Safety/efficacy of atezolizumab + bevacizumab during anti-platelet/anticoagulation therapy in unresectable hepatocellular carcinoma.

BACKGROUND AND AIMS: This study aimed to determine the safety and efficacy of atezolizumab + bevacizumab therapy in hepatocellular carcinoma patients receiving anti-platelet agents or anticoagulants. METHODS: Patients were divided into those using (IM out) and those not using (IM in) anti-platelet agents or anticoagulants, who violated the exclusion criteria of the IMbrave150 trial, and were retrospectively examined. RESULTS: The study included 185 patients (IM in: 157; IM out: 28). For first-line treatment, progression-free survival was 184 days for IM in and 266 days for IM out (p = .136). Overall survival was 603 days for IM in and not reached for IM out (p = .265), with no significant between-group difference. Similarly, there were no significant between-group differences in progression-free survival or overall survival for later-line treatment. Haemorrhagic adverse events of ≥grade 3 were observed in 11 IM in patients and 3 IM out patients. No significant factors associated with haemorrhagic adverse events of ≥grade 3 were identified in the multivariate analysis including IM out classification, whose p value was .547. Regarding thrombotic/embolic adverse events in the IM out group, one case of exacerbation of portal vein thrombosis was observed. No deaths were directly attributable to bleeding events or exacerbations of thrombosis. CONCLUSION: Atezolizumab + bevacizumab therapy shows similar safety and efficacy in patients receiving and those not receiving anti-platelet agents or anticoagulants; therefore, it can be considered for patients with hepatocellular carcinoma receiving anti-platelet agents or anticoagulants.

A nomogram to predict the absence of clinically significant prostate cancer in males with negative MRI

ABSTRACT Purpose: To create a nomogram to predict the absence of clinically significant prostate cancer (CSPCa) in males with non-suspicion multiparametric magnetic resonance imaging (mpMRI) undergoing prostate biopsy (PBx). Materials and Methods: We identified consecutive patients who underwent 3T mpMRI followed by PBx for suspicion of PCa or surveillance follow-up. All patients had Prostate Imaging Reporting and Data System score 1-2 (negative mpMRI). CSPCa was defined as Grade Group ≥2. Multivariate logistic regression analysis was performed via backward elimination. Discrimination was evaluated with area under the receiver operating characteristic (AUROC). Internal validation with 1,000x bootstrapping for estimating the optimism corrected AUROC. Results: Total 327 patients met inclusion criteria. The median (IQR) age and PSA density (PSAD) were 64 years (58-70) and 0.10 ng/mL2 (0.07-0.15), respectively. Biopsy history was as follows: 117 (36%) males were PBx-naive, 130 (40%) had previous negative PBx and 80 (24%) had previous positive PBx. The majority were White (65%); 6% of males self-reported Black. Overall, 44 (13%) patients were diagnosed with CSPCa on PBx. Black race, history of previous negative PBx and PSAD ≥0.15ng/mL2 were independent predictors for CSPCa on PBx and were included in the nomogram. The AUROC of the nomogram was 0.78 and the optimism corrected AUROC was 0.75. Conclusions: Our nomogram facilitates evaluating individual probability of CSPCa on PBx in males with PIRADS 1-2 mpMRI and may be used to identify those in whom PBx may be safely avoided. Black males have increased risk of CSPCa on PBx, even in the setting of PIRADS 1-2 mpMRI

Oxygenation saturation index in neonatal hypoxemic respiratory failure.

BACKGROUND: This study aimed to assess the validity of the oxygenation saturation index (OSI) and the ratio of oxygen saturation to the fraction of inspired oxygen (FIO2) (S/F ratio) with percutaneous oxygen saturation (OSISpO2 and the Sp/F ratio) and to evaluate the correlation between these values and the oxygen index (OI). It also determined their cut-off values for predicting OI in accordance with neonatal hypoxic respiratory failure severity. METHODS: We reviewed the data of 77 neonates (gestational age 31.7 ± 6.1 weeks; birthweight, 1768 ± 983 g) requiring invasive mechanical ventilation between 2013 and 2020, 1233 arterial blood gas samples in total. We calculated the OI, OSISpO2, OSI with arterial oxygen saturation (SaO2) (OSISaO2), Sp/F ratio, and the ratio of SaO2 to FIO2 (Sa/F ratio). RESULTS: The regression and Bland-Altman analysis showed good agreement between OSISpO2 or the Sp/F ratio and OSISaO2 or the Sa/F ratio. Although a significant positive correlation was found between OSISpO2 and OI, OSISpO2 was overestimated in SpO2 > 98% with a higher slope of the fitted regression line than that below 98% of SpO2. Furthermore, receiver-operating characteristic curve analysis using only SpO2 ≤ 98% samples showed that the optimal cut-off points of OSISpO2 and the Sp/F ratio for predicting OI were: OI 5, 3.0 and 332; OI 10, 5.3 and 231; OI 15, 7.7 and 108; OI 20, 11.0 and 149; and OI 25, 17.1 and 103, respectively. CONCLUSION: The cut-off OSISpO2 and Sp/F ratio values could allow continuous monitoring for oxygenation changes in neonates with the potential for wider clinical applications.

