Changes in cerebrovascular disease-related deaths and their location during the COVID-19 pandemic in Japan.

OBJECTIVE: The COVID-19 pandemic placed an enormous strain on healthcare systems and raised concerns for delays in the management of patients with acute cerebrovascular events. In this study, we investigated cerebrovascular excess deaths in Japan. STUDY DESIGN: Vital mortality statistics from January 2012 to May 2022 were obtained from the Japanese Ministry of Health, Labour and Welfare. METHODS: Using quasi-Poisson regression models, we estimated the expected weekly number of cerebrovascular deaths in Japan from January 2020 through May 2022 by place of death. Estimates were calculated for deaths in all locations, as well as for deaths in hospitals, in geriatric health service facilities, and at home. The age subgroups of ≥75 and <75 years were also considered. Weeks with a statistically significant excess of cerebrovascular deaths were determined when the weekly number of observed deaths exceeded the upper bound of 97.5% prediction interval. RESULTS: Excess deaths were noted in June 2021 and became more pronounced from February 2022 onward. The trend was notable among those aged ≥75 years and for those who died in hospitals. With respect to the location of deaths, the excess was significant in geriatric health services facilities from April 2020 to June 2021, whereas no evidence of excess hospital deaths was observed during the same period. CONCLUSIONS: Beginning in the late 2021, excess cerebrovascular deaths coincided with the spread of the Omicron variant and may be associated with increased healthcare burden. In 2020, COVID-19 altered the geography of cerebrovascular deaths, with fewer people dying in hospitals and more dying in geriatric health service facilities and at home.

Excess deaths from COVID-19 in Japan and 47 prefectures from January through June 2021.

OBJECTIVES: In Japan, several studies have reported no excess all-cause deaths (the difference between the observed and expected number of deaths) during the coronavirus disease 2019 (COVID-19) pandemic in 2020. This study aimed to estimate the weekly excess deaths in Japan's 47 prefectures for 2021 until June 27. STUDY DESIGN: Vital statistical data on deaths were obtained from the Ministry of Health, Labour and Welfare of Japan. For this analysis, we used data from January 2012 to June 2021. METHODS: A quasi-Poisson regression was used to estimate the expected weekly number of deaths. Excess deaths were expressed as the range of differences between the observed and expected number of all-cause deaths and the 95% upper bound of the one-sided prediction interval. RESULTS: Since January 2021, excess deaths were observed for the first time in the week corresponding to April 12-18 and have continued through mid-June, with the highest excess percentage occurring in the week corresponding to May 31-June 6 (excess deaths: 1431-2587; excess percentage: 5.95-10.77%). Similarly, excess deaths were observed in consecutive weeks from April to June 2021 in 18 of 47 prefectures. CONCLUSIONS: For the first time since February 2020, when the first COVID-19 death was reported in Japan, excess deaths possibly related to COVID-19 were observed in April 2021 in Japan, during the fourth wave. This may reflect the deaths of non-infected people owing to the disruption that the pandemic has caused.

Human papillomavirus vaccine effectiveness within a cervical cancer screening programme: cohort study.

OBJECTIVE: To assess the effectiveness of an HPV vaccination programme in reducing the risk of cervical abnormalities identified at subsequent screening. DESIGN: Retrospective cohort study using administrative health data. SETTING: General population of Ferrara Province, Italy. POPULATION: Female residents born in 1986-1993 and participating in the organized cervical screening programme in 2011-2018, who were eligible for HPV vaccination in catch-up cohorts. METHODS: Logistic regression to evaluate the potential association between abnormal cervical cytology and one, two, three or at least one dose of HPV vaccine. MAIN OUTCOME MEASURES: Cervical abnormalities, as predicted by low-grade or high-grade cytology, by number of vaccine doses, stratified by age. RESULTS: The sample consisted of 7785 women (mean age 27.5 years, SD 2.3). Overall, 391 (5.0%) were vaccinated with ≥1 dose and 893 (11.5%) had abnormal cytology. Women receiving at least one vaccine dose were significantly less likely to have an abnormal cytology (adjusted odds ratio 0.52; 95% confidence interval 0.34-0.79). Similar results were observed for women receiving a single dose, for both bivalent and quadrivalent vaccines, and applying buffer periods (excluding cytological outcomes within 1 month, 6 months and 1 year of the first dose). CONCLUSIONS: In the context of an organised cervical screening programme in Italy, catch-up HPV vaccination almost halved the risk of cytological abnormalities. TWEETABLE ABSTRACT: Among Ferrara women, vaccination against human papillomavirus halved the risk of screening cervical abnormalities.

