Exploring the Association of Hemoglobin Level and Adverse Events in Children with Cancer Presenting with Fever in Neutropenia

Background

In children and adolescents with fever in neutropenia (FN) during chemotherapy for cancer, hemoglobin ≥90 g/L at presentation with FN had been associated with adverse events (AE). This analysis explored three hypothetical pathophysiological mechanisms potentially explaining this counterintuitive finding, and further analyzed the statistical association between hemoglobin and AE.

Methods

Two of 8 centers, reporting on 311 of 421 FN episodes in 138 of 215 patients participated in this retrospective analysis based on prospectively collected data from three databases (SPOG 2003 FN, transfusion and hematology laboratories). Associations with AE were analyzed using mixed logistic regression.

Results

Hemoglobin was ≥90 g/L in 141 (45%) of 311 FN episodes, specifically in 59/103 (57%) episodes with AE, and in 82/208 (39%) without (OR, 2.3; 99%CI, 1.1–4.9; P = 0.004). In FN with AE, hemoglobin was bimodally distributed with a dip around 85 g/L. There were no significant interactions for center, age and sex. In multivariate mixed logistic regression, AE was significantly and independently associated with leukopenia (leukocytes <0.3 G/L; OR, 3.3; 99%CI, 1.1–99; P = 0.004), dehydration (hemoglobin_Presentation/hemoglobin_{8–72 hours} ≥1.10 in untransfused patients; OR, 3.5; 99%CI, 1.1–11.4; P = 0.006) and non-moderate anemia (difference from 85 g/L; 1.6 per 10 g/L; 1.0–2.6; P = 0.005), but not with recent transfusion of packed red blood cells (pRBC), very recent transfusion of pRBC or platelets, or with hemoglobin ≥90 g/L as such.

Conclusions

Non-moderate anemia and dehydration were significantly and relevantly associated with the risk of AE in children with cancer and FN. These results need validation in prospective cohorts before clinical implementation.     

Recovery from Anemia in Patients with Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation – Prevalence,Predictors and Clinical Outcome

Introduction

Preoperative anemia is common in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and has been linked to a poorer outcome – including a higher 1-year mortality. The aim of this study was to investigate the impact of successful TAVI on baseline anemia.

Methods

A total of 253 patients who survived at least 1 year following TAVI were included in this study. The prevalence, predictors and clinical outcome of hemoglobin (Hb)-recovery were assessed.

Results

The prevalence of baseline anemia was 49% (n = 124) – recovery from anemia occurred in 40% of the anemic patients (n = 49) at 1 year after TAVI with an increase in mean Hb-level of 1.35 g/dL from baseline. This increase was not related to an improvement in renal function. At multivariate analysis, a high peak gradient (OR 4.82, P = 0.003) was shown to be an independent predictor for Hb-recovery, while blood transfusion (OR 0.31, P = 0.038) and chronic kidney disease (CKD, OR 0.33, P = 0.043) were identified as negative predictors at, respectively, one and two years after TAVI. When compared to patients without baseline anemia, those anemic patients with Hb-recovery had a similar functional improvement (OR 0.98, P = 0.975), whereas those without Hb-recovery had a significantly lower likelihood of functional improvement with ≧2 NYHA classes (OR 0.49, P = 0.034) and a higher likelihood of re-hospitalization within the first year after TAVI (OR 1.91, P = 0.024).

Conclusion

Recovery from anemia occurs in 40% of anemic patients at 1 year after TAVI – mainly in those with a high gradient and without CKD. Blood transfusion was found to have a transient adverse effect on this Hb-recovery. Finally, anemic patients without Hb-recovery experience less functional improvement and have a higher re-hospitalization rate within the first year after TAVI.     

New Insight in Loss of Gut Barrier during Major Non-Abdominal Surgery

Background

Gut barrier loss has been implicated as a critical event in the occurrence of postoperative complications. We aimed to study the development of gut barrier loss in patients undergoing major non-abdominal surgery.

