BMJ Case Rep. 2024 Apr 17;17(4):e257572. doi: 10.1136/bcr-2023-257572.

ABSTRACT

Aplasia cutis congenita (ACC) is a group of rare heterogeneous disorders characterised by absent areas of skin at birth. The majority of cases involve the scalp region. ACC limited to one lower limb is extremely rare. We report an usual case of ACC limited to the left thigh of which healing occurred in utero. The case was managed conservatively and the disease course has been favourable with no limitations in limb function and an entirely normal development. Most cases of ACC are self-healing, justifying a conservative approach. This holds further true for ACC limited to one lower limb where the majority of cases reported to date show a favourable disease course with minimal conservative treatment.

PMID:38631814 | DOI:10.1136/bcr-2023-257572

Lancet Neurol. 2024 May;23(5):447. doi: 10.1016/S1474-4422(24)00136-4.

NO ABSTRACT

PMID:38631752 | DOI:10.1016/S1474-4422(24)00136-4

BMC Med Genomics. 2024 Apr 17;17(Suppl 1):92. doi: 10.1186/s12920-024-01860-4.

ABSTRACT

BACKGROUND: Repressor element 1 (RE1) silencing transcription factor (REST) is a transcriptional repressor abundantly expressed in aging human brains. It is known to regulate genes associated with oxidative stress, inflammation, and neurological disorders by binding to a canonical form of sequence motif and its non-canonical variations. Although analysis of genomic sequence motifs is crucial to understand transcriptional regulation by transcription factors (TFs), a comprehensive characterization of various forms of RE1 motifs in human cell lines has not been performed.

RESULTS: Here, we analyzed 23 ENCODE REST ChIP-seq datasets from diverse human cell lines and identified a non-redundant set of 68,975 loci with ChIP-seq peaks. Our systematic characterization of these binding sites revealed that the canonical form of REST binding motif was found primarily in ChIP-seq peaks shared across multiple cell lines, while non-canonical forms of motifs were identified in both cell-line-specific binding sites and those shared across cell lines. Remarkably, we observed a notable prevalence of non-canonical motifs that corresponded to half segments of the canonical motif. Furthermore, our analysis unveiled the presence of cell-line-specific REST binding patterns, as evidenced by the clustering of ChIP-seq experiments according to their respective cell lines. This observation underscores the cell-line specificity of REST binding at certain genomic loci, implying intricate cell-line-specific regulatory mechanisms.

CONCLUSIONS: Overall, our study provides a comprehensive characterization of REST binding motifs in human cell lines and genome-wide RE1 motif profiles. These findings contribute to a deeper understanding of REST-mediated transcriptional regulation and highlight the importance of considering cell-line-specific effects in future investigations.

PMID:38632583 | DOI:10.1186/s12920-024-01860-4

Tex Heart Inst J. 2024 Apr 16;51(1):e238382. doi: 10.14503/THIJ-23-8382.

ABSTRACT

Dextrocardia with situs inversus totalis is a rare hereditary condition characterized by reversed orientation of the major thoracic and abdominal organs. Though dextrocardia itself is not believed to increase the risk of coronary artery disease, the workup and surgical management of patients with this condition may be technically challenging to heart team clinicians. This report describes the case management of a high-risk 56-year-old man with dextrocardia who presented with multivessel coronary artery disease.

PMID:38623731 | DOI:10.14503/THIJ-23-8382

Orv Hetil. 2024 Apr 14;165(15):595-600. doi: 10.1556/650.2024.33021. Print 2024 Apr 14.

