The Impact of Higher BMI on Wound Complications Following Adolescent Breast Reduction: A Retrospective Study of 1215 Cases.

BACKGROUND: Macromastia is a physically and psychologically distressing condition for adolescents. While reduction mammaplasty is often the best treatment, risk factors for adolescent wound complications remain unclear. This study aims to investigate the impact of obesity and other predictors of postoperative wound complications following adolescent reduction mammaplasty using a national database. METHODS: The 2012-2019 National Surgical Quality Improvement Program Pediatric (NSQIP-P) databases were reviewed to identify primary reduction mammaplasty encounters. World Health Organization Body Mass Index (BMI), alongside patient and case characteristics, were assessed for association for 30-day wound disruption or surgical site complications. Statistical analyses were performed to identify independent predictors for complications and determine a potential BMI cutoff for risk stratification. RESULTS: There were 1215 patients with an average age of 16.6 years. The average BMI was 30.7 kg/m2, and 593 (48.8%) patients were nonobese while 622 (51.2%) were obese. The incidence of complications was 5.27%. Independent predictors of complications included a BMI 35-39.9, BMI > 40, and an American Society of Anesthesiologists (ASA) Classification > 3. A receiver operating characteristic curve determined that a BMI of 34.6 can be a potential cutoff for increased complication risk. CONCLUSIONS: Higher obesity increases risk of wound complications; however, complication rates remain low. A BMI of 34.6 is a potential screening metric for counseling and monitoring patients. Reduction mammaplasty should remain a viable option as it can significantly improve quality of life. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Discovery and engineering of the antibody response against a prominent skin commensal.

The ubiquitous skin colonist Staphylococcus epidermidis elicits a CD8 + T cell response pre-emptively, in the absence of an infection 1 . However, the scope and purpose of this anti-commensal immune program are not well defined, limiting our ability to harness it therapeutically. Here, we show that this colonist also induces a potent, durable, and specific antibody response that is conserved in humans and non-human primates. A series of S. epidermidis cell-wall mutants revealed that the cell surface protein Aap is a predominant target. By colonizing mice with a strain of S. epidermidis in which the parallel ß-helix domain of Aap is replaced by tetanus toxin fragment C, we elicit a potent neutralizing antibody response that protects mice against a lethal challenge. A similar strain of S. epidermidis expressing an Aap-SpyCatcher chimera can be conjugated with recombinant immunogens; the resulting labeled commensal elicits high titers of antibody under conditions of physiologic colonization, including a robust IgA response in the nasal mucosa. Thus, immunity to a common skin colonist involves a coordinated T and B cell response, the latter of which can be redirected against pathogens as a novel form of topical vaccination.

A Survey Study of Surgeons and Anesthesiologists Regarding Perioperative Multimodal Analgesia for Opioid-Tolerant Patients.

PURPOSE: Perioperative pain management of opioid-tolerant patients can be challenging. Although regional anesthesia and multimodal analgesics may be beneficial, these modalities are often underused. It is unclear whether practice patterns for perioperative pain management are determined by the knowledge, attitudes, and beliefs of surgeons and anesthesiologists. DESIGN: Descriptive survey. METHODS: Using a Qualtrics survey, we polled a randomly selected group of 25 surgeons and 25 anesthesiologists regarding their knowledge, attitudes, beliefs, and practices for pain management in an opioid-tolerant patient. FINDINGS: Of 25, 23 anesthesiologists and 18/25 surgeons responded to the survey. Demographics were similar between the 2 groups. Most of the participant surgeons and anesthesiologists believed that pain management may be challenging in an opioid-tolerant patient. However, only 56% of surgeons would recommend a preoperative pain consultation. Most surgeons and anesthesiologists believed in the efficacy of regional anesthetics. However, 43% of surgeons would not advocate for a regional block, perhaps due to their perception of the added perioperative time. Multimodal analgesics were widely accepted by both surgeons and anesthesiologists. CONCLUSIONS: There is an urgent need to reinforce the importance of patient-centered care, with a specific focus on addressing knowledge gaps and improving perceptions for all the members of the team, including surgeons, anesthesiologists, and perioperative nursing teams, if optimal outcomes are to be achieved for our patients.

