Up-regulation of the monocyte chemotactic protein-3 in sera from bone marrow transplanted children with torquetenovirus infection

BackgroundTorquetenovirus (TTV) represents a commensal human virus producing life-long viremia in approximately 80% of healthy individuals of all ages. A potential pathogenic role for TTV has been suggested in immunocompromised patients with hepatitis of unknown etiology sustained by strong proinflammatory cytokines.ObjectivesThe aim of this study was to investigate the sera immunological profile linked to TTV infection in bone marrow transplant (BMT) children with liver injury.Study designTTV infection was assessed in sera from 27 BMT patients with altered hepatic parameters and histological features, by the use of quantitative real-time PCR, along with TTV genogroups and coinfection with HEV. The qualitative and quantitative nature of soluble inflammatory factors was evaluated studying a large set of cytokines using the Bioplex platform. As controls, sera from 22 healthy children negative for serological and molecular hepatitis markers including TTV and HEV, and for autoimmune diseases, were selected.Results and conclusionsTTV was detected in 81.4% of BMT patients with a viral load ranging from 10⁵ to 10⁹ copies/mL. All samples were HEV-RNA negative. A pattern of cytokines, IFN-γ, TNF-α, FGF-basic (p < 0.01) and MCP-3 (p < 0.001) was found significantly highly expressed in TTV-positive patients compared to TTV-negative and controls. Of note, MCP-3 chemokine showed the highest sera concentration independently of the amount of TTV load and the status of immune system deregulation (p < 0.001). In this pilot study for the first time, a positive association was found between TTV and increased level of MCP-3 suggesting a indirect role of TTV in liver injury.     

Crucial parameter of the outcome in Crimean Congo hemorrhagic fever: Viral load

BackgroundCrimean Congo hemorrhagic fever (CCHF) is a fatal disease with a mortality rate of 5–30%. CCHF can be asymptomatic or it may progress with bleeding and cause mortality.ObjectivesTo evaluate relation of viral load with mortality, clinical and laboratory findings in CCHF.Study designA total of 126 CCHF patients were included. Serum samples obtained from all patients on admission for measurement of viral load.ResultsIn our study, mortality rate was 11.1%. The most important prognostic factor was viral load. Mean viral load was 8.3 × 10⁷ copy/ml and 4.6 × 10⁹ copy/ml in survived and dead patients, respectively (p < 0.005). Probability of survival is found to be significantly reduced where AST >1130 U/l, ALT >490 U/l, CPK >505 U/l, LDH >980 U/l, platelet count <23 × 10³/l, creatinine >1.4 mg/dl, INR >1.3, d-dimer >7100 ng/dl, and viral load >1.03 × 10⁸ copy/ml. Patients with 10⁸ copy/ml or higher viral load had diarrhea, headache, unconsciousness, bleeding, and seizure significantly more frequently (p < 0.05). WBC, hemoglobin, platelet counts were significantly lower whereas AST, ALT, CPK, LDH, creatinine levels, PT and aPTT time, d-dimer levels, and INR were found to be significantly higher in these group.ConclusionsThere are several severity criteria for prognosis of CCHF. In addition to these parameters, we introduce creatinine as a predictive factor for prognosis. Our study, which has the largest number of patients among studies that evaluate viral load on CCHF shows that viral load is the most effective parameter on mortality.     

Association of cytologic grade of anal “Pap” smears with viral loads of human papillomavirus types 16, 18, and 52 detected in the same specimens from men who have sex with men

BackgroundHuman papilloma virus (HPV) load has been linked to cellular abnormalities of the uterine cervix, and proposed as predictors of HPV persistence and progression of dysplasia to cervical cancer. However, the association of HPV viral load and anal dysplasia and cancer has not been as thoroughly investigated.ObjectivesTo examine the association of the viral loads of high-risk HPV types 16, 18, and 52, with the cytologic severity grading in anal-swab specimens of MSM with and without HIV-1 co-infection.Study designA cross-sectional study recruited 200 MSM in northern Thailand from July 2012 to January 2013. Real-time qPCR amplified portion of the HPV E6E7 gene, as well as the human β-globin gene to validate adequacy of the anal specimens and to normalize interpatient viral-load comparisons. Genotyping by linear-array assay identified and distinguished types 16, 18, and 52.ResultsHPV-16, and -18 viral loads increased with respect to the abnormality of the cytologic diagnoses (p < 0.05 for HPV-16, p < 0.01 for HPV-18). HIV-1 positivity was associated with higher HPV-18 viral load (p = 0.006). HPV-16 viral loads ≥10^2.24 copies per 5000 anal cells, and HPV-18 loads ≥10^3.15, were independently associated with abnormal cytology on logistic regression (p = 0.022, p = 0.041, respectively). Positive predictive values were 85.2% (23/27) and 80.0% (44/55) for the high viral load of a particular HPV-16 and the combined HPV-16, -18 and -52 types, respectively.ConclusionsHigh viral loads of HPV types 16 and 18 appear to be associated with anal cytologic abnormalities. The clinical utility of HPV viral loads to predict risk for anal cancer remains to be determined by a larger prospective cohort with sufficient frequency of high-grade dysplasia.     

