Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial.

BACKGROUND: Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy might be enhanced by immunotherapy. In this phase 3 trial, we assessed the efficacy and safety of adding pembrolizumab to chemoradiotherapy in locally advanced cervical cancer. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 clinical trial, adults (age ≥18 years) at 176 medical centres in 30 countries with newly diagnosed, high-risk, locally advanced cervical cancer were randomly assigned (1:1) using an interactive voice-response system with integrated web response to receive 5 cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Randomisation was stratified by planned external beam radiotherapy type (intensity-modulated radiotherapy or volumetric-modulated arc therapy vs non-intensity-modulated radiotherapy or non-volumetric-modulated arc therapy), cervical cancer stage at screening (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB node positive vs stage III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy equivalent dose in 2 Gy fractions). Primary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumours version 1.1-by investigator or by histopathologic confirmation of suspected disease progression-and overall survival. Primary analysis was conducted in the intention-to-treat population, which included all randomly allocated participants. Safety was assessed in the as-treated population, which included all randomly allocated patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04221945, and is closed to new participants. FINDINGS: Between June 9, 2020, and Dec 15, 2022, 1060 participants were randomly assigned to treatment, with 529 assigned to the pembrolizumab-chemoradiotherapy group and 531 to the placebo-chemoradiotherapy group. At data cutoff (Jan 9, 2023), median follow-up was 17·9 months (IQR 11·3-22·3) in both treatment groups. Median progression-free survival was not reached in either group; rates at 24 months were 68% in the pembrolizumab-chemoradiotherapy group versus 57% in the placebo-chemoradiotherapy group. The hazard ratio (HR) for disease progression or death was 0·70 (95% CI 0·55-0·89, p=0·0020), meeting the protocol-specified primary objective. Overall survival at 24 months was 87% in the pembrolizumab-chemoradiotherapy group and 81% in the placebo-chemoradiotherapy group (information fraction 42·9%). The HR for death was 0·73 (0·49-1·07); these data have not crossed the boundary of statistical significance. Grade 3 or higher adverse event rates were 75% in the pembrolizumab-chemoradiotherapy group and 69% in the placebo-chemoradiotherapy group. INTERPRETATION: Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co (MSD).

Prostate-specific antigen (PSA) decline with apalutamide therapy is associated with longer survival and improved outcomes in individuals with metastatic prostate cancer: a plain language summary of the TITAN study.

WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from an additional (or post hoc) analysis of the TITAN study. The TITAN study looked at whether the prostate cancer treatment apalutamide could be used to treat individuals with metastatic castration-sensitive prostate cancer (or mCSPC). A total of 1052 participants with mCSPC were included in the TITAN study. Treatment with apalutamide was compared with treatment with placebo. All participants received androgen deprivation therapy (or ADT), which is a type of hormone therapy that has been part of the main treatment for mCSPC for many years. The results showed that apalutamide plus ADT increased the length of time that participants remained alive compared with placebo plus ADT. Apalutamide plus ADT also controlled the growth of the cancer for a longer length of time compared with placebo plus ADT. Additionally, participants who received apalutamide plus ADT experienced a greater reduction in the blood levels of prostate-specific antigen (or PSA), called a deep PSA decline, compared with those who received placebo plus ADT. An additional (or post hoc) analysis was carried out to understand whether a decrease in blood PSA levels, in response to treatment, was associated with improved outcomes, including longer survival time. WHAT WERE THE RESULTS OF THE ADDITIONAL ANALYSIS?: In participants who received apalutamide plus ADT, a deep PSA decline in response to treatment was associated with longer survival time and improved outcomes. WHAT DO THESE RESULTS MEAN FOR INDIVIDUALS WITH MCSPC?: These results demonstrate that individuals with mCSPC can benefit from treatment with apalutamide plus ADT. The association seen between deep PSA decline and the longer survival time and improved outcomes highlights how PSA measurements can be used to help monitor cancer disease evolution in response to treatment. Monitoring PSA levels will assist doctors and other healthcare professionals to understand how effectively a treatment is working for a patient and to tailor their treatment approach to improve PSA decline.

Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer.

BACKGROUND: Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined. METHODS: In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival. RESULTS: A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group. CONCLUSIONS: In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.).

Getting back on track: a group psychoeducational intervention for patients and families living with head and neck cancer.

