Mastitis and Mammary Abscess Management Audit (MAMMA) in the UK and Ireland.

BACKGROUND: The aim of this multicentre prospective audit was to describe the current practice in the management of mastitis and breast abscesses in the UK and Ireland, with a specific focus on rates of surgical intervention. METHODS: This audit was conducted in two phases from August 2020 to August 2021; a phase 1 practice survey and a phase 2 prospective audit. Primary outcome measurements for phase 2 included patient management pathway characteristics and treatment type (medical/radiological/surgical). RESULTS: A total of 69 hospitals participated in phase 2 (1312 patients). The key findings were a high overall rate of incision and drainage (21.0 per cent) and a lower than anticipated proportion of ultrasound-guided aspiration of breast abscesses (61.0 per cent). Significant variations were observed regarding the rate of incision and drainage (range 0-100 per cent; P < 0.001) and the rate of needle aspiration (range 12.5-100 per cent; P < 0.001) between individual units. Overall, 22.5 per cent of patients were admitted for inpatient treatment, out of whom which 72.9 per cent were commenced on intravenous antibiotics. The odds of undergoing incision and drainage for a breast abscess or being admitted for inpatient treatment were significantly higher if patients presented at the weekend compared with a weekday (P ≤ 0.023). Breast specialists reviewed 40.9 per cent of all patients directly, despite the majority of patients (74.2 per cent) presenting within working hours on weekdays. CONCLUSIONS: Variation in practice exists in the management of mastitis and breast abscesses, with high rates of incision and drainage in certain regions of the UK. There is an urgent need for a national best-practice toolbox to minimize practice variation and standardize patient care.

Mastitis and breast abscess is a painful infection of the breast. It is an extremely common breast problem. One in three women can get this condition at some stage in their life. To treat a breast abscess, the pus inside should be drained out of the body. This can be done either by cutting into the breast using surgery or by inserting a fine needle using an ultrasonography scan (which uses ultrasound). Fine-needle drainage has the benefit that it does not require admission to hospital. Surgery can cause the breast to look misshapen. It is unknown which method is used more often in the UK and Ireland. The aim of this study was to describe how mastitis and breast abscesses are treated in the UK and Ireland. This study involved a survey of practice (phase 1) and collection of data, which are routinely recorded for these patients (phase 2). This study involved 69 hospitals and 1312 patient records. One in five women had an operation for a breast abscess. This was higher than expected. Six in 10 women had a pus drainage using a fine needle. The chance of having an operation depended on the hospital. Women that came to hospital at the weekend were almost twice as likely to have an operation. One in five women were admitted to hospital. The chances of that more than doubled if a woman came to hospital at the weekend. There are differences in treatment of mastitis and breast abscesses across the UK and Ireland. Changes need to be put in place to make access to treatment more equal.

Long-term Impact of Bariatric Surgery on Venous Thromboembolic Risk: A Matched Cohort Study.

OBJECTIVE: The aim of this study is to evaluate the effect of bariatric surgery on long-term risk of VTEs in a large cohort of patients with obesity. BACKGROUND: Obesity is a well-established risk factor for VTEs, such as pulmonary embolism and deep vein thrombosis. The rising prevalence of obesity and its associated co-morbidities, including VTE, represent a growing public health issue. METHODS: A nested, retrospective matched cohort study was designed and conducted on prospectively collected national electronic healthcare records data from the Clinical Practice Research Datalink. Eight thousand, one hundred twelve patients were included in the study: the 4056 patients on the database who had undergone bariatric surgery, and equal numbers of age, sex, and body mass index matched controls. The primary endpoint was the occurrence of VTEs; secondary endpoints were the occurrence of deep vein thrombosis alone, pulmonary embolism alone. RESULTS: Patients were followed up for a median of 10.7 years. The bariatric surgery cohort had a significantly lower occurrence of the primary outcome [hazard ratio (HR) 0.601; 95% confidence interval (CI) 0.430-0.841, P = 0.003]; mainly driven by a reduction in deep vein thrombosis (HR 0.523; 95% CI 0.349-0.783, P = 0·002) and not in pulmonary embolism (HR 0.882; 95% CI 0.511-1.521, P = 0.651). CONCLUSIONS: The results of this nation-wide study set out to characterize the impact of bariatric surgery on long-term risk of thromboembolic events outline a significant reduction in thromboembolic events, driven by a reduction in deep vein thrombosis.

