Medicine (Baltimore). 2023 Mar 31;102(13):e32662. doi: 10.1097/MD.0000000000032662.

ABSTRACT

Pseudomonas aeruginosa infective endocarditis (IE) is a rare disease associated with high mortality and complications. Here, we describe a contemporary set of patients aiming to improve the understanding of risk factors, clinical features, treatments, and outcomes. This retrospective case series reviewed cases from 3 tertiary metropolitan hospitals between January 1999 and January 2019. prespecified data were collected for each case, with a review of risk factors, valve involvement, acquisition, treatment, and complications. Fifteen patients were identified over a 20 years period. All patients presented with fever, 5/15 had preexisting prosthetic valve with valvular heart disease in 7/15 patients making it the most common risk factor. Intravenous drug use (IVDU) was the source in only 6/15 cases with healthcare associated infection and left-sided valvular involvement being more common than previous reports both occurring in 9/15 cases. Complications occurred in 11/15 patients with a 30 days mortality of 13%. Surgery was performed in 7/15 patients and 9/15 patients received antibiotic combination therapy. One year mortality was higher in those with increasing age, comorbidities, left-sided valve involvement, presence of predefined complications, and antibiotic monotherapy. Development of resistance occurred in 2 cases that received monotherapy. P aeruginosa IE remains a rare disease with high mortality and secondary complications.

PMID:37000062 | PMC:PMC10063303 | DOI:10.1097/MD.0000000000032662

Turk Kardiyol Dern Ars. 2023 Apr;51(3):212-216. doi: 10.5543/tkda.2022.23460.

ABSTRACT

This article presents the case of a 24-year-old woman with Poland syndrome who developed primary right atrial cardiac angiosarcoma. The patient presented to the hospital with dyspnea and chest pain, and imaging studies revealed a large mass attached to the right atrium. Urgent surgery was performed to remove the tumor, and the patient underwent adjuvant chemotherapy afterward. Follow-up exams showed no signs of the tumor or any complications from treatment. Poland syndrome is a rare congenital disorder characterized by the absence of unilateral large pectoral muscle, ipsilateral symbrachydactyly, and other malformations of the anterior chest wall and breast. Although the condition does not predispose patients to malignancy, different pathologies can be seen in these patients due to the unknown etiology of the syndrome. Primary right atrial cardiac angiosarcoma is a rare malignancy, and its coexistence with Poland syndrome has not been well established in the literature. This case report highlights the need to consider cardiac angiosarcoma as a possible diagnosis in patients with Poland syndrome who present with cardiac symptoms.

PMID:36999325 | DOI:10.5543/tkda.2022.23460

Ann Clin Transl Neurol. 2023 Mar 31. doi: 10.1002/acn3.51767. Online ahead of print.

ABSTRACT

OBJECTIVE: The goal of this study is to demonstrate the utility of a growth assay to quantify the functional impact of single nucleotide variants (SNVs) in SLC2A1, the gene responsible for Glut1DS.

METHODS: The functional impact of 40 SNVs in SLC2A1 was quantitatively determined in HAP1 cells in which SLC2A1 is required for growth. Donor libraries were introduced into the endogenous SLC2A1 gene in HAP1-Lig4KO cells using CRISPR/Cas9. Cell populations were harvested and sequenced to quantify the effect of variants on growth and generate a functional score. Quantitative functional scores were compared to 3-OMG uptake, SLC2A1 cell surface expression, CADD score, and clinical data, including CSF/blood glucose ratio.

RESULTS: Nonsense variants (N = 3) were reduced in cell culture over time resulting in negative scores (mean score: -1.15 ± 0.17), whereas synonymous variants (N = 10) were not depleted (mean score: 0.25 ± 0.12) (P < 2e-16). Missense variants (N = 27) yielded a range of functional scores including slightly negative scores, supporting a partial function and intermediate phenotype. Several variants with normal results on either cell surface expression (p.N34S and p.W65R) or 3-OMG uptake (p.W65R) had negative functional scores. There is a moderate but significant correlation between our functional scores and CADD scores.