Alteration in faecal bile acids, gut microbial composition and diversity after laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a well established treatment for severe obesity and type 2 diabetes. Although the gut microbiota is linked to the efficacy of LSG, the underlying mechanisms remain elusive. The effect of LSG for morbid obesity on the gut microbiota and bile acids was assessed here. METHODS: Severely obese subjects who were candidates for LSG were included and followed until 6 months after surgery. The composition and abundance of the microbiota and bile acids in faeces were assessed by 16S ribosomal RNA sequencing, quantitative PCR and liquid chromatography-mass spectrometry. RESULTS: In total, 28 patients with a mean(s.d.) BMI of 44·2(6·6) kg/m2 were enrolled. These patients had achieved excess weight loss of 53·2(19·0) per cent and showed improvement in metabolic diseases by 6 months after LSG, accompanied by an alteration in the faecal microbial community. The increase in α-diversity and abundance of specific taxa, such as Rikenellaceae and Christensenellaceae, was strongly associated with reduced faecal bile acid levels. These changes had a significant positive association with excess weight loss and metabolic alterations. However, the total number of faecal bacteria was lower in patients before (mean(s.d.) 10·26(0·36) log10 cells per g faeces) and after (10·39(0·29) log10 cells per g faeces) operation than in healthy subjects (10·83(0·27) log10 cells per g faeces). CONCLUSION: LSG is associated with a reduction in faecal bile acids and greater abundance of specific bacterial taxa and α-diversity that may contribute to the metabolic changes.

ANTECEDENTES: La gastrectomía vertical laparoscópica (laparoscopic sleeve gastrectomy, LSG) es un tratamiento bien establecido para la obesidad grave y la diabetes tipo 2. Aunque la microbiota intestinal se ha vinculado con la eficacia de LSG, los mecanismos subyacentes siguen siendo poco conocidos. En este estudio se evaluó el efecto de LSG en la obesidad mórbida sobre la microbiota del intestino y de los ácidos biliares (bile acids, BA). MÉTODOS: Tras la aprobación del Comité ético y la obtención del consentimiento informado, los sujetos con obesidad grave que eran candidatos para LSG fueron incluidos en el estudio y seguidos durante 6 meses después de la operación. Se evaluaron la composición y abundancia de la microbiota y BA en las heces mediante secuenciación del gen 16S rRNA, PCR cuantitativa y cromatografía líquida-espectrometría de masas. RESULTADOS: En total, 28 pacientes con una mediana (rango) del IMC de 43,9 kg/m2 (35,0-61,9) fueron reclutados y a los 6 meses tras una LSG, consiguieron una pérdida del exceso de peso de 47,3% (20,7-95,1) y mejoría de las enfermedades metabólicas acompañada de una alteración en la comunidad microbiana fecal. El aumento en la diversidad α y abundancia de especies taxonómicas específicas como Rikenellaceae y Christensenellaceae, se asociaba fuertemente con niveles fecales reducidos de BA. Estos cambios se asociaban de manera positiva y significativa con la pérdida del exceso de peso y las alteraciones metabólicas. Sin embargo, el número total de bacterias fecales en los pacientes fue inferior al de los sujetos sanos (10,84 log10 células/g heces (9,46-11,35)) antes de la operación (10,26 log10 células/g heces (9,44-10,91)) y después de la misma (10,42 log10 células/g heces (9,57-10,96)). CONCLUSIÓN: LSG se asoció con menos BA fecal y mayor abundancia de especies bacterianas específicas y diversidad α lo que puede contribuir a los cambios metabólicos.

Blockade of interleukin-6 receptor enhances the anti-arthritic effect of glucocorticoids without decreasing bone mineral density in mice with collagen-induced arthritis.

