Idiopathic ventricular tachycardia detected after coronavirus disease 2019.

We present a 23-year-old woman with depression and long COVID in whom a diagnosis of idiopathic ventricular tachycardia (VT) was made. Although the relationship between idiopathic VT and long COVID remains unknown, this is the first report of idiopathic VT detected in a patient with long COVID.

Adherence to and clinical utility of "quality indicators" for Staphylococcus aureus bacteremia: a retrospective, multicenter study.

BACKGROUND: We aimed to improve the prognosis, treatment, and management of Staphylococcus aureus bacteremia (SAB) by evaluating the association between adherence to quality indicators (QIs) and clinical outcomes in patients with their clinical outcomes. METHODS: We retrospectively collected clinical and microbiological data on hospitalized patients with SAB from 14 hospitals (three with > 600, two with 401-600, five with 201-400, and four with ≤ 200 beds) in Japan from January to December 2022. The SAB management quality was evaluated using the SAB-QI score (ranging from 0 to 13 points), which consists of 13 QIs (grouped into five categories) based on previous literature. RESULTS: Of the 4,448 positive blood culture episodes, 289 patients with SAB (6.5%) were enrolled. The SAB-QI scores ranged from 3 to 13, with a median score of 9 points. The SAB-QI score was highest in middle-sized hospitals with 401-600 beds. Adherence to each of the four QI categories (blood culture, echocardiography, source control, and antibiotic treatment) was significantly higher in survived cases than in fatal cases. Kaplan-Meier curves with log-rank tests demonstrated that higher adherence to SAB-QIs indicated a better prognosis. Logistic regression analysis revealed that age, methicillin resistance, multiple comorbidities (≥ 2), and low SAB-QI score were significantly associated with 30-day mortality in patients with SAB. CONCLUSIONS: Our study highlights that greater adherence to the SAB-QIs correlates with improved patient outcomes. Management of patients with SAB should follow these recommended indicators to maintain the quality of care, especially for patients with poor prognosticators.

Trends of correlations between serum levels of growth hormone and insulin-like growth factor-I in general practice.

Serum levels of growth hormone (GH) and insulin-like growth factor (IGF)-I are crucial in the diagnosis and management of GH-related diseases. However, these levels are affected by nutritional and metabolic status. To elucidate the correlations between GH and IGF-I in various conditions, a retrospective analysis was performed for adult patients in which GH levels were examined by general practitioners during the period from January 2019 to December 2021. Of 642 patients, 33 patients were diagnosed with acromegaly, 21 were diagnosed with GH deficiency (GHD), and 588 were diagnosed with non-GH-related diseases (NGRD). In contrast to the positive correlations found between the levels of GH and IGF-I in patients with acromegaly (R=0.50; P<0.001) and patients with GHD (R=0.39; P=0.08), a negative correlation was found in the NGRD group (R=-0.23; P<0.001). In that group, the results of multivariable analysis showed that GH levels were predominantly influenced by gender and body mass index (BMI), whereas IGF-I levels were modulated by albumin in addition to age and GH. Of note, in the NGRD group, there was an enhanced negative correlation between GH and IGF-I under conditions of BMI < 22 and albumin < 4.0 g/dL (R=-0.45; P<0.001), and the negative correlation between GH and IGF-I was reinforced by excluding patients with other pituitary diseases and patients taking oral steroids (R=-0.51; P<0.001 and R=-0.59; P<0.001, respectively). Collectively, the results indicate that attention should be given to the presence of a negative correlation between serum levels of GH and IGF-I, especially in lean and low-nutritious conditions.

Calcium polystyrene sulfonate-induced rectal ulcer causing E. coli native-valve infective endocarditis.

