The role of Fusobacterium nucleatum in the pathogenesis of colon cancer.

Previously, many studies have reported changes in the gut microbiota of patients with colorectal cancer (CRC). While CRC is a well-described disease, the relationship between its development and features of the intestinal microbiome is still being understood. Evidence linking Fusobacterium nucleatum enrichment in colorectal tumor tissue has prompted the elucidation of various molecular mechanisms and tumor-promoting attributes. In this review we highlight various aspects of our understanding of the relationship between the development of CRC and the alteration of intestinal microbiome, focusing specifically on the role of F. nucleatum. As the amount of F. nucleatum DNA in CRC tissue is associated with shorter survival, it may potentially serve as a prognostic biomarker, and most importantly may open the door for a role in CRC treatment.

Unraveling the NH3-SCR-DeNOx Mechanism of Cu-SSZ-13 Variants by Spectroscopic and Transient Techniques.

Commercial SSZ-13 zeolite with different n(Si)/n(Al) ratios and from different suppliers were subjected to a post-synthetic treatment in order to create mesopores of up to 10 nm. Furthermore, the materials were modified with copper ions and thoroughly physico-chemically characterized. The modified textural properties varied the nature of copper species, and thus, activity in the selective catalytic reduction of NOx with ammonia (NH3-SCR-DeNOx). Pulsed-field gradient nuclear magnetic resonance (PFG-NMR) studies with hexane as probe liquid revealed improved intracrystalline diffusion for some Cu-containing SSZ-13 materials. The NH3-SCR-DeNOx pathway is verified viain situ DR UV-Vis, in situ FT-IR and EPR, temperature-programmed studies as well as SSITKA studies that provide a mechanistic understanding of the reaction. Kinetic modelling results demonstrate the highest NH3-SCR-DeNOx reaction rates and up to 20 % lower energy barriers with n(Si)/n(Al) ratio of 6.5 for all modified forms (i.e., (NH4)Cu-SSZ-13_6.5 and Cu-SSZ-13_6.5_NaOH/0.1) and cause only negligible parasitic ammonia oxidation. The modelling of the stop-flow experiments further demonstrates that the SCR pathway via the HONO surface intermediate is present but barely contributes to the overall NO conversion compared to the dominant path between adsorbed NH3 and NO from the gas phase.

Hepatic Encephalopathy Secondary to Non-cirrhotic Portosystemic Shunt.

Hepatic encephalopathy is uncommon in the absence of cirrhosis. We report a 71-year-old woman who presented with altered mental status in the setting of hyperammonemia for the second time in 6 months. Magnetic resonance imaging of the abdomen revealed an uncommon portosystemic shunt involving an enlarged posterior branch of the right portal vein and an accessory right hepatic vein, with no features of cirrhosis. Appropriate management of these patients with ammonia-lowering therapy can reduce repeat episodes and improve quality of life. This case demonstrates the importance of diagnosing non-cirrhotic hepatic encephalopathy in patients with altered mental status.

Plasma levels of complement components C5 and C9 are associated with thrombin generation.

BACKGROUND: The thrombin generation assay (TGA) evaluates the potential of plasma to generate thrombin over time, providing a global picture of an individual's hemostatic balance. OBJECTIVES: This study aimed to identify novel biological determinants of thrombin generation using a multiomics approach. METHODS: Associations between TGA parameters and plasma levels of 377 antibodies targeting 236 candidate proteins for cardiovascular risk were tested using multiple linear regression analysis in 770 individuals with venous thrombosis from the Marseille Thrombosis Association (MARTHA) study. Proteins associated with at least 3 TGA parameters were selected for validation in an independent population of 536 healthy individuals (Etablissement Français du Sang Alpes-Méditerranée [EFS-AM]). Proteins with strongest associations in both groups underwent additional genetic analyses and in vitro experiments. RESULTS: Eighteen proteins were associated (P < 1.33 × 10⁻4) with at least 3 TGA parameters in MARTHA, among which 13 demonstrated a similar pattern of associations in EFS-AM. Complement proteins C5 and C9 had the strongest associations in both groups. Ex vivo supplementation of platelet-poor plasma with purified C9 protein had a significant dose-dependent effect on TGA parameters. No effect was observed with purified C5. Several single nucleotide polymorphisms associated with C5 and C9 plasma levels were identified, with the strongest association for the C5 missense variant rs17611, which was associated with a decrease in C5 levels, endogenous thrombin potential, and peak in MARTHA. No association of this variant with TGA parameters was observed in EFS-AM. CONCLUSION: This study identified complement proteins C5 and C9 as potential determinants of thrombin generation. Further studies are warranted to establish causality and elucidate the underlying mechanisms.

