Thoracic aortic aneurysm in patients with loss of function Filamin A mutations: Clinical characterization, genetics, and recommendations.

Am J Med Genet A. 2018 Feb;176(2):337-350

Authors: Chen MH, Choudhury S, Hirata M, Khalsa S, Chang B, Walsh CA

Abstract
The frequency and gender distribution of thoracic aortic aneurysm as a cardiovascular manifestation of loss-of-function (LOF) X-linked FilaminA (FLNA) mutations are not known. Furthermore, there is very limited cardiovascular morbidity or mortality data in children and adults. We analyzed cardiac data on the largest series of 114 patients with LOF FLNA mutations, both children and adults, with periventricular nodular heterotopia (PVNH), including 48 study patients and 66 literature patients, median age of 22.0 years (88 F, 26 M, range: 0-71 years), with 75 FLNA mutations observed in 80 families. Most (64.9%) subjects had a cardiac anomaly or vascular abnormality (80.8% of males and 60.2% of females). Thoracic aortic aneurysms or dilatation (TAA) were found in 18.4% (n = 21), and were associated with other structural cardiac malformations in 57.1% of patients, most commonly patent ductus arteriosus (PDA) and valvular abnormalities. TAA most frequently involved the aortic root and ascending aorta, and sinus of Valsalva aneurysms were present in one third of TAA patients. Six TAA patients (28.5%) required surgery (median age 37 yrs, range 13-41 yrs). TAA with its associated complications was also the only recorded cause of premature, non-accidental mortality in adults (2 M, 2 F). Two adult patients (1 F, 1 M, median 38.5 yrs), died of spontaneous aortic rupture at aortic dimensions smaller than current recommendations for surgery for other aortopathies. Data from this largest series of LOF FLNA mutation patients underscore the importance of serial follow-up to identify and manage these potentially devastating cardiovascular complications.

PMID: 29334594 [PubMed - in process]

Finding patients using similarity measures in a rare diseases-oriented clinical data warehouse: Dr. Warehouse and the needle in the needle stack.

J Biomed Inform. 2017 Sep;73:51-61

Authors: Garcelon N, Neuraz A, Benoit V, Salomon R, Kracker S, Suarez F, Bahi-Buisson N, Hadj-Rabia S, Fischer A, Munnich A, Burgun A

Abstract
OBJECTIVE: In the context of rare diseases, it may be helpful to detect patients with similar medical histories, diagnoses and outcomes from a large number of cases with automated methods. To reduce the time to find new cases, we developed a method to find similar patients given an index case leveraging data from the electronic health records.
MATERIALS AND METHODS: We used the clinical data warehouse of a children academic hospital in Paris, France (Necker-Enfants Malades), containing about 400,000 patients. Our model was based on a vector space model (VSM) to compute the similarity distance between an index patient and all the patients of the data warehouse. The dimensions of the VSM were built upon Unified Medical Language System concepts extracted from clinical narratives stored in the clinical data warehouse. The VSM was enhanced using three parameters: a pertinence score (TF-IDF of the concepts), the polarity of the concept (negated/not negated) and the minimum number of concepts in common. We evaluated this model by displaying the most similar patients for five different rare diseases: Lowe Syndrome (LOWE), Dystrophic Epidermolysis Bullosa (DEB), Activated PI3K delta Syndrome (APDS), Rett Syndrome (RETT) and Dowling Meara (EBS-DM), from the clinical data warehouse representing 18, 103, 21, 84 and 7 patients respectively.
RESULTS: The percentages of index patients returning at least one true positive similar patient in the Top30 similar patients were 94% for LOWE, 97% for DEB, 86% for APDS, 71% for EBS-DM and 99% for RETT. The mean number of patients with the exact same genetic diseases among the 30 returned patients was 51%.
CONCLUSION: This tool offers new perspectives in a translational context to identify patients for genetic research. Moreover, when new molecular bases are discovered, our strategy will help to identify additional eligible patients for genetic screening.

