Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Formulation and evaluation of simvastatin polymeric nanoparticles loaded in hydrogel for optimum wound healing purpose

Usama Farghaly Aly,1 Heba A Abou-Taleb,2 Ahmed AH Abdellatif,3,4 Nahla Sameh Tolba21Department of Pharmaceutics, Faculty of Pharmacy, Minia University, EL-Minia, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Nahda University (NUB), Beni-Suef, Egypt; 3Department of Pharmaceutics, College of Pharmacy, Qassim University, Al Qassim, Kingdom of Saudi Arabia; 4Department of Pharmaceutics and Industrial Pharmacy, Al-Azhar University, Assiut, Egypt Purpose: The aim of this study was to formulate a hydrogel loaded with polymeric nanoparticles (PoNPs) of simvastatin (SIM) for topical wound healing application. Materials and methods: The SIM PoNPs were prepared by using the nanoprecipitation method to improve the drug solubility and skin permeation. Furthermore, drug content, solubility, particle size, surface charge, and transmission electron microscopy of the prepared PoNPs were evaluated. Then, the PoNPs were loaded on hydrogel, and physical characteristics, in vitro release, and ex vivo permeation of the hydrogel were evaluated. Finally, the prepared gel was applied on rat wounds, and a histopathological study was performed. Results: The results showed that the drug content in the PoNPs was 86.4%. The PoNPs were spherical in shape with a smooth surface and a uniform size distribution. The particle size was 268.4&plusmn;2.6, polydispersity index was &le;0.302, and zeta potential was -33&plusmn;1.67&nbsp;mV. The hydrogel loaded with SIM PoNPs was homogenous, and the pH was accepted and compatible with the skin. Moreover, the viscosity and spreadability assured its ease of application. The drug content was 97.25&plusmn;0.02%. Furthermore, about 81% of SIM was released within 24&nbsp;hours, while in the ex vivo permeation study 69.19% of SIM passed through the skin after 24&nbsp;hours. Finally, the histopathological studies confirmed the efficacy of the SIM PoNPs-loaded hydrogel in wound healing due to the formation of the normal epithelial layer on day 11 after wound creation.Conclusion: The hydrogel loaded with SIM PoNPs showed a good efficacy in accelerating the healing of the rat wound with complete epithelialization and minimal inflammatory cell infiltration. Keywords: simvastatin,&nbsp;Carbopol&reg; gel, ex vivo permeation, nanoprecipitaion method, wound healin

The Effect of Various Sparsity Structures on Parallelism and Algorithms to Reveal Those Structures

Structured sparse matrices can greatly benefit parallel numerical methods in terms of parallel performance and convergence. In this chapter, we present combinatorial models for obtaining several different sparse matrix forms. There are four basic forms we focus on: singly-bordered block-diagonal form, doubly-bordered block-diagonal form, nonempty off-diagonal block minimization, and block diagonal with overlap form. For each of these forms, we first present the form in detail and describe what goals are sought within the form, and then examine the combinatorial models that attain the respective form while targeting the sought goals, and finally explain in which aspects the forms benefit certain parallel numerical methods and their relationship with the models. Our work focuses especially on graph and hypergraph partitioning models in obtaining the mentioned forms. Despite their relatively high preprocessing overhead compared to other heuristics, they have proven to model the given problem more accurately and this overhead can be often amortized due the fact that matrix structure does not change much during a typical numerical simulation. This chapter presents a number of models and their relationship with parallel numerical methods