Objective: We analyzed the characteristics of ligands of G-protein coupled receptor (GPCR) of new drugs approved, and the time dependent changes of these new drug approvals over three decades from 1980 to 2009 in Japan.
Methods: The receptor therapeutic targets of 185 new drugs were distributed 20 receptor families of GPCR.  Most of new drugs which targeted GPCR were the ligands of class A receptors.  Among the class A receptors, the receptors of amine family, such as adrenaline, dopamine, histamine, serotonin and muscarinic receptor were the targets of new drugs.  One hundred and ten of 185 new drugs were the antagonist and other 75 were the agonist of GPCR.  Whether the new drug is agonist or antagonist depended on the receptor subtype.  The time dependent changes of new drug approval were different among the drugs depending on which GPCR was targeted.  Approval of new drugs which targeted some GPCR decreased time dependently.  In contrast, approval of new drugs which targeted other GPCR increased time dependently or continuously retained.
Results: The results obtained in this study indicated characteristics of targeted GPCR, and time dependent changes of new drugs approvals, and suggest the future aspect of new drugs.

Background: Kampo medicine is the traditional form of medicine practiced in Japan, based on ancient Chinese medicine. Kampo medicine includes acupuncture and moxibustion, as well as herbal medicine. Physicians are allowed to prescribe ethical Kampo extract granules used in various formulae and practice acupuncture and moxibustion as acupuncturists and moxibustionists. However, medical schools do not offer many classes in traditional medicine. This study aims to analyze the use of Kampo formulae and practice of acupuncture and moxibustion in contemporary community health care.
Methods: The subjects (1538 clinicians) were graduates of Jichi Medical University on or after 1978, affiliated with a clinic or hospital with 300 beds or less on July 2010, and surveyed by postal questionnaire in October 2010.
Results: The effective response rate across Japan was 44% (n=679). Of these responders, 30%, 45%, and 22% were found to prescribe Kampo formulae regularly, occasionally, and rarely, respectively, in daily clinical care. Frequently prescribed formulae included shakuyakukanzoto, daikenchuto, kakkonto, rikkunshito, and hochuekkito. The reasons for using Kampo formulae given by 61% and 58% of the responders were, respectively, applicability for common diseases and ease of use for unidentified complaints and psychosomatic disease. Among the reasons for unlikely use, unclear applicability was chosen by 34% of the responders; difficulty stocking many formulations by 33%; and insufficient evidence of efficacy by 30%. Practitioners of acupuncture and moxibustion accounted for 4% of the responders. The main indications for acupuncture and moxibustion included low back pain and shoulder stiffness.
Conclusions: A large number of primary care physicians use Kampo formulae, implying their usefulness. However, one out of three physicians complains of unclear applicability and insufficient evidence of efficacy for Kampo formulae. In the future, appropriate education and research will be needed to clarify these issues.

An 81-year-old man was referred to our hospital with bilateral multiple patchy opacities on chest radiography. His chief complaints were a few months’ history of intermittent mild cough and slightly yellow sputum. Chest computed tomography (CT) showed non-segmental air-space consolidations with ground-glass opacities. Amyloid deposition with organizing pneumonia (OP) was seen in transbronchial lung biopsy (TBLB) specimens from the left S8. Three months later, the infiltration originally seen in the left lower lobe was remarkably diminished, and new infiltrations in the lingual and right lower lobes were detected on chest CT. Amyloid deposition with OP was seen in TBLB specimens from the left S4. Transthyretin was detected following immunohistochemical examination. The presence of wild-type transthyretin (ATTRwt) was proven using genetic analysis. The present report describes a rare case of ATTRwt amyloidosis associated with OP.

　　A 56-year-old woman was referred to our hospital because of an abnormal finding in the right pulmonary hilum on chest X-ray. Enhanced chest computed tomography showed hyperplastic bronchial arteries dilating and winding around the trachea and bronchi. A racemose hemangioma of the bronchial artery with multiple bronchial artery aneurysms (diameter <20mm) was seen displacing the trachea and both main bronchi. Bronchoscopy showed submucosal tumor-like lesions at the distal trachea and in both main bronchi, and a dusky-red elevated pulsatile lesion at the orifice of the left B3b＋c. We performed coil embolization of the bronchial artery aneurysm to prevent abrupt rupture of the bronchial aneurysm.

Background: The impact of COVID-19 infection on workers' work function persists even after the acute phase of the infection. We studied this phenomenon in Japanese workers. Methods: We conducted a one-year prospective cohort study online, starting with a baseline survey in December 2020. We tracked workers without baseline work functioning impairment and incorporated data from 14,421 eligible individuals into the analysis. We estimated the incidence rate ratio for new onset of work functioning impairment due to COVID-19 infection during follow-up, using mixed-effects Poisson regression analysis with robust variance. Results: Participants reporting infection between January and December 2021 showed a significantly higher incidence of new work functioning impairment (adjusted incidence rate ratio: 2.18, 95% confidence interval: 1.75–2.71, p < 0.001). The formality of the recuperation environment correlated with a higher risk of work functioning deterioration in infected individuals (p for trend <0.001). Conclusion COVID-19-infected workers may continue to experience work difficulties due to persistent, post-acute infection symptoms. Companies and society must urgently provide rehabilitation and social support for people with persistent symptoms, recognizing that COVID-19 is not just a transient acute infection.

