BMJ. 2023 Feb 28;380:p483. doi: 10.1136/bmj.p483.

NO ABSTRACT

PMID:36854467 | DOI:10.1136/bmj.p483

MMW Fortschr Med. 2023 Feb;165(Suppl 1):6-10. doi: 10.1007/s15006-023-2322-4.

NO ABSTRACT

PMID:36849763 | DOI:10.1007/s15006-023-2322-4

MMW Fortschr Med. 2023 Feb;165(Suppl 1):3. doi: 10.1007/s15006-023-2338-9.

NO ABSTRACT

PMID:36849762 | DOI:10.1007/s15006-023-2338-9

PLoS Genet. 2023 Feb 27;19(2):e1010587. doi: 10.1371/journal.pgen.1010587. eCollection 2023 Feb.

ABSTRACT

Photoreceptor cells (PRCs) are the light-detecting cells of the retina. Such cells can be non-invasively imaged using optical coherence tomography (OCT) which is used in clinical settings to diagnose and monitor ocular diseases. Here we present the largest genome-wide association study of PRC morphology to date utilising quantitative phenotypes extracted from OCT images within the UK Biobank. We discovered 111 loci associated with the thickness of one or more of the PRC layers, many of which had prior associations to ocular phenotypes and pathologies, and 27 with no prior associations. We further identified 10 genes associated with PRC thickness through gene burden testing using exome data. In both cases there was a significant enrichment for genes involved in rare eye pathologies, in particular retinitis pigmentosa. There was evidence for an interaction effect between common genetic variants, VSX2 involved in eye development and PRPH2 known to be involved in retinal dystrophies. We further identified a number of genetic variants with a differential effect across the macular spatial field. Our results suggest a continuum between common and rare variation which impacts retinal structure, sometimes leading to disease.

PMID:36848389 | PMC:PMC9997913 | DOI:10.1371/journal.pgen.1010587

J Ayub Med Coll Abbottabad. 2023 Feb-Mar;35(1):177-179. doi: 10.55519/JAMC-01-11210.

ABSTRACT

Proteus syndrome is a rare disease manifested by progressive segmental overgrowth involving the skeletal, Cutaneous, subcutaneous, and nervous systems. We report the case of a 24-year-old female who was born with no obvious abnormality at birth. From the age of 1 year, she developed asymmetric enlargement of her left upper limb and bilateral lower limbs leading to enlargement of the right-hand phalanges with radial deviation, enlargement of the right big toe, lateral deviation of left foot, and discrepancy in the length of lower extremities and kyphoscoliosis. She had become bed-bound for the last few years due to increasing disability. She was diagnosed with Proteus syndrome based on clinical features of progressive course, mosaic distribution, and sporadic occurrence of the lesions.

PMID:36849404 | DOI:10.55519/JAMC-01-11210

Dtsch Med Wochenschr. 2023 Mar;148(5):242-245. doi: 10.1055/a-1976-4185. Epub 2023 Feb 27.

ABSTRACT

INTRODUCTION: Cystic adventitial degeneration (CAD) is a rare vascular disease, affects mostly middle-aged men, and as a nonatherosclerotic disease, is an uncommon differential diagnosis of intermittent claudication.

CASE HISTORY: A 56-year-old female patient presented to our medical office because of unexplained right-sided calf pain that was not constantly load-dependent. The complaints fluctuated considerably with longer symptom-free intervals.

EXAMINATION AND FINDINGS: Clinically, the patient presented regular pulses, which were maintained even with provocative maneuvers such as plantar flexion and knee flexion. Duplex sonography showed cystic masses around the popliteal artery. On MRI examination, a tubular tortuous connection to the knee joint capsule also appeared to be visualizable. A diagnosis of cystic adventitial degeneration was made.

THERAPY AND COURSE: In the absence of constant impairment of walking performance with symptom-free intervals as well as morphological and functional signs of stenosis, interventional or surgical therapy was not desired by the patient. Short-term follow-up revealed stable clinical and sonomorphologic findings over an observation period of 6 months so far.

DISCUSSION: CAD should also be considered in female patients with atypical leg symptoms. There are no uniform treatment recommendations for CAD, which is why it is a challenge to select the optimal, usually interventional procedure. In patients with few symptoms and no critical ischemia, a conservative approach with close follow-up may be justified, as in our case report.

PMID:36848887 | DOI:10.1055/a-1976-4185

Proc Natl Acad Sci U S A. 2023 Mar 7;120(10):e2300988120. doi: 10.1073/pnas.2300988120. Epub 2023 Feb 27.

