Colchicine is not effective for reducing osteoarthritic hand pain compared to placebo: a randomised, placebo-controlled trial (COLAH).

BACKGROUND: Colchicine may offer relief in osteoarthritis. This has never been investigated for hand osteoarthritis. OBJECTIVES: To investigate the effect of 1 mg daily colchicine vs placebo on hand pain and function over 12 weeks in older adults with hand osteoarthritis. METHODS: Community-dwelling adults with diagnosed osteoarthritis of the hand aged 40-80 years were randomised to receive colchicine (0.5 mg twice daily) or matching placebo. Primary outcome measure was VAS hand pain score (0-100 mm). Secondary outcome measures included tender and swollen joint count, grip strength, C-reactive protein, and Michigan Hand Questionnaire total, function and pain scores. In an exploratory assessment, we compared synovial grade and power Doppler. All outcome measures were obtained at baseline and week 12. Stata v16 was used to perform constrained longitudinal data analysis models. RESULTS: 64 adults (54 females, 10 males) aged 48-79 years of age were enrolled. 59 participants completed the study (N = 28 colchicine, N = 31 placebo) (withdrawal rate 8%). Adverse reactions to the study medication occurred in nine patients. VAS score was not significantly different at baseline (61 ± 17 mm in the colchicine, 64 ± 17 mm in the placebo group). Between-group difference for VAS score at week 12 was 7.6 mm (95% CI -3.5-18.7, p-value 0.18). There were no significant differences between groups for any secondary outcomes at baseline or week 12. CONCLUSIONS: 1 mg colchicine daily for 12 weeks was not effective for reducing pain, tender and swollen joint count or increasing grip strength in symptomatic hand osteoarthritis. Our results do not support the use of colchicine in hand osteoarthritis.

Percentile curves for the knee injury and osteoarthritis outcome score in the middle-aged Dutch population.

OBJECTIVE: To improve the interpretation of the Knee injury and Osteoarthritis Outcome Score (KOOS) in individual patients, we explored associations with age, sex, BMI, history of knee injury and presence of clinical knee osteoarthritis, and developed percentile curves. METHODS: We used cross-sectional data of middle-aged individuals from the population-based Netherlands Epidemiology of Obesity (NEO) study. Clinical knee osteoarthritis was defined using the ACR classification criteria. KOOS scores were handled according to the manual (zero = extreme problems, 100 = no problems). Patient characteristics associated with KOOS were explored using ordered logistic regression, and sex and body mass index (BMI)-specific percentile curves were developed using quantile regression with fractional polynomials. The curves were applied as a benchmark for comparison of KOOS scores of participants with knee osteoarthritis and comorbidities. RESULTS: The population consisted of 6,643 participants (56% women, mean (SD) age 56(6) years). Population-based KOOS subscale scores (median; interquartile range) near optimum: pain (100;94-100), symptoms (96;86-100), ADL function (100;96-100), sport/recreation function (100;80-100), quality of life (100;75-100). Worse KOOS scores were observed in women and in participants with higher BMI. Clinical knee osteoarthritis was defined in 15% of participants, and was, in comparison to other patient characteristics, associated with the highest odds of worse KOOS scores. Furthermore, presence of any comorbidity and cardiovascular disease specifically, was associated with worse KOOS scores, particularly in women. CONCLUSIONS: In the middle-aged Dutch population KOOS scores were generally good, but worse in women and with higher BMI. These percentile curves may be used as benchmarks in research and clinical practice.

Assessment of osteoarthritic features in the thumb base with the newly developed OMERACT magnetic resonance imaging scoring system is a valid addition to standard radiography.

