Karim A. Sarhane

Injectable bioadhesive hydrogels with innate antibacterial properties

Surgical site infections cause significant postoperative morbidity and increased healthcare costs. Bioadhesives used to fill surgical voids and support wound healing are typically devoid of antibacterial activity. Here, we report novel syringe-injectable bioadhesive hydrogels with inherent antibacterial properties prepared from mixing polydextran aldehyde (PDA) and branched polyethylenimine (PEI). These adhesives kill both Gram-negative and Gram–positive bacteria, while sparing human erythrocytes. An optimal composition of 2.5 wt % oxidized dextran and 6.9 wt % PEI sets within seconds forming a mechanically rigid (~1700 Pa) gel offering a maximum adhesive stress of ~ 2.8 kPa. A murine infection model showed that the adhesive is capable of killing S. pyogenes introduced subcutaneously at the bioadhesive’s surface, with minimal inflammatory response. The adhesive was also effective in a cecal ligation and puncture model, preventing sepsis and significantly improving survival. These bioadhesives represent novel, inherently antibacterial materials for wound filling applications.

A Critical Analysis of Rejection in Vascularized Composite Allotransplantation: Clinical, Cellular and Molecular Aspects, Current Challenges, and Novel Concepts

Advances in microsurgical techniques and immunomodulatory protocols have contributed to the expansion of vascularized composite allotransplantation (VCA) with very encouraging immunological, functional, and cosmetic results. Rejection remains however a major hurdle that portends serious threats to recipients. Rejection features in VCA have been described in a number of studies, and an international consensus on the classification of rejection was established. Unfortunately, current available diagnostic methods carry many shortcomings that, in certain cases, pose a great diagnostic challenge to physicians especially in borderline rejection cases. In this review, we revisit the features of acute skin rejection in hand and face transplantation at the clinical, cellular, and molecular levels. The multiple challenges in diagnosing rejection and in defining chronic and antibody-mediated rejection in VCA are then presented, and we finish by analyzing current research directions and novel concepts aiming at improving available diagnostic measures.

Transoral Robotic Reconstructive Surgery

Transoral robotic surgery (TORS) has emerged as a technique that allows head and neck surgeons to safely resect large and complex oropharyngeal tumors without dividing the mandible or performing a lip-split incision. These resections provide a reconstructive challenge because the cylinder of the oropharynx remains closed and both physical access and visualization of oropharyngeal anatomy is severely restricted. Transoral robotic reconstruction (TORRS) of such defects allows the reconstructive surgeon to inset free flaps or perform adjacent tissue transfer while seeing what the resecting surgeon sees. Early experience with this technique has proved feasible and effective. Robotic reconstruction has many distinct advantages over conventional surgery, and offers patients a less morbid surgical course. In this review, we discuss the clinical applicability of transoral robotic surgery in head and neck reconstruction, highlighting the benefits and limitations of such an approach, and outlining the guidelines for its utilization.

Mesenchymal Stem Cells Enhance Nerve Regeneration in a Rat Sciatic Nerve Repair and Hindlimb Transplant Model

This study investigates the efficacy of local and intravenous mesenchymal stem cell (MSC) administration to augment neuroregeneration in both a sciatic nerve cut-and-repair and rat hindlimb transplant model. Bone marrow-derived MSCs were harvested and purified from Brown-Norway (BN) rats. Sciatic nerve transections and repairs were performed in three groups of Lewis (LEW) rats: negative controls (n = 4), local MSCs (epineural) injection (n = 4), and systemic MSCs (intravenous) injection (n = 4). Syngeneic (LEW-LEW) (n = 4) and allogeneic (BN-LEW) (n = 4) hindlimb transplants were performed and assessed for neuroregeneration after local or systemic MSC treatment. Rats undergoing sciatic nerve cut-and-repair and treated with either local or systemic injection of MSCs had significant improvement in the speed of recovery of compound muscle action potential amplitudes and axon counts when compared with negative controls. Similarly, rats undergoing allogeneic hindlimb transplants treated with local injection of MSCs exhibited significantly increased axon counts. Similarly, systemic MSC treatment resulted in improved nerve regeneration following allogeneic hindlimb transplants. Systemic administration had a more pronounced effect on electromotor recovery while local injection was more effective at increasing fiber counts, suggesting different targets of action. Local and systemic MSC injections significantly improve the pace and degree of nerve regeneration after nerve injury and hindlimb transplantation.

