Pestilence, Plague and Pandemics: A Troubled History.

Humankind has lived with the danger of endemic, epidemic and pandemic disease for thousands of years. The effects of these outbreaks have often devastated human populations. Sixteen pandemic events causing an estimated 147 million deaths have occurred since the eighth century, The Black Death and the influenza pandemic of 1918-1920 probably having the greatest impact. Animal populations, both wild and domestic, have similarly suffered devastating outbreaks of disease which, on occasions, have translated into serious effects on human health. The deliberate or accidental introduction of animals into virgin areas has given rise to unforeseen disease events occasionally leading to extinction. Similarly, human intent or negligence and the vagaries of nature itself has resulted in ill health and loss of life. This paper describes the history of pandemics, epidemics and disasters, and the attempts to bring them under control.

The relationship between pre-operative psoas and skeletal muscle parameters and survival following endovascular aneurysm repair: a systematic review and meta-analysis.

Sarcopenia is characterised by chronically reduced skeletal muscle volume and function, and is determined radiologically by psoas and skeletal muscle measurement. The present systematic review and meta-analysis aims to examine the relationship between pre-operative CT-derived psoas and skeletal muscle parameters and outcomes in patients undergoing EVAR and F/B-EVAR for aortic aneurysm. The MEDLINE database was interrogated for studies investigating the effect of pre-operative CT-diagnosed sarcopenia on outcomes following EVAR and F/B-EVAR. The systematic review was carried out in accordance with PRISMA guidelines. The primary outcome was overall mortality. RevMan 5.4.1 was used to perform meta-analysis. PROSPERO Database Registration Number: CRD42021273085. Ten relevant studies were identified, one reporting skeletal muscle parameters, and the remaining nine reporting psoas muscle parameters, which were used for meta-analysis. There were a total of 2563 patients included (2062 EVAR, 501 F/B-EVAR), with mean follow-up ranging from 25 to 101 months. 836 patients (33%) were defined as radiologically sarcopenic. In all studies, the combined HR for all-cause mortality in sarcopenic versus non-sarcopenic patients was 2.61 (1.67-4.08), p < .001. Two studies reported outcomes on patients undergoing F/B-EVAR; the combined HR for all-cause mortality in sarcopenic versus non-sarcopenic patients was 3.08 (1.66-5.71), p = .004. Radiological sarcopenia defined by psoas or skeletal muscle parameters was associated with inferior survival in patients undergoing both EVAR and F/B-EVAR. Current evidence is limited by heterogeneity in assessment of body composition and lack of a consensus definition of radiological sarcopenia.

Mid-term follow-up of percutaneous access for standard and complex EVAR using the ProGlide device.

OBJECTIVES: Endovascular Aneurysm Repair is an established treatment for abdominal aortic aneurysm which requires arterial access via the groin. Most centres perform percutaneous ultrasound-guided access into the common femoral artery for delivery of the stent graft. The profile of endovascular devices necessitates large sheath sizes, therefore formal closure of the arterial puncture site is required. Various percutaneous devices are available, with data lacking on efficacy and mid-term safety profile. We present outcomes from a single centre with the Perclose ProGlide™ (Abbott Vascular Devices, CA, USA) suture-mediated system, using the well described "pre-close" technique. MATERIALS & METHODS: Data were collected from operative records and electronic medical records. Patients undergoing standard (EVAR) or complex (F/B-EVAR) aneurysm repair between March 2015 and September 2019 were included. Complications were recorded per-patient and per-groin procedure. RESULTS: 266 patients were included; 182 (68.4%) standard infrarenal EVAR, 84 (31.6%) F/B-EVAR. There were a total of 484 groin procedures performed. Intraoperative Perclose ProGlide™ success was 98.1% (per patient) or 99.0% (per groin procedure). 30-day groin complication rate was 6.1% (per patient) or 3.1% (per groin procedure). There were no pre- or peri-operative factors which predicted the occurrence of groin complications. The rate of groin complications was not related to sheath size. CONCLUSIONS: Our data support the use of percutaneous access with a pre-close technique for a variety of endovascular aneurysm repair procedures with both large- and small-bore access. The Perclose ProGlide™ system provides excellent mid-term complication-free and reintervention-free outcomes for groin procedures.

A SHORT HISTORY OF OCCUPATIONAL DISEASE: 2. ASBESTOS, CHEMICALS, RADIUM AND BEYOND.

Historically, the weighing out and manipulation of dangerous chemicals frequently occurred without adequate protection from inhalation or accidental ingestion. The use of gloves, eye protection using goggles, masks or visors was scant. From Canary Girls and chimney sweeps to miners, stone cutters and silo fillers, these are classic exemplars of the subtle (and in some cases not so subtle) effects that substances, environments and practices can have on individual health.