ABSTRACT

A gerincfájdalom hátterében a gyakoribb benignus kórképek mellett malignus elváltozások és súlyos gyulladással jellemezhető kórképek is előfordulhatnak. A kivizsgálás során a részletes laboratóriumi vizsgálatok mellett a képalkotó diagnosztikának kiemelkedő jelentősége van. A csontfájdalom hátterében ritkán a krónikus nem bakteriális osteomyelitis is állhat. A szerzők egy 9 éves leánygyermek esetét mutatják be, aki több hónapja fennálló, progrediáló háti gerincfájdalommal jelentkezett szakvizsgálaton. A laboratóriumi vizsgálatok során enyhén emelkedett gyulladásos aktivitáson kívül kórjelző eltérés nem volt. A mágnesesrezonancia-vizsgálat (MRI) a thoracalis VIII. csigolyakompresszió mellett a csigolyatestben, az alsó zárólemez mentén körülírt, hiperintenzíven halmozó képletet írt le. A pontos etiológia tisztázására biopsziás mintavétel történt. A szövettani vizsgálat a malignitást kizárta, krónikus gyulladásra utaló eltérést mutatott. A beteg átmenetileg szteroidkezelésben részesült, de relapsus jelentkezett, ezért biológiai terápia, adalimumab került bevezetésre. A terápia hatásosnak bizonyult, mind a klinikai tünetek, mind a képalkotó vizsgálatok alapján tartós remisszió észlelhető. A jelen esettanulmány a gerincfájdalom hátterében álló ritka kórképre hívja fel a figyelmet. A kórkép diagnózisában az MRI kiemelkedő fontossággal bír. A betegség kezelésében immunszuppresszív terápia alkalmazása szükséges. Orv Hetil. 2024; 165(15): 595–600.

PMID:38619881 | DOI:10.1556/650.2024.33021

Int J Health Policy Manag. 2024;13:7494. doi: 10.34172/ijhpm.2024.7494. Epub 2024 Feb 10.

ABSTRACT

BACKGROUND: There is a lack of guidance on approaches to formulary management and funding for high-cost drugs and therapeutics by individual healthcare institutions. The objective of this review was to assess institutional approaches to resource allocation for such therapeutics, with a particular focus on paediatric and rare disease populations.

METHODS: A search of Embase and MEDLINE was conducted for studies relevant to decision-making for off-formulary, high-cost drugs and therapeutics. Abstracts were evaluated for inclusion based on the Simple Multiple-Attribute Rating Techniques (SMART) criteria. A framework of 30 topics across 4 categories was used to guide data extraction and was based on findings from the initial abstract review and previous health technology assessment (HTA) publications. Reflexive thematic analysis was conducted using QSR NVivo 12 software.

RESULTS: A total of 168 studies were included for analysis. Only 4 (2%) focused on paediatrics, while 21 (12%) centred on adults and the remainder (85%) did not specify. Thirty-two (19%) studies discussed the importance of high-cost therapeutics and 34 (23%) focused on rare/orphan drugs. Five themes were identified as being relevant to institutional decision-making for high-cost therapeutics: institutional strategy, substantive criteria, procedural considerations, guiding principles and frameworks, and operational activities. Each of these themes encompassed several sub-themes and was complemented by a sixth category specific to paediatrics and rare diseases.

CONCLUSION: The rising cost of novel drugs and therapeutics underscores the need for robust, evidence-based, and ethically defensible decision-making processes for health technology funding, particularly at the hospital level. Our study highlights practices and themes to aid decision-makers in thinking critically about institutional, substantive, procedural, and operational considerations in support of legitimate decisions about institutional funding of high-cost drugs and therapeutics, as well as opportunities and challenges that exist for paediatric and rare disease populations.

PMID:38618836 | DOI:10.34172/ijhpm.2024.7494

Tremor Other Hyperkinet Mov (N Y). 2024 Apr 10;14:16. doi: 10.5334/tohm.858. eCollection 2024.

ABSTRACT

BACKGROUND: Spinocerebellar ataxia 21 (SCA21) is a rare neurological disorder caused by heterozygous variants in TMEM240. A growing, yet still limited number of reports suggested that hyperkinetic movements should be considered a defining component of the disease.

