The Italian Consensus Conference on the role of rehabilitation for children and adolescents with leukemia, central nervous system tumors, and bone cancer, part 2: general principles for the rehabilitation treatment of motor function impairments.

In Italy, 1400 children and 800 adolescents are diagnosed with cancer every year. About 80% of them can be cured but are at high risk of experiencing severe side effects, many of which respond to rehabilitation treatment. Due to the paucity of literature on this topic, the Italian Association of Pediatric Hematology and Oncology organized a Consensus Conference on the role of rehabilitation of motor impairments in children/adolescents affected by leukemia, central nervous system tumors, and bone cancer to state recommendations to improve clinical practice. This paper includes the consensus on the rehabilitation of children and adolescents with these cancers.

Telehealth vs in-person education for enhancing self-care of ostomy patients (Self-Stoma): Protocol for a noninferiority, randomized, open-label, controlled trial.

INTRODUCTION: Postoperative patients with ostomies experience significant changes in their lives as a result of the device implantation. Self-care is important to improve their health outcomes. Telehealth provides an opportunity to expand access to self-care education. AIM: This is a multicenter, non-inferiority randomized, open-label, controlled trial to evaluate the non-inferiority of a telehealth intervention to the standard in-person approach in improving self-care behaviors. METHODS AND ANALYSIS: Three hundred and eighty-four patients aged ≥ 18 years, with a recently placed ostomy, no stomal/peristomal complications, and documented cognitive integrity will be randomly assigned (1:1) to receive either a telehealth intervention (four remote educational sessions) or a standard educational approach (four in-person sessions) delivered in outpatient settings. Every session (remote and in-person) will occur on Days 25, 32, 40, and 60 after discharge. Follow-ups will occur 1, 3, and 6 months after the last intervention session. Primary outcome is self-care maintenance measured using the Ostomy Self-care Index (OSCI). Secondary outcomes include self-care monitoring, self-care management, self-efficacy (OSCI), quality of life (Stoma specific quality of Life), depression (Patient Health Questionnaire-9), adjustment (Ostomy Adjustment Inventory-23), stomal and peristomal complication rates, healthcare services utilization, mobility, and number of working days lost. Analyses will be performed per intention-to-treat and per protocol. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of the main center (registration number: 119/22). Following completion of the trial, dissemination meetings will be held to share the results of the study with the participants and the health-care team. Adoption of telehealth technologies for ostomy patients can improve service organization by ensuring better integration and continuity of care. If the remote intervention produces comparable effects to the in-person intervention, it would be wise to make telehealth education an alternative treatment for addressing the educational needs of uncomplicated postoperative ostomy patients. TRIAL REGISTRATION: ClinicalTrials.gov (identifier number: NCT05796544).

Short-, mid- and long-term efficacy of dupilumab in moderate to severe atopic dermatitis: a real life multicenter Italian study on 2576 patients.

BACKGROUND: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long term treatment outcomes are currently available to inform clinical decisions. OBJECTIVES: to describe long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD. METHODS: a multicenter, retrospective, dynamic cohort study was conducted to assess long term effectiveness and safety of dupilumab in patients with moderate to severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria (defined as the simultaneous achievement of EASI90, itch NRS score ≤1, sleep NRS score ≤1 and DLQI ≤1) were investigated. RESULTS: 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506 (21.91%), 769 (40.63%), 628 (50.36%), 330 (55.37%) and 58 (54.72%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AE) were mild and were observed in 373 (15.78%), 166 (7.02%), 83 (6.43%), 27 (4.50%) and 5 (4.55%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AE led to treatment discontinuation in <1% of patients during the evaluated time periods. CONCLUSION: High long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate to severe AD, regardless of clinical phenotype and course at baseline. Further research will be needed to investigate the effect of Th2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD.

Exploring the interplay of atopic dermatitis severity with sleep and mental health: a case-control study in adult patients.

