Martin Brand

A Mismatch Between Aortic Pulse Pressure and Pulse Wave Velocity Predicts Advanced Peripheral Arterial Disease

OBJECTIVES To determine whether increases in central aortic pulse pressure (PPc), but decreases in carotid-femoral pulse wave velocity (PWV) predict the presence of advanced peripheral arterial disease (PAD). METHODS Applanation tonometry and vascular ultrasound were employed to assess carotid-femoral PWV, PPc, and carotid intima media thickness (IMT) in 136 patients of African ancestry with chronic critical lower limb ischaemia (CLI) and in 1,030 randomly selected healthy adults of African ancestry, 194 of whom were age- and sex matched (controls). RESULTS With adjustments for confounders, compared with age- and sex-matched controls, participants with CLI had an increased carotid IMT (p = .0001) and PPc (p < .0001), but a markedly reduced PWV (m/second) (CLI = 5.7 ± 3.7, controls = 8.6 ± 3.4, p < .0001). PWV was correlated with PPc in controls (r = .52, p < .0001), but not in CLI (r = -.06). A PPc/PWV mismatch index showed increased values in participants with CLI over the full adult age range assessed. With carotid IMT, PPc, or aortic augmentation index in the same regression model, an increase in the PPc/PWV mismatch index was independently associated with CLI (p < .0001) and a PPc/PWV value upper 95% confidence interval in the community sample predicted CLI (odds ratio = 32 [6-169], p < .0001). PPc/PWV predicted CLI with a similar level of performance and accuracy and a greater specificity (98%) than that of IMT (82%). CONCLUSION In CLI, while PPc increases, carotid-femoral PWV is markedly reduced. A PPc/PWV mismatch may be a new risk marker for advanced PAD.

Cytokines as Biomarkers of Pancreatic Ductal Adenocarcinoma: A Systematic Review

Objectives A systematic review of the role of cytokines in clinical medicine as diagnostic, prognostic, or predictive biomarkers in pancreatic ductal adenocarcinoma was undertaken. Materials and Methods A systematic review was conducted according to the 2009 PRISMA guidelines. PubMed database was searched for all original articles on the topic of interest published until June 2015, and this was supplemented with references cited in relevant articles. Studies were evaluated for risk of bias using the Quality in Prognosis Studies tools. Results Forty one cytokines were investigated with relation to pancreatic ductal adenocarcinoma (PDAC) in 65 studies, ten of which were analyzed by more than three studies. Six cytokines (interleukin[IL]-1β, -6, -8, -10, vascular endothelial growth factor, and transforming growth factor) were consistently reported to be increased in PDAC by more than four studies; irrespective of sample type; method of measurement; or statistical analysis model used. When evaluated as part of distinct panels that included CA19-9, IL-1β, -6 and -8 improved the performance of CA19-9 alone in differentiating PDAC from healthy controls. For example, a panel comprising IL-1β, IL-8, and CA 19–9 had a sensitivity of 94.1% vs 85.9%, specificity of 100% vs 96.3%, and area under the curve of 0.984 vs 0.925. The above-mentioned cytokines were associated with the severity of PDAC. IL-2, -6, -10, VEGF, and TGF levels were reported to be altered after patients received therapy or surgery. However, studies did not show any evidence of their ability to predict treatment response. Conclusion Our review demonstrates that there is insufficient evidence to support the role of individual cytokines as diagnostic, predictive or prognostic biomarkers for PDAC. However, emerging evidence indicates that a panel of cytokines may be a better tool for discriminating PDAC from other non-malignant pancreatic diseases or healthy individuals.

Large vessel adventitial vasculitis characterizes patients with critical lower limb ischemia with as compared to without human immunodeficiency virus infection.

Objectives Whether a human immunodeficiency virus (HIV)-associated vasculitis in-part accounts for occlusive large artery disease remains uncertain. We aimed to identify the histopathological features that characterize large vessel changes in HIV sero-positive as compared to sero-negative patients with critical lower limb ischemia (CLI). Materials and Methods Femoral arteries obtained from 10 HIV positive and 10 HIV negative black African male patients admitted to a single vascular unit with CLI requiring above knee amputation were subjected to histopathological assessment. None of the HIV positive patients were receiving antiretroviral therapy. Results As compared to HIV negative patients with CLI, HIV positive patients were younger (p<0.01) and had a lower prevalence of hypertension (10 vs 90%, p<0.005) and diabetes mellitus (0 vs 50%, p<0.05), but a similar proportion of patients previously or currently smoked (80 vs 60%). 90% of HIV positive patients, but no HIV negative patient had evidence of adventitial leukocytoclastic vasculitis of the vasa vasorum (p<0.0001). In addition, 70% of HIV positive, but no HIV negative patient had evidence of adventitial slit-like vessels. Whilst T-lymphocytes were noted in the adventitia in 80% of HIV positive patients, T-lymphocytes were noted only in the intima in HIV negative patients. The presence of femoral artery calcified multilayered fibro-atheroma was noted in 40% of HIV positive and 90% of HIV negative patients with CLI. Conclusions An adventitial vasculitis which characterizes large artery changes in CLI in HIV-infected as compared to non-infected patients, may contribute toward HIV-associated occlusive large artery disease.

