Outcomes in Subfascial versus Subglandular Planes in Breast Augmentation: A Systematic Review and Meta-Analysis.

Breast augmentation is the most commonly performed aesthetic surgery procedure in women worldwide. The use of the subfascial plane has been suggested to decrease the incidence of capsular contracture compared to the subglandular plane, while simultaneously avoiding the complication of animation deformity in the subpectoral plane. The aim of this systematic review and meta-analysis was to compare the adverse outcomes of subfascial compared to subglandular planes in breast augmentation. This review was registered a priori on OSF (https://osf.io/pm92e/). A search from inception to June 2023 was performed on Medline, Embase, and CENTRAL. A hand search was also performed. All randomized and comparative cohort studies were included that assessed the use of the subfascial plane for breast augmentation. Outcomes evaluated included the incidences of seroma, hematoma, infection, rippling, capsular contracture, and revision surgery. Ten studies were included in this systematic review. Three randomized controlled trials and seven comparative cohort studies were used for quantitative synthesis. There was a significant difference favoring subfascial compared to subglandular planes in the incidence of hematoma, rippling, and capsular contracture. All included studies had high risk of bias. The current evidence suggests that the subfascial plane for breast augmentation decreases risk of capsular contracture, hematoma, and rippling compared to the subglandular plane. Further randomized evidence with high methodological rigor is still required to validate these findings.

Hemodynamic Deterioration of Trauma Patients Undergoing Interhospital Transfer.

INTRODUCTION: Organized trauma systems reduce morbidity and mortality after serious injury. Rapid transport to high-level trauma centers is ideal, but not always feasible. Thus, interhospital transfers are an important component of trauma systems. However, transferring a seriously injured patient carries the risk of worsening condition before reaching definitive care. In this study, we evaluated characteristics and outcomes of patients whose hemodynamic status worsened during the transfer process. METHODS: We conducted a retrospective cohort study using data from the Pennsylvania Trauma Outcomes Study database from 2011 to 2018. Patients were included if they had a heart rate ≤ 100 and systolic blood pressure ≥ 100 at presentation to the referring hospital and were transferred within 24 h. We defined hemodynamic deterioration (HDD) as admitting heart rate > 100 or systolic blood pressure < 100 at the receiving center. We compared demographics, mechanism of injury, injury severity, management, and outcomes between patients with and without HDD using descriptive statistics and multivariable regression analysis. RESULTS: Of 52,919 included patients, 5331 (10.1%) had HDD. HDD patients were more often moderately-severely injured (injury severity score 9-15; 40.4% versus 39.4%, P < 0.001) and injured via motor vehicle collision (23.2% versus 16.6%, P < 0.001) or gunshot wound (2.1% versus 1.3%, P < 0.001). HDD patients more often had extremity or torso injuries and after transfer were more likely to be transferred to the intensive care unit (35% versus 28.5%, P < 0.001), go directly to surgery (8.4% versus 5.9%, P < 0.001), or interventional radiology (0.8% versus 0.3%, P < 0.001). Overall mortality in the HDD group was 4.9% versus 2.1% in the group who remained stable. These results were confirmed using multivariable analysis. CONCLUSIONS: Interhospital transfers are essential in trauma, but one in 10 transferred patients deteriorated hemodynamically in that process. This high-risk component of the trauma system requires close attention to the important aspects of transfer such as patient selection, pretransfer management/stabilization, and communication between facilities.

The cost of human papillomavirus vaccination delivery at the administrative and health facility levels in the Philippines.

Background: The World Health Organization has recommended the inclusion of human papillomavirus (HPV) vaccines in national immunization programs to address the global problem of cervical cancer. In the Philippines, HPV vaccination was introduced in a phased approach in 2015. This study seeks to estimate the cost of delivery of the HPV vaccination program and its operational context in the Philippines. Methods: This was a retrospective, cross-sectional micro-costing study focused on ongoing HPV vaccination delivery and its operational context across all levels of the health system. Using structured questionnaires and data collection from secondary sources, the weighted mean financial and economic costs and costs per dose at the national, subnational, and health facility levels were estimated. Results: The weighted mean financial and economic costs per dose of the HPV vaccination program aggregated across all levels of the health system were $US3.72and $29.74, respectively. Activities contributing most significantly to costs were service delivery and vaccine collection or distribution and storage at the health facility and administrative levels, respectively. The opportunity costs for health worker and non-health worker time accounted for 77% of the economic cost per dose. Conclusion: The total weighted mean financial and economic costs of HPV delivery are within range of those reported in other countries. Costing studies can help identify cost drivers with local operational context to help inform policymakers and program managers in budgeting and planning interventions to improve program implementation.

