Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past

© 2020 Elsevier B.V. Coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus strain disease, has recently emerged in China and rapidly spread worldwide. This novel strain is highly transmittable and severe disease has been reported in up to 16% of hospitalized cases. More than 600,000 cases have been confirmed and the number of deaths is constantly increasing. COVID-19 hospitalized patients, especially those suffering from severe respiratory or systemic manifestations, fall under the spectrum of the acutely ill medical population, which is at increased venous thromboembolism risk. Thrombotic complications seem to emerge as an important issue in patients infected with COVID-19. Preliminary reports on COVID-19 patients’ clinical and laboratory findings include thrombocytopenia, elevated D-dimer, prolonged prothrombin time, and disseminated intravascular coagulation. As the pandemic is spreading and the whole picture is yet unknown, we highlight the importance of coagulation disorders in COVID-19 infected patients and review relevant data of previous coronavirus epidemics caused by the severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the Middle East Respiratory Syndrome coronavirus (MERS-CoV)

Challenges in Abdominal Organ Transplantation During the COVID-19 Pandemic

© Copyright © 2020 Esagian, Ziogas, Giannis, Hayat, Elias and Tsoulfas. As the coronavirus disease 2019 (COVID-19) outbreak has rapidly evolved into a global pandemic, abdominal organ transplantation programs are currently facing multiple challenges. Transplant candidates and recipients are considered high-risk populations for severe disease and death due to COVID-19 as a result of their numerous underlying comorbidities, advanced age and impaired immune function. Emerging reports of atypical and delayed clinical presentations in these patients generate further concerns for widespread disease transmission to medical personnel and the community. The striking similarities between COVID-19 and other outbreaks that took place over the past two decades, like Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome, highlight the severity of the situation and dictate that extra measures should be taken by the transplant programs to avoid adverse outcomes. Transplant organizations are currently calling for strict screening and isolation protocols to be established in all transplant programs, for both organ donors and recipients. As the situation escalates, more radical measures might be necessary, including a temporary hold on non-urgent transplantations, resulting in serious ethical dilemmas between the survival of these patients and the safety of the community. Further data about these special populations could result in more individualized guidelines for abdominal organ transplantation in the era of COVID-19

Surgical Outcomes in Syndromic Tetralogy of Fallot: A Systematic Review and Evidence Quality Assessment

Tetralogy of Fallot (ToF) is one of the most common cyanotic congenital heart defects. We sought to summarize all available data regarding the epidemiology and perioperative outcomes of syndromic ToF patients. A PRISMA-compliant systematic literature review of PubMed and Cochrane Library was performed. Twelve original studies were included. The incidence of syndromic ToF was 15.3% (n = 549/3597). The most prevalent genetic syndromes were 22q11.2 deletion (47.8%; 95% CI 43.4–52.2) and trisomy 21 (41.9%; 95% CI 37.7–46.3). Complete surgical repair was performed in 75.2% of the patients (n = 161/214; 95% CI 69.0–80.1) and staged repair in 24.8% (n = 53/214; 95 CI 19.4–30.9). Relief of RVOT obstruction was performed with transannular patch in 64.7% (n = 79/122; 95% CI 55.9–72.7) of the patients, pulmonary valve-sparing technique in 17.2% (n = 21/122; 95% CI 11.5–24.9), and RV-PA conduit in 18.0% (n = 22/122; 95% CI 12.1–25.9). Pleural effusions were the most common postoperative complications (n = 28/549; 5.1%; 95% CI 3.5–7.3). Reoperations were performed in 4.4% (n = 24/549; 95% CI 2.9–6.4) of the patients. All-cause mortality rate was 9.8% (n = 51/521; 95% CI 7.5–12.7). Genetic syndromes are seen in approximately 15% of ToF patients. Long-term survival exceeds 90%, suggesting that surgical management should be dictated by anatomy regardless of genetics

