BMJ Case Rep. 2021 Feb 10;14(2):e239981. doi: 10.1136/bcr-2020-239981.

ABSTRACT

Cocaine, an alkaloid, is an addictive drug and its abuse as a recreational drug is on the increasing side with its associated complications. Gastrointestinal complications, after cocaine abuse, are less known and need to be addressed since the abuse is on the rise and the existing evidence is scarce. We report a case of a 22-year-old male patient who presented with abdominal pain following a cocaine injection. On examination, signs of peritonitis were noted and laparotomy revealed a 2×1 cm perforation in the distal ileum. The unhealthy intestinal segment was resected and taken out as a double-barrel ileostomy. The patient had an episode of severe lower gastrointestinal bleeding on postoperative day 6. CT and colonoscopy revealed signs of ischaemic bowel and tissue biopsy showed oedematous, inflamed and haemorrhagic bowel mucosa. The patient was managed conservatively and is doing well under follow-up in a de-addiction centre.

PMID:33568413 | DOI:10.1136/bcr-2020-239981

BMJ Case Rep. 2021 Feb 10;14(2):e232266. doi: 10.1136/bcr-2019-232266.

ABSTRACT

We present a case of a 19-year-old man with right shoulder pain lasting for several months. Abdominal imaging revealed a right adrenal mass directly invading vascular structures into the right atrium. Widespread metastatic adrenocortical carcinoma was confirmed on biopsy. He opted for palliative mitotane treatment with home hospice care. This case emphasises the importance of considering abdominal masses in the differential diagnosis of persistent right shoulder pain after common causes have been ruled out. Early diagnosis could be potentially life-saving.

PMID:33568404 | DOI:10.1136/bcr-2019-232266

Ebstein's anomaly of tricuspid valve with aortic stenosis and coarctation of aorta: Successful single-stage repair of a rare adult congenital heart disease.

J Card Surg. 2020 Nov;35(11):3160-3165

Authors: Mishra AK, Barwad P, Bansal V, Mandal B, Srivastava A, Naganur SH

Abstract
Ebstein's anomaly of the tricuspid valve is infrequently associated with left heart anomalies. The association of aortic stenosis in Ebstein's anomaly has been reported to be extremely rare and the association of coarctation of aorta is even rarer especially in adults. The combination of all three of these lesions is virtually unknown without any references in literature. We report here an unusual case of Ebstein's anomaly of the tricuspid valve and severe aortic stenosis with coarctation of aorta in an adult who presented to us with exertional dyspnoea in the third decade and underwent a successful single-stage intracardiac repair.

PMID: 32939805 [PubMed - indexed for MEDLINE]

New Patient-Centric Approaches to the Management of Alpha-1 Antitrypsin Deficiency.

Int J Chron Obstruct Pulmon Dis. 2020;15:345-355

Authors: Chorostowska-Wynimko J, Barrecheguren M, Ferrarotti I, Greulich T, Sandhaus RA, Campos M

Abstract
Alpha-1 antitrypsin deficiency (AATD) is a rare and underdiagnosed genetic predisposition for COPD and emphysema and other conditions, including liver disease. Although there have been improvements in terms of awareness of AATD and understanding of its treatment in recent years, current challenges center on optimizing detection and management of patients with AATD, and improving access to intravenous (IV) AAT therapy - the only available pharmacological intervention that can slow disease progression. However, as an orphan disease with geographically dispersed patients, international cooperation is essential to address these issues. To achieve this, new European initiatives in the form of the European Reference Network for Rare Lung Diseases (ERN-LUNG) and the European Alpha-1 Research Collaboration (EARCO) have been established. These organizations are striving to address the current challenges in AATD, and provide a new platform for future research efforts in AATD. The first objectives of ERN-LUNG are to establish a quality control program for European AATD laboratories and create a disease management program for AATD, following the success of such programs in the United States. The main purpose of EARCO is to create a pan-European registry, with the aim of understanding the natural history of the disease and supporting the development of new treatment modalities in AATD and access to AAT therapy. Going further, other patient-centric initiatives involve improving the convenience of intravenous AAT therapy infusions through extended-interval dosing and self-administration. The present review will discuss the implementation of these initiatives and their potential contribution to the optimization of patient care in AATD.

PMID: 32103933 [PubMed - indexed for MEDLINE]

11 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2021/02/09

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Ann R Coll Surg Engl. 2021 Feb;103(2):e50-e52. doi: 10.1308/rcsann.2020.7000.

