Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial.

BACKGROUND: The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practiced, but has been associated with harm in paediatric patients. We aimed to evaluate whether conservative oxygenation would reduce duration of organ support or incidence of death compared to standard care. METHODS: Oxy-PICU was a pragmatic, multicentre, open-label, randomised controlled trial in 15 UK paediatric intensive care units (PICUs). Children admitted as an emergency, who were older than 38 weeks corrected gestational age and younger than 16 years receiving invasive ventilation and supplemental oxygen were randomly allocated in a 1:1 ratio via a concealed, central, web-based randomisation system to conservative peripheral oxygen saturations ([SpO2] 88-92%) or liberal (SpO2 >94%) targets. The primary outcome was the duration of organ support at 30 days following random allocation, a rank-based endpoint with death either on or before day 30 as the worst outcome (a score equating to 31 days of organ support), with survivors assigned a score between 1 and 30 depending on the number of calendar days of organ support received. The primary effect estimate was the probabilistic index, a value greater than 0·5 indicating more than 50% probability that conservative oxygenation is superior to liberal oxygenation for a randomly selected patient. All participants in whom consent was available were included in the intention-to-treat analysis. The completed study was registered with the ISRCTN registry (ISRCTN92103439). FINDINGS: Between Sept 1, 2020, and May 15, 2022, 2040 children were randomly allocated to conservative or liberal oxygenation groups. Consent was available for 1872 (92%) of 2040 children. The conservative oxygenation group comprised 939 children (528 [57%] of 927 were female and 399 [43%] of 927 were male) and the liberal oxygenation group included 933 children (511 [56%] of 920 were female and 409 [45%] of 920 were male). Duration of organ support or death in the first 30 days was significantly lower in the conservative oxygenation group (probabilistic index 0·53, 95% CI 0·50-0·55; p=0·04 Wilcoxon rank-sum test, adjusted odds ratio 0·84 [95% CI 0·72-0·99]). Prespecified adverse events were reported in 24 (3%) of 939 patients in the conservative oxygenation group and 36 (4%) of 933 patients in the liberal oxygenation group. INTERPRETATION: Among invasively ventilated children who were admitted as an emergency to a PICU receiving supplemental oxygen, a conservative oxygenation target resulted in a small, but significant, greater probability of a better outcome in terms of duration of organ support at 30 days or death when compared with a liberal oxygenation target. Widespread adoption of a conservative oxygenation saturation target (SpO2 88-92%) could help improve outcomes and reduce costs for the sickest children admitted to PICUs. FUNDING: UK National Institute for Health and Care Research Health Technology Assessment Programme.

Data Requirement for Animal-Derived Wound Care Devices: Limitations of the 510(k) Regulatory Pathway.

BACKGROUND: Device classification and preclinical data requirements for animal-derived wound care products were recently reviewed by the FDA. Given the possible performance differences for these products, we evaluated the FDA data requirements as well as the published literature for all animal-derived wound care products ever cleared through the FDA. STUDY DESIGN: The publicly available online database was queried for all animal-derived wound products; premarket data requirements for each product were recorded. A PubMed search was conducted to determine the number of published clinical studies for each product, and manufacturer websites were accessed to obtain the price for each product. RESULTS: A total of 132 animal-derived wound products have been cleared by the FDA since the Center for Devices and Radiological Health was established in 1976. Of these, 114 had a publicly available clearance statement online. Preclinical biocompatibility testing was performed in 85 products (74.6%) and referenced in 10 (8.8%). Preclinical animal wound healing testing took place in 17 (14.9%). Only 9 products (7.9%) had clinical safety testing, and no products had clinical effectiveness data. We found no published peer-reviewed clinical data for 97 products (73%). Cost was infrequently available but ranged from $4.79 to $2,178 per unit. CONCLUSIONS: Although the current pathway is appropriate for efficiently clearing new wound care products, clinical effectiveness is not included in the regulatory review process. Wound care products are primarily evaluated by the FDA for safety and biocompatibility. Thus, any claims of clinical effectiveness require independent validation, which is often lacking.

