Prior Treatment Research Articles

Impact of proton pump inhibitors on the efficacy of androgen receptor signaling inhibitors in metastatic castration-resistant prostate cancer patients.

Proton pump inhibitors (PPIs) are widely used due to their affordability and minimal severe side effects. However, their influence on the efficacy of cancer treatments, particularly androgen receptor signaling inhibitors (ARSIs), remains unclear. This study investigates the impact of PPI usage on the treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 117 mCRPC patients were retrospectively analyzed and divided into two groups based on the concomitant use of PPI at the initiation of ARSI treatment: PPI+ (n = 38) and PPI- (n = 79). Patient characteristics, including age at ARSI treatment administered, prostate-specific antigen (PSA) value at ARSI treatment administered, International Society of Urological Pathology grade group at prostate biopsy, metastatic site at ARSI treatment administered, prior docetaxel (DTX) treatment, and type of ARSI (abiraterone acetate or enzalutamide) were recorded. Progression-free survival (PFS), overall survival (OS), and PSA response rates were compared between the two groups. Patients were further stratified by clinical background to compare PFS and OS between the two groups. The PPI- group exhibited significantly extended PFS and a trend toward improved OS. For PSA response (reduction of 50% or more from baseline), the rates were 62.3% and 45.9% in the PPI- group and the PPI+ group, respectively. For deep PSA response (reductions of 90% or more from baseline), the rates were 36.4% and 24.3% in the PPI- group and the PPI+ group, respectively. The effects were consistent across subgroups divided by prior DTX treatment and type of ARSI administered. The administration of PPIs appears to diminish the therapeutic efficacy of ARSIs in mCRPC patients. Further prospective studies are needed to confirm these findings and explore the biological mechanisms involved.

Pericatheter Leak Associated With Earlier Peritoneal Dialysis Initiation Does Not Influence Long-Term Outcomes

Internationally, peritoneal dialysis (PD) is increasingly being commenced within 2 weeks of catheter insertion. Studies are warranted to evaluate outcomes of this strategy. This study examines outcomes of early-start PD (ESPD) and conventional-start PD (CSPD), commencing at≤14 days and >14 days after catheter insertion, respectively. All adults with kidney failure within a large metropolitan PD unit initiating PD through a new catheter, inserted using laparoscopic or modified Seldinger technique, between August 2019 and August 2022, were included in this retrospective observational study. Demographic data and episodes of infectious and mechanical complications were collected using electronic medical records. Analysis was conducted using analysis of variance and Chi-square testing. A P-value< 0.05 was significant with Bonferroni correction performed where relevant. Kaplan-Meier and competing risks analyses were performed for time to PD-related peritonitis and transfer to hemodialysis. A total of 297 patients (70% male, mean age 58.7 years) were included, with 130 (43.8%) patients undertaking ESPD. Most patients had laparoscopically inserted catheters (65.3%) and 65 patients (22.0%) received prior hemodialysis. When compared to CSPD, ESPD was associated with a higher number of pericatheter leaks (6.9% vs. 0.6%, P= 0.003), with otherwise similar complication episodes and no significant difference with respect to time to PD-related peritonitis or transfer to hemodialysis. Catheter insertion technique or prior hemodialysis treatment did not significantly influence outcomes. ESPD is associated with increased pericatheter leaks when compared to CSPD, with an otherwise similar complication profile.

Unveiling the formation of nanotwin-mediated metastable ζ-hydrides in fatigued Zr-1Nb-0.01Cu cladding tube

The impact of internal pressure fatigue treatment on the α-Zr matrix and hydride precipitates in Zr-1Nb-0.01Cu cladding tube has been systematically investigated using synchrotron-based high-energy X-ray diffraction, electron backscatter diffraction and transmission electron microscopy techniques. The evolution in d-spacings of the basal plane (0002), the pyramidal plane {101¯1} and the prismatic plane {101¯0} at azimuths from 0° to 360° indicates that the internal pressure fatigue treatment has imparted a degree of plastic deformation upon the α-Zr phase, which is further confirmed by the presence of {101¯2} deformation twins within the α-Zr phase. Concurrently, the prior internal pressure fatigue treatment at 400 °C significantly increased nucleation sites for zirconium hydrides during the subsequent furnace cooling process. High-density dislocations can be seen in both the δ-hydride precipitate ({111}<110> type) and the α-Zr matrix ({101¯0}<a> type) near the hydride-matrix interface. Additionally, δ-hydride {111}<112¯> nanotwins were observed within the micro-sized δ-hydrides in the fatigued cladding tube, resulting from the nucleation and growth of intra-granular δ-hydrides at different regions of the same parent α-Zr grain. Furthermore, the HCP-structured ζ-hydride phase was detected at the δ-hydride nanotwin forefront along the growth direction and at the curved δ-hydride nanotwin boundaries, providing direct experimental evidence to the notion that the metastable ζ-hydride serves as the precursor to the stable δ-hydride phase during the precipitation process. The current experimental findings contribute to the fundamental understanding of microscopic mechanisms underlying the delayed hydride cracking and the stress-induced hydride reorientation in Zr alloys.

