BMC Pulm Med. 2021 May 5;21(1):148. doi: 10.1186/s12890-021-01513-7.

ABSTRACT

BACKGROUND: The role of immunotherapy in cancer is now well-established, and therapeutic options such as checkpoint inhibitors are increasingly being approved in many cancers such as non-small cell lung cancer (NSCLC). Malignant pleural mesothelioma (MPM) is a rare orphan disease associated with prior exposure to asbestos, with a dismal prognosis. Evidence from clinical trials of checkpoint inhibitors in this rare disease, suggest that such therapies may play a role as a treatment option for a proportion of patients with this cancer.

MAIN TEXT: While the majority of studies currently focus on the established checkpoint inhibitors (CTLA4 and PD1/PDL1), there are many other potential checkpoints that could also be targeted. In this review I provide a synopsis of current clinical trials of immunotherapies in MPM, explore potential candidate new avenues that may become future targets for immunotherapy and discuss aspects of immunotherapy that may affect the clinical outcomes of such therapies in this cancer.

CONCLUSIONS: The current situation regarding checkpoint inhibitors in the management of MPM whilst encouraging, despite impressive durable responses, immune checkpoint inhibitors do not provide a long-term benefit to the majority of patients with cancer. Additional studies are therefore required to further delineate and improve our understanding of both checkpoint inhibitors and the immune system in MPM. Moreover, many new potential checkpoints have yet to be studied for their therapeutic potential in MPM. All these plus the existing checkpoint inhibitors will require the development of new biomarkers for patient stratification, response and also for predicting or monitoring the emergence of resistance to these agents in MPM patients. Other potential therapeutic avenues such CAR-T therapy or treatments like oncolytic viruses or agents that target the interferon pathway designed to recruit more immune cells to the tumor also hold great promise in this hard to treat cancer.

PMID:33952230 | DOI:10.1186/s12890-021-01513-7

Sci Data. 2021 May 4;8(1):124. doi: 10.1038/s41597-021-00905-y.

ABSTRACT

Here, we describe a dataset with information about monogenic, rare diseases with a known genetic background, supplemented with manually extracted provenance for the disease itself and the discovery of the underlying genetic cause. We assembled a collection of 4166 rare monogenic diseases and linked them to 3163 causative genes, annotated with OMIM and Ensembl identifiers and HGNC symbols. The PubMed identifiers of the scientific publications, which for the first time described the rare diseases, and the publications, which found the genes causing the diseases were added using information from OMIM, PubMed, Wikipedia, whonamedit.com, and Google Scholar. The data are available under CC0 license as spreadsheet and as RDF in a semantic model modified from DisGeNET, and was added to Wikidata. This dataset relies on publicly available data and publications with a PubMed identifier, but by our effort to make the data interoperable and linked, we can now analyse this data. Our analysis revealed the timeline of rare disease and causative gene discovery and links them to developments in methods.

PMID:33947870 | PMC:PMC8096966 | DOI:10.1038/s41597-021-00905-y

J Dtsch Dermatol Ges. 2021 May 5. doi: 10.1111/ddg.14446. Online ahead of print.

ABSTRACT

If blistering occurs in childhood, the possibility of hereditary epidermolysis bullosa should be considered even if the symptoms are mild. Besides clinical and histological examination, molecular genetic screening is diagnostically relevant. For localized forms, symptomatic, topical therapy options are currently still the primary choice. Of particular interest is the new option of topical therapy with diacerein 1 % cream. In the case of a pronounced clinical picture with extracutaneous organ involvement, multidisciplinary management is required. In the future, new forms of therapy such as autologous epidermal stem cell transplantation and gene therapeutic procedures may be applied. Human genetic counselling is indispensable.

PMID:33951274 | DOI:10.1111/ddg.14446

Epilepsia. 2021 May 5. doi: 10.1111/epi.16899. Online ahead of print.