OBJECTIVES: Atopic dermatitis (AD) is a chronic inflammatory skin disease often associated with non-atopic comorbidities. Recently, a severity-dependent relationship between AD and sleep/mental health diseases has been proposed. However, few studies investigated these comorbidities and their association with AD severity through validated questionnaires. This study aimed to use a set of validated instruments to assess the impact of AD on sleep and psychological disorders and estimate the association of itch and AD severity with sleep disorders and psychological symptoms, distinguishing between clinical-oriented and patient-oriented measures. METHODS: We conducted a case-control study, recruiting 57 adult AD patients (mean age ± std. dev. 34.28 years ± 13.07; 27 males) matched for age and sex with 57 healthy adults (34.39 years ± 13.09; 27 males). To investigate the differences in sleep quality, insomnia, depression, and anxiety between the two groups, we performed independent sample t-Tests. Moreover, we conducted univariate linear regression analyses to examine the relationship between itch and objective/subjective severity of AD and sleep quality, insomnia, and psychological symptoms. RESULTS: AD patients reported lower sleep quality (p = 0.002), more severe insomnia (p = 0.006) and depression (p = 0.013), and higher stress levels than healthy adults (p = 0.049). Itch intensity was linked to sleep disturbances and psychological symptoms (R2range = 0.13-0.19, prange = 0.02-<0.001). Objective and subjective AD severity were similarly associated with worse sleep quality (R2 = 0.26, p < 0.001; R2 = 0.24, p < 0.001; respectively), anxiety (R2 = 0.15, p = 0.04; R2 = 0.17, p = 0.001; respectively), and self-perceived stress (R2 = 0.10, p = 0.02; R2 = 0.07, p = 0.049; respectively). However, subjective AD severity was more strongly associated with insomnia (R2 = 0.31, p < 0.001) and depression (R2 = 0.20, p < 0.001) than clinical-oriented AD severity (R2 = 0.19, p < 0.001; R2 = 0.05, p = 0.098; respectively). CONCLUSIONS: The study demonstrated poor sleep quality and high levels of insomnia, depression, and stress in AD patients, with an aggravated psychological status for adults with more severe skin disease. We suggest implementing a multidisciplinary approach to AD management/treatment that considers objective and subjective measures of disease severity.

Patient and Provider Perceptions of Barriers and Facilitators to Pre-exposure Prophylaxis Access and Adherence in Black and Latinx Young Men Who Have Sex with Men.

In the United States, the use of pre-exposure prophylaxis (PrEP) has led to a substantial decrease in HIV prevalence and incidence. However, some populations, including young men who have sex with men (YMSM) of color, continue to be disproportionately impacted, highlighting the need for tailored interventions addressing barriers to adequate PrEP access. In collaboration with partner clinics, we recruited 19 PrEP clients and 19 PrEP providers (n = 35) to participate in hour-long in-depth interviews. Although client interviews explored personal experiences with stigma, barriers, and motivators to PrEP and information preferences, provider interviews explored providers' perceived stigma in their clinic, perceived barriers and motivators to meeting clients' PrEP needs, and rapport building with clients. Most participants were affiliated with one of the southern partner clinics. Clients and providers noted similar determinants to PrEP access, uptake, and adherence. Both recognized the impact of personal barriers such as routine adjustments and perception of need, as well as institutional barriers such as transportation and financial difficulties. Clients emphasized the role of the client-provider relationship as part of contributing to willingness to disclose information such as HIV status and sexual practices. Providers noted the importance of sexual health and LGBTQ+ topics in their training. Despite limited geographical scope and the sensitive nature of HIV-related topics, this study has several implications. PrEP clinics may benefit from hiring providers who share identities and experiences with YMSM clients of color and operating with a flexible schedule. Medical provider training should include comprehensive sexual health and LGBTQ+ competencies to reduce bias in care.

Validation and molecular integration of the RR6 model to predict survival after 6 months of therapy with ruxolitinib.

Not available.