Neonatal uterine bleeding: Risk factors and its association with endometriosis-related symptoms later in life.

OBJECTIVE: We examined the prevalence and risk factors in association with neonatal uterine bleeding (NUB) by retrospective search of contemporary and historical medical records and investigated the possible association between the history of NUB at birth and endometriosis-related symptoms later in life who are now young women. STUDY DESIGN: This was a retrospective case-controlled cohort study and prospective evaluation of web-based questionnaire survey on symptoms related to endometriosis among young women born with and without NUB. Multiple regression analysis was performed incorporating various confounding variables that may influence the occurrence of NUB or the reporting of endometriosis symptoms later in life. RESULTS: Among the 1093 female neonates born between 1996 and 2000, 105 of them had NUB, yielding with a prevalence of 9.6 %. Of the 807 female babies born between 2013 and 2017, 25 (3.1 %) had NUB. Multiple Logistic regression analysis indicated that younger age of the mother [odds ratio (OR) = 0.92, 95 % confidence interval (CI) = 0.85-1.00, P = 0.048] and longer gestational age of 39 weeks (OR = 3.04, 95 % CI = 1.43-6.45, P = 0.004) and of ≥ 40 weeks (OR = 4.54, 95 % CI = 2.20-9.39, P < 0.0001) of gestation were significantly associated with the occurrence of NUB. While the possibility of recall bias cannot be ruled out, newborn females who had a history of NUB appeared to complain of various endometriosis-related symptoms later in life during adulthood. CONCLUSIONS: We confirmed the validity of the reported prevalence and risk factors of NUB. NUB indeed occurs with a prevalence of 3-10% during the historical and contemporary period. Longer gestational age and younger maternal age may be considered as high-risk factors for the occurrence of NUB. The clinical relevance of our findings remains to be elucidated. Future prospective studies, preferably with larger sample sizes and the inclusion of NUB cases after discharge from the hospital, may further illuminate some unresolved issues. We also need to confirm the endometriosis-related symptoms in women with and without history of NUB via more definitive diagnosis such as imaging and histology.

A nomogram to predict the absence of clinically significant prostate cancer in males with negative MRI

PURPOSE: To create a nomogram to predict the absence of clinically significant prostate cancer (CSPCa) in males with non-suspicion multiparametric magnetic resonance imaging (mpMRI) undergoing prostate biopsy (PBx). MATERIALS AND METHODS: We identified consecutive patients who underwent 3T mpMRI followed by PBx for suspicion of PCa or surveillance follow-up. All patients had Prostate Imaging Reporting and Data System score 1-2 (negative mpMRI). CSPCa was defined as Grade Group ≥2. Multivariate logistic regression analysis was performed via backward elimination. Discrimination was evaluated with area under the receiver operating characteristic (AUROC). Internal validation with 1,000x bootstrapping for estimating the optimism corrected AUROC. RESULTS: Total 327 patients met inclusion criteria. The median (IQR) age and PSA density (PSAD) were 64 years (58-70) and 0.10 ng/mL2 (0.07-0.15), respectively. Biopsy history was as follows: 117 (36%) males were PBx-naive, 130 (40%) had previous negative PBx and 80 (24%) had previous positive PBx. The majority were White (65%); 6% of males self-reported Black. Overall, 44 (13%) patients were diagnosed with CSPCa on PBx. Black race, history of previous negative PBx and PSAD ≥0.15ng/mL2 were independent predictors for CSPCa on PBx and were included in the nomogram. The AUROC of the nomogram was 0.78 and the optimism corrected AUROC was 0.75. CONCLUSIONS: Our nomogram facilitates evaluating individual probability of CSPCa on PBx in males with PIRADS 1-2 mpMRI and may be used to identify those in whom PBx may be safely avoided. Black males have increased risk of CSPCa on PBx, even in the setting of PIRADS 1-2 mpMRI.

