Sarcopenia as a Predictive Factor for Carboplatin Toxicity in Patients with Advanced Non-Small Cell Lung Cancer.

Sarcopenia in cancer patients often negatively impacts various outcomes. Carboplatin, a first-line chemotherapy for non-small cell lung cancer (NSCLC), is dosed based on body weight, which doesn't account for sarcopenia. This study evaluated the association between sarcopenia and carboplatin-related toxicity in NSCLC patients. Patients with locally advanced or metastatic NSCLC treated with carboplatin were included. Toxicity events during the first two cycles of treatment were recorded. Sarcopenia was assessed using pretreatment computed tomography scans analyzed with Slice-O-Matic V4.2 software, defining sarcopenia as a skeletal muscle index (SMI) of <52.4 cm2/m2 for men and <38.5 cm2/m2 for women. Among 146 patients, 52% had sarcopenia. Hematological toxicity occurred in 71.2% of all patients and 77.6% of those with sarcopenia. The fat-free mass index (FFMI) was independently associated with hematological toxicity and dose-limiting toxicity (DLT), which was observed in 55.5% of patients. Sarcopenia significantly correlates with hematological toxicity and DLT during carboplatin treatment in NSCLC patients. Given its prevalence and noninvasive detection, further research is needed to understand its impact on treatment outcomes.

Psychosocial and biological pathways to aging : The role(s) of the behavioral and social sciences in geroscience.

While the biological hallmarks of aging are widely recognized as fundamental mechanisms of biological aging, more recently, there have been calls within geroscience to understand the aging process more comprehensively by adding a perspective of the social hallmarks of aging. Social and behavioral factors, such as socioeconomic status, life events or behavior and beliefs can alter the aging process per se and act in complex interactions with biological pathways. In addition, underlying biological pathways have been proposed for various psychosocial concepts, such as views on age and relationship quality. The aim of the present article is to provide narrative insights into theoretical and empirical developments between social and behavioral gerontology and geroscience or biogerontology. This article focuses on the potential of an interdisciplinary aging research but it also sets out the critical perspective that social gerontology provides.

Depressive symptoms among individuals identifying as asexual: a cross-sectional study.

Although asexuality became a growing research subject over the last decade, data on the mental health of individuals identifying as asexual is still rare. The key objective of the present study was to examine depressive symptoms among individuals identifying as asexual. Data of LGBTQIA+ (Lesbian, Gay, Bi-sexual, Trans*, Queer, Inter*, Asexual and/or + indicating others within the community) and cisgender heterosexual individuals was collected through an online survey during the COVID-19 lockdowns in Germany. The survey included questions about sexual and gender identity, depressive symptoms, and asexual identity. An analysis of N = 6601 participants was conducted. A total of n = 445 individuals identified as asexual. Regression results indicated identifying as asexual being significantly associated with higher depressive symptoms. Results suggest that individuals identifying as asexual represent a vulnerable group within the group of sexual minorities, one that fundamentally requires special psychosocial support, especially in times of pandemics.

3D printed ventilation tubes and their effect on biological models.

BACKGROUND: Acute otitis media (AOM) causes inflammation and hearing loss. Ventilation tubes are key in treatment. 3D printing improves prostheses in otorhinolaryngology, offering precision and greater adaptability. MATERIALS AND METHODS: An experimental study was conducted with Wistar rats from July to December 2020. 3D tympanostomy tube models were designed, with technical specifications and tests performed on inexpensive 3D printers. The tympanostomy tube was inserted endoscopically. RESULTS: Procedures were performed on five rats with implants in both ears. Pre-intervention pathologies, such as atical retraction and glue ear, were found. The PLA-printed tympanostomy tube showed improvement after adjustments. Histopathological results revealed significant middle and inner ear damage. CONCLUSION: In our study, the design and 3D printing of implants fulfilled the desired functions when modified, with a height of 5 mm. Complications included PLA degradation and ear damage. There were no adverse events during observation, highlighting the need for further research on 3D-printed implants.