OBJECTIVE: To investigate the construct validity of the new thumb base OA magnetic resonance imaging (MRI) scoring system (TOMS) by comparing TOMS scores with radiographic scores in patients with primary hand OA. DESIGN: In 200 patients (83.5% women, mean (SD) age 61.0 (8.4) years), postero-anterior radiographs and MR scans (1.5 T) of the right first carpometacarpal (CMC-1) and scaphotrapeziotrapezoid (STT) joints, were scored using the OARSI atlas and TOMS, respectively. The distributions of the TOMS scores (specified in results section) were stratified for the OARSI scores of corresponding radiographic features and investigated using boxplots and non-parametric tests. Furthermore, Spearman's rank or Phi correlation coefficients (ρ/φ) were calculated. RESULTS: For all features, especially for erosions and osteophytes, the prevalence found with MRI was higher than with radiography. TOMS osteophyte and cartilage loss scores differed statistically significant between corresponding OARSI scores in CMC-1 (0 vs 1; 1 vs 2). TOMS scores were positively correlated with radiographic scores in CMC-1 for osteophytes (coefficient [95% confidence interval], ρ = 0.75 [0.69; 0.81]), cartilage loss/joint space narrowing (ρ = 0.70 [0.62; 0.76]), subchondral bone defects (SBDs)/erosion-cyst (ρ = 0.41 [0.29; 0.52]), bone marrow lesions (BMLs)/subchondral sclerosis (ρ = 0.65 [0.56; 0.73]) and subluxation (φ = 0.65 [0.57; 0.73]); and in STT for osteophytes (ρ = 0.30 [0.17; 0.42]) and cartilage loss/joint space narrowing (ρ = 0.53 [0.42; 0.62]). CONCLUSIONS: In patients with hand OA, TOMS scores positively correlated with radiographic scores, indicating good construct validity. However, the prevalence of features on MR images was higher compared to radiographs, suggesting that TOMS might be more sensitive than radiography. The clinical meaning of these extra MR detected cases is currently still unknown.

The role of leptin and adiponectin as mediators in the relationship between adiposity and hand and knee osteoarthritis.

OBJECTIVES: To investigate associations of leptin and adiponectin levels with knee and hand osteoarthritis, and explore whether these mediate the association between adiposity and osteoarthritis. METHODS: This is a cross-sectional analysis of baseline data from the population-based Netherlands Epidemiology of Obesity study. Adiposity was assessed with body mass index (BMI) and percentage total body fat (%TBF). Osteoarthritis, defined as hand or knee osteoarthritis, was determined using American College of Rheumatology criteria. Fasting serum adipokine levels were measured using immunoassays. Associations between adiposity and osteoarthritis were examined with logistic regression, adjusted for age, sex, ethnicity and education, and additionally for leptin and adiponectin as potential mediators. RESULTS: In 6408 participants (56% women, median age 56 years), prevalence of osteoarthritis was 22% (10% isolated knee and 8% isolated hand osteoarthritis). Leptin levels were positively associated with osteoarthritis, while adiponectin levels were not. Leptin partially mediated the association of adiposity with osteoarthritis (OR 1.40 (95%CI 1.30; 1.52) attenuated to 1.38 (1.24; 1.54) per 5 units BMI and OR 1.25 (1.17; 1.35) to 1.20 (1.10; 1.32) per 5 units %TBF, representing 4% and 17% mediation, respectively). Larger proportion mediation by leptin was found in knee (13%/27%) than in hand osteoarthritis (9%/18%). Sex-stratified analyses generally showed stronger associations between adiposity, leptin and osteoarthritis in women than in men. CONCLUSIONS: Serum leptin levels were associated with osteoarthritis, and partially mediated the association between adiposity and osteoarthritis, while adiponectin levels were not associated with osteoarthritis. These findings provide evidence for systemic effects of adipose tissue in osteoarthritis.

Performance of the Michigan Hand Outcomes Questionnaire in hand osteoarthritis.

OBJECTIVE: To investigate the performance of the Michigan Hand Outcomes Questionnaire (MHQ) in hand osteoarthritis (OA) by evaluating truth, discrimination and feasibility. DESIGN: Symptomatic hand OA patients from the Hand Osteoarthritis in Secondary Care (HOSTAS) cohort completed questionnaires (demographics, MHQ, Australian/Canadian Hand Osteoarthritis Index [AUSCAN], Functional Index for Hand Osteoarthritis [FIHOA] and visual analogue scale [VAS] pain) at baseline (n = 383), 1- and 2-year follow-up (n = 312, n = 293). Anchor questions at follow-up assessed whether pain/function levels were (un)acceptable and had changed compared to baseline. Correlations between MHQ and other pain/function questionnaires were calculated. Validity of unique MHQ domains (work performance, aesthetics, satisfaction), discrimination across disease stages, and responsiveness were assessed by categorizing patients by external anchors (employment, joint deformities, erosions, and anchor questions). Between-group differences were assessed with linear regression, probability plots and comparison of medians. RESULTS: MHQ pain and function subscales correlated moderately-to-good with other instruments (rs 0.63-0.81). Work performance scores were worse in patients with reduced working capacity than in employed patients. Aesthetics scores were worse in patients with more deformities. Patients with unacceptable complaints had worse satisfaction scores. All pain/function instruments discriminated between patients with acceptable vs unacceptable pain/function, while only MHQ activities of daily living (ADL), FIHOA, and MHQ aesthetics could discriminate between erosive and non-erosive disease. MHQ and AUSCAN were most responsive. CONCLUSIONS: MHQ has several unique aspects and advantages justifying its use in hand OA, including the unique assessment of work performance, aesthetics, and satisfaction. However, MHQ, AUSCAN and FIHOA appear to measure different aspects of pain and function.