Three-dimensional Versus Two-dimensional Laparoscopic Bariatric Surgery: A Systematic Review and Meta-analysis.

Three-dimensional (3D) laparoscopy has several advantages in gastrointestinal surgery. This systematic review determined whether similar benefits exist for bariatric surgical procedures by systematically searching the MEDLINE, Embase, and Scopus databases. Six studies including 629 patients who underwent 2D (386) and 3D (243) laparoscopic bariatric surgeries were selected. Operative time was significantly shorter in patients undergoing 3D laparoscopic gastric bypass (pooled standardized mean difference [SMD] 1.19, 95% confidence interval [CI] 2.22-0.15). Similarly, a shorter hospital stay was detected both during sleeve gastrectomy (SMD 0.42, 95% CI 0.70-0.13) and gastric bypass (SMD 0.39, 95% CI 0.64-0.14) with 3D laparoscopy. The study showed the potential benefit of 3D imaging in preventing intra- and postoperative complications. Despite the limited evidence, surgeons may benefit from 3D laparoscopy during bariatric surgery.

Photodynamic Therapy for the Treatment of Bowen's Disease: A Review on Efficacy, Non-Invasive Treatment Monitoring, Tolerability, and Cosmetic Outcome.

Bowen's disease represents the in situ form of cutaneous squamous cell carcinoma; although it has an excellent prognosis, 3-5% of lesions progress to invasive cutaneous squamous cell carcinoma, with a higher risk in immunocompromised patients. Treatment is therefore always necessary, and conventional photodynamic therapy is a first-line option. The aim of this review is to provide an overview of the clinical response, recurrence rates, safety, and cosmetic outcome of photodynamic therapy in the treatment of Bowen's disease, considering different protocols in terms of photosensitizers, light source, and combination treatments. Photodynamic therapy is a valuable option for tumors at sites where wound healing is poor/delayed, in the case of multiple and/or large tumors, and where surgery would be difficult or invasive. Dermoscopy and reflectance confocal microscopy can be used as valuable tools for monitoring the therapeutic response. The treatment is generally well tolerated, with mild side effects, and is associated with a good/excellent cosmetic outcome. Periodic follow-up after photodynamic therapy is essential because of the risk of recurrence and progression to cSCC. As the incidence of keratinocyte tumors increases, the therapeutic space for photodynamic therapy will further increase.

Identification of an ultra-rare Alu insertion in the CFTR gene: Pitfalls and challenges in genetic test interpretation.

Cystic fibrosis (CF) is a life-limiting genetic disorder characterized by defective chloride ion transport due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Early detection through newborn screening programs significantly improves outcomes for individuals with CF by enabling timely intervention. Here, we report the identification of an Alu element insertion within the exon 15 of CFTR gene, initially overlooked in standard next-generation sequencing analyses. However, using traditional molecular techniques, based on polymerase chain reaction and Sanger sequencing, allowed the identification of the Alu element and the reporting of a correct diagnosis. Our analysis, based on bioinformatics tools and molecular techniques, revealed that the Alu element insertion severely affects the gene expression, splicing patterns, and structure of CFTR protein. In conclusion, this study emphasizes the importance of how the integration of human expertise and modern technologies represents a pivotal step forward in genomic medicine, ensuring the delivery of precision healthcare to individuals affected by genetic diseases.

Reproductive toxicity assessment of cellulose nanofibers, citric acid, and branched polyethylenimine in sea urchins: Eco-design of nanostructured cellulose sponge framework (Part B).