Cochlear Implant Device Failures Falling Under the 2020 FDA Voluntary Field Corrective Action: A Systematic Review and Meta-analysis.

OBJECTIVE: To compare the rate of device failure for those cochlear implants (CIs) involved in the 2020 Food and Drug Administration (FDA) voluntary field corrective action (VFCA). DATABASES REVIEWED: Medline, Embase, and Scopus. METHODS: A systematic review was performed according to the PRISMA guidelines. Publications reporting institutional experiences with implants affected by the VFCA were included. Outcomes assessed included etiology of, rate of, and time to failure and pre-/post-device failure speech perception testing. All outcomes reported in at least two independent studies were included in a meta-analysis. RESULTS: Six studies met criteria for analysis. The overall pooled failure rate was 23.7% (95% CI, 11.6-38.4%). The pooled device, inconclusive, and medical failure rates were 21.5%, 0.2%, and 0.7%, respectively. Pediatric failure rates were higher than those of adults (46.9% [95% CI, 11.2-84.5%] versus 32.6% [95% CI, 8.2-63.7%]). WRS declined with primary implant failure (55.1% [95% CI, 48.0-62.1%] to 34.1% [95% CI, 30.2-38.0%]) but improved after reimplantation (34.1% [95% CI, 30.2-38.0%] to 50.1% [95% CI, 45.2-55.1%]). CONCLUSIONS: The rate of pooled reported failure for CIs falling under the 2020 VFCA in the literature thus far is 23.7%. The overwhelming majority of these failures were device related, the rates of which were higher in children. Speech perception improved significantly after reimplantation.

Prevalence of pathogenic or likely pathogenic germline variants in cancer predisposition genes among selected patients with lung adenocarcinoma: The GERMLUNG study.

INTRODUCTION: Pathogenic or likely pathogenic germline variants (PGVs) in cancer predisposition genes may play a role in lung cancer (LC) susceptibility. However, determining an eligible population for genetic testing remains uncertain. This study aimed to assess the prevalence of PGVs in a selected cohort of individuals with lung adenocarcinoma. METHODS: A cross-sectional cohort study was conducted to assess the PGVs rate in lung adenocarcinoma patients with a family history of LC, young-onset presentation, history of never/light smoking, or actionable genomic alterations (AGAs). Sequencing was performed using Sophia Hereditary Cancer Solution panel F, including 144 cancer predisposition genes. Variants classified as pathogenic or likely pathogenic were included for further analysis. RESULTS: Of 201 patients, 43 (21.4 %) exhibited PGVs, among which 64.5 % were DNA damage repair genes, and 86.1 % were clinically actionable. The main PGVs were in ATM (9.3 %), TP53 (6.9 %), BRCA2 (6.9 %), and CHEK2 (6.9 %) genes. PGVs were associated with male sex (adjusted odds ratio [aOR] 2.46, 95 % CI 1.15-5.32, p = 0.021), along with a trend toward association with AGAs (aOR 6.04, 95 % CI 0.77-49.74, p = 0.094). CONCLUSIONS: In this study, a high PGVs prevalence was identified based on our selection criteria, which represents an effective strategy to identify candidates for germline genomic testing, potential screening strategies in close relatives, and personalized therapeutic modalities. Our results warrant further exploration in other populations to confirm them.

Cladosporium psychrotolerans strain T01 enhances plant biomass and also exhibits antifungal activity against pathogens.

