Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial.

BACKGROUND: In a phase 2 study, kidney transplant recipients of low immunologic risk who switched from a calcineurin inhibitor (CNI) to belatacept had improved kidney function at 12 months postconversion versus those continuing CNI therapy, with a low rate of acute rejection and no transplant loss. STUDY DESIGN: 36-month follow-up of the intention-to-treat population. SETTING & PARTICIPANTS: CNI-treated adult kidney transplant recipients with stable transplant function (estimated glomerular filtration rate [eGFR], 35-75mL/min/1.73m2). INTERVENTIONS: At 6 to 36 months posttransplantation, patients were randomly assigned to switch to belatacept-based immunosuppression (n=84) or continue CNI-based therapy (n=89). OUTCOMES: Safety was the primary outcome. eGFR, acute rejection, transplant loss, and death were also assessed. MEASUREMENTS: Treatment exposure-adjusted incidence rates for safety, repeated-measures modeling for eGFR, Kaplan-Meier analyses for efficacy. RESULTS: Serious adverse events occurred in 33 (39%) belatacept-treated patients and 36 (40%) patients in the CNI group. Treatment exposure-adjusted incidence rates for serious infections (belatacept vs CNI, 10.21 vs 9.31 per 100 person-years) and malignancies (3.01 vs 3.41 per 100 person-years) were similar. More patients in the belatacept versus CNI group had any-grade viral infections (14.60 vs 11.00 per 100 person-years). No posttransplantation lymphoproliferative disorder was reported. Belatacept-treated patients had a significantly greater estimated gain in mean eGFR (1.90 vs 0.07mL/min/1.73m2 per year; P for time-by-treatment interaction effect = 0.01). The probability of acute rejection was not significantly different for belatacept (8.38% vs 3.60%; HR, 2.50 [95% CI, 0.65-9.65; P=0.2). HR for the comparison of belatacept to the CNI group for time to death or transplant loss was 1.00 (95% CI, 0.14-7.07; P=0.9). LIMITATIONS: Exploratory post hoc analysis with a small sample size. CONCLUSIONS: Switching patients from a CNI to belatacept may represent a safe approach to immunosuppression and is being further explored in an ongoing phase 3b trial.

Modulation of wound healing and scar formation by MG53 protein-mediated cell membrane repair.

Cell membrane repair is an important aspect of physiology, and disruption of this process can result in pathophysiology in a number of different tissues, including wound healing, chronic ulcer and scarring. We have previously identified a novel tripartite motif family protein, MG53, as an essential component of the cell membrane repair machinery. Here we report the functional role of MG53 in the modulation of wound healing and scarring. Although MG53 is absent from keratinocytes and fibroblasts, remarkable defects in skin architecture and collagen overproduction are observed in mg53(-/-) mice, and these animals display delayed wound healing and abnormal scarring. Recombinant human MG53 (rhMG53) protein, encapsulated in a hydrogel formulation, facilitates wound healing and prevents scarring in rodent models of dermal injuries. An in vitro study shows that rhMG53 protects against acute injury to keratinocytes and facilitates the migration of fibroblasts in response to scratch wounding. During fibrotic remodeling, rhMG53 interferes with TGF-ß-dependent activation of myofibroblast differentiation. The resulting down-regulation of α smooth muscle actin and extracellular matrix proteins contributes to reduced scarring. Overall, these studies establish a trifunctional role for MG53 as a facilitator of rapid injury repair, a mediator of cell migration, and a modulator of myofibroblast differentiation during wound healing. Targeting the functional interaction between MG53 and TGF-ß signaling may present a potentially effective means for promoting scarless wound healing.

Switching STudy of Kidney TRansplant PAtients with Tremor to LCP-TacrO (STRATO): an open-label, multicenter, prospective phase 3b study.

