Pre-first-line chemotherapy risk stratification for overall survival in advanced urothelial carcinoma in sequential therapy era.

PURPOSE: To explore pre-treatment risk factors for overall survival (OS) in advanced urothelial carcinoma (UC) patients treated with first-line (1L) chemotherapy in sequential therapy (ST) era. Additionally, to evaluate the proportion of patients who were not able to undergo subsequent immune checkpoint inhibitor (ICI) therapy according to the subgroups stratified by the risk factors. METHODS: A multicenter retrospective study was conducted. Metastatic or locally advanced UC patients treated between 2017 and 2022 were included. The Kaplan-Meier method with the log-rank test and multivariate Cox regression models were used to address OS. RESULTS: Three hundred and fourteen patients treated with 1L chemotherapy were included in the study and 57 (18.2%) patients were not able to proceed to subsequent ICI therapy. Pre-chemotherapy risk factors for OS in 314 patients were ECOG-PS 1 or more, having no primary site resection, C-reactive protein (CRP) level of 3 mg/dL or more, and non-cisplatin-based regimen. Patients having 3 or 4 risk factors had higher risk for not being able to receive ST (Mann-Whitney U test, P < 0.001). As risk factors for OS in 230 patients who were able to receive ST, having no primary site resection, a neutrophil to lymphocyte ratio of 3 or more, and the presence of liver metastasis were identified. CONCLUSION: We reported the risk factors for OS in advanced UC patients treated with 1L chemotherapy in ST era. Patients with high risk for OS may not be able to proceed to subsequent ICI therapy even in the ST era.

Soluble Immune Checkpoint Molecules as Predictors of Efficacy in Immuno-Oncology Combination Therapy in Advanced Renal Cell Carcinoma.

Immuno-oncology (IO) combination therapy is the first-line treatment for advanced renal cell carcinoma (RCC). However, biomarkers for predicting the response to IO combination therapy are lacking. Here, we investigated the association between the expression of soluble immune checkpoint molecules and the therapeutic efficacy of IO combination therapy in advanced RCC. The expression of soluble programmed cell death-1 (sPD-1), soluble programmed cell death ligand-1 (sPD-L1), soluble PD-L2 (sPD-L2), and lymphocyte activation gene-3 (sLAG-3) was assessed in plasma samples from 42 patients with advanced RCC who received first-line IO combination therapy. All IMDC risk classifications were represented among the patients, including 14.3, 57.1, and 28.6% with favorable, intermediate, and poor risk, respectively. Univariate analysis revealed that prior nephrectomy, sPD-L2 levels, and sLAG-3 levels were significant factors affecting progression-free survival (PFS), whereas multivariate analyses suggested that sPD-L2 and sLAG-3 levels were independent prognostic factors for PFS. In a univariate analysis of the overall survival, prior nephrectomy and sPD-L2 levels were significant factors; no significant differences were observed in the multivariate analysis. No significant correlation was observed between the sPD-L2 and sLAG-3 levels and PD-L2 and LAG-3 expression via immunohistochemistry. In conclusion, sPD-L2 and sLAG-3 expression may serve as a potential biomarker for predicting IO combination therapy efficacy.

Prostate brachytherapy seed migration to the right renal artery due to right-to-left shunting across a patent foramen ovale.

Introduction: The seeds used in brachytherapy for prostate cancer may migrate through the surrounding venous plexus to other sites in the body, most commonly to the pulmonary vasculature. Case presentation: A 78-year-old Japanese man received iodine-125 low-dose-rate prostate brachytherapy. Computed tomography revealed that one seed had migrated to the right kidney. No seed was observed in the ureter upon ureteroscopy. Transesophageal echocardiography confirmed a right-to-left shunt due to a patent foramen ovale, suggesting that the seed had migrated into the right renal artery. Three years after treatment, no recurrence of prostate cancer and no adverse events due to seed migration or due to the patent foramen ovale occurred. Conclusion: Arteriovenous malformations and a right-to-left shunt should be suspected if a brachytherapy seed has migrated to an artery of the systemic circulatory system.

