Risk factors for tibial infections following osteosynthesis - a systematic review and meta-analysis.

Aim: This study aimed to quantitatively summarise risk factors associated with surgical site infection (SSI) following surgically managed tibial fractures. Method: We searched the Embase/Medline, Cochrane Library, and Scopus databases for relevant studies in October 2023. We included original studies investigating risk factors for SSI following surgically managed traumatic tibial fractures that included ≥10 adult patients with SSIs. Meta-analysis was performed when >5 studies investigated the same risk factor. The risk of bias was assessed using the critical appraisal checklist from Joanna Briggs Institute for cohort studies. Results: This study included 42 studies comprising 24,610 patients with surgically managed tibial fractures and 2,418 SSI cases. The following were identified as significant risk factors for SSI (p < 0.05): compartment syndrome (odds ratio [OR] = 3.8, 95% confidence interval [CI]: 2.4-6.0), blood transfusion (OR = 3.8, 95% CI: 2.1-6.6), open fracture (OR = 3.6, 95% CI: 2.5-5.1), Gustilo-Anderson classification >2 (OR = 3.1, 95% CI: 2.1-4.6), external fixation (OR = 2.9, 95% CI: 2.3-3.8), American Society of Anesthesiologists classification >2 (OR = 2.5, 95% CI: 1.5-4.1), polytrauma (OR = 2.4, 95% CI: 1.5-4.0), dual incision approach (OR = 2.1, 95% CI: 1.5-3.0), smoking (OR = 1.8, 95% CI: 1.5-2.1), male sex (OR = 1.6, 95% CI: 1.3-1.8), high energy trauma (OR = 1.5, 95% CI: 1.1-2.1), and prolonged surgery time (OR = 0.62, 0.43-0.82). Other factors, including diabetes, hypertension, and time to surgery, were not identified as risk factors for SSI. However, the included studies were generally of poor quality and at risk of bias. Conclusions: The review provides a basis for preoperatively assessing a patient's risk of developing an SSI, which could be used to initiate adjusted antibiotic regimes and more frequent postoperative controls. Furthermore, it indicates the risk factors future research should include when adjusting for confounding factors.

Cytoreductive Nephrectomy in Select Primary Metastatic Renal Cell Carcinoma Patients: A Comprehensive Nationwide Outcome Analysis.

(1) Background: The role of cytoreductive nephrectomy (CN) is controversial in patients with primary metastatic renal cell carcinoma (mRCC). (2) Methods: We evaluated the impact of CN, or no CN, followed by first-line targeted therapy (TT) in a nationwide unselected cohort of 437 consecutive patients with primary mRCC over a two-year period with a minimum of five years of follow-up. Data sources were national registries supplemented with manually extracted information from individual patient medical records. Cox proportional hazards estimated the hazard ratio (HR) of overall death and cancer-specific death after one and three years. (3) Results: 210 patients underwent CN and 227 did not. A total of 176 patients (40%) had CN followed by TT, 160 (37%) had TT alone, 34 (8%) underwent CN followed by observation, and 67 (15%) received no treatment. After adjustments in Model 2, patients treated with TT alone demonstrated a worsened overall survival (OS) compared to those treated with CN + TT, HR 0.63 (95% CI: 0.19-2.04). (4) Conclusions: In this nationwide study, CN was associated with enhanced outcomes in carefully selected patients with primary mRCC. Further randomized trials are warranted.

Profiling of ERBB receptors and downstream pathways reveals selectivity and hidden properties of ERBB4 antagonists.

ERBB receptor tyrosine kinases are involved in development and diseases like cancer, cardiovascular, neurodevelopmental, and mental disorders. Although existing drugs target ERBB receptors, the next generation of drugs requires enhanced selectivity and understanding of physiological pathway responses to improve efficiency and reduce side effects. To address this, we developed a multilevel barcoded reporter profiling assay, termed 'ERBBprofiler', in living cells to monitor the activity of all ERBB targets and key physiological pathways simultaneously. This assay helps differentiate on-target therapeutic effects from off-target and off-pathway side effects of ERBB antagonists. To challenge the assay, eight established ERBB antagonists were profiled. Known effects were confirmed, and previously uncharacterized properties were discovered, such as pyrotinib's preference for ERBB4 over EGFR. Additionally, two lead compounds selectively targeting ERBB4 were profiled, showing promise for clinical trials. Taken together, this multiparametric profiling approach can guide early-stage drug development and lead to improved future therapeutic interventions.

