Search

Background: Type 3 von Willebrand disease (VWD) is the most severe form of this disease owing to the almost complete deficiency of von Willebrand factor (VWF). Replacement therapy with plasma-derived products containing VWF or recombinant VWF rarely cause the development of alloantibodies against VWF that may be accompanied by anaphylactic reactions. Objective: The objective of this study was to assess the prevalence of anti-VWF alloantibodies in subjects with type 3 VWD enrolled in the 3WINTERS-IPS. Methods: An indirect in-house enzyme-linked immunosorbent assay has been used to test all the alloantibodies against VWF. Neutralizing antibodies (inhibitors) have been tested with a Bethesda-based method by using a VWF collagen binding (VWF:CB) assay. Samples positive for anti-VWF antibodies were further tested with Bethesda-based methods by using the semiautomated gain-of-function glycoprotein-Ib binding (VWF:GPIbM) and a VWF antigen (VWF:Ag) enzyme-linked immunosorbent assay. Results: In total, 18 of the 213 (8.4%) subjects tested positive for anti-VWF antibodies and 13 of 213 (6%) had VWF:CB inhibitors. These 13 were among the 18 with anti-VWF antibodies. Of the 5 without VWF:CB inhibitors, 3 had non-neutralizing antibodies, 1 only inhibitor against VWF:GPIbM, and one could not be tested further. Ten of the 13 subjects with VWF:CB inhibitors also had VWF:GPIbM inhibitors, 6 of whom also had VWF:Ag inhibitors. Subjects with inhibitors were homozygous for VWF null alleles (11/14), homozygous for a missense variant (1/14), or partially characterized (2/14). Conclusions: Anti-VWF antibodies were found in 8.4% of subjects with type 3 VWD, whereas neutralizing VWF inhibitors were found in 6%, mainly in subjects homozygous for VWF null alleles. Because inhibitors may be directed toward different VWF epitopes, their detection is dependent on the assay used.

Introduction: Factor IX replacement therapy is used for treatment and prophylaxis of bleeding in haemophilia B. rIX-FP is an extended half-life albumin-fusion protein, which, in clinical studies, has demonstrated prolonged dosing intervals up to 21 days for routine prophylaxis, providing therapeutic benefit.Aims: To describe dosing frequency and consumption (primary endpoint), efficacy and safety of rIX-FP treatment during routine clinical practice in Italy.Methods: Patients with moderate/severe haemophilia B on prophylaxis with rIX-FP for >= 6 months, were enrolled in this observational study from October 2017 to February 2019 and followed-up for 2 years. Descriptive analysis included prospective and retrospective data (12 months prior to switching to rIX-FP).Results: Data were collected from 59 male patients (median age 30.1 years) enrolled by 23 Italian centres. Of them, 50 were on prophylaxis during the entire observation period and completed the study. The infusion frequency changed from 2-3 times/week in 86.0% of patients with previous treatment, to less than once a week in 84.0% of patients treated with rIX-FP at the 2nd-year fol low-up. The annual number of infusions decreased by about 70%, whereas the mean FIX activity trough level increased from 3.8% to 14.4% (mean > 10% in all the infusion regimens). Median Annualised Bleeding Rate of .0 was achieved across all prophylaxis regimens. Subjects with zero bleedings increased from 66.0% to 78.0% with rIX-FP.Conclusion: Treatment with rIX-FP reduced infusion frequency, while providing higher FIX trough levels with substantial benefit in terms of annualised bleeding rate and a good safety profile.

BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population. ispartof: THROMBOSIS RESEARCH vol:222 pages:31-39 ispartof: location:United States status: published

In this paper, based on fieldwork and herbaria surveys, new data concerning the presence of 32 native and alien vascular species for Sicily (Italy) are provided. Among the native species, the occurrence of the following taxa is reported for the first time or confirmed after many decades of non-observation: Aira multiculmis, Arum maculatum, Carex flacca subsp. flacca, Mentha longifolia, Oxybasis chenopodioides, Najas minor and Xiphion junceum. Furthermore, we document the presence of three native species (Cornus mas, Juncus foliosus and Limonium avei) that, despite being repeatedly observed in Sicily and reported in the literature, are inexplicably omitted by the most recent authoritative checklists regarding the flora of Italy. Finally, fifteen alien species new to Sicily (including one new to Europe, i.e., Pyrus betulifolia) are reported and seven poorly documented allochthonous taxa are confirmed for the island, and for two of them, a status change is proposed. These new or confirmed records allow us to better define the European and national distribution of the targeted taxa and offer new insights on the native and alien flora of Sicily.

To evaluate the neurovascular bundle preservation grades during robotic-assisted radical prostatectomy and compared to the trifecta combined outcome (oncologic control, continence, and sexual function) twelve months after the surgery.Cohort of patients who underwent nerve-sparing robotic-assisted radical prostatectomy had the neurovascular bundle preservation retrospectively graded from 0 to 8 according to the Hopkins subjective visual classification. Patients then were divided into two groups, according to the median of nerve-sparing grading: those with score six or high and those with score less than six. Main outcome was the trifecta combined outcome and secondary outcomes was the individual trifecta criteria (prospective analysis). A secondary analysis with groups divided according to pre-operatory SHIM score was made.One hundred robotic-assisted nerve-sparing radical prostatectomy were performed, of which 83 were included. There were 53 patients with grading greater than or equal to six (group 1) and 30 patients less than six (group 2). 66.6% patients (35/53) in group 1 had a trifecta combined outcome of compared to 33.3% (10/30) in group 2 (p = 0.017). Individually, the erectile function was higher in group 1 (73.6%) compared to group 2 (46.7%) (p = 0.014). Both the results of the combined endpoint trifecta and erection were also maintained in the group with preoperative SHIM ≥ 17.The grading of preservation of the neurovascular bundle in radical prostatectomy is related to a better combined trifecta outcome one year after surgery.