Methodology/Principal Findings

Twenty consecutive children undergoing spinal fusion surgery were included. This kind of surgery is characterized by long operation time, significant blood loss, prolonged systemic hypotension, without directly leading to compromise of the intestines by intestinal manipulation or use of extracorporeal circulation. Blood was collected preoperatively, every two hours during surgery and 2, 4, 15 and 24 hours postoperatively. Gut mucosal barrier was assessed by plasma markers for enterocyte damage (I-FABP, I-BABP) and urinary presence of tight junction protein claudin-3. Intestinal mucosal perfusion was measured by gastric tonometry (P_rCO₂, P_r-aCO₂-gap). Plasma concentration of I-FABP, I-BABP and urinary expression of claudin-3 increased rapidly and significantly after the onset of surgery in most children. Postoperatively, all markers decreased promptly towards baseline values together with normalisation of MAP. Plasma levels of I-FABP, I-BABP were significantly negatively correlated with MAP at ½ hour before blood sampling (−0.726 (p<0.001), −0.483 (P<0.001), respectively). Furthermore, circulating I-FABP correlated with gastric mucosal P_rCO₂, P_r-aCO₂-gap measured at the same time points (0.553 (p = 0.040), 0.585 (p = 0.028), respectively).

Conclusions/Significance

This study shows the development of gut barrier loss in children undergoing major non-abdominal surgery, which is related to preceding hypotension and mesenterial hypoperfusion. These data shed new light on the potential role of peroperative circulatory perturbation and intestinal barrier loss.     

SSRIs Increase Risk of Blood Transfusion in Patients Admitted for Hip Surgery

Background

Recent studies have shown that an increased bleeding tendency can be caused by Selective Serotonin Reuptake Inhibitors (SSRI) use. We aimed to investigate the occurrence and risk of blood transfusion in SSRI users compared to non-SSRI users in a cohort of patients admitted for hip-surgery.

Methods

We conducted a retrospective cohort study of patients who underwent planned or emergency hip surgery from 1996 to 2011 in the Academic Medical Center in Amsterdam. Primary outcome measure was risk of blood transfusion. Secondary outcome measures were pre- and postoperative hemoglobin level. Multivariate logistic regression was used to adjust for potential confounders.

Results

One-hundred and fourteen SSRI users were compared to 1773 non-SSRI users. Risk of blood transfusion during admission was increased for SSRI users in multivariate analyses (OR 1.7 [95% CI 1.1–2.5]). Also, pre-operative hemoglobin levels were lower in SSRI users (7.8±1.0 mmol/L) compared to non-SSRI users (8.0±1.0 mmol/L) (p = 0.042)), as were postoperative hemoglobin levels (6.2±1.0 mmol/L vs. 6.4±1.0 mmol/L respectively) (p = 0.017)).

Conclusions

SSRI users undergoing hip surgery have an increased risk for blood transfusion during admission, potentially explained by a lower hemoglobin level before surgery. SSRI use should be considered as a potential risk indicator for increased blood loss in patients admitted for hip surgery. These results need to be confirmed in a prospective study.     

Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua: A Hospital-Based Surveillance Study

Background

The burden of anemia attributable to non-falciparum malarias in regions with Plasmodium co-endemicity is poorly documented. We compared the hematological profile of patients with and without malaria in southern Papua, Indonesia.

Methods and Findings

Clinical and laboratory data were linked for all patients presenting to a referral hospital between April 2004 and December 2012. Data were available on patient demographics, malaria diagnosis, hemoglobin concentration, and clinical outcome, but other potential causes of anemia could not be identified reliably. Of 922,120 patient episodes (837,989 as outpatients and 84,131 as inpatients), a total of 219,845 (23.8%) were associated with a hemoglobin measurement, of whom 67,696 (30.8%) had malaria. Patients with P. malariae infection had the lowest hemoglobin concentration (n = 1,608, mean = 8.93 [95% CI 8.81–9.06]), followed by those with mixed species infections (n = 8,645, mean = 9.22 [95% CI 9.16–9.28]), P. falciparum (n = 37,554, mean = 9.47 [95% CI 9.44–9.50]), and P. vivax (n = 19,858, mean = 9.53 [95% CI 9.49–9.57]); p-value for all comparisons <0.001. Severe anemia (hemoglobin <5 g/dl) was present in 8,151 (3.7%) patients. Compared to patients without malaria, those with mixed Plasmodium infection were at greatest risk of severe anemia (adjusted odds ratio [AOR] 3.25 [95% CI 2.99–3.54]); AORs for severe anaemia associated with P. falciparum, P. vivax, and P. malariae were 2.11 (95% CI 2.00–2.23), 1.87 (95% CI 1.74–2.01), and 2.18 (95% CI 1.76–2.67), respectively, p<0.001. Overall, 12.2% (95% CI 11.2%–13.3%) of severe anemia was attributable to non-falciparum infections compared with 15.1% (95% CI 13.9%–16.3%) for P. falciparum monoinfections. Patients with severe anemia had an increased risk of death (AOR = 5.80 [95% CI 5.17–6.50]; p<0.001). Not all patients had a hemoglobin measurement, thus limitations of the study include the potential for selection bias, and possible residual confounding in multivariable analyses.