ABSTRACT

OBJECTIVE: Focal cortical dysplasia (FCD) is a major cause of difficult-to-treat epilepsy in children and young adults, and the diagnosis is currently based on microscopic review of surgical brain tissue using the International League Against Epilepsy classification scheme of 2011. We developed an iterative histopathological agreement trial with genetic testing to identify areas of diagnostic challenges in this widely used classification scheme.

METHODS: Four web-based digital pathology trials were completed by 20 neuropathologists from 15 countries using a consecutive series of 196 surgical tissue blocks obtained from 22 epilepsy patients at a single center. Five independent genetic laboratories performed screening or validation sequencing of FCD-relevant genes in paired brain and blood samples from the same 22 epilepsy patients.

RESULTS: Histopathology agreement based solely on hematoxylin and eosin stainings was low in Round 1, and gradually increased by adding a panel of immunostainings in Round 2 and the Delphi consensus method in Round 3. Interobserver agreement was good in Round 4 (kappa = .65), when the results of genetic tests were disclosed, namely, MTOR, AKT3, and SLC35A2 brain somatic mutations in five cases and germline mutations in DEPDC5 and NPRL3 in two cases.

SIGNIFICANCE: The diagnoses of FCD 1 and 3 subtypes remained most challenging and were often difficult to differentiate from a normal homotypic or heterotypic cortical architecture. Immunohistochemistry was helpful, however, to confirm the diagnosis of FCD or no lesion. We observed a genotype-phenotype association for brain somatic mutations in SLC35A2 in two cases with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Our results suggest that the current FCD classification should recognize a panel of immunohistochemical stainings for a better histopathological workup and definition of FCD subtypes. We also propose adding the level of genetic findings to obtain a comprehensive, reliable, and integrative genotype-phenotype diagnosis in the near future.

PMID:33949696 | DOI:10.1111/epi.16899

J Bone Oncol. 2021 Apr 7;28:100362. doi: 10.1016/j.jbo.2021.100362. eCollection 2021 Jun.

ABSTRACT

PURPOSE: Conventional osteosarcoma is an orphan disease. Current treatment approaches include combining a three drug chemotherapy schedule and surgery. The 3- and 5-year event-free survival (EFS) in localized disease is roughly 65 and 60%, respectively. The registration study of mifamurtide reported survival benefit, but some methodological controversies have been insufficient for FDA market authorization in contrast to EMA.

METHODS: prospective single centre survival analysis of a mifamurtide addition to conventional therapy in 23 patients over a 5.5 year enrolment period is reported and compared to a historical control of 26 patient with localized disease. Bias arising from observational methodology was addressed using Landmark analysis and time-dependent Cox models. Blood count dynamics were analysed during the treatment.

RESULTS: The adverse event profile was as expected with no dose limiting toxicities. There were no local relapses observed, one patient died in the first complete remission due to doxorubicin cardiotoxicity, one patient had pulmonary metastatic relapse. The observed 3- and 5-year EFS was 87.4% (CI 72.4-100%) and 87.4% (CI 72.4-100%), progression free survival (PFS) was 92.9% (CI 80.3-100%) and 92.9% (CI 80.3-100%), overall survival was 94.1% (CI 83.6-100) and 80.7% (CI 58.3-100), respectively. Comparison to the historical control showed statistically significant better PFS for mifamurtide patients (Landmark analysis; p = 0.044). Risk of progression was 5-times lower for the mifamurtide group (Cox model; HR 0.21, p = 0.136). Only subtle differences in lymphocyte counts were observed across treatment.

CONCLUSION: the PFS benefit of mifamurtide is reported herein. The addition of mifamurtide could be considered as a best treatment option for localized osteosarcoma.

PMID:33948428 | PMC:PMC8080518 | DOI:10.1016/j.jbo.2021.100362

Acta Biomed. 2021 Apr 30;92(S1):e2021148. doi: 10.23750/abm.v92iS1.9825.

