Impelling Factors for Contracting COVID-19 Among Surgical Professionals During the Pandemic: A Multinational Cohort Study.

Background: Medical workers, including surgical professionals working in coronavirus disease 2019 (COVID-19) treating hospitals, were under enormous stress during the pandemic. This global study investigated factors endowing COVID-19 amongst surgical professionals and students. Methods: This global cross-sectional survey was made live on February 18, 2021 and closed for analysis on March 13, 2021. It was freely shared on social and scientific media platforms and was sent via email groups and circulated through a personal network of authors. Chi-square test for independence, and binary logistic regression analysis were carried out on determining predictors of surgical professionals contracting COVID-19. Results: This survey captured the response of 520 surgical professionals from 66 countries. Of the professionals, 92.5% (481/520) reported practising in hospitals managing COVID-19 patients. More than one-fourth (25.6%) of the respondents (133/520) reported suffering from COVID-19 which was more frequent in surgical professionals practising in public sector healthcare institutions (P = 0.001). Thirty-seven percent of those who reported never contracting COVID-19 (139/376) reported being still asked to practice self-isolation and wear a shield without the diagnosis (P = 0.001). Of those who did not contract COVID-19, 75.7% (283/376) were vaccinated (P < 0.001). Surgical professionals undergoing practice in the private sector (odds ratio (OR): 0.33; 95% confidence interval (CI): 0.14 - 0.77; P = 0.011) and receiving two doses of vaccine (OR: 0.55; 95% CI: 0.32 - 0.95; P = 0.031) were identified to enjoy decreased odds of contracting COVID-19. Only 6.9% of those who reported not contracting COVID-19 (26/376) were calculated to have the highest "overall composite level of harm" score (P < 0.001). Conclusions: High prevalence of respondents got COVID-19, which was more frequent in participants working in public sector hospitals. Those who reported contracting COVID-19 were calculated to have the highest level of harm score. Self-isolation or shield, getting two doses of vaccines decreases the odds of contracting COVID-19.

Assessment and management after corrosive ingestion: when is specialist centre referral needed? A 10-year UK experience.

BACKGROUND: Corrosive ingestion injuries are rare but clinically significant events, potentially associated with high morbidity and mortality. The low volume of cases limits guideline development. We report a 10-year experience of our tertiary centre focusing on cases requiring specialist care. METHODS: All adults treated following corrosive ingestion between 2010 and 2020 were included. Blood results, imaging and endoscopic findings were reviewed. Patients were stratified based on endoscopic findings. Emergency and delayed management was analysed along with short and long-term outcomes. Predictive value of early outcome indicators was investigated. RESULTS: Eighty-one patients were included, with an average follow-up of 5 years. Patients with injuries ≤ Zargar 2A (n = 15) had long-term outcomes similar to the ones with negative endoscopic findings (n = 51). All fifteen patients suffering injuries Zargar ≥ 2B required ITU and four died (26.6%). All deaths occurred within 50 days of ingestion, had Zargar grade ≥ 3 and airway involvement. Five patients (33%) required emergency operations, two of which died. All Zargar ≥ 2B injury survivors (n = 11) developed strictures and/or tracheo-esophageal fistulae (18%), required multiple admissions and prolonged nutritional support; five required delayed resections. Zargar grade ≥ 2B, airway damage, and increased CRP on admission correlated with unfavourable outcomes. CONCLUSION: Corrosive ingestion injuries up to Zargar 2A do not cause long-term sequelae and can be managed locally. Injuries > 2B bear high mortality and will cause sequelae. Early identification of severe injuries and transfer to specialist centres with multidisciplinary ITU, OG, thoracic and ENT expertise is recommended.

The global level of harm among surgical professionals during the COVID-19 pandemic: A multinational cross-sectional cohort study.