Review: Flow Diversion for the Treatment of Middle Cerebral Artery Aneurysms.

The invention of flow diverting stents (FDS) is a novel milestone in the field of endovascular aneurysm therapy, promoting physiological healing of the vessel segment contrary to prior deconstructive treatment strategies, such as coiling. The effects of FDS are based on changes in flow patterns, segmental wall stabilization, and the growth of a neointima. Although flow diversion is already well established for cerebral aneurysms in proximal segments, peripheral locations remain challenging. Especially the middle cerebral artery (MCA) with its predominance of non-collateralized perforators and functional end arteries that supply the eloquent areas of the brain is of major concern.The literature was reviewed for flow diversion of the MCA and antiplatelet therapy.Resulting from the special anatomical characteristics of the MCA, FDS implantation in this territory is completely different from the proximal vessel segments. Still, flow diversion represents an effective endovascular strategy, especially in otherwise non-accessible or sufficiently treatable lesions. However, the risk of ischemic adverse events might be increased. Special attention to the individual decision regarding device selection, antiplatelet regimen, and exact definition of the proximal and distal landing zone considering the jailed side branches is essential for a good angiographic and clinical outcome. · MCA aneurysms can be sufficiently treated by FDS.. · The anatomic and hemodynamic characteristics of the MCA result in an increased risk of thromboembolism.. · Individual device selection and antiplatelet regimen are essential for treatment success.. · Schüngel M, Wohlgemuth WA, Elolf E et al. Review: Flow Diversion for the Treatment of Middle Cerebral Artery Aneurysms. Fortschr Röntgenstr 2024; DOI 10.1055/a-2343-0046.

Impact of DAA Treatment for HCV on Hepatocellular Carcinoma in a Predominately African American Population.

This study tested the hypothesis that our predominately AA medical center population would demonstrate a decline in HCV-driven HCC diagnosis following the initiation of DAA treatment in 2014. Also evaluated was whether achieving an SVR prior to diagnosis of HCC improved outcomes in patients who had an HCV diagnosis after completion of treatment. All patients with HCC seen at the Detroit Medical Center from 2009 to 2021 were identified using ICD-10 codes, and medical records were evaluated. Outcomes were evaluated as either alive or death/hospice as of December of 2022. There were 461 patients with HCC of whom 433 (94%) had racial information in the database (AA = 351; non-AA = 82). HCC incidence regardless of race peaked in 2017, with a subsequent decline through 2021. HCV as a risk factor was higher in AA as compared to non-AA (85% vs. 53% p = 0.0001). Outcome (alive vs. death/hospice) was better for SVR patients compared to untreated patients (54% vs. 19%; p = 0.0009). HCC patients who achieved SVR also had better liver function at diagnosis as defined by Child-Pugh score (74% vs. 49% Class A p = 0.04) at the time of diagnosis. Racial disparity in HCC etiology was confirmed with AA more likely to have HCV than non-AA. The reduction in HCC patients with HCV confirms the impact of DAA treatment and prior successful treatment of HCV yields better outcomes. Increasing HCV treatment rates especially in AA patients will have a major impact on HCC development and treatment outcomes. • African Americans are more likely to have HCV infection as compared to non-AA. • Hepatocellular carcinoma is increasing in incidence in the US. • The role of HCV in the development of HCC remains to be further investigated. • HCC diagnosis in a single urban medical center study increased from 2009 as a result of HCV as a risk factor. • HCC declined post 2018 due primarily to a reduction in HCV infection as the risk factor. • African Americans were more likely to have HCV as the risk factor as compared to non-AA patients who were more likely to have no known risk factor on record (i.e., cryptogenic).

