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Objective: When socioeconomic status is measured at the individual and/or family level, it has long been associated with cognition in children. However, the association between neighborhood deprivation, an index of community-level socioeconomic status, and child cognition is not fully understood. The goal of this study was to investigate (1) the relationship between neighborhood deprivation and child cognitive functioning and (2) whether child age moderates the relationship between cognitive functioning and neighborhood deprivation., Methods: This study included 9878 children, ages 3 through 17 years (M = 10.4 yrs, SD = 3.4 yrs). Data were gathered from children referred for and evaluated at an urban, outpatient neuropsychology assessment clinic between 2006 and 2022, located in the Mid-Atlantic region of the United States. Neighborhood socioeconomic status was measured at the census block level using the Area Deprivation Index composite., Results: There was a 20-point median difference in overall intelligence between the neighborhoods with the lowest and highest levels of deprivation. Overall intelligence and verbal comprehension, compared with working memory, fluid reasoning, and processing speed, demonstrated the strongest negative association with neighborhood deprivation (all p < 0.05). Older children had lower overall intelligence scores compared with younger children in neighborhoods with high levels of deprivation ( p < 0.01), suggesting a cumulative influence of poverty exposure., Conclusion: This study demonstrates the stark disparities in child cognitive functioning across levels of neighborhood deprivation. Findings support the importance of access to early interventions and services that promote intellectual growth and verbal capacity among children who live in neighborhoods with great deprivation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Summary: Anterior interosseous nerve to ulnar motor nerve supercharged end-to-side (SETS) nerve transfer to restore intrinsic function is a recently adopted nerve transfer in severe ulnar neuropathy. Its success is predicated on the critical threshold number of axons innervating the intrinsic muscles. Given the relative expendability of the abductor digiti minimi (ADM) muscle and the critical function of the other intrinsic muscles, the authors modified their SETS transfer to redirect axons from the ADM to turbocharge the ulnar motor nerve to innervate the more critical intrinsic muscles. They refer to this procedure as a super turbocharged end-to-side (STETS) procedure. The ADM has been used previously as a muscle/tendon transfer for thumb opposition and more recently as a nerve transfer to reinnervate the thenar branch of the median nerve. Although current methods of assessment of reinnervation are likely unable to differentiate between contributions from the anterior interosseous nerve SETS versus ADM STETS transfer, this technique follows the fundamentals of modern nerve surgery, where directing the maximum number of nerve fibers in a timely fashion to the most critical target is paramount for the best functional recovery. The authors suggest that the STETS technique may optimize outcomes in ulnar neuropathy without additional patient morbidity., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Purpose/aims: The aim of this study was to explore the perceptions that experienced and highly specialized nurses have of the clinical nurse specialist (CNS) role through description of the registered nurses' (RNs') experiences., Design: This study used a qualitative descriptive design., Methods: Interviews were conducted with 6 RNs (2 managers, 1 chief nursing officer, 2 educators, and 1 clinician) and 32 RNs who participated in 5 focus groups. Participants were purposively sampled from intensive care units and emergency departments from 4 public and private hospitals. The analysis of the narratives and field notes used thematic content analysis., Results: Common aspects of the CNS competencies and the experienced RN were recognized. These included direct patient care, assessment, and mentoring, with important differences in management, research, and coaching competencies., Conclusion: The findings could facilitate the development of a master's program for the CNS in Chile. Formally recognizing the skills and clinical experiences of expert RNs may motivate nurses to pursue a master's degree that prepares them for advanced practice., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The relationship between fireworks and patient characteristics is not known. Our objective was to examine how severe fireworks-related injuries in children and teens compare to adults., Methods: We conducted a retrospective case series (2005-2015) study of patients who sustained consumer fireworks-related injuries requiring hospital admission and/or operation at a single level 1 trauma/burn center. The distribution of race, use behavior, injury type, body region injured, and firework type was examined by age groups, 1 to 10 years, 11 to 17 years, and 18 years or older., Results: Data from 294 patients 1 to 61 years of age (mean, 24 years) were examined. The majority (91%) were male. The proportion of injuries from different firework types varied by age, with rockets causing the highest proportion in children aged 1 to 10 years, homemade fireworks in those aged 11 to 17 years, and shells/mortars in adults 18 years or older. Compared with adults, children aged 1 to 10 years were more frequently American Indian/Alaska Native, Hispanic, or Asian than White. Compared with adults, children aged 1 to 10 years and 11 to 17 years were more frequently bystanders than active users. Compared with adults, children aged 1 to 10 years and 11 to 17 years had a greater proportion of burn and face injuries. Children aged 1 to 10 years had a decreased proportion of hand injuries. Three patients, 2 adults and 1 child aged 11 to 17 years, died., Conclusions: Children, teens, and adults experience severe fireworks-related injuries differently, by demographic characteristics, injury patterns, and firework types. Tailored public health interventions could target safety messaging and injury prevention outreach efforts to reduce firework injuries among children and adolescents., Competing Interests: Disclosure: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Common peroneal neuropathy shares the same pathophysiology as carpal tunnel syndrome. However, management is often delayed because of the traditional misconception of recognizing foot drop as the defining symptom for diagnosis. The authors believe recognizing common peroneal neuropathy before foot drop can relieve pain and help improve quality of life., Methods: One hundred eighty-five patients who underwent surgical common peroneal neuropathy decompression between 2011 and 2017 were included. The mean follow-up time was 249 ± 28 days. Patients were classified into two stages of severity based on clinical presentation: pre-foot drop and overt foot drop. Demographics, presenting symptoms, clinical signs, electrodiagnostic studies and response to surgery were compared between these two groups. Multivariate regression analysis was used to identify variables that predicted outcome following surgery., Results: Overt foot drop patients presented with significantly lower preoperative motor function (percentage of patients with Medical Research Council grade ≤ 1: overt foot drop, 90 percent; pre-foot drop, 0 percent; p < 0.001). Pre-foot drop patients presented with a significantly higher preoperative pain visual analogue scale score (pre-foot drop, 6.2 ± 0.2; overt foot drop, 4.6 ± 0.3; p < 0.001) and normal electrodiagnostic studies (pre-foot drop, 31.4 percent; overt foot drop, 0.1 percent). Postoperatively, both groups of patients showed significant improvement in quality-of-life score (pre-foot drop, 2.6 ± 0.3; overt foot drop, 2.7 ± 0.3). Patients with obesity or a traumatic cause for common peroneal neuropathy were less likely to have improvements in quality of life after surgical decompression., Conclusion: Increased recognition of common peroneal neuropathy can aid early management, relieve pain, and improve quality of life., Clinical Question/level of Evidence: Risk, II.

