Alizan Khalil

Evolution of methodological standards in surgical trials.

Background:  The Consolidated Standards of Reporting Trials (CONSORT) Statement outlines acceptable ways of performing and reporting clinical trials. The objective of the present study was to identify evolving patterns in the methodological standards of surgical trials.

TUMOUR NECROSIS FACTOR: IMPLICATIONS FOR SURGICAL PATIENTS

Tumour necrosis factor alpha (TNF‐α) is an inflammatory cytokine primarily produced by macrophages. It is a unique protein with contradictive properties; it has the ability to induce cellular death by apoptosis and oncosis, but can also induce cellular regeneration and growth. Genetic polymorphisms in TNFA have been associated with poor outcome in some surgical patients and this may provide a useful tool to screen for high‐risk patients. Manipulating TNF‐α levels in vivo may influence the progression of several pathological conditions. TNF‐α has anti‐cancer properties and has been used to treat cancer patients. Treatment with anti‐TNF‐α drugs and antibodies has been successful in rheumatoid arthritis and other autoimmune diseases, but disappointing in the management of patients with sepsis. This review article focuses on the biological activities, genetic polymorphism of TNFA and the role of TNF‐α and anti‐TNF‐α treatments, based on animal experiments and clinical trials.

The Role of Glutathione in Intestinal Dysfunction

Glutathione plays an important cytoprotective role in the gut. Animal studies have demonstrated that the provision of glutathione precursors are protective for different types of free-radical-mediated cellular injury. There is a need to clarify the potential role of glutathione supplementation in ischemia–reperfusion injury and inflammatory bowel disease. More speculative is whether dietary treatment with glutathione precursors can modify the progress of colorectal cancer.

A comparison study of different physical treatments on cartilage matrix derived porous scaffolds for tissue engineering applications

Abstract Native cartilage matrix derived (CMD) scaffolds from various animal and human sources have drawn attention in cartilage tissue engineering due to the demonstrable presence of bioactive components. Different chemical and physical treatments have been employed to enhance the micro-architecture of CMD scaffolds. In this study we have assessed the typical effects of physical cross-linking methods, namely ultraviolet (UV) light, dehydrothermal (DHT) treatment, and combinations of them on bovine articular CMD porous scaffolds with three different matrix concentrations (5%, 15% and 30%) to assess the relative strengths of each treatment. Our findings suggest that UV and UV–DHT treatments on 15% CMD scaffolds can yield architecturally optimal scaffolds for cartilage tissue engineering.

Chondrogenic potential of physically treated bovine cartilage matrix derived porous scaffolds on human dermal fibroblast cells.

Extracellular matrices have drawn attention in tissue engineering as potential biomaterials for scaffold fabrication because of their bioactive components. Noninvasive techniques of scaffold fabrication and cross-linking treatments are believed to maintain the integrity of bioactive molecules while providing proper architectural and mechanical properties. Cartilage matrix derived scaffolds are designed to support the maintenance of chondrocytes and provide proper signals for differentiation of chondroinducible cells. Chondroinductive potential of bovine articular cartilage matrix derived porous scaffolds on human dermal fibroblasts and the effect of scaffold shrinkage on chondrogenesis were investigated. An increase in sulfated glycosaminoglycans production along with upregulation of chondrogenic genes confirmed that physically treated cartilage matrix derived scaffolds have chondrogenic potential on human dermal fibroblasts.

Evolution of trends in risk management

In the past, the detection and response to adverse clinical events were viewed as an inherent part of professionalism; and, if perceived problems were not sorted out at that level, the ultimate expression of dissatisfaction was litigation. There are now demands for the adoption of more transparent and effective processes for risk management. Reviews of surgical practice have highlighted the presence of unacceptable levels of avoidable adverse events. This is being resolved in two ways. First, attention is being directed to the extent that training and experience have on outcomes after surgery, and both appear to be important. Second, a greater appreciation of human factors engineering has promoted a greater involvement of surgeons in processes involving teamwork and non‐technical skills. The community wants surgeons who are competent and health‐care systems that minimize risk. In recent times attention has been focused on the turmoil associated with change; but, when events are viewed over a period of several decades, there has been considerable progress towards these ideals. Further advancement would be aided by removing the adversarial nature of malpractice systems that have failed to maintain standards.