Relationship between depression and frailty in older adults: A systematic review and meta-analysis

AimDepression and frailty are prevalent and burdensome in older age. However, the relationships between these entities are unclear and no quantitative meta- analysis exists. We conducted a systematic review and meta-analysis to investigate the associations between depression and frailty.MethodsTwo authors searched major electronic databases from inception until November-2016 for cross-sectional/longitudinal studies investigating depression and frailty. The strength of the reciprocal associations between frailty and depression was assessed through odds ratios (ORs) adjusted for potential confounders.ResultsFrom 2306 non duplicated hits, 24 studies were included. The overall prevalence of depression in 8023 people with frailty was 38.60% (95% CI 30.07–47.10, I² = 94%). Those with frailty were at increased odds of having depression (OR adjusted for publication bias 4.42, 95%CI 2.66–7.35, k = 11), also after adjusting for potential confounders (OR = 2.64; 95%CI: 1.59–4.37, I² = 55%, k = 4). The prevalence of frailty in 2167 people with depression was 40.40% (95%CI 27.00–55.30, I² = 97%). People with depression were at increased odds of having frailty (OR = 4.07, 95%CI 1.93–8.55, k = 8). The pooled OR for incident frailty, adjusted for a median of 7 confounders, was 3.72 (95%CI 1.95–7.08, I² = 98%, k = 4), whilst in two studies frailty increased the risk of incident depression with an OR = 1.90 (95%CI 1.55–2.32, I² = 0%).ConclusionThis meta-analysis points to a reciprocal interaction between depression and frailty in older adults. Specifically, each condition is associated with an increased prevalence and incidence of the other, and may be a risk factor for the development of the other. However, further prospective investigations are warranted.     

Comparative Detection and Quantification of Arcobacter butzleri in Stools from Diarrheic and Nondiarrheic People in Southwestern Alberta,Canada

Arcobacter butzleri has been linked to enteric disease in humans, but its pathogenicity and epidemiology remain poorly understood. The lack of suitable detection methods is a major limitation. Using comparative genome analysis, we developed PCR primers for direct detection and quantification of A. butzleri DNA in microbiologically complex matrices. These primers, along with existing molecular and culture-based methods, were used to detect A. butzleri and enteric pathogens in stools of diarrheic and nondiarrheic people (n = 1,596) living in southwestern Alberta, Canada, from May to November 2008. In addition, quantitative PCR was used to compare A. butzleri densities in diarrheic and nondiarrheic stools. Arcobacter butzleri was detected more often by PCR (59.6%) than by isolation methods (0.8%). Comparison by PCR-based detection found no difference in the prevalence of A. butzleri between diarrheic (56.7%) and nondiarrheic (45.5%) individuals. Rates of detection in diarrheic stools peaked in June (71.1%) and October (68.7%), but there was no statistically significant correlation between the presence of A. butzleri and patient age, sex, or place of habitation. Densities of A. butzleri DNA in diarrheic stools (1.6 ± 0.59 log₁₀ copies mg⁻¹) were higher (P = 0.007) than in nondiarrheic stools (1.3 ± 0.63 log₁₀ copies mg⁻¹). Of the 892 diarrheic samples that were positive for A. butzleri, 74.1% were not positive for other bacterial and/or viral pathogens. The current study supports previous work suggesting that A. butzleri pathogenicity is strain specific and/or dependent on other factors, such as the level of host resistance.     