Cough is one of the most common respiratory complaints leading to medical consultation. Fractional exhaled nitric oxide (FeNO) testing detects eosinophilic inflammation of the airway. We evaluated the diagnostic efficacy of FeNO testing in patients with cough. Patients who presented to the respiratory medicine department of our hospital with a chief complaint of cough and underwent FeNO testing were included in this study and divided into asthma and non-asthma groups. Patients with confounding factors such as allergic rhinitis and atopic predispositions were also identified and those with and without confounding factors, respectively, were further divided into the asthma and non-asthma groups. Median FeNO in the asthma and non-asthma groups was respectively 31 and 19 ppb in all patients and 31 and 18 ppb in those without confounding factors, with significant differences between the groups in both populations. The corresponding values in patients with confounding factors were 46 and 23 ppb, with no significant difference between the groups. A cut-off of 27 ppb differentiated between the asthma and non-asthma groups with sensitivity of 0.603 and specificity of 0.776. These results suggest FeNO testing is effective in the differential diagnosis of cough in patients without confounding factors.

In patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer (LC) who have acquired resistance to first and/or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), detection of EGFR T790M (T790M) mutation is essential before administration of osimertinib. Tissue sample is the main specimen used to detect the T790M mutation, and so cell block preparation using pleural or pericardial fluid should be considered. The utility of body cavity effusion cell block methods in T790M mutation detection have not yet been fully evaluated. This study aimed to evaluate the clinical background and treatment course of LC patients harboring the T790M mutation by using body cavity effusion cell block methods at our hospital. All patients were treated with first and/or second-generation EGFR-TKIs and had developed malignant pleural or pericardial fluid as a result of progressive disease. T790M mutation status was evaluated using body cavity effusion cell block method in 9 patients, from April 2016 to August 2017. We retrospectively evaluated the clinical characteristics and treatment course of these 9 patients (3 males and 6 females; median age 76 years). At the first diagnosis of LC, 7 patients had stage IV cancer; 4 patients were diagnosed by bronchial fibroscopy and 3 were diagnosed from pleural fluid examination. Regarding EGFR mutation, 3 and 6 patients carried the exon 19 deletion and L858R mutation, respectively. Median time interval between the first diagnosis of LC and T790M mutation evaluation was 30.8 months; 7 patients were diagnosed with positive T790M mutation by using body cavity effusion cell block methods. The T790M mutation was highly detected by examination of body cavity effusion cell blocks. Further evaluation is necessary with respect to variations in T790M detection rate based on the specimen collection site and/or progressive disease pattern in different patients.

A 68-year-old man was admitted to our hospital with complaints of fatigue, polyuria, and loss of appetite, and was diagnosed with diabetic ketosis. Chest and abdominal computed tomography (CT) showed a pulmonary tumor on the right S3 and multiple liver tumors. Blood chemistry revealed elevated levels of amylase and hepatobiliary enzymes. Pathological examination of a biopsy specimen from the liver tumor showed a small cell carcinoma. Based on the imaging and pathological findings, we made a diagnosis of extensive disease small-cell lung cancer (ED-SCLC), cT1aN3M1b (HEP, ADR). Treatment with carboplatin and etoposide evoked partial response and the serum level of amylase decreased. Immunohistochemical staining of liver biopsy specimen was positive for amylase, leading to a diagnosis of SCLC with amylase production. About 22 months after the diagnosis of SCLC, he was admitted to our hospital with fatigue, muscular weakness, edema, and hyperpigmentation. Laboratory findings showed elevated serum levels of hepatobiliary enzymes, adrenocorticotropic hormone (ACTH), and cortisol, and a decreased serum potassium level. Urinary potassium level was elevated. Pituitary magnetic resonance imaging showed a normal morphology. We made a diagnosis of SCLC complicated by Cushing’s syndrome. We report this rare case of SCLC with amylase and ACTH production, which was detected in the course of treatment of SCLC.

Background: Cell blocks (CBs) from pleural fluid are frequently used in the practice of respiratory medicine, but there have been few reports on the use of CBs from forceps and brush washing fluid in bronchoscopy for pathological diagnosis. We retrospectively analyzed the usefulness of CBs from forceps and brush washing fluid. 　Patients and Methods: Patients who underwent bronchoscopy and had CBs made from forceps and brush washing fluid in bronchoscopy at our institution between June 2016 and May 2021 were included. Cases in which additional information was obtained from CBs were reviewed in detail. 　Results: In total, 138 patients had CBs made from forceps and brush washing fluid in bronchoscopy during the study period. EBUS-GS (endobronchial ultrasound-guide sheath) was used for 102 of these patients. The final diagnosis was lung cancer in 114 cases, infection disease in 10 cases, metastatic lung tumor in 8 cases, lymphoproliferative disease in 2 cases, sarcoidosis in 1 case, and organizing pneumonia in 1 case. There were 13 cases with additional information obtained from CBs, all of which were cases of malignant tumors. 　Conclusions: CBs from forceps and brush washing fluid in bronchoscopy were useful for pathological diagnosis in some cases.

Objective: The utility of topotecan monotherapy for relapsed small-cell lung cancer (SCLC) after failure of amrubicin monotherapy has not been evaluated. We aimed to investigate the efficacy and safety of topotecan monotherapy in patients with relapsed SCLC after amrubicin monotherapy.Patients and Methods: We retrospectively analyzed data from 16 patients with relapsed SCLC who were treated with topotecan monotherapy after amrubicin monotherapy at our hospital.Results: The response rate, progression-free survival, and overall survival were 0%, 32.5 days (95% confidence interval [CI] = 18–51), and 112 days (95% CI = 55–267), respectively. The most common adverse events (grade ≥3) were leukopenia (31.3%) and thrombocytopenia (31.3%), followed by anemia, anorexia, edema, and lung infections.Conclusion: The efficacy of topotecan monotherapy for relapsed SCLC after amrubicin monotherapy is inconclusive. Therefore, further studies are warranted.