DaBlaCa-17: nationwide observational study in Denmark on survival before and after implementation of neoadjuvant chemotherapy prior to cystectomy for muscle-invasive bladder cancer.

OBJECTIVE: To investigate the impact of neoadjuvant chemotherapy implementation with gemcitabine-cisplatin on survival outcomes for patients with muscle-invasive bladder cancer in Denmark. MATERIALS AND METHODS: Data were collected on all patients in Denmark undergoing radical cystectomy who were potential candidates for neoadjuvant chemotherapy from 2010 to 2015 (n = 851). A cohort before the implementation of neoadjuvant chemotherapy (Cohort 2010-12) was compared with a cohort after implementation (Cohort 2013-15). Patients in Cohort 2013-15 receiving neoadjuvant chemotherapy (+NAC, n = 213) were compared with patients in Cohort 2013-15 not receiving neoadjuvant chemotherapy (-NAC, n = 139). Pathological results after radical cystectomy and oncological outcomes were compared between the study cohorts. Overall survival, disease-free survival, and disease-specific survival were compared with Kaplan-Meier plots and with univariable and multivariable Cox regression. Kaplan-Meier estimates of overall survival were also performed separately for treating hospital and for pathological stage. RESULTS: Pathological T0 (pT0) was more frequent in patients who received neoadjuvant chemotherapy: 34% versus 18% when comparing Cohort 2013-15 with Cohort 2010-12 (p < 0.001), and 46% versus 16% in +NAC compared with -NAC (p < 0.001). Overall survival, disease-free survival, and disease-specific survival at 5 years after cystectomy were not improved in Cohort 2013-15 compared with Cohort 2010-12 with adjusted hazard ratios of 1.11 (95% confidence interval [CI]: 0.87-1.43), 1.02 (95% CI: 0.81-1.29), and 1.06 (95% CI: 0.80-1.41), respectively. CONCLUSIONS: This observational study found no improved survival in a national cohort of patients with muscle-invasive bladder cancer undergoing radical cystectomy after implementation of NAC. However, reservations should be made regarding the study design and the true effect of NAC on survival outcomes.

STAR® total ankle replacements with BONIT® coating: A prospective 2-17 year follow-up study of 474 ankles from a single center.

BACKGROUND: Different coatings of the metal implants of STAR prostheses have been used since 1999. In Europe metal implants with a double calcium-phosphate coating (BONIT) on a titanium sprayed surface have been available since 1999. METHODS: We present a 2-17 year follow-up of a consecutive series from a single center with 474 STAR ankle replacements where the BONIT type of coating has been used. RESULTS: 55 prostheses (12%) have been revised, the majority of them due to fracture of the mobile bearing. 22 prostheses (5%) have been converted to an arthrodesis. Analysis of survival of the specific components showed an estimated 10-year survival rate of the tibia component, talus component and polyethylene mobile bearing of 99%, 98% and 84%, respectively. The corresponding estimated 15-year survival was 98%, 98% and 74%, respectively. CONCLUSION: This study showed an extraordinary high survival rate of the metal implants. LEVEL OF EVIDENCE: Level III, prospective cohort series.

Lifestyle and Clinical Factors in a Nationwide Stage III and IV Renal Cell Carcinoma Study.

