OpenMed/multicare-articles huggingface dataset:
Mismatch repair deficiency associated with complete remission to combination programmed cell death ligand immune therapy in a patient with sporadic urothelial carcinoma: immunotheranostic considerations
Authors: Michael P Castro, Neal Goldstein
Journal: J Immunother Cancer (2015)
Keywords: hypermutator, immunotheranostic, immunotherapy, msh2, msh6, microsatellite instability, mismatch repair deficiency, mutation load, pd-l1, pd1-l2, precision immunology, urothelial cancer

Background:
Mismatch repair deficiency (MMRD) is a common pathway of malignant transformation accounting for approximately 15-20 % of human carcinogensis. It has been postulated that MMRD increases tumor antigenicity and highlights a role for immunotherapeutic approach MMR-deficient cancers. This strategy was pursued in a patient with upper tract urothelial carcinoma, and the results are reported here.
Case presentation:
Molecular profiling was performed using next generation DNA sequencing and (IHC) testing for MMR and PD-L1. A patient with sporadic, high grade urothelial carcinoma of the renal pelvis was found to have a hypermutator genotype with 73 mutations occurring amidst 62 known drivers of malignancy, and 340 VUS alterations. MMR deficiency phenotype was confirmed by the absence of MSH2 and MSH6 as well as deleterious mutations in these genes. IHC staining for programmed cell death ligand-1 [PD-L1] revealed 2+ staining in 80 % of cells. The patient gained access to combination immunotherapy trial utilizing MEDI4736 and MEDI0680 through a clinical trial. The patient achieved a prolonged, complete remission within two months and had no severe ill effects from the treatment.
Conclusion:
Given their ability to generate neo-antigens, MMR-deficient cancers may be uniquely susceptible to immune checkpoint inhibitor strategies, including urothelial tract cancers. Screening for MMR deficient cancers has the potential to become a routine strategy for evaluating the role of PD-L1 inhibitors for patient with advanced disease. (
Trial registration:
Clinicaltrials.gov NCT00938834. Registered 13 July 2009).
Mosaic genome-wide maternal isodiploidy: an extreme form of imprinting disorder presenting as prenatal diagnostic challenge
Authors: Susanne Bens, Manuel Luedeke, Tanja Richter, Melanie Graf, Julia Kolarova, Gotthold Barbi, Krisztian Lato, Thomas F Barth, Reiner Siebert
Journal: Clin Epigenetics (2017)
Keywords: dna methylation, genome-wide maternal uniparental disomy, imprinting, multilocus imprinting disturbances, prenatal diagnostics
MeSH terms: Genomic Imprinting, Ultrasonography, Prenatal / methods, Uniparental Disomy / genetics, Case Reports, Research Support, Non-U.S. Gov't, Adult, DNA Methylation, Female, Genome-Wide Association Study, Humans, Mosaicism, Pregnancy

Background:
Uniparental disomy of certain chromosomes are associated with a group of well-known genetic syndromes referred to as imprinting disorders. However, the extreme form of uniparental disomy affecting the whole genome is usually not compatible with life, with the exception of very rare cases of patients with mosaic genome-wide uniparental disomy reported in the literature.
Results:
We here report on a fetus with intrauterine growth retardation and malformations observed on prenatal ultrasound leading to invasive prenatal testing. By cytogenetic (conventional karyotyping), molecular cytogenetic (QF-PCR, FISH, array), and methylation (MS-MLPA) analyses of amniotic fluid, we detected mosaicism for one cell line with genome-wide maternal uniparental disomy and a second diploid cell line of biparental inheritance with trisomy X due to paternal isodisomy X. As expected for this constellation, we observed DNA methylation changes at all imprinted loci investigated.
Conclusions:
This report adds new information on phenotypic outcome of mosaic genome-wide maternal uniparental disomy leading to an extreme form of multilocus imprinting disturbance. Moreover, the findings highlight the technical challenges of detecting these rare chromosome disorders prenatally.
Deciding a Treatment Plan for an Older Patient With Severe Idiopathic Pulmonary Fibrosis: A Case Report
Authors: Yusuke Akashi, Yuta Horinishi, Chiaki Sano, Ryuichi Ohta
Journal: Cureus (2023)
Keywords: advanced care planning, general medicine, idiopathic pulmonary fibrosis, interstitial pneumonia, rural hospital
MeSH terms: Case Reports

