Chemical Immobilization Effects on Cougar (Felis concolor) Movement.

Capturing and handling wildlife is a common practice for both management and research. As telemetry use has become common, the need to capture and chemically immobilize wildlife has increased. Understanding how long the effects of immobilizing agents last after releasing the animal is often poorly understood but needed to ensure that analyses use data that reflect natural behavior. Between 2016 and 2021, 87 cougars (Puma concolor) were chemically immobilized with medetomidine, zolazepam, and tiletamine (MZT) and collared across west-central Alberta, Canada, 27 of which were individuals being recollared. We examined the distance an individual traveled per day and compared equivalent periods before and after the recollaring event to determine whether postcapture movement rates were significantly different from precapture rates. Within 1 d of the recollaring, daily movement rates had returned to precapture rates (t20=2.09, P=0.18). Our results provide insight on how MZT used in cougars affects their postcapture movement and thus may be helpful in interpreting movement data after release.

Surveillance for Violent Deaths - National Violent Death Reporting System, 48 States, the District of Columbia, and Puerto Rico, 2021.

Problem/Condition: In 2021, approximately 75,000 persons died of violence-related injuries in the United States. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) on violent deaths that occurred in 48 states, the District of Columbia, and Puerto Rico in 2021. Results are reported by sex, age group, race and ethnicity, method of injury, type of location where the injury occurred, circumstances of injury, and other selected characteristics. This report introduces additional incident and circumstance variables, which now include child victim-specific circumstance information. This report also incorporates new U.S. Census Bureau race and ethnicity categories, which now account for more than one race and Native Hawaiian or other Pacific Islander categories and include updated denominators to calculate rates for these populations. Period Covered: 2021. Description of System: NVDRS collects data regarding violent deaths from death certificates, coroner and medical examiner records, and law enforcement reports. This report includes data collected for violent deaths that occurred in 2021. Data were collected from 48 states (all states with exception of Florida and Hawaii), the District of Columbia, and Puerto Rico. Forty-six states had statewide data, two additional states had data from counties representing a subset of their population (31 California counties, representing 64% of its population, and 13 Texas counties, representing 63% of its population), and the District of Columbia and Puerto Rico had jurisdiction-wide data. NVDRS collates information for each violent death and links deaths that are related (e.g., multiple homicides, homicide followed by suicide, or multiple suicides) into a single incident. Results: For 2021, NVDRS collected information on 68,866 fatal incidents involving 70,688 deaths that occurred in 48 states (46 states collecting statewide data, 31 California counties, and 13 Texas counties), and the District of Columbia. The deaths captured in NVDRS accounted for 86.5% of all homicides, legal intervention deaths, suicides, unintentional firearm injury deaths, and deaths of undetermined intent in the United States in 2021. In addition, information was collected for 816 fatal incidents involving 880 deaths in Puerto Rico. Data for Puerto Rico were analyzed separately. Of the 70,688 deaths, the majority (58.2%) were suicides, followed by homicides (31.5%), deaths of undetermined intent that might be due to violence (8.2%), legal intervention deaths (1.3%) (i.e., deaths caused by law enforcement and other persons with legal authority to use deadly force acting in the line of duty, excluding legal executions), and unintentional firearm injury deaths (<1.0%). The term "legal intervention" is a classification incorporated into the International Classification of Diseases, Tenth Revision, and does not denote the lawfulness or legality of the circumstances surrounding a death caused by law enforcement.Demographic patterns and circumstances varied by manner of death. The suicide rate was higher for males than for females. Across all age groups, the suicide rate was highest among adults aged ≥85 years. In addition, non-Hispanic American Indian or Alaska Native (AI/AN) persons had the highest suicide rates among all racial and ethnic groups. Among both males and females, the most common method of injury for suicide was a firearm. Among all suicide victims, when circumstances were known (84.4%), suicide was most often preceded by a mental health, intimate partner, or physical health problem or by a recent or impending crisis during the previous or upcoming 2 weeks. The homicide rate was higher for males than for females. Among all homicide victims, the homicide rate was highest among persons aged 20-24 years compared with other age groups. Non-Hispanic Black or African American (Black) males experienced the highest homicide rate of any racial or ethnic group. Among all homicide victims, the most common method of injury was a firearm. When the relationship between a homicide victim and a suspect was known, the suspect was most frequently an acquaintance or friend for male victims and a current or former intimate partner for female victims. Homicide most often was precipitated by an argument or conflict, occurred in conjunction with another crime, or, for female victims, was related to intimate partner violence. Nearly all victims of legal intervention deaths were male, and the legal intervention death rate was highest among men aged 30-34 years. The legal intervention death rate was highest among AI/AN males, followed by Black males. A firearm was used in the majority of legal intervention deaths. When circumstances were known, the most frequent circumstances reported for legal intervention deaths were as follows: the victim used a weapon in the incident and the victim had a substance use problem (other than alcohol use). Other causes of death included unintentional firearm injury deaths and deaths of undetermined intent. Unintentional firearm injury deaths were most frequently experienced by males, non-Hispanic White (White) persons, and persons aged 15-24 years. These deaths most frequently occurred while the shooter was playing with a firearm and were precipitated by a person unintentionally pulling the trigger. The rate of deaths of undetermined intent was highest among males, particularly among AI/AN and Black males, and among adults aged 30-54 years. Poisoning was the most common method of injury in deaths of undetermined intent, and opioids were detected in nearly 80% of decedents tested for those substances. Interpretation: This report provides a detailed summary of data from NVDRS on violent deaths that occurred in 2021. The suicide rate was highest among AI/AN and White males, whereas the homicide rate was highest among Black males. Intimate partner violence precipitated a large proportion of homicides for females. Mental health problems, intimate partner problems, interpersonal conflicts, and acute life stressors were primary precipitating circumstances for multiple types of deaths examined. Public Health Action: Violence is preventable, and data can guide public health action. NVDRS data are used to monitor the occurrence of violence-related fatal injuries and assist public health authorities in developing, implementing, and evaluating programs, policies, and practices to reduce and prevent violent deaths. NVDRS data can be used to enhance prevention efforts into actionable strategies. States or jurisdictions have used their Violent Death Reporting System (VDRS) data to guide suicide prevention efforts and highlight where additional focus is needed. For example, North Carolina VDRS program data have played a significant role in expanding activities related to firearm safety and injury prevention. The program served as a primary data source for partners, which led to the creation of the Office of Violence Prevention in the state, focusing on combatting firearm-related deaths. In Maine, the VDRS provided data on law enforcement officer suicides that were used to help support a bill mandating mental health resiliency and awareness training in the state's law enforcement training academy, along with plans for similar training addressing mental health, substance use, and alcohol problems among corrections officers. In addition, states and jurisdictions have also used their VDRS data to examine factors related to homicide in their state or jurisdiction. For example, Georgia VDRS collaborated with the City of Atlanta Mayor's Office of Violence Reduction to develop two public dashboards that not only offer comprehensive data on violent deaths but also present data on the geographic distribution of populations disproportionately affected by violence to help inform violence prevention interventions.

Accelerating onchocerciasis elimination in humanitarian settings: lessons from South Sudan.

There is persistent meso- and hyperendemicity of onchocerciasis (river blindness) in South Sudan, a country that has endured armed conflict for many years. In 2018, Amref Health Africa, in collaboration with local communities, the South Sudan Ministry of Health and other stakeholders, initiated some interventions, among which was Innovative Approaches to Reduce the Burden of Disease Caused by Onchocerciasis (IARDO) project. This project implemented several strategies, including identifying areas where onchocerciasis elimination programs need strengthening, switching from annual to biannual community-directed treatment with ivermectin (CDTI), additional ivermectin administration to postpartum women and school children and a community-based 'slash and clear' vector control strategy. These measures resulted in increased CDTI coverage, fewer bites from blackfly vectors and decreased onchocerciasis-related morbidity. The feasibility of these interventions, low cost, national government support and community ownership suggest their long-term sustainability.

