30 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 2018/07/17

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Regulating Rare Disease: Safely Facilitating Access to Orphan Drugs.

Fordham Law Rev. 2018 Mar;86(4):1889-921

Authors: Bannister JB

Abstract
While approximately one in ten Americans suffers from a rare disease, only 5 percent of rare diseases have a U.S. Food and Drug Administration (FDA) approved treatment. Congressional and regulatory efforts to stimulate the development of rare-disease treatments, while laudable, have not resolved the fundamental issues surrounding rare-disease treatment development. Indeed, small patient populations, incomplete scientific understanding of rare diseases, and high development costs continually limit the availability of rare-disease treatments. To illustrate the struggle of developing and approving safe rare-disease treatments, this Note begins by discussing the approval of Eteplirsen, the first drug approved for treating a rare disease called Duchenne muscular dystrophy. After exploring the current drug regulation system and how this impacts the availability of rare-disease treatments, this Note examines the 21st Century Cures Act's patient experience data provisions and the currently pending Trickett Wendler Right to Try Act. Ultimately, the unmet therapeutic needs of rare-disease patients can be met while protecting patient safety. This Note reasons that, if carefully implemented, the 21st Century Cures Act and the Trickett Wendler Right to Try Act could work in tandem to safely facilitate patient access to rare-disease treatments.

PMID: 29993206 [PubMed - indexed for MEDLINE]

Retrovesical malignant fibrous histiocytoma: a rare tumor.

BMJ Case Rep. 2017 Dec 02;2017:

Authors: Pathak S, Soni TP, Gupta AK, Sharma LM

Abstract
Malignant fibrous histiocytoma (MFH) originating from the retrovesical space is a very rare tumour. A 61-year-old man presented to our hospital with complaints of retention of urine and burning sensation during micturition since 6 months. CT scan abdomen showed a large retrovesical mass between the urinary bladder and rectum, measuring 11×9×12 cm, displacing the urinary bladder. Serum PSA (Prostate Specific Antigen) value was within normal range. Biopsy from retrovesical mass and immunohistochemistry was suggestive of MFH. Wide excision of the retrovesical mass was done. Histopathology confirmed the diagnosis of MFH. He received adjuvant radiotherapy. He is on regular follow-up since the last 2 years after radiotherapy with no signs and symptoms of disease recurrence.

PMID: 29197849 [PubMed - indexed for MEDLINE]

Prior opioid exposure influences parents' sharing of their children's CYP2D6 research results.

Pharmacogenomics. 2017 Aug;18(13):1199-1213

Authors: Myers MF, Zhang X, McLaughlin B, Kissell D, Perry CL, Veerkamp M, Zhang K, Holm IA, Prows CA

Abstract
AIM: To determine parents' use of their children's CYP2D6 research result. We hypothesized that perceived utility, likelihood of sharing and actual sharing of results would differ between parents with children previously exposed (cases) or unexposed (controls) to opioids.
METHODS: We returned results by phone (baseline). We surveyed parents about perceived utility and likelihood of sharing their child's research result at baseline, and actual sharing at 3 and 12 months.
RESULTS: Cases were more likely than controls to agree that they (p = 0.022) and the doctors (p = 0.041) could use the results to care for their child, to report higher likelihood of sharing (p = 0.042) and to actually share results with the child's doctor (p = 0.026).
CONCLUSION: Prior opioid exposure influenced perceived clinical utility and sharing behaviors.

PMID: 28745549 [PubMed - indexed for MEDLINE]

Anaplastic Large T-Cell Lymphoma Associated with Breast Implants - Rare Disease.

Isr Med Assoc J. 2017 Jun;19(6):390-392

Authors: Ben-Nun O, Bitterman N, Tadmor T, Bejar J, Shalata A, Yarin H, Calderon N

PMID: 28647941 [PubMed - indexed for MEDLINE]

Mental Health and Well-Being in Mothers of Children With Rare Genetic Syndromes Showing Chronic Challenging Behavior: A Cross-Sectional and Longitudinal Study.