Performance of a rapid antigen test (Binax NOW® RSV) for diagnosis of respiratory syncytial virus compared with real-time polymerase chain reaction in a pediatric population

BackgroundInfants from Alaska's Yukon–Kuskokwim Delta (YKD) have a high respiratory syncytial virus (RSV) hospitalization rate (104/1000/yr). Appropriate patient management requires rapid and accurate RSV diagnosis. Antigen-based methods are often used in clinical settings, but these tests can lack sensitivity.ObjectiveWe compared Binax NOW^® RSV (BN) used for RSV diagnosis in the YKD hospital with a real-time polymerase chain reaction assay (RT-qPCR) used for viral surveillance.Study designBetween October 2005 and September 2007 we obtained nasopharyngeal washes (NPW) from children <3 years hospitalized with a lower respiratory tract infection. The NPW were tested using BN and RT-qPCR.Results79/311 (25%) children had RSV infection as determined by RT-qPCR. As compared with RT-qPCR, sensitivity and specificity of BN were 72% and 97%, respectively. The sensitivity of BN was higher in children <1 year compared with children ≥1 year (79% vs. 52%; p = 0.025), children with bronchiolitis compared with children without bronchiolitis (89% vs. 38%; p < 0.001), and children with a shorter duration of symptoms before testing (0–1 (92%) vs. 2–4 (78%) vs. 5+ (65%) days; p = 0.04). The median RSV viral load in NPW positive by BN and RT-qPCR was 1.01 × 10⁹ copies/mL vs. a median of 5.25 × 10⁷ copies/mL for NPW positive by RT-qPCR only (p < 0.001).ConclusionRT-qPCR is more sensitive than BN in detecting RSV infection. BN sensitivity is high in children with bronchiolitis, but the sensitivity is low when children present with a non-bronchiolitis illness, especially after a longer duration of symptoms before testing.     

Sitting time increases the overweight and obesity risk independently of walking time in elderly people from Spain

IntroductionObesity, defined as an excess of total body fat, is a matter of concern all over the world, and its prevalence is still increasing among elderly people.ObjectivesTo examine whether sedentary behaviour (hours sitting per day) is associated with higher risk of central obesity, overweight-obesity and overfat in a representative sample of non-institutionalized Spanish elderly population and if so, whether hours walking per day modified this association.Study designA cross-sectional study in a sample of 3136 people ≥65 years of age.Main outcomes measuresAnthropometric measurements were obtained using standardized techniques and equipment. Active and sedentary behaviours were recorded by questionnaire.ResultsFor both men and women, the higher prevalence of overweight-obesity, central obesity and overfat was found in those who spent sitting more than 4 h per day and walk less than 1 h, compared with those who spent sitting less than 4 h per day and walk more than 1 h (all p < 0.001, except for central obesity in women). In men, more than 4 h sitting per day was associated with 1.7-fold higher odds of having central obesity compared with those sitting less than 4 h per day (p < 0.01). In women, this sedentary behaviour increased the risk of overweight-obesity and overfat by 1.5 and 1.4, respectively (p < 0.01). Age or time spent walking did not significantly change these results.ConclusionSitting time increases the risk of overweight-obesity and overfat in women and the risk of central obesity in men, independently of walking time.     

Norovirus prevalence and estimated viral load in symptomatic and asymptomatic children from rural communities of Vhembe district,South Africa

BackgroundHuman Norovirus (NoV) is recognized as a major etiological agent of sporadic acute gastroenteritis worldwide.ObjectivesThis study describes the clinical features associated with Human NoV occurrence in children and determines the prevalence and estimated viral burden of NoV in symptomatic and asymptomatic children in rural South Africa.Study designBetween July 2014 and April 2015, outpatient children under 5 years of age from rural communities of Vhembe district, South Africa, were enrolled for the study. A total of 303 stool specimens were collected from those with diarrhea (n = 253) and without (n = 50) diarrhea. NoVs were identified using real-time one-step RT-PCR.ResultsOne hundred and four (41.1%) NoVs were detected (62[59.6%] GII, 16[15.4%] GI, and 26[25%] mixed GI/GII) in cases and 18 (36%) including 9(50%) GII, 2(11.1%) GI and 7(38.9%) mixed GI/GII in controls. NoV detection rates in symptomatic and asymptomatic children (OR = 1.24; 95% CI 0.66⿿2.33) were not significantly different. Comparison of the median C_T values for NoV in symptomatic and asymptomatic children revealed significant statistical difference of estimated GII viral load from both groups, with a much higher viral burden in symptomatic children.ConclusionsThough not proven predictive of diarrhea disease in this study, the high detection rate of NoV reflects the substantial exposure of children from rural communities to enteric pathogens possibly due to poor sanitation and hygiene practices. The results suggest that the difference between asymptomatic and symptomatic children with NoV may be at the level of the viral load of NoV genogroups involved.     