A qualitative study on the process of dietitians working in pharmacies to practice dietary habit improvement support in their daily work

Background: Recently in Japan, there have been some cases of pharmacies staffed with dietitians in an effort to improve their health support functions. However, there have been few reports on the effects of these efforts, and it has been pointed out that dietitians may not be fully exercising their professional abilities. We conducted a before-and-after comparison study in 2022 to confirm the effectiveness of collaboration between pharmacy dietitians and pharmacists in supporting patients with type 2 diabetes. Objective: This study aimed to investigate the process by which dietitians who participated in our research project became accustomed to providing continuous dietary counseling as a matter of habit. Methods: Semi-structured interviews were conducted with three dietitians and two pharmacists. The main questions asked were about 1) the nature of their work before they began providing the interventions, 2) the aspects they paid attention to while providing the interventions, 3) what they felt they had changed during the intervention period, and4) what they considered obstacles to providing nutritional guidance in their pharmacies. Results: The responses of the participants regarding the nature of their work before they began providing interventions were mostly related to their “work as a dispensing clerk.” The dietitians also indicated their desire for more continuous dietary support. The responses of the participants regarding what they felt had changed during the intervention period included numerous references to having an “opportunity for trial and error” and obtaining the “cooperation of staff.” In the responses regarding what the participants considered obstacles, the dietitians mentioned “recognition by patients” and “an environment in which they can consult with patients.”... (AU)

The Accuracy and Potential Racial and Ethnic Biases of GPT-4 in the Diagnosis and Triage of Health Conditions: Evaluation Study.

BACKGROUND: Whether GPT-4, the conversational artificial intelligence, can accurately diagnose and triage health conditions and whether it presents racial and ethnic biases in its decisions remain unclear. OBJECTIVE: We aim to assess the accuracy of GPT-4 in the diagnosis and triage of health conditions and whether its performance varies by patient race and ethnicity. METHODS: We compared the performance of GPT-4 and physicians, using 45 typical clinical vignettes, each with a correct diagnosis and triage level, in February and March 2023. For each of the 45 clinical vignettes, GPT-4 and 3 board-certified physicians provided the most likely primary diagnosis and triage level (emergency, nonemergency, or self-care). Independent reviewers evaluated the diagnoses as "correct" or "incorrect." Physician diagnosis was defined as the consensus of the 3 physicians. We evaluated whether the performance of GPT-4 varies by patient race and ethnicity, by adding the information on patient race and ethnicity to the clinical vignettes. RESULTS: The accuracy of diagnosis was comparable between GPT-4 and physicians (the percentage of correct diagnosis was 97.8% (44/45; 95% CI 88.2%-99.9%) for GPT-4 and 91.1% (41/45; 95% CI 78.8%-97.5%) for physicians; P=.38). GPT-4 provided appropriate reasoning for 97.8% (44/45) of the vignettes. The appropriateness of triage was comparable between GPT-4 and physicians (GPT-4: 30/45, 66.7%; 95% CI 51.0%-80.0%; physicians: 30/45, 66.7%; 95% CI 51.0%-80.0%; P=.99). The performance of GPT-4 in diagnosing health conditions did not vary among different races and ethnicities (Black, White, Asian, and Hispanic), with an accuracy of 100% (95% CI 78.2%-100%). P values, compared to the GPT-4 output without incorporating race and ethnicity information, were all .99. The accuracy of triage was not significantly different even if patients' race and ethnicity information was added. The accuracy of triage was 62.2% (95% CI 46.5%-76.2%; P=.50) for Black patients; 66.7% (95% CI 51.0%-80.0%; P=.99) for White patients; 66.7% (95% CI 51.0%-80.0%; P=.99) for Asian patients, and 62.2% (95% CI 46.5%-76.2%; P=.69) for Hispanic patients. P values were calculated by comparing the outputs with and without conditioning on race and ethnicity. CONCLUSIONS: GPT-4's ability to diagnose and triage typical clinical vignettes was comparable to that of board-certified physicians. The performance of GPT-4 did not vary by patient race and ethnicity. These findings should be informative for health systems looking to introduce conversational artificial intelligence to improve the efficiency of patient diagnosis and triage.

Prevention of local symptoms in muscle invasive bladder cancer patients: clinical significance of local radiation therapy.