A brief report of aspiring medical student perceptions and behaviours concerning research experiences for selection into Canadian medical schools.

Background: Aspiring medical students behave based on their perception of what is valued in the selection process. While research experience is not explicitly considered in most Canadian admissions policies, it is commonly held as valuable within aspiring medical student communities. The purpose of this study is to describe the perceptions and behaviours of aspiring medical students with respect to gaining research experience in support of their medical school applications. Methods: We surveyed prospective applicants of Canadian medical schools between August 2021 and November 2021, then compiled descriptive statistics pertaining to their perceptions and behaviours. Results: Respondents affirmed the belief that research experience is valued in medical school admissions processes. They reported spending approximately 13 hours per week engaged in research, which usually did not yield publication or presentation recognition. Conclusion: Aspiring medical students invest substantial time and energy in research experiences to benefit their applications. There is room for medical schools to be more transparent about the value of research experience in their admissions processes.

Contexte: Le comportement des candidats aux études de médecine est déterminé par leur perception de ce qui est valorisé dans le processus de sélection. Tandis que la plupart des établissements canadiens ne mentionnent pas explicitement l'expérience en recherche comme prérequis d'admission, les futurs candidats, eux, voient une telle expérience comme un atout précieux. L'objectif de cette étude est de décrire les perceptions et les comportements des futurs étudiants en médecine par rapport à l'acquisition d'une expérience en recherche en appui à leur demande d'admission dans une école de médecine. Méthodes: Nous avons interrogé des postulants potentiels aux programmes de médecine au Canada entre août 2021 et novembre 2021, et nous avons compilé des statistiques descriptives relatives à leurs perceptions et à leurs comportements. Résultats: Les répondants ont affirmé croire que l'expérience en recherche est valorisée dans les processus d'admission aux facultés de médecine. Ils ont déclaré consacrer environ 13 heures par semaine à la recherche, qui, le plus souvent, n'a pas mené à des publications ou des présentations. Conclusion: Les futurs candidats aux études de médecine investissent beaucoup de temps et d'énergie dans des activités de recherche afin d'améliorer leur dossier de candidature. Les facultés de médecine devraient se prononcer de manière transparente sur l'importance attribuée à l'expérience en recherche dans le cadre de leur processus d'admission.

Training in Team-Based Practices: A Descriptive Analysis of Family Medicine Postgraduate Site Distribution across Canada.

Background: College of Family Physicians of Canada accreditation policies contemplate exemplary ratings for postgraduate family medicine programs that train residents in sites aligned with the Patient's Medical Home (PMH) vision. This may overrepresent the PMH in training relative to what is available in independent practice. Methods: We appraised training sites to describe the degree to which PMH features are present in family medicine education across the country. Results: More than half (70.7%) of Canadian training sites reflect PMH features. Conclusion: Education policy that incentivizes PMH in training may create downstream tension for physicians who find these practices unavailable upon graduation.

Assessing the Effect of Time from Injection of Collagenase to Manipulation on Success Rates in Dupuytren Disease.

PURPOSE: Dupuytren disease can be managed with an injection of collagenase Clostridium histolyticum enzyme followed by manual manipulation. Although the recommended time from injection to manipulation is 24-72 hours, patient and physician schedules may not accommodate this time frame. Therefore, we sought to study the impact of time from injection to manipulation on outcomes and complications of collagenase injection. METHODS: We performed a review of 309 patients who underwent an injection of collagenase Clostridium histolyticum for Dupuytren disease with manipulation at two, five, or seven days after injection. We compared preinjection and postinjection contracture angles as well as frequency of skin tears and tendon ruptures. RESULTS: Of the 309 patients, 207 underwent manipulation at two days, 32 at five days, and 70 at seven days. Patients had similar preinjection contracture angles. All patients demonstrated improvement in contracture after manipulation. Rates of skin tears and tendon ruptures were similar in all three groups. Significant predictors of complications included number of cords injected and history of previous collagenase injection, but not history of previous Dupuytren diagnosis. CONCLUSIONS: Although collagenase injection for Dupuytren disease is typically performed with plans for manipulation at 24-72 hours, postinjection manipulation could be performed as late as seven days without adversely affecting the frequency of skin and tendon complications. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

The Versatile Role of Fat Injection During Various Genioplasties.