A Fully Automated Artificial Intelligence System to Assist Pathologists' Diagnosis to Predict Histologically High-grade Urothelial Carcinoma from Digitized Urine Cytology Slides Using Deep Learning.

BACKGROUND: Urine cytology, although a useful screening method for urothelial carcinoma, lacks sensitivity. As an emerging technology, artificial intelligence (AI) improved image analysis accuracy significantly. OBJECTIVE: To develop a fully automated AI system to assist pathologists in the histological prediction of high-grade urothelial carcinoma (HGUC) from digitized urine cytology slides. DESIGN, SETTING, AND PARTICIPANTS: We digitized 535 consecutive urine cytology slides for AI use. Among these slides, 181 were used for AI development, 39 were used as AI test data to identify HGUC by cell-level classification, and 315 were used as AI test data for slide-level classification. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Out of the 315 slides, 171 were collected immediately prior to bladder biopsy or transurethral resection of bladder tumor, and then outcomes were compared with the histological presence of HGUC in the surgical specimen. The primary aim was to compare AI prediction of the histological presence of HGUC with the pathologist's histological diagnosis of HGUC. Secondary aims were to compare the time required for AI evaluation and concordance between the AI's classification and pathologist's cytology diagnosis. RESULTS AND LIMITATIONS: The AI capability for predicting the histological presence of HGUC was 0.78 for the area under the curve. Comparing the AI predictive performance with pathologists' diagnosis, the AI sensitivity of 63% for histological HGUC prediction was superior to a pathologists' cytology sensitivity of 46% (p = 0.0037). On the contrary, there was no significant difference between the AI specificity of 83% and pathologists' specificity of 89% (p = 0.13), and AI accuracy of 74% and pathologists' accuracy of 68% (p = 0.08). The time required for AI evaluation was 139 s. With respect to the concordance between the AI prediction and pathologist's cytology diagnosis, the accuracy was 86%. Agreements with positive and negative findings were 92% and 84%, respectively. CONCLUSIONS: We developed a fully automated AI system to assist pathologists' histological diagnosis of HGUC using digitized slides. This AI system showed significantly higher sensitivity than a board-certified cytopathologist and may assist pathologists in making urine cytology diagnoses, reducing their workload. PATIENT SUMMARY: In this study, we present a deep learning-based artificial intelligence (AI) system that classifies urine cytology slides according to the Paris system. An automated AI system was developed and validated with 535 consecutive urine cytology slides. The AI predicted histological high-grade urothelial carcinoma from digitized urine cytology slides with superior sensitivity than pathologists, while maintaining comparable specificity and accuracy.

Endoscopist-related factors affecting adenoma detection during colonoscopy: Data from the J-SCOUT study.

OBJECTIVES: Colonoscopy withdrawal times are associated with the adenoma detection rate (ADR). However, the relationship between ADR and cecal insertion time has been inadequately characterized. We aimed to evaluate endoscopist-related factors involved in the ADR, including the average individual colonoscopy insertion and withdrawal times. METHODS: This observational study used a colonoscopy database with pathology data from routine clinical practice in Japanese institutions. The odds ratios (OR) of endoscopist-related factors related to ADRs were examined using a generalized linear mixed model. RESULTS: Of the 186,293 colonoscopies performed during the study period, 47,705 colonoscopies by 189 endoscopists in four hospitals were analyzed for ADR. The overall ADR was 38.3% (95% confidence interval [CI] 37.8, 38.7). Compared to endoscopists with mean cecal insertion times of <5 min, the OR of ADR for those with mean cecal insertion times of 5-9, 10-14, and ≥15 min were 0.84 (95% CI 0.71, 0.99), 0.68 (95% CI 0.52, 0.90), and 0.45 (95% CI 0.25, 0.78), respectively. Compared to endoscopists with mean withdrawal times of <6 min, the OR of ADR for those with mean withdrawal times of 6-9, 10-14, and ≥15 min were 1.38 (95% CI 1.03, 1.85), 1.48 (95% CI 1.09, 2.02), and 1.68 (95% CI 1.04, 2.61), respectively. There were no significant differences in ADRs by endoscopist specialty, gender, or the total number of examinations performed. CONCLUSION: Individual mean colonoscopy insertion time was associated with ADR and might be considered as a colonoscopy quality indicator as well as withdrawal time.

In-hospital mortality and cardiovascular treatment during hospitalization for heart failure among patients with schizophrenia: a nationwide cohort study.

