Monocyte Infiltration and Kidney Allograft Dysfunction During Acute Rejection

Multiple cell types infiltrate acutely rejecting renal allografts. Typically, monocytes and T cells predominate. Although T cells are known to be required for acute rejection, the degree to which monocytes influence this process remains incompletely defined. Specifically, it has not been established to what degree monocytes impact the clinical phenotype of rejection or how their influence compares to that of T cells. We therefore investigated the relative impact of T cells and monocytes by correlating their presence as measured by immunohistochemical staining with the magnitude of the acute change in renal function at the time of biopsy in 78 consecutive patients with histological acute rejection. We found that functional impairment was strongly associated with the degree of overall cellular infiltration as scored using Banff criteria. However, when cell types were considered, monocyte infiltration was quantitatively associated with renal dysfunction while T-cell infiltration was not. Similarly, renal tubular stress, as indicated by HLA-DR expression, increased with monocyte but not T-cell infiltration. These data suggest that acute allograft dysfunction is most closely related to monocyte infiltration and that isolated T-cell infiltration has less acute functional impact. This relationship may be useful in assigning acute clinical relevance to biopsy findings.     

Interventions to improve or facilitate linkage to or retention in pre-ART (HIV) care and initiation of ART in low- and middle-income settings – a systematic review

Introduction

Several approaches have been taken to reduce pre-antiretroviral therapy (ART) losses between HIV testing and ART initiation in low- and middle-income countries, but a systematic assessment of the evidence has not yet been undertaken. The aim of this systematic review is to assess the potential for interventions to improve or facilitate linkage to or retention in pre-ART care and initiation of ART in low- and middle-income settings.

Methods

An electronic search was conducted on Medline, Embase, Global Health, Web of Science and conference databases to identify studies describing interventions aimed at improving linkage to or retention in pre-ART care or initiation of ART. Additional searches were conducted to identify on-going trials on this topic, and experts in the field were contacted. An assessment of the risk of bias was conducted. Interventions were categorized according to key domains in the existing literature.

Results

A total of 11,129 potentially relevant citations were identified, of which 24 were eligible for inclusion, with the majority (n=21) from sub-Saharan Africa. In addition, 15 on-going trials were identified. The most common interventions described under key domains included: health system interventions (i.e. integration in the setting of antenatal care); patient convenience and accessibility (i.e. point-of-care CD4 count (POC) testing with immediate results, home-based ART initiation); behaviour interventions and peer support (i.e. improved communication, patient referral and education) and incentives (i.e. food support). Several interventions showed favourable outcomes: integration of care and peer supporters increased enrolment into HIV care, medical incentives increased pre-ART retention, POC CD4 testing and food incentives increased completion of ART eligibility screening and ART initiation. Most studies focused on the general adult patient population or pregnant women. The majority of published studies were observational cohort studies, subject to an unclear risk of bias.

Conclusions

Findings suggest that streamlining services to minimize patient visits, providing adequate medical and peer support, and providing incentives may decrease attrition, but the quality of the current evidence base is low. Few studies have investigated combined interventions, or assessed the impact of interventions across the HIV cascade. Results from on-going trials investigating POC CD4 count testing, patient navigation, rapid ART initiation and mobile phone technology may fill the quality of evidence gap. Further high-quality studies on key population groups are required, with interventions informed by previously reported barriers to care.     

Olecranon fractures: factors influencing re-operation

Purpose

We evaluated factors influencing re-operation in tension band and plating of isolated olecranon fractures.

Methods

Four hundred eighty-nine patients with isolated olecranon fractures who underwent tension band (TB) or open reduction internal fixation (ORIF) from 2003 to 2013 were identified at an urban level 1 trauma centre. Medical records were reviewed for patient information and complications, including infection, nonunion, malunion, loss of function or hardware complication requiring an unplanned surgical intervention. Electronic radiographs of these patients were reviewed to identify Orthopaedic Trauma Association (OTA) fracture classification and patients who underwent TB or ORIF.

Results

One hundred seventy-seven patients met inclusion criteria of isolated olecranon fractures. TB was used for fixation in 43 patients and ORIF in 134. No statistical significance was found when comparing complication rates in open versus closed olecranon fractures. In a multivariate analysis, the key factor in outcome was method of fixation. Overall, there were higher rates of infection and hardware removal in the TB compared with the ORIF group.