In the framework of a safe-by-design approach, we previously assessed the eco-safety of nanostructured cellulose sponge (CNS) leachate on sea urchin reproduction. It impaired gamete quality, gamete fertilization competence, and embryo development possibly due to the leaching of chemical additives used during the CNS synthesis process. To extend this observation and identify the component(s) that contribute to CNS ecotoxicity, in the present study, we individually screened the cytotoxic effects on sea urchin Arbacia lixula and Paracentrotus lividus gametes and embryos of the three main constituents of CNS, namely cellulose nanofibers, citric acid, and branched polyethylenimine. The study aimed to minimize any potential safety risk of these components and to obtain an eco-safe CNS. Among the three CNS constituents, branched polyethylenimine resulted in the most toxic agent. Indeed, it affected the physiology and fertilization competence of male and female gametes as well as embryo development in both sea urchin species. These results are consistent with those previously reported for CNS leachate. Moreover, the characterisation of CNS leachate confirmed the presence of detectable branched polyethylenimine in the conditioned seawater even though in a very limited amount. Altogether, these data indicate that the presence of branched polyethylenimine is a cause-effect associated with a significant risk in CNS formulations due to its leaching upon contact with seawater. Nevertheless, the suggested safety protocol consisting of consecutive leaching treatments and conditioning of CNS in seawater can successfully ameliorate the CNS ecotoxicity while maintaining the efficacy of its sorbent properties supporting potential environmental applications.

Short-term effectiveness of guselkumab in psoriatic arthritis patients and suggestive features of axial involvement: results from a real-life multicentre cohort.

OBJECTIVE: To evaluate the short-term effectiveness of guselkumab in patients with psoriatic arthritis (PsA) and suggestive features of axial involvement in a prospective "real-life" multicentre cohort. METHODS: Between June 2022 and June 2023, PsA patients with axial involvement were evaluated if treated at least for 4 months with guselkumab. The effectiveness was evaluated by BASDAI, ASDAS, DAPSA, and achievement of BASDAI ≤ 4, also exploiting predictive factors. In a group of patients, MRI findings on sacroiliac joints were assessed before and after guselkumab administration. RESULTS: Sixty-seven patients with PsA and suggestive features of axial involvement (age 53.4 ± 11.2 years, male sex 26.9%) were treated with guselkumab. After 4 months, a significant reduction of BASDAI, ASDAS, and DAPSA was observed. A ΔBASDAI of -2.11 ± 0.43 was estimated assessing the mean difference values before and after guselkumab administration and 52.2% of patients reached a BASDAI ≤ 4. In 27 patients, MRI findings on sacroiliac joints were assessed before and after guselkumab administration. A reduction of 0.80 or larger of the sacroiliac joint lesion score was observed in the majority of patients (70.3%) based on MRI improvements, paralleling with the clinical response.No life-threatening side effects were recorded; 17.9% of patients reported minor adverse events mainly injection site reactions. CONCLUSIONS: The short-term effectiveness of guselkumab in patients with PsA and suggestive features of axial involvement was shown. Although further studies are needed, our multicentre "real-life" study may suggest the clinical usability of guselkumab in this context.

Comparative Study of Spheroids (3D) and Monolayer Cultures (2D) for the In Vitro Assessment of Cytotoxicity Induced by the Mycotoxins Sterigmatocystin, Ochratoxin A and Patulin.

Mycotoxins are secondary metabolites produced by filamentous fungi associated with a variety of acute and chronic foodborne diseases. Current toxicology studies mainly rely on monolayer cell cultures and animal models, which are undeniably affected by several limitations. To bridge the gap between the current in vitro toxicology approach and the in vivo predictability of the data, we here investigated the cytotoxic effects induced by the mycotoxins sterigmatocystin (STE), ochratoxin A (OTA) and patulin (PAT) on different 2D and 3D cell cultures. We focused on human tumours (neuroblastoma SH-SY5Y cells and epithelial breast cancer MDA-MB-213 cells) and healthy cells (bone marrow-derived mesenchymal stem cells, BM-MSC, and umbilical vein endothelial cells, HUVECs). The cytotoxicity of STE, OTA, and PAT was determined after 24, 48 and 72 h of exposure using an ATP assay in both culture models. Three-dimensional spheroids' morphology was also analysed using the MATLAB-based open source software AnaSP 1.4 version. Our results highlight how each cell line and different culture models showed specific sensitivities, reinforcing the importance of using more complex models for toxicology studies and a multiple cell line approach for an improved and more comprehensive risk assessment.

