Surgical treatment of brain arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia: a single-center experience.

OBJECTIVE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant disorder characterized by multiple vascular malformations. Brain arteriovenous malformations (bAVMs) are a significant manifestation of HHT. The surgical management of these lesions in patients with HHT remains debated, with limited literature on postoperative outcomes. The goal of this study was to evaluate the safety and efficacy of surgical treatment for bAVMs in patients with HHT and propose a treatment rationale based on a single-center experience. METHODS: This retrospective review included 20 patients diagnosed with HHT who underwent resection of 23 bAVMs at the Stanford University Medical Center between January 2007 and September 2023. Data were also collected on bAVMs treated conservatively, with embolization, or with radiosurgery at the authors' institution, for comparison. RESULTS: There were 16 Spetzler-Martin (SM) grade I, 6 SM grade II, and 1 SM grade IV bAVM. Six of the bAVMs presented with neurological symptoms (3 with hemorrhage and 3 with focal neurological deficits), while the rest were detected on routine screening. Complete excision was angiographically confirmed in all patients, with a mean overall hospital stay of 2.1 days and a mean follow-up of 36 months. Postoperative complications were limited to transient mild weakness in 2 patients, 1 of whom also had transient speech deficits, and visual field deficits in 3 patients, 2 of whom improved on long-term follow-up. CONCLUSIONS: In this most extensive surgical series published to date, resection of bAVMs in patients with HHT showed favorable outcomes with a low complication rate, suggesting that the benefits of surgery outweigh the risks, especially considering the potential cumulative lifetime risk of hemorrhage. MR arterial spin labeling was found to be the most sensitive noninvasive measure of detecting bAVMs in patients with HHT.

Properties of the iron-sulfur cluster electron transfer relay in an [FeFe]-hydrogenase that is tuned for H2 oxidation catalysis.

[FeFe]-hydrogenases catalyze the reversible oxidation of H2 from electrons and protons at an organometallic active site cofactor named the H-cluster. In addition to the H-cluster, most [FeFe]-hydrogenases possess accessory FeS cluster (F-cluster) relays that function in mediating electron transfer with catalysis. There is significant variation in the structural properties of F-cluster relays among the [FeFe]-hydrogenases; however, it is unknown how this variation relates to the electronic and thermodynamic properties, and thus the electron transfer properties, of enzymes. Clostridium pasteurianum [FeFe]-hydrogenase II (CpII) exhibits a large catalytic bias for H2 oxidation (compared to H2 production), making it a notable system for examining if F-cluster properties contribute to the overall function and efficiency of the enzyme. By applying a combination of multifrequency and potentiometric electron paramagnetic resonance, we resolved two electron paramagnetic resonance signals with distinct power- and temperature-dependent properties at g = 2.058 1.931 1.891 (F2.058) and g = 2.061 1.920 1.887 (F2.061), with assigned midpoint potentials of -140 ± 18 mV and -406 ± 12 mV versus normal hydrogen electrode, respectively. Spectral analysis revealed features consistent with spin-spin coupling between the two [4Fe-4S] F-clusters, and possible functional models are discussed that account for the contribution of coupling to the electron transfer landscape. The results signify the interplay of electronic coupling and free energy properties and parameters of the FeS clusters to the electron transfer mechanism through the relay and provide new insight as to how relays functionally complement the catalytic directionality of active sites to achieve highly efficient catalysis.

Clinical and prognostic differences in oropharyngeal squamous cell carcinoma in USA and Denmark, two HPV high-prevalence areas.

