Hospital-based Prospective Cohort Research Articles

Ageing, exposure to pollution, and interactions between climate change and local seasons as oxidant conditions predicting incident hematologic malignancy at KINSHASA University clinics, Democratic Republic of CONGO (DRC)

BackgroundThe global burden of hematologic malignancy (HM) is rapidly rising with aging, exposure to polluted environments, and global and local climate variability all being well-established conditions of oxidative stress. However, there is currently no information on the extent and predictors of HM at Kinshasa University Clinics (KUC), DR Congo (DRC). This study evaluated the impact of bio-clinical factors, exposure to polluted environments, and interactions between global climate changes (EL Nino and La Nina) and local climate (dry and rainy seasons) on the incidence of HM.MethodsThis hospital-based prospective cohort study was conducted at Kinshasa University Clinics in DR Congo. A total of 105 black African adult patients with anaemia between 2009 and 2016 were included. HM was confirmed by morphological typing according to the French-American-British (FAB) Classification System. Gender, age, exposure to traffic pollution and garages/stations, global climate variability (El Nino and La Nina), and local climate (dry and rainy seasons) were potential independent variables to predict incident HM using Cox regression analysis and Kaplan Meier curves.ResultsOut of the total 105 patients, 63 experienced incident HM, with an incidence rate of 60%. After adjusting for gender, HIV/AIDS, and other bio-clinical factors, the most significant independent predictors of HM were age ≥ 55 years (HR = 2.4; 95% CI 1.4–4.3; P = 0.003), exposure to pollution and garages or stations (HR = 4.9; 95% CI 2–12.1; P < 0.001), combined local dry season + La Nina (HR = 4.6; 95%CI 1.8–11.8; P < 0.001), and combined local dry season + El Nino (HR = 4; 95% CI 1.6–9.7; P = 0.004). HM types included acute myeloid leukaemia (28.6% n = 18), multiple myeloma (22.2% n = 14), myelodysplastic syndromes (15.9% n = 10), chronic myeloid leukaemia (15.9% n = 10), chronic lymphoid leukaemia (9.5% n = 6), and acute lymphoid leukaemia (7.9% n = 5). After adjusting for confounders using Cox regression analysis, age ≥ 55 years, exposure to pollution, combined local dry season + La Nina and combined local dry season + El Nino were the most significant predictors of incident hematologic malignancy.ConclusionThese findings highlight the importance of aging, pollution, the dry season, El Nino and La Nina as related to global warming as determinants of hematologic malignancies among African patients from Kinshasa, DR Congo. Cancer registries in DRC and other African countries will provide more robust database for future researches on haematological malignancies in the region.

A Hospital-Based Prospective Cohort Study of Aged People to Elucidate the Predictive Factors for Chronic Disease and Mortality: HAPPY Cohort

A Hospital-Based Prospective Cohort Study of Aged People to Elucidate the Predictive Factors for Chronic Disease and Mortality: HAPPY Cohort

Relationship between Changes in Fatty Acid Composition of the Erythrocyte Membranes and Fatty Acid Intake during Pregnancy in Pregnant Japanese Women

Objective: Docosahexaenoic acid (DHA) is an important nutrient required by pregnant women and fetuses. Several studies suggest that fatty acid composition changes during pregnancy. However, the association of longitudinal changes in erythrocyte fatty acid composition and dietary fatty acid intake during pregnancy is not well understood. We assessed the relationship between fatty acid composition of the erythrocyte membranes and fatty acid intake at each trimester in pregnant Japanese women. Methods: We conducted a prospective hospital-based cohort study. We investigated fatty acid composition of the erythrocyte membranes and intake of fatty acids during the three trimesters in 178 healthy, pregnant Japanese women. Results: The eicosapentaenoic acid and arachidonic acid percentage of the erythrocyte membranes significantly decreased. The percentages of linoleic acid and α-linolenic acid significantly increased during pregnancy. The DHA percentage in the erythrocyte membranes decreased from the second to the third trimester. The DHA percentage in the erythrocyte membranes positively correlated with DHA intake in the third trimester. Conclusion: In pregnant Japanese women, the fatty acid composition of the erythrocyte membranes markedly changed throughout pregnancy. The DHA intake in the third trimester may be insufficient to maintain DHA percentage in the maternal erythrocyte membranes.

