The Keystone Perforator Island Flap: Review of Utility and Versatile Clinical Applications.

Background: The keystone perforator island flap (KPIF) was described almost a decade ago. However, this flap has only recently been recognized for its advantages in various clinical applications in plastic surgery. A better understanding of the versatility of KPIFs can help promote the widespread adoption of this technique for complex wounds in various anatomical regions. Methods: A retrospective chart review was conducted of patients undergoing KPIFs from December 2018 to March 2022 at the authors' home institution. The indications, surgical approaches, patient characteristics, and outcomes were extracted for review and analysis. Results: A total of 12 patients (ages 13-86 years) underwent reconstruction with KPIFs for oncologic and nononcologic defects. By anatomic region, three cases involved the upper back, six involved the lumbosacral region, one involved the perineum, and two involved the midfoot. Half of the patients (n = 6) had failed previous attempts at wound closure. The mean defect size was 13.8 × 10.0 cm for the upper back lesions, 13.7 × 4.8 for the lumbosacral defects, and 3.5 × 2.0 for the metatarsal wounds. Median follow-up time for all patients was 7.5 months (IQR: 4-10.5). On follow-up, there was 100% flap survival. Conclusion: KPIFs are a simple, safe, and suitable option for reconstructive closure of defects in many anatomical areas, including wounds complicated by previous failed closure attempts, with low complication risk profile.

Correction: Academic global surgical competencies: A modified Delphi consensus study.

[This corrects the article DOI: 10.1371/journal.pgph.0002102.].

Poor accessibility to consumer pricing exists for elective hernia repair surgery.

BACKGROUND: Hospital price transparency is federally mandated to improve consumer accessibility. We aimed to evaluate how hospitals were complying with these regulations for elective hernia repairs. METHODS: Searches were performed for different hospital systems in attempt to find a price for the procedure using author's own health insurance. Data collected included time to reach the cost estimate tool, time to obtain price estimates, and price ranges. With prices for inguinal and ventral hernia repairs varying across the state's medical centers. RESULTS: Fourteen medical centers across the country were included, all had a cost estimate calculator. The average success rate of obtaining a cost for inguinal hernia was 48%. Comparatively, the average success rate of obtaining a cost for ventral hernia was 12%. Of the successful searches for price, significant variation exists amongst the accessed hernia procedure cost. CONCLUSION: Despite federal mandates for hospital price transparency, online cost-estimate calculators are underperforming, thus exposing a need for more accessible cost-estimates for patients undergoing elective hernia repair.

Academic global surgical competencies: A modified Delphi consensus study.

Academic global surgery is a rapidly growing field that aims to improve access to safe surgical care worldwide. However, no universally accepted competencies exist to inform this developing field. A consensus-based approach, with input from a diverse group of experts, is needed to identify essential competencies that will lead to standardization in this field. A task force was set up using snowball sampling to recruit a broad group of content and context experts in global surgical and perioperative care. A draft set of competencies was revised through the modified Delphi process with two rounds of anonymous input. A threshold of 80% consensus was used to determine whether a competency or sub-competency learning objective was relevant to the skillset needed within academic global surgery and perioperative care. A diverse task force recruited experts from 22 countries to participate in both rounds of the Delphi process. Of the n = 59 respondents completing both rounds of iterative polling, 63% were from low- or middle-income countries. After two rounds of anonymous feedback, participants reached consensus on nine core competencies and 31 sub-competency objectives. The greatest consensus pertained to competency in ethics and professionalism in global surgery (100%) with emphasis on justice, equity, and decolonization across multiple competencies. This Delphi process, with input from experts worldwide, identified nine competencies which can be used to develop standardized academic global surgery and perioperative care curricula worldwide. Further work needs to be done to validate these competencies and establish assessments to ensure that they are taught effectively.

Variable Accessibility to Consumer Pricing Among Breast Cancer Operations.

BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) mandate that every US hospital provide public online pricing information for services rendered. This allows patients to compare prices across hospital systems before establishing care. The goal of this project was to evaluate hospital compliance and patient-level accessibility to price transparency for common breast cancer surgical procedures. METHODS: A sample case of a 62-year-old female with a T2N0 breast cancer was chosen. The patient would have the option of undergoing a partial mastectomy or mastectomy, both with sentinel lymph node biopsy (SLNB). Eight Massachusetts academic medical centers were evaluated. Searches were performed by authors for each hospital system and procedure using the sample case. RESULTS: Every hospital had a cost calculator on its website. The average success rate of establishing a cost for partial mastectomy, mastectomy, and SLNB was 58, 35, and 25%, respectively. The median time to reach the cost calculator tool was 32 s (range 25-37 s). In successful attempts, the median pre-insurance estimated cost of a partial mastectomy was $16,509 (range $11,776-22,169), compared with $24,541 (range $16,921-25,543) for mastectomy and $12,342 (range $4034-20,644) for SLNB. SLNB costs varied significantly across hospitals (p = 0.025), but no statistically significant difference was observed for partial mastectomy or mastectomy. CONCLUSION: Despite new regulatory requirements by CMS for increased price transparency for surgical procedures, our results demonstrate poor success rates in obtaining cost estimates and significant variability of reported hospital charges. Further efforts to improve the quality of hospital cost estimate calculators are necessary for informed decision-making for patients with breast cancer.

Perceptions and Early Outcomes of the Acuity Circles Allocation Policy Among Liver Transplant Centers in the United States.

Recently, a new liver allocation policy called the acuity circles (AC) framework was implemented to decrease geographic disparities in transplant metrics across donor service areas. Early analyses have examined the changes in outcomes because of the AC policy. However, perceptions among transplant surgeons and staff regarding the new policy remain unknown. Methods: A 28-item survey was sent to division chiefs and surgical directors of liver transplantation across the United States. Questions assessed the respondents' perceptions regarding center-level metrics and staff satisfaction. We used Organ Procurement and Transplantation Network data to study differences in allocation between the pre-AC implementation period (2019) and the post-AC implementation period (2020-2021). Results: A total of 40 participants completed this ongoing survey study. Most responses were from region 8 (13%), region 10 (15%), and region 11 (13%). Sixty-three percent of respondents stated that the wait time for a suitable offer for recipients with model of end-stage liver disease score <30 has decreased, whereas 50% stated that wait time for a suitable offer for recipients with model of end-stage liver disease score >30 has increased. However, most respondents (75%) felt that the average cost per transplant had increased and that the rate of surgical complications and 1-y graft survival had remained the same. In most states, an observable decrease in in-state liver transplantations occurred each year between 2019 and 2021. In addition, most allocation regions reported an increase in donations after circulatory deaths between 2019 and 2021. Conclusions: Perceptions of the new AC policy among liver transplant surgeons in the United States remain mixed, highlighting the potential strengths and concerns regarding its future impact. Further studies should assess the effects of the AC policy on clinical outcomes and liver transplantation access.

Structure of the pre-mRNA leakage 39-kDa protein reveals a single domain of integrated zf-C3HC and Rsm1 modules.

In Saccharomyces cerevisiae, the pre-mRNA leakage 39-kDa protein (ScPml39) was reported to retain unspliced pre-mRNA prior to export through nuclear pore complexes (NPCs). Pml39 homologs outside the Saccharomycetaceae family are currently unknown, and mechanistic insight into Pml39 function is lacking. Here we determined the crystal structure of ScPml39 at 2.5 Å resolution to facilitate the discovery of orthologs beyond Saccharomycetaceae, e.g. in Schizosaccharomyces pombe or human. The crystal structure revealed integrated zf-C3HC and Rsm1 modules, which are tightly associated through a hydrophobic interface to form a single domain. Both zf-C3HC and Rsm1 modules belong to the Zn-containing BIR (Baculovirus IAP repeat)-like super family, with key residues of the canonical BIR domain being conserved. Features unique to the Pml39 modules refer to the spacing between the Zn-coordinating residues, giving rise to a substantially tilted helix αC in the zf-C3HC and Rsm1 modules, and an extra helix αAB' in the Rsm1 module. Conservation of key residues responsible for its distinct features identifies S. pombe Rsm1 and Homo sapiens NIPA/ZC3HC1 as structural orthologs of ScPml39. Based on the recent functional characterization of NIPA/ZC3HC1 as a scaffold protein that stabilizes the nuclear basket of the NPC, our data suggest an analogous function of ScPml39 in S. cerevisiae.

Comparing oncoplastic breast reduction with immediate symmetry surgery to standard breast reduction surgery: Are postoperative complications worse?