ABSTRACT

Appendix-associated hernias are extremely rare. They have been described sporadically in the literature, mostly as inguinal hernias. Appendix-associated incisional hernias are even more unusual. High clinical awareness is needed as complications can arise if misdiagnosis or delay occurs. We present an 80-year-old man with acute appendicitis in an incisional hernia. After successful surgery, the patient made a full recovery.

PMID:33559554 | DOI:10.1308/rcsann.2020.7000

J Lipid Res. 2021 Feb 5:100035. doi: 10.1194/jlr.TR120000618. Online ahead of print.

NO ABSTRACT

PMID:33556438 | DOI:10.1194/jlr.TR120000618

J Natl Cancer Inst. 2021 Feb 8:djab019. doi: 10.1093/jnci/djab019. Online ahead of print.

ABSTRACT

BACKGROUND: TP53 mutations occur in more than 50% of cancers. We sought to determine the effect of the intragenic P72R SNP (rs1042522) on the oncogenic properties of mutant p53.

METHODS: P72R allelic selection in tumors was determined from genotype calls and a Gaussian distributed mixture model. The SNP effect on mutant p53 was determined in p53-negative cancer cell lines. RNA-sequencing, chromatin immunoprecipitation, and survival analysis were performed to describe the SNP effect. All statistical tests were 2-sided.

RESULTS: Among 409 patients with germline heterozygous P72R SNP who harbored somatic mutations in TP53, we observed a selection bias against missense TP53 mutants encoding the P72 SNP (P = 1.64 x 10-13). Exogenously expressed hotspot p53 mutants with the P72 SNP were negatively selected in cancer cells. Gene expression analyses showed the enrichment of p53 pathway genes and inflammatory genes in cancer cells transduced with mutants encoding P72 SNP. Immune gene signature is enriched in patients harboring missense TP53 mutations with homozygous P72 SNP. These patients have improved overall survival as compared to those with the R72 SNP (P = 0.04).

CONCLUSION: This is the largest study demonstrating a selection against the P72 SNP. Missense p53 mutants with the P72 SNP retain partial wild type tumor-suppressive functions, which may explain the selection bias against P72 SNP across cancer types. Ovarian cancer patients with the P72 SNP have a better prognosis than with the R72 SNP. Our study describes a previously unknown role through which the rs1042522 SNP modifies tumor suppressor activities of mutant p53 in patients.

PMID:33555293 | DOI:10.1093/jnci/djab019

Uncommon manifestations of a rare disease: a case of autoimmune GFAP astrocytopathy.

BMC Neurol. 2021 Jan 27;21(1):37

Authors: Di H, Yin Y, Chen R, Zhang Y, Ni J, Zeng X

Abstract
BACKGROUND: Manifestations of intractable hyponatremia and hypokalemia in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy have been rarely reported.
CASE PRESENTATION: A 75-year-old male patient presented as the case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) and intractable hypokalemia, showed fever, fatigue, and mental disorders. Signs and symptoms of meningoencephalitis, ataxia, and cognitive abnormalities. Magnetic resonance imaging (MRI) revealed multiple white matter lesions of the central nervous system. He had GFAP-IgG in the cerebrospinal fluid (CSF). After treatment with corticosteroids, his symptoms were alleviated gradually, and the level of electrolytes was normal. However, head contrast-enhanced MRI + susceptibility-weighted imaging (SWI) showed a wide afflicted region, and the serum GFAP-IgG turned positive. Considering the relapse of the disease, ha was treated with immunoglobulin and mycophenolate mofetil (MMF) to stabilize his condition.
CONCLUSION: This case showed a rare disease with uncommon manifestations, suggesting that careful examination and timely diagnosis are essential for disease management and satisfactory prognosis.

PMID: 33504323 [PubMed - indexed for MEDLINE]

The EuRRECa Project as a Model for Data Access and Governance Policies for Rare Disease Registries That Collect Clinical Outcomes.

Int J Environ Res Public Health. 2020 11 25;17(23):

Authors: Ali SR, Bryce J, Tan LE, Hiort O, Pereira AM, van den Akker ELT, Appelman-Dijkstra NM, Bertherat J, Cools M, Dekkers OM, Kodra Y, Persani L, Smyth A, Smythe C, Taruscio D, Ahmed SF

Abstract
Rare disease (RD) registries are important platforms that facilitate communication between health care professionals, patients and other members of the multidisciplinary team. RD registries enable data sharing and promotion of research and audits, often in an international setting, with the overall aim of improving patient care. RD registries also have a fundamental role in supporting the work of clinical networks such as the European Reference Networks (ERNs) for rare diseases. With the recent expansion of RD registries, it has become even more essential to outline standards of good practice in relation to governance, infrastructure, documentation, training, audits and adopting the Findable, Accessible, Interoperable and Reusable (FAIR) data principles to maintain registries of high quality. For the purpose of this paper, we highlight vital aspects of data access and data governance policies for RD registries, using the European Registries for Rare Endocrine Conditions (EuRRECa) as an example of a project that aims to promote good standards of practice for improving the quality of utilization of RD registries.

