Association between ABO blood group and COVID-19 infection: an updated systematic review and meta-analysis.

The relationship between ABO blood group and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 - coronavirus disease 19 [COVID-19]) infection has been investigated, and several studies have reported discordant findings. This systematic review and meta-analysis study were conducted to investigate the relationship between ABO blood group and COVID-19 infection. The international databases Institute for Scientific Information (ISI)/Web of Science, PubMed, and Scopus were systematically searched from 1 January 2020 through 14 June 2021. Twenty-seven studies met the inclusion criteria for meta-analysis including 23,285 COVID-19 case subjects and 590,593 control subjects. The odds of having each blood group among COVID-19 patients compared with control subjects were calculated. The random effects model was used to obtain the overall pooled odds ratio (OR). Publication bias and subgroup and sensitivity analyses were performed to explore the source of heterogeneity. According to the random effects model, the results indicated that the pooled estimates of OR (95% confidence interval) for blood groups A, O, B, and AB were 1.26 (1.13-1.40), 0.77 (0.71-0.82), 1.05 (0.99-1.12), and 1.11 (0.99-1.25), respectively. Therefore, individuals infected with COVID-19 have higher odds of having blood group A and lower odds of having blood group O. In conclusion, this study indicated that individuals with blood group A are more susceptible to COVID-19 infection, whereas those with blood group O are less susceptible to COVID-19 infection. However, further studies are warranted to support these findings.

Calprotectin (S100A8/S100A9)-induced cytotoxicity and apoptosis in human gastric cancer AGS cells: Alteration in expression levels of Bax, Bcl-2, and ERK2.

Calprotectin is a heterodimeric EF-hand Ca2+ binding protein that is typically released by infiltrating polymorphonuclear leukocytes and macrophages. This protein is a key player linking inflammation and cancer. Due to the increased levels of calprotectin in different inflammatory diseases and cancer, it is considered as a marker for diagnostic purposes. In this study, we evaluated the mechanism of cell viability and apoptotic-inducing effects of recombinant human calprotectin (rhS100A8/S100A9) on the gastric adenocarcinoma (AGS), the most common type of gastric cancer cell line. AGS cells were exposed to the different concentrations (5-100 µg/ml) of calprotectin for 24, 48, and 72 h, and cell viability was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptotic-inducing effects of calprotectin were evaluated by sub-G1 cell cycle assay and Annexin V/propidium iodide double staining. Furthermore, real-time polymerase chain reaction and Western blot analysis were performed to evaluate the mechanism of action of calprotectin. Our findings indicated that calprotectin inhibits growth and viability of AGS cells in a time- and dose-dependent manner. The half-maximal inhibitory concentration values were measured as 85.77, 79.14, and 65.39 µg/ml for 24, 48, and 72 h, respectively. Additionally, we found that calprotectin downregulated the expression of antiapoptotic protein Bcl-2 and upregulated proapoptotic protein Bax in a time- and concentration-dependent fashion. Calprotectin also slightly upregulated the expression of extracellular signal-regulated protein kinase 2 (ERK2), while it significantly decreased the levels of phospho-ERK in a time-dependent manner. Overall, these findings indicated that calprotectin has cytotoxicity and apoptosis-inducing effects on AGS cell lines in high concentration by modulating Bax/Bcl-2 expression ratio accompanied by inhibition of ERK activation.

Common contra-indications and interactions of drugs in orthopaedic practice.

Drug therapy forms an integral part of the management of many orthopaedic conditions. However, many medicines can produce serious adverse reactions if prescribed inappropriately, either alone or in combination with other drugs. Often these hazards are not appreciated. In response to this, the European Union recently issued legislation regarding safety measures which member states must adopt to minimise the risk of errors of medication. In March 2014 the Medicines and Healthcare products Regulatory Agency and NHS England released a Patient Safety Alert initiative focussed on errors of medication. There have been similar initiatives in the United States under the auspices of The National Coordinating Council for Medication Error and The Joint Commission on the Accreditation of Healthcare Organizations. These initiatives have highlighted the importance of informing and educating clinicians. Here, we discuss common drug interactions and contra-indications in orthopaedic practice. This is germane to safe and effective clinical care.

FRAX and the assessment of the risk of developing a fragility fracture.