Peptide Amphiphilic-Based Supramolecular Structures with Anti-HIV-1 Activity.

In a previous work, we defined a novel HIV-1 fusion inhibitor peptide (E1P47) with a broad spectrum of activity against viruses from different clades, subtypes, and tropisms. With the aim to enhance its efficacy, in the present work we address the design and synthesis of several peptide amphiphiles (PAs) based on the E1P47 peptide sequence to target the lipid rafts of the cell membrane where the cell-cell fusion process takes place. We report the synthesis of novel PAs having a hydrophobic moiety covalently attached to the peptide sequence through a hydrophilic spacer of polyethylene glycol. Characterization of self-assembly in condensed phase and aqueous solution as well as their interaction with model membranes was analyzed by several biophysical methods. Our results demonstrated that the length of the spacer of polyethylene glycol, the position of the peptide conjugation as well as the type of the hydrophobic residue determine the antiviral activity of the construct. Peptide amphiphiles with one alkyl tail either in C-terminus (C-PAmonoalkyl) or in N-terminus (N-PAmonoalkyl) showed the highest anti-HIV-1 activities in the cellular model of TZM-bl cells or in a preclinical model of the human mucosal tissue explants.

Effect of bariatric surgery on long-term cardiovascular outcomes: a nationwide nested cohort study.

AIMS: This study aims to evaluate the long-term effect of bariatric surgery on cardiovascular outcomes of patients with obesity. METHODS AND RESULTS: A nested cohort study was carried out within the Clinical Practice Research Datalink. The study cohort included the 3701 patients on the database who had undergone bariatric surgery and 3701 age, gender, and body mass index-matched controls. The primary endpoint was the composite of fatal or non-fatal myocardial infarction and fatal or non-fatal ischaemic stroke. Secondary endpoints included fatal or non-fatal myocardial infarction alone, fatal or non-fatal ischaemic stroke alone, incident heart failure, and mortality. The median follow-up achieved was 11.2 years. Patients who had undergone bariatric surgery had a significantly lower occurrence of major adverse cardiovascular events [hazard ratio (HR) 0.410, 95% confidence interval (CI) 0.274-0.615; P < 0.001]. This was mainly driven by a reduction in myocardial infarction (HR 0.412, 95% CI 0.280-0.606; P < 0.001) and not in acute ischaemic stroke (HR 0.536, 95% CI 0.164-1.748; P = 0.301). A reduction was also observed in new diagnoses of heart failure (HR 0.403, 95% CI 0.181-0.897; P = 0.026) and mortality (HR 0.254, 95% CI 0.183-0.353; P < 0.001). CONCLUSION: The results of this large, nationwide cohort study support the association of bariatric surgery with lower long-term risk of major cardiovascular events and incident heart failure in patients with obesity.

The clinical application of electrical impedance technology in the detection of malignant neoplasms: a systematic review.

