Meta-analysis and trial sequential analysis of randomized evidence comparing general anesthesia vs regional anesthesia for laparoscopic cholecystectomy

BACKGROUND In an effort to further reduce the morbidity and mortality profile of laparoscopic cholecystectomy, the outcomes of such procedure under regional anesthesia(RA) have been evaluated. In the context of cholecystectomy, combining a minimally invasive surgical procedure with a minimally invasive anesthetic technique can potentially be associated with less postoperative pain and earlier ambulation.AIM To evaluate comparative outcomes of RA and general anesthesia(GA) in patients undergoing laparoscopic cholecystectomy.METHODS A comprehensive systematic review of randomized controlled trials with subsequent meta-analysis and trial sequential analysis of outcomes were conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards.RESULTS Thirteen randomized controlled trials enrolling 1111 patients were included. The study populations in the RA and GA groups were of comparable age(P = 0.41),gender(P = 0.98) and body mass index(P = 0.24). The conversion rate from RA to GA was 2.3%. RA was associated with significantly less postoperative pain at 4 h [mean difference(MD):-2.22, P 0.00001], 8 h(MD:-1.53, P = 0.0006), 12 h(MD:-2.08, P 0.00001), and 24 h(MD:-0.90, P 0.00001) compared to GA. Moreover, it was associated with significantly lower rate of nausea and vomiting [risk ratio(RR): 0.40, P 0.0001]. However, RA significantly increased postoperative headaches(RR: 4.69, P = 0.03), and urinary retention(RR: 2.73, P = 0.03). The trial sequential analysis demonstrated that the meta-analysis was conclusive for most outcomes, with the exception of a risk of type 1 error for headache and urinary retention and a risk of type 2 error for total procedure time.CONCLUSION Our findings indicate that RA may be an attractive anesthetic modality for daycase laparoscopic cholecystectomy considering its associated lower postoperative pain and nausea and vomiting compared to GA. However, its associated risk of urinary retention and headache and lack of knowledge on its impact on procedure-related outcomes do not justify using RA as the first line anesthetic choice for laparoscopic cholecystectomy.     

The effect of leflunomide on the eye dryness in secondary Sjögren’s syndrome associated with rheumatoid arthritis and in rheumatoid arthritis patients

The aim of this work was to clarify the effect of leflunomide (LEF) on the eye dryness in patients with secondary Sjögren’s syndrome associated with rheumatoid arthritis (RA-sSS) and in patients with rheumatoid arthritis (RA). Seventy-five female patients, 45 with RA-sSS (group A) and 30 with RA (group B), taking methotrexate at a dose of 20 mg/week for more than 6 months were enrolled in this study. They all had a loading dose of leflunomide then were maintained at a dose of 20 mg/day in addition to methotrexate for another 3 months. The modified disease activity score (DAS28) was calculated and modified Schirmer’s-I test was performed. Assessment of disease parameters was done to all patients before and after 3 months of taking LEF. The mean modified Schirmer’s-I test showed a significant decrease after 3 months of taking LEF in group A (3?±?1.6 before versus 1.9?±?1.6 after 3 months, P?<?0.001), while this difference was non-significant in group B (21.3?±?10 versus 19.9?±?11). One patient (group A) developed peripheral ulcerative keratitis (PUK) with exacerbation of disease activity (DAS-28?=?6.9) that improved by taking corticosteroids. Three patients (group A) had aggravation of punctate keratocojunctivitis sicca with punctate erosions without PUK. The condition improved dramatically by stopping LEF and using topical lubricants. We report in this study a significant deterioration of the eye dryness in patients with sSS-RA after 3 months of receiving LEF inspite of the significant improvement of their DAS28. This finding was not clearly detected in RA patients. Close monitoring of eye dryness changes by special tests in patients using LEF is recommended, especially in cases with sSS-RA having very low baseline values.     

Ultrasound-based tumor movement compensation during navigated laparoscopic liver interventions

Background

Image-guided navigation aims to provide better orientation and accuracy in laparoscopic interventions. However, the ability of the navigation system to reflect anatomical changes and maintain high accuracy during the procedure is crucial. This is particularly challenging in soft organs such as the liver, where surgical manipulation causes significant tumor movements. We propose a fast approach to obtain an accurate estimation of the tumor position throughout the procedure.

Methods

Initially, a three-dimensional (3D) ultrasound image is reconstructed and the tumor is segmented. During surgery, the position of the tumor is updated based on newly acquired tracked ultrasound images. The initial segmentation of the tumor is used to automatically detect the tumor and update its position in the navigation system. Two experiments were conducted. First, a controlled phantom motion using a robot was performed to validate the tracking accuracy. Second, a needle navigation scenario based on pseudotumors injected into ex vivo porcine liver was studied.

Result

In the robot-based evaluation, the approach estimated the target location with an accuracy of 0.4 ± 0.3 mm. The mean navigation error in the needle experiment was 1.2 ± 0.6 mm, and the algorithm compensated for tumor shifts up to 38 mm in an average time of 1 s.