Objective: Mild forms of HIV-associated neurocognitive disorder (HAND) remain prevalent in the combination antiretroviral therapy (cART) era. This study's objective was to identify neuropsychological subgroups within the Multicenter AIDS Cohort Study (MACS) based on the participant-based latent structure of cognitive function and to identify factors associated with subgroups., Design: The MACS is a four-site longitudinal study of the natural and treated history of HIV disease among gay and bisexual men., Methods: Using neuropsychological domain scores, we used a cluster variable selection algorithm to identify the optimal subset of domains with cluster information. Latent profile analysis was applied using scores from identified domains. Exploratory and posthoc analyses were conducted to identify factors associated with cluster membership and the drivers of the observed associations., Results: Cluster variable selection identified all domains as containing cluster information except for Working Memory. A three-profile solution produced the best fit for the data. Profile 1 performed below average on all domains, Profile 2 performed average on executive functioning, motor, and speed and below average on learning and memory, Profile 3 performed at or above average across all domains. Several demographic, cognitive, and social factors were associated with profile membership; these associations were driven by differences between Profile 1 and the other profiles., Conclusion: There is an identifiable pattern of neuropsychological performance among MACS members determined by all domains except Working Memory. Neither HIV nor HIV-related biomarkers were related with cluster membership, consistent with other findings that cognitive performance patterns do not map directly onto HIV serostatus.

