Severe immunosuppression is related to poorer immunogenicity to SARS-CoV-2 vaccines among people living with HIV

ObjectivesThe aim of this study was to assess the immunogenicity of SARS-CoV-2 available vaccines among people living with HIV (PLWH) after a complete vaccination scheme, and determine predictors of seroconversion.MethodsThis multicentre prospective cohort study included 420 PLWH who had received a standard immunization, either with mRNA or adenoviral-vectored COVID-19 vaccines. Antibody response was evaluated within 1 to 2 months after the last dose of the vaccine with a quantitative determination of antitrimeric spike protein-specific IgG antibodies and IgG neutralizing antibodies.ResultsOverall, 384 of 420 PLWH (91%) showed antibody response to vaccination. Seroconversion was observed in 308 of 326 individuals with cluster of differentiation 4 (CD4) counts ≥350 cells/mm³ (95%), 55 of 61 PLWH with 200 to 349 cells/mm³ (90%), and 21 of 33 PLWH with CD4 counts <200 cells/mm³ (64%; p < 0.001). The median log₁₀ IgG neutralization levels were 2.4 IU/mL (Q1–Q3, 1.0–3.1) among PLWH with CD4 counts <200 cells/mm³, 3.1 IU/mL (Q1–Q3, 2.8–3.4) for the 200 to 349 cells/mm³ group, and 3.1 IU/mL (Q1–Q3, 2.7–3.4) for PLWH with CD4 counts ≥350 cells/mm³ (p = 0.016). In the multivariate analysis, CD4 counts ≥350 cells/mm³ (OR: 7.10; 95% CI, 1.91–26.46; p = 0.004) and receiving mRNA-vectored COVID-19 vaccines (OR: 8.19; 95% CI, 3.24–20.70; p ≤ 0.001) were independently associated with a higher probability of response to vaccination.DiscussionHIV-related immunosuppression impairs the antibody response to SARS-CoV-2 vaccines. Specific vaccination schemes should be urgently tailored in this setting, particularly in patients with CD4 cell counts <200 cells/μL. Adenoviral-vectored vaccines should be avoided in PLWH whenever possible.     

A risk score for identifying patients at a low risk of bacterial meningitis amongst adults with cerebrospinal fluid leucocytosis and a negative gram stain result: a derivation and validation study

ObjectivesWe aimed to derive and validate a risk score to differentiate patients with bacterial meningitis from those with viral meningitis or encephalitis amongst patients presenting with cerebrospinal fluid (CSF) leucocytosis and a negative Gram staining result.MethodsWe included adults with bacterial and viral meningitis or encephalitis presenting with CSF leukocyte counts of >10 per mm³ and a negative Gram staining result from cohorts in Houston, Texas (2004–2019), and the Netherlands (2012–2021). Derivation and the first validation were performed in the American patients and further validation in the Dutch patients.ResultsDerivation was performed in 109 American patients with bacterial meningitis (median age, 56 years; interquartile range [IQR], 46–66 years; 46% women) and 194 with viral meningitis or encephalitis (median age, 46 years; IQR, 33–60 years; 53% women). Serum leukocyte counts of >10.0 × 10⁹/L, CSF leukocyte counts of >2000 per mm³, granulocyte counts of >1180 per mm³, protein levels of >2.2 g/L, glucose levels of <1.9 mmol/L and fever on admission were included in the risk score, which was dichotomized into ‘low risk’ (0 present) and ‘high risk’ (>0 present). The first validation showed a sensitivity of 100% (95% CI, 96.6–100) and specificity of 34.0% (95% CI, 27.4–41.2). Further validation in 262 Dutch patients with bacterial meningitis (median age, 57 years; IQR 44–70 years; 45% women) and 68 with viral meningitis (median age, 34 years; IQR, 28–45 years; 60% women) showed a sensitivity of 99.6% (95% CI, 97.9–100) and specificity of 41.2% (95% CI, 29.4–53.7).ConclusionsOur risk score may be able to rule out bacterial meningitis amongst patients presenting with CSF leucocytosis and a negative Gram staining result. However, it needs prospective testing prior to clinical implementation.     

