<strong class="sub-title"> Background: </strong> Severe acute respiratory syndrome coronavirus <em>2</em> (SARS-CoV-<em>2</em>) stimulates pro-thrombotic changes. This, combined with its tropism for endothelium and lung structures, may explain its association with thrombotic events, reduction of pulmonary gas exchange, acute respiratory distress syndrome (AR<em>D</em>S) and a composite end-point (intensive care unit, invasive ventilation, death). This study aims to highlight the correlation between elevated <em>D</em>-<em>dimer</em> (an indirect thrombosis marker) and the increased rate of poor prognosis-associated conditions, and to introduce <em>D</em>-<em>dimer</em>-labelled anticoagulant administration as a potentially useful tool to prevent complications and positively influence coronavirus disease <em>2</em>019 (COVI<em>D</em>-19) course.

<strong class="sub-title"> Methods: </strong> An online database search (PubMed, Google Scholar, Scopus, Web of Science and Cochrane) was performed between 13 March and 10 April <em>2</em>0<em>2</em>0. The most relevant keywords were "<em>D</em>-<em>dimer</em>", "SARS-CoV-<em>2</em>", "COVI<em>D</em>-19", "thrombosis" and "AR<em>D</em>S". Selection was independently conducted by three reviewers. References and previews of accepted articles were evaluated. <em>D</em>ata inclusion/extraction inaccuracy was limited by the work of three reviewers. Selection bias reduction was addressed by thoughtfully designing the search protocol. Quality assessment was performed with the Newcastle-Ottawa Scale. The systematic review protocol was not registered because we anticipated the very limited available evidence on the topic and due to the urgency of the study.

Results: 16 studies were evaluated. Good-quality criteria were reached in 13 out of 16 studies. D-dimer was increased and significantly higher in COVID-19 patients compared with healthy controls, in COVID-19 patients with severe disease or a composite end-point compared with non-severe disease, in ARDS compared with non-ARDS patients and in deceased ARDS patients compared with ARDS patients who survived (all p<0.001). COVID-19 patients treated with anticoagulants demonstrated lower mortality compared with those not treated (p=0.017).

Conclusions: Correlations exist between COVID-19 infection, severe elevation of D-dimer levels, and increase in the rate of complications and composite end-point. The appropriateness of early and continuous D-dimer monitoring and labelled anticoagulation as management tools for COVID-19 disease deserves accurate investigation, to prevent complications and reduce interventions.

The effects of pH and aniline trapping on the partitioning of the A-<em>2</em>1 cyclic anhydride intermediate of human insulin into deamidated insulin and covalent <em>dimer</em> were investigated at low pH and 35 degrees C. Characterization of the covalent <em>dimer</em> was achieved by proteolytic cleavage and electrospray mass spectrometry and indicated that the deamidated A-<em>2</em>1 asparagine of one insulin molecule and the B-1 phenylalanine residue of another are involved. Anhydride trapping with aniline at pH 4.0 provided evidence that the rate-limiting generation of a cyclic anhydride intermediate is involved in the formation of both deamidated and <em>dimer</em>ic insulin. In the presence of aniline at pH 4.0 insulin formed two anilide products, A-<em>2</em>1 N <em>delta</em> <em>2</em>-phenylasparagine and N <em>delta</em> <em>2</em>-phenylasparagine and N gamma <em>2</em>-phenylaspartic acid human insulin at the expense of both desamido A-<em>2</em>1 and covalent <em>dimer</em> formation, consistent with the formation of a common intermediate. At 35 degrees C and under conditions where the insulin monomer predominates, the fraction of insulin reacting to form [desamidoA-<em>2</em>1] insulin decreased with a concurrent increase in formation of [desamidoA-<em>2</em>1-PheB-1] <em>dimer</em> with an increase in pH from <em>2</em>.0 to 5.0. The pH dependence of insulin product distribution could not be quantitatively rationalized solely in terms of the fraction of the PheB-1 amine group in un-ionized form. Rather, consideration of the charge states of ionizable residues near the reacting groups was necessary to fully account for the observed pH effects on product formation.

<strong class="sub-title"> Introduction: </strong> Rapid spread of coronavirus disease <em>2</em>019 (COVID-19) in the United States, especially in New York City (NYC), led to a tremendous increase in hospitalizations and mortality. There is very limited data available that associates outcomes during hospitalization in patients with COVID-19.

<strong class="sub-title"> Methods: </strong> In this retrospective cohort study, we reviewed the health records of patients with COVID-19 who were admitted from March 9-April 9, <em>2</em>0<em>2</em>0, to a community hospital in NYC. Subjects with confirmed reverse transcriptase-polymerase chain reaction (RT-PCR) of the nasopharyngeal swab for severe acute respiratory syndrome coronavirus-<em>2</em> (SARS-CoV-<em>2</em>) were included. We collected data related to demographics, laboratory results, and outcome of hospitalization. Outcome was measured based on whether the patient was discharged home or died during hospitalization.

<strong class="sub-title"> Results: </strong> There were 888 consecutive admissions with COVID-19 during the study period, of which 513 were excluded with pending outcome or incomplete information. We included a total of 375 patients in the study, of whom <em>2</em>15 (57%) survived and 160 (43%) died during hospitalization. The majority of patients were male (63%) and of Hispanic origin (66%) followed by Blacks (<em>2</em>5%), and others (9%). Hypertension (60%) stands out to be the most common comorbidity followed by diabetes mellitus (47%), cardiovascular disease (17%), chronic kidney disease (17%), and human immunodeficiency virus/acquired immunodeficiency syndrome (9%). On multiple regression analysis, increasing odds of mortality during hospitalization was associated with older age (odds ratio [OR] 1.04; 95% confidence interval [CI], 1.01-1.06 per year increase; p < 0.0001), admission D-dimer more than 1000 nanograms per milliliter (ng/mL) (OR 3.16; 95% CI, 1.75-5.73; p<0.0001), admission C-reactive protein (CRP) levels of more than <em>2</em>00 milligrams per liter (mg/L) (OR <em>2</em>.43; 95% CI, 1.36-4.34; p = 0.00<em>2</em>8), and admission lymphopenia (OR <em>2</em>.63; CI, 1.47-4.69; p 0.0010).

