Cryptogenic multifocal ulcerous stenosing enteritis: Radiologic features and clinical behavior.

World J Gastroenterol. 2017 Jul 07;23(25):4615-4623

Authors: Hwang J, Kim JS, Kim AY, Lim JS, Kim SH, Kim MJ, Kim MS, Song KD, Woo JY

Abstract
AIM: To investigate the characteristic radiologic findings of cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) which can be differentiated from other similar bowel disease and to assess their clinical behavior.
METHODS: Twenty pathologically and clinically confirmed CMUSE patients (males:females = 8:12; mean age: 40.4 years) between March 2002 and August 2015 from seven academic centers in South Korea were retrospectively reviewed. We evaluated small bowel series (SBS; n = 25), computed tomography (CT) enterography (n = 21), magnetic resonance (MR) enterography (n = 2), and abdominopelvic CT (n = 18) images, focusing on enteric and perienteric manifestations. Any change in radiologic features during follow-up period was recorded. We evaluated clinical data including presenting symptoms, laboratory finding and presence of relapse from electronic medical records. Histopathologic findings were also evaluated.
RESULTS: The main symptoms were abdominal pain (n = 12) and anemia (n = 10). All patients showed small bowel strictures (n = 52, mean: 2.6 per patient) on initial CT/MR, located in the ileum (n = 47) or jejunum (n = 5). Strictures showed short-length (mean: 10.44 mm) and circumferential bowel wall thickening (mean: 5.56 mm) with layered enhancement (n = 48) that were also noted on initial SBS (n = 36) with shallow ulcers (n = 10). Some ulcerative lesions or wall thickening progressed into strictures on follow-up SBS/CT, and some strictures revealed recurrent ulceration on follow-up SBS. There were no penetrating disease features like fistula or abscess and no gastrointestinal tract involvement except the small bowel. Nine patients experienced disease recurrence (median relapse-free period: 32 mo) even post-operatively. Histopathologic features of surgically resected specimens were characterized as multiple superficial ulcerations confined to mucosa or submucosa and multiple strictures.
CONCLUSION: Under characteristic radiologic findings with multiple short-segmental strictures and/or shallow ulcers of the small intestine, CMUSE should be considered when assessing patients with recurrent abdominal pain and anemia.

PMID: 28740350 [PubMed - indexed for MEDLINE]

[Raising the internist's know-how in the field of rare diseases: mitochondrial diseases as an illustrative example].

Rev Med Suisse. 2017 Jan 18;13(546):159-163

Authors: Tran C, Serratrice J, Nuoffer JM, Schaller A, Favrat B, Barbey F, Lobrinus JA, Kern I, Kuntzer T, Ballhausen D

Abstract
Rare Diseases, defined by a prevalence of less than 1 per 2000 persons, affect 36 million people in Europe, 500 000 in Switzerland, corresponding to 6-8% of the general population. 7000 rare diseases are currently recorded.Mitochondrial diseases are a heterogeneous group of genetic diseases. They are characterized by intracellular failure of energy production and affect predominantly energy-dependent tissues. The clinical presentation is not always suggestive, particularly in adulthood. In order to reach the diagnosis, a prerequisite is to think of them. In this article, we will focus on the clinical aspects of mitochondrial disorders in order to give the internist simple tools on how not to miss those rare diseases in his daily practice.

PMID: 28703515 [PubMed - indexed for MEDLINE]

The FDA Breakthrough-Drug Designation - Four Years of Experience.

N Engl J Med. 2018 04 12;378(15):1444-1453

Authors: Darrow JJ, Avorn J, Kesselheim AS

PMID: 29641970 [PubMed - indexed for MEDLINE]

Affordability Challenges to Value-Based Pricing: Mass Diseases, Orphan Diseases, and Cures.