Comparison of histological and morphometrical changes underlying subchondral bone abnormalities in inflammatory and degenerative musculoskeletal disorders: a systematic review.

OBJECTIVE: Subchondral bone abnormalities (SBAs) on magnetic resonance imaging (MRI) are observed frequently and associated with disease course in various musculoskeletal disorders. This review aims to map the existing knowledge of their underlying histological features, and to identify needs for future research. DESIGN: We conducted a systematic review following PRISMA guidelines until September 2017, including all studies correlating histological features to on MRI defined SBAs in patients with osteoarthritis (OA), rheumatoid arthritis (RA), spondyloarthritis (SpA) and degenerative disc disease (DDD). Two authors independently retrieved articles and assessed study quality. RESULTS: A total of 21 studies (466 patients) correlated histological features to SBAs in OA (n = 13), RA (n = 3), ankylosing spondylitis (AS) (n = 1) and DDD (n = 4). Reported changes in OA were substitution of normal subchondral bone with fibrosis and necrosis, and increased bone remodeling. In contrast, in RA, AS or DDD fibrosis was not reported and SBAs correlated to an increase in inflammatory cell number. In DDD necrosis was observed. Similar to OA, increased bone remodeling was shown in RA and DDD. The risk of bias assessment showed a lack in described patient criteria, blinding and/or adequate topographic correlation in approximately half of studies. There was heterogeneity regarding the investigated histological features between the different disorders. CONCLUSIONS: Current studies suggest that SBAs correlate to various histological features, including fibrosis, cell death, inflammation and bone remodeling. In the majority of studies most quality criteria were not met. Future studies should aim for high quality research, and consistency in investigated features between different disorders.

In thumb base osteoarthritis structural damage is more strongly associated with pain than synovitis.

OBJECTIVE: Osteoarthritis in thumb base joints (first carpometacarpal (CMC-1), scaphotrapeziotrapezoid (STT)) is prevalent and disabling, yet focussed studies are scarce. Our aim was to investigate associations between ultrasonographic and magnetic resonance imaging (MRI) inflammatory features, radiographic osteophytes, and thumb base pain in hand osteoarthritis patients. DESIGN: Cross-sectional analyses were performed in cohorts with MRI (n = 202) and ultrasound measurements (n = 87). Pain upon thumb base palpation was assessed. Radiographs were scored for CMC-1/STT osteophytes. Synovial thickening, effusion and power Doppler signal in CMC-1 joints were assessed with ultrasound. MRIs were scored for synovitis and bone marrow lesions (BMLs) in CMC-1 and STT joints using OMERACT-TOMS. Associations between ultrasound/MRI features, osteophytes, and thumb base pain were assessed. Interaction between MRI features and osteophytes was explored. RESULTS: In 289 patients (mean age 60.2, 83% women) 139/376 thumb bases were painful. Osteophyte presence was associated with pain (MRI cohort: odds ratio (OR) 5.1 (2.7-9.8)). Ultrasound features were present in 25-33% of CMC-1 joints, though no associations were seen with pain. MRI-synovitis and BMLs grade ≥2 were scored in 25% and 43% of thumb bases, and positively associated with pain (OR 3.6 (95% CI 1.7-7.6) and 3.0 (1.6-5.5)). Associations attenuated after adjustment for osteophyte presence. Combined presence of osteophytes and MRI-synovitis had an additive effect. CONCLUSIONS: Ultrasonographic and MRI inflammatory features were often present in the thumb base. Osteophytes were more strongly associated with thumb base pain than inflammatory features, in contrast to findings in finger OA studies, supporting thumb base osteoarthritis as a distinct phenotype.