Systematic review and meta-analysis of postoperative outcomes after combined stoma reversal and incisional hernia repair versus stoma reversal alone.

BACKGROUND: The optimal management and timing of the abdominal wall reconstruction concomitantly performed with stoma closure are controversial. This study aims to compare short-term postoperative outcomes after concurrent stoma reversal (SR) with incisional hernia repair (IHR) and SR alone. METHODS: PubMed/MEDLINE, Scopus and Web of Science databases were consulted to identify comparative studies. Random and common-effect models were used for the pooled analysis of the proportions and means. RESULTS: Three studies met the inclusion criteria and a total of 504 patients who underwent simultaneous SR and IHR (N.=200) or SR alone (N.=304) were included in the meta-analysis. Postoperative morbidity increased after combined stoma and hernia surgery with a pooled OR for Surgical Site Occurrence (SSO) and severe postoperative complications (Clavien-Dindo ≥III) of 1.72 (95% CI 1.02-2.90) and 3.83 (95% CI 1.46-10.02), respectively. No significant difference was found between the two groups in terms of mortality (OR: 1.66; 95% CI 0.64-4.27), length of hospital stay (OR: 1.37; 95% CI 0.73-3.47). and readmission rate (OR: 1.17; 95% CI 0.67-2.06). CONCLUSIONS: There is limited evidence suggesting that synchronous repair of SR and IH appears to be associated with a higher risk of SSO and severe postoperative complications. Therefore, a stepwise approach may be considered the best strategy in this setting.

Bimekizumab for the Treatment of Plaque Psoriasis with Involvement of Genitalia: A 16-Week Multicenter Real-World Experience - IL PSO (Italian Landscape Psoriasis).

INTRODUCTION: Genital involvement is observed in approximately 60% of patients with psoriasis, presenting clinicians with formidable challenges in treatment. While new biologic drugs have emerged as safe and effective options for managing psoriasis, their efficacy in challenging-to-treat areas remains inadequately explored. Intriguingly, studies have shown that interleukin (IL)-17 inhibitors exhibit effectiveness in addressing genital psoriasis. OBJECTIVES: We aimed to determine the effectiveness profile of bimekizumab in patients affected by moderate-to-severe plaque psoriasis with involvement of genitalia. METHODS: Bimekizumab, a dual inhibitor of both IL-17A and IL-17F, was the focus of our 16-week study, demonstrating highly favorable outcomes for patients with genital psoriasis. The effectiveness of bimekizumab was evaluated in terms of improvement in Static Physician Global Assessment of Genitalia (sPGA-G) and Psoriasis Area and Severity Index. RESULTS: Sixty-five adult patients were enrolled. Remarkably, 98.4% of our participants achieved a clear sPGA-G score (s-PGA-g = 0) within 16 weeks. Moreover, consistent improvements were observed in Psoriasis Area and Severity Index scores, accompanied by a significant reduction in the mean Dermatology Life Quality Index, signifying enhanced quality of life. Notably, none of the patients reported a severe impairment in their quality of life after 16 weeks of treatment. In our cohort of 65 patients, subgroup analyses unveiled that the effectiveness of bimekizumab remained unaffected by prior exposure to other biologics or by obesity. CONCLUSIONS: Our initial findings suggest that bimekizumab may serve as a valuable treatment option for genital psoriasis. Nevertheless, further research with larger sample sizes and longer-term follow-up is imperative to conclusively validate these results.

AtopyReg®, the Prospective Italian Patient Registry for Moderate-to-Severe Atopic Dermatitis in Adults: Baseline Demographics, Disease Characteristics, Comorbidities, and Treatment History.