Educational Values of Latino Families Participating in a School Readiness Intervention: Hopes and Implications for Pediatrics.

OBJECTIVE: To explore Latino parents' educational values and hopes for their preschool-aged children after a clinic school readiness (SR) intervention. METHODS: Qualitative analysis of semi-structured interviews of Latino parents regarding their perceptions of a novel SR coaching intervention (2016-2017). Parents who received the intervention were approached for interview (n = 74); 59 postintervention interviews were completed in English or Spanish, audio recorded, transcribed, and translated into English. Iterative team-based coding and inductive thematic analysis of 47 interviews were conducted by 3 team members using Dedoose. RESULTS: Children were on average 4.5 years old, with the majority speaking Spanish at home (57%), and having preschool experience (81%). Mothers mostly had no paid employment (53%) and limited formal education. Four domains emerged: 1) education is valued and seen as a pathway to a successful life for children, and 2) while structural and cultural barriers exist, 3) Latino families are motivated and 4) trust providers to offer SR support. Parents suggested pediatricians could provide more SR knowledge to families and offer programs within primary care. Integration of findings are summarized in a framework for clinical practice. CONCLUSION: Latino parents' trust in their pediatric providers, combined with their strong educational aspirations for their children, offers the pediatric clinic an opportunity to partner with families to reduce systemic SR barriers. Pediatric providers can support Latino parents in preparing their children for school through culturally responsive, strengths-based approaches that build on their educational aspirations, value existing SR efforts, offer SR knowledge around early literacy and math, and build connections to early childhood programs.

Disorders of Gut-brain Interaction on the US-Mexico Border: A Survey Using Rome IV Criteria.

BACKGROUND: Disorders of gut-brain interaction (DGBI) cause a substantial health burden. Herein we studied the prevalence and characteristics of DGBI and symptoms of bloating/distension in El Paso, Texas on the US-Mexico border, providing a unique opportunity to study the effects of acculturation. METHODS: Subjects from community centers completed the Rome IV questionnaire for DGBI, short acculturation scale for Hispanics questionnaire, and bloating/distention Pictograms. Data were presented as prevalence (95% CI) and compared using χ 2 . RESULTS: Of 216 participants, 197 (127 Hispanics, 90 with English acculturation) were included and 177 completed the Pictograms. Fifty-one [25.9% (20 to 32.6)] subjects fulfilled the criteria for at least one DGBI. Globus and functional dyspepsia were the most common upper DGBI, each in [3.0% (1.1 to 6.5)]. Unspecified functional bowel disorders [8.6% (5.1 to 13.5)], followed by functional abdominal bloating/distention [8.1% (4.7 to 12.9], and irritable bowel syndrome [6.1% (3.2 to 10.4] were the most common functional bowel disorder. Ninety-one (51.4%) reported bloating and/or distension with Pictograms; more frequently in those with DGBI (80.9% vs 40.8%, P < 0.001). Bloating and/or distension were reported by Pictograms in 30% of those not reporting it in the Rome IV Questionnaire. There were no differences based on acculturation or in Hispanics versus non-Hispanics. CONCLUSIONS: On the US-Mexico border, we found a lower prevalence of DGBI than in the US or Mexico. Functional abdominal bloating/distention was more prevalent on the US-Mexico border than in either country. Bloating/distension was more commonly reported with Pictograms than with verbal descriptors. There were no differences between Hispanics and non-Hispanics, suggesting shared environmental/acquired including dietary factors as the underlying mechanisms.

Autoantibodies against the chemokine receptor 3 predict cardiovascular risk.

