Current Trends in Use of Epinephrine in Hand Surgery.

BACKGROUND: Epinephrine use during hand surgery has been stigmatized due to a fear of digital necrosis. Clinical experience in the past 2 decades has shown epinephrine in local anesthetic to be safe. We sought to analyze the use of epinephrine among hand surgeons and identify variables associated with it. METHODS: A deidentified 21-question survey was distributed via email to the 914 and 415 members of the American Association for Hand Surgery and the Canadian Society for Surgery of the Hand, respectively. Questions included residency type, years of practice, practice setup/ownership, practice leadership, usage of epinephrine, availability of reversal agents, and reasons for or against usage. RESULTS: Of 188 responders, 170 (90%) used epinephrine in local anesthetic for hand surgery procedures. By nationality, 100% (43) of Canadian surgeons and 89% (108) of US surgeons use epinephrine (P = .01). Among surgeons with practice ownership, 88% (102) used epinephrine compared with 93% (85) of those surgeons that we employed (P = .28). Comparing surgeons with teaching responsibilities versus those without training responsibilities showed that surgeons who did not teach used epinephrine at a higher rate (87% vs 98%, P = .04). In addition, plastic surgery-trained surgeons (111) used epinephrine in 97.2% of cases while orthopedic surgery-trained surgeons (57) used epinephrine in 80.2% of cases (P = .0003). No difference was found when examining the use of epinephrine and surgeon age (P = .28). CONCLUSIONS: Most respondents believe that epinephrine is safe. Training background, location, and practice setup are significant factors in the use of epinephrine, whereas practice ownership and physician age are not major factors.

Squamous Cell Carcinoma of the Hand: A Retrospective Study in Immunosuppressed and Immunocompetent Individuals.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) of the hand presents a treatment challenge because of the anatomical complexity of this location. Immunosuppressed patients are disproportionately affected by cutaneous SCC. Existing data on SCC of the hand are primarily presented in the orthopedic literature, and may thus be affected by referral bias. OBJECTIVE: Characterization of epidemiology and treatment outcomes for hand versus nonhand cutaneous SCC in immunosuppressed versus immunocompetent patients, across all clinical departments. MATERIALS AND METHODS: Single-institution retrospective cohort study of cutaneous SCC evaluated over 3 years and hand SCC over an additional 5 years. RESULTS: A cohort of 522 hand SCC cases (1,746 total SCC) was ascertained among 1,064 patients, of whom 175 were immunosuppressed. Occurrence on the hand was more common for SCC arising in immunosuppressed versus immunocompetent patients (38% vs 24% of cases respectively). Hand SCC cases demonstrated balanced laterality and comparable spectra of differentiation regardless of immunosuppression. No cases of hand SCC metastasis were observed over greater than 2 years' mean follow-up, and digital amputation was only required in approximately 1% of hand SCCs. CONCLUSION: In our cohort, assessment of hand SCC across all clinical departments suggests more favorable prognosis than reflected in the previous literature.

Development and Validation of a Prognostic, Risk-Adjusted Scoring System for Operative Upper-Extremity Infections.

PURPOSE: Acute infections of the distal upper extremity (UE) can require one and possibly multiple debridements. We aimed to develop and validate a prognostic scoring system based on patient, infection, and microbiology risk factors to help with operative planning and patient counseling. METHODS: We studied all acute surgical UE infections distal to the elbow joint over a 5-year period. A split-sample design was created with 1:1 randomization into development and validation samples. The primary outcome was infection persistence, defined as the need for additional operative drainage according to usual indications. Multivariable logistic regression identified risk factors for persistent infections in the development sample, which was translated to a simple clinical scoring system derived from regression coefficients. The model was then tested separately against the validation sample. RESULTS: A total of 602 patients were included; 31% of all infections exhibited persistence. Independent risk factors from the development sample included diabetes (3 points), smoking (2 points), leukocytosis at presentation (2 points), animal bite mechanism (3 points), osteomyelitis (4 points), tenosynovitis (7 points), pyarthrosis (3 points), necrotizing fasciitis (11 points), and methicillin-resistant Staphylococcus aureus (3 points). These were all confirmed in the validation sample. Infections were categorized into 3 groups based on risk for persistent infection: low (less than 8 points), medium (8-11 points), and high (12 points or more). In the validation sample, the probability of persistent infection for these 3 groups was 23%, 57%, and 79%, respectively. The c statistic for the model in the validation sample was 0.79. CONCLUSIONS: Persistence of acute surgical distal UE infections is mediated by patient and microbiology factors, as well as infection mechanism and type. Surgeons can use this risk-adjusted prognostic scoring system to anticipate which infections may require additional therapeutic debridement and plan operative schedules and counsel patients accordingly. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Surgical Upper Extremity Infections in Immunosuppressed Patients: A Comparative Analysis With Diagnosis and Treatment Recommendations for Hand Surgeons.