An increasing number of microorganisms are being identified to enhance plant growth and inhibit phytopathogens. Some Cladosporium species form beneficial associations with plants, either as endophytes or by colonizing the rhizosphere. Herein, we evaluated the influence of the Cladosporium psychrotolerans (T01 strain) fungus on the in vitro growth of Arabidopsis thaliana plantlets through direct and split interactions. After 9 days post-inoculation with C. psychrotolerans, Arabidopsis plantlets exhibited a notable increase in fresh weight and lateral roots, particularly in split interactions. Chlorophyll content increased in both plant-fungus interaction conditions, whereas the primary root was inhibited during direct interaction. We observed an increase in the GUS signal from the Arabidopsis auxin-inducible DR5:uidA marker in lateral root tips in both contact and split fungal interactions, and primary root tips in a split interaction. Arabidopsis and tomato plants cultivated in soil pots and inoculated with C. psychrotolerans (T01 strain) showed a positive effect on biomass production. GC/MS analysis detected that the T01 strain emitted volatile organic compounds (VOCs), predominantly alcohols and aldehydes. These VOCs displayed potent inhibitory effects, with a 60% inhibition against Botrytis cinerea and a 50% inhibition against C. gloeosporioides. Our study demonstrates that C. psychrotolerans T01 has the potential to enhance biomass production and inhibit pathogens, making it a promising candidate for green technology applications.

Diagnosis and Characterization of Plant Viruses Using HTS to Support Virus Management and Tomato Breeding.

Viral diseases pose a significant threat to tomato crops (Solanum lycopersicum L.), one of the world's most economically important vegetable crops. The limited genetic diversity of cultivated tomatoes contributes to their high susceptibility to viral infections. To address this challenge, tomato breeding programs must harness the genetic resources found in native populations and wild relatives. Breeding efforts may aim to develop broad-spectrum resistance against the virome. To identify the viruses naturally infecting 19 advanced lines, derived from native tomatoes, high-throughput sequencing (HTS) of small RNAs and confirmation with PCR and RT-PCR were used. Single and mixed infections with tomato mosaic virus (ToMV), tomato golden mosaic virus (ToGMoV), and pepper huasteco yellow vein virus (PHYVV) were detected. The complete consensus genomes of three variants of Mexican ToMV isolates were reconstructed, potentially forming a new ToMV clade with a distinct 3' UTR. The absence of reported mutations associated with resistance-breaking to ToMV suggests that the Tm-1, Tm-2, and Tm-22 genes could theoretically be used to confer resistance. However, the high mutation rates and a 63 nucleotide insertion in the 3' UTR, as well as amino acid mutations in the ORFs encoding 126 KDa, 183 KDa, and MP of Mexican ToMV isolates, suggest that it is necessary to evaluate the capacity of these variants to overcome Tm-1, Tm-2, and Tm-22 resistance genes. This evaluation, along with the characterization of advanced lines using molecular markers linked to these resistant genes, will be addressed in future studies as part of the breeding strategy. This study emphasizes the importance of using HTS for accurate identification and characterization of plant viruses that naturally infect tomato germplasm based on the consensus genome sequences. This study provides crucial insights to select appropriate disease management strategies and resistance genes and guide breeding efforts toward the development of virus-resistant tomato varieties.

Intersectional Inequalities in the Transition to Grandparenthood and Cognitive Functioning: A Longitudinal Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy.

OBJECTIVES: In aging societies, more people become vulnerable to experiencing cognitive decline. Simultaneously, the role of grandparenthood is central for older adults and their families. Our study investigates inequalities in the level and trajectories of cognitive functioning among older adults, focusing on possible intersectional effects of social determinants and grandparenthood as a life course transition that may contribute to delaying cognitive decline. METHODS: Using longitudinal data from the Survey of Health, Aging, and Retirement in Europe, we analyzed a sample of 19,953 individuals aged 50-85 without grandchildren at baseline. We applied multilevel analysis of individual heterogeneity and discriminatory accuracy to investigate variation in cognitive functioning across 48 intersectional strata, defined by sex/gender, migration, education, and occupation. We allowed the impact of becoming a grandparent on cognitive functioning trajectories to vary across strata by including random slopes. RESULTS: Intersectional strata accounted for 17.43% of the overall variance in cognitive functioning, with most of the stratum-level variation explained by additive effects of the stratum-defining characteristics. Transition to grandparenthood was associated with higher cognitive functioning, showing a stronger effect for women. Stratum-level variation in the grandparenthood effect was modest, especially after accounting for interactions between grandparenthood and the stratum-defining variables. DISCUSSION: This study highlights the importance of social determinants for understanding heterogeneities in older adults' level of cognitive functioning and its association with the transition to grandparenthood. Cumulative disadvantages negatively affect cognitive functioning, hence adopting an intersectional lens is useful to decompose inequalities and derive tailored interventions to promote equal healthy aging.