Escherichia coli-associated native-valve infective endocarditis is a rare disease that affects elderly patients with underlying risk factors such as diabetes mellitus, malignancy, and renal failure. Long-term use of calcium polystyrene sulfonate is a potential risk factor for gastrointestinal mucosal damage or even colorectal ulcers. Herein, we describe a fatal case of a 66-year-old Japanese man with diabetes mellitus and renal failure who was prescribed calcium polystyrene sulfonate (CPS) for 11 years and developed a CPS-induced rectal ulcer, leading to E. coli native-valve infective endocarditis. The patient was admitted to our hospital due to acute-onset impaired consciousness. As a result of the systemic investigation, he was diagnosed with E. coli bacteremia accompanied by multiple cerebral infarctions and an acute hemorrhagic rectal ulcer. Transesophageal echocardiography revealed a 20-mm vegetative structure on the mitral valve, resulting in a final diagnosis of E. coli-associated infective endocarditis. After rectal resection, mitral valve replacement surgery was performed; however, the patient died shortly after surgery. Pathological findings of the resected rectum showed deposition of a basophilic crystalline material suggesting the presence of CPS. Our case highlights the potential risk of colorectal ulcers in a long-term CPS user, which can trigger bacterial translocation and endocarditis as fatal complications.

Occult endocrine disorders newly diagnosed in patients with post-COVID-19 symptoms.

Determination of long COVID requires ruling out alternative diagnoses, but there has been no report on the features of alternative diagnoses. This study was a single-center retrospective study of outpatients who visited our clinic between February 2021 and June 2023 that was carried out to determine the characteristics of alternative diagnoses in patients with post-COVID-19 symptoms. In a total of 731 patients, 50 patients (6.8%) were newly diagnosed with 52 diseases requiring medical intervention, and 16 (32%) of those 50 patients (2.2% of the total) were considered to have priority for treatment of the newly diagnosed disorders over long COVID treatment. The proportion of patients with a new diagnosis increased with advance of age, with 15.7% of the patients aged 60 years or older having a new diagnosis. Endocrine and metabolic diseases and hematological and respiratory diseases were the most common, being detected in eight patients (16%) each. Although 35 of the 52 diseases (67%) were related to their symptoms, endocrine and metabolic diseases were the least associated with specific symptoms. Other disorders that require attention were found especially in elderly patients with symptomatic long COVID. Thus, appropriate assessment and differentiation from alternative diagnoses are necessary for managing long COVID.

Zinc deficiency is a potential risk factor for COVID-19 progression to pneumonia requiring oxygen therapy.

INTRODUCTION: Various risk factors for developing severe coronavirus disease 2019 (COVID-19) have been reported. However, studies on the nutritional-related risk factors are limited. In this study, we investigated the effects of serum zinc deficiency on the severity of COVID-19. METHODS: The study included a total of 60 COVID-19 patients who were admitted to Tsuyama Chuo Hospital between March 2020 and April 2021. We divided the patients into two categories based on serum levels of zinc (normal and latent zinc deficiency vs. zinc deficiency [<60 µg/dL]) at the time of diagnosis. Severity of COVID-19 was defined as the most exaggerated disease status during admission. The associations between serum zinc deficiency and the severity of COVID-19 were examined using a logistic regression model adjusted for potential confounders. RESULTS: Patients who required oxygen therapy had a higher prevalence of comorbidities and poorer nutritional status, including zinc deficiency, than those who did not require oxygen therapy. Zinc deficiency was associated with an increased risk of COVID-19 severity, with an adjusted odds ratio of 7.29 (95% confidence interval: 1.70-31.18). This result remained significant in the sensitivity analyses conducted after adjusting for patient background factors. CONCLUSIONS: Zinc deficiency at the time of COVID-19 diagnosis is an independent risk factor for severe disease. Our findings need to be validated in external studies.

Changes in the place of death before and during the COVID-19 pandemic in Japan.

BACKGROUND: In the global aging, the coronavirus disease 2019 (COVID-19) pandemic may have affected the place of death (PoD) in Japan, where hospital deaths have dominated for decades. We analyzed the PoD trends before and during the COVID-19 pandemic in Japan. METHODS: This nationwide observational study used vital statistics based on death certificates from Japan between 1951 and 2021. The proportion of PoD; deaths at home, hospitals, and nursing homes; and annual percentage change (APC) were estimated using joinpoint regression analysis. Analyses were stratified by age groups and causes of death. RESULTS: After 2019, home deaths exhibited upward trends, while hospital death turned into downward trends. By age, no significant trend change was seen in the 0-19 age group, while hospital deaths decreased in the 20-64 age group in 2019. The trend change in home death in the ≥65 age group significantly increased since 2019 with an APC of 12.3% (95% confidence interval [CI]: 9.0 to 15.7), while their hospital death trends decreased by -4.0% (95% CI: -4.9 to -3.1) in 2019-2021. By cause of death, home death due to cancer and the old age increased since 2019 with an APC of 29.3% (95% CI: 25.4 to 33.2) and 8.8% (95% CI: 5.5 to 12.2), respectively. CONCLUSION: PoD has shifted from hospital to home during the COVID-19 pandemic in Japan. The majority of whom were older population with cancer or old age.