BACKGROUND: The aim was to investigate whether patient-related or clinical risk factors present at the diagnosis of advanced stage renal cell carcinoma (RCC) had an impact on the overall mortality, cancer-specific mortality, and recurrence risk in a national cohort. METHODS: Patients registered with stage III and IV RCC in the Danish Renal Cancer Database (DaRenCa) in 2014-2016 were included in the study and followed up until recurrence or death. We conducted a Cox Proportional Hazard Model to examine the association between several variables and the development of RCC. These variables included BMI, hypertension, smoking status, symptoms at diagnosis, performance status, multidisciplinary team (MDT) discussion, surgical margin, and primary metastasis. Separate analyses were performed for cc-RCC and non-ccRCC patients. RESULTS: In our cohort of 929 patients, 424 individuals died from RCC during the follow-up period, with a median follow-up time of 4.1 (95% CI: 0.8-5.0) years for ccRCC and 2.0 (95% CI: 0.1-5.0) years for non-ccRCC. A multivariate analysis demonstrated that a positive surgical margin (HR 1.53 and 1.43), synchronous metastasis (HR 2.06 and 3.23), and poor performance status (HR 4.73 and 5.27) were significantly associated with a decreased 5-year overall and cancer-specific survival, respectively. Furthermore, a positive surgical margin was associated with a higher risk of recurrence in ccRCC. MDT discussion was found to reduce mortality risk in non-ccRCC. CONCLUSION: Clinical- and disease-related variables have a greater impact on RCC mortality and recurrence than the selected lifestyle-related factors. The inclusion of MDT discussion in the diagnosis and management of advanced RCC should be further evaluated for its potential to improve patient outcomes.

We meat again: a field study on the moderating role of location-specific consumer preferences in nudging vegetarian options.

This field study set out to test whether consumers' history of making decisions in a particular choice context moderated the effectiveness of a nudge intervention to reduce meat consumption. In a Danish hospital canteen that served both staff members and visitors, a combination of nudges (Chef's recommendation sticker + prominent positioning) was implemented to promote vegetarian sandwiches. The sales of these sandwiches increased from 16.45% during the baseline period to 25.16% during the nudge intervention period. Most notably, this increase was caused by the visitors, who had weak location-bound preferences. Hospital staff members (who had strong location-bound preferences) were unaffected by the nudge in their choice. This is an important finding because the two consumer groups did not differ on their person-bound preferences for meat. It seems that behaviour change is best predicted by location-bound preferences, whereas the behaviour itself is best predicted by person-bound preferences. These findings can help organizations in estimating whether a nudge intervention has enough potential for behaviour change, or whether more directive policies are required.

Validation of a semi-automatic software for optical coherence tomography - analysis in heart transplanted patients.

Optical Coherence Tomography (OCT) is an intravascular imaging modality enabling detailed evaluation of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). However, its clinical application remains hampered by time-consuming manual quantitative analysis. We aimed to validate a semi-automated quantitative OCT analysis software (Iowa Coronary Wall Analyzer, ICWA-OCT) to improve OCT-analysis in HTx patients. 23 patients underwent OCT evaluation of all three major coronary arteries at 3 months (3M) and 12 months (12M) after HTx. We analyzed OCT recordings using the semiautomatic software and compared results with measurements from a validated manual software. For semi-automated analysis, 31,228 frames from 114 vessels were available. The validation was based on a subset of 4287 matched frames. We applied mixed model statistics to accommodate the multilevel data structure with method as a fixed effect. Lumen (minimum, mean, maximum) and media (mean, maximum) metrics showed no significant differences. Mean and maximum intima area were underestimated by the semi-automated method (ß-methodmean = - 0.289 mm2, p < 0.01; ß-methodmax = - 0.695 mm2, p < 0.01). Bland-Altman analyses showed increasing semi-automatic underestimation of intima measurements with increasing intimal extent. Comparing 3M to 12M progression between methods, mean intimal area showed minor underestimation (ß-methodmean = - 1.03 mm2, p = 0.04). Lumen and media metrics showed excellent agreement between the manual and semi-automated method. Intima metrics and progressions from 3M to 12M were slightly underestimated by the semi-automated OCT software with unknown clinical relevance. The semi-automated software has the future potential to provide robust and time-saving evaluation of CAV progression.

Speech Tracking in Complex Auditory Scenes with Differentiated In- and Out-Field-Of-View Processing in Hearing Aids.