Uniform Li Deposition through the Graphene-Based Ion-Flux Regulator for High-Rate Li Metal Batteries.

Lithium (Li) metal is considered an ultimate anode owing to its high specific capacity and energy density. However, uncontrolled Li dendrite growth and low Coulombic efficiency have limited the application of Li metal. Among various strategies introduced to address these limitations, the surface modification of polyolefin separators with functional materials has been widely adopted for improving the mechanical and thermal stabilities of polymer separators and to protect the separator from the penetration of Li dendrites. Herein, we report a new functional polymer separator that is surface-altered with a graphene-based Li-ion flux regulator (GLR) to homogenize the Li-ion flux and suppress the growth of sharp dendritic Li in Li metal batteries. The nanopores distributed through the GLR structure serve as channels for ion transport and junctions for electron transfer, facilitating efficient electrolyte penetration and rapid charge transfer between graphene (Gr) sheets. Owing to these favorable features of porous GLR, a Li-Cu cell with the GLR surface-altered polypropylene separator (GLR-PP) delivers excellent cycle and rate performances compared to a Li-Cu cell with a Gr surface-altered polypropylene separator. In addition, among the tested cells, Li-sulfur cells with GLR-PP exhibit the most stable cycle performance over 500 cycles. These results demonstrate that the concept of tailoring the surface of a polymer separator with porous 2D materials is an effective strategy for improving the long-term cycle stability and electrochemical kinetics of Li metal-based batteries and would trigger further relevant studies.

Photocoagulation Up to Ora Serrata in Diabetic Vitrectomy to Prevent Recurrent Vitreous Hemorrhage.

PURPOSE: To evaluate the role of performing photocoagulation up to ora serrata during vitrectomy in preventing recurrent vitreous hemorrhage (VH) in patients undergoing pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). METHODS: This retrospective, nonrandomized study included 60 eyes from 60 patients who had undergone PPV for VH due to PDR. These patients were divided into two groups: group 1, those who underwent photocoagulation up to ora serrata using the scleral indentation technique during surgery; and group 2, those who did not undergo scleral indentation when photocoagulation and underwent photocoagulation up to vortex veins. Their hospital records were analyzed to investigate the recurrence rate of VH, the time until recurrence of VH after surgery, logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) measured before surgery and at 1, 2, and 3 years after surgery, and the occurrence of complications such as neovascular glaucoma (NVG) during follow-up. RESULTS: Group 1 exhibited lower recurrence rate of VH (2 of 30 [6.7%] vs. 10 of 30 [33.3%], p = 0.01) and lower occurrence of postoperative NVG (2 of 30 [6.7%] vs. 8 of 30 [26.7%], p = 0.038) compared with group 2. There were no statistically significant differences in logMAR BCVA measured at 1, 2, and 3 years between the two groups (at 1 year: 0.54 ± 0.43 vs. 0.54 ± 0.44, p = 0.954; at 2 years: 0.48 ± 0.47 vs. 0.55 ± 0.64, p = 0.235; at 3 years: 0.51 ± 0.50 vs. 0.61 ± 0.77, p = 0.200). Logistic regression analysis showed that among several factors that could affect recurrence rate of VH, only range of photocoagulation performed was a statistically significant factor (odds ratio, 0.119; 95% confidence interval, 0.022-0.659; p = 0.015). CONCLUSIONS: Photocoagulation treatment over a wider range with scleral indentation could be a beneficial adjunct procedure for preventing postoperative recurrent VH following diabetic vitrectomy.

A Systematic Review and Meta-Analysis of Injection Site Reactions in Randomized-Controlled Trials of Biologic Injections.

