Predicting gallstone pancreatitis in HIV infected patients.

BACKGROUND: Human immunodeficiency virus (HIV) infection, low cluster of differentiation (CD)4 counts and antiretroviral therapy can cause cholestasis and raised transaminases. In acute pancreatitis, this may render biochemical predictors of a gallstone aetiology inaccurate. METHODS: In a prospective observational study, acute pancreatitis was diagnosed by standard criteria. Cholecystolithiasis and bile duct diameter were diagnosed by ultrasound. Cholestasis was defined as two of the following: bilirubin ≥ 21 umol/l, γ glutamyl transferase ≥ 78 U/l, alkaline phosphatase ≥ 121 U/l. Cholangitis was defined as cholestasis and any two sepsis criteria: (temperature > 38˚C, WCC > 12.6 ×109/L, pulse > 90 beats/min). Cholangitis, cholestasis, and bile duct diameter greater that 1 cm were indications for endoscopic retrograde cholangiopancreatography (ERCP). These parameters' ability to predict gallstone pancreatitis (GSP) and choledocholithiasis were compared in HIV+ve and HIV-ve patients. RESULTS: Sixty-two (26%) of 216 patients had GSP. Twenty four were HIV+ve patients. More HIV+ve patients had cholestasis (p = 0.059) and ERCP (p = 0.004). In HIV+ve patients alanine aminotransferase (ALT) > 100 U/L, gamma glutamyl transferase (GGT) > 2 upper limit of normal and cholestasis had a negative predictive value of 92%, 96.7% and 95.2% respectively. In HIV-ve patients, negative predictive value (NPV) was 84%, 83.8% and 84.6% respectively. Bile duct stones were demonstrated at ERCP in 6 (25%) and 3 (8%) of HIV+ve and HIV-ve patients respectively (p = 0.077). Five of 14 ERCP patients had no bile duct stones. HIV+ve and HIV-ve groups had two deaths each. CONCLUSION: Absence at presentation of the abnormal parameters analysed were good predictors of a non-gallstone aetiology particularly in HIV+ve patients. Prior, magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) would reduce the number of non-therapeutic ERCPs.

Association between chronic pancreatitis and pancreatic cancer at a central hospital in KwaZulu-Natal, South Africa.

BACKGROUND: The frequency of histological chronic pancreatitis (CP) evidence in the resident pancreas of resected periampullary cancers (PACs) has never been studied in Africa. This study aims to describe the spectrum of pathology and outcomes of pancreatic surgeries and address this deficit from a South African central hospital cohort. METHODS: A retrospective audit of patients undergoing pancreatic surgery at Inkosi Albert Luthuli Central Hospital (IALCH) between 2003 and 2023 was conducted. The patient demographics, human immunodeficiency virus (HIV) status, histological subtypes, type and extent of surgery, and 30-day and overall mortality were captured from medical records. The presence of CP in the resident pancreas of patients resected for pancreatic and PAC was obtained from the pathology reports. RESULTS: Of the cohort, 72% were Africans, presenting at an earlier average age than other races. Surgery was performed on 126 (107 for cancer, 19 for CP) patients. Of these, 77 were pancreaticoduodenectomy (PD), of which 34 were for pancreatic ductal adenocarcinoma (PDAC). The prevalence of CP in the resident pancreas was 29.9%, and 55.9% in PDAC. Age was the only factor significantly associated with 30-day mortality, as well as long-term survival amongst patients with pancreatic and PAC. The overall median survival for patients with PAC was seven months; 11 patients are alive. CONCLUSION: In a predominantly African cohort undergoing pancreatic surgery, PDAC presents at a younger age. The high perioperative mortality and low overall survival (OS) in the setting of high CP prevalence in the resident pancreas requires further investigation of its role in the aetiopathogenesis and prognosis in PDAC.

HIV associated malignancies presenting as acute pancreatitis: a case series.