Species distribution patterns and epidemiological characteristics of otomycosis in Southeastern Serbia

IntroductionOtomycosis, a superficial fungal infection of the external auditory canal (EAC), is a disease with exceptionally high prevalence.AimThe aim of this study was to determine the prevalence of otomycosis, the distribution of causative species and to evaluate epidemiological characteristics of these infections.MethodologyThe patients’ data were collected from record book and database of mycological examinations conducted at Public Health Institute Nis, Serbia. In the period from 2014 to 2018 samples of 1287 patients with symptoms and signs of EAC infection were investigated. Standard mycological methods were used for isolation and determination of fungi.ResultsHigh prevalence of otomycosis was determined in examined patients (22.7%). However, the prevalence rates did not differ significantly in the studied period (p = 0.931). The majority of patients were diagnosed with only unilateral EAC infection (82.9%). Considering all patients with otomycosis, mold infections caused by the genus Aspergillus (143/48.9%) were more frequent than Candida spp. ear infections (133/45.6%), with Aspergillus niger and Candida аlbicans being predominant causative agents. Mixed Aspergillus and Candida otomycosis was established in 16 (5.5%) patients. Otomycosis was more common in male subjects (26.8%, p = 0.003) who also suffered from Aspergillus otomycosis more frequently (17.5%, p < 0.001). The prevalence of these infections increases with age (p = 0.005), while they do not show seasonal pattern (p > 0.05).ConclusionNoted high prevalence of otomycosis, with both yeasts and non-dermatophyte molds acting as infectious agents which require different treatment, implies the necessity for further epidemiological monitoring of this form of superficial mycoses.     

Association between KIR genotypes and HLA-B alleles on viral load in Southern Brazilian individuals infected by HIV-1 subtypes B and C

There is a great variety of HIV-1 subtypes circulating in Brazil, including subtype C, whose prevalence is on the rise, particularly in the southern region. Many host and viral genetic factors may be involved in this trend. We evaluated the influence of human leukocyte antigen (HLA) class I alleles and killer-cell immunoglobulin-like receptor (KIR) genotypes on viral set point and T-CD4⁺ parameters in 84 treatment-naïve HIV-1-positive individuals. Frequency data in the infected group were compared to data of 548 healthy control subjects. Individuals with the KIR AA genotype had a higher viral load (VL) than individuals with the KIR Bx genotype. The HIV-1 group was subdivided into three subgroups according to HLA-B allele presence: those with protection to disease alleles (HLA-B⁺), accelerated disease progression alleles (HLA-B⁻), or neither (HLA-B^o) were grouped. We observed a significant effect of the HLA-B allele presence on VL. The HLA-B⁺ group had significantly lower VL than the HLA-B⁻ group and trended toward a lower VL than the HLA-B^o group. There were significant differences between groups expressing extreme VL values: KIR-AA + HLA-B⁻ vs. KIR Bx + HLA-B⁺ and KIR-AA + HLA-B^o vs. KIR Bx + HLA-B⁺. The relationship of KIR/HLA host genetics with slow HIV disease progression in southern Brazil may be useful for vaccine developers, epidemiologists, and clinicians.     

Aggravation of left ventricular dysfunction in patients with biopsy-proven cardiac human herpesvirus A and B infection