Am J Intellect Dev Disabil. 2018 05;123(3):241-253

Authors: Adams D, Clarke S, Griffith G, Howlin P, Moss J, Petty J, Tunnicliffe P, Oliver C

Abstract
It is well documented that mothers of children with challenging behavior (CB) experience elevated levels of stress and that this persists over time, but less is known about the experience of mothers of children with rare genetic syndromes. This article describes 2 studies, 1 cross-sectional and 1 longitudinal, comparing well-being in mothers of children with Angelman, Cornelia de Lange and Cri du Chat syndrome who have either shown chronic CB ( n = 18) or low/no CB ( n = 26) in the preceding 7 years. The presence of chronic, long-term CB increased maternal stress but not depression or anxiety, and did not influence positive well-being. Stress relating specifically to their child's genetic syndrome reduced with age, highlighting the need for further exploration in this area.

PMID: 29671635 [PubMed - indexed for MEDLINE]

A Case of Kleine-Levin Syndrome: Diagnostic and Therapeutic Challenge.

Acta Med Iran. 2018 Jan;56(1):62-66

Authors: Marčić M, Marčić L, Titlić M

Abstract
Kleine-Levin syndrome (KLS) is a rare sleep disorder mainly affecting teenage boys in which the main features are intermittent hypersomnolence, behavioral and cognitive disturbances, hyperphagia, and in some cases hyper sexuality. Etiology is unknown, and there is no specific clinical or imaging test for this syndrome even though the illness has well-defined clinical features. Also, there is no effective treatment for KLS. KLS is self-limited, so the prognosis for these patients is not so bad. This study presents our case report and comprehensive workout that led to diagnosis which is primarily clinical. Our patient is a 20-year-old man referred to our clinic because of sleeping problems. At the age of 14, he presented with complaints of the excessive duration of sleep, increased appetite, excessive daytime sleepiness, loss of interest in social activities during attendance of high school and hallucinations. The excessive diagnostic procedure does not find pathological. Kleine-Levin syndrome (KLS) is a rare sleep disorder of unknown etiology which diagnosis is clinical and diagnostic workup is mainly to exclude other similar conditions. There is no specific therapy, but the disease is self-limited and with good prognosis.

PMID: 29436797 [PubMed - indexed for MEDLINE]

Novel ETFDH mutations in four cases of riboflavin responsive multiple acyl-CoA dehydrogenase deficiency.

Mol Genet Metab Rep. 2018 Sep;16:15-19

Authors: Fan X, Xie B, Zou J, Luo J, Qin Z, D'Gama AM, Shi J, Yi S, Yang Q, Wang J, Luo S, Chen S, Agrawal PB, Li Q, Shen Y

Abstract
Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid, amino acid, and choline metabolism caused by mutations in EFTA, EFTB, or ETFDH. Many MADD patients are responsive to treatment with riboflavin, termed riboflavin-responsive MADD (RR-MADD). Here, we report three novel mutations and one previously reported mutation in ETFDH in four RR-MADD patients who presented at various ages, and characterize the corresponding changes in ETF-QO protein structure. Clinicians should consider MADD in the differential diagnosis when patients present with muscle weakness and biochemical abnormalities. Gene testing plays a critical role in confirming the diagnosis of MADD, and may not only prevent patients from invasive testing, but also allow timely initiation of riboflavin treatment. The novel variants in ETFDH and the corresponding clinical features reported here enrich the allelic heterogeneity of RR-MADD and provide insight into genotype-phenotype relationships.

PMID: 29988809 [PubMed]

The BabySeq project: implementing genomic sequencing in newborns.

BMC Pediatr. 2018 Jul 09;18(1):225

Authors: Holm IA, Agrawal PB, Ceyhan-Birsoy O, Christensen KD, Fayer S, Frankel LA, Genetti CA, Krier JB, LaMay RC, Levy HL, McGuire AL, Parad RB, Park PJ, Pereira S, Rehm HL, Schwartz TS, Waisbren SE, Yu TW, BabySeq Project Team, Green RC, Beggs AH

Abstract
BACKGROUND: The greatest opportunity for lifelong impact of genomic sequencing is during the newborn period. The "BabySeq Project" is a randomized trial that explores the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns.
METHODS: Families of newborns are enrolled from Boston Children's Hospital and Brigham and Women's Hospital nurseries, and half are randomized to receive genomic sequencing and a report that includes monogenic disease variants, recessive carrier variants for childhood onset or actionable disorders, and pharmacogenomic variants. All families participate in a disclosure session, which includes the return of results for those in the sequencing arm. Outcomes are collected through review of medical records and surveys of parents and health care providers and include the rationale for choice of genes and variants to report; what genomic data adds to the medical management of sick and healthy babies; and the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns.
DISCUSSION: The BabySeq Project will provide empirical data about the risks, benefits and costs of newborn genomic sequencing and will inform policy decisions related to universal genomic screening of newborns.
TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov Identifier: NCT02422511 . Registration date: 10 April 2015.