Tremor is a common side effect of tacrolimus correlated with peak-dose drug concentration. LCPT, a novel, once-daily, extended-release formulation of tacrolimus, has a reduced Cmax with comparable AUC exposure, requiring a ~30% dose reduction vs. immediate-release tacrolimus. In this phase 3b study, kidney transplant recipients (KTR) on a stable dose of tacrolimus and with a reported clinically significant tremor were offered a switch to LCPT. Tremor pre- and seven d post-conversion was evaluated by independent, blinded movement disorder neurologists using the Fahn-Tolosa-Marin (FTM) scale and by an accelerometry device; patients completed the QUEST (quality of life in essential tremor) and the Patient Global Impression of Change. There were 38 patients in the mITT population. A statistically and clinically significant improvement in tremor (FTM score, amplitude as measured by the accelerometry device and QOL [p-values < 0.05]) resulted post-conversion. Change in QUEST was significantly (p = 0.006) correlated (R = 0.44) with change in FTM; 78.9% of patients reported an improvement after switching to LCPT (p < 0.0005). To our knowledge this is the first trial in KTR that utilizes a sophisticated and reproducible measurement of tremor. Results suggest LCPT is associated with clinically meaningful improvement of hand tremor and may be an alternative management approach in lieu of further dose reduction of immediate-release tacrolimus for patients experiencing tremor.

Risk factors for retained surgical items: a meta-analysis and proposed risk stratification system.

BACKGROUND: Retained surgical items (RSI) are designated as completely preventable "never events". Despite numerous case reports, clinical series, and expert opinions few studies provide quantitative insight into RSI risk factors and their relative contributions to the overall RSI risk profile. Existing case-control studies lack the ability to reliably detect clinically important differences within the long list of proposed risks. This meta-analysis examines the best available data for RSI risk factors, seeking to provide a clinically relevant risk stratification system. METHODS: Nineteen candidate studies were considered for this meta-analysis. Three retrospective, case-control studies of RSI-related risk factors contained suitable group comparisons between patients with and without RSI, thus qualifying for further analysis. Comprehensive Meta-Analysis 2.0 (BioStat, Inc, Englewood, NJ) software was used to analyze the following "common factor" variables compiled from the above studies: body-mass index, emergency procedure, estimated operative blood loss >500 mL, incorrect surgical count, lack of surgical count, >1 subprocedure, >1 surgical team, nursing staff shift change, operation "afterhours" (i.e., between 5 PM and 7 AM), operative time, trainee presence, and unexpected intraoperative factors. We further stratified resulting RSI risk factors into low, intermediate, and high risk. RESULTS: Despite the fact that only between three and six risk factors were associated with increased RSI risk across the three studies, our analysis of pooled data demonstrates that seven risk factors are significantly associated with increased RSI risk. Variables found to elevate the RSI risk include intraoperative blood loss >500 mL (odds ratio [OR] 1.6); duration of operation (OR 1.7); >1 subprocedure (OR 2.1); lack of surgical counts (OR 2.5); >1 surgical team (OR 3.0); unexpected intraoperative factors (OR 3.4); and incorrect surgical count (OR 6.1). Changes in nursing staff, emergency surgery, body-mass index, and operation "afterhours" were not significantly associated with increased RSI risk. CONCLUSIONS: Among the "common risk factors" reported by all three case-control studies, seven synergistically show elevated RSI risk across the pooled data. Based on these results, we propose a risk stratification scheme and issue a call to arms for large, prospective, and multicenter studies evaluating effects of specific changes at the institutional level (i.e., universal surgical counts, radiographic verification of the absence of RSI, and radiofrequency labeling of surgical instruments and sponges) on the risk of RSI. Overall, our findings provide a meaningful foundation for future patient safety initiatives and clinical studies of RSI occurrence and prevention.

Comorbidity-polypharmacy score: a novel adjunct in post-emergency department trauma triage.