INTERPRETATION: Cell growth is useful to quantitatively determine the functional effects of SLC2A1 variants. Nonsense variants were reliably distinguished from benign variants in this in vitro functional assay. For facilitating early diagnosis and therapeutic intervention, future work is needed to determine the functional effect of every possible variant in SLC2A1.

PMID:37000947 | DOI:10.1002/acn3.51767

Res Sq. 2023 Mar 20:rs.3.rs-2566253. doi: 10.21203/rs.3.rs-2566253/v1. Preprint.

ABSTRACT

Objective: Recent advances in the understanding of neurodevelopmental disorders such as Rett syndrome (RTT) has enabled development of novel therapeutic approaches that are currently undergoing clinical evaluation or are proposed to move into clinical development. Clinical trial success depends on outcome measures that assess clinical features that are most impactful for affected individuals. To determine the top concerns in RTT and RTT-related disorders we asked caregivers to list the top clinical concerns in order to gain information to guide the development and selection of outcome measures for future clinical trials. Methods: Caregivers of participants enrolled in the US Natural History Study of RTT and related disorders were asked to identify the top 3 concerning problems impacting the affected participant. We generated a weighted list of top caregiver concerns for each of the diagnostic categories and compared results between the disorders. Further, for Classic RTT, caregiver concerns were analyzed by age, clinical severity, and common RTT-causing mutations in MECP2 . Results: The top caregiver concerns for Classic RTT were effective communication, seizures, walking/balance issues, lack of hand use, and constipation. The rank order of the frequency of the top caregiver concerns for Classic RTT varied by age, clinical severity, and specific mutations, consistent with known variation in the frequency of clinical features across these domains. The frequency of caregiver concern for seizures, hand use, and spoken language increased in relation to clinician assessed severity in these clinical domains, showing consistency between clinician assessments and caregiver concerns. Comparison across disorders found commonalities in the top caregiver concerns between Classic RTT, Atypical RTT, MECP2 Duplication Syndrome, CDKL5 Deficiency Disorder, and FOXG1 Syndrome; however, distinct differences in caregiver concerns between these disorders are consistent with the relative prevalence and impact of specific clinical features. Conclusion: The top caregiver concerns for individuals with RTT and the RTT-related disorders reflect the impact of the primary clinical symptoms of these disorders. This work is critical in the development of meaningful therapies, as optimal therapy should address these concerns. Further, outcome measures to be utilized in clinical trials should assess these clinical issues identified as most concerning by caregivers.

PMID:36993737 | PMC:PMC10055548 | DOI:10.21203/rs.3.rs-2566253/v1

Rofo. 2023 Apr;195(4):333-334. doi: 10.1055/a-2030-1114. Epub 2023 Mar 30.

NO ABSTRACT

PMID:36996825 | DOI:10.1055/a-2030-1114

Diabetologia. 2023 Mar 30. doi: 10.1007/s00125-023-05905-8. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Wolfram syndrome is a rare autosomal recessive disorder caused by pathogenic variants in the WFS1 gene. It is characterised by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing loss and neurodegeneration. Considering the unmet treatment need for this orphan disease, this study aimed to evaluate the therapeutic potential of glucagon-like peptide 1 receptor (GLP-1R) agonists under wolframin (WFS1) deficiency with a particular focus on human beta cells and neurons.

METHODS: The effect of the GLP-1R agonists dulaglutide and exenatide was examined in Wfs1 knockout mice and in an array of human preclinical models of Wolfram syndrome, including WFS1-deficient human beta cells, human induced pluripotent stem cell (iPSC)-derived beta-like cells and neurons from control individuals and individuals affected by Wolfram syndrome, and humanised mice.

