Sodium-glucose cotransporter 2 inhibitor therapy reduces the administration frequency of steroid injection in patients with diabetic macular edema: A cohort study using the Japanese health insurance claims database.

AIMS/INTRODUCTION: Severe diabetic macular edema (DME) is often resistant to anti-vascular endothelial growth factor therapy. Steroids are particularly effective at reducing edema by suppressing inflammation; they are also used as an alternative to expensive anti-vascular endothelial growth factor therapy in some patients. Therefore, the use of steroids in DME reflects an unmet need for anti-vascular endothelial growth factor therapy. Notably, triamcinolone acetonide (TA) injections are widely used in Japan. Here, we evaluated the frequency of TA as an indicator of the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in DME treatment using a health insurance claims database. MATERIALS AND METHODS: In this cohort study, we retrospectively analyzed the health insurance claims data of 11 million Japanese individuals from 2005 to 2019. The frequency and duration of TA injection after the initiation of SGLT2is or other antidiabetic drugs were analyzed. RESULTS: Among the 2,412 matched patients with DME, the incidence rate of TA injection was 63.8 times per 1,000 person-years in SGLT2i users and 94.9 times per 1,000 person-years in non-users. SGLT2is reduced the risk for the first (P = 0.0024, hazard ratio 0.66, 95% confidence interval 0.50-0.87), second (P = 0.0019, hazard ratio 0.53, 95% confidence interval 0.35-0.80) and third TA (P = 0.0053, hazard ratio 0.44, 95% confidence interval 0.25-0.80) injections. A subanalysis of each baseline characteristic of the patients showed that SGLT2is were effective regardless of the background factors. CONCLUSIONS: The use of SGLT2is reduced the frequency of TA injection in patients with DME. Therefore, SGLT2i therapy might be a novel, noninvasive and low-cost adjunctive therapy for DME.

Volume-Outcome Relationships for Intra-Aortic Balloon Pump in Acute Myocardial Infarction.

BACKGROUND: Acute myocardial infarction (AMI) is a major scenario for the use of an intra-aortic balloon pump (IABP), particularly when complicated by cardiogenic shock, although the utilization of mechanical circulatory support devices varies widely per hospital. We evaluated the relationship, at the hospital level, between the volume of IABP use and mortality in AMI. METHODS AND RESULTS: Using a Japanese nationwide administrative database, 26,490 patients with AMI undergoing primary percutaneous coronary intervention (PCI) from 154 hospitals were included in this study. The primary endpoint was the observed-to-predicted in-hospital mortality ratio. Predicted mortality per patient was calculated using baseline variables and averaged for each hospital. The associations among PCI volume for AMI, observed and predicted in-hospital mortality, and observed and predicted IABP use were assessed per hospital. Of 26,490 patients, 2,959 (11.2%) were treated with IABP and 1,283 (4.8%) died during hospitalization. The annualized number of uses of IABP per hospital in AMI was 4.5. In lower-volume primary PCI centers, IABP was more likely to be underused than expected, and the observed-to-predicted in-hospital mortality ratio was higher than in higher-volume centers. CONCLUSIONS: A lower annual number of IABP use was associated with an increased mortality risk at the hospital level, suggesting that IABP use can be an institutional quality indicator in the setting of AMI.

Serum Albumin as an Independent Predictor of Long-Term Survival in Patients with Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma Treated with Nivolumab.

Background: Nivolumab has been shown to improve the overall survival (OS) of patients with recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, there is a need to identify factors associated with long-term survival (beyond 2 years) in these patients. This study investigated the relationship between pretreatment factors and long-term survival in patients with R/M HNSCC treated with nivolumab. Methods: Forty-nine patients with R/M HNSCC who were treated with nivolumab were retrospectively reviewed. Baseline characteristics, clinical data, and survival outcomes were evaluated. Univariate and multivariate analyses were performed to identify factors associated with long-term survival (OS ≥ 2 years). Results: The median OS in the overall cohort was 11.0 months, and the 2-year survival rate was 34.7%. Long-term survivors (OS ≥ 2 years) had significantly higher proportions of patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of 0 or 1, serum albumin levels ≥ 3.5 g/dL, and neutrophil-to-eosinophil ratio (NER) < 32.0 compared to non-long-term survivors. On multivariate analysis, serum albumin levels ≥ 3.5 g/dL, in addition to ECOG-PS score of 0 or 1, were independent predictors of long-term survival. Conclusions: Pretreatment serum albumin levels may be useful for predicting long-term survival in R/M HNSCC patients treated with nivolumab.