The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection.

SARS-CoV-2 infection can cause severe pneumonia, wherein exacerbated inflammation plays a major role. This is reminiscent of the process commonly termed cytokine storm, a condition dependent on a disproportionated production of cytokines. This state involves the activation of the innate immune response by viral patterns and coincides with the biosynthesis of the biomass required for viral replication, which may overwhelm the capacity of the endoplasmic reticulum and drive the unfolded protein response (UPR). The UPR is a signal transduction pathway composed of three branches that is initiated by a set of sensors: inositol-requiring protein 1 (IRE1), protein kinase RNA-like ER kinase (PERK), and activating transcription factor 6 (ATF6). These sensors control adaptive processes, including the transcriptional regulation of proinflammatory cytokines. Based on this background, the role of the UPR in SARS-CoV-2 replication and the ensuing inflammatory response was investigated using in vivo and in vitro models of infection. Mice and Syrian hamsters infected with SARS-CoV-2 showed a sole activation of the Ire1α-Xbp1 arm of the UPR associated with a robust production of proinflammatory cytokines. Human lung epithelial cells showed the dependence of viral replication on the expression of UPR-target proteins branching on the IRE1α-XBP1 arm and to a lower extent on the PERK route. Likewise, activation of the IRE1α-XBP1 branch by Spike (S) proteins from different variants of concern was a uniform finding. These results show that the IRE1α-XBP1 system enhances viral replication and cytokine expression and may represent a potential therapeutic target in SARS-CoV-2 severe pneumonia.

Long-term outcomes following pediatric endoscopic titanium ossiculoplasty: A single-institution experience.

INTRODUCTION: Endoscopic ossicular chain reconstruction (OCR) in adults has demonstrated equivalent outcomes to the traditional microscopic approach. Less data exist on endoscopic OCR outcomes in children, who have unique considerations including a smaller transcanal corridor and variable pathology. The purpose of this study was to investigate surgical and audiometric outcomes in children undergoing fully endoscopic and endoscopic-assisted OCR in both the short and long-term. METHODS: Retrospective review of all children (<17 years) who underwent endoscopic OCR at one tertiary care center between 2017 and 2021. Children undergoing primary and revision endoscopic OCR with either partial (PORP) and total ossicular reconstruction prostheses (TORP) were included. Children undergoing surgery for juvenile otosclerosis or congenital stapes fixation, or any child receiving a stapes prosthesis were excluded. Primary outcome measures were post-operative change in 4 frequency (500 Hz, 1, 2, 4 KHz) air conduction pure tone average (AC PTA) and change in air-bone gap (ABG). Secondary measures included need for readmission and/or revision surgery, complication rate, and surgery duration. RESULTS: Seventeen patients met inclusion criteria. Average age was 11.3 years (range, 5-17 years); 14 were male. A variety of fixed length, titanium total and partial prostheses were used. The most common prosthesis length was 2 mm (range 2-5 mm), and there were no intra- or perioperative complications. Mean long-term follow-up was 2.6 years. Most common pathology was congenital cholesteatoma (11/17, 64%), followed by chronic otitis media with tympanic membrane perforation (5/17, 29.4%), and extruded prosthesis (1/17, 5.9%). Intraoperatively, the most common finding was incus erosion (10/17, 58.8%), followed by malleus erosion (6/17, 35.3%), stapes erosion (4/17, 23.5%), and stapes absence (4/17, 23.5%). Eight children (47%) were reconstructed with PORPs, and 9 children (52.9%) were reconstructed with TORPs. Average ABG improved from 36.8 dB preoperatively to 19.9 dB postoperatively in the short-term and remained stable at 19.5 dB in the long-term. Average short-term ABG improvement was 4.2 dB for PORPs and 18 dB for TORPs. In the long-term, average ABG improved by 2.3 dB in PORPs and 13.4 dB in TORPs. PORPs had higher rates of ABG closure and lower AC PTAs than TORPs in the long-term. DISCUSSION: Endoscopic ossiculoplasty is a viable option in children presenting with ossicular erosion from various causes. Audiometric improvement following endoscopic partial and total ossicular reconstruction remains stable over time, with a preference towards partial in the long-term, and mirrors published outcomes for microscopic surgery.