RESULTS: Our study shows that the long-lasting GLP-1R agonist dulaglutide reverses impaired glucose tolerance in WFS1-deficient mice, and that exenatide and dulaglutide improve beta cell function and prevent apoptosis in different human WFS1-deficient models including iPSC-derived beta cells from people with Wolfram syndrome. Exenatide improved mitochondrial function, reduced oxidative stress and prevented apoptosis in Wolfram syndrome iPSC-derived neural precursors and cerebellar neurons.

CONCLUSIONS/INTERPRETATION: Our study provides novel evidence for the beneficial effect of GLP-1R agonists on WFS1-deficient human pancreatic beta cells and neurons, suggesting that these drugs may be considered as a treatment for individuals with Wolfram syndrome.

PMID:36995380 | DOI:10.1007/s00125-023-05905-8

bioRxiv. 2023 Mar 19:2023.02.01.526672. doi: 10.1101/2023.02.01.526672. Preprint.

ABSTRACT

Appendiceal adenocarcinomas (AAs) are a rare and heterogeneous mix of tumors for which few preclinical models exist. The rarity of AA has made performing prospective clinical trials difficult, and in part because of this AA remains an orphan disease with no chemotherapeutic agents approved by the FDA for its treatment. AA has a unique biology in which it frequently forms diffuse peritoneal metastases, but almost never spreads via a hematogenous route and rarely spreads to lymphatics. Given its localization to the peritoneal space we hypothesized that intraperitoneal (IP) delivery of chemotherapy could be an effective treatment strategy. Here we tested the efficacy paclitaxel given by IP administration using three orthotopic PDX models of AA established in NSG mice. Weekly treatment of 25.0 mg/kg of IP paclitaxel dramatically reduced AA tumor growth in TM00351 (81.9% reduction vs. control), PMP-2 (98.3% reduction vs. control), and PMCA-3 (71.4% reduction vs. control) PDX models. Comparing the safety and efficacy of intravenous (IV) to IP administration in PMCA-3, neither 6.25 nor 12.5 mg/kg of IV paclitaxel significantly reduced tumor growth. These results suggest that IP administration of paclitaxel is favorable to IV administration. Given the established safety record of IP paclitaxel in gastric and ovarian cancers, and lack of effective chemotherapeutics for AA, these data showing the activity of IP paclitaxel in orthotopic PDX models of mucinous AA support the evaluation of IP paclitaxel in a prospective clinical trial.

PMID:36993681 | PMC:PMC10055008 | DOI:10.1101/2023.02.01.526672

Int J Environ Res Public Health. 2023 Mar 8;20(6):4732. doi: 10.3390/ijerph20064732.

ABSTRACT

This document provides a comprehensive summary of evidence on the current situation of rare diseases (RDs) globally and regionally, including conditions, practices, policies, and regulations, as well as the challenges and barriers faced by RD patients, their families, and caregivers. The document builds on a review of academic literature and policies and a process of validation and feedback by a group of seven experts from across the globe. Panelists were selected based on their academic merit, expertise, and knowledge regarding the RD environment. The document is divided into five main sections: (1) methodology and objective; (2) background and context; (3) overview of the current situation and key challenges related to RDs covering six dimensions: burden of disease, patient journey, social impact, disease management, RD-related policies, and research and development; (4) recommendations; and (5) conclusions. The recommendations are derived from the discussion undertaken by the experts on the findings of this review and provide a set of actionable solutions to the challenges and barriers to improving access to RD diagnosis and treatment around the world. The recommendations can support critical decision-making, guiding efforts by a broad range of RDs stakeholders, including governments, international organizations, manufacturers, researchers, and patient advocacy groups.

PMID:36981643 | DOI:10.3390/ijerph20064732

Genes (Basel). 2023 Mar 16;14(3):727. doi: 10.3390/genes14030727.