CASE SERIES: We describe two newly identified families harboring the recurrent pathogenic TMEM240 p.Pro170Leu variant. Both index patients and the mother of the first proband developed movement disorders, manifesting as myoclonic dystonia and action-induced dystonia without co-occurring ataxia in one case, and pancerebellar syndrome complicated by action-induced dystonia in the other. We reviewed the literature on TMEM240 variants linked to hyperkinetic disorders, comparing our cases to described phenotypes.

DISCUSSION: Adding to prior preliminary observations, our series highlights the relevance of hyperkinetic movements as clinically meaningful features of SCA21. TMEM240 mutation should be included in the differential diagnosis of myoclonic dystonia and ataxia-dystonia syndromes.

PMID:38617829 | PMC:PMC11012930 | DOI:10.5334/tohm.858

Harefuah. 2024 Apr;163(4):217-219.

ABSTRACT

INTRODUCTION: Thyroid hemiagenesis is a rare congenital anomaly characterized by the absence of one thyroid lobe and the isthmus. This case report presents a 4-year-old girl with a history of prematurity. Incidentally, during a routine ultrasound evaluation of the neck, thyroid hemiagenesis was detected along with the presence of normal lymph nodes. The right thyroid lobe was absent, while the left thyroid lobe was preserved. No previous neck or thyroid surgeries were reported.

DISCUSSION: This provides an overview of thyroid hemiagenesis, including its prevalence, predominant involvement of the left lobe, possible genetic and environmental factors, and associations with thyroid and extrathyroidal pathologies. Imaging modalities, such as ultrasound and scintigraphy, play a crucial role in diagnosing thyroid hemiagenesis and identifying additional thyroid gland abnormalities. Long-term follow-up and careful monitoring are recommended to assess thyroid function and identify potential structural abnormalities. The optimal therapeutic approach for thyroid hemiagenesis remains controversial, and further studies are needed to determine the clinical significance and long-term outcomes of this rare condition.

PMID:38616630

J Cardiothorac Surg. 2024 Apr 15;19(1):209. doi: 10.1186/s13019-024-02681-3.

ABSTRACT

Uterine leiomyoma invading internal iliac vein and consequently disseminating into the right atrium is an extremely rare condition, and surgical strategy is controversial. Here, we reported a specific case with successful surgical resection through one-stage total hysterectomy, bilateral oophorectomy, and the intracardiovascular lesion. This procedure would be an optimal choice for uterine leiomyoma invading inferior vena cava and spreading to right atrium.

PMID:38616243 | PMC:PMC11017587 | DOI:10.1186/s13019-024-02681-3

J Nepal Health Res Counc. 2024 Mar 22;21(3):530-533. doi: 10.33314/jnhrc.v21i3.4573.

ABSTRACT

Mayer-Rokitansky-Kuster-Hauser syndrome also known as mullerian agenesis is a rare congenital condition in which there is absence of uterus along with upper vagina. Patient usually presents with primary amenorrhea with or without cyclical lower abdominal pain but have normal secondary sexual characters. Modified McIndoe Vaginoplasty with amnion graft is the commonest surgery performed worldwide. A 23 year old girl with normal secondary sexual characters presented with primary amenorrhea with cyclical lower abdominal pain; on examination blind vagina was present. Vaginoplasty with amnion graft was done and vaginal mould was placed. Vaginal dilatation with Hegar's dilator was done weekly until 6 weeks. She is under regular follow-up at present and advised for regular manual dilation at home. McIndoe Vaginoplasty with amnion graft is a simple yet rewarding procedure especially in low resource countries like ours, with good success rate and with minimal postoperative complications. Keywords: Amnion graft; Mayer-Rokitansky-Kuster-Hauser Syndrome; Modified McIndoe Vaginoplasty; Primary amenorrhea; Secondary sexual characters.

PMID:38615228 | DOI:10.33314/jnhrc.v21i3.4573

ESMO Open. 2024 Apr;9(4):102981. doi: 10.1016/j.esmoop.2024.102981. Epub 2024 Apr 12.

