Citations

Background Complications from prosthetic breast reconstruction are distressing for patients, and their management is challenging. For decades, negative-pressure wound therapy (NPWT) has been successfully used for the closure of complex wounds. This study analyzes the outcomes of NPWT use in the prevention and management of complications from prosthetic breast reconstruction. Method A systematic search of studies published until August 2020 was conducted using the PubMed/MEDLINE, EMBASE, and Ebscohost/CINAHL databases and using the following key words: “negative-pressure wound therapy,” “breast reconstruction,” and “prosthesis” (including breast implants and tissue expanders). Analyzed endpoints were outcomes of NPWT use in prosthetic breast reconstruction compared with conventional dressings. The methodological quality of included studies was assessed independently. Comparative studies were further meta-analyzed to obtain pooled odds ratios (ORs) describing the effectiveness of NPWT in prosthetic breast reconstruction. Results/Discussion Ten studies were included with a total of 787 patients (1230 breasts) undergoing prosthetic breast reconstruction with breast implants or tissue expanders. Three case-control studies focused on preventing breast wound complications. The meta-analysis of the 3 studies included 502 breasts receiving NPWT and 698 breasts receiving conventional wound care. The meta-analysis favored NPWT for less mastectomy flap necrosis (5.6% vs 14.3%; OR, 0.46; 95% confidence interval, 0.27 –0.77; P = 0.004; I 2 = 0%) and less overall wound complications (10.6% vs 21.1%; OR, 0.49; 95% confidence interval, 0.35–0.70; P < 0.00001; I 2 = 0%). In the management of nipple-areolar complex venous congestion, 1 case report demonstrated 85% rescue of nipple-areolar complex after using NPWT (−75 mm Hg) for a total of 12 days. In the management of periprosthetic infections, 2 case series used NPWT with instillation. It accelerated the treatment of infection and maintained the breast cavity for future reconstruction. Conventional NPWT also showed good salvage outcome in four studies. Conclusions Current evidence suggests that prophylactic use of NPWT in prosthetic breast reconstruction reduces the rate of overall wound complications and mastectomy flap necrosis. In the management of complications from prosthetic breast reconstructions, NPWT may be a promising option showing beneficial results. Additional high-quality trials are warranted to corroborate the findings of this systematic review.

Abstract One of the greatest barriers to curative treatment of neuroblastoma is its frequent metastatic outgrowth prior to diagnosis, especially in cases driven by amplification of the MYCN oncogene. However, only a limited number of regulatory proteins that contribute to this complex MYCN-mediated process have been elucidated. Here we show that the growth arrest-specific 7 (GAS7) gene, located at chromosome band 17p13.1, is preferentially deleted in high-risk MYCN-driven neuroblastoma. GAS7 expression was also suppressed in MYCN-amplified neuroblastoma lacking 17p deletion. GAS7 deficiency led to accelerated metastasis in both zebrafish and mammalian models of neuroblastoma with overexpression or amplification of MYCN. Analysis of expression profiles and the ultrastructure of zebrafish neuroblastoma tumors with MYCN overexpression identified that GAS7 deficiency led to (i) downregulation of genes involved in cell–cell interaction, (ii) loss of contact among tumor cells as critical determinants of accelerated metastasis, and (iii) increased levels of MYCN protein. These results provide the first genetic evidence that GAS7 depletion is a critical early step in the cascade of events culminating in neuroblastoma metastasis in the context of MYCN overexpression. Significance: Heterozygous deletion or MYCN-mediated repression of GAS7 in neuroblastoma releases an important brake on tumor cell dispersion and migration to distant sites, providing a novel mechanism underlying tumor metastasis in MYCN-driven neuroblastoma. See related commentary by Menard, p. 2815

Significance The multiple-domain protein ZMYND8 is well known as a chromatin reader that recognizes methylated, acetylated, and/or mutated histones. Here we report that ZMYND8 is overexpressed in human ccRCC, and that it preferentially binds T487-phosphorylated EZH2. We show that in hypoxia-stimulated or von Hippel–Lindau–deficient cells, ZMYND8 binding of EZH2 is important for maintenance of EZH2 phosphorylation level, inhibition of PRC2 complex formation, and enhanced interaction between EZH2 and FOXM1. Our results reveal a reader function of ZMYND8 in recognizing a phosphorylation “code” on a nonhistone protein. Our findings also identify ZMYND8 binding as a facet of regulation and function of EZH2 phosphorylation in the Polycomb-dependent to -independent switch of EZH2/PRC2 activities.