BackgroundHuman herpesvirus 6 (HHV-6) A and B are lymphotropic viruses with life-long persistence, primarily associated with non-cardiac diseases, and discussed as a possible etiologic factor of myocarditis and cardiomyopathy.ObjectiveTo analyze the long-term spontaneous course of cardiac patients suffering from suspected inflammatory cardiomyopathy (CMi) with persisting HHV-6 A and B infections by follow-up biopsies.Study designWe prospectively evaluated patients (n = 73) with biopsy-proven viral HHV-6 A and B infection in endomyocardial biopsies (EMBs), followed up by reanalysis of EMBs and left ventricular ejection fraction (LV-EF) measurements after a median period of 8.8 months (range 4–73 months). Beyond, we studied HHV-6 prevalence in isolated peripheral blood cells (PBCs) and HHV-6 species in EMBs. HHV-6 species-specific cellular infection sites within the myocardium were identified by immunohistochemistry (IHC).ResultsWe identified 73 patients with cardiac HHV-6 A and B persistence or newly detected in follow-up EMB (95.0% B). Proof of HHV-6 in PBCs was primarily associated with A. Persistence of cardiac HHV-6 B genome was significantly associated with cardiac dysfunction at follow-up (LV-EF deteriorated from 58.2 ± 16.0 to 51.8 ± 17.2%, p < 0.001), and LV improvement was observed when HHV-6 B persistence resolved (LV-EF increased from 54.9 ± 15.4 to 60.7 ± 13.1%, p < 0.001).ConclusionsPersistence of cardiac HHV-6 B genomes was significantly associated with cardiac dysfunction, and hemodynamic parameters improved in association with HHV-6 B clearance.     

Hepatitis B virus prevalence,risk factors and genotype distribution in HIV infected patients from West Java,Indonesia

BackgroundIndonesia currently faces both an increasing HIV incidence and a high hepatitis B virus (HBV) burden.ObjectiveThe objective of our study is to examine the prevalence, risk factors, and genotypic distribution of HBV infection among HIV infected patients in West Java, Indonesia.Study designA cross sectional study was conducted among a cohort of HIV infected patients in 2008. Demographic and disease related variables were compared between HBV negative and positive patients. Logistic regression was applied to determine risk factors for HBV co-infection. HBV and HIV genotyping was performed in co-infected patients.ResultsOf 636 HIV-infected patients, the rate of HBV co-infection was 7%. The proportion of males was higher in HBV/HIV co-infected patients than in HIV mono-infected patients (93% vs. 72%, P = 0.001). A history of injecting drug use (IDU), but not tattooing, was associated with HBV co-infection [P = 0.035 OR 2.41 (95% CI 1.06–5.47)]. In the HIV and HBV treatment naive patients, CD4 cells counts <50 cells/mm³, HIV-RNA plasma ≥10,000 copies/ml and AST level above normal were more often found in patients with high HBV-DNA levels (≥20,000 IU/ml) as compared to those with low HBV DNA (<20.000  IU/ml) (P < 0.05). As in the general population, B3 was the dominant subtype in HBV co-infected patients.ConclusionThe prevalence of active HBV infection and the genotype distribution among HIV infected individuals is similar to the overall population in Java. However, an increased prevalence was observed in men with a history of IDU, underlining the need for routine HBV screening and monitoring.     

Gender and sex differences in prevalence of major depression in coronary artery disease patients: A meta-analysis

BackgroundDepression is related to increased morbidity and mortality in the general population and among patients with coronary artery disease (CAD). The prevalence of major depression is two-times higher in women than men in the general population, but whether this pattern holds true in the CAD population has not been established.ObjectiveTo test, through quantitative synthesis, whether women with CAD have a greater prevalence of major depression than men.MethodMEDLINE, EMBASE, and PsycINFO electronic databases were searched. Authors of key articles were contacted to identify other relevant publications. The titles and abstracts were screened by the first author and the selected full-text articles were independently screened by the first and second authors based on pre-defined inclusion criteria. Major depression had to be diagnosed through structured clinical interviews during cardiac-related hospitalization or post-CAD hospitalization. Meta-analysis was undertaken using the Review Manager 5 software program. All pooled analyses were based on random-effects models.ResultsEight eligible cohort and cross-sectional studies reporting data for 2072 participants (509 [24.6%] women) were included. Overall, major depression was observed in 95 (18.7%) women and 187 (12.0%) men. In the pooled analysis, prevalence of major depression was significantly greater in women compared to men (odds ratio = 1.77, 95% confidence interval = 1.21–2.58, p < .01). Heterogeneity was considered low to moderate (I² = 36.0%).ConclusionConsistent with the general population, the prevalence of major depression is two-times greater in women than men with CAD. Women with CAD may warrant greater emphasis in efforts to identify and treat depression.     