Predictors of response to cardiac resynchronization therapy: A prospective cohort study

IntroductionCardiac resynchronization therapy (CRT) has modified the prognosis of chronic heart failure (HF) with left ventricular systolic dysfunction. However, 30% of patients do not have a favorable response. The big question is how to determine predictors of response. AimsTo identify baseline characteristics that might influence echocardiographic response to CRT. Methods and ResultsWe performed a prospective single-center hospital-based cohort study of consecutive HF patients selected to CRT (NYHA class II-IV, left ventricular ejection fraction (LVEF) <35% and QRS complex ≥120 ms). Responders were defined as those with a ≥5% absolute increase in LVEF at six months. Clinical, electrocardiographic, laboratory, echocardiographic, autonomic, endothelial and cardiopulmonary function parameters were assessed before CRT device implantation. Logistic regression models were used. Seventy-nine patients were included, 54 male (68.4%), age 68.1 years (standard deviation 10.2), 19 with ischemic etiology (24%).At six months, 51 patients (64.6%) were considered responders. Although by univariate analysis baseline tricuspid annular plane systolic excursion (TAPSE) and serum creatinine were significantly different in responders, on multivariate analysis only TAPSE was independently associated with response, with higher values predicting a positive response to CRT (OR=1.13; 95% CI: 1.02-1.26; p=0.020). TAPSE ≥15 mm was strongly associated with response, and TAPSE <15 mm with non-response (p=0.005). Responders had no TAPSE values below 10 mm. ConclusionFrom a range of clinical and technical baseline characteristics, multivariate analysis only identified TAPSE as an independent predictor of CRT response, with TAPSE <15 mm associated with non-response. This study highlights the importance of right ventricular dysfunction in CRT response.ClinicalTrials.gov identifier: NCT02413151.

β-Blocker use and reduced disease progression in patients with thick melanoma: 8 years of follow-up.

Previous observational studies have reported the protective effect of β-blockers on the progression of different types of cancers. In 2011, we published a prospective study, including patients with histologically confirmed malignant melanoma in stage II-IIIA. In total, 25% of them reported previous use of β-blockers that were administered at any time for any other diseases. After a median follow-up of 2.5 years, 34% of the patients in the untreated group showed disease progression. In contrast, only 3% of the patients in the treated group showed progression. We report the findings obtained in the same cohort after a longer period of β-blocker therapy and follow-up (8 years). We prospectively reviewed data of the patients enrolled in the original prospective study. Disease progression was assessed by evaluating the presence of lymphatic, in-transit or visceral metastases. Deaths by any cause and deaths because of melanoma were recorded. A multivariate Cox proportional hazards model was used to evaluate the effect of β-blocker use on disease-free survival and overall survival, adjusting for significant confounders. After a median follow-up of 8 years and a median duration of β-blocker use of 7.6 years, 45% of the patients in the untreated group and 30% of the patients in the treated group showed disease progression. Notably, in the untreated group 35% patients died from melanoma and only 17% patients died from melanoma in the treated group. Results of this hospital-based prospective cohort study with a median follow-up of 8 years confirmed our previous results that the use of β-blockers significantly reduced the risk of recurrence and mortality in melanoma patients.

Predictors of response to cardiac resynchronization therapy: A prospective cohort study

IntroductionCardiac resynchronization therapy (CRT) has modified the prognosis of chronic heart failure (HF) with left ventricular systolic dysfunction. However, 30% of patients do not have a favorable response. The big question is how to determine predictors of response. AimsTo identify baseline characteristics that might influence echocardiographic response to CRT. Methods and ResultsWe performed a prospective single-center hospital-based cohort study of consecutive HF patients selected to CRT (NYHA class II-IV, left ventricular ejection fraction (LVEF) <35% and QRS complex ≥120 ms). Responders were defined as those with a ≥5% absolute increase in LVEF at six months. Clinical, electrocardiographic, laboratory, echocardiographic, autonomic, endothelial and cardiopulmonary function parameters were assessed before CRT device implantation. Logistic regression models were used. Seventy-nine patients were included, 54 male (68.4%), age 68.1 years (standard deviation 10.2), 19 with ischemic etiology (24%).At six months, 51 patients (64.6%) were considered responders. Although by univariate analysis baseline tricuspid annular plane systolic excursion (TAPSE) and serum creatinine were significantly different in responders, on multivariate analysis only TAPSE was independently associated with response, with higher values predicting a positive response to CRT (OR=1.13; 95% CI: 1.02-1.26; p=0.020). TAPSE ≥15 mm was strongly associated with response, and TAPSE <15 mm with non-response (p=0.005). Responders had no TAPSE values below 10 mm. ConclusionFrom a range of clinical and technical baseline characteristics, multivariate analysis only identified TAPSE as an independent predictor of CRT response, with TAPSE <15 mm associated with non-response. This study highlights the importance of right ventricular dysfunction in CRT response.ClinicalTrials.gov identifier: NCT02413151.