NO ABSTRACT

PMID:36848568 | DOI:10.1073/pnas.2300988120

Turk J Ophthalmol. 2023 Feb 24;53(1):70-73. doi: 10.4274/tjo.galenos.2022.37605.

ABSTRACT

Fibrous dysplasia is a benign, rare bone disease in which bone is replaced by fibro-osseous tissue to varying degrees. It can present differently depending on the amount of compression caused by the fibro-osseous tissue. Patients are usually asymptomatic, but symptoms related to cranial nerve compression may occur. In this case report, we describe a 45-year-old woman with sphenoid bone dysplasia which compressed the optic nerve and caused unilateral optic disc cupping that mimicked glaucoma. Our case highlights the importance of including compressive etiologies associated with optic disc cupping in the differential diagnosis of glaucoma.

PMID:36847644 | PMC:PMC9973207 | DOI:10.4274/tjo.galenos.2022.37605

Turk J Ophthalmol. 2023 Feb 24;53(1):44-57. doi: 10.4274/tjo.galenos.2022.76436.

ABSTRACT

Avascular peripheral retina in an infant is a common characteristic of numerous pediatric retinal vascular disorders and often presents a diagnostic challenge to the clinician. In this review, key features of each disease in the differential diagnosis, from retinopathy of prematurity, familial exudative vitreoretinopathy, Coats disease, incontinentia pigmenti, Norrie disease, and persistent fetal vasculature, to other rare hematologic conditions and telomere disorders, will be discussed by expert ophthalmologists in the field.

PMID:36847634 | PMC:PMC9973209 | DOI:10.4274/tjo.galenos.2022.76436

J Oncol. 2023 Feb 17;2023:3144086. doi: 10.1155/2023/3144086. eCollection 2023.

ABSTRACT

BACKGROUND: Non-small cell lung cancer (NSCLC) is still a slightly less orphan disease after immunotherapy, and routine treatment has low efficiency and adverse events. Ginseng is commonly used in the treatment of NSCLC. The purpose of this study is to assess the efficacy and hemorheological indexes of ginseng and its active components in patients with non-small cell lung cancer.

METHODS: A comprehensive literature search was performed in PubMed, the Cochrane Library, Medline (Ovid), the Web of Science, Embase, CKNI, Wan Fang, VIP, and SinoMed up to July 2021. Only randomized controlled trials evaluating ginseng in combination with chemotherapy versus chemotherapy alone in NSCLC patients were included. Primary outcomes included patients' condition after using ginseng or its active components. Secondary outcomes included changes in immune cells, cytokines, and secretions in serum. Data were extracted by two independent individuals, and the Cochrane Risk of Bias tool version 2.0 was applied for the included studies. Systematic review and meta-analysis were performed by RevMan 5.3 software.

RESULTS: The results included 1480 cases in 17 studies. The results of the integration of clinical outcomes showed that the treatment of ginseng (or combination of ginseng with chemotherapy) can improve the quality of life for patients with NSCLC. Analysis of immune cell subtypes revealed that ginseng and its active ingredients can upregulate the percentages of antitumor immunocyte subtypes and downregulate the accounts of immunosuppressive cells. In addition, a reduction of the inflammatory level and an increase of antitumor indicators in serum were reported. Meta-analysis showed that Karnofsky score: WMD = 16, 95% CI (9.52, 22.47); quality-of-life score: WMD = 8.55, 95%CI (6.08, 11.03); lesion diameter: WMD = -0.45, 95% CI (-0.75, -0.15); weight: WMD = 4.49, 95% CI (1.18, 7.80); CD3+: WMD = 8.46, 95% CI (5.71, 11.20); CD4+: WMD = 8.45, 95% CI (6.32, 10.57)+; CD8+: WMD = -3.76, 95% CI (-6.34, -1.18); CD4+/CD8+: WMD = 0.32, 95% CI (0.10, 0.53); MDSC: WMD = -2.88, 95% CI (-4.59, -1.17); NK: WMD = 3.67, 95% CI (2.63, 4.71); Treg: WMD = -1.42, 95% CI (-2.33, -0.51); CEA: WMD = -4.01, 95% CI (-4.12, -3.90); NSE: WMD = -4.00, 95% CI (-4.14, -3.86); IL-2: WMD = 9.45, 95% CI (8.08, 10.82); IL-4: WMD = -9.61, 95% CI (-11.16, -8.06); IL-5: WMD = -11.95, 95% CI (-13.51, -10.39); IL-6: WMD = -7.65, 95% CI (-8.70, -6.60); IL-2/IL-5: WMD = 0.51, 95% CI (0.47, 0.55); IFN-γ: WMD = 15.19, 95% CI (3.16, 27.23); IFN-γ/IL-4: WMD = 0.91, 95% CI (0.85, 0.97); VEGF: WMD = -59.29, 95% CI (-72.99, -45.58); TGF-α: WMD = -10.09, 95% CI (-12.24, -7.94); TGF-β: WMD = -135.62, 95% CI (-147.00, -124.24); TGF-β1: WMD = -4.22, 95% CI (-5.04, -3.41); arginase: WMD = -1.81, 95% CI (-3.57, -0.05); IgG: WMD = 1.62, 95% CI (0.18, 3.06); IgM: WMD = -0.45, 95% CI (-0.59, -0.31). All results are statistically significant. No adverse events were reported in the included articles.