BACKGROUND AND AIMS: Chronic inflammation and autoimmunity contribute to cardiovascular (CV) disease. Recently, autoantibodies (aAbs) against the CXC-motif-chemokine receptor 3 (CXCR3), a G protein-coupled receptor with a key role in atherosclerosis, have been identified. The role of anti-CXCR3 aAbs for CV risk and disease is unclear. METHODS: Anti-CXCR3 aAbs were quantified by a commercially available enzyme-linked immunosorbent assay in 5000 participants (availability: 97.1%) of the population-based Gutenberg Health Study with extensive clinical phenotyping. Regression analyses were carried out to identify determinants of anti-CXCR3 aAbs and relevance for clinical outcome (i.e. all-cause mortality, cardiac death, heart failure, and major adverse cardiac events comprising incident coronary artery disease, myocardial infarction, and cardiac death). Last, immunization with CXCR3 and passive transfer of aAbs were performed in ApoE(-/-) mice for preclinical validation. RESULTS: The analysis sample included 4195 individuals (48% female, mean age 55.5 ± 11 years) after exclusion of individuals with autoimmune disease, immunomodulatory medication, acute infection, and history of cancer. Independent of age, sex, renal function, and traditional CV risk factors, increasing concentrations of anti-CXCR3 aAbs translated into higher intima-media thickness, left ventricular mass, and N-terminal pro-B-type natriuretic peptide. Adjusted for age and sex, anti-CXCR3 aAbs above the 75th percentile predicted all-cause death [hazard ratio (HR) (95% confidence interval) 1.25 (1.02, 1.52), P = .029], driven by excess cardiac mortality [HR 2.51 (1.21, 5.22), P = .014]. A trend towards a higher risk for major adverse cardiac events [HR 1.42 (1.0, 2.0), P = .05] along with increased risk of incident heart failure [HR per standard deviation increase of anti-CXCR3 aAbs: 1.26 (1.02, 1.56), P = .03] may contribute to this observation. Targeted proteomics revealed a molecular signature of anti-CXCR3 aAbs reflecting immune cell activation and cytokine-cytokine receptor interactions associated with an ongoing T helper cell 1 response. Finally, ApoE(-/-) mice immunized against CXCR3 displayed increased anti-CXCR3 aAbs and exhibited a higher burden of atherosclerosis compared to non-immunized controls, correlating with concentrations of anti-CXCR3 aAbs in the passive transfer model. CONCLUSIONS: In individuals free of autoimmune disease, anti-CXCR3 aAbs were abundant, related to CV end-organ damage, and predicted all-cause death as well as cardiac morbidity and mortality in conjunction with the acceleration of experimental atherosclerosis.

Circulating microRNAs predict recurrence and death following venous thromboembolism.

BACKGROUND: Recurrent events frequently occur after venous thromboembolism (VTE) and remain difficult to predict based on established genetic, clinical, and proteomic contributors. The role of circulating microRNAs (miRNAs) has yet to be explored in detail. OBJECTIVES: To identify circulating miRNAs predictive of recurrent VTE or death, and to interpret their mechanistic involvement. METHODS: Data from 181 participants of a cohort study of acute VTE and 302 individuals with a history of VTE from a population-based cohort were investigated. Next-generation sequencing was performed on EDTA plasma samples to detect circulating miRNAs. The endpoint of interest was recurrent VTE or death. Penalized regression was applied to identify an outcome-relevant miRNA signature, and results were validated in the population-based cohort. The involvement of miRNAs in coregulatory networks was assessed using principal component analysis, and the associated clinical and molecular phenotypes were investigated. Mechanistic insights were obtained from target gene and pathway enrichment analyses. RESULTS: A total of 1950 miRNAs were detected across cohorts after postprocessing. In the discovery cohort, 50 miRNAs were associated with recurrent VTE or death (cross-validated C-index, 0.65). A weighted miRNA score predicted outcome over an 8-year follow-up period (HRSD, 2.39; 95% CI, 1.98-2.88; P < .0001). The independent validation cohort validated 20 miRNAs (ORSD for score, 3.47; 95% CI, 2.37-5.07; P < .0001; cross-validated-area under the curve, 0.61). Principal component analysis revealed 5 miRNA networks with distinct relationships to clinical phenotype and outcome. Mapping of target genes indicated regulation via transcription factors and kinases involved in signaling pathways associated with fibrinolysis. CONCLUSION: Circulating miRNAs predicted the risk of recurrence or death after VTE over several years, both in the acute and chronic phases.