A SHORT HISTORY OF OCCUPATIONAL DISEASE: 1. LABORATORY-ACQUIRED INFECTIONS.

Laboratory-acquired infections are as old as laboratories themselves. As soon as the culture of microorganisms was introduced, so too was their transfer to laboratory workers. It is only in relatively recent history that such infections have been fully understood, and methods of spread and their prevention or avoidance developed. This paper endeavours to provide an overview of the history of laboratory-acquired infection and the steps taken, particularly in the UK, for its prevention.

A SHORT HISTORY OF OCCUPATIONAL DISEASE: 3. LEISURE CAN MAKE YOU SICK.

The risk of infection associated with occupations can, and does, extend to certain leisure and sports activities. Generally, such pastimes are regarded as important for human health and mental wellbeing. However, infections may, rarely, be acquired during leisure activities that include water sports and water-related relaxation, and certain sports.

A case of dissection in an ACUSEAL-modified HeRO graft.

BACKGROUND: The use of the HeRO system with the early-access ACUSEAL graft avoids the need for a tunnelled dialysis catheter as a bridge for vascular access. Established complications of this system include thrombosis, graft infection, haematoma, and pseudoaneurysm formation. CASE DESCRIPTION: A 72-year-old patient found to have a dissection flap at the venous cannulation point (ACUSEAL component) of a right arm HeRO graft. The ACUSEAL was replaced in theatre and subsequent duplex imaging confirmed satisfactory graft function. CONCLUSION: This case demonstrates a serious yet previously undescribed complication of cannulation of an ACUSEAL graft. The trilaminar construction of the graft may increase the likelihood of disruption of the luminal layer during repeated needling and predispose it to dissection. Given the consequences of graft failure in such patients, urgent intervention is warranted when graft dissection is suspected.

Plant-based sterols and stanols in health & disease: "Consequences of human development in a plant-based environment?"

Dietary plant sterols and stanols as present in our diet and in functional foods are well-known for their inhibitory effects on intestinal cholesterol absorption, which translates into lower low-density lipoprotein cholesterol concentrations. However, emerging evidence suggests that plant sterols and stanols have numerous additional health effects, which are largely unnoticed in the current scientific literature. Therefore, in this review we pose the intriguing question "What would have occurred if plant sterols and stanols had been discovered and embraced by disciplines such as immunology, hepatology, pulmonology or gastroenterology before being positioned as cholesterol-lowering molecules?" What would then have been the main benefits and fields of application of plant sterols and stanols today? We here discuss potential effects ranging from its presence and function intrauterine and in breast milk towards a potential role in the development of non-alcoholic steatohepatitis (NASH), cardiovascular disease (CVD), inflammatory bowel diseases (IBD) and allergic asthma. Interestingly, effects clearly depend on the route of entrance as observed in intestinal-failure associated liver disease (IFALD) during parenteral nutrition regimens. It is only until recently that effects beyond lowering of cholesterol concentrations are being explored systematically. Thus, there is a clear need to understand the full health effects of plant sterols and stanols.

Vascular training in Scotland and Northern Ireland: The trainee perspective prior to introduction of the new vascular curriculum.

BACKGROUND: The last decade has seen the evolution of vascular surgery from a sub-specialty of general surgery to that of an independent, stand-alone specialty. The introduction of a vascular-only curriculum is anticipated to require significant change from the current provision for vascular surgical training to allow vascular trainees to acquire the specialist skills in elective, emergency, and endovascular surgery to provide endovascular services in the future. AIM: To provide an insight into current vascular training in Scotland and Northern Ireland. METHOD: Specialty trainees in general surgery, with a sub-specialty interest in vascular in Scotland and Northern Ireland were asked to carry out a voluntary online survey between May 2012 and July 2012. RESULTS: 22 specialty trainees/specialist registrars who have declared a sub-specialty interest in vascular surgery were identified and polled. 20 trainees completed the survey. 13 trainees still participated in general surgical on-call rotas. Formal teaching opportunities were readily available but only 10 trainees could attend regularly. All trainees worked in units offering endovascular treatment for aneurysm and occlusive disease, but few had dedicated training sessions in endovascular skills. All endovascular simulation-based training was industry sponsored. The majority of trainees report a good overall training experience and are keen to see the implementation of a vascular-specific curriculum. 15 trainees had undertaken a dedicated period of research towards a higher degree, with only 50% based on a vascular topic. CONCLUSION: The majority of trainees reported a positive training experience with Scotland and Northern Ireland having great potential as vascular training deaneries. The survey identifies specific areas that could be improved by the development of the new curriculum in vascular surgery to provide excellent vascular training in Scotland and Northern Ireland.