Study Preregistration: Testing a Digital Suicide Risk Reduction Platform for Adolescents: A Pragmatic Randomized Controlled Trial.

Suicide is the second leading cause of death among adolescents, and rates of suicidal thoughts and behaviors (STBs) are climbing.1 Promising interventions such as dialectical behavior therapy (DBT) are available to treat suicidal youth, and new approaches may facilitate greater intervention engagement, adherence, and effectiveness.2 Digital tools (eg, personal smartphones) are a particularly promising avenue and could enhance existing, evidence-based interventions by providing new opportunities for assessment and intervention between sessions.

Homicides of American Indians/Alaska Natives in urban versus rural areas: United States National Violent Death Reporting System, 2003-2020.

BACKGROUND: Missing and Murdered Indigenous People is a historic and contemporary issue that has gained national attention. In 2021, homicide was the eighth leading cause of death among American Indian/Alaska Native (AIAN) persons aged between 1 and 54 years old, and homicide is the sixth leading cause of death among all AIAN males aged 1-54 years old. AIM: These data will build knowledge around AIAN homicides and to identify circumstances that can aid in comprehensive Missing and Murdered Indigenous People prevention efforts. METHODS: AIAN homicide data came from Centers for Disease Control and Prevention's National Violent Death Reporting System, a state/jurisdiction-based surveillance system that collects detailed information about characteristics and circumstances of violent deaths. We examined data from 2003 to 2020 (all available years) from participating states/jurisdictions. We also assessed sociodemographic characteristics of victims and suspects, incident characteristics and differences across dichotomised urban/rural status. The study was conducted in 2022. RESULTS: The National Violent Death Reporting System provided data on 2959 AIAN homicides from 2003 to 2020 (54.2% urban and 45.8% rural). Significant differences based on the two locations included type of weapon used, the location of the injury, race of the primary suspect, the victim's relationship to the suspect and select circumstances precipitating the homicide including crimes precipitating the homicide and homicides stemming from intimate partner violence. OUTCOMES: These findings provide crucial information to strengthen public health efforts for prevention.

Spermatocytes have the capacity to segregate chromosomes despite centriole duplication failure.

Centrosomes are the canonical microtubule organizing centers (MTOCs) of most mammalian cells, including spermatocytes. Centrosomes comprise a centriole pair within a structurally ordered and dynamic pericentriolar matrix (PCM). Unlike in mitosis, where centrioles duplicate once per cycle, centrioles undergo two rounds of duplication during spermatogenesis. The first duplication is during early meiotic prophase I, and the second is during interkinesis. Using mouse mutants and chemical inhibition, we have blocked centriole duplication during spermatogenesis and determined that non-centrosomal MTOCs (ncMTOCs) can mediate chromosome segregation. This mechanism is different from the acentriolar MTOCs that form bipolar spindles in oocytes, which require PCM components, including gamma-tubulin and CEP192. From an in-depth analysis, we identified six microtubule-associated proteins, TPX2, KIF11, NuMA, and CAMSAP1-3, that localized to the non-centrosomal MTOC. These factors contribute to a mechanism that ensures bipolar MTOC formation and chromosome segregation during spermatogenesis when centriole duplication fails. However, despite the successful completion of meiosis and round spermatid formation, centriole inheritance and PLK4 function are required for normal spermiogenesis and flagella assembly, which are critical to ensure fertility.

Phase Ib dose-escalation trial of taselisib (GDC-0032) in combination with HER2-directed therapies in patients with advanced HER2+ breast cancer.

