Combined Targeted Muscle Reinnervation With Regenerative Peripheral Nerve Interfaces Decreases Long-Term Narcotic Use in Amputees: A Case Control Study.

PURPOSE: Combined targeted muscle reinnervation with regenerative peripheral nerve interfaces ("TMRpni") is a recently described nerve management strategy that leverages beneficial elements of targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) techniques. This study aimed to evaluate the effect of TMRpni on long-term opioid consumption after amputation. We hypothesize that TMRpni decreases chronic opioid consumption in amputees. METHODS: This is a retrospective cohort study of all patients who underwent TMRpni between 2019 and 2021. These patients were age-matched at a 1:1 ratio with a control group of patients who underwent amputation without TMRpni. Statistical analysis was performed using SPSS Version 28.0. RESULTS: Thirty-one age-matched pairs of patients in the TMRpni and control groups were included. At 30 days after surgery, there was no significant difference in number of patients who required an additional refill of their opioid prescriptions (45% vs 55%, P = 0.45) or patients who continued to actively use opioids (36% vs 42%, P = 0.60). However, at 90 days after surgery, there was a significantly lower number of patients from the TMRpni group who reported continued opioid use compared with the control group (10% vs 32%, P = 0.03). CONCLUSIONS: This study demonstrates that TMRpni may translate to decreased rates of chronic opiate use. Continued study is indicated to optimize TMRpni techniques and patient selection and to determine its long-term efficacy.

Autologous Fat Grafting Does Not Increase Risk of Oncologic Recurrence in the Reconstructed Breast.

INTRODUCTION: Autologous fat grafting (AFG) is a popular and effective method of breast reconstruction after mastectomy; however, the oncological safety of AFG remains in question. The aim of this study was to determine whether AFG increases the risk of cancer recurrence in the reconstructed breast. METHODS: A matched, case-control study was conducted from 2000 to 2017 at the senior author's institution. Inclusion was limited to female patients who underwent mastectomy and breast reconstruction with or without AFG. Data were further subdivided at the breast level. χ analyses were used to test the association between AFG status and oncologic recurrence. A Cox proportional-hazards model was constructed to assess for possible differences in time to oncologic recurrence. The probability of recurrence was determined by Kaplan-Meier analyses and confirmed with log-rank testing. RESULTS: Overall, 428 breasts met study criteria. Of those, 116 breasts (27.1%) received AFG, whereas 312 (72.9%) did not. No differences in the rates of oncologic recurrence were found between the groups (8.2% vs 9.0%, P < 1.000). Unadjusted (hazard ratio = 1.03, confidence interval = 0.41-2.60, P < 0.957) and adjusted hazard models showed no statistically significant increase in time to oncologic recurrence when comparing AFG to non-AFG. In addition, no statistical differences in disease-free survival were found (P = 0.96 by log rank test). CONCLUSION: Autologous fat grafting for breast reconstruction is oncologically safe and does not increase the likelihood of oncologic recurrence. Larger studies (eg, meta analyses) with longer follow-up are needed to further elucidate the long-term safety of AFG as a reconstructive adjunct.

HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy.

Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1(∗)01:02-DQB1(∗)06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1(∗)01:03-DPB1(∗)04:02 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10(-6)) and HLA-DPA1(∗)01:03-DPB1(∗)04:01 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10(-4)) and predisposing effects of HLA-DPB1(∗)05:01 in Asians (OR = 1.76 [1.34-2.31], p = 4.71 × 10(-05)). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38-0.55] p = 8.99 × 10(-17)) and DP0501 (OR = 1.38 [1.18-1.61], p = 7.11 × 10(-5)). HLA-class-II-independent associations with HLA-A(∗)11:01 (OR = 1.32 [1.13-1.54], p = 4.92 × 10(-4)), HLA-B(∗)35:03 (OR = 1.96 [1.41-2.70], p = 5.14 × 10(-5)), and HLA-B(∗)51:01 (OR = 1.49 [1.25-1.78], p = 1.09 × 10(-5)) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza.

Evidence of the immunomodulatory role of dual PI3K/mTOR inhibitors in transplantation: an experimental study in mice.

The PI3K/mTOR signaling cascade is fundamental in T-cell activation and fate decisions. We showed the distinct regulation of PI3K/mTOR in regulatory and effector T-cells and proposed the potential therapeutic benefit of targeting this pathway to control the balance between effector and regulatory T-cell activities. Substantial adverse effects in long-term clinical usage of rapamycin suggest the use of alternative treatments in restraining effector T-cell function in transplant patients. We hypothesize that dual PI3K/mTOR inhibitors may represent an immunosuppressant alternative. Here we show that dual PI3K/mTOR PI-103 and PKI-587 inhibitors interfered IL-2-dependent responses in T-cells. However, in contrast to the inhibitory effects in non-Treg T-cell proliferation and effector functions, dual inhibitors increased the differentiation, preferential expansion, and suppressor activity of iTregs. Rapamycin, PI-103, and PKI-587 targeted different signaling events and induced different metabolic patterns in primary T-cells. Similar to rapamycin, in vivo administration of PI-103 and PKI-587 controlled effectively the immunological response against allogeneic skin graft. These results characterize specific regulatory mechanisms of dual PI3K/mTOR inhibitors in T-cells and support their potential as a novel therapeutic option in transplantation.