Clinical profile and outcome of isolated pulmonary embolism: a systematic review and meta-analysis.

Background: Isolated pulmonary embolism (PE) appears to be associated with a specific clinical profile and sequelae compared to deep vein thrombosis (DVT)-associated PE. The objective of this study was to identify clinical characteristics that discriminate both phenotypes, and to characterize their differences in clinical outcome. Methods: We performed a systematic review and meta-analysis of studies comparing PE phenotypes. A systematic search of the electronic databases PubMed and CENTRAL was conducted, from inception until January 27, 2023. Exclusion criteria were irrelevant content, inability to retrieve the article, language other than English or German, the article comprising a review or case study/series, and inappropriate study design. Data on risk factors, clinical characteristics and clinical endpoints were pooled using random-effects meta-analyses. Findings: Fifty studies with 435,768 PE patients were included. In low risk of bias studies, 30% [95% CI 19-42%, I 2 = 97%] of PE were isolated. The Factor V Leiden [OR: 0.47, 95% CI 0.37-0.58, I 2 = 0%] and prothrombin G20210A mutations [OR: 0.55, 95% CI 0.41-0.75, I 2 = 0%] were significantly less prevalent among patients with isolated PE. Female sex [OR: 1.30, 95% CI 1.17-1.45, I 2 = 79%], recent invasive surgery [OR: 1.31, 95% CI 1.23-1.41, I 2 = 65%], a history of myocardial infarction [OR: 2.07, 95% CI 1.85-2.32, I 2 = 0%], left-sided heart failure [OR: 1.70, 95% CI 1.37-2.10, I 2 = 76%], peripheral artery disease [OR: 1.36, 95% CI 1.31-1.42, I 2 = 0%] and diabetes mellitus [OR: 1.23, 95% CI 1.21-1.25, I 2 = 0%] were significantly more frequently represented among isolated PE patients. In a synthesis of clinical outcome data, the risk of recurrent VTE in isolated PE was half that of DVT-associated PE [RR: 0.55, 95% CI 0.44-0.69, I 2 = 0%], while the risk of arterial thrombosis was nearly 3-fold higher [RR: 2.93, 95% CI 1.43-6.02, I 2 = 0%]. Interpretation: Our findings suggest that isolated PE appears to be a specific entity that may signal a long-term risk of arterial thrombosis. Randomised controlled trials are necessary to establish whether alternative treatment regimens are beneficial for this patient subgroup. Funding: None.

Unsupervised clustering of venous thromboembolism patients by clinical features at presentation identifies novel endotypes that improve prognostic stratification.

BACKGROUND: Individuals with acute venous thromboembolism (VTE) constitute a heterogeneous group of patients with diverse clinical characteristics and outcome. OBJECTIVES: To identify endotypes of individuals with acute VTE based on clinical characteristics at presentation through unsupervised cluster analysis and to evaluate their molecular proteomic profile and clinical outcome. METHODS: Data from 591 individuals from the Genotyping and Molecular phenotyping of Venous thromboembolism (GMP-VTE) project were explored. Hierarchical clustering was applied to 58 variables to define VTE endotypes. Clinical characteristics, three-year incidence of thromboembolic events or death, and acute-phase plasma proteomics were assessed. RESULTS: Four endotypes were identified, exhibiting different patterns of clinical characteristics and clinical course. Endotype 1 (n = 300), comprising older individuals with comorbidities, had the highest incidence of thromboembolic events or death (HR [95 % CI]: 3.76 [1.96-7.19]), followed by endotype 4 (n = 127) (HR [95 % CI]: 2.55 [1.26-5.16]), characterised by men with history of VTE and provoking risk factors, and endotype 3 (n = 57) (HR [95 % CI]: 1.57 [0.63-3.87]), composed of young women with provoking risk factors, vs. reference endotype 2 (n = 107). The reference endotype was constituted by individuals diagnosed with PE without comorbidities, who had the lowest incidence of the investigated endpoint. Differentially expressed proteins associated with the endotypes were related to distinct biological processes, supporting differences in molecular pathophysiology. The endotypes had superior prognostic ability compared to existing risk stratifications such as provoked vs unprovoked VTE and D-dimer levels. CONCLUSION: Four endotypes of VTE were identified by unsupervised phenotype-based clustering that diverge in clinical outcome and plasmatic protein signature. This approach might support the future development of individualized treatment in VTE.

