Direct‐acting antivirals are effective and safe in HCV/HIV‐coinfected liver transplant recipients who experience recurrence of hepatitis C: A prospective nationwide cohort study

Direct‐acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV‐coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV‐coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV‐monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV‐coinfected patients had a median (IQR) CD4 T‐cell count of 366 (256‐467) cells/µL. HIV‐RNA was <50 copies/mL in 96% of patients. The DAA regimens administered were SOF + LDV ± RBV (34%), SOF + SMV ± RBV (31%), SOF + DCV ± RBV (27%), SMV + DCV ± RBV (5%), and 3D (3%), with no differences between the groups. Treatment was well tolerated in both groups. Rates of SVR (negative serum HCV‐RNA at 12 weeks after the end of treatment) were high and similar for coinfected and monoinfected patients (95% and 94%, respectively; P = .239). Albeit not significant, a trend toward lower SVR rates among patients with advanced fibrosis (P = .093) and genotype 4 (P = .088) was observed. In conclusion, interferon‐free regimens with DAAs for post‐LT recurrence of HCV infection in HIV‐infected individuals were highly effective and well tolerated, with results comparable to those of HCV‐monoinfected patients.     

Prevalence of selected organ-specific autoantibodies in rheumatoid arthritis and primary Sj?gren's syndrome patients

Objectives

The aim of the study was to investigate the prevalence of selected organ-specific autoantibodies in rheumatoid arthritis (RA) and primary Sjögren''s syndrome (pSS) patients, and discuss their clinical significance.

Material and methods

The study included 121 RA and 30 pSS patients. Sera were tested for the presence of autoantibodies to thyroid peroxidase (anti-TPO), thyroglobulin (anti-TG), TSH receptor (TRAbs), mitochondrial antigen M2 (AMA-M2-3E) and gliadin-analogous fusion peptides (anti-GAF(3X)) using the ELISA method. Non-organ-specific antibodies were determined: rheumatoid factor in IgM class, anti-citrullinated peptide antibodies and antinuclear antibodies. The occurrence of antibodies was also examined with regards to RA activity.

Results

The following autoantibodies were detected in RA patients: anti-TPO – 13 (10.7%), anti-TG – 6 (5%), AMA-M2-3E – 3 (2.5%), anti-GAF(3X) – 5 (4.1%). The respective levels of these autoantibodies in pSS patients were 3 (10%), 2 (6.7%), 4 (13.3%) and 2 (6.7%). Polyautoimmunity was confirmed in 34 RA patients (including 20 cases of autoimmune thyroid disease [AITD]) and in 6 pSS patients (6 cases of AITD). When RA patients were divided into anti-TPO positive and anti-TPO negative groups, we found a statistically significant relationship between groups regarding age and hemoglobin concentration. In pSS patients the anti-TPO positive group was less likely to use immunosuppressive drugs as compared with the anti-TPO negative group. Anti-TPO was significantly more frequently detected in RA + AITD vs. RA, RA + SS + AITD vs. RA and in pSS + AITD vs. pSS patients.

Conclusions

Organ-specific autoantibodies are relatively frequently observed in patients with RA and pSS. Their presence is connected with the clinical picture of the diseases.     

The influence of amalgam fillings on the detection of approximal caries by cone beam CT: in vitro study

Objectives:

The aim of this CBCT investigation on the detection of caries was to assess the influence of artefacts produced by the presence of amalgam fillings located in the vicinity.

Methods:

102 non-cavitated pre-molar and molar teeth were placed in blocks of silicone with approximal contacts consisting of 3 sound or carious teeth and 1 mesial–occlusal–distal amalgam-filled tooth in-between. Radiographs of all the teeth were recorded using the CBCT system (NewTom™ 3G; QR Srl, Verona, Italy; field of view, 9 inches). Data from the CBCT unit were reconstructed and sectioned in the mesiodistal tooth plane. Images were evaluated twice by two observers, using a five-step confidence scale. After the CBCT examination, the teeth were individually sectioned in the mesiodistal direction with a diamond saw. Using a light microscope at ×40 magnification, the true morphological status of all approximal surfaces was established.

Results:

Sensitivity of the CBCT for the detection of caries on surfaces located proximally and distally to an amalgam filing ranged from 0.27 to 0.30 for enamel and from 0.47 to 0.56 for dentin. Specificity values for enamel proximal and distal lesions were 0.48 and 0.53, respectively, for enamel and 0.33 to 0.38, respectively, for proximal and distal dentin cases. Intra-observer reliability was 0.84, and interobserver reliability was 0.49.

Conclusions:

Owing to its low specificity, scans from a CBCT examination should not be used to determine the presence of demineralization of the tooth surface when amalgam fillings are present in the region of interest.     

