Gut microbiota exerts a crucial role in gastrointestinal (GI) and extra-intestinal (EI) disorders. In this context, Akkermansia muciniphila is pivotal for the maintenance of host health and has been ...correlated with several disorders.
To explore the potential role of A. muciniphila as common dysbiotic marker linked to the disease status.
A cohort of patients affected by GI and EI disorders was enrolled and compared to healthy controls (CTRLs). A targeted-metagenomics approach combined to unsupervised cluster and machine learning (ML) analyses provided microbiota signatures.
Microbiota composition was associated to disease phenotype, therapies, diet and anthropometric features, identifying phenotype and therapies as the most impacting variables on microbiota ecology. Unsupervised cluster analyses identified one cluster composed by the majority of patients. DESeq2 algorithm identified ten microbial discriminatory features of patients and CTRLs clusters. Among these microbes, Akkermansia muciniphila resulted the discriminating ML node between patients and CTRLs, independently of specific GI/EI disease or confounding effects. A. muciniphila decrease represented a transversal signature of gut microbiota alteration, showing also an inverse correlation with α-diversity.
Overall, A. muciniphila decline may have a crucial role in affecting microbial ecology and in discriminating patients from healthy subjects. Its grading may be considered as a gut dysbiosis feature associated to disease-related microbiota profile.
Abstract Background The diagnosis and treatment of disseminated intravascular coagulation (DIC) remain extremely controversial. Purpose The Italian Society for Thrombosis and Haemostasis commissioned ...a project to develop clinical practice guidelines for the diagnosis and treatment of DIC. Methods Key questions about the diagnosis and treatment of DIC were formulated by a multidisciplinary working group consisting of experts in clinical medicine and research. After a systematic review and discussion of the literature, recommendations were formulated and graded according to the supporting evidence. In the absence of evidence, evidence of low quality, or contradictory evidence, a formal consensus method was used to issue clinical recommendations. Results and Conclusions In suspected DIC, we suggest the use of the diagnostic scores ISTH (grade C), JMHW (grade C) or JAAM (grade D) over stand alone tests. The cornerstone of the management of DIC remains the treatment of the underlying triggering disease. We do not suggest the use of antithrombin (grade D), dermatan sulphate (grade D), gabexate (grade D), recombinant factor VIIa (grade D), activated protein C (grade D), thrombomodulin (grade B). The use of unfractionated heparin or low-molecular-weight heparin is not suggested except for thromboembombolic prophylaxis in patients a high risk who do not have active bleeding (grade D). In patients with severe sepsis/septic shock and DIC we suggest the use of human recombinant activated protein C (grade D). In patients with DIC and active bleeding we suggest the use of transfusion therapy (platelets, plasma, cryoprecipitate) (grade D).
The current interest in recombinant factor VIII (rFVIII) products stems from the fact that they offer a technological solution to prolonging the half-life of and reducing the risk of formation of ...alloantibodies (inhibitors) against FVIII in treated patients with hemophilia A (HA). The Italian health care system has authorized the use of a wide range of rFVIII concentrates of the first, second, and third generation, as well as new innovative rFVIII preparates with an extended half-life (EHL) (Kogenate FS®-Bayer, belonging to the second generation and replaced since 2017 by a product consisting of the same modified molecule; because it is only available until the end of the current year, it will not be considered in this review). Some of these products have unique pharmacodynamic and pharmacokinetic (PK) profiles, including an EHL. The first-generation full-length rFVIII (FL-rFVIII), octocog alfa (Recombinate® Baxter/BIOVIIIx), although the oldest rFVIII product, has several desirable features. Third-generation products include two modified octocog alfa molecules (Advate®, Shire; Kovaltry®, Bayer) as well as the B domain-deleted rFVIII (BDD-rFVIII) moroctocog alfa (ReFacto®-Pfizer). The B domain-truncated (BDT-rFVIII) turoctocog alfa (NovoEight®, Novo Nordisk), the BDD-rFVIII simoctocog alfa (Nuwiq®, Kedrion), the single-chain BDT-rVIII lonoctocog alfa (Afstyla®, CSL Behring), and the BDD-rFVIIIFc efmoroctocog alfa (Elocta®, Sobi-Biogen) are new, innovative products. Simoctocog alfa, because its peculiarities, is considered a fourth-generation rFVIII concentrate. Turoctocog alfa, simoctocog alfa, and lonoctocog alfa have a high affinity for von Willebrand factor (vWF) that reduces renal clearance and prolongs the half-life of rFVIII. Efmoroctocog alfa, a first-in-class rFVIII-Fc fusion protein (rFVIIIFc), has a half-life 1.5-1.8 times longer than that of conventional plasma-derived FVIII (pd-rFVIII) and other rFVIII products. Clinical studies have evaluated the efficacy, safety, and inhibitor development of all these innovative concentrates in both previously treated (PTPs) and untreated patients (PUPs). This review considers the rFVIII products that are indicated for the treatment of patients with severe HA, focusing on those that are commercially available in Italy. Their PK characteristics, immunogenicity, and clinical benefits are discussed and compared.