BACKGROUND: Acute pancreatitis (AP) may be the presenting symptom in a small percentage of patients harbouring pancreatic or extra pancreatic tumours. This case series aims to describe the pathological spectrum of tumours detected in two AP cohorts from a high HIV-endemic region. METHODS: Prospectively collected databases of patients admitted with AP over two periods 2001 to 2010 and 2013 to 2015, were retrospectively evaluated to detect those with pancreatic and extra-pancreatic tumours. The diagnosis of AP was by standard criteria. HIV infection and CD4 counts were routinely tested for in the latter period and only tested on clinical grounds in the initial period. CT scan was performed when there was diagnostic doubt, predicted severe disease, and failure to improve clinically after one week. Demographic, clinical, investigative, and pathology details were collected and presented. RESULTS: HIV-positive patients admitted with AP were 106 (17%) of 628 in the first period and 90 (38%) of 238 of the second period. No tumours were diagnosed in the HIV-negative patients. Seven of the HIV-positive patients had tumours diagnosed at endoscopy, CT scan, and endoscopic retrograde cholangiography. Of the seven HIV-positive patients with tumours, two patients had a CD4 count above 200. There were four patients with lymphoma involving the pancreatic head, three having associated cholestasis, and three patients with Kaposi's Sarcoma. One Kaposi's sarcoma patient died three months after presentation. One patient with lymphoma died on day 14 and another two months after initial presentation, and the remaining four patients were referred to oncology. CONCLUSION: Despite their rarity (< 4%), when HIV-positive patients with low CD4 count and cholestasis present with AP, tumours should be suspected and evaluated by cross sectional imaging and endoscopic ultrasound.

Development and internal validation of the survival time risk score in patients treated for oesophageal cancer with palliative intent in South Africa.

BACKGROUND: Most patients who present to South African state hospitals with advanced stage oesophageal squamous cell cancer (OSCC) disease receive palliative treatment. This study aimed to assess the factors that influence survival in patients with OSCC who received palliative management and to develop a prognostic score to aid clinicians in decisionmaking. METHODS: Analysis of a prospectively collected database assessed factors influencing survival of patients diagnosed with OSCC receiving palliative treatment. Factors assessed included patient demographics, clinical and laboratory data and tumour factors. A multivariable logistic regression model was used to assess for significant factors associated with survival time and a prognostic score was developed and internally validated based on these factors. RESULTS: There were 384 patients with a male-to-female ratio of 1.3:1. The median survival of the cohort was 3.7 months. Factors that influenced survival on multivariate analysis included area of residence (aOR 1.82, 95% CI 1.02-3.24), performance status (aOR 2.56, 95% CI 1.50-4.35), body mass index (aOR 1.87, 95% CI 1.14-3.06) and serum albumin (aOR 3.06, 95% CI 1.46-6.42). The final prognostic score contained three of the four independent variables based on the regression coefficient for each variable. After internal validation, the risk score maintained fair discrimination and good calibration. CONCLUSION: The prognostic scoring system based on patient performance status, body mass index and serum albumin, if validated on an independent cohort, would allow more objective decisions on whether to stage or not prior to embarking on palliative treatment, streamlining care and improving quality of life.

HIV associated malignancies presenting as acute pancreatitis: a case series.

BACKGROUND: Acute pancreatitis (AP) may be the presenting symptom in a small percentage of patients harbouring pancreatic or extra pancreatic tumours. This case series aims to describe the pathological spectrum of tumours detected in two AP cohorts from a high HIV-endemic region. METHODS: Prospectively collected databases of patients admitted with AP over two periods 2001 to 2010 and 2013 to 2015, were retrospectively evaluated to detect those with pancreatic and extra-pancreatic tumours. The diagnosis of AP was by standard criteria. HIV infection and CD4 counts were routinely tested for in the latter period and only tested on clinical grounds in the initial period. CT scan was performed when there was diagnostic doubt, predicted severe disease, and failure to improve clinically after one week. Demographic, clinical, investigative, and pathology details were collected and presented. RESULTS: HIV-positive patients admitted with AP were 106 (17%) of 628 in the first period and 90 (38%) of 238 of the second period. No tumours were diagnosed in the HIV-negative patients. Seven of the HIV-positive patients had tumours diagnosed at endoscopy, CT scan, and endoscopic retrograde cholangiography. Of the seven HIV-positive patients with tumours, two patients had a CD4 count above 200. There were four patients with lymphoma involving the pancreatic head, three having associated cholestasis, and three patients with Kaposi's Sarcoma. One Kaposi's sarcoma patient died three months after presentation. One patient with lymphoma died on day 14 and another two months after initial presentation, and the remaining four patients were referred to oncology. CONCLUSION: Despite their rarity (< 4%), when HIV-positive patients with low CD4 count and cholestasis present with AP,tumours should be suspected and evaluated by cross sectional imaging and endoscopic ultrasound.

The unfolded protein response and apoptotic regulation in the human placenta due to maternal cigarette smoking and pre-eclampsia.