Improvement of pneumococcal pneumonia diagnosis using quantitative real-time PCR targeting lytA in adult patients: a prospective cohort study

ObjectivesThe aim of the study was to assess the performance of real-time PCR targeting the lytA gene (rtPCR-lytA) in plasma, urine and nasopharyngeal (NP) samples for the diagnosis of pneumococcal community-acquired pneumonia (P-CAP).MethodsProspective observational study including all consecutive adults with CAP from November 2015 to May 2017. P-CAP was defined if pneumococcus was identified using conventional methods (CM) and/or a positive rtPCR-lytA was detected in blood, urine or NP samples (NP cut-off ≥8000 copies/mL). Diagnostic performance of each test was calculated.ResultsA total of 133 individuals with CAP were included. Of these, P-CAP was diagnosed in 62 (46.6%). The proportion of P-CAP diagnosed by rtPCR-lytA methods was significantly higher than that diagnosed by CM (87.1% versus 59.7%, p 0.005). The rtPCR-lytA identified Streptococcus pneumoniae in 25 patients (40.3% of all individuals with P-CAP) whose diagnosis would have been missed by CM. NP-rtPCR-lytA allowed diagnosis of 62.3% of P-CAP. A nasopharyngeal colonization density ≥2351 copies/mL predicted P-CAP diagnosis (area under the curve = 0.82, sensitivity 83.3%, specificity 80.9%). There was a positive correlation between increasing bacterial load in blood and CURB-65 score (Spearman correlation coefficient r = 0.4, p 0.001), pneumonia severity index (r = 0.3, p 0.02) and time to clinical stability (r = 0.33, p 0.01). Median bacterial load in blood was higher in P-CAP patients with bacteraemia (0.65 × 10³ versus 0 × 10³ copies/mL, p 0.002), intensive care unit admission (0.68 × 10³ versus 0 × 10³ copies/mL, p 0.04) or mechanical ventilation (7.45 × 10³ versus 0 × 10³ copies/mL, p 0.04).ConclusionsThe use of rtPCR-lytA methods significantly increased the diagnosis of P-CAP compared with CM. Nasopharyngeal swabs rtPCR-lytA detection, with an accurate cut-off value, was the most promising among molecular methods for the diagnosis of P-CAP.     

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.     

HIV-associated DLBCL: Clinicopathological factors including dual-colour chromogenic in situ hybridisation to assess MYC gene copies

IntroductionDiffuse large B-cell lymphoma (DLBCL) comprises up to 43% of non-Hodgkin lymphomas in South Africa due to the high seroprevalence of human immunodeficiency virus (HIV) infection in the southern African region. We explored the prognostic influence of an array of clinicopathological factors, including MYC gene copy numbers, within HIV-associated DLBCL.MethodsThe retrospective inclusion of 123 tumours was followed by c-MYC immunohistochemistry and dual-colour MYC and centromere 8 (CEN8) chromogenic in situ hybridisation on formalin-fixed paraffin-embedded sections. Clinicopathological data were collected, interpreted and analysed.ResultsHIV seropositive patients comprised 81% (93/115), mean age 42 (SD 10.8) years, with 55% males, HIV negative patients comprised 19% (22/115), mean age 57 (SD 16.7) years (p = 0.001), with 59% males and the HIV status was unknown for 8 patients. The median CD4 count was 162 (IQR 215) cells/mm³, 33% of patients presented with CD4 counts <100 cells/mm³ and the median viral load was 217 (IQR 182 981) copies/mL. There was advanced stage at presentation (i.e., III-IV, 87%), with Ki-67 proliferation indices ≥90% in 85%- and c-MYC expression (i.e., ≥40%) in 58% of tumours. Double expression of c-MYC and BCL2 was associated with a non-germinal center immunophenotype (p < 0.01). Low-level increase of MYC gene copy numbers and MYC rearrangements occurred in 57% and 12%, respectively. C8 polysomy, MYC gene clusters and concurrent MYC rearrangement/increased MYC gene copies were also detected. Inferior median overall survival (OS) occurred when the CD4 counts were <100 cells/mm³ (149 days 95% CI 44-254, p 0,04) and when IPI scores were 3–5 [155 days (95% CI 37–273), p = 0.01]. Concomitant infections negatively impacted the survival outcome, multivariate regression analysis (HR 4.01, 95% CI 1.86–12.20, p = 0.02).Conclusionc-MYC protein expression, low-level increase in MYC gene copy numbers, rearrangement, C8 polysomy, MYC gene clusters and concurrent MYC rearrangement/low-level gains are present in HIV+ DLBCL. CD4 counts < 100 cells/mm³, IPI scores 3-5 and concomitant infections negatively impact the survival outcome.     

