Rajiv Sood

Cultured epithelial autografts for coverage of large burn wounds in eighty-eight patients: The Indiana university experience

Since 1990, the authors have used a new technique for coverage of large burns, which begins with early tangential excision and coverage with cadaver allograft (A), followed by placement of cultured epithelial autograft (CEA) onto an allodermis base (CEA/A). They present their 18-year experience (1990–present) using CEA in 88 patients (20 children and 68 adults) with age range of 6 months to 73 years. A review of prospectively collected data was conducted on adult and pediatric patients grafted with CEA at the Indiana University Medical Center for definitive wound coverage (TBSA 28–98%). These patients were followed up for 3 to 90 months. Complications, take rates, and outpatient follow-ups were noted. The mean final take rate of CEA/A was 72.7%, and the overall patient survival rate was 91% (80 of 88 patients). Complications were classified as early and late, they included: (early) blistering and shearing (31%), pruritis and itching (4.7%), (late) CEA loss (2 patients, 2.3%), and wound contractures (66%). Contracture releases were performed on 32 patients (36%); of which, 18 were children (56%). Cultured keratinocytes provide an excellent alternative or adjunct to conventional split-thickness skin grafting in treating large burn wounds. A dedicated team of physicians, nurses, and therapists well rehearsed in CEA care are vital for success in keratinocyte grafting. The final graft take of 72.7% with a 91% overall survival rate gives much optimism for continuing to use CEA in critically burned patients.

Lymphoscintigraphy with sentinel lymph node biopsy in cutaneous merkel cell carcinoma

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy characterized by an aggressive clinical behavior with high rates of locoregional and systemic recurrence. Regional disease and distant metastases are associated with poor prognosis. Despite a predisposition of MCC to spread via the lymphatics, prophylactic lymph node dissection in the absence of clinically apparent lymph node involvement is controversial. The value of lymphoscintigraphy in cutaneous melanoma is established in lesions with ambiguous lymphatic drainage patterns. When used with sentinel lymph node biopsy (SLNB), it can identify subjects with occult regional node metastasis. The authors present 2 patients with MCC who underwent regional node staging with lymphoscintigraphy-directed SLNB. Both patients had sentinel nodes that were positive for metastatic disease. In patients with MCC, minimally invasive regional node staging SLNB may be useful in limiting the sequelae of routine lymphadenectomies. Whether early identification and treatment of patients with occult regional node disease can influence survival in MCC is not known.

Effects of reduction mammaplasty on pulmonary function and symptoms of macromastia.

&NA; A number of studies have documented subjective improvement in somatic and psychological symptoms following breast reduction surgery. Objective data demonstrating improved postoperative function have been more difficult to assess, and particularly with respect to pulmonary function, the results have been contradictory. In this prospective study, patients completed a comprehensive preoperative questionnaire modified from the American Thoracic Society Division of Lung Diseases Epidemiology Standardization Project (1978). This questionnaire noted subjective pulmonary symptoms and pulmonary medical history. In addition, subjective symptoms related to breast size, including back and neck pain and shoulder pain and grooving, and a subjective evaluation of body image, were evaluated. All subjects received preoperative pulmonary function testing, including spirometry, lung volume measurements, and measurement of peak inspiratory and expiratory flow rates and pressures. Eight weeks after breast reduction, a repeat questionnaire and pulmonary function testing were administered. Preoperative and postoperative pulmonary function values were compared using Cochran‐Mantel‐Haenszel tests, and correlations were tested between changes in pulmonary function test values and subjective symptom improvement. Forty‐four patients underwent an average of 2228‐g bilateral reduction. All of these patients had their surgical procedures preauthorized as medically necessary by their insurance carriers. All subjective parameters examined were statistically significantly improved following breast reduction (p < 0.001). Of the 17 patients with preoperative complaints of shortness of breath, all noted significant improvement following breast reduction surgery (p < 0.001). Of the objective pulmonary criteria evaluated, inspiratory capacity, peak expiratory flow rate, and maximal voluntary ventilation showed a statistically significant improvement following surgery (p < 0.05). These changes correlated with body mass index; the greater the index, the greater the change in maximal voluntary ventilation and peak expiratory flow rate. Smokers in this group had the largest change in maximal voluntary ventilation (p < 0.008). No correlation could be found between preoperative pulmonary symptoms, a single subjective symptom, or grams of breast weight reduction and changes in pulmonary function tests. The results show that pulmonary parameters, related primarily to work of breathing (inspiratory capacity, maximal voluntary ventilation, peak expiratory flow rate), were statistically improved following breast reduction surgery, and these changes correlated with body mass index. (Plast. Reconstr. Surg. 111: 688, 2003.)

Recombinant thrombin: safety and immunogenicity in burn wound excision and grafting.