BACKGROUND: Uncertainty persists regarding clinical and treatment variations crucial to consider when comparing high human papillomavirus (HPV)-prevalence oropharyngeal squamous cell carcinoma (OPSCC) cohorts for accurate patient stratification and replicability of clinical trials across different geographical areas. METHODS: OPSCC patients were included from The University of Texas MD Anderson Cancer Center (UTMDACC), USA and from The University Hospital of Copenhagen, Denmark from 2015-2020, (n = 2484). Outcomes were 3-year overall survival (OS) and recurrence-free interval (RFI). Subgroup analyses were made for low-risk OPSCC patients (T1-2N0M0) and high-risk patients (UICC8 III-IV). RESULTS: There were significantly more HPV-positive (88.2 % vs. 63.1 %), males (89.4 % vs. 74.1 %), never-smokers (52.1 % vs. 23.7 %), lower UICC8-stage (I/II: 79.3 % vs. 68 %), and fewer patients treated with radiotherapy (RT) alone (14.8 % vs. 30.3 %) in the UTMDACC cohort. No difference in the adjusted OS was observed (hazard ratio [HR] 1.21, p = 0.23), but a significantly increased RFI HR was observed for the Copenhagen cohort (HR: 1.74, p = 0.003). Subgroup analyses of low- and high-risk patients revealed significant clinical and treatment differences. No difference in prognosis was observed for low-risk patients, but the prognosis for high-risk patients in the Copenhagen cohort was worse (OS HR 2.20, p = 0.004, RFI HR 2.80, p = 0.002). CONCLUSIONS: We identified significant differences in clinical characteristics, treatment modalities, and prognosis between a Northern European and Northern American OPSCC population. These differences are important to consider when comparing outcomes and for patient stratification in clinical trials, as reproducibility might be challenging.

Depletion of Mettl3 in cholinergic neurons causes adult-onset neuromuscular degeneration.

Motor neuron (MN) demise is a hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Post-transcriptional gene regulation can control RNA's fate, and defects in RNA processing are critical determinants of MN degeneration. N6-methyladenosine (m6A) is a post-transcriptional RNA modification that controls diverse aspects of RNA metabolism. To assess the m6A requirement in MNs, we depleted the m6A methyltransferase-like 3 (METTL3) in cells and mice. METTL3 depletion in embryonic stem cell-derived MNs has profound and selective effects on survival and neurite outgrowth. Mice with cholinergic neuron-specific METTL3 depletion display a progressive decline in motor behavior, accompanied by MN loss and muscle denervation, culminating in paralysis and death. Reader proteins convey m6A effects, and their silencing phenocopies METTL3 depletion. Among the m6A targets, we identified transactive response DNA-binding protein 43 (TDP-43) and discovered that its expression is under epitranscriptomic control. Thus, impaired m6A signaling disrupts MN homeostasis and triggers neurodegeneration conceivably through TDP-43 deregulation.

Depletion of complement factor 3 delays the neuroinflammatory response to intracortical microelectrodes.

The neuroinflammatory response to intracortical microelectrodes (IMEs) used with brain-machine interfacing (BMI) applications is regarded as the primary contributor to poor chronic performance. Recent developments in high-plex gene expression technologies have allowed for an evolution in the investigation of individual proteins or genes to be able to identify specific pathways of upregulated genes that may contribute to the neuroinflammatory response. Several key pathways that are upregulated following IME implantation are involved with the complement system. The complement system is part of the innate immune system involved in recognizing and eliminating pathogens - a significant contributor to the foreign body response against biomaterials. Specifically, we have identified Complement 3 (C3) as a gene of interest because it is the intersection of several key complement pathways. In this study, we investigated the role of C3 in the IME inflammatory response by comparing the neuroinflammatory gene expression at the microelectrode implant site between C3 knockout (C3-/-) and wild-type (WT) mice. We have found that, like in WT mice, implantation of intracortical microelectrodes in C3-/- mice yields a dramatic increase in the neuroinflammatory gene expression at all post-surgery time points investigated. However, compared to WT mice, C3 depletion showed reduced expression of many neuroinflammatory genes pre-surgery and 4 weeks post-surgery. Conversely, depletion of C3 increased the expression of many neuroinflammatory genes at 8 weeks and 16 weeks post-surgery, compared to WT mice. Our results suggest that C3 depletion may be a promising therapeutic target for acute, but not chronic, relief of the neuroinflammatory response to IME implantation. Additional compensatory targets may also be required for comprehensive long-term reduction of the neuroinflammatory response for improved intracortical microelectrode performance.

