Corticosteroid Therapy, Vitamin D Status, and Inflammatory Cytokine Profile in the HIV-Tuberculosis Immune Reconstitution Inflammatory Syndrome

Background.?Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) in patients coinfected with human immunodeficiency virus (HIV) and tuberculosis starting antiretroviral therapy (ART) is associated with hypercytokinemia. As adjunctive corticosteroid therapy and vitamin D have immunomodulatory properties, we investigated the relationship between cytokine/chemokine profiles, corticosteroid use, and vitamin D deficiency in TB-IRIS patients. Methods.?Plasma from 39 TB-IRIS and 42 non-IRIS patients was collected during a prospective study of HIV-associated tuberculosis patients starting ART. In total, 26% of patients received corticosteroid (CTC) therapy pre-ART for severe tuberculosis. Concentrations of total 25-hydroxyvitamin D (25(OH)D) and 14 cytokines/chemokines were determined at ART initiation and 2 weeks later. Results.?Patients prescribed concurrent CTC had lower interferon γ (IFN-γ), IP-10, tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, IL-10, IL-12p40, and IL-18 pre-ART (P?≤?.02). TB-IRIS presented at 12 days (median) of ART, irrespective of CTC use. In patients who developed TB-IRIS (not on CTC) IL-6, IL-8, IL-12p40, IL-18, IP-10, and TNF increased during 2 weeks (P?≤?.04) of ART. Vitamin D deficiency (total 25(OH)D <75?nmol/L) was highly prevalent (89%) at baseline. Although vitamin D deficiency at either baseline or 2 weeks was not associated with TB-IRIS, in those not on CTC the median 25(OH)D decreased during 2 weeks (P?=?.004) of ART. Severe vitamin D deficiency (total 25(OH)D <25?nmol/L) was associated with higher baseline TNF, IL-6, and IL-8 irrespective of IRIS status. Conclusions.?CTC modifies the inflammatory profile of those who develop TB-IRIS. The association between severe vitamin D deficiency and elevated proinflammatory cytokines support a study of vitamin D supplementation in HIV-TB co-infected patients starting ART.     

Brief report: Focused transthoracic echocardiography training in a cohort of Canadian anesthesiology residents: a pilot study

Purpose

Bedside transthoracic echocardiography (TTE) is useful for rapid assessment and treatment of hemodynamic disturbances. Transthoracic echocardiography is not standard in Canadian anesthesia training even though undifferentiated hemodynamic disturbances are common in the perioperative setting. The objectives of this pilot study were to determine 1) whether it is feasible to implement a focused bedside TTE curriculum within core anesthesiology training, 2) whether changes could be detected and quantified following the program of study, and 3) whether curriculum implementation might lead to a significant increase in anesthesiology residents’ TTE knowledge-base.

Methods

In this single-centre cohort pilot investigation, anesthesiology residents at Queen’s University received focused bedside TTE training during the winter of 2011. The curriculum consisted of four three-hour sessions with both didactic and practical components. Pre- and post-curriculum examinations were administered, and examination results were compared using non-parametric tests. The primary outcome was the difference in mean pre- and post-curriculum examination scores.

Results

Ten participants completed pre- and post-curriculum examinations. Four residents were unable to participate in the curriculum but served as controls. Mean pretest scores (out of 50) were similar between the two groups (participants 23.9 vs controls 23.5; P = 0.83, Mann-Whitney U). Mean scores improved by 13.0 points following intervention but improved by only 1.3 points for controls, (P = 0.009, Mann-Whitney U).

Conclusion

This pilot investigation suggests that implementation of a focused bedside TTE curriculum within anesthesia training is feasible, quantifiable, and effective for increasing anesthesia residents’ TTE knowledge-base. This pilot study suggests that further investigation is warranted to determine the impact of this perioperative TTE curriculum.     

Endolumenal colon occlusion device for transanal and transrectal surgery—a porcine feasibility study

Purpose

Although several studies have demonstrated the feasibility of transrectal natural orifice translumenal endoscopic surgery (NOTES), its clinical application has been hindered by concerns regarding potential infectious complications. The aim of this study was to evaluate the feasibility of a newly developed device for endolumenal colon occlusion (ColoShield) in an acute porcine model.

Methods

The principle of the ColoShield device is based on two balloons, with negative pressure in between. The ColoShield device and a gauze tamponade as a control group were evaluated in a non-survival study on 16 pigs. The efficacy of the occlusion system in establishing a leak-proof pneumorectum and in sealing the colon from proximal (watertight sealing) was tested by a standardized study course. Finally, the colon/rectum was explanted for macroscopic and microscopic examination.

Results

A 20-mmHg leak-proof pneumorectum over a period of 10 min could be achieved in seven of eight (87 %) animals with the ColoShield device and in none of eight (0 %) animals with gauze tamponade (p?<?0.001). In the watertight sealing test, mean intracolonic pressures of 23.5?±?18.1 (0–53) mmHg using the ColoShield device and 0?±?1.1 (0–3) mmHg using gauze tamponade (p?=?0.003) were documented proximal to the occlusion system before a leakage occurred. Macroscopic and histopathological examinations revealed no significant impairment of the colon specimen in either group.

Conclusions

ColoShield proved to be a safe and effective device for a reversible endolumenal colon occlusion. Further studies should evaluate its impact on procedural sterility during transrectal NOTES.     