Idiopathic pulmonary fibrosis (IPF) is a group of diseases in which the main loci of lesions, mainly inflammatory and fibrotic, are within the interstitium of the alveolar and bronchiolar regions. Steroid therapy is the standard treatment for acute exacerbation of IPF, whereas antifibrotic agents are the standard treatment for chronic IPF. However, the vulnerability of older patients indicates that these treatments may be discontinued. Here, we report the case of an 86-year-old woman who had a dry cough for over a year and was subsequently diagnosed with IPF based on imaging studies. After using steroid pulses to treat acute exacerbations, the patient was transitioned to the chronic management phase, and time was allowed to plan the patient's advanced care with her family. The use of high-dose steroids in older patients with frailty is contraindicated. This case emphasizes the importance of considering initial intensive treatment for IPF in older patients for better palliative care.
Autoimmune polyendocrine syndrome 3 onset with severe ketoacidosis in a 74-year-old woman
Authors: Stefano Benedini, Antonietta Tufano, Elena Passeri, Marco Mendola, Livio Luzi, Sabrina Corbetta
Journal: Case Rep Endocrinol (2015)

Type 1 diabetes mellitus (T1D), autoimmune thyroid disease, and autoimmune gastritis often occur together forming the so-called autoimmune polyendocrine syndrome type 3 (APS3). We here report a clinical case of a 74-year-old woman who presented for the first time with severe hyperglycemia and ketoacidosis diagnosed as T1D. Further clinical investigations revealed concomitant severe hypothyroidism with autoimmune thyroid disease and severe cobalamin deficiency due to chronic atrophic gastritis. The diagnosis of type 1 diabetes mellitus was confirmed by the detection of autoantibodies against glutamic acid decarboxylase 65, islet cell antibodies, and anti-insulin autoantibodies. Anti-thyroperoxidase, anti-thyroglobulin, and anti-gastric parietal cell antibodies were also clearly positive. The case emphasized that new onset diabetic ketoacidosis, hypothyroidism, and cobalamin deficiency may simultaneously occur, and one disease can mask the features of the other, thereby making diagnosis difficult. It is noteworthy that an APS3 acute episode occurred in an asymptomatic elder woman for any autoimmune diseases.
Synchronic renal cell carcinoma associated with fibromixoid sarcoma: A rare finding
Authors: Jose Genilson Alves Ribeiro, Ângelo Maurílio Fosse Junior, Victor Bastos Frade, Guilherme Gonçalves Rocha, Lucas Alves Sarmento Pires, Caio Fernando Cardoso Souza, Marcio Antonio Babinski
Journal: Int J Surg Case Rep (2020)
Keywords: case report, clear cell type, nephrectomy, renal cell carcinoma, tumor resection, woman
MeSH terms: Case Reports

Introduction:
Renal cell carcinoma comprises over 90% of renal cancers, thus, it is the most common form of renal neoplasia. This carcinoma can often present itself in a variable fashion, ranging from incidentalomas to metastatic diseases. Furthermore, the most common metastasis associated with this type of carcinoma occurs in the lungs, bones or liver. We aim to report a case of renal cell carcinoma which presented together with a fibromixoid sarcoma.
Case presentation:
A 50 year-old woman presented with hematuria, weight loss, asthenia and right lumbar pain that started 7 months prior to the consult. CT scan was performed and revealed a solid injury of 10 cm in the right kidney together with a mass in the left flank. Total right nephrectomy was promptly performed and the patient was submitted 3 months later to a tumoral resection of the abdominal wall. Histopathological findings revealed a primary renal cell carcinoma and the second, metastatic tumor was shown to be a fibromixoid sarcoma. The patient was not submitted to chemotherapy and is currently under follow-up with the surgery and oncology staffs, without showing any symptoms.
Discussion:
Renal cell carcinoma usually presents itself together with secondary tumors on the lungs and bones. The association of this type of carcinoma with a fibromixoid sarcoma of the abdominal wall is rare and poorly reported in the literature.
Conclusion:
This case reports shows a successful treatment regarding this rare association, which can help other physicians to re-evaluate their medical conduct.
BCG as a Case Study for Precision Vaccine Development: Lessons From Vaccine Heterogeneity, Trained Immunity, and Immune Ontogeny
Authors: Asimenia Angelidou, Joann Diray-Arce, Maria Giulia Conti, Kinga K Smolen, Simon Daniël van Haren, David J Dowling, Robert N Husson, Ofer Levy
Journal: Front Microbiol (2020)
Keywords: bcg formulation, immunogenicity, mycobacteria, ontogeny, trained immunity, vaccine
MeSH terms: Review

