Application of fluorescein sodium videoangiography in aneurysm surgery.

BACKGROUND: The use of fluorescent technologies in vascular neurosurgery emerged after indocyanine green video angiography (ICG-VA) was first described in 2003. As data supporting the efficiency of ICG in preventing postoperative complications has grown substantially, it has now established itself as the standard of care. However, the predominant literature centers on ICG techniques, leaving the evaluation of cost-effective fluorescein tools pending. We report the results of a prospective study in which we demonstrated the impact of intraoperative fluorescein videoangiography (FL-VA) in aneurysm surgery. METHODS: Between December 2021 and September 2022, a total of 57 patients underwent craniotomy for intracranial aneurysm surgery. After aneurysm clipping, we administered a 0.5 mg/Kg of sodium fluorescein, and the intracranial area of interest was inspected through the microscope integrated module. The following data were collected: patient age and sex; number of clipped aneurysms; aneurysm location, size, and rupture status; Hunt Hess grade; intraoperative rupture; aneurysm calcification and thrombosed aneurysm; visualization of blood flow in perforating arteries; need for a clip adjustment after FL-VA analysis by neurosurgeon. RESULTS: For the surgical clipping of 64 aneurysms in 57 patients, 80 FL-VA studies were performed. Clip adjustments were performed following FL-VA in 13 aneurysms. FL-VA had an impact on 20 % of the clipping. In seven aneurysms, clip adjustment was due to the "presence of residual aneurysm", in three cases due to the "presence of neck", and in three cases due to "adjacent vessel stenosis". Regarding the evaluation of flow in the perforating vessels, it was possible, with a good and detailed image in all cases. CONCLUSION: The use of FL-VA has a significant impact in aneurysm surgery, enhancing effectiveness and safety. The dosage of 0.5 mg/kg administered is sufficient for assessing both aneurysm occlusion and the presence of flow in adjacent vessels.

Sociodemographic factors and lifestyle behaviours associated with bullying victimization and perpetration in a sample of Brazilian adolescents.

This article aims to identify the association of sociodemographic factors and lifestyle behaviours with bullying perpetration and victimization among high school students. The adolescents (n=852) answered a questionnaire about bullying (victims and perpetrators), sociodemographic factors (sex, age, maternal education, and participant's work status), tobacco use, alcohol use, illicit drug experimentation, physical activity, screen time, and sleep duration. Multilevel logistic regression models were performed. Older adolescents were less likely to be victims of bullying. Females were less likely to be perpetrators or victims of bullying. Adolescents who were working were more likely to be involved in bullying in both forms. Participation in non-sport activities and alcohol consumption were associated with higher odds of bullying victimization. We have identified specific populational subgroups that are more susceptible to being victims and/or perpetrators of bullying, which could support tailor-specific interventions to prevent bullying.

Prognostic impact of corticosteroid and tocilizumab use following chimeric antigen receptor T-cell therapy for multiple myeloma.

Despite being the mainstay of management for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), there is limited data regarding the impact of tocilizumab (TCZ) and corticosteroids (CCS) on chimeric antigen receptor (CAR) T-cell efficacy in multiple myeloma (MM). The present study aims to evaluate the prognostic impact of these immunosuppressants in recipients of BCMA- or GPRC5D-directed CAR T cells for relapsed/refractory MM. Our retrospective cohort involved patients treated with commercial or investigational autologous CAR T-cell products at a single institution from March 2017-March 2023. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), complete response rate (CRR), and overall survival (OS). In total, 101 patients (91% treated with anti-BCMA CAR T cells and 9% treated with anti-GPRC5D CAR T cells) were analyzed. Within 30 days post-infusion, 34% received CCS and 49% received TCZ for CRS/ICANS management. At a median follow-up of 27.4 months, no significant difference in PFS was observed between CCS and non-CCS groups (log-rank p = 0.35) or between TCZ and non-TCZ groups (log-rank p = 0.69). ORR, CRR, and OS were also comparable between evaluated groups. In our multivariable model, administering CCS with/without TCZ for CRS/ICANS management did not independently influence PFS (HR, 0.74; 95% CI, 0.36-1.51). These findings suggest that, among patients with relapsed/refractory MM, the timely and appropriate use of CCS or TCZ for mitigating immune-mediated toxicities does not appear to impact the antitumor activity and long-term outcomes of CAR T-cell therapy.