Periodontal Disease Associated with Aortic Arch Atheroma in Patients with Stroke or Transient Ischemic Attack

Periodontal disease (PD) is associated with recurrent vascular event in stroke or transient ischemic attack (TIA). In this study, we investigated whether PD is independently associated with aortic arch atheroma (AA). We also explored the relationship PD has with AA plaque thickness and other characteristics associated with atheroembolic risk among patients with stroke or TIA. Finally, we confirmed the association between AA and recurrent vascular event in patients with stroke or TIA. In this prospective longitudinal hospital-based cohort study, PD was assessed in patients with stroke and TIA. Patients with confirmed stroke and TIA (n = 106) were assessed by calibrated dental examiners to determine periodontal status and were followed over a median of 24 months for recurrent vascular events (stroke, myocardial infarction, and death). The extent of AA and other plaque characteristics was assessed by transesophageal echocardiography. Within our patient cohort, 27 of the 106 participants had recurrent vascular events (including 16 with stroke or TIA) over the median of 24-month follow-up. Severe PD was associated with increased AA plaque thickness and calcification. The results suggest that PD may be a risk factor for AA. In this cohort, we confirm the association of severe AA with recurrent vascular events. In patients with stroke or TIA, severe PD is associated with increased AA plaque thickness, a risk factor for recurrent events. Further studies are needed to confirm this finding and to determine whether treatment of PD can reduce the rate of AA plaque progression and recurrent vascular events.

Absence of Decline of Kidney Function in Human Immunodeficiency Virus-Infected Patients Under Routine Clinical Management

Background: Since the introduction of antiretroviral therapy (ART), human immunodeficiency virus (HIV)-infected patients have a drastically improved prognosis but at the same time they are also more affected by non-HIV related complications, such as chronic kidney disease. The objective of our study was to investigate the effect of proteinuria and tenofovir (TDF)-containing ART regimens on the temporal evolution of estimated glomerular filtration rate (eGFR). Methods: Between April 2008 and October 2012, we enrolled 395 patients with a complete renal evaluation among patients from the ANRS C03 Aquitaine cohort, a prospective hospital-based cohort of HIV-1-infected patients under routine clinical management in southwestern France. eGFR was estimated at each patient follow-up visit. A linear mixed model was used to analyze eGFR dynamics, accounting for change in TDF by modeling eGFR trajectory according to treatment periods. Results: At inclusion, 56.7% of patients were treated with TDF-containing ART regimens; prevalence of glomerular and tubular proteinuria was 7.9 and 10.8% respectively. A 1-year increase of cumulative exposure to TDF was significantly associated with a mean eGFR decrease of 1.27 mL/min/1.73 m² (95% CI [-2.14 to -0.41]). Only a urine protein to creatinine ratio >100 mg/mmol and/or a urine albumin to creatinine ratio >70 mg/mmol were associated with eGFR trajectory (mean slope 6.18 mL/min/1.73 m² per year; 95% CI [2.71 to 9.65]), whereas TDF use was not associated with such eGFR temporal evolution. Conclusion: Decline in kidney function is limited under routine clinical management with monitoring of renal function and interventions including decision to continue or discontinue TDF.