ABSTRACT

BACKGROUND: Comprehensive genome profiling (CGP) serves as a guide for suitable genomically matched therapies for patients with cancer. However, little is known about the impact of the timing and types of cancer on the therapeutic benefit of CGP.

MATERIALS AND METHODS: A single hospital-based pan-cancer prospective study (TOP-GEAR; UMIN000011141) was conducted to examine the benefit of CGP with respect to the timing and types of cancer. Patients with advanced solid tumors (>30 types) who either progressed with or without standard treatments were genotyped using a single CGP test. The subjects were followed up for a median duration of 590 days to examine therapeutic response, using progression-free survival (PFS), PFS ratio, and factors associated with therapeutic response.

RESULTS: Among the 507 patients, 62 (12.2%) received matched therapies with an overall response rate (ORR) of 32.3%. The PFS ratios (≥1.3) were observed in 46.3% (19/41) of the evaluated patients. The proportion of subjects receiving such therapies in the rare cancer cohort was lower than that in the non-rare cancer cohort (9.6% and 17.4%, respectively; P = 0.010). However, ORR of the rare cancer patients was higher than that in the non-rare cancer cohort (43.8% and 20.0%, respectively; P = 0.046). Moreover, ORR of matched therapies in the first or second line after receiving the CGP test was higher than that in the third or later lines (62.5% and 21.7%, respectively; P = 0.003). Rare cancer and early-line treatment were significantly and independently associated with ORR of matched therapies in multivariable analysis (P = 0.017 and 0.004, respectively).

CONCLUSION: Patients with rare cancer preferentially benefited from tumor mutation profiling by increasing the chances of therapeutic response to matched therapies. Early-line treatments after profiling increase the therapeutic benefit, irrespective of tumor types.

PMID:38613908 | PMC:PMC11033064 | DOI:10.1016/j.esmoop.2024.102981

BMC Anesthesiol. 2024 Apr 13;24(1):143. doi: 10.1186/s12871-024-02508-7.

ABSTRACT

BACKGROUND: The Koolen-de Vries syndrome (KdVS) is a relatively new rare disease caused by micro-deletion of 17q21.31 which was first reported by Koolen in 2006. Typical phenotypes for KdVS include hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Up to now, there was only one case report about anesthesia management of patient diagnosed KdVS. It was a 2-year-old girl who experienced an MRI exam under anesthesia.

CASE PRESENTATION: We described a 21-month-old boy who planned to undergo an orchidopexy under general anesthesia diagnosed with KdVS. He had an intellectual disability, characteristic facial dysmorphism, tracheo/laryngomalacia, patent foramen ovale, and cryptorchidism related to KdVS. Due to the complex condition especially the presence of tracheo/laryngomalacia, we took some special measures, including reducing the amount of long-acting opioid, keeping the spontaneous breath, performing a caudal block, and applying the laryngeal mask. But the laryngeal mask was changed to an endotracheal tube because it failed to provide adequate ventilation. The boy experienced mild laryngeal spasm and hypoxia after extubation, but lateral position and etomidate eased his breathing problem and re-intubation was avoided. It is indicated that anesthesia management for patients with orphan disease is a real challenge for all anesthesia providers.

CONCLUSIONS: The Koolen-de Vries syndrome is a relatively new orphan disease involving multiple systems. Keeping spontaneous breath, evaluating airway potency to anesthetics, applying endotracheal tube, and post-extubation lateral or prone position may be helpful for airway management for patient with hypotonia and tracheo/laryngomalacia. KdVS patient needs prolonged post-anesthesia monitoring and/or medication for airway complications.

PMID:38614993 | DOI:10.1186/s12871-024-02508-7

J R Coll Physicians Edinb. 2024 Mar;54(1):41-43. doi: 10.1177/14782715241237283.