In a mouse arthritis model, we investigated whether interleukin-6 receptor (IL-6R) blockade would enhance the anti-arthritic effect of glucocorticoids (GCs). DBA/1J mice were immunized with type II collagen (CII), and were treated with prednisolone (PSL) and/or anti-mouse IL-6R antibody (MR16-1). Also, the effects of IL-6 on gene expression and the nuclear translocation of glucocorticoid receptors (GRs) were examined in cultured cells treated with dexamethasone (DEX). PSL reduced the arthritis score dose-dependently in the collagen-induced arthritis (CIA) mouse model. The arthritis score in the PSL (3 mg/kg) + MR16-1 group was lower than in the PSL (3 mg/kg) group, and at the same level as in the PSL (6 mg/kg) group. Lumbar vertebra bone mineral density (BMD) was decreased significantly in CIA mice and was higher in the PSL (3 mg/kg) + MR16-1 group than in the PSL (6 mg/kg) group. In the in-vitro synovial cells, IL-6 pretreatment attenuated the inhibitory effect of DEX on cyclooxygenase (COX)-2 expression and inhibited the nuclear translocation of GR induced by DEX. In contrast, in MC3T3-E1 osteoblastic cells, IL-6 pretreatment exacerbated the decrease in expression of osteocalcin and the increase in expression of receptor activator of nuclear factor kappa-B ligand (RANKL) by DEX. We demonstrated that IL-6 signalling blockade by an anti-IL-6R antibody can augment the anti-arthritic effect of GCs and inhibit the bone loss they cause.

Intercellular adhesion molecule-1 on synovial cells attenuated interleukin-6-induced inhibition of osteoclastogenesis induced by receptor activator for nuclear factor κB ligand.

In a co-culture of osteoclast precursor cells and synovial cells, interleukin-6 (IL-6) induces osteoclast formation. In contrast, in a monoculture of osteoclast precursor cells, IL-6 directly suppresses receptor activator for nuclear factor κB ligand (RANKL)-induced differentiation of osteoclast precursor cells into osteoclasts. In the present study, we explored why the effect of IL-6 differed between the monoculture and the co-culture systems. In the monoculture, mouse osteoclast precursor cell line, RAW 264·7 (RAW) cells were cultured with soluble RANKL (sRANKL) for 24 h or 3 days. sRANKL increased both expression of osteoclastogenesis marker, tartrate-resistant acid phosphatase isoform 5b (TRAP5b) and nuclear factor of activated T cells cytoplasmic 1 (NFATc1), whereas the co-addition of IL-6 decreased them both in a dose-dependent manner. In the co-culture, RAW cells and human synovial cell line, SW982 cells were cultured with IL-6+soluble IL-6 receptor (sIL-6R) for 3 days. TRAP5b and NFATc1 expression reduced by IL-6 was increased by the addition of SW982 cells in a manner dependent upon the number of added cells. IL-6+sIL-6R treatment significantly induced RANKL production in SW982 cells, and anti-RANKL antibody inhibited IL-6+sIL-6R-induced osteoclastogenesis. SW982 cells expressed high levels of ICAM-1 originally, and ICAM-1 expression was increased significantly by IL-6+sIL-6R. Anti-ICAM-1 antibody suppressed IL-6-induced osteoclastogenesis. Finally, in the monoculture system, addition of sICAM-1 dose-dependently restored the expression of TRAP5b reduced by IL-6. Similar results were obtained when the formation of TRAP-positive multi-nuclear cells were examined using mouse bone marrow cells. In conclusion, IL-6 gave different results in the co-culture and monoculture systems because in the co-culture, ICAM-1 from the synovial cells restored osteoclastogenesis suppressed by IL-6.

Weather variability and paediatric infectious gastroenteritis.

Investigations of the relationship between weather variability and infectious gastroenteritis (IG) are becoming increasingly important in light of international interest in the potential health effects of climate change. However, few studies have examined the impact on children, despite the fact that children are considered particularly vulnerable to climate change. We acquired data about cases of IG in children aged <15 years and about weather variability in Fukuoka, Japan from 2000 to 2008 and used time-series analyses to assess how weather variability affected IG cases, adjusting for confounding factors. The temperature-IG relationship had an inverted V shape, with fewer cases at temperatures lower and higher than ~13°C. Every 1°C increase in temperature below the threshold (13°C) was associated with a 23·2% [95% confidence interval (CI) 16·6-30·2] increase, while every 1°C increase in temperature above the threshold (13°C) was associated with an 11·8% (95% CI 6·6-17·3) decrease in incidence. The increase in cases per 1% drop in relative humidity was 3·9% (95% CI 2·8-5·0). The percentage increase of IG cases was greatest in the 0-4 years age group and tended to decrease with increasing age. We found a progressive reduction in weather-related IG cases in children aged >4 years. Our results suggest that public health interventions aimed at controlling weather-related IG may be most effective when focused on young children.

