Treatment trends in patients with de novo metastatic prostate cancer in the era of upfront combination therapy.

OBJECTIVES: The objective of this study is to assess the trends in treatment selection for patients with de novo metastatic castration-sensitive prostate cancer in the era of upfront combination therapy. METHODS: This multicenter retrospective study included 595 patients treated with either upfront combination therapy (upfront novel hormonal therapies and taxane-based chemotherapy) or vintage therapy (androgen deprivation therapy with or without bicalutamide) between 2016 and 2021. High tumor burden metastatic disease was defined when a patient met the CHAARTED or LATITUDE criteria. We evaluated trends in treatment selection and reasons for selecting vintage therapy. RESULTS: Of the 595, 123 and 472 patients were classified as having low and high tumor-burden disease, respectively. The Use of upfront combination therapy was found to be rapidly increasing with utilization rates of 72% and 54% in 2021 for high and low tumor-burden disease, respectively. Multivariable logistic regression analysis found older age, poor performance status, and nonacademic center were significantly associated with the selection of vintage therapy. Of the 163 patients who received vintage hormone therapy after approval of upfront therapy, 74.2% had a specific reason for avoiding upfront therapy. The reasons for selecting vintage therapy included refusal (39.8%), older age (67.6%), frailty (56.3%), and comorbidity (40.8%). Furthermore, 16.9% of patients declined upfront combination therapy due to cost concerns. CONCLUSION: Upfront combination therapy use has 72% and 54% prevalence among patients with high and low tumor burden diseases, respectively, in this current practice. Older age, poor performance status, and facility bias were negatively associated with the use of upfront combination therapy.

Effects of apalutamide dose reduction on skin-related adverse events in patients with advanced prostate cancer: A multicenter retrospective study.

BACKGROUND: We aimed to evaluate the effects of apalutamide dose reduction on skin-related adverse events (AEs) and castration-resistant prostate cancer (CRPC)-free survival in patients with advanced prostate cancer (PC). METHODS: We retrospectively evaluated 35 patients with nonmetastatic CRPC and 72 patients with treatment-naïve metastatic castration-sensitive PC (mCSPC) who were treated with apalutamide. The primary outcome was the effect of apalutamide dose reduction on skin-related AEs. The secondary outcomes were the effect of apalutamide dose reduction on skin-related AEs in patients with small body size, postskin AE apalutamide discontinuation rate, and CRPC-free survival in patients with mCSPC treated with upfront apalutamide plus androgen deprivation therapy. RESULTS: Of the 107 patients, 65 (60.7%) and 42 (39.3%) were treated with full and reduced doses of apalutamide, respectively. The skin-related AE rate was not significantly different between the groups (55% vs. 43%, p = 0.761). In the group receiving reduced apalutamide dose, the incidence of skin-related AEs was significantly lower in patients with small body sizes (body weight <67 kg and body mass index <24 kg/m2 ) than in those with other body sizes. The postskin AE apalutamide discontinuation rate was significantly differed between patients receiving the full (50%) and reduced (16.7%) doses. In the 72 patients with mCSPC, CRPC-free survival was not significantly different between the full and reduced dose groups. CONCLUSION: Apalutamide dose reduction was not significantly associated with the incidence of skin-related AEs. However, dose reduction in patients with small body sizes may alleviate skin-related AEs without sacrificing oncological outcomes.

Inhibitory action of B-type natriuretic peptide on adrenocorticotropic hormone in patients with acute coronary syndrome.