Virological and Social Outcomes of HIV-Infected Adolescents and Young Adults in The Netherlands Before and After Transition to Adult Care.

BACKGROUND: As a result of effective combination antiretroviral therapy (cART) and advanced supportive healthcare, a growing number of human immunodeficiency virus (HIV)-infected children survive into adulthood. The period of transition to adult care is often associated with impaired adherence to treatment and discontinuity of care. We aimed to evaluate virological and social outcomes of HIV-infected adolescents and young adults (AYAs) before and after transition, and explore which factors are associated with virological failure. METHODS: We included 59 HIV-infected AYAs from the Netherlands who had entered into pediatric care and transitioned from pediatric to adult healthcare. We used HIV RNA load and cART data from the Dutch Stichting HIV Monitoring database (1996-2014), and collected social and treatment data from patients' medical records from all Dutch pediatric HIV treatment centers and 14 Dutch adult treatment centers involved. We evaluated risk factors for virological failure (VF) in a logistic regression model adjusted for repeated measurements. RESULTS: HIV VF occurred frequently during the study period (14%-36%). During the transition period (from 18 to 19 years of age) there was a significant increase in VF compared with the reference group of children aged 12-13 years (odds ratio, 4.26 [95% confidence interval, 1.12-16.28]; P = .03). Characteristics significantly associated with VF were low educational attainment and lack of autonomy regarding medication adherence at transition. CONCLUSIONS: HIV-infected AYAs are vulnerable to VF, especially during the transition period. Identification of HIV-infected adolescents at high risk for VF might help to improve treatment success in this group.

Soluble CD27 induces IgG production through activation of antigen-primed B cells.

OBJECTIVES: High levels of soluble CD27 (sCD27), a marker of immune activation, are found in several infectious [including human immunodeficiency virus type-I (HIV-1)] and autoimmune diseases; however, a direct biological effect of sCD27 on B cells has not been established. The aim of this study was to investigate whether sCD27, by binding to CD70, can induce immunoglobulin G (IgG) production from B cells. METHODS: B cells from healthy and HIV-1-infected individuals were cultured with recombinant human sCD27 (rhsCD27), and IgG production was measured. The role of rhsCD27 in inducing the expression of transcription factors involved in plasma cell differentiation was evaluated. Furthermore, we investigated the impact of different cytokines on the modulation of CD70 expression on B cells and the relationship between levels of IgG and sCD27 in serum from healthy and HIV-1-infected individuals. RESULTS: We demonstrated that rhsCD27 induced IgG production from antigen-primed (CD27+) B cells. This effect was mediated by rhsCD27 binding to CD70 on B cells leading to activation of Blimp-1 and XBP-1, transcription factors associated with plasma cell differentiation. We found a significant correlation between levels of serum sCD27 and IgG in HIV-1-infected individuals and healthy controls. CONCLUSIONS: sCD27 may act to enhance immunoglobulin production and differentiation of activated memory or recently antigen-experienced B cells, thus providing an activation signal to antigen-experienced B cells. This mechanism may operate during autoimmune and chronic infectious diseases, situations in which continuous immune activation leads to upregulation of CD70 expression and increased sCD27 cleavage.

Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis.

Risk stratification-based duration of trimethoprim-sulfamethoxazole (TMP-SMX) chemoprophylaxis to prevent Pneumocystis pneumonia (PCP) in kidney transplant recipients is not a universally adapted strategy and supporting evidence-based sources are limited. We performed a large retrospective study to identify risk factors for PCP in kidney transplant recipients and to define parameters for use in clinical prophylaxis guidelines. Fifty consecutive patients with confirmed PCP and 2 time-matched controls per case were enrolled. All patients were participants of the kidney transplantation program of the Leiden University Medical Center, a tertiary care hospital in the Netherlands. Potential risk factors were compared between groups by uni- and multivariate matched analyses. At transplantation, age >55 years (adjusted odds ratio [OR] 2.7, 95% confidence interval [CI] 1.3-5.9) and not receiving basiliximab induction therapy (adjusted OR 4.3, 95% CI 1.1-17.1) predicted development of PCP. In the final multivariate analysis, only cytomegalovirus infection (adjusted OR 3.0, 95% CI 1.2-7.9) and rejection treatment (adjusted OR 5.8, 95% CI 1.9-18) were found to be independently associated with PCP. Using the variables identified by the multivariate analyses, effects of different hypothetical chemoprophylaxis strategies were systematically evaluated. Exploring different scenarios showed that chemoprophylaxis in the first 6 months for all renal transplant patients - and during the first year posttransplantation for patients >55 years of age or those treated for rejection - would result in very low PCP incidence and optimal avoidance of TMP-SMX toxicity. The results provide a rationale for further prospective study on targeted provision of chemoprophylaxis to prevent PCP in kidney transplant patients.

