[PROBLEMS ASSOCIATED WITH THE DIAGNOSIS OF PROLONGED/CHRONIC COUGH IN CLINICAL SETTINGS].

BACKGROUND: Many patients visit primary care clinics or local hospitals with a complaint of prolonged/chronic cough. Among the different types of chronic cough, cough variant asthma (CVA) and postinfectious cough may be the most common types, and their differential diagnosis is difficult. Some physicians tend to prescribe inhaled corticosteroids before establishing a definitive diagnosis. METHODS: We retrospectively investigated useful findings for diagnosis in 77 patients with a complaint of prolonged/ chronic cough to detect meaningful findings for differential diagnosis and to identify problems associated with diagnosis in clinical practice. RESULTS: CVA was diagnosed in 39 patients, and postinfectious cough was diagnosed in 19. Compared with postinfectious cough, CVA was associated with significant characteristics such as "diurnal variation of symptoms," "response to inhalation of short acting ß2 agonist (SABA)," and "recurrent episodes of symptoms." CVA was associated with high FeNO levels as well, and high FeNO levels were specific to CVA. However, these useful characteristics were not significant in the patients who had been prescribed ICS before visiting our hospital. CONCLUSIONS: Medical examination and determination of FeNO levels are useful for the differential diagnosis of prolonged/chronic cough, before treatment with ICS.

Prognostic Index for Survival in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Third-Generation Agents.

We retrospectively evaluated clinical data from patients with advanced non-small-cell lung cancer (NSCLC) treated with third-generation chemotherapy agents prior to treatment, to determine a reliable method for predicting prognosis in such patients. We analyzed 100 patients who received third-generation agents (paclitaxel, docetaxel, gemcitabine, irinotecan, and vinorelbine) for the treatment of advanced NSCLC. Factors significantly related to prognosis were evaluated using the Cox regression model, and the prognostic index (PI) was determined by combining these factors. The mean follow-up duration was 12.6 months (0.2-67.0 months). Multivariate analysis identified pleural effusion, absolute neutrophil count (ANC), and C-reactive protein (CRP) level as significant factors that independently contribute to prognosis in patients with advanced NSCLC treated with third-generation agents (p < 0.05). The PI was calculated using these 3 factors, according to the following formula: PI = 0.581 × pleural effusion + 0.125 × ANC + 0.105 × CRP. The death rate in the group with the highest PI scores was significantly higher than in the group with the lowest scores (p < 0.001). Pleural effusion, ANC, and CRP level were the most important factors that contributed to prognosis following chemotherapy with third-generation agents in patients with advanced NSCLC. The PI is suggested to be an appropriate index to predict the prognosis of patients with NSCLC.

Combination of rRT-PCR and Clinical Features to Predict Coronavirus Disease 2019 for Nosocomial Infection Control.

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), immediately became a pandemic. Therefore, nosocomial infection control is necessary to screen for patients with possible COVID-19. Objective: This study aimed to investigate commonly measured clinical variables to predict COVID-19. Methods: This cross-sectional study enrolled 1087 patients in the isolation ward of a university hospital. Conferences were organized to differentiate COVID-19 from non-COVID-19 cases, and multiple nucleic acid tests were mandatory when COVID-19 could not be excluded. Multivariate logistic regression models were employed to determine the clinical factors associated with COVID-19 at the time of hospitalization. Results: Overall, 352 (32.4%) patients were diagnosed with COVID-19. The majority of the non-COVID-19 cases were predominantly caused by bacterial infections. Multivariate analysis indicated that COVID-19 was significantly associated with age, sex, body mass index, lactate dehydrogenase, C-reactive protein, and malignancy. Conclusion: Some clinical factors are useful to predict patients with COVID-19 among those with symptoms similar to COVID-19. This study suggests that at least two real-time reverse-transcription polymerase chain reactions of SARS-CoV-2 are recommended to exclude COVID-19.

Respiratory rhythm affects recalibration of body ownership.