Direct Species Identification in Positive Blood Culture Bottles From Patients With Hematologic Malignancies.

Background In patients with hematologic malignancies, faster species identification is particularly important in the management of bloodstream infection because of their immunocompromised and neutropenic status. In the present study, we analyzed direct species identification in patients with hematologic malignancies, and the factors that might influence the results of species identification. Methods We performed direct species identification using a Sepsityper® kit (Bruker Corporation, Billerica, Massachusetts, United States) and compared the results with a conventional method in patients with hematologic malignancies. Forty-five positive blood culture bottles containing single microorganisms from 37 patients were analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). And patients' clinical data were compared between the groups with spectral scores at acceptable and unacceptable levels. Results Direct species identification correctly identified 42 of 45 isolates and three were misidentified. While 35 of 45 isolates showed a spectral score ≥1.7 (acceptable identification), 10 isolates had a spectral score <1.7 (unacceptable identification) including three misidentified isolates. The group with a spectral score ≥1.7 had significantly lower white blood cell (p<0.01), neutrophil (p<0.01), and platelet (p<0.01) counts in addition to more frequent central venous (CV) line insertion (p=0.01). Multivariate analysis revealed that pathogen type (gram-positive or negative) and CV line insertion were associated with spectral scores. Conclusion Direct species identification using the Sepsityper kit is an upcoming approach for blood culture bottles, which were flagged as positive even in patients with hematologic malignancies when the spectral score was ≥ 1.7. Our study also indicates that direct identification is more accurate in patients with CV lines, and may be less accurate when gram-positive bacteria are detected.

Impact of amyloid and tau positivity on longitudinal brain atrophy in cognitively normal individuals.

BACKGROUND: Individuals on the preclinical Alzheimer's continuum, particularly those with both amyloid and tau positivity (A + T +), display a rapid cognitive decline and elevated disease progression risk. However, limited studies exist on brain atrophy trajectories within this continuum over extended periods. METHODS: This study involved 367 ADNI participants grouped based on combinations of amyloid and tau statuses determined through cerebrospinal fluid tests. Using longitudinal MRI scans, brain atrophy was determined according to the whole brain, lateral ventricle, and hippocampal volumes and cortical thickness in AD-signature regions. Cognitive performance was evaluated with the Preclinical Alzheimer's Cognitive Composite (PACC). A generalized linear mixed-effects model was used to examine group × time interactions for these measures. In addition, progression risks to mild cognitive impairment (MCI) or dementia were compared among the groups using Cox proportional hazards models. RESULTS: A total of 367 participants (48 A + T + , 86 A + T - , 63 A - T + , and 170 A - T - ; mean age 73.8 years, mean follow-up 5.1 years, and 47.4% men) were included. For the lateral ventricle and PACC score, the A + T - and A + T + groups demonstrated statistically significantly greater volume expansion and cognitive decline over time than the A - T - group (lateral ventricle: ß = 0.757 cm3/year [95% confidence interval 0.463 to 1.050], P < .001 for A + T - , and ß = 0.889 cm3/year [0.523 to 1.255], P < .001 for A + T + ; PACC: ß = - 0.19 /year [- 0.36 to - 0.02], P = .029 for A + T - , and ß = - 0.59 /year [- 0.80 to - 0.37], P < .001 for A + T +). Notably, the A + T + group exhibited additional brain atrophy including the whole brain (ß = - 2.782 cm3/year [- 4.060 to - 1.504], P < .001), hippocampus (ß = - 0.057 cm3/year [- 0.085 to - 0.029], P < .001), and AD-signature regions (ß = - 0.02 mm/year [- 0.03 to - 0.01], P < .001). Cox proportional hazards models suggested an increased risk of progressing to MCI or dementia in the A + T + group versus the A - T - group (adjusted hazard ratio = 3.35 [1.76 to 6.39]). CONCLUSIONS: In cognitively normal individuals, A + T + compounds brain atrophy and cognitive deterioration, amplifying the likelihood of disease progression. Therapeutic interventions targeting A + T + individuals could be pivotal in curbing brain atrophy, cognitive decline, and disease progression.

