Influence of pulsatile perfusion preservation on outcomes in kidney transplantation from expanded criteria donors

BACKGROUND: Expanded criteria donors (ECDs) increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns about diminished survival, poorer renal function, and higher rates of delayed graft function. STUDY DESIGN: Retrospective analysis of intermediate-term outcomes in ECD kidney transplantations according to method of preservation at a single center using a standardized approach. RESULTS: Over a 5-year period, we performed 141 donations-after-brain-death ECD kidney transplantations into adult recipients. A total of 114 kidneys (81%) were managed with combined cold-storage and pulsatile perfusion preservation (PPP), and the remaining 27 (19%) were preserved with cold storage (CS). The PPP group had a higher proportion of kidneys preserved for longer than 30 hours (28% versus 0, p < 0.001) and a longer mean cold ischemia time (24.5 hours PPP versus 19 hours CS, p < 0.01). Other donor and recipient characteristics were similar between groups. Incidence of delayed graft function was 11% in PPP-stored kidneys versus 37% in CS kidneys (p = 0.002). With a mean followup of 27 months, patient (91% PPP versus 96% CS) and kidney graft survival (81% PPP versus 81.5% CS) rates were comparable. Mean 12-month serum creatinine (1.9 mg/dL) and calculated Modification of Diet in Renal Disease glomerular filtration rate (41 mL/min) values were similar between groups. CONCLUSIONS: Despite longer cold ischemia times, recipients of ECD kidneys managed with PPP had similar survival and functional outcomes, but experienced a marked reduction in the rate of delayed graft function.     

Biomechanical evaluation of the ligamentous stabilizers of the scaphoid and lunate: part III

PURPOSE: This study continued our previous investigations of the ligaments stabilizing the scaphoid and lunate in which we examined the scapholunate interosseous ligament, the radioscaphocapitate, and the scaphotrapezial ligament. In this current study, we examined the effects of sectioning the dorsal radiocarpal ligament, dorsal intercarpal ligament, scapholunate interosseous ligament, radioscaphocapitate, and scaphotrapezial ligaments. In the current study, the scapholunate interosseous ligament, radioscaphocapitate, and scaphotrapezial ligaments were sectioned in a different order than performed previously. METHODS: Three sets of 8 cadaver wrists were tested in a wrist joint motion simulator. In each set of wrists, only 3 of the 5 ligaments were cut in specific sequences. Each wrist was moved in continuous cycles of flexion-extension and radial-ulnar deviation. Kinematic data for the scaphoid and lunate were recorded for each wrist in the intact state, after the 3 ligaments were sectioned in various sequences and after the wrist was moved through 1,000 cycles of motion. RESULTS: Dividing the dorsal intercarpal or scaphotrapezial ligaments did not alter the motion of the scaphoid or lunate. Dividing the dorsal radiocarpal ligament alone caused a slight statistical increase in lunate radial deviation. Dividing the scapholunate interosseous ligament after first dividing the dorsal intercarpal, dorsal radiocarpal, or scaphotrapezial ligaments caused large increases in scaphoid flexion and lunate extension. CONCLUSIONS: Based on these findings, we concluded that the scapholunate interosseous ligament is the primary stabilizer and that the other ligaments are secondary stabilizers of the scapholunate articulation. Dividing the dorsal radiocarpal, dorsal intercarpal, or scaphotrapezial ligaments after cutting the scapholunate interosseous ligament produces further changes in scapholunate instability or results in changes in the kinematics for a larger portion of the wrist motion cycle.     

Severity of scapholunate instability is related to joint anatomy and congruency

PURPOSE: To determine whether the bony architecture of the distal radius and proximal scaphoid have a role in stabilizing the scaphoid, and to determine whether a relationship between the bony geometry measurements and the amount of wrist constraint could be determined. METHODS: Eight cadaver wrists were tested in a wrist joint motion simulator. The level of scapholunate instability after sectioning the scapholunate interosseous, radioscaphocapitate, and the scaphotrapezium ligaments was determined and related to radiographic measurements of volar tilt, lateral tilt (ulnar tilt of the radioscaphoid fossa), the depth of the radioscaphoid fossa, and 6 radii of curvature measurements of the proximal scaphoid and distal radius. The force to dorsally dislocate the scaphoid out of the radioscaphoid fossa was computed. RESULTS: The radioscaphoid fossa and scaphoid curvatures were larger in those wrists that did not show gross instability after ligamentous sectioning in the wrist simulator. Similarly, those wrists with a deeper radioscaphoid fossa and greater volar tilt were also more stable. The force required to dislocate these wrists was greater than in those wrists that showed gross carpal instability. CONCLUSIONS: This study suggests that the bony anatomy of the radius and scaphoid have a role in stabilizing the carpus after ligament injury. The effect of ligament sectioning on producing carpal instability may be moderated by the bone geometry of the radiocarpal joint. This may explain why some people may have a tear of the scapholunate interosseous ligament but not present with clinical symptoms.     

Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures

An international panel reviewed the methodology for clinical trials of spinal cord injury (SCI), and provided recommendations for the valid conduct of future trials. This is the second of four papers. It examines clinical trial end points that have been used previously, reviews alternative outcome tools and identifies unmet needs for demonstrating the efficacy of an experimental intervention after SCI. The panel focused on outcome measures that are relevant to clinical trials of experimental cell-based and pharmaceutical drug treatments. Outcome measures are of three main classes: (1) those that provide an anatomical or neurological assessment for the connectivity of the spinal cord, (2) those that categorize a subject's functional ability to engage in activities of daily living, and (3) those that measure an individual's quality of life (QoL). The American Spinal Injury Association impairment scale forms the standard basis for measuring neurologic outcomes. Various electrophysiological measures and imaging tools are in development, which may provide more precise information on functional changes following treatment and/or the therapeutic action of experimental agents. When compared to appropriate controls, an improved functional outcome, in response to an experimental treatment, is the necessary goal of a clinical trial program. Several new functional outcome tools are being developed for measuring an individual's ability to engage in activities of daily living. Such clinical end points will need to be incorporated into Phase 2 and Phase 3 trials. QoL measures often do not correlate tightly with the above outcome tools, but may need to form part of Phase 3 trial measures.     

Placental Hofbauer cells assemble and sequester HIV-1 in tetraspanin-positive compartments that are accessible to broadly neutralizing antibodies

Introduction

Within monocyte-derived macrophages, HIV-1 accumulates in intracellular virus-containing compartments (VCCs) that are inaccessible to the external environment, which implicate these cells as latently infected HIV-1 reservoirs. During mother-to-child transmission of HIV-1, human placental macrophages (Hofbauer cells (HCs)) are viral targets, and have been shown to be infected in vivo and sustain low levels of viral replication in vitro; however, the risk of in utero transmission is less than 7%. The role of these primary macrophages as viral reservoirs is largely undefined. The objective of this study is to define potential sites of viral assembly, accumulation and neutralization in HCs given the pivotal role of the placenta in preventing HIV-1 infection in the mother-infant dyad.

Methods

Term placentae from 20 HIV-1 seronegative women were obtained following caesarian section. VCCs were evaluated by 3D confocal and electron microscopy. Colocalization R values (Pearson''s correlation) were quantified with colocalization module of Volocity 5.2.1. Replication kinetics and neutralization studies were evaluated using p24 ELISA.

Results

We demonstrate that primary HCs assemble and sequester HIV-1_BaL in intracellular VCCs, which are enriched in endosomal/lysosomal markers, including CD9, CD81, CD63 and LAMP-1. Following infection, we observed HIV-1 accumulation in potentially acidic compartments, which stained intensely with Lysotracker-Red. Remarkably, these compartments are readily accessible via the cell surface and can be targeted by exogenously applied small molecules and HIV-1-specific broadly neutralizing antibodies. In addition, broadly neutralizing antibodies (4E10 and VRC01) limited viral replication by HIV-1-infected HCs, which may be mediated by FcγRI.

Conclusions

These findings suggest that placental HCs possess intrinsic adaptations facilitating unique sequestration of HIV-1, and may serve as a protective viral reservoir to permit viral neutralization and/or antiretroviral drug entry in utero.     

Endometriosis in Adolescents

Background and Objectives:

Women with endometriosis often report onset of symptoms during adolescence; however, the diagnosis of endometriosis is often delayed. The aim of this study was to describe the experience of adolescents who underwent laparoscopy for pelvic pain and were diagnosed with endometriosis: specifically, the symptoms, time from onset of symptoms to correct diagnosis, number and type of medical professionals seen, diagnosis, treatment, and postoperative outcomes.

Methods:

We reviewed a series of 25 females ≤21 years of age with endometriosis diagnosed during laparoscopy for pelvic pain over an 8-year period. These patients were followed up for 1 year after surgery.

Results:

The mean age at the time of surgery was 17.2 (2.4) years (range, 10–21). The most common complaints were dysmenorrhea (64%), menorrhagia (44%), abnormal/irregular uterine bleeding (60%), ≥1 gastrointestinal symptoms (56%), and ≥1 genitourinary symptoms (52%). The mean time from the onset of symptoms until diagnosis was 22.8 (31.0) months (range, 1–132). The median number of physicians who evaluated their pain was 3 (2.3) (range, 1–12). The adolescents had stage I (68%), stage II (20%), and stage III (12%) disease. Atypical endometriosis lesions were most commonly observed during laparoscopy. At 1 year, 64% reported resolved pain, 16% improved pain, 12% continued pain, and 8% recurrent pain.

Conclusions:

Timely referral to a gynecologist experienced with laparoscopic diagnosis and treatment of endometriosis is critical to expedite care for adolescents with pelvic pain. Once the disease is diagnosed and treated, these patients have favorable outcomes with hormonal and nonhormonal therapy.     