Functional interaction of Clock genes and bone morphogenetic proteins in the adrenal cortex.

The bone morphogenetic protein (BMP) system in the adrenal cortex plays modulatory roles in the control of adrenocortical steroidogenesis. BMP-6 enhances aldosterone production by modulating angiotensin (Ang) II-mitogen-activated protein kinase (MAPK) signaling, whereas activin regulates the adrenocorticotropin (ACTH)-cAMP cascade in adrenocortical cells. A peripheral clock system in the adrenal cortex was discovered and it has been shown to have functional roles in the adjustment of adrenocortical steroidogenesis by interacting with the BMP system. It was found that follistatin, a binding protein of activin, increased Clock mRNA levels, indicating an endogenous function of activin in the regulation of Clock mRNA expression. Elucidation of the interrelationships among the circadian clock system, the BMP system and adrenocortical steroidogenesis regulated by the hypothalamic-pituitary-adrenal (HPA) axis would lead to an understanding of the pathophysiology of adrenal disorders and metabolic disorders and the establishment of better medical treatment from the viewpoint of pharmacokinetics.

Characteristics of Functional Hyperthermia Detected in an Outpatient Clinic for Fever of Unknown Origin.

Background: Functional hyperthermia (FH) is characterized by hyperthermia resulting from sympathetic hyperactivity rather than inflammation, and it is frequently overlooked by medical practitioners due to the absence of abnormalities in a medical examination. Although FH is an important differential diagnosis for fever of unknown origin (FUO), the literature on FUO cases in Japan lacks information on FH. In this study, we aimed to uncover the population of FH patients hidden in FUO cases. Methods: An outpatient clinic for FUO was established at Okayama University Hospital, and 132 patients were examined during the period from May 2019 to February 2022. Results: A diagnosis of FH was made in 31.1% of the FUO cases, and FH predominantly affected individuals in their third and fourth decades of life with a higher incidence in females (68.3%). The frequency of a history of psychiatric illness was higher in patients with FH than in patients with other febrile illnesses. Although the C-reactive protein (CRP) is generally negative in FH cases, some obese patients, with a body mass index ≥ 25 had slightly elevated levels of CRP but were diagnosed with FH. Conclusions: The results showed the importance of identifying FH when encountering patients with FUO without any organic etiology.

Collection efficiency and safety of large-volume leukapheresis for the manufacturing of tisagenlecleucel.

BACKGROUND: In patients with relapsed or refractory B cell acute lymphoblastic leukemia or B cell non-Hodgkin lymphoma (r/r B-ALL/B-NHL) with low CD3+ cells in the peripheral blood (PB), sufficient CD3+ cell yield in a single day may not be obtained with normal-volume leukapheresis (NVL). Large-volume leukapheresis (LVL) refers to the processing of more than three times the total blood volume (TBV) in a single session for PB apheresis; however, the efficiency and safety of LVL for manufacturing of tisagenlecleucel (tisa-cel) remain unclear. This study aimed to investigate the tolerability of LVL. STUDY DESIGN AND METHODS: We retrospectively collected data on LVL (≥3-fold TBV) and NVL (<3-fold TBV) performed for patients with r/r B-ALL/B-NHL in our institution during November 2019 and September 2023. All procedures were performed using a continuous mononuclear cell collection (cMNC) protocol with the Spectra Optia. RESULTS: Although pre-apheresis CD3+ cells in the PB were significantly lower in LVL procedures (900 vs. 348/µL, p < .01), all patients could obtain sufficient CD3+ cell yield in a single day with a comparably successful rate of final products (including out-of-specification) between the two groups (97.2% vs. 100.0%, p = 1.00). The incidence and severity of citrate toxicity (no patients with grade ≥ 3) during procedures was not significantly different between the two groups (22.2% vs. 26.1%, p = .43) and no patient discontinued leukapheresis due to any complications. CONCLUSION: LVL procedures using Spectra Optia cMNC protocol was well tolerated and did not affect the manufacturing of tisa-cel.