BACKGROUND: Health care workers, including surgical professionals, experienced psychological burnout and physical harm during the coronavirus 2019 pandemic. This global survey investigated the coronavirus 2019 pandemic impact on psychological and physical health. METHODS: We conducted a global cross-sectional survey between February 18, 2021 and March 13, 2021. The primary outcome was to assess the psychological burnout, fulfillment, and self-reported physical level of harm. A validated Stanford Professional Fulfilment Index score with a self-reported physical level of harm was employed. We used a practical overall composite level of harm score to calculate the level of harm gradient 1-4, combining psychological burnout with self-reported physical level of harm score. RESULTS: A total of 545 participants from 66 countries participated. The final analysis included 520 (95.4%) surgical professionals barring medical students. Most of the participants (81.3%) were professionally unfulfilled. The psychological burnout was evident in 57.7% and was significantly common in those <50 years (P = .002) and those working in the public sector (P = .005). Approximately 41.7% of respondents showed changes in the physical health with self-remedy and no impact on work, whereas 14.9% reported changes to their physical health with <2 weeks off work, and 10.1% reported changes in physical health requiring >2 weeks off work. Severe harm (level of harm 4) was detected in 10.6%, whereas moderate harm (level of harm 3) affected 40.2% of the participants. Low and no harm (level of harm 2 and level of harm 1) represented 27.5% and 21.7%, respectively. CONCLUSION: Our study showed that high levels of psychological burnout, professional unfulfillment, work exhaustion, and severe level of harm was more frequent in younger professionals working in the public sector. The findings correlated with a high level of harm in surgical professionals impacting surgical services.

Near-Infrared Fluorescence Cholangiography can be a Useful Adjunct during Emergency Cholecystectomies.

Background. Emergency cholecystectomy is the gold standard treatment for acute cholecystitis according to National Institute for Health and Care Excellence recommendations. The procedure is feasible but carries a higher risk of iatrogenic injury to the bile duct, which should be considered preventable. Intraoperative fluorescence cholangiography following injection of indocyanine green (ICG) has been reported to aid identification of the extrahepatic bile duct. Data on its feasibility in the context of emergency cholecystectomies are missing. Materials and Methods. Fluorescent ICG was used intraoperatively to enhance the biliary anatomy during 33 consecutive emergency laparoscopic cholecystectomies at our institution. Primary outcomes of surgery were considered the length of hospital stay, conversion to open and complications rate, including bile duct injury. Secondary outcome was operating time. A historical population of emergency cholecystectomies was used as control. Results. There were no common bile duct injuries, no adverse effects from ICG, no conversion to open surgery and no deaths. 90% of patients went home within 48 hours after the operation in the absence of complications. ICG demonstrated intraoperative biliary anatomy allowing greater confidence to the surgeon performing emergency cholecystectomies. Six patients were operated beyond 72 hours from admission, without experiencing any complication Clavien-Dindo ≥3. ICG population had the same post-operative hospitalisation and complications rate of the control group, with a shorter operating time. Conclusion. Intraoperative augmented visualisation of biliary anatomy with ICG cholangiography can be a useful technology tool, with the potential to extend the 72 hours window of safety for emergency cholecystectomies.

A rare case of heterotopic pancreatitis and intestinal malrotation in a COVID-19 positive patient. COVID-19, causative or coincidence?

INTRODUCTION AND IMPORTANCE: Heterotopic pancreas (HP) is defined as the presence of pancreatic tissue without anatomical and vascular continuity with the main body of the pancreas. HP typically remains asymptomatic, however complications such as acute pancreatitis can arise. Gastrointestinal involvement with coronavirus disease 2019 (COVID-19) is not uncommon and there are reported cases of associated pancreatitis. CASE PRESENTATION: A 31-year-old male presented to the Emergency department (ED) with a 3-day history of right iliac fossa pain. The patient was found to have COVID-19 and a planned laparoscopic appendectomy was later converted to a midline laparotomy when a mass close to the duodeno-jejunal (DJ) flexure was identified. Following a hand-sewn anastomosis the patient made a good post-operative recovery. Histology illustrated the presence of heterotopic pancreatic tissue within the small bowel with underlying fat necrosis typical of acute pancreatitis. Follow-up radiology supported the intraoperative finding of intestinal malrotation. CLINICAL DISCUSSION: Rarely the combined presence of intestinal malrotation and HP in patients has been noted. Heterotopic pancreatitis can present in a multitude of ways and it is a difficult diagnosis to make pre-operatively. Emerging literature documents the potential presentation of COVID-19 with acute pancreatitis. The expression of angiotensin-converting enzyme 2 (ACE2) receptors on the pancreas is believed to play a role. CONCLUSION: This is the first documented case of heterotopic pancreatitis with intestinal malrotation in a COVID-19 positive patient. We hypothesise that the COVID-19 infection contributed to the heterotopic pancreatitis.