<strong class="sub-title"> Conclusion: </strong> In this retrospective cohort study originating in NYC, older age, admission levels of D-dimer of more than 1000 ng/mL, CRP of more than <em>2</em>00 mg/L and lymphopenia were associated with mortality in individuals hospitalized for COVID-19. We recommend using these risk factors on admission to triage patients to critical care units or surge units to maximize the use of surge capacity beds.

Polycystin-<em>2</em> (PC<em>2</em>) is a Ca(<em>2</em>+)-permeable transient receptor potential channel activated and regulated by changes in cytoplasmic Ca(<em>2</em>+). PC<em>2</em> mutations are responsible for ∼15% of autosomal dominant polycystic kidney disease. Although the C-terminal cytoplasmic tail of PC<em>2</em> has been shown to contain a Ca(<em>2</em>+)-binding EF-hand domain, the molecular basis of PC<em>2</em> channel gating by Ca(<em>2</em>+) remains unknown. We propose that the PC<em>2</em> EF-hand is a Ca(<em>2</em>+) sensor required for channel gating. Consistent with this, Ca(<em>2</em>+) binding causes a dramatic decrease in the radius of gyration (R(g)) of the PC<em>2</em> EF-hand by small angle x-ray scattering and significant conformational changes by NMR. Furthermore, increasing Ca(<em>2</em>+) concentrations cause the C-terminal cytoplasmic tail to transition from a mixture of extended oligomers to a single compact <em>dimer</em> by analytical ultracentrifugation, coupled with a >30 Å decrease in maximum interatomic distance (<em>D</em>(max)) by small angle x-ray scattering. Mutant PC<em>2</em> channels unable to bind Ca(<em>2</em>+) via the EF-hand are inactive in single-channel planar lipid bilayers and inhibit Ca(<em>2</em>+) release from ER stores upon overexpression in cells, suggesting dominant negative properties. Our results support a model where PC<em>2</em> channels are gated by discrete conformational changes in the C-terminal cytoplasmic tail in response to changes in cytoplasmic Ca(<em>2</em>+) levels. These properties of PC<em>2</em> are lost in autosomal dominant polycystic kidney disease, emphasizing the importance of PC<em>2</em> to kidney cell function. We speculate that PC<em>2</em> and the Ca(<em>2</em>+)-dependent transient receptor potential channels in general are regulated by similar conformational changes in their cytoplasmic domains that are propagated to the channel pore.

OBJECTIVE

Acute mesenteric ischemia is an infrequent cause of abdominal pain in emergency department (ED) patients; however, mortality for this condition is high. Rapid diagnosis and surgery are key to survival, but presenting signs are often vague or variable, and there is no pathognomonic laboratory screening test. A systematic review and meta-analysis of the available literature was performed to determine diagnostic test characteristics of patient symptoms, objective signs, laboratory studies, and diagnostic modalities to help rule in or out the diagnosis of acute mesenteric ischemia in the ED.

METHODS

In concordance with published guidelines for systematic reviews, the medical literature was searched for relevant articles. The Quality Assessment Tool for Diagnostic Accuracy Studies-<em>2</em> (QUADAS-<em>2</em>) for systematic reviews was used to evaluate the overall quality of the trials included. Summary estimates of diagnostic accuracy were computed by using a random-effects model to combine studies. Those studies without data to fully complete a two-by-two table were not included in the meta-analysis portion of the project.

RESULTS

The literature search identified 1,149 potentially relevant studies, of which <em>2</em>3 were included in the final analysis. The quality of the diagnostic studies was highly variable. A total of 1,970 patients were included in the combined population of all included studies. The prevalence of acute mesenteric ischemia ranged from 8% to 60%. There was a pooled sensitivity for l-lactate of 86% (95% confidence interval [CI] = 73% to 94%) and a pooled specificity of 44% (95% CI = 3<em>2</em>% to 55%). There was a pooled sensitivity for D-dimer of 96% (95% CI = 89% to 99%) and a pooled specificity of 40% (95% CI = 33% to 47%). For computed tomography (CT), we found a pooled sensitivity of 94% (95% CI = 90% to 97%) and specificity of 95% (95% CI = 93% to 97%). The positive likelihood ratio (+LR) for a positive CT was 17.5 (95% CI = 5.99 to 51.<em>2</em>9), and the negative likelihood ratio (-LR) was 0.09 (95% CI = 0.05 to 0.17). The pooled operative mortality rate for mesenteric ischemia was 47% (95% CI = 40% to 54%). Given these findings, the test threshold of <em>2</em>.1% (below this pretest probability, do not test further) and a treatment threshold of 74% (above this pretest probability, proceed to surgical management) were calculated.

CONCLUSIONS

The quality of the overall literature base for mesenteric ischemia is varied. Signs, symptoms, and laboratory testing are insufficiently diagnostic for the condition. Only CT angiography had adequate accuracy to establish the diagnosis of acute mesenteric ischemia in lieu of laparotomy.

<strong class="sub-title"> Background: </strong> Coronavirus disease <em>2</em>019 (COVI<em>D</em>-19) predisposes to arterial and venous thromboembolic complications. We describe the clinical presentation, management, and outcomes of acute arterial ischemia and concomitant infection at the epicenter of cases in the United States.

<strong class="sub-title"> Methods: </strong> Patients with confirmed COVI<em>D</em>-19 infection between March 1, <em>2</em>0<em>2</em>0 and May 15, <em>2</em>0<em>2</em>0 with an acute arterial thromboembolic event were reviewed. <em>D</em>ata collected included demographics, anatomical location of the thromboembolism, treatments, and outcomes.

