Search

Abstract This was a prospective cohort study of eighteen patients with large and debilitating vascular malformations with one or more major systemic complications. In all patients, we discovered activating alterations in either TEK or PIK3CA. Based on these findings, targeted treatment using the PI3K inhibitor alpelisib was started with regular check-ups, therapy duration varied from 6 to 31 months. In all patients, marked improvement in quality of life was observed. We observed radiological improvement in fourteen patients (two of them being on combination with either propranolol or sirolimus), stable disease in 2 patients. For 2 patients, an MRI scan was not available as they were shortly on treatment, however, a clinically visible response in size reduction or structure regression, together with pain relief was observed. In patients with elevated D-dimer levels before alpelisib administration, a major improvement was noted, suggesting its biomarker role. We observed overall very good tolerance of the treatment, documenting a single patient with grade 3 hyperglycemia. Patients with size reduction were offered local therapies wherever possible. Our report presents a promising approach for the treatment of VMs harboring different targetable TEK and PIK3CA gene mutations with a low toxicity profile and high efficacy.

Background von Willebrand disease (VWD) is a genetic bleeding disorder caused by defects of von Willebrand factor (VWF), quantitative (type 1 and 3) or qualitative (type 2). The laboratory phenotyping is heterogenic making diagnosis difficult. Objectives Complete laboratory analysis of VWD as an expansion of the previously reported cross-sectional family-based VWD study in the Czech Republic (BRNO-VWD) and Slovakia (BRA-VWD) under the name “Heart of Europe,” in order to improve the understanding of laboratory phenotype/genotype correlation. Patients and Methods In total, 227 suspected VWD patients were identified from historical records. Complete laboratory analysis was established using all available assays, including VWF multimers and genetic analysis. Results A total of 191 patients (from 119 families) were confirmed as having VWD. The majority was characterized as a type 1 VWD, followed by type 2. Multimeric patterns concordant with laboratory phenotypes were found in approximately 83% of all cases. A phenotype/genotype correlation was present in 84% (77% type 1, 99% type 2, and 61% type 3) of all patients. Another 45 candidate mutations (23 novel variations), not found in the initial study, could be identified (missense 75% and truncating 24%). An exon 1–3 gene deletion was identified in 14 patients where no mutation was found by direct DNA sequencing, increasing the linkage up to 92%, overall. Conclusion This study provides a cross-sectional overview of the VWD population in a part of Central Europe. It is an addition to the previously published BRNO-VWD study, and provides important data to the International Society of Thrombosis and Haemostasis/European Association for Haemophilia and Allied Disorders VWD mutation database with identification of novel causal mutations.

Over recent decades, management of people with hemophilia (PwH) has been greatly improved by scientific advances that have resulted in a rich and varied therapeutic landscape. Nevertheless, treatment limitations continue to drive innovation, and emerging options have the potential to realize further improvement. We advocate four general principles to optimize benefits from innovation: individualizing the treatment approach, targeting ‘normal,’ making the most of available resources, and considering treatment affordability. Ultimately, all PwH—men and women, of all ages and severities, and worldwide—should have access to treatment that fully prevents bleeding, while allowing personal, social, family, and professional lives of choice. Clearly, we are not there yet, but developing goals/milestones based on the principles we describe may help to achieve this.

Recent advances in therapeutics are now providing a wide range of options for adults and children living with hemophilia. Although therapeutic choices are also increasing for the youngest individuals with severe disease, challenges remain about early management decisions, as supporting data are currently limited. Parents and healthcare professionals are tasked with helping children achieve an inclusive quality of life and maintain good joint health into adulthood. Primary prophylaxis is the gold standard to optimize outcomes and is recommended to start before 2 years of age. A range of topics need to be discussed with parents to aid their understanding of the decisions they can make and how these will affect the management of their child/children. For those with a family history of hemophilia, prenatal considerations include the possibility of genetic counseling, prenatal investigations, and planning for delivery, together with monitoring of the mother and neonate, as well as diagnosis of the newborn and treatment of any birth-associated bleeding. Subsequent considerations, which are also applicable to families where infant bleeding has resulted in a new diagnosis of sporadic hemophilia, involve explaining bleed recognition and treatment options, practical aspects of initiating/continuing prophylaxis, dealing with bleeds, and ongoing aspects of treatment, including possible inhibitor development. Over time, optimizing treatment efficacy, in which individualizing therapy around activities can play a role, and long-term considerations, including retaining joint health and tolerance maintenance, become increasingly important. The evolving treatment landscape is creating a need for continually updated guidance. Multidisciplinary teams and peers from patient organizations can help provide relevant information. Easily accessible, multidisciplinary comprehensive care remains a foundation to care. Equipping parents early with the knowledge to facilitate truly informed decision-making will help achieve the best possible longer-term health equity and quality of life for the child and family living with hemophilia. Plain language summary Points to be taken into account to help families make decisions to best care for children born with hemophilia Medical advances are providing a range of treatment options for adults and children with hemophilia. There is, however, relatively limited information about managing newborns with the condition. Doctors and nurses can help parents to understand the choices for infants born with hemophilia. We describe the various points doctors and nurses should ideally discuss with families to enable informed decision-making. We focus on infants who require early treatment to prevent spontaneous or traumatic bleeding (prophylaxis), which is recommended to start before 2 years of age. Families with a history of hemophilia may benefit from discussions before pregnancy, including how an affected child would be treated to protect against bleeds. When mothers are pregnant, doctors can explain investigations that can provide information about their unborn child, plan for the birth, and monitor mother and baby to minimize bleed risks at delivery. Testing will confirm whether the baby is affected by hemophilia. Not all infants with hemophilia will be born to families with a history of the condition. Identification of hemophilia for the first time in a family (which is ‘sporadic hemophilia’) occurs in previously undiagnosed infants who have bleeds requiring medical advice and possibly hospital treatment. Before any mothers and babies with hemophilia are discharged from hospital, doctors and nurses will explain to parents how to recognize bleeding and available treatment options can be discussed. Over time, ongoing discussions will help parents to make informed treatment decisions: • When and how to start, then continue, prophylaxis. • How to deal with bleeds (reinforcing previous discussions about bleed recognition and treatment) and other ongoing aspects of treatment. ○ For instance, children may develop neutralizing antibodies (inhibitors) to treatment they are receiving, requiring a change to the planned approach. • Ensuring treatment remains effective as their child grows, considering the varied needs and activities of their child.