Vaccines have been traditionally developed with the presumption that they exert identical immunogenicity regardless of target population and that they provide protection solely against their target pathogen. However, it is increasingly appreciated that vaccines can have off-target effects and that vaccine immunogenicity can vary substantially with demographic factors such as age and sex. Bacille Calmette-Guérin (BCG), the live attenuated Mycobacterium bovis vaccine against tuberculosis (TB), represents a key example of these concepts. BCG vaccines are manufactured under different conditions across the globe generating divergent formulations. Epidemiologic studies have linked early life immunization with certain BCG formulations to an unanticipated reduction (∼50%) in all-cause mortality, especially in low birthweight males, greatly exceeding that attributable to TB prevention. This mortality benefit has been related to prevention of sepsis and respiratory infections suggesting that BCG induces "heterologous" protection against unrelated pathogens. Proposed mechanisms for heterologous protection include vaccine-induced immunometabolic shifts, epigenetic reprogramming of innate cell populations, and modulation of hematopoietic stem cell progenitors resulting in altered responses to subsequent stimuli, a phenomenon termed "trained immunity." In addition to genetic differences, licensed BCG formulations differ markedly in content of viable mycobacteria key for innate immune activation, potentially contributing to differences in the ability of these diverse formulations to induce TB-specific and heterologous protection. BCG immunomodulatory properties have also sparked interest in its potential use to prevent or alleviate autoimmune and inflammatory diseases, including type 1 diabetes mellitus and multiple sclerosis. BCG can also serve as a model: nanoparticle vaccine formulations incorporating Toll-like receptor 8 agonists can mimic some of BCG's innate immune activation, suggesting that aspects of BCG's effects can be induced with non-replicating stimuli. Overall, BCG represents a paradigm for precision vaccinology, lessons from which will help inform next generation vaccines.
Case Report: Whole exome sequencing identifies variation c.2308G>A p.E770K in RAG1 associated with B- T- NK+ severe combined immunodeficiency
Authors: Geeta Madathil Govindaraj, Shamsudheen Karuthedath Vellarikkal, Rijith Jayarajan, Rowmika Ravi, Ankit Verma, Krishnan Chakkiyar, Machinari Puthenpurayil Jayakrishnan, Riyaz Arakkal, Revathi Raj, Rajeevan Kunnaruvath, Sridhar Sivasubbu, Vinod Scaria
Journal: F1000Res (2016)
Keywords: b- t- nk+ scid, rag1, severe combined immunodeficiency, whole exome sequencing

Severe combined immunodeficiency is a large clinically heterogeneous group of disorders caused by a defect in the development of humoral or cellular immune responses. At least 13 genes are known to be involved in the pathophysiology of the disease and the mutation spectrum in SCID has been well documented. Mutations of the recombination-activating genes RAG 1 and RAG 2 are associated with a range of clinical presentations including, severe combined immunodeficiency and autoimmunity. Recently, our understanding of the molecular basis of immune dysfunction in RAG deficiency has improved tremendously with newer insights into the ultrastructure of the RAG complex. In this report, we describe the application of whole exome sequencing for arriving at a molecular diagnosis in a child suffering from B- T- NK+ severe combined immunodeficiency. Apart from making the accurate molecular diagnosis, we also add a genetic variation c.2308G>A p.E770K to the compendium of variations associated with the disease.
Idiopathic gingival fibromatosis: case report and its management
Authors: Prashant P Jaju, Ankit Desai, Rajiv S Desai, Sushma P Jaju
Journal: Int J Dent (2009)
MeSH terms: Case Reports

Idiopathic gingival fibromatosis is a rare condition. We present a case of idiopathic gingival fibromatosis with its multidisciplinary approach of management. The clinical, radiographic, and histopathological features have been described in detail.
Synchronous Orbital and Gastrointestinal Metastases from Breast Cancer: A Case Report and Review of Literature
Authors: Ramawad Soobrah, Fiona Tsang, Veronica Grassi, Hassan Hirji, Sreelakshmi Mallappa, Robert Reichert
Journal: Case Rep Oncol Med (2015)