Incidence of Surgical Reintervention for Benign Prostatic Hyperplasia Following Prostatic Urethral Lift, Transurethral Resection of the Prostate, and Photoselective Vaporization of the Prostate: A TriNetX Analysis.

Background: Prostatic urethral lift, or UroLift, has gained popularity as a treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH). Surgical reintervention rates are a reliable indicator for treatment durability. Objective: The objective of this study was to utilize TriNetX, a third-party database, to investigate the incidence of surgical reintervention following UroLift, transurethral resection of the prostate (TURP), and photoselective vaporization of the prostate (PVP) procedures for BPH from 2015 to 2018. Design setting and participants: Male patients aged 18-100 yr diagnosed with BPH were identified in the TriNetX Diamond Network database between January 2015 and December 2018. Cohorts of individuals undergoing their first UroLift procedure were built using Current Procedural Terminology and International Classification of Diseases 10th Revision codes. TURP and PVP cohorts were built as comparison groups. The cohorts were then queried for subsequent BPH-related procedures. Outcome measurements and statistical analysis: Reprocedure rates were assessed and descriptive statistics were used. Results and limitations: The mean age at first-time UroLift was 70.1 ± 9.4 yr (n = 14 343). Cumulative reprocedure rates collected after first-time UroLift included 1 yr after UroLift (5.1%, n = 14 343) and 4 yr after UroLift (16.1%, n = 710), with an average annual increase of +3.6% per year following 1 yr after the procedure. Comparatively, TURP (n = 22 071) and PVP (n = 14 110) had 4-yr reprocedure rates of 7.5% and 7.8%, respectively, during the same timeframe. Limitations include a lack of clinical data and loss of follow-up data outside the Diamond Network. Conclusions: The reprocedure rate of UroLift at 4 yr is double the rate of TURP and PVP. In appropriately selected patients, UroLift might be a suitable option for those who desire symptomatic relief from BPH with minimal erectile and ejaculatory side effects. However, the risk of secondary surgical intervention should be considered when considering BPH treatments. Patient summary: We compared the reintervention rates of prostatic urethral lift (PUL), transurethral resection of the prostate (TURP), and photoselective vaporization of the prostate (PVP) using the TriNetX database, and have found that the highest reintervention rates were for PUL of 16% at 4 yr of follow-up, compared with about 8% for those who had TURP and PVP. Interestingly, the most common reintervention was the same operation at 1 yr. This has important implications when counseling patients about the durability of these various outlet procedures for BPH.

National Trends in Surgical Management for Benign Prostatic Hyperplasia From 2013 to 2019 in the United States.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a common urologic pathology for older men. The prevalence and effect on quality of life have prompted the development of new surgical procedures to manage BPH while attempting to minimize treatment side effects. The objective of this study is to utilize TriNetX, a third-party database, to investigate temporal trends in BPH procedures from 2013 to 2019 in the United States. METHODS: Male patients aged 18 to 100 who were diagnosed with BPH from 2013 to 2019 were filtered from the TriNetX Diamond Network. Yearly cohorts undergoing a BPH-related procedure were searched using Current Procedural Terminology and International Classification of Diseases 10th Revision codes. Temporal and descriptive analytics were utilized to describe trends in treatment utilization. RESULTS: There were 302,646 BPH procedures recorded on the TriNetX Diamond Network. Transurethral resection of the prostate was the most commonly performed procedure, accounting for 47.2% of procedures in 2013 and 44.9% in 2019. Photoselective vaporization of the prostate remained a popular treatment but showed the greatest decrease in utilization over time (31.8% in 2013, 21.5% in 2019). Prostatic urethral lift (UroLift) was rapidly embraced as a treatment modality, as usage increased by 18.3% over a 6-year period (0.0% in 2014, up to 18.3% in 2019). Other procedures such as Rezum (5.8%) and holmium laser enucleation of the prostate (5.1%) made up greater proportions of BPH procedures by 2019. CONCLUSIONS: Transurethral resection of the prostate was the most common procedure from 2013 to 2019. However, minimally invasive surgeries represent an increased percentage of BPH surgeries every year.