BACKGROUND: Biologic agents are emerging as an important treatment option for immune-mediated diseases. Injection site reactions following subcutaneous injection of biologic agents is not well described in the literature. OBJECTIVE: To summarize injection site reaction data in phase 3 trials of all biologic agents. METHODS: MEDLINE, Embase, and CENTRAL databases were systematically searched on February 8, 2022. Proportional meta-analysis was conducted to summarize injection site reaction prevalence for each biologic. RESULTS: There were 158 articles included in the review. The most common types of injection site reactions were erythema (42.8%), unspecified reaction (23.3%), pain (12.4%), and pruritus (5.7%). No patients discontinued their treatment due to injection site reactions in 39 of the 48 studies that reported on discontinuation data. There were 16 biologics included in meta-analysis across 80 eligible studies. The biologics with the highest point prevalence of patients reporting injection site reactions were Canakinumab (15.5%; 294 patients), Dupilumab (11.4%; 1888 patients), Etanercept (11.4%; 4363 patients), and Ixekizumab (11.2%; 2205 patients). The biologics with the lowest point prevalence of injection site reactions were Risankizumab (0.8%; 707 patients), Brodalumab (1.3%; 1365 patients), Guselkumab (1.3%; 1852 patients), Secukinumab (1.9%; 1277 patients). CONCLUSIONS: The prevalence of injection site reaction in response to biologics ranges from 0.08 to 15.5%. Canakinumab, Dupilumab, Etanercept, and Ixekizumab had the highest prevalence of injection site reactions. Risankizumab, Brodalumab, Guselkumab, and Secukinumab had the lowest prevalence of injection site reactions. Recommendations are made regarding the improvement of adverse event reporting to better understand the epidemiology of injection site reactions.

The appropriateness and quality of patient-reported outcome measures (PROMs) in plastic surgery randomized controlled trials: A systematic review.

BACKGROUND: Patient-reported outcome measures (PROMs) quantify patient perspectives to measure outcomes that matter to patients. The aim of this study was to assess the reporting of appropriateness and quality of PROM selection in plastic surgery randomized controlled trials (RCTs). METHODS: MEDLINE, Embase, and CENTRAL were searched from January 1, 2000, to June 5, 2022, to identify published RCTs within the plastic surgery literature. Included studies were categorized as follows: 1) a clearly defined patient-reported primary outcome; 2) a primary outcome could be inferred; or 3) no clear or implied primary outcome. The Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) database was consulted to assess the available literature on the PROMs. RESULTS: There were 130 plastic surgery RCTs identified. Of the 43 studies with a clear or inferred primary outcome, the percentage of studies that commented with supporting references on the PROM's appropriateness for the population, disease/condition, and outcome were 20.9% (n = 9/43), 18.6% (n = 8/43), and 27.9% (n = 12/43), respectively. The percentage of studies that commented on the PROM's validity, reliability, and responsiveness with supporting references were 34.9% (n = 15/43), 14.0% (n = 6/43), and 11.7% (n = 5/43), respectively. There were 21 unique PROMs identified; 28.6% (n = 6/21) were available in the COSMIN database. CONCLUSION: The majority of plastic surgery RCTs assessing patient-reported primary outcomes lack transparency surrounding PROM selection and quality. We recommend investigators conducting plastic surgery clinical research report explicitly why they used a particular PROM and support its appropriateness and psychometric properties with supporting references. Finally, they should familiarize themselves with the COSMIN initiative.

"Spin" in Observational Studies in Deep Inferior Epigastric Perforator Flap Breast Reconstruction: A Systematic Review.

The deep inferior epigastric artery perforator (DIEP) flap is widely used in autologous breast reconstruction. However, the technique relies heavily on nonrandomized observational research, which has been found to have high risk of bias. "Spin" can be used to inappropriately present study findings to exaggerate benefits or minimize harms. The primary objective was to assess the prevalence of spin in nonrandomized observational studies on DIEP reconstruction. The secondary objectives were to determine the prevalence of each spin category and strategy. Methods: MEDLINE and Embase databases were searched from January 1, 2015, to November 15, 2022. Spin was assessed in abstracts and full-texts of included studies according to criteria proposed by Lazarus et al. Results: There were 77 studies included for review. The overall prevalence of spin was 87.0%. Studies used a median of two spin strategies (interquartile range: 1-3). The most common strategies identified were causal language or claims (n = 41/77, 53.2%), inadequate extrapolation to larger population, intervention, or outcome (n = 27/77, 35.1%), inadequate implication for clinical practice (n = 25/77, 32.5%), use of linguistic spin (n = 22/77, 28.6%), and no consideration of the limitations (n = 21/77, 27.3%). There were no significant associations between selected study characteristics and the presence of spin. Conclusions: The prevalence of spin is high in nonrandomized observational studies on DIEP reconstruction. Causal language or claims are the most common strategy. Investigators, reviewers, and readers should familiarize themselves with spin strategies to avoid misinterpretation of research in DIEP reconstruction.