PMID: 28754522 [PubMed - indexed for MEDLINE]

The TGF-β System As a Potential Pathogenic Player in Disease Modulation of Amyotrophic Lateral Sclerosis.

Front Neurol. 2017;8:669

Authors: Peters S, Zitzelsperger E, Kuespert S, Iberl S, Heydn R, Johannesen S, Petri S, Aigner L, Thal DR, Hermann A, Weishaupt JH, Bruun TH, Bogdahn U

Abstract
Amyotrophic lateral sclerosis (ALS) represents a fatal orphan disease with high unmet medical need, and a life time risk of approx. 1/400 persons per population. Based on increasing knowledge on pathophysiology including genetic and molecular changes, epigenetics, and immune dysfunction, inflammatory as well as fibrotic processes may contribute to the heterogeneity and dynamics of ALS. Animal and human studies indicate dysregulations of the TGF-β system as a common feature of neurodegenerative disorders in general and ALS in particular. The TGF-β system is involved in different essential developmental and physiological processes and regulates immunity and fibrosis, both affecting neurogenesis and neurodegeneration. Therefore, it has emerged as a potential therapeutic target for ALS: a persistent altered TGF-β system might promote disease progression by inducing an imbalance of neurogenesis and neurodegeneration. The current study assessed the activation state of the TGF-β system within the periphery/in life disease stage (serum samples) and a late stage of disease (central nervous system tissue samples), and a potential influence upon neuronal stem cell (NSC) activity, immune activation, and fibrosis. An upregulated TGF-β system was suggested with significantly increased TGF-β1 protein serum levels, enhanced TGF-β2 mRNA and protein levels, and a strong trend toward an increased TGF-β1 protein expression within the spinal cord (SC). Stem cell activity appeared diminished, reflected by reduced mRNA expression of NSC markers Musashi-1 and Nestin within SC-paralleled by enhanced protein contents of Musashi-1. Doublecortin mRNA and protein expression was reduced, suggesting an arrested neurogenesis at late stage ALS. Chemokine/cytokine analyses suggest a shift from a neuroprotective toward a more neurotoxic immune response: anti-inflammatory chemokines/cytokines were unchanged or reduced, expression of proinflammatory chemokines/cytokines were enhanced in ALS sera and SC postmortem tissue. Finally, we observed upregulated mRNA and protein expression for fibronectin in motor cortex of ALS patients which might suggest increased fibrotic changes. These data suggest that there is an upregulated TGF-β system in specific tissues in ALS that might lead to a "neurotoxic" immune response, promoting disease progression and neurodegeneration. The TGF-β system therefore may represent a promising target in treatment of ALS patients.

PMID: 29326641 [PubMed]

Dysfunctional sarcomere contractility contributes to muscle weakness in ACTA1-related nemaline myopathy (NEM3).

Ann Neurol. 2018 Jan 12;:

Authors: Joureau B, de Winter JM, Conijn S, Bogaards SJP, Kovacevic I, Kalganov A, Persson M, Lindqvist J, Stienen GJM, Irving TC, Ma W, Yuen M, Clarke NF, Rassier DE, Malfatti E, Romero NB, Beggs AH, Ottenheijm CAC