Progression to AIDS or Death as Endpoints in HIV Clinical Trials

Abstract

Purpose: To assess progression to AIDS or death from month 4 after a protease inhibitor-containing regimen is initiated in a cohort of 1,281 patients. Method: We used Kaplan-Meier estimates of probability of clinical progression. RESULT: At month 4, most patients had an HIV-1 RNA plasma value below 500 copies/mL (78%) and a CD4 cell count above 300 cells/mm³ (62%). Starting from month 4, clinical progression at 1 and 2 years of follow-up was low (<3% at 1 year) in patients with HIV RNA <500 copies/mL or 500-10,000 copies/mL and in patients with CD4 between 50 and 300 cells/mm³ or >300 cells/mm³. A higher risk of clinical progression (10% at 1 year) was evidenced only in patients with poor response to antiretroviral therapy, that is, with CD4 <50 cells/mm³ or CD4 between 50-300 cells/mm³ together with an HIV RNA >10,000 copies/mL. Conclusion: In patients currently on antiretroviral therapy, clinical trials with clinical progression as endpoint are almost not feasible, except in patients with a poor immunovirological response to first- or second-line HAART.     

Elevated plasma YKL-40 and risk of infectious disease: a prospective study of 94665 individuals from the general population

ObjectivesYKL-40 is an acute phase protein elevated in patients with infectious and inflammatory diseases. We tested the hypothesis that baseline elevated YKL-40 is associated with increased risk of future infectious disease in healthy individuals in the general population.MethodsWe prospectively followed 94 665 individuals from the Danish general population for up to 23 years and analysed for plasma YKL-40 levels (n = 21 584) and CHI3L1 rs4950928 genotype (n = 94 184). Endpoints were any infection, bacterial pneumonia, urinary tract infection, skin infection, sepsis, diarrhoeal disease, and other infections.ResultsFor YKL-40 percentile category 91–100% versus 0–33%, the multifactorially and C-reactive protein (CRP) adjusted hazard ratios were 1.71 (95% confidence interval 1.50–1.96; p 4 × 10⁻¹⁴) for any infection, 1.97 (1.64–2.37; p 4 × 10⁻¹³) for bacterial pneumonia, 1.62 (1.24–2.11; p 0.002) for urinary tract infection, 1.74 (1.31–2.32; p 2 × 10⁻⁴) for skin infection, 1.76 (1.25–2.46; p 0.004) for sepsis, 1.90 (1.29–2.78; p 0.002) for diarrhoeal disease and 2.71 (1.38–5.35; p 0.01) for other infections. In multifactorially and CRP-adjusted models, a twofold increase in YKL-40 was associated with increased risk of all infectious disease endpoints. Mendelian randomization did not support causality, as CHI3L1 rs4950928 was associated with 94% and 190% higher YKL-40 levels (for CG and CC versus GG genotype), but not with increased risk of any infectious disease endpoint.DiscussionBaseline elevated plasma YKL-40 was not a cause but a strong marker of increased risk of future infectious diseases in individuals in the general population.     

Sickle cell anemia: Intracranial stenosis and silent cerebral infarcts in children with low risk of stroke

Purpose:Children with sickle cell anemia (SCA), who have mean blood flow velocities <170 cm/s in the terminal internal carotid (tICA) or middle cerebral (MCA) arteries on transcranial Doppler ultrasonography (TCD), are considered to be at low risk of stroke. The prevalence of intracranial stenosis, which raises the risk of stroke, is not known in these children. Here, we estimated the prevalence of stenosis and explored its association with silent cerebral infarcts determined based on Magnetic Resonance (MR) scans.Patients/methodsWe studied prospectively a cohort of 67 children with SCA without prior clinically overt stroke or TIA (median age 8.8 years; range limits 2.3–13.1 years; 33 females) and with TCD mean velocity <170 cm/s. They underwent MR imaging of the brain and MR angiography of intracranial arteries.ResultsIn 7 children (10.5%, 95% CI: 4.9–20.3%) we found 10 stenoses, including 4 with isolated left tICA stenosis and 3 with multiple stenoses. We found silent infarcts in 26 children (37.7%, 95% CI: 27.2–49.5%). The median number of infarcts in an affected child was 2 (range limits: 1–9), median volume of infarcts was 171 mm³ (range limits: 7–1060 mm³), and median infarct volume in relation to total brain volume was 0.020% (range limits: 0.001–0.101%). The number and volume of infarcts were significantly higher in children with arterial stenosis (both p = 0.023).ConclusionsThe prevalence of intracranial arterial stenosis in children with SCA classified as at low risk of stroke by TCD mean velocity <170 cm/s is high. Children with stenosis are at higher risk of brain parenchymal injury as they have more silent cerebral infarcts.     