Minimally invasive total adventitial resection of the cardia for tumours of the oesophagogastric junction.

PURPOSE: A cohort study analysing phases and outcomes of the learning curve required to master minimally invasive total adventitial resection of the cardia. METHODS: Data from 198 consecutive oesophagectomies performed by a single surgeon was collected prospectively. Patients' stratification reflected chronologically and technically the four main phases of the learning curve: open surgery (open total adventitial resection of the cardia (TARC), n = 45), hybrid Ivor Lewis oesophagectomy (HILO, n = 50), laparoscopic-thoracoscopic assisted (LTA, n = 56) and totally minimally invasive TARC (TMI TARC, n = 47). Operating time, hospital stay, specimen lymph nodes and resection margins were analysed. Five-year survival was the main long-term outcome measured. RESULTS: Overall 5-year survival was 45%. Perioperative mortality was 1.5% (n = 3). Hospital stay was 22 ± 23 days. Specimen lymph node median was 20 (range: 15-26). Resection margins were negative (R = 0, American College of Pathologists) in 193 cases (97.4%). Five-year survival in the four phases was 37.8%, 44.9%, 42.9% and 55.3%, showing a positive trend towards the end of the learning curve (p = 0.024). Median specimen lymph nodes was 20 (range: 15-22) for open TARC, 18.5 (13-25) for HILO, 19.5 (15-25) for LTA and 23 (18-30) for TMI TARC (p = 0.006). TMI TARC, adenocarcinoma, R >0, T >2, N >0 and LyRa (ratio positive/total specimen nodes) were associated with survival on univariate analysis. T >2 and LyRa independently predicted worse survival on multivariate analysis. CUSUM analysis showed surgical proficiency gain since laparoscopy was introduced. CONCLUSION: Mastering minimally invasive TARC requires a long learning curve. TMI TARC is safe and oncologically appropriate and may benefit long-term survival: it should be validated by randomised trials as a standardised anatomical resection for tumours of the oesophagogastric junction.

Desmoplasia and Biophysics in Pancreatic Ductal Adenocarcinoma: Can We Learn From Breast Cancer?

Pancreatic ductal adenocarcinoma (PDAC) treatments have historically focused on targeting tumor cells directly. However, in pancreatic masses, the stroma encasing the malignant epithelial cells constitutes up to 80% to 90% of the tumor bulk. This extracellular matrix, which was previously neglected when designing cancer therapies, is now considered fundamental for tumor progression and drug delivery. Desmoplastic tissue is extensively cross-linked, resulting in tremendous tensile strength. This key pathological feature is procarcinogenic, linking PDAC and breast cancer (BC). Physical forces exerted onto cellular surfaces are detected intracellularly and transduced via biochemical messengers in a process called mechanotransduction. Mechanotransduction and tensional homeostasis are linked, with an integral role in influencing tumor growth, metastasis, and interactions with the immune system. It is essential to enhance our knowledge of these integral elements of parenchymal tumors. We aim to review the topic, with a special emphasis on desmoplastic processes and their importance in pancreatic and BC development and treatments, mindful that innovative diagnostic and therapeutic strategies cannot focus on biochemical pathways alone. We then focus on common therapeutic targets identified in both PDAC and BC models and/or patients, aiming to understand these treatments and draw similarities between the two tumors.

Functionalised thermally induced phase separation (TIPS) microparticles enabled for "click" chemistry.

Due to their homogeneity, tuneable properties, low cost and ease of manufacture, thermally induced phase separation (TIPS) polymeric microparticles are emerging as an exciting class of injectable device for the treatment of damaged tissue or complex diseases, such as cancer. However, relatively little work has explored enhancing surface functionalisation of this system. Herein, we present the functionalisation of TIPS microparticles with both small molecules and an antibody fragment of Herceptin™, via a heterobifunctional pyridazinedione linker capable of participating in SPAAC "click" chemistry, and compare it to the traditional method of preparing active-targeted microparticle systems, that is, physisorption of antibodies to the microparticle surface. Antigen-binding assays demonstrated that functionalisation of microparticles with Herceptin Fab, via a pyridazinedione linker, provided an enhanced avidity to HER2+ when compared to traditional physisorption methods.