Background: Transversus abdominis release is a novel approach for myofascial advancement in ventral hernia repair and has been hypothesized to have lower rates of wound complication than anterior component separation., Methods: Patients who had a ventral hernia repair with either transversus abdominis release or minimally invasive anterior component separation from January of 2010 to January of 2016 were enrolled in this retrospective cohort study. Patient characteristics were collected through chart review. Primary outcomes were operative time and wound complications. Multiple linear/Poisson regression and Fisher's exact test were used to determine statistical significance., Results: Of 142 patients analyzed, 75 subjects underwent Butler minimally invasive anterior component separation and 67 underwent transversus abdominis release. There were no differences in baseline characteristics between groups, except that the anterior component separation group had more immunosuppressed patients (35 percent versus 19 percent). Median operative time for anterior component separation was 6.3 hours versus 6.1 hours for transversus abdominis release (p = 0.6). Overall wound complications did not differ between the groups (p = 0.5). Compared with anterior component separation, transversus abdominis release had a similar incidence of seroma/hematoma (relative risk, 0.9; 95 percent CI, 0.5 to 1.7), wound infection (relative risk, 1.1; 95 percent CI, 0.5 to 2.2), and mesh infection (relative risk, 0.7; 95 percent CI, 0.2 to 3.4). Hernia recurrence was 12 percent for anterior component separation and 6 percent for transversus abdominis release (relative risk, 0.6; 95 percent CI, 0.2 to 1.7). Reoperation was required in 19 percent of anterior component separation and 12 percent of transversus abdominis release subjects (relative risk, 0.5; 95 percent CI, 0.2 to 1.2)., Conclusions: Transversus abdominis release patients had similar operative times, wound complications, reoperations, and hernia recurrences compared with Butler minimally invasive anterior component separation patients. This contemporary comparison helps inform operative decisions for reconstructive surgeons., Clinical Question/level of Evidence: Therapeutic, III.

Objective: The aim of this article is to determine whether HIV-infected (HIV+) men have either higher incidence or more rapid progression of coronary artery calcium (CAC) compared with HIV-uninfected (HIV-) controls., Design: Prospective observational study., Setting: Multicenter study in four US academic research centers: University of Pittsburgh, Johns Hopkins University, University of California Los Angeles, and Northwestern University., Participants: Eight hundred and twenty-five men (541 HIV+ and 284 HIV-) enrolled in the cardiovascular substudy of the Multicenter AIDS Cohort Study who underwent serial cardiac computed tomography (CT) imaging during a mean follow-up of 5 years (range, 2-8 years)., Main Outcome Measures: Incidence and progression of CAC assessed by cardiac CT., Results: During follow-up, 21% of HIV+ men developed incident CAC compared with 16% of HIV- men. This association persisted after adjustment for traditional and HIV-associated risk factors: hazard ratio 1.64 (1.13-3.14). However, there was no association between HIV serostatus and CAC progression among men with CAC present at baseline. Current smoking and increased insulin resistance, both modifiable risk factors, were independently associated with increased incidence of CAC. No evidence supporting an elevated risk for either CAC progression or incidence was found for either dyslipidemia or long-term usage of antiretroviral therapy., Conclusion: In this large study of HIV+ and HIV- men who underwent serial cardiac CT scan imaging, HIV+ men were at significantly higher risk for development of CAC: hazard ratio 1.64 (1.13-3.14). In addition, two important and modifiable risk factors were identified for increased incidence of CAC. Taken together, these findings underscore the potential importance for smoking cessation and interventions to improve insulin resistance among HIV+ men.

Many patients with cleft palate deformities worldwide receive treatment at a later age than is recommended for normal speech to develop. The outcomes after late palate repairs in terms of speech and quality of life (QOL) still remain largely unstudied. In the current study, questionnaires were used to assess the patients' perception of speech and QOL before and after primary palate repair. All of the patients were operated at a cleft center in northeast India and had a cleft palate with a normal lip or with a cleft lip that had been previously repaired. A total of 134 patients (7-35 years) were interviewed preoperatively and 46 patients (7-32 years) were assessed in the postoperative survey. The survey showed that scores based on the speech handicap index, concerning speech and speech-related QOL, did not improve postoperatively. In fact, the questionnaires indicated that the speech became more unpredictable (P < 0.01) and that nasal regurgitation became worse (P < 0.01) for some patients after surgery. A total of 78% of the patients were still satisfied with the surgery and all of the patients reported that their self-confidence had improved after the operation. Thus, the majority of interviewed patients who underwent late primary palate repair were satisfied with the surgery. At the same time, speech and speech-related QOL did not improve according to the speech handicap index-based survey. Speech predictability may even become worse and nasal regurgitation may increase after late palate repair, according to these results.