PURPOSE: To evaluate the significance of local radiation therapy (LRT) for prevention of local symptoms (LSs) caused by muscle-invasive bladder cancer (MIBC). METHODS: We retrospectively reviewed the clinical records of 133 patients from 13 hospitals. MIBC patients with or without metastases who were treated with LRT alone from January 2015 through December 2020 were enrolled. Exclusion criteria were urinary diversion (UD) prior to LRT, non-MIBC, or lack of clinical information. LSs were defined as hematuria requiring invasive treatment or transfusion, UD after LRT, bladder tamponade, and opioid use for bladder pain. RESULTS: One hundred fourteen patients were finally enrolled in the study. During the median follow-up period of 13.5 months, 30 patients (26.3%) had LSs. Risk factors of LSs in multivariate analysis were a prior history of non-MIBC (NMIBC) (hazard ratio [HR] 2.99; 95% confidence interval [CI], 1.36 to 6.56; P < 0.01), radiation dose of less than 50 Gray (Gy) (HR 3.99; 95% CI, 1.80 to 8.82; P < 0.01), and tumor stage 3 or more (HR 2.43; 95% CI, 1.14 to 5.21; P = 0.02). Risk factors of overall survival (OS) in multivariate analysis were being female (HR 3.32; 95% CI, 1.68 to 6.58; P < 0.01), an age-adjusted Charlson Comorbidity index of 6 or more (HR 2.19; 95% CI, 1.18 to 4.10; P = 0.01), distant metastases (HR 3.20; 95% CI, 1.39 to 6.58; P < 0.01), and tumor size of 40 mm or more (HR 2.38; 95% CI, 1.34 to 4.52; P < 0.01). Toxicity (all grades) occurred in 40.4% of the patients, 4.8% with grade 3 or more and 95.2% with lower grades. CONCLUSIONS: We determined the risk factors for LSs in MIBC patients treated with LRT alone. An escalated-dose of 50 Gy or more may contribute to prevention of LSs caused by MIBC. Thus, dose-escalated LRT for MIBC patients who can expect favorable survival may be a good option to avoid future annoying LSs.

Difference in symptom manifestation between postmenopausal and premenopausal women in acute uncomplicated cystitis: A multi-institutional pilot study.

Objectives: We aimed to prospectively compare lower urinary tract symptoms in premenopausal and postmenopausal women with acute uncomplicated cystitis before and after antibiotic therapy. Materials and methods: This study included adult women with acute uncomplicated cystitis who visited 4 institutions between 2019 and 2020. After registration, we administered oral antibiotics and prospectively documented the changes in lower urinary tract symptoms from the first visit to a follow-up visit at 1 week using the Core Lower Urinary Tract Symptoms Score (CLSS) questionnaire. Results: After treatment, pyuria disappeared in 60 of the 66 patients (14 premenopausal and 46 postmenopausal). The CLSS total score (range) changed from 13 (3-29) to 4 (0-18) with a significant improvement in all CLSS items. At baseline, nocturia, urgency, and urgency incontinence were more prominent in postmenopausal women than in premenopausal women. In contrast, baseline urethral pain and quality of life index were more severe in premenopausal women than in postmenopausal women. After treatment, the CLSS total score was still higher in postmenopausal women, as reflected by the relatively higher scores for nocturia and urgency, irrespective of the comparable scores for urethral pain and the quality of life index in the 2 groups. Conclusions: Our results suggest that if storage symptoms persist, they should be carefully interpreted according to menopausal status.

Prognostic Value of Absolute Lymphocyte Count in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab Plus Ipilimumab.