Abstract
OBJECTIVE: Nemaline myopathy (NM) is one of the most common congenital non-dystrophic myopathies and is characterized by muscle weakness, often from birth. Mutations in ACTA1 are a frequent cause of NM (i.e. NEM3). ACTA1 encodes alpha-actin 1, the main constituent of the sarcomeric thin filament. The mechanisms by which mutations in ACTA1 contribute to muscle weakness in NEM3 are incompletely understood. We hypothesized that sarcomeric dysfunction contributes to muscle weakness in NEM3 patients.
METHODS: To test this hypothesis, we performed contractility measurements in individual muscle fibers and myofibrils obtained from muscle biopsies of fourteen NEM3 patients with different ACTA1 mutations. To identify the structural basis for impaired contractility, low angle x-ray diffraction and stimulated emission-depletion microscopy were applied.
RESULTS: Our findings reveal that muscle fibers of NEM3 patients display a reduced maximal force generating capacity, which is caused by dysfunctional sarcomere contractility in the majority of patients, as revealed by contractility measurements in myofibrils. Low angle x-ray diffraction and stimulated emission-depletion microscopy indicate that dysfunctional sarcomere contractility in NEM3 patients involves a lower number of myosin heads binding to actin during muscle activation. This lower number is not the result of reduced thin filament length. Interestingly, the calcium sensitivity of force is unaffected in some patients, but decreased in others.
INTERPRETATION: Thus, dysfunctional sarcomere contractility is an important contributor to muscle weakness in the majority of NEM3 patients, information which is crucial for patient stratification in future clinical trials. This article is protected by copyright. All rights reserved.

PMID: 29328520 [PubMed - as supplied by publisher]

CAPD Catheter Exit-Site and Tunnel Infection with Fungal Etiology-Treatment and Catheter Reinsertion for an Extremely Rare Complication.

Perit Dial Int. 2017 Mar-Apr;37(2):237-239

Authors: Jhawar MS, Das J, George P, Luther A

Abstract
Fungal infection is an extremely rare etiology of exit-site and tunnel infection in patients on continuous ambulatory peritoneal dialysis (CAPD). There are few data available regarding its management-especially choice of antifungals, duration of therapy, and removal of catheter. There are no guidelines pertaining to reinsertion of the CAPD catheter following fungal exit-site and tunnel infection. This case report highlights Candida albicans as a rare cause of exit-site and tunnel infection of the CAPD catheter. The catheter was removed and the patient received appropriate antifungal therapy followed by reinsertion of the CAPD catheter and re-initiation on CAPD.

PMID: 28360371 [PubMed - indexed for MEDLINE]

Pharmacological Chaperoning: A Potential Treatment for PMM2-CDG.

Hum Mutat. 2017 Feb;38(2):160-168

Authors: Yuste-Checa P, Brasil S, Gámez A, Underhaug J, Desviat LR, Ugarte M, Pérez-Cerdá C, Martinez A, Pérez B

Abstract
The congenital disorder of glycosylation (CDG) due to phosphomannomutase 2 deficiency (PMM2-CDG), the most common N-glycosylation disorder, is a multisystem disease for which no effective treatment is available. The recent functional characterization of disease-causing mutations described in patients with PMM2-CDG led to the idea of a therapeutic strategy involving pharmacological chaperones (PC) to rescue PMM2 loss-of-function mutations. The present work describes the high-throughput screening, by differential scanning fluorimetry, of 10,000 low-molecular-weight compounds from a commercial library, to search for possible PCs for the enzyme PMM2. This exercise identified eight compounds that increased the thermal stability of PMM2. Of these, four compounds functioned as potential PCs that significantly increased the stability of several destabilizing and oligomerization mutants and also increased PMM activity in a disease model of cells overexpressing PMM2 mutations. Structural analysis revealed one of these compounds to provide an excellent starting point for chemical optimization since it passed tests based on a number of pharmacochemical quality filters. The present results provide the first proof-of-concept of a possible treatment for PMM2-CDG and describe a promising chemical structure as a starting point for the development of new therapeutic agents for this severe orphan disease.

PMID: 27774737 [PubMed - indexed for MEDLINE]

[Analysis of Social Network Support for Rare-Disease Patients From a Social Capital Perspective].

Hu Li Za Zhi. 2017 Oct;64(5):18-23

Authors: Tsai TF

PMID: 28948587 [PubMed - indexed for MEDLINE]

[Introduction to Genetic/Rare Disease and the Application of Genetic Counseling].