Progression of fluid infiltration on non-contrast magnetic resonance imaging in breast cancer-related lymphedema: A comparative analysis with indocyanine green lymphography.

BACKGROUND: Non-contrast magnetic resonance imaging (NMRI) has been reported as valuable for the assessment of lymphedema. However, the correlation between NMRI findings and indocyanine green lymphography (ICG-L) findings remains elusive. METHODS: This single-center retrospective study included 26 patients diagnosed with breast cancer-related lymphedema. We examined the prevalence of fluid infiltration in eight regions of the upper extremity, the type of fluid distribution, and the dominant segment of edema on NMRI in comparison to the ICG-L stage. Statistical analysis was performed using the Cochran-Armitage trend test, Spearman's rank correlation test, and Fisher's exact test. RESULTS: The regional fluid infiltration significantly increased with the progression of the ICG-L stage (hand, forearm, elbow, and upper arm: p = 0.003, <0.001, <0.001, and <0.001, respectively). The fluid distribution significantly advanced with the progression of the ICG-L stage as follows (rs = 0.80; p < 0.001): no edema in ICG-L stage 0, edema in either the hand or elbow in ICG-L stage I, edemas in both the elbow and hand in ICG-L stage II, three segmental edemas centered on the forearm or elbow in ICG-L stage III, and edema encompassing the entire upper limb in ICG-L stage IV-V. Additionally, the dominant segment of edema tended to shift from the hand to the elbow and further to the forearm as the ICG-L stage progressed (p < 0.001). CONCLUSIONS: Fluid infiltration observed on NMRI exhibited distinct patterns with the progression of the ICG-L stage. We believe that anatomical information regarding fluid distribution would potentially contribute to optimizing surgical efficacy.

Assessment of pre-extubating recurrent laryngeal nerve palsy using ultrasound in postoperative patients with esophageal cancer: a prospective observational study.

PURPOSE: Ultrasound performed after extubation has been suggested to be useful for the diagnosis of recurrent laryngeal nerve (RLN) paralysis. However, the use of ultrasound for this purpose before extubation has not been examined. The aim of this study was to examine the versatility (interrater reliability) and usefulness of ultrasound for evaluating the movement of vocal cords before extubation. METHODS: The subjects were 30 patients who underwent radical surgery for esophageal cancer from August 2020 to December 2021. An experienced examiner performed an ultrasound examination before and after elective extubation on the day after surgery to evaluate RLN paralysis and record videos. Bronchoscopy was then performed to make a definite diagnosis. Three anesthetists blinded to the diagnosis also evaluated the cases using the videos, and the versatility of the examination was determined using a kappa test. RESULTS: The diagnostic accuracies of the examiner and three anesthetists were 76.7%, 50.0%, 53.3%, and 46.7%, respectively, and the kappa coefficients for the examiner with the anesthetists were 0.310, 0.502, and 0.169, respectively. The sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of RLN paralysis by the examiner using ultrasound before extubation were 0.57, 0.95, 0.80, and 0.87, respectively. CONCLUSION: These results indicate a lack of versatility of the ultrasound examination based on the low kappa coefficients. However, with an experienced examiner, ultrasound can serve as a non-invasive examination that can be performed before extubation with high accuracy and specificity for diagnosis of postoperative RLN paralysis.

Protocolized oxytocin infusion for elective cesarean delivery: a retrospective before-and-after study.