A novel adjuvant drug-device combination tissue scaffold for radical prostatectomy.

Prostate cancer is a leading cause of death in men and despite improved surgical procedures that aid tumor resection, the risk of recurrence after surgery as a result of positive resection margins remains significant. Adjuvant chemotherapy is often required but this is associated with toxicity. Improved ways of delivering highly toxic chemotherapeutic drugs in a more controlled and targeted manner after the prostate has been removed during surgery could reduce the risk of recurrence and avoid systemic toxicity. The aim of this study was to develop a novel drug-device combination tissue scaffold that can be used to deliver the chemotherapeutic agent, docetaxel, into the tissue cavity that is created following radical prostatectomy. The device component investigated consisted of highly porous, poly(dl-lactide-co-glycolide) microparticles made using thermally induced phase separation. A facile method was established for loading docetaxel with high efficiency within one hour. Sustained drug release was observed from the microparticles when placed into a dynamic system simulating tissue perfusion. The drug released from the microparticles into perfusates collected at regular time intervals inhibited colony formation and exhibited sustained cytotoxicity against 3D spheroids of PC3 prostate cancer cells over 10 days. In conclusion, this study demonstrates the concept of combining docetaxel with the biodegradable microparticles at the point of care is technically feasible for achieving an effective drug-device combination tissue scaffold. This approach could provide an effective new approach for delivering adjuvant chemotherapy following radical prostatectomy.

Oesophageal adenocarcinoma following gastric band surgery in two patients.

Oesophageal adenocarcinoma following gastric band surgery has only been reported three times previously. The incidence is higher in morbidly obese patients, and its pathogenesis is correlated to reflux-induced microenvironmental changes. Bariatric surgery is transformative and its potential benefit for a substantial population is huge. Although no causal relationship with bariatric procedures has been evidenced to date, symptoms of adenocarcinoma-particularly anorexia, weight loss and dysphagia-can easily be overshadowed by alterations in eating patterns associated with weight-loss procedures. We report two cases of oesophageal adenocarcinoma in patients who had undergone a gastric banding procedure, and invite readers to consider the role that pre- and post-operative acid reflux dynamics may have precipitating neoplastic disease, and how endoscopic surveillance may play a role in prevention.

Uterocutaneous fistula due to held placenta in a low resource setting.

Postcesarean section complication rate is higher in LMIC (Low and Middle Income Countries) due to lack of resources and specialists availability. A completely or incompletely held infected placenta might underlie a dehiscent cesarean section wound. Humanitarian and local surgeons should consider this differential diagnosis and be ready to practice hysterectomies when needed.

Surgical consent in sub-Saharan Africa: a modern challenge for the humanitarian surgeon.

Surgical consent is one of the pillars of ethical conduct in Western world surgical practice. Recent studies have described the consenting processes for clinical trials in low- and middle-income countries (LMICs), but only a few have explored its practice before surgical procedures. The recent World Medical Association (WMA) Declaration of Lisbon recommends autonomy and independent decision-making. However, informed consent is influenced by cultural background, family structure, socioeconomic status, religion and education. The authors of the paper support the WMA recommendations, but agree the process for obtaining informed consent should be reviewed and developed to integrate in a culturally appropriate manner. This commentary reports the author's personal experience of surgical consent in Burundi and reviews the literature describing its practice and the specific challenges faced in Sub-Saharan Africa. Its aim is to encourage a debate among surgeons as to how surgical consent can be undertaken in different scenarios of LMICs.

The Effect of Film Thickness on the Gas Sensing Properties of Ultra-Thin TiO2 Films Deposited by Atomic Layer Deposition.

Analyte sensitivity for gas sensors based on semiconducting metal oxides should be highly dependent on the film thickness, particularly when that thickness is on the order of the Debye length. This thickness dependence has previously been demonstrated for SnO2 and inferred for TiO2. In this paper, TiO2 thin films have been prepared by Atomic Layer Deposition (ALD) using titanium isopropoxide and water as precursors. The deposition process was performed on standard alumina gas sensor platforms and microscope slides (for analysis purposes), at a temperature of 200 °C. The TiO2 films were exposed to different concentrations of CO, CH4, NO2, NH3 and SO2 to evaluate their gas sensitivities. These experiments showed that the TiO2 film thickness played a dominant role within the conduction mechanism and the pattern of response for the electrical resistance towards CH4 and NH3 exposure indicated typical n-type semiconducting behavior. The effect of relative humidity on the gas sensitivity has also been demonstrated.

