Eligibility for Obesity Treatment and Risk of Mortality in Men

Objective: To evaluate the risk of all‐cause and cardiovascular disease (CVD) mortality associated with each outcome of the NIH obesity treatment algorithm and to examine the effects of cardiorespiratory fitness on the risk of mortality associated with these outcomes. Research Methods and Procedures: The NIH obesity treatment algorithm was applied to 18, 666 men (20 to 64 years of age) from the Aerobics Center Longitudinal Study in Dallas, TX, examined between 1979 and 1995. Risk of all‐cause and CVD mortality was assessed using Cox proportional hazards regression. Results: A total of 7029 men (37.7%) met the criteria for needing weight loss treatment [overweight (BMI = 25 to 29.9 kg/m² or WC > 102 cm) with ≥2 CVD risk factors or obese (BMI ≥ 30 kg/m²)]. Mortality surveillance through 1996 identified 435 deaths (151 from CVD) during 191, 364 man‐years of follow‐up. Compared with the normal weight reference group, the hazard ratios (95% confidence interval) for death from all causes were 0.63 (0.45 to 0.88), 1.23 (0.98 to 1.54), 1.05 (0.60 to 1.85), and 1.71 (1.64 to 2.31) for men who were overweight with <2 CVD risk factors, overweight with ≥2 CVD risk factors, obese with <2 CVD risk factors, and obese with ≥2 CVD risk factors, respectively. Corresponding hazard ratios for CVD mortality were 0.72 (0.38 to 1.37), 1.67 (1.12 to 2.50), 1.69 (0.67 to 4.30), and 3.31 (2.07 to 5.30). Including physical fitness as a covariate significantly attenuated all risk estimates. Discussion: The NIH obesity treatment algorithm is useful in identifying men at increased risk of premature mortality; however, including an assessment of fitness would help improve risk stratification among all groups of patients.     

鲤鱼卵黄发生期血钙水平调节初步研究

在雌鲤卵黄发生期的10月～次年1月和斯坦氏小体(CS)发育静止期进行升高细胞外钙浓度实验,分别用OCPC法测定血浆钙水平的变化,超微结构观察CS的组织学变化.结果表明,鲤鱼血钙水平在卵黄发生期存在一定性别差异,雄鲤水平普遍低于雌鲤,在11月达显著性水平.升高细胞外钙浓度的各处理组中CS的超微结构发生了不同程度的变化,均表现为细胞代谢活动增强.     

Predictors of Death during Tuberculosis Treatment in TB/HIV Co-Infected Patients in Malaysia

Background

Mortality among TB/HIV co-infected patients is still high particularly in developing countries. This study aimed to determine the predictors of death in TB/HIV co-infected patients during TB treatment.

Methods

We reviewed medical records at the time of TB diagnosis and subsequent follow-up of all newly registered TB patients with HIV co-infection at TB clinics in the Institute of Respiratory Medicine and three public hospitals in the Klang Valley between January 2010 and September 2010. We reviewed these medical records again twelve months after their initial diagnosis to determine treatment outcomes and survival. We analysed using Kaplan-Meier and conducted multivariate Cox proportional hazards analysis to identify predictors of death during TB treatment in TB/HIV co-infected patients.

Results

Of the 227 patients studied, 53 (23.3%) had died at the end of the study with 40% of deaths within two months of TB diagnosis. Survival at 2, 6 and 12 months after initiating TB treatment were 90.7%, 82.8% and 78.8% respectively. After adjusting for other factors, death in TB/HIV co-infected patients was associated with being Malay (aHR 4.48; 95%CI 1.73-11.64), CD4 T-lymphocytes count < 200 cells/µl (aHR 3.89; 95% CI 1.20-12.63), three or more opportunistic infections (aHR 3.61; 95% CI 1.04-12.55), not receiving antiretroviral therapy (aHR 3.21; 95% CI 1.76-5.85) and increase per 10³ total white blood cell count per microliter (aHR 1.12; 95% CI 1.05-1.20)

Conclusion

TB/HIV co-infected patients had a high case fatality rate during TB treatment. Initiation of antiretroviral therapy in these patients can improve survival by restoring immune function and preventing opportunistic infections.     