AIMS: Schizophrenia is associated with cardiovascular disease (CVD) risk, and patients with schizophrenia are more likely to receive suboptimal care for CVD. However, there is limited knowledge regarding in-hospital prognosis and quality of care for patients with schizophrenia hospitalized for heart failure (HF). This study sought to elucidate the association between schizophrenia and in-hospital mortality, as well as cardiovascular treatment in patients hospitalized with HF. METHODS: Using the nationwide cardiovascular registry data in Japan, a total of 704,193 patients hospitalized with HF from 2012 to 2019 were included and stratified by age: young age, > 18 to 45 years (n = 20,289); middle age, >45 to 65 years (n = 114,947); and old age, >65 to 85 years (n = 568,957). All and 30-day in-hospital mortality as well as prescription of cardiovascular medications were assessed. After multiple imputation for missing values, mixed-effect multivariable logistic regression analysis was performed using patient and hospital characteristics with hospital identifier as a variable with random effects. RESULTS: Patients with schizophrenia were more likely to experience prolonged hospital stays, and incur higher hospitalization costs. In-hospital mortality for non-elderly patients with schizophrenia was significantly worse than for those without schizophrenia: the mortality rate was 7.6% vs 3.5% and the adjusted odds ratio (OR) was 1.96 (95% confidence interval (CI): 1.24-3.10, P = 0.0037) in young adult patients; 6.2% vs 4.0% and 1.49 (95% CI: 1.17-1.88, P < 0.001) in middle-aged patients. Thirty-day in-hospital mortality was significantly worse in middle-aged patients: the mortality rate was 4.7% vs 3.0% and an adjusted OR was 1.40 (95% CI: 1.07-1.83, P = 0.012). In-hospital mortality in elderly patients did not differ between those with and without schizophrenia. Prescriptions of beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were significantly lower in patients with schizophrenia across all age groups. CONCLUSION: Schizophrenia was identified as a risk factor for in-hospital mortality and reduced prescription of cardioprotective medications in non-elderly patients hospitalized with HF. These findings highlight the necessity for differentiated care and management of HF in patients with severe mental illnesses.

Effects of dapagliflozin on renal function in type 1 diabetes patients in the real world: A retrospective multicenter study of the KAMOGAWA-A cohort.

AIMS: This study aimed to investigate the effects of dapagliflozin on renal function of type 1 diabetes patients. METHODS: This retrospective multicenter cohort study enrolled 295 type 1 diabetes patients. The primary outcome was defined as the change in the estimated glomerular filtration rate (eGFR) after 24 months of dapagliflozin treatment. The secondary outcomes were defined as the changes in HbA1c, daily insulin dosage, and urinary albumin-to-creatinine ratio (UACR) after 24 months. RESULTS: Finally, 255 patients were included in the final analysis (dapagliflozin group; 76 patients, non-use group; 179 patients), with a median eGFR of 74.0 mL/min/1.73 m2. A 1:1 propensity score matching was performed, and 142 patients were analyzed in a linear mixed model. The least squares mean change in eGFR in the dapagliflozin group was -3.14 mL/min/1.73 m2 (95% CI: -5.62 to -0.66), a significantly smaller decrease than in the non-use group (-6.94 mL/min/1.73 m2 (95% CI: -9.39 to -4.50)) (p = 0.032). HbA1c level, total insulin dose, and UACR change were significantly lower in the dapagliflozin group than in the non-use group. CONCLUSIONS: At 24 months, the decline in eGFR was significantly lower in the dapagliflozin group than in the non-use group without increasing diabetic ketoacidosis and hypoglycemia.

Is neonatal uterine bleeding responsible for early-onset endometriosis?