BACKGROUND: Fat injection has become increasingly popular in aesthetic surgery, but there is a sparsity of literature regarding its role during genioplasty. In this study, we present the largest series of patients receiving fat injections to the chin for various indications. METHODS: Data were collected from January 2016 to December 2021 for patients who underwent chin fat injection for a variety of chin refinements. Patients with chin fat injection were divided into isolated genioplasty with fat injection (CF), combined facial and chin fat injection (CFC) and combined chin fat injection and osseous genioplasty (CFG). Complication rates and reoperations were compared using Fischer's exact test between each cohort. RESULTS: 181 patients were included in final analysis, with 14 patients in CF cohort, 130 patients in CFC cohort, 24 patients in CFG cohort, and 13 patients who underwent genioplasty alone. Repeat fat injections were required in 17 (9.4%) patients overall, which included 14 patients (10.8%) of CFC subcohort and three patients (12.5%) of CFG subcohort (p > 0.05). No patients who underwent genioplasty alone or CF required reoperation. There were no significant differences in complications between genioplasty alone group (0%) in comparison to CF (7.1%; p = 1.00), CFC (6.2%; p = .53), or CFG cohorts (7.7%; p = 1.00). CONCLUSION: Fat injection can safely correct minor chin deficiency or asymmetry, as either an isolated procedure or in combination with osteotomies. Additionally, fat injection enables advancement of the caudal segment to achieve superior outcomes by preventing unaesthetic deepening of labiomental groove which will not be advanced during sliding osteotomy. LEVEL OF EVIDENCE IV: 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 the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Logical Sequence of Primary Open Rhinoplasty Founded on the Principles of Rhinoplasty Dynamics.

Rhinoplasty is a perplexing procedure due to the variety of complex interplays between anatomical structures of the nose and the maneuvers used to accomplish the intended objective. Although every rhinoplasty is individualized, having a systematic order and an algorithm is crucial to achieve the designed aesthetic goals and a superior outcome, considering the interactions between maneuvers. Otherwise, the accumulated, unanticipated effects will result in displeasing outcomes due to over or under correction. In this report, we describe the sequential steps of rhinoplasty based on knowledge that the senior author has garnered over four decades of experience and having studied the rhinoplasty dynamics continually. Furthermore, we explain the detailed reasoning for each maneuver based on surgical indications and the resulting interplays.Level of Evidence IV 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 the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

Common Dorsal Flaws Following Preservation Rhinoplasty: A Systemic Analysis.

BACKGROUND: There has recently been a resurgence of interest in preservation rhinoplasty (PR) for dorsal hump elimination or dorsal projection reduction. However, no studies have scrutinized aesthetic outcomes to identify common pattern of flaws seen in published images to aid those with ardent enthusiasm for this technique to become aware of the frequency of these flaws and find ways to reduce imperfections. METHODS: A systematic literature review was performed using search terms ("preservation" OR "let down", "push down") AND "rhinoplasty" on PubMed, Cochrane, SCOPUS, and EMBASE databases for studies between January 2000 and December 2022. Patient images from these studies were analyzed by three reviewers (MWW, IAC, and BG) for dorsal flaws. Raw interrater agreement percentage and Krippendorff's alpha were calculated to determine interrater reliability. A descriptive and comparative analysis with Fisher's exact test was performed for the aggregate data. RESULTS: There were 59 patient images with 464 views from 24 studies included for final analysis. Optimal dorsal aesthetic lines (DAL) were noted in 12 patients (20.3%), while optimal profile was observed in 15 patients (25.4%) (p = 0.66). Combined ideal front and profile view of dorsum was not observed on any patients. The most common flaws were DAL irregularities (n = 45; 78.0%), dorsal deviation (n = 32, 54.2%), and residual hump (n = 25, 42.4%). There was excellent interrater agreement. CONCLUSIONS: While PR may have some advantages, it has shortcomings in outcomes, particularly dorsal irregularities, dorsal deviation, and residual humps. Awareness of these imperfections may compel those performing this procedure to modify their techniques and improve their results. 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 the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Exploring the Resurgence of the Preservation Rhinoplasty: A Systematic Literature Review.