Plasma soluble urokinase plasminogen activator receptor (suPAR) levels in systemic lupus erythematosus

Objective: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of systemic inflammation. We aimed to characterize plasma suPAR levels in SLE patients.

Methods: We measured plasma suPAR, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in 89 SLE patients and 29 healthy controls.

Results: suPAR and ESR values were higher in SLE than in controls, while CRP levels were comparable. ROC analysis of suPAR levels indicated a cut-off value of 5.70?ng/mL to distinguish patients with high disease activity (SLEDAI >8).

Conclusion: suPAR might be an objective marker for identifying SLE patients with active disease.     

Decreased Plasma Histidine Level Predicts Risk of Relapse in Patients with Ulcerative Colitis in Remission

Ulcerative colitis (UC) is characterized by chronic intestinal inflammation. Patients with UC have repeated remission and relapse. Clinical biomarkers that can predict relapse in UC patients in remission have not been identified. To facilitate the prediction of relapse of UC, we investigated the potential of novel multivariate indexes using statistical modeling of plasma free amino acid (PFAA) concentrations. We measured fasting PFAA concentrations in 369 UC patients in clinical remission, and 355 were observed prospectively for up to 1 year. Relapse rate within 1 year was 23% (82 of 355 patients). The age- and gender-adjusted hazard ratio for the lowest quartile compared with the highest quartile of plasma histidine concentration was 2.55 (95% confidence interval: 1.41–4.62; p = 0.0020 (log-rank), p for trend = 0.0005). We demonstrated that plasma amino acid profiles in UC patients in clinical remission can predict the risk of relapse within 1 year. Decreased histidine level in PFAAs was associated with increased risk of relapse. Metabolomics could be promising for the establishment of a non-invasive predictive marker in inflammatory bowel disease.     

sBCMA Plasma Level Dynamics and Anti-BCMA CAR-T-Cell Treatment in Relapsed Multiple Myeloma

BACKGROUND: Novel chimeric antigen receptor T-cells (CAR-T) target the B-cell maturation antigen (BCMA) expressed on multiple myeloma cells. Assays monitoring CAR-T cell expansion and treatment response are being implemented in clinical routine. METHODS: Plasma levels of soluble BCMA (sBCMA) and anti-BCMA CAR-T cell copy numbers were monitored in the blood, following CAR-T cell infusion in patients with relapsed multiple myeloma. sBCMA peptide concentration was determined in the plasma, applying a human BCMA/TNFRS17 ELISA. ddPCR was performed using probes targeting the intracellular signaling domains 4-1BB und CD3zeta of the anti-BCMA CAR-T construct. RESULTS: We report responses in the first five patients who received anti-BCMA CAR- T cell therapy at our center. Four patients achieved a complete remission (CR) in the bone marrow one month after CAR-T infusion, with three patients achieving stringent CR, determined by flow cytometry techniques. Anti-BCMA CAR-T cells were detectable in the peripheral blood for up to 300 days, with copy numbers peaking 7 to 14 days post-infusion. sBCMA plasma levels started declining one to ten days post infusion, reaching minimal levels 30 to 60 days post infusion, before rebounding to normal levels. CONCLUSIONS: Our data confirm a favorable response to treatment in four of the first five patients receiving anti-BCMA CAR-T at our hospital. Anti-BCMA CAR-T cell expansion seems to peak in the peripheral blood in a similar pattern compared to the CAR-T cell products already approved for lymphoma treatment. sBCMA plasma level may be a valid biomarker in assessing response to BCMA-targeting therapies in myeloma patients.     

Increased Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Levels in Plasma of Suicide Attempters

The soluble form of the urokinase receptor, suPAR, has been suggested as a novel biomarker of low-grade inflammation. Activation of the immune system has been proposed to contribute to the development of depression and suicidal behavior. In order to identify depressed and suicidal individuals who could benefit from an anti-inflammatory treatment, a reliable biomarker of low-grade inflammation is vital. This study evaluates plasma suPAR levels as a biomarker of low-grade inflammation in patients with major depressive disorder and in patients who recently attempted suicide. The plasma suPAR and an established biomarker, C reactive protein (CRP) of suicide attempters (n = 54), depressed patients (n = 19) and healthy controls (n = 19) was analyzed with enzyme-linked immunosorbent assays. The biomarker attributes of sensitivity and sensibility were evaluated using ROC curve analysis. Both the depressed patients and suicide attempters had increased plasma suPAR. The levels of suPAR discriminated better between controls and suicide attempters than did CRP. In the future, plasma suPAR might be a superior prognosticator regarding outcome of treatment applying conventional antidepressants in conjunction with anti-inflammatory drugs.     