BACKGROUND: In most patients with advanced human epidermal growth factor receptor-2-positive (HER2+) breast cancer, anti-HER2 therapies fail due to the development of acquired resistance, potentially mediated through phosphoinositide-3-kinase (PI3K) signaling. We investigated adding taselisib, an α-selective potent oral inhibitor of PI3K, to different HER2-directed regimens in order to improve disease control. PATIENTS AND METHODS: Patients (n = 68) with advanced HER2+ breast cancer were enrolled to this open-label, dose-escalation phase Ib study. The primary endpoint was defining the maximal tolerated dose (MTD) for the various taselisib-containing combinations. The secondary endpoint was safety. Exploratory endpoints included circulating tumor DNA analysis. The study included four cohorts: (A) taselisib + trastuzumab emtansine (T-DM1), (C) taselisib + trastuzumab and pertuzumab (TP), (D) taselisib + TP + paclitaxel, and (E) taselisib + TP + fulvestrant. RESULTS: Following dose escalation, the taselisib MTD was defined as 4 mg once daily. Treatment was associated with significant toxicities, as 34 out of 68 patients experienced grade ≥3 adverse events (AEs) attributed to taselisib, the most common all-grade AEs being diarrhea, fatigue, and oral mucositis. At a median follow-up of 43.8 months, median progression-free survival (PFS) for the MTD-treated population in cohorts A, C, and E was 6.3 [95% confidence interval (CI) 3.2-not applicable (NA)] months, 1.7 (95% CI 1.4-NA) months, and 10.6 (95% CI 8.3-NA) months, respectively. The median PFS for patients in cohort A with prior T-DM1 use was 10.4 (95% CI 2.7-NA) months. CONCLUSIONS: PIK3CA targeting with taselisib in combination with HER2-targeted therapies was associated with both promising efficacy and substantial toxicities.

Activation of the Mevalonate Pathway in Response to Anti-cancer Treatments Drives Glioblastoma Recurrences Through Activation of Rac-1.

Glioblastoma (GBM) is the deadliest adult brain cancer. Under the current standard of care, almost all patients succumb to the disease and novel treatments are urgently needed. Recognizing that GBMs are addicted to cholesterol, past clinical trials have repurposed statins against GBM but failed. The purpose of this study was to test whether treatments that upregulate the cholesterol biosynthesis pathway in GBM would generate a metabolic vulnerability that can be exploited using statins and to determine the underlying mechanisms.Effects of radiotherapy and temozolomide or dopamine receptor antagonists on the mevalonate pathway in GBM were assessed in vitro and in vivo. The impact of statins on self-renewal of glioma stem cells and median survival was studied. Branches of the mevalonate pathway were probed to identify relevant effector proteins.Cells surviving combination treatments that converge in activating the immediate early response, universally upregulated the mevalonate pathway and increased stemness of GBM cells through activation of the Rho-GTPase Rac-1. Activation of the mevalonate pathway and Rac-1 was inhibited by statins, which led to improved survival in mouse models of glioblastoma when combined with radiation and drugs that target the glioma stem cell pool and plasticity of glioma cells.We conclude that a combination of dopamine receptor antagonists and statins could potentially improve radiotherapy outcome and warrants further investigation. SIGNIFICANCE: Combination therapies that activate the mevalonate pathway in GBM cells after sublethal treatment enhance self-renewal and migratory capacity through Rac-1 activation, which creates a metabolic vulnerability that can be further potentially exploited using statins.

"The GalaFLEX 'Empanada' for Direct to Implant Prepectoral Breast Reconstruction".

CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

LAND-USE FILTERING FOR NONSTATIONARY SPATIAL PREDICTION OF COLLECTIVE EFFICACY IN AN URBAN ENVIRONMENT.