Association of age and gender with Torque teno virus detection in stools from diarrheic and non-diarrheic people

BackgroundTorque teno virus (TTV) is a small virus belongs to Anelloviridea family. TTV is a disease orphan virus but it has often been associated with a variety of pathologies and co-infections. TTV was recently identified as an infectious agent that could potentially be involved in cases of acute enteritis.ObjectivesTo ascertain the presence of TTV in stools from diarrheic and not diarrheic people, and to investigate an association between infection, and patient age and gender.Study designStool samples from people exhibiting signs of enteritis (954) and from non-diarrheic individuals (76) were collected in the former Chinook Health Region (CHR) in Southwestern Alberta, Canada from May 2008 to April 2009. Viral genetic material was extracted, and detection and quantification of TTV were carried out by real-time PCR. The presence of other viral and bacterial enteric pathogens was also investigated.ResultsMore (P < 0.001) diarrheic people (38.8%) tested positive for TTV DNA than non-diarrheic individuals (18.4%). Furthermore, viral load was greater (P < 0.001) in stools from diarrheic (2.0 × 10⁷ copies/g) than non-diarrheic (2.0 × 10³ copies/g) people. TTV DNA was detected most often in diarrheic individuals that were 0–5 (57.3%) and greater than 81 (59.0%) years of age. Combined across age, the prevalence of TTV was higher among men than women (P = 0.003). Co-infections with other enteric pathogens were observed.ConclusionsThis study revealed a significant association between TTV prevalence and viral load, and enteritis. Also, TTV prevalence was significantly higher in the very young and elderly suggesting that immunological status is important.     

Increased expression of the intercellular adhesion molecule-1 (ICAM-1) on peripheral blood neutrophils in acute pancreatitis

PurposeConsidering the important role of neutrophils’ activation in the pathogenesis of acute pancreatitis (AP), the aim of our study was to evaluate the expression of leukocytes’ adhesion molecules in patients with AP.Patients/methodsThirty-five patients (16 women and 19 men; age 32–77 years, median 56 years) with AP were prospectively included into our study. The absolute number of leukocytes was estimated by haematologic analyser. Surface neutrophils antigens (CD) were assayed by the direct fluorescence method for whole blood, using a flow cytometer.ResultsAt the day 1, significant increase of ICAM-1 expression was found in patients with severe AP (S-AP) (7280 mm⁻³ vs 2850 mm⁻³ in healthy control; p < 0.05). In the days 2, 3 and 5 it sharply decreased and peaked again to 4860 mm⁻³ at the day 10. In patients with mild AP (M-AP), not significant elevation of ICAM-1 quickly returned to normal level. In both forms of AP, neutrophil CD62L (L-selectin) expression reached the highest level at the day 1 (8800 mm⁻³ and 9020 mm⁻³, respectively in M-AP and S-AP, in comparison to 3400 mm⁻³ in control; p < 0.05). Expression of CD69 (neutrophils’ marker of early activation) significantly increased in both M-AP and S-AP.ConclusionsWe have found an early and significant increase of peripheral blood neutrophil CD54/ICAM-1 expression, specific for S-AP but not for M-AP. It may provide a good marker predicting severe course of pancreatitis.     

Neurological manifestations in COVID-19 patients and their application in predicting fatal disease: A retrospective cohort study