Elevated Plasma Total Cholesterol Level Is Associated with the Risk of Asymptomatic Intracranial Arterial Stenosis

Background

Intracranial arterial stenosis (ICAS) is one of the most common causes of stroke, and dyslipidemia was one of the most common risk factors related to ICAS. However, the correlation between the plasma total cholesterol level (PTC) and ICAS, especially asymptomatic ICAS (AICAS) is not clear.

Materials and Methods

5,300 participants were enrolled in this study. The diagnosis of AICAS was made by transcranial Doppler ultrasonography. The participants were then divided into 5 essentially equal-sized groups based on their PTC levels. The multivariate logistic regression was used to analyze the correlation between the PTC level and the prevalence of AICAS.

Results

13.0% of the participants were diagnosed with AICAS. The prevalence of AICAS gradually increased with the increasing PTC level. After adjusted by the possible confounding factors, the Odds Ratios (OR) of the AICAS prevalence between the 1st quintile group and the other 4 groups were 1.13, 1.23, 1.63 and 1.75 with 95% confident intervals (CI) of 0.84–1.52, 0.91–1.66, 1.20–2.22 and 1.23–2.47, respectively. The further subgroup analysis revealed that the PTC level was stronger for males (OR 1.42 95%CI 1.23–1.64), regarding the prevalence of AICAS.

Conclusions

In this large community-based study, the prevalence of AICAS is 13.0%, subjects with higher PTC levels showed a mild increase in the prevalence of AICAS. The PTC level is an independent risk factor of AICAS. Males seem to be significantly more vulnerable to the risk of AICAS.     

High Latent TB Infection Rate and Associated Risk Factors in the Eastern China of Low TB Incidence

Objectives

To disclose the associated risk factors for latent tuberculosis infection (LTBI) and the current situation of LTBI in the eastern China.

Methods

A cross-sectional study was undertaken to evaluate the LTBI rate and risk factors.

Results

A total of 5305 subjects were finally included, with the IGRA positive rate of 19.98% (1060/5305). The LTBI rates were increasing with age (ORs were in significance from 6.60 to 20.92). Male gender significantly increased the risk of LTBI by 0.52 fold (OR = 1.52). Both smoking and drinking significantly increased the risk of LTBI (OR = 1.83 and OR = 1.67, respectively). Meanwhile, overweight and close contact with tuberculosis were risk factors for LTBI (OR = 1.36 and OR = 2.38, respectively). However, higher level of education and BCG vaccination lowered the risk of LTBI (OR = 0.16 and OR = 0.39, respectively). The multivariate logistic regression showed that age, male gender, smoking, overweight and close contacting with tuberculosis were risk factors for LTBI, but BCG vaccination was a protective factor for LTBI.

Conclusions

BCG vaccination exerted protective effect on tuberculosis. However, LTBI rate in the Chinese rural area was critical and subjects above 30 years, male, smoking, overweight and close contact with tuberculosis wound be the targets for LTBI screening and source of tuberculosis.     

Obesity Increases the Risk of Spontaneous Abortion during Infertility Treatment

Objective: This study examines the relationship between body mass and the risk of spontaneous abortion in a large cohort of patients who received infertility treatment. Research Methods and Procedures: This is a retrospective study using data on pregnancies (n = 2349) achieved after treatment in a tertiary medical center from 1987 to 1999. One pregnancy per subject was included, and the subjects were stratified into five body mass groups based on body mass index (BMI): underweight, <18.5 kg/m²; normal, 18.5 to 24.9 kg/m²; overweight, 25 to 29.9 kg/m²; obese, 30 to 34.9 kg/m²; and very obese, ≥35 kg/m². Logistical regression analysis was used. Results: The overall incidence of spontaneous abortion was 20% (476 of 2349). The effect of BMI on the risk of spontaneous abortion was significant after adjusting for several independent risk factors. Compared with the reference group (BMI 18.5 to 24.9 kg/m²), underweight women had a similar risk of spontaneous abortion, whereas there was progressive increase of risk in overweight, obese, and very obese groups (p < 0.05, p < 0.01, and p < 0.001, respectively). Discussion: Of all known risk factors for spontaneous abortion, the control of obesity has great significance because it is noninvasive, potentially modifiable, possibly amenable to low cost, and self‐manageable by patients. This study established a positive relationship between BMI and the risk of spontaneous abortion in women who became pregnant after assisted reproductive technology treatment.     