Nicotinic stimulation of the α7 acetylcholine receptors (α7AChRs) mitigates the lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF-α) and other cytokines release in macrophages. This effect is blocked by α7AChR antagonist, α-bungarotoxin (BTX). We tested and confirmed the hypotheses that LPS upregulates α7AChRs, and the prototypical α7AChR antagonists, vecuronium and BTX, do not block the effects of GTS-21, a specific α7AChR agonist, on TNF-α release. With the knockdown of α7AChR expression by short interference RNA, GTS-21 effects on inhibition of TNF-α release were not demonstrable. In addition, GTS-21 mitigated the LPS-induced growth arrest of macrophages in vitro in J774A.1 cells and ex vivo in peritoneal macrophages obtained from mice at 3 days after burn. Moreover, GTS-21 reduced mortality after burn injury in mice. These results indicate that (i) LPS upregulates α7AChRs; (ii) the therapeutic beneficial effects of GTS-21 on cytokine release are specifically mediated via α7AChRs and are preserved even when cotreated with prototypical antagonist, BTX, or clinically used muscle nicotinic antagonist, vecuronium; (iii) activation of α7AChRs by GTS-21 partially reverses the LPS-induced proliferation arrest; and (iv) GTS-21 reduces mortality in mice with burn injury. The in vivo beneficial effects of GTS-21 in burn injury warrant further studies.

Objective: We studied a case series of peripheral nerve hyperexcitability (PNH) aiming to describe clinical characteristics, immunologic and cancer associations, antibodies against neuronal antigens (voltage-gated potassium channel antibodies [VGKC-Abs] and other), and muscle biopsy findings., Methods: Patients presenting with clinical and electrophysiologic signs of PNH were selected. We studied clinical and electrophysiologic features; a panel of non-neuronal organ-specific antibodies, immunofluorescence on rat nervous tissues, and radioimmunoprecipitation for VGKC-Abs; and muscle biopsies., Results: Thirty-eight patients were included. After the exclusion of 6 cases with axonopathy of known origin, patients were subdivided according to the presence of electrophysiologic findings of motor axonopathy and association with cancer: axonopathic-PNH (group A: 12 patients), isolated nonparaneoplastic PNH (group B: 16 patients), and isolated paraneoplastic PNH (3 with thymoma and myasthenia gravis, 1 with thyroid carcinoma). PNH clinical features were similar in groups A and B. We found an overall high prevalence of clinical autoimmunity (33% of group A and 63% of group B) and systemic non-neuronal autoantibodies (42% of group A and 75% of group B). However, VGKC-Abs were only positive in 2 patients of group B. Ten patients underwent muscle biopsy, which showed inflammatory changes in 2 cases and nonspecific myopathic features in 8., Conclusions: PNH is a heterogeneous disorder involving the peripheral nerves in patients with a high propensity for developing autoimmunity. Associated muscle diseases are frequent in the form of myositis, myasthenia gravis, or nonspecific myopathic pathologic findings. VGKC-Abs were uncommon in this series.

Objective: To assess associations between abacavir (ABC) use and systemic inflammation., Design: Nested case-control study., Methods: The Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS) cohort participants who initiated ABC were matched, using propensity score methods, to ABC-unexposed persons. Levels of high-sensitivity C-reactive protein (hsCRP) (microg/ml), interleukin-6 (IL-6) (pg/ml), and D-dimer (microg/ml) were measured from pre-HAART and on-HAART plasma. Random-effects models compared markers by ABC exposure and by changes from pre-HAART levels., Results: Biomarkers were measured in N = 508 matched pairs (328 women; 180 men). Pre-HAART levels did not differ by exposure group except that hsCRP levels were higher among WIHS women who subsequently used ABC (P = 0.04). Regardless of ABC use, mean hsCRP increases and D-dimer reductions were seen when comparing pre-HAART to on-HAART levels, in the overall group (28 and -27%), for MACS men (28 and -31%) and for WIHS women [29 and -24%, P < 0.01 for all]; IL-6 levels declined in MACS men (P = 0.02). No adjusted biomarker level differences existed by ABC exposure at the on-HAART visit. HIV RNA reductions correlated with D-dimer (r = 0.14, P < 0.01) and IL-6 (r = 0.12, P < 0.01) reductions. Associations between ABC use and mean biomarker levels were modified by pre-HAART antiretroviral therapy experience. Renal dysfunction was equally likely among non-ABC and ABC recipients., Discussion: ABC use was not associated with plasma elevations in hsCRP, IL-6, and D-dimer. Mechanisms other than increased systemic inflammation may account for ABC's reported association with increased cardiovascular disease. HAART-associated reductions in D-dimer and IL-6 were apparent regardless of ABC use and were correlated with HIV RNA reductions.

