Dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600E mutation-positive hairy cell leukemia.

BRAF V600E is the key oncogenic driver mutation in hairy cell leukemia (HCL). We report the efficacy and safety of dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600E mutation-positive HCL. This open-label, phase 2 study enrolled patients with BRAF V600E mutation-positive HCL refractory to first-line treatment with a purine analog or relapsed after ≥2 prior lines of treatment.

Dabrafenib plus trametinib in patients with BRAF-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial.

Background: Effective treatments are needed to improve outcomes for high-grade glioma and low-grade glioma. The activity and safety of dabrafenib plus trametinib were evaluated in adult patients with recurrent or progressive BRAF mutation-positive high-grade glioma and low-grade glioma.

Methods: This study is part of an ongoing open-label, single-arm, phase 2 Rare Oncology Agnostic Research (ROAR) basket trial at 27 community and academic cancer centres in 13 countries (Austria, Belgium, Canada, France, Germany, Italy, Japan, the Netherlands, Norway, South Korea, Spain, Sweden, and the USA).

Decreased plasma l-arginine levels in organic acidurias (MMA and PA) and decreased plasma branched-chain amino acid levels in urea cycle disorders as a potential cause of growth retardation: Options for treatment.

Background And Aim: Patients with methylmalonic acidemia (MMA) and propionic acidemia (PA) and urea cycle disorders (UCD), treated with a protein restricted diet, are prone to growth failure. To obtain optimal growth and thereby efficacious protein incorporation, a diet containing the essential and functional amino acids for growth is necessary. Optimal growth will result in improved protein tolerance and possibly a decrease in the number of decompensations.

Thyroglossal duct cysts in children: a 30-year survey with emphasis on clinical presentation, surgical treatment, and outcome.

Thyroglossal duct cysts (TGDC) are one of the most common congenital anomalies found in the anterior neck region of children. Sistrunk's procedure, described in 1920 already, is still considered as the gold standard. However, clinical reality shows that in a minority of patients, marsupialization and simple cyst excision are still performed as well.

Adaptive behavior impaired in children with low-grade glioma.

Background: Adaptive behavior, i.e., the performance on daily activities required for personal and social independence, is essential to estimate in children with low-grade glioma (LGG) since most of them are long-term survivors.

Phenotype-genotype correlations in Leigh syndrome: new insights from a multicentre study of 96 patients.

Background: Leigh syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder. While some genetic defects are associated with well-described phenotypes, phenotype-genotype correlations in Leigh syndrome are not fully explored.

Objective: We aimed to identify phenotype-genotype correlations in Leigh syndrome in a large cohort of systematically evaluated patients.

A randomized placebo-controlled phase II study of a Pseudomonas vaccine in ventilated ICU patients.

Background: Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases.

Retinal nerve fiber layer thickening in ARSACS carriers.

Purpose: Two Caucasian Belgian families were diagnosed with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The ophthalmological findings in both ARSACS disease and carriers are described.

Methods: In addition to a complete ophthalmological assessment, in both patients and carriers, spectral-domain Optical Coherence Tomography scans of the peri-papillary retinal nerve fiber layer were performed.

Tooth autotransplantation in the anterior maxilla and mandible: retrospective results in young patients.

Objective: This retrospective study evaluated survival rates, prognosis, and overall success of autotransplanted teeth in young patients missing anterior teeth as a result of trauma, agenesis, or developmental disturbances.

Study Design: Retrospective data were collected from the medical records of patients who had undergone tooth autotransplantations to anterior sites between January 2001 and December 2012. Clinical variables, such as gender, age, surgical indications, donor and recipient sites, type of anesthetics, bone augmentation, and complications during follow-up, were assessed.

Removal Rates of Dental Implants Placed in Conjunction With Autologous Bone and Xenogeneic and Synthetic Alloplastic Materials in Finland Between 1994 and 2012.

Purpose: This study aimed to assess the use of bone augmentation materials in Finland from 1994 to 2012 by assessing removal rates of implants placed in combination with autologous bone, xenogeneic grafts, and synthetic alloplastic materials.

Materials And Methods: The National Institute for Health and Welfare in Finland granted permission to access raw data of the Finnish Dental Implant Register for implant augmentation materials and removal rates of implants placed in augmented sites from April 1994 to April 2012.

Results: A total of 198,538 implants were placed in Finland between 1994 and 2012 in 110,543 operations.

The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2: the evolving clinical phenotype.

Background: The disease course and long-term outcome of patients with organic acidurias (OAD) and urea cycle disorders (UCD) are incompletely understood.

Aims: To evaluate the complex clinical phenotype of OAD and UCD patients at different ages.

Results: Acquired microcephaly and movement disorders were common in OAD and UCD highlighting that the brain is the major organ involved in these diseases.