The Potential of the Fibronectin Inhibitor Arg-Gly-Asp-Ser in the Development of Therapies for Glioblastoma.

Glioblastoma (GBM) is the most lethal and common malignant primary brain tumor in adults. An important feature that supports GBM aggressiveness is the unique composition of its extracellular matrix (ECM). Particularly, fibronectin plays an important role in cancer cell adhesion, differentiation, proliferation, and chemoresistance. Thus, herein, a hydrogel with mechanical properties compatible with the brain and the ability to disrupt the dynamic and reciprocal interaction between fibronectin and tumor cells was produced. High-molecular-weight hyaluronic acid (HMW-HA) functionalized with the inhibitory fibronectin peptide Arg-Gly-Asp-Ser (RGDS) was used to produce the polymeric matrix. Liposomes encapsulating doxorubicin (DOX) were also included in the hydrogel to kill GBM cells. The resulting hydrogel containing liposomes with therapeutic DOX concentrations presented rheological properties like a healthy brain. In vitro assays demonstrated that unmodified HMW-HA hydrogels only caused GBM cell killing after DOX incorporation. Conversely, RGDS-functionalized hydrogels displayed per se cytotoxicity. As GBM cells produce several proteolytic enzymes capable of disrupting the peptide-HA bond, we selected MMP-2 to illustrate this phenomenon. Therefore, RGDS internalization can induce GBM cell apoptosis. Importantly, RGDS-functionalized hydrogel incorporating DOX efficiently damaged GBM cells without affecting astrocyte viability, proving its safety. Overall, the results demonstrate the potential of the RGDS-functionalized hydrogel to develop safe and effective GBM treatments.

Factors Associated With Loss to Follow-Up in Surgical Trials: A Systematic Review and Meta-Analysis.

INTRODUCTION: Loss to follow-up (LTFU) distorts results of randomized controlled trials (RCTs). Understanding trial characteristics that contribute to LTFU may enable investigators to anticipate the extent of LTFU and plan retention strategies. The objective of this systematic review and meta-analysis was to investigate the extent of LTFU in surgical RCTs and evaluate associations between trial characteristics and LTFU. METHODS: MEDLINE, Embase, and PubMed Central were searched for surgical RCTs published between January 2002 and December 2021 in the 30 highest impact factor surgical journals. Two-hundred eligible RCTs were randomly selected. The pooled LTFU rate was estimated using random intercept Poisson regression. Associations between trial characteristics and LTFU were assessed using metaregression. RESULTS: The 200 RCTs included 37,914 participants and 1307 LTFU events. The pooled LTFU rate was 3.10 participants per 100 patient-years (95% confidence interval [CI] 1.85-5.17). Trial characteristics associated with reduced LTFU were standard-of-care outcome assessments (rate ratio [RR] 0.17; 95% CI 0.06-0.48), surgery for transplantation (RR 0.08; 95% CI 0.01-0.43), and surgery for cancer (RR 0.10; 95% CI 0.02-0.53). Increased LTFU was associated with patient-reported outcomes (RR 14.21; 95% CI 4.82-41.91) and follow-up duration ≥ three months (odds ratio 10.09; 95% CI 4.79-21.28). CONCLUSIONS: LTFU in surgical RCTs is uncommon. Participants may be at increased risk of LTFU in trials with outcomes assessed beyond the standard of care, surgical indications other than cancer or transplant, patient-reported outcomes, and longer follow-up. Investigators should consider the impact of design on LTFU and plan retention strategies accordingly.