Effect of weather variability on the incidence of mumps in children: a time-series analysis.

The increasing international interest in the potential health effects of climate change has emphasized the importance of investigations into the relationship between weather variability and infectious diseases. However, few studies have examined the impact of weather variability on mumps in children, despite the fact that children are considered particularly vulnerable to climate change. We acquired data about cases of mumps in children aged <15 years and weather variability in Fukuoka, Japan from 2000 to 2008, and then used time-series analyses to assess how weather variability affected mumps cases, adjusting for seasonal variations, inter-annual variations, and temporal variations of two large epidemics in 2001 and 2004-2005. The weekly number of mumps cases increased by 7·5% (95% CI 4·0-11·1) for every 1°C increase in average temperature and by 1·4% (95% CI 0·5-2·4) for every 1% increase in relative humidity. The percentage increase was greatest in the 0-4 years age group and tended to decrease with increasing age. The number of mumps cases in children increased significantly with increased average temperature and relative humidity.

The burden of heat-related mortality attributable to recent human-induced climate change.

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991-2018. Across all study countries, we find that 37.0% (range 20.5-76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change.

Risk factors for portal venous thrombosis after splenectomy in patients with cirrhosis and portal hypertension.

BACKGROUND: Portal venous thrombosis (PVT) is a potentially fatal complication following splenectomy. Its mechanisms and risk factors are poorly understood, especially in patients with cirrhosis and portal hypertension. This study investigated risk factors for PVT following splenectomy in such patients. METHODS: All consecutive patients with cirrhosis who underwent splenectomy in Kyushu University Hospital between 1998 and 2004 were included in this retrospective study. They were divided into two groups based on the presence or absence of postoperative PVT. Preoperative and operative factors were compared, and the relationships between formation of PVT and its independent variables were analysed. In some cases, portal venous flow was measured before and after splenectomy using duplex Doppler ultrasonography. RESULTS: PVT developed after surgery in 17 (24 per cent) of 70 patients studied. Multivariable analysis showed that increased splenic vein diameter and low white cell count were significant independent risk factors for PVT. Portal venous flow after splenectomy was greatly reduced in the PVT group, but not in patients without PVT. CONCLUSION: Large splenic vein diameter and low white cell count are independent risk factors for PVT after splenectomy in patients with cirrhosis and portal hypertension.

Effects of weather variability on infectious gastroenteritis.

Although multiple combinations of weather variability may contribute to an increased incidence of infectious gastrointestinal disease, few studies have investigated the association between weather variability and cases of infectious gastroenteritis. We acquired data for infectious gastroenteritis cases and weather variability in Fukuoka, Japan, from 1999 to 2007 and used time-series analysis to assess the effects of weather variability on infectious gastroenteritis cases, adjusting for confounding factors. In total, 422,176 infectious gastroenteritis cases were reported during the 9-year study period. The weekly number of infectious gastroenteritis cases increased by 7.7% (95% CI 4.6-10.8) for every 1 degrees C increase in the average temperature and by 2.3% (95% CI 1.4-3.1) for every 1% decrease in relative humidity. From 1999 to 2007, infectious gastroenteritis cases increased significantly with increased average temperature and decreased relative humidity in Fukuoka, Japan.

Seasonality of suicide: a multi-country multi-community observational study.