Similar genetic profile in early and late stage urothelial tract cancer

IntroductionUrothelial tract cancer (UTC) ranks as the tenth most prevalent cancer and holds the seventh position in terms of mortality worldwide. Despite its prevalence and mortality ranking, there are still gaps in the knowledge of the mutational landscape in patients with advanced disease who have limited therapeutic options after multiple lines of prior treatment. This study compares the genomic and transcriptomic landscape, and targeted treatment options between metastatic UTC (mUTC) patients treated with multiple lines of therapy compared to newly diagnosed, untreated Muscle Invasive Bladder Cancer (MIBC).MethodsWe compared genomic and clinical data from two cohorts: mUTC patients who received multiple lines of therapy and were referred to the Copenhagen Prospective Personalized Oncology (CoPPO) project at Rigshospitalet, University of Copenhagen. Data for MIBC UTC patients were acquired from the Cancer Genome Atlas Bladder Cancer (TCGA BLCA) cohort. Biopsies in CoPPO were performed at the time of enrollment. 523 highly important cancer-related genes (TrueSight Oncology-500 targeted sequencing panel) were used from both cohorts for comparative analysis. Analyses included RNA count data to compare predicted molecular subtypes in each cohort separately.ResultsPatients from the CoPPO cohort had a lower median age at first-line treatment than the TCGA BLCA cohort, with no significant gender disparity. The predominant histology was urothelial cell carcinoma in both cohorts. Genomic analysis revealed no significant difference between the top mutated genes in the two cohorts, specifically looking into DNA damage repair genes. Molecular subtyping indicated a higher frequency of neuroendocrine differentiation in the CoPPO cohort. 13% of patients in the CoPPO cohort received targeted therapy based on genomic findings, and 16% received non-targeted treatment, totaling 29% receiving CoPPO treatment (9 patients). The remaining 71% received best supportive care. Kaplan-Meier analysis showed a non-significant survival benefit for the intervention group in the CoPPO cohort.ConclusionWhen focusing on 523 highly relevant cancer genes, the mutational profile of mUTC patients who have undergone numerous treatment lines resembles that of newly diagnosed MIBC. These alterations can be targeted, indicating the potential advantage of early genomic testing for personalized treatment within clinical trials.

Impact of previous gestational diabetes management on perinatal outcomes in subsequent pregnancies affected by gestational diabetes mellitus.

To determine the impact of prior gestational diabetes mellitus (GDM) on perinatal outcomes in a subsequent GDM pregnancy. This retrospective cohort study included 544 multiparous patients with two consecutive pregnancies between 2012-2019, where the second (index) pregnancy was affected by GDM. The primary exposure was prior GDM diagnosis, categorized into medical and dietary management. The primary outcome was a composite including need for pharmacotherapy, large-for-gestational age, or neonatal hypoglycemia. Adjusted odds ratios (aOR) were calculated using multivariable logistic regressioncontrolling for maternal age, pre-pregnancy body mass index, and gestational age at GDM diagnosis in the index pregnancy. Of the 544 patients, 164 (30.1%) had prior GDM. Prior GDM significantly increased the likelihood ofcomposite outcome compared to no prior GDM (74.4% vs. 57.4%; P < 0.001). After adjusting for confounders, prior GDM remained significantly associated with the composite outcome (aOR 2.03, 95% confidence interval [CI] 1.31-3.15). Stratifying by prior GDM treatment modality, a significant association was found for prior pharmacotherapy-controlledGDM (aOR 3.29, 95% CI 1.64-6.59), but not for prior diet-controlled GDM (aOR = 1.54, 95% CI 0.92-2.60). A history of pharmacotherapy-controlled GDM in a previous pregnancy increases odds of adverse perinatal outcomes in a subsequent GDM pregnancy.

How do we perform an open myomectomy?

31-year-old woman with symptomatic uterine fibroids who underwent open myomectomy. Despite prior treatment with goserelin, persistent symptoms and desire for future fertility warranted surgical intervention. The surgical technique aimed to optimize hemostasis and minimize morbidity by employing fusiform incisions.