Background: Immunosuppression is encountered in patients with oncologic, transplant, and autoimmune disorders. The purpose of this study is to provide guidance for physicians treating surgical hand and upper extremity (UE) infections in immunosuppressed (IS) patients. Methods: We retrospectively reviewed our database of patients presenting with UE infections over 3 years. IS patients were matched randomly to non-IS patients. Patient background, infection presentation, surgical evaluation, and microbiology variables were recorded. Infection variables included mechanism, location, and type. Outcomes included inpatient length of stay (LOS) and need for repeat drainage. Results: We identified 35 IS and 35 non-IS out of 409 UE infection patients. Patients most commonly had a hematologic malignancy (34%) as their IS class, and the most frequent immunosuppressive medication was glucocorticoids (57%). IS patients were more likely to be older and less likely to have a history of drug abuse or hepatitis C virus infections. IS infections were more likely to have idiopathic mechanisms, more likely to involve deeper anatomy such as joints, bone, tendon sheath, or muscle/fascia, and less likely to present with leukocytosis. IS cultures more commonly exhibited atypical Mycoplasma or fungus. There was no difference between IS and non-IS patients regarding LOS or recurrent drainage. Conclusions: Mechanism and white blood cell count are less reliable markers of infection severity in IS patients. Physicians treating infections in IS patients should maintain a higher suspicion for deeper involved anatomy and atypical microbiology. Nonetheless, with careful inpatient management and closer surveillance, outcomes in IS patients can approach that of non-IS patients.

Quantifying the Effect of Diabetes on Surgical Hand and Forearm Infections.

PURPOSE: Diabetes has long been established as a risk factor for hand and forearm infections. The purpose of this study was to review the effect of glycemic factors on outcomes among diabetic patients with surgical upper-extremity infections. We hypothesized that diabetic inpatients may benefit from stronger peri-infection glycemic control. METHODS: A prospective cohort study enrolled diabetic and nondiabetic surgical hand and forearm infections over 3 years. Glycemic factors included baseline glycosylated hemoglobin, blood glucose (BG) at presentation, and inpatient BG. Poor baseline control was defined as glycosylated hemoglobin of 9.0% or greater and poor inpatient control as average BG of 180 mg/dL or greater. The main outcome of interest was the need for repeat therapeutic drainage. Multivariable logistic regression quantified the association between diabetic factors and this outcome. RESULTS: The study involved 322 patients: 76 diabetic and 246 nondiabetic. Diabetic infections were more likely than nondiabetic infections to result from idiopathic mechanisms, occur in the forearm, and present as osteomyelitis, septic arthritis, and necrotizing fasciitis. Diabetic microbiology was more likely polymicrobial and fungal. After first drainage, diabetic patients were more likely to require repeat drainage and undergo eventual amputation. Among diabetic patients, poor inpatient control was associated with need for repeat drainage. CONCLUSIONS: Diabetes exacerbates the burden of surgical upper-extremity infections: specifically, more proximal locations, deeper involved anatomy at presentation, broader pathogenic microbiology, increased need for repeat drainage, and higher risk for amputation. Among diabetic patients, poor inpatient glycemic control is associated with increased need for repeat drainage. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic I.

Rectus Abdominis Motor Nerves as Donor Option for Free Functional Muscle Transfer: A Cadaver Study and Case Series.

BACKGROUND: Current management of brachial plexus injuries includes nerve grafts and nerve transfers. However, in cases of late presentation or pan plexus injuries, free functional muscle transfers are an option to restore function. The purpose of our study was to describe and evaluate the rectus abdominis motor nerves histomorphologically and functionally as a donor nerve option for free functional muscle transfer for the reconstruction of brachial plexus injuries. METHODS: High intercostal, rectus abdominis, thoracodorsal, and medial pectoral nerves were harvested for histomorphometric analysis from 4 cadavers from levels T3-8. A retrospective chart review was performed of all free functional muscle transfers from 2001 to 2014 by a single surgeon. RESULTS: Rectus abdominis nerve branches provide a significant quantity of motor axons compared with high intercostal nerves and are comparable to the anterior branch of the thoracodorsal nerve and medial pectoral nerve branches. Clinically, the average recovery of elbow flexion was comparable to conventional donors for 2-stage muscle transfer. CONCLUSION: Rectus abdominis motor nerves have similar nerve counts to thoracodorsal, medial pectoral nerves, and significantly more than high intercostal nerves alone. The use of rectus abdominis motor nerve branches allows restoration of elbow flexion comparable to other standard donors. In cases where multiple high intercostal nerves are not available as donors (rib fractures, phrenic nerve injury), rectus abdominis nerves provide a potential option for motor reconstruction without adversely affecting respiration.