CONCLUSION: It is a reasonable choice to use ginseng and its active components as adjuvant therapy for NSCLC. Ginseng is helpful for NSCLC patients' conditions, immune cells, cytokines, and secretions in the serum.

PMID:36844875 | PMC:PMC9957625 | DOI:10.1155/2023/3144086

Medicina (Kaunas). 2023 Jan 30;59(2):266. doi: 10.3390/medicina59020266.

ABSTRACT

Background and Objectives: Rare diseases (RDs) are life-threatening or chronically impairing conditions that affect about 6% of the world's population. RDs are often called 'orphan' diseases, since people suffering from them attract little support from national health systems. Aim: The aim of this study is to describe the clinical characteristics of, and the available laboratory examinations for, patients who were hospitalized in a tertiary referral center and finally received a diagnosis associated with a Rare Neurological Disease (RND). Materials and Methods: Patients that were hospitalized in our clinic from 1 January 2014 to 31 March 2022 and were finally diagnosed with an RND were consecutively included. The RND classification was performed according to the ORPHAcode system. Results: A total of 342 out of 11.850 (2.9%) adult patients admitted to our department during this period received a diagnosis associated with an RND. The most common diagnosis (N = 80, 23%) involved an RND presenting with dementia, followed by a motor neuron disease spectrum disorder (N = 64, 18.7%). Family history indicative of an RND was present in only 21 patients (6.1%). Fifty-five (16%) people had previously been misdiagnosed with another neurological condition. The mean time delay between disease onset and diagnosis was 4.24 ± 0.41 years. Conclusions: Our data indicate that a broad spectrum of RNDs may reach a tertiary Neurological Center after a significant delay. Moreover, our data underline the need for a network of reference centers, both at a national and international level, expected to support research on the diagnosis and treatment of RND.

PMID:36837468 | DOI:10.3390/medicina59020266

Genes (Basel). 2023 Jan 26;14(2):324. doi: 10.3390/genes14020324.

ABSTRACT

Pseudohypoparathyroidism (PHP) is a heterogeneous orphan disease characterized by multihormonal resistance and several phenotypic features. In some cases, PHP is caused by a mutation in the GNAS that encodes the alpha subunit of the G protein, one of the key transmitters of intracellular signals. A correlation between the genotype and phenotype of patients with GNAS mutations has not yet been described. This often makes diagnosis, drug prescription, and timely diagnosis difficult. Information about GNAS functioning and the impact of specific mutations on the clinical course of the disease is limited. Establishing of the pathogenicity by newly identified GNAS mutations will expand the understanding of this gene functioning in the cAMP signaling pathway and may become the basis for personalized treatment. This paper provides a clinical description of a patient with the Ia PHP phenotype caused by a previously unknown mutation in GNAS (NC_000020.11(NM_000516.7)): c.719-29_719-13delinsACCAAAGAGAGCAAAGCCAAG in the heterozygous state. Verification of the pathogenicity of the detected mutation is also described.

PMID:36833251 | DOI:10.3390/genes14020324

Medicine (Baltimore). 2023 Feb 22;102(8):e33084. doi: 10.1097/MD.0000000000033084.

ABSTRACT

RATIONALE: Cholesterol granuloma of the breast is a rare disease defined as chronic reactive inflammation of cholesterol crystals and foreign body giant cells. This disease can mimic breast cancer in the clinic as painless palpable hard nodules, and imaging shows irregular hypoechoic nodules with unclear boundaries. Therefore, the uncommon lesions can be easily misdiagnosed as breast cancer. Meanwhile, it can be easily neglected by clinicians because of poor understanding.