Keratoconjunctivitis sicca of human T cell lymphotropic virus type 1 (HTLV-1) infected individuals is associated with high levels of HTLV-1 proviral load

BackgroundA high HTLV-1 proviral load is found in HTLV-1-associated diseases, mainly HAM/TSP. However, the association between proviral load and keratoconjunctivitis sicca (KCS) has not been well established.AimTo verify the association between KCS and HTLV-1 proviral load.Study design104 HTLV-1 infected patients (51 asymptomatic and 52 with HAM/TSP) from the HTLV reference center in Salvador, Brazil were followed from June 2008 to May 2010. Evaluation of tear secretion was performed by BUT (break-up time), Rose Bengal and Schirmer I tests. The diagnosis of KCS was based upon the presence of symptoms and when at least two of three tests were positive. HTLV-1 proviral load was determined using real-time PCR.ResultsThe prevalence of KCS was 44.2%. KCS was more frequent among HAM/TSP patients (p = 0.022). Patients with KCS had higher proviral load (mean 134,672 ± 150,393 copies/10⁶ PBMC) than patients without the disease (mean 66,880 ± 109,525 copies/10⁶ PBMC) (p = 0.001). HTLV-1 proviral load > 100,000 copies/10⁶ PBMC increased significantly the risk of developing KCS (OR = 4.05 and 95% CI = 1.40–11.76). After age > 45 years and HAM/TSP status were excluded in stepway reward analysis, the variables PVL > 100,000 (OR = 4.77 and 95% CI = 1.83–12.44) still remained statistically significant.ConclusionHTLV-1 proviral loads are higher in patients with KCS and may represent a relevant biological marker of disease.     

Norovirus in feces and nasopharyngeal swab of children with and without acute gastroenteritis symptoms: First report of GI.5 in Brazil and GI.3 in nasopharyngeal swab

BackgroundNoroviruses (NoVs) are an important cause of acute gastroenteritis (AGE), worldwide.ObjectivesTo evaluate the frequency, viral load and molecular profile of NoV in fecal and nasopharyngeal swab samples from hospitalized children, and to determine children’s secretor status.Study designFrom May 2014 to May 2015, 219 children were included in the study, 96 with gastroenteric symptoms and 123 without gastroenteric symptoms. All fecal and nasopharyngeal swab samples were screened by TaqMan RT-qPCR duplex (GI/GII NoV) and quality samples were characterized by genomic sequencing.ResultsNorovirus positivity rate in feces was 15.4% in asymptomatic and 18.8% in the symptomatic group. The median viral loads in feces were 2.69 × 10⁸ GC/g and 4.32 × 10⁷ GC/g from children with or without AGE symptoms, respectively. In nasopharyngeal swab samples, the NoV positivity was 11.4% in symptomatic children, with a median viral load of 2.20 × 10⁷ GC/mL and 6.5% in asymptomatic children, with an average viral load of 1.73 × 10⁶ GC/mL. In only two cases NoV was detected in both samples. A considerable genomic variability was observed in feces, with six genotypes being detected, as follows: GII.4, GII.6, GI.3 and GII.3, GI.2 and GI.5. Two GI.3 was detected in nasopharyngeal swab.ConclusionsOur data reveal considerable NoV frequencies in both nasopharyngeal and fecal samples from symptomatic and asymptomatic children. Higher viral loads were detected in samples from AGE symptomatic children, when compared to asymptomatic children. High genomic variability was observed, with this being the first report of GI.5 NoV in Brazil and of GI.3 in nasopharyngeal swab samples.     

Viro-immunological dynamics in HIV-1-infected subjects receiving once-a-week emtricitabine to delay treatment change after failure: A pilot randomised trial

BackgroundIn HIV-1-infected patients harbouring the M184V mutation (M184V), lamivudine monotherapy leads to a smaller decrease in CD4 percentages (CD4%) than treatment interruption, possibly due to the reduced fitness of the mutated virus.ObjectiveWe assessed whether a minimal dose of a cytidine analogue that is theoretically sufficient to maintain M184V (one emtricitabine tablet once-weekly) may be as effective.Study designIn a proof-of-concept, randomised clinical trial, HIV-1-infected patients with CD4 cells >400/mm³, failing on lamivudine- or emtricitabine-containing combination antiretroviral therapy (cART), received emtricitabine once-a-week (A), or emtricitabine once-a-day (B), or lamivudine once-a-day (C). The primary endpoint was the proportion of subjects without a 12-week loss in CD4%. The patients resumed cART after 24 weeks or in the case of CD4 cells <350/mm³.ResultsThe 38 enrolled patients had similar baseline characteristics across groups. The primary endpoint was reached by 5/13 patients (38.5%) in arm A, 3/13 (23.1%) in arm B, and 3/12 (25%) in arm C (P = 0.644), and respectively 4/13 (30.8%), 4/13 (30.8%) and 5/12 (41.7%) had to resume cART within 24 weeks (P = 0.805). The immunological changes over 24 weeks were similar in the three groups, but there was a higher median viral rebound in once-weekly treatment recipients (A) than in once-daily (B + C): 0.97 versus 0.52 log₁₀ copies/ml (P = 0.033). M184V was maintained in all the participants.ConclusionsOnce-weekly emtricitabine led to a higher viral rebound than once-daily monotherapy, but similar immunological changes, thus suggesting a role of M184V in slowing the decrease in CD4% in treatment failing subjects.     