INTRODUCTION: Oncoplastic breast reduction mammoplasty (ORM) is an excellent treatment option for women with breast cancer and macromastia undergoing breast conservation therapy. Here, we aim to better understand the risks associated with ORM compared to standard reduction mammoplasty (SRM). METHODS: A retrospective chart review was performed of patients undergoing ORM or SRM from 2015 to 2021. Primary outcomes included the occurrence of major or minor postoperative complications in the two groups and delays to adjuvant therapy (>90 days) among the women undergoing ORM. RESULTS: Women in the ORM group (n = 198) were significantly older (p < 0.001) with a higher prevalence of smoking (p < 0.001), diabetes mellitus (p < 0.01), and a Charlson comorbidity index ≥ 3 (p < 0.001) compared to women undergoing SRM (n = 177). After controlling for potential confounders, there were no significant between-group differences in the odds of developing postoperative complications (odds ratio = 0.80, 95% confidence interval: 0.36-1.69). Only 3% (n = 4) of the 150 women undergoing adjuvant radiation or chemotherapy experienced delays related to postoperative complications. CONCLUSION: ORM has a similar safety profile as SRM, despite the older age and higher number of comorbidities often seen in patients undergoing ORM, and is a safe option for achieving contralateral symmetry at the time of partial mastectomy without delays to adjuvant therapy.

What is the prevalence of COVID-19 detection by PCR among deceased individuals in Lusaka, Zambia? A postmortem surveillance study.

OBJECTIVES: To determine the prevalence of COVID-19 postmortem setting in Lusaka, Zambia. DESIGN: A systematic, postmortem prevalence study. SETTING: A busy, inner-city morgue in Lusaka. PARTICIPANTS: We sampled a random subset of all decedents who transited the University Teaching Hospital morgue. We sampled the posterior nasopharynx of decedents using quantitative PCR. Prevalence was weighted to account for age-specific enrolment strategies. INTERVENTIONS: Not applicable-this was an observational study. PRIMARY OUTCOMES: Prevalence of COVID-19 detections by PCR. Results were stratified by setting (facility vs community deaths), age, demographics and geography and time. SECONDARY OUTCOMES: Shifts in viral variants; causal inferences based on cycle threshold values and other features; antemortem testing rates. RESULTS: From 1118 decedents enrolled between January and June 2021, COVID-19 was detected among 32.0% (358/1116). Roughly four COVID-19+ community deaths occurred for every facility death. Antemortem testing occurred for 52.6% (302/574) of facility deaths but only 1.8% (10/544) of community deaths and overall, only ~10% of COVID-19+ deaths were identified in life. During peak transmission periods, COVID-19 was detected in ~90% of all deaths. We observed three waves of transmission that peaked in July 2020, January 2021 and ~June 2021: the AE.1 lineage and the Beta and Delta variants, respectively. PCR signals were strongest among those whose deaths were deemed 'probably due to COVID-19', and weakest among children, with an age-dependent increase in PCR signal intensity. CONCLUSIONS: COVID-19 was common among deceased individuals in Lusaka. Antemortem testing was rarely done, and almost never for community deaths. Suspicion that COVID-19 was the cause of deaths was highest for those with a respiratory syndrome and lowest for individuals <19 years.

Academic Global Surgery Curricula: Current Status and a Call for a More Equitable Approach.

INTRODUCTION: We aimed to search the literature for global surgical curricula, assess if published resources align with existing competency frameworks in global health and surgical education, and determine if there is consensus around a fundamental set of competencies for the developing field of academic global surgery. METHODS: We reviewed SciVerse SCOPUS, PubMed, African Medicus Index, African Journals Online (AJOL), SciELO, Latin American and Caribbean Health Sciences Literature (LILACS) and Bioline for manuscripts on global surgery curricula and evaluated the results using existing competency frameworks in global health and surgical education from Consortium of the Universities for Global Health (CUGH) and Accreditation Council for Graduate Medical Education (ACGME) professional competencies. RESULTS: Our search generated 250 publications, of which 18 were eligible: (1) a total of 10 reported existing competency-based curricula that were concurrent with international experiences, (2) two reported existing pre-departure competency-based curricula, (3) six proposed theoretical competency-based curricula for future global surgery education. All, but one, were based in high-income countries (HICs) and focused on the needs of HIC trainees. None met all 17 competencies, none cited the CUGH competency on "Health Equity and Social Justice" and only one mentioned "Social and Environmental Determinants of Health." Only 22% (n = 4) were available as open-access. CONCLUSION: Currently, there is no universally accepted set of competencies on the fundamentals of academic global surgery. Existing literature are predominantly by and for HIC institutions and trainees. Current frameworks are inadequate for this emerging academic field. The field needs competencies with explicit input from LMIC experts to ensure creation of educational resources that are accessible and relevant to trainees from around the world.

