First-line nivolumab plus ipilimumab with or without chemotherapy for Japanese patients with non-small cell lung cancer: LIGHT-NING study.

OBJECTIVE: As first-line treatment for stage IV or recurrent non-small cell lung cancer, combination immunotherapy with nivolumab and ipilimumab, with or without chemotherapy, had demonstrated survival benefits over chemotherapy; however, data on Japanese patients are limited. METHODS: LIGHT-NING was a multicenter, observational study and retrospectively collected data. In this interim analysis, we analyzed patients who received combination immunotherapy between 27 November 2020 and 31 August 2021 for the treatment status, safety objectives (treatment-related adverse events and immune-related adverse events incidences), and effectiveness objectives (objective response rate and progression-free survival) to determine the characteristics and early safety information. RESULTS: We analyzed 353 patients, with a median follow-up of 7.1 (interquartile range, 5.0-9.7) months. Overall, 60.1 and 39.9% received nivolumab plus ipilimumab with and without chemotherapy, respectively. In these cohorts, the median age was 67 and 72 years; 10.8 and 35.5% were aged ≥75 years; 80.2 and 79.4% were male; 5.2 and 13.5% had a performance score ≥ 2; 32.1 and 27.0% developed grade 3-4 immune-related adverse events; treatment-related deaths were observed in 6 (2.8%) and 5 (3.5%) patients, respectively. Grade 3-4 immune-related adverse event incidence was the highest within the first month of treatment in both cohorts, although the immune-related adverse event risk persisted throughout. No new safety signals were observed at this interim analysis. The median progression-free survival was 6.0 (95% confidence interval, 5.2-7.6) and 5.8 (4.3-7.0) months in nivolumab plus ipilimumab with and without chemotherapy cohorts, respectively. CONCLUSIONS: LIGHT-NING offers valuable insights into combination immunotherapy for untreated patients with stage IV or recurrent non-small cell lung cancer in Japanese real-world settings.

Solo surgery in robot-assisted gastrectomy versus laparoscopic gastrectomy for gastric cancer: a propensity score-matched analysis.

BACKGROUND: Robot-assisted gastrectomy (RG) for gastric cancer is still not well standardized. This study aimed to explore the feasibility and effectiveness of solo surgery in robot-assisted gastrectomy (SRG) for gastric cancer compared to laparoscopic gastrectomy (LG). METHODS: This was a single-center retrospective comparative study between SRG and conventional LG. Between April 2015 and December 2022, 510 patients underwent gastrectomy, and data from a prospectively collected database were analyzed. We identified 372 patients who underwent LG (n = 267) and SRG (n = 105) and the remaining 138 patients were excluded because of remnant gastric cancer, esophagogastric junction cancer, open gastrectomy, concurrent surgery for concomitant malignancies, RG before starting SRG, or cases in which the author was unable to perform or supervise gastrectomy. Propensity score matching was performed at a ratio of 1:1 to reduce bias from confounding patient-related variables, and short-term outcomes were compared between the groups. RESULTS: After propensity score matching, 90 pairs of patients who underwent LG and SRG were selected. In the propensity-matched cohort, the operation time was significantly shorter in the SRG group than that in the LG group (SRG = 305.7 ± 74.0 min vs. LG = 340.3 ± 91.65 min, p < 0.0058), less estimated blood loss was observed in the SRG group than that in the LG group (SRG = 25.6 ± 50.6 mL vs. LG = 76.1 ± 104.2 mL, p < 0.0001) and postoperative hospital stay was shorter in the SRG group than that in the LG group (SRG = 7.1 ± 0.8 days vs. LG = 9.1 ± 7.7 days, p = 0.015). CONCLUSION: We found that SRG for gastric cancer was technically feasible and effective with favorable short-term outcomes, including shorter operative time, less estimated blood loss, shorter hospital stays, and lower postoperative morbidity than those in LG.