BACKGROUND: Electrical impedance technology has been well established for the last 20 years. Recently research has begun to emerge into its potential uses in the detection and diagnosis of pre-malignant and malignant conditions. The aim of this study was to systematically review the clinical application of electrical impedance technology in the detection of malignant neoplasms. METHODS: A search of Embase Classic, Embase and Medline databases was conducted from 1980 to 22/02/2018 to identify studies reporting on the use of bioimpedance technology in the detection of pre-malignant and malignant conditions. The ability to distinguish between tissue types was defined as the primary endpoint, and other points of interest were also reported. RESULTS: 731 articles were identified, of which 51 reported sufficient data for analysis. These studies covered 16 different cancer subtypes in a total of 7035 patients. As the studies took various formats, a qualitative analysis of each cancer subtype's data was undertaken. All the studies were able to show differences in electrical impedance and/or related metrics between malignant and normal tissue. CONCLUSIONS: Electrical impedance technology provides a novel method for the detection of malignant tissue, with large studies of cervical, prostate, skin and breast cancers showing encouraging results. Whilst these studies provide promising insights into the potential of this technology as an adjunct in screening, diagnosis and intra-operative margin assessment, customised development as well as multi-centre clinical trials need to be conducted before it can be reliably employed in the clinical detection of malignant tissue.

Mortality of the Severely Obese: A Population Study.

OBJECTIVE: This study aimed to analyze the Clinical Practice Research Datalink to identify the prognostic factors of all-cause mortality in the severely obese. BACKGROUND: Patients who are severely obese [body mass index (BMI) ≥35 kg/m] are at increased risk of all-cause mortality as a result of metabolic sequelae including hyperlipidemia, hypertension, and diabetes. Bariatric surgery has been shown to reduce the severity of the metabolic complications of obesity. METHOD: A case-controlled analysis was carried out of patients with a BMI of 35 kg/m or more from the Clinical Practice Research Datalink, a UK database of primary care clinics. Clinicopathological characteristics at baseline diagnosis were extracted. Cases of all-cause mortality were identified as a clinical endpoint. A Cox proportional hazard model was used to calculate hazard ratios (HRs) for different patient factors. A P value less than 0.050 was defined as significant. RESULTS: A total of 187,061 records were identified for analysis. Median follow-up time was 98.0 months (range: 3.0-1095.0). A total of 8655(4.6%) were identified as having died during the study period. The median time from baseline obesity diagnosis until death was 137.0 months (range: 3.0-628.7). Multivariate analysis found bariatric surgery to be associated with reduced risk of all-cause mortality (HR: 0.487; P < 0.001). The following were associated with increased risk of death: male sex (HR: 1.805; P < 0.001), BMI of 60 or greater (HR: 2.541; P < 0.001), hypertension (HR: 2.108; P < 0.001), diabetes (HR: 2.766; P < 0.001), and hyperlipidemia (HR: 1.641; P < 0.001). CONCLUSIONS: Factors such as high BMI, diabetes, hyperlipidemia, and hypertension at first diagnosis of severe obesity were each independently associated with an increased risk of death. Bariatric surgery was shown to be associated with reduced risk of all-cause mortality. Improving access to bariatric surgery and public health campaigns can improve the prognosis of severely obese patients.

Breath Volatile Organic Compound Profiling of Colorectal Cancer Using Selected Ion Flow-tube Mass Spectrometry.

OBJECTIVE: BACKGROUND:: Breath VOCs have the potential to noninvasively diagnose cancer. METHODS: Exhaled breath samples were collected using 2-L double-layered Nalophan bags, and were analyzed using selected-ion-flow-tube mass-spectrometry. Gold-standard test for comparison was endoscopy for luminal inspection and computed tomography (CT) to confirm cancer recurrence. Three studies were conducted: RESULTS:: CONCLUSION:: This study suggests the association of a single breath biomarker with the primary presence and recurrence of CRCa. Further multicenter validation studies are required to validate these findings.

Fate of the metabolically healthy obese-is this term a misnomer? A study from the Clinical Practice Research Datalink.