Conclusions

In Papua P. vivax is the dominant cause of severe anemia in early infancy, mixed P. vivax/P. falciparum infections are associated with a greater hematological impairment than either species alone, and in adulthood P. malariae, although rare, is associated with the lowest hemoglobin concentration. These findings highlight the public health importance of integrated genus-wide malaria control strategies in areas of Plasmodium co-endemicity. Please see later in the article for the Editors'' Summary     

The Application of Transcutaneous CO2 Pressure Monitoring in the Anesthesia of Obese Patients Undergoing Laparoscopic Bariatric Surgery

To investigate the correlation and accuracy of transcutaneous carbon dioxide partial pressure (P_TCCO₂) with regard to arterial carbon dioxide partial pressure (P_aCO₂) in severe obese patients undergoing laparoscopic bariatric surgery. Twenty-one patients with BMI>35 kg/m² were enrolled in our study. Their P_aCO₂, end-tidal carbon dioxide partial pressure (P_etCO₂), as well as P_TCCO₂ values were measured at before pneumoperitoneum and 30 min, 60 min, 120 min after pneumoperitoneum respectively. Then the differences between each pair of values (P_etCO₂–P_aCO₂) and_. (P_TCCO₂–P_aCO₂₎ were calculated. Bland–Altman method, correlation and regression analysis, as well as exact probability method and two way contingency table were employed for the data analysis. 21 adults (aged 19–54 yr, mean 29, SD 9 yr; weight 86–160 kg, mean119.3, SD 22.1 kg; BMI 35.3–51.1 kg/m², mean 42.1,SD 5.4 kg/m²) were finally included in this study. One patient was eliminated due to the use of vaso-excitor material phenylephrine during anesthesia induction. Eighty-four sample sets were obtained. The average P_aCO₂–P_TCCO₂ difference was 0.9±1.3 mmHg (mean±SD). And the average P_aCO₂–P_etCO₂ difference was 10.3±2.3 mmHg (mean±SD). The linear regression equation of P_aCO₂–P_etCO₂ is P_etCO₂ = 11.58+0.57×P_aCO₂ (r² = 0.64, P<0.01), whereas the one of P_aCO₂–P_TCCO₂ is P_TCCO₂ = 0.60+0.97×P_aCO₂ (r² = 0.89). The LOA (limits of agreement) of 95% average P_aCO₂–P_etCO₂ difference is 10.3±4.6 mmHg (mean±1.96 SD), while the LOA of 95% average P_aCO₂–P_TCCO2 difference is 0.9±2.6 mmHg (mean±1.96 SD). In conclusion, transcutaneous carbon dioxide monitoring provides a better estimate of PaCO₂ than P_etCO₂ in severe obese patients undergoing laparoscopic bariatric surgery.     

Limited Utility of ITPA Deficiency to Predict Early Anemia in HCV Patients with Advanced Fibrosis Receiving Telaprevir

Background

Severe anemia is a common side effect of Pegylated Interferon + Ribavirin (PR) and Telaprevir (TVR) in hepatitis C virus (HCV) genotype 1 patients with advanced fibrosis or cirrhosis (F3–F4). Inosine triphosphatase (ITPA) genetic variants are associated with RBV- induced anemia and dose reduction.

Aim

To test the association of ITPA polymorphisms rs1127354 and rs7270101 with hemoglobin (Hb) decline, need for RBV dose reduction (RBV DR), erythropoietin (EPO) support and blood transfusions during the first 12 weeks of TVR triple therapy.

Materials and Methods

69 consecutive HCV-1 patients (mean age 57 years) with F3-F4 who received PR and TVR were genotyped for ITPA polymorphisms rs1127354 and rs7270101. Estimated ITPA deficiency was graded on severity (0–3, no deficiency/mild/moderate/severe).