The association between parental age differences and perinatal outcomes.

STUDY QUESTION: Are there significant associations existing between parental age differences and adverse perinatal outcomes? SUMMARY ANSWER: Large differences in parental age are associated with adverse perinatal outcomes, particularly with older mothers paired with younger fathers. WHAT IS KNOWN ALREADY: The association between advanced maternal age and perinatal outcomes is well-documented with women over 35 years showing an increased risk of several adverse outcomes. Other studies have identified potential associations between advanced paternal age and adverse perinatal outcomes. STUDY DESIGN, SIZE, DURATION: A historical (retrospective) cohort analysis was performed utilizing a multivariable logistic regression model to evaluate the association between varying differences in parental age and adverse perinatal outcomes while controlling for demographic and health-related covariates. Data were compiled from the National Vital Statistics System for 20 613 704 births between 2012 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Parental age differences, categorized into eleven 4-year intervals, were stratified by seven maternal age categories and evaluated for their associations with adverse perinatal outcomes. Main outcome measures included low birth weight, very low birth weight, preterm birth, very preterm birth, small size for gestational age, low 5-min appearance, pulse, grimace, activity, and respiration score, congenital defects, and chromosomal anomalies. MAIN RESULTS AND THE ROLE OF CHANCE: Increased parental age differences, in either direction, were associated with significant risks for all adverse outcomes, aside from congenital defects, even when controlling for maternal age. Restricting maternal age to the reference range of 25-29 years, infants born to fathers aged 9-12 years younger (n = 3773) had 27% (odds ratio (OR) 1.27, 95% CI, 1.17-1.37) higher odds of having any adverse perinatal outcome. Infants born to fathers aged >16 years older (n = 98 555) had 14% (OR 1.14, 95% CI, 1.12-1.16) higher odds of having any adverse perinatal outcome. LIMITATIONS, REASONS FOR CAUTION: Data extracted from US birth certificates may be compromised by errors in reporting or documentation. Information regarding the mother's socioeconomic status was estimated using proxy variables and may be susceptible to uncontrolled factors. Use of a pre-compiled dataset may potentially exclude additional maternal comorbidities that could impact perinatal outcomes. WIDER IMPLICATIONS OF FINDINGS: Older mothers paired with younger fathers demonstrated the highest risk, even when maternal age was below the threshold of 35 years. For the clinical setting, parental age differences should be considered alongside maternal and paternal age when assessing risks of adverse perinatal outcomes for potential parents. This is particularly relevant for older women with younger male partners as this may exacerbate the impact of advanced maternal age. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the NIH Research Fellowship T35 Training Grant. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Excited State Properties of Point Defects in Semiconductors and Insulators Investigated with Time-Dependent Density Functional Theory.

We present a formulation of spin-conserving and spin-flip hybrid time-dependent density functional theory (TDDFT), including the calculation of analytical forces, which allows for efficient calculations of excited state properties of solid-state systems with hundreds to thousands of atoms. We discuss an implementation on both GPU- and CPU-based architectures along with several acceleration techniques. We then apply our formulation to the study of several point defects in semiconductors and insulators, specifically the negatively charged nitrogen-vacancy and neutral silicon-vacancy centers in diamond, the neutral divacancy center in 4H silicon carbide, and the neutral oxygen-vacancy center in magnesium oxide. Our results highlight the importance of taking into account structural relaxations in excited states in order to interpret and predict optical absorption and emission mechanisms in spin defects.

First-Principles Investigation of Near-Surface Divacancies in Silicon Carbide.