PMID: 33255540 [PubMed - indexed for MEDLINE]

Diagnosing rare diseases: A sociotechnical approach to the design of complex work systems.

Appl Ergon. 2020 Jul;86:103095

Authors: Hay GJ, Klonek FE, Parker SK

Abstract
How do complex healthcare systems that are organised into distinct speciality areas achieve effective patient care transitions when patients present with a rare constellation of symptoms that affect multiple body systems? How do these patients challenge existing ways of organising tasks, clinical activities, and interdependent responsibilities? The current study applies a sociotechnical systems perspective to understand how these complex work design and care-related challenges were resolved by the Western Australian Undiagnosed Diseases Program. We conducted a two-year longitudinal, qualitative study of this program, conceived to improve the diagnosis and management of patients with rare, multi-system disorders by piloting a re-design of the local system of diagnostic work. Specifically, we (1) compared the configuration and effectiveness of the old system and the re-designed system; and (2) analysed the process of system re-design (i.e., the design, implementation, and operation of the program) in order to understand the factors that contributed to - or inhibited - its success. We discuss the theoretical and practical implications of our findings for effectively re-designing complex, trans-organisational work systems.

PMID: 32342886 [PubMed - indexed for MEDLINE]

An impact analysis of the implementation of health technology assessment for new treatment of orphan diseases in Japan.

Expert Rev Pharmacoecon Outcomes Res. 2020 Oct;20(5):455-471

Authors: Kogushi K, Ogawa T, Ikeda S

Abstract
Objectives: In Japan, a cost-effectiveness evaluation (CEE) for pricing was introduced in April 2019 and potentially covers orphan drugs (ODs) within its scope. The purpose of this study was to explore a reasonable approach to evaluate the utility of health technology assessment (HTA) for ODs in Japan. Methods: We extracted ODs that were approved in Japan from 2009 to 2018, and investigated their appraisals in the United Kingdom, Canada, and Australia, where HTA and different frameworks on ODs have been implemented. Results: Overall, 76 ODs were identified, with high recommendation rates in the three countries (80.6%-90.9%). The major reason for negative recommendation was uncertainty regarding clinical effectiveness, with actual decisions varying across countries. This indicates difficulties in setting an objective evaluation for the uncertainty of clinical effectiveness. The results of the CEE were mainly used to adjust prices. Conclusion: As Japan's CEE is expected to be used only for price adjustment after reimbursement is secured, the approach seems to be similar to the other countries. However, pre-launch clinical data are limited and the peak sales of ODs vary in Japan. Therefore, the careful introduction of CEE and multifaceted measures referring to the policies for ODs in other countries should be considered.

PMID: 31496361 [PubMed - indexed for MEDLINE]

Axenfeld–Rieger syndrome: ophthalmological and dental diagnostic and therapeutic options