Outcomes Following Pelvic Exenteration for Locally Recurrent Rectal Cancer With and Without En Bloc Sacrectomy.

BACKGROUND: Extended radical resection is often the only chance of cure for locally recurrent rectal cancer. Recurrence in the posterior compartment often necessitates en bloc sacrectomy as part of pelvic exenteration to obtain clear resection margins and provide survival benefit. OBJECTIVE: To compare oncological outcomes, morbidity, and quality-of-life outcomes following pelvic exenteration with and without en bloc sacrectomy for recurrent rectal cancer. DESIGN: Comparative cohort study with retrospective analysis of prospectively collected data. SETTING: This study was conducted at a high-volume pelvic exenteration center. PATIENTS: Patients who underwent pelvic exenteration for locally recurrent rectal cancer between 1994 and 2022. MAIN OUTCOME MEASURES: Overall survival, postoperative morbidity, R0 resection margin, and quality-of-life outcomes. RESULTS: Of 965 patients, 305 (31.6%) underwent pelvic exenteration for locally recurrent rectal cancer. Among these patients, 64.3% were men and the median age was 62 years (range, 29-86). One hundred eighty-five patients (60.7%) underwent en bloc sacrectomy, 65 (35.1%) underwent high transection, and 119 (64.3%) had sacrectomy below S2. R0 resection was achieved in 80% of patients with sacrectomy and 72.5% of patients without sacrectomy. Sacrectomy patients experienced more postoperative complications without increased mortality. The median overall survival was 52 months; median survival was 47 months with sacrectomy and 73 months without ( p = 0.059). Quality-of-life scores were not significantly different across physical component ( p = 0.346), mental component ( p = 0.787), or Functional Assessment of Cancer Therapy-Colorectal ( p = 0.679) scores at 24-month follow-up. LIMITATIONS: The generalizability of these findings may be limited outside of subspecialist exenteration units. Selection bias exists in a retrospective analysis. CONCLUSIONS: Patients undergoing pelvic exenteration with and without en bloc sacrectomy for locally recurrent rectal cancer experience similar rates of R0 resection, survival, and quality-of-life outcomes. As R0 remains the most important predictor of survival, the requirement of sacral resection should prompt referral to a subspecialist center that performs sacrectomy routinely. See Video Abstract . RESULTADOS DESPUS DE LA EXENTERACIN PLVICA PARA EL CNCER DE RECTO CON RECURRENCIA LOCAL, CON Y SIN SACRECTOMA EN BLOQUE: ANTECEDENTES:La resección radical ampliada es generalmente la única posibilidad de curación para el cáncer de recto con recurrencia local. La recurrencia en el compartimento posterior generalmente requiere sacrectomía en bloque como parte de la exenteración pélvica para obtener márgenes de resección claros y proporcionar un beneficio de supervivencia.OBJETIVO:Comparar los resultados oncológicos, de morbilidad y de calidad de vida después de la exenteración pélvica con y sin sacrectomía en bloque para el cáncer de recto recurrente.DISEÑO:Estudio de cohorte comparativo con análisis retrospectivo de datos recopilados prospectivamente.AMBIENTE AJUSTE:Estudio realizado en un centro de exenteración pélvica de alto volumen.PACIENTES:Aquellos sometidos a exenteración pélvica por cáncer de recto con recurrencia local entre 1994 y 2022.PRINCIPALES MEDIDAS DE RESULTADO:Supervivencia general, morbilidad posoperatoria, margen de resección R0 y resultados de calidad de vida.RESULTADOS:305 (31,6%) de 965 pacientes se sometieron a exenteración pélvica por cáncer de recto con recurrencia local. El 64,3% de los pacientes eran hombres con una mediana de edad de 62 años (rango 29-86). 185 pacientes (60,7%) fueron sometidos a sacrectomía en bloque, 65 (35,1%) fueron sometidos a transección alta, 119 (64,3%) tuvieron sacrectomía por debajo de S2. La resección R0 se logró en el 80% de los pacientes con sacrectomía y en el 72,5% sin ella. Los pacientes de sacrectomía experimentaron más complicaciones postoperatorias sin aumento de la mortalidad. La mediana de supervivencia global fue de 52 meses, 47 meses con sacrectomía y 73 meses sin sacrectomía ( p = 0,059). Las puntuaciones de calidad de vida no fueron significativamente diferentes entre las puntuaciones del componente físico ( p = 0,346), componente mental ( p = 0,787) o la evaluación funcional de la terapia contra el cáncer - colorrectal ( p = 0,679) a los 24 meses de seguimiento.LIMITACIONES:La generalización de estos hallazgos puede estar limitada fuera de las unidades de exenteración de subespecialistas. Existe un sesgo de selección en un análisis retrospectivo.CONCLUSIONES:Los pacientes sometidos a exenteración pélvica con y sin sacrectomía en bloque por cáncer de recto con recurrencia local experimentan tasas similares de resección R0, supervivencia y resultados de calidad de vida. Como R0 sigue siendo el predictor más importante de supervivencia, la necesidad de resección sacra debe provocar la derivación a un centro subespecialista que realice sacrectomía de forma rutinaria. (Traducción-Dr. Fidel Ruiz Healy ).