Value Health. 2018 03;21(3):252-257

Authors: Danzon PM

Abstract
OBJECTIVES: To analyze how value-based pricing (VBP), which grounds the price paid for pharmaceuticals in their value, can manage "affordability" challenges, defined as drugs that meet cost-effectiveness thresholds but are "unaffordable" within the short-run budget.
METHODS: Three specific contexts are examined, drawing on recent experience. First, an effective new treatment for a chronic, progressive disease, such as hepatitis C, creates a budget spike that is transitory because initial prevalence is high, relative to current incidence. Second, "cures" that potentially provide lifetime benefits may claim abnormally high VBP prices, with high immediate budget impact potentially/partially offset by deferred cost savings. Third, although orphan drugs in principle target rare diseases, in aggregate they pose affordability concerns because of the growing number of orphan indications and increasingly high prices.
RESULTS: For mass diseases, the transitory budget impact of treating the accumulated patient stock can be managed by stratified rollout that delays treatment of stable patients and prioritizes patients at high risk of deterioration. Delay spreads the budget impact and permits potential savings from launch of competing treatments. For cures, installment payments contingent on outcomes could align payment flows and appropriately shift risk to producers. This approach, however, entails high administrative and incentive costs, especially if applied across multiple payers in the United States. For orphan drugs, the available evidence on research and development trends and returns argues against the need for a higher VBP threshold to incentivize research and development in orphan drugs, given existing statutory benefits under orphan drug legislation.

PMID: 29566830 [PubMed - indexed for MEDLINE]

Segmental testicular infarction: a case report.

J Med Case Rep. 2017 May 18;11(1):140

Authors: Smets T, Reichman G, Michielsen DPJ

Abstract
BACKGROUND: Segmental testicular infarction is a very rare condition, which can mimic a testicular torsion or testicular cancer. Correct diagnosis is difficult but it is important to avoid unnecessary radical treatment.
CASE PRESENTATION: We report a clinical case of a 36-year-old white man who presented at our emergency department with subacute testicular pain. A urine analysis, Doppler ultrasound, surgical exploration, blood analysis, and magnetic resonance imaging were performed to diagnose his condition, to exclude a testicular torsion, and to raise confidence in its non-malignancy. He was treated conservatively. At follow-up, a few months after the incident, he no longer had complaints. Ultrasonography showed remaining hypo-echogenicity of the left upper pole, indicating a sequel of ischemia.
CONCLUSIONS: Segmental testicular infarction is a rare condition which can be easily confused with a testicular torsion or a testicular tumor. This case report can be helpful in recognizing and diagnosing this condition. Making the right diagnosis is important since it can prevent an unnecessary radical treatment.

PMID: 28514960 [PubMed - indexed for MEDLINE]

Linear models of coregionalization for multivariate lattice data: Order-dependent and order-free cMCARs.

Stat Methods Med Res. 2016 Aug;25(4):1118-44

Authors: MacNab YC

Abstract
This paper concerns with multivariate conditional autoregressive models defined by linear combination of independent or correlated underlying spatial processes. Known as linear models of coregionalization, the method offers a systematic and unified approach for formulating multivariate extensions to a broad range of univariate conditional autoregressive models. The resulting multivariate spatial models represent classes of coregionalized multivariate conditional autoregressive models that enable flexible modelling of multivariate spatial interactions, yielding coregionalization models with symmetric or asymmetric cross-covariances of different spatial variation and smoothness. In the context of multivariate disease mapping, for example, they facilitate borrowing strength both over space and cross variables, allowing for more flexible multivariate spatial smoothing. Specifically, we present a broadened coregionalization framework to include order-dependent, order-free, and order-robust multivariate models; a new class of order-free coregionalized multivariate conditional autoregressives is introduced. We tackle computational challenges and present solutions that are integral for Bayesian analysis of these models. We also discuss two ways of computing deviance information criterion for comparison among competing hierarchical models with or without unidentifiable prior parameters. The models and related methodology are developed in the broad context of modelling multivariate data on spatial lattice and illustrated in the context of multivariate disease mapping. The coregionalization framework and related methods also present a general approach for building spatially structured cross-covariance functions for multivariate geostatistics.

PMID: 27566769 [PubMed - indexed for MEDLINE]

Reconstruction of complex single-cell trajectories using CellRouter.

Nat Commun. 2018 03 01;9(1):892

Authors: Lummertz da Rocha E, Rowe RG, Lundin V, Malleshaiah M, Jha DK, Rambo CR, Li H, North TE, Collins JJ, Daley GQ

Abstract
A better understanding of the cell-fate transitions that occur in complex cellular ecosystems in normal development and disease could inform cell engineering efforts and lead to improved therapies. However, a major challenge is to simultaneously identify new cell states, and their transitions, to elucidate the gene expression dynamics governing cell-type diversification. Here, we present CellRouter, a multifaceted single-cell analysis platform that identifies complex cell-state transition trajectories by using flow networks to explore the subpopulation structure of multi-dimensional, single-cell omics data. We demonstrate its versatility by applying CellRouter to single-cell RNA sequencing data sets to reconstruct cell-state transition trajectories during hematopoietic stem and progenitor cell (HSPC) differentiation to the erythroid, myeloid and lymphoid lineages, as well as during re-specification of cell identity by cellular reprogramming of monocytes and B-cells to HSPCs. CellRouter opens previously undescribed paths for in-depth characterization of complex cellular ecosystems and establishment of enhanced cell engineering approaches.