ABSTRACT

Whipple's disease is a multisystemic chronic infectious condition caused by Tropheryma whipplei (T. whipplei). Though characterised often by insidious weight loss, diarrhoea, and arthralgia, three other distinct manifestations can be observed, namely localised disease, acute infection and asymptomatic carriage. The diagnosis relies on histopathological examination of duodenal biopsies and polymerase chain reaction analysis of the 16S rRNA gene for T. whipplei. We report the case of a middle-aged man admitted for etiologic investigation of prolonged, migrating, and inflammatory arthralgias and subsequent development of gastrointestinal symptoms. Despite its reputation as a great mimicker of many different illnesses, the difficulty in diagnosis probably lies with its rarity rather than its masking.

PMID:38606805 | DOI:10.1177/14782715241237283

Pathol Oncol Res. 2024 Mar 28;30:1611705. doi: 10.3389/pore.2024.1611705. eCollection 2024.

ABSTRACT

BACKGROUND: Langerhans cell histiocytosis is a rare disease characterized by the abnormal proliferation of Langerhans cells within a single organ or multiple organs. This case report aims to improve the knowledge of the presentation of gastrointestinal Langerhans cell histiocytosis to facilitate the diagnosis and management of this rare disorder.

CASE PRESENTATION: A 19-month-old female presented with repeatedly mucinous bloody stools. The abdominal ultrasound revealed a slightly enlarged spleen. The initial colonoscopy revealed chronic enteritis with a very early onset inflammatory bowel disease. After anti-inflammatory treatment without improvement, an intestinal biopsy was performed at The Forth Affiliated Hospital of Zhejiang University. The final intestinal biopsy and histopathology examination confirmed the presence of Langerhans cell histiocytosis. After diagnosis, additional lung and head imaging examinations revealed no abnormalities. Her condition improved gradually after being treated with chemotherapy (vincristine and prednisone) and molecular-targeted drug(dalafinil) treatment.

CONCLUSION: The clinical symptoms of Langerhans cell histiocytosis involving the gastrointestinal tract are not specific and may resemble symptoms observed in inflammatory bowel disease and other primary gastrointestinal tumors. Therefore, in cases of infants presenting with inflammatory gastrointestinal symptoms that do not resolve after treatment, a biopsy is essential to obtain a differential diagnosis.

PMID:38605931 | PMC:PMC11007090 | DOI:10.3389/pore.2024.1611705

Eur J Paediatr Neurol. 2024 Mar;49:A1. doi: 10.1016/j.ejpn.2024.04.002. Epub 2024 Apr 6.

NO ABSTRACT

PMID:38600015 | DOI:10.1016/j.ejpn.2024.04.002

J Neurol Sci. 2024 May 15;460:122989. doi: 10.1016/j.jns.2024.122989. Epub 2024 Apr 3.

ABSTRACT

Rare diseases are characterized by substantial unmet need mostly because the majority have limited, or no treatment options and a large number also affect children. Since the inception of EU orphan regulation in 2000 the European Medicines Agency Committee for Orphan Medicinal Products has received several applications for paediatric rare neuromuscular diseases (PERAN) however treatment options remain limited. Here we discuss the results form an observational, retrospective, cross-sectional study to characterize the currently authorised orphan medicinal products (OMP) and orphan designations (OD) given to products for PERAN in the last two decades. In the EU about half of PERAN diseases have at least one active OD approved since 2000, and about half of these are for Duchenne muscular dystrophy (DMD). The large majority of PERAN diseases do not have an authorised medicine with only 6 OMP currently authorised for Spinal muscular atrophy (3); DMD (1) and Myasthenia gravis (2). One in five products have inactive or discontinued regulatory development but clinical trials are ongoing for the vast majority of PERAN diseases, and more than half are in the final stage of clinical research with significantly more products with medical plausibility based in clinical data reaching advanced stages in clinical development.

PMID:38581740 | DOI:10.1016/j.jns.2024.122989

Orphanet J Rare Dis. 2024 Apr 6;19(1):147. doi: 10.1186/s13023-024-03162-5.