Maternal cigarette smoking (CS) and pre-eclampsia (PE) alter placental function and expression of important proteins which maintain homeostasis. Two interlinked pathways of interest are the unfolded protein response (UPR) and apoptosis. The UPR is upregulated in the PE placenta, but no data is available on the effects of CS and how it correlates with apoptotic expression. Samples of human placental tissue from normotensive non-smokers (n = 8), women with PE (n = 8), and CS (n = 8) were analysed using immunohistochemistry for 3 UPR markers (phosphorylated PKR-like endoplasmic reticulum (ER) kinase (pPERK), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6)), and an antibody microarray for 19 apoptotic and stress regulating markers. For the PE group compared to the normotensive group, staining for pPERK was increased in decidual tissue and villi, and for IRE1, the overall percentage of stained villi per field of view was increased. There were no differences in UPR expression comparing CS to controls. Of the apoptotic markers, only IκBα (Ser32/36), which is part of an inhibitory pathway, showed a significant decrease in the PE and CS groups compared to controls. These findings suggest UPR regulation is more evident in PE with a general increase in ER stress due to decreased inhibition of apoptosis as compared to CS for which UPR was not altered.

Second surgery for progressive glioblastoma: a multi-centre questionnaire and cohort-based review of clinical decision-making and patient outcomes in current practice.

PURPOSE: Glioblastoma prognosis is poor. Treatment options are limited at progression. Surgery may benefit, but no quality guidelines exist to inform patient selection. We sought to describe variations in surgical management at progression, highlight where further evidence is needed, and build towards a consensus strategy. METHODS: Current practice in selection of patients with progressive GBM for second surgery was surveyed online amongst specialists in the UK and Europe. We complemented this with an assessment of practice in a retrospective cohort study from six United Kingdom neurosurgical units. We used descriptive statistics to analyse the data. RESULTS: 234 questionnaire responses were received. Maintaining or improving patient quality of life was key to decision making, with variation as to whether patient age, performance status or intended extent of resection was relevant. MGMT methylation status was not important. Half considered no minimum time after first surgery. 288 patients were reported in the cohort analysis. Median time to second surgery from first surgery 390 days. Median overall survival 815 days, with no association between time to second surgery and time to death (p = 0.874). CONCLUSIONS: This is the most wide-ranging examination of contemporaneous practice in management of GBM progression. Without evidence-based guidelines, the variation is unsurprising. We propose consensus guidelines for consideration, to reduce heterogeneity in decision making, support data collection and analysis of factors influencing outcomes, and to inform clinical trials to establish whether second surgery improves patient outcomes, or simply selects to patients already performing well.

Assessment and selection of the recipient cows' corpus luteum at the time of embryo transfer, and its influence on conception rate.

OBJECTIVES: To describe the influence of physical traits of the corpus luteum (CL), as described by transrectal ultrasonography on day 6 post-oestrus, on the conception rate following embryo transfer (ET) in recipient beef cows. To investigate if higher recipient utilisation rates were achievable, without compromising conception rates to ET. DESIGN/RESULTS: Data were analysed from Holstein Friesian embryos (n = 1075) frozen in ethylene glycol thawed for direct transfer into one herd of Angus recipient cows. For pregnancies achieved in the program (n = 693), no statistically significant effect was found for the physical traits of the recipients' CL on conception rate (CL volume (P = 0.20), CL side (P = 0.14). Conception rates were similar for recipients with a central lacuna (62%, n = 245) and recipients with no central lacuna (66%, n = 448) (P = 0.10). Of the pregnant recipients with a central lacuna (n = 245), 98.3% had no remaining luteal cavity by the 30-day pregnancy ultrasound. No effect on conception rate was found with either the small (<50% of CL diameter) or large (>50% of CL diameter) central lacunae (P = 0.18). For recipients with CLs that did not meet previous industry selection guidelines (n = 172, 16% of study population), the conception rate (63%) was not significantly different to the routinely selected recipient CLs (n = 903, conception rate 65%) (P = 0.83). CONCLUSIONS: The suitability of a potential ET recipient is determined by observing an appropriately timed oestrus and a detectable CL, regardless of size or quality.

The Hudson Brace technique for emergency burr holes, an aide-memoire for the front-line military surgeon.