ABSTRACT

Müllerianosis is an extremely rare entity consisting of an admixture of 2 or more müllerian tissues. We report the case of a 61 years old woman who came to our attention with hypogastric pain and dysuria. She was in menopause and had a previous history of cesarean section. Ultrasound and CT-scan of the abdomen showed a proliferative bladder lesion close to the left ureteric orifice. Transurethral resection of the bladder (TUR-B) was performed. Histopathological examination of the specimens was negative for bladder cancer and revealed the presence of endosalpingeal tissue. Postoperative course was unremarkable as well as follow up at 12 months. A proper knowledge and awareness of this disease, even if rare, is necessary for an accurate differential diagnosis and to perform an appropriate treatment.

PMID:33944832 | PMC:PMC8142764 | DOI:10.23750/abm.v92iS1.9825

AMIA Annu Symp Proc. 2021 Jan 25;2020:763-772. eCollection 2020.

ABSTRACT

The mortality prediction of diverse rare diseases using electronic health record (EHR) data is a crucial task for intelligent healthcare. However, data insufficiency and the clinical diversity of rare diseases make it hard for deep learning models to be trained. Mortality prediction for these patients with different diseases can be viewed as a multi-task learning problem with insufficient data but a large number of tasks. On the other hand, insufficient training data makes it difficult to train task-specific modules in multi-task learning models. To address the challenges of data insufficiency and task diversity, we propose an initialization-sharing multi-task learning method (Ada-SiT). Ada-Sit can learn the parameter initialization and dynamically measure the tasks' similarities, used for fast adaptation. We use Ada-SiT to train long short-term memory networks (LSTM) based prediction models on longitudinal EHR data. The experimental results demonstrate that the proposed model is effective for mortality prediction of diverse rare diseases.

PMID:33936451 | PMC:PMC8075548

Front Public Health. 2021 Apr 15;9:640282. doi: 10.3389/fpubh.2021.640282. eCollection 2021.

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic has disrupted every aspect of our life. The need to provide high-level care for an enormous number of patients with COVID-19 infection during this pandemic has impacted resourcing for and restricted the routine care of all non-COVID-19 conditions. Since the beginning of the pandemic, the people living with rare disorders, who represent a marginalized group of the population even in a normal world, have not received enough attention that they deserve. Due to the pandemic situation, they have experienced (and experiencing) an extreme inadequacy of regular clinical services, counseling, and therapies they need, which have made their life more vulnerable and feel more marginalized. Besides, the clinicians, researchers, and scientists working on rare genetic diseases face extra challenges due to the pandemic. Many ongoing research projects and clinical trials for rare and genetic diseases were stalled to avoid patients' and research staff's transmission to COVID-19. Still, with all the odds, telehealth and virtual consultations for rare disease patients have shown hope. The clinical, organizational, and economic challenges faced by institutions, patients, their families, and the caregivers during the pandemic indicate the importance of ensuring continuity of care in managing rare diseases, including adequate diagnostics and priority management strategies for emergencies. In this review, we endeavored to shed light on the issues the rare disease community faces during the pandemic and the adaptations that could help the rare disease community to better sustain in the coming days.

PMID:33937170 | PMC:PMC8082070 | DOI:10.3389/fpubh.2021.640282

Rheumatol Int. 2021 Apr 20. doi: 10.1007/s00296-021-04858-8. Online ahead of print.