The realization of quantum sensors using spin defects in semiconductors requires a thorough understanding of the physical properties of the defects in the proximity of surfaces. We report a study of the divacancy (VSiVC) in 3C-SiC, a promising material for quantum applications, as a function of surface reconstruction and termination with -H, -OH, -F and oxygen groups. We show that a VSiVC close to hydrogen-terminated (2 × 1) surfaces is a robust spin-defect with a triplet ground state and no surface states in the band gap and with small variations of many of its physical properties relative to the bulk, including the zero-phonon line and zero-field splitting. However, the Debye-Waller factor decreases in the vicinity of the surface and our calculations indicate it may be improved by strain-engineering. Overall our results show that the VSiVC close to SiC surfaces is a promising spin defect for quantum applications, similar to its bulk counterpart.

Patient perspectives on recall period and response options in patient-reported outcome measures for chronic rhinosinusitis symptomatology: An international multi-centered study.

BACKGROUND: Existing patient-reported outcome measures (PROMs) for chronic rhinosinusitis (CRS) use a variety of recall periods and response scales to assess CRS symptom burden. Global perspectives of CRS patients regarding optimal recall periods and response scales for CRS PROMs are unknown. METHODS: This was a multi-center, cross-sectional study recruiting 461 CRS patients from sites across the United States, Saudi Arabia, New Zealand, and Austria. Participants chose which CRS symptom recall period (1 day, 2 weeks, 1 month, >1 month) was most reflective of their current disease state and upon which to best base treatment recommendations (including surgery). Participants also chose which of six response scales (one visual analogue scale and five Likert scales ranging from four to eight items) was easiest to use, understand, and preferred. RESULTS: A plurality of participants (40.0%) felt their CRS symptoms' current state was best reflected by a 1-month recall period. However, most patients (56.9%) preferred treatment recommendations to be determined by symptoms experienced over a >1 month period. The four- and five-item Likert scales were the easiest to understand (26.0% and 25.4%, respectively) and use (23.4% and 26.7%, respectively). The five-item (26.4% rating it most preferred and 70.9% rating it preferred) and four-item Likert (22.3% rating it most preferred and 56.4% rating it preferred) response scales were most preferred. CONCLUSION: Future PROMs for CRS should consider assessment of symptoms over a 1-month period and use a four- or five-item Likert response scale to reflect global patient preferences. These findings also inform interpretation of current CRS PROMs.

Heterogeneity in the definition of chronic rhinosinusitis disease control: a systematic review of the scientific literature.

PURPOSE: Disease control is conceptually recognized to be an important outcome measure for chronic rhinosinusitis (CRS). However, inconsistent usage is a significant factor in disadoption of important concepts and it is presently unclear how consistently the construct of CRS 'control' is being defined/applied. The objective of this study was to determine the heterogeneity of CRS disease control definitions in the scientific literature. METHODS: Systematic review of PubMed and Web of Science databases from inception through December 31, 2022. Included studies used CRS disease control as an explicitly stated outcome measure. The definitions of CRS disease control were collected. RESULTS: Thirty-one studies were identified with more than half published in 2021 or later. Definitions of CRS control were variable, although 48.4% of studies used the EPOS (2012 or 2020) criteria to define control, 14 other unique definitions of CRS disease control were also implemented. Most studies included the burden CRS symptoms (80.6%), need for antibiotics or systemic corticosteroids (77.4%) or nasal endoscopy findings (61.3%) as criteria in their definitions of CRS disease control. However, the specific combination of these criteria and prior time periods over which they were assessed were highly variable. CONCLUSION: CRS disease control is not consistently defined in the scientific literature. Although many studies conceptually treated 'control' as the goal of CRS treatment, 15 different criteria were used to define CRS disease control, representing significant heterogeneity. Scientific derivation of criteria and collaborative consensus building are needed for the development of a widely-accepted and -applied definition of CRS disease control.

Portal Closure After Segmental Posterior Labral Repair for Posterior Shoulder Instability.