Reduction of Insulin Resistance and Plasma Glucose Level by Salsalate Treatment in Persons With Prediabetes

ObjectiveTo evaluate the effect of salsalate as an antiinflammatory agent on insulin resistance and glycemic control in persons with prediabetes.MethodsIn this double-blind, placebo-controlled clinical trial, 66 persons who had prediabetes on the basis of the American Diabetes Association criteria were enrolled. They were randomly assigned to receive salsalate (3 g daily) or placebo for 12 weeks. Fasting plasma glucose (FPG) and insulin, glucose 2 hours after oral administration of 75 g of glucose, hemoglobin A_1c, lipid profile, homeo stasis model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of beta-cell function were determined before and after treatment.ResultsSalsalate treatment reduced the FPG level from 5.86 ± 0.07 mmol/L to 5.20 ± 0.11 mmol/L and HOMA-IR from 4.2 ± 0.9 to 3.8 ± 0.3 (P = .01 for both changes). Homeostasis model assessment of beta-cell func tion increased in the salsalate-treatment group from 139.8 ± 11.0 to 189.4 ± 24.6 (P = .01). At the end of the study, FPG, HOMA-IR, and insulin levels were significantly different between salsalate and placebo groups (5.20 ± 0.11 mmol/L versus 5.53 ± 0.10 mmol/L, 3.8 ± 0.3 versus 4.4 ± 0.9, and 16.1 ± 1.9 μIU/mL versus 18.2 ± 2 μIU/mL, respectively; P < .05 for all). There were no persistent complications after salsalate therapy.ConclusionTreatment with salsalate can reduce insu lin resistance and the FPG level in subjects with predia betes. Determination of the long-term safety and efficacy of the use of salsalate necessitates further investigation. (Endocr Pract. 2012;18:826-833)     

Experience in Monitoring Gentamicin Therapy during Treatment of Serious Gram-Negative Sepsis

This paper reports our experience in monitoring gentamicin therapy during the treatment of 68 episodes of serious Gram-negative sepsis in 65 hospital patients. Most of the patients had major underlying disease. Of those who were adequately treated (peak serum concentrations of 5 μg/ml or more in 72 hours for septicaemia, urinary tract infection, and wound infection; and 8 μg/ml or more at some time during the course of treatment for pneumonia) 84% (46 out of 55) were cured. These serum concentrations could be achieved only by starting with a regimen of 5 mg/kg/day in three divided doses in all adult patients, subsequent dosage being determined by the results of rapid serum assay. The incidence of nephrotoxicity and symptomatic ototoxicity was no greater than in previous series. The main reason for assaying serum gentamicin is to ensure that an adequate dosage is achieved as soon as possible. In patients with impaired renal function or receiving prolonged high dosage assays also serve to guard against an excessive accumulation of gentamicin and an increased risk of toxicity.     

Association Between Circulating Copeptin Level and Mortality Risk in Patients with Intracerebral Hemorrhage: a Systemic Review and Meta-Analysis

Copeptin has been identified as a biomarker of disease severity and is associated with mortality risk in several common diseases. This study sought to determine the association between circulating copeptin level and mortality risk in patients with intracerebral hemorrhage. PubMed, Web of Science, and Wanfang Medicine Database were searched for studies assessing the association between circulating copeptin level and mortality risk in patients with intracerebral hemorrhage. The pooled hazard ratio (HR) of mortality was calculated and presented with 95 % confidence interval (95 % CI). Data from 1332 intracerebral hemorrhage patients were derived from 9 studies. Meta-analysis showed that intracerebral hemorrhage patients with poor prognosis had much higher copeptin levels than those survivors (standardized mean difference?=?1.68, 95 % CI 1.26–2.11, P?<?0.00001). Meta-analysis of 8 studies with HRs showed that high circulating copeptin level was associated with higher risk of mortality in patients with intracerebral hemorrhage (HR?=?2.42, 95 % CI 1.60–3.65, P?<?0.0001). Meta-analysis of 6 studies with adjusted HRs showed that high circulating copeptin level was independently associated with higher risk of mortality in patients with intracerebral hemorrhage (HR?=?1.67, 95 % CI 1.26–2.22, P?=?0.0003). Our study suggests that there is an obvious association between circulating copeptin level and mortality in patients with intracerebral hemorrhage. High circulating copeptin level is independently associated with higher risk of mortality in patients with intracerebral hemorrhage.     