This study evaluated the safety, immunogenicity, and hemostatic effect of recombinant human Thrombin (rThrombin), in patients undergoing skin grafting for burns. This was a phase 2 multiple site, single-arm, open-label study in patients receiving partial- or full-thickness autologous grafts. rThrombin was applied using a spray applicator to newly excised wounds of 1 to 4% body surface area at 5 minutes intervals for up to 20 minutes, after point source bleeding was stopped. Adverse events, skin graft survival, and formation of anti-rThrombin antibodies were measured at baseline and Day 29. There were no deaths or study drug discontinuations. Adverse events occurred in 63 of 72 patients (88%), and were typical of sequelae of skin grafting. Hemostasis was achieved within 20 minutes after application of rThrombin in 65 of 71 patients (91.5%). Skin graft failure occurred in 4 patients (6%). At the day 29 evaluation, for those patients who returned, 88.9% had ≥90% graft survival. One patient (1 of 70, 1.4%) had specific, low titer antibodies to rThrombin at baseline, but no increase in titer posttreatment; a second patient (1 of 62, 1.6%), developed antibodies to rThrombin at day 29. None of the antibodies neutralized native human thrombin. In excised burn wounds, hemostasis at 20 minutes was achieved in 91.5% of patients and skin graft survival was excellent. There was a low rate of antibodies to rThrombin at baseline (1.4%) and a low rate of anti-rThrombin antibody formation at day 29 (1.6%). rThrombin was well tolerated when administered with a pump spray.

Risk factors for predicting surgical salvage of sternal wound-healing complications.

A retrospective study was performed to determine whether clinical factors can predict which complicated poststernotomy wounds can be managed successfully by debridement and reclosure, and which wounds require a muscle flap for healing. Between January 1990 and December 1996, 3,435 median sternotomies were performed at Indiana University Medical Center and affiliated hospitals. A total of 91 patients (2.6%) were reoperated for sternal wound-healing complications. Seventy-six patients (83.5%) underwent debridement and rewiring, and 15 patients (16.5%) underwent primary flap coverage. Of the 76 patients who underwent initial rewiring, 45 (59%) healed and 31 (41%) required additional operative procedures. Of the 31 rewiring failures, 26 patients (84%) were healed with muscle flaps and 4 patients (13%) were managed with a second successful rewiring. The following clinical factors were correlated with operative procedure and outcome: history of smoking, chronic obstructive pulmonary disease, steroid use, previous sternotomy, age, diabetes, harvest of the left or right internal mammary artery (IMA), emergency operation, operation time, pump time, cross-clamp time, ischemic time, coronary artery bypass grafting alone versus combined with a valve replacement, positive wound cultures, positive blood cultures, elevated white blood cell count, and fever. When comparing patients with successful rewiring with those who had a failed rewiring, positive wound and blood cultures were significant risk factors (p < 0.05) on univariate analysis. Presence of a positive wound culture was significant on multivariate analysis. When comparing risk factors in patients who were rewired successfully versus all patients who had muscle flap coverage, the presence of a positive blood culture was significant on both univariate and multivariate analyses. We conclude patients most likely to fail rewiring and to require muscle flap closure are those with infected wounds, positive blood cultures, and possibly left IMA bypasses.

Coverage of large pediatric wounds with cultured epithelial autografts in congenital nevi and burns: Results and technique

The use of cultured epithelial autografts (CEA) for the treatment of large burn wounds has gained popularity in recent years. This technique may circumvent the restrictions of limited donor site availability and hasten permanent wound coverage for large TBSA burns. The availability of a large amount of skin from a small donor site with the promise of permanent wound coverage suggests its use in other conditions such as giant congenital nevi (GCN) as well. The risk of malignant transformation of GCN to melanoma although somewhat controversial is significant enough to warrant early excision in childhood. Cultured keratinocytes may provide one-stage coverage of these large wounds, lessening the number of surgeries and the inherent staging problems of tissue expansion or autografting. A retrospective single institution review of was done for 29 children (20 burns and 9 patients with GCN) who underwent coverage of their large surface area wounds with CEA over an 18-year period. Excellent take rates were noted; 76.4% for burn patients and 66% for patients with GCN. Several strategies in preoperative, perioperative, and postoperative care have been standardized and have helped improve outcome. The keys to success with the CEA technique have been aggressive control of wound sepsis, surgical technique, specific use of topical antimicrobials, dressings, and the standardization of nursing and physiotherapy care. Although the cost of CEA is high, the benefits to patient care make this technique an appealing choice for large wound coverage in the pediatric population.

Neuroleptic malignant syndrome associated with metoclopramide in a burn patient

Neuroleptic malignant syndrome (NMS) is an uncommon, potentially fatal syndrome that occurs with the use of neuroleptic medications. In view of the rarity of this syndrome and the overlap with the pathophysiologic manifestations of a burn, the burn surgeon may not readily recognize NMS on presentation. We describe the case of a 27-year-old man with 15% TBSA burns who developed NMS as a result of metoclopramide use. Recognition and treatment resulted in a prompt resolution of symptoms. Initial treatment should include immediate withdrawal of all neuroleptic agents, measures aimed at decreasing body temperature, supportive care, and restoration of dopamine balance. Various authors have advocated treatment with various medications, including benzodiazepines, dantrolene, and dopaminergic agents. It is important for burn unit personnel to be aware of this syndrome because the early institution of therapy can be life saving.