Residual type 1 immunity in patients genetically deficient for interleukin 12 receptor beta1 (IL-12Rbeta1): evidence for an IL-12Rbeta1-independent pathway of IL-12 responsiveness in human T cells.

Genetic lack of interleukin 12 receptor beta1 (IL-12Rbeta1) surface expression predisposes to severe infections by poorly pathogenic mycobacteria or Salmonella and causes strongly decreased, but not completely abrogated, interferon (IFN)-gamma production. To study IL-12Rbeta1-independent residual IFN-gamma production, we have generated mycobacterium-specific T cell clones (TCCs) from IL-12Rbeta1-deficient individuals. All TCCs displayed a T helper type 1 phenotype and the majority responded to IL-12 by increased IFN-gamma production and proliferative responses upon activation. This response to IL-12 could be further augmented by exogenous IL-18. IL-12Rbeta2 was found to be normally expressed in the absence of IL-12Rbeta1, and could be upregulated by IFN-alpha. Expression of IL-12Rbeta2 alone, however, was insufficient to induce signal transducer and activator of transcription (Stat)4 activation in response to IL-12, whereas IFN-alpha/IFN-alphaR ligation resulted in Stat4 activation in both control and IL-12Rbeta1-deficient cells. IL-12 failed to upregulate cell surface expression of IL-18R, integrin alpha6, and IL-12Rbeta2 on IL-12Rbeta1-deficient cells, whereas this was normal on control cells. IL-12-induced IFN-gamma production in IL-12Rbeta1-deficient T cells could be inhibited by the p38 mitogen-activated protein kinase (MAP) kinase inhibitor SB203580 and the MAP kinase kinase (MEK) 1/2 inhibitor U0126, suggesting involvement of MAP kinases in this alternative, Stat4-independent, IL-12 signaling pathway.Collectively, these results indicate that IL-12 acts as a partial agonist in the absence of IL-12Rbeta1. Moreover, the results reveal the presence of a novel IL-12Rbeta1/Stat4-independent pathway of IL-12 responsiveness in activated human T cells involving MAP kinases. This pathway is likely to play a role in the residual type 1 immunity in IL-12Rbeta1 deficiency.

Potential influence of more-sensitive HIV-1 load detection by the new Roche Cobas AmpliPrep/Cobas TaqMan version 2.0 assay on clinical management of HIV-positive pregnant women.

With the introduction of the new Roche Cobas AmpliPrep/Cobas TaqMan version 2.0 assay, HIV-1 viral loads will be detected more frequently during the peripartum period in pregnant HIV-positive women. The implications for the clinical management of these patients are discussed in this paper.

Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients.

Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell (TH1) responses and interferon-gamma (IFN-gamma) production. IL-12 binds to high-affinity beta1/beta2 heterodimeric IL-12 receptor (IL-12R) complexes on T cell and natural killer cells. Three unrelated individuals with severe, idiopathic mycobacterial and Salmonella infections were found to lack IL-12Rbeta1 chain expression. Their cells were deficient in IL-12R signaling and IFN-gamma production, and their remaining T cell responses were independent of endogenous IL-12. IL-12Rbeta1 sequence analysis revealed genetic mutations that resulted in premature stop codons in the extracellular domain. The lack of IL-12Rbeta1 expression results in a human immunodeficiency and shows the essential role of IL-12 in resistance to infections due to intracellular bacteria.

The effect of anti-tumour necrosis factor alpha treatment on the antibody response to influenza vaccination.