Assessment and Correlation of Dentofacial Morphology and Lateral Cephalometric Parameters with Smile Characteristics in Lateral and Oblique View: Short Study

Aim: This study evaluated and established correlations between the dentofacial morphology of Angle’s Cl II and Cl I malocclusions, lateral cephalometric parameters, and smile characteristics assessed through lateral and oblique smile views. Methods: A sample of 20 random patients (&gt;15 years, with prior orthodontic treatment) were selected for this study according to their arrival at the department. The selected individuals were grouped according to Angle’s classification of malocclusion, i.e., Angle’s Cl I and Angle’s Cl II malocclusion. Pretreatment records were taken for the study, including lateral cephalogram and extra-oral smile photographs (one lateral smiling and one oblique smiling). In the lateral cephalogram, skeletal, dental, and facial parameters were recorded, and in lateral and oblique smile views, lateral smile index, commissure angle, and incisal displays were recorded. Results: The results showed no significant difference in most cephalometric parameters except for UFH/LFH, which was higher in Angle’s Cl II. Additionally, smile analysis revealed significant differences between the two groups. In addition, significant differences were found in the incisal display, which was greater in Angle’s Cl II malocclusion. Conclusion: Smile characteristics differ between Angle Cl I and Cl II malocclusions. There was a significant difference in lateral and oblique smile parameters when Angle’s malocclusions classified as Cl I and Cl II were evaluated. Lateral and oblique smile index decreased from Cl I to Cl II malocclusion, whereas lateral and oblique smile commissure angle and lateral smile incisor display increased in Cl II malocclusion.

Commentary on: Use of Himplant® for correction of residual deformity following prior treatment of Peyronie's disease: a case report.

Commentary on: Use of Himplant® for correction of residual deformity following prior treatment of Peyronie's disease: a case report.

Real world efficacy and durability of faricimab in patients with neovascular AMD (nAMD) who had sub-optimal response to prior anti-VEGF therapy.

Age-related macular degeneration (AMD) remains a primary cause of blindness, with neovascular AMD (nAMD) presenting particular treatment challenges. Despite anti-vascular endothelial growth factor (anti-VEGF) therapies, many patients exhibit a suboptimal response to the previously available anti-vascular endothelial growth factor (anti-VEGF) therapies. This study evaluates the efficacy and treatment interval extension of faricimab in this patient cohort. In a retrospective single-centre study at University Hospitals of Bristol and Weston, UK, nAMD patients suboptimally responsive to previous anti-VEGF therapies were switched to faricimab. Treatment started with an initiation phase of 4 monthly injections followed by a 'Treat and Extend' protocol. Outcomes included best-recorded visual acuity (BRVA), central subfield thickness (CST), the presence of retinal fluid, and treatment intervals. Among 98 eyes of 79 patients, following faricimab treatment, significant reductions in CST and retinal fluid were noted, indicating decreased disease activity. While BRVA changes were not statistically significant, the anatomical improvements suggest a potential therapeutic benefit. Notably, 40% of patients achieved extended treatment intervals, reducing the treatment burden. Faricimab offers a promising alternative for nAMD patients with suboptimal responses to prior anti-VEGF treatments, demonstrating significant anatomical improvements and the possibility of extended dosing intervals. These findings highlight the need for prospective real-world studies to further assess faricimab's role in nAMD management and its long-term impact on patient outcomes.

Pattern of Testicular Atrophy in Bilateral Orchidectomy Specimens from Patients with Advanced Prostate Cancer

Introduction: One of the palliative treatment modalities for advanced prostate cancer (Pca) is bilateral Orchidectomy. Histopathological analysis of submitted Orchidectomy specimens may display normal to various grades of testicular atrophy. Advancing age may be related to testicular atrophy as well as pre-treatment with luteinizing hormone releasing hormone agonist [LHRH(a)], drugs and chronic illnesses. We retrospectively examined results of Orchidectomy specimens submitted for histopathological analysis. Materials and Methods: Bilateral orchidectomy specimen results of twenty seven (27) patients diagnosed with Pca were retrospectively studied. Their clinical information and ancillary laboratory results were retrieved. Of the 27 patients, two (7.4%) patients had no prior treatments for Pca, while twenty patients (74.1%) and five patients (18.5%) had prior exposure to anti-androgens and LHRH(a) respectively. In the histo-analysis, the specimens were graded from normal to various degrees of atrophy. Data collated were analyzed using Statistical package for social sciences (SPSS) version 20.0 software. Results: The mean age of all patients was 68.52±7.266 years, ranging from 51-87 years. Mean PSA was 59.811+38.84ng/ml, while mean Gleason score was 8.30+8.69. On the whole, 3 patients (11.1%) had normal testes, 16 patients (59.3%) and 8 patients (29.6%) respectively had mild and moderate grades of testicular atrophy. Age correlated positively with the grades of atrophy. Conclusion: Degree of testicular atrophy is widely noted to correlate with age and depends less on pre-treatment in the setting of advanced prostate cancer.