Orv Hetil. 2021 01 31;162(5):192-199

Authors: Bausz M, Csidey M, Csákány B, Németh O, Nagy ZZ, Maka E

Abstract
Összefoglaló. Az Axenfeld-Rieger-szindróma ritka betegség. A közlemény bemutatja a klinikai megjelenési formáit, a diagnosztikus és terápiás lehetőségeket. A szemgolyó elülső szegmentumát érintő fejlődési rendellenességek vizsgálata a hagyományos biomikroszkópos vizsgálat mellett digitális kamerával is történhet, mely a csarnokzugi képleteket nagy nagyításban, éles képet mutatva tudja megjeleníteni. Az elülső szegmentum leképezését segítő optikaikoherencia-tomográfia és ultrahang-biomikroszkópia a fejlődési rendellenességnek és a csarnokvíz-elvezető sönt tubusának vizsgálatára, megjelenítésére is alkalmas. A szemnyomást a gyermek kooperációjának függvényében többféle módon mérhetjük. A szabálytalan alakú, sokszor csak résnyi pupilla, valamint a szemnyomás-emelkedés miatt szemészeti beavatkozás lehet szükséges. A korai pupillaképzés az amblyopia megelőzését, az antiglaucomás műtétek (trabeculectomia, hosszú tubusú sönt implantációja) pedig a látási funkciók megőrzését szolgálják. A szemészeti műtéteket akár már néhány hónapos korban szükséges elvégezni altatásban. A maxillahypoplasia és a fogászati fejlődési anomáliák miatt kétirányú panoráma-röntgenfelvétel szükséges. Többlépcsős fogászati konzervatív és restoratív kezelés hozhat eredményt. A diagnózis felállítása és a kezelés is multidiszciplináris megközelítést igényel. Gyermekgyógyász, genetikus, kardiológus, fogász-szájsebész és gyermekszemész együttes munkája biztosíthat megfelelő eredményt. Orv Hetil. 2021; 162(5): 192-199. Summary. Axenfeld-Rieger syndrome is a rare disease. Our paper presents its clinical manifestations, diagnostic and therapeutic options. Due to maxillary hypoplasia and dental developmental anomalies, bidirectional panoramic radiography is required. Multi-stage dental conservative and restorative treatment can provide better results. In addition to traditional biomicroscopic examination, developmental abnormalities affecting the anterior segment of the eye can also be examined with a digital camera, which can display the angle of the anterior chamber at high magnification, with a sharp image. Anterior segment optical coherence tomography and ultrasound biomicroscopy are also suitable for the examination and display of developmental abnormalities and drainage shunt tubes. Intraocular pressure can be measured in several ways depending on the child's cooperation. Due to the irregular shape of the pupil, often with only a slit aperture, and an increase in intraocular pressure, ophthalmic intervention may be required. The pupilloplasty is important preventing amblyopia prevention and early glaucoma surgery (trabeculectomy, shunt implantation) helps to preserve visual function. Eye surgeries need to be performed under anaesthesia, sometimes at few months of age. Both diagnosis and treatment require a multidisciplinary approach. The joint work of a paediatrician, geneticist, cardiologist, dental-oral surgeon and paediatric ophthalmologist may provide a satisfactory result. Orv Hetil. 2021; 162(5): 192-199.

PMID: 33517333 [PubMed - indexed for MEDLINE]

Giant right ventricular myxoma presenting as right heart failure with systemic congestion: a rare case report.

BMC Surg. 2021 Jan 29;21(1):64

Authors: Lu C, Yang P, Hu J

Abstract
BACKGROUND: Myxoma is an uncommon disease and its symptoms vary greatly depending on size, location and mobility. Right-sided myxoma, especially right ventricular myxoma, is much rarer, and the symptoms are alien and uncharacteristic. The lack of understandings poses challenges to prompt diagnosis and timely treatment.
CASE PRESENTATION: A 44-year-old female patient was diagnosed with giant right ventricular tumor. Right heart failure and systemic congestion caused by right ventricular outflow tract obstruction were observed on this case. Surgery was performed to excise the mass which was measured at 9.5 * 5.0 cm and confirmed as myxoma pathologically.
CONCLUSIONS: Right-side myxoma is easy to be unnoticed due to its low incident rate and atypical symptoms. Delay in surgical intervention might cause unrecoverable complications. More comprehensive understanding of the symptoms is expected to help improving the diagnose and treat of right-sided myxoma.

PMID: 33514381 [PubMed - indexed for MEDLINE]

Quality of Life and Mental Health in Mothers and Fathers Caring for Children and Adolescents with Rare Diseases Requiring Long-Term Mechanical Ventilation.

Int J Environ Res Public Health. 2020 12 02;17(23):

Authors: Boettcher J, Denecke J, Barkmann C, Wiegand-Grefe S

Abstract
(1) Parents caring for children and adolescents with rare diseases fear the long-term progression of the child's disease and the loss of their parental role. The aim of this study was to examine the quality of life, mental health and associated protective factors of mothers and fathers caring for children with rare diseases requiring mechanical long-term ventilation. (2) In a cross-sectional design, data on quality of life, mental health, coping mechanisms, social support and family functioning from n = 75 affected families were collected using standardized psychometric questionnaires. (3) Mothers compared to fathers were significantly more impaired in their quality of life and mental health. Protective factors significantly associated with the respective outcomes for mothers were coping mechanisms, social support and family functioning, whereas for fathers solely the latter was found to be significant. Multiple regression analyses showed that family functioning may be the most important predictor of quality of life and mental health. (4) The results support the need for family-oriented care in parents of children with rare diseases. To reach optimal efficiency, health care providers should not only screen parents for psychosocial impairment but also provide interventions that consider gender-specific differences in psychological health.