BACKGROUND: It has been hypothesized that the origin of early-onset endometriosis could be from endometrial mesenchymal stem cells (eMSCs) in neonatal uterine blood (NUB). There is no information on the possible mechanistic basis linking an association between NUB/neonatal endometrium and development of early-onset endometriosis. In this study we performed a series of experiments to clarify the mechanistic link between NUB and/or neonatal endometrium and development of early-onset endometriosis. METHODS: We retrospectively collected postmortem neonatal endometria (n = 15) and prospectively collected NUB (n = 18) of female babies for the analysis of different biological markers including eMSCs. Immunohistochemical analysis of neonatal endometria was performed to examine the expression patterns of ovarian steroid receptors (ER/PGR), decidualization (prolactin, IGFBP1), pre-decidualization (Glycodelin A, α-SMA), proliferation (Ki-67 index), vascularity (CD31 + cells), immunocompetent CD68+, CD45+, CD56 + cells and some putative markers of eMSCs. Cell transfer method and immunocytochemistry were used to investigate the eMSCs and/or endometrial cells in NUB. RESULTS: Immunohistochemical analysis of postmortem neonatal endometria revealed variable staining response to ER/PGR, decidual markers, and substantial proliferative and angiogenic activity. A moderate to strong immunoexpression of Glycodelin-A was found in both neonatal and adult endometria. The tissue infiltration of CD56+, CD45 + and CD68 + immunocompetent cells was significantly low in neonatal endometria than that in adult endometria (p = 0.0003, p < 0.0001, p = 0.034, respectively). No eMSCs or even endometrial cells were detected in NUB. However, a variable expression of some phenotypes of eMSCs (CD90/CD105) was found in neonatal endometria. CONCLUSIONS: Based on our serial experiments we did not find any supporting evidence for the role of NUB in early-onset endometriosis. Neonatal endometria showed variable expression of ovarian steroid receptors, decidualization, and a substantial amount of proliferative and angiogenic activity. As an alternative mechanism, a significantly less tissue accumulation of immunocompetent cells in neonatal endometria may explain the survival of ER + and PGR + cells should they make entry into the pelvis and consequent development of early endometriosis with the onset of ovarian function. Future study with large sample size and application of modified technological tools is warranted to test the NUB hypothesis and to clarify their biological or clinical significance. TRIAL REGISTRATION: not applicable.

Association between tissue stress reaction and ACE2/TMPRSS2 expression in endometria of reproductive aged women before and during Covid-19 pandemic.

BACKGROUND: A potential concern has been raised regarding fertility and reproductive outcome during the Covid-19 pandemic with growing stress and anxiety. However, information on the association between tissue stress reaction and expression profiles of SARS-CoV-2 viral entry proteins, ACE2 and TMPRSS2, in endometria collected from women before (pre-pandemic) and during the Covid-19 pandemic (in-pandemic) is unknown. We aim to investigate the relationship between the expression of stress-reactive proteins and of ACE2 and TMPRSS2 in endometria collected from women during these two different time frames. METHODS: We retrospectively retrieved tissue blocks of endometrial samples from 25 women in 2019 (pre-pandemic) and 25 women in 2020 (in-pandemic) who underwent hysterectomy for different gynecological indications. Immunohistochemical analysis was performed with endometrial tissue samples that were collected before and during the pandemic, using respective antibodies targeting ACE2/TMPRSS2, ADRB2 and NK1R (stress and anxiety receptor markers, respectively). The quantification of immunoreactive cells for each marker was calculated by the immunoreactive score (IRS) analysis. This retrospective cohort study was limited to small sample size. RESULTS: No significant differences in the IRS of ACE2 and TMPRSS2 were found between the endometria that were collected before and during the pandemic with a lack of correlation between ACE2 and TMPRSS2 expression in respective endometria (r = 0.11, pre-pandemic; r = 0.04, in-pandemic). The immunostaining levels of stress marker, ADRB2 were significantly higher in the endometria of in-pandemic group (p = 0.015) comparing to that of pre-pandemic group. Pearson's correlation coefficient analysis showed a significant correlation in the expression between ADRB2 and TMPRSS2 (r = 0.41, p = 0.042) in the endometria of in-pandemic group but not in the pre-pandemic group. CONCLUSION: The rise in stress and anxiety among women during current pandemic may elicit substantial amount of tissue stress reaction with consequent increase in the expression of SARS-CoV-2 viral entry proteins in their endometria. A lack of correlation between ACE2 and TMPRSS2 expression in endometria may reassure women in their reproductive age that they are not more susceptible to infection by SARS-CoV-2 and suggest that stressful women during this pandemic can safely decide to conceive naturally or by artificial reproductive technology.

Association between patient volume to cardiologist, process of care, and clinical outcomes in heart failure.