The health-related quality of life (HRQoL) of people with hemophilia (PWH) is an important issue, especially considering people suffering from chronic diseases beyond hemophilia. The principal aim of ...this study was to investigate the presence and relevance of psychological symptoms, both internalizing and externalizing, lifestyle, and HRQoL in a group of Italian PWH with chronic bloodborne co-infections and comorbidities. Furthermore, the research describes the association between psychological aspects and the impact of disease-related characteristics (type of hemophilia, presence of co-infections, and comorbidities) on them.
Seventy patients (mean age 46.77±11.3), 64 with severe hemophilia A (Factor VIII: C < 1 IU/dL) and 6 with severe hemophilia B (Factor IX <1 IU/dL), were consecutively recruited from seven Hemophilia Centers in Italy of Italian Association of Hemophilia Centers (AICE). In order to assess psychological symptoms, HRQoL, and lifestyle, three psychological questionnaires were administered (the SCL-90-R, SF-36, and PSQ, respectively).
A general decline in the quality of life and an increase in the tendency to adopt a lifestyle characterized by hyperactivity emerged. Inverse correlations were found between HRQoL and psychological distress. Although the SCL-90-R did not reveal symptoms above the clinical cut-off, co-infections significantly increased anxiety, depression, somatizations, paranoia, and social withdrawal. Lastly, HRQoL is impaired by co-infections as well as comorbidities.
Our preliminary results must be confirmed to deepen the findings between mental health and hemophilia.
Evidence from clinical trials shows rivaroxaban to be effective for the treatment of deep vein thrombosis. Switching to rivaroxaban following failure of indirect anticoagulants in deep vein ...thrombosis has not been demonstrated in a real-life setting.
A 43-year-old white woman was switched from warfarin to rivaroxaban for the treatment of thrombosis of her right common femoral vein after saphenectomy. The reason for the switch was due to the instability of anti-coagulation therapy with vitamin K antagonists over a period of 3 months during which she did not reach the "therapeutic range" of prothrombin time-international normalized ratio. The ineffectiveness of the conventional oral anticoagulant was confirmed by persistence of moderate-high values of fibrin D dimers (780 ng/ml) and by residual vein thrombosis at an ultrasound examination. Objectively, her right leg appeared to be still edematous and warm and pain was elicited by deep palpation. Rivaroxaban was administered after warfarin discontinuation (prothrombin time-international normalized ratio = 1.43) at a dosage of 15 mg every 12 hours for 3 weeks, followed by 20 mg once daily for 3 months. After this period, her objective symptoms significantly improved, with reduction of edema of her lower limb and pain relief. Her fibrin D dimer values returned to normal (210 ng/ml). An ultrasound showed recanalization of the obstructed venous segment.
In this case report, a switch to rivaroxaban from warfarin was shown to be effective and safe for the treatment of postoperative deep vein thrombosis, whereas standard oral anticoagulation therapy, which required dose adjustments over a period of 3 months, was not able to stabilize the therapeutic range of prothrombin time-international normalized ratio nor improve our patient's outcome.
Analyses of the bleeding tendency by means of the bleeding score (BS) have been proposed until now to confirm diagnosis but not to predict clinical outcomes in patients with inherited von Willebrand ...disease (VWD). We prospectively followed up, for 1 year, 796 Italian patients with different types of VWD to determine whether the previous BS of European VWD1 is useful to predict the occurrence of spontaneous bleeds severe enough to require replacement therapy with desmopressin (DDAVP) and/or von Willebrand factor (VWF)/factor VIII concentrates. Among the 796 patients included, 75 (9.4%) needed treatment of 232 spontaneous bleeding events. BS >10 and VWF:ristocetin cofactor activity <10 U/dL were associated with the risk of bleeding, but only a BS >10 remained highly associated in a multivariable Cox proportional hazard model (adjusted hazard ratio: 7.27 95% confidence interval, 3.83-13.83). Although the bleeding event-free survival was different in VWD types, only a BS >10 could predict for each type which patient had bleeding events severe enough to require treatment with DDAVP and/or concentrates. Therefore, BS can be considered a simple predictor of clinical outcomes of VWD and may identify patients needing intensive therapeutic regimens.
•The bleeding score helps to predict clinical outcomes in adult patients with von Willebrand disease.•High bleeding scores correlate with intensive on-demand therapy and may identify cases requiring regular prophylaxis.
Direct oral anticoagulants (DOAC) have been shown to be non-inferior to traditional vitamin K antagonists in preventing stroke and arterial thromboembolism in patients with non-valvular atrial ...fibrillation. Nevertheless, it is mandatory to record side effects and individual adherence to DOAC treatment.