ABSTRACT

Ancient anatomically modern humans (AMHs) encountered other archaic human species, most notably Neanderthals and Denisovans, when they left Africa and spread across Europe and Asia ~60,000 years ago. They interbred with them, and modern human genomes retain DNA inherited from these interbreeding events. High quality (high coverage) ancient human genomes have recently been sequenced allowing for a direct estimation of individual heterozygosity, which has shown that genetic diversity in these archaic human groups was very low, indicating low population sizes. In this study, we analyze ten ancient human genome-wide data, including four sequenced with high-coverage. We screened these ancient genome-wide data for pathogenic mutations associated with monogenic diseases, and established unusual aggregation of pathogenic mutations in individual subjects, including quadruple homozygous cases of pathogenic variants in the PAH gene associated with the condition phenylketonuria in a ~120,000 years old Neanderthal. Such aggregation of pathogenic mutations is extremely rare in contemporary populations, and their existence in ancient humans could be explained by less significant clinical manifestations coupled with small community sizes, leading to higher inbreeding levels. Our results suggest that pathogenic variants associated with rare diseases might be the result of introgression from other archaic human species, and archaic admixture thus could have influenced disease risk in modern humans.

PMID:36980999 | DOI:10.3390/genes14030727

Orphanet J Rare Dis. 2023 Mar 28;18(1):70. doi: 10.1186/s13023-023-02663-z.

ABSTRACT

BACKGROUND AND OBJECTIVE: The diagnosis of rare diseases (RDs) is often challenging due to their rarity, variability and the high number of individual RDs, resulting in a delay in diagnosis with adverse effects for patients and healthcare systems. The development of computer assisted diagnostic decision support systems could help to improve these problems by supporting differential diagnosis and by prompting physicians to initiate the right diagnostic tests. Towards this end, we developed, trained and tested a machine learning model implemented as part of the software called Pain2D to classify four rare diseases (EDS, GBS, FSHD and PROMM), as well as a control group of unspecific chronic pain, from pen-and-paper pain drawings filled in by patients.

METHODS: Pain drawings (PDs) were collected from patients suffering from one of the four RDs, or from unspecific chronic pain. The latter PDs were used as an outgroup in order to test how Pain2D handles more common pain causes. A total of 262 (59 EDS, 29 GBS, 35 FSHD, 89 PROMM, 50 unspecific chronic pain) PDs were collected and used to generate disease specific pain profiles. PDs were then classified by Pain2D in a leave-one-out-cross-validation approach.

RESULTS: Pain2D was able to classify the four rare diseases with an accuracy of 61-77% with its binary classifier. EDS, GBS and FSHD were classified correctly by the Pain2D k-disease classifier with sensitivities between 63 and 86% and specificities between 81 and 89%. For PROMM, the k-disease classifier achieved a sensitivity of 51% and specificity of 90%.

CONCLUSIONS: Pain2D is a scalable, open-source tool that could potentially be trained for all diseases presenting with pain.

PMID:36978184 | DOI:10.1186/s13023-023-02663-z

Anticancer Res. 2023 Apr;43(4):1397-1405. doi: 10.21873/anticanres.16288.

ABSTRACT

BACKGROUND/AIM: Small cell neuroendocrine carcinoma of the cervix (SCNEC) is a rare disease characterized by a higher incidence of lymphatic invasion, metastasis, and recurrence compared to the squamous cell carcinoma and adenocarcinoma subtypes. Furthermore, it is prone to early distant metastasis and has a poor prognosis. Chemotherapy has an important role in the management of cervical SCNEC. The effective treatment schemes for early-stage SCNEC are local treatment with radical surgery and systemic chemotherapy. However no standard treatment regimen exists because of a rare disease. We reviewed previous reports to determine whether etoposide/platinum, which is used for histopathologically similar small cell carcinoma of the lung, is an appropriate initial chemotherapy regimen for SCNEC of the cervix.