PURPOSE: To elucidate the clinical impact of the novel oxytocin protocol using a syringe pump with a stratified dose compared with the conventional practice of putting oxytocin into the bag. METHODS: This is a retrospective cohort study. We collected the data of the patients who underwent elective cesarean delivery under neuraxial anesthesia between June 2019 and May 2020. The patients were allocated to two groups according to oxytocin administration methods; the control group (the attending anesthesiologist put oxytocin 5-10 units in the infusion bag and adjusted manually after childbirth) and the protocol group (the oxytocin protocol gave oxytocin bolus 1 or 3 units depending on the PPH risk, followed by 5 or 10 unit h-1 via a syringe pump). We compared the total amount of oxytocin within 24 h postpartum, estimated blood loss, and adverse clinical events within 24 h postpartum between the two groups. RESULTS: During the study period, 262 parturients were included. Oxytocin doses of intraoperative and postoperative were significantly lower in the protocol group (9.7 vs. 11.7 units, intraoperative, 15.9 vs. 18 units, postoperative). The subgroup analyses showed that the impact was more remarkable in the low PPH risk than in the high PPH risk. The multivariate linear regression analyses also confirmed the difference. The groups had no significant difference in blood loss, requirement of additional uterotonics, and other adverse events. CONCLUSIONS: Our oxytocin infusion protocol significantly reduced oxytocin requirements in elective cesarean delivery under neuraxial anesthesia without increasing blood loss. However, we could not find other clinical benefits of the novel protocol.

Time elapsed from definitive diagnosis to surgery for osteonecrosis of the femoral head: a nationwide observational study in Japan.

OBJECTIVES: This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity. DESIGN: Retrospective observational study of a nationwide database. SETTING: The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint. PARTICIPANTS: This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018. MAIN OUTCOME MEASURE: The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis. RESULTS: The median time to surgery was 9 months (IQR 4-22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p<0.001, respectively), in early stage ONFH with no or mild joint destruction (stages II and III, p<0.001), and with joint preserving surgery (p<0.001). The proportion without surgery was 75.8% at 3 months, 59.6% at 6 months, 48.2% at 9 months, 40.5% at 1 year, 22.2% at 2 years and 8.3% at 5 years. CONCLUSION: ONFH has been considered to be an intractable disease that often requires surgical treatment, but the fact that surgery was performed in more than half of the patients within 9 months from diagnosis suggests severe disease with a significant clinical impact. TRIAL REGISTRATION NUMBER: Chiba University ID1049.

Feasibility of Guided Internet-Based Cognitive Behavioral Therapy for Panic Disorder and Social Anxiety Disorder in Japan: Pilot Single-Arm Trial.

BACKGROUND: Cognitive behavioral therapy (CBT) is effective in treating anxiety disorders. Accessibility to CBT has been limited in Japan due to the shortage of therapists. While an open-source e-learning system can be used to create a simple internet-based cognitive behavioral therapy (ICBT) program, the safety and outpatient acceptance of this treatment approach have not been explored in Japan. OBJECTIVE: The aim of this study was to investigate whether outpatients with anxiety disorders could accept and successfully complete the ICBT program with guidance by CBT therapists when implementing therapeutic modules and CBT tasks. Due to being in the initial phase of a novel treatment in Japan, this study was intended for verification with a small sample size. METHODS: In total, 6 adults, including 4 male participants and 2 female participants, were enrolled in a single-arm trial. The intervention involved guided ICBT comprising 12 sessions, including CBT text, comprehension confirmation tests, and explanatory videos about cognitive behavioral models, accessible through a website. The therapist guided the participants in accessing the ICBT program and answering their questions using a chat tool. The primary outcome was anxiety severity assessed using the State-Trait Anxiety Inventory-Trait. Secondary outcomes included the Panic Disorder Severity Scale, Liebowitz Social Anxiety Scale (LSAS), Beck Anxiety Inventory (BAI), Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Working Alliance Inventory-Short Form (WAI-SF). Statistical analyses were performed using paired 2-tailed t tests to assess the changes in clinical symptoms. The total WAI-SF score at the final session was used to evaluate the therapeutic alliance. For statistical analyses, mean changes for total State-Trait Anxiety Inventory-Trait, BAI, Panic Disorder Severity Scale, LSAS, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 scores were analyzed using the paired 2-tailed t test. The 2-sided significance level for hypothesis testing was set at 5%, and 2-sided 95% CIs were calculated. RESULTS: Most participants diligently engaged with the ICBT program. No adverse events were reported. The mean total scores for the primary outcome decreased by 11.0 (SD 9.6) points (95% CI -22.2 to 0.20; Hedges g=0.95), but it was not statistically significant. The mean total scores for the secondary outcomes that assess clinical symptoms decreased, with a significant reduction observed in the BAI of 15.7 (SD 12.1) points (95% CI -28.4 to -3.0; P=.03; Hedges g=1.24). The mean total scores for PDSS and LSAS decreased significantly, by 12.0 (SD 4.24) points (95% CI -50.1 to 26.1; P=.16; Hedges g=1.79) and 32.4 (SD 11.1) points (95% CI -59.7 to -4.3; P=.04; Hedges g=1.38), respectively. Of the participants, 67% (n=4) showed treatment response, and 50% (n=3) achieved remission after the intervention. The therapeutic alliance, measured using the WAI-SF, was moderate. CONCLUSIONS: Guided ICBT may be feasible for the treatment of outpatients with panic disorder and social anxiety disorder in Japan. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN0000038118; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000043439.

