Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis

Bacterial keratitis continues to be one of the leading causes of corneal blindness in the developed as well as the developing world, despite swift progress since the dawn of the “anti-biotic era”. Although, we have expeditiously developed our understanding about the different causative organisms and associated pathology leading to keratitis, extensive gaps in knowledge continue to dampen the efforts required for early and accurate diagnosis, and management in these patients, resulting in poor clinical outcomes. The ability of the causative bacteria to subdue the therapeutic challenge stems from their large genome encoding complex regulatory networks, variety of unique virulence factors, and rapid secretion of tissue damaging proteases and toxins.In this review article, we provide an overview of the established diagnostic techniques and therapeutics for keratitis caused by various bacteria. We extensively report the recent in-roads through novel tools for accurately diagnosing mono- and poly-bacterial corneal infections. Furthermore, we outline the recent progress by our groups and others in understanding the sub-cellular genomic changes that lead to antibiotic resistance in these organisms. Finally, we discuss in detail, the novel therapies and drug delivery systems in development for the efficacious management of bacterial keratitis.     

Risk factors for major complications after liver resection: A large liver resection study from Morocco and audit of a non-Eastern/non-Western experience

Background and Study AimsIn developing countries, endemic indications, blood shortages, and the scarcity of liver surgeons and intensive care providers can affect liver resection (LR) outcomes, but these have been rarely addressed in the literature. Therefore, in this study we determined risk factors for major complications after LR in a North African general surgery and teaching department.Patients and MethodsFrom January 2010 to December 2015, 213 consecutive LRs were performed on 203 patients. All patients underwent a postoperative follow-up of >90 days. Postoperative complications were assessed according to the Clavien–Dindo (CD) classification of surgical complications. A score of CD ≥III is considered as major postoperative complications. In this study, we analyzed the variables assumed to affect these complications.ResultsThe overall 90-day complication rate was 35.7% (n = 76), including a CD ≥III of 14% (n = 30) and a mortality rate of 6.1% (n = 14). According to the multivariate analysis, a preoperative performance status (PS) of ≥2 (P = 0.011; odds ratios [OR], 6.8; 95% confidence intervals [CI], 1.55–29.8), an estimated intraoperative blood loss of >500 ml (P = 0.002; OR, 3.71; 95% CI, 1.23–11.20), and bilioenteric anastomosis (P < 0.004; OR, 7.76; 95% CI, 1.5–3.89) were independent risk factors for major complications after LR.ConclusionWe recommend that, in the setting of a non-Eastern/non-Western general surgery and teaching department, patients with a PS of ≥2 should undergo a specific selection and preoperative optimization protocol; intermittent clamping indications should be extended; and special attention should paid to patients undergoing LR associated with biliary reconstruction, such as for perihilar cholangiocarcinoma.     

The effects of carnitine supplementation on clinical characteristics of patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials

ObjectiveThe beneficial effects of carnitine supplementation on nonalcoholic fatty liver disease are unclear. We conducted a systematic review and meta-analysis to evaluate the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance in patients with nonalcoholic fatty liver disease.MethodsA comprehensive search of PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar databases were performed. Only randomized placebo-controlled human studies that examined the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance up to September 2019 were included. Fixed effects or random-effects models were applied to compute the pooled effect size. Heterogeneity assessments were performed using Cochran’s Q test and I-squared statistics. The quality of the studies was assessed using the Jaded scale.ResultsA total of 5 articles were selected, including 334 individuals (167 in control and 167 in intervention groups). The results demonstrated that carnitine supplementation significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: −0.91; 95 % CI: −1.11, −0.72; p < 0.001, I² = 0.0 %) and the levels of aspartate aminotransferase (AST) (WMD: −16.62; 95 % CI: −28.11, −5.14; IU/l; p = 0.005, I² = 93.5 %), alanine aminotransferase (ALT) (WMD: -33.39; 95 % CI: −45.13, −21.66; IU/l; p < 0.001, I² = 93.4 %), and triglycerides (TG) (WMD: −22.13; 95 % CI: −38.91, −5.34; mg/dl; p = 0.01; I² = 0.0 %). However, the results of the pooled effect size did not show any significant effect of carnitine supplementation on body mass index (BMI) (WMD: 0.07; 95 % CI: −0.15, 0.29; p = 0.55; I² = 0.0 %), body weight (WMD: −0.28; 95 % CI: −2.23, 1.68; p = 0.78; I² = 45.7 %), the levels of gamma-glutamyl transferase (γGT) (WMD: −11.31; 95 % CI: −24.35, 1.73; IU/l; p = 0.09, I² = 61.1 %), cholesterol (WMD: −13.58; 95 % CI: −46.77, 19.60; mg/dl; p = 0.42; I² = 94.9 %), high-density lipoprotein-cholesterol (HDL-C) (WMD: 1.36; 95 % CI: −0.96, 3.68; mg/dl; p = 0.25; I² = 64.7 %), and low density lipoprotein-cholesterol (LDL-C) (WMD: −14.85; 95 % CI: −45.43, 15.73; mg/dl; p = 0.34; I² = 96.4 %).ConclusionsThis analysis shows that carnitine supplementation for patients with nonalcoholic fatty liver disease demonstrates a reduction in AST, ALT, TG levels and HOMA-IR. However, no significant effect of carnitine supplementation was observed on BMI, body weight, the levels of γGT, TC, HDL-cholesterol and LDL-cholesterol.     