INTRODUCTION: The metabolically healthy obese (MHO) phenotype may express typical characteristics on long-term follow-up. Little is known about the initiation of this phenotypes and its future stability. AIM: The Clinical Practice Research Datalink (CPRD) is a large-scale primary care database. The aim of this study was to assess the stability of, and evaluate the factors associated with a transition into an unhealthy outcome in, a MHO population in the UK. METHODS: The CPRD was interrogated for a diagnosis of 'obesity' and cross-referenced with a body mass index (BMI) ≥35 kg/m2; participants were further classified as MH using a clinical diagnostic code or a relative therapeutic code. A hazard cox regression univariate and multivariate analysis evaluated the time to transition for independent variables. RESULTS: There were 231,399 patients with a recorded BMI of 35 kg/m2 or greater. Incomplete records were eliminated and follow-up limited to 300 months, the cohort was reduced to 180,560 patients. The prevalence of MHO within the obese population from the CPRD was 128,191/180,560 (71%). MHO individuals, who were of male gender (hazard ratio (HR) 1.23 (1.21-1.25), p = < 0.01), older age group (HR 3.93 (3.82-4.04), p = < 0.01), BMI of 50-60 kg/m2 at baseline (HR 1.32(1.26-1.38), p = 0.01), smokers (HR 1.07(1.05-1.09), p = < 0.01) and regionally from North West England (HR 1.15(1.09-1.21), p = < 0.01) were more prone to an unhealthy transition (to develop comorbidities). Overall, of those MH at baseline, 71,485/128,191(55.8%) remained healthy on follow-up, with a mean follow-up of 113.5 (standard deviations (SD) 78.6) months or 9.4 (SD 6.6) years. CONCLUSIONS: From this unique large data set, there is a greater prevalence of MHO individuals in the UK population than in published literature elsewhere. Female gender, younger age group, and lower initial weight and BMI were found to be significant predictors of sustained metabolic health in this cohort. However, there remains a steady progressive transition from a healthy baseline over the years.

Idiopathic intracranial hypertension in the British population with obesity.

PURPOSE: Idiopathic intracranial hypertension (IIH) is a syndrome that is characterized by persistently high intracranial pressure and associated with high rates of morbidity and visual loss. Its exact etiology and clinical picture is poorly understood, but it is known to be associated with obesity. The aim of this study was to investigate the prevalence and clinical manifestations of IIH using a large nationwide database of British subjects. MATERIALS AND METHODS: The anonymized healthcare records of patients with a BMI of ≥ 30 kg/m2 were extracted from the Clinical Practice Research Datalink (CPRD), and analyzed. RESULTS: The patients with IIH were older and more likely to have peripheral vascular disease, ischemic heart disease, and anemia; to have had a previous myocardial infarction; and have used non-steroidal anti-inflammatory drugs (NSAIDs) and steroids. Multivariate analysis with adjustment for confounders showed that anemia (p = 0.033) and the use of NSAIDs (p = 0.011) were the only factors independently associated with IIH. Increases in BMI beyond the threshold of obesity did not independently increase risk of IIH. CONCLUSIONS: IIH is a multifactorial disease; the risk of which is increased in patients with a background of anemia, and those who use NSAIDs. Across BMI categories beyond the threshold for obesity (BMI ≥ 30 kg/m2), there is no continuation of the previously described "dose-response" relationship between BMI and IIH. ETHICAL APPROVAL: Scientific approval for the study was granted from the Regulatory Agency's Independent Scientific Advisory Committee and ethical approval by the Health Research Authority IRAS Project ID: 203143. ISAC approval registration number 16_140R2.

Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies.