Monitoring Change in Child Mortality through Household Surveys

Background

Most low- and middle-income countries lack fully functional civil registration systems. Measures of under-five mortality are typically derived from periodic household surveys collecting detailed information from women on births and child deaths. However, such surveys are expensive and are not appropriate for monitoring short-term changes in child mortality. We explored and tested the validity of two new analysis methods for less-expensive summary histories of births and child deaths for such monitoring in five African countries.

Methods and Findings

The first method we explored uses individual-level survey data on births and child deaths to impute full birth histories from an earlier survey onto summary histories from a more recent survey. The second method uses cohort changes between two surveys in the average number of children born and the number of children dead by single year of age to estimate under-five mortality for the inter-survey period. The first method produces acceptable annual estimates of under-five mortality for two out of six applications to available data sets; the second method produced an acceptable estimate in only one of five applications, though none of the applications used ideal data sets.

Conclusions

The methods we tested were not able to produce consistently good quality estimates of annual under-five mortality from summary birth history data. The key problem we identified was not with the methods themselves, but with the underlying quality of the summary birth histories. If summary birth histories are to be included in general household surveys, considerable emphasis must be placed on quality control.     

Educational Degrees and Adult Mortality Risk in the United States

We present the first published estimates of U. S. adult mortality risk by detailed educational degree, including advanced postsecondary degrees. We use the 1997–2002 National Health Interview Survey (NHIS) Linked Mortality Files and Cox proportional hazards models to reveal wide graded differences in mortality by educational degree. Compared to adults who have a professional degree, those with an MA are 5 percent, those with a BA are 26 percent, those with an AA are 44 percent, those with some college are 65 percent, high school graduates are 80 percent, and those with a GED or 12 or fewer years of schooling are at least 95 percent more likely to die during the follow-up period, net of sociodemographic controls. These differentials vary by gender and cohort. Advanced educational degrees are associated not only with increased workforce skill level but with a reduced risk of death.     

Effects of Treatment on the Mortality Rate in Septicaemia

The results of treatment have been analysed in 173 patients with septicaemia during 1962–8. Between 1962 and 1965 various antibiotics were used, and shock was treated with vasopressor agents. Between 1966 and 1968 kanamycin was given initially, and shock was treated with corticosteroids and with intravenous fluid therapy monitored with a central venous pressure manometer.The mortality rate in 1966–8 fell to half that of the earlier period in patients with Gram-negative infections, and in those with shock. The reduced mortality in the latter was clearly associated with the use of a central venous manometer to control intravenous fluid therapy, though whether the reduction resulted from specific improvement in intravenous therapy or from the necessary closer observation of the patient is not clear. Staphylococcal septicaemia was common during both periods, and its mortality rate did not fall; hence methicillin together with kanamycin is now given initially in all cases.     

Mortality Risk and Survival in the Aftermath of the Medieval Black Death

The medieval Black Death (c. 1347-1351) was one of the most devastating epidemics in human history. It killed tens of millions of Europeans, and recent analyses have shown that the disease targeted elderly adults and individuals who had been previously exposed to physiological stressors. Following the epidemic, there were improvements in standards of living, particularly in dietary quality for all socioeconomic strata. This study investigates whether the combination of the selective mortality of the Black Death and post-epidemic improvements in standards of living had detectable effects on survival and mortality in London. Samples are drawn from several pre- and post-Black Death London cemeteries. The pre-Black Death sample comes from the Guildhall Yard (n = 75) and St. Nicholas Shambles (n = 246) cemeteries, which date to the 11^th–12^th centuries, and from two phases within the St. Mary Spital cemetery, which date to between 1120-1300 (n = 143). The St. Mary Graces cemetery (n = 133) was in use from 1350–1538 and thus represents post-epidemic demographic conditions. By applying Kaplan-Meier analysis and the Gompertz hazard model to transition analysis age estimates, and controlling for changes in birth rates, this study examines differences in survivorship and mortality risk between the pre- and post-Black Death populations of London. The results indicate that there are significant differences in survival and mortality risk, but not birth rates, between the two time periods, which suggest improvements in health following the Black Death, despite repeated outbreaks of plague in the centuries after the Black Death.     