Impact of Time Interval between Radiation and Free Autologous Breast Reconstruction.

Background To evaluate whether the timing of surgery after radiation in autologous breast reconstruction affects major complications. Methods We performed a retrospective review of 454 free flaps (331 patients) for breast reconstruction at a single institution from 2003 to 2014. Charts were reviewed for age, BMI, laterality, flap type (TRAM, msTRAM, DIEP), surgeon, donor vessels (IMA, TD), chemotherapy, smoking, diabetes, hypertension, DVT, venous anastomoses, vein size, and time from radiation (none, < 12 months, or ≥ 12 months). The primary outcome of major complications was defined as partial/total flap loss, thrombosis, ischemia, or hematoma requiring return to the operating room. To identify independent predictors of major complications, a multivariate logistic regression was constructed. Alpha = 0.05 indicated significance in all tests. Results Average age was 47.4 ± 8.4. Free flaps consisted of msTRAM (41.1%), TRAM (29.6%), or DIEP (29.3%). The donor vessel was IMA in 66.9% of flaps or TD in 33.0% of patients with 90.7% using only one vein and 9.3% with two veins. The average IMA/TDV size was 2.5 cm ± 0.5. Preoperative radiation occurred in 31.2% of flaps. There were 54 flaps with at least one major complication (11.7%). On multivariate regression, only flap type (OR =4.04, p < .01) and vein size (OR = 0.13, p = 0.02) independently predicted major complications. Conclusion There was no significant difference in major complications between flaps who had reconstruction within 12 months and greater than 12 months after radiation. Only having a more muscle sparing technique or smaller vein size were independent risk factors for major complications.

Hepatic Adaptations to a High Fat Diet in the MRL Mouse Strain are Associated with an Inefficient Oxidative Phosphorylation System.

The MRL mice are resistant to a 12-week high fat diet (HFD) feeding protocol, with the proximal cause being an increased basal pAMPKT172 expression in the skeletal muscle. Here, we test if this lack of pathology extends to the liver at both the tissue and cellular levels and its correlation to pAMPKT172 levels. MRL and B6 mice were subjected to 12 weeks of diet intervention and tissues were either fixed for histology or snap-frozen for further processing (n= 3-6, per group). The HFD MRL mice remain insulin and glucose sensitive after 12 weeks of HFD. This phenomenon is correlated to increased liver pAMPKT172. The HFD-fed B6 control strain demonstrates the opposite trend with decreased pAMPKT172 expression after the HFD period. We have found further evidence of differential MRL metabolic adaptations. These differences include reduced glycogen content, reduced ectopic fat storage, and increased expression of Complex II (CII) and Complex V of the Electron Transport Chain (ETC). Whereas, B6 HFD control show unchanged glycogen content, increased ectopic fat and increased expression of Complex I and Complex V of the ETC. Taken together, the MRL adaptations point to an inefficient energy-producing phenotype that leads to glycogen depletion and attenuation of ectopic fat as secondary consequences with AMPK as the signaling mediator of these HFD- hepatic adaptations.

Recurrent Compartment Syndrome Leading to the Diagnosis of McArdle Disease: Case Report.

Glycogen storage disorders are rare diseases of metabolism that are usually diagnosed when a patient presents with recurrent fatigue, muscle pains, and exercise intolerance. In this case report, we describe a patient who presented with the second episode of nontraumatic compartment syndrome over a 10-year span. Because of the obscure presentation, we performed a muscle biopsy, which on muscle phosphorylase staining revealed McArdle disease (glycogen storage disease type V).

Successful metabolic adaptations leading to the prevention of high fat diet-induced murine cardiac remodeling.