HHV-8 DNA replication correlates with the clinical status in AIDS-related Kaposi’s sarcoma

BackgroundThe value of plasma levels of human herpesvirus 8 (HHV-8) DNA as a marker of clinical status in acquired immunodeficiency syndrome-related Kaposi’s sarcoma (AIDS-KS) remains to be elucidated.ObjectivesTo investigate the relationship between the plasma HHV-8 DNA viral load and the clinical status of AIDS-KS.Study DesignA total of 378 blood samples were obtained from 62 patients with AIDS-KS followed longitudinally. All patients received antiretroviral therapy (ART) or anti-neoplastic therapy. The patients were divided into four groups according to their clinical status: onset disease (OD), progressive disease (PD), stable or partial remission (S/PR) and complete remission (CR).ResultsPlasma HHV-8 DNAaemia was detected in all samples obtained from patients with OD or PD (100%); in contrast, HHV-8 DNAaemia was found only in a minority of patients with CR (8%) and was invariably undetectable in patients with stable CR. HHV-8 DNA detection in plasma was strongly associated with an unfavourable outcome (odds ratio = 231.9; p < 0.0001). Conversely, neither the HIV-1 viral load nor peripheral CD4⁺ T-cell counts were associated with the KS clinical status, though both parameters did affect HHV-8 DNAaemia levels (p < 0.0001). Multivariate analysis confirmed that HHV-8 DNAaemia was strongly and independently correlated with both clinical status (p < 0.05) and HIV-1 plasma viraemia (p = 0.027).ConclusionsThe strong association of plasma HHV-8 DNAaemia with onset or progressive disease is compatible with an active role of replicating virus in clinically active AIDS-KS. An accurate evaluation of the plasma HHV-8 load might be useful for monitoring AIDS-KS under antiretroviral or antineoplastic therapy.     

TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model

PurposeTo characterize clinically measurable endophenotypes, implicating the TBX6 compound inheritance model.MethodsPatients with congenital scoliosis (CS) from China(N = 345, cohort 1), Japan (N = 142, cohort 2), and the United States (N = 10, cohort 3) were studied. Clinically measurable endophenotypes were compared according to the TBX6 genotypes. A mouse model for Tbx6 compound inheritance (N = 52) was investigated by micro computed tomography (micro-CT). A clinical diagnostic algorithm (TACScore) was developed to assist in clinical recognition of TBX6-associated CS (TACS).ResultsIn cohort 1, TACS patients (N = 33) were significantly younger at onset than the remaining CS patients (P = 0.02), presented with one or more hemivertebrae/butterfly vertebrae (P = 4.9 × 10^‒8), and exhibited vertebral malformations involving the lower part of the spine (T8–S5, P = 4.4 × 10^‒3); observations were confirmed in two replication cohorts. Simple rib anomalies were prevalent in TACS patients (P = 3.1 × 10^‒7), while intraspinal anomalies were uncommon (P = 7.0 × 10^‒7). A clinically usable TACScore was developed with an area under the curve (AUC) of 0.9 (P = 1.6 × 10^‒15). A Tbx6^{-/mh (mild-hypomorphic)} mouse model supported that a gene dosage effect underlies the TACS phenotype.ConclusionTACS is a clinically distinguishable entity with consistent clinically measurable endophenotypes. The type and distribution of vertebral column abnormalities in TBX6/Tbx6 compound inheritance implicate subtle perturbations in gene dosage as a cause of spine developmental birth defects responsible for about 10% of CS.