Diagnostic value of contrast-enhanced ultrasound and shear-wave elastography for small breast nodules.

The study aims to evaluate the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE) in detecting small malignant breast nodules in an effort to inform further refinements of the Breast Imaging Reporting and Data System (BI-RADS) classification system. This study retrospectively analyzed patients with breast nodules who underwent conventional ultrasound, CEUS, and SWE at Gongli Hospital from November 2015 to December 2019. The inclusion criteria were nodules ≤ 2 cm in diameter with pathological outcomes determined by biopsy, no prior treatments, and solid or predominantly solid nodules. The exclusion criteria included pregnancy or lactation and low-quality images. Imaging features were detailed and classified per BI-RADS. Diagnostic accuracy was assessed using receiver operating characteristic curves. The study included 302 patients with 305 breast nodules, 113 of which were malignant. The diagnostic accuracy was significantly improved by combining the BI-RADS classification with CEUS and SWE. The combined approach yielded a sensitivity of 88.5%, specificity of 87.0%, positive predictive value of 80.0%, negative predictive value of 92.8%, and accuracy of 87.5% with an area under the curve of 0.877. Notably, 55.8% of BI-RADS 4A nodules were downgraded to BI-RADS 3 and confirmed as benign after pathological examination, suggesting the potential to avoid unnecessary biopsies. The integrated use of the BI-RADS classification, CEUS, and SWE enhances the accuracy of differentiating benign and malignant small breast nodule, potentially reducing the need for unnecessary biopsies.

O-032 Intravenous immunoglobulin and prednisolone to women with unexplained recurrent pregnancy loss undergoing assisted reproductive technology treatment: a randomized, double-blinded, placebo-controlled trial

Abstract Study question Does intravenous immunoglobulin (IVIG) and prednisolone in combination affect ongoing pregnancy rate among patients with recurrent pregnancy loss (RPL) after assisted reproductive technology (ART) treatment? Summary answer The results of this trial will provide important information about whether immunomodulatory treatment to RPL patients undergoing ART treatment can increase clinical pregnancy rate. What is known already Two retrospective cohort studies suggest that IVIG and prednisolone in combination result in a 34-37% live birth rate in RPL patients undergoing ART which is higher than the expected 12% for patients with RPL after ART. A randomized controlled trial (RCT) testing IVIG in RPL patients conceiving naturally indicated that very early administration of IVIG caused more positive effects than late administration, and prospective cohort studies suggest that treatment efficacy depends on presence of immune disturbances. No RCT has tested the IVIG/prednisolone combination starting before implantation and continued in very early pregnancy for RPL patients undergoing ART. Study design, size, duration In a randomized, double-blinded, placebo-controlled trial, patients undergoing IVF/ICSI/FET were treated with 400mg/kg IVIG and 5-10mg/day oral prednisolone or IV human albumin and oral placebo between January 2021 and March 2024. Oral treatment was administered from day one of menstrual cycle to GW 8 + 4, while IV treatment was given once in a short time interval before or after embryo transfer and repeated three times before GW 8 + 0. Primary outcome was ongoing pregnancy in GW 12 Participants/materials, setting, methods Seventy-four women &amp;lt;41 years old with ≥2 consecutive biochemical or clinical early pregnancy losses after ART were randomized 1:1 and underwent trial treatment along with their next IVF/ICSI/FET treatment. Patients were followed with weekly ultrasound scans in first trimester, however, if no implantation occurred, trial participation ended, and no re-entry was allowed. Exclusion criteria included antiphospholipid syndrome, BMI &amp;gt;35, uterine malformations, parental chromosomal translocations, AMH &amp;lt;4 pmol/l, drug contraindications, thyroid disease, and prior IVIG treatment. Main results and the role of chance Seventy-four patients have been randomized, and currently we are awaiting the last two patients to complete the treatment protocol before the code can be disclosed. Blinded interim analysis after inclusion of 38 patients showed no serious adverse events and an ongoing pregnancy rate of 30.0% and 9.5% (RR 1.8, 95% CI 1.0-3.1, Fisher’s exact test: p = 0.13), in the two allocation groups, respectively. Final, unblinded data on ongoing pregnancy rate, miscarriage rate and adverse events will be presented at the Congress if selected for presentation. Limitations, reasons for caution No published study has tested the same treatments in comparable patient groups which could have been the basis for the sample-size calculation, and the study is therefore at risk for being underpowered to evaluate the treatment effect in patients suffering from a combination of infertility, recurrent implantation failure, and RPL. Wider implications of the findings Blood samples were collected before first IV treatment and approximately 4 weeks later, which allow analysis for immunological disturbances and searching for biomarkers identifying those who will benefit from the treatment. This treatment could potentially increase success rate in patients undergoing ART after multiple unsuccessful treatment attempts. Trial registration number NCT04701034