PMID: 29986673 [PubMed - in process]

RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes.

PLoS Genet. 2018 03;14(3):e1007226

Authors: Bennett AH, O'Donohue MF, Gundry SR, Chan AT, Widrick J, Draper I, Chakraborty A, Zhou Y, Zon LI, Gleizes PE, Beggs AH, Gupta VA

Abstract
Gene expression in a tissue-specific context depends on the combined efforts of epigenetic, transcriptional and post-transcriptional processes that lead to the production of specific proteins that are important determinants of cellular identity. Ribosomes are a central component of the protein biosynthesis machinery in cells; however, their regulatory roles in the translational control of gene expression in skeletal muscle remain to be defined. In a genetic screen to identify critical regulators of myogenesis, we identified a DEAD-Box RNA helicase, DDX27, that is required for skeletal muscle growth and regeneration. We demonstrate that DDX27 regulates ribosomal RNA (rRNA) maturation, and thereby the ribosome biogenesis and the translation of specific transcripts during myogenesis. These findings provide insight into the translational regulation of gene expression in myogenesis and suggest novel functions for ribosomes in regulating gene expression in skeletal muscles.

PMID: 29518074 [PubMed - indexed for MEDLINE]

Pediatric liver transplantation for hepatocellular cancer and rare liver malignancies: US multicenter and single-center experience (1981-2015).

Liver Transpl. 2017 Dec;23(12):1577-1588

Authors: Vinayak R, Cruz RJ, Ranganathan S, Mohanka R, Mazariegos G, Soltys K, Bond G, Tadros S, Humar A, Marsh JW, Selby RR, Reyes J, Sun Q, Haberman K, Sindhi R

Abstract
A tenth of all pediatric liver transplantations (LTs) are performed for unresectable liver malignancies, especially the more common hepatoblastoma (HBL). Less understood are outcomes after LT for the rare hepatocellular carcinoma, nonhepatoblastoma embryonal tumors (EMBs), and slow growing metastatic neuroendocrine tumors of childhood. Pediatric LT is increasingly performed for rare unresectable liver malignancies other than HBL. We performed a retrospective review of outcomes after LT for malignancy in the multicenter US Scientific Registry of Transplant Recipients (SRTR; n = 677; 1987-2015). We then reviewed the Children's Hospital of Pittsburgh (CHP; n = 74; 1981-2014) experience focusing on LT for unresectable hepatocellular cancer (HCC), EMBs, and metastatic liver tumors (METS). HBL was included to provide reference statistics. In the SRTR database, LT for HCC and HBL increased over time (P < 0.001). Compared with other malignancies, the 149 HCC cases received fewer segmental grafts (P < 0.001) and also experienced 10-year patient survival similar to 15,710 adult HCC LT recipients (51.6% versus 49.6%; P = 0.848, not significant [NS], log-rank test). For 22 of 149 cases with incidental HCC, 10-year patient survival was higher than 127 primary HCC cases (85% [95% confidence interval (CI), 70.6%-100%] versus 48.3% [95% CI, 38%-61%]; P = 0.168, NS) and similar to 3392 biliary atresia cases (89.9%; 95% CI, 88.7%-91%). Actuarial 10-year patient survival for 17 EMBs, 10 METS, and 6 leiomyosarcoma patients exceeded 60%. These survival outcomes were similar to those seen for HBL. At CHP, posttransplant recurrence-free and overall survival among 25 HCC, 17 (68%) of whom had preexisting liver disease, was 16/25 or 64%, and 9/25 or 36%, respectively. All 10 patients with incidental HCC and tumor-node-metastasis stage I and II HCC survived recurrence-free. Only vascular invasion predicted poor survival in multivariate analysis (P < 0.0001). A total of 4 of 5 EMB patients (80%) and all patients with METS (neuroendocrine-2, pseudopapillary pancreatic-1) also survived recurrence-free. Among children, LT can be curative for unresectable HCC confined to the liver and without vascular invasion, incidental HCC, embryonal tumors, and metastatic neuroendocrine tumors. Liver Transplantation 23 1577-1588 2017 AASLD.

PMID: 28834194 [PubMed - indexed for MEDLINE]

6 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 2018/07/10

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Insights into the Pharmaceuticals and Mechanisms of Neurological Orphan Diseases: Current Status and Future Expectations.