Best Practices for FACE-Q Aesthetics Research: A Systematic Review of Study Methodology.

BACKGROUND: The FACE-Q Aesthetics module is a validated patient-reported outcome measure (PROM) that evaluates perspectives on facial aesthetic treatments. Improper administration and poor study methodology can compromise the validity and interpretation of this PROM. OBJECTIVES: This systematic review sought to evaluate the administration and scoring of the FACE-Q Aesthetics scales within the literature. METHODS: A search of Ovid Medline, Embase, Cochrane, and Web of Science was performed on December 20, 2022, with the assistance of a health-research librarian (CRD42022383676). Studies that examined facial aesthetic interventions using the FACE-Q Aesthetics module as a primary or secondary outcome measure were included for analysis. RESULTS: There were 114 studies included. The Face Overall (n = 52, 45.6%), Psychological (n = 45, 39.4%), and Social (n = 43, 37.7%) scales were most frequently reported. Errors in FACE-Q administration were identified in 30 (26.3%) studies. The most common error was the presentation of raw ordinal scores rather than the converted Q score (n = 23). Most studies reported a time horizon for their primary analysis (n = 76, 66.7%); however, only 4 studies provided a rationale for this selection. Sample size calculations for the primary outcome were rarely performed (n = 9, 7.9%). CONCLUSIONS: There continues to be limitations in PROM administration and the quality of articles that report FACE-Q Aesthetic scale data. The authors suggest that future investigators using the FACE-Q refer to the User's Guide regarding administration and scoring of this scale, report a rationale for the study time horizon, and provide an a priori sample size calculation for the primary outcome of interest.

Characteristics and Outcomes of Squamous Cell Carcinoma and Other Cutaneous Malignancies in Epidermolysis Bullosa: A Systematic Review.

OBJECTIVE: To identify cases and summarize outcomes of cutaneous malignancies in patients with epidermolysis bullosa (EB). DATA SOURCES: MEDLINE and EMBASE databases were searched on February 8, 2022. STUDY SELECTION: Original observational or experimental studies with cases of cutaneous malignancy in patients with inherited EB were included. DATA EXTRACTION: Data were extracted by two reviewers in duplicate. DATA SYNTHESIS: A total of 87 articles with 367 patients were included in this systematic review. Squamous cell carcinomas were the most common malignancy (94.3%) with a median survival of 60 months. The presence of metastasis was investigated at diagnosis in 77 patients; 18.8% of patients had detectable metastasis. Patients with squamous cell carcinoma with metastasis at diagnosis had significantly shorter median survival (16.8 months) than those without (72 months; P = .027). The remission rate was 47.6%. At the end of follow-up, 15.1% were alive with disease, and 41.6% were deceased. Other malignancies included malignant melanoma and basal cell carcinoma. The most common initial modes of management were excisions (71.9%) and amputations (17.6%). Other modes included chemotherapy (4.6%), radiation (3.9%), and no treatment (2.6%). The overall rate of recurrence or new lesions was 38.8%, with a median time of 16 months to recurrence or new lesions. Immediate recurrence was lowest following amputation (4.3%). There were no statistically significant differences in median survival among initial excision, amputation, and all other modes combined ( P = .30). CONCLUSIONS: Squamous cell carcinomas in patients with EB have a high likelihood of metastasis and mortality. Surgical excision is the most common intervention. There are no significant differences in survival among different initial management options. There is a need for research that documents and monitors outcomes of the treatment options.

Learning curve for endoscopic posterior cervical foraminotomy.