<strong class="sub-title"> Results: </strong> Over the 11-week period, Northwell Health System cared for 1<em>2</em>,630 hospitalized patients with COVI<em>D</em>-19. A total of 49 patients with arterial thromboembolism and confirmed COVI<em>D</em>-19 were identified. Median age was 67 years (58-75) and 37 (76%) were male. The most common preexisting conditions were hypertension (53%) and diabetes (35%). Median <em>D</em>-<em>dimer</em> level was <em>2</em>673 ng/mL (7<em>2</em>3-7139). The distribution of thromboembolic events included upper 7 (14%) and lower 35 (71%) extremity ischemia, bowel ischemia <em>2</em> (4%), and cerebral ischemia 5 (10%). Six patients (1<em>2</em>%) had thrombus in multiple locations. Concomitant deep vein thrombosis was found in 8 patients (16%). Twenty-two (45%) patients presented with signs of acute arterial ischemia and were subsequently diagnosed with COVI<em>D</em>-19. The remaining <em>2</em>7 (55%) developed ischemia during hospitalization. Revascularization was performed in 13 (<em>2</em>7%) patients, primary amputation in 5 (10%), administration of systemic tissue plasminogen activator in 3 (6%), and <em>2</em>8 (57%) were treated with systemic anticoagulation only. The rate of limb loss was 18%. Twenty-one patients (46%) died in the hospital. Twenty-five (51%) were successfully discharged and 3 patients are still in the hospital.

Conclusions: While the mechanism of thromboembolic events in patients with COVID-19 remains unclear, the occurrence of such complication is associated with acute arterial ischemia which results in a high limb loss and mortality.

Keywords: Acute Arterial Thrombosis; COVID-19.

Recent studies suggest that thrombotic complications are a common phenomenon in the novel SARS-CoV-<em>2</em> infection. The main objective of our study is to assess cumulative incidence of pulmonary embolism (PE) in non critically ill COVI<em>D</em>-19 patients and to identify its predicting factors associated to the diagnosis of pulmonary embolism. We retrospectevely reviewed 45<em>2</em> electronic medical records of patients admitted to Internal Medicine <em>D</em>epartment of a secondary hospital in Madrid during Covid 19 pandemic outbreak. We included 91 patients who underwent a multidetector Computed Tomography pulmonary angiography(CTPA) during conventional hospitalization. The cumulative incidence of PE was assessed ant the clinical, analytical and radiological characteristics were compared between patients with and without PE. PE incidence was 6.4% (<em>2</em>9/45<em>2</em> patients). Most patients with a confirmed diagnosed with PE recieved low molecular weight heparin (LMWH): 79.3% (<em>2</em>3/<em>2</em>9). <em>D</em>-<em>dimer</em> peak was significatly elevated in PE vs non PE patients (14,480 vs 7<em>2</em>30 mcg/dL, p = 0.03). In multivariate analysis of patients who underwent a CTPA we found that plasma <em>D</em>-<em>dimer</em> peak was an independen predictor of PE with a best cut off point of > 5000 µg/dl (OR 3.77; IC95% (1.18-1<em>2</em>.16), p = 0.03). We found ninefold increased risk of PE patients not suffering from dyslipidemia (OR 9.06; IC95% (1.88-43.60). Predictive value of AUC for ROC is 75.5%. We found a high incidence of PE in non critically ill hospitalized COVI<em>D</em> 19 patients despite standard thromboprophylaxis. An increase in <em>D</em>-<em>dimer</em> levels is an independent predictor for PE, with a best cut-off point of > 5000 µg/ dl.

Keywords: Antithrombotic therapy; COVID-19; Computed tomography pulmonary angiography; Hypercoagulable state; Pulmonary embolism.

OBJECTIVE

To investigate the clinical characteristics of venous malformation of the limbs and trunk and known but poorly appraised associated coagulation disorders. Venous malformations are ubiquitous, slow-flow vascular anomalies known to be occasionally painful because of thrombotic episodes inside the lesion.

METHODS

Large case series, with screening of accepted standard coagulation tests.

METHODS

Ambulatory multidisciplinary clinics for vascular anomalies.

METHODS

This <em>2</em>-year study (<em>2</em>003-<em>2</em>005) included 118 patients with clinical, radiological, and biological features informative for better defining venous malformation and associated coagulation abnormalities.

METHODS

The primary outcome was coagulation disorders associated with VM. Secondary measures include anatomic location, extent of lesion, localized pain, and impaired motion.

RESULTS

The mean age of patients was <em>2</em>7 years, and there was a female preponderance of 64%. The venous malformation involved the upper extremity, lower extremity, and trunk in 30%, 58%, and 36% of patients, respectively; it was plurifocal in <em>2</em><em>2</em>%. Intralesional pain (in 9<em>2</em>% of patients) had a higher frequency in female (63%) than in male (47%) patients. Tissular involvement concerned the skin (65%), muscle (73%), bone (13%), joints (1<em>2</em>%), and viscera (9%). According to our severity scoring system, cases of less gravity had a score of <em>2</em> or 3 (5<em>2</em>%), cases of intermediate severity had a score of 4 or 5 (3<em>2</em>%), and cases of major severity had a score of 6 to 9 (10%). The most frequent blood coagulation abnormality was a high plasma D-dimer level >> 0.5 microg/mL) (58% of patients), which was correlated with muscle involvement and high severity score and was more frequent in women. The factor VIII-von Willebrand factor complex was documented in 84 patients, and plasma von Willebrand factor level was decreased (<60%) in <em>2</em>3 (<em>2</em>7%) of them; 10 of the 84 patients (1<em>2</em>%) had more notably decreased levels (<50%).

CONCLUSIONS

This study of a large case series of patients with pure venous malformation in the limbs and/or trunk highlights muscle involvement and frequency of pain. It validates that coagulation disorders, present in 58% of our patients, create thrombotic painful events. Under certain circumstances, these disorders entail a risk of hemorrhage because of the progression of localized intravascular coagulopathy to disseminated intravascular coagulopathy.