Conclusion

We demonstrated a navigation approach based on tracked laparoscopic ultrasound (LUS), and focused on the neighborhood of the tumor. Our experimental results indicate that this approach can be used to quickly and accurately compensate for tumor movements caused by surgical manipulation during laparoscopic interventions. The proposed approach has the advantage of being based on the routinely used LUS; however, it upgrades its functionality to estimate the tumor position in 3D. Hence, the approach is repeatable throughout surgery, and enables high navigation accuracy to be maintained.     

病重特护患者压疮的发生率、预防和治疗

研究背景压疮普遍发生于急性和慢性患者.然而危重疾病患者通常是压疮发生的高风险因素.目标这个研究的主导是评估重症护理患者的压疮发生率,个体进入到病重护理状态下时,影响压疮发生率的因素和压疮过程.设计纵向设计.     

Insulin resistance in early untreated rheumatoid arthritis patients

ObjectivesTo assess insulin resistance in early untreated rheumatoid arthritis patients and its relation to the clinical, inflammatory and biochemical characteristics of these patients.Patients and methodsSixty-six untreated rheumatoid arthritis (RA) patients with disease duration less than 1 year along with age and sex matched controls were studied. Disease activity score (DAS28) was used to assess disease activity. Plasma levels of C- reactive protein (CRP), glucose, insulin and complete lipid profile were measured. Insulin resistance (IR) was estimated by the homeostasis model assessment for insulin resistance (HOMA-IR).ResultsRA patients revealed high grade systemic inflammation compared to control group p < 0.0001. Patients with high disease activity were more insulin resistant than patients with moderate disease activity P < 0.0001.ConclusionThe findings of the present study showed that early untreated RA patients are characterized by a severe insulin resistant state that is driven primarily by disease activity and systemic inflammation.     

The preclinical pharmacology of roflumilast – A selective,oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease

After more than two decades of research into phosphodiesterase 4 (PDE4) inhibitors, roflumilast (3-cyclopropylmethoxy-4-difluoromethoxy-N-[3,5-di-chloropyrid-4-yl]-benzamide) may become the first agent in this class to be approved for patient treatment worldwide. Within the PDE family of 11 known isoenzymes, roflumilast is selective for PDE4, showing balanced selectivity for subtypes A–D, and is of high subnanomolar potency. The active principle of roflumilast in man is its dichloropyridyl N-oxide metabolite, which has similar potency as a PDE4 inhibitor as the parent compound. The long half-life and high potency of this metabolite allows for once-daily, oral administration of a single, 500-μg tablet of roflumilast.The molecular mode of action of roflumilast – PDE4 inhibition and subsequent enhancement of cAMP levels – is well established. To further understand its functional mode of action in chronic obstructive pulmonary disease (COPD), for which roflumilast is being developed, a series of in vitro and in vivo preclinical studies has been performed.COPD is a progressive, devastating condition of the lung associated with an abnormal inflammatory response to noxious particles and gases, particularly tobacco smoke. In addition, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), significant extrapulmonary effects, including comorbidities, may add to the severity of the disease in individual patients, and which may be addressed preferentially by orally administered remedies. COPD shows an increasing prevalence and mortality, and its treatment remains a high, unmet medical need.In vivo, roflumilast mitigates key COPD-related disease mechanisms such as tobacco smoke-induced lung inflammation, mucociliary malfunction, lung fibrotic and emphysematous remodelling, oxidative stress, pulmonary vascular remodelling and pulmonary hypertension. In vitro, roflumilast N-oxide has been demonstrated to affect the functions of many cell types, including neutrophils, monocytes/macrophages, CD4+ and CD8+ T-cells, endothelial cells, epithelial cells, smooth muscle cells and fibroblasts. These cellular effects are thought to be responsible for the beneficial effects of roflumilast on the disease mechanisms of COPD, which translate into reduced exacerbations and improved lung function. As a multicomponent disease, COPD requires a broad therapeutic approach that might be achieved by PDE4 inhibition. However, as a PDE4 inhibitor, roflumilast is not a direct bronchodilator.In summary, roflumilast may be the first-in-class PDE4 inhibitor for COPD therapy. In addition to being a non-steroid, anti-inflammatory drug designed to target pulmonary inflammation, the preclinical pharmacology described in this review points to a broad functional mode of action of roflumilast that putatively addresses additional COPD mechanisms. This enables roflumilast to offer effective, oral maintenance treatment for COPD, with an acceptable tolerability profile and the potential to favourably affect the extrapulmonary effects of the disease.     

Detection of gastric contents in tracheal fluid of infants by lactose assay

We designed an in vitro assay to detect the presence of lactose in the tracheal aspirates of premature, ventilator-dependent infants. This method was employed to identify recurrent, unrecognized aspiration, which could prolong the requirements for ventilator support and contribute to the development of chronic lung disease. One hundred five determinations of lactose were performed on the tracheal fluid obtained from 42 ventilator-dependent infants who were receiving enteral feedings. There was a wide range of lactose levels (0 to 3,270 nmol lactose/ml tracheal aspirate). Six infants had samples that were highly suggestive of aspiration (greater than 200 nmol lactose/ml tracheal aspirate). Twenty infants had questionably positive samples (25 to 200 nmol lactose/ml tracheal aspirate), and 16 infants had samples that were considered negative for aspiration (less than 25 nmol lactose/ml tracheal aspirate).