National study of colorectal cancer genetics

Approximately, a third of all colorectal cancer (CRC) is due to inherited susceptibility. However, high-risk mutations in APC, the mismatch repair (MMR) genes, MUTYH/MYH, SMAD4, ALK3 and STK11/LKB1 are rare and account for <5% of cases. Much of the remaining variation in genetic risk is likely to be explained by combinations of more common gene variants that modestly increase risk. Reliable identification of such ‘low penetrance' alleles would provide insight into the aetiology of CRC and might highlight potential therapeutic and preventative interventions. In 2003, the National Study of Colorectal Cancer Genetics (NSCCG) was established with the aim of collecting DNA and clinicopathological data from 20 000 CRC cases and a series of spouse/partner controls, thereby creating a unique resource for identifying low-penetrance CRC susceptibility alleles. The National Cancer Research Network (NCRN) adopted NSCCG onto its portfolio of trials and 148 centres in the United Kingdom (UK) are now actively participating. Over 8700 cases and 2185 controls have so far been entered into NSCCG. Our experience in developing NSCCG serves to illustrate how world-class DNA databases for genetic analyses can be rapidly developed in the United Kingdom

Diagnostic value of anti-cyclic citrullinated peptide antibodies in Greek patients with rheumatoid arthritis

Background: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been of diagnostic value in Northern European Caucasian patients with rheumatoid arthritis ( RA). In these populations, anti-CCP antibodies are associated with the HLA-DRB1 shared epitope. We assessed the diagnostic value of anti-CCP antibodies in Greek patients with RA where the HLA shared epitope was reported in a minority of patients. Methods: Using an enzyme-linked immunosorbent assay ( ELISA) (CCP2) kit, we tested anti-CCP antibodies in serum samples from 155 Greek patients with RA, 178 patients with other rheumatic diseases, and 100 blood donors. We also determined rheumatoid factor (RF) and compared it to anti-CCP antibodies for area under the curve (AUC), sensitivity, specificity and likelihood ratios. Results: Sensitivity of anti-CCP2 antibodies and RF for RA was 63.2% and 59.1%, and specificity was 95.0% and 91.2%, respectively. When considered simultaneously, the AUC for anti-CCP antibodies was 0.90 with 95% CI of 0.87 to 0.93 and the AUC for RF was 0.71 with 95% CI of 0.64 to 0.77. The presence of both antibodies increased specificity to 98.2%. Anti-CCP antibodies were positive in 34.9% of RF-negative RA patients. Anti-CCP antibodies showed a correlation with the radiographic joint damage. Anti-CCP-positive RA patients had increased the swollen joint count and serum CRP concentration compared to anti-CCP-negative RA patients (Mann-Whitney U test, p = 0.01, and p < 0.001, respectively). However, no correlation was found between anti-CCP antibodies and DAS28 score ( r = 0.13, p = 0.12). Conclusion: In Greek patients with RA, anti-CCP2 antibodies exhibit a better diagnostic value than RF and a correlation with radiological joint damage and therefore are useful in everyday rheumatology practice

Operative blood loss and use of blood products after full robotic and conventional low anterior resection with total mesorectal excision for treatment of rectal cancer