Definition of the key parameters mediating effective antibody blocking of HIV-1 acquisition within mucosal tissue may prove critical to effective vaccine development and the prophylactic use of monoclonal antibodies. Although direct antibody-mediated neutralization is highly effective against cell-free virus, antibodies targeting different sites of envelope vulnerability may display differential activity against mucosal infection. Nonneutralizing antibodies (nnAbs) may also impact mucosal transmission events through Fc-gamma receptor (FcγR)-mediated inhibition. In this study, a panel of broadly neutralizing antibodies (bnAbs) and nnAbs, including those associated with protection in the RV144 vaccine trial, were screened for the ability to block HIV-1 acquisition and replication across a range of cellular and mucosal tissue models. Neutralization potency, as determined by the TZM-bl infection assay, did not fully predict activity in mucosal tissue. CD4-binding site (CD4bs)-specific bnAbs, in particular VRC01, were consistent in blocking HIV-1 infection across all cellular and tissue models. Membrane-proximal external region (MPER) (2F5) and outer domain glycan (2G12) bnAbs were also efficient in preventing infection of mucosal tissues, while the protective efficacy of bnAbs targeting V1-V2 glycans (PG9 and PG16) was more variable. In contrast, nnAbs alone and in combinations, while active in a range of cellular assays, were poorly protective against HIV-1 infection of mucosal tissues. These data suggest that tissue resident effector cell numbers and low FcγR expression may limit the potential of nnAbs to prevent establishment of the initial foci of infection. The solid protection provided by specific bnAbs clearly demonstrates their superior potential over that of nonneutralizing antibodies for preventing HIV-1 infection at the mucosal portals of infection. IMPORTANCE: Key parameters mediating effective antibody blocking of HIV-1 acquisition within mucosal tissue have not been defined. While bnAbs are highly effective against cell-free virus, they are not induced by current vaccine candidates. However, nnAbs, readily induced by vaccines, can trigger antibody-dependent cellular effector functions, through engagement of their Fc-gamma receptors. Fc-mediated antiviral activity has been implicated as a secondary correlate of decreased HIV-1 risk in the RV144 vaccine efficacy trial, suggesting that protection might be mediated in the absence of classical neutralization. To aid vaccine design and selection of antibodies for use in passive protection strategies, we assessed a range of bnAbs and nnAbs for their potential to block ex vivo challenge of mucosal tissues. Our data clearly indicate the superior efficacy of neutralizing antibodies in preventing mucosal acquisition of infection. These results underscore the importance of maintaining the central focus of HIV-1 vaccine research on the induction of potently neutralizing antibodies.

Enhanced recovery simulation in colorectal surgery: design of virtual online patients.

BACKGROUND: The aim of the present study was to design virtual patients (VP) involving enhanced recovery programs (ERP) in colorectal surgery, in order to train surgical residents in peri-operative care. Indeed, ERP have changed perioperative care and improved patients outcomes in colorectal surgery. Training, using online VP with different pre- and post-operative cases, may increase implementation of ERP. METHODS: Pre- and post-operative cases were built in the virtual world of Second Life™ according to a linear string design method. All pre- and post-operative cases were storyboarded by a colorectal surgeon in accordance with guidelines in both ERP and colorectal surgery, and reviewed by an expert in colorectal surgery. RESULTS: Four pre-operative and five post-operative cases of VP undergoing colorectal surgery were designed, including both simple and complex cases. Comments were provided through case progression to allow autonomic practice (such as "prescribed", "this is not useful" or "the consultant does not agree with your decision"). Pre-operative cases involved knowledge in colorectal diseases and ERP such as pre-operative counseling, medical review, absence of bowel preparation in colonic surgery, absence of fasting, minimal length incision, and discharge plan. Post-operative cases involved uneventful and complicated outcomes in order to train in both simple implementation of ERP (absence of nasogastric tube, epidural analgesia, early use of oral analgesia, perioperative nutrition, early mobilization) and decision making for more complex cases. CONCLUSION: Virtual colorectal patients have been developed to train in ERP through pre- and post-operative cases. Such patients could be included in a whole pathway care training involving technical and non-technical skills.

The 'onion skin' sign of a low-grade appendiceal mucinous neoplasm: An incidental finding during early pregnancy assessment.

A low-grade appendiceal mucinous neoplasm (LAMN) is a cystic dilatation of the appendix resulting from the accumulation of mucinous secretions caused by a luminal obstruction. Although usually benign, pseudomyxoma peritonei may occur in the event of rupture, and 10% of cases may be secondary to appendiceal cystadenocarcinoma. A LAMN is both more common and more likely to have a malignant association in women, making it an entity with which practitioners of gynaecological ultrasound should be familiar. Although not the primary aim, early pregnancy ultrasound assessments can offer the diagnostic opportunity to identify pelvic pathology. A LAMN can be identified on ultrasonography by visualisation of an adnexal mass separate to the ovary, which due to the layers of secretions has a distinctive appearance previously likened to 'onion-skin' or 'whipped-cream'. Here, we describe an incidental finding of a LAMN during an early pregnancy assessment. Practitioners of early pregnancy ultrasound should be familiar with the characteristic morphology of this rare but important finding.