Traumatic brain injury is the leading cause of death in conflict and early surgical intervention achieves better outcomes. The British Army surgical kit includes a Hudson Brace and bit and Gigli saw for decompression of the cranial cavity. Here we demonstrate the Hudson Brace technique for non-neurosurgeons.

Quantum Quenches in Isolated Quantum Glasses out of Equilibrium.

In this work, we address the question of how a closed quantum system thermalizes in the presence of a random external potential. By investigating the quench dynamics of the isolated quantum spherical p-spin model, a paradigmatic model of a mean-field glass, we aim to shed new light on this complex problem. Employing a closed-time Schwinger-Keldysh path integral formalism, we first initialize the system in a random, infinite-temperature configuration and allow it to equilibrate in contact with a thermal bath before switching off the bath and performing a quench. We find evidence that increasing the strength of either the interactions or the quantum fluctuations can act to lower the effective temperature of the isolated system and stabilize glassy behavior.

Neuro-Oncology and Radiogenomics: Time to Integrate?

Radiogenomics aims to predict genetic markers based on imaging features. The critical importance of molecular markers in the diagnosis and management of intracranial gliomas has led to a rapid growth in radiogenomics research, with progressively increasing complexity. Despite the advances in the techniques being examined, there has been little translation into the clinical domain. This has resulted in a growing disconnect between cutting-edge research and assimilation into clinical practice, though the fundamental goal is for these techniques to improve patient care. The goal of this review, therefore, is to discuss possible clinical scenarios in which the addition of radiogenomics may aid patient management. This includes facilitating patient counseling, determining optimal patient management when complete molecular characterization is not possible, reclassifying tumors, and overcoming some of the limitations of histologic assessment. The review also discusses considerations for selecting relevant radiogenomic features based on the clinical setting.

Collective vibrations of a hydrodynamic active lattice.

Recent experiments show that quasi-one-dimensional lattices of self-propelled droplets exhibit collective instabilities in the form of out-of-phase oscillations and solitary-like waves. This hydrodynamic lattice is driven by the external forcing of a vertically vibrating fluid bath, which invokes a field of subcritical Faraday waves on the bath surface, mediating the spatio-temporal droplet coupling. By modelling the droplet lattice as a memory-endowed system with spatially non-local coupling, we herein rationalize the form and onset of instability in this new class of dynamical oscillator. We identify the memory-driven instability of the lattice as a function of the number of droplets, and determine equispaced lattice configurations precluded by geometrical constraints. Each memory-driven instability is then classified as either a super- or subcritical Hopf bifurcation via a systematic weakly nonlinear analysis, rationalizing experimental observations. We further discover a previously unreported symmetry-breaking instability, manifest as an oscillatory-rotary motion of the lattice. Numerical simulations support our findings and prompt further investigations of this nonlinear dynamical system.

Recurrence after Delorme's procedure in a single and multi-surgeon setting.

BACKGROUND: Delorme's procedure (DP) is a perineal repair reserved for full-thickness rectal prolapse (FTRP) in elderly/comorbid patients due to its low perioperative morbidity. Reported recurrence rates are higher than for abdominal approaches. This study reports the long-term clinical outcomes of recurrence and postoperative bowel function after DP. METHODS: A retrospective cohort study including all patients who underwent a DP for FTRP between February 2001 and March 2014 at two primary study sites: Groote Schuur Hospital (multi-surgeon) and Kingsbury Hospital (singlesurgeon). Primary outcome was the absence of recurrence of FTRP after DP. Secondary outcomes were 30-day mortality and morbidity, postoperative bowel function and length of hospital stay. RESULTS: 70 patients underwent DP: 37 were operated on by the single surgeon and 33 by multiple surgeons. The median age was 76 years (IQR 20 years). Median length of follow-up was 46 months (IQR 55 months). 16 recurrences occurred: 7 in the single-surgeon cohort and 9 in the multi-surgeon cohort (p = 0.4). Median time to recurrence was 23 months (IQR 36 months): 48 months in the single-surgeon cohort and 15 months in the multi-surgeon cohort (p = 0.6). Six patients each had minor and major complications. Three patients died postoperatively. 8 patients required reoperation. Median postoperative hospital stay was three days (IQR 2 days). There were no significant differences between the multi-surgeon and single-surgeon cohorts. CONCLUSION: Long-term follow-up demonstrates a recurrence rate of 23% after DP, with no difference between an experienced colorectal specialist and supervised trainee surgeons.

Anatomically accurate 3D modelling and printing in a case of obstetric brachial plexus injury.

