Background: Japan has remained medium-burden tuberculosis (TB) country for many years. However, a considerable variation was observed in the TB space-time distribution among Japan’s eight regions. This study aimed to investigate the spatial, temporal, and space-time dynamics of TB at the machi-level in Nagasaki prefecture. Methods: Data on the reported TB infections from 2007 to 2018 were collected from the information center for infectious diseases of the Nagasaki Prefectural Institute of Environment and Public Health. The time series, temporal trends, and spatial patterns of TB at the machi-level were explored using Moran’s I and Kulldorff’s space-time scan statistics. Results: A total of 4,364 TB infections were reported between April 2007 and December 2018 in Nagasaki prefecture. The infections were frequently reported in October, June, and January, and they showed spatial clustering with Moran’s I value ranging from 0.07 to 0.17 (p = 0.001). Ten significant clusters were identified, including one most likely cluster and nine secondary clusters, which were mainly concentrated in the densely inhabited districts of the two biggest cities in Nagasaki prefecture (Nagasaki city and Sasebo city), Shimabara peninsula, and Iki island. Conclusion: This study showed significant and unique spatial-temporal characteristics of TB infections in Nagasaki prefecture. Therefore, such information on the prevailing epidemiological situation of TB infections could help develop strategies that could effectively eliminate TB in Japan.

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Background: Dose-dense chemotherapy (DDCT) is a standard treatment for patients with high-risk breast cancer. Although there are numerous reports regarding DDCT, it is unclear whether sequential DDCT is effective or feasible as preoperative treatment for Japanese patients. We evaluated the efficacy and safety of neoadjuvant DDCT for patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Methods: This retrospective study evaluated 39 patients with breast cancer, who were preoperatively treated with anthracyclinecontaining regimens and taxanes. According to the chemotherapy regimens patients were divided into the DDCT group (ddgroup) and the conventional chemotherapy (CCT) group (q3w-group). The efficacy of neoadjuvant chemotherapy was evaluated based on the pathological complete response (pCR) rate. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. Results: There were no apparent differences in tumor stage, histopathological subtype, or surgical procedure. There was not significant difference in the pCR rate (dd-group, 17.6%; q3w-group, 22.7%). Three-year disease-free survival rates were similar in two groups. The rates of dose reduction, delay of treatment, and discontinuation of treatment in the two groups did not differ to a statistically significant extent. There were no significant differences in the adverse events of the two groups. Conclusion: The pCR rate for DDCT was similar to that of CCT. DDCT may be feasible for Japanese breast cancer patients.

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Background. Ultrasonography using Sonazoid, a novel contrast agent containing microbubbles, is a useful diagnostic modality for intrahepatic mass lesions with specific characteristics in two phases: contrast enhancement of early vascular perfusion and perfusion defect of the lesion in the late phase. To improve the diagnostic accuracy of intraoperative ultrasonography (IOUS) in biliary neoplasms, particularly gall bladder, we investigated the usefulness of the Sonazoid contrast agent in a preliminary study. Subjects and Methods. We examined IOUS images of 23 patients with gall bladder disease. Sonazoid was administered intravenously, and early arterial and venous phase images of the tumor were obtained during laparotomy. Results. Tumors included the localized type of adenomyomatosis in the fundus of the gallbladder (GAM) in seven patients as benign controls, adenomatous diseases in three, and gallbladder carcinoma (GC) in 13. Sonazoid IOUS scanning was performed in all patients, with no adverse effects. Although GC showed high enhancement in 77% of the tumors, GAM and adenoma also showed mild enhancement in more than half of them. Pseudo-positivity was observed in one case of hyperplastic polyps, and pseudo-negativity was observed in two patients. Cholesterol polyps and a suspicious lesion of liver metastasis by the computed tomography were not enhanced with Sonazoid treatment. Conclusion. Although there remains a problem of pseud-positivity in the intracystic lesions, Sonazoid IOUS may be a useful tool to detect vascularity and its location or extension of gallbladder diseases; however, neither significance of differential diagnosis with benign diseases nor other clinical significance was found.