1H HR-MAS NMR spectroscopy of tumor-induced local metabolic "field-effects" enables colorectal cancer staging and prognostication.

Colorectal cancer (CRC) is a major cause of morbidity and mortality in developed countries. Despite operative advances and the widespread adoption of combined-modality treatment, the 5-year survival rarely exceeds 60%. Improving our understanding of the biological processes involved in CRC development and progression will help generate new diagnostic and prognostic approaches. Previous studies have identified altered metabolism as a common feature in carcinogenesis, and quantitative measurement of this altered activity (metabonomics/metabolomics) has the potential to generate novel metabolite-based biomarkers for CRC diagnosis, staging and prognostication. In the present study we applied high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy to analyze metabolites in intact tumor samples (n = 83) and samples of adjacent mucosa (n = 87) obtained from 26 patients undergoing surgical resection for CRC. Orthogonal partial least-squares discriminant analysis (OPLS-DA) of metabolic profiles identified marked biochemical differences between cancer tissue and adjacent mucosa (R(2) = 0.72; Q(2) = 0.45; AUC = 0.91). Taurine, isoglutamine, choline, lactate, phenylalanine, tyrosine (increased concentrations in tumor tissue) together with lipids and triglycerides (decreased concentrations in tumor tissue) were the most discriminant metabolites between the two groups in the model. In addition, tumor tissue metabolic profiles were able to distinguish between tumors of different T- and N-stages according to TNM classification. Moreover, we found that tumor-adjacent mucosa (10 cm from the tumor margin) harbors unique metabolic field changes that distinguish tumors according to T- and N-stage with higher predictive capability than tumor tissue itself and are accurately predictive of 5-year survival (AUC = 0.88), offering a highly novel means of tumor classification and prognostication in CRC.

Laparoscopic versus open colorectal resection in the elderly population.

BACKGROUND: Elderly patients are often regarded as high-risk patients for major abdominal surgery because of a lack of functional reserve and associated medical comorbidities. The aim of this systematic review and pooled analysis was to review the current data published regarding the differences in operative outcomes of laparoscopic and open surgery in the elderly population. METHODS: A systematic literature search of Medline, Embase, Web of Science, and Cochrane databases was performed. Studies that compared outcome following laparoscopic and open colorectal resections in the elderly (≥70) population were included. Primary outcomes were operative death, anastomotic leak, pneumonia, length of hospital stay, and return to bowel function. Secondary outcomes were operative time, intraoperative blood loss, postoperative cardiac morbidity, ileus, and postoperative wound infection. RESULTS: The results of this systematic review and pooled analysis demonstrate the safety and potential benefits of laparoscopic colorectal resection in the elderly population. The latter include reduction in length of hospital stay, intraoperative blood loss, incidence of postoperative pneumonia, time to return of normal bowel function, incidence of postoperative cardiac complications, and wound infections. CONCLUSION: The results of this pooled analysis demonstrate the potential short-term advantages of laparoscopic colorectal resection in the elderly population. Further studies are required to examine the long-term survival following laparoscopic and open colorectal resections in the elderly population.

Prophylactic mesh placement in high-risk patients undergoing elective laparotomy: a systematic review.