In addition to the classical actions of hemodynamic regulation, natriuretic peptides (NPs) interact with various neurohumoral factors that are deeply involved in the pathophysiology of cardiovascular diseases. However, their effects on the hypothalamic-pituitary-adrenal (HPA) axis, which is activated under acute high-stress conditions in acute coronary syndrome (ACS), remain largely unknown. We investigated the impact of plasma B-type NP (BNP) on plasma adrenocorticotropic hormone (ACTH)-cortisol levels during the acute phase of ACS ischemic attacks. The study population included 436 consecutive patients with ACS for whom data were collected during emergency cardiac catheterization. Among them, biochemical data after acute-phase treatment were available in 320 cases, defined as the ACS-remission phase (ACS-rem). Multiple regression analyses revealed that plasma BNP levels were significantly negatively associated with plasma ACTH levels only during ACS attacks (P < 0.001), but not in ACS-rem, whereas plasma BNP levels were not significantly associated with plasma cortisol levels at any point. Accordingly, covariance structure analyses were performed to clarify the direct contribution of BNP to ACTH by excluding other confounding factors, confirming that BNP level was negatively correlated with ACTH level only during ACS attacks (ß = -0.152, P = 0.002), whereas BNP did not significantly affect ACTH in ACS-rem. In conclusion, despite the lack of a significant direct association with cortisol levels, BNP negatively regulated ACTH levels during the acute phase of an ACS attack in which the HPA axis ought to be activated. NP may alleviate the acute stress response induced by severe ischemic attacks in patients with ACS.NEW & NOTEWORTHY BNP negatively regulates ACTH during a severe ischemic attack of ACS in which hypothalamic-pituitary-adrenal axis ought to be activated, indicating an important role of natriuretic peptides as a mechanism of adaptation to acute critical stress conditions in humans.

Comparison of efficacy and medical costs between upfront docetaxel and abiraterone treatments of metastatic hormone-sensitive prostate cancer patients in real-world practice: a multicenter retrospective study.

PURPOSE: We compared the real-world efficacy and medical costs for treatment with upfront docetaxel (DOC) and abiraterone acetate (ABI) up to progression-free survival 2 (PFS2) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: This multicenter retrospective study included 340 patients with mHSPC treated with either upfront DOC or upfront ABI between October 2015 and December 2021. We compared PFS2 and medical costs between the two treatment groups. PFS2 was defined as the time from first-line therapy to progression on second-line therapy. Medical costs were estimated using the National Health Insurance drug prices in 2022 in Japan. RESULTS: The upfront DOC and ABI groups included 107 and 233 patients, respectively. The incidence of metastatic castration-resistant PC progression was significantly higher in the upfront DOC group compared with the incidence in the upfront ABI group. However, no significant differences in PFS2 were observed between the two treatment groups. Monthly medical costs per patient were significantly higher in the upfront ABI group ($3453) compared with the costs in the upfront DOC group ($1239, P < 0.001). The cost differences were significantly influenced by differences in the length of androgen deprivation therapy monotherapy (DOC group, 13.4 months vs. ABI group, 0.0 months). CONCLUSIONS: We observed a significant cost benefit in the upfront DOC group in Japanese real-world practice, while the PFS2 rates were similar between the groups. Upfront DOC was a more cost-effective option for men with mHSPC who were eligible for toxic chemotherapy.

Long-term outcomes of percutaneous revascularization for internal mammary artery-left anterior descending artery bypass failure.

Despite the excellent long-term results of internal mammary artery (IMA)-left anterior descending (LAD) bypass, percutaneous revascularization of IMA is sometimes required for IMA-LAD bypass failure. However, its clinical outcomes have not been fully elucidated. The aim of this study was to investigate the long-term clinical outcomes, including target lesion revascularization (TLR) following contemporary percutaneous revascularization of failed IMA bypass graft. We examined data of 59 patients who had undergone percutaneous revascularization of IMA due to IMA-LAD bypass failure at nine hospitals. Patients with IMA graft used for Y-composite graft or sequential bypass graft were excluded. The incidence of TLR was primarily examined, whereas other clinical outcomes including cardiac death, myocardial infarction, and target vessel revascularization were also evaluated. Mean age of the enrolled patients was 67.4 ± 11.3 years, and 74.6% were men. Forty patients (67.8%) had anastomotic lesions, and 17 (28.8%) underwent revascularization within three months after bypass surgery. Procedural success was achieved in 55 (93.2%) patients. Stent implantation was performed in 13 patients (22.0%). During a median follow-up of 1401 days (interquartile range, 282-2521 days), TLR was required in six patients (8.5% at 1, 3, and 5 years). Patients who underwent percutaneous revascularization within 3 months after surgery tended to have a higher incidence of TLR. Clinical outcomes of IMA revascularization for IMA-LAD bypass failure were acceptable.