PURPOSE: Head and neck cancer survivors are increasing in prevalence, and 60-70% still experience at least one unmet emotional and/or physical need after treatment has ended. The purpose of this study was to determine the efficacy of a brief post-treatment psychoeducational intervention on perceived preparedness for coping with recovery using post-session evaluations. METHODS: Between August 2013 and May 2018, a two-session, multidisciplinary "getting back on track" class was delivered to head and neck cancer patients approximately 2 months following radiation treatment at Princess Margaret Cancer Centre in Toronto, Canada. Three hundred and fifty attendees completed evaluations. Statistical analyses of the 310 patients surveyed measured change in level of preparedness to cope with recovery using the b-prepared scale. Qualitative analyses provided insight into potential benefits for future patients. RESULTS: Almost two-thirds (58%) of patients reported an increase in level of preparedness in post-intervention surveys. Comparing self-reported level of preparedness among patients from before to after the class showed an increase in feeling prepared from 50 to 58%, and of those feeling very prepared, from 6 to 34%. The proportion of patients who reported feeling unprepared (11%) or neutral (33%) before the class decreased post-intervention, with 0% feeling unprepared and 7% feeling neutral. There were statistically significant differences in the ideal timing of the class, but overall attendees agreed that the class is an essential part of their recovery. CONCLUSION: Results confirm the efficacy of this brief psychoeducational intervention to improve preparedness in head and neck cancer survivors following radiation treatment.

Effect of photobiomodulation on fatigue in individuals with relapsing-remitting multiple sclerosis: a pilot study.

Multiple sclerosis is an autoimmune disease of the central nervous system characterized by inflammation and destruction of the myelin sheath. Fatigue is one of the main symptoms of this disease, with a negative impact on quality of life and few treatment options. Photobiomodulation is used for several inflammatory conditions and may be beneficial for the treatment of fatigue in individuals with multiple sclerosis. Conduct a pilot study to analyze the effect of photobiomodulation on fatigue in individuals with relapsing-remitting multiple sclerosis. The participants were recruited from the UNINOVE Integrated Health Clinic and randomly allocated to two groups: group 1, administration of photobiomodulation (808 nm, 36 J for 360 s) under the tongue and group 2, administration of photobiomodulation over the radial artery. Fatigue was measured using the Modified Fatigue Impact Scale (MFIS). No significant differences were found regarding the total MFIS score or subscale scores (p < 0.05, two-way ANOVA). Photobiomodulation with the parameters employed in the present study had no effect on fatigue in individuals with multiple sclerosis. ClinicalTrials.gov Identifier: NCT03360487.

Effect of antimicrobial photodynamic therapy with red led and methylene blue on the reduction of halitosis: controlled microbiological clinical trial.

To determine the effect of antimicrobial photodynamic therapy (aPDT) using a red light-emitting diode (LED) on the reduction of halitosis and microbiological levels in the tongue coating immediately after irradiation, 7, 14, and 30 days after treatment. Forty-five young adults diagnosed with halitosis were allocated to three groups: G1, aPDT with 0.005% methylene blue and red LED (660 nm, four irradiation points, 90 s per point, power of 400 mW, 36 J per point, radiant exposure of 95 J/cm2, continuous wave); G2, tongue scraping; and G3, tongue scraping and aPDT. Gas chromatography was performed before and immediately after treatment, as well as at the different follow-up times. Microbiological samples were collected at the same times from the dorsum of the tongue, and bacteria were quantified in the samples using real-time PCRq. The Wilcoxon test was used for the intragroup analyses, and the Kruskal-Wallis test was used for the intergroup analyses. In the intragroup analyses, differences were found before and immediately after treatment in all groups (p < 0.05). The effect was maintained after 7 days only in the tongue scraping group (p < 0.05). In the intergroup analysis, no statistically significant differences were found among the groups (p > 0.05). For the microbiological analyses, no statistically significant differences were found in the groups/bacteria that were analyzed (p > 0.05). aPDT using a red LED and 0.005% methylene blue caused an immediate reduction in halitosis, but the effect was not maintained after 7, 14, or 30 days. No reduction occurred in the number of bacteria investigated or the quantification of universal 16S rRNA. ClinicalTrials.gov Identifier: NCT03656419.

Apalutamide plus Androgen Deprivation Therapy for Metastatic Castration-Sensitive Prostate Cancer: Analysis of Pain and Fatigue in the Phase 3 TITAN Study.