Purpose: To investigate the effect of subconjunctival bevacizumab on primary pterygium., Methods: A patient with an inflamed nasal primary pterygium, refractory to artificial tears and naphazoline, was enrolled in this study. After pretreatment with topical proparacaine and moxifloxacin, 0.05 mL of bevacizumab (1.25 mg/0.05 mL) was injected subconjunctivally at the limbus. Clinical signs of irritation, redness, and vascularization were monitored over 7 weeks., Results: At 1 week postinjection, irritation and hyperemia showed near-total regression. At week 2, the pterygium maintained this appearance. By week 7, the degree of vascularity and symptoms of irritation had regressed to its preinjection state., Conclusions: Treatment of primary pterygium with subconjunctival bevacizumab results in a short-term decrease in vascularization and irritation. Further long-term studies should investigate the efficacy of bevacizumab as an adjunct to surgical excision or combined topical treatment targeting other growth factors involved in pterygium pathogenesis.

Purpose: Despite the established efficacy of mitomycin C (MMC) in preventing recurrence after pterygium surgery, there is no consensus on the optimal operative technique or dose of MMC., Methods: The authors retrospectively evaluated 90 single-headed pterygium resections performed with excision of the entire pterygium to the plica and removal of all Tenon's membrane from the scleral bed and rectus muscle. Bare sclera was exposed to 0.4 mg/mL MMC for 5 minutes for primary pterygia and 6 minutes for recurrent pterygia. These procedures were compared to a previous series of 58 procedures using bare sclera technique with MMC, but without extensive Tenon's membrane removal., Results: Extensive Tenon's membrane removal was associated with significantly fewer recurrences (6.7% vs. 21%; P< or =0.025) and significantly less pyogenic granuloma formation (24.4% vs. 40%; P< or =0.05). In addition, there were no vision-threatening complications, such as scleral melting or persistent corneal epithelial defects, in any of the patients., Conclusions: These findings suggest that complete removal of all Tenon's membrane in the affected quadrant combined with topical MMC in the aforementioned dose is a safe method of pterygium excision with a low rate of recurrence and pyogenic granuloma formation.

Objective: To determine frequency and outcomes of pregnancy in US women with HIV before and after introduction of highly active antiretroviral therapy (HAART)., Design: Prospective cohort study at six US centers., Methods: HIV seropositive and at-risk seronegative women reported pregnancy outcomes at 6-month intervals during the period 1 October 1994 to 31 March 2002. Outcomes were tabulated and pregnancy rates calculated. Logistic regression defined outcome correlates., Results: Pregnancy rates were 7.4 and 15.2 per 100 person-years in seropositive and seronegative women, respectively (P < 0.0001). Among seropositives, 119 (36%) pregnancies ended in live birth, six (2%) in stillbirth, 126 (36%) in abortion, 83 (24%) in miscarriage, 16 (5%) in ectopic pregnancy, and two (1%) in other outcomes (P = nonsignificant versus seronegatives). Independent baseline correlates of conception in seropositives included younger age [odds ratio (OR), 1.20; 95% confidence interval (CI), 1.16-1.23], prior abortion (OR, 1.79; 95% CI, 1.25-2.63), lower HIV RNA levels (OR, 1.30; 95% CI, 1.10-1.54 for each log decrease), and being unmarried (OR, 1.59; 95% CI, 1.02-2.44). Baseline antiretroviral use at baseline was linked to lower conception risk (OR, 0.34; 95% CI, 0.49-0.98 for mono- or combination therapy; OR, 0.34; 95% CI, 0.03-4.28 for HAART). Abortion was less likely during the HAART era, (OR, 0.68; 95% CI, 0.35-1.33 during the early HAART era; OR, 0.46; 95% CI, 0.23-0.90 during the later HAART era, compared with before HAART)., Conclusions: Women with HIV were less likely to conceive than at-risk uninfected women, but pregnancy outcomes were similar. Abortion became less common after the introduction of HAART.