BACKGROUND: Incisional hernia is a significant complication in patients undergoing elective laparotomy. Its incidence is increased in patients with risk factors, such as obesity and chronic respiratory disease. The purpose of this pooled analysis was to evaluate the use of prophylactic mesh placement following laparotomy in high-risk patients. METHODS: A systematic literature search of MEDLINE, Embase, Web of Science, and Cochrane database was conducted. Outcome measures were incidence of postoperative incisional hernia, seroma, and wound infection rates. RESULTS: Five randomized, controlled trials (RCTs) and four comparative studies that met the inclusion criteria were identified. In total, 464 patients who underwent laparotomy closure with mesh placement and 755 patients who underwent conventional laparotomy closure were included. A reduced incidence of incisional hernia was observed when laparotomy was combined with prophylactic mesh placement in pooled analysis of RCTs (pooled odds ratio = 0.32; 95 % confidence interval = 0.12-0.83; P = 0.02) and comparative studies (pooled odds ratio = 0.11; 95 % confidence interval = 0.04-0.33; P < 0.001) respectively. No significant differences were observed in the incidence of seroma or wound infection following prophylactic mesh placement. CONCLUSIONS: The results of this pooled analysis suggest a benefit to prophylactic mesh placement during laparotomy closure in high-risk patients with a significantly reduced incidence of incisional hernia without any significant differences in seroma formation and wound infection rates. Further studies must evaluate the incidence of mesh-specific complications, including foreign body sensation and chronic pain, before strong recommendations can be made.

UK trial of pressurised intraperitoneal aerosolised chemotherapy (PIPAC) with oxaliplatin for colorectal cancer peritoneal metastases (NCT03868228).

Objectives: This is the first UK trial of pressurised intraperitoneal aerosolised chemotherapy (PIPAC) for colorectal cancer peritoneal metastases. This trial aimed to assess the impact of PIPAC in combination with standard of care systemic treatment on: progression free survival (PFS); quality of life (QoL); and short-term complications. In addition, this trial set out to demonstrate that PIPAC can be performed safely in operating theatres within a National Health Service (NHS) setting. Methods: Single-centre clinical trial with prospective data collection for patients undergoing 8-weekly PIPAC with oxaliplatin at 92 mg/m2 from January 2019 till January 2022. Progression free survival was assessed using peritoneal carcinomatosis index (PCI) by CT scans and laparoscopy. Quality of life was assessed by EORTC QLQ-C30 questionnaire. Adverse events were recorded using CTCAE. Results: Five patients underwent a total of ten PIPAC administrations (median 2, range 1-4). Median PFS was 6.0 months. QoL was maintained across repeat PIPAC procedures but a decrease in social functioning and increased fatigue were evident. Three incidences of grade 3 adverse events occurred but PIPAC was well tolerated. Conclusions: The presented data demonstrates that PIPAC is feasible and can be safely delivered within the NHS for patients with colorectal cancer peritoneal metastases, but caution must also be exercised given a risk of adverse events. Systemic chemotherapy can be safely administered at a different unit to the PIPAC procedure if both groups have clear lines of communication and timely data sharing.

The ex vivo pharmacology of HIV-1 antiretrovirals differs between macaques and humans.

Non-human primates (NHP) are widely used for the pre-clinical assessment of antiretrovirals (ARVs) for HIV treatment and prevention. However, the utility of these models is questionable given the differences in ARV pharmacology between humans and macaques. Here, we report a model based on ex vivo ARV exposure and the challenge of mucosal tissue explants to define pharmacological differences between NHPs and humans. For colorectal and cervicovaginal explants in both species, high concentrations of tenofovir (TFV) and maraviroc were predictive of anti-viral efficacy. However, their combinations resulted in increased inhibitory potency in NHP when compared to human explants. In NHPs, higher TFV concentrations were measured in colorectal versus cervicovaginal explants (p = 0.042). In humans, this relationship was inverted with lower levels in colorectal tissue (p = 0.027). TFV-resistance caused greater loss of viral fitness for HIV-1 than SIV. This, tissue explants provide an important bridge to refine and appropriately interpret NHP studies.

Deliberate practice on a virtual reality laparoscopic simulator enhances the quality of surgical technical skills.

