatment with ceftriaxone was initiated, but symptoms continued without progression to respiratory failure or bacteremia. As sputum cultures identified Acinetobacter baumannii, antibiotics were changed to levofloxacin, resulting in complete remission. A. baumannii is a very rare cause of community-acquired pneumonia in Japan. However, in cases of pneumonia where Gram-negative coccobacilli are identified and prove resistant to initial treatment, the possibility of A. baumannii pneumonia should be kept in mind even for healthy subjects with low severity score.

Statistical analysis of anti-mamushi venom serum injection time and clinical course.

AIM: Early injection of anti-mamushi venom serum (antiserum) is believed to be effective for the treatment of patients with mamushi bites. However, there is no firm information that indicates the time range constituting "early" injection. We tried to quantify the cut-off time of antiserum injection that brings favorable clinical courses by clarifying the relationship between the injection time and clinical outcome. METHODS: We retrospectively analyzed the relationships between the time after bite, injection time of the antiserum, swelling grades, and laboratory values. RESULTS: The injection time of the antiserum in severe cases was significantly delayed as compared with non-severe cases. The best cut-off time of the antiserum injection that could distinguish non-severe and severe cases was 14 h. In the group that received the antiserum within 14 h, the antiserum injection may have successfully arrested the grade progression in a substantial number of cases. In the other group receiving the antiserum beyond 14 h, the grades in many cases possibly may have peaked by the time of antiserum injection. CONCLUSION: The cut-off time of early injection for favorable clinical course was determined to be 14 h. A statistical basis concerning the appropriate antiserum injection time was made to help prevent a severe clinical course due to delayed injection.

Inhaled Corticosteroid-Containing Regimens Reduce Hospitalizations and Healthcare Costs among Elderly Asthmatics: Real-World Validation Using the National Health Insurance Claims Database.

The high rates of mortality and hospitalization among elderly asthmatics, as well as their increasing healthcare costs have become an important public health issue. It would be worthwhile to assess whether inhaled corticosteroid (ICS) can resolve these problems. To explore ICS prescription rates for elderly asthmatics and the factors influencing them and to investigate their association with hospitalization and healthcare costs, we analyzed data from the National Health Insurance Claims Database for the same time frame (December 1 to February 28) across three different periods (2011-2012; 2014-2015; and 2017-2018), from which we identified 6,619, 5,619, and 6,880 elderly individuals, respectively. The prescription rates of ICS increased (52.8%, 65.5% and 68.8%, in the first, second and third survey period, respectively) and inversely the hospital admission rates declined (3.7%, 3.2% and 2.5%, in the first, second and third survey period, respectively). The total healthcare costs per month were significantly lower for patients who received ICS-containing regimens than for those who did not. A multivariate analysis revealed that increasing age, rural residence, receiving a prescription from a clinic, hospital admission, and prescription of asthma medications other than ICS were associated with non-prescription of ICS, whereas cross-boundary treatment increased the ICS-prescription rate. Our study suggests that increases in the prescription rate of ICS are associated with reduced hospital admission rates and lower medical costs in the real-world. ICS prescription rates in rural areas and at clinics, which remain low, need to be increased.

Comparative study between Helicobacter pylori and host human genetics in the Dominican Republic.

BACKGROUND: Helicobacter pylori, a bacterium that infects the human stomach, has high genetic diversity. Because its evolution is parallel to human, H. pylori is used as a tool to trace human migration. However, there are few studies about the relationship between phylogeography of H. pylori and its host human. METHODS: We examined both H. pylori DNA and the host mitochondrial DNA and Y-chromosome DNA obtained from a total 119 patients in the Dominican Republic, where human demography consists of various ancestries. DNA extracted from cultured H. pylori were analyzed by multi locus sequence typing. Mitochondrial DNA and Y-chromosome DNA were evaluated by haplogroup analyses. RESULTS: H. pylori strains were divided into 2 populations; 68 strains with African group (hpAfrica1) and 51 strains with European group (hpEurope). In Y-chromosomal haplogroup, European origin was dominant, whereas African origin was dominant both in H. pylori and in mtDNA haplogroup. These results supported the hypothesis that mother-to-child infection is predominant in H. pylori infection. The Amerindian type of mtDNA haplogroup was observed in 11.8% of the patients; however, Amerindian type (hspAmerind) of H. pylori was not observed. Although subpopulation type of most hpAfrica1 strains in Central America and South America were hybrid (hspWAfrica/hpEurope), most Dominican Republic hpAfrica1 strains were similar to those of African continent. CONCLUSIONS: Genetic features of H. pylori, mtDNA, and Y haplogroups reflect the history of colonial migration and slave trade in the Dominican Republic. Discrepancy between H. pylori and the host human genotypes support the hypothesis that adaptability of hspAmerind H. pylori strains are weaker than hpEurope strains. H. pylori strains in the Dominican Republic seem to contain larger proportion of African ancestry compared to other American continent strains.

Epitope peptides of Helicobacter pylori CagA antibodies from sera by whole-peptide mapping.

BACKGROUND: Helicobacter pylori CagA has been found to be immuno-dominant protein and utilized for the diagnosis of the infection with cagA-positive strains. It is important to characterize the peptide epitopes capable of detecting serum anti-CagA antibodies to understand CagA immunogenicity. METHODS: Sera from 171 Japanese patients were subjected for the epitope mapping study. Eighty seven peptides were designed from the CagA consensus sequence and were used for ELISA protocol to test the serum samples. The reacting anti-CagA IgG amounts to specific peptides were measured and compared. RESULTS: The study revealed a strong reactivity of two peptides (c7-NNTEPIYAQVNKKKAGQAT and c8-AGQATSPEEPIYAQVAKKV) in H. pylori-infected group. Interestingly, these two peptides contained the well-known EPIYA-A and EPIYA-B region, respectively, which are two out of three CagA phosphorylation domains. Tyrosine-phosphorylation of these peptides reduced their reactivity in most sera. Moreover, additional peptides' mapping and chimeric-peptides' experiments indicated that the amino acids (QV and KK) accommodated in right-side flanking regions of both EPIYA-motifs were essential for their strong reactivity, whereas the third EPIYA-motif containing peptide (c12-GRSASPEPIYATIDFDEA) with differing flanking amino acids was not reactive in most cases. CONCLUSIONS: Our results suggest that the amino acid sequences constituted in the two reactive peptides are the important immunogenic regions of CagA which would be useful to develop next-generation peptide-based diagnostic assays.

Diffuse Alveolar Hemorrhage Caused by Warfarin after Rifampicin Discontinuation.

An 83-year-old man under warfarin therapy presented for assessment of prolonged prothrombin time and cough. High-resolution computed tomography findings of the chest showed diffuse alveolar hemorrhage. His international normalized ratio (INR) was 11.89. He had been treated with rifampicin for a persistent infection, but this had been discontinued about two months before admission. Rifampicin suppresses the anticoagulant activity of warfarin, which can lead to a need for increased doses of warfarin to achieve and maintain a therapeutic INR. More frequent INR monitoring is needed even after discontinuing rifampicin.