Objective: To characterize fatal blunt aortic injury (BAI)., Methods: A retrospective chart review of 242 cases of fatal BAI in patients who underwent an autopsy at our institution between 1984 and 1997 was performed. Comparisons were made for statistical differences using the z-test., Results: Two hundred forty-two cases of fatal BAI were reviewed, making this the largest BAI autopsy study to date. Mechanisms of BAI included driver/passenger in motor vehicle crash (MVC) (68%), pedestrian versus MVC (17%), and motorcycle crash (8%). When comparing the mechanisms in the time period 1984 to 1988 to the time period 1989 to 1997, only the pedestrian versus MVC mechanism was significantly different (12% vs. 23%, p < 0.05). MVC direction of impact included head-on (45%), lateral (35%), and complex (20%). Two thirds of the victims sustained head injuries, rib fractures, and/or hepatic trauma. Only 58% of the victims had the classic isthmus laceration. There was one preventable death secondary to delay in diagnosis., Conclusion: BAI is not limited to frontal impact crashes; there should be a high index of suspicion of BAI in lateral impact crashes as well as pedestrian versus MVC mechanisms. Nonisthmus and complex aortic lacerations are common in fatal BAI. Finally, BAI is a highly lethal injury with few preventable deaths in this series.

Genomic DNA was obtained from peripheral blood samples of patients JB and DS each of whom received a kidney transplant at 16 years of age from a serologically HLA-DR matched and HLA-class I -mismatched donor. Both patients discontinued immunosuppression after 1-2 years and retained good renal function for an additional 5 years or more. DNA was analyzed for genetic polymorphisms in the tumor necrosis factor-alpha (TNFalpha) and tumor growth factor-beta1 (TGFbeta1) loci. Biopsy samples obtained during stable function (DS, JB) and during rejection (JB) were analyzed by RT/PCR for cytokine gene expression. Both patients had a high responder genotype for TGFbeta1. DS had a low responder TNFalpha genotype, while JB and his donor were both genotypically TNFalpha intermediate responders. DS had a high TGFbeta1: TNFalpha mRNA ratio in two biopsies obtained during tolerance, while JB, who eventually lost his graft, had more TNFalpha than TGFbeta1 mRNA. The results suggest a possible role for cytokine immunogenetics in the stability of peripheral tolerance.

Background: Registry analyses and single-center studies have demonstrated that hypertension significantly increases the risk for chronic graft loss. The graft itself may contribute to posttransplant hypertension, and intragraft vasoactive hormones therefore, may be dysregulated in posttransplant hypertension., Methods: We used the reverse-transcription polymerase chain reaction to assess the intragraft regulation of renin-angiotensin system transcripts in biopsy samples from 42 stable renal transplant patients with posttransplant hypertension. We also examined mRNA expression of inducible nitric oxide synthase, transforming growth factor-beta (TGF-beta), select cytokines, and metalloproteinase transcripts in biopsy tissue. Polymerase chain reaction products were quantitated using high performance liquid chromatography and normalized to beta-actin mRNA expression. Serum creatinine, glomerular filtration rate or creatinine clearance and tubular atrophy on biopsy were concurrently assessed., Results: Renin and select Thl cytokine mRNA expression correlated with blood pressure. Type 1 angiotensin II receptor mRNA expression significantly correlated with glomerular filtration rate or creatinine clearance (P = 0.034) and inversely correlated with Th1 cytokines, inducible nitric oxide synthase, and cyclooxygenase-1 mRNA expression (P< or =0.013 for each). Type 1 angiotensin II receptor mRNA also approached a significant inverse correlation with TGF-beta mRNA expression (P = 0.09). Conversely, angiotensin-converting enzyme mRNA expression directly correlated with Thl cytokine (P< or =0.008 for each) and TGF-beta mRNA expression (P = 0.006). Type 1 angiotensin II receptor mRNA expression also correlated with matrix metalloproteinase-1 promoter region, tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and tissue inhibitor of matrix metalloproteinase-3 mRNA expression. Notably, matrix metalloproteinase-1 promoter region, tissue inhibitor of matrix metalloproteinase-2, and tissue inhibitor of matrix metalloproteinase-3 inversely correlated with TGF-beta mRNA expression (P< or =0.0027 for each). Type 1 angiotensin II receptor mRNA expression at biopsy directly correlated with glomerular filtration rate at 2 year's follow-up. However, angiotensin-converting enzyme mRNA expression at biopsy inversely correlated with glomerular filtration rate at 2 year's follow-up., Conclusions: These data suggest that allograft-level RAS gene expression may be predictive of future graft function in the setting of diastolic hypertension.