OBJECTIVE: Post-emergency department triage of older trauma patients continues to be challenging, as morbidity and mortality for any given level of injury severity tend to increase with age. The comorbidity-polypharmacy score (CPS) combines the number of pre-injury medications with the number of comorbidities to estimate the severity of comorbid conditions. This retrospective study examines the relationship between CPS and triage accuracy for older (≥45y) patients admitted for traumatic injury. METHODS: Patients aged 45y and older presenting to level 1 trauma center from 2005 to 2008 were included. Basic data included patient demographics, injury severity score, morbidity and mortality, and functional outcome measures. CPS was calculated by adding total numbers of comorbid conditions and pre-injury medications. Patients were divided into three triage groups: undertriage (UT), appropriate triage (AT), and overtriage (OT). UT criteria included initial admission to the floor or step-down unit followed by an unplanned transfer to intensive care unit (ICU) within 24h of admission. OT was defined as initial ICU admission for <1d without stated need for ICU level of care (i.e., lack of evidence for tracheal intubation or mechanical ventilation, injury-related hemorrhage, or other traditional ICU indications, such as intracranial bleeding). All other patients were presumed to be correctly triaged. The three triage groups were then analyzed looking for contributors to mistriage. RESULTS: Charts for 711 patients were evaluated (mean age, 63.5y; 55.7% male; mean ISS, 9.02). Of those, 11 (1.55%) met criteria for UT and 14 (1.97%) for OT. The remaining 686 patients had no evidence of mistriage. The three groups were similar in terms of injury severity and GCS. The groups were significantly different with respect to CPS, with UT CPSs (14.9±6.80) being nearly three times higher than OT CPSs (5.14±3.48). There were more similarities between AT and OT groups, with the UT group being characterized by greater number of complications and lower functional outcomes at discharge (all, P<0.05). The UT group had significantly higher mortality (27%) than the AT and OT groups (6% and 0%, respectively). CONCLUSIONS: In the era of medication reconciliation, CPS is easy to obtain and calculate in patients who are not critically injured. This study suggests that CPS may be a promising adjunct in identifying older trauma patients who are more likely to be undertriaged. The significance of our findings is especially important when considering that injury severity in the UT group was similar to that in the other groups. Further evaluation of CPS as a triage tool in acute trauma is warranted.

Intentional foreign object ingestions: need for endoscopy and surgery.

BACKGROUND: Intentional ingestion of foreign objects (IIFO) is common in the incarcerated population. This study was undertaken in order to better define clinical patterns of IIFO among prisoners. We sought to determine factors associated with the need for endoscopic and surgical therapy for IIFO. METHODS: After obtaining permission to conduct IIFO research in incarcerated populations, study patients were identified by ICD-9 codes. Patient charts were reviewed for demographics; past medical history; IIFO characteristics; and diagnostic, endoscopic, and surgical findings. Univariate and multivariate analyses were performed using statistical software. RESULTS: Thirty patients with 141 episodes of IIFO were identified. The mean number of ingested items per episode was 4.60. Endoscopy was performed in 97 of 141 IIFO instances, with failure to retrieve the ingested object in 21 of 97 cases (22%). Eleven instances (7.8%) required surgical intervention. On multivariate analyses, hospital admission was associated with elevated white blood cell count (odds ratio [OR] 1.4, P < 0.05) and number of items ingested (OR 1.3, P < 0.05). The need for endoscopy was independently associated with ingestion of multiple objects (OR 3.3, P < 0.05) and elevated white blood cell count (OR 1.3, P < 0.05). Surgical therapy was significantly associated with elevated white blood cell count (OR 1.6, P < 0.01) and with increasing number of ingested items (OR 1.07 per item, P < 0.05). Endoscopy is associated with significantly lower odds of surgery (OR 0.13, P < 0.01). CONCLUSIONS: Intentional ingestion of foreign objects continues to pose a significant human and economic burden. The need for admission or therapy is frequently associated with leukocytosis. Further investigation is warranted into resource-appropriate triage of patients who present with IIFO.

Intravascular retained surgical items: a multicenter study of risk factors.