Sodium-glucose co-transporter 2 inhibitor therapy reduces the administration frequency of anti-vascular endothelial growth factor agents in patients with diabetic macular oedema with a history of anti-vascular endothelial growth factor agent use: A cohort study using the Japanese health insurance claims database.

AIM: We assessed the effectiveness of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in reducing the administration frequency of anti-vascular endothelial growth factor (VEGF) agents in patients with diabetic macular oedema (DMO) using a health insurance claims database. MATERIALS AND METHODS: This retrospective cohort study analysed health insurance claims data covering 11 million Japanese patients between 2005 and 2019. We analysed the frequency and duration of intravitreal injection of anti-VEGF agents after initiating SGLT2is or other antidiabetic drugs. RESULTS: Among 2412 matched patients with DMO, the incidence rates of anti-VEGF agent injections were 230.1 per 1000 person-year in SGLT2i users and 228.4 times per 1000 person-year in non-users, respectively, and the risk ratio for events was unchanged in both groups. Sub-analysis of each baseline characteristic of the patients showed that SGLT2is were particularly effective in patients with a history of anti-VEGF agent use [p = .027, hazard ratio (HR): 0.44, 95% confidence interval (CI): 0.22-0.91]. SGLT2is reduced the risk for the first (p = .023, HR: 0.45, 95% CI: 0.22-0.91) and second (p = .021, HR: 0.39, 95% CI: 0.17-0.89) anti-VEGF agent injections. CONCLUSIONS: There was no difference in the risk ratio for the addition of anti-VEGF therapy between the two treatment groups. However, the use of SGLT2is reduced the frequency of anti-VEGF agent administration in patients with DMO requiring anti-VEGF therapy. Therefore, SGLT2i therapy may be a novel, non-invasive, low-cost adjunctive therapy for DMO requiring anti-VEGF therapy.

Three-dimensional non-contrast magnetic resonance lymphography severity stage for upper extremity lymphedema.

PURPOSES: Non-contrast magnetic resonance lymphography (NMRL) has recently shown the capability of evaluating anatomical fluid distribution in upper extremity lymphedema (UEL). However, there is still a lack of knowledge about the correlation between the characteristic three-dimensional (3D) NMRL findings and the indocyanine green lymphography (ICG-L) findings. Our goal was to clarify the relationship between the 3D NMRL findings and the ICG-L findings. METHODS: Medical charts of patients with secondary UEL who underwent NMRL and ICG-L between January 2018 to October 2021 were reviewed. The upper extremities were divided into 6 regions; the hand, elbow, and the radial and ulnar aspects of the forearm and the upper arm. We investigated the prevalence of characteristic 3D NMRL patterns (Mist/Spray/Inky) in each region based on the ICG-L stage. We also examined the association between the 3D NMRL stage which we proposed and the ICG-L stage, and other clinical factors. RESULTS: A total of 150 regions of 25 patients with upper extremities lymphedema were enrolled in the study. All of the characteristic patterns increased significantly as the ICG-L stage advanced (p < 0.001, < 0.001, and < 0.001, respectively). The predominant NMRL patterns changed significantly from the Early pattern (Mist pattern) to the Advanced pattern (Inky/Spray pattern) as the ICG-L stage progressed (p < 0.001). The higher Stage of 3D NMRL was significantly associated with the progression of the ICG-L stage (rs = 0.80, p < 0.001). CONCLUSIONS: Characteristic 3D NMRL patterns and the 3D NMRL Stage had a significant relationship with the ICG-L stage and other clinical parameters. This information may be an efficient tool for a more precise and objective evaluation of various treatments for UEL patients.