Impact of nephroureterectomy on postoperative renal function in upper tract urothelial carcinoma: A multicenter retrospective study.

OBJECTIVE: To assess the impact of radical nephroureterectomy on postoperative renal function in patients with upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively evaluated 645 patients with UTUC treated with radical nephroureterectomy between January 2000 and May 2022. The primary outcome was the rate of postoperative estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 . Secondary outcomes included the rate of eGFR decline, identification of factors related to eGFR decline, and the impact of comorbidities (diabetes or cardiovascular disease) on postoperative eGFR at 1 year. RESULTS: The median preoperative and postoperative eGFR levels were 55.6 and 43.3 mL/min/1.73 m2 , respectively. The rate of patients with preoperative and postoperative eGFR ≥60 mL/min/1.73 m2 was 40.9% and 9.0%, respectively. The median decline in eGFR after surgery was 25.1%. The presence of preoperative unilateral hydronephrosis and eGFR <60 mL/min/1.73 m2 was significantly associated with a low decline of postoperative eGFR and poor survival. The impact of the presence of comorbidities on postoperative eGFR at 1 year was significant (p < 0.001). CONCLUSION: Impaired renal function is prevalent in patients with UTUC. The rate of patients with postoperative eGFR ≥60 mL/min/1.73 m2 was 9.0%. The presence of preoperative renal impairment was significantly related to a low decline in postoperative eGFR and poor survival. The presence of comorbidities had a significant effect on eGFR decline 1 year after radical nephroureterectomy.

Trends in the use of local intervention for metastatic hormone-naïve prostate cancer: A multicenter retrospective study.

OBJECTIVE: To evaluated the trends of local intervention and their impact on oncological outcomes in metastatic hormone-naïve prostate cancer (mHNPC) in real-world practice. METHODS: This retrospective multicenter study included 760 patients treated with either androgen deprivation therapy (ADT) without local treatment (no castration-resistant prostate cancer [CRPC] progression within 12 months, control group) or ADT plus local intervention (intervention group) between January 2005 and March 2022. We evaluated the trends in the use of local intervention in patients with mHNPC and factors associated with CRPC-free survival in the intervention group. RESULTS: The use of local intervention gradually increased in combination with upfront combination treatment (docetaxel or androgen receptor axis-targeted agents) for the duration of our study. The number of patients with local intervention combined with upfront treatment was significantly higher in patients with high tumor burden disease than in those with low tumor burden disease. Of the 108 patients who received local intervention, a duration of ≤7 months of initial therapy before local intervention and a level of prostate-specific antigen ≥0.20 ng/mL at the time of local intervention were significantly associated with poor CRPC-free survival. CONCLUSIONS: The use of local intervention in combination with upfront therapy to treat mHNPC increased for the duration of our study regardless of the tumor burden. Local intervention in addition to the standard of care for mHNPC may be a feasible treatment option for selected patients, taking into consideration the duration of and response to initial treatment.

Posterior tibial slope and meniscal slope correlate with in vivo tibial internal rotation during running and drop jump.