Penile cavernosal abscess after urethral injury.

We present a patient catheterized for prostatic lesions who developed sepsis of urinary origin with a penile cavernosal abscess due to urethral injury caused by catheter ballooning. Urethral injury might lead to a life-threatening penile abscess.

Mutual Effects of Orexin and Bone Morphogenetic Proteins on Catecholamine Regulation Using Adrenomedullary Cells.

Orexins are neuronal peptides that play a prominent role in sleep behavior and feeding behavior in the central nervous system, though their receptors also exist in peripheral organs, including the adrenal gland. In this study, the effects of orexins on catecholamine synthesis in the rat adrenomedullary cell line PC12 were investigated by focusing on their interaction with the adrenomedullary bone morphogenetic protein (BMP)-4. Orexin A treatment reduced the mRNA levels of key enzymes for catecholamine synthesis, including tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanie decarboxylase (Ddc) and dopamine ß-hydroxylase (Dbh), in a concentration-dependent manner. On the other hand, treatment with BMP-4 suppressed the expression of Th and Ddc but enhanced that of Dbh with or without co-treatment with orexin A. Of note, orexin A augmented BMP-receptor signaling detected by the phosphorylation of Smad1/5/9 through the suppression of inhibitory Smad6/7 and the upregulation of BMP type-II receptor (BMPRII). Furthermore, treatment with BMP-4 upregulated the mRNA levels of OX1R in PC12 cells. Collectively, the results indicate that orexin and BMP-4 suppress adrenomedullary catecholamine synthesis by mutually upregulating the pathway of each other in adrenomedullary cells.

Trends in the Incidence of Disseminated Cryptococcosis in Japan: A Nationwide Observational Study, 2015-2021.

BACKGROUND: Cryptococcus species can cause severe disseminated infections in immunocompromised hosts. This study investigated the epidemiological features and trends in disseminated cryptococcosis in Japan. METHODS: We used publicly available Infectious Diseases Weekly Reports to obtain data on the incidence of disseminated cryptococcosis in Japan from 2015 to 2021. Patient information, including age, sex, and regional and seasonal data, were extracted. The Joinpoint regression program was used to determine the age-adjusted incidence rate (AAR) per 100,000 population, annual percentage change (APC), and average APC (AAPC). RESULTS: A total of 1047 cases of disseminated cryptococcosis were reported, of which those aged ≥ 70 years accounted for 68.8%. The AAR in men was significantly higher than that in women (median: 0.13 vs. 0.09: p = 0.0024). APC for the overall cases increased by 9.9% (95% confidence interval [95% CI] - 5.4-27.7) from 2015 to 2018 and then decreased by 3.3% (95% CI - 15.5-10.7) from 2018 to 2021. AAPC for the entire study period was 3.1% (95% CI - 1.5-8.0), indicating a possible increase in its number, although not statistically significant. In terms of regional distribution, the average AAR was highest in Shikoku District (0.17) and lowest in Hokkaido District (0.04). Northern Japan exhibited a significantly lower median AAR (median [interquartile range]: 0.06 [0.05, 0.08]) than the Eastern (0.12 [0.12, 0.13]), Western (0.11 [0.10, 0.13]), and Southern (0.14 [0.12, 0.15]) regions. No seasonal variation in incidence was observed. CONCLUSION: The prevalence of disseminated cryptococcosis has not increased in Japan. Geographically, the incidence is lower in Northern Japan. Further investigations that incorporate detailed clinical data are required.

Influence of the coronavirus disease 2019 pandemic on the post-graduate career paths of medical students: a cross-sectional study.