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Background: Preventing coronavirus disease 2019 (COVID-19) in older people is an important public health issue. The purpose of this study was to investigate the relationship between the level of fear regarding COVID-19 and adherence to COVID-19 prevention measures among community-dwelling older adults. Methods: This study was a cross-sectional survey conducted from July 15 to August 19, 2020, in 127 community-dwelling older adults ?65 years old in Japan. A questionnaire including participants’ basic attributes (age, sex, body mass index, and family structure), levels of fear regarding COVID-19, increasing adherence to four behaviors (restrictions on going out, maintaining physical distancing, wearing masks, and washing hands) for COVID-19 prevention, and its stress levels was used. We calculated the relationship between the level of fear of COVID-19 and the level of each behavioral change using Spearman's correlation coefficient (rs). Results: About 95% of older adults displayed fear of COVID-19. Rates of adherence to all four COVID-19 prevention measures increased to approximately 80-95%. However, about 40-55% of older adults were stressed by all behavior modifications except washing hands. The increasing level of fear regarding COVID-19 correlated positively with decreasing frequency of going out (rs=0.280, p=0.001) and increasing frequency of washing hands (rs=0.336, p<0.001). Conclusion: The behavioral changes of COVID-19 prevention measures in community-dwelling older people were excellent with increasing adherence rates. While such high adherence rates may increase the preventive effect in community-dwelling older people, the new lifestyle during the COVID-19 epidemic may cause frailty due to restrictions on going out and stress regarding behavior modifications.

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Aim: Streptococcus pneumoniae is the most frequently detected bacterium in pneumonia. RAPIRUN Streptococcus pneumoniae (RAPIRUN) using sputum and BinaxNow Streptococcus pneumoniae (BinaxNow) using urine have been used as rapid diagnostic methods for S. pneumoniae detection in Japan; however, their correlation with quantitative culture tests has not been well evaluated. Methods: A prospective study was conducted on adult patients with respiratory tract infections whose sputum and urine samples were available in six hospitals. Sputum and urine samples were tested at each site, and quantitative sputum cultures were performed. The performance of RAPIRUN and BinaxNow was compared in cases in which quantitative culture showed S. pneumoniae. Results: A total of 192 patients were analyzed. Of these, 167 were diagnosed with pneumonia (87.0%) including 161 of community-acquired pneumonia. Of the 192 cases, 86 (44.8%) were culture-proven for S. pneumoniae. There were 83 and 57 RAPIRUN- and BinaxNow-positive cases, respectively. The sensitivity and specificity of RAPIRUN were 84.9% and 90.6%, respectively, and those of BinaxNOW were 55.8% and 91.5%, respectively, indicating that RAPIRUN was significantly superior in sensitivity (p < 0.0001) with almost equal specificity (p = 0.317). Positive and negative percent agreements of both tests were 59.3% (κ, 0.114 [95% CI, 0.053?0.281]) and 99.1% (κ, 0.942 [95% CI, 0.830?1]), respectively, indicating they were well matched in specificity but not in sensitivity. The positivity rate of RAPIRUN increased with an increase in the number of bacteria (p< 0.0001) but not BinaxNow (p = 0.275). Conclusion: In adult patients with respiratory tract infections in whom sputum collection is feasible, RAPIRUN will increase the diagnostic efficacy of S. pneumoniae infection.

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Osteoporosis and its related fractures are important public health issues. This study examined the association between the Kessler Psychological Distress Scale (K6) and low bone mass in middle-aged community-dwelling men and women. A cross sectional study was nested in a prospective observational study of 1,101 participants (median age: 57 [49-62] years in men and 58 [50-62] years in women) residing in a rural city in western Japan. Participants were recruited during medical check-ups in 2016 and 2017 from the community-dwelling population. The bone mass of the calcaneus was evaluated using quantitative ultrasound. Of the participants, 56 men (14.9%) and 144 women (19.9%) had a bone mass of less than 70% of the mean of young adults. Univariate analysis revealed that there was a trend toward lower body mass index (BMI) and higher prevalence of low bone mass with an increase in K6 scores in men but not in women. Logistic regression analysis, adjusting for possible confounders (age, BMI, smoking, drinking habits, exercise habits, diabetes, hyperlipidemia, and hypertension), showed significant associations between the K6 scores and low bone mass (odds ratio (OR) = 2.66 for the men with 5 to 12 points of K6, OR = 7.51 for men with ≥ 13 of K6, not for women). We showed an association between psychological distress and low bone mass independent of cofounders among community-dwelling middle-aged men but not women. This suggests that healthy mental health in middle-aged men may be a possible target for the prevention of consequent osteoporosis or fragile bone fractures.