Comparison of infectious complications with BCMA-directed therapies in multiple myeloma.

B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25-0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31-3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05-3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21-0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17-0.59, P < 0.001) of severe infections than BsAb. In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb. Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients.

Comparative efficacy of carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in newly-diagnosed multiple myeloma: A systematic review and meta-analysis.

In view of the increasing data evaluating carfilzomib-based induction for newly-diagnosed multiple myeloma (NDMM), we conducted a systematic review and meta-analysis comparing the efficacy of carfilzomib/lenalidomide/dexamethasone (KRd) versus bortezomib/lenalidomide/dexamethasone (VRd). Three studies totaling 1597 patients (50% KRd-treated, 50% VRd-treated) were included. Despite similar survival outcomes and overall response rate compared with the VRd arm, KRd-treated subjects showed higher odds of achieving complete responses and measurable residual disease negativity. Among patients with high-risk cytogenetics (n = 348), KRd was associated with significant improvement in progression-free survival (HR = 0.70; 95% CI = 0.50-0.97; p = .03; I2 = 0%), suggesting carfilzomib-based induction may be preferable in this NDMM subpopulation.

Perfil da mortalidade de policiais militares por causas violentas, segundo cor da pele, na Bahia, Brasil / Profile of military police officers' mortality from violent causes, according to skin color, in Bahia, Brazil / Perfil de mortalidad por causas violentas de policías militares según el color de piel en Bahía, Brasil

O Brasil é um país com altas taxas de violência, o que afeta, além da sociedade civil, os agentes das forças da segurança pública, cujas taxas de mortalidade por causas violentas são superiores às da população geral. Portanto, objetivou-se caracterizar o perfil da mortalidade de policiais militares por causas violentas, segundo a cor da pele, no estado da Bahia. Neste estudo, foram analisadas as mortes violentas de policiais militares da ativa ocorridas entre 2012 e 2019, considerando variáveis tanto sociodemográficas quanto relacionadas à corporação policial e às circunstâncias da ocorrência. A análise dos resultados foi realizada por meio da linguagem computacional R versão 4.2.2. Foram registradas 110 mortes de policiais militares, em sua maioria negros (83,64%). Em relação à faixa etária, os policiais militares negros morreram mais jovens, entre 30 e 39 anos (41,30%), enquanto os brancos, entre 40 e 49 anos (61,11%). Em 50% dos casos envolvendo policiais militares negros, a motivação do crime permaneceu desconhecida, enquanto 33,33% das mortes envolvendo policiais brancos foram por confronto com criminosos. Conclui-se que o perfil das mortes de policiais militares no estado da Bahia é semelhante ao da população em geral, com predomínio de homens, negros, jovens e solteiros.

Brazil is a country with high rates of violence, which affects, in addition to civil society, public security agents, whose mortality rates from violent causes are higher than those of the general population. Therefore, the objective was to characterize the profile of mortality of military police officers due to violent causes, according to skin color, in the state of Bahia. This study analyzed violent deaths of active military police officers that occurred between 2012 and 2019, considering both sociodemographic variables and those related to the police force and the circumstances of the occurrence. The analysis of the results was carried out using the computational language R version 4.2.2. A total of 110 military police deaths were recorded, most were black (83.64%). Regarding age group, black military police officers died younger, between 30 and 39 years old (41.30%), whereas white military police officers, between 40 and 49 years old (61.11%). In 50% of cases involving black military police officers, the motivation for the crime remained unknown, whereas 33.33% of deaths involving white police officers were due to confrontation with criminals. In conclusion, the profile of military police deaths in the state of Bahia is similar to that of the general population, with a predominance of male, black, young, and single people.

