Prognostic Role of Anemia in COVID-19 Patients: A Meta-Analysis.

INTRODUCTION: The prevalence and prognostic implications of anemia in patients infected by the SARS-CoV-2 remains unclear. We performed a systematic review and meta-analysis to assess the prevalence and mortality risk in COVID-19 patients with anemia. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in abstracting data and assessing validity. We searched MEDLINE and Scopus to locate all the articles published up to 1 September 2021, reporting data on the adjusted OR (aOR) for mortality among COVID-19 patients with anemia. The pooled prevalence of anemia among COVID-19 patients was calculated using a random effects model and presenting the related 95% confidence interval (CI), while the mortality risk was estimated using the Mantel-Haenszel random effects models with odds ratio (aOR) and related 95% CI. Statistical heterogeneity was measured using the Higgins I2 statistic. RESULTS: Five studies, enrolling 9.623 COVID-19 patients [3.707 males (38.5%)], met the inclusion criteria and were included in the final analysis. The pooled prevalence of anemia was 25.6% of cases (95% CI: 8.3-56.5%), with high heterogeneity (I2 = 98.9%). Meta-regression showed that the anemia prevalence was influenced by a direct correlation with age (p = 0.007) and chronic kidney disease (p = 0.004) as moderating variables. Conversely, an inverse relationship was observed with male gender (p < 0.0001). Anemia was significantly associated with higher risk of short-term mortality (aOR: 1.69, 95% CI: 1.28-2.24, p < 0.001), with low heterogeneity (I2 = 0%). CONCLUSIONS: Anemia represents a major comorbidity in about 25% of COVID-19 patients and it is associated with about 70% higher risk of short-term mortality.

Multidisciplinary training in the future of surgical education.

Will I actually be ready to face my first surgical on call night? It is the question that haunts every young specialist when, once he has completed his surgical training, he is alone, often by night to face the unpredictable. It is a question of ethical and intellectual honesty to understand that learning curve is something quite different from being transformed from a surgeon by day into a superhero by night. The training gap in Italy and at the same time the typology of patients (obesity, age, gunshot wounds, and stab wounds) who come to our Emergency Departments have exasperated the need to acquire specific skills among Surgeons. KEY WORDS: Cadaver lab, Emergency surgery, Training.

Training in Emergency Surgery.

Although emergency surgery accounts for 50% of the surgery cases in hospitals in Italy, in 57% of the hospitals emergency surgery is not performed by a dedicated team. In Europe, numerous surveys have shown that 50% of the young surgeons desire a more complete training in emergency general surgery (EGS). A survey conducted by the Association of Surgeons in training in the UK has shown that trainees want greater competence in EGS (92.4%) through the adoption of specific programs and training protocols. The Italian Society of Emergency Surgery and Trauma (SICUT)) has decided to try to make up for this lack of training by organizing specific courses that can serve as a training pathway in EGS. KEY WORDS: Emergency Surgery, Training.

Factor XIII contrasts the effects of metalloproteinases in human dermal fibroblast cultured cells.

Matrix metalloproteinases (MMPs) are overexpressed in venous leg ulcers, determining a breakdown of the main extracellular matrix (ECM) components owing mainly to collagenase activities, and so playing a crucial role in ulcer pathogenesis. The authors studied the effects of coagulation factor XIII (FXIII), which cross-links collagen and other ECM components, in human fibroblast cultured cells in the presence and in the absence of matrix metalloproteinases from Clostridium histolyticum collagenase. Clostridium collagenase at concentrations of 2.0, 1.0, and 0.5 mg/mL was added to normal human dermal fibroblasts cultured in the presence of 0.0, 1.0, and 5.0 U/mL of FXIII concentrate (Fibrogammin P, Aventis Behring). Cell counting and metabolically active fibroblast evaluation in the cultures were monitored for 72 hours, by means of trypan-blue dye and MTT test, respectively. The MTT test showed that at the highest collagenase concentration (2.0 mg/mL), the cell number decreased more than 95% in 72 hours of treatment and no significant differences were observed regardless of the FXIII concentrations utilized. At lower collagenase concentration (1.0 mg/mL), in absence or in presence of FXIII (1.0 U/mL), the cell number decreased by about 80% in 72 hours. In contrast, in the presence of higher FXIII levels (5.0 U/mL), cells suffered globally significantly less collagenase effects (p = 0.011) and the gain was appreciable at each time tested. Finally, at 0.5 mg/mL of collagenase concentration, in the absence of FXIII, the cell number decreased by about 60% in 72 hours, whereas in presence of FXIII 1.0 U/mL and 5.0 U/mL, cells decreased significantly less, by about 35% and 20%, respectively (p < 0.025 and p < 0.01, respectively). These data were also confirmed by direct cell counting utilizing the trypan-blue test. Factor XIII contrasts effectively the detrimental action of Clostridium collagenases in human fibroblast cultured cells. These results support several in vivo reports about the effectiveness of its topical application in order to enhance the venous ulcer healing processes.