Background: Chronic rejection (CR) remains idiopathic, difficult to prospectively identify, and once detected, unresponsive to increased immunosuppression. We hypothesized that clinically stable human renal allografts have ongoing evidence of injury and immune activity, and that this correlates with the worsening of allograft function characteristic of CR., Methods: The allografts of 40 stable renal allograft recipients were biopsied 2-3 years after transplantation. Biopsies were processed for histology and RNA extraction. RNA was evaluated by semi-quantitative RT-polymerase chain reaction for CD3y mRNA (a marker of T cell receptor turnover), and mRNA from cytokine genes previously shown to be transcribed during acute rejection: tumor necrosis factor-alpha, interferon-gamma, interleukin- (IL) 1beta, IL-2, IL-4, IL-6, and IL-8. Clinical parameters including urine protein and glomerular filtration rate were measured the day of biopsy. Findings were then compared with clinical outcome to establish associations between subclinical inflammation and graft dysfunction. Allograft function was measured again 2 years after biopsy and correlated with findings at the time of biopsy., Results: Cytokine transcripts and histological evidence of injury were detected in more than two-thirds of stable grafts. The degree of the lymphocytic infiltrate correlated with the degree of proteinuria (P=0.034) and histological fibrosis (P=0.005). Similarly, the degree of intragraft CD3y transcription correlated with increasing proteinuria (P=0.043). IL-6 and IL-8 transcripts were also correlated with evidence of graft injury. After 2 years, those biopsies originally found to have evidence of fibrosis, tubular atrophy, or CD3gamma transcription had worsening graft function as determined by creatinine and glomerular filtration rate., Conclusions: These data demonstrate that significant injury and immune activity can be detected in patients who are stable on clinical grounds. Undetected subclinical graft injury may be a cause of chronic allograft rejection.

Background: Infection and organ failure are the most common causes of death or serious complication in trauma patients surviving initial resuscitation and operation. Of the many possible causes of these complications, bacterial translocation and release of harmful cytokines and oxygen free radicals may play an important role in the pathogenesis of the complications associated with traumatic hemorrhage. Recombinant human bactericidal/permeability-increasing protein (rBPI21) has antibacterial and antiendotoxin properties, reduces cytokine levels, and increases survival in animal models of hemorrhagic shock. The primary objective of this study was to evaluate the safety and efficacy of prophylactic rBPI21 infusion in patients with hemorrhage due to trauma., Methods: This was a phase II, multicenter, randomized, double-blind, placebo-controlled trial. Patients who required at least 2 U of blood were randomized to receive rBPI21 (4 mg x kg(-1) x d(-1) for 2 consecutive days) or an equivalent volume of placebo by continuous infusion within 12 hours of injury. The primary efficacy end point was mortality or serious complication occurring during the first 15 days of the study. Safety was monitored clinically and by laboratory panels during the study period., Results: A total of 401 patients were treated (202 in the rBPI21 group and 199 in the placebo group). The composite end point rate of mortality or serious complication through day 15 was 46% in the placebo group and 39% in the rBPI21 group (hazard ratio = 0.79; p = 0.13). Secondary analysis, which adjusted for age, mechanism of injury, Injury Severity Score (1990 version), and units of blood received before study drug infusion showed similar results (hazard ratio = 0.79; p = 0.14). The proportion of patients who developed at least one serious organ dysfunction was 22% in the placebo group and 16% in the rBPI21 group (hazard ratio = 0.71; p = 0.14). The proportion of patients who developed either pneumonia or acute respiratory distress syndrome was 32% in the placebo group and 22% in the rBPI21 group (hazard ratio = 0.66; post hocp = 0.03). The beneficial trends of rBPI21 were observed in both blunt and penetrating trauma and were generally observed across different age groups, Injury Severity Scores, and units of blood transfused. No treatment difference was observed in mortality or resource utilization in this phase II study., Conclusion: rBPI21 was well-tolerated and demonstrated a favorable trend in reducing the composite primary end point of mortality or serious complication through day 15, especially respiratory complications, in patients with hemorrhage due to trauma. A phase III study is currently in progress.