PMID: 29497036 [PubMed - indexed for MEDLINE]

Rare desmoplastic trichilemmoma associated with sebaceous nevus.

An Bras Dermatol. 2017 Nov-Dec;92(6):836-837

Authors: Jardim MML, Souza BCE, Fraga RC, Fraga RC

Abstract
Nevus sebaceous of Jadassohn is a congenital hamartoma that usually affects the scalp and face. Several benign or malignant neoplasias may develop in the lesion and the most common are trichoblastoma, syringocystadenoma papilliferum, and basal cell carcinoma. Trichilemmoma is a benign solid tumor originating from external sheath cells of pilosebaceous follicles. When it is characterized by a central zone of desmoplasia, it is called desmoplastic trichilemmoma. We report a case of a 58-year-old patient who developed a tumor in a sebaceous nevus. We performed a total excision of the lesion. Histopathological diagnosis was compatible with desmoplastic trichilemmoma. Our literature review reveals that the occurrence of trichilemmoma desmoplastic is unusual. Moreover, it can mimic an invasive carcinoma on histological and clinical examinations. This fact confirms the importance of reporting the occurrence of this rare cancer in a nevus sebaceous of Jadassohn.

PMID: 29364442 [PubMed - indexed for MEDLINE]

Toward better management of rare and orphan pulmonary diseases.

Eur Respir J. 2016 05;47(5):1334-5

Authors: Harari S, Humbert M

PMID: 27132268 [PubMed - indexed for MEDLINE]

Aging and neurodegeneration are associated with increased mutations in single human neurons.

Science. 2018 02 02;359(6375):555-559

Authors: Lodato MA, Rodin RE, Bohrson CL, Coulter ME, Barton AR, Kwon M, Sherman MA, Vitzthum CM, Luquette LJ, Yandava CN, Yang P, Chittenden TW, Hatem NE, Ryu SC, Woodworth MB, Park PJ, Walsh CA

Abstract
It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of 15 normal individuals (aged 4 months to 82 years), as well as 9 individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. The accumulation of somatic mutations with age-which we term genosenium-shows age-related, region-related, and disease-related molecular signatures and may be important in other human age-associated conditions.

PMID: 29217584 [PubMed - indexed for MEDLINE]

Case of pediatric traditional serrated adenoma resected via endoscopic submucosal dissection.

World J Gastroenterol. 2017 Jun 28;23(24):4462-4466

Authors: Kondo S, Mori H, Nishiyama N, Kondo T, Shimono R, Okada H, Kusaka T

Abstract
Traditional serrated adenoma (TSA) is a type of serrated polyp of the colorectum and is thought to be a precancerous lesion. There are three types of serrated polyps, namely, hyperplastic polyps, sessile serrated adenomas/polyps, and TSAs. TSA is the least common of the three types and accounts for about 5% of serrated polyps. Here we report a pediatric case of TSA that was successfully resected by endoscopic submucosal dissection (ESD). This rare case report describes a pediatric patient with no family history of colonic polyp who was admitted to our hospital with hematochezia. On colonoscopy, we found a polypoid lesion measuring 10 mm in diameter in the lower rectum. We selected ESD as a surgical option for en bloc resection, and histopathological examination revealed TSA. The findings in this case suggest that TSA with precancerous potential can occur in children, and that ESD is useful for treating this lesion.

PMID: 28706430 [PubMed - indexed for MEDLINE]

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

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[Development of a product anti-Shiga toxin for prevention of the hemolytic uremic syndrome].