MATERIALS AND METHODS: In this review the Cochrane library sources, ClinicalTrials.gov, Web of Silence, PubMed and search engine of Google scholar were searched for all interventional studies, reviews, case reports and meta-analyses published in 1997-2021.

RESULTS: Etoposide/platinum (EP) is the most commonly used regimen and paclitaxel/carboplatin is the second most common, used as a part of multimodality therapy for SCNEC of the cervix in most studies. Cisplatin/vincristine/bleomycin, cisplatin/irinotecan, cisplatin/ifosfamide/etoposide were also reported in concurrence with EP; however no clinical trials are dedicated to SCNEC.

CONCLUSION: Etoposide and platinum tend to have a better prognosis compared to other regimens used for other subtypes of cervical cancer. For recurrent cervical SCNEC, treatment options for patients are very limited. The application of molecular testing for targeted mutations may suggest potential future therapies that may be useful in this disease.

PMID:36974776 | DOI:10.21873/anticanres.16288

Prostate. 2023 Jun;83(8):814-819. doi: 10.1002/pros.24521. Epub 2023 Mar 26.

ABSTRACT

BACKGROUND: Metastatic adenoid cystic (basal cell) carcinoma of the prostate is an exceedingly rare disease entity. As a result, no current consensus exists for optimal systemic therapy.

METHODS: We present a patient with metastatic adenoid cystic (basal cell) carcinoma of the prostate who subsequently received systemic treatment, including chemotherapy and immunotherapy. We comprehensively reviewed all published data on therapy outcomes in advanced disease.

RESULTS: Our patient benefited from combination chemotherapy (carboplatin and paclitaxel), with objective radiographic response and reduction in cancer-related pain. However, chemotherapy was stopped due to cumulative neurotoxicity, and subsequent immunotherapy with atezolizumab did not produce any response. Our literature review revealed inconsistent outcomes with various treatments but showed most promise with chemotherapy. Targeted therapy and immunotherapy seem to benefit specific cases, and androgen deprivation therapy had minimal evidence of benefit.

CONCLUSION: Based on the findings of our case report and literature review, we suggest platinum-based chemotherapy doublets as first-line treatment for metastatic cases of adenoid cystic (basal cell) carcinoma of the prostate, reserving targeted therapy or immunotherapy for select cases based upon molecular profiles.

PMID:36967482 | DOI:10.1002/pros.24521

BMC Public Health. 2023 Mar 27;23(1):567. doi: 10.1186/s12889-023-15470-9.

ABSTRACT

BACKGROUND: Neurogenic limb deformity disorder (NLDD) refers to limb deformity disorders caused by various neurogenic disorders. However, there are no studies to systematically summarize and analyze these diseases in China, and we first proposed the concept of NLDD. We describe the epidemiological characteristics of NLDD in China based on the largest case database of limb orthopedics in China.

METHODS: This study analyzed parameters from the Qin Sihe Orthopedic Surgery Case Data (QSHOSCD). The database is based on the Rehabilitation Hospital affiliated to National Research Center for Rehabilitation, which has collected nearly 37,000 patients to date and includes a wide variety of limb deformities. The types of diseases are summarized and classified for all patients studied. Statistical analysis was based on the type of etiology, age, regional distribution, and historical surgical volume. Partial outcomes were statistically analyzed separately by common diseases (polio and cerebral palsy) and rare diseases (37 other diseases).

RESULTS: From 1979 to 2019, 30,194 patients with NLDD were treated surgically for 39 neurogenic disorders. The male to female ratio was 1.48:1, the mean age was 19.65 years, and most patients (82.38%) were aged between 6 and 30 years. Patients included from 32 provinces and cities across China, mainly concentrated in populous central provinces and Heilongjiang Province. The peak of annual surgical procedures was from 1988 to 1994, and the number of annual surgical procedures for common diseases gradually decreased from 1994 onwards, but the trending is opposite for rare diseases.