Prog Neurobiol. 2018 Jul 04;:

Authors: Ramalho TC, de Castro AA, Tavares TS, Silva MC, Silva DR, Cesar PH, Santos LA, da Cunha EFF, Nepovimova E, Kuca K

Abstract
Several rare or orphan diseases have been characterized that singly affect low numbers of people, but cumulatively reach ∼6% - 10% of the population in Europe and in the United States. Human genetics has shown to be broadly effective when evaluating subjacent genetic defects such as orphan genetic diseases, but on the other hand, a modest progress has been achieved toward comprehending the molecular pathologies and designing new therapies. Chemical genetics, placed at the interface of chemistry and genetics, could be employed to understand the molecular mechanisms of subjacent illnesses and for the discovery of new remediation processes. This review debates current progress in chemical genetics, and how a variety of compounds and reaction mechanisms can be used to study and ultimately treat rare genetic diseases. We focus here on a study involving Amyotrophic lateral sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Spinal muscular atrophy (SMA) and Familial Amyloid Polyneuropathy (FAP), approaching different treatment methods and the reaction mechanisms of several compounds, trying to elucidate new routes capable of assisting in the treatment profile.

PMID: 29981392 [PubMed - as supplied by publisher]

Outcome of inflammatory breast cancer in Moroccan patients: clinical, molecular and pathological characteristics of 219 cases from the National Oncology Institute (INO).

BMC Cancer. 2018 Jul 05;18(1):713

Authors: Slaoui M, Zoure AA, Mouh FZ, Bensouda Y, El Mzibri M, Bakri Y, Amrani M

Abstract
BACKGROUND: Usually misdiagnosed, Inflammatory Breast Cancer (IBC) is the most aggressive form of non-metastatic breast cancer. This orphan disease is more frequent in North Africa. Despite intensive treatment, the survival rate remains very low.
METHODS: We have retrospectively studied all breast cancer cases diagnosed at the National Oncology Institute (INO), Rabat between 2005 and 2010. We have collected 219 cases of women with metastatic and non-metastatic IBC. Data have been obtained from patients' personal medical files over a follow-up period of 5 years. We have described IBC's clinicopathological features and analyzed its clinical outcome using SPSS software. HR (hazard Ratio) was calculated using Cox regression analysis.
RESULTS: The frequency of IBC cases is 4.05%. The majority of our patients (65.3%) were under 50 years old. The most prevalent molecular subtype was Luminal A (38.7%) followed by Luminal B HER2+ (27.9%) and Triple negative (21.6%). During the follow-up period, 72 patients (32.9%) had recurrence and 40 patients (18.3%) died. The 3-year OS (Overall Survival) and EFS (Event Free Survival) of non-metastatic patients were 70.4 and 46.5% respectively, while in the metastatic disease, the 3-year OS was only 41.9%. In non-metastatic women, we observed a higher rate of EFS associated to Selective estrogen receptor modulation treatment (p = 0.01), and a lower rate EFS in triple negative breast cancer patients (p = 0.02). In univariate analysis, we found that EFS rate is lower in patients presenting Triple Negative tumors when compared to other molecular subtypes (HR: 3.54; 95%CI: 1.13-11.05; p = 0.02). We also found that Selective estrogen receptor modulation treatment is associated with higher EFS rate (HR: 0.48; 95%CI: 0.07-0.59; p = 0.01).
CONCLUSIONS: IBC in Morocco shows similar characteristics to those in North African countries; however, survival rates are still the highest when compared with neighboring countries. Collaborative studies with prospective aspects are warranted to establish the epidemiological profile and understand the high frequencies of IBC in North Africa. More studies on molecular markers are also needed to improve IBC patients' management and eventually their survival rate.

PMID: 29976157 [PubMed - in process]

Sequence variants in nine different genes underlying rare skin disorders in 10 consanguineous families.