In naturalistic auditory scenes, relevant information is rarely concentrated at a single location, but rather unpredictably scattered in- and out-field-of-view (in-/out-FOV). Although the parsing of a complex auditory scene is a fairly simple job for a healthy human auditory system, the uncertainty represents a major issue in the development of effective hearing aid (HA) processing strategies. Whereas traditional omnidirectional microphones (OM) amplify the complete auditory scene without enhancing signal-to-noise-ratio (SNR) between in- and out-FOV streams, directional microphones (DM) may greatly increase SNR at the cost of preventing HA users to perceive out-FOV information. The present study compares the conventional OM and DM HA settings to a split processing (SP) scheme differentiating between in- and out-FOV processing. We recorded electroencephalographic data of ten young, normal-hearing listeners who solved a cocktail-party-scenario-paradigm with continuous auditory streams and analyzed neural tracking of speech with a stimulus reconstruction (SR) approach. While results for all settings exhibited significantly higher SR accuracies for attended in-FOV than unattended out-FOV streams, there were distinct differences between settings. In-FOV SR performance was dominated by DM and SP and out-FOV SR accuracies were significantly higher for SP compared to OM and DM. Our results demonstrate the potential of a SP approach to combine the advantages of traditional OM and DM settings without introduction of significant compromises.

Spironolactone alleviates schizophrenia-related reversal learning in Tcf4 transgenic mice subjected to social defeat.

Cognitive deficits are a hallmark of schizophrenia, for which no convincing pharmacological treatment option is currently available. Here, we tested spironolactone as a repurposed compound in Tcf4 transgenic mice subjected to psychosocial stress. In this '2-hit' gene by environment mouse (GxE) model, the animals showed schizophrenia-related cognitive deficits. We had previously shown that spironolactone ameliorates working memory deficits and hyperactivity in a mouse model of cortical excitatory/inhibitory (E/I) dysbalance caused by an overactive NRG1-ERBB4 signaling pathway. In an add-on clinical study design, we used spironolactone as adjuvant medication to the standard antipsychotic drug aripiprazole. We characterized the compound effects using our previously established Platform for Systematic Semi-Automated Behavioral and Cognitive Profiling (PsyCoP). PsyCoP is a widely applicable analysis pipeline based on the Research Domain Criteria (RDoC) framework aiming at facilitating translation into the clinic. In addition, we use dimensional reduction to analyze and visualize overall treatment effect profiles. We found that spironolactone and aripiprazole improve deficits of several cognitive domains in Tcf4tg x SD mice but partially interfere with each other's effect in the combination therapy. A similar interaction was detected for the modulation of novelty-induced activity. In addition to its strong activity-dampening effects, we found an increase in negative valence measures as a side effect of aripiprazole treatment in mice. We suggest that repurposed drug candidates should first be tested in an adequate preclinical setting before initiating clinical trials. In addition, a more specific and effective NRG1-ERBB4 pathway inhibitor or more potent E/I balancing drug might enhance the ameliorating effect on cognition even further.

Risk factors for nonunion following surgically managed, traumatic, diaphyseal fractures: a systematic review and meta-analysis.

Background: There are several studies on nonunion, but there are no systematic overviews of the current evidence of risk factors for nonunion. The aim of this study was to systematically review risk factors for nonunion following surgically managed, traumatic, diaphyseal fractures. Methods: Medline, Embase, Scopus, and Cochrane were searched using a search string developed with aid from a scientific librarian. The studies were screened independently by two authors using Covidence. We solely included studies with at least ten nonunions. Eligible study data were extracted, and the studies were critically appraised. We performed random-effects meta-analyses for those risk factors included in five or more studies. PROSPERO registration number: CRD42021235213. Results: Of 11,738 records screened, 30 were eligible, and these included 38,465 patients. Twenty-five studies were eligible for meta-analyses. Nonunion was associated with smoking (odds ratio (OR): 1.7, 95% CI: 1.2-2.4), open fractures (OR: 2.6, 95% CI: 1.8-3.9), diabetes (OR: 1.6, 95% CI: 1.3-2.0), infection (OR: 7.0, 95% CI: 3.2-15.0), obesity (OR: 1.5, 95% CI: 1.1-1.9), increasing Gustilo classification (OR: 2.2, 95% CI: 1.4-3.7), and AO classification (OR: 2.4, 95% CI: 1.5-3.7). The studies were generally assessed to be of poor quality, mainly because of the possible risk of bias due to confounding, unclear outcome measurements, and missing data. Conclusion: Establishing compelling evidence is challenging because the current studies are observational and at risk of bias. We conclude that several risk factors are associated with nonunion following surgically managed, traumatic, diaphyseal fractures and should be included as confounders in future studies.

Effectiveness of a bandage to prevent re-dislocation after total hip arthroplasty in patients with a previous hip dislocation. A randomized controlled trial with 12-week follow-up.