Posterior instability, although an uncommon shoulder pathology, is reported most frequently in the athletic population. Arthroscopic repair has emerged as the main surgical treatment modality for posterior instability. However, when compared with arthroscopic repair for anterior instability, the results of this procedure remain suboptimal. The creation of iatrogenic defects in the capsule, due to cannula placement, is a possible culprit. Because these defects typically do not heal satisfactorily, they become stress risers within the capsule itself, which may lead to recurrent instability or an otherwise compromised repair construct. Therefore, we find that routine intraoperative repair of these defects after repair can reduce the risk of injury and possibly improve long-term outcomes. In this article, we illustrate the repair of a posterior segmental tear using all-suture knotless implants with closure of the posterior and posterior-inferior portals after stabilization.

Engineered skin bacteria induce antitumor T cell responses against melanoma.

Certain bacterial colonists induce a highly specific T cell response. A hallmark of this encounter is that adaptive immunity develops preemptively, in the absence of an infection. However, the functional properties of colonist-induced T cells are not well defined, limiting our ability to understand anticommensal immunity and harness it therapeutically. We addressed both challenges by engineering the skin bacterium Staphylococcus epidermidis to express tumor antigens anchored to secreted or cell-surface proteins. Upon colonization, engineered S. epidermidis elicits tumor-specific T cells that circulate, infiltrate local and metastatic lesions, and exert cytotoxic activity. Thus, the immune response to a skin colonist can promote cellular immunity at a distal site and can be redirected against a target of therapeutic interest by expressing a target-derived antigen in a commensal.

Hospital volume as a predictor of outcomes following pediatric thyroidectomy.

BACKGROUND: Pediatric thyroidectomy (PT) is an uncommon procedure with a risk of significant morbidity. This study utilizes a national database to identify factors associated with short-term (30-day) post-thyroidectomy complications in children with thyroid cancer. METHODS: The 2016 and 2012 Kids' Inpatient Databases (KID) were used in this study. All children with thyroid cancer undergoing thyroidectomy were included. Complications were categorized into endocrine, nervous, pulmonary, and other. Hospital volume was stratified into high-volume (performing the top 10% of total cases, HVC) or non-high-volume centers (NHVC). Risk factors were analyzed using univariable and multivariable statistical tests. RESULTS: Six hundred and sixty-three patients with an average age of 15.93 years met inclusion criteria. Most patients were seen in an NHVC (90.0%) and 37.3% of thyroidectomies were performed with neck dissections. The incidence of any complication was 32.1%. Endocrine complications were the most frequent (32.7%). Independent predictors of any or only endocrine complications were age (odds ratio [OR] = 0.927, p = 0.002, any; OR = 0.926, p = 0.003, endocrine) or concurrent neck dissection (OR = 1.679, p = 0.004, any; OR = 1.683, p = 0.005, endocrine). There was no statistically significant change in odds with hospital volume. CONCLUSIONS: Further investigation into the effect of single surgeon versus hospital volume on the risk of complications in pediatric thyroid cancer surgery is warranted.

Sirolimus suppresses circulating fibrocytes in idiopathic pulmonary fibrosis in a randomized controlled crossover trial.

BACKGROUNDFibrocytes are BM-derived circulating cells that traffic to the injured lungs and contribute to fibrogenesis. The mTOR inhibitor, sirolimus, inhibits fibrocyte CXCR4 expression, reducing fibrocyte traffic and attenuating lung fibrosis in animal models. We sought to test the hypothesis that short-term treatment with sirolimus reduces the concentration of CXCR4+ circulating fibrocytes in patients with idiopathic pulmonary fibrosis (IPF).METHODSWe conducted a short-term randomized double-blind placebo-controlled crossover pilot trial to assess the safety and tolerability of sirolimus in IPF. Participants were randomly assigned to sirolimus or placebo for approximately 6 weeks, and after a 4-week washout, they were assigned to the alternate treatment. Toxicity, lung function, and the concentration of circulating fibrocytes were measured before and after each treatment.RESULTSIn the 28 study participants, sirolimus resulted in a statistically significant 35% decline in the concentration of total fibrocytes, 34% decline in CXCR4+ fibrocytes, and 42% decline in fibrocytes expressing α-smooth muscle actin, but no significant change in these populations occurred on placebo. Respiratory adverse events occurred more frequently during treatment with placebo than sirolimus; the incidence of adverse events and drug tolerability did not otherwise differ during therapy with drug and placebo. Lung function was unaffected by either treatment, with the exception of a small decline in gas transfer during treatment with placebo.CONCLUSIONAs compared with placebo, short-term treatment with sirolimus resulted in reduction of circulating fibrocyte concentrations in participants with IPF, with an acceptable safety profile.TRIAL REGISTRATIONClinicalTrials.gov, accession no. NCT01462006.FUNDINGNIH R01HL098329 and American Heart Association 18TPA34170486.