Impact and Predictors of Noncircular Left Ventricular Outflow Tract Shapes on Estimating Aortic Stenosis Severity by Means of Continuity Equations

Determining aortic stenosis (AS) severity is clinically important. Calculating aortic valve (AV) area by means of the continuity equation assumes a circular left ventricular outflow tract (LVOT). The full impact of this assumption in calculating AV area is unknown. Predictors of noncircular LVOT shape in patients with AS are undefined.In 109 adult patients with AS who underwent multiplanar transesophageal echocardiography, we calculated AV area by means of the standard continuity method and by a modified method involving planimetric LVOT area.We found 54 circular, 37 horizontal-oval, 8 vertical-oval, and 10 irregular LVOTs. Area derived by direct planimetry correlated better with the modified than the standard continuity method (r=0.89 vs r=0.85; both P=0.0001). Valve areas of patients with mild, moderate, or severe AS by planimetry were more often mischaracterized with use of the standard than modified method (29 vs 18; P <0.0001). Horizontal-oval AV area derived by planimetry (1.28 ± 0.55 cm²) was underestimated by the standard method (1.05 ± 0.47 cm²; P=0.001), but not by the modified method. Congenital AV morphology and low cardiac index were the only multivariate predictors of horizontal-oval shape. Low cardiac index was the only predictor of noncircular shape.More than half our patients with AS had noncircular LVOTs. Using the modified method reduces mischaracterizations of AS severity. Congenital AV morphology and low cardiac index predict horizontal-oval or noncircular shape. These data suggest the value of direct LVOT measurement to calculate AS severity in patients who have congenital AV or a low cardiac index.     

Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection

Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5?mg/ml and 10?mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.     

Nutritional therapy for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and presents together with cirrhosis in most cases. In addition to commonly recognized risk factors for HCC development, such as hepatitis B virus/hepatitis C virus infection, age and alcohol/tobacco consumption, there are nutritional risk factors also related to HCC development including high intake of saturated fats derived from red meat, type of cooking (generation of heterocyclic amines) and contamination of foods with aflatoxins. On the contrary, protective nutritional factors include diets rich in fiber, fruits and vegetables, n-3 polyunsaturated fatty acids and coffee. While the patient is being evaluated for staging and treatment of HCC, special attention should be paid to nutritional support, including proper nutritional assessment and therapy by a multidisciplinary team. It must be considered that these patients usually develop HCC on top of long-lasting cirrhosis, and therefore they could present with severe malnutrition. Cirrhosis-related complications should be properly addressed and considered for nutritional care. In addition to traditional methods, functional testing, phase angle and computed tomography scan derived skeletal muscle index-L3 are among the most useful tools for nutritional assessment. Nutritional therapy should be centered on providing enough energy and protein to manage the increased requirements of both cirrhosis and cancer. Supplementation with branched-chain amino acids is also recommended as it improves response to treatment, nutritional status and survival, and finally physical exercise must be encouraged and adapted to individual needs.     

不同剂量地佐辛术后镇痛对老年患者肝功能的影响

目的 探讨地佐辛术后镇痛对高龄患者围术期肝功能的影响。方法 选择2018 年1 月～2020 年6 月吉安市中心人民医院麻醉科收治的ASA 分级Ⅱ～Ⅲ级高龄患者80 例，按照随机数字表法，分为A 组、B 组、C 组、D 组，每组各20 例。分别给予0.4 mg/kg、0.5 mg/kg、0.6 mg/kg、0.7 mg/kg 地佐辛进行术后镇痛，评估术后1、2、6、12、24、48 h 患者的疼痛程度[视觉模拟评分法（VAS）]、术后镇静效果（Ramsay 评分法）及肝功能指标（ALT、AST）水平，评价不同剂量的地佐辛术后镇痛对高龄患者围术期肝功能的影响。结果 C 组术后患者不同时间段VAS 疼痛评分低于A 组、B 组、D 组，差异有统计学意义（P＜0.05）；四组患者术后1、2、6 h Ramsay 镇静评分比较，差异有统计学意义（P＜0.05）；但术后12、24、48 h Ramay 镇痛评分比较，差异无统计学意义（P＞0.05）。C 组肝功能指标ALT、AST优于A 组、B 组、D 组，差异有统计学意义（P＜0.05）。结论 高龄患者术后镇痛应用0.6 mg/kg地佐辛对围术期肝功能的影响最小。