PURPOSE: The relationship between tibial bony and meniscus anatomy and knee kinematics during in vivo, high-impact activities remains unclear. This study aimed to determine if the posterior tibial slope (PTS) and meniscal slope (MS) are associated with in vivo anterior-posterior translation and internal tibia rotation during running and double-leg drop jumps in healthy knees. METHODS: Nineteen collegiate athletes performed fast running at 5.0 m/s on an instrumented treadmill and double-leg drop jump from a 60 cm platform while biplane radiographs of the knee were acquired at 150 Hz. Tibiofemoral kinematics were determined using a validated model-based tracking process. Medial and lateral PTS and MS were measured using magnetic resonance imaging (MRI). RESULTS: In fast running, more internal tibia rotation was associated with greater PTS (ρ = 0.336, P = 0.039) and MS (ρ = 0.405, P = 0.012) in the medial knee compartment. In the double-leg drop jump, more internal tibia rotation was associated with greater PTS (ρ = 0.431, P = 0.007) and MS (ρ = 0.323, P = 0.005) in the medial knee compartment, as well as a greater PTS in the lateral knee compartment (ρ = 0.445, P = 0.005). CONCLUSION: These findings suggest that the medial and lateral PTS and medial MS are associated with the amount of knee rotation during high-impact activities. These in vivo findings improve our understanding of ACL injury risk by linking bone and meniscus morphology to dynamic kinematics.

Effect of upfront intensive therapy on oncological outcomes in older patients with high tumor burden metastatic castration-sensitive prostate cancer: A multicenter retrospective study.

BACKGROUND: The effect of upfront intensive therapy on the prognosis of older patients with metastatic castration-sensitive prostate cancer (mCSPC) remains unclear. Thus, we assessed the impact of older age (≥75 years) on oncological outcomes in mCSPC patients with a high tumor burden. METHODS: This multicenter retrospective study included 252 patients aged ≥75 years treated with either upfront or conventional therapy between 2014 and 2021. We compared castration-resistant prostate cancer (CRPC)-free survival (FS) and overall survival (OS) between patients with androgen deprivation therapy (ADT) plus upfront intensive therapy (docetaxel [DTX] or abiraterone acetate [ABI] plus prednisolone) and conventional therapy (ADT monotherapy or ADT combined with bicalutamide). We evaluated the effect of upfront intensive therapy on prognosis by multivariable Cox regression analysis. RESULTS: The 231 patients enrolled in our study were classified in the conventional group (n = 148) or the upfront group (n = 104; DTX = 27 and ABI = 77). The upfront group had significantly prolonged CRPC-FS and OS compared with the conventional group, and this was also the case in the background-adjusted multivariable Cox regression analysis. CONCLUSION: Patients aged ≥75 years who received upfront intensive therapy had significantly longer CRPC-FS and OS compared with similar age patients treated with conventional therapy in real-world practice. The oncological benefit may not diminish in this older population.

Japanese Orthopaedic Association (JOA) clinical practice guidelines on the management of lateral epicondylitis of the humerus - Secondary publication.

BACKGROUND: The guidelines presented herein provide recommendations for the management of patients with lateral epicondylitis of the humerus. These recommendations are endorsed by the Japanese Orthopaedic Association (JOA) and Japan Elbow Society. METHODS: The JOA lateral epicondylitis guideline committee revised the previous guidelines on the basis of the "Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014", which emphasized the importance of the balance between benefit and harm, and proposed a desirable method for preparing clinical guidelines in Japan. These guidelines consist of 11 clinical questions (CQs), 9 background questions (BQs), and 3 future research questions (FRQs). For each CQ, outcomes from the literature were collected and evaluated systematically according to the adopted study design. RESULTS: The committee proposed recommendations for each CQ by determining the level of evidence and assessing the consensus rate. Physical therapy was the best recommendation with the best evidence. The BQs and FRQs were answered by collecting evidence based on the literature. CONCLUSIONS: The guidelines presented herein were reviewed systematically, and recommendations were proposed for each CQ. These guidelines are expected to be widely used not only by surgeons or physicians but also by other healthcare providers, such as nurses, therapists, and athletic trainers.

Exogenous ANP Treatment Ameliorates Myocardial Insulin Resistance and Protects against Ischemia-Reperfusion Injury in Diet-Induced Obesity.