Posttransplantation late complications increase over time for patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) landmark study.

BACKGROUND: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada onto a retrospective multicenter natural history study of hematopoietic cell transplantation (HCT). OBJECTIVE: We investigated outcomes of HCT for severe combined immunodeficiency (SCID). METHODS: We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982 to 2012 at 32 PIDTC centers. Eligibility criteria included survival to at least 2 years after HCT without need for subsequent cellular therapy. CLE were defined as either conditions present at any time before 2 years from HCT that remained unresolved (chronic), or new conditions that developed beyond 2 years after HCT (late). RESULTS: The cumulative incidence of CLE was 25% in those alive at 2 years, increasing to 41% at 15 years after HCT. CLE were most prevalent in the neurologic (9%), neurodevelopmental (8%), and dental (8%) categories. Chemotherapy-based conditioning was associated with decreased-height z score at 2 to 5 years after HCT (P < .001), and with endocrine (P < .001) and dental (P = .05) CLE. CD4 count of ≤500 cells/µL and/or continued need for immunoglobulin replacement therapy >2 years after transplantation were associated with lower-height z scores. Continued survival from 2 to 15 years after HCT was 90%. The presence of any CLE was associated with increased risk of late death (hazard ratio, 7.21; 95% confidence interval, 2.71-19.18; P < .001). CONCLUSION: Late morbidity after HCT for SCID was substantial, with an adverse impact on overall survival. This study provides evidence for development of survivorship guidelines based on disease characteristics and treatment exposure for patients after HCT for SCID.

Common Pediatric Hand Anomalies.

Upper extremity congenital anomalies in the newborn are second only to congenital heart anomalies. Some of the more commonly encountered upper extremity anomalies are trigger thumb, thumb hypoplasia, polydactyly, syndactyly, and amniotic band syndrome. While some conditions occur in isolation, others are known to commonly occur in association with syndromes. Familiarity with these conditions is important not only to provide adequate evaluation and workup of these patients but also to deliver appropriate surgical intervention and prepare parents with appropriate expectations. In this article, we outline the etiology, classification, surgical management, and outcomes of these five commonly encountered upper extremity congenital anomalies.

Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring.

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other body sites are also significantly associated with survival in colorectal, lung, head and neck, and skin cancers. Our findings demonstrate that lactic acid bacteria in the tumor microenvironment can alter tumor metabolism and lactate signaling pathways, causing therapeutic resistance. Lactic acid bacteria could be promising therapeutic targets across cancer types.

Melanoma literacy among the general population of three western US states.