Factor XIII V34L polymorphism modulates the risk of chronic venous leg ulcer progression and extension.

Low Factor XIII (FXIII) activity has been reported in the blood of patients with chronic venous leg ulcer (CVU). In vivo studies have described increased wound healing in CVU patients treated with FXIII concentrate, and in vitro studies have shown increased regenerative capacity in FXIII-treated fibroblasts. In addition, a common G-to-T polymorphism in the FXIIIA-subunit gene (V34L) significantly increases the activity and modifies the cross-linking properties of the FXIII molecule and this variant has been investigated as a protective factor against thrombosis, a recognized risk factor for CVU establishment. Therefore, the role of FXIII levels, FXIII V34L, FVR506Q, and FIIG20210A, common gene polymorphisms in the pathogenesis of CVU was investigated. Ninety-one patients with CVU and 195 healthy controls (91 of them sex- and age-matched) were PCR-genotyped for the FXIIIV34L, FVR506Q, and FIIG20210A substitutions and FXIIIA-subunit levels were determined by immuno-electrophoresis. The extent of the venous ulcer surface in patients was measured by computer software. The allele frequency and the genotype distribution of the FXIII polymorphism did not show significant differences between the whole group of cases and controls as well as prothrombin variants did. On the contrary, the FVR506Q variant (FV Leiden) allele was more frequent in patients, yielding a significant OR value of 5.93 (95 percent CI, 1.83-19.17; p= 0.003). Considering only CVU cases secondary to a post-thrombotic syndrome (n= 24), FV Leiden yielded a greater OR value of 16.08 (95 percent CI, 4.33-59.6; p < 0.0001). When the CVU cases were stratified by the three possible FXIII genotypes, a significant trend toward a lower mean value of the ulcerated area was clearly evident as the number of the polymorphic alleles (L34) increased in the genotype of patients (VV = 11.9 cm(2,)+/- 23.6; VL = 6.1 cm(2,)+/- 6.9; LL = 4.1 cm(2,)+/- 2.8; p= 0.01). On the other hand, FXIIIA antigen levels were similar between CVU cases and matched controls, but 11 percent of cases had FXIII deficiency (FXIIIA

Urine hemosiderin: a novel marker to assess the severity of chronic venous disease.

OBJECTIVE: Impaired venous drainage in severe chronic venous insufficiency (CVI) leads to microcirculatory overload, characterized by erythrocyte diapedesis and subsequent extravascular hemolysis, resulting in typical dermal hemosiderin deposition. We hypothesized that hemosiderin, normally absent, could be present in the urine in CVI. METHODS: The three-phase study included 117 patients with CVI and 12 healthy control subjects, all of whom had undergone clinical examination and duplex scanning. In phase 1, current methods were used to test urine for hemosiderin in 61 persons: 12 healthy control subjects, 24 patients with mild CVI (clinical class C1 to C3), and 25 patients with severe CVI (clinical class C4 to C6). In phase 2, the concentration of urinary hemosiderin was determined in 45 consecutive patients with CVI, CEAP class 1 to 6. A score of 0 was assigned when typical hemosiderin granules were absent at microscopic examination, a score of 1 when one to three granules per field were detected; 2 when four to six granules were detected; and 3 when more than six granules were observed. Phase 3 included 23 patients with CVI (clinical class 2 to 6). Hemosiderin concentration was determined and a score assigned before patients underwent surgical procedures to correct primary CVI. Both hemosiderin testing and duplex scanning were repeated after 6 months. RESULTS: Phase 1: Urine hemosiderin testing to determine presence or absence of CVI in patients with reflux detectable at duplex scanning yielded the following values: positive predictive value, 96% (95% confidence interval [CI], 86% to 100%); negative predictive value, 88% (CI, 68% to 97%); sensitivity, 94% (CI, 72% to 99%); specificity, 91% (CI, 83% to 99%); and diagnostic accuracy, 95% (CI, 86% to 99%). Phase 2: Hemosiderinuria score enabled classification of clinical severity of CVI. Mean scores, respectively, were clinical class 1, 0.18 +/- 0.12; class 2, 0.75 +/- 0.47; class 3, 1.67 +/- 0.21; class 4, 1.86 +/- 0.26; class 5, 2.50 +/- 0.28; and class 6, 1.92 +/- 0.21 (P <.001). Phase 3: At 6-month follow-up, hemosiderin score was improved, from 2.48 +/- 0.12 preoperatively to 0.78 +/- 0.18 postoperatively (P <.0001). A score of 0 or 1 was associated with successful surgery, whereas a score of 2 or 3 reflected persistence of reflux. CONCLUSIONS: Determination of presence of hemosiderin in the urine is a new, sensitive, cost-effective, noninvasive, and repeatable test that enables detection of substantial microcirculatory overload in patients with CVI.