Breast cancer is the most common malignancy among women and is a significant cause of morbidity and mortality worldwide. With the advent of improved imaging techniques and screening programmes, only a small proportion of women present with metastatic disease. Metastases involving the gastrointestinal (GI) tract and orbit are rare occurrences. We describe the case of a woman with simultaneous GI and orbital metastases from breast cancer who initially presented with abdominal pain and blurred vision and also summarise a review of the literature.
Diagnosis of familial Wolf-Hirschhorn syndrome due to a paternal cryptic chromosomal rearrangement by conventional and molecular cytogenetic techniques
Authors: Carlos A Venegas-Vega, Fernando Fernández-Ramírez, Luis M Zepeda, Karem Nieto-Martínez, Laura Gómez-Laguna, Luz M Garduño-Zarazúa, Jaime Berumen, Susana Kofman, Alicia Cervantes
Journal: Biomed Res Int (2013)
MeSH terms: In Situ Hybridization, Fluorescence, Karyotyping, Mutagenesis, Insertional, Polymorphism, Single Nucleotide, Siblings, Wolf-Hirschhorn Syndrome / genetics, Case Reports, Research Support, Non-U.S. Gov't, Adult, Child, Chromosome Deletion, Chromosomes, Human, Pair 15 / genetics, Female, Humans, Male, Wolf-Hirschhorn Syndrome / pathology, Chromosome 15q, partial deletion

The use of conventional cytogenetic techniques in combination with fluorescent in situ hybridization (FISH) and single-nucleotide polymorphism (SNP) microarrays is necessary for the identification of cryptic rearrangements in the diagnosis of chromosomal syndromes. We report two siblings, a boy of 9 years and 9 months of age and his 7-years- and 5-month-old sister, with the classic Wolf-Hirschhorn syndrome (WHS) phenotype. Using high-resolution GTG- and NOR-banding karyotypes, as well as FISH analysis, we characterized a pure 4p deletion in both sibs and a balanced rearrangement in their father, consisting in an insertion of 4p material within a nucleolar organizing region of chromosome 15. Copy number variant (CNV) analysis using SNP arrays showed that both siblings have a similar size of 4p deletion (~6.5 Mb). Our results strongly support the need for conventional cytogenetic and FISH analysis, as well as high-density microarray mapping for the optimal characterization of the genetic imbalance in patients with WHS; parents must always be studied for recognizing cryptic balanced chromosomal rearrangements for an adequate genetic counseling.
Proximal subungual onychomycosis of digitus minimus due to Aspergillus brasiliensis
Authors: Manjula Mehta, Jyoti Sharma, Sonia Bhonchal Bhardwaj
Journal: Pan Afr Med J (2020)
Keywords: aspergillus brasiliensis, onychomycosis, dermatophytes
MeSH terms: Aspergillosis / diagnosis, Hand Dermatoses / diagnosis, Onychomycosis / diagnosis, Case Reports, Aspergillosis / microbiology, Aspergillus / isolation & purification, Female, Hand Dermatoses / microbiology, Humans, Middle Aged, Onychomycosis / microbiology, Aspergillus brasiliensis

Onychomycosis is a common nail infection caused by dermatophytes, non-dermatophytic molds (NDMs) and yeast. Aspergillus spp. are emerging etiological agents of non-dermatophyte mold onychomycosis (NDMO). Though this is usually of cosmetic concern, it may also cause pain and discomfort to the patient. The toenail is more commonly involved as compared to fingernail. The nails are discoloured and disfigured. Onychomycosis may expose the patient to cellulitis of lower extremities. The clinical presentation of dermatophytic and NDM onychomycosis is more or less similar, which creates problem in the diagnosis. Fingernail infection may cause social and psychological problem to the patient if fingernail is involved. Incidence of onychomycosis has been seen more in immunosuppressed individuals, where it is of more serious medical concern. In the present study we are reporting a case of proximal subungual onychomycosis (PSO) due to Aspergillus brasiliensis.
Hormone dependent metastatic salivary gland carcinoma: a case report
Authors: Abed Agbarya, Salem Billan, Haitam Nasrallah, Addie Dvir, Lior Soussan-Gutman, Orit Kaidar-Person
Journal: Springerplus (2014)
Keywords: anti-androgen treatment, bicalutamide, salivary gland adenocarcinoma

Adenocarcinoma of the salivary gland is a histology subtype of salivary gland carcinoma (SGC). Salivary gland carcinomas are rare tumors accounting for less than 5% of all cancers of the head and neck. Consequently, clinical data for systemic treatment including targeted treatment in metastatic SGC is limited and supported mainly by sporadic cases, retrospective reports, and early phase trials with a limited number of patients. We present a case of a patient who suffered from metastatic SGC, in whom novel molecular testing that uses immunohistochemical analysis and DNA microarray implied that the tumor would respond to anti-androgen treatment. The patient was given bicalutamide and achieved complete objective response.
Skull base osteomyelitis in the emergency department: a case report
Authors: Mustafa Burak Sayhan, Cemil Kavalci, Ozgur Sogüt, Eylem Sezenler
Journal: Emerg Med Int (2011)
MeSH terms: Case Reports