Impact of KRASG12D subtype and concurrent pathogenic mutations on advanced non-small cell lung cancer outcomes / Impacto del subtipo KRASG12D y mutaciones patogénicas concurrentes en los resultados del cáncer de pulmón de células no pequeñas avanzado

Purpose: Mutations in the Kirsten rat sarcoma viral (KRAS) oncogene constitute a significant driver of lung adenocarcinoma, present in 10–40% of patients, which exhibit heterogeneous clinical outcomes, mainly driven by concurrent genetic alterations. However, characterization of KRAS mutational subtypes and their impact on clinical outcomes in Latin America is limited. Methods: A cohort study was conducted at the National Cancer Institute (INCan) of Mexico. Individuals with advance-staged of adenocarcinoma and KRAS mutations, detected by next-generation sequencing, having undergone at least one line of therapy were included for analysis. Clinical and pathological characteristics were retrieved from institutional database from June 2014 to March 2023. Results: KRAS was identified in fifty-four (15.6%) of 346 patients, among which 50 cases were included for analysis. KRASG12D (n = 16, 32%) and KRASG12C (n = 16, 32%) represented the most prevalent subtypes. KRASG12D mutations were associated with female (p = 0.018), never smokers (p = 0.108), and concurrences with EGFR (25.0% vs. 17.6%, p = 0.124) and CDKN2A (18.8% vs. 14.7%, p = 0.157). KRASG12D patients showed a better ORR (66.6% vs. 30.0%; OR 4.66, 95% CI 1.23–17.60, p = 0.023) and on multivariate analysis was significantly associated with better PFS (HR 0.36, 95% CI 0.16–0.80; p = 0.012) and OS (HR 0.24, 95% CI 0.08–0.70; p = 0.009). Conclusions: To our knowledge, this study represents the first effort to comprehensively characterize the molecular heterogeneity of KRAS-mutant NSCLC in Latin American patients. Our data reinforce the current view that KRAS-mutated NSCLC is not a single oncogene-driven disease and emphasizes the prognostic impact of diverse molecular profiles in this genomically defined subset of NSCLC. Further validation is warranted in larger multicenter Latin American cohorts to confirm our findings.(AU)

Graft Reorientation and Lateral Extra-articular Tenodesis in Revision Surgery for Persistent Rotational Instability of a Verticalized Anterior Cruciate Ligament Graft.

Persistent rotational instability after anterior cruciate ligament reconstruction is a relatively common postoperative complication, typically associated with graft verticalization due to improper femoral tunnel placement, especially with classic transtibial femoral tunnel techniques. This article describes a technique designed to reorient a verticalized anterior cruciate ligament graft at its femoral insertion to a more anatomic position in the coronal and sagittal planes, aiming to restore knee stability without the need for a complete revision operation. Additionally, a lateral extra-articular tenodesis with fascia lata is added to reinforce rotational stability.

