Hepatitis B virus genotypes and lamivudine resistance mutations in HIV/hepatitis B virus-coinfected patients

BACKGROUND: Differences in subtypes, hepatitis B early antigen (HBeAg)-negative variants, and drug resistance mutations all seem to influence the clinical and therapeutic outcome in patients with chronic hepatitis B virus (HBV) infection. Information available on the prevalence and distribution of distinct HBV variants in HIV-positive patients is scarce. METHODS: All HIV-infected patients with persistent serum hepatitis B surface antigen and detectable HBV viremia were identified in a reference HIV clinic located in Madrid, Spain. HBV load, subtypes, precore (PC) and basal core promoter (BCP) variants, and lamivudine (LAM) resistance mutations were analyzed. RESULTS: A total of 81 HBV/HIV-coinfected patients (4.1%) were identified in a population of 1968 HIV-positive patients. Plasma specimens with detectable HBV viremia could be obtained from 62 subjects, and this was the study population that underwent further virologic characterization. HBV genotype distribution was as follows: A (n = 27), D (n = 27), E (n = 1), F (n = 2), and G (n = 3). Two patients had mixed HBV genotypes (A/E and A/F). HBV subtype A was predominant (74%) among patients infected through sexual contact, whereas HBV-D was most frequent (74%) among intravenous drug users (P < 0.001). PC/BCP mutants were more frequent in patients with HBV-D than in those with HBV-A (63% vs. 18%; P < 0.01). Median time on LAM was 40 months; patients with HBV-A tended to show LAM resistance mutations more often (53% vs. 44%) and to develop them earlier (35 vs. 45 months) than patients with HBV-D. The dual L180M + M204V/I mutant was the predominant resistance pattern, although a triple rt173V + 180M + 204V, which acts as a vaccine escape mutant, was found in 1 individual. In the multivariate analysis, patients with LAM resistance mutations were significantly more frequently HBeAg-positive and older than individuals with wild-type HBV. Hepatitis-delta was recognized in 13 (21%) of these 62 HBV viremic patients, with no association with specific HBV variants. CONCLUSION: Risk transmission group, age, and positive serum HBeAg are the main determinants of distinct HBV virologic variants, including HBV genotypes and LAM-resistant mutants, in HBV/HIV-coinfected patients.     

Assessment of cancer immunotherapy outcome in terms of the immune response time features.

A cytokine-based periodic immunotherapy treatment is included in a model of tumour growth with a delay. The effects of dose schedule are studied in the case of a weak immune system and a growing tumour. We find the existence of 'metastable' states (that may last for tens of years) induced by the treatment and also potentially adverse effects of the dosage frequency on the stabilization of the tumour. These two effects depend on the delay between the tumour growth and the immune system response, the cytokine dose burden, and other parameters considered in the model.     

Does bupivacaine in laparoscopic ports reduce postsurgery pain in tubal ligation by electrocoagulation? A randomized controlled trial

BackgroundTubal ligation (TL) is the most popular method of permanent contraception. In order to reduce postoperative pain, different analgesic techniques have been proposed. The objective of this study was to compare the level of postoperative pain in patients submitted to TL with electrocoagulation, under general anesthesia, using bupivacaine infiltration vs. placebo in trocar ports.Study DesignConsecutive patients scheduled for laparoscopic TL were randomized by sequenced coded envelopes to receive bupivacaine 0.5% (n=29) or placebo (n=24). Pain was blindly assessed at 15 min, 30 min, 120 min and 14 h postoperatively, by verbal analogue scale (VAS). Standard pain medications (morphine, dipyrone and sodium diclofenac) were prescribed for the subjects and compared between groups.ResultsNo difference in pain assessment was found between bupivacaine and placebo groups at all times [median (25–75 quartiles)] (all p>.05): 15 min: 3 (1–6.3) vs. 4 (0–7); 30 min: 1.5 (0–4.3) vs. 2 (0–5); 2 h: 0 (0–0.5) vs. 0 (0–1); 14 h: 1 (0–4) vs. 0 (0–4); and for use of analgesics: dipyrone (g): 1 (0–1) vs. 1 (0–1); morphine (mg): 3 (0–3) vs. 3 (0–3.5); sodium diclofenac (mg): 0 (0–50) vs. 0 (0–50).ConclusionThe use of local injection of bupivacaine 0.5% in the trocar ports was not superior to placebo to reduce pain after laparoscopic TL with electrocoagulation under general anesthesia.     

Cholestasis as the initial feature of Kawasaki disease

Hepatobiliary involvement is uncommon in Kawasaki disease, and it is usually described as obstructive jaundice. From January 01, 2000 to August 31, 2010, 31 Kawasaki disease cases were diagnosed in our center. Three of them (9.7%) developed jaundice, but there were no gallbladder or bile duct abnormalities by ultrasonography, a feature rarely reported. Resolution of cholestasis paralleled improvement of the illness.     