BACKGROUND: Cardiomyopathy is a devastating complication of obesity and type 2 diabetes mellitus (T2DM). It arises even in patients with normoglycemia (glycosylated hemoglobin, A1C ≤7 %). As obesity and T2DM are approaching epidemic levels worldwide, the cardiomyopathy associated with these diseases must be therapeutically addressed. We have recently analyzed the systemic effects of a 12-week high fat diet (HFD) on wild type mice from the C57Bl/6 (B6) strain and the wild type super-healing Murphy Roths Large (MRL) mouse strain. The MRL HFD mice gained significantly more weight than their control diet counterparts, but did not present any of the other usual systemic T2DM phenotypes. METHODS: Cardiac pathology and adaptation to HFD-induced obesity in the MRL mouse strain compared to the HFD C57Bl/6 mice were thoroughly analyzed with echocardiography, histology, qPCR, electron microscopy and immunoblots. RESULTS: The obese HFD C57Bl/6 mice develop cardiac hypertrophy, cardiomyocyte lipid droplets, and initiate an ineffective metabolic adaptation of an overall increase in electron transport chain complexes. In contrast, the obese HFD MRL hearts do not display hypertrophy nor lipid droplets and their metabolism adapts quite robustly by decreasing pAMPK levels, decreasing proteins in the carbohydrate metabolism pathway and increasing proteins utilized in the ß-oxidation pathway. The result of these metabolic shifts is the reduction of toxic lipid deposits and reactive oxygen species in the hearts of the obese HFD fed MRL hearts. CONCLUSIONS: We have identified changes in metabolic signaling in obese HFD fed MRL mice that confer resistance to diabetic cardiomyopathy. The changes include a reduction of cardiac pAMPK, Glut4 and hexokinase2 in the MRL HFD hearts. Overall the MRL hearts down regulate glucose metabolism and favor lipid metabolism. These adaptations are essential to pursue for the identification of novel therapeutic targets to combat obesity related cardiomyopathy.

Biochemical and Functional Comparisons of mdx and Sgcg(-/-) Muscular Dystrophy Mouse Models.

Mouse models have provided an essential platform to investigate facets of human diseases, from etiology, diagnosis, and prognosis, to potential treatments. Muscular dystrophy (MD) is the most common human genetic disease occurring in approximately 1 in 2500 births. The mdx mouse, which is dystrophin-deficient, has long been used to model this disease. However, this mouse strain displays a rather mild disease course compared to human patients. The mdx mice have been bred to additional genetically engineered mice to worsen the disease. Alternatively, other genes which cause human MD have been genetically disrupted in mice. We are now comparing disease progression from one of these alternative gene disruptions, the γ-sarcoglycan null mouse Sgcg(-/-) on the DBA2/J background, to the mdx mouse line. This paper aims to assess the time-course severity of the disease in the mouse models and determine which is best for MD research. The Sgcg(-/-) mice have a more severe phenotype than the mdx mice. Muscle function was assessed by plethysmography and echocardiography. Histologically the Sgcg(-/-) mice displayed increased fibrosis and variable fiber size. By quantitative Evan's blue dye uptake and hydroxyproline content two key disease determinants, membrane permeability and fibrosis respectively, were also proven worse in the Sgcg(-/-) mice.

LMO7-null mice exhibit phenotypes consistent with emery-dreifuss muscular dystrophy.

INTRODUCTION: Mutations in the inner nuclear envelope protein emerin cause Emery-Dreifuss muscular dystrophy (EDMD), which is characterized by progressive skeletal muscle wasting, cardiac conduction defects, and tendon contractures. We previously showed that emerin binds directly to the transcription regulator Lmo7 and attenuates its activity to regulate the proper temporal expression of important myogenic differentiation genes. METHODS: The skeletal muscle and cardiac phenotypes were analyzed in a newly generated Lmo7-null mouse using histological analysis, echocardiography, and various neuromuscular tests to determine if Lmo7 was important for skeletal muscle and cardiac function. RESULTS: Lmo7-null mice had growth retardation, decreased fiber size, and impaired skeletal muscle and cardiac function. Lmo7-null mice also had lower levels of phosphorylated retinoblastoma (Rb), extracellular signal-regulated kinase, and c-Jun N-terminal kinase, which is consistent with altered Rb and mitogen-activated protein kinase signaling. CONCLUSIONS: These findings demonstrate that loss of Lmo7 in mice causes myopathic phenotypes similar to those seen in other EDMD mouse models.

The Murphy Roths Large (MRL) mouse strain is naturally resistant to high fat diet-induced hyperglycemia.