BACKGROUND: The World Health Organization first declared the coronavirus disease 2019 (COVID-19) pandemic in March 2020 and announced the end of the emergency in May 2023. Additionally, the COVID-19 pandemic significantly impacted individuals globally, including medical students. Although the COVID-19 pandemic increased online education, it restricted clinical training, extracurricular activities, and interprovincial travel. Therefore, this study aimed to examine whether the COVID-19 pandemic influenced the choice of training hospitals and career paths among 3rd- to 6th-year medical students in Japan. METHODS: We developed a questionnaire comprising 21 multiple-choice and 1 open-ended questions, which was administered anonymously via online platforms. The survey targeted Japanese medical students to obtain insights into their preferences for training hospitals and career paths during the COVID-19 pandemic. Participants included 4th- to 6th-year medical students from 51 medical schools in Japan. The survey was conducted through student networks from 8 February 2022 to 20 March 2022. RESULTS: Overall, 507 medical students participated in the survey, with representation from various academic years as follows: 102 (20.1%), 134 (26.4%), 121 (23.9%), and 150 (29.6%) students from the 3rd, 4th, 5th, and 6th year, respectively. Of these, 338 (66.6%) students reported that the COVID-19 pandemic had influenced their choice of training hospitals. The degree of the influence varied based on the university region and the student year. However, most of the students (473, 93.3%) did not change their course for clinical, basic research, or administrative pathways due to the COVID-19 pandemic. Among the clinically oriented students, 391 (77.2%) did not change their preferred speciality. CONCLUSIONS: The COVID-19 pandemic influenced medical students' choice of training hospitals. Although many students believed that the pandemic would not change their career choices, our results indicate a potential subconscious trend to avoid internal medicine, which is the speciality most directly involved in treating patients with COVID-19.

Clinical characteristics of female long COVID patients with menstrual symptoms: a retrospective study from a Japanese outpatient clinic.

PURPOSE: To elucidate the impact of long COVID on menstruation and mental health, medical records of patients with long COVID were evaluated. METHODS: Symptoms of long COVID, QOL, mental health, and related endocrine data were compared between two groups with and without menstrual disturbances. RESULTS: Of 349 female patients who visited our clinic between February 2021 and March 2023, 223 patients with long COVID (aged 18-50 years) were included. Forty-four (19.7%) of the patients had menstrual symptoms associated with long COVID. The patients with menstrual symptoms were older than those without menstrual symptoms (42.5 vs. 38 years). The percentage of patients with menstrual symptoms was higher during the Omicron phase (24%) than during the Preceding (13%) and Delta (12%) phases. Cycle irregularity was the most frequent (in 63.6% of the patients), followed by severe pain (25%), heavy bleeding (20.5%), perimenopausal symptoms (18.2%), and premenstrual syndrome (15.9%). Fatigue and depression were the most frequent complications. Scores for fatigue and for QOL were significantly worse in long COVID patients with menstrual symptoms. Results of endocrine examinations showed significantly increased cortisol levels in patients with menstrual complaints. CONCLUSION: Long COVID has an impact on menstrual conditions and on QOL related to menstrual conditions.

In vitro Activity of Cefmetazole and Flomoxef among Extended-Spectrum Beta-Lactamase producing Enterobacterales.

In this age of antimicrobial resistance (AMR), improving treatment using existing antibiotics is desirable. Extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) are high priority AMR pathogens according to the World Health Organization. Cephamycin-class beta- lactams are tolerant to hydrolysis by ESBL activity and have bactericidal effects on ESBL-E. The aim of the present study was to compare the in vitro minimum inhibitory concentration (MIC) of cefmetazole (CMZ) and flomoxef (FMOX) among ESBL-E strains. This was a retrospective study using microbiology laboratory data from Okayama University Hospital (Japan) from January 2014 to June 2022. The MIC was determined by broth microdilution method and the ESBL phenotypes were determined by double-disk method. Antimicrobial use density (AUD) data for CMZ and FMOX were also gathered. Annual proportions of ESBL-producing organisms in Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae complex were 20.4-30.6%, 3.5-13.7%, and 0-3.1%, respectively. The ESBL-producing bacteria with MIC levels ≤1 µg/mL for CMZ and FMOX ranged from 57 to 84% and 97 to 100%, respectively, for E. coli, and from 50 to 92% and 80 to 100%, respectively, for K. pneumoniae. E. cloacae strains showed MIC levels ≥32 µg/mL for both agents. The AUD ratio for CMZ to FMOX ranged from 5.31 to 12.27, with no apparent upward or downward trend. Proportions of ESBL-producing E. coli and K. pneumoniae strains with MIC ≤1 µg/mL were greater in FMOX than in CMZ. To corroborate the clinical superiority of FMOX in treating ESBL-E infections, a randomized controlled study, as well as pharmacokinetic/pharmacodynamic analysis, is required.