AIMS: The impact of hospital volume on clinical performance has been investigated by many researchers to date and thought that it is associated with quality of care and outcome for patients with heart failure (HF). This study sought to determine whether annual admissions of HF per cardiologist are associated with process of care, mortality, and readmission. METHODS AND RESULTS: Among the nationwide registry 'Japanese registry of all cardiac and vascular diseases - diagnostics procedure combination' data collected from 2012 to 2019, a total of 1 127 113 adult patients with HF and 1046 hospitals were included in the study. Primary outcome was in-hospital mortality, and secondary outcome was 30 day in-hospital mortality and readmission at 30 days and 6 months. Hospital and patient characteristics and process of care measures were also assessed. Mixed-effect logistic regression and Cox proportional-hazards model was used for multivariable analysis, and adjusted odds ratio and hazard ratio were evaluated. Process of care measures had inverse trends for annual admissions of HF per cardiologist (P < 0.01 for all measures: prescription rate of beta-blocker, angiotensin converting enzyme inhibitor or angiotensin II receptor blocker, mineralocorticoid receptor antagonist, and anticoagulant for atrial fibrillation). Adjusted odds ratio for in-hospital mortality was 1.04 (95% confidence interval (CI): 1.04-1.08, P = 0.04) and 30 day in-hospital mortality was 1.05 (95% CI: 1.01-1.09, P = 0.01) for interval of 50 annual admissions of HF per cardiologist. Adjusted hazard ratio for 30 day readmission was 1.05 (95% CI: 1.02-1.08, P < 0.01) and 6 month readmission was 1.07 (95% CI: 1.03-1.11, P < 0.01). Plots of the adjusted odds indicated 300 as the threshold of annual admissions of HF per cardiologist for substantial increase of in-hospital mortality risk. CONCLUSIONS: Our findings demonstrated that annual admissions of HF per cardiologist are associated with worse process of care, mortality, and readmission with the threshold for mortality risk increased, emphasizing the optimal proportion of patients admitted with HF to cardiologist for better clinical performance.

A big data-based prediction model for prostate cancer incidence in Japanese men.

To define a normal range for PSA values (ng/mL) by age and create a prediction model for prostate cancer incidence. We conducted a retrospective analysis using 263,073 observations of PSA values in Japanese men aged 18-98 years (2007-2017), including healthy men and those diagnosed with prostate cancer. Percentiles for 262,639 PSA observations in healthy men aged 18-70 years were calculated and plotted to elucidate the normal fluctuation range for PSA values by age. Univariable and multivariable logistic regression analyses were performed to develop a predictive model for prostate cancer incidence. PSA levels and PSA velocity increased with age in healthy men. However, there was no difference in PSA velocity with age in men diagnosed with prostate cancer. Logistic regression analysis showed an increased risk of prostate cancer for PSA slopes ranging from 0.5 to 3.5 ng/mL/year. This study provides age-specific normal fluctuation ranges for PSA levels in men aged 18-75 years and presents a novel and personalized prediction model for prostate cancer incidence. We found that PSA slope values of > 3.5 ng/mL/year may indicate a rapid increase in PSA levels caused by pathological condition such as inflammation but are unlikely to indicate cancer risk.

Time-of-flight magnetic resonance angiography for detection of postoperative recurrence in patients with chronic subdural hematoma.

PURPOSE: Chronic subdural hematoma (CSDH) is associated with postoperative recurrence. Although various factors are involved in postoperative recurrence of CSDH, blood flow, especially in the middle meningeal artery (MMA), is considered to play an important role. We investigated whether the degree of signal intensity (SI) of the MMA on time-of-flight magnetic resonance angiography (TOF MRA) and various clinical factors are involved in recurrence of CSDH. METHODS: The maximum SI of both MMAs was measured on TOF MRA images within 1 month before or after the initial surgery. RESULTS: In total, 185 patients (20 with and 165 without recurrence of CSDH) were included in the analysis. The SI ratio and dementia were significant predictors of recurrence of CSDH (SI ratio: odds ratio [95% confidence interval (CI)] = 1.71 [1.32, 2.22], p < 0.0001; dementia: odds ratio [95% CI] = 7.41 [1.83, 30.1], p = 0.005). The estimated regression coefficients in the final model were 6.14 for the SI ratio and 1.28 for dementia. The risk score was derived according to these regression coefficients as follows: score = 5 × SI ratio + 1 (dementia: yes). With a score of 5, the predicted probability of recurrence was 2% [95% CI 0.7, 5.7], whereas with scores of 8 and 10, the probability was 43.3% [27.0, 61.1] and 89.5% [65.7, 97.5], respectively, which increased the risk of recurrence. CONCLUSION: Patients with an increased SI ratio of the affected MMA on TOF MRA who underwent surgery for CSDH were significantly more likely to experience recurrence.

"Endoscopic" adenoma detection rate as a quality indicator of colonoscopy: First report from the J-SCOUT study.