PURPOSE: We performed an exploratory analysis of prostate cancer-related pain and fatigue on health-related quality of life in patients with metastatic castration-sensitive prostate cancer receiving apalutamide (240 mg/day) or placebo, with continuous androgen deprivation therapy (ADT), in the phase 3, randomized, double-blind, placebo controlled TITAN trial (NCT02489318). MATERIALS AND METHODS: Patient-reported outcomes for pain and fatigue were evaluated using the Brief Pain Inventory-Short Form and Brief Fatigue Inventory. Time to deterioration (TTD) was estimated by Kaplan-Meier method; hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards model. General estimating equations for logistic regression estimated treatment-related differences in the likelihood of worsening pain or fatigue. RESULTS: Compliance for completing the Brief Pain Inventory-Short Form and Brief Fatigue Inventory was high (96% to 97%) in the first year. Median followup times were similar between treatments (19 to 22 months). Median pain TTD was longer with apalutamide than placebo for "pain at its least in the last 24 hours" (28.7 vs 21.8 months, respectively; p=0.0146), "pain interfered with mood" (not estimable vs 22.4 months; p=0.0017), "pain interfered with walking ability" (28.7 vs 20.2 months; p=0.0027), "pain interfered with relations" (not estimable vs 23.0 months; p=0.0139) and "pain interfered with sleep" (28.7 vs 20.9 months; p=0.0167). Likelihood for fatigue and worsening fatigue were similar between groups. CONCLUSIONS: Patients with metastatic castration-sensitive prostate cancer receiving apalutamide plus ADT vs placebo plus ADT reported consistently favorable TTD of pain. No difference for change in fatigue was observed with apalutamide vs placebo.

Pre-treatment psychoeducational intervention and outcomes in head and neck cancer patients undergoing radiotherapy.

BACKGROUND: To investigate the relationship between attendance to a pre-treatment psychoeducational intervention (prehab) with treatment outcomes and toxicities in patients receiving radiotherapy for head and neck cancers (HNCs). METHODS: Patients were included from prehab inception in 2013 to 2017, comparing overall survival (OS), locoregional recurrence-free survival (LRFS), and locoregional recurrence (LRR) between prehab attendees (PA) and non-attendees (PNA). Multivariable analysis was performed for OS and LRFS. RESULTS: Among 864 PA and 1128 PNA, 2-year OS was 88% vs 80% (p < 0.001), and LRFS was 84% vs 75% (p < 0.001). On multivariable analysis (MVA), OS and LRFS were independently and unfavourably associated with PNA. The PA cohort had a lower frequency of a "rocky treatment course" compared with the PNA cohort (52/150, 35% vs 71/150, 47%; p = 0.034). CONCLUSIONS: Prehab at our institution is associated with improved long-term oncologic outcomes. Prospective data is needed to better understand this association.

Sensory and motor responses after photobiomodulation associated with physiotherapy in patients with incomplete spinal cord injury: clinical, randomized trial.

Complete or incomplete spinal cord injury (SCI) results in permanent neurological deficits due to the interruption of nerve impulses, causing the loss of motor and sensory function, which leads to a reduction in quality of life. The focus of rehabilitation for such individuals is to improve quality of life and promote functional recovery. Photobiomodulation (PBM) has proved to be promising complementary treatment in cases of SCI. The aim of the present study was to investigate the effects of PBM combined with physiotherapy on sensory-motor responses below the level of the injury and quality of life in individuals with SCI. Thirty participants were randomized for allocation to the PBM group (active PBM + physiotherapy) or sham group (sham PBM + physiotherapy). Physiotherapy was administered three times a week. Sensitivity and motor skills were evaluated using the ASIA impairment scale. Quality of life was assessed using the WHOQOL-BREF questionnaire. The data were analyzed with the level of significance set to 5%. Improvements in sensitivity and an increase in the perception of muscle contraction were found in the active PBM group 30 days after treatment compared with the sham group. The results of the WHOQOL-BREF questionnaire revealed a significant difference in general quality of life favoring the active PBM group over the sham group after treatment. Physiotherapy combined with PBM leads to better sensory-motor recovery in patients with SCI as well as a better perception of health and quality of life. Trial registration identifier: NCT03031223.

Health-related quality of life after apalutamide treatment in patients with metastatic castration-sensitive prostate cancer (TITAN): a randomised, placebo-controlled, phase 3 study.