Coinfection is an important factor in epidemiological studies: the first serosurvey of the aoudad (<Emphasis Type="Italic">Ammotragus lervia</Emphasis>)

Despite being considered an invasive ungulate outside its native range (North Africa), little information exists regarding the role of the aoudad (also called Barbary sheep, Ammotragus lervia) as a pathogen reservoir. Furthermore, in most epidemiological surveys the potential role of coinfections (e.g. a first infection may make the host more immuno-competent or susceptible against a second pathogen) as a risk factor is often neglected. In this study we first performed a serological survey for selected pathogens (Mycobacterium bovis, M. avium subsp. paratuberculosis, Chlamydophila abortus, bovine viral diarrhoea/border disease viruses (BVDV-BDV), Salmonella spp., Brucella melitensis and Toxoplasma gondii) on free (n = 66) and captive (n = 25) aoudad from south-east Spain. Then, by using Akaike’s information criterion, we evaluated the importance of coinfection in two statistical models that included the effects of population, age, and sex. Our results show that neither free nor captive aoudad had antibodies against Brucella melitensis, Chlamydophila abortus, or BVDV-BDV. However, compared to other wild ungulates in Spain, aoudads have high prevalence of antibodies against M. bovis (free = 49.5%; captive = 8%), very high prevalence of antibodies against M. avium subsp. paratuberculosis (free = 19.4%; captive = 56%), and intermediate prevalence of antibodies against Salmonella spp. (free = 13.4%; captive = 0%) or T. gondii (free = 1.5%; captive = 24%). Although the additive effects of population and age were included in our set of selected models, coinfection was the most influential factor to detect antibodies response against mycobacterials and salmonella infections. The direction of this influence could be exclusion of disease between tuberculosis and paratuberculosis seroreactor animals, or enhanced susceptibility to disease between tuberculosis and salmonella seroreactor animals. In conclusion, we believe that wildlife managers must pay more attention to the potential risk posed by aoudads as hosts (and probably reservoirs) of paratuberculosis and tuberculosis mycobacterials, while epidemiologists should be more aware of coinfection as an important factor in epidemiological surveys, especially in wildlife populations where multiple infections are common.     

Genotypes of the C677T and A1298C polymorphisms of the MTHFR gene as a cause of human spontaneous embryo loss

BACKGROUND Polymorphisms C677T and A1298C of the MTHFR gene have been implicated in fetal viability. In this study, we determined the allele and genotype frequencies of these polymorphisms in different populations, including spontaneous abortion (SA) fetal tissues, with the objective of evaluating their impact on fetal viability. METHODS 342 samples of fetal tissues, selected from SA occurring during the 1980s, 230 samples from subjects born in the 1980s and a third set of samples from 204 subjects born in the 1950s, were genotyped by using TaqMan probes. RESULTS The wild CC genotype of the C677T polymorphism showed a strong protective effect against abortion (0.03 in SA versus 0.47 in 1950s and 0.43 in 1980s) (P < 0.0001). Genotypes of three mutations in the combinations of polymorphisms for C677T and A1298C showed a very low frequency in the living population; however, the three mutations genotypes were over expressed in the SA group (0.02 in 1950s; 0.03 in 1980s and 0.17 in SA) (P < 0.0001). Samples with four mutations (n = 2) were found only in the SA group. CONCLUSIONS There is no linkage disequilibrium between C667T and A1298C polymorphisms. Fetal viability is directly related to the CC genotype as a protector while the three and four mutation MTHFR genotypes appear to be a determinant on fetal non-viability and SA.     

Utilization of ancillary studies in the cytologic diagnosis of respiratory lesions: The papanicolaou society of cytopathology consensus recommendations for respiratory cytology

The Papanicolaou Society of Cytopathology has developed a set of guidelines for respiratory cytology including indications for sputum examination, bronchial washings and brushings, CT‐guided FNA and endobronchial ultrasound guided fine needle aspiration (EBUS‐FNA), as well as recommendations for classification and criteria, ancillary testing and post‐cytologic diagnosis management and follow‐up. All recommendation documents are based on the expertise of committee members, an extensive literature review, and feedback from presentations at national and international conferences. The guideline documents selectively present the results of these discussions. The present document summarizes recommendations for ancillary testing of cytologic samples. Ancillary testing including microbiologic, immunocytochemical, flow cytometric, and molecular testing, including next‐generation sequencing are discussed. Diagn. Cytopathol. 2016;44:1000–1009. © 2016 Wiley Periodicals, Inc.     

Pro‐inflammatory self‐reactive T cells are found within murine TCR‐αβ+CD4−CD8−PD‐1+ cells

TCR‐αβ⁺ double negative (DN) T cells (CD3⁺TCR‐αβ⁺CD4^?CD8^?NK1.1^?CD49b^?) represent a minor heterogeneous population in healthy humans and mice. These cells have been ascribed pro‐inflammatory and regulatory capacities and are known to expand during the course of several autoimmune diseases. Importantly, previous studies have shown that self‐reactive CD8⁺ T cells become DN after activation by self‐antigens, suggesting that self‐reactive T cells may exist within the DN T‐cell population. Here, we demonstrate that programmed cell death 1 (PD‐1) expression in unmanipulated mice identifies a subset of DN T cells with expression of activation‐associated markers and a phenotype that strongly suggests they are derived from self‐reactive CD8⁺ cells. We also found that, within DN T cells, the PD‐1⁺ subset generates the majority of pro‐inflammatory cytokines. Finally, using a TCR‐activation reporter mouse (Nur77‐GFP), we confirmed that in the steady‐state PD‐1⁺ DN T cells engage endogenous antigens in healthy mice. In conclusion, we provide evidence that indicates that the PD‐1⁺ fraction of DN T cells represents self‐reactive cells.