Nivolumab and ipilimumab (NIVO + IPI) is standard therapy for patients with advanced renal cell carcinoma (RCC). Absolute lymphocyte count (ALC) is a valuable prognostic factor in patients with various cancers treated with immune checkpoint inhibitors. Herein, we determined the prognostic value of pretreatment ALC in advanced RCC patients treated with NIVO + IPI as first-line therapy. Data from 46 advanced RCC patients treated with NIVO + IPI between September 2018 and August 2022 were retrospectively reviewed and analyzed. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with low than high ALC (PFS: p = 0.0095; OS: p = 0.0182). Multivariate analysis suggested that prior nephrectomy [hazard ratio (HR) = 3.854, 95% confidence interval (CI) = 1.433-10.359, p = 0.0075] and pretreatment ALC (HR = 2.513, 95% CI = 1.119-5.648, p = 0.0257) were independent factors for PFS. Our new prognostic ALNx model based on ALC and prior nephrectomy suggested that the poor-risk group was a predictor of significantly worse PFS (p < 0.0001) and OS (p = 0.0016). Collectively, the developed ALNx model may be a novel predictor of response in advanced RCC patients treated with NIVO + IPI.

Ferric derisomaltose for the treatment of iron deficiency anemia with postpartum hemorrhage: Results of a single-arm, open-label, phase 3 study in Japan.

AIM: Single-arm, open-label, phase 3 study to evaluate the efficacy and safety of ferric derisomaltose (FDI) for iron deficiency anemia (IDA) in Japanese women with postpartum hemorrhage (PPH). METHODS: Postpartum women aged 20-39 years with serum ferritin <25.0 ng/ml, hemoglobin (Hb) <10.0 g/dl, and blood loss ≥500 ml within 24 h post-delivery were eligible to receive high-dose intravenous FDI. The primary endpoint was the maximum change in Hb concentration by Week 8. Key secondary endpoints included change in iron parameters and percentage of patients with a total Edinburgh Postnatal Depression Score (EPDS) ≥9. Safety assessments included treatment-emergent adverse events (TEAEs) and iron concentrations in maternal milk. RESULTS: All (n = 21 [100.0%]) patients received the predetermined total iron dose by Day 8. Hb concentrations increased rapidly and significantly (p < 0.001) following FDI. Serum ferritin levels also increased rapidly and were maintained near or above the upper limit of normal reference value (250 ng/ml). Following FDI, two (9.5%) patients had a total EPDS score of ≥9. TEAEs occurred in 23 of 42 (54.8%) patients and neonates overall, including 18 of 21 (85.7%) patients and 5 of 21 (23.8%) neonates. TEAEs were mild in all adult patients and four neonates, and moderate in one neonate. Iron concentrations in maternal milk remained within normal reference values. Appropriate patient selection and patient-adjusted dosage selection facilitated safe and effective administration of high-dose (≥1000 mg) FDI. CONCLUSIONS: Rapid and sustained improvements in Hb and iron stores occurred following FDI for IDA with PPH, with no new safety signals identified. CLINICAL TRIAL IDENTIFIER: JapicCTI-194888.

A case of emphysematous pyelonephritis caused by the hypermucoviscosity phenotype of Klebsiella pneumoniae.

A 70-year-old woman presented to our hospital with 38.2 °C fever. She was diagnosed with high-risk emphysematous pyelonephritis caused by string test-positive Klebsiella pneumoniae and treated with multidisciplinary therapy. The patient developed pyogenic spondylitis during the course of the disease. This is the first reported case of emphysematous pyelonephritis caused by the hypermucoviscosity phenotype of K. pneumoniae and the second reported case of pyogenic spondylitis. The hypermucoviscosity phenotype of K. pneumoniae should be considered as an etiologic agent of emphysematous pyelonephritis.

Olfactory identification ability in patients with mild cognitive impairment and Alzheimer's disease.

[Purpose] To examine the olfactory identification abilities and specify the difficult-to-identify odors in community-dwelling individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD). [Participants and Methods] We included, 12 and 17 patients with MCI (MCI group) and AD (AD group), respectively, and 30 community-dwelling older adults with no history of MCI or a dementia diagnosis (control group). Scores on the Japanese odor stick identification test (OSIT-J), an olfactory identification ability test, were compared among the three groups with intergroup differences examined accordingly. Next, we performed intergroup comparisons of the ratios of correct responses for each odor, and the difficult-to-identify odors were examined. [Results] OSIT-J scores of the MCI and AD groups were significantly lower than those of the control group. There were no intergroup differences in the correct identification of pungent odors. No patients in the AD group could identify the odor of cooking gas. The ability to identify food-related odors was reduced in the MCI and AD groups. [Conclusion] Patients with MCI and AD had reduced olfactory identification abilities in comparison to community-dwelling older adults without cognitive decline. These findings suggest the importance of olfactory evaluation before providing patients with dementia with therapeutic interventions associated with olfactory stimuli.