Conclusions

Our results demonstrate that the dominant factor driving re-operation in isolated olecranon fractures is type of fixation. When controlling for all variables, there is an increased chance of re-operation in patients with TB fixation.     

Screening for blunt cerebrovascular injuries in pediatric trauma patients

BackgroundAdult imaging for blunt cerebrovascular injuries (BCVI) is based on the Denver and Memphis screening criteria where CT angiogram (CTA) is performed for any one of the criteria being positive. These guidelines have been extrapolated to the pediatric population. We hypothesize that the current adult criteria applied to pediatrics lead to unnecessary CTA in pediatric trauma patients.Study designAt our center, a 9-year retrospective study revealed that strict adherence to the Denver and Memphis criteria would have resulted in 332 unnecessary CTAs out of 2795 trauma patients with only 0.3% positive for BCVI. We also conducted a retrospective chart review of 776,355 pediatric trauma patients in the National Trauma Data Bank (NTDB) from 2007 to 2014. Data collection included children between ages 0 and 18, ICD-9 search for blunt cerebrovascular injury, and ICD-9 codes that applied to both Denver and Memphis criteria.ResultsOf 776,355 pediatric trauma activations, 81,294 pediatric patients in the NTDB fit the Denver/Memphis criteria for screening CTA neck or angiography based on ICD-9 codes, while only 2136 patients suffered BCVI. Strict utilization of the Denver/Memphis criteria would have led to a negative CTA in 79,158 (97.4%) patients. Multivariate regression analysis indicates that patients with skull base fracture, cervical spine fractures, cervical spine fracture with cervical cord injury, traumatic jugular venous injury, and cranial nerve injury should be considered part of the screening criteria for BCVI.ConclusionOur study suggests the Denver and Memphis criteria are inadequate screening criteria for CTA looking for BCVI in the pediatric blunt trauma population. New criteria are needed to adequately indicate the need for CT angiography in the pediatric trauma population.Level of evidenceIV.     

A comparison of the microarchitectural bone adaptations of the concave and convex thoracic spinal facets in idiopathic scoliosis

BACKGROUND: A limited number of studies have assessed the changes in bone microarchitecture in spinal facets with use of light microscopy but not with use of electron microscopy techniques. The purpose of this study was to analyze the facets in patients with scoliosis to determine whether there are differences in the bone microarchitecture of contralateral facets at the same anatomic level. METHODS: In eight patients undergoing posterior spinal arthrodesis for the treatment of idiopathic scoliosis, biopsy specimens of facet pairs at matched anatomic levels were obtained from three locations: (1). the curve apex, (2). one level cephalad to the apex, and (3). one level caudad to the apex. The facets were analyzed for cortical bone porosity and thickness with use of scanning electron microscopy and National Institutes of Health imaging software. The concave and convex facets were compared with use of a paired t test. RESULTS: The mean porosity (and standard deviation) for the concave and convex facets was 16.5% +/- 5.8% and 24.1% +/- 6.2%, respectively. Those on the convex side were significantly more porous than those on the concave side (p 相似文献   

Interferon gamma inhibits inter-enterocyte communication by reducing connexin 43 phosphorylation