Combined liver-kidney transplantation for polycystic liver and kidney disease: analysis from the United Network for Organ Sharing dataset.

BACKGROUND & AIMS: The purpose of this study was to evaluate predictors of outcomes in combined liver-kidney transplants for polycystic liver and kidney disease. METHODS: We queried the United Network for Organ Sharing dataset for combined liver-kidney transplants performed from 1988 to 2013. RESULTS: Out of 107 patients who had combined liver-kidney transplants for polycystic liver and kidney disease, 84 were women (78.5%) with a mean age of 54.9 ±7.2 years. Kaplan-Meier analysis demonstrated that patients undergoing liver-kidney transplantation for polycystic liver and kidney disease had better survival than patients with polycystic liver disease undergoing liver transplant alone and those undergoing liver-kidney transplantation for other indications. This group had a 1-, 3- and 5-year survival of 91%, 90% and 90%, respectively. Multivariable analysis demonstrated that an indication of polycystic liver and kidney disease for combined liver-kidney transplant (hazard ratio, 0.29; 95% confidence interval, 0.129-0.526; P < 0.001) and Model for End-Stage Liver Disease score (hazard ratio, 1.271; 95% confidence interval, 1.093-1.477; P = 0.002) are independently associated with patient survival. In a propensity score analysis adjusting for age, gender, cold ischaemia time and total bilirubin and excluding hepatitis C, we found that patients transplanted with combined liver-kidney for other indications have similar survival compared with our study group. CONCLUSIONS: Combined liver-kidney transplantation for polycystic liver and kidney disease can achieve good outcomes in selected patients. On Cox regression analysis, patients with polycystic liver and kidney disease undergoing liver-kidney transplantation had better survival compared with patients with combined liver-kidney for other indications. After excluding hepatitis C patients, those transplanted for polycystic liver and kidney disease vs other indications had similar survival after combined liver-kidney transplantation. Interestingly, patients in the combined polycystic liver and kidney disease group have significantly better outcomes than patients with polycystic liver disease undergoing liver transplant alone.

Thin and Thinned Anterolateral Thigh Flaps for Upper Extremity Reconstruction.

Upper extremity reconstruction remains challenging due to the high functional and esthetic demands of this location. The anterolateral thigh (ALT) flap is a workhorse flap for microsurgical reconstruction of the upper extremity and can be elevated in various planes depending on desired thickness of the flap. Microsurgical reconstruction of the upper extremity often benefits from a thin flap that can resurface the extremity, which can provide improved functional and esthetic outcomes. This article reviews the anatomy, preoperative planning, and operative technique, as well as presents 4 cases to illustrate the outcomes and benefits of thin and thinned ALT flaps.

Comparing Plastic Surgeon Versus Orthopedic Surgeon Outcomes Following Distal Upper Extremity Amputations: A Study of the National Surgical Quality Improvement Program (NSQIP) Database.

BACKGROUND: Both plastic and orthopedic surgeons manage care for urgent/emergent hand conditions. It is unclear if surgeon specialty affects patient outcomes of these cases. The purpose of this study was to evaluate differences in 30-day perioperative outcomes between plastic and orthopedic surgeons following distal upper extremity amputations. METHODS: Patients who underwent distal upper extremity amputations between 2005 and 2016 were identified within the National Surgical Quality Improvement Program (NSQIP) database using Current Procedural Terminology (CPT) codes. Differences in operative procedures, patient demographics, patient comorbidities, and 30-day perioperative complications were compared between orthopedic and plastic surgeons by univariate analysis. A Bonferroni correction was applied to account for multiple comparisons of complications. RESULTS: A total of 1583 cases met inclusion criteria. Orthopedic surgeons performed 981 cases (62.0%) and plastic surgeons performed 602 cases (38.0%). Finger amputations comprised the majority of procedures for both orthopedic and plastic surgeons (95.5% and 94.4%, respectively). Orthopedic surgeons had a lower operative time (41.7 ± 36.2 minutes vs 47.1 ± 40.9 minutes, P = .008). There were no differences in proportion of emergency surgery, inpatients, or wound class. There were no differences in age, gender, or body mass index. The most common indications for amputation were trauma, gangrene, and osteomyelitis. There were no differences between surgical specialties in 18 30-day perioperative complications assessed, including death, reoperation, surgical site infection, or wound dehiscence. CONCLUSIONS: Plastic and orthopedic surgeons achieved equivalent outcomes comparing 30-day perioperative complications following upper extremity amputations. These results support that both orthopedic and plastic surgeons provide similar quality distal upper extremity amputation care.

