IL28B polymorphisms predict the virological response to standard therapy in patients with chronic hepatitis C virus genotype 4 infection

Background

Genome-wide association studies have recently revealed that several single-nucleotide polymorphisms (SNPs) in the interleukin (IL) 28B genes can predict the sustained virological response (SVR) to pegylated interferon-α2a/b plus ribavirin in hepatitis C virus (HCV)-genotype 1 patients. However, data for patients infected with HCV genotype 4 (HCV-G4) are limited.

Aim

We analyzed the association of IL28B SNPs (hematological, biochemical, virological, and pathological factors) with SVR in the HCV-G4 monoinfected cohort of patients.

Patients and methods

One hundred twenty-nine treatment-naïve HCV-G4 patients undergoing treatment were recruited from three tertiary care centers in Saudi Arabia. Five IL28B SNPs (rs12979860, rs12980275, rs8105790, rs8099917, and rs72486680) were identified by polymerase chain reaction and DNA sequencing. SVR was statistically correlated with various clinical, histopathological, virological, and genetic parameters.

Results

SVR was significantly associated with the CC and AA alleles of rs12979860 (p = 0.008) and rs12980275 (p = 0.004), respectively. Moreover, albumin levels (p = 0.002) and platelet count (p = 0.039) showed significant differences in the SVR and No SVR groups. On multivariate analysis, the CC allele of rs12979860 (OR, 2.89; 95 % CI 1.6–6.2, p = 0.006) and albumin levels (OR, 1.2; 95 % CI 1.1–1.4, p = 0.001) independently predicted SVR.

Conclusions

IL28B polymorphism (CC allele of rs12979860) predicts the sustained response to antiviral therapy in HCV-G4.     

Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines

Purpose

To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness.

Methods

We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined “early” EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds.

Results

We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion.

Conclusions

We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access.

     

Corticosteroid therapy for COVID-19: A systematic review and meta-analysis of randomized controlled trials

Background:Corticosteroid treatment is an effective and common therapeutic strategy for various inflammatory lung pathologies and may be an effective treatment for coronavirus disease 2019 (COVID-19). The purpose of this systematic review and meta-analysis of current literature was to investigate the clinical outcomes associated with corticosteroid treatment of COVID-19.Methods:We systematically searched PubMed, medRxiv, Web of Science, and Scopus databases through March 10, 2021 to identify randomized controlled trials (RCTs) that evaluated the effects of corticosteroid therapies for COVID-19 treatment. Outcomes of interest were mortality, need for mechanical ventilation, serious adverse events (SAEs), and superinfection.Results:A total of 7737 patients from 8 RCTs were included in the quantitative meta-analysis, of which 2795 (36.1%) patients received corticosteroids plus standard of care (SOC) while 4942 (63.9%) patients received placebo and/or SOC alone. The odds of mortality were significantly lower in patients that received corticosteroids as compared to SOC (odds ratio [OR] = 0.85 [95% CI: 0.76; 0.95], P = .003). Corticosteroid treatment reduced the odds of a need for mechanical ventilation as compared to SOC (OR = 0.76 [95% CI: 0.59; 0.97], P = .030). There was no significant difference between the corticosteroid and SOC groups with regards to SAEs and superinfections.Conclusion:Corticosteroid treatment can reduce the odds for mortality and the need for mechanical ventilation in severe COVID-19 patients.     

Does reconstruction affect outcomes following exclusively endoscopic endonasal resection of benign orbital tumors: A systematic review with meta-analysis

Objective::As exclusively endoscopic endonasal resection of benign orbital tumors has become more widespread, high-quality outcomes data are lacking regarding t...     

Trabeculectomy with Ologen implant versus perfluoropropane gas bubble for open angle glaucoma in pseudophakic eyes

AIM:To evaluate the safety and efficacy of augmented trabeculotomy with Ologen versus perfluoropropane in management of pseudophakic glaucoma.METHODS:This is a comparative randomized study included 57 pseudophakic eyes of 57 patients with medically uncontrolled open angle glaucoma(OAG).Twentynine patients were allocated in group I(trabeculectomy with Ologen;trab-ologen group),while 28 patients were assigned in group II(trabeculectomy with perfluoropropane gas bubble;trab-C3 F8 gas bubble group).RESULTS:The intraocular pressure(IOP)was significantly reduced in both study groups at all postoperative follow up intervals(1 wk,3,6,12,18,24,30 and 36 mo,P<0.001).The differences between the mean IOP values of both groups remained statistically insignificance during the early 12 months of follow up.However,the trab-ologen group achieved a statistically significant reduction over the trab-C3 F8 gas bubble group during the last 24 months of follow up.CONCLUSION:Augmentation of trabeculectomy with either Ologen implant or perfluoropropane gas bubble are associated with strict long term IOP control and evident safety in medically-uncontrolled pseudophakic eyes with OAG.     