BACKGROUND: In the phase 3 TITAN study, the addition of apalutamide to androgen deprivation therapy (ADT) significantly improved the primary endpoints of overall survival and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer. We aimed to assess health-related quality of life (HRQOL) in TITAN, including pain and fatigue. METHODS: In this randomised, placebo-controlled, double-blind, phase 3 study, patients with metastatic castration-sensitive prostate cancer (defined as not receiving ADT at the time of metastatic disease progression) aged 18 years and older, receiving continuous ADT (selected at the investigator's discretion), and with an Eastern Cooperative Oncology Group performance status score of 0 or 1 were randomly assigned (1:1), using an interactive web response system, to receive oral apalutamide (four 60 mg tablets, once daily) or matching placebo. Previous localised disease treatment or previous docetaxel for metastatic castration-sensitive prostate cancer were allowed. Randomisation was stratified by Gleason score at diagnosis, region, and previous docetaxel treatment. Randomisation was done using randomly permuted blocks (block size of four). Investigators, research staff, sponsor study team, and patients were masked to the identities of test and control treatments. Patient-reported outcomes were prespecified exploratory endpoints and were the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EuroQoL 5D questionnaire 5 level (EQ-5D-5L). BPI and BFI were completed for 7 consecutive days (days -6 to 1 inclusive of each cycle visit), then at months 4, 8, and 12 in follow-up. FACT-P and EQ-5D-5L were completed during cycles 1-7, then every other cycle until the end of treatment, and at months 4, 8, and 12 in follow-up. Analyses were based on the intention-to-treat population. Missing patient-reported outcome assessments were calculated as the expected number of assessments for a visit minus the actual number of assessments received for that visit. For time-to-event endpoints, when median values could not be calculated because less than 50% of patients had degradation, 25th percentiles were compared. This study is registered with ClinicalTrials.gov, number NCT02489318, and is ongoing. FINDINGS: Between Dec 9, 2015, and July 25, 2017, 1052 eligible patients were enrolled randomly assigned to apalutamide (n=525) or placebo (n=527). Data cutoff for this analysis of patient-reported outcomes was Nov 23, 2018. Median follow-up for time to pain-related endpoints ranged from 19·4 to 22·1 months. Patients were mostly asymptomatic at baseline: on the BPI-SF pain severity scale of 0-10, median pain scores (indicating worst pain in the past 24 h) were 1·14 (IQR 0-3·17) in the apalutamide group and 1·00 (0-2·86) in the placebo group, and median worst fatigue scores on the BFI were 1·29 (IQR 0-3·29) in the apalutamide group and 1·43 (0·14-3·14) in the placebo group. Patient experience of pain and fatigue (intensity and interference) did not differ between the groups for the duration of treatment. Median time to worst pain intensity progression was 19·09 months (95% CI 11·04-not reached) in the apalutamide group versus 11·99 months (8·28-18·46) in the placebo group (HR 0·89 [95% CI 0·75-1·06]; p=0·20). Median time to pain interference progression was not reached in either group (95% CI 28·58-not reached in the apalutamide group; not reached-not reached in the placebo group). 25th percentiles for time to pain interference progression were 9·17 months (5·55-11·96) in the apalutamide group and 6·24 months (4·63-7·43) in the placebo group (HR 0·90 [95% CI 0·73-1·10]; p=0·29). FACT-P total scores and EQ-5D-5L data showed preservation of HRQOL in both groups. The median time to deterioration as determined by FACT-P total score was 8·87 months (95% CI 4·70-11·10) in the apalutamide group and 9·23 months (7·39-12·91) in the placebo group (HR 1·02 [95% CI 0·85-1·22]; p=0·85). INTERPRETATION: Apalutamide with ADT is a well-tolerated and effective option for men with metastatic castration-sensitive prostate cancer. The combination significantly improves survival outcomes compared with ADT alone while maintaining HRQOL despite additive androgen blockade. FUNDING: Janssen Research & Development.

Is there still room to explore cyclodextrin glycosyltransferase-producers in Brazilian biodiversity?

In the present work, different Brazilian biomes aiming to identify and select cyclodextrin glycosyltransferase-producer bacteria are explored. This enzyme is responsible for converting starch to cyclodextrin, which are interesting molecules to carry other substances of economic interest applied by textile, pharmaceutical, food, and other industries. Based on the enzymatic index, 12 bacteria were selected and evaluated, considering their capacity to produce the enzyme in culture media containing different starch sources. It was observed that the highest yields were presented by the bacteria when grown in cornstarch. These bacteria were also characterized by sequencing of the 16S rRNA region and were classified as Bacillus, Paenibacillus, Gracilibacillus and Solibacillus.

Photobiomodulation improves motor response in patients with spinal cord injury submitted to electromyographic evaluation: randomized clinical trial.

