Artificial dermis for major burns. A multi-center randomized clinical trial.

This communication presents an 11-center prospective randomized trial using the artificial dermis invented by Burke and Yannas. Patients with life-threatening burns who underwent primary excision and grafting within 7 days of injury had comparable sites randomized to receive either the artificial dermis (study site) or the investigator's usual skin grafting material (control site). Control materials were autograft, allograft, xenograft, or a synthetic dressing. Epidermal grafts were applied to the study site during a second operation, and surviving patients were followed for 1 year after grafting. One hundred thirty-nine sites on 106 patients were studied. Mean burn size was 46.5 +/- 15% mean total body surface (TBSA). Overall mortality was 13%, and mean hospital stay was 68 +/- 45 days. Median artificial dermis take was 80% compared with 95% for all comparative sites, but the take was equivalent to that of all nonautograft control materials. Results with the artificial dermis improved slightly as the investigators became more familiar with the material. Donor site thickness for the study site averaged .006' +/- .002' compared to .013' +/- .018' for control (p less than .0001) and the epidermal donor site healed an average of 4 days sooner (10 +/- 6 vs. 14 +/- 8 days) (p less than .0001). As the wounds matured during the first year, both patients and surgeons felt that both sites became more comparable in appearance and function. At the completion of the study, there was less hypertrophic scarring of the artificial dermis, and more patients preferred the artificial dermis to the control graft. Artificial dermis with an epidermal graft provides a permanent cover that is at least as satisfactory as currently available skin grafting techniques, and uses donor grafts that are thinner and donor sites that heal faster.     

Inpatient depression in persons with burns.

In this investigation the authors collected data regarding trait anxiety, well-being, and depression from 209 men and women who had been screened for prior psychiatric diagnosis and treated in an acute-care setting for burn injuries. Well-being was measured in reference to the month before the burn injury, whereas level of depression was self-rated by patients within 2 days of hospitalization, 5 days later, and 5 days after that. Ratings of depression were also obtained 1 month after hospital discharge. Results indicated that few patients rated their depression as severe at any point in time. Depression scores decreased significantly across the hospitalization period and were correlated with burn size, trait anxiety, and well-being. Depression ratings after discharge were significantly related to depression scores obtained at the end of the inpatient phase of the study. Although most patients did not report experiencing severe levels of depression, the stability of scores across time suggests the usefulness of early screening procedures. Catching such problems early may head off longer-term difficulties.     

A series of potent HIV-1 protease inhibitors containing a hydroxyethyl secondary amine transition state isostere: synthesis, enzyme inhibition, and antiviral activity.

A series of HIV-1 protease inhibitors containing a novel hydroxyethyl secondary amine transition state isostere has been synthesized. The compounds exhibit a strong preference for the (R) stereochemistry at the transition state hydroxyl group. Molecular modeling studies with the prototype compound 11 have provided important insights into the structural requirements for good inhibitor-active site binding interaction. N-Terminal extension of 11 into the P2-P3 region led to the discovery of 19, the most potent enzyme inhibitor in the series (IC50 = 5.4 nM). 19 was shown to have potent antiviral activity in cultured MT-4 human T-lymphoid cells. Comparison of analogs of 19 with analogs of 1 (Ro31-8959) demonstrates that considerably different structure-activity relationships exist between these two subclasses of hydroxyethylamine HIV-protease inhibitors.     

Laser Doppler monitoring of microcirculatory changes in acute burn wounds

Because burns are dynamic wounds that can change in apparent depth during the first 72 hours, we asked whether measuring changes in cutaneous blood flow might help predict the ultimate fate of burns that were not obviously shallow or deep. A laser Doppler flowmeter was used to study cutaneous perfusion for at least 72 hours in partial-thickness wounds on patients with burns of less than 15% TBSA and in experimental wounds of similar size on rats. Clinical wounds that healed without grafting consistently showed elevated perfusion levels which increased further within 72 hours, whereas wounds eventually requiring grafting experienced lower perfusion levels with no obvious pattern of increase. Differences between average flow levels for healing and nonhealing burns were statistically significant throughout the study period. Perfusion levels in experimental wounds were stratified according to burn severity, with shallower wounds showing a pattern of increase similar to the clinical wounds.     

Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.     

Hydronephrosis after aorto bifemoral graft surgery: a marker for late graft complications

Ureteral obstructions are serious late complications after aortoiliac reconstructive vascular surgery, which lead to loss of kidney function if they remain untreated. One case report serves to describe the incidence, aetiology, clinical presentation and treatment options of an obstructive uropathy following graft surgery. Hydronephrosis due to a ureteral obstruction is considered as a "marker" of graft complication. Therefore, ultrasound examination and close follow-up beyond 1 year are recommended in all patients who undergo aortoiliac surgery.     

Current status of burn wound pathophysiology

Healing is a continuum that can be unpredictable. Despite many advances and understanding of the multiple cellular processes and molecules involved in burn wound healing, physicians and patients have yet to reap the full benefit of this knowledge. The advances have occurred in a very short period, and with the exponential growth of molecular biology techniques and transgenic animal models, our understanding and treatment of burn wound healing could change exponentially over the next 10 years. The goal must be to continue to improve functional outcomes for burn survivors just as we have conquered critical care management for acutely injured burn patients.     

Modern techniques for wound coverage of the thermally injured upper extremity

The use of flaps; synthetic, dermal analogues; cultured skin substitutes; or a combination of these may one day help return severely burned arms to normal function and appearance. The complexity and expense of these alternatives limits their use in commonplace burns. As the techniques are refined with increased experience, so also will the roles for each of these options. Fortunately, an excellent result is still possible in most situations using simple autograft. The availability of these numerous choices to acutely cover the thermally injured upper extremity should not distract us from the gold standard of split-thickness skin graft (Fig. 7).     

Guide to designing, conducting, publishing and communicating results of clinical studies involving probiotic applications in human participants

The heterogeneity of human clinical trials to assess the effectiveness of probiotics presents challenges regarding interpretation and comparison. Evidence obtained from clinical trials among a population with a disease or specific risk factors may not be generalizable to healthy individuals. The evaluation of interventions in healthy persons requires careful selection of outcomes due to the absence of health indicators and the low incidence of preventable conditions. Given the tremendous resources invested in such trials, development of consistent approaches to assessing the effectiveness of probiotics would be beneficial. Furthermore, the reporting, presentation and communication of results may also affect the validity of the scientific evidence obtained from a trial. This review outlines the challenges associated with the design, implementation, data analysis and interpretation of clinical trials in humans involving probiotics. Best practices related to their design are offered along with recommendations for enhanced collaboration to advance research in this emerging field.