Collective efficacy-the capacity of communities to exert social control toward the realization of their shared goals-is a foundational concept in the urban sociology and neighborhood effects literature. Traditionally, empirical studies of collective efficacy use large sample surveys to estimate collective efficacy of different neighborhoods within an urban setting. Such studies have demonstrated an association between collective efficacy and local variation in community violence, educational achievement, and health. Unlike traditional collective efficacy measurement strategies, the Adolescent Health and Development in Context (AHDC) Study implemented a new approach, obtaining spatially-referenced, place-based ratings of collective efficacy from a representative sample of individuals residing in Columbus, OH. In this paper we introduce a novel nonstationary spatial model for interpolation of the AHDC collective efficacy ratings across the study area, which leverages administrative data on land use. Our constructive model specification strategy involves dimension expansion of a latent spatial process and the use of a filter defined by the land-use partition of the study region to connect the latent multivariate spatial process to the observed ordinal ratings of collective efficacy. Careful consideration is given to the issues of parameter identifiability, computational efficiency of an MCMC algorithm for model fitting, and fine-scale spatial prediction of collective efficacy.

Designing and synthesizing peptide-based quorum sensing modulators.

Quorum sensing (QS) is a density-dependent bacterial communication system that uses small molecules as regulatory modulators. Synthetic changes to these molecules can up-or-down-regulate this system, leading to control of phenotypes, like competence and virulence factor production, that have implications in human health. In this chapter, a methodology for library design and screening of synthetic autoinducing peptides (AIPs) to uncover QS SARs is delineated. Additionally, procedures for the synthesis, purification and analysis of linear and cyclic AIPs are detailed. This includes solutions for potential synthetic challenges including diketopiperazine formation when using N-methyl amino acids and cyclization of peptides containing N-terminal cysteine residues. These procedures have and are currently being applied to develop potent QS modulators in Streptococcus pneumoniae, Bacillus cereus, Streptococcus gordonii and Lactiplantibacillus plantarum.

Etiology of hospital mortality in children living in low- and middle-income countries: a systematic review and meta-analysis.

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, and total admissions. We excluded studies with data before 2,000 or without a full text. Two authors independently screened and extracted data. We performed methodological assessment using domains adapted from the Quality in Prognosis Studies tool. Data were pooled using random-effects models where possible. We reported prevalence as a proportion of cause of death or admission per 1,000 admissions with 95% confidence intervals (95% CI). Our search identified 29,637 texts. After duplicate removal and screening, we analyzed 253 studies representing 21.8 million pediatric hospitalizations in 59 LMICs. All-cause pediatric hospital mortality was 4.1% [95% CI 3.4%-4.7%]. The most common causes of mortality (deaths/1,000 admissions) were infectious [12 (95% CI 9-14)]; respiratory [9 (95% CI 5-13)]; and gastrointestinal [9 (95% CI 6-11)]. Common causes of admission (cases/1,000 admissions) were respiratory [255 (95% CI 231-280)]; infectious [214 (95% CI 193-234)]; and gastrointestinal [166 (95% CI 143-190)]. We observed regional variation in estimates. Pediatric hospital mortality remains high in LMICs. Global child health efforts must include measures to reduce hospital mortality including basic emergency and critical care services tailored to the local disease burden. Resources are urgently needed to promote equity in child health research, support researchers, and collect high-quality data in LMICs to further guide priority setting and resource allocation.

Correlation Between H-Index, M-Index, and Academic Rank in Urology.

OBJECTIVE: To evaluate the h- and m-indices of academic urologists across all U.S. accredited urology residency programs to determine the relationship between these metrics and an author's academic rank, academic degrees, and gender. METHODS: A total of 136 urology residency programs with available faculty information on their websites were evaluated. The academic rank, academic degrees, and gender were recorded for each clinical and research faculty member. Each author's h-index was determined using the Scopus database. The m-indices for each author were then calculated. Statistical analysis was performed using the Wilcoxon rank-sum test. RESULTS: This study demonstrated that the h- and m-indices positively correlate with an author's academic rank. Among the 2253 academic urologists evaluated, chairs/chiefs and professors had the highest median h- and m-indices (h-index 26, m-index 1.046 for chairs/chiefs; h-index 30, m-index 1.094 for professors). This was followed by associate professors (h-index 14, m-index 0.750), assistant professors (h-index 6, m-index 0.667), and clinical instructors (h-index 6, m-index 0.511). The median h- and m-indices were overall statistically higher for males than females. Faculty members with only a PhD were found to have the highest h- and m-indices followed by MD PhD, MD MBA, MD MPH, MD only, and DO only in descending order of index value. CONCLUSION: The h- and m-indices of academic urologists positively correlate with their academic rank. These metrics may serve as an additional tool in measuring an individual's academic productivity in consideration of job hirings, positional promotions, societal memberships, achievement awards, research grants, and more.