Brasil tiene altos índices de violencia que no solo afectan a la sociedad civil, sino también a los agentes de seguridad pública, cuyas tasas de mortalidad por causas violentas superan a las de la población general. Así, el objetivo de este estudio fue caracterizar el perfil de mortalidad por causas violentas de los policías militares según el color de la piel, en el estado de Bahía (Brasil). En este estudio se analizaron muertes violentas de policías militares en activo, ocurridas entre 2012 y 2019, considerando variables sociodemográficas relacionadas con el cuerpo policial y las circunstancias de la ocurrencia. El análisis de los resultados se realizó utilizando el lenguaje computacional R, versión 4.2.2. Se registraron 110 muertes de policías militares, la mayoría negros (83,64%). Con relación al grupo de edad, los policías militares negros murieron más jóvenes, de entre 30 y 39 años (41,30%), que los policías militares blancos, de entre 40 y 49 años (61,11%). En el 50% de los casos que involucraron a policías militares negros, la motivación del crimen seguía siendo desconocida, mientras que en el 33,33% de las muertes que involucraron a policías blancos se debieron a enfrentamientos con delincuentes. Se concluye que el perfil de las muertes de policías militares en Bahía es similar al de la población general, con predominio de hombres, negros, jóvenes y solteros.

Mortalidade por homicídio de policiais civis do estado da Bahia, Brasil / Mortality by murder of civil police officials in the state of Bahia, Brazil / Mortalidad por asesinato de policías civiles en el estado de Bahía, Brasil

Os homicídios de policiais estão associados a fatores individuais, sociais e do trabalho. Dessa forma, o objetivo deste artigo é caracterizar a mortalidade por homicídio de policiais civis da Bahia entre 2012 e 2019. Trata-se de estudo descritivo de vigilância da mortalidade de homicídios de policiais civis da ativa. As variáveis estudadas foram sociodemográficas, da atividade policial e da ocorrência. Na análise foram realizados cálculos de taxas de mortalidade e da estatística descritiva, por meio da linguagem computacional R versão 4.2.2. Foram registrados 27 homicídios de policiais civis da ativa, o que equivale a uma taxa média de 0,58/1000. Na caracterização, todos eram homens, com idade média de 52,5 anos (42 a 63 anos) e 95% negros. Em relação à atividade policial, 76% eram investigadores, com média de 17,9 anos (3 a 33 anos) de serviço e 81% das mortes ocorreram em horário de folga. Em 90% dos homicídios a arma de fogo foi o instrumento causador da morte, e em 62% dos casos a autoria não foi identificada. Conclui-se que o perfil sociodemográfico, do trabalho e das ocorrências de homicídios de policiais civis é semelhante ao perfil encontrado entre policiais militares e sobretudo aos homicídios da população geral.

Police homicides are associated with individual, social, and work-related factors. To characterize mortality due to homicide cases of civil police officers in the State of Bahia from 2012 to 2019.This is a descriptive study of mortality surveillance regarding the homicides of active civil police officers. The variables studied included sociodemographic, police activity, and event occurrence rates. In the analysis, mortality rates and descriptive statistics were calculated using the computational language R, version 4.2.2. Overall, 27 cases of homicide of civil police officers were registered, with an average rate of 0.58/1000 civil police officers. In the characterization, all victims were men with an average age of 52.5 years (42 to 63 years) and a 95% percent Black ethnicity. Regarding police activity, 76% were investigators, with an average of 17.9 years (3 to 33 years) of service, and 81% of deaths occurred during off-duty hours. In 90% of homicide cases, firearms were the instrument that caused death, and in 62% of cases the perpetrator was unidentified. The sociodemographic, work, and homicide profile of civil police officers resembles the profile among military police officers and especially that of homicides in the general population.