The SPEED (sepsis patient evaluation in the emergency department) score: a risk stratification and outcome prediction tool.

Objectives The aim of the study was to identify covariates associated with 28-day mortality in septic patients admitted to the emergency department and derive and validate a score that stratifies mortality risk utilizing parameters that are readily available. Methods Patients with an admission diagnosis of suspected or confirmed infection and fulfilling at least two criteria for severe inflammatory response syndrome were included in this study. Patients’ characteristics, vital signs, and laboratory values were used to identify prognostic factors for mortality. A scoring system was derived and validated. The primary outcome was the 28-day mortality rate. Results A total of 440 patients were included in the study. The 28-day hospital mortality rate was 32.4 and 25.2% for the derivation (293 patients) and validation (147 patients) sets, respectively. Factors associated with a higher mortality were immune-suppressed state (odds ratio 4.7; 95% confidence interval 2.0–11.4), systolic blood pressure on arrival less than 90 mmHg (3.8; 1.7–8.3), body temperature less than 36.0°C (4.1; 1.3–12.9), oxygen saturation less than 90% (2.3; 1.1–4.8), hematocrit less than 0.38 (3.1; 1.6–5.9), blood pH less than 7.35 (2.0; 1.04–3.9), lactate level more than 2.4 mmol/l (2.27; 1.2–4.2), and pneumonia as the source of infection (2.7; 1.5–5.0). The area under the receiver operating characteristic curve was 0.81 (0.75–0.86) in the derivation and 0.81 (0.73–0.90) in the validation set. The SPEED (sepsis patient evaluation in the emergency department) score performed better (P=0.02) than the Mortality in Emergency Department Sepsis score when applied to the complete study population with an area under the curve of 0.81 (0.76–0.85) as compared with 0.74 (0.70–0.79). Conclusion The SPEED score predicts 28-day mortality in septic patients. It is simple and its predictive value is comparable to that of other scoring systems.

Challenges in the management of massive intraorbital and hemifacial arteriovenous malformation as causing life-threatening epistaxis

Arteriovenous malformations are congenital lesions that may evolve with time and manifest in a plethora of presentations. They can occur as torrential epistaxis when it extensively involves the facial region. Multi-imaging modalities are available to assist in characterizing the structure of the lesion as well as its location and extent. This complex disease requires a multidisciplinary team approach with preoperative embolization and surgery. We present a rare cause of life-threatening epistaxis in a gentleman with a longstanding orbital and hemifacial arteriovenous malformation and discuss the complexities involved in its management.

Genomic sequence and expression profile of murine Bat1a and Nfkbil1

In humans, susceptibility to several immunopathologic diseases maps to a conserved block encompassing the polymorphic BAT1, NFKBIL1 (IKBL) and TNF genes in the central MHC. As a pre-requisite for studies of these genes in animal models, we characterized Bat1a and Nfkbil1 in inbred mice differing in their H2 haplotype. We identified two indels and nine single nucleotide polymorphisms (SNP) upstream of Nfkbil1, one indel, nine SNP upstream of Bat1a and a synonymous SNP in exon 2 of Bat1a. H2g7 and H2b mice yielded identical Bat1a and Nfkbil1 sequences. Real time PCR (RT-PCR) showed Bat1a was expressed in adult brain, heart, kidney, liver, lung, pancreas and spleen. Expression of Bat1a was higher in brain and liver of 15-day embryos compared to 1-day old mice and increased moderately in liver and lung of adult mice 2–4 h after LPS challenge. Nfkbil1 expression was low or undetetectable in all tissues and cell lines.