Radiation-Induced Cellular Plasticity: A Strategy for Combatting Glioblastoma.

Glioblastoma is the deadliest brain cancer in adults and almost all patients succumb to the tumor. While surgery followed by chemo-radiotherapy significantly delays disease progression, these treatments do not lead to long-term tumor control and targeted therapies or biologics have so far failed to further improve survival. Utilizing a transient radiation-induced state of multipotency we used the adenylcyclase activator forskolin to alter the cellular fate of glioma cells in response to radiation. The combined treatment induced the expression of neuronal markers in glioma cells, reduced proliferation and led to a distinct gene expression profile. scRNAseq revealed that the combined treatment forced glioma cells into a microglia- and neuron-like phenotypes. In vivo this treatment led to a loss of glioma stem cells and prolonged median survival in mouse models of glioblastoma. Collectively, our data suggest that revisiting a differentiation therapy with forskolin in combination with radiation could lead to clinical benefit.

The effects of family support and smartphone-derived homestay on daily mood and depression among sexual and gender minority adolescents.

Sexual and gender minority (SGM) adolescents are at elevated risk for depression. This risk is especially pronounced among adolescents whose home environment is unsupportive or nonaffirming, as these adolescents may face familial rejection due to their identity. Therefore, it is critical to better understand the mechanisms underlying this risk by probing temporally sensitive associations between negative mood and time spent in potentially hostile home environments. The current study included adolescents (N = 141; 43% SGM; 13-18 years old), oversampled for depression history, who completed clinical interviews assessing lifetime psychiatric history and depression severity as well as self-report measures of social support. Participants also installed an app on their personal smartphones, which assessed their daily mood and geolocation-determined mobility patterns over a 6-month follow-up period. Over the 6-month follow-up period, SGM adolescents reported elevated depression severity and lower daily mood relative to non-SGM youth. Interestingly, SGM adolescents who reported low family support experienced lower daily mood than non-SGM adolescents, particularly on days when they spent more time at home. Current findings reinforce evidence for disparities in depression severity among SGM adolescents and highlight family support as a key factor. Specifically, more time spent in home environments with low family support was associated with worse mood among SGM adolescents. These results underscore the need for clinical interventions to support SGM youth, particularly interventions that focus on familial relationships and social support within the home environment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Modular and divergent synthesis of 2,N3-disubstituted 4-quinazolinones facilitated by regioselective N-alkylation.

The synthesis of a biologically relevant 2-amino-N3-alkylamido 4-quinazolinone has been accomplished in four steps from commercially available materials using design principles from both modular and divergent synthesis. N3-Alkylation of 2-chloro-4(3H)-quinazolinone using methyl bromoacetate, followed by C2-amination produced a suitable scaffold for introducing molecular diversity. Optimization of alkylation conditions afforded full regioselectivity, enabling exclusive access to the N-alkylated isomer. Subsequent C2-amination using piperidine, pyrrolidine, or diethylamine, followed by amide bond formation using variously substituted phenethylamines, generated fifteen unique 4-quinazolinones bearing C2-amino and N3-alkylamido substituents. These efforts highlight the reciprocal influence of C2 and N3 substitution on functionalization at either position, establish an effective synthetic pathway toward 2,N3-disubstituted 4-quinazolinones, and enable preliminary bioactivity studies while providing an experiential learning opportunity for undergraduate student researchers.

Prepectoral versus Subpectoral Breast Reconstruction after Nipple-sparing Mastectomy: A Systematic Review and Meta-Analysis.