Duration of Lactation and Incidence of the Metabolic Syndrome in Women of Reproductive Age According to Gestational Diabetes Mellitus Status: A 20-Year Prospective Study in CARDIA (Coronary Artery Risk Development in Young Adults)

OBJECTIVE

The objective of the study was to prospectively assess the association between lactation duration and incidence of the metabolic syndrome among women of reproductive age.

RESEARCH DESIGN AND METHODS

Participants were 1,399 women (39% black, aged 18–30 years) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, an ongoing multicenter, population-based, prospective observational cohort study conducted in the U.S. Women were nulliparous and free of the metabolic syndrome at baseline (1985–1986) and before subsequent pregnancies, and reexamined 7, 10, 15, and/or 20 years after baseline. Incident metabolic syndrome case participants were identified according to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Complementary log-log models estimated relative hazards of incident metabolic syndrome among time-dependent lactation duration categories by gestational diabetes mellitus (GDM) adjusted for age, race, study center, baseline covariates (BMI, metabolic syndrome components, education, smoking, physical activity), and time-dependent parity.

RESULTS

Among 704 parous women (620 non-GDM, 84 GDM), there were 120 incident metabolic syndrome case participants in 9,993 person-years (overall incidence rate 12.0 per 1,000 person-years; 10.8 for non-GDM, 22.1 for GDM). Increased lactation duration was associated with lower crude metabolic syndrome incidence rates from 0–1 month through >9 months (P < 0.001). Fully adjusted relative hazards showed that risk reductions associated with longer lactation were stronger among GDM (relative hazard range 0.14–0.56; P = 0.03) than non-GDM groups (relative hazard range 0.44–0.61; P = 0.03).

CONCLUSIONS

Longer duration of lactation was associated with lower incidence of the metabolic syndrome years after weaning among women with a history of GDM and without GDM, controlling for preconception measurements, BMI, and sociodemographic and lifestyle traits. Lactation may have persistent favorable effects on women''s cardiometabolic health.Lactation has favorable effects on cardiometabolic risk factors in women with and without a history of gestational diabetes mellitus (GDM), a strong predictor of type 2 diabetes (1,2) and the metabolic syndrome after pregnancy (3). In the general population, lactating compared with nonlactating women exhibit a less atherogenic lipid profile (4) and lower blood glucose and insulin concentrations (5). Consistent with these findings, lactating women with recent GDM experience lower fasting plasma glucose and insulin levels, higher plasma HDL cholesterol levels, and 50% lower prevalence of type 2 diabetes at 12–16 weeks postpartum (6,7).Yet, few studies have investigated whether lactation''s favorable effects on cardiometabolic risk factors persist after weaning to protect women against future disease. The only study, to our knowledge, to measure changes from preconception to after weaning reported 6-mg/dl higher average HDL cholesterol levels among women who lactated for ≥3 months versus <3 months independent of preconception plasma HDL cholesterol levels and weight gain (8). Epidemiologic studies have reported weak to modest protective associations between lactation and disease risk in midlife to late life, including lower prevalence of the metabolic syndrome (9,10) or cardiovascular risk factors (11) and lower incidence of myocardial infarction (12) and type 2 diabetes (13). Yet, evidence is lacking that directly links risk factor changes that persist after weaning to subsequent disease onset, because disease status and lactation history were ascertained decades after pregnancy, and preconception and/or postweaning risk factor measurements were not available (9–13). Other limitations include classification of outcomes via self-report only (11–13), and failure to account for mediating or confounding effects of lifestyle habits during the reproductive years. Lastly, lactation duration in relation to disease risk has not been examined separately among women with a history of GDM, with the exception of one study reporting a null association with incident diabetes (13).To our knowledge, studies have never examined lactation and incidence of the metabolic syndrome, or variation in disease risk by GDM status. To address these gaps, we prospectively examined whether increasing duration of lactation was associated with lower incidence of the metabolic syndrome during a 20-year period among women of childbearing age. We examined incidence rates for GDM and non-GDM pregnancies and controlled for preconception risk factor levels, sociodemographics, and follow-up behavioral attributes.     

Initial Surgeon Training for Single Port Access Surgery: Our First Year Experience

Background:

We have developed a single port access (SPA) surgical technique that allows for procedures to be done through a single umbilical port incision <20 mm in length. For a new approach to be universally beneficial, it needs to be easily learned and applied.

Methods:

Single port access abdominal procedures are performed through one umbilical incision where skin and soft tissue flaps are raised from the underlying fascia to allow insertion of up to 4 instruments. Fifty surgeons with varying degrees of laparoscopic training participated in SPA training programs at Drexel University to learn and apply the SPA technique through participation in an animate (porcine) laboratory.

Results:

All surgeons successfully performed the SPA access technique without difficulty and completed the cholecystectomy in <55 minutes (average, 42). Eight surgeons successfully performed placement of a cholangiogram catheter. All recognized the value of a formal training symposium to learn SPA techniques before performing SPA procedures in their practice.

Conclusions:

The SPA technique has been successfully shown to be an approach that is easily learned and accomplished. We believe this is a necessary and important bridge towards proficiency in performing SPA procedures in clinical patients.