Vacunar a la embarazada puede prevenir la bronquiolitis por virus respiratorio sincitial en el lactante / Vaccinating pregnant women can prevent respiratory syncytial virus bronchiolitis in infants

Conclusiones de los autores del estudio: la vacuna de proteína F prefusión contra el virus respiratorio sincitial, administrada a embarazadas en el último trimestre de embarazo, previene de infecciones respiratorias graves por dicho virus en sus lactantes, sin efectos adversos de importancia. Comentario de los revisores: la vacuna parece eficaz y segura, aunque las estimaciones de eficacia son imprecisas. Constituye una opción preventiva alternativa a la administración de nirsevimab en el recién nacido, con expectativas de impacto equiparables. (AU)

Authors´ conclusions: prefusion F protein vaccine against respiratory syncytial virus administered to pregnant women in the last trimester of pregnancy prevents this virus severe respiratory infections in their infants, without important adverse effects. Reviewers´ commentary: the vaccine appears effective and safe, although its efficacy estimates are imprecise. It constitutes an alternative preventive option to the administration of nirsevimab in the newborn, with comparable impact expectations. (AU)

Suicidio consumado en Gran Canaria en el periodo 2017-2022 y su relación con antecedentes de trastorno mental / Consummated suicide in Gran Canaria in the period 2017-2022, and its relationship with a history of mental disorder

Introducción el suicidio sigue siendo una de las principales causas de muerte en todo el mundo. Debido a la relación entre la conducta suicida y el trastorno mental, nuestro objetivo es determinar el número de personas que recibían atención por la Red de Salud Mental entre el total de suicidios consumados entre 2017 y 2022 en Gran Canaria, así como las características de dicha población y de la atención recibida. Material y métodos estudio longitudinal observacional retrospectivo en el que la población de estudio fue extraída del total de suicidios de la base de datos del Instituto de Medicina Legal de Gran Canaria. Posteriormente, los datos fueron cotejados por las bases de datos de la Red de Salud Mental. Por último, se realizó un análisis estadístico univariante y los resultados fueron comparados en función del sexo y la atención en la Unidad de Salud Mental Comunitaria. Resultados solo un 39,4% había recibido atención por parte de la unidad de salud mental, siendo la mayoría mujeres (55,3% vs. 34,6%), con una media de edad de 50,9 años para ambos sexos. Los antecedentes de intentos previos fueron mucho más frecuentes en la población que recibía atención (45,4% vs. 7%), así como la atención en urgencias (42% vs. 5,7%) y los ingresos hospitalarios (25,3% vs. 0,7%). Conclusión menos de la mitad de las personas fallecidas tuvieron contacto con una unidad de salud mental comunitaria. Además, la atención por esta es mayor entre aquellas personas con intentos previos y entre el sexo femenino, siendo el diagnóstico más frecuente el de los trastornos afectivos monopolares. (AU)

Introduction Suicide remains one of the leading causes of death worldwide. Due to the relationship between suicidal behavior and mental disorder, our aim is to determine the number of people who received care by the Mental Health Network among the total number of suicides consummated between 2017 and 2022 in Gran Canaria, as well as the characteristics of that population and the care received. Material and methods Longitudinal observational retrospective study in which the study population was extracted from the total number of suicides in the database of the Legal Medicine Institute. Subsequently, the data were cross-checked by the Mental Health Network databases. Finally, a univariate statistical analysis was carried out and the results were compared according to sex and care in the Community Mental Health Unit. Results Only 39.4% had received care at the Mental Health Unit, the majority being women (55.3% vs. 34.6%), with a mean age of 50.9 years for both sexes. History of previous attempts was much more frequent in the population receiving care (45.4% vs. 7%), as well as emergency care (42% vs. 5.7%) and hospital admissions (25.3% vs. 0.7%). Conclusion Less than half of the deceased persons had contact with a Community Mental Health Unit. In addition, care by this unit was higher among those with previous attempts and among the female sex, with the most frequent diagnosis being monopolar affective disorders. (AU)

Intersectional analysis of social disparities in type 2 diabetes risk among adults in Germany: results from a nationwide population-based survey.