The single nucleotide polymorphism (SNP) Ser1<em>2</em>8Arg in the E-selectin gene is overrepresented in certain patient groups with atherosclerosis or restenosis. We hypothesized and tested whether it may affect cytokine-induced levels of soluble (s) E-selectin, or be associated with proinflammatory or procoagulant properties in a well-standardized inflammation model. Healthy male volunteers (n = 157) received a lipopolysaccharide (LPS) infusion and were genotyped for the S1<em>2</em>8R SNP, and outcome parameters were measured by enzyme immunoassays and real-time polymerase chain reaction (RT-PCR, Taqman). The S1<em>2</em>8R SNP had no pronounced effects on basal or inducible sE-selectin levels, or levels of tumor necrosis factor or interleukin-6. However, carriers of the S1<em>2</em>8R SNP had <em>2</em>0% higher monocyte counts at <em>2</em>4 hours after LPS infusion. Importantly, the S1<em>2</em>8R allele enhanced thrombin generation by 50% to 80%, as measured by prothrombin fragment F(1+<em>2</em>) (P < .01), and hence fibrin formation (<em>D</em>-<em>dimer</em>) <em>2</em>-fold (P = .01 to P = .00<em>2</em>). However, tissue factor (TF) mRNA levels were not affected. The S1<em>2</em>8R E-selectin genotype is associated with procoagulant effects in a human model of endotoxin-induced, TF-triggered coagulation. This could contribute to its linkage with various thrombotic cardiovascular disorders.

This study examined the relationship between the severity of aphasia and regional cerebral perfusion on brain SPECT using statistical parametric mapping (SPM) and a statistical probabilistic anatomic map (SPAM) in patients with a striatocapsular infarction (SCI) along with the other clinical and imaging findings.

METHODS

The subjects were 16 right-handed Korean-speaking patients with a left SCI who underwent 99mTc-ethylcyteinate dimer (99mTc-ECD) SPECT (8.1 +/- 4.8 d [mean +/- SD] after onset). MRI showed that no patient had any abnormality in the cerebral cortex (6.8 +/- 6.0 d after onset). The aphasia quotient (AQ), which is a measure of the severity of aphasia, was obtained by using the Korean version of the Western Aphasia Battery (5.3 +/- 3.9 d after onset). For quantitative evaluation of cerebral perfusion, the asymmetry indices (AIs) for subcortical and cortical areas were calculated using SPM and SPAM. The infarct size was measured using MRI.

RESULTS

Aphasia occurred in 15 (2 global, 7 transcortical, and 6 anomic aphasia) of the 16 patients. Left cerebral cortical hypoperfusion was observed in all 15 patients with subcortical aphasia. Aphasia was more severe in 6 patients with extensive cerebral cortical hypoperfusion than in the remaining 10 patients (AQ = 41.8 +/- 25.2 points vs. 84.2 +/- 7.7 points [mean +/- SD], P = 0.001). There was an association between the AQ and age (rho = -0.665), infarct size (rho = -0.594), AIs of the frontal cortex (rho = -0.653), temporal cortex (rho = -0.782), parietal cortex (rho = -0.694), whole cerebral cortex (rho = -0.768), and the cerebellar cortex (rho = 0.765). Voxel-based SPM analysis showed a significant positive correlation between the AQ and the perfusion of the left temporal cortex and the right cerebellum.

CONCLUSIONS

The severity of subcortical aphasia after a left SCI without cortical abnormalities on MRI is associated with the extent and severity of the left cerebral cortical hypoperfusion on brain perfusion SPECT performed during the subacute stage, particularly in the left temporal cortex. Quantitative brain perfusion SPECT using SPM and SPAM can help in evaluating subcortical aphasia in a SCI because it provides functional information that cannot be obtained by morphologic imaging.

Anterior gra<em>d</em>ient <em>2</em> (AGR<em>2</em>) is a normal en<em>d</em>oplasmic reticulum protein that has two important abnormal functions, amphibian limb regeneration an<em>d</em> human cancer metastasis promotion. These normal intracellular an<em>d</em> abnormal extracellular roles can be attribute<em>d</em> to the multi<em>d</em>omain structure of AGR<em>2</em>. The NMR structure shows that AGR<em>2</em> consists of an unstructure<em>d</em> N-terminal region followe<em>d</em> by a thiore<em>d</em>oxin fol<em>d</em>. The protein exists in monomer-<em>dimer</em> equilibrium with a K(<em>d</em>) of 8.83μM, an<em>d</em> intermolecular salt bri<em>d</em>ges involving E60 an<em>d</em> K64 within the fol<em>d</em>e<em>d</em> <em>d</em>omain serve to stabilize the <em>dimer</em>. The unstructure<em>d</em> region is primarily responsible for the ability of AGR<em>2</em> to promote cell a<em>d</em>hesion, while <em>dimer</em>ization is less important for this activity. The structural <em>d</em>ata of AGR<em>2</em> show a separation between potential catalytic re<em>d</em>ox activity an<em>d</em> a<em>d</em>hesion function within the context of metastasis an<em>d</em> <em>d</em>evelopment.

Sepsis is a frequent source of morbidity and mortality in critically ill patients. The goal of this case control study was to measure hemostatic changes in dogs with naturally occurring sepsis. Blood was collected within <em>2</em>4 hours of admission from <em>2</em>0 dogs that fulfilled the criteria for sepsis. Sepsis was defined as histologic or microbiological confirmation of infection and <em>2</em> or more of the following criteria: hypo- or hyperthermia, tachycardia, tachypnea, or leukopenia, leukocytosis, or>> 3% bands. Culture and sensitivities were performed on appropriate samples from all septic dogs. Twenty-eight control dogs were enrolled on the basis of normal results of physical examination, CBC, serum biochemistry, and coagulation profile. Plasma samples were analyzed for prothrombin time (PT), partial thromboplastin time (PTT), fibrin(ogen) degradation products (F<em>D</em>P), <em>D</em>-<em>dimer</em> (<em>D</em><em>D</em>) concentrations, antithrombin (AT) activity, and protein C (PC) activity. <em>D</em>ata were compared between groups by chi-square or independent t-tests. PC (P < .001) and AT (P < .001) activities were significantly lower in dogs with sepsis compared to controls. <em>D</em>ogs with sepsis had significantly higher PT (P = .007), PTT (P = .005), <em>D</em>-<em>dimer</em> (P = .005), and F<em>D</em>P (P = .001) compared to controls. Platelet counts were not significantly different between groups. Ten of the <em>2</em>0 septic dogs (50%) died, but no association was identified between any of the measured variables and outcome. These findings are consistent with previous studies in animals with experimentally induced disease and in clinical studies of humans. On the basis of these results, further investigation of the role of AT and PC in canine sepsis is warranted.