AIMS: We aimed to investigate the heterogeneity of seasonal suicide patterns among multiple geographically, demographically and socioeconomically diverse populations. METHODS: Weekly time-series data of suicide counts for 354 communities in 12 countries during 1986-2016 were analysed. Two-stage analysis was performed. In the first stage, a generalised linear model, including cyclic splines, was used to estimate seasonal patterns of suicide for each community. In the second stage, the community-specific seasonal patterns were combined for each country using meta-regression. In addition, the community-specific seasonal patterns were regressed onto community-level socioeconomic, demographic and environmental indicators using meta-regression. RESULTS: We observed seasonal patterns in suicide, with the counts peaking in spring and declining to a trough in winter in most of the countries. However, the shape of seasonal patterns varied among countries from bimodal to unimodal seasonality. The amplitude of seasonal patterns (i.e. the peak/trough relative risk) also varied from 1.47 (95% confidence interval [CI]: 1.33-1.62) to 1.05 (95% CI: 1.01-1.1) among 12 countries. The subgroup difference in the seasonal pattern also varied over countries. In some countries, larger amplitude was shown for females and for the elderly population (≥65 years of age) than for males and for younger people, respectively. The subperiod difference also varied; some countries showed increasing seasonality while others showed a decrease or little change. Finally, the amplitude was larger for communities with colder climates, higher proportions of elderly people and lower unemployment rates (p-values < 0.05). CONCLUSIONS: Despite the common features of a spring peak and a winter trough, seasonal suicide patterns were largely heterogeneous in shape, amplitude, subgroup differences and temporal changes among different populations, as influenced by climate, demographic and socioeconomic conditions. Our findings may help elucidate the underlying mechanisms of seasonal suicide patterns and aid in improving the design of population-specific suicide prevention programmes based on these patterns.

Impact of weather factors on Mycoplasma pneumoniae pneumonia.

BACKGROUND: Although multiple combinations of weather factors may contribute to an increased incidence of Mycoplasma pneumoniae pneumonia, few studies have investigated the association between weather factors and cases of M pneumoniae pneumonia. METHODS: Data on cases of M pneumoniae pneumonia and weather factors in Fukuoka, Japan from 1999 to 2007 were obtained and time-series analysis was used to assess the effects of weather variables on M pneumoniae pneumonia cases, adjusting for confounding factors. A total of 13 056 M pneumoniae pneumonia cases were reported during the 9-year study period, of which 12 234 (93.7%) were under 15 years of age. RESULTS: The weekly number of M pneumoniae pneumonia cases increased by 16.9% (95% CI 11.3% to 22.8%) for every 1 degrees C increase in the average temperature and by 4.1% (95% CI 2.7% to 5.5%) for every 1% increase in relative humidity. CONCLUSIONS: From 1999 to 2007, cases of M pneumoniae pneumonia increased significantly with increased average temperature and relative humidity in Fukuoka, Japan.

Desirable effect of combination therapy with high molecular weight hyaluronate and NSAIDs on MMP production.

OBJECTIVE: We previously reported that nonsteroidal anti-inflammatory drugs (NSAIDs) aggravated cartilage degeneration and that hyaluronate (HA) reversed the cartilage destruction accelerated by NSAIDs in a rabbit osteoarthritis (OA) model. In the present study, we analyzed the mechanisms of these effects of NSAIDs and HA. METHOD: An experimental rabbit model of OA was induced by partial meniscectomy and treated with NSAIDs, HA and the combination of NSAIDs and HA over 2 weeks. After sacrifice, cartilage degeneration and the levels of matrix metalloproteases (MMP)-1, MMP-3 and MMP-13 in synovial lavage fluid were measured. In an in vitro study, human articular chondrocytes were cultured with NSAIDs and HA in the presence of interleukin (IL)-1beta or IL-6+sIL-6 for 24 h. After culture, the production of MMPs, IL-1beta, and IL-6 was measured. RESULTS: The levels of MMP-1, MMP-3 and MMP-13 in synovial fluid from the NSAID-treated group were significantly higher than in controls. The increased production of MMPs induced by NSAIDs was counteracted by the concomitant administration of HA. In vitro studies showed that NSAIDs augmented IL-1beta- and IL-6-induced production of MMPs from human chondrocytes, while completely inhibiting the IL-1beta- and IL-6/sIL-6R-induced production of prostaglandin E(2) (PGE(2)). The addition of PGE(2) did not reduce the augmentation of MMP production. HA inhibited the promotion of cytokine-induced MMP and cytokine production by NSAIDs. CONCLUSIONS: Our data clearly showed that HA inhibited NSAID-accelerated MMP production which was followed by inflammatory cytokine production from cytokine-activated chondrocytes. The results warrant further evaluation of the potential chondroprotective effects of co-administration of HA with NSAIDs.

Development of an articulating ultrasonically activated device for laparoscopic surgery.