Comorbidity and Operative Time are Stronger Predictors than Age for Palatoplasty Adverse Airway Events, A NSQIP-P Study of 6668 Cases.

BACKGROUND: Adverse airway events (AAEs) are rare but devastating complications following palatoplasty. The purpose of this study is to evaluate patient risk factors for their effect on these complications. We hypothesize that prolonged operative time and the presence of multiple medical comorbidities are risk factors for AAEs. DESIGN: Retrospective cohort study. SETTING: Participant hospitals in the Pediatric American College of Surgeons National Surgical Quality Improvement Program year 2016-2019. PATIENTS: Cases of palatoplasty in children under 3 years of age. OUTCOMES: Adverse airway events including postoperative reintubation or any requirement of postoperative mechanical ventilation. RESULTS: A total of 6668 patients met inclusion criteria. The median operative time was 126 min (IQR 82). AAEs were identified in 107 (1.6%) patients. The incidence of risk factors was found to increase with age and AAEs were more prevalent in younger and older patients. Although patients in the older age groups had significantly higher burden of comorbidities, differences in age were not independently associated with AAEs. Following multivariable logistic regressions, operative times greater than 2 h, ASA class ≥3, >3 medical comorbidities, and black race were found to be significant independent risk factors. CONCLUSIONS: In this large, retrospective database study in palatoplasty, increased operative time, ASA classification ≥3, multiple comorbidities, and black race were independently associated with AAEs.

p62/SQSTM1 in liver diseases: the usual suspect with multifarious identities.

p62/Sequestosome-1 (SQSTM1) is a selective autophagy receptor that recruits and delivers intracellular substrates for bulk clearance through the autophagy lysosomal pathway. Interestingly, p62 also serves as a signaling scaffold to participate in the regulation of multiple physiological processes, including oxidative stress response, metabolism, inflammation, and programmed cell death. Perturbation of p62 activity has been frequently found to be associated with the pathogenesis of many liver diseases. p62 has been identified as a critical component of protein aggregates in the forms of Mallory-Denk bodies (MDBs) or intracellular hyaline bodies (IHBs), which are known to be frequently detected in biopsy samples from alcoholic steatohepatitis (ASH), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC) patients. Importantly, abundance of these p62 inclusion bodies is increasingly recognized as a biomarker for NASH and HCC. Although the level of p62 bodies seems to predict the progression and prognosis of these liver diseases, understanding of the underlying mechanisms by which p62 regulates and contributes to the development and progression of these diseases remains incomplete. In this review, we will focus on the function and regulation of p62, and its pathophysiological roles in the liver, by critically reviewing the findings from preclinical models that recapitulate the pathogenesis and manifestation of these liver diseases in humans. In addition, we will also explore the suitability of p62 as a predictive biomarker and a potential therapeutic target for the treatment of liver diseases, including NASH and HCC, as well as recent development of small-molecule compounds for targeting the p62 signaling axis.

Combined Liver-Kidney Transplant for Juvenile Polycystic Kidney Disease and Concomitant Hereditary Factor V Deficiency.

Factor V deficiency is a congenital bleeding diathesis that, in selected cases, may be managed with liver transplant. In this case, we describe the treatment of an adult patient with kidney failure secondary to juvenile onset polycystic kidney disease who received a combined liver-kidney transplant as a method to manage the risks associated with the need for a kidney transplantin the setting of factorV deficiency and high sensitization.