Adaptive Immune Cell Dysregulation and Role in Acute Pancreatitis Disease Progression and Treatment

Acute pancreatitis (AP) is an inflammation of the pancreas caused by various stimuli including excessive alcohol consumption, gallstone disease and certain viral infections. Managing specifically the severe form of AP is limited due to lack of an understanding of the complex immune events that occur during AP involving immune cells and inflammatory molecules such as cytokines. The relative abundance of various immune cells resulting from the immune dysregulation drives disease progression. In this review, we examine the literature on the adaptive immune cells in AP, the prognostic value of these cells in stratifying patients into appropriate care and treatment strategies based on cell frequency in different AP severities are discussed.

Value of Diagnostic and Therapeutic Laparoscopy for Abdominal Stab Wounds

I read with interest and would like to commend Lin et al. on their article [1]. They give an excellent description of how to perform a diagnostic laparoscopy in trauma, including therapeutic maneuvers and tips on how not miss injuries, specifically occult bowel perforations. I have a few questions regarding the management algorithm of the two patient groups. Omental evisceration in a clinically benign abdomen is not an immediate indication for laparotomy [2, 3]. Peritonitis itself should have been included as a criterion leading to laparotomy in both groups. Why did bowel evisceration go to laparotomy in group B and not to laparoscopy? Were the surgeons involved able to repair bowel perforations? The argument that non-therapeutic laparoscopy is less invasive than non-therapeutic laparotomy, though true, is not a reason to perform laparoscopy on all patients with penetrating trauma. I also question the very high rate of non-therapeutic laparotomy in group A (22/38). If they had no signs of peritonitis or bowel evisceration should they not have had radiological investigation and/or serial abdominal examinations in the ward? Selective nonoperative management has been shown to be safe and effective [4]. Depending on the site of injury, radiological imaging may have been the more appropriate diagnostic tool. An example is the right upper quadrant. Most stable liver injuries can be managed conservatively [5]. Is it possible that laparoscopy may have been avoided in the 17 patients with liver injuries? I think an interesting study from your institution would examine the use of therapeutic laparoscopy in hemodynamically stable patients following penetrating trauma that have peritonitis or CT scan evidence of significant injuries that in the past would have mandated a laparotomy.

Trainees, Trainers, and Training; Where Does Their Destiny Lie ?

The first formal Trainee’s session during International Surgery Week was held in Yokohama, Japan, in 2011, and it heralded a new initiative by the International Surgical Society (ISS). This gave trainees the opportunity to participate in debates with world-renowned trainers and to explore topical and crucial issues relating to training and research. The primary concern was that training had changed, and that the exact formula for producing competent and safe surgeons in today’s environment has yet to be determined. Is the key factor the number of hours, the number of core procedures, the number of cases? The concept of a residency program, fathered by Sir William Osler, is seen today as outdated, and ‘‘work-life balance’’ is the new descriptor. In the United States, the 80 h working week resulted from a medical misadventure following which lawyers realized that an unrestricted training environment was not safe, either for patients or for doctors. In the European Union, the 48 h work-week directive initially was designed to improve truck driver and fishermen safety; it was then expanded to include all workers. At the same time, it was agreed that the EU time directive of a 48 h work week is far too restrictive and inadequate for surgical training. The Royal College of Surgeons has called for a 65 h work week, and the American College of Surgeons is calling for an increase in the current 80 h work week. Developing countries have no such restrictions. In the end we need to enhance patient safety, as well as improve surgical training while maintaining a realistic work-life balance. What is becoming increasingly clear is that trainees need to learn the principles of managing clinical problems, and this will never be achieved by experience alone, which is mere service, or by reflection alone, which is pedantry. Surgical trainees need both reflection and experience, and the time to acquire both. How should surgery be taught? Learning through a simple apprenticeship in a non-time-limited environment is no longer possible, nor is it academically or socially acceptable. Richard Reznick’s competency-based residency program is being adopted in North America, the United Kingdom, and Australia/New Zealand in varying degrees. This system requires proficient trainers and technology that serves to hone skills in simulated environments, that provides workplace-based assessments, and that encourages performance-related progress, eventually allowing the trainee to operate on patients. This process has limitations, especially in developing countries: a lack of both appropriate technology and motivated and trained trainers. The new surgical environment is causing the attitude of modern trainees to change as well. No longer can they simply be directed as to what to do and where to go, but trainees need to become proactive as well as reflective. Conversely, nurturing and support, rather than dictatorship, is required from their trainers. For trainers, the gauntlet to be run involves finding ways to objectively assess their prodigies. What is an adequate logbook, how is experience M. Brand (&) Department of Surgery, University of the Witwatersrand, Johannesburg, South Africa e-mail: martinbrand78@gmail.com

The dynamic continence challenge - a simple test to predict faecal continence prior to colostomy closure

BACKGROUND A common problem in clinical practice is predicting whether a patient will be continent after treatment of a severe perineal injury. Several tests have been described. Anal manometry is unreliable; continence can be normal with low pressures, and poor with high or normal pressures. Endo-anal ultrasound only illustrates anatomical sphincter integrity. The saline continence test involves the quite unphysiological instilling of saline into the rectum, and assessing seepage. What is needed in the prediction of continence is a normal stool simulator. METHOD We propose the use of powdered instant mashed potato reconstituted with water to the consistency of faeces. About 100 - 150 ml is introduced into the rectum using a catheter-tipped syringe. The patient is instructed to walk around for half an hour. On return the underwear is examined for any soiling. If there is no leakage the colostomy may be reversed. RESULTS Over the past 15 years, 53 patients have undergone this test. In 47 patients there was no leakage, all had their stomas reversed, and none was incontinent during follow-up. CONCLUSION The dynamic continence challenge is an accurate physiological test that allows clinicians to simulate the effects of colostomy reversal and assess a patients continence before actually proceeding to the reversal.