Double-Wall Nanotubes and Graphene Nanoplatelets for Hybrid Conductive Adhesives with Enhanced Thermal and Electrical Conductivity.

Improving the electrical and thermal properties of conductive adhesives is essential for the fabrication of compact microelectronic and optoelectronic power devices. Here we report on the addition of a commercially available conductive resin with double-wall carbon nanotubes and graphene nanoplatelets that yields simultaneously improved thermal and electrical conductivity. Using isopropanol as a common solvent for the debundling of nanotubes, exfoliation of graphene, and dispersion of the carbon nanostructures in the epoxy resin, we obtain a nanostructured conducting adhesive with thermal conductivity of ∼12 W/mK and resistivity down to 30 µΩ cm at very small loadings (1% w/w for nanotubes and 0.01% w/w for graphene). The low filler content allows one to keep almost unchanged the glass-transition temperature, the viscosity, and the curing parameters. Die shear measurements show that the nanostructured resins fulfill the MIL-STD-883 requirements when bonding gold-metalized SMD components, even after repeated thermal cycling. The same procedure has been validated on a high-conductivity resin characterized by a higher viscosity, on which we have doubled the thermal conductivity and quadrupled the electrical conductivity. Graphene yields better performances with respect to nanotubes in terms of conductivity and filler quantity needed to improve the resin. We have finally applied the nanostructured resins to bond GaN-based high-electron-mobility transistors in power-amplifier circuits. We observe a decrease of the GaN peak and average temperatures of, respectively, ∼30 °C and ∼10 °C, with respect to the pristine resin. The obtained results are important for the fabrication of advanced packaging materials in power electronic and microwave applications and fit the technological roadmap for CNTs, graphene, and hybrid systems.

Pancreatic stellate cells regulate blood vessel density in the stroma of pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVES: The vascular heterogeneity of pancreatic ductal adenocarcinoma (PDAC) has never been characterised. We analysed the heterogeneous vascular density of human PDAC along with its prognostic correlation. METHODS: Tissue Microarrays of 87 patients with different pancreatico-biliary pathologies were analysed in an automated manner (Ariol™) after CD31 staining to assess vascular density in juxta-tumoral and panstromal compartments. In vitro and ex vivo assays were carried out to assess the role of PSC. RESULTS: PDAC has a distinct vascular density and distribution of vessels compared to cholangiocarcinoma. The PDAC juxta-tumoral stroma was hypovascular and the normal adjacent rim was hypervascular compared to the panstromal compartment. These features adversely affected patient prognosis, suggesting a model for spatio-temporal PDAC evolution. Mice aortic rings and 3D organotypic cultures demonstrated pro- and anti-angiogenic signalling from activated PSC and cancer cells respectively. ATRA-induced quiescence suppressed the pro-angiogenic activity of PSC. CONCLUSION: Human PDAC has variable vascularity at microscopic level suggesting that novel stromal directed therapies would need to be determined by pathological characteristics.

Imbalance of desmoplastic stromal cell numbers drives aggressive cancer processes.

Epithelial tissues have sparse stroma, in contrast to their corresponding tumours. The effect of cancer cells on stromal cells is well recognized. Increasingly, stromal components, such as endothelial and immune cells, are considered indispensable for cancer progression. The role of desmoplastic stroma, in contrast, is poorly understood. Targeting such cellular components within the tumour is attractive. Recent evidence strongly points towards a dynamic stromal cell participation in cancer progression that impacts patient prognosis. The role of specific desmoplastic stromal cells, such as stellate cells and myofibroblasts in pancreatic, oesophageal and skin cancers, was studied in bio-engineered, physiomimetic organotypic cultures and by regression analysis. For pancreatic cancer, the maximal effect on increasing cancer cell proliferation and invasion, as well as decreasing cancer cell apoptosis, occurs when stromal (pancreatic stellate cells) cells constitute the majority of the cellular population (maximal effect at a stromal cell proportion of 0.66-0.83), accompanied by change in expression of key molecules such as E-cadherin and ß-catenin. Gene-expression microarrays, across three tumour types, indicate that stromal cells consistently and significantly alter global cancer cell functions such as cell cycle, cell-cell signalling, cell movement, cell death and inflammatory response. However, these changes are mediated through cancer type-specific alteration of expression, with very few common targets across tumour types. As highlighted by these in vitro data, the reciprocal relationship of E-cadherin and polymeric immunoglobulin receptor (PIGR) expression in cancer cells could be shown, in vivo, to be dependent on the stromal content of human pancreatic cancer. These studies demonstrate that context-specific cancer-stroma crosstalk requires to be precisely defined for effective therapeutic targeting. These data may be relevant to non-malignant processes where epithelial cells interact with stromal cells, such as chronic inflammatory and fibrotic conditions.