Soluble Tumor Necrosis Factor Related Apoptosis Inducing Ligand Level as a Predictor of Severity of Sepsis and the Risk of Mortality in Septic Patients

Background

Tumor necrosis factor related apoptosis inducing ligand (TRAIL) as a member of the TNF gene superfamily induces apoptosis primarily in tumor cells. TRAIL also plays an important role in the modulation of inflammatory responses, especially in the process of immune paralysis. The aim of the present study was to examine soluble TRAIL (sTRAIL) levels in septic patients in an attempt to explore the association between sTRAIL level and the risk of mortality.

Methods

Plasma sTRAIL levels were detected by ELISA in 50 septic patients and 20 healthy volunteers. HLA-DR expression in monocytes was detected by flow cytometry. Selective biochemical parameters were recorded, and patients were monitored in a 28-day period for mortality.

Results

The mean plasma sTRAIL level in septic patients was significantly lower than that in healthy controls (16.9±8.3 vs. 68.3±8.6 pg/ml, P<0.01), and was significantly higher in 28-day survivors than those in non-survivors (19.4±9.8 vs. 13.9±4.7 pg/ml, P<0.05). Univariate analysis indicated that plasma sTRAIL level was positively correlated with monocyte and lymphocyte counts and HLA-DR expression level (r = 0.5, P<0.01; r = 0.3, P<0.05; r = 0.43, P<0.01, respectively). STRAIL level was negatively correlated with APACHE II score, BUN and age (r = −0.48, P<0.01; r = −0.29, P<0.05; r = −0.45, P<0.01, respectively). Multiple linear regression analysis indicated that the predictor of plasma soluble TRAIL level was HLA-DR expression (P<0.01).

Conclusion

Low plasma sTRAIL levels were associated with immune paralysis and a high risk of mortality in patients with septic shock. sTRAIL may prove to be a potential biomarker of immune function and predict the survival of septic patients.     

TAIMA (Stop) TB: The Impact of a Multifaceted TB Awareness and Door-to-Door Campaign in Residential Areas of High Risk for TB in Iqaluit,Nunavut

Background

The incidence rate of active tuberculosis (TB) disease in the Canadian Territory of Nunavut has shown a rising trend over the past 10 years. In 2010 it was 60 times greater than the national incidence rate. The objective of the Taima (translates to “stop” in Inuktitut) TB study was to implement and evaluate a public health campaign to enhance existing TB prevention efforts in Nunavut.

Methods

A TB awareness campaign followed by a door-to-door screening campaign was carried out in Iqaluit, Nunavut. The aim of the campaign was to raise awareness about TB, and to provide in-home screening and treatment for people living in residential areas at high risk for TB. Screening was based on geographic location rather than on individual risk factors.

Results

During the general awareness campaign an increase in the number of people who requested TB testing at the local public health clinic was observed. However, this increase was not sustained following cessation of the awareness campaign. Targeted TB screening in high risk residential areas in Iqaluit resulted in 224 individuals having TSTs read, and detection of 42 previously unidentified cases of latent TB, (overall yield of 18.8% or number needed to screen = 5.3). These cases of latent TB infection (LTBI) were extra cases that had not been picked up by traditional screening practices (34% relative increase within the community). This resulted in a 33% relative increase in the completion of LTBI treatment within the community. The program directly and indirectly identified 5/17 new cases of active TB disease in Iqaluit during the study period (29.5% of all incident cases).

Conclusions

While contact tracing investigations remain a cornerstone of TB prevention, additional awareness, screening, and treatment programs like Taima TB may contribute to the successful control of TB in Aboriginal communities.