BACKGROUND AND OBJECTIVE: AtopyReg® is a multicenter, prospective, observational, non-profit cohort study on moderate-to-severe atopic dermatitis in adults promoted in 2018 by the Italian Society of Dermatology and Venereology (SIDeMaST). We aimed to describe baseline demographics, disease characteristics, comorbidities, and therapeutic data of adult patients affected by moderate-to-severe atopic dermatitis. METHODS: Patients were selected based on the following inclusion criteria: age ≥ 18 years; Eczema Area and Severity Index score ≥ 16 or localization in visible or sensitive areas (face, neck, hands, or genitalia), or a Numeric Rating Scale itch score ≥ 7 or a Numeric Rating Scale sleep loss score ≥ 7, or a Dermatology Life Quality Index score ≥ 10. Demographic and clinical data at baseline were recorded and analyzed. RESULTS: A total of 1170 patients (male 51.1%; mean age: 44.7 years; range 18-90 years) were enrolled by 12 Italian Dermatology Units between January 2019 and November 2022. Skin lesions were eczematous in 83.2% of patients, the most involved site were the flexures (53.9%), face (50.9%), and neck (48.0%). Mean Eczema Area and Severity Index score was 22.3, mean Dermatology Life Quality Index value was 17.6, mean Patient Oriented Eczema Measure score was 13.1, and mean Numeric Rating Scale itch and sleep loss scores were 7.6 and 5.9, respectively. Previous systemic therapies were corticosteroids in 77.7% of patients, antihistamines in 50.3% of patients, and cyclosporine A in 42.6% of patients. CONCLUSIONS: This baseline data analysis deriving from AtopyReg® provides real-life evidence on patients with moderate-to-severe atopic dermatitis in Italy confirming the high burden of atopic dermatitis with a significant impact on patients' quality of life.

One-step NGS molecular analysis of the CFTR gene on newborn dried blood spots gives a higher diagnostic sensitivity in affected and carrier subjects: A pilot study.

BACKGROUND: Cystic fibrosis is the most common hereditary recessive disease with an incidence of about 1:2500/3000. It has long been known that the disease is caused by deleterious mutations in the CFTR gene. Conventionally, the disease is diagnosed in several phases. The analysis of all the possible disease-causing molecular alterations is time consuming and may not lead to a definitive diagnosis in several cases. Consequently, we propose, in this paper, a rapid sequencing method that, in a single procedural asset, reveals the presence of small mutations and also the copy number variants (CNVs) from the DNA extracted from the Guthrie Spot. MATERIALS AND METHODS: We first sequenced 30 blood spots, then we validated the method on 100 spots that underwent both traditional analyses and this complete NGS sequencing, and lastly, we tested the strategy on patients who normally do not reach the molecular sequencing step because of low level of Immune-Reactive Trypsinogen. RESULTS: Using this procedure, we identified 97 variants in the CFTR gene of our samples and 6 CNVs. Notably, the significant data were obtained in the group of patients with borderline or negative IRT who routinely would not undergo molecular testing. We also identified 6 carriers of "disease-causing" variants. CONCLUSION: This method is very robust. Indeed, there was a 100% concordance with Sanger sequencing validation, and 6 mutation carriers were identified who normally escaped molecular testing with actual conventional procedure. There were also 3 duplications of almost the entire gene in heterozygosity, which were not seen with traditional methods. Being quick and easy to perform, we suggest that complete sequencing of the CFTR gene, as in this study be considered for all newborns.

The prognostic contribution of CBL, NRAS, KRAS, RUNX1, and TP53 mutations to mutation-enhanced international prognostic score systems (MIPSS70/plus/plus v2.0) for primary myelofibrosis.