The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation.

Background: The clinical presentation of patients with organic acidurias (OAD) and urea cycle disorders (UCD) is variable; symptoms are often non-specific.

Aims/methods: To improve the knowledge about OAD and UCD the E-IMD consortium established a web-based patient registry.

Results: We registered 795 patients with OAD (n = 452) and UCD (n = 343), with ornithine transcarbamylase (OTC) deficiency (n = 196), glutaric aciduria type 1 (GA1; n = 150) and methylmalonic aciduria (MMA; n = 149) being the most frequent diseases.

Adult polyglucosan body disease masquerading as "ALS with dementia of the Alzheimer type": an exceptional phenotype in a rare pathology.

We describe an exceptional clinical picture, namely, cognitive impairment of the Alzheimer disease type in a man who later developed manifestations typical of amyotrophic lateral sclerosis and who was subsequently found to have adult polyglucosan body disease (APGBD) upon postmortem neuropathologic explorations. The combined occurrence of amyotrophic lateral sclerosis and cognitive impairment of the Alzheimer disease type in APGBD has not been reported before. This case also underlines the diverse clinical presentation of this rare clinicopathologic entity (namely APGBD) and highlights the importance of recognizing the unusual association of clinical features in making the diagnosis.

Haemorrhoids, rectal prolapse, anal fissure, peri-anal fistulae and sexually transmitted diseases.

Anorectal disorders like haemorrhoids, rectal prolapse, anal fissures, peri-anal fistulae and sexually transmitted diseases are bothersome benign conditions that warrant special attention. They, however, can all be diagnosed by inspection or proctoscopy (sexually transmitted proctitis). Constipation can play an underlying role in haemorrhoids, rectal prolapse and anal fissures, and it is important to treat these conditions in order to avoid recurrences.

The association of hemodilution and transfusion of red blood cells with biochemical markers of splanchnic and renal injury during cardiopulmonary bypass.

Background: Hemodilution is the main cause of a low hematocrit concentration during cardiopulmonary bypass. This low hematocrit may be insufficient for optimal tissue oxygen delivery and often results in packed cell transfusion. Our objective in this study was to find a relationship between intraoperative hematocrit and allogeneic blood transfusion on release of postoperative injury markers from the kidneys and the splanchnic area.

Rectal prolapse, rectal intussusception, rectocele, solitary rectal ulcer syndrome, and enterocele.

Rectal prolapse is best diagnosed by physical examination and by having the patient strain as if to defecate; a laparoscopic rectopexy is the preferred treatment approach. Intussusception is more an epiphenomena than a defecatory disorder and should be managed conservatively. Solitary rectal ulcer syndrome is a consequence of chronic straining and therapy should be aimed at restoring a normal bowel habit with behavioral approaches including biofeedback therapy.

Photodynamic therapy in advanced tracheobronchial cancers.

Photodynamic therapy (PDT) has been introduced in the early eighties for treating patients with malignancies in the tracheobronchial tract. After intravenous injection of the photosensitizers, the tumor area in the tracheobronchial tree is illuminated bronchoscopically using a laser fiber to transmit light of a specific wavelength during the procedure. Secondary tissue necrosis ensues, because of the thrombosis of the tumor vasculature leading to late tissue hypoxia.

Results of two years expenience with fluorescence bronchoscopy in detection of preinvasive bronchial neoplasia.

The aim of the study was to determine whether use of fluorescence bronchoscopy improves the detection of preinvasive neoplastic bronchial lesions. The data of all patients who underwent fluorescence bronchoscopy and in whom bronchial biopsies were taken, were analyzed. Most patients were at risk for preinvasive lesions.

A new system for right atrial cooling.

Purpose: Controlled hypothermia of the right atrium has been shown to reduce postoperative atrial fibrillation after on-pump coronary artery bypass grafting. A device has been developed that couples right atrial and nodal cooling with modified dual-stage venous drainage by circulating cold sterile saline through an intracavity, shape-memory balloon.

Description: The atrial cooling device was used in 41 patients undergoing elective coronary artery bypass grafting.

The role of impaired transport in (pre)clinical resistance to methotrexate: insights on new antifolates.

Impaired transport appears to be a common mechanism of resistance of neoplastic cells to the antifolate methotrexate. The extensive knowledge of the molecular, biochemical and functional properties of the membrane transport systems for folates, in particular the reduced folate carrier (RFC) and membrane folate receptors (MFR), has made an important contribution to the rational design of novel antifolates that are either more efficiently internalized via these transporters or can simply bypass these transport routes. The current status of exploiting the RFC and MFR for transport of novel antifolates active in preclinical model systems and a clinical setting will be reviewed, with a special reference to childhood acute lymphoblastic leukemia (ALL) and acute non-lymphoblastic leukemia (ANLL).