OBJECTIVES: The effect of anti-tumour necrosis factor (TNF) therapy on the antibody responses to vaccines is the subject of ongoing debate. Therefore, we investigated the effect of the three currently available anti-TNF agents on influenza vaccination outcomes in a patient population with long-standing disease. METHODS: In a prospective cohort study, we assessed the antibody response upon influenza vaccination in 112 patients with long-standing autoimmune disease treated with immunosuppressive medication either with anti-TNF (etanercept, adalimumab or infliximab; n = 64) or without anti-TNF (n = 48) and a control group of 18 healthy individuals. Antibody responses were determined by haemagglutination inhibition assay, before and 4 weeks after vaccination. RESULTS: The proportion of individuals with a protective titre (>or=40) after vaccination was large (80-94%) and did not significantly differ between the three groups. Post-vaccination geometric mean antibody titres against influenza (A/H3N2 and B) were significantly lower in the 64 patients treated with anti-TNF compared with the 48 patients not receiving anti-TNF, and the healthy controls. CONCLUSIONS: The antibody response to influenza vaccination in patients treated with anti-TNF is only modestly impaired. The proportion of patients that achieves a protective titre is not significantly diminished by the use of TNF blocking therapies.

[Practical advice for travellers with immune disorders]. / Praktische adviezen voor reizigers met een afweerstoornis.

For patients with immune disorders, the risk of infection during travel depends on the cause and severity of the immune disorder and the type of travel. Immunocompromised travellers experience more severe effects of illness than those without immune disorders. Some risks can be reduced or avoided by taking adequate precautions and, in some cases, modifying travel plans. Ensuring adequate medication use during the trip requires careful planning prior to travel. Regarding vaccination, immunocompromised travellers may have an impaired ability to generate antibodies; live attenuated vaccines are often contraindicated. The treating physician must take a proactive role when an immunocompromised patient indicates that he or she plans to travel. Protocols developed by the Dutch National Coordination Centre for Travellers Health (LCR) provide practical advice regarding a number of situations. Provided that they are given proper individualised advice, there is little concrete evidence to suggest that these patients should not travel anywhere they wish.

[Twenty years of combination antiretroviral therapy for HIV infection in the Netherlands: progression and new challenges]. / 20 jaar hiv-combinatietherapie in Nederland.

Due to the introduction of combination antiretroviral therapy (cART) 20 years ago, HIV infection in the Netherlands has changed from a fatal disease to a chronic condition with a near normalized life expectancy. The average age of HIV-positive patients continues to increase, as does the prevalence of non-HIV-related comorbidity. The number of new HIV diagnoses seems to be decreasing in the Netherlands, which is partly due to increased testing, earlier diagnosis, prompt cART initiation, and achievement of high levels of viral suppression, resulting in a reduced likelihood of onward transmission. In order to further curb the epidemic, it is important that as yet undiagnosed people living with HIV are identified as soon as possible. All practicing physicians in the Netherlands can contribute to this goal.

Acute hepatitis C in the Netherlands: characteristics of the epidemic in 2014.

Within the Dutch Acute HCV in HIV Study, a surveillance system was initiated to estimate the incidence of hepatitis C virus (HCV) infections in 2014. Following the Dutch HIV treatment guidelines, HIV-positive men having sex with men (MSM) in 19 participating centers were screened. Ninety-nine acute HCV infections were reported, which resulted in a mean incidence of 11 per 1000 patient-years of follow-up. Unfortunately, the HCV epidemic among Dutch HIV-positive MSM is not coming to a halt.

Pneumocystis carinii pneumonia in patients without AIDS, 1980 through 1993. An analysis of 78 cases.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) occurs in immunocompromised patients without the acquired immunodeficiency syndrome (AIDS). There has been an increasing yearly number of cases of PCP in our patients without AIDS. OBJECTIVE: To determine the nature of the underlying disorder and previous immunosuppressive treatment in patients with PCP without AIDS. METHOD: A study of the charts of 78 such patients admitted to our hospital from 1980 through 1993. RESULTS: The number of PCP cases per year increased during the period studied. All patients had an underlying disorder, either hematologic malignancy (49%), solid organ tumor (4%), vasculitis or other immunologic disorder (22%), or they had undergone renal transplantation (17%) or bone marrow transplantation (9%). Previous immunosuppressive medication consisted of prednisone or other corticosteroids in 72 (92%) of 78 patients, cytotoxic drugs in 55 (71%) of 78 patients, both in 50 (64%) of 78 patients, and none in one patient. Quantification of previous corticosteroid treatment showed a large variability among patients. The overall mortality rate for patients was 35% (27/78). Mortality was significantly higher in patients with a concomitant pulmonary infection (P = .01), an underlying disorder other than that which resulted in renal transplantation (P = .03), mechanical ventilation (P < .001), previous chemotherapy (P = .04), as well as previous cyclophosphamide treatment (P = .01). A trend toward a higher mortality in patients with previous corticosteroid use was detected (P = .06). CONCLUSION: Pneumocystis carinii pneumonia may complicate a variety of immunocompromised states, with considerable mortality. Pneumocystis carinii pneumonia occurred at all levels of immunosuppression; no threshold level could be defined.