OBJECTIVE: To investigate if using a hip bandage is more effective than standard care in the prevention of total hip arthroplasty re-dislocation in patients with a previous total hip arthroplasty dislocation. DESIGN: randomized controlled trial. SETTING: Holstebro Regional Hospital and Viborg Regional Hospital. SUBJECTS: A total of 99 patients, 51 women, mean 70.7 (SD 9.9) years were enrolled in an un-blinded, clinical randomized controlled trial. INTERVENTIONS: Participants with at least one previous total hip arthroplasty dislocation were randomized to either wearing a bandage reducing flexion, adduction, and internal rotation of the hip (intervention group) or to standard care (control group). The participants were followed for 12 weeks. Main follow-up measures were as follows: number of re-dislocations (primary outcome), hip disability measured with the Oxford Hip Score (0-48, 48 best), quality of life measured with the 36-Item Short Form Survey (0-100, 100 best), satisfaction with treatment and serious adverse events. Statistical analyses followed the intention-to-treat principle. RESULTS: No significant group differences were observed for the primary outcome re-dislocations (9 versus 15, P = 0.143) or for disability (11.3 versus 14.4, P = 0.161), quality of life (57.7 versus 48.3, P = 0.050) or satisfaction with treatment (P = 0.562). There were 3 serious adverse events leading to total hip arthroplasty revision in the intervention group and 4 in the control group. CONCLUSION: We found that a hip bandage is not superior to standard care in the prevention of total hip arthroplasty re-dislocation in those with a previous total hip arthroplasty dislocation.

How 3D printing and physical reconstruction of a skull helped in a complex pathological case.

Taphonomic changes can mimic pathological bone lesions and make it difficult to distinguish between ante- and postmortem abnormalities and to perform differential diagnostics. 3D methods, such as CT scanning and 3D printing, can be used as complementary tools to overcome the taphonomic changes. Here, we reconstructed a skull of an interesting archeological case showing severe pathological changes using 3D printing and physical reconstruction. The skeleton belonged to an approximately 18-year-old female. The bones of the entire skeleton exhibited several pathological changes. Both cranium and mandible were asymmetric, with a malformed foramen magnum and left zygomatic process, agenesis of the left external acoustic meatus, cribra orbitalia, and a bilateral absence of mental foramen. The overall diagnostic interpretation was hampered by the extensive taphonomic damage that affected the left side of the skull. In particular, the frontal bone showed taphonomic breakage and plastic deformations were present on the left side of the cranium. The skull was CT-scanned and 3D models of all the single bones were 3D printed and manually re-assembled. The intact reconstructed skull was used to estimate the endocranial volume (ECV). We showed how 3D printing and physical reconstruction of the skull helped overcome the extensive taphonomic alterations; the reconstructed skull provides important diagnostic information such as ECV and a better picture of the original ante-mortem pathological state of the skull.

The use of negative pressure wound therapy for fracture-related infections following internal osteosynthesis of the extremity: A systematic review.

This study aimed to systematically review the current literature on studies using negative pressure wound therapy (NPWT) or dressings following fracture-related infection (FRI) in internal osteosynthesis of the extremity. Articles were analyzed on fracture and wound healing and included when comparing or describing the use of either NPWT or dressings in FRI. We conducted a systematic literature search in four electronic databases: Embase, Medline, the Cochrane Library, and Scopus. The studies were screened by two authors using Covidence.org and evaluated for risk of bias. A total of 8576 records were identified. No articles compared NPWT to dressings. Seven case reports and three case series included a total of 115 patients treated for FRI. Fracture healing was achieved in 21 out of 67 patients treated with NPWT (4 amputations and 46 not described) and all 48 patients in the dressing group (4 patients needed additional sequestrectomy procedures). Five studies did not describe fracture healing. In 57 out of 67 patients treated with NPWT, the wounds were described as healed, closed, or requiring soft tissue reconstruction (4 amputations and six lacking description). The dressing group had complete wound coverage in 18 patients and partial coverage in 30 patients. Studies were generally at high risk of bias because of insufficient descriptions of both patient demographics and outcomes. No studies compared NPWT to dressings, and the existing literature is at high risk of bias. The included studies were of low-level evidence. NPWT can be neither recommended nor advised against to cover infected osteosynthesis.