Los homicidios de policías están asociados a factores individuales, sociales y laborales. El objetivo de este artículo fue caracterizar la mortalidad por homicidio de policías civiles en el estado de Bahía (Brasil), en el período entre 2012 y 2019. Se trata de un estudio descriptivo de la vigilancia de la mortalidad por homicidios de policías civiles en activo. Las variables estudiadas fueron sociodemográficas, actividad policial y ocurrencia. En el análisis se realizaron cálculos de tasas de mortalidad y estadísticas descriptivas utilizando el lenguaje computacional R, versión 4.2.2.Se registraron 27 homicidios de policías civiles en activo, con una media de 0,58/1000 policías civiles. En la caracterización, todos eran hombres, con media de edad de 52,5 años (42 a 63 años), y el 95%, negros. Con relación a la actividad policial, el 76% se desempeñaban como investigadores, con un promedio de 17,9 años (3 a 33 años) de servicio y el 81% de las muertes ocurrieron fuera de servicio. En el 90% de los homicidios, el arma de fuego fue el instrumento que provocó la muerte y en el 62% de los casos no se identificó al autor. Se concluye que el perfil sociodemográfico, laboral y de homicidios de los policías civiles es similar al perfil encontrado entre los policías militares y, especialmente, a los homicidios en la población general.

Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Systematic Review and Patient-Level Meta-Analysis.

Importance: Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor. Objective: To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI. Data Sources: MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction. Study Selection: Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI. Data Extraction and Synthesis: Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data. Main Outcomes and Measures: The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding. Results: Analyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority > .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P < .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P < .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04). Conclusions and Relevance: This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.

Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta-analysis.

Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease as well as the therapies themselves. Overall, available evidence is inconclusive about the differential thrombogenicity of carfilzomib/lenalidomide/dexamethasone (KRd) and bortezomib/lenalidomide/dexamethasone (VRd). This meta-analysis compares the risk for venous thromboembolism (VTE; including deep venous thrombosis and pulmonary embolism) and arterial thromboembolism (ATE; including myocardial infarction and ischemic stroke) with KRd versus VRd as primary therapy for newly diagnosed MM (NDMM). Out of 510 studies identified after deduplication, one randomized controlled trial and five retrospective cohort studies were included. We analyzed 2304 patients (VRd: 1380; KRd: 924) for VTE events and 2179 patients (VRd: 1316; KRd: 863) for ATE events. Lower rates of VTE were observed in the VRd group when compared with the KRd group (6.16% vs. 8.87%; odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.88; p = .01). Both treatment groups exhibited minimal ATE incidence, with no significant difference between them (0.91% vs. 1.16%; OR, 1.01; 95% CI, 0.24-4.20; p = .99). In view of potential biases from retrospective studies, heterogeneity of baseline population characteristics, and limited access to patient-level data (e.g., VTE risk stratification and type of thromboprophylaxis regimen used) inherent to this meta-analysis, additional research is warranted to further validate our findings and refine strategies for thrombosis prevention in MM.

Comparison of Infectious Complications with BCMA-directed Therapies in Multiple Myeloma.

B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥ 3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25-0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31-3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05-3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21-0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17-0.59, P < 0.001) of severe infections than BsAb. In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb. Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients.

Soluble B-cell maturation antigen in multiple myeloma.

B-cell maturation antigen (BCMA) has emerged as a promising immunotherapeutic target in multiple myeloma (MM) management, with the successive approval of antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T-cell therapies directed to this membrane receptor. Soluble BCMA (sBCMA), a truncated version produced through gamma-secretase cleavage, can be quantified in serum/plasma samples from patients with MM via electrochemiluminescence, fluorescence, or enzyme-linked immunosorbent assays, as well as through mass spectrometry-based proteomics. Besides its short serum half-life and independence from kidney function, sBCMA represents a reliable and convenient tool for MM monitoring in patients with nonsecretory or oligosecretory disease. Numerous studies have suggested a potential utility of this bioanalyte in the risk stratification of premalignant plasma cell disorders, diagnosis and prognostication of MM, and response evaluation following anti-myeloma therapies. In short, sBCMA might be the "Swiss army knife" of MM laboratory testing, but is it ready for prime time?