Hu Li Za Zhi. 2017 Oct;64(5):11-17

Authors: Chu SY, Weng CY

Abstract
Genetic disease or hereditary disease is a group of disorders that is caused by mutations in an individual's genome. The mutated genome or gene may be transmitted through the germ line during reproduction, causing certain recurrence risk in offspring and other family members. The heritability of these disorders is thus an important issue to deal with clinically. In Taiwan, a rare disease is defined as a disease that is prevalent in fewer than 1 in 10,000 individuals. As up to 80% of rare disease cases in Taiwan are genetic disease disorders, genetic disease may not rare. The pathophysiology of genetic/ rare disease is very complicated. Individual disorders may have their own unique mechanisms (such as Fragile X syndrome), with most of these mechanisms still unclear or unknown. The symptoms and signs of genetic/rare disease thus present the greatest variabilities and cause difficulties in making diagnoses. Most related patients may present multiple congenital anomalies, metabolic disorders, growth and developmental delays, defects in cognition, neuromuscular abnormalities, and defects in vision, hearing or other organ functions. Symptomatic and supportive treatment still comprise a major component of treatment of genetic/rare disease (with the exception of special formulae for several inborn errors of metabolic disease and enzyme replacement therapy in some lysosomal storage disease). Poor self-care ability is common and the burden on caregivers is huge. Most rare disease patients are treated using a comprehensive rehabilitation program that begins during very early childhood, receive individual educational programs, and are continuously monitored with regard to their growth, developmental, and nutritional status. Inter-professional patient care, genetic counseling, and the creation of family support networks play an important role in family management. Public awareness and the creation of appropriate social systems and resources allocation are mandatory for proper care. The incidence of each genetic/rare disease is rare, but collectively they are important public health issue and a challenge to medical care.

PMID: 28948586 [PubMed - indexed for MEDLINE]

Workshop Proceedings: Streamlined Development of Safety Assessment Programs Supporting Orphan/Rare Diseases-Are We There Yet?

Int J Toxicol. 2016 Jul;35(4):393-409

Authors: Allamneni KP, Parker S, O'Neill CA, Wright TL, King S, Andrews L

Abstract
A workshop entitled "Streamlined Development of Safety Assessment Programs Supporting Orphan/Rare Diseases-Are We There Yet?" was held at the 36th Annual Meeting of the American College of Toxicology in Summerlin, Nevada. The workshop was sponsored by Shire and Ultragenyx and was designed to present the nonclinical considerations for the development of various products for rare diseases. A panel of experts from industry and government highlighted the nonclinical considerations in developing toxicology programs supporting rare disease therapeutics, challenges in preclinical safety assessment, reviewed the current guidance, and presented the progress that has been made to date. The main learning from the workshop was that nonclinical testing of therapeutics targeting rare disease warrants special considerations, and early collaboration between sponsors and health authorities may help optimize the scope and timing of the supportive studies. Specific examples for nonclinical development programs for enzyme replacement therapy (ERT) were presented. Although the symposium focused on ERTs, the concepts are broadly applicable.

PMID: 27272885 [PubMed - indexed for MEDLINE]

[Rare syndromes in intensive care medicine : Presentation of two cases].

Med Klin Intensivmed Notfmed. 2016 Jun;111(5):400-6

Authors: Gierlinger A, Siostrzonek P, Reisinger J

Abstract
This article presents two cases of young women with spontaneous life-threatening bleeding events. Both had a history of gastrointestinal rupture or arterial dissection. Based on their medical history and genetic testing, Ehlers-Danlos syndrome (EDS) IV (vascular type) was diagnosed. In this very rare disorder which accounts for only 5 % of all EDS cases, fibroblasts synthesize reduced and abnormal procollagen type III. This is caused by mutations in the COL3A1 gene coding for type III procollagen. Life expectancy in these patients is significantly reduced. In many cases spontaneous arterial ruptures or dissections and organ ruptures are the first manifestations of this disease. More than 80 % of patients with EDS IV suffer from a severe complication before 40 years of age. Treatment options are very limited. Most important is to avoid invasive procedures (open surgery as well as endovascular interventions) because of its high morbidity and mortality. Celiprolol, a cardioselective β‑blocker, seems to have a beneficial effect by reducing the incidence of vascular complications.