Pilot non dialysis chronic renal insufficiency study (P-ND-CRIS): a pilot study of an open prospective hospital-based French cohort

BackgroundBefore establishing a prospective cohort, an initial pilot study is recommended. However, there are no precise guidelines on this subject.This paper reports the findings of a French regional pilot study carried out in three nephrology departments, before realizing a major prospective Non Dialysis Chronic Renal Insufficiency study (ND-CRIS).MethodsWe carried out an internal pilot study. The objectives of this pilot study were to validate the feasibility (regulatory approval, providing patients with information, availability of variables, refusal rate of eligible patients) and quality criteria (missing data, rate of patients lost to follow-up, characteristics of the patients included and non-included eligible patients, quality control of the data gathered) and estimate the human resources necessary (number of clinical research associates required).ResultsThe authorizations obtained (CCTIRS – CNIL) and the contracts signed with hospitals have fulfilled the regulatory requirements. After validating the information on the study provided to patients, 1849 of them were included in three centres (university hospital, intercommunal hospital, town hospital) between April 2012 and September 2015. The low refusal rate (51 patients) and the characteristics of non-included patients have confirmed the benefit for patients of participating in the study and provide evidence of the feasibility and representativeness of the population studied. The lack of missing data on the variables studied, the quality of the data analyzed and the low number of patients lost to follow-up are evidence of the quality of the study. By taking into account the time spent by CRAs to enter data and to travel, as well as the annual patient numbers in each hospital, we estimate that five CRAs will be required in total.ConclusionWith no specific guidelines on how to realize a pilot study before implementing a major prospective cohort, we considered it pertinent to report our experience of P-ND-CRIS. This experience confirms that i) feasibility, ii) quality of data and iii) evaluating the resources required must be validated before carrying out a large prospective cohort study such as ND-CRIS.

Integrative Analysis of Immunological Data to Explore Chronic Immune T-Cell Activation in Successfully Treated HIV Patients.

ObjectivesTo unravel the complex relationships between cytomegalovirus-induced-, autoimmune-induced responses, microbial translocation and chronic immune activation (CIA) in successfully treated HIV-infected patients and to explore the mediating role of alpha-interferon in these processes.DesignCross-sectional study nested in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients in South-Western France.MethodsPatients initiated antiretroviral therapy between 2005 and 2008 and were treated with sustained virological suppression for at least two years. CIA was defined by the percentage of HLA-DR+/CD38+ among CD8+T-cells. Integrative analyses were performed using structural equation modelling (SEM).ResultsThe main analysis was performed in 57 HLA-A*0201 positive patients, due to availability of percentages of actin-, vimentin-, lamin-specific CD8+T-cells (HLA-A2-restricted tests) to further characterize autoimmune response. Cytomegalovirus-induced response was assessed by Quantiferon and pp-65 ELISPOT. SEM revealed a direct effect of cytomegalovirus-induced response on CIA (standardized estimate βstd = 0.56, p-value = 0.0004). The effect of autoimmune-induced response on CIA was indirect through alpha-interferon pathway, assessed by expression levels of 5 alpha-interferon-stimulated genes ADAR, ISG15, IFIT1, Mx1 and OAS1 (effect of autoimmune response on alpha-interferon: βstd = 0.36, p-value = 0.0401; effect of alpha-interferon on CIA: βstd = 0.39, p-value = 0.0044). There was no direct effect of autoimmune-induced response on CIA (p-value = 0.3169). Microbial translocation as measured by 16SrDNA and sCD14 in plasma was not associated with CIA. Results were consistent in 142 patients in whom cytomegalovirus and auto-immunity responses were measured by Quantiferon and anti-nuclear antibodies, respectively. All analyses performed in HLA-A*0201 positive patients and in the overall population revealed a significant effect of IFN-α latent variable on CIA.ConclusionThe role of cytomegalovirus-induced response on CIA was confirmed as well as the involvement of alpha-interferon on CIA. The indirect effect of auto-immunity response on CIA revealed through the alpha-interferon pathway requires further investigation to confirm the potential role of auto-immunity for CIA in HIV-infected patients.

Neonatal near miss and mortality: factors associated with life-threatening conditions in newborns at six public maternity hospitals in Southeast Brazil.