Aroun<em>d</em> 80 enzymes are implicate<em>d</em> in the generic starch an<em>d</em> sucrose pathways. One of these enzymes is sucrose phosphorylase, which reversibly catalyzes the conversion of sucrose an<em>d</em> orthophosphate to <em>d</em>-Fructose an<em>d</em> alpha-<em>d</em>-glucose 1-phosphate. Here, we present the crystal structure of sucrose phosphorylase from Bifi<em>d</em>obacterium a<em>d</em>olescentis (BiSP) refine<em>d</em> at 1.77 A resolution. It represents the first 3D structure of a sucrose phosphorylase an<em>d</em> is the first structure of a phosphate-<em>d</em>epen<em>d</em>ent enzyme from the glycosi<em>d</em>e hy<em>d</em>rolase family 13. The structure of BiSP is compose<em>d</em> of the four <em>d</em>omains A, B, B', an<em>d</em> C. Domain A comprises the (beta/alpha)(8)-barrel common to family 13. The catalytic active-site resi<em>d</em>ues (Asp19<em>2</em> an<em>d</em> Glu<em>2</em>3<em>2</em>) are locate<em>d</em> at the tips of beta-sheets 4 an<em>d</em> 5 in the (beta/alpha)(8)-barrel, as require<em>d</em> for family 13 members. The topology of the B' <em>d</em>omain <em>d</em>isfavors oligosacchari<em>d</em>e bin<em>d</em>ing an<em>d</em> re<em>d</em>uces the size of the substrate access channel compare<em>d</em> to other family 13 members, un<em>d</em>erlining the role of this <em>d</em>omain in mo<em>d</em>ulating the function of these enzymes. It is remarkable that the fol<em>d</em> of the C <em>d</em>omain is not observe<em>d</em> in any other known hy<em>d</em>rolases of family 13. BiSP was foun<em>d</em> as a homo<em>dimer</em> in the crystal, an<em>d</em> a <em>dimer</em> contact surface area of 960 A(<em>2</em>) per monomer was calculate<em>d</em>. The majority of the interactions are confine<em>d</em> to the two B <em>d</em>omains, but interactions between the loop 8 regions of the two barrels are also observe<em>d</em>. This results in a large cavity in the <em>dimer</em>, inclu<em>d</em>ing the entrance to the two active sites.

BACKGROUND

Computed tomography (CT) pulmonary angiography use has increased dramatically, raising concerns for patient safety. Adherence to recommendations and guidelines may protect patients. We measured adherence to the recommendations of Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED II) investigators for evaluation of suspected pulmonary embolism and the rate of potential false-positive pulmonary embolism diagnoses when recommendations of PIOPED II investigators were not followed.

METHODS

We used a structured record review to identify 3500 consecutive CT pulmonary angiograms performed to investigate suspected pulmonary embolism in <em>2</em> urban emergency departments, calculating the revised Geneva score (RGS) to classify patients as "pulmonary embolism unlikely" (RGS≤10) or "pulmonary embolism likely" (RGS>10). CT pulmonary angiograms were concordant with PIOPE<em>D</em> II investigator recommendations if pulmonary embolism was likely or pulmonary embolism was unlikely and a highly sensitive <em>D</em>-<em>dimer</em> test result was positive. We independently reviewed 48<em>2</em> CT pulmonary angiograms to measure the rate of potential false-positive pulmonary embolism diagnoses.

RESULTS

A total of 159<em>2</em> of 3500 CT pulmonary angiograms (45.5%) followed the recommendations of PIOPE<em>D</em> II investigators. The remaining 1908 CT pulmonary angiograms were performed on patients with an RGS≤10 without a <em>D</em>-<em>dimer</em> test (n=1588) or after a negative <em>D</em>-<em>dimer</em> test result (n=3<em>2</em>0). The overall rate of pulmonary embolism was 9.7%. Potential false-positive diagnoses of pulmonary embolism occurred in <em>2</em> of 3 patients with an RGS≤10 and a negative <em>D</em>-<em>dimer</em> test result.

CONCLUSIONS

Nonadherence to recommendations for CT pulmonary angiography is common and exposes patients to increased risks, including potential false-positive diagnoses of pulmonary embolism.

This study was planned for searching possible changes of the total coagulation and fibrinolysis system in inflammatory bowel disease (IB<em>D</em>) in order to obtain some clues for explaining the relation between IB<em>D</em> and hypercoagulability. A total of <em>2</em>4 patients with ulcerative colitis, 1<em>2</em> patients with Crohn disease, and <em>2</em>0 healthy controls were studied. Platelets; prothrombin time (PT); partial thromboplastin time (PTT); fibrinogen; <em>D</em>-<em>dimer</em>; fibrinogen degradation products; protein C; protein S; antithrombin; thrombin time; von Willebrand factor; coagulation factors V, VII, VIII, IX, XI, and XIII; plasminogen; antiplasmin; tissue plasminogen activator; plasminogen activator inhibitor 1; and prothrombin fragments 1 + <em>2</em> were studied. Most of the procoagulants (platelets, fibrinogen, von Willebrand factor, coagulation factor IX, and plasminogen activator inhibitor 1) were found increased together with decreases in some anticoagulants (protein S and antithrombin) in IB<em>D</em>. Also the activation markers of coagulation (<em>D</em>-<em>dimer</em>, fibrinogen degradation products, and prothrombin fragments 1 + <em>2</em>) were all increased. The parameters of the total coagulation-fibrinolysis system were increased in IB<em>D</em>, regardless of the form and the activity of the disease.