PMID: 27259332 [PubMed - indexed for MEDLINE]

The promise of immunotherapy in anal squamous cell carcinoma: a novel approach for an orphan disease.

Clin Adv Hematol Oncol. 2017 Dec;15(12):968-961

Authors: Johnson B, Eng C

Abstract
An estimated 8200 men and women in the United States will receive a diagnosis of squamous cell carcinoma of the anal canal (SCCA) in 2017. Although SCCA is rare, accounting for 2.6% of gastrointestinal cancers, its incidence rate has been steadily increasing over the last few decades in the United States and around the world. More than 90% of cases of SCCA occur in the context of prior human papillomavirus (HPV) infection. To date, preventive vaccinations against HPV remain markedly underutilized. Most patients who have SCCA present with locoregional disease that is cured with chemoradiation. However, metastatic disease develops in 25% of patients. The management of metastatic SCCA is based on single-institutional case series, with no accepted consensus regarding standard of care. Given the complex interplay between the incorporation of HPV DNA into the host cell genome and the oncogenesis of SCCA, immunotherapeutic strategies have become a strong focus of research efforts regarding the management of SCCA. Recently, a phase 2 trial of an anti-programmed death 1 antibody for refractory SCCA has shown positive results. This review summarizes novel immunotherapies that are under active clinical investigation and describes their potential use in the management of metastatic SCCA.

PMID: 29315288 [PubMed - in process]

A Rare Case of Giant Basal Cell Carcinoma of the Abdominal Wall: Excision and Immediate Reconstruction with a Pedicled Deep Inferior Epigastric Artery Perforator (DIEP) Flap.

Am J Case Rep. 2017 Dec 04;18:1284-1288

Authors: Di Lorenzo S, Zabbia G, Corradino B, Tripoli M, Pirrello R, Cordova A

Abstract
BACKGROUND Basal cell carcinoma (BCC) greater than 5 cm in diameter is called giant basal cell carcinoma (GBCC), or super giant basal cell carcinoma if it has a diameter larger than 20 cm. Giant BCC only accounts for 0.5% of BCCs and super giant BCC is exceedingly rare. On account of their rarity, there are no established guidelines for GBCC treatment. CASE REPORT We describe a peculiar case of an 82-year-old woman with a GBCC carcinoma of the lower abdominal wall. The tumor was surgically removed with ipsilateral inguinal lymph nodes and the abdominal wall was reconstructed immediately with a pedicled deep inferior epigastric artery perforator (DIEP) flap. CONCLUSIONS Treatment of giant basal cell carcinoma is often difficult, especially in elderly patients with poor general health and multiple pathologies. The pedicled DIEP flap is rotated to cover the loss of substance without tension, and it is easy to harvest and transfer. This flap allowed a good result without local or systemic complication. We present this report as a reminder of the occasional occurrence of extremely aggressive BCCs. We believe that, especially for rare tumors like these, it is very useful for the entire scientific community to publish these cases and the therapeutic strategies used to treat them.

PMID: 29199268 [PubMed - indexed for MEDLINE]

A Rare Case of Bochdalek Hernia with Concomitant Para-Esophageal Hernia, Repaired Laparoscopically in an Octogenarian.