Int J Dermatol. 2017 Dec;56(12):1406-1413

Authors: Shah K, Mehmood S, Jan A, Abbe I, Hussain Ali R, Khan A, Chishti MS, Lee K, Ahmad F, Ansar M, University of Washington Center for Mendelian Genomics, Shahzad S, Nickerson DA, Bamshad MJ, Coucke PJ, Santos-Cortez RLP, Spritz RA, Leal SM, Ahmad W

Abstract
BACKGROUND: Genodermatoses represent genetic anomalies of skin tissues including hair follicles, sebaceous glands, eccrine glands, nails, and teeth. Ten consanguineous families segregating various genodermatosis phenotypes were investigated in the present study.
METHODS: Homozygosity mapping, exome, and Sanger sequencing were employed to search for the disease-causing variants in the 10 families.
RESULTS: Exome sequencing identified seven homozygous sequence variants in different families, including: c.27delT in FERMT1; c.836delA in ABHD5; c.2453C>T in ERCC5; c.5314C>T in COL7A1; c.1630C>T in ALOXE3; c.502C>T in PPOX; and c.10G>T in ALDH3A2. Sanger sequencing revealed three homozygous variants: c.1718 + 2A>G in FERMT1; c.10459A>T in FLG; and c.92delT in the KRT14 genes as the underlying genetic cause of skin phenotypes.
CONCLUSION: This study supports the use of exome sequencing as a powerful, efficient tool for identifying genes that underlie rare monogenic skin disorders.

PMID: 29130490 [PubMed - indexed for MEDLINE]

Understanding the phenotypic similarities between IFAP and Olmsted syndrome from a molecular perspective: the interaction of MBTPS2 and TRPV3.

Arch Dermatol Res. 2017 Oct;309(8):637-643

Authors: Nemer G, Safi R, Kreidieh F, Usta J, Bergqvist C, Ballout F, Btadini W, Hamzeh N, Abbas O, Kibbi AG, Shimomura Y, Kurban M

Abstract
Ichthyosis Follicularis, Atrichia, and Photophobia (IFAP) is a severe rare genetic disorder caused by mutations in the gene encoding the Membrane-Bound Transcription Factor Peptidase, Site 2 (MBTPS2). Olmsted syndrome is another rare genetic disease with overlapping clinical features caused by mutations in the gene encoding the Transient Receptor Potential Cation Channel, subfamily V (TRPV3). Mutations in MBTPS2 have been recently reported in Olmsted syndrome, underscoring the overlap and the confusion in separating Olmsted from IFAP syndrome. We studied a Lebanese family with IFAP syndrome both, clinically and molecularly, and investigated whether there is a cross relation between TRPV3 and MBTPS2. We identified a recurrent mutation designated p.F475S in MBTPS2 in the affected individuals. This mutation was not found in 100 control individuals from the same population. We determined that TRPV3 regulatory region is a target for MBTPS2. In addition, there was an increased cell death in the cells transfected with the mutant versus the wild-type MBTPS2. In conclusion, we identified a direct regulatory effect of MBTPS2 on TRPV3 which can partially contribute to the overlapping clinical features of IFAP and Olmsted syndromes under a common signaling pathway.

PMID: 28717930 [PubMed - indexed for MEDLINE]

Mohs micrographic surgery of rare cutaneous tumours.

J Eur Acad Dermatol Venereol. 2017 Aug;31(8):1285-1288

Authors: Flohil SC, van Lee CB, Beisenherz J, Mureau MAM, Overbeek LIH, Nijsten T, van den Bos RR

Abstract
BACKGROUND: Recurrence rates after Mohs micrographic surgery (MMS) for rare cutaneous tumours are poorly defined.
OBJECTIVE: To investigate the recurrence rate after MMS for rare cutaneous tumours at a university centre.
METHODS & MATERIALS: Retrospective review of all rare cutaneous tumours treated with MMS at a large university centre between January 2008 and December 2012. To detect all recurrences, patients were linked to The Nationwide Network and registry of histo- and cytopathology (PALGA).
RESULTS: In total, 80 patients with 80 tumours were included. Tumour types included dermatofibrosarcoma protuberans (27), atypical fibroxanthoma (22), Merkel cell carcinoma (8), microcystic adnexal carcinoma (9), sebaceous carcinoma (6), extramammary Paget's disease (2) and other (6). Mean follow-up time was 3.7 years (standard deviation 1.4) during which two atypical fibroxanthomas recurred (2.5%).
CONCLUSION: This large case series shows that MMS is an appropriate treatment for rare cutaneous tumours with a recurrence rate less than 3%. Preferably, MMS for rare cutaneous tumours is performed in experienced multidisciplinary centres to further improve the quality of treatment.

PMID: 27976423 [PubMed - indexed for MEDLINE]

Effect of Anti-Leishmania Drugs on the Structural and Elastic Properties of Ultra-Deformable Lipid Membranes.