Predictive value for increased activated factor XI activity in acute venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is associated with excessive coagulation activity, which in part can be attributed to activation of contact system. However, the knowledge regarding the impact of contact activation in acute VTE is limited. OBJECTIVE: To unravel the involvement of contact activation in acute VTE. METHODS: Contact activation was investigated in patients with acute VTE (n = 321) and population controls without a history of VTE (n = 300). For comparison, Factor XI(a) levels, activity, and plasma kallikrein (PKa) activity were determined in plasma samples with an activated partial thromboplastin time- or thrombin generation-based assay (free FXI concentration [FXI:c] and calibrated automated thrombogram:FXIa, respectively) and with enzyme-linked immunosorbent assays for enzyme-inhibitor complexes (FXIa:alpha-1-antitrypsin [α1AT], FXIa:antithrombin [AT], FXIa:C1-inhibitor [C1Inh], and PKa:C1-inh). RESULTS: In patients with VTE, higher FXI:c levels (124 ± 37% vs 114 ± 28%), but lower calibrated automated thrombogram:FXIa levels were apparent. This was accompanied by increased FXIa:α1AT, FXIa:AT, and PKa:C1-inh levels in patients compared with controls (312pM [238-424] vs 203pM [144-288]; 29pM [23-38] vs 23pM [20-30]; 1.9nM [1.2-4.7] vs 1.4nM [0.7-3.5], respectively), whereas FXIa:C1-inh levels did not differ. Logistic regression models showed good discriminatory values for FXI:c and FXIa:α1AT (area under the curve = 0.64 [0.6/0.69] and 0.73 [0.69/0.77], respectively). After a 2-year follow-up, 81 recurrent VTE events or deaths occurred in the patient cohort, for which the baseline levels of FXIa:α1AT and FXIa:C1Inh had a significant prognostic value (Hazard ratios per SD [95% CI], 1.26 [1.10-1.45]; p =.0012 and 1.19 [1.05-1.36]; p =.0082, respectively). CONCLUSION: Our study revealed elevated FXIa levels and activity in acute VTE, which was also associated with recurrent VTE, suggesting an important risk contribution of FXI activation to VTE. The evidence provided by this study supports the utility of FXIa inhibition in the setting of acute VTE.

Residual Venous Obstruction as an Indicator of Clinical Outcomes following Deep Vein Thrombosis: A Management Study.

BACKGROUND: Residual venous obstruction (RVO) is considered a risk factor of recurrence and possibly other clinical outcomes following deep vein thrombosis (DVT). Current guidelines do not support an RVO-tailored duration of anticoagulant therapy; contemporary data of such management strategies are scarce. We aimed to evaluate an RVO-based management strategy and to assess associations of RVO with recurrence, post-thrombotic syndrome (PTS), arterial events and cancer. To gain further insight, D-dimer levels were measured 1 month after stopping anticoagulant therapy. METHODS: Consecutive patients with symptomatic, proximal DVT were treated in a 2-year clinical care pathway (CCP) at Maastricht University Medical Center and were followed up to 5 years. RVO was assessed at the end of regular duration of anticoagulant therapy, which was extended once if RVO was detected. The study was approved by the medical ethics committee. RESULT: From a total of 825 patients, 804 patients (97.5%) completed the CCP and 755 (93.9%) were available for extended follow-up. Most patients (76.5%) stopped anticoagulant therapy. Incidence rates of recurrence, PTS, arterial events, and cancer were 4.4, 11.9, 1.7, and 1.8 per 100 patient-years, respectively. RVO was independently associated with PTS (hazard ratio [HR]: 1.66 [1.19-2.32]) and arterial events (HR: 2.07 [1.18-3.65]), but not with recurrence or cancer. High D-dimer was associated with recurrence (HR: 3.51 [2.24-5.48]). CONCLUSION: Our RVO-based management strategy might have attenuated the association of RVO with recurrence. In addition, RVO identified patients at increased risk of PTS and arterial events, which might be used to identify patients in need of alternative treatment strategies.

Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.

The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The "coagulome" as a critical driver of cardiovascular disease. Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow, and kidney. Four investigators shared their views on these organ-specific topics. Theme 2: Novel mechanisms of thrombosis. Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbiome status. Virus infection-associated coagulopathies perturb the hemostatic balance resulting in thrombosis and/or bleeding. Theme 3: How to limit bleeding risks: insights from translational studies. This theme included state-of-the-art methodology for exploring the contribution of genetic determinants of a bleeding diathesis; determination of polymorphisms in genes that control the rate of metabolism by the liver of P2Y12 inhibitors, to improve safety of antithrombotic therapy. Novel reversal agents for direct oral anticoagulants are discussed. Theme 4: Hemostasis in extracorporeal systems: the value and limitations of ex vivo models. Perfusion flow chamber and nanotechnology developments are developed for studying bleeding and thrombosis tendencies. Vascularized organoids are utilized for disease modeling and drug development studies. Strategies for tackling extracorporeal membrane oxygenation-associated coagulopathy are discussed. Theme 5: Clinical dilemmas in thrombosis and antithrombotic management. Plenary presentations addressed controversial areas, i.e., thrombophilia testing, thrombosis risk assessment in hemophilia, novel antiplatelet strategies, and clinically tested factor XI(a) inhibitors, both possibly with reduced bleeding risk. Finally, COVID-19-associated coagulopathy is revisited.

Exploring phenotypes of deep vein thrombosis in relation to clinical outcomes beyond recurrence.

BACKGROUND: Deep vein thrombosis (DVT) is a multifactorial disease with several outcomes, but current classifications solely stratify it based on recurrence risk. OBJECTIVES: We aimed to identify DVT phenotypes and assess their relation to recurrent venous thromboembolism (VTE), postthrombotic syndrome, arterial events, and cancer. PATIENTS/METHODS: Hierarchical clustering was performed on a DVT cohort with a follow-up of up to 5 years using 23 baseline characteristics. Phenotypes were summarized by discriminative characteristics. Hazard ratios (HRs) were calculated using Cox regression; the recurrence risk was adjusted for the anticoagulant therapy duration. The study was carried out in accordance with the Declaration of Helsinki and approved by the medical ethics committee. RESULTS: In total, 825 patients were clustered into 4 phenotypes: 1. women using estrogen therapy (n = 112); 2. patients with a cardiovascular risk profile (n = 268); 3. patients with previous VTE (n = 128); and 4. patients without discriminant characteristics (n = 317). Overall, the risks of recurrence, postthrombotic syndrome, arterial events, and cancer were low in phenotype 1 (reference), intermediate in phenotype 4 (HR: 4.6, 1.2, 2.2, 1.8), and high in phenotypes 2 (HR: 6.1, 1.6, 4.5, 2.9) and 3 (HR: 5.7, 2.5, 2.3, 3.7). CONCLUSIONS: This study identified 4 distinct phenotypes among patients with DVT that are not only associated with the increasing recurrence risk but also with outcomes beyond recurrence. Our results thereby highlight the limitations of current risk stratifications that stratify based on the predictors of the recurrence risk only. Overall, risks were lowest in women using estrogen therapy and highest in patients with a cardiovascular risk profile. These findings might inform a more personalized approach to clinical management.

Impaired pulmonary and muscle function during moderate exercise in female patients recovered from SARS-CoV-2.