INTRODUCTION: Virtual reality (VR) simulation provides unique training opportunities. This study evaluates whether the deliberate practice (DP) can be successfully applied to simulated laparoscopic cholecystectomy (LC) for enhancement of the quality of surgical skills. METHODS: Twenty-six inexperienced surgeons underwent a training program for LC on a VR simulator. Trainees were randomly allocated to 1 of 2 specific protocols of 10 sessions comprising a total of 20 LCs. For each session, the control group performed 2 LCs separated by 30 minutes of occupational activities; the DP group were assigned 30 minutes of DP activities in between 2 LCs. Each participant then performed 2 LCs on a cadaveric porcine model. Quantitative parameters were recorded from the simulator and a motion tracking device; qualitative assessment utilized validated rating scales. RESULTS: Twenty-two subjects completed training. Learning curves on the VR simulator were significant for time taken and number of movements in both groups. The DP group was slower from the third LC (1373 vs. 872 seconds, P = 0.022) and utilized more movements from the seventh (942 vs. 701, P = 0.033). Global rating scores improved significantly in both groups over repeated LCs. The DP group revealed higher scores than control from tenth (19.5 vs. 14, P = 0.014) until the twentieth LC (22 vs. 16, P = 0.003). On the porcine model, the DP group also achieved higher global rating scores (25.5 vs. 19.5, P = 0.002). CONCLUSIONS: VR training improved dexterity for both groups, and led to transfer of skill onto a porcine LC model. The DP group achieved higher quality, and demonstrated superior transfer onto real tissues.

Open surgery simulation of inguinal hernia repair.

Inguinal hernia repair procedures are often one of the first surgical procedures faced by junior surgeons. The biggest challenge in this procedure for novice trainees is understanding the 3D spatial relations of the complex anatomy of the inguinal region, which is crucial for the effective and careful handling of the present anatomical structures in order to perform a successful and lasting repair. Such relationships are difficult to illustrate and comprehend through standard learning material. This paper presents our work in progress to develop a simulation-based teaching tool allowing junior surgeons to train the Lichtenstein tension-free open inguinal hernia repair technique for direct and indirect hernias, as well as to enforce their understanding of the spatial relations of the involved anatomy.

The entry inhibitor DS003 (BMS-599793): a BMS-806 analogue, provides superior activity as a pre-exposure prophylaxis candidate.

OBJECTIVE: Small molecule inhibitors able to bind to gp120 and prevent CD4+-induced HIV-1 envelope conformational change provide an important class of inhibitors. Currently, only Fostemsavir is approved for HAART, which makes this class of inhibitors attractive candidates for prevention. We assessed the activity of DS003 (BMS-599793), an analogue of BMS-378806, in different mucosal tissues and elucidated its mechanism of action. DESIGN: Preclinical analysis was performed with human mucosal tissue models as surrogates of in-vivo activity. METHODS: Antiviral efficacy of DS003 was assessed in mucosal tissue explants (ecto-cervical, penile and colorectal) and in trans-infection models (co-cultures of dendritic or mucosal migratory cells with CD4+ T cells) with several dosing times (2, 24 h and sustained) and in combination with a fusion inhibitor. Binding of DS003 to gp120 was assessed by flow cytometry and bio-layer interferometry and further probed in competitive studies using soluble CD4+ (sCD4+) and an anti-CD4+ induced antibody, 17b. RESULTS: In all models, the inhibitory activity of DS003 was increased with longer periods of exposure and by combination with a fusion inhibitor. Pre-exposure to sCD4+ impeded DS003 binding to viral envelope. In contrast, DS003 did not impact subsequent binding of sCD4+. Furthermore, sCD4+-induced epitope exposure as assessed by 17b binding was significantly reduced in the presence of DS003. CONCLUSION: DS003 inhibits HIV-1 infection by binding to or near the CD4+ binding site of gp120, preventing CD4+-induced conformational change essential for viral fusion. These data highlight the potential of DS003 for development as a pre-exposure prophylaxis candidate.