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.

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.

Exophiala dermatitidis pneumonia successfully treated with long-term itraconazole therapy.

Exophiala dermatitidis pneumonia is extremely rare. Here we report a case of E. dermatitidis pneumonia successfully treated with long-term itraconazole therapy. A 63-year-old woman without a remarkable medical history developed a dry and chest pain. Chest radiographs revealed consolidation in the middle lobe of the lung. Cytologic examination by bronchoscopy showed filamentous fungi and E. dermatitidis was detected in the bronchoalveolar lavage fluid. After 5 months of itraconazole therapy, her symptoms improved and the area of consolidation diminished. Two weeks after discontinuing the itraconazole therapy, the area of consolidation reappeared. Itraconazole therapy was restarted and continued for 7 months. The abnormal shadow observed on the chest X-ray gradually diminished. Over a 27-month follow-up with periodic examination, there was no relapse and the patient had a favorable clinical course.

Interventricular septal thickening as an early manifestation of cardiac sarcoidosis.

We report an unusual case of cardiac sarcoidosis demonstrated by interventricular septal thickening. A 64-year-old woman was diagnosed with sarcoidosis involving the lungs, eyes, and skin. Three years later, renal dysfunction was detected during a periodic examination and a renal biopsy revealed non-caseating granulomas. Electrocardiogram results were normal, but an echocardiogram revealed thickening of the interventricular septum. Abnormal accumulation of gallium-67 and a perfusion defect in tecnetium-99-methoxyisobutylisonitrile scintigrams occurred in the interventricular septum. Magnetic resonance images showed T2-high intensity in the lesion. We considered the thickening to represent cardiac involvement of sarcoidosis. Oral prednisolone therapy diminished the interventricular septal thickening.

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.

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.

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.

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.

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.

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.

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.

CD203c expression on human basophils is associated with asthma exacerbation.

BACKGROUND: CD203c is a basophil cell surface marker used to diagnose and monitor various allergic diseases, but its relationship to asthma is not clear. OBJECTIVE: We determined whether CD203c expression levels are associated with stable and exacerbated asthma. METHODS: We used flow cytometry to compare spontaneous expression levels of surface markers on basophils from patients with stable or exacerbated asthma and from healthy subjects. Longitudinal changes in these expression levels were measured after basophil stimulation by IgE-dependent or IgE-independent mechanisms and compared with patients' asthma status. RESULTS: Spontaneous expression levels of CD203c were significantly higher on basophils from patients with asthma exacerbation than patients with stable asthma or healthy subjects. In contrast, no differences in spontaneous expression levels of CD63 or CD69 were observed among the 3 groups. Anti-IgE-induced expression of CD203c significantly increased in basophils during asthma exacerbation (P = .005). Low concentrations of Dermatophagoides pteronyssinus or IL-3 induced higher expression levels of CD203c during asthma exacerbation than during clinical improvement; induction of CD203c expression by these antigens therefore correlates with asthma control. In the patients with clinical improvement, there was a correlation between spontaneous CD203c expression levels and the percent predicted values of FEV(1) (r = -0.761; P = .022). CONCLUSION: Asthma exacerbation was accompanied by increased expression of CD203c on basophils that decreased significantly during remission. Basophil expression levels of CD203c might therefore be used to monitor asthma in patients.

Increase in salivary cysteinyl-leukotriene concentration in patients with aspirin-intolerant asthma.

BACKGROUND: Cysteinyl-leukotrienes (CysLTs; LTC4, LTD4, and LTE4) play a considerable role in the pathophysiology of aspirin-intolerant asthma (AIA). Saliva has recently been validated as novel, simple, and noninvasive method for investigating inflammation in patients with asthma. The aim of this study is to clarify the molecular species of CysLT in saliva and to evaluate the CysLT and LTB4 concentrations in saliva in AIA patients. We also examined how the CysLT concentration in saliva reflects that of their corresponding urinary metabolite. METHODS: We preformed an analytical cross-sectional study. CysLT and LTB4 concentrations in saliva were quantified by enzyme immunoassay (EIA) following purification by high-performance liquid chromatography (HPLC). RESULTS: 1. When analyzed by EIA in combination with HPLC, saliva was found to consist of LTC4, LTD4 and LTE4 in similar amounts. 2. In saliva analysis among the three groups (AIA patients, aspirin-tolerant asthma [ATA] patients, and healthy subjects), both the concentrations of CysLTs and LTB4 were significantly higher in AIA patients than in ATA patients and healthy subjects. 3. We found significant correlations between CysLT concentration and LTB4 concentration in saliva in each group. 4. No significant correlation was found between the concentration of LTE4 in urine and that of CysLTs in saliva. CONCLUSIONS: In this study, we found higher concentrations of CysLTs and LTB4 in saliva from AIA patients than in saliva from ATA patients, suggesting that the quantification of CysLT and LTB4 concentrations in saliva may be another diagnostic strategy for AIA.

