Accuracy of preoperative routine MRI for hepatic lesion detection

BACKGROUND: The outcome of liver resections depends on complete removal of all detectable foci. Our aim was to determine the value of preoperative routine magnetic resonance imaging (MRI) for complete detection of hepatic lesions. METHODS: We compared 271 lesions seen on MRI in 182 patients to intraoperative findings (including intraoperative ultrasonography) and histology. RESULTS: The overall rate of lesions was 7% each for segments 2 and 3, as compared to 14-17% each for segments 5, 6, 7, and 8. Twenty-three additional lesions were found intraoperatively, two thirds of them in the left lobe (mean size: 1.4 cm; mean total number of lesions in those patients: 2.2). In segments 2 and 3, the relative frequency for intraoperative diagnosis of additional lesions was 17% and 20%, respectively. On the other hand, most of the 15 MRI lesions not verified intra- or postoperatively had been described in the right hepatic lobe (maximum: segment 6). CONCLUSION: MRI provided reliable preoperative lesion detection. Special attention should be paid to segments 2 and 3, which showed a lower total number of lesions but an elevated relative frequency of intraoperatively detected additional foci.     

A phase I, first-in-human dose-escalation study of amuvatinib, a multi-targeted tyrosine kinase inhibitor, in patients with advanced solid tumors

Purpose

Amuvatinib is a novel orally administered tyrosine kinase inhibitor with in vitro pharmacological activity against mutant KIT, platelet-derived growth factor receptor alpha (PDGFRα), and Rad51. Amuvatinib was investigated in a first-in-human, single-agent, phase I, accelerated titration, dose-escalation trial (clinicaltrials.gov identifier: NCT00894894) in patients with solid tumors refractory to prior therapies or for which no standard therapy existed.

Methods

Twenty-two patients received amuvatinib dry powder capsules (DPC) from 100 to 1,500 mg daily in 28-day cycles. Safety, preliminary efficacy, pharmacologic activity, and pharmacokinetics were investigated.

Results

No dose-limiting toxicities were reported with amuvatinib DPC up to 1,500 mg/day, given as one or in divided doses, for 1–6 cycles. No maximum tolerated dose was reached. Five patients had serious adverse events, all unrelated to treatment. Exposure levels were low and variable. One gastrointestinal stromal tumor (GIST) patient who previously failed imatinib and sunitinib had a 2–[18F]fluoro-2-deoxyglucose positron emission tomography response and clinical stable disease. A second GIST patient had decreased Rad51 expression in a skin punch biopsy on days 15 and 29.

Conclusions

Amuvatinib shows in vitro inhibitory activity against multiple human tyrosine kinases including mutant KIT and PDGFRα and in vivo activity in human xenograft models in mice. Amuvatinib is also active as a DNA repair protein Rad51 inhibitor following chemotherapy. In this study, the amuvatinib DPC formulation was well tolerated up to 1,500 mg/day. While exposures were low and variable, a transient response in a refractory GIST patient warrants further investigation into single-agent amuvatinib in refractory GIST.     

Study of Predictive Value of Pediatric Risk of Mortality (PRISM) Score in Children with End Stage Liver Disease and Fulminant Hepatic Failure

Objective  

To evaluate the use of the PRISM score as a predictor of outcome in patients with end stage liver disease (ESLD) and fulminant hepatic failure (FHF).     

Pupillary block after phakic anterior chamber intraocular lens implantation

A 49-year-old patient developed pupillary block glaucoma with an intraocular pressure (IOP) of 29 mm hg after implantation of a phakic intraocular lens (IOL) (NuVita, Bausch & Lomb) in the left eye. the anterior chamber deepened again, and the iop decreased to 16 mm hg after a neodymium: YAG iridotomy. Pupillary block glaucoma may occur after phakic IOL implantation without iridotomy, and we advocate that routine iridotomy be performed during phakic IOL surgeries.     

Common polymorphisms in the interleukin-22 gene are not associated with chronic plaque psoriasis

Background:  Psoriasis is a chronic inflammatory skin disease. Among other cytokines, interleukin 22 (IL-22) has been implicated in the pathogenesis of chronic plaque psoriasis. The purpose of this study was to investigate a hypothesized association between common IL-22 gene polymorphisms and chronic plaque psoriasis.
Methods:  Genotypes of 10 common polymorphisms of the IL-22 gene were determined by fluorogenic 5' exonuclease assays (TaqMan) in 475 patients with chronic plaque psoriasis and 252 controls.
Results:  Two blocks of high linkage disequilibrium, formed by eight polymorphisms upstream of exon 5 (rs2227485, rs2227491, rs2046068, rs1179251, rs1012356, rs2227501, rs2227503, rs976748) and two polymorphisms in the 3' near gene region (rs1182844, rs1179246), were observed within the IL-22 gene. Neither single polymorphisms nor haplotypes were significantly associated with the presence or clinical features of chronic plaque psoriasis ( P  > 0.05).
Conclusions:  Our data suggest that the investigated IL-22 gene polymorphisms are unlikely major risk factors for chronic plaque psoriasis.     