Medicina (B Aires). 2018;78(2):107-112

Authors: Hiriart Y, Pardo R, Bukata L, Lauché C, Muñoz L, Colonna M, Goldbaum F, Sanguineti S, Zylberman V

Abstract
The typical hemolytic uremic syndrome (HUS) is an orphan disease caused by Shiga toxin(Stx) producing Escherichia coli strains and characterized by acute kidney damage, microangiopathic hemolytic anemia and low platelet count. It is endemic in Argentina, the country with the highest incidence of HUS in the world. Stx is essential for its development and therefore, HUS is considered a toxemic non-bacteremic disorder, which could be treated with antibodies. Herein we describe the development of a new treatment capable of neutralizing the toxic effect of Stx and its variants. The treatment consists of F(ab')2 fragments from an equine antiserum whose efficacy and potency against Stx1 and Stx2 were proved in different preclinical models. The product was shown to be safe in animals. Furthermore, the anti-Stx F(ab')2 pharmacokinetic was shown to be similar to that of analogous compounds and a therapeutic window for its administration was determined. Altogether, these preclinical results warrant testing in humans. The phase I clinical trial will be performed at the Hospital Italiano in Buenos Aires to evaluate the safety and pharmacokinetics of the product in healthy adult volunteers. Based on the results of this study, a phase II clinical trial will be planned in pediatric patients diagnosed with infection by Stx-producing E. coli strains.

PMID: 29659360 [PubMed - in process]

Large cell neuroendocrine lung carcinoma induces peripheral T-cell repertoire alterations with predictive and prognostic significance.

Lung Cancer. 2018 May;119:48-55

Authors: Christopoulos P, Schneider MA, Bozorgmehr F, Kuon J, Engel-Riedel W, Kollmeier J, Baum V, Muley T, Schnabel PA, Bischoff H, Grohé C, Serke M, Thomas M, Fisch P, Meister M

Abstract
OBJECTIVES: This study was performed to evaluate for a potentially important role of T cells in the pathophysiology and treatment sensitivity of large cell neuroendocrine lung carcinoma (LCNEC), an orphan disease with poor prognosis and scarce data to guide novel therapeutic strategies.
MATERIALS AND METHODS: We performed T-cell receptor (TCR) β-chain spectratyping on blood samples of patients treated within the CRAD001KDE37 trial (n = 35) using age-matched current or former (n = 11) and never smokers (n = 10) as controls. The data were analyzed in conjunction with the complete blood counts of the probands as well as the data about response to treatment and overall survival in the clinical trial.
RESULTS AND CONCLUSION: Untreated stage IV LCNEC patients had significant T-cell repertoire alterations (p < 0.001) compared to age-matched smokers. These changes correlated positively with blood lymphocyte counts (r = 0.49, p < 0.01), suggesting antigen-induced T-cell proliferation as the causative mechanism. At the same time, LCNEC patients showed mild lymphopenia (1.54 vs. 2.51/nl in median, p < 0.01), which reveals a second, antigen-independent mechanism of systemic immune dysregulation. More pronounced T-cell repertoire alterations and higher blood lymphocyte counts at diagnosis were associated with a better treatment response by RECIST and with a longer overall survival (441 vs. 157 days in median, p = 0.019). A higher degree of T-cell repertoire normalization after 3 months of therapy also distinguished a patient group with more favourable prognosis (median overall survival 617 vs. 316 days, p = 0.036) independent of radiological response. Thus, LCNEC induces clinically relevant changes of the T-cell repertoire, which are measurable in the blood and could be exploited for prognostic, predictive and therapeutic purposes. Their pathogenesis appears to involve antigen-induced oligoclonal T-cell expansions superimposed on TCR-independent lymphopenia.

PMID: 29656752 [PubMed - in process]

Sustainable public health systems for rare diseases.

Ann Ist Super Sanita. 2017 Apr-Jun;53(2):170-175

Authors: Ferrelli RM, Gentile AE, De Santis M, Taruscio D

Abstract
INTRODUCTION: In the framework of the Joint Action for Rare Diseases (RD-ACTION), a specific task was defined to identify mechanisms influencing sustainability, equity and resilience of health systems for rare diseases (RDs).
METHOD: Literature narrative review on health systems sustainability and resilience for RDs. Years: 2000-2015. Databases: PubMed, Scopus, EBSCOHost, EMBAL, PASCAL, EMBASE, STN International and GoogleScholar.
ANALYSIS: interpretive synthesis concept and thematic analysis (Dixon-Wood, et al.).
RESULTS: 97 papers and 4 grey literature publications were identified. Two main topics stand out: economic evaluation and networks. The first topic did not identify widely accepted criterion to assign more weight to individuals with greater health needs. Healthcare network are identified as increasingly important for sustainability and resilience, in all of their aspects: professional "expertise", "experience" networks of users and carers; policy, learning, and interest networks.
CONCLUSION: Possible mechanisms for ensuring sustainability can be identified in networking, patients' empowerment and reorienting healthcare towards integrated community and home care.