INTRODUCTION: The underlying principles of preservation rhinoplasty (PR) center around maintaining the soft tissue envelope, dorsum, and alar cartilage through surgical manipulations and tip suture techniques. In particular, the let-down (LD) and push-down (PD) techniques have been described, although reports of indications and outcomes in the literature are sparse. METHODS: A systematic review of the literature was performed using search terms "preservation" OR "let down" OR "push down" AND "rhinoplasty" on PubMed, Cochrane, SCOPUS, and EMBASE databases. Patient demographic information, operative details, and surgical outcomes were recorded. Sub-cohorts for patients who underwent LD and PD techniques were analyzed utilizing Fischer's exact test for categorical variables and Student's t test for continuous variables. RESULTS: Overall, there were 5967 PR patients in 30 studies in the final analysis, with 307 patients in the PD cohort and 529 patients in the LD cohort. The Rhinoplasty Outcome Evaluation Questionnaire showed a significant increase of patient satisfaction after PR compared to before PR (62.13 vs 91.14; p < 0.001). There was a significantly lower rate of residual dorsal hump or recurrence of 1.3% (n = 4) in the PD when compared to 4.6% (n = 23) in LD cohorts (p = 0.02). The revision rate of PD (0%, n = 0) was also significantly lower than that of LD (5.0%, n = 25) (p < 0.001). CONCLUSION: Based on these published articles, it seems that preservation rhinoplasty is safe and efficacious procedure with improved dorsal aesthetic lines, reduced dorsal contour irregularities, and claimed excellent patient satisfaction. In particular, the PD technique has fewer reported complications and revisions than LD approach, although PD is often indicated in patients with smaller dorsal humps. 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 the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Nonpharmacologic Treatments for Chronic and Episodic Migraine: A Systematic Review and Meta-Analysis.

BACKGROUND: Minimally invasive techniques for treatment-resistant migraine have been developed on recent insights into the peripheral pathogenesis of migraines. Although there is a growing body of evidence supporting these techniques, no study has yet compared the effects of these treatments on headache frequency, severity, duration, and cost. METHODS: PubMed, Embase, and Cochrane Library databases were searched to identify randomized placebo-controlled trials that compared radiofrequency ablation, botulinum toxin type A (BT-A), nerve block, neurostimulation, or migraine surgery to placebo for preventive treatment. Data on changes from baseline to follow-up in headache frequency, severity, duration, and quality of life were analyzed. RESULTS: A total of 30 randomized controlled trials and 2680 patients were included. Compared with placebo, there was a significant decrease in headache frequency in patients with nerve block ( P = 0.04) and surgery ( P < 0.001). Headache severity decreased in all treatments. Duration of headaches was significantly reduced in the BT-A ( P < 0.001) and surgery cohorts ( P = 0.01). Quality of life improved significantly in patients with BT-A, nerve stimulator, and migraine surgery. Migraine surgery had the longest lasting effects (11.5 months) compared with nerve ablation (6 months), BT-A (3.2 months), and nerve block (11.9 days). CONCLUSIONS: Migraine surgery is a cost-effective, long-term treatment to reduce headache frequency, severity, and duration without significant risk of complication. BT-A reduces headache severity and duration, but it is short-lasting and associated with greater adverse events and lifetime cost. Although efficacious, radiofrequency ablation and implanted nerve stimulators have high risks of adverse events and explantation, whereas benefits of nerve blocks are short in duration.

Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association.

ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency, and an abnormal type II transferrin glycosylation pattern. Here, we present 11 new patients and clinical updates with biochemical characterization on one previously reported patient. We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma, and lysosomal abnormalities on hepatic histology. Three of our subjects received successful liver transplantation. We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring.