BackgroundTo explore the development of central nervous system (CNS) symptoms and clinical application in predicting the clinical outcomes of SARS-COV-2 patients.MethodsA retrospective cohort study was performed on the hospitalized patients with SARS-COV-2 recruited from four hospitals in Hubei Province, China from 18 January to 10 March 2020. The patients with CNS symptoms were determined. Data regarding clinical symptoms and laboratory tests were collected from medical records.ResultsOf 1268 patients studied, 162 (12.8%) had CNS symptoms, manifested as unconsciousness (71, 5.6%), coma (69, 5.4%), dysphoria (50, 3.9%), somnolence (34, 2.7%) and convulsion (3, 0.2%), which were observed at median of 14 (interquartile range 9–18) days after symptom onset and significantly associated with older age (OR = 5.71, 95% confidence interval [CI] 2.78–11.73), male (OR = 1.73, 95% CI 1.22–2.47) and preexisting hypertension (OR = 1.78, 95% CI 1.23–2.57). The presence of CNS symptoms could be predicted by abnormal laboratory tests across various clinical stages, including by lymphocyte counts of <0.93 × 10⁹/L, LDH≥435 U/L and IL-6≥28.83 pg/L at 0–10 days post disease; by lymphocyte count<0.86 × 10⁹/L, IL-2R ≥ 949 U/L, LDH≥382 U/L and WBC≥8.06 × 10⁹/L at 11–20 days post disease. More patients with CNS symptoms developed fatal outcome compared with patients without CNS symptoms (HR = 33.96, 95% CI 20.87–55.16).ConclusionNeurological symptoms of COVID-19 were related to increased odds of developing poor prognosis and even fatal infection.     

Design of a Mechanobioreactor to Apply Anisotropic,Biaxial Strain to Large Thin Biomaterials for Tissue Engineered Heart Valve Applications

Repair and replacement solutions for congenitally diseased heart valves capable of post-surgery growth and adaptation have remained elusive. Tissue engineered heart valves (TEHVs) offer a potential biological solution that addresses the drawbacks of existing valve replacements. Typically, TEHVs are made from thin, fibrous biomaterials that either become cell populated in vitro or in situ. Often, TEHV designs poorly mimic the anisotropic mechanical properties of healthy native valves leading to inadequate biomechanical function. Mechanical conditioning of engineered tissues with anisotropic strain application can induce extracellular matrix remodelling to alter the anisotropic mechanical properties of a construct, but implementation has been limited to small-scale set-ups. To address this limitation for TEHV applications, we designed and built a mechanobioreactor capable of modulating biaxial strain anisotropy applied to large, thin, biomaterial sheets in vitro. The bioreactor can independently control two orthogonal stretch axes to modulate applied strain anisotropy on biomaterial sheets from 13 × 13 mm² to 70 × 40 mm². A design of experiments was performed using experimentally validated finite element (FE) models and demonstrated that biaxial strain was applied uniformly over a larger percentage of the cell seeded area for larger sheets (13 × 13 mm²: 58% of sheet area vs. 52 × 31 mm²: 86% of sheet area). Furthermore, bioreactor prototypes demonstrated that over 70% of the cell seeding area remained uniformly strained under different prescribed protocols: equibiaxial amplitudes between 5 to 40%, cyclic frequencies between 0.1 to 2.5 Hz and anisotropic strain ratios between 0:1 (constrained uniaxial) to 2:1. Lastly, proof-of-concept experiments were conducted where we applied equibiaxial (ε_x = ε_y = 8.75%) and anisotropic (ε_x = 12.5%, ε_y = 5%) strain protocols to cell-seeded, electrospun scaffolds. Cell nuclei and F-actin aligned to the vector-sum strain direction of each prescribed protocol (nuclei alignment: equibiaxial: 43.2° ± 1.8°, anisotropic: 17.5° ± 1.7°; p < 0.001). The abilities of this bioreactor to prescribe different strain amplitude, frequency and strain anisotropy protocols to cell-seeded scaffolds will enable future studies into the effects of anisotropic loading protocols on mechanically conditioned TEHVs and other engineered planar connective tissues.

     

Causes of fever in Tanzanian adults attending outpatient clinics: a prospective cohort study

ObjectivesExploring fever aetiologies improves patient management. Most febrile adults are outpatients, but all previous studies were conducted in inpatients. This study describes the spectrum of diseases in adults attending outpatient clinics in urban Tanzania.MethodsWe recruited consecutive adults with temperature ≥38°C in a prospective cohort study. We collected medical history and performed a clinical examination. We performed 27 364 microbiological diagnostic tests (rapid tests, serologies, cultures and molecular analyses) for a large range of pathogens on blood and nasopharyngeal samples. We based our diagnosis on predefined clinical and microbiological criteria.ResultsOf 519 individuals, 469 (89%) had a clinically or microbiologically documented infection and 128 (25%) were human immunodeficiency virus (HIV) -infected. We identified 643 diagnoses: 264 (41%) acute respiratory infections (36 (5.6%) pneumonia, 39 (6.1%) tuberculosis), 71 (11%) infections with another focus (31 (4.8%) gastrointestinal, 26 (4.0%) urogenital, 8 (1.2%) central nervous system) and 252 (39%) infections without focus (134 (21%) dengue, 30 (4.7%) malaria, 28 (4.4%) typhoid). Of the 519 individuals, 318 (61%), 179 (34%), 30 (6%) and 15 (3%), respectively, had a viral, bacterial, parasitic and fungal acute infection. HIV-infected individuals had more bacterial infections than HIV-negative (80/122 (66%) versus 100/391 (26%); p < 0.001). Patients with advanced HIV disease had a higher proportion of bacterial infections (55/76 (72%) if CD4 ≤200 cells/mm³ and 25/52 (48%) if CD4 >200 cells/mm³, p 0.02).ConclusionsViral diseases caused most febrile episodes in adults attending outpatient clinics except in HIV-infected patients. HIV status and a low CD4 level strongly determined the need for antibiotics. Systematic HIV screening is essential to appropriately manage febrile patients.     