Infections due to dysregulated immunity: an emerging complication of cancer immunotherapy.

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment. However, immune-related adverse events (irAEs) are a common side effect which can mimic infection. Additionally, treatment of irAEs with corticosteroids and other immunosuppressant agents can lead to opportunistic infection, which we have classed as immunotherapy infections due to immunosuppression. However, emerging reports demonstrate that some infections can be precipitated by ICIs in the absence of immunosuppressive treatment, in contrast to the majority of reported cases. These infections are characterised by a dysregulated inflammatory immune response, and so we propose they are described as immunotherapy infections due to dysregulated immunity. This review summarises the rapidly emerging evidence of these phenomena and proposes a new framework for considering infection in the context of cancer immunotherapy.

Serial interferon-gamma release assay in lung cancer patients receiving immune checkpoint inhibitors: a prospective cohort study.

Recent advancements in cancer immunotherapy using immune checkpoint inhibitors (ICIs) have received considerable attention. Although advantageous, ICI therapies cause unique immune-related adverse events (irAEs) in some patients. Moreover, infectious diseases, such as tuberculosis, have been recognized as emerging concerns during immunotherapy. We aimed to evaluate the interferon-gamma release assay (IGRA) conversion rate and active tuberculosis incidence during immunotherapy to elucidate the incidence of tuberculosis reactivation after ICI therapy induction.We prospectively assessed IGRA results in lung cancer patients who received ICI monotherapy before ICI treatment and at 6 and 12 months after ICI treatment. We also assessed computed tomography findings to determine the presence of active tuberculosis when positive IGRA results were obtained. The ICIs used were nivolumab, pembrolizumab, atezolizumab, and durvalumab.In all, 178 patients were prospectively recruited between March 2017 and March 2020. Of these, 123 completed serial IGRAs, of whom 18, 101, and 4, respectively, had positive, negative, and indeterminate IGRAs at baseline. Three and four patients, respectively, showed IGRA reversion and conversion during immunotherapy. One patient with a sustained, stable positive IGRA and one with IGRA conversion developed active pulmonary tuberculosis during immunotherapy.We found that 3.3% and 1.6% of the patients developed IGRA conversion and active tuberculosis, respectively. Of the four patients who developed IGRA conversion, one developed active pulmonary tuberculosis during immunotherapy. Another patient with sustained, stable positive IGRA developed active tuberculosis. Physicians should be alert to tuberculosis development during ICI therapy, and IGRA testing is a useful tool to assess the risk of developing active tuberculosis.

Mechanisms of Long-Latency Paired Pulse Suppression: MEG Study.

Paired pulse suppression is an electrophysiological method used to evaluate sensory suppression and often applied to patients with psychiatric disorders. However, it remains unclear whether the suppression comes from specific inhibitory mechanisms, refractoriness, or fatigue. In the present study, to investigate mechanisms of suppression induced by an auditory paired pulse paradigm in 19 healthy subjects, magnetoencephalography was employed. The control stimulus was a train of 25-ms pure tones of 65 dB SPL for 2500 ms. In order to evoke a test response, the sound pressure of two consecutive tones at 2200 ms in the control sound was increased to 80 dB (Test stimulus). Similar sound pressure changes were also inserted at 1000 (CS2) and 1600 (CS1) ms as conditioning stimuli. Four stimulus conditions were used; (1) Test alone, (2) Test + CS1, (3) Test + CS1 + CS2, and (4) Test + CS2, with the four sound stimuli randomly presented and cortical responses averaged at least 100 times for each condition. The baseline-to-peak and peak-to-peak amplitudes of the P50m, N100m, and P200m components of the test response were compared among the four conditions. In addition, the response to CS1 was compared between conditions (2) and (3). The results showed significant test response suppression by CS1. While the response to CS1 was significantly suppressed when CS2 was present, it did not affect suppression of the test response by CS1. It was thus suggested that the amplitude of the response to a conditioning stimulus is not a factor to determine the inhibitory effects of the test response, indicating that suppression is due to an external influence on the excitatory pathway.