Increasing evidence suggests natriuretic peptides (NPs) coordinate interorgan metabolic crosstalk. We recently reported exogenous ANP treatment ameliorated systemic insulin resistance by inducing adipose tissue browning and attenuating hepatic steatosis in diet-induced obesity (DIO). We herein investigated whether ANP treatment also ameliorates myocardial insulin resistance, leading to cardioprotection during ischemia-reperfusion injury (IRI) in DIO. Mice fed a high-fat diet (HFD) or normal-fat diet for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. Left ventricular BNP expression was substantially reduced in HFD hearts. Intraperitoneal-insulin-administration-induced Akt phosphorylation was impaired in HFD hearts, which was restored by ANP treatment, suggesting that ANP treatment ameliorated myocardial insulin resistance. After ischemia-reperfusion using the Langendorff model, HFD impaired cardiac functional recovery with a corresponding increased infarct size. However, ANP treatment improved functional recovery and reduced injury while restoring impaired IRI-induced Akt phosphorylation in HFD hearts. Myocardial ultrastructural analyses showed increased peri-mitochondrial lipid droplets with concomitantly decreased ATGL and HSL phosphorylation levels in ANP-treated HFD, suggesting that ANP protects mitochondria from lipid overload by trapping lipids. Accordingly, ANP treatment attenuated mitochondria cristae disruption after IRI in HFD hearts. In summary, exogenous ANP treatment ameliorates myocardial insulin resistance and protects against IRI associated with mitochondrial ultrastructure modifications in DIO. Replenishing biologically active NPs substantially affects HFD hearts in which endogenous NP production is impaired.

Possible Association Between Body Temperature and B-Type Natriuretic Peptide in Patients With Cardiovascular Diseases.

BACKGROUND: In addition to various biological effects of natriuretic peptides (NP) on cardiovascular systems, we recently reported that NP raises intracellular temperature in cultured adipocytes. We herein examined the possible thermogenic action of NP in consideration of hemodynamic parameters and inflammatory reaction by proposing structural equation models. METHODS AND RESULTS: The study population consisted of 1985 consecutive patients who underwent cardiac catheterization. Covariance structure analyses were performed to clarify the direct contribution of plasma B-type NP (BNP) to body temperature (BT) by excluding other confounding factors. A hierarchical path model showed increase in BNP, increase in C-reactive protein and decrease in left ventricular ejection fraction were mutually associated. As expected, C-reactive protein was positively correlated with BT. Importantly, despite a negative correlation between BNP and left ventricular ejection fraction, a decrease in the left ventricular ejection fraction was associated with BT decrease, whereas elevation in BNP level was associated with BT increase independently of C-reactive protein level (P = .007). CONCLUSIONS: Patients with LV dysfunction tend to manifest a decrease in BT, whereas BNP elevation is associated with an increase in BT independently of inflammatory response. These findings suggest the adaptive heat-retaining property of NP (and/or NP-associated factors) when BT falls owing to unfavorable hemodynamic conditions in a state of impaired cardiac function.

Impact of pretreatment anemia on upfront abiraterone acetate therapy for metastatic hormone-sensitive prostate cancer: a multicenter retrospective study.