This study aimed to assess pulmonary and muscle dysfunction by analyzing the slow component of oxygen uptake (VO2SC), and mechanical and ventilatory efficiency in adult women recovered from the severe acute respiratory syndrome coronavirus type II (SARS-CoV-2) during a constant load test. 32 women (N = 17 patients with SARS-CoV-2; N = 15 control group) performed two cardiopulmonary exercise tests (CPX) on a cycle ergometer. In the first test, the participants performed incremental CPX until extenuation. In the second test the participants performed a 10-min CPX at a constant load intensity (watts) corresponding to the first ventilatory threshold. There was a 48-72 h rest period between the two tests. There was a significant increase in the VO2SC in the patients recovered from SARS-CoV-2 (160.4 ± 60 mL min-1) in comparison with the healthy participants (59.6 ± 65 mL min-1) (P < 0.001). Mechanical efficiency significantly decreased in patients recovered from SARS-CoV-2 compared to the control group (P = 0.04). Ventilatory inefficiency significantly increased in the patients recovered from SARS-CoV-2 compared with the control group (P < 0.001). Adult women recovered from SARS-CoV-2 infection have important pulmonary and muscular dysfunction and fatigue which contributes to increasing the VO2SC and reducing mechanical and ventilatory efficiency during mild-moderate exercise at a constant load.

Atypical Mycobacteriosis Due to Mycobacterium abscessus subsp. massiliense: Our Experince.

BACKGROUND: Members of Micobacterium. abscessus complex comprises three subspecies (M. abscessus subsp. Abscessus, M. abscessus subsp. Bolletii, and M. abscessus subsp. Massiliense) and are a rapid-growing nontuberculous mycobacteria present in different aquatic habitats and soil. It often causes a wide spectrum of infections involving pulmonary infections, surgical wound infections, and infections related to mesotherapy, catheters, hemodialysis devices, endocarditis, and disseminated infections in immunocompromised individuals. METHODS: In this article we comment on the most relevant aspects of nine patients with skin lesions caused by M. abscessus subsp. massiliense infection. Clinical characteristics, histopathology, and molecular identification were performed. RESULTS: The patients in the clinical cases presented a history of trauma, tattoos, and physical therapy techniques. The most common treatments were minocycline and clindamycin, doxycycline, ceftriaxone, cephalexin, moxifloxacin, rifampicin, and trimethoprim-sulfamethoxazole. The evolution of the treated patients was acceptable, except for one patient, who showed a partial improvement. M. massiliense were identified in all clinical cases using a species-specific PCR. CONCLUSION: Our series consisted of nine cases of skin biopsies recorded in different years; for this reason, we do not have all the data necessary for a complete description, in particular in four cases, causing limitations in the manuscript, especially in the therapy used and the evolution of patients due to lack of follow-up.

Hipoplasia del lóbulo hepático izquierdo asintomático, hallazgo transquirúrgico, tomográfico y patológico. Presentación de una rara entidad / Asymptomatic Hypoplasia of the Left Hepatic Lobe: Surgical Tomographic and Pathological Findings. Presentation of a Rare Entity

Resumen Antecedentes Las anomalías de la morfología hepática son raras, y se dividen en 2 categorías: las que resultan del desarrollo excesivo de tejido hepático, como el lóbulo de Riedel y otros lóbulos accesorios, y las de desarrollo deficiente del hígado, que incluyen agenesia, hipoplasia y aplasia de los lóbulos hepáticos. Presentación del caso Paciente del sexo masculino de 57 años de edad, sometido a plastia inguinal laparoscópica programada, donde se dio el hallazgo de hipoplasia hepática. Conclusión La hipoplasia hepática es poco frecuente, no presenta síntomas, ni repercusiones clínicas a largo plazo, suele ser un hallazgo incidental durante un estudio de imagen o durante un procedimiento quirúrgico abdominal.

Abstract Background: Abnormalities of liver morphology are rare, divided into two categories: those resulting from overgrowth of liver tissue, such as the Riedel lobe and other accessory lobes, and those with poor liver development include agenesis, hypoplasia and aplasia of the hepatic lobes. Presentation of the case 57-year-old man, subjected to laparoscopic programmed inguinal surgery, finding liver hypoplasia. Conclusions Hepatic hypoplasia is rare, has no symptoms or long-term clinical repercussions, is usually an incidental finding during an imaging study or during an abdominal surgical procedure.