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.

Osteopontin levels are elevated in patients with eosinophilic pneumonia.

BACKGROUND AND OBJECTIVE: Osteopontin is a key cytokine involved in pro-inflammatory T helper type 1 (Th1)-associated immune responses, which has recently been implicated in allergic diseases. We investigated the pathogenic role of osteopontin in eosinophilic pneumonia. METHODS: The concentrations of osteopontin and Th1- or Th2-associated cytokines were measured in BAL fluid (BALF) from 41 patients with eosinophilic pneumonia, including those with acute (AEP, n = 12), chronic (CEP, n = 16), or drug-induced eosinophilic pneumonia (DEP, n = 13). The results were compared with those from patients with other interstitial lung diseases. Immunocytochemistry and double immunofluorescence labelling were performed to determine the cellular source of osteopontin. RESULTS: Osteopontin was significantly elevated in BALF from patients with eosinophilic pneumonia as compared with BALF from patients with drug-induced interstitial pneumonia, hypersensitivity pneumonitis, idiopathic interstitial pneumonia, or sarcoidosis, and also compared with BALF from healthy volunteers. Osteopontin concentrations elevated at the time of exacerbation decreased during clinical improvement, either spontaneously or as a result of corticosteroid therapy. Elevated concentrations of CXCL10, CCL17 and IL-10 were also detected in BALF from patients with eosinophilic pneumonia. Osteopontin concentrations in BALF of AEP patients were correlated with IL-5, as well as IL-10, CCL11, CCL17 and CXCL10 concentrations. In AEP and DEP patients, serum osteopontin concentrations were also elevated. Double immunofluorescence labelling showed that in patients with eosinophilic pneumonia, osteopontin was expressed in lung eosinophils. CONCLUSIONS: Osteopontin is likely to contribute to the development of inflammation in patients with eosinophilic pneumonia.

Significance of serum vascular endothelial growth factor level in patients with idiopathic pulmonary fibrosis.

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis, which has been implicated in the pathogenesis of fibrotic lung diseases, including idiopathic pulmonary fibrosis (IPF). The aim of this study was to examine the clinical significance of the serum VEGF level for evaluating disease severity and progression. The levels of VEGF in serum were measured in 41 patients with IPF, 14 patients with lung cancer, and 43 healthy volunteers. We measured the serum levels of CRP, LDH, KL-6, SP-D, and the parameters obtained from arterial blood gas analysis and pulmonary function tests. High-resolution computed tomography (HRCT) was performed to determine the extent of the interstitial and the alveolar opacities. The ability of each biomarker to predict disease severity was estimated by measuring the area under the receiver operating characteristic curve (AUC). The VEGF levels of IPF patients with high alveolar-arterial difference of oxygen (AaDO(2)) levels were significantly elevated than those with low AaDO(2) levels and those of healthy volunteers. When examined within the IPF group, a significant positive correlation was found between the VEGF levels and the HRCT interstitial score (p = 0.027) and the KL-6 levels (p = 0.037). Among several serum biomarkers, VEGF showed the largest AUC for predicting disease severity as defined by a high AaDO(2) value. There was an inverse correlation between the baseline VEGF level and the monthly change in percent predicted vital capacity. The serum VEGF level may reflect the severity of IPF and offer clinical benefits to predict the disease's progression.

Low podoplanin expression of tumor cells predicts poor prognosis in pathological stage IB squamous cell carcinoma of the lung, tissue microarray analysis of 136 patients using 24 antibodies.

The aim of this study was to identify clinicopathological and biological prognostic markers for patients who had undergone complete resection of pathological stage IB squamous cell carcinoma (SqCC) of the lung. A total of 136 consecutive stage IB SqCC patients fulfilled eligibility criteria, and their clinicopathological factors were evaluated. Tissue microarrays were also constracted, and immunohistochemical staining with 24 antibodies was performed. Correlations between clinicopathological factors, antibody immunohistochemical reactions, the patients' overall survival (OS) and relapse-free survival (RFS) were evaluated. The univariate analysis showed that 70-year-old and over elderly group had a shorter OS time and RFS time than the younger group (p=0.0086 and p=0.0091, respectively). The univariate analysis for immunohistochemical staining showed that the podoplanin-negative group had a shorter OS time and RFS time than the podoplanin-positive group (p=0.0106 and p=0.0308, respectively). Multivariate analysis revealed a significant correlation between both the 70-year-old and over elderly group and the podoplanin-negative group and poor outcome (OS, p=0.007 and p=0.008, respectively; RFS, p=0.008 and p=0.024, respectively). The results showed that patient age and a novel biological prognostic marker, podoplanin, are useful for predicting a poor outcome of patients after complete resection of stage IB SqCC of the lung.