BACKGROUND: Anemia has been a known prognostic factor in metastatic hormone-sensitive prostate cancer (mHSPC). We therefore examined the effect of anemia on the efficacy of upfront abiraterone acetate (ABI) in patients with mHSPC. METHODS: We retrospectively evaluated 66 mHSPC patients with high tumor burden who received upfront ABI between 2018 and 2020 (upfront ABI group). We divided these patients into two groups: the anemia-ABI group (hemoglobin < 13.0 g/dL, n = 20) and the non-anemia-ABI group (n = 46). The primary objective was to examine the impact of anemia on the progression-free survival (PFS; clinical progression or PC death before development of castration resistant PC) of patients in the upfront ABI group. Secondary objectives included an evaluation of the prognostic significance of upfront ABI and a comparison with a historical cohort (131 mHSPC patients with high tumor burden who received androgen deprivation therapy (ADT/complete androgen blockade [CAB] group) between 2014 and 2019). RESULTS: We found that the anemia-ABI group had a significantly shorter PFS than the non-anemia-ABI group. A multivariate Cox regression analysis showed that anemia was an independent prognostic factor of PFS in the upfront ABI group (hazard ratio, 4.66; P = 0.014). Patients in the non-anemia-ABI group were determined to have a significantly longer PFS than those in the non-anemia-ADT/CAB group (n = 68) (P < 0.001). However, no significant difference was observed in the PFS between patients in the anemia-ABI and the anemia-ADT/CAB groups (n = 63). Multivariate analyses showed that upfront ABI could significantly prolong the PFS of patients without anemia (hazard ratio, 0.17; P < 0.001), whereas ABI did not prolong the PFS of patients with anemia. CONCLUSION: Pretreatment anemia was a prognostic factor among mHSPC patients who received upfront ABI. Although the upfront ABI significantly improved the PFS of mHSPC patients without anemia, its efficacy in patients with anemia might be limited.

Trends in the use of neoadjuvant chemotherapy and oncological outcomes for high-risk upper tract urothelial carcinoma: a multicentre retrospective study.

OBJECTIVE: To evaluate temporal trends in neoadjuvant chemotherapy (NAC) utilisation and outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: We included 289 patients from seven hospitals who underwent radical nephroureterectomy (RNU) for locally advanced UTUC (≥cT3 or cN+) between 2000 and 2020. These patients received RNU alone or two to four courses of NAC with either a cisplatin- or carboplatin-based regimen. We evaluated the temporal changes in NAC use and compared the visceral recurrence-free, cancer-specific, and overall survival rates. The effect of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models. RESULTS: Of 289 patients, 144 underwent NAC followed by RNU (NAC group) and 145 underwent RNU alone (Control [Ctrl] group). NAC use increased significantly from 19% (2006-2010), 58% (2011-2015), to 79% (2016-2020). Pathological downstaging was significantly higher in the NAC group than in the Ctrl group. The IPTW-adjusted multivariable analyses showed that NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group. Moreover, carboplatin-based NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group among patients with chronic kidney disease Stage ≥3. There were no significant differences in oncological outcomes between the cisplatin- and carboplatin-based regimens. CONCLUSIONS: The use of NAC for high-risk UTUC increased significantly after 2010. Platinum-based short-term NAC followed by immediate RNU may not impede and potentially improves oncological outcomes.

Clinical Outcomes Following Emergent Percutaneous Coronary Intervention for Acute Total/Subtotal Occlusion of the Left Main Coronary Artery.

BACKGROUND: Data regarding the clinical features, outcomes and prognostic factors in patients presenting with acute total/subtotal occlusion of the unprotected left main coronary artery (LMCA) remain limited.Methods and Results:From a multi-center registry, 134 patients due to acute total/subtotal occlusion of the unprotected LMCA were reviewed. Emergency room (ER) status classification was defined according to the presence of cardiogenic shock and cardiopulmonary arrest (CPA) in the ER (class 1=no cardiogenic shock; class 2= cardiogenic shock but not CPA; and class 3=CPA). In-hospital mortality and cerebral performance category (CPC) as the endpoints were evaluated. One-half (67/134) of the enrolled patients presented with total occlusion of the unprotected LMCA. Regarding ER status classification, class 1, 2, and 3 were observed in 30.6%, 45.5%, and 23.9% of the patients, respectively. In-hospital mortality occurred in 73 (54.5%) patients; of the remaining patients, 52 (85.3%) could be discharged with a CPC 1 or 2. ER status classification (odds ratio 4.4 [95% confidence interval: 2.33-10.67]; P<0.001) and total occlusion of the unprotected LMCA (odds ratio 8.29 [95% confidence interval 2.93-23.46]; P<0.001) were strong predictors of in-hospital mortality. CONCLUSIONS: Acute total/subtotal occlusion involving the unprotected LMCA appeared to be associated with high in-hospital mortality. ER status classification and initial flow in the unprotected LMCA were significant predictive factors of in-hospital mortality.