A 4-month-old male Himalayan cat presented with clinical signs of acute lethargy and motor incoordination after being treated with amitraz for parasite control. On clinical examination, the patient was lethargic and ataxic with severe pulicosis, hypothermia, pale mucous membranes, bradycardia, weak femoral pulses, hyperglycemia, and bilateral mydriasis. Blood tests revealed non-regenerative hypochromic microcytic anemia. Serum alanine levels were elevated tenfold. The patient received supportive treatment with atipamezole (an α2-adrenergic antagonist) at a dose of 0.1 mg/kg intramuscularly. After 24 h of hospitalization and constant monitoring, the patient recovered and was discharged. The published literature showed that the active ingredient amitraz is effective in the treatment of some parasitic diseases in cats, such as scabies and demodicosis; therefore, it is still used for this purpose. Given the small therapeutic margin of this insecticide, veterinarians should caution owners about its potential toxicity. This report emphasized the significance of amitraz intoxication in feline species and the success of the treatment, which should be initiated in the first hour after intoxication. RESUMO: Um gato da raça Himalaia, macho, com quatro meses de idade, apresentou sinais clínicos de letargia aguda e incoordenação motora após ser medicado com amitraz para controle de parasitas. No exame clínico, o paciente se apresentava letárgico e atáxico, com pulicose grave, hipotermia, mucosaspálidas, bradicardia, pulso femoral fraco, hiperglicemia e midríase bilateral. O exame de sangue revelou anemia microcítica hipocrômica não regenerativa. Os níveis séricos de ALT estavam 10x elevados. O paciente recebeu tratamento de suporte e administração de atipamezol (antagonista α2-adrenérgico) na dose de 0,1 mg/kg por via intramuscular. Após 24 horas de internação e acompanhamento constante, o paciente se recuperou e recebeu alta. Dados publicados na literatura demonstram que o princípio ativo amitraz é eficaz no tratamento de algumas doenças parasitárias em gatos como sarna e demodicose e, portanto, ainda é utilizado para esta finalidade. Dada a pequena margem terapêutica deste inseticida, os veterinários devem informar os proprietários sobre o seu potencial de toxicidade. O objetivo deste relato é enfatizar a importância da intoxicação por amitraz na espécie felina e o sucesso do tratamento, que deve ocorrer nas primeiras horas após a intoxicação.

Background and Aims Patients with inflammatory bowel disease [IBD] have an attenuated response to initial COVID-19 vaccination. We sought to characterize the impact of IBD and its treatment on responses after the third vaccine against SARS-CoV-2. Methods This was a prospective multicentre observational study of patients with IBD [n = 202] and healthy controls [HC, n = 92]. Serological response to vaccination was assessed by quantification of anti-spike protein [SP] immunoglobulin [Ig]G levels [anti-SPIgG] and in vitro neutralization of binding to angiotensin-converting enzyme 2 [ACE2]. Peripheral blood B-cell phenotype populations were assessed by flow cytometry. SARS-CoV-2 antigen-specific B-cell responses were assessed in ex vivo culture. Results Median anti-SP IgG post-third vaccination in our IBD cohort was significantly lower than HCs [7862 vs 19 622 AU/mL, p Conclusions Patients with IBD have an attenuated response to three doses of SARS-CoV-2 vaccine. Physicians should consider patients with higher anti-TNF drug levels and/or zinc deficiency as potentially at higher risk of attenuated response to vaccination.

Adelaide Ristori was among the first actresses to build an iconic image of herself, which spread internationally since her Parisian debut in 1855. Aware of the importance of photography, she did not hesitate to be portrayed by the most important photographers. Ristori thus entered the pantheon of illustrious people, known throughout Europe and beyond its borders. Her portraits in carte de visite format quickly integrated into the circuit of the press, establishing a complex relationship with pre-existing graphic techniques, such as engraving. The article analyses the progressive diffusion of Adelaide Ristori’s photographs, focusing in particular on the carte de visite format and on newspapers. The corpus includes three photographs of the actress kept at the Bibliothèque Nationale de France (BNF): a portrait by August Bertsch and two cartes de visite by André Adolphe Eugène Disdéri and Étienne Carjat. What image of the actress do these pictures convey? How do press, graphic arts and photography interact in creating the iconic image of the actress?

In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records, confirmations, exclusions, and status changes for Italy or for Italian administrative regions. Nomenclatural and distribution updates published elsewhere are provided as Suppl. material 1.

Esplorando dal punto di vista storico, antropologico e artistico l'incredibile successo e diffusione del motivo della Madonna Lactans, il presente scritto si propone di indagare le dinamiche politiche associate al motivo stesso e alla devozione ad esso correlata. Il motivo è un utile punto di accesso per indagare quali orizzonti simbolici, soprattutto legati alla corporeità, vengano attivati nel difficile rapporto tra élite di potere e cultura popolare nello stabilire la legittimità politica. Questa indagine si prefigge di esplorare questo rapporto in diversi contesti socio-culturali del Mediterraneo arricchendo l'analisi tramite una comparazione tra la censura post-tridentina sul motivo e la ripresa del tema nell’impero mughal tra il secolo XVI ed il XVII.

von Willebrand disease (VWD) is the most common inherited bleeding disorder. The management of patients with VWD who are undergoing surgeries is crucial to prevent bleeding complications. We systematically summarized the evidence on the management of patients with VWD who are undergoing major and minor surgeries to support the development of practice guidelines. We searched Medline and EMBASE from inception through October 2019 for randomized clinical trials (RCTs), comparative observational studies, and case series that compared maintaining factor VIII (FVIII) levels or von Willebrand factor (VWF) levels at >0.50 IU/mL for at least 3 days in patients undergoing major surgery, and those with options for perioperative management of patients undergoing minor surgery. Two authors screened and abstracted data and assessed the risk of bias. We conducted meta-analyses when possible. We evaluated the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We included 7 case series for major surgeries and 2 RCTs and 12 case series for minor surgeries. Very-low-certainty evidence showed that maintaining FVIII levels or VWF levels of >0.50 IU/mL for at least 3 consecutive days showed excellent hemostatic efficacy (as labeled by the researchers) after 74% to 100% of major surgeries. Low- to very-low-certainty evidence showed that prescribing tranexamic acid and increasing VWF levels to 0.50 IU/mL resulted in fewer bleeding complications after minor procedures compared with increasing VWF levels to 0.50 IU/mL alone. Given the low-quality evidence for guiding management decisions, a shared-decision model leading to individualized therapy plans will be important in patients with VWD who are undergoing surgical and invasive procedures.