Comparison of robotic gastrectomy and laparoscopic gastrectomy for gastric cancer: a propensity score-matched analysis.

BACKGROUND: The benefits of robotic gastrectomy (RG) over laparoscopic gastrectomy (LG) remain controversial. This single-center, propensity score-matched study aimed to compare the outcomes of RG with those of LG for treating gastric cancer. METHODS: We searched the prospective gastric cancer database of our institute for patients with gastric cancer who underwent RG or LG between January 2014 and December 2019, excluding patients with remnant stomach cancer and those who underwent concurrent surgery for comorbid malignancies. One-to-one propensity score matching was performed to reduce bias from confounding patient-related variables, and short- and long-term outcomes were compared between the groups. RESULTS: We identified 1189 patients who underwent LG (n = 979) or RG (n = 210). After propensity score matching, we selected 210 pairs of patients who underwent LG (distal gastrectomy, 138; total or proximal gastrectomy, 72) or RG (distal gastrectomy, 143; total or proximal gastrectomy, 67). RG was associated with a significantly shorter operative time (RG = 201 min vs. LG = 231 min, p = 0.0051), less blood loss (RG = 13 mL vs. LG = 42 mL, p < 0.0001), lower postoperative morbidity (RG = 1.0% vs. LG = 4.8%, p = 0.0066), and a shorter postoperative hospital stay (p = 0.0002) than LG. Drain amylase levels on postoperative Days 1 and 3 in the RG group were significantly lower than those in the LG group (p < 0.0001). CONCLUSIONS: RG is a safe and feasible treatment for gastric cancer, with a shorter operative time, less blood loss, and lower postoperative morbidity than LG. The application of robotics in minimally invasive gastric cancer surgery may offer an alternative to conventional surgery. Multicenter, prospective, randomized controlled trials comparing RG with conventional LG are needed to establish the feasibility and efficacy of minimally invasive gastric cancer surgery.

Clinical importance of carcinoembryonic antigen messenger RNA level in peritoneal lavage fluids measured by transcription-reverse transcription concerted reaction for advanced gastric cancer in laparoscopic surgery.

BACKGROUND: Transcription-reverse transcription concerted reaction (TRC) is recognized as a useful method for detecting free cancer cells in the peritoneal cavity and predicting peritoneal recurrence in patients with gastric cancer. Nonetheless, the clinical significance of TRC in laparoscopic surgery remains unclear. This study aimed to evaluate the clinical importance of carcinoembryonic antigen (CEA) messenger RNA (mRNA) level in peritoneal lavage fluids measured by TRC in laparoscopic surgery for locally advanced gastric cancer. METHODS: We enrolled patients with locally advanced gastric cancer who underwent laparoscopic gastrectomy. Peritoneal lavage fluids were collected prior to gastrectomy, and the TRC method was employed to quantify CEA mRNA in peritoneal washes. Overall survival (OS), recurrence-free survival (RFS), and peritoneal recurrence-free survival (PRFS) were analyzed using the Kaplan-Meier method and compared using the log-rank test. Adjusted Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) for CEA mRNA positivity. RESULTS: A total of 100 patients were analyzed in this study. Overall, 22 patients (22%) exhibited CEA mRNA positivity in peritoneal lavage fluids, as measured by TRC. No significant association between CEA mRNA levels and clinicopathological characteristics was observed. Patients who were CEA mRNA-positive in peritoneal lavage fluids had significantly worse OS, RFS, and PRFS than those who were CEA mRNA-negative (p = 0.0059, p < 0.0001, and p = 0.0022, respectively). In the univariate Cox model, the HR for all-cause mortality in CEA mRNA-positive versus CEA mRNA-negative patients was 3.60 (95% CI, 1.33-9.55; p = 0.0129). Multivariate analysis revealed that CEA mRNA positivity was a significant independent factor for recurrence. CONCLUSIONS: TRC enables the detection of free cancer cells in the peritoneal cavity and CEA mRNA levels can help predict the prognosis, even in laparoscopic gastrectomy.