Contemporary risk models in primary myelofibrosis (PMF) include the mutation (MIPSS70) and mutation/karyotype enhanced (MIPSS70 plus/v2.0) international prognostic scoring systems. High molecular risk (HMR) mutations incorporated in one or both of these models include ASXL1, SRSF2, EZH2, IDH1/2, and U2AF1Q157; the current study examines additional prognostic contribution from more recently described HMR mutations, including CBL, NRAS, KRAS, RUNX1, and TP53. In a cohort of 363 informative cases (median age 58 years; 60% males), mutations included JAK2 61%, CALR 24%, MPL 6%, ASXL1 29%, SRSF2 10%, U2AF1Q157 5%, EZH2 10%, IDH1/2 4%, TP53 5%, CBL 5%, NRAS 7%, KRAS 4%, and RUNX1 4%. At a median follow-up of 4.6 years, 135 (37%) deaths and 42 (11.6%) leukemic transformations were recorded. Univariate analysis confirmed significant survival impact from the original MIPSS70/plus/v2.0 HMR mutations as well as CBL (HR 2.8; p < .001), NRAS (HR 2.4; p < .001), KRAS (HR 2.1; p = .01), and TP53 (HR 2.4; p = .004), but not RUNX1 mutations (HR 1.8; p = .08). Multivariate analysis (MVA) that included both the original and more recently described HMR mutations confirmed independent prognostic contribution from ASXL1 (HR 1.8; p = .007), SRSF2 (HR 4.3; p < .001), U2AF1Q157 (HR 2.9, p = .004), and EZH2 (HR 2.4; p < .001), but not from IDH1/2 (p = .3), TP53 (p = .2), CBL (p = .3), NRAS (p = .8) or KRAS (p = .2) mutations. The lack of additional prognostic value from CBL, NRAS, KRAS, RUNX1, and TP53 was further demonstrated in the setting of (i) MVA of mutations and karyotype, (ii) MVA of MIPSS70/plus/v2.0 composite scores and each one of the recently described HMR mutations, except TP53, and iii) modified MIPSS70/plus/plus v2.0 that included CBL, NRAS, KRAS, and TP53 as part of the HMR constituency, operationally referred to as "HMR+" category. Furthermore, "HMR+" enhancement of MIPSS70/plus/plus v2.0 did not result in improved model performance, as measured by C-statistics. We conclude that prognostic integrity of MIPSS70/plus/plus v2.0, as well as their genetic components, was sustained and their value not significantly upgraded by the inclusion of more recently described HMR mutations, including CBL, NRAS, KRAS, and RUNX1. Additional studies are needed to clarify the apparent additional prognostic value of TP53 mutation and its allelic state.

Availability of medical and endovascular therapies for venous thromboembolism: a global survey for World Thrombosis Day.

BACKGROUND: Data on availability, affordability, and accessibility is key for the planning of global strategies to reduce the burden of venous thromboembolism (VTE). OBJECTIVES: A survey was conducted for the 10th anniversary of World Thrombosis Day to assess the availability of VTE therapies worldwide and challenges in uniform implementation. METHODS: We gathered information on the approval status, availability, utilization, occurrence of shortages, and spread of medical and interventional therapies for VTE. Furthermore, we collected information by accessing or contacting national or continental medicines agencies, manufacturers or distributors, and online drug repositories. RESULTS: We obtained data from a total of 69 countries: 33 countries in Europe, 19 in Asia, 7 in the Americas, 9 in Africa, and 1 in Oceania. Unfractionated heparin, low-molecular-weight heparin, and vitamin K antagonists were available in almost all countries, but shortages were recorded in 13%, 19%, and 15% of them, respectively. Direct oral anticoagulants were available in approximately three-quarters of the surveyed countries. At least one parenteral medication for heparin-induced thrombocytopenia was available in 57% of countries and a shortage was reported in 9% of these. Shortage of thrombolytics was recorded in 50% of countries. Overall, at least one type of catheter-directed therapy system was approved for use in 77% of countries and available in 23% of surveyed institutions. Our findings revealed notable geographic disparities in the worldwide availability of VTE therapies, the access to which appeared to be limited by economic and geopolitical factors. CONCLUSION: We anticipate that this comprehensive information will play a pivotal role in highlighting the shortcomings of VTE therapies and the lack of homogeneous availability globally.