PMID: 28617266 [PubMed - indexed for MEDLINE]

Expanding the clinical spectrum of biallelic ZNF335 variants.

Clin Genet. 2018 Apr 13;:

Authors: Stouffs K, Stergachis AB, Vanderhasselt T, Dica A, Janssens S, Vandervore L, Gheldof A, Bodamer O, Keymolen K, Seneca S, Liebaers I, Jayaraman D, Hill HE, Partlow JN, Walsh CA, Jansen AC

Abstract
ZNF335 plays an essential role in neurogenesis and biallelic variants in ZNF335 have been identified as the cause of severe primary autosomal recessive microcephaly in two unrelated families. We describe herein two additional affected individuals with biallelic ZNF335 variants, one individual with a homozygous c.1399T>C, p.(Cys467Arg) variant, and a second individual with compound heterozygous c.2171_2173delTCT, p.(Phe724del) and c.3998A>G, p.(Glu1333Gly) variants in ZNF335; with the latter variant predicted to affect splicing. Whereas the first case presented with early death and a severe phenotype characterized by anterior agyria with prominent extra-axial spaces, absent basal ganglia, and hypoplasia of the brainstem and cerebellum, the second case had a milder clinical presentation with hypomyelination and otherwise preserved brain structures on MRI. Our findings expand the clinical spectrum of ZNF335 associated microcephaly.

PMID: 29652087 [PubMed - as supplied by publisher]

Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size.

Nature. 2018 Apr 11;:

Authors: Johnson MB, Sun X, Kodani A, Borges-Monroy R, Girskis KM, Ryu SC, Wang PP, Patel K, Gonzalez DM, Woo YM, Yan Z, Liang B, Smith RS, Chatterjee M, Coman D, Papademetris X, Staib LH, Hyder F, Mandeville JB, Grant PE, Im K, Kwak H, Engelhardt JF, Walsh CA, Bae BI

Abstract
The human cerebral cortex is distinguished by its large size and abundant gyrification, or folding. However, the evolutionary mechanisms that drive cortical size and structure are unknown. Although genes that are essential for cortical developmental expansion have been identified from the genetics of human primary microcephaly (a disorder associated with reduced brain size and intellectual disability) 1 , studies of these genes in mice, which have a smooth cortex that is one thousand times smaller than the cortex of humans, have provided limited insight. Mutations in abnormal spindle-like microcephaly-associated (ASPM), the most common recessive microcephaly gene, reduce cortical volume by at least 50% in humans2-4, but have little effect on the brains of mice5-9; this probably reflects evolutionarily divergent functions of ASPM10,11. Here we used genome editing to create a germline knockout of Aspm in the ferret (Mustela putorius furo), a species with a larger, gyrified cortex and greater neural progenitor cell diversity12-14 than mice, and closer protein sequence homology to the human ASPM protein. Aspm knockout ferrets exhibit severe microcephaly (25-40% decreases in brain weight), reflecting reduced cortical surface area without significant change in cortical thickness, as has been found in human patients3,4, suggesting that loss of 'cortical units' has occurred. The cortex of fetal Aspm knockout ferrets displays a very large premature displacement of ventricular radial glial cells to the outer subventricular zone, where many resemble outer radial glia, a subtype of neural progenitor cells that are essentially absent in mice and have been implicated in cerebral cortical expansion in primates12-16. These data suggest an evolutionary mechanism by which ASPM regulates cortical expansion by controlling the affinity of ventricular radial glial cells for the ventricular surface, thus modulating the ratio of ventricular radial glial cells, the most undifferentiated cell type, to outer radial glia, a more differentiated progenitor.

PMID: 29643508 [PubMed - as supplied by publisher]

Drugs for rare disorders.