The dispersal of marine organisms can be restricted by a set of isolation mechanisms including hard barriers or hydrological features. In the Western Atlantic Ocean, the Amazon River discharge has been shown to act as a biogeographical barrier responsible for the differences in reef fish communities between Caribbean Sea and Northeast Brazil continental shelves. Here, we compare the diversity of all Animalia phyla from biogeographic ecoregions along the Tropical Western Atlantic continental shelf to test the hypothesis that the Amazon River plume spatially structures species diversity. For that, we used beta diversity estimators and multivariate ecological analysis on a database of species occurrence of the whole animal kingdom including 175,477 occurrences of 8,375 species from six ecoregions along the Western Tropical Atlantic. Results of the whole animal kingdom and the richest phyla showed that the Caribbean Sea and Tropical Brazil ecoregions are isolated by the Amazon River Plume, broadening and confirming the hypothesis that it acts as a soft barrier to animal dispersal in the Western Tropical Atlantic. Species sharing is larger northwestwards, in direction of the Caribbean than the opposite direction. Beyond species isolation due to local characteristics such as low salinity and high turbidity, our results suggest the dominant northwestward currents probably play a major role in animal dispersion: it enhances the flux of larvae and other planktonic organisms with reduced mobility from Brazil to Caribbean and hinders their contrary movement. Thus, the Amazon area is a strong barrier for taxa with reduced dispersal capacity, while species of pelagic taxa with active swimming may transpose it more easily.

There is a rapid and extensive decline of our marine biodiversity due to human impacts. However, our ability to understand the extent of these effects is hindered by our lack of knowledge of the occurrence and ecology of some species groups. One such group of understudied organisms are marine flatworms of the order Polycladida, a conspicuous component of southeastern Australia’s marine ecosystems that has received little attention over the years. Intertidal boulder beaches support a diverse range of polyclad flatworms in other countries, but the role of these environments in maintaining biodiversity is not well understood. In this study, we identified hotspots of flatworm occurrence by assessing the diversity and overall abundance of flatworms at boulder beaches along the southeast Australian coast. Bottle and Glass, Sydney Harbour, was found to be the most diverse site for flatworms. We also identified a higher occurrence of flatworms under large boulders and less exposed beaches and noted an increased presence of flatworms at higher latitudes. Probable influences on these patterns such as the requirement for shelter and protection are discussed. This study contributes to our knowledge of Australia’s coastal biodiversity and can be used to assist in the management and conservation of our marine environments.

The gut microbiota regulates chronic inflammation and has been implicated in the pathogenesis of a broad spectrum of disease including autoimmunity and cancer. Microbial short-chain fatty acids (SCFAs) e.g., butyrate have demonstrated immunomodulatory effects and are thought to be key mediators of the host-microbiome interaction. Here, we investigated the effect of butyrate on effector functions of blood derived human NK cells stimulated for 18 h with a combination of IL-12/IL-15, a potent mix of cytokines that drive NK cell activation. We show that butyrate has a strong anti-inflammatory effect on NK cells. NK cells cultured in the presence of butyrate expressed lower levels of activating receptors (TRAIL, NKp30, NKp44) and produced lower levels of cytokines (IFNγ, TNF-α, IL-22, granzyme B, granzyme A, perforin) in response to IL-12/IL-15. Butyrate restricted NK cell function by downregulation of mTORC1 activity, c-Myc mRNA expression and metabolism. Using a shotgun proteomic approach, we confirmed the effect of butyrate on NK cell cytokine signaling and metabolism and identified BRD2, MAT2A and EHD1 as downstream mediators of these effects. This insight into the immunomodulatory activity of butyrate on human NK cell function might help to develop new ways to limit NK cell function during chronic inflammation.

Background Robotic laparoscopically assisted radical prostatectomy (RARP) is an option for the treatment of localized prostate cancer. The objective of the present study was to evaluate the pentafecta outcomes (biochemical recurrence, continence, potency, surgical complications and surgical margins) in patients undergoing RARP during the initial experience in a university hospital. Methods This is a retrospective study of patients who had RARP for localized prostate adenocarcinoma at a university hospital from August 2013 to October 2019 to evaluate pentafecta outcomes (biochemical recurrence, continence, potency, surgical complications and surgical margins). Data were collected and stored via Microsoft Office Excel program and analyzed using SPSS Software, version 20.0. Results One hundred and sixty-three RARP were performed, the mean age is 64.16 ± 6.54 years, PSA 6.20 (IQR = 4.91–8.95) ng/dl, BMI 27.14 (IQR = 24.22–29.26) kg/m2, D’Amico risk classification was 35 (22.3%) low risk, 81 (51.6%) intermediate risk and 41 (26.1%) high risk. One hundred and fifty-four patients entered the analysis of pentafecta with a rate of 38.3% reaching this outcome. Complications: Twenty-three (14.1%) patients had minor complications (Clavien I and II) and eight patients had major complications (Clavien IIIa, IIIb and IVa). Surgical margins were negative in 69.9% of patients. The biochemical recurrence-free rate was 89.5%. The overall continence rate was 93.5%, and the potency rate was 63.5%. Multivariate analysis showed that T2 patients are 2.7 times more likely to achieve pentafecta outcome than patients ≥ T3 (p Conclusions Preliminary pentafecta outcome of RARP in this university hospital is promising.