100 Jahre erfolgreiche Hornhauttransplantation

Zusammenfassung  Die Hornhaut war vor nun mehr als 100 Jahren das erste erfolgreich transplantierte Gewebe. W?hrend das Verst?ndnis für ein erfolgreiches Hornhauttransplantat vor 100 Jahren noch fehlte, haben sich sowohl die Operationstechniken, als auch die konservative Therapie in den letzten Jahrzehnten zum Teil grundlegend ge?ndert. Die Hornhaut ist nun weltweit nicht nur das am h?ufigsten transplantierte Gewebe, sondern auch das mit der besten Prognose. Die Erfolgsgeschichte der Keratoplastik begann mit dem Verst?ndnis des immunologischen Aspektes und der Einführung lokaler und systemischer Immunsuppressiva. Heutzutage stehen uns zahlreiche dieser Wirkstoffe zur Verfügung, um ein gutes Transplantationsergebnis auch bei Patienten mit hohem Absto?ungsrisiko zu erreichen. Auch die Renaissance der lamell?ren Keratoplastik hat die Ergebnisse der Hornhauttransplantation deutlich verbessert. In dieser übersichtsarbeit beschreiben wir sowohl die Geschichte der Keratoplastik als auch die neuen lokalen, systemischen und chirurgischen Optionen um die Erfolge von Hornhauttransplantaten zu verbessern.      

Burden of pediatric hepatitis C

Hepatitis C virus(HCV)is a major health burden infecting 170-210 million people worldwide.Additional 3-4millions are newly-infected annually.Prevalence of pediatric infection varies from 0.05%-0.36%in the United States and Europe;up to 1.8%-5.8%in some developing countries.The highest prevalence occurs in Egypt,sub-Saharan Africa,Amazon basin and Mongolia.HCV has been present in some populations for several centuries,notably genotypes 1 and 2 in West Africa.Parenteral anti-schistosomal therapy practiced in the 1960s until the early 1980s had spread HCV infection throughout Egypt.Parenteral acquisition of HCV remains a major route for infection among Egyptian children.Insufficient screening of transfusions,unsterilized injection equipment and re-used needles and syringes continue to be major routes of HCV transmission in developing countries,whereas vertical transmission and adolescent high-risk behaviors(e.g.,injection drug abuse)are the major routes in developed countries.The risk of vertical transmission from an infected mother to her unborn/newborn infant is approximately 5%.Early stages of HCV infection in children do not lead to marked impairment in the quality of life nor to cognitive,behavioral or emotional dysfunction;however,caregiver stress and family system strain may occur.HCV slowly progresses to serious complications as cirrhosis(1%-2%)and hepatocellular carcinoma(HCC)especially in the presence of risk factors as hemolytic anemias,obesity,treated malignancy,and concomitant human immune deficiency and/or hepatitis B virus co-infection.HCV vaccine remains elusive to date.Understanding the immune mechanisms in patients who successfully cleared the infection is essential for vaccine development.The pediatric standard of care treatment consists of pegylated interferon-α2a or b plus ribavirin for 24-48 wk.The new oral direct acting antivirals,approved for adults,need further evaluation in children.Sustained virologic response varies depending on the viral load,genotype,duration of infection,degree of am     

Novel CERKL variant in consanguineous Jordanian pedigrees with inherited retinal dystrophies

Objective

To identify the disease-causing variants in 2 families with autosomal recessive inherited retinal dystrophies (IRDs) and to characterize phenotypic variability across the affected family members.

Chemotherapeutic intensification in germ cell tumors

Chemotherapy has dramatically improved the prognosis of non-seminomatous germ cell tumors (NSGCT). However, some patients relapse and others are refractory to first line chemotherapy. We studied a salvage chemotherapeutic regimen with etoposide 75 gm/m2/day, and cisplatin 40 mg/m2/day, days 1-5 and Ifosfamide 3 g/m2/day, days 1 and 2 (VIhP regimen) in 32 patients. We observed 8 complete remissions with 4 long-term NED patients. Hematological, neurological and renal complications were frequent. In 16 other cases, a protocol using high dose chemotherapy, followed by autologous bone marrow rescue was studied. We observed 8 complete remissions with 4 long-term NED patients. These observations support a dose/effect relationship. A French randomized trial testing high dose chemotherapy, followed in some cases by an autologous marrow graft in poor risk advanced NSGCT, has recently been activated.