Generalizing remotely supervised transcranial direct current stimulation (tDCS): feasibility and benefit in Parkinson's disease.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has been shown to improve common symptoms of neurological disorders like depressed mood, fatigue, motor deficits and cognitive dysfunction. tDCS requires daily treatment sessions in order to be effective. We developed a remotely supervised tDCS (RS-tDCS) protocol for participants with multiple sclerosis (MS) to increase accessibility of tDCS, reducing clinician, patient, and caregiver burden. The goal of this protocol is to facilitate home use for larger trials with extended treatment periods. In this study we determine the generalizability of RS-tDCS paired with cognitive training (CT) by testing its feasibility in participants with Parkinson's disease (PD). METHODS: Following the methods in our MS protocol development, we enrolled sixteen participants (n = 12 male, n = 4 female; mean age 66 years) with PD to complete ten open-label sessions of RS-tDCS paired with CT (2.0 mA × 20 min) at home under the remote supervision of a trained study technician. Tolerability data were collected before, during, and after each individual session. Baseline and follow-up measures included symptom inventories (fatigue and sleep) and cognitive assessments. RESULTS: RS-tDCS was feasible and tolerable for patients with PD, with at-home access leading to high protocol compliance. Side effects were mostly limited to mild sensations of transient itching and burning under the electrode sites. Similar to prior finding sin MS, we found preliminary efficacy for improvement of fatigue and cognitive processing speed in PD. CONCLUSIONS: RS-tDCS paired with CT is feasible for participants with PD to receive at home treatment. Signals of benefit for reduced fatigue and improved cognitive processing speed are consistent across the PD and MS samples. RS-tDCS can be generalized to provide tDCS to a range of patients with neurologic disorders for at-home rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02746705 . Registered April 21st 2016.

Remotely-supervised transcranial direct current stimulation paired with cognitive training in Parkinson's disease: An open-label study.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been explored as a potential intervention in Parkinson's disease (PD) and recent studies have shown promising results in cognitive, gait and motor function. However, evidence of efficacy is limited due to small size studies, short treatment periods, lack of standardization of methodologies and other study design limitations. Remotely supervised-tDCS (RS-tDCS) allows "at-home" study participation, potentially easing recruitment, compliance and overall feasibility for clinical studies. OBJECTIVE: Here, we aim to explore preliminary effects of RS-tDCS paired with cognitive training in PD by delivering RS-tDCS neuromodulation at participant's home while still maintaining clinical trial standards. METHODS: This was a prospective, open-label study using RS-tDCS paired with cognitive training. Each PD participant completed 10 tDCS sessions (20-min, 1.5-2.0-mA, bi-hemispheric DLPFC montage, left anodal), over a span of two weeks. All tDCS sessions were supervised in real-time through videoconferencing. Outcomes included the Unified Parkinson's Disease Rating Scale (UPDRS) and Grooved Pegboard Test. RESULTS: All RS-tDCS sessions were well tolerated and completed successfully. Total UPDRS and motor UPDRS-III scores decreased significantly. Pegboard completion time improved significantly for the non-dominant hand. There was a strong positive correlation between the time of the sessions, and motor improvements in UPDRS part-III. CONCLUSION: RS-tDCS paradigm through a 'telemedicine protocol' holds therapeutic potential for motor symptoms in PD while maximizing compliance and ease of recruitment. Conducting afternoon sessions might be more effective than during the morning. Our paradigm may be influential in designing future studies and facilitating larger and longer duration clinical trials.

Remotely Supervised Transcranial Direct Current Stimulation: An Update on Safety and Tolerability.