Comparison of nivolumab plus ipilimumab with tyrosine kinase inhibitors as first-line therapies for metastatic renal-cell carcinoma: a multicenter retrospective study.

BACKGROUND: This study compared real-world outcomes of metastatic renal-cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors or nivolumab plus ipilimumab. METHODS: Using the International mRCC Database Consortium (IMDC), we retrospectively evaluated intermediate- and poor-risk mRCC patients who were treated with nivolumab plus ipilimumab (Nivo-Ipi), tyrosine kinase inhibitors (TKIs) as the first-line therapy between August 2015 and January 2020. We compared oncological outcomes between the Nivo-Ipi group and TKIs group using multivariate logistic regression analysis with the inverse probability of treatment weighting (IPTW) method. RESULTS: In this study 278 patients were included. There were 52 and 226 patients in the Nivo-Ipi and TKIs groups (sunitinib 97, axitinib 118, sorafenib 9, pazopanib 2), respectively. The median age in the Nivo-Ipi and TKIs groups were 69 and 67 years, respectively. There was no significant difference in age, performance status, history of nephrectomy, and the IMDC risk group distribution between the groups. The objective response rate was significantly higher in the Nivo-Ipi group (38%) than in the TKIs group (23%, P = 0.018). The IPTW-adjusted Cox regression analysis showed that a significantly longer progression-free survival (hazard ratio 0.60, P = 0.039) and overall survival (hazard ratio 0.51, P = 0.037) rates in the Nivo-Ipi group than those in the TKIs group. CONCLUSIONS: The oncological outcomes of patients receiving the first-line therapy of nivolumab plus ipilimumab in real-world practice were significantly improved in comparison with first-line TKIs therapy.

Comparison of pembrolizumab with conventional chemotherapy after first-line platinum-based chemotherapy for advanced urothelial carcinoma in real-world practice: A multicenter retrospective study.

OBJECTIVES: To assess the clinical benefit of pembrolizumab as second-line therapy for advanced urothelial carcinoma. METHODS: We retrospectively compared the effects of pembrolizumab with those of conventional chemotherapy on the prognosis of patients with advanced urothelial carcinoma at six hospitals between January 2004 and August 2020. We compared the oncological outcomes between the patients treated with pembrolizumab and those treated with conventional chemotherapy using Kaplan-Meier curve analysis and multivariate Cox regression analysis with the inverse probability of treatment weighting method. RESULTS: The numbers of patients in the pembrolizumab and chemotherapy groups were 121 and 67, respectively. Patients in the pembrolizumab group were significantly older (median 72 vs 66 years, P = 0.001), and had poor Eastern Cooperative Oncology Group performance status (median 1 vs 0, P = 0.001). The unadjusted Kaplan-Meier curve analysis showed no significant differences in the median overall survival from the first-line chemotherapy (24.7 months vs 16.3 months, P = 0.159). Inverse probability of treatment weighting-adjusted multivariate Cox proportional hazards analyses showed a significant difference between the pembrolizumab and chemotherapy groups in overall survival (P = 0.003, hazard ratio 0.63). CONCLUSIONS: Despite the non-negligible age difference between the trial and our clinical practice, our study supports the benefit of second-line pembrolizumab over chemotherapy in real-world practice.

Diagnosis of cardiac sarcoidosis despite negative findings on serial late gadolinium enhancement with cardiac magnetic resonance imaging/18F-fluorodeoxyglucose positron emission tomography examinations.