Change in body perception requires recalibration of various sensory inputs. However, it is less known how information other than sensations relates to the recalibration of body perception. Here, we focused on the relationship between respiration and cognition and investigated whether respiratory rhythms are related to the recalibration of hand perception. We built a visual feedback environment, in which a mannequin hand moved in conjunction with its own respiratory rhythm, and participants performed an experiment under conditions in congruency/incongruency for spatial and temporal factors. The temporal and spatial congruency between own respiratory rhythm and the mannequin hand markedly facilitated the phenomenon of hand ownership sense transfer to the mannequin hand, while incongruency had little effect on the change in hand ownership. The finding suggests that an internal model in the brain allows respiratory rhythms to be involved in the adaptation of the body's neural representations.

Pneumothorax with Eosinophilia is an Important Diagnostic Clue for Distinguishing Paragonimiasis from Chronic Eosinophilic Pneumonia: A Case Report.

The Paragonimus westermani infection is a parasitic foodborne infection that induces systemic symptoms with eosinophilia in humans. Here, we described pneumothorax in addition to pulmonary opacities with eosinophilia in a man with a positive P. westermani serology. He was misdiagnosed with chronic eosinophilic pneumonia (CEP) during the initial phase. Paragonimiasis can share similar clinical findings with CEP in cases where the worm is confined to the lungs. The findings of the current study suggest that paragonimiasis and CEP can be distinguished from each other by the presence of various symptoms. Notably, eosinophilia with pneumothorax should be an important diagnostic factor for paragonimiasis.

Surgical Resection to Treat a Japanese Patient with Pulmonary Coccidioidomycosis.

Coccidioidomycosis is an endemic disease that is particularly prevalent in the United States. However, its geographic distribution is becoming widespread. Here, we present a Japanese male who resided in the United States for 1 year, where he was diagnosed with pulmonary coccidioidomycosis that was accompanied by cavity formation. He did not tolerate antifungal therapy and consequently underwent partial resection of the upper lobe of his left lung upon his return to Japan. The patient's symptoms improved after surgery. The trend toward global networking and logistics means that a diagnosis of coccidioidomycosis should be considered in routine practice in nonendemic areas. Due to the rarity of surgical treatment for this disease, prolonged follow-up is necessary. During the last follow-up, the patient was symptom-free.

Effect of tocilizumab treatment in mildly-obese patients with coronavirus disease 2019: a case series.

Background: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an increasingly widespread international medical problem. Several randomized trials and observational studies in patients with COVID-19 have been performed. However, the standard treatment strategy has not yet been established. The purpose of this study is to report effect of tocilizumab treatment combined with remdesivir, dexamethasone, and heparin on obese Japanese patients with COVID-19. Tocilizumab is a monoclonal antibody against the interleukin-6 (IL-6) receptor. Obesity, characterized by systemic enlarged adipocytes, promotes proinflammatory cytokine expression in adipose tissue. More specifically, obesity induces detrimental adipocytokine production including tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and IL-6. In addition, its production in the adipose tissue is associated with body mass index (BMI) and adipocyte size. IL-6 can promote inflammation not only in the adipose tissues but also in endothelial cells and triggers systemic inflammation. Methods: A cross-sectional observational study was conducted. The study sample consisted of 96 patients between August 2020 and January 2021 at Showa University Fujigaoka Hospital. Results: Overall, 56.3% (54 of 96) were administered with remdesivir, 54.2% (52 of 96) with dexamethasone, 19.8% (19 of 96) with anticoagulant therapy with heparin. Of the patients, nine were administered tocilizumab with remdesivir, dexamethasone, and heparin. The current study indicated that single-dose treatment of tocilizumab in combination with remdesivir, dexamethasone, and heparin is beneficial for obese Japanese patients with COVID-19. Conclusions: We believe that the severity of obesity is related to the anti-IL-6 treatment sensitivity in patients with COVID-19.