ABSTRACT

Granulomatosis with polyangiitis (GPA) is an orphan disease with multifaceted clinical presentations and delayed diagnosis. Given the risks of delayed diagnosis and treatment, improving clinicians' awareness of atypical course of this disease is critically important. The aim of this report is to analyze a case of delayed diagnosis of GPA in view of similar publications. We analyzed articles retrieved from Scopus and MEDLINE/PubMed. The following keywords were used: "granulomatosis with polyangiitis", "Wegener granulomatosis", and "diagnostic errors". All case studies that fulfilled the Chapel Hill Consensus Conference and the American College of Rheumatology GPA criteria were retrieved. We report a 71-year-old female patient with a facial defect in the nasal region, nasal congestion, and serosanguineous discharge. Her final diagnosis of GPA was reached after a series of incorrect diagnoses in the past 40 years. A deforming facial lesion developed during this period of uncertainty and absence of appropriate treatment. This patient presented with atypical features of laboratory and instrumental examinations. Anti-neutrophil cytoplasmic antibodies (ANCA) were negative, while rheumatoid factor (RF; 46.3 IU/mL) and anti-citrullinated protein antibody (ACPA; 25.6 IU/mL) were elevated. The histological analysis of the nasal mucous membrane specimen did not indicate definite signs of vasculitis. However, it revealed a granuloma with aggregation of macrophages and massive infiltration of lymphocytes, ruling out previous diagnosis of carcinoma. We analyzed delayed diagnosis of GPA in our patient in the context of 12 previously reported similar cases of limited form of GPA. We emphasize the importance of histological examination for differential diagnosis of GPA.

PMID:33939014 | DOI:10.1007/s00296-021-04858-8

iScience. 2021 Mar 29;24(4):102376. doi: 10.1016/j.isci.2021.102376. eCollection 2021 Apr 23.

ABSTRACT

The group of retinal degenerations, retinitis pigmentosa (RP), comprises more than 150 genetic abnormalities affecting photoreceptors. Finding degenerative pathways common to all genetic abnormalities may allow general treatment such as neuroprotection. Neuroprotection may include enhancing the function of cells that directly support photoreceptors, retinal pigment epithelial cells, and Müller glia. Treatment with fibroblast growth factor 21 (FGF21), a neuroprotectant, from postnatal week 4-10, during rod and cone loss in P23H mice (an RP model) with retinal degeneration, preserved photoreceptor function and normalized Müller glial cell morphology. Single-cell transcriptomics of retinal cells showed that FGF21 receptor Fgfr1 was specifically expressed in Müller glia/astrocytes. Of all retinal cells, FGF21 predominantly affected genes in Müller glia/astrocytes with increased expression of axon development and synapse formation pathway genes. Therefore, enhancing retinal glial axon and synapse formation with neurons may preserve retinal function in RP and may suggest a general therapeutic approach for retinal degenerative diseases.

PMID:33937726 | PMC:PMC8079476 | DOI:10.1016/j.isci.2021.102376

Int J Mol Sci. 2021 Apr 26;22(9):4521. doi: 10.3390/ijms22094521.

ABSTRACT

Platelets play a major role in hemostasis as ppwell as in many other physiological and pathological processes. Accordingly, production of about 1011 platelet per day as well as appropriate survival and functions are life essential events. Inherited platelet disorders (IPDs), affecting either platelet count or platelet functions, comprise a heterogenous group of about sixty rare diseases caused by molecular anomalies in many culprit genes. Their clinical relevance is highly variable according to the specific disease and even within the same type, ranging from almost negligible to life-threatening. Mucocutaneous bleeding diathesis (epistaxis, gum bleeding, purpura, menorrhagia), but also multisystemic disorders and/or malignancy comprise the clinical spectrum of IPDs. The early and accurate diagnosis of IPDs and a close patient medical follow-up is of great importance. A genotype-phenotype relationship in many IPDs makes a molecular diagnosis especially relevant to proper clinical management. Genetic diagnosis of IPDs has been greatly facilitated by the introduction of high throughput sequencing (HTS) techniques into mainstream investigation practice in these diseases. However, there are still unsolved ethical concerns on general genetic investigations. Patients should be informed and comprehend the potential implications of their genetic analysis. Unlike the progress in diagnosis, there have been no major advances in the clinical management of IPDs. Educational and preventive measures, few hemostatic drugs, platelet transfusions, thrombopoietin receptor agonists, and in life-threatening IPDs, allogeneic hematopoietic stem cell transplantation are therapeutic possibilities. Gene therapy may be a future option. Regular follow-up by a specialized hematology service with multidisciplinary support especially for syndromic IPDs is mandatory.