PATIENT CONCERNS: In this report, we present a rare case of multiple cholesterol granulomas of the breast, which was analyzed retrospectively and combined with all 11 relevant available studies in the last 50 years.

INTERVENTIONS: The patient had undergone multiple breast imaging inspections for breast nodules and had the local resection of nodules.

DIAGNOSES: The patient was confirmed to have a final diagnosis of benign cholesterol granulomas but was initially considered as breast cancer.

OUTCOMES: The patient did not complain of discomfort after surgery, and ultrasound reexamination 5 months after surgery showed no recurrence.

LESSONS: By retrospective analysis, dynamic contrast-enhanced magnetic resonance imaging and core needle biopsy can synergistically help clinicians distinguish it from other breast disease. To raise awareness of such a rare disease and reduce related misdiagnoses, we summarize the characteristics of cholesterol granulomas and recommend appropriate novel diagnosis and treatment regimens for patients with cholesterol granulomas.

PMID:36827045 | DOI:10.1097/MD.0000000000033084

MMW Fortschr Med. 2023 Mar;165(4):20. doi: 10.1007/s15006-023-2431-0.

NO ABSTRACT

PMID:36826644 | DOI:10.1007/s15006-023-2431-0

Orphanet J Rare Dis. 2023 Feb 24;18(1):41. doi: 10.1186/s13023-023-02635-3.

ABSTRACT

BACKGROUND: In recent years, significant advances have been made in the field of rare diseases (RDs). However, there is a large number of RDs without specific treatment and half of these treatments have public funding in Spain. The aim of the FINEERR project was to carry out a multidisciplinary strategic discussion on the challenge of funding and access to RD-targeted drugs in Spain, in order to agree on specific proposals for medium-term improvement and hence support decision-making in the Spanish National Healthcare System (SNHS).

RESULTS: The FINEERR Project was organized around a CORE Advisory Committee, which provided an overview, agreed on the design and scope of the project, and selected the members within each of four working groups (WG). Overall, 40 experts discussed and reached a consensus on different relevant aspects, such as conditioning factors for initial funding and access, evaluation and access to RD-targeted therapies, funding of these therapies, and implementation of a new funding and access model. From these meetings, 50 proposals were defined and classified by their level of relevance according to the experts. A descriptive analysis of responses was performed for each proposal. Thereafter, experts completed another questionnaire where they ranked the 25 most relevant proposals according to their level of feasibility of being implemented in the SNHS. The most relevant and feasible proposals were to improve: process of referral of patients with RDs, control over monitoring mechanisms, and communication between healthcare professionals and patients.

CONCLUSIONS: The FINEERR project may provide a starting point for stakeholders involved in the process of funding and access to RD-targeted therapies in Spain to provide the necessary resources and implement measures to improve both the quality of life and life expectancy of patients with RDs.

PMID:36823598 | PMC:PMC9950008 | DOI:10.1186/s13023-023-02635-3

Lancet Diabetes Endocrinol. 2023 Mar;11(3):139. doi: 10.1016/S2213-8587(23)00042-6.

NO ABSTRACT

PMID:36822740 | DOI:10.1016/S2213-8587(23)00042-6

Front Cell Dev Biol. 2023 Feb 2;11:1105565. doi: 10.3389/fcell.2023.1105565. eCollection 2023.

ABSTRACT

Pulmonary arterial hypertension (PAH) is an orphan disease of the cardiopulmonary unit that reflects an obstructive pulmonary vasculopathy and presents with hypertrophy, inflammation, fibrosis, and ultimately failure of the right ventricle (RVF). Despite treatment using pulmonary hypertension (PH)-targeted therapies, persistent functional impairment reduces the quality of life for people with PAH and death from RVF occurs in approximately 40% of patients within 5 years of diagnosis. PH-targeted therapeutics are primarily vasodilators and none, alone or in combination, are curative. This highlights a need to therapeutically explore molecular targets in other pathways that are involved in the pathogenesis of PAH. Several candidate pathways in PAH involve acquired mitochondrial dysfunction. These mitochondrial disorders include: 1) a shift in metabolism related to increased expression of pyruvate dehydrogenase kinase and pyruvate kinase, which together increase uncoupled glycolysis (Warburg metabolism); 2) disruption of oxygen-sensing related to increased expression of hypoxia-inducible factor 1α, resulting in a state of pseudohypoxia; 3) altered mitochondrial calcium homeostasis related to impaired function of the mitochondrial calcium uniporter complex, which elevates cytosolic calcium and reduces intramitochondrial calcium; and 4) abnormal mitochondrial dynamics related to increased expression of dynamin-related protein 1 and its binding partners, such as mitochondrial dynamics proteins of 49 kDa and 51 kDa, and depressed expression of mitofusin 2, resulting in increased mitotic fission. These acquired mitochondrial abnormalities increase proliferation and impair apoptosis in most pulmonary vascular cells (including endothelial cells, smooth muscle cells and fibroblasts). In the RV, Warburg metabolism and induction of glutaminolysis impairs bioenergetics and promotes hypokinesis, hypertrophy, and fibrosis. This review will explore our current knowledge of the causes and consequences of disordered mitochondrial function in PAH.