In-hospital blood collection increases the rate of indeterminate results in interferon-gamma release assays.

BACKGROUND: The interferon (IFN)-γ release assay (IGRA) has recently been established as a method to evaluate the infection status of tuberculosis instead of the tuberculin skin test. However, indeterminate results can create challenges to interpretation. The IGRA has been available in Japan since 2005, including the recently launched QuantiFERON-TB Gold Plus (QFT-plus) assay. OBJECTIVES: The aim of this study was to investigate the clinical features and predictors of indeterminate results by the QFT-plus test in routine practice. METHODS: This was a cross-sectional study of 1258 patients. Multivariate logistic regression models were employed to investigate the clinical factors related to indeterminate results by the QFT-plus. RESULTS: Overall, 91.8% of results were found to be conclusive and 8.2% were indeterminate. The QFT-plus indeterminate results were predominantly due to a low level of IFN-γ production by mitogens. Multivariate analysis indicated that an indeterminate result was significantly associated with age, sex, corticosteroid use, autoimmune disease, and inpatient setting. CONCLUSION: Certain types of individuals are at higher risk of an indeterminate IGRA result. The QFT-plus test for hospitalized patients should be avoided as much as possible, and it is better to perform the test for those patients in outpatient settings.

Combination of anti-glycopeptidolipid-core IgA antibody and clinical features for diagnosing potential nontuberculous mycobacterium pulmonary disease in routine practice.

BACKGROUND: The anti-Mycobacterium avium complex (MAC) antibody test measures levels of IgA antibody against the glycopeptidolipid (GPL) core in the bacterial cell walls and is a useful clinical indicator of nontuberculous mycobacterium pulmonary disease (NTM-PD). However, it is not currently possible to diagnose the disease using anti-MAC antibodies alone. OBJECTIVES: The study aim was to assess the efficacy of the combination of anti-MAC antibodies and clinical findings for diagnosing potential NTM-PD. METHODS: This cross-sectional study included 938 patients tested using the anti-MAC antibody. NTM-PD was diagnosed by multiple positive cultures of the same species in sputum samples. Multivariate logistic regression models were used to identify the clinical factors related to NTM-PD. RESULTS: Overall, 19.6% (184/938) of participants were diagnosed with NTM-PD. In multivariate analysis, positive anti-MAC antibodies, low body mass index, absence of malignancy, and cavity-forming lung lesions were significantly associated with NTM-PD at diagnosis. The positive rates of the anti-MAC antibody test were 79.4% (135/170) for MAC and 55.6% (5/9) for Mycobacterium abscessus complex, respectively. CONCLUSIONS: Bronchoscopic examinations should be performed especially in certain types of individuals from whom sputum samples cannot be obtained. Anti-MAC antibodies are also positive in patients other than those harboring MAC, but the rate may be low because of the different components in GPLs.

[CPT-11 chemotherapy for a hemodialysis patient with small-cell lung cancer].

We report a hemodialysis patient with extensive small-cell lung cancer who was administered CPT-11(50mg/m2)chemotherapy and achieved a partial response after four courses of chemotherapy. Hemodialysis was performed 24 hours after the first course of CPT-11 was completed. Because the patient developed thrombocytopenia and pneumonia, hemodialysis was performed 4 hours following the second course of chemotherapy, after which grade III bone marrow suppression was observed. The plasma concentrations of CPT-11 and its metabolic products(SN-38 and SN-38G)were measured during both courses. A pharmacokinetic study showed that the plasma concentration of CPT-11 after the first course was relatively high, and that the kinetics was similar to that in a non-dialysis case. However, 4 hours after hemodialysis, the concentrations of CPT-11 and SN-38G were re-elevated, and showed a sustained level higher than that obtained 24 hours after hemodialysis. Further study is needed to determine the optimal dosages of CPT-11, and the best time to conduct hemodialysis for chronic cancer patients requiring it.

Correlation Between Thymoma and Soluble Interleukin-2 Receptor Expression in a Patient with Good Syndrome.