Am J Case Rep. 2017 Nov 29;18:1261-1265

Authors: Susmallian S, Raziel A

Abstract
BACKGROUND A Bochdalek hernia (BH) is a rare congenital condition consisting of a posterolateral defect in the diaphragm. A para-esophageal hernia (PEH) is a rare variant of hiatus hernia. BH and PEH may present with gastric volvulus or incarceration, requiring emergency treatment. Minimally invasive surgery is the preferred treatment, particularly for elderly patients and patients with comorbidities. The occurrence of BH with concomitant PEH is a very rare event. We describe a case of an octogenarian patient with BH and concomitant PEH treated laparoscopically. CASE REPORT An 81-year-old male patient, without significant comorbidities, presented with a two-month history of severe chest pain and vomiting after eating. Cardiological investigations ruled out cardiac ischemia, infarction, or other cardiovascular abnormalities. Chest and abdominal computed tomography (CT) imaging demonstrated a large diaphragmatic hernia, with the entire stomach in the left thorax. Laboratory results showed mild anemia and a low iron level. The patient underwent simultaneous laparoscopic repair of a BH and a PEH with mesh reinforcement without antireflux fundoplication. The patient's postoperative recovery was uneventful. CONCLUSIONS We have presented a rare case of BH with concomitant PEH in an octogenarian that was successfully treated with laparoscopic surgery. Although these two forms of hernia are a very rare association, this case report illustrates that the surgical approach should be individualized in each patient's case to ensure a successful surgical outcome. In this case, the decision was made to suture the diaphragmatic crura and reinforce the diaphragm repair with mesh, rather than by fundoplication.

PMID: 29184050 [PubMed - indexed for MEDLINE]

Lead-related infective endocarditis: Factors influencing early and long-term survival in patients undergoing transvenous lead extraction.

Heart Rhythm. 2017 Jan;14(1):43-49

Authors: Polewczyk A, Jacheć W, Tomaszewski A, Brzozowski W, Czajkowski M, Opolski G, Grabowski M, Janion M, Kutarski A

Abstract
BACKGROUND: Lead-related infective endocarditis (LRIE) is a serious infectious disease with uncertain prognosis.
OBJECTIVE: The purpose of this study was to evaluate the factors that influence survival in patients with LRIE undergoing transvenous lead extraction (TLE).
METHODS: Clinical data obtained from 500 consecutive patients with LRIE undergoing TLE in the reference center in the years 2006 to 2015 were retrospectively analyzed. We evaluated the effect of demographic, clinical, and procedure-related factors on 30-day and long-term survival (mean 3-year follow-up).
RESULTS: Analysis of 30-day survival after TLE revealed 19 deaths (3.8%), with long-term mortality (mean 3-year follow-up) of 29.3% (146 deaths). Multivariate analysis showed unfavorable effects of age (hazard ratio [HR] 1.056, 95% confidence interval [CI] 1.030-1.082); decreased left ventricular ejection fraction (HR 0.687, 95% CI 0.545-0.866); renal failure (HR 3.099, 95% CI 1.865-5.150); and presence of vegetation fragments remaining after TLE (HR 1.384, 95% CI 1.089-1.760). Log-rank test and Kaplan-Meier survival curves demonstrated statistically worse prognosis in patients with large vegetations (>2 cm) and with vegetation remnants. Better prognosis was associated with LRIE coexisting with generator pocket infection.
CONCLUSION: Long-term mortality in LRIE patients is still high. Factors that influence negatively on prognosis include large cardiac vegetations and their remnants after TLE. Such vegetations develop most frequently in patients with decreased left ventricular ejection fraction and renal failure. Probably, early detection of LRIE would tend to limit the formation of large vegetations that invade the adjacent cardiac structures.

PMID: 27725287 [PubMed - indexed for MEDLINE]

A practical approach to ichthyoses with systemic manifestations.