Variability in sonographic anterior drawer test measurements of the ankle: Experienced versus beginner examiners.

BACKGROUND: This study aimed to clarify the variability in the measurements of stress sonography of the ankle and determine the effects of examiner experience on the measurements. METHODS: Twenty examiners (10 experienced and 10 beginners) were included in the study. Each examiner performed stress ultrasonography on a patient with a chronic anterior talofibular ligament injury and a patient with an intact ligament using the reverse anterior drawer method. Changes in ligament length before versus after stress were determined. The same 20 examiners performed ultrasonography on two other patients with an injured or intact ATFL using the anterior drawer method. The length change values and variance were compared between the groups using t-tests and F-tests. RESULTS: Using the reverse anterior drawer method, the change in the anterior talofibular ligament length was 3.3 mm (range, 2.2-4.8 mm) in the experienced group and 2.7 mm (0.0-4.1 mm) in the beginner group for the ligament injured patient. The length changes for the patient with intact anterior talofibular ligament were 0.5 mm (0.1-0.9 mm) and 0.4 mm (-0.1-1.5 mm) in the experienced and beginner groups, respectively. There were no significant intergroup differences in measurement amount (P = 0.37) or variance (P = 0.72). Similarly, using the anterior drawer method, no significant differences between the groups were found in measurement amount or variance. CONCLUSION: The quantitative evaluation of stress sonography of the ankle was variable regardless of examiner experience or stress method, particularly in patients with an anterior talofibular ligament injury. The amount of variability appeared to be unacceptably large for clinical application. Our study results highlight the need for technical standardization.

A Descriptive Study of the Characteristics of Homicide-Suicide in Forensic Autopsy Cases.

Homicide followed by suicide (HS) is a tragic event with varied characteristics across countries and regions. Compared to Western countries, there are limited studies on HS in Asian countries. Therefore, this study aimed to clarify the characteristics of recent HS cases by examining forensic autopsy records from 2008 to 2020 collected from the Department of Legal Medicine, Chiba University, in Japan. A total of 77 HS cases were identified, involving 77 perpetrators (52 completed suicides, 25 attempted suicides), with 28 perpetrator and 89 victim autopsies. Our findings showed that older adults accounted for nearly half of the victims; victims were mostly females, whereas most perpetrators were male. The most common HS relationship was that between a parent and a child. Autopsy findings showed that the most common cause of death was strangulation, and illegal drugs were detected only in a few cases; however, psychotropic drugs were detected in child victims. No obvious evidence of past child physical abuse by caregivers was found. In contrast, intimate partner violence (IPV) was present, with a history of IPV found in half of HS cases involving adult intimate partner relationships. Notably, gender differences in age and relationship to the victim were identified. Likewise, some perpetrators may have expressed their plans and intentions for HS before the event, which may represent an important sign for HS prevention. However, to accurately reveal the course of HS, nationwide integrated statistics, forensic autopsies, including toxicological analyses of the deceased; and forensic psychiatric perspectives, including psychological autopsy, are required.

A multicenter phase II trial of the triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for a cisplatin-containing regimen. - PATROL-I.

Dexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after short-term administration. Therefore, developing a steroid-free antiemetic regimen is an important issue to consider. Thus, the purpose of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine in a multi-institutional phase II study. Chemotherapy-naive patients scheduled to receive cisplatin were enrolled and evaluated for the occurrence of chemotherapy-induced nausea and vomiting during 120 h after chemotherapy. The primary endpoint of the study was total control (TC) in the overall phase. The key secondary endpoint was complete response (CR), which was assessed in the acute, delayed, and overall phase, respectively. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events. Eighty-five patients were enrolled from 8 centers in Japan, of which 83 were evaluable for analyses. The percentage of patients who achieved TC during the overall phase was 31.3%. CR was achieved in 61.4%, 84.3%, and 65.1% of patients during the overall, acute, and delayed phases, respectively. The most frequently reported adverse event was anorexia. The primary endpoint was below the threshold and we could not find benefit in the dexamethasone-free regimen, but CR during the overall phase was similar to that of the conventional three-drug regimen. This antiemetic regimen without dexamethasone might be an option for patients for whom corticosteroids should not be an active application.