Detection and characterization of male sex chromosome abnormalities in the UK Biobank study

PurposeThe study aimed to systematically ascertain male sex chromosome abnormalities, 47,XXY (Klinefelter syndrome [KS]) and 47,XYY, and characterize their risks of adverse health outcomes.MethodsWe analyzed genotyping array or exome sequence data in 207,067 men of European ancestry aged 40 to 70 years from the UK Biobank and related these to extensive routine health record data.ResultsOnly 49 of 213 (23%) of men whom we identified with KS and only 1 of 143 (0.7%) with 47,XYY had a diagnosis of abnormal karyotype on their medical records or self-report. We observed expected associations for KS with reproductive dysfunction (late puberty: risk ratio [RR] = 2.7; childlessness: RR = 4.2; testosterone concentration: RR = –3.8 nmol/L, all P < 2 × 10^–8), whereas XYY men appeared to have normal reproductive function. Despite this difference, we identified several higher disease risks shared across both KS and 47,XYY, including type 2 diabetes (RR = 3.0 and 2.6, respectively), venous thrombosis (RR = 6.4 and 7.4, respectively), pulmonary embolism (RR = 3.3 and 3.7, respectively), and chronic obstructive pulmonary disease (RR = 4.4 and 4.6, respectively) (all P < 7 × 10^–6).ConclusionKS and 47,XYY were mostly unrecognized but conferred substantially higher risks for metabolic, vascular, and respiratory diseases, which were only partially explained by higher levels of body mass index, deprivation, and smoking.     

Long-term outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome) enrolled in two prospective trials

The purpose of this study was to assess the outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (EGPA) enrolled in 2 prospective, randomized, open-label clinical trials (1994–2005), with or without Five-Factor Score (FFS)-defined poor-prognosis factors, focusing on survival, disease-free survival, relapses, clinical and laboratory findings, therapeutic responses, and factors predictive of relapse. Forty-four patients with FFS ≥ 1 were assigned to receive 6 or 12 cyclophosphamide pulses plus corticosteroids and the seventy-four with FFS = 0 received corticosteroids alone, with immunosuppressant adjunction when corticosteroids failed. Patients were followed (2005–2011) under routine clinical care in an extended study and data were recorded prospectively. Mean ± SD follow-up was 81.3 ± 39.6 months. Among the 118 patients studied, 29% achieved long-term remission and 10% died. Among the 115 patients achieving a first remission, 41% experienced ≥1 relapses, 26.1 ± 26.8 months after treatment onset, with 57% of relapses occurring when corticosteroid-tapering reached <10 mg/day. Treatment achieved new remissions in >90%, but relapses recurred in 38%. Overall survival was good, reaching 90% at 7 years, regardless of baseline severity. Age ≥65 years was the only factor associated with a higher risk of death during follow-up. The risk of relapse was higher for patients with anti-myeloperoxidase antibodies and lower for those with >3000 eosinophils/mm³. Sequelae remained frequent, usually chronic asthma and peripheral neuropathy. In conclusion, EGPA patients' survival rate is very good when treatment is stratified according to the baseline FFS. Relapses are frequent, especially in patients with anti-myeloperoxidase antibodies and baseline eosinophilia <3000/mm³.     