Naphthalenediimide dye was used to fabricate polymeric 3D printed colorimetric sensors for bases, to detect aqueous, vapor and organic phases.

The so-called nefs were an important ‘presence’ in the European courts starting from the Late Middle Ages. They were precious miniature ships, shown during banquets held in the halls of the nobility. In addition to delighting the sight of diners thanks to their ornamental richness, they were used as containers of spices, drinks, or luxury silverware. The preciousness of the vessel and of its content were just some of the elements that determined the function of ostentation of power through the nefs. Taking into consideration sources and examples ranging from the fourteenth century to the early sixteenth century, the purpose of this contribution is to investigate both the spatial relationships in the practices of use of the object and those intrinsic to the object itself. The main trajectories of analysis refer to three spatial relationships: that of container and content, that of long-distance travel embedded in the object, and the geography of power in noble banqueting rituals. These spatial relationships reflect power relationships that will be investigated on a case-by-case basis in the course of our study.

In western boundary current systems (WBCSs), strong currents flow coastward carrying oceanic water masses and their associated planktonic fauna. Variation in the intensity of these currents and in the continental runoff may affect the dynamic interplay between oceanic and coastal communities. In addition, changes in the continental runoff and the thermohaline structure modulate the primary production, adding complexity to the dynamics of these oligotrophic systems. These dynamics likely shape the planktonic cnidarian communities. To further understand such relationships, we used a comprehensive dataset encompassing samples collected above the shelf and slope and around oceanic seamounts and islands of the Fernando de Noronha Ridge in the western tropical South Atlantic, in two seasons characterised by distinct thermohaline structure and circulation patterns. Results show that in the tropical South Atlantic and, likely, other western boundary systems with narrow continental shelves, coastward currents spread oceanic waters and their associated cnidarian species over the continental shelf. However, while both coastal and oceanic communities co-occur when the continental runoff is notable, oceanic species dominate almost the entire shelf during the dry season characterised by a stronger boundary current intensity. We also conclude that when the mixed-layer depth and associated nutricline are shallower, the enhanced primary productivity supports larger populations of planktonic cnidarian species through a bottom–up control.

Direct oral anticoagulants (DOAC) measurement is recommended in specific conditions. A point-of-care testing should be used in emergency to qualitatively rule out relevant DOAC concentrations. The DOAC-CHECK Study aims to evaluate whether the use of CoaguChek® Pro II (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) coagulation testing device can provide reliable information in patients treated with DOAC. The study was carried out in two FCSA (Italian Federation of Thrombosis Centers) centers. We choose 3 different concentration thresholds for our analysis (30, 50 and 100 ng/mL) and by ROC curves the ideal cut-off point was selected to be the one that yielded a sensitivity of at least 95% associated with the highest possible specificity. 512 patients were enrolled. For Edoxaban and Rivaroxaban, both CoaguChek® Pro II prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests showed a sensitivity >95% corresponding to satisfying specificity values; negative predictive values resulted in the range 90-100%. At variance, CoaguChek® Pro II PT and aPTT tests did not seem to be useful for identifying Apixaban and Dabigatran concentrations higher than the pre-defined thresholds. Our results suggest that CoaguChek® Pro II coagulation testing device can be used to qualitatively identify relevant concentrations of Edoxaban or Rivaroxaban, but not of Apixaban or Dabigatran.

Not available.

Aim Water column acoustic backscatter is regularly registered during oceanographic surveys, providing valuable information on the composition and distribution of pelagic life in the ocean. We propose an objective approach based on functional data analysis to classify these acoustic seascapes into biogeographical regions. Location Tropical South Atlantic Ocean off northeastern Brazil. Taxon Sound-scattering pelagic fauna detected with acoustic echosounders, principally small fish, crustaceans, squid and diverse gelatinous life-forms. Methods We use acoustic backscatter as a function of depth, simultaneously at three frequencies, to numerically describe the vertical distribution and composition of sound-scattering organisms in the water column. This information is used to classify the acoustic seascape through functional principal component analysis. The analysis routine is tested and illustrated with data collected at 38, 70 and 120 kHz in waters affected by contrasting environmental conditions. Results Acoustic seascape partitioning mirrored the distribution of current systems, fronts and taxonomically based regionalization. The study area was divided between slope-boundary and open-ocean waters, and between spring and fall hydrological regimes. Main Conclusions The acoustic seascape consistency and the spatiotemporal coherence of the regions classified show that the method is efficient at identifying homogeneous and cohesive sound-scattering communities. Comparisons against hydrological and biological regionalization prove that the method is reliable at delineating distinct pelagic ecosystems in a cost-efficient and non-intrusive way.