Br J Clin Pharmacol. 2017 Aug;83(8):1607-1613

Authors: Cremers S, Aronson JK

Abstract
Estimates of the frequencies of rare disorders vary from country to country; the global average defined prevalence is 40 per 100 000 (0.04%). Some occur in only one or a few patients. However, collectively rare disorders are fairly common, affecting 6-8% of the US population, or about 30 million people, and a similar number in the European Union. Most of them affect children and most are genetically determined. Diagnosis can be difficult, partly because of variable presentations and partly because few clinicians have experience of individual rare disorders, although they may be assisted by searching databases. Relatively few rare disorders have specific pharmacological treatments (so-called orphan drugs), partly because of difficulties in designing trials large enough to determine benefits and harms alike. Incentives have been introduced to encourage the development of orphan drugs, including tax credits and research aids, simplification of marketing authorization procedures and exemption from fees, and extended market exclusivity. Consequently, the number of applications for orphan drugs has grown, as have the costs of using them, so much so that treatments may not be cost-effective. It has therefore been suggested that not-for-profit organizations that are socially motivated to reduce those costs should be tasked with producing them. A growing role for patient organizations, improved clinical and translational infrastructures, and developments in genetics have also contributed to successful drug development. The translational discipline of clinical pharmacology is an essential component in drug development, including orphan drugs. Clinical pharmacologists, skilled in basic pharmacology and its links to clinical medicine, can be involved at all stages. They can contribute to the delineation of genetic factors that determine clinical outcomes of pharmacological interventions, develop biomarkers, design and perform clinical trials, assist regulatory decision making, and conduct postmarketing surveillance and pharmacoepidemiological and pharmacoeconomic assessments.

PMID: 28653488 [PubMed - indexed for MEDLINE]

Comparative study of p16 protein expression in squamous cell carcinomas from patients with epidermodysplasia verruciformis and patients without the disease.

Arch Dermatol Res. 2017 Aug;309(6):479-483

Authors: Mattos MSG, Oliveira WR, Sotto MN

Abstract
Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with susceptibility to beta-human papilloma virus (HPV) infection. EV patients develop disseminated warts and non-melanoma skin cancer, mainly squamous cell carcinomas (SCC) that are locally aggressive. EV pathogenesis is not yet fully understood, but alterations in the p16 gene play a role in the pathogenesis of neoplasms caused by high-risk genital HPV. To explore its role in EV lesions, we compared p16 expression in SCC from patients with and without EV. Tissue microarray slides composed of 27 SCC from EV patients, and 35 from non-EV patients were stained with an anti-p16 antibody. Twenty (74%) EV tumors exhibited diffuse (nuclear and cytoplasmic) p16 expression, one (4%) displayed focal expression, and six (22%) displayed no p16 staining. Eleven (31%) SCC from non-EV patients presented diffuse p16 staining, 14 (40%) displayed focal expression and 10 (29%) did not express p16. The frequency of diffuse p16 expression was higher in EV tumors than in SCC from patients without EV. The frequency of diffuse p16 expression in moderately and poorly differentiated EV-SCC was similarly higher than non-EV tumors with the same degree of differentiation. The diffuse expression of p16 in EV-SCC suggests that changes in the p16 gene, probably resulting in a functionally defective protein, may be one factor determining the locally aggressive clinical behavior of SCC in young EV patients.

PMID: 28439661 [PubMed - indexed for MEDLINE]

PhenX measures for phenotyping rare genetic conditions.

Genet Med. 2017 Jul;19(7):834-837

Authors: Phillips M, Grant T, Giampietro P, Bodurtha J, Valdez R, Maiese DR, Hendershot T, Terry SF, Hamilton CM

Abstract
INTRODUCTION: The PhenX Toolkit, an online resource of well-established measures of phenotypes and exposures, now has 16 new measures recommended for assessing rare genetic conditions.
MATERIALS AND METHODS: These measures and their protocols were selected by a working group of domain experts with input from the scientific community.
RESULTS: The measures, which cover life stages from birth through adulthood, include clinical scales, characterization of rare genetic conditions, bioassays, and questionnaires. Most are broadly applicable to rare genetic conditions (e.g., family history, growth charts, bone age, and body proportions). Some protocols (e.g., sweat chloride test) target specific conditions.
DISCUSSION: The rare genetic condition measures complement the existing measures in the PhenX Toolkit that cover anthropometrics, demographics, mental health, and reproductive history. They are directed at research pertaining to common and complex diseases. PhenX measures are publicly available and are recommended to help standardize assessments across a range of biomedical study designs. To facilitate incorporation of measures into human subjects' research, the Toolkit offers data collection worksheets and compatible data dictionaries.
CONCLUSION: Widespread use of standard PhenX measures in clinical, translational, and epidemiological research will enable more uniform cross-study comparisons and increase statistical power with the potential for enhancing scientific discovery.Genet Med advance online publication 12 January 2017.

PMID: 28079902 [PubMed - indexed for MEDLINE]