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Background: Medical resources on remote islands are limited, which makes it difficult for patients to receive specialized medical care. Purpose: This study aimed to develop and evaluate a method to perform doctor-to-doctor-to-patient (D-to-D-to-P) telemedicine. Methods: The-D-to-D-to-P telemedicine was implemented to provide specialized medical support from a neurologist at Nagasaki University Hospital to a rural physician wearing camera-equipped smart glasses at Goto Chuoh Hospital on a remote island, which was called a virtual neurological outpatient (VNO). For the first six months, the rural physician independently saw patients with Parkinson’s disease (PD), and then for the next six months, VNO was implemented. Comparisons were made before and after the implementation of the VNO. Next, by adding a 4 K overhead camera, in-person examinations of a single outpatient were compared between the rural physician with VNO and another neurologist unrelated to the VNO. Results: The clinical efficacy of VNO was not superior to no VNO, but had a learning effect on rural physicians and was satisfactory for patients. By adding a 4 K overhead camera to the VNO, the accuracy of the in-person examination by the rural physician was shown to be equivalent to that of an in-person neurologist. Conclusion: VNO using smart glasses could be applied for D-to-D-to-P telemedicine in neurology. However, to promote telemedicine on remote islands, it will be necessary to improve the system to make it more accessible to rural physicians.

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Background: Minimally invasive surgery with a step-up approach is essential for treating infected walled - off necrosis (WON)　which has a high mortality rate. Percutaneous endoscopic necrosectomy with a flexible overtube which has various advantages is performed in our institution. We herein introduce safety and easy percutaneous endoscopy with flexible overtube technique for minimally invasive surgical necrosectomy. Case presentation: The patient was placed in the supine position and tilted to the right lateral side. The skin was incised 8cm according to the situated percutaneous drains. Following the tract of the drain, the cavity of infected WON was reached in the retroperitoneum. The percutaneous drain was removed, and a flexible overtube was inserted. An endoscope was inserted through the flexible overtube. The necrosis was then crushed with saline flushing and removed by suction or forceps. A new drain was placed in the cavity to allow continuous drainage after surgery. Necrosectomy should be limited to a glimpse of normal granulation tissue, as aggressive debridement carries a risk of bleeding and/or organ injury. Using the step-up approach, endoscopy may be useful in cases of minimal residual necrosis. Conclusion: Percutaneous endoscopy with the flexible overtube technique for minimally invasive surgical necrosectomy is easy to perform and safe for treating infected WON.

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Crizotinib demonstrates dramatic effects for the patients with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase gene (ALK) fusion or c-ros oncogene 1 (ROS-1) fusion-positive lung cancer, with some characteristic　toxicities. Although several studies reported that serious esophagitis was induced by crizotinib, the detailed mechanisms　and ways to ameliorate the esophagitis have not been clarified. In this report, we report two cases with lung cancer who had been treated with crizotinib and developed severe esophagitis. Polarizing microscope examination clearly revealed that the accumulation of crizotinib-residue in the esophageal biopsy samples at the second anatomical narrowing of the esophagus in both cases. Since it seemed that the accumulation of crizotinib-residue in the esophageal mucosa directly caused the esophageal inflammation, we recommended taking crizotinib with a large amount of water (more than 200 ml) and to stay sitting upright for 30 minutes after intake. After that, the esophagitis gradually improved and the patients could continue taking crizotinib without dose reduction or withdrawal. Our experiences suggest that this crizotinib-induced esophagitis could be easily prevented by proper administration of crizotinib.

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