Abnormal hippocampal structure and function in clinical anxiety and comorbid depression

Given the high prevalence rates of comorbidity of anxiety and depressive disorders, identifying a common neural pathway to both disorders is important not only for better diagnosis and treatment, but also for a more complete conceptualization of each disease. Hippocampal abnormalities have been implicated in anxiety and depression, separately; however, it remains unknown whether these abnormalities are also implicated in their comorbidity. Here we address this question by testing 32 adults with generalized anxiety disorder (15 GAD only and 17 comorbid MDD) and 25 healthy controls (HC) using multimodal MRI (structure, diffusion and functional) and automated hippocampal segmentation. We demonstrate that (i) abnormal microstructure of the CA1 and CA2‐3 is associated with GAD/MDD comorbidity and (ii) decreased anterior hippocampal reactivity in response to repetition of the threat cue is associated with GAD (with or without MDD comorbidity). In addition, mediation‐structural equation modeling (SEM) reveals that our hippocampal and dimensional symptom data are best explained by a model describing a significant influence of abnormal hippocampal microstructure on both anxiety and depression—mediated through its impact on abnormal hippocampal threat processing. Collectively, our findings show a strong association between changes in hippocampal microstructure and threat processing, which together may present a common neural pathway to comorbidity of anxiety and depression. © 2016 Wiley Periodicals, Inc.     

Are spine injuries sustained in battle truly different?

Background contextThe severity and prognosis of combat-related injuries to the spine and spine injuries sustained unrelated to direct combat have not been previously compared. Differences may have implications on tactics, treatment strategies, and directions for future research.PurposeCompare the severity and prognosis of battle and nonbattle injuries to the spine.Study designRetrospective study.Patient sampleAmerican military personnel who were injured in a combat zone and whose medical data were abstracted in the Joint Theater Trauma Registry (JTTR).MethodsThe JTTR was queried using International Statistical Classification of Diseases, Ninth Revision codes to identify all individuals who sustained battle and nonbattle injuries to the neck, back, spinal column, or spinal cord in Operation Iraqi Freedom or Operation Enduring Freedom from October 2001 to December 2009. Medical records of all identified servicemembers were individually reviewed. Demographic information, including sex, age, military rank, date of injury, and final disposition, was obtained for all patients. Spinal injuries were categorized according to anatomic location, associated neurologic involvement, precipitating mechanism of injury (MOI), and concomitant wounds. These data points were compared for the groups battle spine injuries (BSIs) and nonbattle spine injuries (NBSIs).ResultsFive hundred two servicemembers sustained a total of 1,834 battle injuries to the spinal column, including 1,687 fractures (92%), compared with 92 servicemembers sustaining 267 nonbattle spinal column injuries, with 241 (90%) fractures. Ninety-one BSI servicemembers (18% of patients) sustained spinal cord injuries (SCIs) with 41 (45%) complete SCIs, compared with 13 (14% of patients) nonbattle SCIs with six (46.2%) complete injuries (p=.92). The reported MOI for 335 BSI servicemembers (66.7%) was an explosion compared with one NBSI explosive injury. Eighty-four patients (17%) sustained gunshot wounds (GSWs) in battle compared with five (5.2%) nonbattle GSWs. Fifteen patients (3.0%) sustained a battle-related fall compared with 29 (30%) nonbattle-related falls. Battle spine injury servicemembers underwent significantly higher rates of surgical interventions (p<.0001), were injured by high-energy injury mechanisms at a significantly greater rate (p<.0001), and demonstrated a trend toward lower neurologic recovery rates after SCI (p=.16).ConclusionsBattle spine injury and NBSI are separate entities that may ultimately have disparate long-term prognoses. Nonbattle spine injury patients, although having similar MOIs compared with civilian spinal trauma, maintain a different patient demographic. Further research must be directed at accurately quantifying the long-term disabilities of all spine injuries sustained in a combat theater, whether they are the result of battle or not.     