PMID:33926054 | PMC:PMC8123627 | DOI:10.3390/ijms22094521

Int J Environ Res Public Health. 2021 Apr 2;18(7):3724. doi: 10.3390/ijerph18073724.

ABSTRACT

In this paper, we propose a vision of the role of parent/caregiver with children affected by a rare disease. This vision is rooted in data obtained from our own research; however, our analysis and interpretation of this data have been subsequently checked against existing theoretical models. The research aims to explore how parents who look after children with a rare disease experience their role as caregivers and how they assimilate their role identity in this task. Semi-structured interviews were performed with parents of 10 children, and a qualitative data analysis was conducted using grounded theory. We have identified ten main categories using a grounded theory approach: stress, disorientation, insecurity, isolation, faith, trust, attention, communication with professionals, private proactivity and public proactivity. Our results also show that when parents perceive a greater burden due to looking after a child with a rare disease, the result is a change in the usual parental role. In our contribution, we offer a general outline of how parents build a role identity centred on caring for a child with a rare disease. We posit that this role identity is the outcome of the parents' success or failure in gradually overcoming fear through love. We have conceptualized this process as navigating between love and fear.

PMID:33918362 | PMC:PMC8038217 | DOI:10.3390/ijerph18073724

Medicina (Kaunas). 2021 Apr 23;57(5):411. doi: 10.3390/medicina57050411.

ABSTRACT

Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy which represents a consequence of a previous cesarean section. It is associated with major maternal morbidity and mortality and has potential implications on future fertility. Because of possible serious complications, CSP should be swiftly diagnosed and treated. There is no management protocol for this rare, life-threatening condition, and each patient should be evaluated individually. Several types of conservative treatment have been used to treat cesarean scar pregnancy: dilation and curettage (D&C), excision of trophoblastic tissues, local or systemic administration of methotrexate, bilateral hypogastric artery ligation, and selective uterine artery embolization with curettage and/or methotrexate administration. In our study we present a cesarean scar pregnancy of a 40-year-old woman who was treated with angiographic uterine artery embolization (UAE) followed by hysteroscopic diode laser resection. Our combined UAE-hysteroscopic laser surgery appears to offer an effective, safe, and minimally invasive surgical treatment.

PMID:33922785 | DOI:10.3390/medicina57050411

Int J Mol Sci. 2021 Apr 3;22(7):3735. doi: 10.3390/ijms22073735.

ABSTRACT

DNA methylation (DNAme) profiling is used to establish specific biomarkers to improve the diagnosis of patients with inherited neurodevelopmental disorders and to guide mutation screening. In the specific case of mendelian disorders of the epigenetic machinery, it also provides the basis to infer mechanistic aspects with regard to DNAme determinants and interplay between histone and DNAme that apply to humans. Here, we present comparative methylomes from patients with mutations in the de novo DNA methyltransferases DNMT3A and DNMT3B, in their catalytic domain or their N-terminal parts involved in reading histone methylation, or in histone H3 lysine (K) methylases NSD1 or SETD2 (H3 K36) or KMT2D/MLL2 (H3 K4). We provide disease-specific DNAme signatures and document the distinct consequences of mutations in enzymes with very similar or intertwined functions, including at repeated sequences and imprinted loci. We found that KMT2D and SETD2 germline mutations have little impact on DNAme profiles. In contrast, the overlapping DNAme alterations downstream of NSD1 or DNMT3 mutations underlines functional links, more specifically between NSD1 and DNMT3B at heterochromatin regions or DNMT3A at regulatory elements. Together, these data indicate certain discrepancy with the mechanisms described in animal models or the existence of redundant or complementary functions unforeseen in humans.

PMID:33916664 | PMC:PMC8038329 | DOI:10.3390/ijms22073735

Int J Mol Sci. 2021 Apr 12;22(8):3980. doi: 10.3390/ijms22083980.