BACKGROUND: Differences in type 2 diabetes risk have been reported for several sociodemographic determinants including sex/gender or socioeconomic status. From an intersectional perspective, it is important to not only consider the role of social dimensions individually, but also their intersections. This allows for a deeper understanding of diabetes risk and preventive needs among diverse population groups. METHODS: As an intersectionality-informed approach, multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) was used in a population-based sample of adults without known diabetes in Germany from the cross-sectional survey "Disease knowledge and information needs- Diabetes mellitus (2017)". Diabetes risk was assessed by the German Diabetes Risk Score (GDRS, range 0-122 points), estimating the individual risk of developing type 2 diabetes within the next 5 years based on established self-reported risk factors. Nesting individuals in 12 intersectional strata defined by combining sex/gender, educational level, and history of migration, we calculated measures to quantify the extent to which individual differences in diabetes risk were explained at strata level, and how much this was due to additive or multiplicative intersectional effects of social determinants. RESULTS: Drawing on data of 2,253 participants, we found good discriminatory accuracy of intersectional strata (variance partition coefficient = 14.00% in the simple intersectional model). Model-predicted GDRS means varied between 29.97 (corresponding to a "low risk" of < 2%) in women with high educational level and a history of migration, and 52.73 ("still low risk" of 2-5%) in men with low educational level without a history of migration. Variance in GDRS between strata was mainly explained by additive effects of social determinants (proportional change in variance to intersectional interaction model = 77.95%) with being male and having low educational level being associated with higher GDRS. There was no evidence of multiplicative effects in individual strata. CONCLUSIONS: Type 2 diabetes risk differed between intersectional strata and can to some extent be explained at strata level. The role of intersectional effects was minor and needs to be further investigated. Findings suggest a need for specific preventive measures targeted at large groups with increased diabetes risk, such as men and persons with low educational level.

The Role of Lumbar Drains in the Perioperative Management of Primary Spontaneous Temporal Lobe Encephaloceles and Cerebrospinal Fluid Leaks.

OBJECTIVE: To examine the role of lumbar drains (LDs) in the success of spontaneous temporal cerebrospinal fluid (CSF) leak and encephalocele repair. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic health system. PATIENTS: Patients undergoing repair of spontaneous temporal lobe encephaloceles or middle fossa CSF leaks during years 2017 to 2023. INTERVENTIONS: Transmastoid, middle fossa craniotomy, or combination approaches to CSF leak repair. OUTCOME MEASURES: Failure rate, complication rate, length of stay (LOS), readmission. RESULTS: Sixty-nine patients were included, with a combination approach performed in 78.3%, transmastoid in 17.4%, and isolated middle fossa craniotomy in 4.3%. Mean body mass index was 33.2, mean bony defect size width was 6.51 mm, and defect locations included the epitympanum, antrum, mastoid, and petrous apex. Multilayer closure with three or more layers was performed in 87.0%. LD was used in 73.9% of cases for a mean duration 2.27 days and was associated with longer LOS (3.27 vs. 1.56 d, p = 0.006) but not with failure rate, complications, discharge destination, or readmission. Only one major complication occurred as a result of the drain, but low-pressure headache was anecdotally common. CONCLUSIONS: Use of LD in the repair of spontaneous CSF leaks and temporal lobe encephaloceles is associated with longer LOS but not failure rates or other admission-level outcomes.

Unlocking the Potential of Adequate Bacillus Calmette-Guérin Immunotherapy in Very-high-risk Non-muscle-invasive Bladder Carcinoma: A Multicenter Analysis of Oncological Outcomes and Risk Dynamics.