J Phys Chem B. 2018 Jul 04;:

Authors: Peralta MF, Smith H, Moody D, Tristram-Nagle S, Carrer DC

Abstract
Drugs for treating Leishmaniasis, a parasitic Tropical Orphan Disease, currently have several limitations on their use which topical treatments could alleviate. Topical treatment requires penetration of the drugs to deep skin, which is aided by encapsulation within ultra-deformable liposomes. Penetrability depends on the flexibility of the lipid membrane, which may be affected by the drugs. We have studied the biophysical effects of four anti-Leishmania drugs (Miltefosine (Milt), Amphotericin B (AmpB), Indole (Ind) and Imiquimod (Imiq)) on a soy phosphatidylcholine/sodium cholate membrane. Using diffuse X-ray scattering techniques, we determined bending modulus (KC) and chain order parameter (Sxray) of the membrane at several drug concentrations. Form factor scattering data allowed construction of Electron Density Profiles, which yielded bilayer thickness and area per lipid. Results show that AmpB had the largest effect on KC and Sxray, causing the bilayer to lose integrity at high concentrations. Imiq and Ind induced slight membrane stiffening, while Milt had little effect. Imiq also noticeably decreased chain order at high concentrations. These results will aid in design of new topical treatments, where Milt, Ind and Imiq could be used at any concentration without affecting liposome integrity or physical properties, while AmpB should not be used at high concentrations.

PMID: 29972641 [PubMed - as supplied by publisher]

Metformin inhibits Branched Chain Amino Acid (BCAA) derived ketoacidosis and promotes metabolic homeostasis in MSUD.

Sci Rep. 2016 07 04;6:28775

Authors: S Sonnet D, N O'Leary M, A Gutierrez M, M Nguyen S, Mateen S, Hsu Y, P Mitchell K, J Lopez A, Vockley J, K Kennedy B, Ramanathan A

Abstract
Maple Syrup Urine Disease (MSUD) is an inherited disorder caused by the dysfunction in the branched chain keto-acid dehydrogenase (BCKDH) enzyme. This leads to buildup of branched-chain keto-acids (BCKA) and branched-chain amino acids (BCAA) in body fluids (e.g. keto-isocaproic acid from the BCAA leucine), leading to numerous clinical features including a less understood skeletal muscle dysfunction in patients. KIC is an inhibitor of mitochondrial function at disease relevant concentrations. A murine model of intermediate MSUD (iMSUD) shows significant skeletal muscle dysfunction as by judged decreased muscle fiber diameter. MSUD is an orphan disease with a need for novel drug interventions. Here using a 96-well plate (liquid chromatography- mass spectrometry (LC-MS) based drug-screening platform we show that Metformin, a widely used anti-diabetic drug, reduces levels of KIC in patient-derived fibroblasts by 20-50%. This Metformin-mediated effect was conserved in vivo; Metformin-treatment significantly reduced levels of KIC in the muscle (by 69%) and serum (by 56%) isolated from iMSUD mice, and restored levels of mitochondrial metabolites (e.g. AMP and other TCA). The drug also decreased the expression of mitochondrial branched chain amino transferase (BCAT) which produces KIC in skeletal muscle. This suggests that Metformin can restore skeletal muscle homeostasis in MSUD by decreasing mitochondrial KIC production.

PMID: 27373929 [PubMed - indexed for MEDLINE]

Cryptococcus neoformans osteomyelitis and intramuscular abscess in a liver transplant patient.

BMJ Case Rep. 2017 Oct 11;2017:

Authors: Poenaru SM, Rofaiel R, Hosseini-Moghaddam SM

Abstract
Cryptococcus neoformans is an important pathogen that can cause severe illness and mortality in immunocompromised patients. We highlight here the case of a 53-year-old man presenting to hospital 4 years postliver transplant with fever, acute renal failure and a medial thigh lesion. Initially treated as bacterial sepsis, the patient failed to improve on broad-spectrum antibiotics. Further investigations revealed disseminated cryptococcemia complicated by patellar osteomyelitis and an intramuscular abscess. Unfortunately, although the patient initially showed signs of clinical improvement after starting standard antifungal agents, he deteriorated and died secondary to acute renal failure. Osteomyelitis is a rare manifestation of cryptococcal infection for which there is often a significant delay to diagnosis and treatment. This is the fourth reported case of cryptococcal osteomyelitis in a liver transplant patient and underlines the importance of considering fungal infections in the differential diagnosis of osseous lesions in solid organ transplant and other immunocompromised patients.

PMID: 29025780 [PubMed - indexed for MEDLINE]