The DOLFIN method: a novel laparoscopic Billroth-I gastroduodenostomy for gastric cancer with duodenal invasion.

BACKGROUND: Laparoscopic Billroth-I gastroduodenostomy using a delta-shaped anastomosis is safe and feasible. However, it is often difficult to perform in patients who have a short posterior wall of the duodenum. Thus, we have developed a new method named duodenal overlap functional anastomosis with linear stapler (DOLFIN). We hereby report the technical details of the new method and our preliminary experience performing it. METHODS: After the completion of lymphadenectomy, the duodenum was transected craniocaudally with an endoscopic linear stapler. The hepatoduodenal mesentery was dissected approximately 4 cm along the duodenal bulb, and the anastomosis between the posterior wall of the stomach and the lesser curvature of the duodenum was created. The common entry hole was then transected using an endoscopic linear stapler, and the anastomosis was finally completed. RESULTS: There were 36 patients with gastric cancer who underwent laparoscopic distal gastrectomy (LDG) or robotic distal gastrectomy (RDG) with B-I reconstruction using DOLFIN. There were no postoperative complications classified as C-D grade 3 or more and complications related to anastomosis, such as anastomotic leak or stenosis. CONCLUSIONS: Our DOLFIN gastroduodenostomy can be performed safely. In addition, it results in good postoperative outcomes. A long-term comparative study is required to further evaluate the clinical usefulness of this method.

Comparison of frailty in patients with nontuberculous mycobacterial lung disease and bronchiectasis: a prospective cohort study.

BACKGROUND: The incidence of nontuberculous mycobacterial lung disease (NTM-LD) peaks in middle- and old age groups, coinciding with senescence; thus, chronic infectious diseases can accelerate frailty and worsen mental health in the elderly. In this study, we aimed to compare the prevalence of physical and psychiatric frailty between patients with NTM-LD and bronchiectasis (BE). METHODS: The Kihon Checklist Questionnaire (KCQ) was used to assess physical and psychiatric frailties and identify those at risk of requiring care among patients with newly diagnosed NTM-LD and BE. Additionally, the Hospital Anxiety and Depression Scale (HADS) scores and chronic inflammatory biomarkers of the alveolar region (surfactant protein [SP]-A, SP-D, and human cationic antibacterial protein [hCAP]/LL-37) were assessed and compared between NTM-LD and BE patients. RESULTS: There were no significant differences in the background characteristics between the 33 NTM and 36 BE patients recruited. The KCQ revealed that the proportion of frail NTM patients at diagnosis was higher than that of frail BE patients (48.5% vs. 22.2%, p = 0.026). HADS scores were significantly higher in the NTM group than in the BE group (p < 0.01). Bronchoalveolar lavage fluid (BALF) hCAP/LL-37 and SP-D levels were significantly higher (p = 0.001), but serum hCAP/LL-37 levels were significantly lower in the NTM group than in the BE group (p = 0.023). However, there were no significant differences in the BALF and serum SP-D levels between the two groups. CONCLUSIONS: The number of frail NTM patients at diagnosis was significantly higher than that of frail BE patients. Biomarker analysis suggested that the former had more localized lung inflammation than the latter. TRIAL REGISTRATION: This trial was prospectively registered in the Clinical Trials Registry (UMIN 000027652).

Serum creatinine/cystatin C ratio is a surrogate marker for sarcopenia in patients with idiopathic pulmonary fibrosis.