Ubiquitin-mediated mitochondrial regulation by MITOL/MARCHF5 at a glance.

Mitochondria are involved in various cellular processes, such as energy production, inflammatory responses and cell death. Mitochondrial dysfunction is associated with many age-related diseases, including neurological disorders and heart failure. Mitochondrial quality is strictly maintained by mitochondrial dynamics linked to an adequate supply of phospholipids and other substances from the endoplasmic reticulum (ER). The outer mitochondrial membrane-localized E3 ubiquitin ligase MITOL/MARCHF5 is responsible for mitochondrial quality control through the regulation of mitochondrial dynamics, formation of mitochondria-ER contacts and mitophagy. MITOL deficiency has been shown to impair mitochondrial function, cause an excessive inflammatory response and increase vulnerability to stress, resulting in the exacerbation of the disease. In this study, we overview the ubiquitin-mediated regulation of mitochondrial function by MITOL and the relationship between MITOL and diseases.

Improved Survival of Real-world Japanese Patients With Advanced Renal Cell Carcinoma Treated With Immuno-oncology Combination Therapy.

BACKGROUND/AIM: Immuno-oncology (IO) combination therapy has become the standard of treatment for advanced renal cell carcinoma (RCC). In this retrospective study, we compared the efficacy of first-line molecular targeted therapy (MTT), administered as monotherapy, and IO combination therapy using real-world data of Japanese patients. PATIENTS AND METHODS: The clinical information of 202 patients with RCC who received MTT (n=144) or IO combination therapy (n=58) at the Kurume University Hospital from May 2008 to May 2022 was collected and retrospectively analyzed. The Cox proportional hazards model was used for univariate and multivariate analyses, with hazard ratios (HRs) and 95% confidence intervals (CIs) calculated. RESULTS: The patients treated with IO combination therapy had a prolonged progression-free survival (PFS) compared with those treated with MTT (p=0.0038). IO combination therapy was significantly associated with a better PFS in patients with intermediate (p=0.0072) and poor risk (p=0.0411) but not in those with favorable risk (p=0.5434). Furthermore, overall survival with IO combination therapy was significantly better in patients at poor risk (p=0.0335). Multivariate analyses suggested that prior nephrectomy (HR=1.501, 95%CI=1.048-2.150, p=0.0268) and first-line therapy (HR=1.962, 95%CI=1.288-2.986, p=0.0017) were independent prognostic factors for PFS. CONCLUSION: IO combination therapy significantly improved the PFS of patients with advanced RCC, especially those with intermediate- and poor-risk disease. Further investigations focusing on the improvement of survival are warranted.

A pilot study of Pharmacist-Dietician Collaborative support and Advice (PDCA) for patients with type 2 diabetes in community pharmacy: A single-arm, pre-post study.

Background: In Japan, there is a pressing need to improve community health care to cope with the rapid aging of the population. In this context, there have been private-sector-led approaches to enhance community dietary support by employing dietitians in pharmacies. Objectives: To evaluate the effects of collaboration between dietitians and pharmacists working in pharmacies to support patients with type 2 diabetes. Methods: A single group pre- and post-comparative study was conducted on patients with type 2 diabetes mellitus. The intervention period was 6 months. During the intervention period, the dietitians provided dietary support to the patients after first providing them with medication guidance. The contents of these instructions were shared with the pharmacists. The contents of the instructions were recorded, and confirmed in monthly meetings with the principal investigator. The primary endpoint was the Hemoglobin A1c(HbA1c) level, and the secondary endpoints were high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), Triglyceride (TG), degree of dietary self-management, degree of unbalanced diet and satisfaction with pharmacy services. Results: Eight patients completed the intervention period. The first patient's intervention started in March 2021, and all patients' interventions were completed by December 2021. The primary endpoint, the mean (SD) HbA1c, was 7.26 (0.96) at baseline and decreased to 6.63 (0.79) after 6 months (p=0.028, r=0.72). Also, the HDL-c increased from 55.00 (14.81) to 63.14 (10.11) (p=0.110, r=0.51) and the Diabetes Mellitus Dietary Self Efficacy Scale score increased from 51.67 (8.31) to 60.17 (8.45) (p=0.025, r=0.79) and the patient satisfaction score increased 24.0 (4.0) to 26.1 (3.3) (p=0.161, r=0.51). Moderate decreases were also observed in LDL-c (p=0.235, r=0.47) and TG (p=0.368, r=0.37). Conclusions: Collaboration between dietitians and pharmacists working in pharmacies may improve the dietary habits and glycemic control of patients with type 2 diabetes. To verify this hypothesis more reliably, randomized controlled trials need to be conducted.