In the Czech Republic, the strategic data-based and organizational support for individual regions and for providers of acute care at the nationwide level is coordinated by the Ministry of Health. At the beginning of the COVID-19 pandemic, the country needed to very quickly implement a system for the monitoring, reporting, and overall management of hospital capacities. The aim of this viewpoint is to describe the purpose and basic functions of a web-based application named “Control Centre for Intensive Care,” which was developed and made available to meet the needs of systematic online technical support for the management of intensive inpatient care across the Czech Republic during the first wave of the pandemic in spring 2020. Two tools of key importance are described in the context of national methodology: one module for regular online updates and overall monitoring of currently free capacities of intensive care in real time, and a second module for online entering and overall record-keeping of requirements on medications for COVID-19 patients. A total of 134 intensive care providers and 927 users from hospitals across all 14 regions of the Czech Republic were registered in the central Control Centre for Intensive Care database as of March 31, 2021. This web-based application enabled continuous monitoring and decision-making during the mass surge of critical care from autumn 2020 to spring 2021. The Control Center for Intensive Care has become an indispensable part of a set of online tools that are employed on a regular basis for crisis management at the time of the COVID-19 pandemic.

At the time of the COVID-19 pandemic, providing access to data (properly optimised regarding personal data protection) plays a crucial role in providing the general public and media with up-to-date information. Open datasets also represent one of the means for evaluation of the pandemic on a global level. The primary aim of this paper is to describe the methodological and technical framework for publishing datasets describing characteristics related to the COVID-19 epidemic in the Czech Republic (epidemiology, hospital-based care, vaccination), including the use of these datasets in practice. Practical aspects and experience with data sharing are discussed. As a reaction to the epidemic situation, a new portal COVID-19: Current Situation in the Czech Republic (https://onemocneni-aktualne.mzcr.cz/covid-19) was developed and launched in March 2020 to provide a fully-fledged and trustworthy source of information for the public and media. The portal also contains a section for the publication of (i) public open datasets available for download in CSV and JSON formats and (ii) authorised-access-only section where the authorised persons can (through an online generated token) safely visualise or download regional datasets with aggregated data at the level of the individual municipalities and regions. The data are also provided to the local open data catalogue (covering only open data on healthcare, provided by the Ministry of Health) and to the National Catalogue of Open Data (covering all open data sets, provided by various authorities/publishers, and harversting all data from local catalogues). The datasets have been published in various authentication regimes and widely used by general public, scientists, public authorities and decision-makers. The total number of API calls since its launch in March 2020 to 15 December 2020 exceeded 13 million. The datasets have been adopted as an official and guaranteed source for outputs of third parties, including public authorities, non-governmental organisations, scientists and online news portals. Datasets currently published as open data meet the 3-star open data requirements, which makes them machine-readable and facilitates their further usage without restrictions. This is essential for making the data more easily understandable and usable for data consumers. In conjunction with the strategy of the MH in the field of data opening, additional datasets meeting the already implemented standards will be also released, both on COVID-19 related and unrelated topics.

At the time of the COVID-19 pandemic, providing access to data (properly optimised regarding personal data protection) plays a crucial role in providing the general public and media with up-to-date information. Open datasets also represent one of the means for evaluation of the pandemic on a global level. The primary aim of this paper is to describe the methodological and technical framework for publishing datasets describing characteristics related to the COVID-19 epidemic in the Czech Republic (epidemiology, hospital-based care, vaccination), including the use of these datasets in practice. Practical aspects and experience with data sharing are discussed. As a reaction to the epidemic situation, a new portal COVID-19: Current Situation in the Czech Republic (https://onemocneni-aktualne.mzcr.cz/covid-19) was developed and launched in March 2020 to provide a fully-fledged and trustworthy source of information for the public and media. The portal also contains a section for the publication of (i) public open datasets available for download in CSV and JSON formats and (ii) authorised-access-only section where the authorised persons can (through an online generated token) safely visualise or download regional datasets with aggregated data at the level of the individual municipalities and regions. The data are also provided to the local open data catalogue (covering only open data on healthcare, provided by the Ministry of Health) and to the National Catalogue of Open Data (covering all open data sets, provided by various authorities/publishers, and harversting all data from local catalogues). The datasets have been published in various authentication regimes and widely used by general public, scientists, public authorities and decision-makers. The total number of API calls since its launch in March 2020 to 15 December 2020 exceeded 13 million. The datasets have been adopted as an official and guaranteed source for outputs of third parties, including public authorities, non-governmental organisations, scientists and online news portals. Datasets currently published as open data meet the 3-star open data requirements, which makes them machine-readable and facilitates their further usage without restrictions. This is essential for making the data more easily understandable and usable for data consumers. In conjunction with the strategy of the MH in the field of data opening, additional datasets meeting the already implemented standards will be also released, both on COVID-19 related and unrelated topics.