Itraconazole as 'bridge therapy' to anti-IgE in a patient with severe asthma with fungal sensitisation.

Sensitisation to fungi has been reported to play an important role in a particular phenotype of severe asthma, the so-called severe asthma with fungal sensitisation, characterised by high levels of total IgE, which may be an obstacle to anti-IgE therapy. We describe here the case of a polysensitised woman with refractory asthma, sensitised to Aspergillus fumigatus with high total IgE values (1793 kUA/l), but without the diagnostic criteria for allergic bronchopulmonary aspergillosis. Additional therapy with itraconazole leads to the decrease of total IgE to the limits recommended for proper omalizumab dosing (30–1500 kUA/l). Itraconazole, used as bridge therapy, provided us the opportunity to start anti-IgE treatment in a patient with high levels of total IgE, beyond the upper limits recommended for proper prescription of omalizumab

Xanthogranulomatous pyelonephritis: presentation and management

Xanthogranulomatous pyelonephritis (XGP) is characterized by the presence of lipid-laden foamy macrophages with both acute and chronic phase inflammatory cells. The aim of the study is to present our experience about patients with Xanthogranulomatous pyelonephritis. 29 patients were evaluated through a complete anamnesis and the preoperative management included routine blood and biochemical tests, urine culture and renal ultrasound, intravenous urography and computed tomography (CT). All patients underwent open nephrectomy followed by the pathological exam. The main symptoms of these patients were fever and flank pain. Preoperative laboratory tests revealed anemia, leukocytosis and increasing levels of blood urea nitrogen (BUN) and creatinine. Kidney failure was noticed in almost half of the cases. This study succeeded to evaluate the demographic, clinical, biological, surgical and histological characteristics. A pathological diagnosis is mandatory mainly for the evaluation of its coexistence with renal carcinoma

Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks

Background For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). Objective To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). Methods Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). Results A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. Conclusions In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms

Nucleus-specific abnormalities of GABAergic synaptic transmission in a genetic model of absence seizures

Human and experimental studies indicate that molecular genetic changes in GABAA receptors may underlie the expression of spike-and-waves discharges (SWDs) occurring during absence seizures. However, the full spectrum of the genetic defects underlying these seizures has only been partially elucidated, the expression and functional profiles of putative abnormal protein(s) within the thalamocortical network are undefined, and the pathophysiological mechanism(s) by which these proteins would lead to absence paroxysms are poorly understood. Here we investigated GABAA inhibitory postsynaptic currents (IPSCs) in key thalamocortical areas, i.e., the somatosensory cortex, ventrobasal thalamus (VB) and nucleus reticularis thalami (NRT), in preseizure genetic absence epilepsy rats from Strasbourg (GAERS), a well-established genetic model of typical absence seizures that shows no additional neurological abnormalities, and compared their properties to age-matched non-epileptic controls (NECs). Miniature GABAA IPSCs of VB and cortical layers II/III neurons were similar in GAERS and NEC, whereas in GAERS NRT neurons they had 25% larger amplitude, 40% faster decay. In addition, baclofen was significantly less effective in decreasing the frequency of NRT mIPSCs in GAERS than in NEC, whereas no difference was observed for cortical and VB mIPSCS between the two strains. Paired-pulse depression was 45% smaller in GAERS NRT, but not in VB, and was insensitive to GABAB antagonists. These results point to subtle, nucleus-specific, GABAA receptor abnormalities underlying SWDs of typical absence seizures rather than a full block of these receptors across the whole thalamocortical network, and their occurrence prior to seizure onset suggests that they might be of epileptogenic significance