INTRODUCTION: Retained surgical items (RSIs) have been previously studied in patients undergoing major surgical procedures. This is the first study that specifically examines potential risk factors for intravascular RSI (ivRSI). METHODS: Multicenter retrospective review of 83 RSIs was performed. Among these, 13 cases involved ivRSI. Cases in the ivRSI group were compared with a group of similar control cases to determine potential risk factors for ivRSI, including procedural factors (urgency and complicating factors), patient factors (body mass index), equipment failure (structural or functional), and safety variances. Fisher's exact testing was performed. RESULTS: Thirteen ivRSI cases and 14 controls were examined. There were no differences between the two groups with regard to age, gender, or body mass index. ivRSI items included guide wires (8/13), catheter/catheter fragments (4/13), and a coil (1/13). The incidence of unexpected procedural factors was significantly higher among ivRSI cases (10/13) than among controls (3/14) (P < 0.007). Equipment failure occurred in five ivRSI cases, with none among controls (P < 0.016). There were no differences between the two groups with regard to number of urgent procedures, bleeding >500 mL, evening procedures, or trainee involvement. Both groups had a very high proportion of safety variances (8 in ivRSI and 11 in control group, P = not significant). In addition, seven of 13 ivRSIs were missed on initial confirmatory postprocedural imaging. DISCUSSION: Unexpected procedural factors and equipment failure are significantly associated with ivRSI. Of concern, over half of all ivRSIs were missed on confirmatory postprocedural imaging. Strict adherence to established protocols and stringent radiographic review for intravascular procedures is required to prevent ivRSI.

Tree stands, not guns, are the midwestern hunter's most dangerous weapon.

Although the prevailing stereotype is that most hunting injuries are gunshot wounds inflicted by intoxicated hunting buddies, our experience led us to hypothesize that falls comprise a significant proportion of hunting related injuries. Trauma databases of two Level I trauma centers in central Ohio were queried for all hunting related injuries during a 10-year period. One hundred and thirty patients were identified (90% male, mean age 41.0 years, range 17-76). Fifty per cent of injuries resulted from falls, whereas gunshot wounds accounted for 29 per cent. Most hunters were hunting deer and 92 per cent of falls were from tree stands. Alcohol was involved in only 2.3 per cent, and drugs of abuse in 4.6 per cent. Of gunshots, 58 per cent were self-inflicted, and 42 per cent were shot by another hunter. Tree stand falls were highly morbid, with 59 per cent of fall victims suffering spinal fractures, 47 per cent lower extremity fractures, 18 per cent upper extremity fractures, and 18 per cent closed head injuries. Surgery was required for 81 per cent of fall-related injuries, and 8.2 per cent of fall victims had permanent neurological deficits. In contrast to prevailing beliefs, in our geographic area tree-stand falls are the most common mechanism of hunting related injury requiring admission to a Level 1 trauma center.

Level I versus Level II trauma centers: an outcomes-based assessment.

OBJECTIVE: Trauma centers improve outcomes compared with nontrauma centers, although the relative benefit of different levels of major trauma centers (Level I vs. Level II hospitals) remains unclear. We sought to determine whether there was a difference in the patient outcome in trauma victims taken to Level I versus Level II trauma centers. METHODS: A multicenter, retrospective cohort analysis of all patients with trauma (>15 years), meeting State of Ohio trauma criteria, transported directly from the scene to a Level I or a Level II hospital (27 centers) between January 2003 and December 2006. Propensity score adjustment was used to adjust for nonrandom selection of hospital destination (I vs. II) and included age, emergency medical services (EMS) Glasgow Coma Score, comorbidities, EMS systolic blood pressure, injury type, injury severity, EMS procedures, emergency department procedures, gender, insurance status, and race. A propensity-adjusted multivariable logistic regression model was used to test the association between trauma center level and patient outcomes. Outcomes included in-hospital mortality and discharge destination (skilled nursing facility, rehabilitation center, home). RESULTS: A total of 18,103 patients were included in the analysis; 10,070 (56%) were transported to a Level I center. Patients taken to Level I centers had more severe injuries, more penetrating injuries, more complications, yet similar unadjusted mortality compared with Level II centers. In adjusted analyses, patients taken to Level I hospitals had improved survival compared with Level II centers (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.56-0.98). Similar results were seen when restricting the analyses to patients with serious injuries (Injury Severity Score > 15; EMS Glasgow Coma Score < 9). Patients treated at Level I hospitals were more likely to be discharged home (OR 1.14, 95% CI 1.05-1.25), or a rehabilitation center or skilled nursing facility (OR 1.39, 95% CI 1.27-1.52). CONCLUSIONS: Patients taken to Level I centers had improved survival and better functional outcomes compared with injured persons taken to Level II hospitals.