The objective of this trial is to analyze the diagnosed profile of developmental dysplasia of the hip (DDQ) the number of babies born alive in Brazil from 2016 to 2020. This is a descriptive, retrospective and analytical study, about the hospitalizations resulting from DDQ, International Code of Diseases (ICD) Q650 to Q659, elaborated through secondary data obtained from the Sistema de Informações sobre Nascidos Vivos do Sistema Único de Saúde (SISNAC/SUS), made available by the Departamento de Informática do SUS (DATASUS), in newborns, during the period from 2016 to 2020, in Brazil. During the analyzed period, 1.150 diagnoses for congenital hip deformities were registered in the number of babies born alive in Brazil. Regarding the ICD of congenital hip deformities, the largest number of cases is concentrated in ICD Q650, unilateral congenital dislocation of the hip, with 410 cases (35.65%), followed by ICD Q652, specific congenital hip dislocation, responsible for 202 cases (21.29%). As reported about the ethnicity of the new borns, the highest number of cases prevailed in children of brown ethnicity, with a total of 553 cases (448.08%). In the second place was the white ethnicity accounted for 475 cases (41.30%). Conclusion: Therefore, this survey shows that the cases of developmental dysplasia of the hip per year, in newborns, present an approximate value, without great variations. This highlights the need for epidemiological delimitation, so that public policies, aimed at both treatment and prevention, can be directed. El objetivo de este ensayo es analizar el perfil de diagnóstico de la displasia del desarrollo de la cadera (DDQ) en el número de bebés nacidos vivos en Brasil de 2016 a 2020. Se trata de un estudio descriptivo, retrospectivo y analítico, sobre las hospitalizaciones resultantes de la DDQ, Código Internacional de Enfermedades (CIE) Q650 a Q659, elaborado a través de datos secundarios obtenidos del Sistema de Informaciones sobre Nacidos Vivos del Sistema Único de Salud (SISNAC/SUS), puesto a disposición por el Departamento de Informática del SUS (DATASUS), en recién nacidos, durante el período de 2016 a 2020, en Brasil. Durante el período analizado, se registraron 1.150 diagnósticos de deformidades congénitas de cadera en el número de bebés nacidos vivos en Brasil. En cuanto a la CIE de deformidades congénitas de la cadera, el mayor número de casos se concentra en la CIE Q650, luxación congénita unilateral de la cadera, con 410 casos (35,65%), seguido de la CIE Q652, luxación congénita específica de la cadera, responsable de 202 casos (21,29%). En cuanto a la etnia de los recién nacidos, el mayor número de casos prevaleció en los niños de etnia parda, con un total de 553 casos (448,08%). En segundo lugar se situó la etnia blanca con 475 casos (41,30%). Conclusiones: Por lo tanto, esta encuesta muestra que los casos de displasia del desarrollo de la cadera por año, en recién nacidos, presentan un valor aproximado, sin grandes variaciones. Esto resalta la necesidad de delimitación epidemiológica, para que las políticas públicas, dirigidas tanto al tratamiento como a la prevención, puedan ser dirigidas. O objetivodesteestudoéanalisar o perfil dos diagnósticos por displasia do desenvolvimento do quadril (DDQ), em nascidos vivos, no Brasil, no período de 2016 a 2020. Trata-se de um estudo descritivo, retrospectivo e analítico, acerca das internações decorrentes de DDQ, Código Internacional de Doenças (CID) Q650 a Q659, elaborado através de dados secundários obtidos do Sistema de Informações sobre Nascidos Vivos do Sistema Único de Saúde (SISNAC/SUS), disponibilizados pelo Departamento de Informática do SUS (DATASUS), em recém nascidos, no período de 2016 e 2020, no Brasil. No período analisado, foram registradas 1.150 diagnósticos por deformidades congênitas do quadril, em nascidos vivos, no Brasil. No que tange ao CID das deformidades congênitas do quadril, o maior número de casos concentra-se no CID Q650, luxação congênita unilateral do quadril, com 410 casos (35,65%), seguida do CID Q652, luxação congênita específica do quadril, responsável por 202 casos (21,29%). Quanto à etnia informada dos nascidos vivos, o maior número de casos prevaleceu nas crianças de etnia parda, com um total de 553 casos (448,08%). Em seguida, a etnia branca foi responsável por 475 casos (41,30%). Conclusão: Portanto, esse levantamento evidencia que os casos por displasia do desenvolvimento do quadril por ano, em nascidos vivos, apresentam um valor aproximado, sem grandes variações. Isso ressalta a necessidade de delimitação epidemiológica, para que as políticas públicas, voltadas tanto para o tratamento quanto para a prevenção, sejam direcionadas.

INTRODUCTION: Rheumatic heart disease with mechanical heart valve (MHV) replacement is common in Africa. However, MHV requires long-life anticoagulation and managing this can be challenging.METHODS AND RESULTS: We report data of a prospective observational study conducted between August 2018 and September 2019 in MHV patients in the Salam Centre for Cardiac Surgery built in Khartoum, by Emergency, an Italian Non-Governmental Organization, to evaluate the quality of anticoagulation control and the risk of thrombotic complications.RESULTS: We studied 3647 patients (median age 25.1 years; 53.9 % female). Median Time in Therapeutic Range (TTR) was 53 % (interquartile range 37 % to 67 %) and 70 thrombotic events (rate 1.8 × 100 pt-years [95 % CI 1.38-2.23]) were recorded. Among patients in the first quartile of TTR (≤37 %), we recorded 34/70 (48.6 %) of all thrombotic events (rate 3.7 × 100 pt-years [95 % CI 2.5-5.1]), with a high mortality rate (2.2 × 100 pt-years [95 % CI 1.3-3.3]). In patients with guideline-recommended TTR (≥65 %) the event rate was 0.8 × 100 pt-years for thrombotic events [95 % CI 0.3-1.5] and 0.4 × 100 pt-years for mortality [95 % CI 0.1-0.9]. Multivariable analysis showed that having a TTR in the lowest quartile (≤37 %) and being noncompliant are significantly associated with increased thrombotic risk. Aspirin use or different valve type did not influence the thrombotic risk. Almost 40 % of all thromboembolic complications could have been potentially prevented by further improving VKA management to obtain a TTR > 37 %.CONCLUSION: The thrombotic risk of MHV patients on VKAs living in a low-income country like Sudan is associated with low quality of anticoagulation control. Efforts should be made to decrease the number of non-compliant patients and to reach a guideline-recommended TTR of ≥65 %.