BACKGROUND: The serum creatinine/cystatin C (Cr/CysC) ratio has attracted attention as a marker for sarcopenia, but has not been studied in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to confirm the utility of the serum Cr/CysC ratio in predicting sarcopenia and investigate its clinical relevance. METHODS: This cross-sectional pilot study prospectively enrolled patients with stable IPF. IPF was diagnosed through multidisciplinary discussions according to the 2018 international guidelines, and sarcopenia was diagnosed according to the 2019 consensus report of the Asian Working Group for Sarcopenia. Patient-reported outcomes (PROs) were evaluated using the modified Medical Research Council (mMRC) dyspnea scale, chronic obstructive pulmonary disease assessment test (CAT), and King's Brief Interstitial Lung Disease (K-BILD) questionnaire. The associations between serum Cr/CysC ratio and the presence of sarcopenia and other clinical parameters, including PROs scores, were examined. RESULTS: The study enrolled 49 Japanese patients with IPF with a mean age of 73.0 ± 7.7 years and a mean percentage of predicted forced vital capacity of 80.4 ± 15.5%. Sarcopenia was diagnosed in 18 patients (36.7%), and the serum Cr/CysC ratio was 0.86 [0.76-0.94] (median [interquartile range]). The receiver operating characteristic curve analyses for the detection of sarcopenia according to the serum Cr/CysC showed that the area under the curve, optimal cutoff value, specificity, and sensitivity were 0.85, 0.88, 0.65, and 0.94, respectively. Sarcopenia was identified in 13% of patients with a high serum Cr/CysC ratio (≥ 0.88) and 60% of patients with a low serum Cr/CysC ratio (< 0.88) (P < 0.001). Multiple linear regression analysis showed that the serum Cr/CysC ratio was an independent predictive marker of worse PROs evaluated using mMRC (P < 0.05), CAT (P < 0.05), and K-BILD (P < 0.05). CONCLUSIONS: This study showed that the serum Cr/CysC ratio may be a surrogate marker of sarcopenia in patients with IPF. Furthermore, it is important to pay attention to the serum Cr/CysC ratio because a lower serum Cr/CysC ratio is associated with worse PROs. Further studies are required to validate these observations to determine whether the Cr/CysC ratio can be used to detect sarcopenia in patients with IPF.

Cell-autonomous FLT3L shedding via ADAM10 mediates conventional dendritic cell development in mouse spleen.

Conventional dendritic cells (cDCs) derive from bone marrow (BM) precursors that undergo cascades of developmental programs to terminally differentiate in peripheral tissues. Pre-cDC1s and pre-cDC2s commit in the BM to each differentiate into CD8α+/CD103+ cDC1s and CD11b+ cDC2s, respectively. Although both cDCs rely on the cytokine FLT3L during development, mechanisms that ensure cDC accessibility to FLT3L have yet to be elucidated. Here, we generated mice that lacked a disintegrin and metalloproteinase (ADAM) 10 in DCs (Itgax-cre × Adam10-fl/fl; ADAM10∆DC) and found that ADAM10 deletion markedly impacted splenic cDC2 development. Pre-cDC2s accumulated in the spleen with transcriptomic alterations that reflected their inability to differentiate and exhibited abrupt failure to survive as terminally differentiated cDC2s. Induced ADAM10 ablation also led to the reduction of terminally differentiated cDC2s, and restoration of Notch signaling, a major pathway downstream of ADAM10, only modestly rescued them. ADAM10∆DC BM failed to generate cDC2s in BM chimeric mice with or without cotransferred ADAM10-sufficient BM, indicating that cDC2 development required cell-autonomous ADAM10. We determined cDC2s to be sources of soluble FLT3L, as supported by decreased serum FLT3L concentration and the retention of membrane-bound FLT3L on cDC2 surfaces in ADAM10∆DC mice, and by demonstrating the release of soluble FLT3L by cDC2 in ex vivo culture supernatants. Through in vitro studies utilizing murine embryonic fibroblasts, we determined FLT3L to be a substrate for ADAM10. These data collectively reveal cDC2s as FLT3L sources and highlight a cell-autonomous mechanism that may enhance FLT3L accessibility for cDC2 development and survival.