Missed surgical intensive care unit billing: potential financial impact of 24/7 faculty presence.

BACKGROUND: To efficiently capture evaluation and management (E&M) and procedural billing in our surgical intensive care unit (SICU), we have developed an electronic billing system that links to the electronic medical record (EMR). In this system, only notes electronically signed and coded by an attending generate billing charges. We hypothesized that capture of missed billing during nighttime and weekends might be sufficient to subsidize 24/7 in-house attending coverage. METHODS: A retrospective chart EMR review was performed of the EMRs for all SICU patients during a 2-month period. Note type, date, time, attending signature, and coding were analyzed. Notes without attending signature, diagnosis, or current procedural terminology (CPT) code were considered incomplete and identified as "missed billing." RESULTS: Four hundred and forty-three patients had 465 admissions generating 2,896 notes. Overall, 76% of notes were signed and coded by an attending and billed. Incomplete (not billed) notes represented an overall missed billing opportunity of $159,138 for the 2-month time period (approximately $954,000 annually). Unbilled E&M encounters during weekdays totaled $54,758, whereas unbilled E&M and procedures from weeknights and weekends totaled $88,408 ($44,566 and $43,842, respectively). Missed billing after-hours thus represents approximately $530K annually, extrapolating to approximately $220K in collections from our payer mix. Surprisingly, missed E&M and procedural billing during weekdays totaled $70,730 (approximately $425K billing, approximately $170K collections annually), and typically represented patients seen, but transferred from the SICU before attending documentation was completed. CONCLUSIONS: Capture of nighttime and weekend ICU collections alone may be insufficient to add faculty or incentivize in-house coverage, but could certainly complement other in-house derived revenues to such ends. In addition, missed daytime billing in busy modern ICUs can be substantial, and use of an EMR to identify missed billing opportunities can help create solutions to recover these revenues.

Hyperglycemic events in non-intensive care unit patients receiving parenteral nutrition.

BACKGROUND: Evidence supports the benefits of tight glycemic control in many patient populations. There is no consensus on appropriate targets for blood glucose (BG) values in patients receiving parenteral nutrition (PN). Characterization of the frequency of BG abnormalities is necessary to identify effective strategies to improve glycemic control in this patient population. METHODS: Data were retrospectively collected over a 2-month period from 50 non-intensive care unit (ICU) patients who received PN. Frequencies of abnormal BG (defined as BG outside the range of 2 criteria: 80-200 mg/dL and 100-150 mg/dL) were determined. An event of hyperglycemia was defined as the 48-hour period following a BG value outside of 80-200 mg/dL. Each event was evaluated for resolution within 48 hours of the triggering BG value. RESULTS: Hyperglycemia (at least 1 BG value >200 mg/dL) occurred in 22 patients (44%). Of the 1738 BG values measured, 8.7% were >200 mg/dL, resulting in 1.4 events of hyperglycemia per patient. The average blood glucose value for the population was 140 mg/dL. The frequency of hyperglycemia and hypoglycemia increased substantially, with only 1 patient having a PN course with normoglycemia using the 100-150 mg/dL criterion. CONCLUSION: The frequency of hyperglycemia in non-ICU PN patients is high according to either evaluation criterion. A method is described for using events to characterize hyperglycemia, which may be more useful than traditional methods in clinical decision making and identification of need for process improvements. These data suggest the need to develop better methods for BG control in non-ICU PN patients.