A Glasgow-Blatchford Bleeding Score of >2 Is a Poor Predictor of Endoscopic Intervention in Nonvariceal Upper GI Bleeding.

OBJECTIVES: Recent data show that a Glasgow-Blatchford Bleeding Score (GBS) >2 does not identify patients with upper gastrointestinal (GI) bleeding who benefit from inpatient esophagogastroduodenoscopy (EGD). This study aimed to determine the rate of endoscopic hemostatic interventions (HI) in patients with nonvariceal acute GI bleeding (NVAUGIB) admitted with a GBS >2. Secondary aims included comparison of clinical outcomes in patients with and without HI and cost of nontherapeutic EGDs. METHODS: We conducted a retrospective review of medical records of patients admitted to a referral hospital for NVAUGIB from January 2015 to December 2017. Mortality, blood transfusion rates, length of stay, length of intensive care unit stay, and cost of a nontherapeutic EGD were outcomes of interest. Patients 18 years of age and older of both sexes were included. The accuracy of the GBS >2 cutoff was determined using receiver operating characteristic curve analysis. RESULTS: A total of 357 patients were included and only 58 (16.2%) required HI. The area under the curve for GBS >2 as a predictor of HI was 0.57. The performance of HI did not influence mortality (P = 0.33), blood transfusion rates (P = 0.51), length of stay (P = 0.2), or length of intensive care unit stay (P = 0.36). The estimated cost of performing nontherapeutic EGD was approximately $855,000 for the 299 patients who did not need HI. CONCLUSIONS: A GBS cutoff of >2 is not an accurate criterion to triage patients with NVAUGIB for inpatient emergent EGD. More clinically meaningful and cost-effective methods to triage these patients are necessary.

A Comparative Mini-Review on Transition Metal Oxides Applied for the Selective Catalytic Ammonia Oxidation (NH3-SCO).

The selective catalytic oxidation of NH3 (NH3-SCO) into N2 and H2O is an efficient technology for NH3 abatement in diesel vehicles. However, the catalysts dedicated to NH3-SCO are still under development. One of the groups of such catalysts constituted transition metal-based catalysts, including hydrotalcite-derived mixed metal oxides. This class of materials is characterized by tailored composition, homogenously dispersed mixed metal oxides, exhibiting high specific surface area and thermal stability. Thus, firstly, we give a short introduction to the structure and composition of hydrotalcite-like materials and their applications in NH3-SCO. Secondly, an overview of other transition metal-based catalysts reported in the literature is given, following a comparison of both groups. The challenges in NH3-SCO applications are provided, while the reaction mechanisms are discussed for particular systems.

Association of FXI activity with thrombo-inflammation, extracellular matrix, lipid metabolism and apoptosis in venous thrombosis.

Animal experiments and early phase human trials suggest that inhibition of factor XIa (FXIa) safely prevents venous thromboembolism (VTE), and specific murine models of sepsis have shown potential efficacy in alleviating cytokine storm. These latter findings support the role of FXI beyond coagulation. Here, we combine targeted proteomics, machine learning and bioinformatics, to discover associations between FXI activity (FXI:C) and the plasma protein profile of patients with VTE. FXI:C was measured with a modified activated partial prothrombin time (APTT) clotting time assay. Proximity extension assay-based protein profiling was performed on plasma collected from subjects from the Genotyping and Molecular Phenotyping of Venous Thromboembolism (GMP-VTE) Project, collected during an acute VTE event (n = 549) and 12-months after (n = 187). Among 444 proteins investigated, N = 21 and N = 66 were associated with FXI:C during the acute VTE event and at 12 months follow-up, respectively. Seven proteins were identified as FXI:C-associated at both time points. These FXI-related proteins were enriched in immune pathways related to causes of thrombo-inflammation, extracellular matrix interaction, lipid metabolism, and apoptosis. The results of this study offer important new avenues for future research into the multiple properties of FXI, which are of high clinical interest given the current development of FXI inhibitors.