Relevance of HOTAIR rs920778 and rs12826786 Genetic Variants in Bladder Cancer Risk and Survival.

The long non-coding RNA HOX transcript antisense intergenic RNA (HOTAIR) is associated with oncogenic features in bladder cancer and is predictive of poor clinical outcomes in patients diagnosed with this disease. In this study, we evaluated the impact of the HOTAIR single nucleotide polymorphisms rs920778 and rs12826786 on bladder cancer risk and survival. This case-control study included 106 bladder cancer patients and 199 cancer-free controls. Polymorphisms were evaluated through PCR-restriction fragment length polymorphism. The odds ratio and 95% confidence intervals were tested using univariable and multivariable logistic regressions. The effects on patient survival were evaluated using the log-rank test and Cox regression models. Our data showed that the HOTAIR rs920778 and rs12826786 genetic variants are not associated with the risk of developing bladder cancer. Nevertheless, survival analyses suggested that the HOTAIR rs920778 TT genotype and rs12826786 CC genotype are associated with increased survival in male bladder cancer patients and in patients, both male and female, who have primary tumors with a pathological stage of pT2. Together, these results suggest that, despite not being associated with bladder cancer risk, HOTAIR rs920778 and rs12826786 polymorphisms might represent new prognostic factors in this type of cancer. This is particularly important as these polymorphisms might be easily evaluated in bladder cancer patients in a minimally invasive manner to better predict their clinical outcomes.

Intrauterine Correction of Fetal Myelomeningocele Through Minihysterotomy.

Spina bifida is the most common congenital central nervous system anomaly, resulting in lifelong neurologic, urinary, motor, and bowel disability.1 Its most frequent form is myelomeningocele, characterized by spinal cord extrusion into a sac filled with cerebrospinal fluid.1 We report the case of a 28-year-old pregnant female with no comorbidities. At 16 weeks of pregnancy, fetal ultrasound presented ventriculomegaly, cerebellar herniation, and lumbar myelomeningocele. At 22 weeks, intrauterine surgical correction was performed (Video 1). A minihysterotomy spanning approximately 3 cm was performed. The defect was opened, and the neural placode was dissected and released. This was followed by the isolation of the peripheric dura, which was molded into a tube and closed with watertight suture. Finally, the minihysterotomy was sutured and the skin was closed. The pregnancy followed its course with no complications, and the child was born at term with the lesion closed and no necessity of intensive care. Recent studies have demonstrated that infants who undergo open in utero myelomeningocele repair have better neurologic outcomes than those who are treated after birth.1,2 However, maternal morbidity is nonnegligible with the classical open surgery.2 Peralta et al2 propose a modification of the classic 6.0- to 8.0-cm hysterotomy in which the same multilayer correction of the spinal defect is performed through a 2.5- to 3.5-cm hysterotomy. This modification, called minihysterotomy, has been successfully performed outside of its creation center and was associated with reduced risks of preterm delivery and maternal, fetal, and neonatal complications.2,3.

Mini-Open Fascia Lata Interposition Graft Results In Superior 2-Year Clinical Outcomes When Compared to Arthroscopic Partial Repair for Irreparable Rotator Cuff Tear: A Single-Blind Randomized Controlled Trial.