We aimed to evaluate factors associated with cases of neonatal near miss and neonatal deaths at six public maternity hospitals in São Paulo and Rio de Janeiro States, Brazil, in 2011. A prospective hospital-based birth cohort investigated these outcomes among live births with life-threatening conditions. Associations were tested using multinomial logistic regression models with hierarchical levels. High rates of near miss were observed for maternal syphilis (52.2‰ live births) and lack of prenatal care (80.8‰ live births). Maternal black skin color (OR = 1.9; 95%CI: 1.2-3.2), hemorrhage (OR = 2.2; 95%CI: 1.3-3.9), hypertension (OR = 3.0; 95%CI: 2.0-4.4), syphilis (OR = 3.3; 95%CI: 1.5-7.2), lack of prenatal care (OR = 5.6; 95%CI: 2.6-11.7), cesarean section and hospital, were associated with near miss; while hemorrhage (OR = 4.6; 95%CI: 1,8-11.3), lack of prenatal care (OR = 17.4; 95%CI: 6.5-46.8) and hospital, with death. Improvements in access to qualified care for pregnant women and newborns are necessary to reduce neonatal life-threatening conditions.

Correlation of Radio-anatomic Site of Stroke with Motor Recovery and Functional Outcome in Ischemic Stroke Patients: A Hospital-based Prospective Cohort Study

Correlation of Radio-anatomic Site of Stroke with Motor Recovery and Functional Outcome in Ischemic Stroke Patients: A Hospital-based Prospective Cohort Study

Burnout is associated with poor recovery of physical performance and low quality of life in patients after their first episode of acute coronary syndrome: A hospital-based prospective cohort study

Objectives“Burnout” is an affective response that is different to depression or anxiety. Studies on the relationship between burnout and physical recovery after acute coronary syndrome (ACS) in the long-term are lacking, hence the rationale of this study. MethodsParticipants were patients after their first onset of ACS divided into the high burnout group (HBG) and low burnout group (LBG) based on the upper quartile of their burnout score on the day before discharge. At three times (1month, 6months, and 1year) after ACS, participants were scheduled for assessment of physical function and quality of life (QoL). To determine the association between burnout and physical function at different times, as well as for burnout and the QoL scores, generalized estimating equations were conducted. ResultsOf the 208 participants, 68 participants were assigned to HBG, and 140 were assigned to LBG. QoL scores in both groups at three times showed that HBG had lower scores than LBG (p<0.01). HBG had lower physical scores at three times (z=7.28, p<0.001). Even after adjustment for confounding factors (age, sex, marital status, socioeconomic status, cigarette/alcohol consumption, ACS type, Killip class upon hospital admission), the difference was significant (z=7.78, p<0.001). ConclusionsPatients with high burnout have poor physical recovery and low quality of life after ACS.

Incidence of HIV-infected infants born to HIV- infected mothers with prophylactic therapy: Preliminary report of hospital birth cohort study

Background Human immunodeficiency virus (HIV) is expandingrapidly and was reported double in several places in Indonesia Toour knowledge, reports regarding HIV-infected infants are stillscarce.Objectives To investigate the incidence of HIV-infected infantsborn to HIV- mothers who had received prophylaxis therapy at birth.Methods A prospective hospital-based cohort study was held fromJanuary 2003 until December 2004 in Cipto Mangunkusumo Hos-pital, Jakarta. The inclusion criteria were mothers with positive HIVand their infants had been given anti retroviral (ARV) therapy. Thebabies were followed up monthly and the status of infection wasdetermined by PCR at the age of 4 weeks and 6 months. Outcomewas measured based on PCR assays or clinical signs of HIV in-fection.Results The mothers’ age ranged from 19 to 27 years. All of themwere carrying their first child and only 41% mothers took ARV pro-phylaxis. Almost all mothers underwent caesarean section and theinfants had formula feeding. HIV infection was diagnosed in 7 in-fants and 2 of them had RNA assays more than 5,000 copies/ml.Six infants were negatives whereas 3 infants were diagnosed asindeterminate HIV infection and needed further examination. Oneneeded no further investigation as the mother was seronegative.Conclusions Preventing HIV transmission from mother to infantcan be done by giving ARV during prenatal, intrapartum, and post-natal period to the newborn. In our hospital, transmission was con-firmed in 6 of 17 infants. Unison protocol must be used and popu-lation of HIV-pregnant mother must be registered in order to knowhow high the transmission rate among Indonesian HIV people