ABSTRACT

Rare diseases affect a small part of the population, and the most affected are children. Because of the low availability of patients for testing, the pharmaceutical industry cannot develop drugs for the diagnosis of many of these orphan diseases. In this sense, the use of benzothiazole compounds that are highly selective and can act as spectroscopy probes, especially the compound 2-(4'-aminophenyl)benzothiazole (ABT), has been highlighted. This article reports the design of potential contrast agents based on ABT and iron to develop a new material with an efficient mechanism to raise the relaxation rate, facilitating diagnosis. The ABT/δ-FeOOH hybrid material was prepared by grafting (N-(4'-aminophenyl) benzothiazole-2-bromoacetamide) on the surface of the iron oxyhydroxide particles. FTIR spectra confirmed the material formations of the hybrid material ABT/δ-FeOOH. SEM analysis checked the covering of nanoflakes' surfaces in relation to the morphology of the samples. The theoretical calculations test a better binding mode of compound with iron oxyhydroxide. Theoretical findings show the radical capture mechanism in the stabilization of this new material. In this context, Fe3+ ions are an electron acceptor from the organic phase.

PMID:33921510 | PMC:PMC8070218 | DOI:10.3390/ijms22083980

Am J Med Genet A. 2021 Apr 29. doi: 10.1002/ajmg.a.62223. Online ahead of print.

ABSTRACT

Filippi syndrome (MIM #272440), one of the craniodigital syndromes, is a rare genetic entity with autosomal recessive inheritance and characterized by pre- and postnatal growth retardation, microcephaly, distinctive facial appearance, developmental delay/intellectual disability, and variable syndactylies of the fingers and toes. In this report, a further female patient of Filippi syndrome who additionally had a unilateral congenital talipes equinovarus (CTEV), a feature not previously recorded, is described. Genetic testing revealed a novel homozygous frameshift pathogenic variant (c.552_555delCAAA, p.Asn184Lysfs*8) in CKAP2L and thus confirmed the diagnosis of Filippi syndrome. We hope that the newly recognized feature (CTEV) will contribute to expand the clinical spectrum of this extremely rare condition. In view of the paucity of reported cases, the full spectrum of clinical findings of Filippi syndrome necessitates obviously further affected individuals/pedigrees delineation in order to elucidate the etiological and phenotypic aspects of this orphan disease appropriately.

PMID:33913579 | DOI:10.1002/ajmg.a.62223

Expert Opin Investig Drugs. 2021 Apr 28. doi: 10.1080/13543784.2021.1923693. Online ahead of print.

ABSTRACT

INTRODUCTION: Systemic sclerosis (SSc), also known as scleroderma, is a complex orphan disease characterized by early inflammatory features, vascular hyper-reactivity, and fibrosis of the skin and internal organs. Although substantial progress has been made in the understanding of the pathogenesis of SSc, there is still no disease-modifying drug that could significantly impact the natural history of the disease.

AREAS COVERED: This review discusses the rationale, preclinical evidence, first clinical evidence and pending issues concerning new promising therapeutic options that are under investigation in SSc. The search strategy was based on PubMed database and clinical trial.gov, highlighting recent key pathogenic aspects and phase I or II trials of investigational drugs in SSc.

EXPERT OPINION: The identification of new molecular entities that potentially impact inflammation and fibrosis may constitute promising options for a disease modifying-agent in SSc. The early combinations of antifibrotic drugs (such as pirfenidone) with immunomodulatory agents (such as mycophenolate mofetil) may also participate to achieve such a goal. A more refined stratification of patients, based on clinical features, molecular signature, and identification of subpopulations with distinct clinical trajectories, may also improve management strategies in the future.

PMID:33909517 | DOI:10.1080/13543784.2021.1923693

Hum Mol Genet. 2021 Apr 28:ddab112. doi: 10.1093/hmg/ddab112. Online ahead of print.