A Long-Term Safety and Tolerability Study of TV-46000 for Subcutaneous Use in Patients with Schizophrenia: A Phase 3, Randomized, Double-Blinded Clinical Trial.

TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) formulation of risperidone that is approved by the United States Food and Drug Administration for the treatment of schizophrenia in adults. In the phase 3, randomized, double-blind RIsperidone Subcutaneous Extended-release (RISE) study, TV-46000 once monthly (q1m) and once every 2months (q2m) significantly prolonged time to impending relapse compared with placebo [5.0-fold (q1m) and 2.7-fold (q2m)]. This phase 3, randomized, double-blind Safety in Humans of TV-46000 subcutaneous INjection Evaluation (SHINE) study was designed to evaluate the long-term safety, tolerability, and exposure of TV-46000 in schizophrenia. Patients who completed RISE without relapse (rollover) or who were newly recruited (de novo) were eligible for the SHINE study. Patients were initially stabilized on oral risperidone for 12 weeks (completed in RISE for rollover, or in SHINE for de novo). Patients in the de novo cohort and patients who received placebo in RISE were randomized 1:1 in SHINE to receive TV-46000 q1m or q2m for up to 56 weeks. Primary endpoint for SHINE was frequency of reported adverse events (AEs); event rates [ER; events per 100 patient-years (PYs)] were calculated for each AE by patients upon general questioning. Overall, 336patients were randomized in SHINE [TV-46000 q1m, n = 174; TV-46000 q2m, n = 162; of these, de novo, n = 109 and rollover, n = 227 (n = 172 patients were treated and n = 55 received placebo)]. A total of 334 patientswere evaluated for safety [q1m, n = 172 (PY = 97.8); q2m, n = 162 (PY = 104.5)]. Proportions of patients (ER) with ≥ 1 AE and ≥ 1 treatment-related AE were 37% (180.0) and 21% (84.9) for TV-46000 q1m and 46% (157.9) and 20% (70.8) for TV-46000 q2m, respectively. Frequent treatment-related AEs [≥ 3% of patients in either group; proportion of patients (ER)] were injection site pain [q1m, 5% (24.5); q2m, 4% (22.0)] and injection site nodule [q1m, 2% (9.2); q2m, 6%(12.4)]. The proportions of patients with serious AEs was 5% for TV-46000 q1m and 7% for TV-46000 q2m; serious AEs reported for ≥ 2 patients overall were worsening schizophrenia [q1m, n = 1 (< 1%; ER, 1.02); q2m, n = 2 (1%; ER, 1.91)] and hyperglycemia [q1m, n = 1 (< 1%; ER, 1.02); q2m, n = 1 (< 1%; ER, 0.96)]. Ofthreereported deaths, none were related to treatment. Overall, eight patients discontinued treatment because of AEs. Similar or somewhat lower rates of AEs were reported for patients who rolled over from TV-46000 treatment compared with those who had no prior TV-46000 treatment (de novo and placebo rollover). Most AEs related to injection site reactions were mild; no patient had a severe reaction. Results from this long-term safety study add to the favorable safety profiles of TV-46000 q1m and q2m, consistent with other formulations of risperidone and previous studies with TV-46000. ClinicalTrials.gov, NCT03893825; 27 March 2019.

Metataxonomic Studies to Evaluate the Beneficial Effect of Enzymatic Pretreatment on the Anaerobic Digestion of Waste Generated in Turkey Farming.