OBJECTIVES: To examine whether reasonable detection rate of endoscopically diagnosed lesions as adenoma ("endoscopic" adenoma detection rate [ADR]) could be calculated with a database generated from colonoscopy reports and whether it could be used as a surrogate colonoscopy quality indicator of "pathological" ADR. METHODS: A lesion-by-lesion database of colonoscopies performed between 2010 and 2020 at eight Japanese endoscopy centers and corresponding pathology database were integrated. Differences in numbers of detected polyps, "endoscopic" and "pathological" adenomas, and what these differences could be attributed to were examined. Polyp detection rate (PDR), "endoscopic" and "pathological" ADRs, and correlation coefficients between "pathological" ADR and PDR or "endoscopic" ADR by each endoscopist were calculated. RESULTS: Overall, 129,065 colonoscopy reports were analyzed. Among a total of 146,854 polyps, more "endoscopic" adenomas (n = 117,359) were observed than "pathological" adenomas (n = 70,076), primarily because adenomas were not resected on site, rather than because of a misdiagnosis. In all patients analyzed, PDR, "endoscopic" and "pathological" ADRs were 56.4% (95% confidence interval [CI] 56.2-56.7), 48.0% (95% CI 47.7-48.3), and 32.7% (95% CI 32.5-33.0), respectively. "Endoscopic" and "pathological" ADRs from each endoscopist showed a high correlation in hospitals where adenomas were usually resected at the time of examination. CONCLUSIONS: By appropriately describing endoscopically diagnosed lesions as "adenomas" in endoscopy reports, "endoscopic" ADR might be used as a surrogate colonoscopy quality indicator of "pathological" ADR (UMIN000040690).

A targeted educational programme improves fundamental knowledge of menstrual pain and endometriosis in young women: The Endometriosis Awareness Promotion Project.

RESEARCH QUESTION: Would a properly designed educational programme offered to young women improve their awareness and fundamental knowledge of menstrual pain and endometriosis? DESIGN: A multinational cross-sectional study using a pen-and-paper questionnaire among women aged 19-24 years was conducted between 2017 and 2019 to assess fundamental knowledge of menstrual pain and endometriosis. Improvement in knowledge was also analysed using a separate questionnaire completed before, and 1-3 months after, a group discussion, lecture on menstrual pain and endometriosis, or both. RESULTS: Among three groups of students (college [n = 271], medical [n = 877] and nursing [n = 763]), knowledge of menstrual pain and endometriosis was lowest among college students, modest among nursing students and fair among medical students (P < 0.001 for each). The experience of cyclical pain, even when painkillers were taken, was reported by 15.5%, 4.6% and 3.8% of students, respectively. Most students managed their cyclical pain by enduring it or by taking over-the-counter medication. An informative education programme with group discussions, lectures, or both, was successful in improving knowledge and consequences of menstrual pain and endometriosis. Proper education and dissemination of knowledge to college students failed to motivate them to visit gynaecologists; however, medical and nursing students became highly interested in visiting gynaecologists. CONCLUSIONS: An educational programme can improve awareness and knowledge of endometriosis and dysmenorrhoea among young women. The programme motivated nursing and medical students, but not college students, to seek medical attention for early detection and management of endometriosis.

Toxicity of Amphotericin B in Rabbit Corneal Epithelial Cells Stored in Optisol™-GS: Corneal Epithelial Cell Morphology and Migration.

PURPOSE: To evaluate the toxicity of Amphotericin B (AmB) in Optisol™-GS Corneal Storage Media (Bausch & Lomb) on corneal epithelial cell (CEC) morphology and migration ability. METHODS: Sclerocorneal strips were removed from male Japanese white rabbits, and then stored at 4 °C in Optisol™-GS containing 0 µg/ml of AmB (control group) and 2.5, 5, 25, and 50 µg/ml of AmB (AmB groups; four eyes per group). After 7 days of storage, CEC morphology was evaluated by hematoxylin-eosin staining, immunohistochemical staining (ZO-1), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Moreover, to evaluate CEC migration ability, three corneal blocks (6-8 × 3 mm each) from one preserved cornea were cultured for 24 h, and the area of CEC migration (2 mm at the central region) onto the stromal surface was then measured. RESULTS: At 5, 25, and 50 µg/ml of AmB, deformation and vacuolation of CECs were observed in all preserved corneas. ZO-1 expression was significantly reduced in corneas preserved at AmB concentrations of 25 and 50 µg/ml. TUNEL Labeling Index was significantly increased at AmB concentrations of ≥5 µg/ml. CEC migration was inhibited in a dose-dependent manner at AmB concentrations of 25 and 50 µg/ml compared to the control group. CONCLUSIONS: The addition of AmB to Optisol™-GS can be toxic to CECs and inhibit their migration at a concentration of ≥5 µg/ml. AmB at a concentration of 2.5 µg/ml can be considered safe for the preservation of donor corneal tissue used in corneal epithelial transplantation surgery.