Severe cardiovascular complications due to the pituitary adenoma with acromegaly. An interdisciplinary approach to the treatment. A case report

Acromegaly reduces life expectancy and leads to 3-5-fold increase in mortality. The main causes are cardiovascular, pulmonary and enhanced prevalence of deaths from malignancy. Successful therapy ought to normalize GH, IGF-I secretion, remove the adenoma mass and its local pressure effects and preserve pituitary functions intact to improve systemic morbidity and normalize mortality. The primary therapy for most patients with acromegaly is still transsphenoidal adenomectomy. The authors present a 64-year-old woman with diagnosed GH-secreting pituitary macroadenoma suffering from severe coronary heart disease and diabetes mellitus. Somatostatin analogue therapy was ineffective in our patient. She was unfit for transsphenoidal adenomectomy. The patient was qualified for coronary artery bypass grafting after cardiological investigation. We have decided to carry out the bypass grafting and transsphenoidal adenomectomy during one anaesthesia. Both surgical procedures and postoperative time were uncomplicated. Our patient feels well and she is in outpatient follow-up.     

Neuroendoscopic techniques in the treatment of arachnoid cysts in children and comparison with other operative methods

Objective: The authors intended to evaluate the application of neuroendoscopic techniques for the treatment of arachnoid cysts in children and compare it with other operative methods. Methods: The analysis covered the results of treatment of 44 children with arachnoid cysts who were subjected to neuroendoscopic procedures and 62 patients who underwent other operations. Results: The neuroendoscopic treatment of arachnoid cysts was very effective because of low rate of reoperative treatment (six out of 44 patients), no need to change the operative method (40 effective out of total 44 operative procedures), and low rate of persistent worsening (none of 44 patients worsened). Conclusions: Summing up all the mentioned aspects of neuroendoscopic techniques, the neuroendoscopic techniques were the most suitable operative procedures in the treatment of arachnoid cysts in the presented group of patients, providing that the connection between the lumen of the arachnoid cyst and the cerebrospinal fluid cisterns was of good quality.     

Single nucleotide polymorphisms and mRNA expression for melatonin MT(2) receptor in depression

Polymorphisms (rs 4753426 and rs 794837) and expression of the melatonin MT₂ receptor gene were evaluated in 181 patients with recurrent depressive disorder (rDD) and 149 healthy subjects of Polish origin. We found an increased risk for rDD in patients with the C allele and a decreased risk in patients with the T allele (rs4753426). Patients with the AT heterozygote (rs794837) had an increased mRNA level. The significance of the MT₂ receptor gene and the risk of rDD are suggested.     

A new missense <Emphasis Type="Italic">GDAP1</Emphasis> mutation disturbing targeting to the mitochondrial membrane causes a severe form of AR-CMT2C disease

Charcot–Marie–Tooth disease (CMT) caused by mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene is characterized by a spectrum of phenotypes. Recurrent nonsense mutations (Q163X and S194X) showing regional distribution segregate with an early onset, severe course of recessive CMT disease with early loss of ambulancy. Missense mutations in GDAP1 have been reported in sporadic CMT cases with variable course of disease, among them the recurrent L239F missense GDAP1 mutation occurring in the European population. Finally, some GDAP1 mutations are associated with a mild form of CMT inherited as an autosomal dominant trait. In this study, we characterize the CMT phenotype in one Polish family with recessive trait of inheritance at the clinical, electrophysiological, morphological, cellular, and genetic level associated with a new Gly327Asp mutation in the GDAP1 gene. In spite of the nature of Gly327Asp mutation (missense), the CMT phenotype associated with this variant may be characterized as an early onset, severe axonal neuropathy, with severe skeletal deformities. The mutation lies within the transmembrane domain of GDAP1 and interferes with the mitochondrial targeting of the protein, similar to the loss of the domain in the previously reported Q163X and S194X mutations. We conclude that the loss of mitochondrial targeting is associated with a severe course of disease. Our study shows that clinical outcome of CMT disease caused by mutations in the GDAP1 gene cannot be predicted solely on the basis of genetic results (missense/nonsense mutations).     

Diverse behavioral, monoaminergic and Fos protein responses to opioids in Warsaw high-alcohol preferring and Warsaw low-alcohol preferring rats

Predisposition to addictions is presumably related to a dysfunction of the brain reward system, which can be ‘compensated’ by the intake of different psychoactive drugs. Hence, animals showing propensity for developing dependence to a specific drug class may also be useful for modeling other addictions. We compared the effects of repeated (14 daily doses) morphine (10 mg/kg) or methadone (2 mg/kg) treatment followed by a 2-week withdrawal and a morphine challenge (5 mg/kg) on locomotor activity, brain Fos expression and selected brain regional levels of dopamine, serotonin and their metabolites in the 38th generations of selectively bred Warsaw low-alcohol-preferring (WLP) and Warsaw high-alcohol-preferring (WHP) rat lines. The rats were given the opioids during the active (i.e. dark) phase of their daily cycle. Drug-naïve WHP rats compared to their WLP counterparts showed higher locomotor activity in an open field test and higher propensity for lasting behavioral sensitization to morphine. Morphine did not significantly enhance, but suppressed Fos expression in certain brain regions of drug-naïve WLP and WHP rats. Fos expression revealed considerable differences in the responses of WLP and WHP rats to morphine challenge, particularly after methadone pretreatment. These differences were associated with differences in monoamine metabolite levels that were suggestive of elevated basal ganglia and lowered frontal cortical dopamine function, and of lowered somatosensory cortex serotonin function, in the morphine-challenged WHP rats (irrespective of the pretreatment type). Hence, the WLP/WHP line pair may be useful for the search of factors that underlie the propensity for developing opiate dependence.