Osteoporosis is common and the health and financial cost of fragility fractures is considerable. The burden of cardiovascular disease has been reduced dramatically by identifying and targeting those most at risk. A similar approach is potentially possible in the context of fragility fractures. The World Health Organization created and endorsed the use of FRAX, a fracture risk assessment tool, which uses selected risk factors to calculate a quantitative, patient-specific, ten-year risk of sustaining a fragility fracture. Treatment can thus be based on this as well as on measured bone mineral density. It may also be used to determine at-risk individuals, who should undergo bone densitometry. FRAX has been incorporated into the national osteoporosis guidelines of countries in the Americas, Europe, the Far East and Australasia. The United Kingdom National Institute for Health and Clinical Excellence also advocates its use in their guidance on the assessment of the risk of fragility fracture, and it may become an important tool to combat the health challenges posed by fragility fractures.

Anti-tumor Activity of N [(E)-1-(2-hydroxyphenyl) Methylidene], N-[(E)-2-Phenylethylidene], N [(E,2E)-3-Phenyl-2-propenylidene], and N [(E)ethylidene] Isonicotinohydrazide on K562 and Jurkat Cell Lines.

Using the water eliminated mechanism, reactions of 4-pyridinecarboxylic acid hydrazide and salicylaldehyde, benzaldehyde, cinnamaldehyde, and formaldehyde afforded the corresponding N(4)[(E)-1-(2-hydroxyphenyl) methylidene] (NHPM), N(4)-[(E)-2-phenylethylidene] (NPI), N(4)[(E,2E)-3-phenyl-2-propenylidene] (NPPI), and N(4)[(E) ethylidene] (NEI) isonicotinohydrazide, in high yields, after several minutes, as reported. These new compounds have shown antitumor activity against two kinds of cancer cells, which are K562 (human chronic myeloid leukemia) and Jurkat (human T lymphocyte carcinoma).

Simple whiplash?

We describe a case of type-I Arnold-Chiari malformation in a 27-year-old woman who presented on two separate occasions with an apparent whiplash injury. She developed debilitating symptoms after two apparently low velocity vehicle collisions. MRI revealed a type-I Arnold-Chiari malformation. She was referred for consideration of neurosurgical decompression. Type-I Arnold-Chiari malformation is the downward herniation of the cerebellar tonsils through the foramen magnum. It is usually asymptomatic but may present after apparently insignificant trauma with a wide range of possible symptoms. The protean nature of its presentation and the similarity of the symptoms to those of a whiplash injury mean that it is easily overlooked. It is, however, important that it is detected early.

The oxidative inactivation of tissue inhibitor of metalloproteinase-1 (TIMP-1) by hypochlorous acid (HOCI) is suppressed by anti-rheumatic drugs.

Tissue inhibitors of metalloproteinases (TIMPs) prevent uncontrolled connective tissue destruction by limiting the activity of matrix metalloproteinases (MMPs). That TIMPs should be susceptible to oxidative inactivation is suggested by their complex tertiary structure which is dependent upon 6 disulphide bonds. We examined the oxidative inactivation of human recombinant TIMP-1 (hr TIMP-1) by HOCl and the inhibition of this process by anti-rheumatic agents. TIMP-1 was exposed to HOCl in the presence of a variety of disease modifying anti-rheumatic drugs. TIMP-1 activity was measured by its ability to inhibit BC1 collagenase activity as measured by a fluorimetric assay using the synthetic peptide substrate (DNP-Pro-Leu-Ala-Leu-Trp-Ala-Arg), best cleaved by MMP-1. The neutrophil derived oxidant HOCl, but not the derived oxidant N-chlorotaurine, can inactivate TIMP-1 at concentrations achieved at sites of inflammation. Anti-rheumatic drugs have the ability to protect hrTIMP-1 from inactivation by HOCl. For D-penicillamine, this effect occurs at plasma levels achieved with patients taking the drug but for other anti-rheumatic drugs tested this occurs at relatively high concentrations that are unlikely to be achieved in vivo, except possibly in a microenvironment. These results are in keeping with the concept that biologically derived oxidants can potentiate tissue damage by inactivating key but susceptible protein inhibitors such as TIMP-1 which form the major local defence against MMP induced tissue breakdown.

Angiographic features of vein grafts versus ungrafted coronary arteries in patients with unstable angina and previous bypass surgery.