Chronic urticaria (CU) is a skin disorder characterized by the recurrent eruption of short-lived wheals accompanied by redness and itching for at least 6 weeks. The wheals can be associated with angioedema. CU is considered an autoimmune disease in about 50% of cases with the presence of circulating histamine releasing autoantibodies mainly directed against the high affinity IgE receptor FcepsilonRI on mast cells and basophils or against IgE. In several CU cases regarded as idiopathic; the actual pathophysiological mechanisms are still unknown. Some patients with CU do not respond to antihistamines and require the use of systemic steroids or cyclosporin, which are, however, not always effective. In CU, several investigators have demonstrated the activation of coagulation that is due to the involvement of eosinophils and a tissue factor pathway with generation of thrombin potentially contributing to an increased vascular permeability. CU patients often present with elevation of coagulation and fibrinolysis markers, such as prothrombin fragment F1+<em>2</em> and <em>D</em>: -<em>dimer</em>, which correlate with the disease severity. Preliminary data indicate that anticoagulant treatment with heparin and warfarin may be effective in reducing the symptoms of this disorder. Taken together, all these findings provide the rationale for proposing clinical trials on the use of anticoagulant drugs as adjuvant treatment in CU patients.

Background: Spain has been one of the countries most affected by the COVID-19 pandemic.

Objective: To create a registry of patients with COVID-19 hospitalized in Spain, in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease.

Methods: A multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records.

Results: Up to June 30th 2020, 15,111 patients from 150 hospitals were included. Their median age was 69.4 years (range: 18-102 years) and 57.2% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.9%, 39.7%, and 19.4%, respectively. The most frequent symptoms were fever (84.2%) and cough (73.5%). High values of ferritin (73.5%), lactate dehydrogenase (73.9%), and D-dimer (63.8%), as well as lymphopenia (52.8%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.6%) and lopinavir/ritonavir (61.4%); 33.1% developed respiratory distress. Overall mortality rate was 21.0%, with a marked increase with age (50-59 years: 4.7%, 60-69 years: 10.5%, 70-79 years: 26.9%, ≥ 80 years: 46.0%).

Conclusions: The SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality.

Antecedentes: España ha sido uno de los países más afectados por la pandemia de COVID-19.

Objetivo: Crear un registro de pacientes hospitalizados en España por COVID-19 para mejorar nuestro conocimiento sobre los aspectos clínicos, diagnósticos, terapéuticos y pronósticos de esta enfermedad.

Métodos: Estudio de cohorte retrospectiva, multicéntrico, que incluye pacientes consecutivos hospitalizados con COVID-19 confirmada en toda España. Se obtuvieron los datos epidemiológicos y clínicos, las pruebas complementarias al ingreso y a los 7 días de la admisión, los tratamientos administrados y la evolución a los 30 días de hospitalización de las historias clínicas electrónicas.

Resultados: Hasta el 30 de junio de 2020 se incluyeron 15.111 pacientes de 150 hospitales. Su mediana de edad fue 69,4 años (rango: 18-102 años) y el 57,2% eran hombres. Las prevalencias de hipertensión, dislipemia y diabetes mellitus fueron 50,9%, 39,7% y 19,4%, respectivamente. Los síntomas más frecuentes fueron fiebre (84,2%) y tos (73,5%). Fueron frecuentes los valores elevados de ferritina (73,5%), lactato deshidrogenasa (73,9%) y dímero D (63,8%), así como la linfopenia (52,8%). Los fármacos antivirales más utilizados fueron la hidroxicloroquina (85,6%) y el lopinavir/ritonavir (61,4%). El 33,1% desarrolló distrés respiratorio. La tasa de mortalidad global fue del 21,0%, con un marcado incremento con la edad (50-59 años: 4,7%; 60-69 años: 10,5%; 70-79 años: 26,9%; ≥ 80 años: 46%).

Conclusiones: El Registro SEMI-COVID-19 proporciona información sobre las características clínicas de los pacientes con COVID-19 hospitalizados en España. Los pacientes con COVID-19 hospitalizados en España son en su mayoría casos graves, ya que uno de cada 3 pacientes desarrolló distrés respiratorio y uno de cada 5 pacientes falleció. Nuestros datos confirman una estrecha relación entre la edad avanzada y la mortalidad.

Keywords: 2019-nCoV; COVID-19; Coronavirus; SARS-CoV-2; Spain.

BACKGROUND

Cigarette smoking is associated with cardiovascular morbidity and mortality. Exposure to cigarette smoke can cause endothelial dysfunction with impaired endothelium-dependent vasodilation and 'endothelial activation', which predispose to atherothrombosis. The effects of continued smoking and smoking cessation on the level of endothelial, platelet and clotting activation have not been described previously. Here, we prospectively monitored changes in circulating endothelial-coagulative activation markers in smokers undertaking smoking cessation.

METHODS

This 1<em>2</em>-month prospective stu<em>d</em>y of 174 smokers with no commonly acquire<em>d</em> atherothrombotic risk factors un<em>d</em>erwent an intensive smoking-cessation programme investigating the effect of quitting on circulating levels of von Willebran<em>d</em>'s Factor Antigen (vWF:Ag), soluble Thrombomo<em>d</em>ulin (sTM), <em>d</em>-<em>Dimer</em> (<em>d</em>-<em>D</em>), prothrombin fragment F1+<em>2</em> (F1+<em>2</em>), platelet factor-4 (PF4) an<em>d</em> β-Thromboglobulin (β-TG). Bloo<em>d</em> samples an<em>d</em> stu<em>d</em>y measures were collecte<em>d</em> an<em>d</em> compare<em>d</em> at baseline an<em>d</em> at <em>2</em>, 6 an<em>d</em> 1<em>2</em>months after smoking cessation from quitters an<em>d</em> relapsers'.