Melanoma is a significant cause of cancer death, despite being detectable without specialized or invasive technologies. Understanding barriers to preventive behaviors such as skin self-examination (SSE) could help to define interventions for increasing the frequency of early detection. To determine melanoma knowledge and beliefs across three high-incidence US states, 15,000 surveys were sent to a population-representative sample. We aimed to assess (1) melanoma literacy (i.e., knowledge about melanoma risks, attitudes, and preventive behaviors) and (2) self-reported SSE and its association with melanoma literacy, self-efficacy, and belief in the benefits of SSE. Of 2326 respondents, only 21.2% provided responses indicating high knowledge of melanoma, and 62.8% reported performing an SSE at any time in their lives. Only 38.3% and 7.3% reported being "fairly" or "very" confident about doing SSE, respectively. SSE performance among respondents was most strongly associated with higher melanoma knowledge, higher self-efficacy, and personal history of melanoma. Melanoma literacy among survey respondents was modest, with greater literacy associated with a higher likelihood of reported preventive behavior. This assessment establishes a baseline and provides guidance for public health campaigns designed to increase prevention and early detection of this lethal cancer.

HPV-related anal cancer is associated with changes in the anorectal microbiome during cancer development.

Background: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease. Methods: Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade lower genital tract dysplasia. Anorectal tumor swabs were prospectively collected from patients with biopsy-confirmed locally advanced SCCA prior to receiving standard-of-care chemoradiotherapy (CRT). Patients with high-grade lower genital tract dysplasia without anal dysplasia were considered high-risk (HR Normal). 16S V4 rRNA Microbiome sequencing was performed for anal swabs. Alpha and Beta Diversity and composition were compared for HR Normal, anal dysplasia, and anal cancer. Results: 60 patients with high-grade lower genital tract dysplasia were initially enrolled. Seven patients had concurrent anal dysplasia and 44 patients were considered HR Normal. Anorectal swabs from 21 patients with localized SCCA were included, sequenced, and analyzed in the study. Analysis of weighted and unweighted UniFrac distances demonstrated significant differences in microbial community composition between anal cancer and HR normal (p=0.018). LEfSe identified that all three groups exhibited differential enrichment of specific taxa. Peptoniphilus (p=0.028), Fusobacteria (p=0.0295), Porphyromonas (p=0.034), and Prevotella (p=0.029) were enriched in anal cancer specimens when compared to HR normal. Conclusion: Although alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased anorectal Peptoniphilus, Fusobacteria, Porphyromonas, and Prevotella abundance were associated with anal cancer. These organisms have been reported in various gastrointestinal cancers with roles in facilitating the proinflammatory microenvironment and neoplasia progression. Future work should investigate a potential role of microbiome analysis in screening for anal dysplasia and investigation into potential mechanisms of how these microbial imbalances influence the immune system and anal carcinogenesis.

The Association Between Borderline Dysnatremia and Perioperative Morbidity and Mortality: Retrospective Cohort Study of the American College of Surgeons National Surgical Quality Improvement Program Database.