Photobiomodulation is a treatment that has been widely used in neurotrauma and neurodegenerative diseases. In the present study, low-level laser therapy was administered to patients with spinal cord injury. Twenty-five individuals were divided into two groups: placebo photobiomodulation plus physiotherapy and active photobiomodulation plus physiotherapy. Electromyographic evaluations were performed before and after 12 sessions of phototherapy as well as 30 days after the end of treatment. In the active phototherapy group, median frequency values of the brachial biceps and femoral quadriceps muscles were higher at rest and during isotonic contraction 30 days after photobiomodulation (p = 0.0258). No significant results were found regarding the rest and isotonic conditions in the pre-photobiomodulation period (p = 0.950) or immediately following photobiomodulation (p = 0.262). The data provide evidence that phototherapy improves motor responses in individuals with spinal cord injury, as demonstrated by differences in the EMG signal before and after treatment. TRIAL REGISTRATION: NCT 03031223.

Patient safety: characterization of YouTube videos. / Segurança do paciente: caracterização de vídeos do YouTube.

OBJECTIVE: To describe how patient safety is addressed in YouTube videos. METHODS: descriptive study with a quantitative approach. Data was collected in May 2015, at YouTube's search field, with descriptor "patient safety". The sample included 92 videos, which were analyzed using descriptive statistics. RESULTS: The videos showed a positive concept of patient safety, based on a systemic vision that attempts to eliminate the traditional punitive culture by promoting a culture of safety. CONCLUSIONS: The use of videos containing high quality information may improve the training process of health students and professionals, as well as raise the individuals' awareness of the importance of their participation in safety issues.

Predicting malignant neck lymphadenopathy using color duplex sonography based on multivariate analysis.

PURPOSE: To select the best predictors of cervical lymph node malignancy based on gray-scale and power Doppler sonography using multivariate analysis. METHODS: We evaluated sonographically a total of 97 lymph nodes in the neck that were subjected to fine-needle aspiration biopsy. The gray-scale and power Doppler sonography parameters that we analyzed using multivariate logistic regression included size, shape, echogenicity, echotexture, margins, hilum, presence of microcalcifications or necrosis, vascularization, and resistance index (RI). RESULTS: The three variables with a diagnostic accuracy exceeding 80% were an altered vascularization, heterogeneous echotexture, and abnormal hilum. Malignant nodes exhibited higher RI and larger sizes than benign nodes, and the best cutoff values to distinguish malignant from benign lymph nodes were an RI of 0.77 and a short axis ≥ 0.9 cm. Altered vascularization, a short axis ≥ 0.9 cm, and abnormal hilum were the best predictors of malignancy. CONCLUSIONS: The best sonographic predictors of lymph node malignancy are, in descending order, an altered vascularization, a short axis ≥ 0.9 cm, an abnormal hilum, and a heterogeneous echotexture. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:587-594, 2016.

The skin-to-calyx distance measured by renal ct scan and ultrasound.

PURPOSE: We developed a stereotactic device to guide the puncture for percutaneous nephrolithotripsy, which uses the distance from the target calyx to its perpendicular point on skin (SCD) to calculate the needle´s entry angle. This study seeks to validate the use of measurements obtained by ultrasound (US) and computerized tomography (CT) for needle´s entry angle calculation and to study factors that may interfere in this procedure. MATERIALS AND METHODS: Height, weight, abdominal circumference, CT of the urinary tract in dorsal decubitus (DD) and ventral decubitus (VD), and US of the kidneys in VD were obtained from thirty-five renal calculi patients. SCD obtained were compared and correlated with body-mass index (BMI). RESULTS: BMI was 28.66 ± 4.6 Kg/m2. SCD on CT in DD was 8.40 ± 2.06cm, in VD was 8.32 ± 1.95cm, in US was 6.74 ± 1.68cm. SCD measured by US and CT were statistically different (p < 0.001), whereas between CT in DD and VD were not. SCD of the lower calyx presented moderate correlation with BMI. CONCLUSION: SCD obtained by CT in ventral and dorsal decubitus may be used for calculation of the needle´s entry angle. SCD obtained by US cannot be used. A rule for the correlation between BMI and the SCD could not be determined.

[Harnessing of corneas captured and processed for transplantation in an ocular tissue bank of North-eastern Brazil]. / Aproveitamento das córneas captadas e processadas para transplante em um banco de tecidos oculares do Nordeste.