Post-operative bilateral adrenal haemorrhage: A case report.

INTRODUCTION: Bilateral adrenal haemorrhage is a rare, but serious, illness carrying an estimated 15% mortality.(1,2) The majority of cases occur in patients with acute, stressful illness, however the exact mechanism underlying adrenal haemorrhage remains unclear. This medical emergency carries significant diagnostic difficulty(4) with non-specific clinical symptoms and variations in electrolyte abnormalities. Timely treatment is important as it prevents both the acute and long-term sequelae of adrenal failure. PRESENTATION OF CASE: This report describes a medical emergency in a surgical patient following emergency surgery for intra-abdominal sepsis. The patient reported non-specific symptoms of confusion, mild pyrexia and vague abdominal pain during the post-operative phase, with subtle electrolyte abnormalities and a low serum cortisol suggestive of adrenal crisis. Timely medical treatment, with intravenous hydrocortisone and intensive monitoring, and appropriate medical follow-up with addition of long-term fludrocortisone resulted in a satisfactory outcome. DISCUSSION: This report describes a potentially life-threatening complication of intra-abdominal sepsis with adrenal crisis secondary to bilateral adrenal haemorrhage. In particular, this case highlights the diagnostic difficulty in such surgical patients due to vague symptoms and, in this case, the presence of a presentation variant with acute hyponatraemia and normal potassium. CONCLUSION: This case highlights the importance of awareness of both the symptoms and signs and variation in electrolyte profile when assessing surgical patients post-operatively. In addition, this case highlights the benefit of early recognition and initiation of treatment and the importance of follow-up as long-term medical management is often required to prevent further relapse.

Effectiveness of 0.05% oxymetazoline (Vicks Sinex Micromist®) nasal spray in the treatment of objective nasal congestion demonstrated to 12 h post-administration by magnetic resonance imaging.

INTRODUCTION: This study aimed to assess the qualitative and quantitative utility of MRI imaging to illustrate the magnitude and duration of the effect of a standard 100 µg dose of oxymetazoline in a commercially available formulation that also contains aromatic oils. METHODS: This was a randomized, open label, single dose, parallel group study in 21 adult male and female subjects who reported moderate to severe nasal congestion due to acute upper respiratory tract infection or hay fever. MRI scans were acquired using a 3T Philips Achieva scanner with a 16 channel head receive coil. High resolution MRI scans of the nasal turbinates were obtained immediately prior to dosing (baseline) and at approximately 1, 8, 10, 11, and 12 h after dosing. The efficacy variables of primary interest were inferior turbinate total volume at 8 and 12 h post-dosing. The secondary efficacy variables analysed were inferior turbinate total volume at 1, 10, and 11 h post-dosing, middle turbinate total volume at 1, 8, 10, 11, and 12 h post-dosing. RESULTS: Changes from baseline volumes measured for the inferior and middle turbinates of subjects receiving the oxymetazoline formulation showed significant (P < 0.05) decreases at all times up to and including 12 h post-administration. No significant decreases from baseline were detected in subjects receiving a sham 'spray' (untreated control - spray bottles with no spray solution). Statistical ANCOVA results of inferior and middle turbinate volume indicated significant differences (P < 0.05) at all measurement points up to and including 12 h post-administration between the oxymetazoline treatment group and the untreated control with the only exception the middle turbinate volume at 10 h (P = 0.0896). The significant changes were likely to be clinically relevant though this was not measured in the study. No AEs were reported during this study and no other safety evaluations were made. CONCLUSIONS: This study showed that MRI assessment of nasal congestion in human volunteers is a robust, repeatable and viable measurement technique. The application of a 100 µg Vicks Sinex Micromist(®) nasal decongestant (0.05% oxymetazoline solution) delivered a highly significant reduction in inferior and middle turbinate volumes compared with the application of a control, measurable by the MRI method up to and including a 12 h post-dose scan.

Comparison of visual and automated assessment of tumour inflammatory infiltrates in patients with colorectal cancer.