OBJECTIVE: Due to their previously identified naturally and chronically increased levels of skeletal muscle pAMPK we hypothesized and now investigated whether the MRL/MpJ (MRL) mice would be resistant to high fat diet (HFD)-induced metabolic changes. MATERIALS/METHODS: Three-week old male MRL and control C57Bl/6 (B6) mice were randomly assigned to 12weeks of high fat diets (HFD) or control diets (CD). Weekly animal masses and fasting blood glucose measurements were acquired. During the last week of diet intervention, fasted animals were subjected to glucose and insulin tolerance tests. At harvest, tissues were dissected for immunoblots and serum was collected for ELISA assays. RESULTS: The MRL mouse strain is known for its ability to regenerate ear punch wounds, cardiac cryoinjury, and skeletal muscle disease. Despite gaining weight and increasing their fat deposits the MRL mice were resistant to all other indicators of HFD-induced metabolic alterations assayed. Only the HFD-B6 mice displayed fasting hyperglycemia, hyperinsulinemia and hypersensitivity to glucose challenge. HFD-MRL mice were indistinguishable from their CD-MRL counterparts in these metrics. Skeletal muscles from the HFD-MRL contained heightened levels of pAMPK, even above their CD counterparts. CONCLUSIONS: The MRL mouse strain is the first naturally occurring mouse strain that we are aware of that is resistant to HFD-induced metabolic changes. Furthermore, the increased pAMPK suggests a proximal mechanism for these beneficial metabolic differences. We further hypothesize that these metabolic differences and plasticity provide the basis for the MRL mouse strain's super healing characteristics. This project's ultimate aim is to identify novel therapeutic targets, which specifically increase pAMPK.

Increased AMP-activated protein kinase in skeletal muscles of Murphy Roth Large mice and its potential role in altered metabolism.

Abstract Wild-type Murphy Roth Large (MRL) mice have long been investigated for their superior healing ability when subjected to various wound and disease models. Despite this long history, the mechanisms causing their extraordinary healing ability remain undefined. As we have recently demonstrated that MRL mice with muscular dystrophy are resistant to the associated fibrosis and the Heber-Katz group has demonstrated MRL mitochondrial mutations, we decided to investigate the skeletal muscle metabolic characteristics of the MRL mouse strain compared to the commonly utilized C57BL/6J control mouse strain. We now have evidence demonstrating an altered metabolism in the MRL quadriceps, triceps brachii, and diaphragm of 8-week-old animals compared to tissues from control animals. The MRL skeletal muscles have increased activated phosphorylated AMP-activated protein kinase (pAMPK). The increased pAMPK signaling coincides with increased skeletal muscle mitochondrial content. These metabolic changes may compensate for insufficient oxidative phosphorylation which is demonstrated by altered quantities of proteins involved in oxidative phosphorylation and ex vivo metabolic investigations. We also demonstrate that the MRL muscle cells have increased metabolic physiologic reserve. These data further the investigations into this important and unique mouse strain. Why the MRL mice have increased pAMPK and how increased pAMPK and the resultant metabolic alterations affect the healing ability in the MRL mouse strain is discussed. Understanding the molecular mechanisms surrounding the super healing characteristics of these mice will lead to relevant clinical intervention points. In conclusion, we present novel data of increased mitochondrial content, pAMPK, and glycolytic indicators in MRL skeletal muscles.

Early reexploration for suspected thrombosis after pancreas transplantation.

BACKGROUND: Graft thrombosis is the most common cause of early graft loss after pancreas transplantation. Early reexploration may permit salvage or timely removal of the thrombosed graft. METHODS: This was a retrospective review of 345 pancreas transplants performed at a single center between January 2003 and December 2009. Early reexploration was defined as within 1 week of pancreas transplantation. RESULTS: Of the 345 transplants, there were 35 early reexplorations. The graft was compromised in 20 cases (57%): 10 venous thromboses, 3 arterial thromboses, 2 combined arterial and venous thrombosis, 2 thromboses secondary to allograft pancreatitis, and 3 cases of positional ischemia without thrombosis. Of these allografts, three reperfused once repositioned and six were successfully thrombectomized for a graft salvage rate of 45%. One of the thrombectomized grafts remained perfused but never functioned and was removed at retransplantation. The 10 remaining compromised grafts that were deemed unsalvageable and required allograft pancreatectomy. Nine of these recipients were retransplanted (eight within 2 weeks) and one was not a retransplantation candidate. CONCLUSIONS: Reexploration for suspected graft thrombosis after pancreas transplantation resulted in a negative laparotomy rate of 43%, but permitted graft salvage in 45% of compromised grafts.