Timing of eczema onset and risk of food allergy at 3 years of age: A hospital-based prospective birth cohort study

BackgroundAlthough recent studies suggest that eczema in early childhood is important in the development of food allergy, the importance of the timing of eczema onset has not been fully clarified. ObjectiveThis study aim to identify an association between the timing of eczema onset and development of food allergy in a prospective birth cohort study. MethodsData were obtained from the Tokyo Children’s Health, Illness and Development (T-CHILD) study, which is a hospital-based birth cohort study currently in progress in Japan. A total of 1550 children were born to the recruited women. Outcome data for children were collected from questionnaires completed at 6 months, 1 and 3 years of age. Association between the timing of eczema onset and development of food allergy was estimated by logistic regression analyses. All analysis were performed using SPSS software with a two-sided 5% significance level. ResultsEczema in the first year of life was a significant risk factor in multivariate analysis (aOR 3.90, 95% CI 2.34–6.52, p<0.001). In each age (by month) stratum, infants with onset of eczema within the first 1–2 months after birth had the highest risk of food allergy at 3 years of age (aOR 6.61, 95% CI 3.27–13.34, p<0.001). ConclusionInfants with early eczema onset (especially within the first 1–4 months after birth) were found to have an increased risk of developing food allergy at 3 years of age. Our findings may contribute to a better understanding of the timing of eczema onset as a potentially modifiable risk factor and to defining those who may need to be on guard for food allergy.

The Non-Dialysis Chronic Renal Insufficiency study (ND-CRIS): an open prospective hospital-based cohort study in France.

BackgroundChronic kidney disease (CKD) amounts to a heavy burden for health services. There is no long-running epidemiological tool for CKD before dialysis. We here present the protocol for a cohort of patients with “non-dialysis” CKD receiving care in the Bourgogne-Franche-Comté region of France. The aim of this cohort was to periodically describe the characteristics of patients included and their care provision, to analyse evolution in care and patients’ kidney function outcomes.MethodsThe ND-CRIS cohort is prevalent and incident. Patients are included in the cohort if over 18, with a glomerula filtration rate (GFR) <60 ml/min/1.73 m2, non-dialysed, informed on the research and not having opposed it, and followed by a nephrologist in one of the 9 centres in the region, (3 pilot centres joined by 6 others in 2015). All the patients are followed up, with varying time lapses according to the degree of GFR deterioration. Data is collected by clinical research assistants (CRAs) using a dedicated computerised case-report form (CRF). Professional practices are assessed using indicators defined by the French Health Authority. The follow-up of patients included should enable assessment of the evolution of their GFR and co-morbidities. The periodic descriptions should give insight into evolution in epidemiological terms.DiscussionThe ND-CRIS meets a need in epidemiological tools in France for CKD. The cohort does claim to be representative, of ND-CKD patients receiving care from nephrologists. The open and incident nature of the cohort and the number of patients included in the ND-CRIS should provide answers to questions that cannot be answered by smaller solely prevalent cohorts. The numbers of patients included over the study period (2391 patients in 3 centres in 3 years) suggests that the figure of 5000 patients should be reached by 2017. The participation of nephrologists and the rate of inclusions point to the feasibility of the implementation of this cohort. Beyond the information to be found in the CRFs, this cohort should also enable ad hoc studies, in particular in the area of pharmaco-epidemiology, and it could later serve as a research platform and as a public health surveillance tool.

Structural network efficiency predicts conversion to dementia.

To examine whether structural network connectivity at baseline predicts incident all-cause dementia in a prospective hospital-based cohort of elderly participants with MRI evidence of small vessel disease (SVD). A total of 436 participants from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC), a prospective hospital-based cohort of elderly without dementia with cerebral SVD, were included in 2006. During follow-up (2011-2012), dementia was diagnosed. The structural network was constructed from baseline diffusion tensor imaging followed by deterministic tractography and measures of efficiency using graph theory were calculated. Cox proportional regression analyses were conducted. During 5 years of follow-up, 32 patients developed dementia. MRI markers for SVD were strongly associated with network measures. Patients with dementia showed lower total network strength and global and local efficiency at baseline as compared with the group without dementia. Lower global network efficiency was independently associated with increased risk of incident all-cause dementia (hazard ratio 0.63, 95% confidence interval 0.42-0.96, p = 0.032); in contrast, individual SVD markers including lacunes, white matter hyperintensities volume, and atrophy were not independently associated. These results support a role of network disruption playing a pivotal role in the genesis of dementia in SVD, and suggest network analysis of the connectivity of white matter has potential as a predictive marker in the disease.