The aim of this study was to describe the harnessing of corneas captured and processed for transplantation in an ocular tissue bank in north-eastern Brazil.This was a transverse and retrospective study, with a sample group of 612 individuals whose corneas were do- nated and captured between January/2007 and July/2012. This study was approved by the Research Ethics Committee under number 007.0.294.000-10, and research was based on an instrument consisting of social, demographic and clinical data of the donors. Of the 1209 corneas captured, 868 were used and 341 were discarded. Of the 612 donors, the corneas of 597 (97.5%) were captured from both eyes, being that 423 (70.9%) of these corneas were used. Further studies are required on the reasons for discarding corneas and clarifications as to the conduct of professionals when processing corneas, considering the increase in the quantity of donors and the elevated number of discarded ocular tissue.

Apalutamide plus androgen deprivation therapy in clinical subgroups of patients with metastatic castration-sensitive prostate cancer: A subgroup analysis of the randomised clinical TITAN study.

BACKGROUND: Whether disease burden in patients with metastatic castration-sensitive prostate cancer (mCSPC) predicts treatment outcomes is unknown. We assessed apalutamide treatment effect in TITAN patients with mCSPC by disease volume, metastasis number and timing of metastasis presentation. METHODS: These protocol-defined and post hoc analyses of the phase III randomised TITAN study evaluated clinical outcomes in patients receiving 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy (ADT). Subgroups were defined by volume (high: visceral and ≥1 bone metastases or ≥4 bone lesions with ≥1 beyond vertebral column/pelvis), development of metastases per conventional imaging (synchronous: at initial diagnosis; metachronous: after localised disease) and oligometastases (≤5 bone-only metastases) or polymetastases (>5 in bone ± other locations or ≤5 in bone plus other locations). Overall survival (OS), radiographic or second progression-free survival, and time to prostate-specific antigen progression or castration resistance were assessed using Cox proportional hazards models. RESULTS: Of 1052 patients, 63%, 81%, 54%, 27%, 5.7%, and 8.0% had high-volume, synchronous, synchronous/high-volume, synchronous/low-volume, metachronous/high-volume, and metachronous/low-volume disease, respectively. The OS benefit favoured apalutamide plus ADT versus ADT alone in synchronous/high-volume (hazard ratio = 0.68 [95% confidence interval: 0.53-0.87]; p = 0.002), synchronous/low-volume (0.65 [0.40-1.05]; p = 0.08), metachronous/high-volume (0.69 [0.33-1.44]; p = 0.32) and metachronous/low-volume (0.22 [0.09-0.55]; p = 0.001) subgroups. Apalutamide improved other clinical outcomes regardless of subgroup, with similar safety profiles. Most favourable outcomes were observed in oligometastatic disease. CONCLUSION: TITAN patients derived a robust benefit with apalutamide plus ADT regardless of disease volume and timing of metastasis presentation without differences in safety, supporting early apalutamide intensification in mCSPC. CLINICAL TRIAL REGISTRATION: NCT02489318.

Effect of Photobiomodulation Combined with Physiotherapy on Functional Performance in Children with Myelomeningo-Cele-Randomized, Blind, Clinical Trial.

BACKGROUND: This study aimed to evaluate the electrical activity of the rectus femoris, tibialis anterior, and lateral gastrocnemius muscles during the sit-to-stand task and functional mobility after a neurofunctional physiotherapy protocol associated with PBM. METHODS: Twenty-five children were randomly allocated to either Active PBM + physiotherapy (n = 13) or PBM sham + physiotherapy (n = 12). PBM was carried out with a LED device (850 nm, 25 J, 50 s per point and 200 mW) at four points over the area with absence of a spiny process. Both groups completed a twelve-week supervised program with two weekly 45-60 min sessions. Pre-training and post-training assessments involved the Pediatric Evaluation of Disability Inventory (PEDI). Muscle activity was assessed using portable electromyography (BTS Engineering) and the electrodes were positioned on the lateral gastrocnemius, anterior tibialis, and rectus femoris muscles. The RMS data were recorded and analyzed. RESULTS: After 24 sessions of the treatment protocol, improvements were found in the PEDI score. The participants presented greater independence in performing the tasks, requiring less assistance from their caregivers. More significant electrical activity was found in the three muscles evaluated between the rest period and execution of the sit-to-stand tasks, both in the more compromised or less compromised lower limbs. CONCLUSION: Neurofunctional physiotherapy with or without PBM improved functional mobility and electrical muscle activity in children with myelomeningocele.

Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition. METHODS: MAGNITUDE (ClinicalTrials.gov identifier: NCT03748641) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR-, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR- cohort. RESULTS: Median rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR- cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events. CONCLUSION: Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.[Media: see text].