Clin Genet. 2017 Jun;91(6):799-812

Authors: Saral S, Vural A, Wollenberg A, Ruzicka T

Abstract
Inherited ichthyoses are rare disorders in terms of patient numbers, but abundant in terms of clinical-genetic subtypes. These disorders are often associated with severe systemic manifestations, in addition to significant medical, cosmetic and social problems. There are 17 subtypes of syndromic ichthyosis identified so far and most patients with these syndromes are living in countries with high consanguinity rates. Frequently, clinicians cannot make a definitive diagnosis and patients are not managed properly owing to the rarity and complexity of these disorders. These difficulties make this group of ichthyosis and the patients living with them 'orphan'. After skin and skin appendages, nervous system is the most frequently involved system in ichthyosis syndromes. Thus, association of ichthyosis with neurological symptoms provides an important clue for diagnosis. In this article, we aim to increase clinicians' comprehension of ichthyosis syndromes by providing a symptomatology-based approach based on this observation. Additionally, we provide a review of ichthyosis syndromes, with special emphasis on neurological symptoms, hoping to attract interest to this complicated field.

PMID: 27377997 [PubMed - indexed for MEDLINE]

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Trials and Tribulations: An Industry Perspective on Conducting Registrational Trials in Alpha-1 Antitrypsin Deficiency.

Ann Am Thorac Soc. 2016 Aug;13 Suppl 4:S374-7

Authors: Forshag MS

Abstract
Registrational trials in rare and orphan diseases present complexities related to the identification of subjects, recruitment, logistical hurdles incumbent with far-flung study sites, and end points that are often less well defined than are those used in more common illnesses. Alpha-1 antitrypsin deficiency is an orphan disease of genetic origin that carries the additional challenges of variable penetration and slow disease progression. Registrational trials of augmentation therapy using plasma-derived alpha-1 antitrypsin carry all of the above-noted burdens, as well as competition from commercially available augmentation therapy in many countries.

PMID: 27564675 [PubMed - indexed for MEDLINE]

Biological and molecular characterization of a rare case of cutaneous Richter syndrome.

Hematol Oncol. 2017 Dec;35(4):869-874

Authors: Reda G, Cassin R, Fabris S, Ciceri G, Fattizzo B, Sciumè M, Orofino N, Gianelli U, Neri A, Cortelezzi A

Abstract
Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia in a high-grade lymphoma usually presenting nodal and bone marrow involvement. Richter syndrome can be localized at extranodal sites including the gastrointestinal tract, lungs, and skin. Cutaneous RS is an extremely rare disease apparently showing a less aggressive course than common presentations. While nodal RS has been extensively investigated in literature, pathogenesis and prognosis of cutaneous RS are still partially unknown, even if a role of Epstein-Barr virus infection and p53 disruption has been suggested. Herein, we characterized the histopathological, immunohistochemical features and cytogenetics and molecular alterations of a case of cutaneous RS developed after 8 years chronic lymphocytic leukemia history. Moreover, we reviewed the literature reports concerning cutaneous RS and made a focus on biological patterns and prognostic implications.

PMID: 27400669 [PubMed - indexed for MEDLINE]

What does the arthropathy of alkaptonuria teach us about disease mechanisms in osteoarthritis and ageing of joints?

Rheumatology (Oxford). 2016 07;55(7):1151-2

Authors: Gallagher JA, Ranganath LR, Boyde A

PMID: 26712212 [PubMed - indexed for MEDLINE]

Philadelphia Chromosome Positive de novo Acute Myeloid Leukemia.

J Coll Physicians Surg Pak. 2016 Nov;26(11):100-102

Authors: Quraishi AM, Akram M, Saeed S, Tahir M

Abstract
Philadelphia chromosome positive de novoacute myeloid leukemia (AML)is a rare disease with reported incidence of less than 1% of newly diagnosed cases of AML. Outcome of the disease is poor, owing to its resistance to conventional chemotherapy and variable response to imatinib besylate. We report a case of 24-year man who reported to our unit in November 2014 and was treated with conventional induction and consolidation chemotherapy with imatinib besylate. He achieved complete remission after induction chemotherapy and remained in remission. His cytogenetics also reverted to normal after consolidation chemotherapy. He relapsed after 3 months of maintenance imatinib besylate.

PMID: 28666495 [PubMed - indexed for MEDLINE]