BACKGROUND: Cancer-associated inflammation is increasingly recognised to be an important determinant of oncological outcome. In colorectal cancer, the presence of peri-tumoural inflammatory/lymphocytic infiltrates predicts improved survival. To date, these infiltrates, assessed visually on haematoxylin and eosin (H&E) stained sections, have failed to enter routine clinical practice, partly due to their subjective assessment and considerable inter-observer variation. The present study aims to develop an automated scoring method to enable consistent and reproducible assessment of tumour inflammatory infiltrates in colorectal cancer. METHODS: 154 colorectal cancer patients who underwent curative resection were included in the study. The local inflammatory infiltrate was assessed using the method described by Klintrup-Makinen. H&E tumour sections were uploaded to an image analysis programme (Slidepath, Leica Biosystems). An image analysis algorithm was developed to count the inflammatory cells at the invasive margin. The manual and automated assessments of the tumour inflammatory infiltrates were then compared. RESULTS: The automated inflammatory cell counts assessed using the freehand annotation method (p<0.001) and the rectangular box method (p<0.001) were significantly associated with both K-M score (p<0.001) and K-M grade (p<0.001). The inflammatory cell counts were divided using quartiles to group tumours with similar inflammatory cell densities. There was good agreement between the manual and automated scoring methods (intraclass correlation coefficient (ICC)=0.82). Similar to the visual K-M scoring system, the automated K-M classification of the inflammatory cell counts, using quartiles, was significantly associated with venous invasion (p<0.05) and modified Glasgow Prognostic Score (mGPS) (p⩽0.05). On univariate survival analysis, both automated K-M category (p<0.05) and automated K-M grade (p<0.005) were associated with cancer-specific survival. CONCLUSION: The results of the present study demonstrate that automated assessment effectively recapitulates the clinical value of visual assessment of the local inflammatory cell infiltrate at the invasive margin of colorectal tumours. In addition, it is possible to obtain an objective assessment of tumour inflammatory infiltrates using routinely stained H&E sections. An automated, computer-based scoring method is therefore a workable and cost-effective approach to clinical assessment of local immune cell infiltrates in colorectal cancer.

Bevacizumab as an adjunct to vitreoretinal surgery for diabetic retinopathy in East Africa.

PURPOSE: The purpose of this study is to evaluate the efficacy of preoperative intravitreal bevacizumab (IVB) for improving outcomes in vitrectomy for diabetic retinopathy-related non-clearing vitreous haemorrhage and/or tractional retinal detachment. METHODS: Medical record from patients undergoing vitrectomy for proliferative diabetic retinopathy (PDR) were retrospectively analysed (2003-2011). From 2007, IVB (1.25 mg 2-4 days before operating) was used on all eyes. Eyes receiving IVB were compared with those that did not receive IVB. Intraoperative complications, reoperation rates, and final visual acuity were the core outcome measures. RESULTS: Data were analysed for 88 patients (101 eyes). In all, 41 (41%) patients had received IVB, whereas 60 (59%) patients had not. Significant intraoperative haemorrhage occurred in six eyes (10%) in the non-IVB group and in one (2.4%) IVB eyes (P=0.24). Silicon oil was used in 29 (48%) non-IVB eyes and in 11 (27%) IVB eyes (P=0.03). The non-IVB eyes underwent significantly more vitreoretinal reoperations (P=0.01) and were significantly more likely to lose two or more lines of vision at the final follow-up (P=0.03). The numbers needed to treat (NNT) blindness (<3/60) was four for non-IVB eyes and two for the IVB group. CONCLUSIONS: IVB reduces surgical complications, the use of silicon oil, and the need for further retinal surgery. The NNT to restore useful vision (≥3/60) to a blind eye were significantly lower in the IVB group. Vitreoretinal surgery for the complications of PDR is effective in an East African context, and IVB should be considered a valuable adjunct.

Circulating IL-6 concentrations link tumour necrosis and systemic and local inflammatory responses in patients undergoing resection for colorectal cancer.

BACKGROUND: Cancer-associated inflammation, in the form of local and systemic inflammatory responses, appear to be linked to tumour necrosis and have prognostic value in patients with colorectal cancer. However, their relationship with circulating biochemical mediators is unclear. The aim of the present study was to examine the interrelationships between circulating mediators, in particular interleukin-6 (IL-6) and tumour necrosis, and local and systemic inflammatory responses in patients undergoing resection for colorectal cancer. METHODS: Data were collected from preoperative blood tests for 118 patients who underwent resection for colorectal cancer. Analysis of circulating IL-6, IL-10, vascular endothelial growth factor (VEGF), differential white cell count, C-reactive protein, and albumin were carried out. Routine pathology specimens were examined for tumour characteristics including necrosis and the extent of the inflammatory cell infiltrate. Body composition was examined using body mass index (BMI), total body fat, subcutaneous body fat, visceral fat, and skeletal muscle mass. RESULTS: Circulating IL-6 concentrations were significantly associated with increased T stage (P<0.05), tumour necrosis (P<0.001), IL-10 (P<0.001), VEGF (P<0.001), modified Glasgow Prognostic Score (mGPS; P<0.001), white cell (P<0.01) and platelet (P<0.01) counts, and low skeletal muscle index (P<0.01). When normalised for T stage, tumour necrosis was associated with IL-6 (P<0.001), IL-10 (P<0.01), VEGF (P<0.001), mGPS (P<0.001), neutrophil-lymphocyte ratio (NLR; P<0.05), white cell (P<0.001), neutrophil (P<0.05), and platelet counts (P<0.005), and skeletal muscle index (P<0.001). CONCLUSION: The present study provides, for the first time, supportive evidence for the hypothesis that tumour necrosis, independent of T stage, is associated with elevated circulating IL-6 concentrations, thereby modulating both local and systemic inflammatory responses including angiogenesis that, in turn, may promote tumour progression and metastases.