Relevance of complement immunity with brain fog in patients with long COVID.

INTRODUCTION: This study aimed to elucidate the prevalence and clinical characteristics of patients with long COVID (coronavirus disease 2019), especially focusing on 50% hemolytic complement activity (CH50). METHODS: This retrospective observational study focused on patients who visited Okayama University Hospital (Japan) for the treatment of long COVID between February 2021 and March 2023. CH50 levels were measured using liposome immunometric assay (Autokit CH50 Assay, FUJIFILM Wako Pure Chemical Corporation, Japan); high CH50 was defined as ≥59 U/mL. Univariate analyses assessed differences in the clinical background, long COVID symptoms, inflammatory markers, and clinical scores of patients with normal and high CH50. Logistic regression model investigated the association between high CH50 levels and these factors. RESULTS: Of 659 patients who visited our hospital, 478 patients were included. Of these, 284 (59.4%) patients had high CH50 levels. Poor concentration was significantly more frequent in the high CH50 group (7.2% vs. 13.7%), whereas no differences were observed in other subjective symptoms (fatigue, headache, insomnia, dyspnea, tiredness, and brain fog). Multivariate analysis was performed on factors that could be associated with poor concentration, suggesting a significant relationship to high CH50 levels (adjusted odds ratio [aOR], 2.70; 95% confidence interval [CI], 1.33-5.49). Also, high CH50 was significantly associated with brain fog (aOR, 1.66; 95% CI, 1.04-2.66). CONCLUSIONS: High CH50 levels were frequently reported in individuals with long COVID, indicating a relationship with brain fog. Future in-depth research should examine the pathological role and causal link between complement immunity and the development of long COVID.

Recognition and Practice of Hypopituitarism After Traumatic Brain Injury and Subarachnoid Hemorrhage in Japan: A Survey.

INTRODUCTION: Individuals with traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH) are at a high risk of hypopituitarism, and should benefit from early diagnosis and management. However, data on awareness, attitudes, and practices of physicians treating hypopituitarism post-TBI/SAH are limited. The objectives of this study were to gain an understanding of the awareness of Japanese neurosurgeons and endocrinologists towards hypopituitarism post-TBI/SAH and the need for pituitary function assessments in these patients; and to assess the practices and perspectives of these specialists on screening patients with this condition. METHODS: An observational, cross-sectional study was performed that included a Web-based survey of practicing neurosurgeons managing ≥ 1 new patients with TBI/SAH per year or endocrinologists with ≥ 1 new patients per year with a history of TBI/SAH. RESULTS: Of the 316 respondents (201 neurosurgeons [male, 95.5%]; 115 endocrinologists [male, 77.4%]), 75.6% of neurosurgeons and 81.7% of endocrinologists were aware of the probable occurrence of hypopituitarism post-TBI/SAH, and 79% neurosurgeons and 93.8% endocrinologists considered pituitary function impairment after TBI/SAH to be either very important or important. Hypopituitarism after TBI/SAH was recognized as an important concern by both neurosurgeons (79%) and endocrinologists (93.8%). Although many respondents agreed that such patients remain undiagnosed and untreated, pituitary function assessment post-TBI/SAH has only been performed to a limited extent. The awareness that post-TBI/SAH hypopituitarism is often transient and can progress over several weeks or months was lower in neurosurgeons (46.8%) than in endocrinologists (66.1%). CONCLUSIONS: The level of awareness of hypopituitarism post-TBI/SAH was lower among Japanese neurosurgeons than among endocrinologists. Educational programs and detailed guidance for the diagnosis and treatment of hypopituitarism post-TBI/SAH are warranted.