Microwave focal therapy of prostate cancer: a non-clinical study and exploratory clinical trial.

OBJECTIVE: To examine the safety and efficacy of microwave tissue coagulation (MTC) for prostate cancer and assess its use in lesion-targeted focal therapy in a non-clinical study and a clinical phase II trial. METHODS: In the non-clinical study using Microtaze® -AFM-712 (Alfresa Pharma Corporation, Osaka, Japan) with an MTC needle, MTC was performed using a transperineal approach to targeted canine prostatic tissue under real-time ultrasonography guidance. Using various MTC output and irradiation time combinations, the targeted and surrounding tissues (rectum, bladder and fat) were examined to confirm the extent of coagulative necrosis or potential cell death, and to compare intra-operative ultrasonography and pathology findings. The exploratory clinical trial was conducted to examine the safety and efficacy of MTC. Five selected patients underwent transperineal MTC to clinically single lesion magnetic resonance imaging (MRI)-visible lesions with Gleason score 3 + 4 or 4 + 4. Prostate-specific antigen (PSA), MRI and Expanded Prostate Cancer Index Composite questionnaire findings were compared before and 6 months after surgery. RESULTS: The region of coagulative necrosis was predictable by monitoring of ultrasonically visible vaporization; thus, by placing the MTC needle at a certain distance, we were able to perform a safe procedure without adverse events affecting the surrounding organs. Based on the non-clinical study, which used various combinations of output and irradiation time, MTC with 30-W output for 60-s irradiation was selected for the prostate. Based on the predictable necrosis, the therapeutic plan (where to place the MTC needle to achieve complete ablation of the target and how many sessions) was strictly determined per patient. There were no serious adverse events in any patient and only temporary urinary symptoms related to MTC therapy were observed. Furthermore, post-treatment satisfaction was very high. All preoperative MRI-visible lesions disappeared, and PSA decreased by 55% 6 months after surgery. CONCLUSION: Microwave tissue coagulation may be an option for lesion-targeted focal therapy for prostate cancer.

Present State of the Infection Protection System and Effects of a Change in the In-Hospital System in Endovascular Treatment for Large Vessel Occlusion in Acute Stroke Patients at a Single Institution.

Objective: Endovascular treatment (EVT) for large vessel occlusion in acute ischemic stroke patients during the SARS-CoV-2 epidemic requires the implementation of an in-hospital system to guard against infection. Changes to this system may be needed upon aggravation of the epidemic in a particular region. The objective of this study was to clarify the present state of infection protection and the effects of a change in the in-hospital system in EVT at a single institution. Methods: The subjects were consecutive patients treated by EVT under the protocol of infection protection using medical history and chest CT at our hospital between April 2020 and February 2021. For the subjects, background factors, time metrics, including door-to-puncture time (D2P), clinical outcome, and success of infection protection for medical staff were examined. The patients were divided into a group of those with PCR measurement after EVT (Group C; from April 2020 to November 2020) and a group of all with PCR measurement before EVT (Group P; from December 2020 to February 2021). Time metrics and clinical outcome were compared between the groups. Results: There were 69 subjects, including 40 and 29 patients in groups C and P, respectively. The median age was 82, which was higher in group P. The median D2P was 70 min, which did not differ significantly between the two groups, but it was slightly longer in group P than in group C by multivariate analysis. A favorable outcome (modified Rankin Scale 0-2 at 3 months) was observed in 23 patients (38%), which did not differ significantly between the two groups, but the rate of a favorable outcome was slightly lower in group P than in group C by multivariate analysis. Although medical staff wearing full personal protection equipment were needed for 15 patients (22%), 12 of whom were suspected of being positive and three (4%) were confirmed positive for SARS-CoV-2 by PCR, no staff member who participated in EVT was infected. Conclusion: The median D2P was 70 min and 38% had a favorable outcome of EVT under the present state of infection protection. After a change in the in-hospital system for clinical settings during the SARS-CoV-2 epidemic, the D2P increased and the rate of a favorable clinical outcome slightly decreased, but both were not significantly affected and infection protection for medical staff was effective. Therefore, the effects of a change were acceptable considering the circumstances.