Good syndrome is a rare condition characterized by the presence of thymoma in combination with adult-onset hypogammaglobulinemia. Immunological features of Good syndrome include various immunodeficiencies accompanied with hypogammaglobulinemia. In patients with thymoma, paraneoplastic syndromes including hypogammaglobulinemia worsen the prognosis. We herein describe a patient with advanced-stage type A thymoma who was effectively treated with chemotherapy and exhibited a parallel decrease in the serum level of soluble interleukin-2 receptor (sIL-2R), which depends on cellular immunity. The present case suggests the efficacy of sIL-2R as a potential prognostic biomarker in a subset of patients with Good syndrome.

PCR amplification of the erm(41) gene can be used to predict the sensitivity of Mycobacterium abscessus complex strains to clarithromycin.

A worldwide increase in the Mycobacterium abscessus (M. abscessus) complex has been observed. Therefore, the aim of the present study was to investigate the diversity of the rrl and erm(41) genes, both of which are associated with macrolide sensitivity in the M. abscessus complex. The current study also examined the efficacy of mass spectrometry as an alternative to molecular testing to classify subspecies of the M. abscessus complex. A total of 14 strains of the M. abscessus complex were obtained, and based on conventional analyses using housekeeping genes, 57% were determined to be M. abscessus subsp. abscessus, 43% were M. abscessus subsp. massiliense, and none were identified as M. abscessus subsp. bolletii. However, depending on the strain, it was not always possible to distinguish between the subspecies by mass spectrometry. Consequently, PCR products for the rrl and erm(41) genes were directly sequenced. Overall, 7.1% of the strains were identified to have a rrl mutation, and 92.9% carried a T at position 28 of erm(41). Results presented here suggest that the principal cause of treatment failure for M. abscessus complex infections is inducible macrolide resistance encoded by the erm(41) gene. From a strictly pragmatic standpoint, the phenotypic function of a putative erm(41) gene is the most important piece of information required by clinicians in order to prescribe an effective treatment. Although PCR amplification of erm(41) is not sufficient to differentiate between the M. abscessus complex subspecies, PCR can be easily and efficiently used to predict the sensitivity of members of the M. abscessus complex to clarithromycin.

Impact of the interferon-γ release assay and glomerular filtration rate on the estimation of active tuberculosis risk before bronchoscopic examinations: a retrospective pilot study.

BACKGROUND: Bronchoscopic examinations are vital to diagnose pulmonary diseases. However, as coughing is triggered during and after the procedure, it is imperative to take measures against nosocomial infections, especially for airborne infections like tuberculosis (TB). The interferon-γ release assay (IGRA) has recently been established as a method to evaluate the infection status of TB. We aimed to ascertain the efficacy of IGRA and clinical findings in estimating the prevalence of active TB before bronchoscopy. METHODS: We obtained IGRA results from 136 inpatients using a QuantiFERON-TB Gold In-Tube test. Bronchoscopy samples were cultured in Mycobacteria Growth indicator tubes and 2% Ogawa solid medium. We evaluated the adjusted effects of multiple clinical variables on active TB status using a logistic regression model. In addition, multiple variables were converted into a decision tree to predict active TB. RESULTS: Five (3.7%) patients were diagnosed with culture-positive TB, two of whom were simultaneously diagnosed with non-small-cell lung carcinoma or small-cell lung carcinoma. The multivariate analysis suggested the probability of predicting active TB using the IGRA [odds ratio (OR), 72.7; 95% confidence interval (CI), 3.169-1668; P=0.007] and decreased estimated glomerular filtration rate (eGFR) (OR, 0.937; 95% CI, 0.882-0.996; P=0.038) in patients undergoing bronchoscopy. A decision tree validated the use of these two variables to predict active TB. CONCLUSIONS: IGRA test results are useful for predicting active TB before bronchoscopy. This strategy could identify patients who require antibiotic therapy to prevent TB or who are in the active phase of TB.