Ultrasonographic assessment of splenic volume and its correlation with body parameters in a Jordanian population

Objectives:

To estimate normal linear dimensions and volume of spleen in Jordanians using ultrasonography, and to correlate splenic volume with age and body parameters: height, weight, body surface area (BSA), and body mass index (BMI).

Methods:

A prospective pilot study was conducted on 205 volunteers (115 males and 90 females) not known to have any conditions likely to be associated with splenomegaly. The study was performed at the Radiology Department, Jordanian University Hospital, Amman, Jordan, between December 2013 and August 2014. All linear dimensions of spleen were measured, and splenic volume (index) was calculated using the standard prolate ellipsoid formula (length × width × depth × 0.523). The splenic volume was then analyzed with age and body parameters using the Pearson’s correlation coefficient.

Results:

The mean (± SD) splenic dimensions were 10.72±1.37 cm in length, 7.40±1.52 cm in width, 4.40±1.47 cm in depth, and 184.15±79.56 cm³ in volume. Men had larger spleens than women (p<0.0001). Age had no significant effect on spleen volume (r=0.11, p=0.12). There was a significant moderate positive correlation (p<0.0001), using Pearson’s correlation coefficient, between the spleen volume, and other parameters (height, weight, BSA, and BMI), with correlation coefficients exceeding 0.3.

Conclusion:

A local reference of spleen dimensions was established with a different range of values reported previously.The spleen is the largest organ in the reticulo endothelial system.1 Spleen size is important in the evaluation of gastrointestinal and hematological diseases for both radiologists and clinicians.2 A normal spleen weighs 150-200 g, and is 10.9 ± 1.4 cm long, 4.0 ± 0.45 cm deep, and 6.8 ± 0.71 cm in diameter. It is located in the left hypogastric quadrant of the abdomen beneath the 9th to the 11th intercostal spaces. It is a crescent shaped structure, with a convex outer margin, and indented inner margin.3 Splenomegaly is a well-known manifestation of several diseases that may involve the liver, immune system, and hematopoietic system.4,5 The reliability of clinical palpation is imprecise; the normal spleen is usually not palpable, whereas a non-palpable spleen is not always normal sized.6 The spleen volume can be measured by various techniques such as radiography, scintigraphy, CT, MRI, and ultrasonography.3,7 Ultrasonography is the first imaging method to assess splenomegaly.8,9 It is a non-invasive, commonly available, and an affordable imaging method without the risk of ionizing radiation. Current knowledge of spleen size is based on different populations or derived from autopsy studies.10 So far, established normal limits of spleen dimensions remain scanty in the Jordanian population, and the ultrasound data from the previous studies demonstrated that racial differences could affect the splenic volume; this necessitates the establishment of normative data of spleen dimensions for different areas.11,12The aim of this prospective pilot screening survey was to establish reference values of splenic dimensions and volume in a population of adult healthy Jordanians, and to determine the relationship of splenic volume with gender, age, body height, weight, body surface area (BSA), and body mass index (BMI). This study was conducted as a first step in an attempt to improve the study design prior to performance of a full scale investigation of splenic volumes in a Mediterranean population.     

Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase‐2 study (NordCML006)

We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100 mg QD or imatinib 400 mg QD and report outcome as an intention‐to‐treat analysis with 36 months follow‐up. Early cytogenetic and molecular responses were superior in the dasatinib group, with a tendency that imatinib patients caught up with time. For instance, MR^3.0 was reached at 3 months in 36% vs. 8% (P = 0.02), at 12 months in 81% vs. 46% (P = 0.02) and at 18 months in 73% vs. 65% (n.s.) of the patients in the two groups. In contrast, MR^4.5 was consistently superior in the dasatinib group at all time points from 6 months onwards, reaching 61% vs. 21% (P < 0.05) at 36 months. Sixty‐four vs. 71% of the patients in the dasatinib and imatinib arms, respectively, remained on assigned drug. Dasatinib dose was frequently reduced, but with maintained excellent effect. One imatinib patient progressed to blastic phase, but no CML‐related deaths occurred. In conclusion, our data compare favourably with those of the dasatinib registration study, DASISION. The fast and deep molecular responses induced by dasatinib compared with imatinib may be exploited to increase the proportion of patients who can achieve a treatment‐free remission after treatment discontinuation.