Discrepancy in Initial Pediatric Burn Estimates and Its Impact on Fluid Resuscitation

One of the fundamental aspects of initial burn care is the ability to accurately measure the TBSA of injured tissue. Discrepancies between initial estimates of burn size and actual TBSA (determined at the burn unit) have long been reported. These inconsistencies have the potential for unnecessary patient transfer and inappropriate fluid administration which may result in morbidity. In an effort to study these inconsistencies and their impact on initial care, we evaluated the differences between initial TBSA estimates and its impact on fluid resuscitation at an American Burn Association–verified pediatric burn center. A prospective observational study of 50 consecutive burn patients admitted to Shriner’s Hospital for Children in Boston, Massachusetts, between October 2011 and April 2012 was performed. Data collected included age, mechanism of burn injury, type of referral center, referring hospital TBSA, and volume of fluid administration as well as admission TBSA and volume of fluid administration. Determination of over or under resuscitation was based on comparing the amount of fluids received at the referral center to that received at the pediatric burn center. A total of 50 patients were admitted during the 7-month study period. The average age was 4.1 years old (25 days–16 years) and the average TBSA was 2.5% (0.25–55%). There were significant differences in the TBSA calculations between referring centers and the pediatric burn center. Overestimation of scald and contact burn size (P < .05) was noted with no difference in flame burn size estimation. Community referrals were more likely than tertiary centers to overestimate TBSA (P < .05 vs P = .29). Overall, 59% of study patients were administered more fluid at the referring hospital than would have been expected by the burn size calculated at our facility. Inconsistencies with the estimation of TBSA burn between referring hospitals and tertiary referral centers remains a problem in pediatric patients and may lead to inappropriate resuscitation. This study highlights the continued need for educational outreach programs and for the provision of novel resources to initial burn providers. Additional support through online resources (eg, Lund–Browder diagram) and remotely assisting providers during their TBSA measurements are potential options which may help to improve the initial care of burn patients.

Pyoderma Gangrenosum After Breast Surgery: Diagnostic Pearls and Treatment Recommendations Based on a Systematic Literature Review.

BackgroundPyoderma gangrenosum (PG) is a rare cutaneous disorder that poses a diagnostic challenge in the postoperative period. A systematic literature review was performed to determine distinguishing characteristics of PG in the setting of breast surgery that can facilitate timely diagnosis and appropriate treatment. MethodsPubMed, EMBASE, Scopus, and Web of Science databases were systematically searched for articles with cases of PG occurring after breast surgery. Forty-three relevant articles, including 49 case reports, were identified. ResultsPG manifested bilaterally in 30 of 34 cases (88%) in which bilateral surgery was performed. Abdominal wounds were present in 6 of 7 cases in which an abdominal donor site was used for breast reconstruction. Nipples were spared from wound involvement in 33 of 37 cases (89%) in which nipples were present after surgery. Presence of fever was noted in 27 cases (55%) and leukocytosis in 21 cases (43%). A total of 33 patients (67%) underwent wound debridement. Successful medical treatment most commonly involved steroids (41 cases, 84%) and cyclosporine (10 cases, 20%). ConclusionsPertinent clinical features were identified that may aid in timely diagnosis and treatment of PG after breast surgery. Appearance of discrete wounds involving multiple surgical sites that surround but spare the nipples should raise suspicion for PG rather than infection or ischemia, even with concomitant fever and leukocytosis. Wound debridement should be minimized and skin grafting considered only after medical therapy is initiated. Cognizance of these features may enable prompt therapeutic intervention that minimizes morbidity and improves outcomes.

The emerging role of tissue plasminogen activator in the management of severe frostbite.

This article presents a small case series demonstrating clinical success with thrombolytic agents for severe frostbite injury to the lower extremities. The authors report three patients with severe frostbite injuries to their distal lower extremities who were managed with urgent interventional radiology and intra-arterial tissue plasminogen activator infusion according to a prespecified protocol. Limbs and digits were successfully salvaged and patients returned to normal activity within 2 weeks. Although further studies are needed, results of this study support a new approach in the management of frostbite: from conservative management and observation to urgent interventional radiology and possible tissue plasminogen activator infusion. A protocol for the management of such injuries is presented.

Neoadjuvant Chemotherapy and Short-term Morbidity in Patients Undergoing Mastectomy With and Without Breast Reconstruction