Obstetric brachial plexus injury is reported in 0.42 per 1000 births in UK and Ireland and are associated with a reduction in quality of life for the patient and their carers. In this report we describe the first use of a patient specific, anatomically accurate 3D model as a communication tool in the treatment of a complex case of posterior shoulder subluxation secondary to glenohumeral deformity resulting from obstetric brachial plexus injury. The use of 3D models for surgical planning is associated with decreased operating time and reduction of intra-operative blood loss, whilst their use in patient education increases patient understanding. In this case all surgeons surveyed agreed that it was useful and will use 3D modelling to improve consent processes and to conceptualise novel techniques for complex cases in future. This highly reproducible, low cost technique may be adapted to a variety of upper limb reconstructive surgeries, and as the resolution of image acquisition and additive manufacturing capabilities increase so too do the potential applications of this precise 3D printed surgical adjunct.

A systematic review of chyle leaks and their management following axillary surgery.

INTRODUCTION: Chyle leaks following surgery to the axilla are seldom encountered with an incidence <0.7%. Management varies with no consensus in the literature. Injury to branching tributaries of the thoracic duct may require lengthy management at significant cost to patient and clinical team. This paper aims to provide an up-to-date review to support clinical management. METHODS: The term 'chyle' was combined with 'breast' or 'axilla.' EMBASE, Medline and PubMed database searches were conducted. All papers published in English were included with no exclusion date limits. RESULTS: 51 cases from 31 papers. All were female (mean age = 53.3yrs). 47/51 leaks were left-sided. 5/51 underwent sentinel node biopsy, 19/51 level II axillary node clearance (ANC), 23/51 level III ANC, 5/51 not specified. 59% (30/51) of leaks were identified within 2 postoperative days (mean = 3.3days). 96% initially managed conservatively: Drain = 38/51; low-fat diet = 34/51; compression bandaging = 20/51; Aspiration = 6/51. 40/51 (78%) were successfully managed conservatively, 11 patients returned to theater for secondary management. 7/11 recorded volumes >500mls/24 hrs before secondary surgery. Mean resolution time from initial surgery was 17.3days (range = 4-64days). No statistically significant difference (p = 0.72) in time to resolution between conservatively and surgically managed patients. CONCLUSIONS: Chyle leaks are rarely seen following axillary surgery. Aberrant thoracic duct anatomy represents the likeliest aetiology. We advocate early recognition and tailored individual management. Conservative management with non-suction drainage, low-fat diet and axillary compression bandaging appear effective where output <500ml/24 hrs. Secondary surgical management should be considered in high chylous output (<500mls/24 hrs) patients unresponsive to conservative measures. We propose a management algorithm to aide clinicians.

Do upper GI bleed guidelines reach patient care: effect of a quality improvement initiative.

BACKGROUND: Adherence is variable in clinical practice to consensus guidelines on the management of upper gastrointestinal bleeding. We aimed to assess the effect of a quality improvement program (QIP) on guideline adherence. METHODS: A QIP was undertaken over a two-month period. Data were collected retrospectively, for the one-year pre QIP and prospectively for one-year post QIP. The QIP goals were adherence to criteria for the timing of oesophagogastroduodenoscopy (OGD), achievement of dual endotherapy and blood transfusion triggers. RESULTS: Fifty-one patients were pre QIP and 58 post QIP. The two groups' baseline data were comparable. Over 80% had their OGD within 24 hours (pre QIP 82.3%, post QIP 81.0%). The overall and high-risk groups (variceal and MBS > 10) had an insignificantly longer time to OGD (mean 19.2 and 17.8 hours respectively) in the post QIP cohort (mean 14.2 and 15.2 hours).The practice of dual endotherapy improved post QIP (p = 0.02) for non-variceal bleeding. The Hb g/dL (mean + SD) in stable patients who were transfused was significantly different pre QIP (6.3 + 2) and post QIP (5.7 + 1.69) (p = 0.04). Twelve patients (23.5%) were transfused for Hb above 7 g/dl pre QIP and six (10.3%) post QIP (p = 0.047). Thirty-day mortality rate was 9.8% (pre QIP) and 10.3% (post QIP). Univariate analysis showed that Grade III shock was the only significant factor in determining 30-day mortality. CONCLUSION: This QIP had no effect on time to OGD adherence which compares favorably to similar audits. Adherence to transfusion triggers and the ability to deliver dual endotherapy routinely were positive QIP outcomes.