RESULTS

No significant <em>d</em>ifferences in <em>d</em>emographic or laboratory parameters at baseline were observe<em>d</em> between the stu<em>d</em>y groups. Significant changes in von Willebran<em>d</em>'s Factor activity were observe<em>d</em> at <em>2</em>months after smoking cessation, with levels <em>d</em>ecreasing from 141·8% to 113·6%. Substantial mo<em>d</em>ifications in <em>d</em>-<em>Dimer</em>, prothrombin fragment F1 +<em>2</em>, platelet factor-4 an<em>d</em> β-thromboglobulin concentrations were observe<em>d</em> only at 6 an<em>d</em> 1<em>2</em>months after smoking cessation. Positive associations between baseline levels of these biomarkers an<em>d</em> number of pack per years have been <em>d</em>emonstrate<em>d</em>.

CONCLUSIONS

Chronic exposure to cigarette smoke sustains the activation of the endothelial-coagulative system and abstinence may result in the improvement of several endothelial-coagulative abnormalities in regular smokers. This may translate into an overall decline in cardiovascular risk.

Objective: To describe the clinical and epidemiological characteristics of hospitalized children with Multisystem Inflammatory Syndrome in Children (MIS-C) in Santiago, Chile.

<strong class="sub-title"> Methods: </strong> Observational study, on children with MIS-C (May 1- June <em>2</em>4, <em>2</em>0<em>2</em>0), in 3 pediatric hospitals in Santiago. <em>D</em>emographics and epidemiologic data; medical history; laboratory tests; cardiologic evaluation; treatment; and clinical outcome were analyzed.

<strong class="sub-title"> Results: </strong> <em>2</em>7 patients (median age 6 (0-14) years) were admitted; 16/<em>2</em>7 (59%) required intensive care admission with no deaths. 74% had no-comorbidities, and median days of symptoms before admission was 4 (<em>2</em>-9). Gastrointestinal symptoms were the most frequent, and inflammatory markers were increased at admission. A recent SARS-CoV-<em>2</em> infection was detected in 8<em>2</em>% of cases. The severe group showed significantly lower hemoglobin and albumin, decreased platelet counts, and higher <em>D</em>-<em>dimer</em> during evolution. Echocardiography showed abnormalities (myocardial, pericardial, or coronary) on 1<em>2</em> patients (46%) during hospital stay. Anti-inflammatory treatment (immune globulin and/or corticosteroids) was prescribed in <em>2</em>4 patients. MIS-C appeared in clusters weeks after the peak of SARS-CoV-<em>2</em> cases, especially in Santiago's most vulnerable areas.

<strong class="sub-title"> Conclusions: </strong> We describe the first series, of <em>2</em>7 children with MIS-C, in a Latin-American countrywith favorable clinical outcomes. Education and alerts are required for clinical teams to establish an early diagnosis and prompt treatment.

<strong class="sub-title"> Keywords: </strong> COVI<em>D</em>-19; MIS-C multisystem inflammatory syndrome in children; SARS-CoV-<em>2</em>.

<strong class="sub-title"> Study objective: </strong> The large number of clinical variables associated with coronavirus disease <em>2</em>019 (COVI<em>D</em>-19) infection makes it challenging for frontline physicians to effectively triage COVI<em>D</em>-19 patients during the pandemic. This study aimed to develop an efficient deep-learning artificial intelligence algorithm to identify top clinical variable predictors and derive a risk stratification score system to help clinicians triage COVI<em>D</em>-19 patients.

<strong class="sub-title"> Methods: </strong> This retrospective study consisted of 181 hospitalized patients with confirmed COVI<em>D</em>-19 infection from January <em>2</em>9, <em>2</em>0<em>2</em>0 to March <em>2</em>1, <em>2</em>0<em>2</em>0 from a major hospital in Wuhan, China. The primary outcome was mortality. <em>D</em>emographics, comorbidities, vital signs, symptoms, and laboratory tests were collected at initial presentation, totaling 78 clinical variables. A deep-learning algorithm and a risk stratification score system were developed to predict mortality. <em>D</em>ata were split into 85% training and 15% testing. Prediction performance were compared with those using COVI<em>D</em>-19 severity score, CURB-65 score and pneumonia severity index (PSI).

<strong class="sub-title"> Results: </strong> Of the 181 COVI<em>D</em>-19 patients, 39 expired and 14<em>2</em> survived. Five top predictors of mortality were <em>D</em>-<em>dimer</em>, O_<em>2</em> Index, neutrophil:lymphocyte ratio, C-reactive protein, and lactate dehydrogenase. The top 5 predictors and the resultant risk score yielded, respectively, an area under curve (AUC) of 0.968 ([95% CI:0.87-1.0]) and 0.954 ([95% CI:0.80-0.99]) for the testing dataset. Our models outperformed COVI<em>D</em>-19 severity score (AUC = 0.756), CURB-65 score (AUC = 0.671), and PSI (AUC = 0.838). The mortality rates for our risk stratification scores (0-5) were 0, 0, 6.7, 18.<em>2</em>, 67.7, and 83.3%, respectively.

Conclusions and relevance: Deep-learning prediction model and the resultant risk stratification score may prove useful in clinical decision-making under time-sensitive and resource-constrained environment.This article is protected by copyright. All rights reserved.

Keywords: artificial intelligence; coronavirus; machine learning; pneumonia; prediction model.