Results

ITPA deficiency was absent in 48 patients (70%), mild in 12 (17%) and moderate in 9 patients (13%). Mean week 4 Hb decline was higher in non ITPA deficient patients (3,85 g/dL) than in mildly or moderately ITPA deficient patients (3,07 g/dL and 1,67 g/dL, p<0.0001). Grade 3–4 anemia developed in 81% non ITPA deficient patients versus 67% mild deficient and 55% moderate deficient patients (p = ns). Grade of ITPA deficiency was not associated with RbvDR (no deficiency: 60%, mild: 58%, moderate: 67%; p = ns), EPO use (no deficiency: 65%, mild: 58%, moderate:56%; p = ns) or need for blood transfusion (no deficiency: 27%, mild: 17%, moderate: 33%; p = ns).

Conclusions

In patients with F3–F4 chronic hepatitis C receiving TVR based therapy, ITPA genotype does not impact on the management of early anemia.     

The Relationship between Type D Personality,Affective Symptoms and Hemoglobin Levels in Chronic Heart Failure

Background

Anemia is associated with poor prognosis in heart failure (HF) patients. Contributors to the risk of anemia in HF include hemodilution, renal dysfunction and inflammation. Hemoglobin levels may also be negatively affected by alterations in stress regulatory systems. Therefore, psychological distress characterized by such alterations may adversely affect hemoglobin in HF. The association between hemoglobin and Type D personality and affective symptomatology in the context of HF is poorly understood.

Aim

To examine the relationship between Type D personality and affective symptomatology with hemoglobin levels at inclusion and 12-month follow-up, controlling for relevant clinical factors.

Methods

Plasma levels of hemoglobin and creatinine were assessed in 264 HF patients at inclusion and at 12-month follow-up. Type D personality and affective symptomatology were assessed at inclusion.

Results

At inclusion, hemoglobin levels were similar for Type D and non-Type D HF patients (p = .23), and were moderately associated with affective symptomatology (r = –.14, p = .02). Multivariable regression showed that Type D personality (β = –.15; p = .02), was independently associated with future hemoglobin levels, while controlling for renal dysfunction, gender, NYHA class, time since diagnosis, BMI, the use of angiotensin-related medication, and levels of affective symptomatology. Change in renal function was associated with Type D personality (β = .20) and hemoglobin at 12 months (β = –.25). Sobel mediation analysis showed significant partial mediation of the Type D – hemoglobin association by renal function deterioration (p = .01). Anemia prevalence increased over time, especially in Type D patients. Female gender, poorer baseline renal function, deterioration of renal function and a longer HF history predicted the observed increase in anemia prevalence over time, while higher baseline hemoglobin was protective.

Conclusion

Type D personality, but not affective symptomatology, was associated with reduced future hemoglobin levels, independent of clinical factors. The relation between Type D personality and future hemoglobin levels was mediated by renal function deterioration.     

Brain MRI CO2 Stress Testing: A Pilot Study in Patients with Concussion

Background

There is a real need for quantifiable neuro-imaging biomarkers in concussion. Here we outline a brain BOLD-MRI CO₂ stress test to assess the condition.

Methods

This study was approved by the REB at the University of Manitoba. A group of volunteers without prior concussion were compared to post-concussion syndrome (PCS) patients – both symptomatic and recovered asymptomatic. Five 3-minute periods of BOLD imaging at 3.0 T were studied – baseline 1 (BL1– at basal CO₂ tension), hypocapnia (CO₂ decreased ∼5 mmHg), BL2, hypercapnia (CO₂ increased ∼10 mmHg) and BL3. Data were processed using statistical parametric mapping (SPM) for 1^st level analysis to compare each subject’s response to the CO₂ stress at the p = 0.001 level. A 2^nd level analysis compared each PCS patient’s response to the mean response of the control subjects at the p = 0.05 level.

Results

We report on 5 control subjects, 8 symptomatic and 4 asymptomatic PCS patients. Both increased and decreased response to CO₂ was seen in all PCS patients in the 2^nd level analysis. The responses were quantified as reactive voxel counts: whole brain voxel counts (2.0±1.6%, p = 0.012 for symptomatic patients for CO₂ response < controls and 3.0±5.1%, p = 0.139 for CO₂ response > controls: 0.49±0.31%, p = 0.053 for asymptomatic patients for CO₂ response < controls and 4.4±6.8%, p = 0.281 for CO₂ response > controls).