Turkey litter waste is lignocellulosic and keratinous, requiring prior enzymatic treatment to facilitate fiber hydrolysis and utilization by microorganisms in anaerobic digestion (AD) process. The understanding of the performance of microorganisms in AD can be facilitated through molecular biology and bioinformatics tools. This study aimed to determine the taxonomic profile and functional prediction of microbial communities in the AD of turkey litter waste subjected to enzymatic pretreatment and correlate it with operational parameters. The tests involved the use of turkey litter (T) at 25gL-1 of volatile solids, a granular inoculum (S) (10% m/v), and the addition of cellulase (C), and pectinase (P) enzymes at four concentrations. The use of enzymes increased methane production by 19% (turkey litter, inoculum, and cellulase-TSC4) and 15% (turkey litter, inoculum, and enzymatic pectinase-TSP4) compared to the control (turkey litter and inoculum-TS), being more effective in TSC4 (667.52 mLCH4), where there was consumption of acetic, butyric, and propionic acids. The pectinase assay (TSP4) showed a methane production of 648 mLCH4 and there was the accumulation of metabolites. Cellulolytic microorganisms Bacteroides, Ruminofilibacter, Lachnospiraceae, Ruminococcaceae, and Methanosaeta were favored in TSC4. In TSP4, the predominant genus was Macellibacteroides and Methanosarcina, and genes involved in methylotrophic methanogenesis were also found (mtaB, mtmB, and mtbB). Enzymes involved in hydrogenotrophic methanogenesis were identified in both assays (TSC4 and TSP4). Molecular tools helped to understand the metabolic routes involved in AD with enzymatic treatment, allowing the elaboration of strategies to improve the sustainable degradation of turkey litter waste.

Clinical Effectiveness of Targeted Therapies Following Nivolumab Therapy in Patients with Metastatic Renal Cell Carcinoma: A Real-World Study.

Background: The treatment and escape for metastatic renal cell carcinoma (RCC) has rapidly evolved, particularly with the integration of immune therapies into first-line regimens. However, optimal strategies following progression in first-line immunotherapy remain uncertain. This study aims to evaluate the efficacy and safety of axitinib and cabozantinib as third-line therapies after progression on nivolumab following first-line VEGF-TKI therapy. Methods: Patients with metastatic RCC who progressed on prior nivolumab treatment after receiving first-line VEGF-TKI therapy were included. Data on patient characteristics, treatment regimens, response rates, progression-free survival (PFS), and overall survival (OS) were collected. Statistical analyses were conducted to assess the prognostic factors and treatment outcomes. Results: A total of 46 patients were included who were predominantly male (83%) with clear-cell histology (89%). The median PFS on first-line TKI therapy was 10.2 months. All the patients received nivolumab as a second-line therapy, with a median of 12 cycles. The median second-line PFS was seven months. Third-line therapies included axitinib (24 patients) and cabozantinib (20 patients). The median PFS for axitinib and cabozantinib was six months, with comparable survival outcomes. The IMDC risk group and treatment tolerability were significant predictors of survival in multivariate analysis. Adverse events were manageable, with hypertension, fatigue, and diarrhea being the most common. Conclusion: Axitinib and cabozantinib show promise as third-line therapies post-nivolumab progression in metastatic RCC, though prospective validation is warranted. This study underscores the need for further research to establish treatment standards in this evolving landscape.

Radioactive Iodine Treatment of Graves' Disease: Predictors of Time Interval Greater than 90 Days for Treatment Success.

Radioactive iodine (RAI) is often used for treating Graves' disease. We study predictors for a time interval greater than 90 days between RAI treatment and success. This was a retrospective study of 106 patients with Graves' disease seen at a public hospital in suburban New York City. Predictor variables were from demographics, prior treatment history, iodine 131 RAI treatment, and thyroid function prior to RAI treatment. There were 62.3% that had a time interval greater than 90 days between RAI treatment and success. Only the thyroid function prior to RAI treatment variable of free thyroxine (FT4) had statistically significantly increased odds for time interval greater than 90 days between RAI treatment and success (OR:1.28, 95% CI:1.02, 1.61, p = 0.03). Demographics, prior treatment history, and iodine 131 RAI treatment variables were not significantly associated with time interval greater than 90 days between RAI treatment and success. Thyroid function measured by FT4 was significantly associated with time interval greater than 90 days between RAI treatment and success. We suggest that the thyroid function variable of FT4 levels at initial diagnosis is most helpful for understanding the prognosis and success rate for using RAI treatment in patients with Graves' disease.