BACKGROUND: The European Association of Urology (EAU) recommends discussing upfront radical cystectomy for all patients with very high risk (VHR) non-muscle-invasive bladder carcinoma (NMIBC), but the role of bacillus Calmette-Guérin (BCG) treatment remains controversial. OBJECTIVE: To analyze oncological outcomes in VHR NMIBC patients (EAU risk groups) treated with adequate BCG. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional retrospective study involving patients with VHR NMIBC who received adequate BCG therapy from 2007 to 2020 was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A survival analysis estimated recurrence-free survival (RFS), progression-free survival (PFS), and the cumulative incidence of cancer-specific mortality (CSM) after accounting for other causes of mortality as competing risk events and of the overall mortality (OM). Conditional survival probabilities for 0-4 yr without events were computed. Cox regression assessed the predictors of oncological outcomes. RESULTS AND LIMITATION: A total of 640 patients, with a median 47 (32-67) mo follow-up for event-free individuals, were analyzed. High-grade RFS and PFS at 5 yr were 53% (49-57%) and 78% (74-82%), respectively. The cumulative incidence of CSM and OM at 5 yr was 13% (10-16%) and 16% (13-19%), respectively. Conditional RFS, PFS, overall survival, and cancer-specific survival at 4 yr were 91%, 96%, 87%, and 94%, respectively. Cox regression identified tumor grade (hazard ratio [HR]: 1.54; 1.1-2) and size (HR: 1.3; 1.1-1.7) as RFS predictors. Tumor multiplicity predicted RFS (HR: 1.6; 1.3-2), PFS (HR: 2; 1.2-3.3), and CSM (HR: 2; 1.2-3.2), while age predicted OM (HR: 1.48; 1.1-2). CONCLUSIONS: Patients with VHR NMIBC who receive adequate BCG therapy have a more favorable prognosis than predicted by EAU risk groups, especially among those with a sustained response, in whom continuing maintenance therapy emerges as a viable alternative to radical cystectomy. PATIENT SUMMARY: Our research shows that a sustained response to bacillus Calmette-Guérin in patients can lead to favorable outcomes, serving as a viable alternative to cystectomy for select cases.

L4 fixation is not necessary in L5-Iliac spinopelvic fixation after trauma, but coadjutant transilio-transsacral fixation is.

INTRODUCTION: Spinopelvic dissociation (SPD) is a severe injury characterized by a discontinuity between the spine and the bony pelvis consisting of a bilateral longitudinal sacral fracture, most of the times through sacral neuroforamen, and a horizontal fracture, usually through the S1 or S2 body. The introduction of the concept of triangular osteosynthesis has shown to be an advance in the stability of spinopelvic fixation (SPF). However, a controversy exists as to whether the spinal fixation should reach up to L4 and, if so, it should be combined with transiliac-transsacral screws (TTS). OBJECTIVE: The purpose of this study is to compare the biomechanical behavior in the laboratory of four different osteosynthesis constructs for SPD, including spinopelvic fixation of L5 versus L4 and L5; along with or without TTS in both cases. MATERIAL AND METHODS: By means of a formerly described method by the authors, an unstable standardized H-type sacral fracture in twenty synthetic replicas of a male pelvis articulated to the lumbar spine, L1 to sacrum, (Model: 1300, SawbonesTM; Pacific Research Laboratories, Vashon, WA, USA), instrumented with four different techniques, were mechanically tested. We made 4 different constructs in 5 specimen samples for each construct. Groups: Group 1. Instrumentation of the L5-Iliac bones with TTS. Group 2. Instrumentation of the L4-L5-Iliac bones with TTS. Group 3. Instrumentation of L5-Iliac bones without TTS. Group 4: Instrumentation of L4-L5-Iliac bones without TTS. RESULTS AND CONCLUSIONS: According to our results, it can be concluded that in SPD, better stability is obtained when proximal fixation is only up to L5, without including L4 (alternative hypothesis), the addition of transiliac-transsacral fixations is essential.