Elevated oxysterol and N-palmitoyl-O-phosphocholineserine levels in congenital disorders of glycosylation.

Congenital disorders of glycosylation (CDG) and Niemann-Pick type C (NPC) disease are inborn errors of metabolism that can both present with infantile-onset severe liver disease and other multisystemic manifestations. Plasma bile acid and N-palmitoyl-O-phosphocholineserine (PPCS) are screening biomarkers with proposed improved sensitivity and specificity for NPC. We report an infant with ATP6AP1-CDG who presented with cholestatic liver failure and elevated plasma oxysterols and bile acid, mimicking NPC clinically and biochemically. On further investigation, PPCS, but not the bile acid derivative N-(3ß,5α,6ß-trihydroxy-cholan-24-oyl) glycine (TCG), were elevated in plasma samples from individuals with ATP6AP1-, ALG1-, ALG8-, and PMM2-CDG. These findings highlight the importance of keeping CDG within the diagnostic differential when evaluating children with early onset severe liver disease and elevated bile acid or PPCS to prevent delayed diagnosis and treatment.

Frequency, Indications and Intraoperative Dynamics of Repositioning of the Lateral Crura of the Lower Lateral Cartilage: A 35-Year Experience.

BACKGROUND: Lower lateral cartilage repositioning (LLCR) is an effective technique that places the lateral crus in a newly created caudal pocket, and is utilized for a variety of indications including cephalic malposition, alar asymmetries and tip rotation/projection alteration. However, there is a relative sparsity in the literature regarding this procedure and the dynamic changes that it produces. In this study, we report our experience with LLCR in regard to its indications and related interplays. METHODS: Data from our institution were collected from the most recent 100 primary rhinoplasties, most recent 100 secondary rhinoplasties and all LLCRs performed. For each LLCR, patient demographics and concurrent surgical techniques were compiled. A descriptive analysis was performed for all cohorts, while Fischer's exact test was performed to compare the associations of categorical data for the respective sample sizes of the primary and secondary rhinoplasty cohorts. RESULTS: Overall, 127 patients underwent LLCR, with eleven (11%) LLCRs in the primary rhinoplasty cohort and twelve (12%) LLCRs in the secondary rhinoplasty cohort. The most common indication for LLCR was cephalic malposition, followed by over-projection and asymmetry of the lower lateral cartilages. Intraoperative observation of dynamic changes included invariable cephalic rotation of the tip, ability to precisely control the tip projection, drastic narrowing of the domal arch often minimizing the need for the transdomal suture, alar repositioning caudally, correction of alar retraction and more elegant tip definition. However, the external valve lost its strength on majority of LLCR patients, which required almost routine use of Gunter lateral crus strut. CONCLUSION: LLCR is a powerful and versatile tool that can be utilized in either primary or secondary rhinoplasty. Its transposition results in cephalic rotation of the tip, narrowing of the domal arch, caudal reposition of the alar rim and superior tip definition. LEVEL OF EVIDENCE IV: 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 the Table of Contents or the online Instructions to Authors   www.springer.com/00266.

Postsurgical Outcomes with Meshes for Two-stage Prosthetic Breast Reconstruction in 20,817 Patients.

Use of acellular dermal matrices (ADMs) for tissue expander breast reconstruction remains controversial with an uncertain safety and efficacy profile. This study analyzes the rates and factors for reoperation and postoperative infection in patients who underwent tissue expander breast reconstruction with and without ADM. Methods: Patients who underwent breast reconstruction with and without ADM were identified from the National Surgical Quality Improvement Program database utilizing CPT codes. Covariates included patient demographics, preoperative comorbidities, and operative characteristics, while outcomes of interest were postoperative infection and reoperation. Univariate and multivariate analyses were performed to identify predictors of adverse outcomes. Results: There were 8334 patients in the ADM cohort and 12,451 patients who underwent tissue expander breast reconstruction without ADM. There were significantly fewer reoperations in the non-ADM cohort (5.4%) compared to the ADM cohort (7.7%) (P < 0.0001), with infection and hematoma as the most common etiologies in both cohorts. Surgical infections were also more prevalent in the ADM cohort (4.7%) compared with the non-ADM cohort (3.6%) (P < 0.0001). Univariate and multivariate analysis of the tissue expander breast reconstruction cohort revealed race, obesity, hypertension, smoking status, albumin, and operative time as predictive for infection risk, while race, obesity, hypertension, smoking, albumin, operative time, and age were significant for reoperation. Conclusion: Our study of 20,817 patients revealed significantly higher risk of infection and reoperation in patients who underwent breast reconstruction utilizing ADM versus without ADM. Patients considering ADM for breast reconstruction should engage in discussion with their surgeon about complications, aesthetics, and cost.