Skull base osteomyelitis (SBO) is a rare clinical presentation and usually occurs as a complication of trauma or sinusitis. A 5-year-old child presented to the emergency department with a three-week history of fever associated with drowsiness and left parietal headache, and a week's history of swelling on the left frontoparietal soft tissue. He had suffered a penetrating scalp injury four month ago. On physical examination, there was a tender swelling with purulent stream on the lateral half of his scalp. His vital signs are within normal limits. Plain X-ray of the skull showed a lytic lesion on the left frontoparietal bone. A cranial computed tomography (CT) scan demonstrated a large subgaleal abscess at the left frontoparietal region. SBO possesses a high morbidity and mortality; therefore, prompt diagnosis and appropriate treatment are mandatory to prevent further complications and to reduce morbidity and mortality significantly.
Unilateral Optic Neuropathy and Acute Angle-Closure Glaucoma following Snake Envenomation
Authors: Osman Okan Olcaysu, Kenan Cadirci, Ahmet Altun, Afak Durur Karakaya, Huseyin Bayramlar
Journal: Case Rep Ophthalmol Med (2015)

Purpose. We aimed to describe a unique case in which a patient developed unilateral optic neuritis and angle-closure glaucoma as a result of snake envenomation. Case Report. Approximately 18 hours after envenomation, a 67-year-old female patient described visual impairment and severe pain in her left eye (LE). The patient's best corrected visual acuity was 10/10 in the RE and hand motion in the LE. Cranial magnetic resonance imaging showed signs of neuropathy in the left optic nerve. In the LE, corneal haziness, closure of the iridocorneal angle, and mild mydriasis were observed and pupillary light reflex was absent. Intraocular pressure was 25 mmHg and 57 mmHg in the RE and LE, respectively. The patient was diagnosed with acute angle-closure glaucoma in the LE. Optic neuropathy was treated with intravenous pulse methylprednisolone. Left intraocular pressure was within normal range starting on the fourth day. One month after the incident, there was no sign of optic neuropathy; relative afferent pupillary defect and optic nerve swelling disappeared. Conclusions. Patients with severe headache and visual loss after snake envenomation must be carefully examined for possible optic neuropathy and angle-closure glaucoma. Early diagnosis and treatment of these cases are necessary to prevent permanent damage to optic nerves.
Optimizing Fertility in Primary Ovarian Insufficiency: Case Report and Literature Review
Authors: Kensuly C Piedade, Hillary Spencer, Luca Persani, Lawrence M Nelson
Journal: Front Genet (2021)
Keywords: hormone replacement therapy, intrauterine insemination, luteinized follicles, pregnancy, primary ovarian insufficiency
MeSH terms: Case Reports

Primary ovarian insufficiency (POI) is a clinical spectrum of ovarian dysfunction. Overt POI presents with oligo/amenorrhea and hypergonadotropic hypogonadism before age 40 years. Overt POI involves chronic health problems to include increased morbidity and mortality related to estradiol deficiency and the associated osteoporosis and cardiovascular disease as well as psychological and psychiatric disorders related to the loss of reproductive hormones and infertility. Presently, with standard clinical testing, a mechanism for Overt POI can only be identified in about 10% of cases. Now discovery of new mechanisms permits an etiology to be identified in a research setting in 25-30% of overt cases. The most common genetic cause of Overt POI is premutation in FMR1. The associated infertility is life altering. Oocyte donation is effective, although many women prefer to conceive with their own ova. Surprisingly, the majority who have Overt POI still have detectable ovarian follicles (70%). The major mechanism of follicle dysfunction in Overt POI has been histologically defined by a prospective NIH study: inappropriate follicle luteinization due to the tonically elevated serum LH levels. A trial of physiologic hormone replacement therapy, clinically proven to suppress the elevated LH levels in these women, may improve follicle function and increase the chance of ovulation. Here, we report the case of a woman with Overt POI diagnosed at age 35 years. To attempt pregnancy, she elected a trial of intrauterine insemination (IUI) in conjunction with follicle monitoring and physiologic hormone replacement therapy. She conceived on the eighth cycle of treatment and delivered a healthy baby. Our report calls for a concerted effort to define the best methods by which to optimize fertility for women who have POI.