Comparison of the effect of surgical versus transcatheter aortic valve replacement on the development of postoperative acute kidney injury.

Acute kidney injury (AKI) frequently occurs after cardiac surgery. Recently, transcatheter aortic valve implantation (TAVI), a less invasive option for aortic stenosis (AS), has been increasingly performed, particularly in elderly patients. We retrospectively investigated and compared the incidence and risk factors of postoperative AKI in patients who underwent surgical aortic valve replacement (SAVR) and TAVI. This was a retrospective single-center study. Seven days postoperatively, data were obtained from medical records. Patients were classified into SAVR and TAVI groups based on age, according to the policy of the Japanese Circulation Society. A total of 155 patients underwent surgery for AS between January 2020 and December 2021. Variables included age, sex, risk score, preoperative left ventricular ejection fraction, hypertension, and renal dysfunction. AKI was defined in accordance with the Kidney Disease: Improving Global Outcomes criteria. A total of 33 SAVR and 79 TAVI procedures were included in this study. The incidences of AKI in the SAVR and TAVI groups were 45.5% and 43.0%, respectively. No significant differences existed between the two groups. Weight (p = 0.0392) and pre-renal dysfunction (p = 0.0308) affected the incidence of AKI in the SAVR group, whereas no such variables were identified in the TAVI group. Within the current age-based treatment selection criteria for AS, no significant difference in the incidence of AKI was observed between the two procedures.Although preoperative renal function may be associated with postoperative AKI, further studies are required to select the optimal surgical procedure for patients with renal dysfunction.

The effect of assisted reproductive technology on postpartum bleeding: hormonal cycle frozen embryo transfer might increase blood loss.

BACKGROUND: Among assisted reproductive technologies, frozen thawed embryo transfer (FET) is associated with increased blood loss at delivery. Anesthesiologists need to be aware of new factors that affect postpartum blood loss. This study investigated whether FET cycles with or without hormonal support affect the amount of postpartum bleeding. METHODS: We conducted a retrospective cohort study of patients admitted for delivery at a single university hospital between January 2015 and December 2018. Patients were divided into no-assisted reproductive technology (No-ART), hormonal cycle FET (HC-FET) and natural cycle FET (NC-FET) group. The primary outcome was the amount of blood loss after delivery (median [interquartile range]), which was compared among the three groups. Multiple regression analysis was performed to investigate the factors affecting blood loss. RESULTS: Between 2015 and 2018, 3187 women delivered neonates. In vaginal delivery, postpartum blood loss in the HC-FET group (1060 [830] g) was significantly greater than in the NC-FET group (650 [485] g, P = 0.001) and in the No-ART group (590 [420] g P < 0.001). Multiple linear regression analysis showed that HC-FET (P < 0.001) was one of the independent factors for the amount of bleeding. In cesarean delivery, the HC-FET group had more blood loss than the No-ART group (910 [676] g vs. 784 [524] g, P = 0.039). However, HC-FET was not an independent factor for postpartum blood loss. CONCLUSIONS: The HC-FET group had more blood loss than the No-ART group for both vaginal and cesarean deliveries. Furthermore, HC-FET was an independent factor that increased postpartum blood loss in vaginal deliveries.

Lymphatic venous anastomosis and complex decongestive therapy for lymphoedema: randomized clinical trial.