Adrenal gland injury secondary to blunt traumatic mechanisms: a marker of overall injury severity.

INTRODUCTION: Adrenal gland injuries (AGI) are seen increasingly frequently owing to advances in modern imaging techniques. This study describes a series of patients with blunt AGI, with the emphasis on AGI as a marker of injury severity, CT-radiographic classification of AGI and associated injury patterns. MATERIAL AND METHODS: A retrospective review of blunt trauma patients with AGI was performed. Variables examined included demographics, mechanism of injury, length of hospital and ICU stay, clinical status on admission, AGI characteristics, associated injuries, complications, procedures, mortality and discharge disposition. RESULTS: There were 29 AGI patients with a mean injury severity score of 25. The most common injury mechanisms were motor-vehicular collisions (15/29) and falls (5/29). Right-sided AGI (16/29) outnumbered left-sided (12/29) injuries. The most common CT-radiographic types of AGI were adrenal gland contusions and lacerations with limited "blush". While patterns of injuries differed between right and left-sided AGI, the mean number of injuries did not. The most common associated injuries included extremity (21/29), rib (20/29) and spinal fractures (18/29). Common procedures included orthopaedic fixation (10/29), vena cava filter (8/29) and tracheostomy (5/29). A median of two complications per patient was reported, including adrenal insufficiency in two patients. Mortality was 17%. The median hospital and ICU length of stay were 15 and 12 days, respectively. CONCLUSIONS: Adrenal gland injury is associated with significant morbidity and mortality. With modern imaging modalities capable of reliably detecting adrenal injury, the presence of AGI should be considered a marker of overall injury severity. The authors provide a CT-radiographic classification of adrenal injuries.

Risk of acute kidney injury in critically ill surgical patients with presumed pneumonia is not impacted by choice of methicillin-resistant staphylococcus aureus therapy.

BACKGROUND: Vancomycin and linezolid are standard treatment options for nosocomial methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. While acute kidney injury (AKI) is commonly attributed to vancomycin, existing data has not definitely confirmed vancomycin as an independent risk factor for AKI. AIMS: This study aimed to quantify the incidence of AKI in Surgical Intensive Care Unit (ICU) patients receiving empiric vancomycin or linezolid for nosocomial pneumonia and to identify risk factors for AKI with a focus on MRSA antibiotic therapy. MATERIALS AND METHODS: A retrospective cohort analysis of surgical ICU patients who received at least 48 h of vancomycin or linezolid for pneumonia was performed. Patients who received vancomycin were compared to those who received linezolid with a primary endpoint of AKI as defined by the risk/injury/failure/loss/end-stage renal disease (RIFLE) criteria. A modified RIFLE criteria assessing only changes in serum creatinine was also used. RESULTS: One hundred one patients were evaluated (63 vancomycin and 38 linezolid). AKI occurred in 51 (81.0%) and 32 (84.2%) patients in the vancomycin and linezolid groups (P = 0.79), respectively. Using the modified RIFLE criteria, AKI occurred in 19 (30.2%) and 14 (36.8%) patients in the vancomycin and linezolid groups (P = 0.448). After adjustment for age, diabetes mellitus, Charlson comorbidity index, and concomitant nephrotoxins, there was no difference in risk of AKI between groups (P = 0.773). CONCLUSIONS: Patients who received empiric vancomycin or linezolid for nosocomial pneumonia experienced high, but similar rates of AKI. The results suggest MRSA antibacterial therapy in this setting may not be independently indicative of AKI risk, rather the risk is likely multifactorial.