ρ-Kinase inhibition reduces early microvascular leukocyte accumulation in the rat kidney following ischemia-reperfusion injury: roles of nitric oxide and blood flow.

AIM: To study whether microvascular leukocyte accumulation after rat renal ischemia and reperfusion (IR) is decreased by Rho kinase inhibition, independently of effects upon nitric oxide (NO) and renal blood flow. METHODS: Male Wistar rats were subjected to 60 min of ischemia by bilateral clamping and 60 min of reperfusion of the renal arteries, or a sham procedure. Haemodynamics were monitored and microsphere blood flow to the kidneys was measured. The infusion of the Rho kinase inhibitor (Y27632) was commenced before clamping and IR. The NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), was administered after the start of reperfusion whilst the dopamine-1 receptor agonist fenoldopam, a renal vasodilator, was infused during the reperfusion period. Digital imaging microscopy analysis of cryosections was done to determine leukocyte accumulation and vasodilator-stimulated phosphoprotein serine 239 phosphorylation (p-VASP ser 239), a marker of endothelial NO. RESULTS: Leukocytes (60-70% neutrophils) accumulated within blood vessels in the corticomedullary junction and medulla of the kidney. Leukocyte accumulation was markedly reduced by the Rho kinase inhibitor but not by fenoldopam. However, both drugs improved renal blood flow and microvascular expression of p-VASP ser 239 in the corticomedullary junction and medulla, which were decreased following IR. L-NAME treatment of IR animals pretreated with the Rho kinase inhibitor reduced blood flow and p-VASP ser 239 expression and increased leukocyte accumulation. CONCLUSION: Early microvascular leukocyte accumulation in the corticomedullary junction and medulla of the rat kidney after IR is ameliorated by Rho kinase inhibition. This effect is partly independent upon attenuation of decreased NO and renal blood flow.

Biomarkers of acute renal injury and renal failure.

Acute renal failure (ARF) is a frequent problem in the intensive care unit and is associated with a high mortality. Early recognition could help clinical management, but current indices lack sufficient predictive value for ARF. Therefore, there might be a need for biomarkers in detecting renal tubular injury and/or dysfunction at an early stage before a decline in glomerular filtration rate is noted by an increased serum creatinine. A MEDLINE/PubMed search was performed, including all articles about biomarkers for ARF. All publication types, human and animal studies, or subsets were searched in English language. An extraction of relevant articles was made for the purpose of this narrative review. These biomarkers include tubular enzymes (alpha- and pi-glutathione S-transferase, N-acetyl-glucosaminidase, alkaline phosphatase, gamma-glutamyl transpeptidase, Ala-(Leu-Gly)-aminopeptidase, and fructose-1,6-biphosphatase), low-molecular weight urinary proteins (alpha1- and beta2-microglobulin, retinol-binding protein, adenosine deaminase-binding protein, and cystatin C), Na+/H+ exchanger, neutrophil gelatinase-associated lipocalin, cysteine-rich protein 61, kidney injury molecule 1, urinary interleukins/adhesion molecules, and markers of glomerular filtration such as proatrial natriuretic peptide (1-98) and cystatin C. These biomarkers, detected in urine or serum shortly after tubular injury, have been suggested to contribute to prediction of ARF and need for renal replacement therapy. However, excretion of these biomarkers may also increase after reversible and mild dysfunction and may not necessarily be associated with persistent or irreversible damage. Large prospective studies in human are needed to demonstrate an improved outcome of biomarker-driven management of the patient at risk for ARF.