PURPOSE: While anterior cervical discectomy and fusion as well as cervical disk arthroplasty are gold standard treatments for the surgical treatment of cervical radiculopathy, posterior endoscopic cervical foraminotomy (PECF) as a substitute procedure is gaining popularity. To date, studies investigating the number of surgeries needed to achieve proficiency in this procedure are lacking. The purpose of the study is to examine the learning curve for PECF. METHODS: The learning curve in operative time for two fellowship-trained spine surgeons at independent institutions was retrospectively assessed for 90 uniportal PECF procedures (PBD: n = 26, CPH: n = 64) performed from 2015 to 2022. Operative time was assessed across consecutive cases using a nonparametric monotone regression, and a plateau in operative time was used as a proxy to define the learning curve. Secondary outcomes assessing achievement of endoscopic prowess before and after the initial learning curve included number of fluoroscopy images, visual analog scale (VAS) for neck and arm, Neck Disability Index (NDI), and the need for reoperation. RESULTS: There was no significant difference in operative time between surgeons (p = 0.420). The start of a plateau for Surgeon 1 occurred at 9 cases and 111.6 min. The start of a plateau for Surgeon 2 occurred at 29 cases and 114.7 min. A second plateau for Surgeon 2 occurred at 49 cases and 91.8 min. Fluoroscopy use did not significantly change before and after surmounting the learning curve. The majority of patients achieved minimally clinically important differences in VAS and NDI after PECF, but postoperative VAS and NDI did not significantly differ before and after achieving the learning curve. There were no significant differences in revisions or postoperative cervical injections before and after reaching a steady state in the learning curve. CONCLUSION: PECF is an advanced endoscopic technique with an initial improvement in operative time that occurred after as few as 8 cases to as many as 28 cases in this series. A second learning curve may occur with additional cases. Patient-reported outcomes improve following surgery, and these outcomes are independent of the surgeon's position on the learning curve. Fluoroscopy use does not change significantly along the learning curve. PECF is a safe and effective technique that current and future spine surgeons should consider as part of their armamentarium.

A comparison of skin grafts versus local flaps for facial skin cancer from the patient perspective: protocol for a feasibility study.

BRIEF ABSTRACT: This is a protocol to assess feasibility of conducting a prospective cohort study comparing local flaps versus skin grafts for surgical excision of skin cancer from the face. INTRODUCTION: Skin cancer is the most common malignancy worldwide and the face is one of the most common locations of occurrence. Surgical excision is the most popular treatment for small lesions of the face. Defects can be reconstructed using local flaps or skin grafts. There is a paucity of literature evaluating outcomes after skin cancer surgery from the patient's perspective using valid measurement tools. The purpose of this study is to assess the feasibility of conducting a prospective observational cohort study. The primary outcomes include recruitment rates, eligibility rate, compliance of intervention and rate of completion of the primary outcome (FACE-Q scales) at 3 months. Secondary outcomes include examining patient characteristic and FACE-Q score differences between local flaps to skin grafts and adverse events. METHODS AND ANALYSIS: This study is a prospective cohort study consisting of an anticipated 30 patients aged ≥18 years. The study population will consist of a consecutive sample of non-melanoma facial skin cancer patients undergoing a skin graft or local flap. Patients will be followed and evaluated with the FACE-Q questionnaire at 2 weeks, 3 months, 6 months and 1 year post-operation. The following criteria will determine success: patients who meet eligibility criteria >70%; recruitment rate >70%; compliance with intervention >90%; rate of completion of full-scale prospective study primary outcome (FACE-Q at 3 months) >80%; retention rate at 6-month follow-up visit >70%. DISCUSSION: The findings of this study will be used to guide the sample size calculation for a future, large-scale prospective study.Trial registration: ClinicalTrials.gov (NCT04842279).

Inhibition of mitochondrial translocase SLC25A5 and histone deacetylation is an effective combination therapy in neuroblastoma.

The mitochondrion is a gatekeeper of apoptotic processes, and mediates drug resistance to several chemotherapy agents used to treat cancer. Neuroblastoma is a common solid cancer in young children with poor clinical outcomes following conventional chemotherapy. We sought druggable mitochondrial protein targets in neuroblastoma cells. Among mitochondria-associated gene targets, we found that high expression of the mitochondrial adenine nucleotide translocase 2 (SLC25A5/ANT2), was a strong predictor of poor neuroblastoma patient prognosis and contributed to a more malignant phenotype in pre-clinical models. Inhibiting this transporter with PENAO reduced cell viability in a panel of neuroblastoma cell lines in a TP53-status-dependant manner. We identified the histone deacetylase inhibitor, suberanilohydroxamic acid (SAHA), as the most effective drug in clinical use against mutant TP53 neuroblastoma cells. SAHA and PENAO synergistically reduced cell viability, and induced apoptosis, in neuroblastoma cells independent of TP53-status. The SAHA and PENAO drug combination significantly delayed tumour progression in pre-clinical neuroblastoma mouse models, suggesting that these clinically advanced inhibitors may be effective in treating the disease.

Incidence of melanoma and non-melanoma skin cancer in patients with celiac disease: a systematic review and meta-analysis.