Donor‐Derived Fungal Infections in Organ Transplant Recipients: Guidelines of the American Society of Transplantation,Infectious Diseases Community of Practice†

Donor‐derived fungal infections can be associated with serious complications in transplant recipients. Most cases of donor‐derived candidiasis have occurred in kidney transplant recipients in whom contaminated preservation fluid is a commonly proposed source. Donors with cryptococcal disease, including those with unrecognized cryptococcal meningoencephalitis may transmit the infection with the allograft. Active histoplasmosis or undiagnosed and presumably asymptomatic infection in the donor that had not resolved by the time of death can result in donor‐derived histoplasmosis in the recipient. Potential donors from an endemic area with either active or occult infection can also transmit coccidioidomycosis. Rare instances of aspergillosis and other mycoses, including agents of mucormycosis may also be transmitted from infected donors. Appropriate diagnostic evaluation and prompt initiation of appropriate antifungal therapy are warranted if donor‐derived fungal infections are a consideration. This document discusses the characteristics, evaluation and approach to the management of donor‐derived fungal infections in organ transplant recipients.     

Alterations in T-Cell Subset Frequency in Peripheral Blood in Obesity

Background: Obesity affects the regulation of immune and inflammatory responses. This study characterizes differences in peripheral blood lymphocyte phenotype in obese humans. Methods: Frequencies of lymphocyte subsets among peripheral blood mononuclear cells were compared between 10 obese (BMI ≥35) and 10 lean subjects, as determined by antibodies directed against cluster differentiation (CD) markers. Results: Obese patients demonstrated an increased frequency of CD3+CD4+ T-cells (mean difference 12%, P=0.004), a decreased frequency of CD3+CD8+ T-cells (mean difference 9.4%, P=0.016) and an increased frequency of CD3+CD8+CD95+ T-cells (mean difference 13.3%, P=0.032). No other differences among T-cell or monocyte subsets were noted. Conclusions: Obesity is associated with alterations in frequencies of peripheral CD4+ and CD8+ T-cells and aberrations in the expression of CD95 among CD8+ T-cells. These data suggest both CD4+ and CD8+ T-cell compartments, as well as the regulation of CD95 expression on CD8+ T-cells, as targets for further study into obesity's effects on the immune system.     

Experience with Neoral versus Sandimmune in primary liver transplant recipients

We compared results using Neoral versus Sandimmune, each in combination with steroid and azathioprine immunosuppression, in primary liver transplantation recipients. There were 15 patients in each group with similar demographic distributions. Intravenous cyclosporine was stopped at 4.3 ± 1.9 days in the Neoral group vs 7.8 ± 4.9 days in the Sandimmune group (P < 0.025). Cyclosporine levels in the first 10 days were higher (mean 306 ng/ml vs 231 ng/ml) in the Neoral group than the Sandimmune group (P < 0.05). The Neoral dose was less than the Sandimmune dose (mean 5.5 ng/kg per day vs 7.9 ng/kg per day) to achieve these levels in that time period (P < 0.05). Two patients (13 %) experienced three episodes of biopsy-proven rejection in the Neoral group compared to nine patients (60 %) with 12 episodes of rejection in the Sandimmune group (P < 0.025). Incidences of neurological and renal complications were similar between the groups. Infections requiring treatment were also similar. Liver function, renal function, and marrow function, evaluated at days 7, 14, 21, 28, and 2, 4, 6, and 12 months post-transplant, were not different between the groups. In summary, shorter use of intravenous cyclosporine and quicker stabilization of trough cyclosporine levels was achieved with Neoral than with Sandimmune. In the early posttransplant period, higher levels with lower doses were achieved with Neoral than with Sandimmune. In our experience, the incidence of rejection was lower with Neoral than with Sandimmune. There were similar lengths of hospitalization, mortality, adverse events, retransplantation, and similar liver, renal, and marrow function up to 1 year posttransplantation. Because of this experience, we continued to use Neoral in a total of 59 primary liver transplant recipients. We have not used intravenous cyclosporine in the last 44 patients. Follow-up was a mean of 11.4 months, ranging from 1 to 27 months. The incidence of rejection was 24 % in these 59 patients compared to our historical experience of 70 % using Sandimmune.     

Risk factors for postoperative sepsis in laparoscopic gastric bypass

Introduction

Postoperative sepsis is a rare but serious complication following elective surgery. The purpose of this study was to identify the rate of postoperative sepsis following elective laparoscopic gastric bypass (LGBP) and to identify patients’ modifiable, preoperative risk factors.