Conclusions

Quantifiable alterations in regional cerebrovascular responsiveness are present in concussion patients during provocative CO₂ challenge and BOLD MRI and not in healthy controls. Future longitudinal studies must aim to clarify the relationship between CO₂ responsiveness and individual patient symptoms and outcomes.     

Gender-Specific Effects of Genetic Variants within Th1 and Th17 Cell-Mediated Immune Response Genes on the Risk of Developing Rheumatoid Arthritis

The present study was conducted to explore whether single nucleotide polymorphisms (SNPs) in Th1 and Th17 cell-mediated immune response genes differentially influence the risk of rheumatoid arthritis (RA) in women and men. In phase one, 27 functional/tagging polymorphisms in C-type lectins and MCP-1/CCR2 axis were genotyped in 458 RA patients and 512 controls. Carriers of Dectin-2 _rs4264222T allele had an increased risk of RA (OR = 1.47, 95%CI 1.10–1.96) whereas patients harboring the DC-SIGN _rs4804803G, MCP-1 _rs1024611G, MCP-1 _rs13900T and MCP-1 _rs4586C alleles had a decreased risk of developing the disease (OR = 0.66, 95%CI 0.49–0.88; OR = 0.66, 95%CI 0.50–0.89; OR = 0.73, 95%CI 0.55–0.97 and OR = 0.68, 95%CI 0.51–0.91). Interestingly, significant gender-specific differences were observed for Dectin-2 _rs4264222 and Dectin-2 _rs7134303: women carrying the Dectin-2 _rs4264222T and Dectin-2 _rs7134303G alleles had an increased risk of RA (OR = 1.93, 95%CI 1.34–2.79 and OR = 1.90, 95%CI 1.29–2.80). Also five other SNPs showed significant associations only with one gender: women carrying the MCP-1 _rs1024611G, MCP-1 _rs13900T and MCP-1 _rs4586C alleles had a decreased risk of RA (OR = 0.61, 95%CI 0.43–0.87; OR = 0.67, 95%CI 0.47–0.95 and OR = 0.60, 95%CI 0.42–0.86). In men, carriers of the DC-SIGN _rs2287886A allele had an increased risk of RA (OR = 1.70, 95%CI 1.03–2.78), whereas carriers of the DC-SIGN _rs4804803G had a decreased risk of developing the disease (OR = 0.53, 95%CI 0.32–0.89). In phase 2, we genotyped these SNPs in 754 RA patients and 519 controls, leading to consistent gender-specific associations for Dectin-2 _rs4264222, MCP-1 _rs1024611, MCP-1 _rs13900 and DC-SIGN _rs4804803 polymorphisms in the pooled sample (OR = 1.38, 95%CI 1.08–1.77; OR = 0.74, 95%CI 0.58–0.94; OR = 0.76, 95%CI 0.59–0.97 and OR = 0.56, 95%CI 0.34–0.93). SNP-SNP interaction analysis of significant SNPs also showed a significant two-locus interaction model in women that was not seen in men. This model consisted of Dectin-2 _rs4264222 and Dectin-2 _rs7134303 SNPs and suggested a synergistic effect between the variants. These findings suggest that Dectin-2, MCP-1 and DC-SIGN polymorphisms may, at least in part, account for gender-associated differences in susceptibility to RA.     

Severity of Anemia among Children under 36 Months Old in Rural Western China

Objective

To describe severity of anemia and explore its determinants among children under 36 months old in rural western China.

Study Design

The family information of 6711 children was collected and their hemoglobin was measured in 2005. A generalized estimated equation (GEE) linear model was used to identify the determinants of severity of childhood anemia.

Results

The prevalence of mild, moderate and severe anemia among these children was 27.4%, 21.9% and 3.2% respectively. GEE model analysis showed that province-level region and severity of maternal anemia affected the severity of childhood anemia not only in 0–5 months but also beyond 5 months. In addition, children aged 0–5 months in families using iron pot (coefficient = −0.26 95%CI −0.41,−0.12) had seldom more severe anemia, and children aged 6–36 months in families more than 4 members (coefficient = −0.03 95%CI −0.06,−0.01) or of Han ethnicity (coefficient = −0.08 95%CI −0.13,−0.04) seldom had more severe anemia but boys (coefficient = 0.03 95%CI 0.01,0.06) or younger children (6–11 month vs 30–36 month: coefficient = 0.23 95%CI 0.17, 0.28; 12–17 month vs 30–36 month: coefficient = 0.19 95%CI 0.15,0.24; 18–23 vs 30–36 month: coefficient = 0.09 95%CI 0.04,0.13) had more severe anemia.