Decreased peak expiratory flow rate associated with mortality in idiopathic pulmonary fibrosis: A preliminary report.

OBJECTIVES: The peak expiratory flow rate (PEFR) is known to decrease in patients with sarcopenia. However, little is known about the clinical impact of the PEFR in idiopathic pulmonary fibrosis (IPF). This study aimed to confirm whether a decrease in PEFR over 6 months was associated with survival in IPF patients. METHODS: Consecutive IPF patients who had been assessed at a single center were retrospectively analyzed. The relative decline in PEFR over 6 months was assessed. Survival analyses were performed by univariate and multivariate Cox proportional hazard models. RESULTS: A total of 61 eligible cases (average age 70 years) were examined, and 21 patients (34.4%) died. The univariate Cox regression analysis showed that the body mass index, baseline % predicted forced vital capacity (FVC), baseline % predicted PEFR, % predicted diffusion capacity for carbon monoxide (DLCO), relative decline in FVC, and relative decline in PEFR were prognostic factors. On multivariate analyses, relative decline in PEFR (hazard ratio [HR] 1.037, p < .05) and baseline % predicted FVC (HR 0.932, p < .001) were independent prognostic factors, whereas relative decline in FVC was not. CONCLUSION: A decrease in PEFR after 6 months may predict worse survival in patients with IPF.

Frequency and impact on clinical outcomes of sarcopenia in patients with idiopathic pulmonary fibrosis.

OBJECTIVES: Sarcopenia is a syndrome characterized by reduced muscle mass and function. It is well-recognized as a complication in chronic diseases such as chronic obstructive pulmonary disease. However, little is known about sarcopenia in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the clinical characteristics of sarcopenia and the association between quality of life and sarcopenia in patients with IPF. METHODS: In this pilot cross-sectional study, 56 Japanese outpatients with IPF (49 men) were enrolled prospectively. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia 2019. Its associations with clinical parameters including age, pulmonary functions, physical performance, and patient-reported outcomes (PROs) were examined. RESULTS: The frequency of sarcopenia was 39.3% (n = 22) in this cohort. There were significant differences in St George's Respiratory Questionnaire (p = .005), modified Medical Research Council score (p = .004), and Hospital and Anxiety Depression Scale depression score (p = .030) between the sarcopenic and non-sarcopenic groups. On multivariate regression analysis, 6-min walk distance (6MWD) was an independent factor associated with sarcopenia (odds ratio 1.241, 95% confidence interval 1.016-1.515, p = .034). CONCLUSION: Sarcopenia was associated with PROs and physical performance in patients with IPF.

Oral hygiene status and factors related to oral health in hospitalized patients with schizophrenia.

OBJECTIVE: This study aimed to elucidate the oral hygiene status and the factors associated with poor oral hygiene among patients with schizophrenia. METHODS: The relationships of oral hygiene status (calculus index [CI], debris index [DI]), the mean number of decayed-missing-filled teeth (mean DMFT), and Revised Oral Assessment Guide (ROAG) with related factors (hospitalization, chlorpromazine equivalents [CPZE], age, Barthel Index [BI], frequency of cleaning teeth, and self-oral hygiene ability) among 249 hospitalized schizophrenic patients were investigated. RESULTS: The results for oral hygiene status were as follows: median (range); CI 0.5 (0-6.0), DI 1.7 (0-6.0), ROAG 10.0 (7.0-15.0); and mean DMFT 21.7 ± 7.3. The average CPZE was 524.4 ± 353.6 mg (mean ± SD), and the BI was 76.4 ± 30.7. There was a negative correlation between BI and DI (r = -0.34), and a positive correlation between age and mean DMFT (r = 0.57). Male patients tended to have worse oral conditions (ROAG) than females. The least-squares multiple regression analysis revealed that BI for DI, age for mean DMFT, sex for ROAG, and self-oral hygiene ability for CI, DI, and mean DMFT were factors related to oral health status. CONCLUSION: Patients with schizophrenia tended to have poor oral hygiene. BI, being male, and low activities of daily living were associated with poor oral hygiene. Furthermore, advanced age was associated with an increased risk of dental caries.