Maxillary and Mandibular Healing After Facial Allotransplantation.

INTRODUCTION: Facial transplantation has emerged as a viable option in treating devastating facial injuries.Despite the high healing rate of Le Fort III and bilateral sagittal split osteotomies (BSSO) in nontransplant patients, few studies have reported assessment of maxillary and mandibular healing in face transplant patients compared with nontransplant patients. The aim of this study was to examine differences in bone healing in our patients. PATIENTS AND METHODS: A retrospective chart review was conducted of facial allotransplantation patients at the Cleveland Clinic from December 2008 to inception. Demographics such as age, date of birth, and sex were recorded. Additional variables included procedures, revisions, reoperations, medications, and bone stability and healing. Computed tomography (CT) images assessed the alignment of skeletal components, bony union quality, and stability of fixation. RESULTS: Three patients were included: 2 had Le Fort III segment transplantation, and 1 had transplantation of both a Le Fort III segment and mandibular BSSO. The Le Fort III segment in all patients exhibited mobility and fibrous union at the Le Fort III osteotomy on CT. In contrast, the BSSO healed uneventfully after transplantation and revision surgery, with bony union confirmed by both CT and histology of the fixation area between the donor and recipient mandible bilaterally. No patients with midfacial fibrous union required revision of the nonunion as they were clinically asymptomatic. CONCLUSION: Le Fort osteotomy demonstrates inferior healing in facial transplantation compared with the nontransplant population. In contrast, the successful healing in the mandible is likely owing to the high density of rich cancellous bone.

Dual Fluorescent Tracers for Surgical Guidance: Preventing Donor-site Lymphedema in Vascularized Lymph Node Transfer.

Introduction: Vascularized lymph node transfer (VLNT) restores physiological lymphatic function. Although effective, postoperative impairment of donor-site lymphatic function and iatrogenic lymphedema following lymph node transfer remains a pressing concern. Methods: Prospective analysis of VLNT patients undergoing dual fluorescent tracers-assisted harvest was performed at our institution from September 2013 to April 2022. Reverse lymphatic mapping of the lower extremity was performed with indocyanine green (ICG). Blue dye was utilized in both white light and near-infrared spectra for visualization of donor-site lymphatic structures. Demographics, intraoperative details, and surgical outcomes were recorded. Results: Twenty-five patients were included. Median age was 52.9 years with a body mass index of 29.1 kg/m2 and mean follow-up of 44 months (range 24 to 90 months). Lymphedema stage ranged from Campisi 2 to 4. Inguinal VLNT was performed in 13 patients, and 12 patients received combined VLNT and free flap breast reconstruction. No patients required change in lymph node donor site intraoperatively. All ICG stained nodes were preserved in situ. No cases of iatrogenic lower extremity lymphedema were observed. Postoperative bioimpedance spectroscopy, circumferential, and volumetric measurements of the donor-site limb did not show evidence of subclinical or clinical lymphedema. The donor site healed appropriately in 92% of patients; one patient developed methylene blue-induced skin necrosis. Conclusion: Reverse lymphatic mapping and surgical guidance with dual ICG and blue dye fluorescent tracers provides surgeons with real-time surgical guidance without radioisotope, improves surgical visualization in both white light and near-infrared spectra, and avoids iatrogenic lymphatic dysfunction in the donor limb.