CONCLUSIONS: This study is the first to demonstrate the disease types, population characteristics and incidence trends of NLDD in China. It suggests that the prevention and treatment of NLDD should focus on the adolescent population and enhance the treatment of neurogenic diseases that cause limb deformities. The growth and adaption of the Ilizarov technique and its practice in Chinese orthopedic benefits the treatment of neurogenic limb deformity disorders.

PMID:36973707 | DOI:10.1186/s12889-023-15470-9

BMC Infect Dis. 2023 Mar 27;23(1):180. doi: 10.1186/s12879-023-08148-5.

ABSTRACT

BACKGROUND: Whipple's disease is known to cause multiple varied systemic symptoms, and is a well-documented cause of culture-negative endocarditis. Endocarditis secondary to Whipple disease, however, has rarely been known to present primarily as a cause of acute limb ischemia. We describe such a case here.

CASE PRESENTATION: A previously healthy 40 year old man presented to the emergency department with acute-onset right arm paresthesias. On exam, he was found to be tachycardic with a VI/VI systolic ejection murmur. He was diagnosed with critical limb ischemia and severe aortic regurgitation, and echocardiography showed a large mass on his bicuspid aortic valve. Thrombectomy was performed urgently, with aortic valve repair the following day. As blood cultures and valvular tissue culture remained unrevealing, the patient remained on empiric vancomycin and ceftriaxone for culture-negative endocarditis. 16 s rRNA nucleic acid amplification testing (NAAT) of his formalin-fixed, paraffin-embedded valvular tissue detected T. whipplei, after which the patient was transitioned to ceftriaxone and trimethoprim-sulfamethoxazole for a year of therapy. He continues to do clinically well.

CONCLUSIONS: We report an unusual presentation of Whipple endocarditis as an acute upper limb ischemia, absent other classic symptoms of Whipple's disease, and with diagnosis made by 16 s rRNA NAAT of valvular tissue in the setting of culture-negative endocarditis.

PMID:36973675 | DOI:10.1186/s12879-023-08148-5

Intern Med J. 2023 Mar;53(3):449-450. doi: 10.1111/imj.16018.

NO ABSTRACT

PMID:36972997 | DOI:10.1111/imj.16018

Front Neurol. 2023 Mar 8;14:1098454. doi: 10.3389/fneur.2023.1098454. eCollection 2023.

ABSTRACT

Substantial challenges in study design and methodology exist during clinical trial development to examine treatment response in patients with a rare disease, especially those with predominant central nervous system involvement and heterogeneity in clinical manifestations and natural history. Here we discuss crucial decisions which may significantly impact success of the study, including patient selection and recruitment, identification and selection of endpoints, determination of the study duration, consideration of control groups including natural history controls, and selection of appropriate statistical analyses. We review strategies for the successful development of a clinical trial to evaluate treatment of a rare disease with a focus on inborn errors of metabolism (IEMs) that present with movement disorders. The strategies presented using pantothenate kinase-associated neurodegeneration (PKAN) as the rare disease example can be applied to other rare diseases, particularly IEMs with movement disorders (e.g., other neurodegeneration with brain iron accumulation disorders, lysosomal storage disorders). The significant challenges associated with designing a clinical trial in rare disease can sometimes be successfully met through strategic engagement with experts in the rare disease, seeking regulatory and biostatistical guidance, and early involvement of patients and families. In addition to these strategies, we discuss the urgent need for a paradigm shift within the regulatory processes to help accelerate medical product development and bring new innovations and advances to patients with rare neurodegenerative diseases who need them earlier in disease progression and prior to clinical manifestations.

PMID:36970548 | PMC:PMC10032345 | DOI:10.3389/fneur.2023.1098454

Nat Commun. 2023 Mar 25;14(1):1677. doi: 10.1038/s41467-023-37092-w.