To date, no studies have investigated the estimated blood loss (EBL) after full robotic low anterior resection (R-LAR) in a case-matched model, comparing it with the conventional open approach (O-LAR). Forty-nine patients in the R-LAR and 105 in the O-LAR group were matched for age, gender, BMI (body mass index), ASA (American Society of Anesthesiology) class, tumor–node–metastasis (TNM) classification and UICC (Union for International Cancer Control) stage, distance of the lower edge of the tumor from the anal verge, presence of comorbidities, and preoperative hemoglobin (Hb). EBL was significantly higher in the O-LAR group (P < 0.001); twelve units of packed red blood cells were globally transfused in the O-LAR group, compared to one unit only in the R-LAR (P = 0.051). A significantly higher postoperative Hb drop (3.0 vs. 2.4 g/dL, P = 0.015) was registered in the O-LAR patients. The length of hospital stay was much lower for the R-LAR group (8.4 vs. 12.4 days, P < 0.001). The number of harvested lymph nodes (17.4 vs. 13.5, P = 0.006) and extent of distal margin (2.9 vs. 1.9 cm, P < 0.001) were significantly higher in the R-LAR group. Open surgery was confirmed as the sole variable significantly associated (P < 0.001) with blood loss (odds ratio = 4.41, 95% CI 2.06–9.43). It was a confirmed prognosticator of blood loss (P = 0.006) when a preoperative clinical predictive model was built, using multivariate analysis (odds ratio = 3.95, 95% CI 1.47–10.6). In conclusion, R-LAR produced less operative blood loss and less drop in postoperative hemoglobin when compared to O-LAR. Other clinically relevant outcomes were similar or superior to O-LAR

An evaluation of pharmacology curricula in Australian science and health-related degree programs

Background: Pharmacology is a biomedical discipline taught in basic science and professional degree programs. In order to provide information that would facilitate pharmacology curricula to be refined and developed, and approaches to teaching to be updated, a national survey was undertaken in Australia that investigated pharmacology course content, teaching and summative assessment methods. Methods: Twenty-two institutions participated in a purpose-built online questionnaire, which enabled an evaluation of 147 courses taught in 10 different degrees. To enable comparison, degrees were grouped into four major degree programs, namely science, pharmacy, medicine and nursing. The pharmacology content was then classified into 16 lecture themes, with 2-21 lecture topics identified per theme. The resultant data were analysed for similarities and differences in pharmacology curricula across the degree programs. Results: While all lecture themes were taught across degree programs, curriculum content differed with respect to the breadth and hours of coverage. Overall, lecture themes were taught most broadly in medicine and with greatest coverage in pharmacy. Reflecting a more traditional approach, lectures were a dominant teaching method (at least 90% of courses). Sixty-three percent of science courses provided practical classes but such sessions occurred much less frequently in other degree programs, while tutorials were much more common in pharmacy degree programs (70%). Notably, problem-based learning was common across medical programs. Considerable diversity was found in the types of summative assessment tasks employed. In science courses the most common form of in-semester assessment was practical reports, whereas in other programs pen-and-paper quizzes predominated. End-of-semester assessment contributed 50-80% to overall assessment across degree programs. Conclusion: The similarity in lecture themes taught across the four different degree programs shows that common knowledge- and competency-based learning outcomes can be defined for pharmacology. The authors contend that it is the differences in breadth and coverage of material for each lecture theme, and the differing teaching modes and assessment that characterise particular degree programs. Adoption of pharmacology knowledge-based learning outcomes that could be tailored to suit individual degree programs would better facilitate the sharing of expertise and teaching practice than the current model where pharmacology curricula are degree-specific.Hilary Lloyd, Tina Hinton, Shane Bullock, Anna-Marie Babey, Elizabeth Davis, Lynette Fernandes, Joanne Hart, Ian Musgrave and James Zioga

Impact of minimal residual disease detection by next-generation flow cytometry in multiple myeloma patients with sustained complete remission after frontline therapy

Minimal residual disease (MRD) was monitored in 52 patients with sustained CR (≥2 years) after frontline therapy using next-generation flow (NGF) cytometry. 25% of patients initially MRD- reversed to MRD+. 56% of patients in sustained CR were MRD+; 45% at the level of 10−5; 17% at 10−6. All patients who relapsed during follow-up were MRD+ at the latest MRD assessment, including those with ultra-low tumor burden. MRD persistence was associated with specific phenotypic profiles: higher erythroblasts’ and tumor-associated monocytes/macrophages’ predominance in the bone marrow niche. NGF emerges as a suitable method for periodic, reproducible, highly-sensitive MRD-detection at the level of 10−6