Effect of osimertinib treatment on lung adenocarcinoma with squamous cell transformation harboring the T790M mutation: A case report and literature review.

We herein report a case of squamous cell transformation combined with the epidermal growth factor receptor (EGFR) mutation T790M associated with acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in a 73-year-old male patient diagnosed with stage IVA lung adenocarcinoma. Gene alterations were analyzed by collecting and studying pleural effusion at the time of diagnosis. Examination revealed an exon 19 deletion in the EGFR gene. Following treatment with the second-generation EGFR-TKI afatinib, squamous cell carcinoma was identified by performing a re-biopsy of the recurrent site. Although the levels of cytokeratin 19 fragment, which is a tumor marker for the follow-up of squamous cell carcinoma, were increased at that point, the levels of carcinoembryonic antigen, a marker particularly associated with adenocarcinoma, remained within normal limits. The T790M mutation and the original exon 19 deletion were detected simultaneously. The patient received treatment with the third-generation EGFR-TKI osimertinib, achieving a good clinical response. These findings suggest that osimertinib is beneficial for lung adenocarcinoma patients with squamous cell transformation harboring the T790M mutation.

Hemoptysis following Talc Pleurodesis in a Pneumothorax Patient.

The purpose of this article is to report a case of hemoptysis occurring in combination with secondary spontaneous pneumothorax following chemical pleurodesis by talc. A Japanese male with cancer of renal pelvis was found with the left pneumothorax and multiple lung metastases. A computed-tomography scan revealed severe emphysema throughout the lungs. Talc pleurodesis was employed to arrest air leakage. The patient developed hemoptysis 45 minutes after talc injection into the thorax. This is the first report of hemoptysis following talc pleurodesis. The agent could induce severe inflammation in capillary vessels of the lung following visceral pleura infiltration.

[A case of Mycobacterium abscessus pulmonary infection; effectiveness of clarithromycin, amikacin and imipenem/cilastatin].

A 42-year-old woman presented with persistent cough, bloody sputum and fever. Her chest X-ray film showed an infiltrative shadow with cavitation in the upper lobe of the left lung. Acid-fast-bacilli were shown by sputum smear staining. The anti-tuberculosis drugs isoniazid, refampicin, ethambutol and pyrazinamide were prescribed, but her symptoms and chest X-ray findings did not improve. Findings of MTD and MAC-PCR were negative but Mycobacterium abscessus was confirmed by sputum culture with the DNA hybridization method. Combination therapy with clarithromycin, amikacin and imipenem/cilastatin for one month improved her symptoms and chest X-ray shadow, and clarithromycin monotherapy was carried out for another ten months. Drug susceptibility tests revealed this mycobacterium was sensitive to clarithromycin and amikacin. To determine the environmental factors related to this infection, several samples were examined. Acid-fast-bacilli were present in a smear from the bath room drain. However, to confirm the infectious routes, longer observation is needed. Moreover, serum amyloid protein A and ESR were useful markers to estimate the clinical course.

[A case of spontaneous epidural emphysema occurring during sleep].

A 19-year-old man consulted a doctor for swelling of his neck and shortness of breath. The day before, he woke up with a slight cough and upper chest pain early in the morning. He went to school and spent the day as usual. He did not have a history of asthma or violent cough. The next day, chest radiography showed subcutaneous emphysema and pneumomediastinum. Computed tomography not only confirmed the presence of mediastinal and subcutaneous air, but also demonstrated a linear radiolucent stripe in the spinal canal corresponding to epidural emphysema. The patient did not have any neurologic findings. His general condition remained good except that his arterial blood oxygen saturation slightly decreased to 95%. Laboratory data were normal, except for serum IgE, which was elevated (2072 IU/ml). He stayed at rest and was treated conservatively and his symptoms improved within a few days. Seven days later, the intraspinal air and pneumomediastinum had resolved spontaneously on follow-up chest computed tomography (CT).