Comparison of the prognostic value of longitudinal measurements of systemic inflammation in patients undergoing curative resection of colorectal cancer.

BACKGROUND: The systemic inflammation-based prognostic scores, modified Glasgow Prognostic Score (mGPS) and the neutrophil-lymphocyte ratio (NLR) are now recognised to be useful in predicting survival in a variety of solid organ malignancies, including colorectal cancer (CRC) before treatment. However, there would appear to have been no direct comparison of these longitudinal measurements of systemic inflammation. Therefore, the aim of the present study was to compare the prognostic value of longitudinal measures of systemic inflammation, the mGPS and NLR in patients undergoing potentially curative resection for CRC. METHODS: Three hundred and twenty-six patients underwent potentially curative resection for CRC between 2006 and 2010. Full biochemical and haematological data both pre- and post-operatively (3-6 months) were available for 206 patients. RESULTS: In 206 patients, there was no significant overall change in either the mGPS or the NLR, from pre- to post-operatively. On univariate survival analysis, T-stage (P<0.001), tumour, node, metastasis stage (P<0.005), pre-operative mGPS (P<0.05), pre-operative NLR (<0.05), post-operative mGPS (P<0.001) and post-operative NLR (P<0.005) were associated with cancer-specific survival. On multivariate survival analysis, comparing pre-operative mGPS and NLR, both pre-operative mGPS and NLR were independently associated with reduced cancer-specific survival (mGPS hazard ratio (HR) 1.97, CI 1.16-3.34, P<0.05, and NLR HR 3.07, CI 1.23-7.63, P<0.05). When the same multivariate comparison was carried out on post-operative data, only the post-operative mGPS was independently associated with cancer-specific survival (HR 4.81, CI 2.13-10.83, P<0.001). CONCLUSION: The results of the present study support the longitudinal assessment of the systemic inflammatory response, in particular the mGPS, in patients undergoing potentially curative resection for CRC.

Gastric Schwannoma or GIST: accuracy of preoperative diagnosis?

Mesenchymal cell tumours of the gastrointestinal tract are rare in western society. Gastrointestinal stromal tumour (GIST) is the most common of this group of tumours. Gastric schwannoma is rarer, accounting for only 0.2% of all gastric tumours and 4% of all benign gastric neoplasms. Indeed, schwannoma has only been recognized as a primary gastrointestinal tumour in the last 20 years through advances in pathological techniques. We report a rare case of gastric schwannoma, the endoscopic and radiological features of which were indistinguishable from a GIST. Due to the diagnostic uncertainty, surgical resection is the treatment of choice. Development of more reliable diagnostic methods, such as endoscopic core biopsy, may help the accuracy of preoperative diagnosis.

Comparison of the prognostic value of tumour- and patient-related factors in patients undergoing potentially curative surgery for colon cancer.

AIM: To comprehensively compare the prognostic value of tumour- and patient-related factors in patients undergoing curative surgery for colon cancer. METHOD: From a database of 287 patients who underwent elective resection between 1997 and 2005, tumour factors including stage and host factors including systemic inflammatory response [modified Glasgow Prognostic Score (mGPS)] were identified. RESULTS: Median follow-up was 65 months. Over this period, 125 patients died, 80 from cancer. On multivariate analysis of all significant patient and tumour related factors, Dukes stage (P < 0.01), vascular invasion (P < 0.01) and the mGPS (P < 0.01) were independently associated with cancer-survival. Of the patient-related factors, age (P < 0.01), haemoglobin (P < 0.01), white-cell (P < 0.01), neutrophil (P < 0.01) and platelet (P < 0.01) counts, and alkaline phosphatase (P < 0.01) were most significantly associated with the mGPS. CONCLUSION: In addition to tumour-related factors such as Dukes stage and vascular invasion, the preoperative mGPS should be included to guide prognosis in patients undergoing curative resection for colon cancer.