Improved Split TEV GPCR ß-arrestin-2 Recruitment Assays via Systematic Analysis of Signal Peptide and ß-arrestin Binding Motif Variants.

G protein-coupled receptors (GPCRs) are major disease-relevant drug targets; robust monitoring of their activities upon drug treatment is key to drug discovery. The split TEV cell-based assay technique monitors the interaction of an activated GPCR with ß-arrestin-2 through TEV protein fragment complementation using a luminescent signal as the readout. In this work, split TEV GPCR ß-arrestin-2 recruitment assays were optimized to monitor the endogenous ligand-induced activities of six GPCRs (DRD1, DRD2, HTR2A, GCGR, AVPR2, and GLP1R). Each GPCR was tested in four forms; i.e., its wildtype form, a variant with a signal peptide (SP) to facilitate receptor expression, a variant containing the C-terminal tail from the V2 vasopressin receptor (V2R tail) to promote ß-arrestin-2 recruitment, and a variant containing both the SP and V2R tail. These 24 GPCR variants were systematically tested for assay performance in four cell lines (HEK-293, PC12 Tet-Off, U-2 OS, and HeLa). We found that the assay performance differed significantly for each GPCR variant and was dependent on the cell line. We found that V2R improved the DRD2 split TEV assays and that HEK-293 cells were the preferred cell line across the GPCRs tested. When taking these considerations into account, the defined selection of assay modifications and conditions may improve the performance of drug development campaigns that apply the split TEV technique as a screening tool.

Bringing discrete-time Langevin splitting methods into agreement with thermodynamics.

In light of the recently published complete set of statistically correct Grønbech-Jensen (GJ) methods for discrete-time thermodynamics, we revise a differential operator splitting method for the Langevin equation in order to comply with the basic GJ thermodynamic sampling features, namely, the Boltzmann distribution and Einstein diffusion, in linear systems. This revision, which is based on the introduction of time scaling along with flexibility of a discrete-time velocity attenuation parameter, provides a direct link between the ABO splitting formalism and the GJ methods. This link brings about the conclusion that any GJ method has at least weak second order accuracy in the applied time step. It further helps identify a novel half-step velocity, which simultaneously produces both correct kinetic statistics and correct transport measures for any of the statistically sound GJ methods. Explicit algorithmic expressions are given for the integration of the new half-step velocity into the GJ set of methods. Numerical simulations, including quantum-based molecular dynamics (QMD) using the QMD suite Los Alamos Transferable Tight-Binding for Energetics, highlight the discussed properties of the algorithms as well as exhibit the direct application of robust, time-step-independent stochastic integrators to QMD.

Dissipation-Dependent Thermal Escape from a Potential Well.

Langevin simulations are conducted to investigate the Josephson escape statistics over a large set of parameter values for damping and temperature. The results are compared to both Kramers and Büttiker-Harris-Landauer (BHL) models, and good agreement is found with the Kramers model for high to moderate damping, while the BHL model provides further good agreement down to lower damping values. However, for extremely low damping, even the BHL model fails to reproduce the progression of the escape statistics. In order to explain this discrepancy, we develop a new model which shows that the bias sweep effectively cools the system below the thermodynamic value as the potential well broadens due to the increasing bias. A simple expression for the temperature is derived, and the model is validated against direct Langevin simulations for extremely low damping values.

Real-world Treatment Patterns and Overall Survival in Locally Advanced and Metastatic Urothelial Tract Cancer Patients Treated with Chemotherapy in Denmark in the Preimmunotherapy Era: A Nationwide, Population-based Study.