D-dimer assay is used to stratify patients with unprovoked venous thromboembolism (VTE) for the risk of recurrence. However, this approach was never evaluated since direct oral anticoagulants are available. With this multicenter, prospective cohort study, we aimed to assess the value of an algorithm incorporating serial D-dimer testing and administration of reduced-dose apixaban (2.5 mg twice daily) only to patients with a positive test. A total of 732 outpatients aged 18 to 74 years, anticoagulated for ≥12 months after a first unprovoked VTE, were included. Patients underwent D-dimer testing with commercial assays and preestablished cutoffs. If the baseline D-dimer during anticoagulation was negative, anticoagulation was stopped and testing repeated after 15, 30, and 60 days. Patients with serially negative results (286 [39.1%]) were left without anticoagulation. At the first positive result, the remaining 446 patients (60.9%) were given apixaban for 18 months. All patients underwent follow-up planned for 18 months. The study was interrupted after a planned interim analysis for the high rate of primary outcomes (7.3%; 95% confidence interval [CI], 4.5-11.2), including symptomatic proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) recurrence, death for VTE, and major bleeding occurring in patients off anticoagulation vs that in those receiving apixaban (1.1%; 95% CI, 0.4-2.6; adjusted hazard ratio [HR], 8.2; 95% CI, 3.2-25.3). In conclusion, in patients anticoagulated for ≥1 year after a first unprovoked VTE, the decision to further extend anticoagulation should not be based on D-dimer testing. The results confirmed the high efficacy and safety of reduced-dose apixaban against recurrences. This trial was registered at www.clinicaltrials.gov as #NCT03678506.

Cancer children experience long periods of hospitalization, which are associated with limited performance in several developmental domains and participation restrictions in age appropriate occupations. Fine motor abilities represent building blocks in performing daily life skills and have been found to be closely connected with later academic success. Moreover, medical and psychological sequelae for cancer inpatients may result in diminished daily activities functioning, poor perceived health related quality of life (HRQOL), and increase the likelihood of long-term impairments. This study examines the variations in the occupational performance of children hospitalized for acute lymphoblastic leukemia (ALL) after their participation to a stimulation program designed to enhance fine motor skills. Parents reported significant gains in children’s motor functioning, a slight improvement in overall occupational performance related to an increase in the area of productivity and self-care, and a better quality of life perception following the stimulation activities. Feasibility of the stimulation program in a health care setting are discussed evaluating its benefits for cancer children and their families.

Background: Proton pump inhibitors (PPIs) are one of the most prescribed drugs in the world. Frequent use and long-term maintenance of these drugs drew the attention of researchers for sporadic adverse effects reports. Objective: The purpose of this narrative review is to discuss appropriate data and causality related to these adverse events and PPIs. Methods: A narrative review was conducted by systematizing information about safety and adverse events on PPIs from 2015 to 2020. A structured search on Pubmed was performed to identify systematic reviews and meta-analysis investigating the following situations: a) gastric cancer; b) micronutrients deficiency; c) acid rebound; d) infections; e) fractures; f) dementia; g) kidney disease; and h) sudden death and cardiovascular changes. Results: Recent studies have potentially associated PPIs with some adverse events as osteoporosis-related fractures. There are also reports of intestinal infections, including Clostridium difficile, besides poor vitamins absorption and minerals such as vitamin B12, magnesium, and iron. Furthermore, there are some dementia, pneumonia, kidney disease, myocardial infarction, and stroke reports. For kidney diseases, studies consistently suggest that the use of PPI may be associated with an increased risk of adverse kidney events, especially in the elderly, with long-term PPI use and pre-existing kidney disease. Another additional question is whether chronic PPI use would also lead to the onset of gastric cancer. The abrupt discontinuation of PPIs is also related to increased gastric acid production above pre-PPI treatment levels; this phenomenon is called acid rebound. Conclusion: The key to mitigate adverse effects is the rational use of PPIs at the lowest effective dose and in the shortest possible duration. Although these adverse effects have a potential clinical impact, their causal association is still subject to validation. RESUMO: Contexto: Os inibidores da bomba de prótons (IBPs) são um dos medicamentos mais prescritos no mundo. O uso frequente e a manutenção a longo prazo dessas drogas chamaram a atenção dos pesquisadores devido aos relatos esporádicos de efeitos adversos. Objetivo: Esta revisão narrativa tem o objetivo de discutir os dados e a causalidade relacionada a esses eventos adversos e o uso de IBPs. Métodos: Uma revisão narrativa foi conduzida através da sistematização das informações sobre segurança e eventos adversos de IBPs de 2015 a 2020. Uma busca estruturada na base de dados PubMed foi realizada visando identificar revisões sistemáticas e meta-análises investigando as situações a seguir: a) câncer gástrico; b) deficiência de microelementos; c) acidez de rebote; d) infecções; e) fraturas; f) demência; g) doença renal; e h) morte súbita e alterações cardiovasculares. Resultados: Estudos recentes têm potencialmente associado IBPs a alguns eventos adversos, como fraturas relacionadas à osteoporose. Também há relatos de infecções intestinais, incluindo Clostridium difficile, além de má absorção de vitaminas e minerais como vitamina B12, magnésio e ferro. Além disso, há alguns relatos de demência, pneumonia, doença renal, infarto do miocárdio e acidente vascular cerebral. Na doença renal, os estudos sugerem consistentemente que o uso de IBPs pode estar associado a um risco aumentado de eventos renais adversos, especialmente em idosos, com o uso de IBPs a longo prazo e doença renal preexistente. Outra questão adicional é se o uso crônico de IBPs também levaria ao aparecimento de câncer gástrico. A descontinuação abrupta de IBPs também está relacionada ao aumento da produção de ácido gástrico acima dos níveis de tratamento pré-IBPs; este fenômeno é conhecido como rebote ácido. Conclusão: A chave para mitigar esses efeitos adversos é o uso racional de IBPs na menor dose efetiva e com a menor duração possível. Embora esses efeitos adversos tenham um impacto clínico potencial, sua associação causal ainda está pendente de uma validação.