Effect of primary versus revisional Roux-en-Y gastric bypass: inferior weight loss of revisional surgery after gastric banding

BackgroundLaparoscopic adjustable gastric banding is a popular and effective restrictive bariatric procedure. However, with longer follow-up, it has become clear that a considerable number of patients require revisional surgery, of which Roux-en-Y gastric bypass (RYGB) is the most commonly performed procedure. Studies that compared the outcomes of primary RYGB and revisional RYGB have not been conclusive. Our objective was to determine whether significant differences exist in the 1-year outcomes between primary RYGB (prim-RYGB) and revisional RYGB after laparoscopic adjustable gastric banding (rev-RYGB) at a major training hospital in The Netherlands.MethodsAll prim-RYGB and rev-RYGB procedures performed from 2007 to 2009 were analyzed. Data were collected regarding weight loss, hospitalization, operative time, postoperative complications, and co-morbidities.ResultsA total of 292 RYGB procedures were performed: 66 rev-RYGB and 226 prim-RYGB procedures. The operative time was significantly shorter in the prim-RYGB group (136.6 ± 37.5 versus 167.5 ± 40.6 min; P < .0001). No significant differences were found in hospitalization time (4.4 ± 1.7 versus 4.9 ± 2.4 d; P = .063) or complication rate (14.7% versus 15.2%; P = .962). No deaths occurred in either group. The number of patients with resolved diabetes and hypertension did not differ between the 2 groups (50.1% versus 23.1%; P = .116; and 40.7% versus 25.0%; P = .384, respectively). Weight loss was significantly greater in the prim-RYGB group in terms of excess weight loss (71.6% ± 20.8% versus 48.4% ± 26.8%; P < .0001), body mass index reduction (13.0 ± 3.8 versus 10.2 ± 5.6 kg/m²; P < .0001), absolute weight loss (37.4 ± 11.5 versus 29.3 ± 17.2 kg; P = .001), and percentage of weight loss (29.7% ± 8% versus 21.7% ± 11.5%; P < .0001).Conclusionrev-RYGB is a safe procedure with outcomes similar to those of prim-RYGB in terms of complication rate, hospitalization time, and effect on co-morbidity. Weight loss, however, was significantly less after rev-RYGB than after prim-RYGB.     

Attitudes about the safety and efficacy of bariatric surgery among patients with type 2 diabetes and a body mass index of 30–40 kg/m2

BackgroundDespite increasing awareness within the medical community about the benefits of bariatric surgery for type 2 diabetes mellitus (T2DM), little is known about patients’ attitudes toward bariatric surgery as a treatment for T2DM. The objective of this study was to investigate the attitudes of individuals with T2DM and a body mass index of 30 to 40 kg/m² concerning bariatric surgery for the treatment of T2DM.MethodsPatients identified from the Pennsylvania Integrated Clinical and Administrative Research Database (PICARD) were surveyed about perceptions of the safety profile and efficacy of bariatric surgery as a treatment for obesity and T2DM and their willingness to be randomly assigned to receive a surgical procedure.ResultsA total of 130 individuals of 513 (25.3%) responded. Respondents had a median (interquartile range) age of 58.0 (range 51.0–63.0) years and self-reported body mass index of 32.9 (range 30.9–35.2) kg/m². Roughly half (66 of 130) were female. Overall, only 20.3% of respondents had positive views of bariatric surgery, with few reporting that it is a safe (14.3%) and effective (28.5%) treatment for T2DM. Less than 20% of respondents were willing to be randomly assigned to undergo a surgical procedure for the treatment of diabetes (16.1%) or obesity (17.5%).ConclusionsFew obese individuals with T2DM who responded to the survey had positive views about bariatric surgery. Patients’ concerns about the procedure’s safety profile and efficacy must be addressed to improve the acceptability of bariatric surgery as well as the feasibility of randomized, controlled trials of bariatric surgery for these individuals.     

Maximized song learning of juvenile male zebra finches following BDNF expression in the HVC

During song learning, vocal patterns are matched to an auditory memory acquired from a tutor, a process involving sensorimotor feedback. Song sensorimotor learning and song production of birds is controlled by a set of interconnected brain nuclei, the song control system. In male zebra finches, the beginning of the sensorimotor phase of song learning parallels an increase of the brain‐derived neurotrophic factor (BDNF) in just one part of the song control system, the forebrain nucleus HVC. We report here that transient BDNF‐mRNA upregulation in the HVC results in a maximized copying of song syllables. Each treated bird shows motor learning to an extent similar to that of the selected best learners among untreated zebra finches. Because this result was not found following BDNF overexpression in the target areas of HVC within the song system, HVC‐anchored mechanisms are limiting sensorimotor vocal learning.     

Scorpion venoms and associated toxins as anticancer agents: update on their application and mechanism of action

Cancer remains one of the deadliest non-infectious diseases of the 21^st century, causing millions of mortalities per year worldwide. Analyses of conventional treatments, such as radiotherapy and chemotherapy, have shown not only a lower therapeutic efficiency rate but also plethora of side-effects. Considering the desperate need to identify promising anticancer agents, researchers are in quest to design and develop new tumoricidal drugs from natural sources. Over the past few years, scorpion venoms have shown exemplary roles as pivotal anticancer agents. Scorpion venoms associated metabolites, particularly toxins demonstrated in vitro anticancer attributes against diversified cell lines by inhibiting the growth and progression of the cell cycle, inhibiting metastasis by blocking ion channels such as K⁺ and Cl⁻, and/or inducing apoptosis by intrinsic and extrinsic pathways. This review sheds light not only on in vitro anticancer properties of distinct scorpion venoms and their toxins, but also on their mechanism of action for designing and developing new therapeutic drugs in future.