There is conflicting observational evidence regarding the association between skin cancer and celiac disease (CD). The purpose of this review was to investigate the incidence rate ratio (IRR) of skin cancer incidence between patients with and without CD. MEDLINE and EMBASE databases were searched on October 27th, 2021 and eight articles were identified for review. Quality assessment was conducted using the Newcastle Ottawa Scale. Seven articles were included in meta-analysis for a pooled estimate of IRR across all skin cancers, malignant melanoma (MM), and non-melanoma skin cancers (NMSC). In total, 74,860 CD patients were followed for 710,214 person-years in the meta-analysis. Overall combined incidence was 99.8 cases per 100,000 person-years. Meta-analysis of all skin cancer incidence showed no significant difference in CD patients compared to controls (IRR: 1.06; 95% CI: 0.95, 1.17; p=0.29; I2: 0%). Five studies reported on MM incidence; there was no significant difference in incidence compared to controls (IRR: 0.87, 95% CI: 0.72, 1.06; p=0.22; I2: 9%). Five studies reported on NMSC incidence, revealing a significantly increased risk of NMSC in CD patients (IRR: 1.14; 95% CI: 1.01, 1.28; p=0.04; I2: 0%). Our findings suggest a significantly increased incidence of NMSC in CD patients compared to control data and no significant association between CD and MM incidence. The findings are limited by the quantity and quality of the evidence. Nonetheless, clinicians should emphasize the importance of sun protection, such as sunscreen usage and self-examination for patients with CD.

Efficient derivation of chimeric-antigen receptor-modified TSCM cells.

Chimeric-antigen receptor (CAR) T-cell immunotherapy employs autologous-T cells modified with an antigen-specific CAR. Current CAR-T manufacturing processes tend to yield products dominated by effector T cells and relatively small proportions of long-lived memory T cells. Those few cells are a so-called stem cell memory T (TSCM) subset, which express naïve T-cell markers and are capable of self-renewal and oligopotent differentiation into effector phenotypes. Increasing the proportion of this subset may lead to more effective therapies by improving CAR-T persistence; however, there is currently no standardized protocol for the effective generation of CAR-TSCM cells. Here we present a simplified protocol enabling efficient derivation of gene-modified TSCM cells: Stimulation of naïve CD8+ T cells with only soluble anti-CD3 antibody and culture with IL-7 and IL-15 was sufficient for derivation of CD8+ T cells harboring TSCM phenotypes and oligopotent capabilities. These in-vitro expanded TSCM cells were engineered with CARs targeting the HIV-1 envelope protein as well as the CD19 molecule and demonstrated effector activity both in vitro and in a xenograft mouse model. This simple protocol for the derivation of CAR-TSCM cells may facilitate improved adoptive immunotherapy.

A Compromised Airway in the Setting of Failed Extracorporeal Membrane Oxygenation Cannulation.

We report a case involving failed extracorporeal membrane oxygenation (ECMO) cannulation in the setting of critical airway stenosis secondary to a large anterior mediastinal mass. The most invasive management option, ECMO, was initially pursued solely to avoid manipulation of a critical airway in case of intubation failure or life-threatening airway bleeding. However, after unexpectedly failing cannulation in two separate cannulation sites with an impending respiratory collapse, awake fiberoptic or emergent rigid bronchoscopy was the remaining viable option. The patient was ultimately intubated via awake fiberoptic intubation even though this modality carried a high complication risk and potential mortality if failed. This case report illustrates both the potential role of ECMO within the airway management hierarchy and the persistent need for contingency planning should ECMO cannulation fail. With the recent enthusiasm for ECMO incorporation into difficult airway management, our report serves to highlight the very serious issue of cannulation failure. There is a limited amount of case reports describing ECMO failure in a critical airway, and little has been described about rescue methods when ECMO fails. Our goal is to remind readers that although ECMO can be an excellent rescue option for a critically ill patient, it cannot be viewed as a last line of therapy. If one is able to rapidly recognize impending ECMO cannulation failure and is prepared for cannulation failure, they can save invaluable time in a decompensating patient.

Biologic Use in Pediatric Patients With Hidradenitis Suppurativa: A Systematic Review.