The Rate of Re-treatment in Patients Treated with Teprotumumab: A Multicenter Study of 119 Patients with 1 Year of Follow-up

Objective or PurposeTo determine the rate of retreatment in patients who receive a full course of teprotumumab therapy for Thyroid Eye Disease (TED) and drivers of retreatment. DesignMulti center, retrospective study SubjectsAll patients who received a full course of treatment and had available data at 1 year post initial treatment were included. MethodsCharts were reviewed for the following information: age, gender, months since diagnosis of TED, smoking status, prior treatments. Further, the clinical activity score (CAS), proptosis and the Gorman diplopia score were reviewed at baseline, at the end of the first course and at baseline for the second course in those who received it. A logistic regression model was created to review the drivers of retreatment. Main Outcome MeasuresRate of retreatment and the drivers of retreatment. Results119 patients were included from 3 centers across the US. The overall retreatment rate was 24% (29/119). There was no difference between the 3 sites (p = 0.6). In univariate analyses, at baseline, there was no difference in proptosis (p = 0.07), diplopia score (p = 0.4) or duration of TED (p = 0.4), between retreated and non-retreated patients. From the retreated group, 82% had a significant proptosis response (≥ 2 mms reduction from baseline) following their initial course, while 68% of patients had a clinically significant proptosis response in the non-retreated group (p = 0.16). The use of other treatments prior to the first infusion of teprotumumab and baseline thyroid dysfunction, were not significantly different between the retreated and non-retreated groups (p = 0.06 and 0.09, respectively). The mean (SD) difference between the end of first treatment and at baseline prior to second treatment (in those who received it) was 2 (2) for CAS, 2 mms (4) for proptosis and 1 (1) for diplopia. Age as the only significant driver of retreatment (p < 0.05). Retreated patients were 7 years older than their non retreated counterparts (age 60 vs 53 (p < 0.05). ConclusionsIn patients receiving a full course of teprotumumab therapy, the rate of retreatment is 24%. Age is the only driver of retreatment.

Clavicular tunnel widening in chronic acromioclavicular joint instabilities after primary versus revision arthroscopically-assisted acromio- and coracoclavicular stabilization.

To evaluate joint reduction (loss of reduction [LOR]; dynamic posterior translation [DPT]) and clavicular tunnel widening (cTW) in patients treated with arthroscopically-assisted acromioclavicular joint (ACJ) stabilization after previously failed nonoperative versus surgical treatment. Patients undergoing arthroscopically-assisted ACJ stabilization (bidirectional tendon allograft with a low-profile TightRope) after previously failed nonoperative versus surgical treatment were included retrospectively. Bilateral anteroposterior stress views served for evaluating LOR (side-comparative coracoclavicular distance [CCD]) and cTW at a 6-weeks- and 6-months-follow-up (FU) and for evaluating the filling ratio (FR, vertical device insertion depth relative to clavicle height) at the 6-weeks-FU. Postoperative DPT was assessed on Alexander's views. Twenty-seven patients (20 male, mean age 46.1 ± 14.8 years) were included (prior treatment: nonoperative: n = 15; surgical: n = 12). There were no differences in LOR, DPT or cTW between groups postoperatively. Initial CCD-symmetry at the 6-weeks-FU (CCD: -0.1 mm [95% confidence interval, CI, -2 to 1.4 mm]) was followed by LOR at the 6-months-FU (CCD: -3.5 mm [95% CI, -5.2 to -1.9 mm]; p < 0.001). cTW increased towards the inferior cortex, compared to the superior cortex and the intermediate level (p < 0.001, respectively). cTW at the inferior cortex was associated with more LOR (r = -0.449; p = 0.024) and DPT (r = 0.421; p = 0.036), dependent on a smaller FR (r = -0.430; p = 0.032). Patients undergoing arthroscopically-assisted ACJ stabilization for chronic bidirectional ACJ instabilities showed comparable radiologic results after previous nonoperative versus surgical treatment. cTW increased towards the inferior cortex and was associated with recurrent vertical and horizontal instability, related to a smaller FR. More research into reduced cTW, for example, by a more filling device, should be performed. Level III, retrospective comparative study.