<AbstractText>The search for potential markers for a timely and accurate diagnosis of periprosthetic joint infection (PJI) is ongoing. Previous studies have focused on inflammatory markers and have rarely examined coagulation-related indicators. The purpose of this study was to evaluate the values of plasma fibrinogen, <em>D</em>-<em>dimer</em>, and other blood markers for the diagnosis of PJI through a multicenter retrospective study.</AbstractText><AbstractText>A total of 565 revision total hip and knee arthroplasty cases were enrolled in this study from January <em>2</em>016 through <em>D</em>ecember <em>2</em>017, 1<em>2</em>6 of which had coagulation-related comorbidities and were analyzed separately. The remaining 439 cases included 76 PJI and 363 non-PJI patients. The definition of PJI was based on the International Consensus Meeting (ICM) on Periprosthetic Infection criteria. The diagnostic values of <em>D</em>-<em>dimer</em>, plasma fibrinogen, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and white blood-cell (WBC) count were analyzed using receiver operating characteristic (ROC) curves.</AbstractText><AbstractText>ROC curves showed that plasma fibrinogen had the highest area under the curve (AUC), 0.85<em>2</em>, followed by <em>2</em> classical markers, the CRP level and ESR, which had an AUC of 0.810 and 0.808, respectively. <em>D</em>-<em>dimer</em> had an AUC of 0.657, which was the second lowest value and only slightly higher than that of the WBC count, 0.590. The optimal threshold for plasma <em>D</em>-<em>dimer</em> was 1.<em>2</em>5 μg/mL, with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.645, 0.650, 0.<em>2</em>78, and 0.897, respectively. The optimal threshold for plasma fibrinogen was 4.01 g/L, which showed good sensitivity, specificity, PPV, and NPV, with values of 0.763, 0.86<em>2</em>, 0.537, and 0.946, respectively.</AbstractText><AbstractText>Plasma <em>D</em>-<em>dimer</em> may have a very limited diagnostic value for PJI, while plasma fibrinogen, another coagulation-related indicator, exhibits promising performance. Plasma fibrinogen has good sensitivity and specificity for diagnosing PJI, with values similar to those of classical markers, including CRP level and ESR.</AbstractText><AbstractText><em>D</em>iagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.</AbstractText>

Comprehensive studies of fibrinolysis in non-small cell lung carcinoma have been limited, and assignment of patients to high/low prognosis groups based on arbitrary cut-offs utilizing fibrinolytic measurements is unstandardized. This study was performed in 166 patients to examine the effects of cut-off values determined in three ways. Model 1 assigned patients to one of three equal groups (low, medium, high) based on fibrinolytic measurements made at diagnosis, Model <em>2</em> divided patients into low/high groups using median values, and Model 3 grouped according to the parameter being above/below normal range. In model 1, raised plasma fibrinogen, <em>D</em>-<em>dimer</em> and soluble fibrin were positively associated with poorer survival. In model <em>2</em>, tissue plasminogen activator antigen was additionally related to poorer prognosis. Model 3 identified seven parameters as significantly related to survival, two not identified by the other models becoming significant [plasmin-antiplasmin, tissue plasminogen activator inhibitor-1 (PAI-1) antigen]. Using multivariate analysis, plasma fibrinogen level was the most uniformly significant parameter. Relative risk estimates indicated that raised plasma fibrinogen, soluble fibrin and <em>D</em>-<em>dimer</em> were associated with increased risk of death. Use of the normal/above normal cut-off is recommended to provide the maximum number of significant parameters relating to prognosis, and increased plasma <em>D</em>-<em>dimer</em>, PAI-1 antigen and fibrinogen were most closely related to survival/prognosis.

Background: Limited pediatric cases with coronavirus disease 2019 (COVID-19) have been reported and the clinical profiles regarding COVID-19 in children remain obscure. Our aim was to investigate the clinical characteristics of COVID-19 in children.

Methods: PUBMED and EMBASE were searched through June 20, 2020, for case reports and case series reporting pediatric COVID-19 cases. Epidemiological, clinical, laboratory, and radiological data were collected and analyzed to compare by age.

Results: Our search identified 46 eligible case reports and case series. A total of 114 pediatric cases with COVID-19 were included. The main clinical features were mild symptoms including fever (64%), cough (35%), and rhinorrhea (16%), or no symptoms (15%). Ground-like opacities were common radiological findings (54%). The main laboratory findings were lymphopenia (33%) and elevated D-dimer (52%) and C-reactive protein (40%) levels. We identified 17 patients (15%) with multisystem inflammatory syndrome in children (MIS-C) manifesting with symptoms overlapping with, but distinct from, Kawasaki disease, including gastrointestinal symptoms, left ventricular systolic dysfunction, shock, and marked elevated inflammatory biomarkers. Twelve percent of the patients including 65% of the MIS-C cases required intensive care because of hypotension. No deaths were reported.

Conclusion: This systematic review found that children with COVID-19 are generally less severe or asymptomatic. However, infants might be seriously ill and older children might develop MIS-C with severe illness. Early detection of children with mild symptoms or an asymptomatic state and early diagnosis of MIS-C are mandatory for the management of COVID-19 and the prevention of transmission and a severe inflammatory state. This article is protected by copyright. All rights reserved.

Keywords: COVID-19; Kawasaki disease; SARS-CoV-2; clinical features; multisystem inflammatory syndrome in children (MIS-C).

BACKGROUND

There is an increased risk of venous thrombosis after air travel, but the underlying mechanism is unclear. Our aim was to ascertain whether flying leads to a hypercoagulable state.

METHODS

We did a crossover study in 71 healthy volunteers (15 men, 56 women), in whom we measured markers of activation of coagulation and fibrinolysis before, during, and after an 8-h flight. The same individuals participated in two control exposure situations (8-h movie marathon and daily life) to separate the effect of air travel on the coagulation system from those of immobilisation and circadian rhythm. To study the effect of risk factors for thrombosis, we included participants with the factor V Leiden mutation (n=11), those who took oral contraceptives (n=15), or both (n=15), as well as 30 individuals with no specific risk factors.

RESULTS

After the flight, median concentrations of thrombin-antithrombin (TAT) complex increased by 30.1% (95% CI 11.<em>2</em>-63.<em>2</em>), but decreased by <em>2</em>.1% (-11.<em>2</em> to 14) after the cinema and by 7.9% (-16.<em>2</em> to -1.<em>2</em>) after the daily life situation. We recorded a high response in TAT levels in 17% (11 of 66) of individuals after air travel (3% [<em>2</em> of 68] for movie marathon; 1% [1 of 70] in daily life). These findings were most evident in the group with the factor V Leiden mutation who used oral contraceptives. We noted a high response in all variables (prothrombin fragment 1 and <em>2</em>, TAT, and <em>D</em>-<em>dimer</em>) in four of 63 (6.3%) volunteers after the flight, but in no-one after either of the control situations.

CONCLUSIONS

Activation of coagulation occurs in some individuals after an 8-h flight, indicating an additional mechanism to immobilisation underlying air travel related thrombosis.