Amphiol, an Antifungal Fungal Pigment from Pseudogymnoascus sp. PF1464.

An antifungal metabolite, designated amphiol (1), was isolated from the culture broth of the fungus Pseudogymnoascus sp. PF1464. It exists as a mixture of inseparable tautomers, an acetal form and a keto form. The chemical structure was determined by spectroscopic analyses and chemical derivatization. Amphiol (1) showed antifungal but not antibacterial activities, while yeast mutant cells lacking ergosterol biosynthetic genes were less sensitive, implying a fungal specific, membrane-related mechanism of action.

Temporal changes in magnetic resonance imaging appearance of adult granulosa cell tumor.

Granulosa cell tumors (GCTs) can have a wide variety of appearances on magnetic resonance imaging (MRI), ranging from entirely solid to multilocular cystic, suggesting that GCTs undergo remarkable morphological changes during growth. These temporal changes in MRI appearance of individual GCTs have not been documented. A 54-year-old asymptomatic postmenopausal woman was referred to our department for a small ovarian mass. This 3-cm solid mass showed high intensity on diffusion-weighted MRI and low intensity on apparent diffusion coefficient mapping. Close clinical follow-up was recommended, but she did not return to our hospital until the age of 63, when she was referred for a large ovarian tumor. MRI showed a 15-cm multilocular cyst containing a solid component with hemorrhaging. Postoperative diagnosis was adult GCT (AGCT). These temporal changes demonstrate a possible reason why GCTs can have such a wide range of MRI appearance. This knowledge might promote accurate preoperative diagnosis of AGCTs.

Factors contributing to favourable neonatal outcomes in early-onset severe preeclampsia.

We collected data from all the women with singleton pregnancies complicated by early-onset severe preeclampsia between 2008 and 2018 to identify the factor(s) that contributed to favourable neonatal outcome. Thirty women delivered the neonates with favourable outcome and the remaining 21 women delivered those with unfavourable outcome. Univariate logistic regression analysis revealed that gestational age at diagnosis ≥28 weeks (crude odds ratio [OR], 6.00), protocol-based management (crude OR 5.83), use of magnesium sulphate (crude OR, 6.00), gestational age at delivery ≥32 weeks (crude OR, 31.90), and birthweight ≥1000 g (crude OR, 10.36) were significantly associated with favourable neonatal outcome. Among these five factors, multivariate logistic regression analysis extracted gestational age at delivery ≥32 weeks (adjusted OR, 17.62) as an only independent factor contributing to favourable neonatal outcome. These data suggest that prolongation of pregnancy up to 32 weeks of gestation is a key factor to improve neonatal outcome in the expectant management of early-onset severe preeclampsia.This study was approved by the ethics committee of Otsu Red Cross Hospital (reference number: 363, date of approval: April 28th, 2016).Impact statementWhat is already known on this subject? It has been demonstrated that expectant management for the women with early-onset severe preeclampsia is associated with decreased neonatal morbidity as compared to the aggressive management, suggesting that prolongation of the pregnancy period contributes to improved neonatal outcomes.What do the results of this study add? Among multiple elements composing expectant management for the women with early-onset severe preeclampsia, 'gestational age at delivery ≥32 weeks' was extracted as an only independent factor that significantly contributes to favourable neonatal outcomes. Importantly, small for gestational age was not significantly associated with poor neonatal outcomes.What are the implications of these findings for clinical practice and/or further research? The obstetrician should aim to prolong the pregnancies complicated by early-onset severe preeclampsia up to 32 gestational weeks even in the presence of foetal growth restriction, as far as maternal conditions allow. Such management policy could contribute to improvement of the neonatal outcomes.