Fertility in the aging male: a systematic review.

The negative effect of advanced female age on fertility and offspring health is well understood. In comparison, much less is known about the implications of male age on fertility, with many studies showing conflicting results. Nevertheless, increasing evidence suggests that advanced paternal age has negative effects on sperm parameters, reproductive success, and offspring health. Herein, we summarize the current body of knowledge on this controversial topic, with the belief that this review will serve as a resource for the clinicians providing fertility counseling to couples with older male partners.

MqsR is a noncanonical microbial RNase toxin that is inhibited by antitoxin MqsA via steric blockage of substrate binding.

The MqsRA toxin-antitoxin system is a component of the Escherichia coli stress response. Free MqsR, a ribonuclease, cleaves mRNAs containing a 5'-GC-3' sequence causing a global shutdown of translation and the cell to enter a state of dormancy. Despite a general understanding of MqsR function, the molecular mechanism(s) by which MqsR binds and cleaves RNA and how one or more of these activities is inhibited by its cognate antitoxin MqsA is still poorly understood. Here, we used NMR spectroscopy coupled with mRNA cleavage assays to identify the molecular mechanism of MqsR substrate recognition and the MqsR residues that are essential for its catalytic activity. We show that MqsR preferentially binds substrates that contain purines in the -2 and -1 position relative to the MqsR consensus cleavage sequence and that two residues of MqsR, Tyr81, and Lys56 are strictly required for mRNA cleavage. We also show that MqsA inhibits MqsR activity by sterically blocking mRNA substrates from binding while leaving the active site fully accessible to mononucleotides. Together, these data identify the residues of MqsR that mediate RNA cleavage and reveal a novel mechanism that regulates MqsR substrate specificity.

GPU Acceleration of Large-Scale Full-Frequency GW Calculations.

Many-body perturbation theory is a powerful method to simulate electronic excitations in molecules and materials starting from the output of density functional theory calculations. By implementing the theory efficiently so as to run at scale on the latest leadership high-performance computing systems it is possible to extend the scope of GW calculations. We present a GPU acceleration study of the full-frequency GW method as implemented in the WEST code. Excellent performance is achieved through the use of (i) optimized GPU libraries, e.g., cuFFT and cuBLAS, (ii) a hierarchical parallelization strategy that minimizes CPU-CPU, CPU-GPU, and GPU-GPU data transfer operations, (iii) nonblocking MPI communications that overlap with GPU computations, and (iv) mixed precision in selected portions of the code. A series of performance benchmarks has been carried out on leadership high-performance computing systems, showing a substantial speedup of the GPU-accelerated version of WEST with respect to its CPU version. Good strong and weak scaling is demonstrated using up to 25 920 GPUs. Finally, we showcase the capability of the GPU version of WEST for large-scale, full-frequency GW calculations of realistic systems, e.g., a nanostructure, an interface, and a defect, comprising up to 10 368 valence electrons.

Trajectory of immune evasion and cancer progression in hepatocellular carcinoma.

Immune evasion is key to cancer initiation and later at metastasis, but its dynamics at intermediate stages, where potential therapeutic interventions could be applied, is undefined. Here we show, using multi-dimensional analyses of resected tumours, their adjacent non-tumour tissues and peripheral blood, that extensive immune remodelling takes place in patients with stage I to III hepatocellular carcinoma (HCC). We demonstrate the depletion of anti-tumoural immune subsets and accumulation of immunosuppressive or exhausted subsets along with reduced tumour infiltration of CD8 T cells peaking at stage II tumours. Corresponding transcriptomic modification occur in the genes related to antigen presentation, immune responses, and chemotaxis. The progressive immune evasion is validated in a murine model of HCC. Our results show evidence of ongoing tumour-immune co-evolution during HCC progression and offer insights into potential interventions to reverse, prevent or limit the progression of the disease.