Efficacy and Safety of a Tofacitinib-based Immunosuppressive Regimen After Kidney Transplantation: Results From a Long-term Extension Trial.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor. This open-label, long-term extension (LTE) study (NCT00658359) evaluated long-term tofacitinib treatment in stable kidney transplant recipients (n = 178) posttransplant. METHODS: Patients who completed 12 months of cyclosporine (CsA) or tofacitinib treatment in the phase IIb parent study (NCT00483756) were enrolled into this LTE study, evaluating long-term tofacitinib treatment over months 12 to 72 posttransplant. Patients were analyzed by tofacitinib less-intensive (LI) or more-intensive (MI) regimens received in the parent study. For both groups, tofacitinib dose was reduced from 10 to 5 mg twice daily by 6 months into the LTE. Patients were followed up through month 72 posttransplant, with a focus on month 36 results. RESULTS: Tofacitinib demonstrated similar 36-month patient and graft survival rates to CsA. Biopsy-proven acute rejection rates at month 36 were 11.2% for CsA, versus 10.0% and 7.4% (both P > 0.05) for tofacitinib LI and MI, respectively. Least squares mean estimated glomerular filtration rates were 9 to 15 mL/min per 1.73 m2 higher for tofacitinib versus CsA at month 36. The proportions of patients with grade 2/3 interstitial fibrosis and tubular atrophy in month 36 protocol biopsies were 20.0% for LI and 18.2% for MI (both P > 0.05) versus 33.3% for CsA. Kaplan-Meier cumulative serious infection rates at month 36 were numerically higher for tofacitinib LI (43.9%; P = 0.45) and significantly higher for MI (55.9%; P < 0.05) versus CsA (37.1%). CONCLUSIONS: Long-term tofacitinib continued to be effective in preventing renal allograft acute rejection and preserving renal function. However, long-term tofacitinib and mycophenolic acid product combination was associated with persistent serious infection risk.

Zinc in Wound Healing Modulation.

Wound care is a major healthcare expenditure. Treatment of burns, surgical and trauma wounds, diabetic lower limb ulcers and skin wounds is a major medical challenge with current therapies largely focused on supportive care measures. Successful wound repair requires a series of tightly coordinated steps including coagulation, inflammation, angiogenesis, new tissue formation and extracellular matrix remodelling. Zinc is an essential trace element (micronutrient) which plays important roles in human physiology. Zinc is a cofactor for many metalloenzymes required for cell membrane repair, cell proliferation, growth and immune system function. The pathological effects of zinc deficiency include the occurrence of skin lesions, growth retardation, impaired immune function and compromised would healing. Here, we discuss investigations on the cellular and molecular mechanisms of zinc in modulating the wound healing process. Knowledge gained from this body of research will help to translate these findings into future clinical management of wound healing.

Randomized, open-label preference study of two cyclosporine capsule formulations (usp modified) in stable solid-organ transplant recipients.