PMID: 33276595 [PubMed - indexed for MEDLINE]

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors.

Clin Cancer Res. 2020 05 15;26(10):2290-2296

Authors: Patel SP, Othus M, Chae YK, Giles FJ, Hansel DE, Singh PP, Fontaine A, Shah MH, Kasi A, Baghdadi TA, Matrana M, Gatalica Z, Korn WM, Hayward J, McLeod C, Chen HX, Sharon E, Mayerson E, Ryan CW, Plets M, Blanke CD, Kurzrock R

Abstract
PURPOSE: Immune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).
PATIENTS AND METHODS: We performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease >6 months, and toxicity.
RESULTS: Thirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events.
CONCLUSIONS: Ipilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease.

PMID: 31969335 [PubMed - indexed for MEDLINE]

BMJ Case Rep. 2021 Feb 4;14(2):e239244. doi: 10.1136/bcr-2020-239244.

ABSTRACT

Rosai-Dorfman disease is a rare benign histiocytic proliferative disease of unknown cause that, in exceptional cases, presents with lesions confined to the skin. Clinically variable types of lesions such as papules, nodules and plaques have been reported. We present a case of a 27-year-old woman with a 1-year history of erythematous papular and nodular lesions on the malar and right axillary regions, previously misdiagnosed as acne. She reported no fever, malaise or weight loss, while physical examination and laboratory workup were normal. Bacteriological and mycobacteriological cultures were negative. Histopathological findings showed dense infiltration of inflammatory cells involving the entire dermis, consisting of large macrophages with emperipolesis, S100 and CD68 positive, neutrophils, eosinophils, lymphocytes and plasma cells. The patient was treated with oral prednisolone without improvement. Dapsone was subsequently initiated with favourable clinical response. The present article aimed to emphasise the clinical and histological differential diagnosis and share the treatment experience.

PMID:33541998 | PMC:PMC7868278 | DOI:10.1136/bcr-2020-239244

BMJ Case Rep. 2021 Feb 4;14(2):e235158. doi: 10.1136/bcr-2020-235158.

ABSTRACT

Haemorrhagic suprarenal pseudocysts are very rare and are often incidental findings at surgery or autopsy, though they can sometimes present with predominantly gastrointestinal or endocrine symptoms, including intraperitoneal bleeding or sepsis. Our case report is of a 48-year-old man who presented at our primary healthcare centre with 2-month history of predominantly respiratory symptoms of cough and shortness of breath. CT scan revealed a suprarenal cyst measuring 14.2×13.5×13.1 cm for which he was operated and made a full recovery. A detailed literature review reveals that there has never been a case of a haemorrhagic suprarenal pseudocyst presenting with predominantly respiratory symptoms, which is why we decided to document this case report.

PMID:33542027 | PMC:PMC7868216 | DOI:10.1136/bcr-2020-235158

BMJ Case Rep. 2021 Feb 4;14(2):e234914. doi: 10.1136/bcr-2020-234914.

ABSTRACT

Chronic eosinophilic pneumonia (CEP) is a rare disorder of unknown aetiology which comes under the class of diffuse parenchymal lung diseases with eosinophilia. It is classically characterised by blood and pulmonary eosinophilia, peripheral consolidation on chest radiograph and prompt response to corticosteroid therapy. We report a case of CEP in a 66-year-old man, smoker showing bilateral pulmonary infiltrates with mild peripheral eosinophilia. Our study shows that CEP can be kept as a possibility if radiological pictures are consistent, even if peripheral blood eosinophilia is mild.

PMID:33542024 | PMC:PMC7868209 | DOI:10.1136/bcr-2020-234914

BMJ Case Rep. 2021 Feb 4;14(2):e237604. doi: 10.1136/bcr-2020-237604.

ABSTRACT

A 44-year-old woman with known trichorhinophalangeal syndrome presented with an unheralded out of hospital cardiac arrest. Transthoracic echocardiography showed severe left ventricular systolic dysfunction with an ejection fraction <25% and cardiac MRI confirmed a diagnosis of congenital non-ischaemic dilated cardiomyopathy. The case highlights a very rare syndrome, it is previously unknown association with dilated cardiomyopathy and the possible benefit of cardiac screening for patients with known trichorhinophalangeal syndrome.

PMID:33542011 | PMC:PMC7868179 | DOI:10.1136/bcr-2020-237604