Low mother-to-child-transmission rate of Hepatitis C virus in cART treated HIV-1 infected mothers.

BACKGROUND: Maternal transmission is the most common cause of HCV infection in children. HIV co-infection and high levels of plasma HCV-RNA have been associated with increased HCV transmission rates. OBJECTIVES: We assessed the vertical HCV transmission rate in the HIV-HCV co-infected group of pregnant women on cART. STUDY DESIGN: We conducted a retrospective study in a Dutch cohort of HIV-positive pregnant women and their children. We identified co-infected mothers. Results of the HCV tests of the children were obtained. RESULTS: All 21 women were on cART at the time of delivery. We analyzed data of the 24 live-born children at risk for mother-to-child transmission (MTCT) of HCV between 1996 and 2009. HIV-RNA was <500 copies/ml during 18/24 [75%] deliveries, the median CD4(+) cell count was 419 cells/µl (290-768). There was no transmission of HIV. The median plasma HCV-RNA in our cohort of 23 non-transmitting deliveries in 21 women was 3.5×10E5 viral eq/ml (IQR 9.6×104-1.5×106veq/mL). One of 24 live-born children was found to be infected with HCV genotype 1. At the time of delivery the maternal plasma HIV-RNA was <50 copies/ml, the CD4(+) cell count was 160 cells/µl and maternal plasma HCV-RNA was 4.6×10E6 veq/ml. This amounted to a prevalence of HCV-MTCT of 4%. CONCLUSION: In this well-defined cohort of HIV-HCV co-infected pregnant women, all treated with cART during pregnancy, a modest rate of vertical HCV transmission was observed.

Antibody response to influenza, tetanus and pneumococcal vaccines in HIV-seropositive individuals in relation to the number of CD4+ lymphocytes.

OBJECTIVE: To establish when the formation of antibodies against T-lymphocyte-dependent and -independent antigens is impaired during HIV infection. DESIGN: Prospective study on antibody formation before and 30 days and 60 days after vaccination with tetravalent influenza vaccine, tetanus toxoid and pneumococcal vaccine; booster with influenza vaccine was administered 30 days after initial vaccination. SETTING: Outpatient clinic of University Hospital Leiden. PARTICIPANTS: Fifty-one HIV-infected individuals and 10 healthy controls. RESULTS: In HIV-infected individuals with < 100 x 10(6)/l CD4+ lymphocytes almost no influenza antibodies were formed; CD4+ counts between 100 and 300 x 10(6)/l correlated with suboptimal antibody formation; CD4+ counts > or = 300 x 10(6)/l yielded more individuals with protective antibody titres. Thirty days after vaccination, protective antibody titres against the four influenza strains had been achieved in 24% of all HIV-infected individuals for A/Beijing (H3N2) (controls, 90%), 59% for A/Taiwan (H1N1) (controls, 80%), 18% for B/Beijing (controls, 30%) and 37% for B/Panama (controls 90%). Booster vaccination after 1 month did not increase antibody levels. Anti-tetanus toxin antibody formation, which is also T-lymphocyte-dependent, was correlated with the number of CD4+ lymphocytes. After pneumococcal vaccination (T-lymphocyte-independent), normal antibody formation was observed in HIV-infected individuals, including those with low CD4+ counts. CONCLUSIONS: Influenza vaccination should not be administered to HIV-infected individuals with CD4+ counts < 100 x 10(6)/l; pneumococcal vaccination can be offered to all HIV-infected individuals and a tetanus toxoid booster should be administered when indicated.