BACKGROUND: Prior research has indicated patient dissatisfaction with the odor, size, and taste of cyclosporine capsules, as well as the halitosis and body odor the capsules can cause. OBJECTIVES: The purposes of this investigation were to (1) compare the overall cyclosporine capsule preference (Gengraf vs Neoral) in stable, solid-organ transplant recipients, (2) assess patient preference based on specific capsule attributes, and (3) determine the reliability of the Cyclosporine Capsule SatiSfaCtion Survey (original to this study). METHODS: In this multicenter, randomized, open-label, parallel-group, preference study, patients were recruited from 144 centers in North America with established transplant programs. Solid-organ transplant recipients who had taken stable doses of cyclosporine (Neoral) for >/=2 consecutive months were randomized in a 9:1 ratio to receive another cyclosporine formulation (Gengraf) or to remain on Neoral therapy. Patients completed the Cyclosporine Capsule Satisfaction Survey prior to randomization (baseline survey) and after taking the study drug for 4 weeks (final survey). The survey consisted of multiple attribute items with high face validity in assessing patients' perceptions and preferences with regard to their overall experience, as well as specific attributes of cyclosporine capsules known to affect patient acceptance. RESULTS: The intent-to-treat population included 1906 patients (1211 men, 693 women [sex unknown in 2 patients]; mean [SD] age, 50.2 [12.4] years). A total of 1708 patients were switched to Gengraf; 198 continued on Neoral. Based on their overall experience with both capsule formulations, the majority of patients switched to Gengraf (61.9%) responded that they preferred the Gengraf capsule, compared with 13.7% who preferred the Neoral capsule and 24.4% who indicated no preference (P < 0.001). A similar preference for Gengraf was observed based on capsule odor (66.3%), ease of swallowing (51.5%), taste (57.1%), and impact on breath odor (52.5%) and body odor (48.4%) (P < 0.001 for each test). The results of internal consistency and reproducibility calculations were high for the Cyclosporine Capsule Satisfaction Survey. Internal consistency ranged from alpha = 0.84 to 0.95 for the subscales and was alpha = 0.95 for the overall score. Ranges for reproducibility in the subscales were r = 0.75 to 0.79, with an overall reproducibility of r = 0.85. Guyatt's responsiveness statistics for the subscale and overall scores were moderately high to very high, indicating that the survey is capable of measuring change in response to treatment. CONCLUSIONS: Of the transplant recipients receiving Gengraf in this study, most preferred Gengraf to Neoral based on overall experience, capsule odor, difficulty swallowing, taste, breath odor, and body odor. Among all study patients, fewer patients receiving Gengraf were bothered by capsule odor, difficulty in swallowing, taste, or the impact on breath or body odor compared with patients who continued to receive Neoral. Internal consistency, reproducibility, and responsiveness results show that the Cyclosporine Capsule Satisfaction Survey is a psychometrically valid instrument that is appropriate for use in clinical trials.

Bacterial translocation: what it is and what it is not.

The reasons our critically ill patients die have been a matter of great interest for many decades, with the hope that if we can identify the mechanisms responsible for death, we might be able to intervene and improve outcome. Over the last 1 to 2 decades, the concept of bacterial translocation-the movement of gut origin microbes across the intact gastrointestinal tract into normally sterile tissues where the organisms may then directly cause infection or incite an inflammatory response that causes tissue injury, organ failure, and death-has grown to the point where it is virtually impossible to make rounds in any intensive care setting without a resident or student blaming some complication or another on bacterial translocation. We will attempt to review the clinically relevant information that supports and refutes the concept of bacterial translocation as a cause of our critically ill patients to exhibit the symptoms and signs of sepsis, develop organ failure, and ultimately die.

How early is early laparoscopic treatment of acute cholecystitis?

BACKGROUND: Despite the well-accepted success of laparoscopic cholecystectomy in elective treatment of symptomatic cholelithiasis, the efficacy and timing of this technique has been subject to some debate in the setting of acute cholecystitis. This study was undertaken to evaluate our institution's experience with early cholecystectomy as a safe, effective treatment of acute cholecystitis. METHODS: Charts of all patients who had undergone laparoscopic cholecystectomy for the diagnosis of acute cholecystitis were reviewed. Patients were divided into two groups based on the length of time from onset of symptoms to surgical intervention: less than 48 hours in the early group (n = 14) and more than 48 hours in the late group (n = 31). RESULTS: Comparing the two groups, the conversion rate to an open procedure was significantly less (0 versus 29%, P <0.04) in the early treated patients. Furthermore, the operative time (73 versus 96 minutes, P <0.004), postoperative hospitalization (1.2 versus 3.9 days, P <0.001), and total hospital stay (2.1 versus 5.4 days, P <0.004) were significantly reduced in patients undergoing early laparoscopic cholecystectomy. CONCLUSIONS: Laparoscopic cholecystectomy performed by experienced surgeons is a safe, effective technique for treatment of acute cholecystitis. Patients treated within 48 hours of onset of symptoms experience a lower conversion rate to an open procedure, shorter operative time and reduced hospitalization.