BACKGROUND: There is currently at least 1 biologic (adalimumab) approved in North America for treatment of Hidradenitis Suppurativa in the pediatric population. However, no reviews or clinical trials have specifically analyzed the effectiveness and safety data of biologic use in this population. The objective of this systematic review is to identify and summarize the outcomes of biologic therapy in pediatric patients with HS. METHODS: MEDLINE and EMBASE databases were used to conduct the search on Sept 18, 2020. RESULTS: The 15 included studies consisted of 26 patients, with the mean age of 15 ± 2.3 years. Females accounted for 53.8% (n = 14/26) of cases. The mean duration of HS prior to biologic initiation was 3.5 ± 2.9 years, with the majority having Hurley Stage II. The 26 patients received 34 biologics in total: 85.3% treated with TNF alpha inhibitors (adalimumab n = 17, infliximab n = 10, etanercept n = 1, unspecified n = 1), 5.9% with IL-12/23 inhibitors (ustekinumab n = 2), 5.9% with IL-1 inhibitors (i.e., anakinra n = 2) and 2.9% received IL-23 inhibitors (i.e., guselkumab n = 1) biologics. Of the 26 patients, 23.1% (n = 6/26) experienced complete resolution (CR), 73.1% (n = 19/26) experienced partial resolution (PR), and 3.8% (n = 1/26) had no resolution outcomes reported. The time to resolution of HS lesions after biologic initiation ranged from 10 days to 11.5 months (mean: 5.1 months). No adverse events were reported in the studies. CONCLUSION: Although anti-TNF alpha were the most common biologics used for HS in pediatric cases, large-scale trials specific to pediatric patients with HS are needed to confirm these findings.

Stewart-Treves syndrome and other cutaneous malignancies in the context of chronic lymphedema: a systematic review.

INTRODUCTION: Angiosarcoma developing in chronically lymphedematous tissue, or Stewart-Treves syndrome (STS), is a rare and lethal complication of lymphedema. This systematic review summarizes characteristics and outcomes of STS and other cutaneous malignancies arising in chronic lymphedema. METHODS: MEDLINE and EMBASE databases were searched on February 19th, 2021, to identify 200 articles included in the analysis. RESULTS: Of 369 included patients, 89.7% (n = 331/369) had STS and 10.3% (n = 38/369) had other associated malignancies. Mean age of onset was 61.2 years, and 85.9% (n = 317/369) of cases were female. Common risk factors were previous cancer history (69.8%, n = 258/369) and radiation history (53.7%, n = 198/369). Lymphedema was most commonly attributed to surgical causes (68.3%, n = 252/369). STS begins on average 14.9 years after lymphedema with mortality of 53.9% (n = 178/331) and remission rate of 16.1% (n = 53/331). Other malignancies begin on average 23.7 years after lymphedema, with mortality of 10.5% (n = 4/38) and remission rate of 31.6% (n = 12/38). STS and other malignancies had 5-year survivals of 22.4% and 65.2%, respectively (P = 0.00145). For all patients, patients initially treated with excision had the best survival (median: 48 months, 5-year survival: 43.3%) and radiotherapy had the worst survival (median: 10 months, 5-year survival: 6.5%) (P = 0.0141). CONCLUSION: Malignancy can appear in lymphedematous tissue many years after lymphedema onset. STS has poorer prognosis compared to other malignancies. Further research should be conducted to better understand the causes, risk factors, and management of this phenomenon.

SIRT2 regulates mitochondrial dynamics and reprogramming via MEK1-ERK-DRP1 and AKT1-DRP1 axes.

During somatic reprogramming, cellular energy metabolism fundamentally switches from predominantly mitochondrial oxidative phosphorylation toward glycolysis. This metabolic reprogramming, also called the Warburg effect, is critical for the induction of pluripotency, but its molecular mechanisms remain poorly defined. Notably, SIRT2 is consistently downregulated during the reprogramming process and regulates glycolytic switch. Here, we report that downregulation of SIRT2 increases acetylation of mitogen-activated protein kinase (MAPK) kinase-1 (MEK1) at Lys175, resulting in activation of extracellular signal-regulated kinases (ERKs) and subsequent activation of the pro-fission factor dynamin-related protein 1 (DRP1). In parallel, downregulation of SIRT2 hyperacetylates the serine/threonine protein kinase AKT1 at Lys20 in a non-canonical way, activating DRP1 and metabolic reprogramming. Together, our study identified two axes, SIRT2-MEK1-ERK-DRP1 and SIRT2-AKT1-DRP1, that critically link mitochondrial dynamics and oxidative phosphorylation to the somatic reprogramming process. These upstream signals, together with SIRT2's role in glycolytic switching, may underlie the Warburg effect observed in human somatic cell reprogramming.