Comment: Network disruption as a common framework for factors contributing to dementia.

There is mounting evidence that large-scale functional brain networks are fundamental to the pathophysiology of dementing illnesses.1 Functional networks require intact white matter, and small vessel disease (SVD) may disrupt this infrastructure. Tuladhar et al.2 conducted an analysis of imaging biomarkers as predictors of all-cause dementia in a prospective hospital-based cohort of patients with presumed evidence of SVD. The imaging biomarkers included white matter network–based graph theoretical metrics (e.g., global network efficiency), white matter volume, gray matter volume, hippocampal volume, manually segmented white matter hyperintensity volume, and presence/absence of lacunes and microbleeds.

Prognostic markers among Egyptian children with sepsis in the Intensive Care Units, Cairo University Hospitals

BackgroundEarly identification of septic patients at risk of mortality is important in their prognosis. ObjectiveIdentification of septic patients at risk of mortality in Pediatric Intensive Care Units (PICUs) at Cairo University Hospitals, through measuring the levels of certain immunological parameters. MethodsA hospital-based prospective cohort study was conducted in two PICUs at Cairo University Hospitals; all patients with diagnosis of severe sepsis or septic shock on admission were included. A total of 57 patients were prospectively followed at the selected PICUs and their demographic and clinical data were recorded. Microbiological and immunological workup (at days 1 and 7) was conducted for all patients to detect the causative organism of sepsis and to measure the levels of immunoglobulins (IgG, IgM and IgA), complement factors (C3 and C4), mature lymphocyte subpopulations (CD3+) and natural killer (NK) cells (CD3-CD16+CD56+), respectively. ResultsMortality rate was 24.6%; the most frequent causes of death were multi-organ dysfunction and refractory shock. PELOD and PRISM III scores were significantly higher among non-survivors. At day 1, non-survivors had significantly higher levels of IgG, C4 and NK cells than survivors. However, from day 1 to day 7, survivors had a progressive increase in most of the immunological parameters (IgG, IgM, C4and CD3+ T lymphocytes). Survival curve analysis revealed the significant predictive ability of NK cells to detect early mortality. ConclusionMonitoring the levels of cellular and humoral immunological parameters together with assessing PELOD and PRISM III scores can significantly affect prognosis and survival of septic children.

Comprehensive analysis of hospital-based prospective cohort reveals the unique effectiveness and safety for nucleos(t)ide analogues in HBV patients

Nucleos(t)ide analogues (NAs) including lamivudine (LAM), telbivudine (LDT), adefovir dipivoxil(ADV), and entecavir (ETV) have been widely used as anti-HBV drugs. We aimed to study the effectiveness and safety of various NAs. Two thousand three hundred and eighty patients with chronic hepatitis B (CHB) were enrolled. The rate of virologic response, optimization therapy, and serologic responses were analyzed. HBV DNA inhibitory capacity was shown to be LAM+ADV≈ETV>LDT>LAM>ADV. Virologic breakthrough rate and proportion of optimized treatment were LAM>ADV>LDT>LAM+ADV>ETV. However, virological response rate showed the opposite trend. The selection of anti-virals, HBeAg-negative, and lower HBV DNA levels after one year of anti-viral treatment, are favorable factors for the maintenance of virologic response. This study's results were consistent with the major clinical guidelines to recommend ETV and TDF as the preferred treatment for CHB patients. LAM could be used for patients with lower HBV DNA load; ADV may be more applicable to non-cirrhotic patients with HBeAg-negative and lower HBV DNA load. LDT can be used to treat patients with HBeAg-positive, low HBV DNA load, and higher ALT levels due to higher HBeAg conversion rate in a baseline optimized population. The effectiveness of LAM+ADV is similar to and sometimes better than ETV treatment in a CHB population.