Decreased handgrip strength can predict lung function impairment in male workers: a cross sectional study.

BACKGROUND: Spirometry is useful for evaluating respiratory health status and predicting health-related outcomes. As spirometry requires skilled technician and takes time, it is useful to find simple way for predicting lung function impairment. The aim of this study was to investigate which tests could predict lung function impairment among workers. METHODS: This prospective study included workers of manufacturing industry who underwent health check-ups in 2017. Subjects underwent the chronic obstructive pulmonary disease (COPD) assessment test (CAT), spirometry, and physical fitness assessments, including handgrip strength (HGS). Lung function impairment was defined as a decline in any of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), or a FEV1/FVC ratio less than the lower limit of normal (LLN). RESULTS: Complete data on 475 workers (366 men, 50.4% ever smokers) were available. Lung function impairment was observed in 99 subjects (64 men). Men with lung function impairment had significantly higher rate of ever-smoking, passive smoking at home in childhood, high CAT scores, and decreased HGS, compared with those without. On multivariate analyses, ever-smoking (odds ratio [OR], 2.50; 95% confidence intervals [CI], 1.25-4.97), passive smoking at home in childhood (OR, 2.71; 95% CI, 1.16-6.32), CAT scores (OR, 1.06; 95% CI, 1.01-1.12), and HGS (OR, 0.73; 95% CI, 0.57-0.92) were independently associated with lung function impairment in men. CONCLUSIONS: Ever-smoking, passive smoking at home in childhood, high CAT scores, and decreased HGS are significantly associated with lung function impairment in men. TRIAL REGISTRATION: Registration number: UMIN000028011. Date of registration: July 1, 2017.

Vision-Based Building Seismic Displacement Measurement by Stratification of Projective Rectification Using Lines.

We propose a new flexible technique for accurate vision-based seismic displacement measurement of building structures via a single non-stationary camera with any perspective view. No a priori information about the camera's parameters or only partial knowledge of the internal camera parameters is required, and geometric constraints in the world coordinate system are employed for projective rectification in this research. Whereas most projective rectifications are conducted by specifying the positions of four or more fixed reference points, our method adopts a stratified approach to partially determine the projective transformation from line-based geometric relationships on the world plane. Since line features are natural and plentiful in a man-made architectural building environment, robust estimation techniques for automatic projective/affine distortion removal can be applied in a more practical way. Both simulations and real-recorded data were used to verify the effectiveness and robustness of the proposed method. We hope that the proposed method could advance the consumer-grade camera system for vision-based structural measurement one more step, from laboratory environments to real-world structural health monitoring systems.

[Neutrophil-Lymphocyte Ratio as a Prognostic Indicator in Patients Treated with Nivolumab for Gastric Cancer].

BACKGROUND: Immune checkpoint inhibitors(nivolumab)have been recommended as third-line chemotherapy for advanced gastric cancer(AGC)according to the Guidelines of Gastric Cancer(5th edition). Therefore, they have been used in daily clinical practice. On the other hand, the neutrophil-lymphocyte ratio(NLR)has been reported to be associated with the prognosis of cancer patients. METHODS: Twenty patients treated with nivolumab for AGC between January 2018 and November 2019 were retrospectively examined. RESULTS: Median age of the 20 patients(18 males, 2 females)was 70 years(55- 84 years). Nivolumab was administered as second-, third-, fourth-, and fifth-line therapy in 1, 11, 7, and 1 case, respectively. The best tumor response evaluation was observed in PR 1, SD 7 and PD 10 cases. Median overall survival(OS)was 10 months, and median progression-free survival(PFS)was 3 months. No serious adverse events occurred. Compared to the NLR>2.0 group, OS significantly prolonged(2.2 months vs 21.9 months)and PFS tended to prolong(1.4 months vs 6.2 months)in the NLR≤2.0 group. CONCLUSION: NLR may be an effective prognostic factor in patients with AGC receiving nivolumab treatment.