OBJECTIVES: The aim of the study was to compare the angiographic features of culprit coronary lesions located in grafts with those in native coronary arteries in patients with unstable angina and previous coronary artery bypass graft surgery (CABG). BACKGROUND: Deterioration of angina in patients with previous CABG is usually due to progression of atherosclerosis in coronary arteries or in vein grafts, but the relative importance of graft versus native coronary artery disease as well as the morphologic features of the culprit lesions in unstable angina have not been systematically assessed. METHODS: Disease progression and angiographic features of vein grafts and ungrafted and grafted coronary arteries were assessed in 95 consecutive patients admitted with unstable angina or non-Q wave myocardial infarction with CABG > 6 months previously. All patients were receiving aspirin and heparin, and 46 had received streptokinase during the acute phase in a doubleblind, placebo-controlled study. Coronary and vein angiography was performed within 8 days after admission (mean [+/- SD] 5 +/- 2 days). The most recent angiogram served to assess disease progression by quantitative angiography. RESULTS: The culprit lesion was located in a vein graft in 51 patients, an ungrafted coronary artery in 17 and a grafted artery (proximal and distal to the site of graft insertion) in 9 and was of undetermined site in the remaining 18. The proportion of grafts accounting for acute disease increased to 85% with CABG > or = 5 years. Total occlusion occurred in 25 vein grafts and 4 ungrafted coronary arteries (49% vs. 24%, p = 0.02). Intravessel thrombus was found in 18 culprit vein grafts but in only 2 ungrafted coronary arteries (37% vs. 12%, p = 0.04). Both intravessel thrombus and total occlusion were demonstrated in six culprit vein grafts but in none of the ungrafted coronary arteries (12% vs. 0%, p = NS). The prevalence of total occlusion and thrombus was not influenced by trial medication, streptokinase or placebo. CONCLUSIONS: Unstable angina in patients with previous CABG is most often due to graft disease and is associated with more frequent thrombi that are more refractory to medical therapy.

Randomized double-blind comparison of two doses of Hirulog with heparin as adjunctive therapy to streptokinase to promote early patency of the infarct-related artery in acute myocardial infarction.

BACKGROUND: An improved survival rate is a consequence of successful reperfusion of the infarct-related artery. This double-blind, randomized trial investigated the potential of Hirulog, a direct thrombin inhibitor, to improve the early patency rates obtained with streptokinase and aspirin. METHODS AND RESULTS: Angiographic patency of the culprit coronary artery lesion was assessed 90 and 120 minutes after the initiation of streptokinase and aspirin and again after 4 +/- 2 days in 68 patients with acute myocardial infarction. Patients were randomized to Hirulog 0.5 mg/kg per hour for 12 hours followed by 0.1 mg/kg per hour (low dose), Hirulog 1.0 mg/kg per hour for 12 hours followed by placebo (high dose), or to heparin 5000 U bolus followed by 1000 U/h titrated to an activated partial thromboplastin time (aPTT) 2 to 2.5 times control after 12 hours. At 90 minutes, TIMI flow grade 2 or 3 was observed in 96% of patients treated with the low dose of Hirulog, in 79% with the high dose, and in 46% with heparin (P = .006) and TIMI flow grade 3 was observed in 85%, 61%, and 31% of patients, respectively (P = .008). At 120 minutes, these figures were 100%, 82%, and 62% for TIMI flow grades 2 and 3 (P = .046) and 92%, 68%, and 46% for TIMI flow grade 3 (P = .014). At 90 minutes, the relative risk for restoring TIMI flow grade 3 was 2.77 with Hirulog 0.5 mg/kg per hour compared with heparin (95% confidence limits, 1.21 to 6.35; P < .001) and 1.4 compared with Hirulog 1.0 mg/kg per minute (95% confidence limits, 1.00 to 1.51; P = .04). Patients who received a placebo infusion after 12 hours experienced more clinical events and reocclusion during the following 4 days than patients in the other two groups. CONCLUSION: Hirulog yields higher early patency rates in the culprit coronary artery than heparin when used as adjunctive therapy to streptokinase and aspirin in the early phase of acute myocardial infarction. High doses are not required and may be less effective than lower doses, which suggests that too much thrombin inhibition may be harmful.