IMPORTANCE Neoadjuvant chemotherapy (NC) is increasingly being used in patients with breast cancer, and evidence-based reports related to its independent effects on morbidity after mastectomy with immediate breast reconstruction are limited. OBJECTIVE To determine the effect of NC on 30-day postoperative morbidity in women undergoing mastectomy with or without immediate breast reconstruction. DESIGN, SETTING, AND PARTICIPANTS All women undergoing mastectomy with or without immediate breast reconstruction from January 1, 2005, through December 31, 2011, at university and private hospitals internationally were analyzed using the American College of Surgeons National Surgical Quality Improvement Program 2005-2011 databases. Patients who received NC were compared with those without a history of NC to estimate the relative odds of 30-day postoperative overall, systemic, and surgical site morbidity using model-wise multivariable logistic regression. EXPOSURE Neoadjuvant chemotherapy. MAIN OUTCOMES AND MEASURES Thirty-day postoperative morbidity (overall, systemic, and surgical site). RESULTS Of 85,851 women, 66,593 (77.6%) underwent mastectomy without breast reconstruction, with 2876 (4.3%) receiving NC; 7893 patients were excluded because of missing exposure data. The immediate breast reconstruction population included 19,258 patients (22.4%), with 820 (4.3%) receiving NC. After univariable analysis, NC was associated with a 20% lower odds of overall morbidity in the group undergoing mastectomy without breast reconstruction (odds ratio [OR], 0.80; 95% CI, 0.71-0.91) but had no significant effect in the immediate breast reconstruction group (OR, 0.98; 95% CI, 0.79-1.23). After adjustment for confounding, NC was independently associated with lower overall morbidity in the group undergoing mastectomy without breast reconstruction (OR, 0.61; 95% CI, 0.51-0.73) and the immediate tissue expander reconstruction subgroup (OR, 0.49; 95% CI, 0.30-0.84). Neoadjuvant chemotherapy was associated with decreased odds of systemic morbidity in 4 different populations: complete sample (OR, 0.59; 95% CI, 0.49-0.71), mastectomy without breast reconstruction (OR, 0.59; 95% CI, 0.48-0.72), any immediate breast reconstruction (OR, 0.57; 95% CI, 0.37-0.88), and the tissue expander subgroup (OR, 0.41; 95% CI, 0.23-0.72). CONCLUSIONS AND RELEVANCE Our study supports the safety of NC in women undergoing mastectomy with or without immediate breast reconstruction. Neoadjuvant chemotherapy is associated with lower overall morbidity in the patients undergoing mastectomy without breast reconstruction and in those undergoing tissue expander breast reconstruction. In addition, the odds of systemic morbidity were decreased in patients undergoing mastectomy with and without immediate breast reconstruction. The mechanisms behind the protective association of NC remain unknown and warrant further investigation.

De-epithelialized dermal barrier for a safe immediate prosthetic breast reconstruction post circumvertical skin sparing/reducing mastectomy (SSM/SRM)

BackgroundSkin-sparing mastectomy (SSM) and skin-reducing mastectomy (SRM) with immediate breast reconstruction (IBR) is oncologically safe and has become increasingly popular as an effective treatment for patients with early stage breast cancer requiring mastectomy. Cosmetic appearance following IBR depends largely on the location of the skin incision, the quantity of breast skin left as well as the pocket for prosthetic placement, whether submuscular, subcutaneous, or both. SRM with Le Jour pattern skin excision has already been described in conjunction with autogenous tissue reconstruction. This technique is not recommended for implant-based IBR because any compromise of skin viability can result in exposure of the implant or expander.MethodsWe propose SRM with a circumvertical skin excision pattern and IBR comprising a de-epithelialized dermal barrier to reinforce the vertical suture line. We performed this technique on 10 breast cancer patients.ResultsEight patients underwent SSM with IBR using textured anatomical cohesive gel implants. One patient had Becker tear drop implants for both breasts (right SSM with IBR, and delayed left breast reconstruction); and the last patient had completion mastectomies with IBR using Becker tear drop implants. None of the patients developed complications.ConclusionThis technique is reliable and safe for implant-based IBR, ensuring minimal scarring and pleasing aesthetic results.Level of Evidence: Level IV, therapeutic study.

Growth Hormone Therapy Accelerates Axonal Regeneration, Promotes Motor Reinnervation, and Reduces Muscle Atrophy following Peripheral Nerve Injury.

Background: Therapies to improve outcomes following peripheral nerve injury are lacking. Prolonged denervation of muscle and Schwann cells contributes to poor outcomes. In this study, the authors assess the effects of growth hormone therapy on axonal regeneration, Schwann cell and muscle maintenance, and end-organ reinnervation in rats. Methods: Male Sprague-Dawley rats underwent sciatic nerve transection and repair and femoral nerve transection without repair and received either daily subcutaneous growth hormone (0.4 mg/day) or no treatment (n = 8 per group). At 5 weeks, the authors assessed axonal regeneration within the sciatic nerve, muscle atrophy within the gastrocnemius muscle, motor endplate reinnervation within the soleus muscle, and Schwann cell proliferation within the denervated distal femoral nerve. Results: Growth hormone–treated animals demonstrated greater percentage increase in body mass (12.2 ± 1.8 versus 8.5 ± 1.5; p = 0.0044), greater number of regenerating myelinated axons (13,876 ± 2036 versus 8645 ± 3279; p = 0.0018) and g-ratio (0.64 ± 0.11 versus 0.51 ± 0.06; p = 0.01), greater percentage reinnervation of motor endplates (75.8 ± 8.7 versus 38.2 ± 22.6; p = 0.0008), and greater muscle myofibril cross-sectional area (731.8 ± 157 &mgr;m versus 545.2 ± 144.3 &mgr;m; p = 0.027). Conclusions: In male rats, growth hormone therapy accelerates axonal regeneration, reduces muscle atrophy, and promotes muscle reinnervation. Growth hormone therapy may also maintain proliferating Schwann cells in the setting of prolonged denervation. These findings suggest potential for improved outcomes with growth hormone therapy after peripheral nerve injuries.