BACKGROUND: Hyponatremia and hypernatremia, as conventionally defined (<135 mEq/L and >145 mEq/L, respectively), are associated with increased perioperative morbidity and mortality. However, the effects of subtle deviations in serum sodium concentration within the normal range are not well-characterized. OBJECTIVE: The purpose of this analysis is to determine the association between borderline hyponatremia (135-137 mEq/L) and hypernatremia (143-145 mEq/L) on perioperative morbidity and mortality. METHODS: A retrospective cohort study was performed using data from the American College of Surgeons National Surgical Quality Improvement Program database. This database is a repository of surgical outcome data collected from over 600 hospitals across the United States. The National Surgical Quality Improvement Program database was queried to extract all patients undergoing elective, noncardiac surgery from 2015 to 2019. The primary predictor variable was preoperative serum sodium concentration, measured less than 5 days before the index surgery. The 2 primary outcomes were the odds of morbidity and mortality occurring within 30 days of surgery. The risk of both outcomes in relation to preoperative serum sodium concentration was modeled using weighted generalized additive models to minimize the effect of selection bias while controlling for covariates. RESULTS: In the overall cohort, 1,003,956 of 4,551,726 available patients had a serum sodium concentration drawn within 5 days of their index surgery. The odds of morbidity and mortality across sodium levels of 130-150 mEq/L relative to a sodium level of 140 mEq/L followed a nonnormally distributed U-shaped curve. The mean serum sodium concentration in the study population was 139 mEq/L. All continuous covariates were significantly associated with both morbidity and mortality (P<.001). Preoperative serum sodium concentrations of less than 139 mEq/L and those greater than 144 mEq/L were independently associated with increased morbidity probabilities. Serum sodium concentrations of less than 138 mEq/L and those greater than 142 mEq/L were associated with increased mortality probabilities. Hypernatremia was associated with higher odds of both morbidity and mortality than corresponding degrees of hyponatremia. CONCLUSIONS: Among patients undergoing elective, noncardiac surgery, this retrospective analysis found that preoperative serum sodium levels less than 138 mEq/L and those greater than 142 mEq/L are associated with increased morbidity and mortality, even within currently accepted "normal" ranges. The retrospective nature of this investigation limits the ability to make causal determinations for these findings. Given the U-shaped distribution of risk, past investigations that assume a linear relationship between serum sodium concentration and surgical outcomes may need to be revisited. Likewise, these results question the current definition of perioperative eunatremia, which may require future prospective investigations.

Impact of testosterone use on the vaginal microbiota of transgender men, including susceptibility to bacterial vaginosis: study protocol for a prospective, observational study.

INTRODUCTION: The effect of testosterone (T) therapy on the vaginal microbiota of transgender men (TGM) is not well characterised, although one cross-sectional study comparing the vaginal microbiota of cisgender women to TGM on T≥1 year found that, in 71% of the TGM, the vaginal microbiota was less likely to be Lactobacillus-dominated and more likely to be enriched with >30 other bacterial species, many associated with bacterial vaginosis (BV). This prospective study aims to investigate changes in the composition of the vaginal microbiota over time in TGM who retain their natal genitalia (ie, vagina) and initiate T. In addition, we will identify changes in the vaginal microbiota preceding incident BV (iBV) in this cohort while investigating behavioural factors, along with hormonal shifts, which may be associated with iBV. METHODS AND ANALYSIS: T-naïve TGM who have not undergone gender-affirming genital surgery with normal baseline vaginal microbiota (ie, no Amsel criteria, normal Nugent Score with no Gardnerella vaginalis morphotypes) will self-collect daily vaginal specimens for 7 days prior to initiating T and for 90 days thereafter. These specimens will be used for vaginal Gram stain, 16S rRNA gene sequencing and shotgun metagenomic sequencing to characterise shifts in the vaginal microbiota over time, including development of iBV. Participants will complete daily diaries on douching, menses and behavioural factors including sexual activity during the study. ETHICS AND DISSEMINATION: This protocol is approved through the single Institutional Review Board mechanism by the University of Alabama at Birmingham. External relying sites are the Louisiana State University Health Sciences Center, New Orleans Human Research Protection Program and the Indiana University Human Research Protection Program. Study findings will be presented at scientific conferences and peer-reviewed journals as well as shared with community advisory boards at participating gender health clinics and community-based organisations servicing transgender people. REGISTRATION DETAILS: Protocol # IRB-300008073.

Tumor volume definitions in head and neck squamous cell carcinoma - Comparing PET/MRI and histopathology.