AbstractTargeted muscle reinnervation enables native muscles to send electromyographic signals to myoelectric receptors, which drive movements in a prosthesis. This system requires voluntary contracture of muscles for sequential control of powered prosthetic joints. This report describes a surgical solution for cases where the chest wall is depleted of muscle targets. A 13‐year‐old boy with left forequarter amputation and pectoralis major resection as a result of extended necrotizing facilities 8 years prior received a neurotized free Vertical Rectus Abdominus Mycocutaneous (VRAM) flap (28 × 10 cm) designed to produce myoelectric signals, reduce pain, and provide stability for prosthetic fitting. Five intercostal nerves from the VRAM were coapted to portions of the brachial plexus to create a myoelectric interface for targeted muscle reinnervation. The postoperative course was uneventful. At 39 months of follow‐up, the patient gained control of the transferred VRAM and was able to operate a custom‐fitted myoelectric prosthesis together with contraction of the ipsilateral infraspinatus muscle. The neurotized VRAM transfer created a neural interface in an area with depleted neuromuscular targets while decreasing pain and adding tissue bulk for proper prosthesis fitting. Such a surgical strategy may have applications in other areas of the body.

BACKGROUND: The American Board of Anesthesiology administers the APPLIED Examination as a part of initial certification, which as of 2018 includes 2 components—the Standardized Oral Examination (SOE) and the Objective Structured Clinical Examination (OSCE). The goal of this study is to investigate the measurement construct(s) of the APPLIED Examination to assess whether the SOE and the OSCE measure distinct constructs (ie, factors). METHODS: Exploratory item factor analysis of candidates’ performance ratings was used to determine the number of constructs, and confirmatory item factor analysis to estimate factor loadings within each construct and correlation(s) between the constructs. RESULTS: In exploratory item factor analysis, the log-likelihood ratio test and Akaike information criterion index favored the 3-factor model, with factors reflecting the SOE, OSCE Communication and Professionalism, and OSCE Technical Skills. The Bayesian information criterion index favored the 2-factor model, with factors reflecting the SOE and the OSCE. In confirmatory item factor analysis, both models suggest moderate correlation between the SOE factor and the OSCE factor; the correlation was 0.49 (95% confidence interval [CI], 0.42-0.55) for the 3-factor model and 0.61 (95% CI, 0.54-0.64) for the 2-factor model. The factor loadings were lower for Technical Skills stations of the OSCE (ranging from 0.11 to 0.25) compared with those of the SOE and Communication and Professionalism stations of the OSCE (ranging from 0.36 to 0.50). CONCLUSIONS: The analyses provide evidence that the SOE and the OSCE measure distinct constructs, supporting the rationale for administering both components of the APPLIED Examination for initial certification in anesthesiology.

Abstract BackgroundOsteoarthritis (OA) is a common shoulder disorder that impacts shoulder functions. Shoulder arthroplasty is often required to restore function and quality of life. Reverse total shoulder arthroplasty (RSA), which was originally designed mainly for irreparable rotator cuff damage, has gained popularity in recent years for the treatment of advanced shoulder OA instead of the clinically standard total shoulder arthroplasty (TSA). However, this RSA has some nonnegligible flaws such as higher complications rate and economic cost, not mention the following problems caused by irreversible physical structural damage. Therefore, the employment of RSA needs to be carefully considered.PurposeThis study aimed to compare TSA and RSA in OA patients with or without rotator cuff damage to better guide clinical decision making. We believe the radical use of RSA in patients without rotator cuff deficiency may cause more harm than good.Study designCross-sectional studyMethodsWe queried the Nationwide Inpatient Sample (NIS) database from 2011 to 2014 to collect information on OA patients who received TSA and RSA. Patients were divided into 2 groups of comparison according to the presence of rotator cuff deficiency and matched with propensity score analysis.Results A total of 57,156 shoulder arthroplasties were identified. RSA patients in the rotator cuff deficiency group had significant higher transfusion rates and longer hospital stays. RSA patients without rotator cuff deficiency had a statistically significantly higher number of implant-related mechanical complications, acute upper respiratory infections and postoperative pain. Overall, RSA incurred higher costs in both groups.ConclusionFor OA patients with rotator cuff deficiencies, RSA has its benefits as complication rates were comparable to TSA. For those patients without rotator cuff deficiencies, the use of RSA should be reconsidered as there were more complications with higher severity.