Methods

The American College of Surgeons National Surgical Quality Improvement Program database was queried from 2005 to 2013 for factors associated with the development of postoperative sepsis following elective LGBP. Patients who developed sepsis were compared to those who did not. Results were analyzed using the Chi-square test for categorical variables and Wilcoxon two-sample test for continuous variables. A multivariate logistic regression analysis was utilized to calculate adjusted odds ratios for factors contributing to sepsis.

Results

During the study period, 66,838 patients underwent LGBP. Of those, 546 patients developed postoperative sepsis (0.82 %). The development of sepsis was associated with increased operative time (161 ± 77.8 vs. 135.10 ± 56.5 min; p < 0.0001) and a greater number of preoperative comorbidities, including diabetes (39.6 vs. 30.6 %; p < 0.0001), hypertension requiring medication (65.2 vs. 54 %; p < 0.0001), current tobacco use (16.7 vs. 11.5 %; p = 0.0002), and increased pack-year history of smoking (8.6 ± 18.3 vs. 5.6 ± 14.2; p = 0.0006), and the Charlson Comorbidity Index (0.51 ± 0.74 vs. 0.35 ± 0.57, p < 0.0001). Sepsis resulted in an increased length of stay (10.1 ± 14.4 vs. 2.4 ± 4.8 days; p < 0.0001) and a 30 times greater chance of 30-day mortality (4.03 vs. 0.11 %, p < 0.0001). Multivariate logistic regression analysis showed that current smokers had a 63 % greater chance of developing sepsis compared to non-smokers, controlling for age, race, gender, BMI, and CCI score (OR 1.63, 95 % CI 1.23–2.14; p = 0.0006).

Conclusions

Laparoscopic gastric bypass is uncommonly associated with postoperative sepsis. When it occurs, it portends a 30 times increased risk of death. A patient history of diabetes, hypertension, and increasing pack-years of smoking portend an increased risk of sepsis. Current smoking status, a preoperative modifiable risk factor, is independently associated with the chance of postoperative sepsis. Preoperative patient optimization and risk reduction should be a priority for elective surgery, and patients should be encouraged to stop smoking prior to gastric bypass.

     

Safety and performance evaluation of a next‐generation antimicrobial dressing in patients with chronic venous leg ulcers

The objective of this study was to investigate the safety and performance of AQUACEL? Ag+ dressing, a wound dressing containing a combination of anti‐biofilm and antimicrobial agents, in the management of chronic wounds. Patients (n = 42) with venous leg ulcers exhibiting signs of clinical infection were treated for 4 weeks with AQUACEL? Ag+ dressing, followed by management with AQUACEL? wound dressings for 4 weeks. Wound progression, wound size, ulcer pain and clinical evolution of the wound were assessed for up to 8 weeks. Adverse events were recorded throughout the study. AQUACEL? Ag+ dressing had an acceptable safety profile, with only one patient discontinuing from the study, because of a non‐treatment‐related adverse event. After 8 weeks, substantial wound improvements were observed: 5 patients (11·9%) had healed ulcers and 32 patients (76·2%) showed improvement in ulcer condition. The mean ulcer size had reduced by 54·5%. Patients reported less pain as the study progressed. Notable improvements were observed in patients with ulcers that were considered to require treatment with systemic antibiotics or topical antimicrobials at baseline (n = 10), with a mean 70·2% reduction in wound area. These data indicate that AQUACEL? Ag+ dressing has an acceptable safety profile in the management of venous leg ulcers that may be impeded by biofilm.     

Thyroid-stimulating hormone, thyroid hormones, and bone loss

It has become accepted by virtue of rich anecdotal experience and clinical research that thyrotoxicosis is associated with high-turnover osteoporosis. The bone loss, primarily due to accelerated resorption that is not compensated by a coupled increase in bone formation, has been attributed solely to elevated thyroid hormone levels. Evidence using mice lacking the thyroid hormone receptors α and β establishes a role for thyroid hormones in regulating bone remodeling but does not exclude an independent action of thyroid-stimulating hormone (TSH), levels of which are low in hyperthyroid states, even when thyroid hormones are normal, as after thyroxine supplementation and in subclinical hyperthyroidism. We show that TSH directly suppresses bone remodeling and that TSH receptor null mice have profound bone loss, suggesting that reduced TSH signaling contributes to hyperthyroid osteoporosis. TSH and its receptor could become valuable drug targets in treating bone loss.