PURPOSE: To evaluate and compare the results of surgical treatment for irreparable rotator cuff tear (IRCT) by the mini-open interposition procedure using fascia lata autograft against outcomes of the arthroscopic partial repair technique. METHODS: An interventional, prospective, controlled, randomized, single-blinded study involving 2 study groups was conducted. The graft group (n = 20) underwent the mini-open interposition procedure using fascia lata autograft. The control group (n = 22) underwent arthroscopic partial repair. Patients were evaluated using the University of California Los Angeles (UCLA) Shoulder scale, the American Shoulder and Elbow Surgeons (ASES) score, the Constant-Murley (Constant) score, the visual analogue scale (VAS) pain score, active range of motion, frontal flexion strength, retear rates evaluated by magnetic resonance imaging analysis, occurrence of complications, and the minimal clinically important difference (MCID). RESULTS: The graft group had better UCLA (31.5 vs 28.18, P = .035) (100% exceeded the MCID for the graft group and 95% for the control group), ASES (88.62 vs 77.06, P = .016) (100% exceeded the MCID for both groups), Constant (78.85 vs 61.68, P < .001), and VAS (0.95 vs 2.59, P = .01) scores at the 24-month follow-up. For active forward elevation range, both groups showed no statistically significant differences (168.5 vs 164.54, P = .538). The results for active external and internal rotation were better in the graft group (60.25 vs 40, and 9.1 vs 6.9, P < .001), as was frontal flexion strength (4.24 vs 2.67, P = .005). The graft group also had lower retear rates (15% vs 45.5%, P = .033). No complications were reported. CONCLUSIONS: Outcomes of surgeries for IRCT by the mini-open interposition procedure using fascia lata autograft and by the arthroscopic partial repair technique showed good results in both groups over time and exceeded the MCID. However, most comparative outcomes between groups showed better results for the interposition procedure. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Sociodemographic factors and lifestyle behaviours associated with bullying victimization and perpetration in a sample of Brazilian adolescents / Fatores sociodemográficos e comportamentos de estilo de vida associados à vitimização e perpetração do bullying em uma amostra de adolescentes brasileiros

Abstract This article aims to identify the association of sociodemographic factors and lifestyle behaviours with bullying perpetration and victimization among high school students. The adolescents (n=852) answered a questionnaire about bullying (victims and perpetrators), sociodemographic factors (sex, age, maternal education, and participant's work status), tobacco use, alcohol use, illicit drug experimentation, physical activity, screen time, and sleep duration. Multilevel logistic regression models were performed. Older adolescents were less likely to be victims of bullying. Females were less likely to be perpetrators or victims of bullying. Adolescents who were working were more likely to be involved in bullying in both forms. Participation in non-sport activities and alcohol consumption were associated with higher odds of bullying victimization. We have identified specific populational subgroups that are more susceptible to being victims and/or perpetrators of bullying, which could support tailor-specific interventions to prevent bullying.

Resumo O objetivo deste artigo é identificar a associação de fatores sociodemográficos e comportamentos de estilo de vida com a perpetração do bullying e da vitimização entre os alunos do ensino médio. Os adolescentes (n=852) responderam a um questionário sobre bullying (vítimas e perpetradores), fatores sociodemográficos (sexo, idade, educação materna e status profissional dos participantes), uso de tabaco, uso de álcool, experimentação de drogas ilícitas, atividade física, tempo de tela e duração do sono. Modelos de regressão logística multinível foram realizados. Os adolescentes mais velhos eram menos propensos a serem vítimas de bullying. As mulheres tinham menos probabilidade de serem perpetradoras ou vítimas de bullying. Os adolescentes que estavam trabalhando tinham maior probabilidade de estarem envolvidos em bullying em ambas as formas. A participação em atividades não esportivas e o consumo de álcool estavam associados a maiores probabilidades de vitimização por bullying. Identificamos subgrupos populacionais específicos que são mais suscetíveis a serem vítimas e/ou perpetradores de bullying, o que poderia apoiar intervenções específicas sob medida para evitar o bullying.

Levels of organic pollutants and metals/metalloids in infant formula marketed in Brazil: Risks to early-life health.