BACKGROUND: Ultrasonically activated devices (USADs) offer excellent coagulating dissection performance and are broadly used, particularly in endoscopic operations. Traditional USADs, however, have fixed linear shape and are thus limited in the directions from which organs can be approached. We have developed a small USAD transducer attached to the tip of an articulating device, offering a new kind of USAD in which the tip can bend as desired. We describe herein an evaluation of the coagulating dissection performance of this new articulating USAD and an in vivo confirmation of clinical usefulness. METHODS: To evaluate coagulating dissection performance, we compared coagulating shearing on porcine splenic arteries between the articulating USAD and a Harmonic Scalpel II (HSII), representing a traditional USAD. Changing the amplitude of vibration between 60 microm and 80 microm and grip force among 1, 2, and 3 N, we measured the time required for division and bursting pressure of coagulating dissection. An in vivo experiment in a pig was also used to confirm the usefulness of the articulating USAD in laparoscopic operations. RESULTS: Division time did not differ significantly between the articulating USAD and HSII with an 80-microm amplitude of vibration and a grip force of 2 or 3 N. Bursting pressure of blood vessels showed no significant difference between articulating USAD and HSII under all experimental conditions. In the in vivo experiment, the new bendable tip of the articulating USAD displayed coagulating dissection performance equivalent to that of the traditional USAD. CONCLUSIONS: We have developed a new articulating USAD that can broaden the range of methods and approaches available for USADs and improve usefulness and safety.

IL-6 trans-signalling directly induces RANKL on fibroblast-like synovial cells and is involved in RANKL induction by TNF-alpha and IL-17.

OBJECTIVES: We investigated the influence of cytokines on the expression of RANK ligand (RANKL) in fibroblast-like synoviocytes from RA patients (RA-FLS). METHODS: RA-FLS were stimulated by IL-6, TNF-alpha, IL-17 and IL-1beta with or without soluble IL-6 receptor (sIL-6R) for 24 h. The expression of RANKL was measured by real-time PCR, western blotting and immunostaining. In proliferation assay, RA-FLS were cultured with cytokines for 3 days. RA-FLS were co-cultured with RAW cell in the presence of IL-6/sIL-6R for 3 days and then NFATc1 mRNA expression in RAW cells was examined. RA-FLS was cultured with parthenolide [PAR, signal transducer and activator of transcription (STAT) inhibitor] or PD98059 (PD, mitogen-activated protein kinase inhibitor) in the presence of IL-6/sIL-6R and then the influence of these drugs on phosphorylation of STAT3 and ERK1/2, and RANKL expression was examined. RESULTS: RANKL expression was induced by IL-6/sIL-6R (but not IL-6 alone) and by IL-1beta. On the other hand, TNF-alpha and IL-17 did not induce RANKL expression, although TNF-alpha, IL-17 or IL-1beta stimulated cell growth and IL-6 production. However, in the presence of sIL-6R, TNF-alpha or IL-17 induced RANKL expression. By the co-culture of RA-FLS, NFATc1 mRNA expression was induced in RAW cells. Finally, IL-6/sIL-6R induced phosphorylation of STAT3 and ERK1/2 in RA-FLS, and was completely inhibited by PAR and PD, respectively. PAR completely inhibited IL-6/sIL-6R-induced RANKL expression, but PD did not. CONCLUSIONS: IL-6/sIL-6R directly induced RANKL expression in RA-FLS and it is essential for RANKL induction by TNF-alpha and IL-17. Moreover, RANKL induction by IL-6/sIL-6R is mediated by the janus kinase/STAT signalling pathway.

Effectiveness of endoscopic surgery training for medical students using a virtual reality simulator versus a box trainer: a randomized controlled trial.

BACKGROUND: The first step toward increasing the level of patient safety in endoscopic surgery is for all endoscopic surgeons to acquire fundamental skills, including psychomotor skills, in the preoperation stage of training. The current study aimed to evaluate the effectiveness of virtual reality (VR) simulator training and box training for training the fundamental skills of endoscopic surgery. METHODS: For this study, 35 medical students at Kyushu University were divided into three groups: simulator (SIM) group (n = 20), box trainer (BOX) group (n = 20), and control group (n = 15). None of the students had any experience assisting with endoscopic surgery or any previous training for endoscopic surgery. The students in the SIM group underwent training using a VR simulator, the Procedicus MIST, 2 h per day for 2 days. The students in the BOX group underwent training using a box trainer 2 h per day for 2 days. The students in the control group watched an educational video for 30 min. The endoscopic surgical skills of all the students were evaluated before and after training with a task of suturing and knot tying using a box trainer. RESULTS: Although no significant differences were found between the three groups in the total time taken to complete the evaluation task before training, there were significant improvements in the SIM and BOX groups after training compared with the control group. Box training increased errors during the task, but simulator training did not. CONCLUSION: The findings showed that box training and VR training have different outcomes. The authors expect that the best curriculum for their training center would involve a combination that uses the merits of both methods.