PMID:36819102 | PMC:PMC9933518 | DOI:10.3389/fcell.2023.1105565

Probl Sotsialnoi Gig Zdravookhranenniiai Istor Med. 2023 Jan 15;31(1):33-43. doi: 10.32687/0869-866X-2023-31-1-33-43.

ABSTRACT

In Russia, the orphan diseases for many years are the object of intent attention both of the national legislation and health care system. The lower prevalence of these diseases in population causes predicaments to timely diagnosis, drug provision and medical care. Besides, absence of integrated approach to issues of diagnosis and treatment of rare diseases contribute nothing to fast solving of actual problems in this field. Frequently, impossibility to get necessary course of treatment forces patients with orphan diseases to seek for alternative sources. The article assesses current situation with medications support of patients suffering from diseases included in the list of life-threatening and chronic progressive rare (orphan) diseases that result in shortening life-span or disability and diseases included in the Federal Program "The 14 high-cost nosologies". The issues of keeping record of patients and financing medications purchase are touched upon. The study results identified problems of organization of medication support of patients with orphan diseases associated with complexity of accounting their number and absence of integral system of preferential medication support.

PMID:36801872 | DOI:10.32687/0869-866X-2023-31-1-33-43

Probl Sotsialnoi Gig Zdravookhranenniiai Istor Med. 2023 Jan 15;31(1):16-19. doi: 10.32687/0869-866X-2023-31-1-16-19.

ABSTRACT

The rare diseases are characterized both by relatively small prevalence in population and complexity of medical care support of patients. In this particular case, the legal regulation of medical care takes its particular placement in health care. The uniqueness of rare diseases requires development of special normative legal acts, definitions and treating approaches. One of such approaches are orphan drugs that also are unique, complicated in development and require special legislative regulation. The article presents corresponding legislative terminology in modern Russian health care, actual listings of rare diseases and orphan drugs. The directions to improve current terminology and normative legal regulation are proposed.

PMID:36801869 | DOI:10.32687/0869-866X-2023-31-1-16-19

Lab Invest. 2023 Jan 18;103(5):100062. doi: 10.1016/j.labinv.2023.100062. Online ahead of print.

ABSTRACT

Tissue microarrays (TMA) have become an important tool in high-throughput molecular profiling of tissue samples in the translational research setting. Unfortunately, high-throughput profiling in small biopsy specimens or rare tumor samples (eg, orphan diseases or unusual tumors) is often precluded owing to limited amounts of tissue. To overcome these challenges, we devised a method that allows tissue transfer and construction of TMAs from individual 2- to 5-μm sections for subsequent molecular profiling. We named the technique slide-to-slide (STS) transfer, and it requires a series of chemical exposures (so-called xylene-methacrylate exchange) in combination with rehydrated lifting, microdissection of donor tissues into multiple small tissue fragments (methacrylate-tissue tiles), and subsequent remounting on separate recipient slides (STS array slide). We developed the STS technique by assessing the efficacy and analytical performance using the following key metrics: (a) dropout rate, (b) transfer efficacy, (c) success rates using different antigen-retrieval methods, (d) success rates of immunohistochemical stains, (e) fluorescent in situ hybridization success rates, and (f) DNA and (g) RNA extraction yields from single slides, which all functioned appropriately. The dropout rate ranged from 0.7% to 6.2%; however, we applied the same STS technique successfully to fill these dropouts ("rescue" transfer). Hematoxylin and eosin assessment of donor slides confirmed a transfer efficacy of >93%, depending on the size of the tissue (range, 76%-100%). Fluorescent in situ hybridization success rates and nucleic acid yields were comparable with those of traditional workflows. In this study, we present a quick, reliable, and cost-effective method that offers the key advantages of TMAs and other molecular techniques-even when tissue is sparse. The perspectives of this technology in biomedical sciences and clinical practice are promising, given that it allows laboratories to create more data with less tissue.

PMID:36801639 | DOI:10.1016/j.labinv.2023.100062