Infant formula intake is recommended to ensure comprehensive nutritional and caloric fulfillment when exclusive breastfeeding is not possible. However, similarly to breast milk, infant formulas may also contain pollutants capable of inducing endocrine-disrupting and neurotoxic effects. Thus, considering the sensitivity of their developing physiological systems and that infants have heightened susceptibility to environmental influences, this study was aimed at assessing the contents of essential elements, and inorganic and organic pollutants in infant formulas marketed in Brazil. Additionally, health risk assessments for selected contaminants were also performed. Measured contents of essential elements (Ca, Fe, Mg, Mn, Cu, Se, and Zn) were congruent with label information. Nevertheless, some toxic elements (Pb, Cd, As, Ni, and Al) were also detected. Notably, in the upper-bound scenario, Pb and Cd surpassed established threshold values when comparing the estimated daily intake (EDI) and tolerable daily intake (TDI - 3.57 and 0.36 µg/kg bw, respectively). Bisphenol P (BPP) and benzyl butyl phthalate (BBP) were frequently detected (84 % detection rate both) with elevated contents (BPP median = 4.28 ng/g and BBP median = 0.24 ng/g). Furthermore, a positive correlation (0.41) was observed between BPP and BBP, implying a potential co-occurrence within packaging materials. Methyl-paraben also correlated positively with BBP (0.57), showing a detection rate of 53 %. The cumulative PBDE contents ranged from 0.33 to 1.62 ng/g, with BDE-154 and BDE-47 the dominant congeners. When comparing EDI values with TDIs, all organic pollutants remained below the thresholds across all exposure scenarios. Moreover, non-carcinogenic risks were below the threshold (HQ > 1) when dividing the EDIs by the respective reference doses for chronic exposure. While the current findings may suggest that infant formula intake poses no immediate risk in terms of the evaluated chemicals, it remains imperative to conduct further research to safeguard the health of infants considering other chemicals, as well as their potential cumulative effects.

Quality control of psychoactive substances in human breastmilk samples from a human milk bank by disposable pipette extraction-gas chromatography-mass spectrometry.

The lack of data regarding infant exposure to drugs of abuse consumed by lactating mothers has become a major health concern. Investigating psychoactive substances and their metabolites in breastmilk is an analytical approach to estimate the rate at which drugs of abuse are excreted and how much infants are exposed to them. In this study, we have developed and validated a GC-MS method using disposable pipette tips for simultaneously extracting ten analytes from breastmilk samples obtained from a milk bank in the city of Ribeirão Preto, Brazil. All the 67 analyzed samples tested negative for all the analytes. This is the first study that has applied disposable pipette extraction to analyze drugs of abuse in breastmilk samples.

Breastfeeding, the most effective single strategy to reduce child mortality, provides numerous benefits for both the mother and the infant. The mother's consumption habits during breastfeeding strongly influence breastmilk quality and the newborn's nutrition. Given that drugs of abuse negatively affect both the mother's and the infant's health, analyzing breastmilk samples helps to estimate infant exposure to these drugs and to evaluate how severe this public health issue is. We have developed a new method to monitor ten substances in breastmilk, to improve our understanding of this issue in Brazil. None of the substances were detected in the few samples obtained from a milk bank, which showed that this organization successfully analyzes the donor's profile and conducts effective anamnesis. Future analysis of a larger number of samples and hence more data could help to describe the current scenario in more detail.

CAR T-Cell Therapy for Multiple Myeloma: A Clinical Practice-Oriented Review.

The emergence of chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, including multiple myeloma (MM). Two BCMA-directed CAR T-cell products - idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) - have received US Food and Drug Administration (FDA) approval for patients with relapsed/refractory MM who underwent four or more prior lines of therapy (including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody). Despite producing unprecedented response rates in an otherwise difficult to treat patient population, CAR T-cell therapies are commonly associated with immune-related adverse events (e.g., cytokine release syndrome and neurotoxicity), cytopenias, and infections. Moreover, many patients continue to exhibit relapse post-treatment, with resistance mechanisms yet to be fully understood. Ongoing basic, translational, and clinical research efforts are poised to generate deeper insights into the optimal utilization of these therapies, improve their efficacy, minimize associated toxicity, and identify new target antigens in patients with MM.