A rapid and non-invasive proteomic analysis using DBS and buccal swab for multiplexed second-tier screening of Pompe disease and Mucopolysaccharidosis type I.

PURPOSE: Current newborn screening programs for Pompe disease (PD) and mucopolysaccharidosis type I (MPS I) suffer from a high false positive rate and long turnaround time for clinical follow up. This study aimed to develop a novel proteomics-based assay for rapid and accurate second-tier screening of PD and MPS I. A fast turnaround assay would enable the identification of severe cases who need immediate clinical follow up and treatment. METHODS: We developed an immunocapture coupled with mass spectrometry-based proteomics (Immuno-SRM) assay to quantify GAA and IDUA proteins in dried blood spots (DBS) and buccal swabs. Sensitivity, linearity, reproducibility, and protein concentration range in healthy control samples were determined. Clinical performance was evaluated in known PD and MPS I patients as well as pseudodeficiency and carrier cases. RESULTS: Using three 3.2 mm punches (~13.1 µL of blood) of DBS, the assay showed reproducible and sensitive quantification of GAA and IDUA. Both proteins can also be quantified in buccal swabs with high reproducibility and sensitivity. Infantile onset Pompe disease (IOPD) and severe MPS I cases are readily identifiable due to the absence of GAA and IDUA, respectively. In addition, late onset Pompe disease (LOPD) and attenuated MPS I patients showed much reduced levels of the target protein. By contrast, pseudodeficiency and carrier cases exhibited significant higher target protein levels compared to true patients. CONCLUSION: Direct quantification of endogenous GAA and IDUA peptides in DBS by Immuno-SRM can be used for second-tier screening to rapidly identify severe PD and MPS I patients with a turnaround time of <1 week. Such patients could benefit from immediate clinical follow up and possibly earlier treatment.

The Hairline Brow Lift.

Effective rejuvenation of the upper face results when effective brow repositioning is combined with maintenance or improvement of brow shape. Endoscopic brow lift techniques have increased in popularity as surgeons have investigated less invasive surgical procedures. This article provides a comparison of hairline brow lift with other open and endoscopic techniques used for improving brow position. It includes a detailed description of hairline brow lift with videos illustrating the authors' preferred technique. It also provides a description of ideal candidates including indications and contraindications to procedure, and common modifications to technique used in select patient populations.

Protocol for a Randomized Multiple Center Trial of Conservative Versus Liberal Oxygenation Targets in Critically Ill Children (Oxy-PICU): Oxygen in Pediatric Intensive Care.

OBJECTIVES: Oxygen administration is a fundamental part of pediatric critical care, with supplemental oxygen offered to nearly every acutely unwell child. However, optimal targets for systemic oxygenation are unknown. Oxy-PICU aims to evaluate the clinical effectiveness and cost-effectiveness of a conservative peripheral oxygen saturation (Sp o2 ) target of 88-92% compared with a liberal target of more than 94%. DESIGN: Pragmatic, open, multiple-center, parallel group randomized control trial with integrated economic evaluation. SETTING: Fifteen PICUs across England, Wales, and Scotland. PATIENTS: Infants and children age more than 38 week-corrected gestational age to 16 years who are accepted to a participating PICU as an unplanned admission and receiving invasive mechanical ventilation with supplemental oxygen for abnormal gas exchange. INTERVENTION: Adjustment of ventilation and inspired oxygen settings to achieve an Sp o2 target of 88-92% during invasive mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Randomization is 1:1 to a liberal Sp o2 target of more than 94% or a conservative Sp o2 target of 88-92% (inclusive), using minimization with a random component. Minimization will be performed on: age, site, primary reason for admission, and severity of abnormality of gas exchange. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred to after randomization. The primary clinical outcome is a composite of death and days of organ support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of oxygenation and organ support, and discharge outcomes. This trial received Health Research Authority approval on December 23, 2019 (reference: 272768), including a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee (reference number: 19/EE/0362). Trial findings will be disseminated in national and international conferences and peer-reviewed journals.