ABSTRACT

DICER1 syndrome is a tumor predisposition syndrome that is associated with up to 30 different neoplastic lesions, usually affecting children and adolescents. Here we identify a group of mesenchymal tumors which is highly associated with DICER1 syndrome, and molecularly distinct from other DICER1-associated tumors. This group of DICER1-associated mesenchymal tumors encompasses multiple well-established clinicopathological tumor entities and can be further divided into three clinically meaningful classes designated "low-grade mesenchymal tumor with DICER1 alteration" (LGMT DICER1), "sarcoma with DICER1 alteration" (SARC DICER1), and primary intracranial sarcoma with DICER1 alteration (PIS DICER1). Our study not only provides a combined approach to classify DICER1-associated neoplasms for improved clinical management but also suggests a role for global hypomethylation and other recurrent molecular events in sarcomatous differentiation in mesenchymal tumors with DICER1 alteration. Our results will facilitate future investigations into prognostication and therapeutic approaches for affected patients.

PMID:36966138 | PMC:PMC10039902 | DOI:10.1038/s41467-023-37092-w

Curr Neuropharmacol. 2023;21(3):438-439. doi: 10.2174/1570159X2103230207104332.

NO ABSTRACT

PMID:36960641 | DOI:10.2174/1570159X2103230207104332

Expert Rev Clin Immunol. 2023 Mar 24. doi: 10.1080/1744666X.2023.2195165. Online ahead of print.

ABSTRACT

INTRODUCTION: Generalized pustular psoriasis (GPP), is a rare cutaneous and systemic inflammatory disease which is characterized by flares of widespread painful pustulation of the skin, often associated with fever and elevated inflammatory markers. Although it has historically been regarded as a severe variant of plaque psoriasis, genetic and immunological developments over the past decade have revealed that it is a distinct auto-inflammatory entity, in which over-activity of the interleukin-36 signaling pathway is fundamental. Treatments targeting the IL-36 pathway are under investigation, and in 2022 spesolimab, a monoclonal antibody against the IL-36 receptor, was licensed for treating flares of GPP.

AREAS COVERED: In this review I discuss the epidemiology, clinical features, genetics, patho-mechanisms and current treatment options for GPP. I describe the results of clinical trials that led to the licensing of spesolimab for flares of GPP.

EXPERT OPINION: The marked efficacy of spesolimab in GPP opens a new era of highly effective, scientifically-rational and evidence-based treatment for this orphan disease, and has implications for other diseases in which interleukin 36 signaling is involved.

PMID:36960829 | DOI:10.1080/1744666X.2023.2195165

Front Oncol. 2023 Mar 7;13:1128994. doi: 10.3389/fonc.2023.1128994. eCollection 2023.

ABSTRACT

Thrombosis is the most common and a life-threatening complication in patients with Paroxysmal Nocturnal Hemoglobinuria. One-third of patients with PNH experience at least one thromboembolic event during the course of the disease, with thrombosis being the most common cause of death in these patients. The mechanism of thrombosis in PNH is complex and continues to be of great research interest. Since the introduction of C5 complement inhibitors in the treatment of PNH, the incidence of thromboembolic events has decreased substantially. We retrospectively analyzed data concerning the thrombotic episodes of 41 patients with PNH from 14 different national hematology centers in Greece. Sixteen patients (39%) experienced at least one episode of thrombosis, including, seven (43.8%) at diagnosis, seven (43.8%) during the course of the disease and two (12.5%) patients prior to PNH diagnosis. Nearly half of these individuals (n=7, 43.8%) had multiple episodes of thrombosis during the course of their disease. The most common sites of thrombosis were intra-abdominal veins. Three out of 26 patients developed thrombosis while on eculizumab. In none of the 16 patients, the thrombotic event was fatal. Our findings, despite the small number of patients, confirmed that thrombosis continues to be a significant complication of PNH affecting more than one third of the patients.

PMID:36959785 | PMC:PMC10028290 | DOI:10.3389/fonc.2023.1128994