Introduction. Restitution of the intestinal barrier requires inter-enterocyte communication via the phosphorylated gap junction protein connexin 43. Experimental necrotizing enterocolitis (NEC) is characterized by elevated interferon gamma (IFN) and impaired restitution. We therefore hypothesized that IFN impairs gap junction (GJ) function and restitution by inhibiting phosphorylation of connexin43. We further sought to determine whether connexin 43 phosphorylation was altered in human NEC. Methods. Connexin 43 expression and phosphorylation was assessed in IEC-6 cells ± IFN (1000 u/ml) by SDS--PAGE and confocal microscopy. GJ function was detected by microinjecting IEC-6 cells ± IFN with the GJ tracer lucifer yellow (LY) and impermeant rhodamine dextran. GJ function was inhibited with oleamide (10 μM). In vitro restitution was assessed using time lapsed video microscopy of IEC-6 cells ± IFN migrating across a scraped wound. Small bowel mucosal scrapings were acquired from infants undergoing bowel resection for NEC and compared to specimens taken from infants without NEC. Data are mean ± SEM. Results. IFN significantly reduced phosphorylation of connexin 43 (band density relative to actin, Ctrl: 0.86 ± 0.3 versus IFNγ 0.37 ± 0.1, P < 0.05) and decreased membrane localization of the phosphorylated gap junctions. This correlated with decreased gap junction function as detected by loss of LY transfer (levels of intercellular transfer: Ctrl: 3.2 ± 0.2, IFN 2.4 ± 0.3, oleamide 0, P < 0.05). Oleamide and IFN significantly reduced enterocyte restitution (ctrl: 5 μm/h, oleam: 1.5 μm/h, IFN: 1.6 μm/h, P < 0.05), correlating with a lack of intercellular communication. Strikingly, phosphorylation of connexin 43 in the mucosa of infants with NEC was significantly reduced as compared to control bowel, which correlated with the extent of mucosal disease. Conclusion. IFN inhibits phosphorylation of connexin 43, leading to impaired inter-enterocyte communication and reduced restitution. The finding of decreased phosphoconnexin 43 in human NEC suggests that impaired inter-enterocyte communication may underlie the barrier dysfunction in this disease.     

Jejunal mucosal DNA content and maturation

Although pentagastrin has a tropic action on intestinal mucosa in suckling rat pups, and at weaning a rise in gastrin levels coincides with maturation of the intestinal mucosa, direct correlations of serum gastrin levels and intestinal maturation have yet to be made. Ten-day-old rats were subjected either to antrectomy to produce a 43% decrease in serum gastrin levels or to fundectomy to produce a 319% increase over gastrin levels in rumenectomized or normal animals. These changes were not associated with tropic or adaptive changes in jejunal or colonic mucosa as determined by jejunal and colonic DNA content, jejunal sucrase activity, jejunal villous height, or crypt depths in jejunum and colon at the beginning (day 15), middle (day 21), or end (day 27) of the weaning period. To the contrary, an inverse relation was found between serum gastrin levels and both jejunal mucosal DNA content and sucrase activity as an index of maturation.     

Association Between Ankle Fractures and Obesity

Obesity is an epidemic in the United States and is associated with an increased risk of musculoskeletal problems. Rotational injuries of the ankle with a Weber C fibula fracture have a greater risk of syndesmosis disruption and instability. The goal of the present study was to explore the association between obesity and ankle fractures. Using a retrospective review, the radiographs of 280 patients with an ankle fracture were reviewed and classified using the Weber classification, which was then associated with the body mass index, gender, age, diabetes, tobacco use, and osteoporosis. Patients with a body mass index of 30 kg/m² or greater (odds ratio 1.78), men (odds ratio 1.74), and age 25 years or younger (odds ratio 3.97) had greater odds of having a Weber C ankle fracture (compared with Weber A and B) and Weber C and B (compared with Weber A). Diabetes mellitus, osteoporosis/osteopenia, and current tobacco use were not significantly associated with the severity of the ankle fracture. The results from the present study suggest that obesity presents a greater risk of sustaining a more proximal distal fibula fracture.     

External Iliac Endofibrosis in Endurance Athletes: A Novel Case in an Endurance Runner and a Review of the Literature

BACKGROUND: There is increasing recognition that high-performance athletes can develop symptomatic arterial flow restriction in one or both (15%) legs due to kinking and/or endofibrosis of their iliac arteries. METHODS: Case report and review based on a Medline search of the literature. RESULTS: A 51-year-old female, 24-hour endurance runner presented with a six-month history of rapidly progressing intermittent claudication affecting her right thigh and calf in the absence of classical risk factors for atherosclerosis. On the basis of invasive and non-invasive investigations, a provisional diagnosis of endofibrosis was made and she was treated successfully with angioplasty. CONCLUSIONS: The epidemiology, optimal investigation and treatment of iliac endofibrosis in endurance athletes is poorly described. Each individual unit's experience is likely to be very small. A European register of such cases would increase our understanding of the condition and improve patient outcomes.