[21-year-old man with squamous cell carcinoma of the lung].

Lung cancer among people in their twenties is rare and accounts for only 0.1-0.4% of all cases. We describe a case of squamous cell carcinoma of the lung in a 21-year-old man. The otherwise healthy patient presented with a 1 month history of cough. Chest radiography showed a well-defined round mass 5 cm in size in the right lower lobe. Computed tomography also showed a 3 cm hilar lymph node. Bronchoscopy revealed a white polypoid mass obstructing the right basal bronchus. Transbronchial biopsy revealed poorly differentiated squamous cell carcinoma of the lung. Clinical diagnosis was T2N1M0, stage IIB lung cancer. Right lower lobectomy with mediastinal lymph node dissection was performed. Lymph node metastases were proven histologically in the pretracheal, subcarinal, hilar, and intrapulmonary regions. Pathological diagnosis was T2N2M0, stage IIIA lung cancer. Endobronchial and mediastinal lymph node metastases were found 2 months after surgery. He received 3 rounds of chemotherapy with cisplatin and docetaxel and irradiation to the right hilum and mediastinum at a total dose of 60 Gy in 30 fractions. He is alive 6 months after surgery.

[Endobronchial neurinoma treated with left lower lobectomy].

Benign endobronchial tumors are rare, and among these endobronchial neurinoma is extremely rare. We describe a case of endobronchial neurinoma successfully treated with left lower lobectomy. A 58-year-old man presented with an 8-month history of cough. During this period he was repeatedly treated with antibiotics for pneumonia of the left lower lobe. Chest X-ray showed atelectasis of the left lower lobe. Computed tomography (CT) of the chest showed a mass in the left main and lower lobe bronchi. Bronchoscopy revealed the mass almost completely obstructing the left main bronchus. Although transbronchial biopsy was inconclusive and yielded necrotic tissue with Aspergillus hyphae, lung cancer was highly suspected based on clinical and radiographic findings. He underwent left lower lobectomy and was discharged 14 days after surgery in good condition. Pathological diagnosis was an endobronchial neurinoma 4 cm in size arising from the left basal bronchus. On immunohistochemical staining, the tumor was positive for S-100 protein and negative for a-smooth muscle actin. He took itraconazole at a daily dose of 200 mg orally for 6 months. He remains well 52 months after surgery without any evidence of recurrence.

Enhanced sealing strength of a hydrophobically-modified Alaska pollock gelatin-based sealant.

The aim of this study was the development of an innovative biocompatible sealant composed of Alaska pollock-derived gelatin partially modified with a dodecyl group (C12-ApGltn) and a poly(ethylene glycol)-based crosslinker, pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate. The burst strength of the developed sealants was measured using porcine aorta and rat lungs. The maximum burst strength of a C12-ApGltn-based sealant against the porcine aorta was 4-fold higher than that of an original ApGltn (Org-ApGltn)-based sealant. No significant increase in the burst strength was observed between C12-ApGltn-based sealants with 4.2 and 8.9 mol% modification ratios. From histological observation after burst strength measurement, tissue tearing was observed when a C12-ApGltn-based sealant was applied. In contrast, the Org-ApGltn-based sealant was peeled away from the aorta surface due to cohesion failure. Similar to the porcine aorta, the burst strength of C12-ApGltn-based sealants applied on a rat lung defect was 3-fold higher than that of an Org-ApGltn-based sealant. The curing time of the C12-ApGltn-based sealant measured by a simple mixing method was shorter (2.6 ± 0.1 s) than that of the Org-ApGltn-based sealant (4.1 ± 0.3 s). The swelling ratio of the C12-ApGltn-based sealant (23.7 ± 3.1) was significantly lower than that of the Org-ApGltn-based sealant (32.3 ± 1.1). The C12-ApGltn-based sealant was completely degraded within 28 days after implantation in the backs of rats without a severe inflammation reaction. However, the Org-ApGltn-based sealant disappeared within 14 days. These results indicated that hydrophobically-modified ApGltn has an effective sealing effect on moist tissues and biocompatibility in vivo.