Background: Implant-based breast reconstruction after nipple-sparing mastectomy (NSM) presents unique benefits and challenges. The literature has compared outcomes among total submuscular (TSM), dual-plane (DP), and prepectoral (PP) planes; however, a dedicated meta-analysis relevant to NSM is lacking. Methods: We conducted a systematic review of studies on immediate breast reconstruction after NSM using TSM, DP, or PP prosthesis placement in PubMed, Embase, and Cochrane databases. In total, 1317 unique articles were identified, of which 49 were included in the systematic review and six met inclusion criteria for meta-analysis. Pooled descriptive outcomes were analyzed for each cohort for all 49 studies. Fixed-effects meta-analytic methods were used to compare PP with subpectoral (TSM and DP) reconstructions. Results: A total of 1432 TSM, 1546 DP, and 1668 PP reconstructions were identified for descriptive analysis. Demographics were similar between cohorts. Pooled descriptive outcomes demonstrated overall similar rates of reconstructive failure (3.3%-5.1%) as well as capsular contracture (0%-3.9%) among cohorts. Fixed-effects meta-analysis of six comparative studies demonstrated a significantly lower rate of mastectomy flap necrosis in the PP cohort compared with the subpectoral cohort (relative risk 0.24, 95% confidence interval [0.08-0.74]). All other consistently reported outcomes, including, hematoma, seroma, infection, mastectomy flap necrosis, nipple -areola complex necrosis, and explantation were comparable. Conclusions: A systematic review of the literature and meta-analysis demonstrated the safety of immediate prepectoral breast reconstruction after NSM, compared with submuscular techniques. Submuscular reconstruction had a higher risk of mastectomy flap necrosis, though potentially influenced by selection bias.

Minimizing Nipple-Areolar Complex Complications in Prepectoral Breast Reconstruction After Nipple-Sparing Mastectomy.

PURPOSE: Nipple-areolar complex (NAC) viability remains a significant concern following prepectoral tissue expander (TE) reconstruction after nipple-sparing mastectomy (NSM). This study assesses the impact of intraoperative TE fill on NAC necrosis and identifies strategies for mitigating this risk. METHODS: A chart review of all consecutive, prepectoral TEs placed immediately after NSM was performed between March 2017 and December 2022 at a single center. Demographics, mastectomy weight, intraoperative TE fill, and complications were extracted for all patients. Partial NAC necrosis was defined as any thickness of skin loss including part of the NAC, whereas total NAC necrosis was defined as full-thickness skin loss involving the entirety of the NAC. P < 0.05 was considered statistically significant. RESULTS: Forty-six patients (83 breasts) with an average follow-up of 22 months were included. Women were on average 46 years old, nonsmoker (98%), and nondiabetic (100%) and had a body mass index of 23 kg/m2. All reconstructions were performed immediately following prophylactic mastectomies in 49% and therapeutic mastectomies in 51% of cases. Three breasts (4%) were radiated, and 15 patients (33%) received chemotherapy. Mean mastectomy weight was 346 ± 274 g, median intraoperative TE fill was 150 ± 225 mL, and median final TE fill was 350 ± 170 mL. Partial NAC necrosis occurred in 7 breasts (8%), and there were zero instances of complete NAC necrosis. On univariate analysis, partial NAC necrosis was not associated with any patient demographic or operative characteristics, including intraoperative TE fill. In multivariable models controlling for age, body mass index, mastectomy weight, prior breast surgery, and intraoperative TE fill, partial NAC necrosis was associated with lower body mass index (odds ratio, 0.53; confidence interval [CI], 0.29-0.98; P < 0.05) and higher mastectomy weight (odds ratio, 1.1; CI, 1.01-1.20; P < 0.05). Prior breast surgery approached significance, as those breasts had a 19.4 times higher odds of partial NAC necrosis (95% CI, 0.88-427.6; P = 0.06). CONCLUSIONS: Nipple-areolar complex necrosis following prepectoral TE reconstruction is a rare but serious complication. In this study of 83 breasts, 7 (8%) developed partial NAC necrosis, and all but one were able to be salvaged.