The influences of time-of-day and sleep deprivation on postural control

The aim of this study was to check the combined and/or dissociated influences of time-of-day and sleep deprivation on postural control. Twenty subjects participated in test sessions which took place at 6:00 am, 10:00 am, 2:00 pm and 6:00 pm either after a normal night’s sleep or after a night of total sleep deprivation. Postural control was evaluated by COP surface area, LFS ratio and Romberg’s index. The results showed that postural control fluctuates diurnally according to three different periods, pronounced by sleep deprivation: (1) at 6:00 am, there was no modification by sleep deprivation; (2) at 10:00 am and 2:00 pm, an interaction effect was observed for COP surface area and LFS ratio after sleep deprivation. Values of COP surface area were significantly higher (P < 0.01) following the night of sleep deprivation than after the normal night’s sleep (139.36 ± 63.82 mm² vs. 221.72 ± 137.13 mm² and 143.78 ± 75.31 mm² vs. 228.65 ± 125.09 mm², respectively); (3) at 6:00 pm, the LFS ratio was higher than during the two other periods (P < 0.001) whereas COP surface area decreased to the level observed at 6:00 am. At this time-of-day, only the LFS ratio was significantly increased (P < 0.05) by the night of sleep deprivation (0.89 ± 0.14 vs. 1.03 ± 0.30). This temporal evolution in postural control does not seem to be related to any deterioration in visual input as Romberg’s index (150.09 ± 97.91) was not modified, regardless of the test session.     

The association of obesity and dengue severity in hospitalized adult patients

BackgroundObesity is associated with unfavorable outcomes for infectious diseases. Most researches exploring the association between nutritional status and dengue severity have focused on pediatric populations, with only few studies assessing adult patients.MethodsAdult patients with laboratory-confirmed dengue admitted to a tertiary hospital in southern Taiwan between 2014 and 2015 were enrolled retrospectively. Demographics, comorbidities, clinical presentation, laboratory findings, and outcomes were obtained from case-record forms. Patients were categorized into obese group and nonobese group. The obese group comprised patients with a body mass index of ≥27.5 kg/m².ResultsA total of 1417 hospitalized patients with dengue were evaluated. The mean age was 57.9 years (range: 18–92 years). The obese and nonobese groups comprised 333 (23.5%) and 1084 (76.5%) patients, respectively. The obese group included more patients with hypertension (85%, p < 0.001), diabetes mellitus (33%, p < 0.001), and congestive heart failure (6.3%, p = 0.049). Multivariate analysis revealed that the obese group had more petechiae (AOR: 1.353, 95% CI: 1.025–1.786, p = 0.033), more dyspnea (AOR: 1.380, 95% CI: 1.015–1.876, p = 0.040), and more severe hepatitis (AOR: 2.061, 95% CI: 1.050–4.048, p = 0.036). The obese group also had higher peak hematocrit values (44.1%, p < 0.001) and lower nadir platelet count (45.3 × 10³/μL, p = 0.049) than the nonobese group.ConclusionIn adult patients with dengue, obese group had more petechiae, dyspnea, severe hepatitis, lower nadir of platelet count, and higher peak hematocrit level. We observed no difference in severe dengue or mortality between obese and nonobese group.     

An observational study on the incidence of tuberculosis among a cohort of HIV infected adults in a setting with low prevalence of tuberculosis

Background: Tuberculosis (TB) remains a main cause of morbidity and mortality among individuals infected with HIV. We investigated the incidence of TB among a cohort of HIV infected patients attending a setting with low TB burden where screening for latent TB infection is not routinely carried out.

Methods: an observational cohort study on HIV-infected adults attending the HIV clinic at Queen Elizabeth Hospital Birmingham, UK between 1 January 2011 and 30 September 2015. Patients with culture-proven TB after HIV diagnosis, or those treated for clinical diagnosis of the infection, were classified as having “active TB”.

Results: 1824 patients were included in the study (5347 patient years of follow up), of whom 21 patients developed TB (16 microbiology confirmed). Of the 666 new HIV diagnoses, six patients developed TB within one month, giving a TB prevalence at the time of HIV diagnosis of 0.9%. The total TB incidence for the remaining 1818 patients was 2.81 cases per 1000 patient years (95% CI: 1.63–4.53). TB incidence was significantly more common among patients with CD4 ≤ 200 cells/mm³ compared to those with CD4 > 500 cells/mm³ (28.2 vs. 1.22 per 1000 patient years, p < 0.001), and in patients with VL ≥ 40 copies/mL compared to <40 copies/mL (8.30 vs. 1.42, p < 0.001).

Conclusion: In settings with low TB prevalence, early start of combined antiretroviral therapy and intensified TB case finding protocols may significantly reduce the incidence of TB.