BACKGROUND AND PURPOSE: In cancer treatment precise definition of the tumor volume is essential, but despite development in imaging modalities, this remains a challenge. Here, pathological tumor volumes from the surgical specimens were obtained and compared to tumor volumes defined from modern PET/MRI hybrid imaging. The purpose is to evaluate mismatch between the volumes defined from imaging and pathology was estimated and potential clinical impact. METHODS AND MATERIALS: Twenty-five patients with head and neck squamous cell carcinoma were scanned on an integrated PET/MRI system prior to surgery. Three gross tumor volumes (GTVs) from the primary tumor site were delineated defined from MRI (GTVMRI), PET (GTVPET) and one by utilizing both anatomical images and clinical information (GTVONCO). Twenty-five primary tumor specimens were extracted en bloc, scanned with PET/MRI and co-registered to the patient images. Each specimen was sectioned in blocks, sliced and stained with haematoxylin and eosin. All slices were digitalized and tumor delineated by a head and neck pathologist. The pathological tumor areas in all slices were interpolated yielding a pathological 3D tumor volume (GTVPATO). GTVPATOwas compared with the imaging GTV's and potential mismatch was estimated. RESULTS: Thirteen patients were included. The mean volume of GTVONCOwas larger than the GTV's defined from PET or MRI. The mean mismatch of the GTVPATOcompared to the GTVPET, GTVMRIand GTVONCOwas 31.9 %, 54.5 % and 27.9 % respectively, and the entire GTVPATO was only fully encompassed in GTVONCO in 1 of 13 patients. However, after the addition of a clinical 5 mm margin the GTVPATO was fully encompassed in GTVONCO in 11 out of 13 patients. CONCLUSIONS: Despite modern hybrid imaging modalities, a mismatch between imaging and pathological defined tumor volumes was observed in all patients.A 5 mm clinical margin was sufficient to ensure inclusion of the entire pathological volume in 11 out of 13 patients.

Venous Sinus Stenting: Safety and Health Care Resource Evaluation for Optimal Recovery in an Evolving Health Care Environment.

BACKGROUND: Increasing evidence supports the effectiveness of venous sinus stenting (VSS) with favorable outcomes, safety, and expenses compared with shunting for idiopathic intracranial hypertension. Yet, no evidence is available regarding optimal postoperative recovery, which has increasing importance with the burdens on health care imposed by the coronavirus disease 2019 pandemic. We examined adverse events and costs after VSS and propose an optimal recovery pathway to maximize patient safety and reduce stress on health care resources. METHODS: A retrospective review was undertaken of elective VSS operations performed from May 2008 to August 2021 at a single institution. Primary data included hospital length of stay, intensive care unit (ICU) length of stay, adverse events, need for ICU interventions, and hospital costs. RESULTS: Fifty-three patients (98.1% female) met the inclusion criteria. Of these patients, 51 (96.2%) were discharged on postoperative day (POD) 1 and 2 patients were discharged on POD 2. Both patients discharged on POD 2 remained because of groin hematomas from femoral artery access. There were no major complications or care that required an ICU. Eight patients (15.1%) were lateralized to other ICUs or remained in a postanesthesia care unit because the neurosciences ICU was above capacity. Total estimated cost for initial recovery day in a neurosciences ICU room was $2361 versus $882 for a neurosurgery/neurology ward room. In our cohort, ward convalescence would save an estimated $79,866 for bed placement alone and increase ICU bed availability. CONCLUSIONS: Our findings reaffirm the safety of VSS. These patients should recover on a neurosurgery/neurology ward, which would save health care costs and increase ICU bed availability.

Robotic-Assisted Nipple Sparing Mastectomy.

Minimally invasive approaches to breast surgery have evolved from endoscopic techniques to recent developments in robotic-assisted mastectomies. Initial studies on robotic-assisted nipple-sparing mastectomy (RNSM) have shown improved patient satisfaction and aesthetic outcomes with similar complication rates and oncological outcomes in selected patients. This chapter reviews techniques used and available data on complications and clinical outcomes for RNSM. Currently, RNSM is an investigational technique in the United States and should be performed in clinical trials with U.S. Food & Drug Administration approval to rigorously evaluate the safety and effectiveness of this approach.

Robotics in Implant-Based and Autologous Breast Reconstruction.

Autologous and implant-based breast reconstruction continues to evolve as new technology and mastectomy techniques become available. Robotic-assisted breast reconstruction represents a growing field within plastic surgery, with the potential to improve aesthetic and functional outcomes, as well as patient satisfaction. This article provides a review of indications, techniques, and outcome data supporting the use of robotic assistance in both implant-based and autologous breast reconstruction from surgeons around the world.