Slc12a8 in the lateral hypothalamus maintains energy metabolism and skeletal muscle functions during aging.

Sarcopenia and frailty are urgent socio-economic problems worldwide. Here we demonstrate a functional connection between the lateral hypothalamus (LH) and skeletal muscle through Slc12a8, a recently identified nicotinamide mononucleotide transporter, and its relationship to sarcopenia and frailty. Slc12a8-expressing cells are mainly localized in the LH. LH-specific knockdown of Slc12a8 in young mice decreases activity-dependent energy and carbohydrate expenditure and skeletal muscle functions, including muscle mass, muscle force, intramuscular glycolysis, and protein synthesis. LH-specific Slc12a8 knockdown also decreases sympathetic nerve signals at neuromuscular junctions and ß2-adrenergic receptors in skeletal muscle, indicating the importance of the LH-sympathetic nerve-ß2-adrenergic receptor axis. LH-specific overexpression of Slc12a8 in aged mice significantly ameliorates age-associated decreases in energy expenditure and skeletal muscle functions. Our results highlight an important role of Slc12a8 in the LH for regulation of whole-body metabolism and skeletal muscle functions and provide insights into the pathogenesis of sarcopenia and frailty during aging.

Protective roles of MITOL against myocardial senescence and ischemic injury partly via Drp1 regulation.

Abnormal mitochondrial fragmentation by dynamin-related protein1 (Drp1) is associated with the progression of aging-associated heart diseases, including heart failure and myocardial infarction (MI). Here, we report a protective role of outer mitochondrial membrane (OMM)-localized E3 ubiquitin ligase MITOL/MARCH5 against cardiac senescence and MI, partly through Drp1 clearance by OMM-associated degradation (OMMAD). Persistent Drp1 accumulation in cardiomyocyte-specific MITOL conditional-knockout mice induced mitochondrial fragmentation and dysfunction, including reduced ATP production and increased ROS generation, ultimately leading to myocardial senescence and chronic heart failure. Furthermore, ischemic stress-induced acute downregulation of MITOL, which permitted mitochondrial accumulation of Drp1, resulted in mitochondrial fragmentation. Adeno-associated virus-mediated delivery of the MITOL gene to cardiomyocytes ameliorated cardiac dysfunction induced by MI. Our findings suggest that OMMAD activation by MITOL can be a therapeutic target for aging-associated heart diseases, including heart failure and MI.

Are there differences in the characteristics of patients who respond to gemcitabine plus cisplatin chemotherapy and those who respond to pembrolizumab therapy for metastatic urothelial carcinoma? Multicenter retrospective study.

OBJECTIVES: To evaluate factors to predict overall survival of metastatic urothelial carcinoma patients treated with gemcitabine plus cisplatin chemotherapy or pembrolizumab therapy. METHODS: We retrospectively evaluated two metastatic urothelial carcinoma cohorts treated with (i) gemcitabine plus cisplatin or (ii) pembrolizumab. The gemcitabine plus cisplatin cohort was treated from December 2005 through December 2014 while the pembrolizumab cohort was treated from January 2018 through December 2020. Using multivariate analyses, we evaluated the risk factors for overall survival in each cohort and compared them. None of the gemcitabine plus cisplatin cohort patients were treated with pembrolizumab. All patients in the pembrolizumab cohort were treated with prior platinum-based chemotherapy. RESULTS: There were 184 patients in the gemcitabine plus cisplatin cohort and 91 in the pembrolizumab cohort. The mean follow-up periods were 714 and 284 days, respectively. In multivariate analysis, the risk factors for overall survival in the gemcitabine plus cisplatin cohort were liver metastasis, worse Eastern Cooperative Oncology Group performance status (1 or more), no primary site resection, and a high prognostic index (1 or more). In the pembrolizumab cohort, liver metastasis, bone metastasis, and worse Eastern Cooperative Oncology Group-performance status (1 or more), and high prognostic index (1 or more) were the risk factors for overall survival. In the pembrolizumab cohort, patients with a complete response or partial response during prior platinum-based chemotherapy had better overall survival with the following pembrolizumab treatment than those with stable or progressive disease (P = 0.004). CONCLUSIONS: Considering the similarity of these risk factors in two sequential treatments, it may be possible to predict the response to pembrolizumab according to the response to prior chemotherapy.