In this single-centre experience, patients with non-valvular atrial fibrillation were prospectively observed after switching from a vitamin K antagonist to dabigatran or rivaroxaban. The efficacy, safety, and tolerability of the novel treatment, and adherence to it, were evaluated over a period of 1 year. Clinical data were integrated with records of haemorrhagic and non-haemorrhagic complications. All the subjects were given an anonymous self-report questionnaire on the degree of their adherence/satisfaction with the treatment.
Of 196 patients with non-valvular atrial fibrillation (median age, 78.5 years) who switched from a vitamin K antagonist to DOAC, 178 completed the 1-year follow up, of whom 87 were given dabigatran and 91 rivaroxaban. The efficacy of the two DOAC was similar. Patients given dabigatran had a higher frequency (n=32) of non-haemorrhagic complications (OR: 3.3; 95% CI: 1.7-7.8), which occurred earlier (HR: 6.1; 95% CI: 3.0-12.6) than those (n=7) recorded in subjects on rivaroxaban. The degree of satisfaction with therapy was higher among patients on rivaroxaban (mean score 9.1, SD 1.0) than among those on dabigatran (mean score 8.7; SD 0.9; p=0.01).
Overall, in this experience, DOAC were shown to be effective, safe alternatives to vitamin K antagonists. Nevertheless, compared with rivaroxaban, dabigatran resulted in a higher rate and earlier occurrence of non-haemorrhagic events, and a lower satisfaction score.
As meticulously observed and recorded by Darwin, the leaves of the carnivorous plant Drosera capensis L. slowly fold around insects trapped on their sticky surface in order to ensure their digestion. ...While the biochemical signaling driving leaf closure has been associated with plant growth hormones, how mechanical forces actuate the process is still unknown. Here, we combine experimental tests of leaf mechanics with quantitative measurements of the leaf microstructure and biochemistry to demonstrate that the closure mechanism is programmed into the cellular architecture of D. capensis leaves, which converts a homogeneous biochemical signal into an asymmetric response. Inspired by the leaf closure mechanism, we devise and test a mechanical metamaterial, which curls under homogeneous mechanical stimuli. This kind of metamaterial could find possible applications as a component in soft robotics and provides an example of bioinspired design.
The comparative effectiveness of treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or their combination in people with albuminuria and ...cardiovascular risk factors is unclear.
In a multicenter, randomized, open label, blinded end point trial, we evaluated the effectiveness on cardiovascular events of ACE or ARB monotherapy or combination therapy, targeting BP<130/80 in patients with moderate or severe albuminuria and diabetes or other cardiovascular risk factors. End points included a primary composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for cardiovascular causes and a revised end point of all-cause mortality. Additional end points included ESRD, doubling of serum creatinine, albuminuria, eGFR, BP, and adverse events.
Because of slow enrollment, the trial was modified and stopped 41% short of targeted enrollment of 2100 participants, corresponding to 35% power to detect a 25% reduced risk in the primary outcome. Our analysis included 1243 adults, with median follow-up of 2.7 years. Efficacy outcomes were similar between groups (ACE inhibitor versus ARB, ACE inhibitor versus combination, ARB versus combination) as were rates of serious adverse events. The rate of permanent discontinuation for ARB monotherapy (6.3%) was significantly lower than for ACE inhibitor monotherapy (15.7%) or combined therapy (18.3%).
Patients may tolerate ARB monotherapy better than ACE inhibitor monotherapy. However, data from this trial and similar trials, although as yet inconclusive, show no trend suggesting differences in mortality and renal outcomes with ACE inhibitors or ARBs as dual or monotherapy in patients with albuminuria and diabetes or other cardiovascular risk factors.
Background: The health-related quality of life (HRQoL) of people with hemophilia (PWH) is an important issue, especially considering people suffering from chronic diseases beyond hemophilia. The ...principal aim of this study was to investigate the presence and relevance of psychological symptoms, both internalizing and externalizing, lifestyle, and HRQoL in a group of Italian PWH with chronic bloodborne co-infections and comorbidities. Furthermore, the research describes the association between psychological aspects and the impact of disease-related characteristics (type of hemophilia, presence of co-infections, and comorbidities) on them.
Methods: Seventy patients (mean age 46.77±11.3), 64 with severe hemophilia A (Factor VIII: C < 1 IU/dL) and 6 with severe hemophilia B (Factor IX <1 IU/dL), were consecutively recruited from seven Hemophilia Centers in Italy of Italian Association of Hemophilia Centers (AICE). In order to assess psychological symptoms, HRQoL, and lifestyle, three psychological questionnaires were administered (the SCL-90-R, SF-36, and PSQ, respectively).
Results: A general decline in the quality of life and an increase in the tendency to adopt a lifestyle characterized by hyperactivity emerged. Inverse correlations were found between HRQoL and psychological distress. Although the SCL-90-R did not reveal symptoms above the clinical cut-off, co-infections significantly increased anxiety, depression, somatizations, paranoia, and social withdrawal. Lastly, HRQoL is impaired by co-infections as well as comorbidities.
Conclusion: Our preliminary results must be confirmed to deepen the findings between mental health and hemophilia.
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