ABSTRACT

Nemaline myopathy, a disease of the actin-based thin filament, is one of the most frequent congenital myopathies. To date, no specific therapy is available to treat muscle weakness in nemaline myopathy. We tested the ability of tirasemtiv, a fast skeletal troponin activator that targets the thin filament, to augment muscle force-both in vivo and in vitro-in a nemaline myopathy mouse model with a mutation (H40Y) in Acta1. In Acta1H40Y mice, treatment with tirasemtiv increased the force response of muscles to submaximal stimulation frequencies. This resulted in a reduced energetic cost of force generation, which increases the tolerance to fatigue. The inotropic effects of tirasemtiv were present in locomotor muscles and, albeit to a lesser extent, in respiratory muscles, and they persisted during chronic treatment, an important finding as respiratory failure is the main cause of death in patients with congenital myopathy. Finally, translational studies on permeabilized muscle fibers isolated from a biopsy of a patient with the ACTA1H40Y mutation revealed that at physiological Ca2+ concentrations, tirasemtiv increased force generation to values that were close to those generated in muscle fibers of healthy subjects. These findings indicate the therapeutic potential of fast skeletal muscle troponin activators to improve muscle function in nemaline myopathy due to the ACTA1H40Y mutation, and future studies should assess their merit for other forms of nemaline myopathy and for other congenital myopathies.

PMID:33909041 | DOI:10.1093/hmg/ddab112

Bull Cancer. 2021 May;108(5):521-527. doi: 10.1016/j.bulcan.2021.01.014. Epub 2021 Apr 23.

ABSTRACT

Richter syndrome (RS) is defined as the occurrence of an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL) and rarely Hodgkin lymphoma (HL), in a patient with prior or concomitant chronic lymphocytic leukemia (CLL). RS is estimated to occur in 0.5-1 % per year and is associated with adverse outcome. In the vast majority of patients (80 %), RS is clonally related to the prior CLL. Those with unrelated RS appear to have better outcome. The therapeutic approach is based on those of de novo DLBCL or HL. However, even with modern immunochemotherapy regimens, response rate remains low. In eligible patients with related RS, a consolidation by autologous or allogeneic stem-cell transplantation must be proposed. Combinations including therapies targeting BCR or BCL2 and effective in CLL are currently being evaluated in RS. Novels immunotherapies could be promising approaches based on preliminary results.

PMID:33896586 | DOI:10.1016/j.bulcan.2021.01.014

Probl Sotsialnoi Gig Zdravookhranenniiai Istor Med. 2021 Mar;29(2):270-277. doi: 10.32687/0869-866X-2021-29-2-270-277.

ABSTRACT

The article considers the results of legal regulation analysis of medical care support including medication maintenance of adult patients suffering from rare diseases exemplified by life-threatened and chronic progressed rare (orphan) diseases resulting in life expectancy decrease and or disability ("List-24").

MATERIALS AND METHODS: Law database was analyzed in terms of current orders of medical care provision, standards of medical care, and clinical guidelines for rare diseases from "List-24" regarding to adult patients.

RESULTS: It is concluded that there are no determined rules of medical care provision to adult population in case of rare diseases from "List-24". There are standards of medical care on 6 rare diseases (25% of total diseases amount) from this list for adult patients. However, based on content analysis data of approved standards it was established that there are only 3 from 11 standards (27.28%) for primary medical care support, 4 standards (33.34%) for medical care provision in planned condition, and only 1 standard (9.09%) had appropriate legal basis for its development (clinical guidelines availability). Nevertheless, there is negative prognosis for this the only standard due to legal necessity of all clinical guidelines revision till the end of 2021.

CONCLUSION: Revision and creation of clinical guidelines and standards of medical care afterwards are needed for adult patients treatment with rare diseases from "List-24". The conclusion was made in terms of medical care standardization improvement for adult patients suffering from rare diseases from "List-24" based on its alignment with current legal regulation.

PMID:33901367 | DOI:10.32687/0869-866X-2021-29-2-270-277