Pregnancy Outcomes With Exposure to Second-Generation Antipsychotics During the First Trimester.

Objective: To investigate the risk of major congenital malformations associated with exposure to second-generation antipsychotics (SGAs) in the first trimester.Methods: Pregnant women who received consultation on drug exposure from the Japan Drug Information Institute in Pregnancy from October 2005 to December 2016 were asked to complete a questionnaire at 1 month after the expected delivery date. The questionnaire included items on pregnancy outcome, date of delivery, gestational age at delivery, malformations in the infant that were confirmed by the pediatrician's report, and the following parameters at birth: height, weight, head circumference, and chest circumference. Odds ratios (ORs) for major congenital malformations among live-born children of pregnant women with SGA exposure during the first trimester (SGA group) relative to children of women not exposed to SGAs and medications known to be teratogenic (comparison group) were estimated using an inverse probability of treatment weighting approach.Results: Of 404 women with SGA exposure during the first trimester, there were 351 live births, 3 stillbirths, 34 spontaneous abortions, and 16 elective abortions. The rate of major congenital malformations among live-born children was 0.9% (3/351) in the SGA group and 1.8% (70/3,899) in the comparison group. No statistically significant differences were observed in the adjusted OR for major congenital malformations (adjusted OR = 0.44; 95% CI, 0.12-1.48; P = .179).Conclusions: SGA exposure during the first trimester is not associated with an increased risk of major congenital malformations. These findings might be reassuring for pregnant women who require SGAs.

A cross-sectional study of demonstrating expertise and job satisfaction in pharmacists and dietitians working in community pharmacies in Japan.

Background: In Japan, there has been a private-sector initiative to register dietitians in pharmacies. There is not yet an adequate amount of data on the attitudes of dietitians in pharmacies regarding their work. Objectives: To assess the attitudes of pharmacists and dietitians working in community pharmacies in Japan about their work, and particularly about demonstrating expertise and overall job satisfaction. Methods: We administered a web-based questionnaire to pharmacists and dietitians working in pharmacy branches with registered dietitians at two pharmacy chains that agreed to cooperate. We used our own 7-item questionnaire and compared the scores for each item between pharmacists and dietitians. Results: A total of 61 persons (22 pharmacists and 39 dietitians) answered the questionnaire. The item with the highest mean score (standard deviation) for pharmacists was "I feel that I am helpful to patients," at 3.50 (0.74), and for dietitians it was "I have colleagues at my workplace whom I can talk to when I have a problem," at 3.51 (1.00). Conversely, the items with the lowest mean score (standard deviation) were "I am satisfied with my current job" for pharmacists, at 3.14 (0.83), and "I can grow sufficiently as a professional" for dietitians, at 2.41 (0.97). As a result of factor analysis, the seven-item question could be divided into two factors: "demonstrating expertise" and "overall job satisfaction." The factor-score for "demonstrating expertise" was significantly lower for dietitians than for pharmacists (p<0.01), but there was no significant difference in overall job satisfaction between the two professions (p=0.36). Further research is needed to understand why dietitians find "demonstrating expertise" difficult in pharmacies. Conclusions: The attitudes of pharmacists and dietitians working in pharmacies in Japan toward their jobs were shown to consist of "demonstration of expertise" and "overall job satisfaction. Dietitians had significantly lower scores on "demonstration of expertise" than pharmacists.