BACKGROUND: Lymphatic venous anastomosis is associated with a low incidence of lower extremity lymphoedema-associated cellulitis; however, the exact relationship is unknown. This multicentre RCT evaluated the effect of lymphatic venous anastomosis on prevention of cellulitis. METHODS: Patients with secondary lower extremity lymphoedema who underwent at least 3 months of non-operative decongestive therapy were assigned randomly to lymphatic venous anastomosis or conservative therapy. The primary and secondary outcomes were cellulitis frequency, and assessments of circumference, hardness, and pain respectively. RESULTS: Overall, 336 patients were divided into two groups: 225 in the full-analysis set (primary outcome 225; secondary outcomes 170) and 156 in the per-protocol set (primary outcome 156; secondary outcomes 110). In both analyses, lymphatic venous anastomosis with non-operative decongestive therapy was more effective in preventing cellulitis than non-operative decongestive therapy alone; the difference between groups in reducing cellulitis frequency over 6 months was -0.35 (95 per cent c.i. -0.62 to -0.09; P = 0.010) in the full-analysis set (FAS) and -0.60 (-0.94 to -0.27; P = 0.001) in the per-protocol set (PPS) Limb circumference and pain were not significantly different, but lymphatic venous anastomosis reduced thigh area hardness (proximal medial and distal and lateral proximal). Four patients experienced contact dermatitis with non-operative decongestive therapy alone. CONCLUSION: Lymphatic venous anastomosis in combination with non-operative decongestive therapy prevents cellulitis. REGISTRATION NUMBER: UMIN00025137, UMIN00031462.

Volume-outcome relationships for extracorporeal membrane oxygenation in acute myocardial infarction.

Acute myocardial infarction (MI) is one of the major scenarios of extracorporeal membrane oxygenation (ECMO) use. The utilization of mechanical circulatory support systems including ECMO varies widely at the hospital level, while whether ECMO volume per hospital is associated with outcomes in acute MI is unclear. Using a Japanese nationwide administrative database, a total of 26,913 patients with acute MI undergoing percutaneous coronary intervention from 154 hospitals were included. The relations among PCI volume for acute MI, observed and predicted in-hospital mortality, and observed and predicted rates of ECMO use were evaluated at the hospital level. Of 26,913 patients, 423 (1.6%) were treated with ECMO, and 1561 (5.8%) died during the hospitalization. Median ECMO use per hospital per year was 0.5. An observed rate of ECMO use was linearly correlated with the predicted probability of ECMO use and was not associated with the observed/predicted in-hospital mortality ratio. The observed/predicted mortality ratio was lowest in hospitals with the observed/predicted ECMO use ratio of around one. In conclusion, ECMO was infrequently used in a setting of acute MI at each hospital annually. An observed rate of ECMO use was not associated with observed/predicted in-hospital mortality ratio, while the observed/predicted in-hospital mortality ratio was lowest when ECMO was used as predicted, suggesting that standardized ECMO use may be an institutional quality indicator in acute MI.

The association between intraoperative anesthesia methods used during gastric cancer surgery and long-term mortality: A retrospective observational study using a Japanese claims database.

PURPOSE: Various basic and clinical studies have investigated the association between the types of anesthetic agents and prognosis. However, the results have varied among studies and remain controversial. In the present study, we aimed to investigate whether the risk of all-cause mortality differs between inhaled or intravenous anesthetics in patients with gastric cancer undergoing gastrectomy. METHODS: Using a Japanese nationwide insurance claims database, we analyzed patients who underwent gastrectomy under general anesthesia for gastric cancer between January 2005 and September 2019. Postoperative outcomes were compared between two groups: those who received inhaled anesthetics (Sevoflurane, Isoflurane, or Desflurane) and those who received intravenous anesthetics (propofol), using a multivariable Cox proportional hazards model. The primary outcome was overall survival. RESULTS: Among 2671 eligible patients, 2105 were in the inhaled anesthetic group, and 566 were in the intravenous anesthetic group. The median (interquartile range) age was 58 (51-63) years, and 1979 (74.1%) were men. The median follow-up period was 795 days. We identified 56 (2.7%) and 16 (2.8%) deaths during the follow-up period in the inhaled and intravenous anesthetic use groups, respectively. There was no difference in postoperative overall survival between the two groups (hazard ratio, 0.97; 95% confidence interval, 0.56-1.70; P = 0.93). CONCLUSIONS: We found no significant difference in the postoperative risks of overall survival between inhaled and intravenous anesthesia in patients with gastric cancer undergoing gastrectomy.