BACKGROUND: Real-world treatment patterns and survival outcomes of locally advanced, unresectable, and metastatic urinary tract cancer (mUTC) patients have not previously been studied in a nationwide, population-based cohort. OBJECTIVE: To describe treatment patterns and survival outcomes in mUTC patients treated in the real-world clinical setting. DESIGN SETTING AND PARTICIPANTS: This nationwide, population-based study included all mUTC patients initiating first-line chemotherapy at Danish oncology departments from January 2010 to March 2016. Data were retrospectively obtained from electronic medical records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcome measurements were descriptive. Kaplan-Meier was used for survival analysis. RESULTS AND LIMITATIONS: Of 952 patients included in the study, 46.2% initiated standard gemcitabine/cisplatin (GC) and 21.1% gemcitabine/carboplatin (CaG); the remaining patients initiated other treatment regimens. Median follow-up was 11.6 mo. The overall response rate and disease control rate were 43.0% and 61.7% in all patients, 51.4% and 69.1% in GC-treated patients, and 34.4% and 58.8% in CaG-treated patients, respectively. Median overall survival (OS) was 11.7 (95% confidence interval [CI]: 10.8-12.5) mo in all patients, 14.0 (95% CI: 12.5-15.5) mo in GC-treated patients, and 9.8 (95% CI: 8.7-10.9) mo in CaG-treated patients. Limitations include the retrospective study design. CONCLUSIONS: Real-world mUTC patients are older and less fit than patients enrolled in clinical trials; despite this, tumor responses and survival are comparable. Survival in our patient cohort is also comparable with that reported from other real-world studies in this patient group. PATIENT SUMMARY: We studied treatment patterns and survival in urinary tract cancer patients receiving chemotherapy in the real-world clinical practice. Survival in our patient cohort was comparable with that reported from clinical trials and other real-world studies in this patient group.

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma.

PURPOSE: Pembrolizumab, a programmed death 1 inhibitor, demonstrated promising single-agent activity in untreated patients with various cancer types. The phase II KEYNOTE-427 study evaluated efficacy and safety of single-agent pembrolizumab in treatment-naive patients with advanced clear cell renal cell carcinoma (ccRCC; cohort A) and advanced non-ccRCC (cohort B). Results of cohort A are reported. METHODS: In this open-label, single-arm phase II study, patients with advanced ccRCC received pembrolizumab 200 mg every 3 weeks for ≤ 24 months. The primary end point was objective response rate by RECIST, version 1.1. RESULTS: In the total population (N = 110), median time from enrollment to data cutoff was 35.9 (range, 29.5-40.3) months. Objective response rate was 36.4% with four (3.6%) complete responses and 36 (32.7%) partial responses; disease control rate was 58.2% (95% CI, 48.4 to 67.5). Most patients (68.2%) had a decrease in target lesions, including 30.9% with a reduction ≥ 60%. Median duration of response was 18.9 (range, 2.3-37.6+) months; 64.1% of responders had a response ≥ 12 months (Kaplan-Meier). Median progression-free survival was 7.1 months (95% CI, 5.6 to 11.0). Median overall survival was not reached; 12-month and 24-month overall survival rates were 88.2% and 70.8%, respectively. Durable responses were observed across all International Metastatic RCC Database Consortium categories. Grade 3-5 treatment-related adverse events were reported in 30.0% of patients, of which colitis and diarrhea were most frequent. CONCLUSION: Single-agent pembrolizumab showed promising antitumor activity as a first-line treatment in patients with advanced ccRCC, with durable responses across International Metastatic RCC Database Consortium categories. Safety and tolerability profile of pembrolizumab monotherapy was comparable to what has been previously described in other tumor types.

Imaging of Cardiac Transplantation: An Overview.

Heart transplantation (HTx) remains the optimal treatment for selected patients with end-stage advanced heart failure. However, survival is limited early by acute rejection and long term by cardiac allograft vasculopathy (CAV). Even though the diagnosis of rejection is based on histology, cardiac imaging provides a pivotal role for early detection and severity assessment of these hazards. The present review focuses on the use and reliability of different invasive and non-invasive imaging modalities to detect and monitor CAV and rejection after HTx. Coronary angiography remains the corner stone in routine CAV surveillance. However, angiograms are invasive and underestimates the CAV severity especially in the early phase. Intravascular ultrasound and optical coherence tomography are invasive methods for intracoronary imaging that detects early CAV lesions not evident by angiograms. Non-invasive imaging can be divided into myocardial perfusion imaging, anatomical/structural imaging and myocardial functional imaging. The different non-invasive imaging modalities all provide clinical and prognostic information and may have a gatekeeper role for invasive monitoring. Acute rejection and CAV are still significant clinical problems after HTx. No imaging modality provides complete information on graft function, coronary anatomy and myocardial perfusion. However, a combination of invasive and non-invasive modalities at different stages following HTx should be considered for optimal personalized surveillance and risk stratification.