HISTORIQUE: Tant les plasticiens que les chirurgiens orthopédiques prennent en charge les cas d'affections urgentes ou d'extrême urgence touchant les mains. On ne sait pas si la spécialité chirurgicale a une incidence sur le pronostic des patients atteints de ces problèmes. La présente étude visait à évaluer les différences entre les résultats périopératoires des plasticiens et des chirurgiens orthopédiques 30 jours après des amputations distales des extrémités supérieures. MÉTHODOLOGIE: Les patients qui ont subi une amputation distale des extrémités supérieures entre 2005 et 2016 ont été extraits de la base de données du Programme national d'amélioration de la qualité des soins chirurgicaux (NSQIP) à l'aide des codes du Catalogue des actes médicaux (CPT). Au moyen d'une analyse univariée, les chercheurs ont comparé les différences entre les interventions opératoires effectuées par les chirurgiens orthopédiques et les plasticiens, les caractéristiques démographiques des patients, leurs autres affections et leurs complications périopératoires au bout de 30 jours. Ils ont utilisé une correction de Bonferroni pour tenir compte de multiples comparaisons entre les complications. RÉSULTATS: Au total, 1 583 cas respectaient les critères d'inclusion. Les chirurgiens orthopédiques ont opéré 981 cas (62,0 %) et les plasticiens, 602 cas (38,0 %). Les amputations des doigts représentaient la majorité des interventions effectuées par les chirurgiens orthopédiques et les plasticiens (95,5 % et 94,4 % respectivement). Les opérations pratiquées par les chirurgiens orthopédiques étaient plus courtes (41,7 ± 36,2 minutes par rapport à 47,1 ± 40,9 minutes, p = 0,008). Il n'y avait pas de différence quant à la proportion d'opérations d'urgence, de patients hospitalisés ou de catégories de plaies ni pour ce qui est de l'âge, du genre et de l'indice de masse corporelle. Les principales indications d'amputation étaient des traumatismes, la gangrène et l'ostéomyélite. Il n'y avait pas de différence entre les spécialités chirurgicales lors de l'évaluation des complications périopératoires au bout de 18 et 30 jours, y compris les décès, les réopérations, l'infection au foyer des infections et la déhiscence des plaies. CONCLUSIONS: Les plasticiens et les chirurgiens orthopédiques ont obtenu des résultats équivalents si l'on comparait les complications périopératoires après des amputations des extrémités supérieures au bout de 30 jours. Selon ces résultats, à la fois les chirurgiens orthopédiques et les plasticiens fournissent des soins de qualité semblables lors d'amputations distales des membres supérieurs.

HLA DQB1*06:02 negative narcolepsy with hypocretin/orexin deficiency.

STUDY OBJECTIVES: To identify rare allelic variants and HLA alleles in narcolepsy patients with hypocretin (orexin, HCRT) deficiency but lacking DQB1*06:02. SETTINGS: China (Peking University People's Hospital), Czech Republic (Charles University), Denmark (Golstrup Hospital), Italy (University of Bologna), Korea (Catholic University), and USA (Stanford University). DESIGN: CSF hypocretin-1, DQB1*06:02, clinical and polysomnographic data were collected in narcolepsy patients (552 with and 144 without cataplexy) from 6 sites. Numbers of cases with and without DQB1*06:02 and low CSF hypocretin-1 were compiled. HLA class I (A, B, C), class II (DRBs, DQA1, DQB1, DPA1, and DPB1), and whole exome sequencing were conducted in 9 DQB1*06:02 negative cases with low CSF hypocretin-1. Sanger sequencing of selected exons in DNMT1, HCRT, and MOG was performed to exclude mutations in known narcolepsy-associated genes. MEASUREMENTS AND RESULTS: Classic narcolepsy markers DQB1*06:02 and low CSF hypocretin-1 were found in 87.4% of cases with cataplexy, and in 20.0% without cataplexy. Nine cases (all with cataplexy) were DQB1*06:02 negative with low CSF hypocretin-1, constituting 1.7% [0.8%-3.4%] of all cases with cataplexy and 1.8% [0.8%-3.4%] of cases with low CSF hypocretin independent of cataplexy across sites. Five HLA negative subjects had severe cataplexy, often occurring without clear triggers. Subjects had diverse ethnic backgrounds and HLA alleles at all loci, suggesting no single secondary HLA association. The rare subtype DPB1*0901, and homologous DPB1*10:01 subtype, were present in 5 subjects, suggesting a secondary association with HLA-DP. Preprohypocretin sequencing revealed no mutations beyond one previously reported in a very early onset case. No new MOG or DNMT1 mutations were found, nor were suspicious or private variants in novel genes identified through exome sequencing. CONCLUSIONS: Hypocretin, MOG, or DNMT1 mutations are exceptional findings in DQB1*06:02 negative cases with hypocretin deficiency. A secondary HLA-DP association may be present in these cases. These represent particularly difficult diagnostic challenges.