ABSTRACT

BACKGROUND: Patient registries and databases are essential tools for advancing clinical research in the area of rare diseases, as well as for enhancing patient care and healthcare planning. The primary aim of this study is a landscape analysis of available European data sources amenable to machine learning (ML) and their usability for Rare Diseases screening, in terms of findable, accessible, interoperable, reusable(FAIR), legal, and business considerations. Second, recommendations will be proposed to provide a better understanding of the health data ecosystem.

METHODS: In the period of March 2022 to December 2022, a cross-sectional study using a semi-structured questionnaire was conducted among potential respondents, identified as main contact person of a health-related databases. The design of the self-completed questionnaire survey instrument was based on information drawn from relevant scientific publications, quantitative and qualitative research, and scoping review on challenges in mapping European rare disease (RD) databases. To determine database characteristics associated with the adherence to the FAIR principles, legal and business aspects of database management Bayesian models were fitted.

RESULTS: In total, 330 unique replies were processed and analyzed, reflecting the same number of distinct databases (no duplicates included). In terms of geographical scope, we observed 24.2% (n = 80) national, 10.0% (n = 33) regional, 8.8% (n = 29) European, and 5.5% (n = 18) international registries coordinated in Europe. Over 80.0% (n = 269) of the databases were still active, with approximately 60.0% (n = 191) established after the year 2000 and 71.0% last collected new data in 2022. Regarding their geographical scope, European registries were associated with the highest overall FAIR adherence, while registries with regional and "other" geographical scope were ranked at the bottom of the list with the lowest proportion. Responders' willingness to share data as a contribution to the goals of the Screen4Care project was evaluated at the end of the survey. This question was completed by 108 respondents; however, only 18 of them (16.7%) expressed a direct willingness to contribute to the project by sharing their databases. Among them, an equal split between pro-bono and paid services was observed.

CONCLUSIONS: The most important results of our study demonstrate not enough sufficient FAIR principles adherence and low willingness of the EU health databases to share patient information, combined with some legislation incapacities, resulting in barriers to the secondary use of data.

PMID:38582900 | DOI:10.1186/s13023-024-03162-5

Transfus Med Rev. 2024 Apr;38(2):150825. doi: 10.1016/j.tmrv.2024.150825. Epub 2024 Mar 15.

NO ABSTRACT

PMID:38579548 | DOI:10.1016/j.tmrv.2024.150825

Immunol Allergy Clin North Am. 2024 May;44(2):293-298. doi: 10.1016/j.iac.2024.01.002. Epub 2024 Feb 19.

ABSTRACT

Eosinophilic gastrointestinal diseases (EGIDs) including eosinophilic esophagitis (EoE) are rare diseases in which eosinophils abnormally infiltrate the gastrointestinal tract. Because these are rare diseases, there is limited information regarding race and ethnicity in EGIDs and even less is known about the impact of socioeconomic factors. There is some evidence that access to care in rural settings may be affecting epidemiologic understanding of EGIDs in the pediatric populations. Future work should try to evaluate bias in research and strive for representation in clinical trials and medicine.

PMID:38575224 | DOI:10.1016/j.iac.2024.01.002

Rev Med Suisse. 2024 Apr 3;20(868):699-704. doi: 10.53738/REVMED.2024.20.868.699.

ABSTRACT

Mixed connective tissue disease (MCTD) is a rare autoimmune condition. Since its first description 50 years ago, its mere existence has been debated, given that it shares features of other autoimmune diseases, such as systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory myopathy, rheumatoid arthritis and Sjogren's syndrome. Also, while antibodies to U1-RNP are essential for the diagnosis of MCTD, these antibodies may be expressed in other circumstances, such as in case of SLE. Nevertheless, the patient fulfilling criteria for MCTD needs specific management. In this review, we describe the clinical features and the potential complications of this complex disease, often wrongly disregarded as benign. We will also emphasize the recommended follow-up exams and address treatment, which is currently lacking formal recommendations.

PMID:38568063 | DOI:10.53738/REVMED.2024.20.868.699