The remotely supervised tDCS (RS-tDCS) protocol enables participation from home through guided and monitored self-administration of tDCS treatment while maintaining clinical standards. The current consensus regarding the efficacy of tDCS is that multiple treatment sessions are needed to observe targeted behavioral reductions in symptom burden. However, the requirement for patients to travel to clinic daily for stimulation sessions presents a major obstacle for potential participants, due to work or family obligations or limited ability to travel. This study presents a protocol that directly overcomes these obstacles by eliminating the need to travel to clinic for daily sessions. This is an updated protocol for remotely supervised self-administration of tDCS for daily treatment sessions paired with a program of computer-based cognitive training for use in clinical trials. Participants only need to attend clinic twice, for a baseline and study-end visit. At baseline, participants are trained and provided with a study stimulation device, and a small laptop computer. Participants then complete the remainder of their stimulation sessions at home while they are monitored via videoconferencing software. Participants complete computerized cognitive remediation during stimulation sessions, which may serve a therapeutic role or as a "placeholder" for other computer-based activity. Computers are enabled for real-time monitoring and remote control by study staff. Outcome measures that assess feasibility and tolerance are administered remotely with the aid of visual analogue scales that are presented onscreen. Following completion of all RS-tDCS sessions, participants return to clinic for a study end visit in which all study equipment is returned. Results support the safety, feasibility, and scalability of the RS-tDCS protocol for use in clinical trials. Across 46 patients, 748 RS-tDCS sessions have been completed. This protocol serves as a model for use in future clinical trials involving tDCS.

Adverse Childhood Experiences Are Linked to Age of Onset and Reading Recognition in Multiple Sclerosis.

BACKGROUND: Adverse childhood experiences (ACEs) exert a psychological and physiological toll that increases risk of chronic conditions, poorer social functioning, and cognitive impairment in adulthood. OBJECTIVE: To investigate the relationship between childhood adversity and clinical disease features in multiple sclerosis (MS). METHODS: Sixty-seven participants with MS completed the ACE assessment and neuropsychological assessments as part of a larger clinical trial of cognitive remediation. RESULTS: Adverse childhood experience scores, a measure of exposure to adverse events in childhood, significantly predicted age of MS onset (r = -0.30, p = 0.04). ACEs were also linked to reading recognition (a proxy for premorbid IQ) (r = -0.25, p = 0.04). ACE scores were not related to age, current disability, or current level of cognitive impairment measured by the Symbol Digit Modalities Test (SDMT). CONCLUSION: Childhood adversity may increase the likelihood of earlier age of onset and poorer estimated premorbid IQ in MS.

AMPAkines Target the Nucleus Accumbens to Relieve Postoperative Pain.

BACKGROUND: AMPAkines augment the function of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the brain to increase excitatory outputs. These drugs are known to relieve persistent pain. However, their role in acute pain is unknown. Furthermore, a specific molecular and anatomic target for these novel analgesics remains elusive. METHODS: The authors studied the analgesic role of an AMPAkine, CX546, in a rat paw incision (PI) model of acute postoperative pain. The authors measured the effect of AMPAkines on sensory and depressive symptoms of pain using mechanical hypersensitivity and forced swim tests. The authors asked whether AMPA receptors in the nucleus accumbens (NAc), a key node in the brain's reward and pain circuitry, can be a target for AMPAkine analgesia. RESULTS: Systemic administration of CX546 (n = 13), compared with control (n = 13), reduced mechanical hypersensitivity (50% withdrawal threshold of 6.05 ± 1.30 g [mean ± SEM] vs. 0.62 ± 0.13 g), and it reduced depressive features of pain by decreasing immobility on the forced swim test in PI-treated rats (89.0 ± 15.5 vs. 156.7 ± 18.5 s). Meanwhile, CX546 delivered locally into the NAc provided pain-relieving effects in both PI (50% withdrawal threshold of 6.81 ± 1.91 vs. 0.50 ± 0.03 g; control, n = 6; CX546, n = 8) and persistent postoperative pain (spared nerve injury) models (50% withdrawal threshold of 3.85 ± 1.23 vs. 0.45 ± 0.00 g; control, n = 7; CX546, n = 11). Blocking AMPA receptors in the NAc with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione inhibited these pain-relieving effects (50% withdrawal threshold of 7.18 ± 1.52 vs. 1.59 ± 0.66 g; n = 8 for PI groups; 10.70 ± 3.45 vs. 1.39 ± 0.88 g; n = 4 for spared nerve injury groups). CONCLUSIONS: AMPAkines relieve postoperative pain by acting through AMPA receptors in the NAc.