A systematic review of vancomycin dosing and monitoring in burn patients

Vancomycin pharmacokinetics are significantly altered following burn injury, requiring a higher total daily dose to achieve adequate serum concentrations. Wide interpatient variability necessitates close, frequent monitoring of serum concentrations for efficacy and safety. The aim of this study is to systematically evaluate published data regarding vancomycin pharmacokinetic alterations in burn patients, to determine whether evidence-based recommendations for dosing and monitoring can be formulated, and to identify future research opportunities. The systematic review included studies published in English, involved human subjects with at least a 10% TBSA burn who received vancomycin intravenously, and obtained serum concentration(s). Database searches returned 130 titles for review. Twelve studies met a priori inclusion criteria. The most common dosing regimens in adult and pediatric patients were 5 to 20 mg/kg/dose every 6 to 8 hours. Mean trough concentrations were 7.24 ± 1.5 mg/L. Only 12.5% of reported trough concentrations were within the currently recommended range of 10 to 20 mg/L. Although no consistent dosing recommendations were provided, all studies recommended close monitoring of trough concentrations. Based on limited clinical outcomes data, standardized recommendations for vancomycin dosing and monitoring in burn patients cannot be made. Higher total daily doses (40–70 mg/kg/day) and increased dosing frequency (every 6–12 hr in adults) may be necessary to achieve current target trough concentrations. Future research goals include prospective investigation of clinical outcomes related to initial doses, loading doses, monitoring peak and trough concentrations, and adverse effects. Further data on the effects of burn size, concomitant diseases, inhalation injury, and time since injury may improve the accuracy of vancomycin dosing in burn patients.

A paper-based in vitro model for on-chip investigation of the human respiratory system

Culturing cells at the air-liquid interface (ALI) is essential for creating functional in vitro models of lung tissues. We present the use of direct-patterned laser-treated hydrophobic paper as an effective semi-permeable membrane, ideal for ALI cell culture. The surface properties of the paper are modified through a selective CO2 laser-assisted treatment to create a unique porous substrate with hydrophilic regions that regulate fluid diffusion and cell attachment. To select the appropriate model, four promising hydrophobic films were compared with each other in terms of gas permeability and long-term strength in an aqueous environment (wet-strength). Among the investigated substrates, parchment paper showed the fastest rate of oxygen permeability (3 times more than conventional transwell cell culture membranes), with the least variation in its dry and wet tensile strengths (124 MPa and 58 MPa, remaining unchanged after 7 days of submersion in PBS).The final paper-based platform provides an ideal, robust, and inexpensive device for generating monolayers of lung epithelial cells on-chip in a high-throughput fashion for disease modelling and in vitro drug testing.

Mandibular Distraction Osteogenesis in Low-Weight Neonates with Robin Sequence: Is It Safe?

Background: The aim of this study was to evaluate the efficacy, safety profile, and complications associated with mandibular distraction osteogenesis performed in infants weighing less than 4 kg with Robin sequence. Methods: An 11-year retrospective review of all infants (younger than 6 months) with mandibular distraction osteogenesis–treated Robin sequence was performed. Patients weighing less than 4 kg (experimental) and 4 kg or more (control) who underwent mandibular distraction osteogenesis were compared. Demographics, medical comorbidities, improvement in apnea/hypopnea index, need for tracheostomy, repeated distraction, and complications were evaluated. Results: One hundred twenty-one patients underwent mandibular distraction osteogenesis. Eighty-one patients weighed less than 4 kg and 40 weighed 4 kg or more. The mean follow-up was 2.8 years in patients weighing less than 4 kg and 3.0 years in the control group. Mean age and weight at the time of distraction were 23 days and 3.1 kg, respectively, in the study group; and 2.7 years and 11 kg, respectively, in the control group. There was no significant difference in success of mandibular distraction osteogenesis to treat airway obstruction in the group weighing less than 4 kg compared with the control group (92.6 percent versus 88.9 percent; p = 0.49). The most common complication in each group was surgical-site infection (9.9 percent and 20.0 percent; p = 0.15). Overall complication rates were similar between the two groups (17.3 percent versus 25.0 percent; p = 0.34). The rates of repeated distraction were similar between the two groups (6.3 percent and 13.5 percent; p = 0.28). Conclusions: Mandibular distraction osteogenesis is a safe and effective treatment modality for infants weighing less than 4 kg with severe airway obstruction. The efficacy, safety, and complication profiles are not significantly different from those of larger patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.