We present a case of a 42-year-old Japanese man with ocular and pulmonary sarcoidosis who eventually led to a diagnosis with cardiac sarcoidosis (CS) through endomyocardial biopsy (EMB), despite negative findings on both late gadolinium enhancement with cardiac magnetic resonance (LGE-CMR) imaging and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Cardiac sarcoidosis (CS) develops in only 5% of patients with systemic sarcoidosis. Previous studies have reported that CS was found in up to 50% of autopsy series with fatal sarcoidosis, implying that CS is frequently underdiagnosed with potentially life-threatening consequences. Therefore, the diagnostic accuracy and prognostic value of CS are important. Currently, LGE-CMR and FDG-PET play an important role in establishing a diagnosis of CS with high sensitivity. In the presented case, regardless of serial examinations with LGE-CMR and FDG-PET, confirmed diagnosis of CS could not be achieved; ultimately, a definitive diagnosis of CS was obtained through EMB. To the best of our knowledge, this is the first reported case showing the diagnosis of CS despite negative findings on serial LGE-CMR and FDG-PET examinations.

Efficacy and safety of nivolumab for renal cell carcinoma in patients over 75 years old from multiple Japanese institutes.

PURPOSE: Despite nivolumab being increasingly used for treating metastatic renal cell carcinoma (mRCC), differing findings have been reported about its efficacy and safety in elderly patients. Thus, this study was aimed at evaluating nivolumab's efficacy and safety for treating mRCC in Japanese patients aged ≥ 75 years. METHODS: From March 2013 to August 2019, 118 mRCC patients (89 men and 29 women) were treated with nivolumab. The objective response rates (ORRs) were compared between patients aged ≥ 75 and < 75 years. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were also compared between the two age-groups. RESULTS: The median follow-up duration after nivolumab initiation was 10 months. At the time of nivolumab initiation, 22 and 96 patients were aged ≥ 75 and < 75 years, respectively. Intergroup differences in patient characteristics except for age were not significant. Furthermore, intergroup differences in ORR (14 vs 23%; P = 0.367), PFS (HR 0.74, 95% CI 0.37-1.51; P = 0.414), and median OS (HR 1.29, 95% CI 0.68-2.46; P = 0.433) were not significant. The incidence of nivolumab discontinuation due to AEs was significantly higher in the ≥ 75 years group (27% vs 7%; P = 0.028), although the intergroup difference in the AE incidence rate was not significant (55% vs 43.8%; P = 0.535). CONCLUSIONS: Nivolumab's effectiveness was comparable between the two patient groups, except for early AE-related discontinuation in the ≥ 75 year group.

Effect of elbow MRI with axial traction on articular cartilage visibility-a feasibility study.

OBJECTIVE: Accurate evaluation of the articular cartilage of the elbow using MRI is sometimes challenging because of its anatomical complexity and relatively small size. Moreover, the articular cartilage of the humerus is in close contact with the opposing cartilage surfaces. Magnetic resonance arthrography with traction was reported to resolve this issue; however, less invasive methods are desirable. This study aimed to assess the effect of MRI with axial traction (without arthrography) on joint space widening and cartilage outline visibility of the elbow. MATERIALS AND METHODS: We enrolled 10 volunteers (female = 1; mean age, 36.7 ± 8.6; range 28-56) and performed MRI with and without axial traction on the elbow. Joint space widths were measured, and the humeral articular cartilage outline visibility was evaluated at the radiocapitellar joint and lateral one-third and medial one-third of the ulnohumeral joints. Measurements were compared using the Wilcoxon signed-rank test. Significance was set at p < 0.05. Volunteers scored pain and discomfort during MRI with traction using the visual analog scale in a questionnaire format. RESULTS: Traction significantly increased joint space width at the radiocapitellar joint. Humeral articular cartilage outline visibility also significantly improved at the radiocapitellar joint. Pain and discomfort scores during traction MRI were low. CONCLUSION: MRI of the elbow with traction widens joint space and enables better articular cartilage visibility at the radiocapitellar joint. Anatomical features of the elbow might have affected these results. Therefore, it would be safe and useful for evaluating elbow injuries involving articular cartilage lesions.