BACKGROUND: A temporary decrease in anesthesiology residency graduates that occurred around the turn of the millennium may have workforce implications. The aims of this study are to describe, between 2005 and 2015, (1) demographic changes in the workforce of physicians trained as anesthesiologists; (2) national and state densities of these physicians, as well as temporal changes in the densities; and (3) retention of medical licenses by mid- and later-career anesthesiologists. METHODS: Using records from the American Board of Anesthesiology and state medical and osteopathic boards, the numbers of licensed physicians aged 30–59 years who had completed Accreditation Council for Graduate Medical Education–accredited anesthesiology residency training were calculated cross-sectionally for 2005, 2010, and 2015. Demographic trends were then described. Census data were used to calculate national and state densities of licensed physicians. Individual longitudinal data were used to describe retention of medical licenses among older physicians. RESULTS: The number of licensed physicians trained as anesthesiologists aged 30–59 years increased from 32,644 in 2005 to 36,543 in 2010 and 36,624 in 2015, representing a national density of 1.10, 1.18, and 1.14 per 10,000 population in those years, respectively. The density of anesthesiologists among states ranged from 0.37 to 3.10 per 10,000 population. The age distribution differed across the years. For example, anesthesiologists aged 40–49 years predominated in 2005 (47%), but by 2015, only 31% of anesthesiologists were aged 40–49 years. The proportion of female anesthesiologists grew from 22% in 2005, to 24% in 2010, and to 28% in 2015, particularly among early-career anesthesiologists. For anesthesiologists with licenses in 2005, the number who still had active licenses in 2015 decreased by 9.6% for those aged 45–49 years, by 14.1% for those aged 50–54 years, and by 19.7% for those aged 55–59 years. CONCLUSIONS: The temporary decrease in anesthesiology residency graduates around the turn of the 21st century decreased the proportion of anesthesiologists who were midcareer as of 2015. This may affect the future availability of senior leaders as well as the future overall workforce in the specialty as older anesthesiologists retire. National efforts to plan for workforce needs should recognize the geographical variability in the distribution of anesthesiologists.

Abstract The tumor-suppressor protein RB acts as a transcription repressor via interaction of its pocket domain with an LXCXE motif in histone deacetylase (HDAC) proteins such as HDAC1. Here, we demonstrate that HDAC5 deficient for the LXCXE motif interacts with both RB-N (via an FXXXV motif) and RB-C segments, and such interactions are diminished by phosphorylation of RB serine-249/threonine-252 and threonine-821. HDAC5 was frequently downregulated or deleted in human cancers such as prostate cancer. Loss of HDAC5 increased histone H3 lysine 27 acetylation (H3K27-ac) and circumvented RB-mediated repression of cell-cycle–related pro-oncogenic genes. HDAC5 loss also conferred resistance to CDK4/6 inhibitors such as palbociclib in prostate and breast cancer cells in vitro and prostate tumors in vivo, but this effect was overcome by the BET-CBP/p300 dual inhibitor NEO2734. Our findings reveal an unknown role of HDAC5 in RB-mediated histone deacetylation and gene repression and define a new mechanism modulating CDK4/6 inhibitor therapeutic sensitivity in cancer cells. Significance: This study defines a previously uncharacterized role of HDAC5 in tumor suppression and provides a viable strategy to overcome CDK4/6 inhibitor resistance in HDAC5-deficent cancer.

Abstract BackgroundAcute respiratory failure associated with sepsis contributes to higher in-hospital mortality. Intubation and invasive mechanical ventilation is a common rescue procedure. However, the 2016 International Guidelines for Management of Sepsis and Septic Shock does not provide any recommendation on indication nor timing of intubation. Timely intubation may improve outcome. The decision to intubate those patients is often hampered by the fear of further hemodynamic deterioration following intubation. MethodsThis study aimed at evaluating the impact of timely intubation on outcome in sepsis associated respiratory failure. We conducted an ancillary analysis of a prospective registry od adult ICU patients with septic shock admitted to the medical ICU in a tertiary medical center, between April 30th, 2014 and December 31st, 2017. All cases of sepsis with lactate >4 mmol/L, mean arterial pressure <65 mmHg, or vasopressor use after 30 mL/kg fluid boluses and suspected or confirmed infection. Patients who remained hospitalized at 24 hours following sepsis onset were separated into intubated and non-intubated groups. The primary outcome was hospital mortality. Univariate and multivariable analyses were used, adjusted for admission characteristics and stabilization of shock within 6 hours. In a secondary analysis, time-dependent propensity score matching was used to match intubated and non-intubated patients.ResultsWe identified 345 (33%) patients intubated within 24 hours and 707 (67%) not intubated. Intubated patients were younger, transferred more often from an outside facility, had higher severity of illness scores, more lung infection, achieved blood pressure goals more often but less often lactate normalization within 6 hours. The crude in-hospital mortality was higher, 89 (26%) vs. 82 (12%), p<0.001, as were ICU mortality, and ICU and hospital length of stay. After adjustment, intubation showed no effect on hospital mortality but fewer hospital-free days through day 28. After 1:1 propensity score matching, there was no difference in hospital mortality, but fewer hospital-free days in the intubated group. ConclusionsIntubation within 24 hours of sepsis onset was safe and not associated with hospital mortality, but was associated with less 28-day hospital-free days. Intubation should not be discouraged in appropriate patients with septic shock.