BACKGROUND Infection is an important complication of epidermolysis bullosa (EB), and Staphylococcus aureus has been pointed out as the most common pathogen among this population. The objective of this study was to investigate the prevalence and antimicrobial resistance profile of S. aureus colonizing EB patients in Brazil. METHODS This cross-sectional multicenter study was conducted between December 2015 and December 2017. We included a total of 89 individuals with EB from medical centers across Brazil. Data were obtained through clinical and bacteriological investigation. S. aureus were identified by biochemical tests. The nuc and mecA genes were confirmed by PCR assay. Antimicrobial susceptibility was investigated by disk diffusion method. RESULTS The overall prevalence of S. aureus was 51.7% (46/89). Methicillin-resistant S. aureus (MRSA) was detected in 24.7% (19/77) of all S. aureus isolates, colonizing 15.7% (14/89) of all patients. Community-associated (CA)-MRSA strains were resistant against sulfamethoxazole/trimethoprim and levofloxacin (P

A Tuberculose (TB) é a principal causa de morte em razão de um único agente infeccioso em adultos em todo o mundo. Deste total, a doença osteoarticular constitui de 10 a 20% dos casos e de 1 a 3% de todos os casos de tuberculose. Dessa forma, o objetivo deste estudo é analisar as internações por tuberculose óssea (TBO), em pessoas entre 40 e 80 anos ou mais, no Brasil e suas regiões, nos últimos 5 anos. Trata-se de um estudo epidemiológico, acerca das internações decorrentes de TBO, elaborado através de dados secundários, em pessoas entre 40 e 80 anos ou mais, no período de 2018 a 2022, no Brasil e suas macrorregiões. No período analisado, foram registradas 242 internações por tuberculose óssea, em pessoas entre 40 e 80 anos ou mais, no Brasil. No que tange às regiões geográficas, o maior número de internações concentra-se na região Sudeste. Em relação à faixa etária, os pacientes de 50 a 59 anos foram as mais acometidas. Em relação ao sexo biológico, o sexo masculino foi o que predominou, totalizando 183 das internações. Esta pesquisa demonstra que a tuberculose óssea é um problema de saúde pública, sendo passível de diagnóstico precoce e cuidados preventivos, devendo haver ações como educação em saúde, visando minimizar gastos desnecessários e melhorar a qualidade de vida das pessoas.

Background: von Willebrand disease (VWD) is a common inherited bleeding disorder. Significant variability exists in management options offered to patients. Objective: These evidence-based guidelines from the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemophilia (WFH) are intended to support patients, clinicians, and health care professionals in their decisions about management of VWD. Methods: ASH, ISTH, NHF, and WFH formed a multidisciplinary guideline panel. Three patient representatives were included. The panel was balanced to minimize potential bias from conflicts of interest. The University of Kansas Outcomes and Implementation Research Unit and the McMaster Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process, including performing and updating systematic evidence reviews (through November 2019). The panel prioritized clinical questions and outcomes according to their importance to clinicians and patients. The panel used the GRADE approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 12 recommendations and outlined future research priorities. Conclusions: These guidelines make key recommendations regarding prophylaxis for frequent recurrent bleeding, desmopressin trials to determine therapy, use of antiplatelet agents and anticoagulant therapy, target VWF and factor VIII activity levels for major surgery, strategies to reduce bleeding during minor surgery or invasive procedures, management options for heavy menstrual bleeding, management of VWD in the context of neuraxial anesthesia during labor and delivery, and management in the postpartum setting.

O uso descontrolado de agrotóxicos em lavouras nos sistemas de produção agrícola nos impulsionou a buscar por medidas alternativas no controle de doença fúngica de potencial relevante como é o caso da antracnose em lavouras de banana e de maracujá, tornando estas medidas de controle menos agressivas ao meio ambiente e ao ser humano. Neste contexto, o trabalho teve como objetivo reunir publicações com potencial antifúngico de óleos essenciais no controle alternativo de Colletotrichum sp.

Background and Aims Inflammatory bowel diseases [IBD], comprising Crohn’s disease [CD] and ulcerative colitis [UC], are chronic conditions characterized by severe dysregulation of innate and adaptive immunity resulting in the destruction of the intestinal mucosa. Natural killer [NK] cells play a pivotal role in the dynamic interaction between the innate and adaptive immune response. There is an increasing appreciation for the key role immunometabolism plays in the regulation of NK cell function, yet little remains known about the metabolic profile, cytokine secretion, and killing capacity of human NK cells during active IBD. Methods Peripheral blood mononuclear cells were isolated from peripheral blood of patients with moderate to severely active IBD and healthy controls. NK cells were stained with a combination of cell surface receptors, intracellular cytokines, and proteins and analyzed by flow cytometry. For measurements of NK cell cytotoxicity, the calcein-AM release assay was performed. The metabolic profile was analyzed by an extracellular flux analyzer. Results NK cells from IBD patients produce large quantities of pro-inflammatory cytokines, IL-17A and TNF-α ex vivo, but have limited killing capability. Furthermore, patient NK cells have reduced mitochondrial mass and oxidative phosphorylation. mTORC1, an important cell and metabolic regulator, demonstrated limited activity in both freshly isolated cells and cytokine-stimulated cells. Conclusions Our results demonstrate that circulating NK cells of IBD patients have an unbalanced metabolic profile, with faulty mitochondria and reduced capacity to kill. These aberrations in NK cell metabolism may contribute to defective killing and thus the secondary infections and increased risk of cancer observed in IBD patients.

Bluelined goatfish (Upeneichthys lineatus) exhibit dynamic body colour changes and transform rapidly from a pale, buff/white, horizontally banded pattern to a conspicuous, vertically striped, red pattern when foraging. This red pattern is potentially an important foraging signal for communication with conspecifics, provided that U. lineatus can detect and discriminate the pattern. Using both physiological and behavioural experiments, we first examined whether U. lineatus possess visual pigments with sensitivity to long (“red”) wavelengths of light, and whether they can discriminate the colour red. Microspectrophotometric measurements of retinal photoreceptors showed that while U. lineatuslack visual pigments dedicated to the red part of the spectrum, their pigments likely confer some sensitivity in this spectral band. Behavioural colour discrimination experiments suggested that U. lineatuscan distinguish a red reward stimulus from a grey distractor stimulus of variable brightness. Furthermore, when presented with red stimuli of varying brightness they could mostly discriminate the darker and lighter reds from the grey distractor. We also obtained anatomical estimates of visual acuity, which suggest that U. lineatus can resolve the contrasting bands of conspecifics approximately 7 m away in clear waters. Finally, we measured the spectral reflectance of the red and white colouration on the goatfish body. Visual models suggest that U. lineatus can discriminate both chromatic and achromatic differences in body colouration where longer wavelength light is available. This study demonstrates that U. lineatus have the capacity for colour vision and can likely discriminate colours in the long-wavelength region of the spectrum where the red body pattern reflects light strongly. The ability to see red may therefore provide an advantage in recognising visual signals from conspecifics. This research furthers our understanding of how visual signals have co-evolved with visual abilities, and the role of visual communication in the marine environment.

Research Letter

Background: Intracranial hemorrhage (ICH) is a highly serious event in patients with haemophilia (PWH) which leads to disability and in some cases to death. ICH occurs among all ages but is particularly frequent in newborns. Aim: The primary aim was to assess the incidence and mortality due to ICH in an Italian population of PWH. Secondary aims were to evaluate the risk factors for ICH, the role of prophylaxis, and the clinical management of patients presenting ICH. Methods: A retrospective-prospective registry was established in the network of the Italian Association of Haemophilia Centers to collect all ICHs in PWH from 2009 to 2019 reporting clinical features, treatments, and outcomes. Results: Forty-six ICHs were collected from 13 Centers. The ICHs occurred in 15 children (10 < 2 years), and in 31 adults, 45.2% of them with mild hemophilia. Overall, 60.9% patients had severe haemophilia (15/15 children). Overall ICH incidence (×1000 person/year) was 0.360 (0.270–0.480 95% CI), higher in children

Emicizumab has been approved in several countries for regular prophylaxis in patients with congenital haemophilia A and FVIII inhibitors because it substantially reduces their bleeding risk and improves quality of life. However, although significantly less frequent, some breakthrough bleeds may still occur while on emicizumab, requiring treatment with bypassing or other haemostatic agents. Thrombotic complications have been reported with the associated use of activated prothrombin complex concentrates. In addition, when surgery/invasive procedures are needed while on emicizumab, their management requires multidisciplinary competences and direct supervision by experts in the use of this agent. Given this, and in order to expand the current knowledge on the use of emicizumab and concomitant haemostatic agents, and reduce the risk of complications in this setting, the Italian Association of Haemophilia Centres (AICE) here provides guidance on the management of breakthrough bleeds and surgery in emergency situations in patients with haemophilia A and inhibitors on emicizumab prophylaxis. This paper has been shared with other National Scientific Societies involved in the field.

Inherited epidermolysis bullosa is a group of genetic diseases characterized by skin fragility and blistering on the skin and mucous membranes in response to minimal trauma. Epidermolysis bullosa is clinically and genetically very heterogeneous, being classified into four main types according to the layer of skin in which blistering occurs: epidermolysis bullosa simplex (intraepidermal), junctional epidermolysis bullosa (within the lamina lucida of the basement membrane), dystrophic epidermolysis bullosa (below the basement membrane), and Kindler epidermolysis bullosa (mixed skin cleavage pattern). Furthermore, epidermolysis bullosa is stratified into several subtypes, which consider the clinical characteristics, the distribution of the blisters, and the severity of cutaneous and extracutaneous signs. Pathogenic variants in at least 16 genes that encode proteins essential for the integrity and adhesion of skin layers have already been associated with different subtypes of epidermolysis bullosa. The marked heterogeneity of the disease, which includes phenotypes with a broad spectrum of severity and many causal genes, hinders its classification and diagnosis. For this reason, dermatologists and geneticists regularly review and update the classification criteria. This review aimed to update the state of the art on inherited epidermolysis bullosa, with a special focus on the associated clinical and genetic aspects, presenting data from the most recent reclassification consensus, published in 2020.

Essential thrombocythemia (ET) is characterized by abnormal megakaryopoiesis and enhanced thrombotic risk. Once-daily low-dose aspirin is the recommended antithrombotic regimen, but accelerated platelet generation may reduce the duration of platelet cyclooxygenase-1 (COX-1) inhibition. We performed a multicenter double-blind trial to investigate the efficacy of 3 aspirin regimens in optimizing platelet COX-1 inhibition while preserving COX-2–dependent vascular thromboresistance. Patients on chronic once-daily low-dose aspirin (n = 245) were randomized (1:1:1) to receive 100 mg of aspirin 1, 2, or 3 times daily for 2 weeks. Serum thromboxane B2 (sTXB2), a validated biomarker of platelet COX-1 activity, and urinary prostacyclin metabolite (PGIM) excretion were measured at randomization and after 2 weeks, as primary surrogate end points of efficacy and safety, respectively. Urinary TX metabolite (TXM) excretion, gastrointestinal tolerance, and ET-related symptoms were also investigated. Evaluable patients assigned to the twice-daily and thrice-daily regimens showed substantially reduced interindividual variability and lower median (interquartile range) values for sTXB2 (ng/mL) compared with the once-daily arm: 4 (2.1-6.7; n = 79), 2.5 (1.4-5.65, n = 79), and 19.3 (9.7-40; n = 85), respectively. Urinary PGIM was comparable in the 3 arms. Urinary TXM was reduced by 35% in both experimental arms. Patients in the thrice-daily arm reported a higher abdominal discomfort score. In conclusion, the currently recommended aspirin regimen of 75 to 100 once daily for cardiovascular prophylaxis appears to be largely inadequate in reducing platelet activation in the vast majority of patients with ET. The antiplatelet response to low-dose aspirin can be markedly improved by shortening the dosing interval to 12 hours, with no improvement with further reductions (EudraCT 2016-002885-30).