Conclusion

The prevalence of moderate-to-severe anemia in these children was about 25%. Province-level region, iron pot use, family size, ethnicity, age and gender of children and severity of maternal anemia were important determinants of the severity of childhood anemia. These findings have some important implications for health policy decision for childhood anemia in rural western China.     

Prognostic Value of Lactate and Central Venous Oxygen Saturation after Early Resuscitation in Sepsis Patients

The objective of this study was to evaluate the prognostic value of static and dynamic variables of central venous oxygen saturation (ScvO₂) and lactate in patients with severe sepsis or septic shock who underwent early quantitative resuscitation. We also investigated whether ScvO₂ measured after initial resuscitation could provide additive prognostic value to that of lactate. We analyzed the sepsis registry for patients presenting to the emergency department and included patients with simultaneous measurements of lactate and ScvO₂ at the time of presentation (H0) and 6 hours (H6) after resuscitation. The primary outcome was 28-day mortality and multivariable logistic analysis was used to adjust for confounders. A total of 363 patients were included, and the overall 28-day mortality was 18%. The area under the receiver operator characteristic curve for predicting 28-day mortality was as follows: lactate (H6), 0.81; lactate (H0), 0.73; relative lactate change, 0.67; ScvO₂ (H6), 0.65; relative ScvO₂ change 0.59; ScvO₂ (H0), 0.58. Patients with lactate normalization showed significantly lower 28-day mortality compared to patients without lactate normalization (3% vs. 28%, P<0.01). However, in those who achieved ScvO₂ (H6) ≥70%, there was a significant difference in 28-mortality only in patients without lactate normalization (21% vs. 39%, P<0.01) but no difference in those with lactate normalization (4% vs. 3%, P = 0.71). In multivariable analysis, lactate normalization was significantly associated with 28-day mortality (adjusted odds ratio [OR] for 28-day mortality, 0.20; 95% confidence interval [CI], 0.07–0.54; P <0.01), but ScvO₂ (H6) ≥70% showed only a marginal association (the adjusted OR for 28-day mortality, 0.51; 95% CI, 0.26–1.01; P = 0.05). ScvO₂ (H6) ≥70% was associated with 28-day mortality only in cases without lactate normalization in subgroup analysis (adjusted OR 0.37, 95% CI, 0.18–0.79; P = 0.01). Six-hour lactate was the strongest predictor of 28-day mortality in patients with severe sepsis or septic shock. Six-hour ScvO₂ provided additional prognostic value only in cases where lactate values were not normalized after resuscitation.     

Anemia and Risk Factors in HAART Na?ve and HAART Experienced HIV Positive Persons in South West Ethiopia: A Comparative Study

Background

Human immunodeficiency virus (HIV) infection and its treatment cause a range of hematological abnormalities. Anemia is one of the commonly observed hematologic manifestations in HIV positive persons and it has multifactorial origin.

Objective

We aimed to determine the prevalence and risk factors of anemia in highly active antiretroviral therapy (HAART) naïve and HAART experienced HIV positive persons.

Methods

A facility-based comparative cross sectional study was conducted in Jimma University Specialized Hospital from February 1 to March 30, 2012. A total of 234 HIV positive persons, 117 HAART naïve and 117 HAART experienced, were enrolled in this study. Blood and stool specimens were collected from each participant. Blood specimens were examined for complete blood count, CD4 count and blood film for malaria hemoparasite; whereas stool specimens were checked for ova of intestinal parasites. Socio-demographic characteristics and clinical data of the participants were collected using pre-tested questionnaire. Statistical analysis of the data (Chi-square, student’s t-test, logistic regression) was done using SPSS V-16.

Results

The overall prevalence of anemia was 23.1%. The prevalence of anemia in HAART naïve and HAART experienced persons was 29.9% and 16.2%, respectively (P = 0.014). Presence of opportunistic infections (P = 0.004, 95% CI = 1.69–15.46), CD4 count <200 cells/µl (P = 0.001, 95% CI = 2.57–36.89) and rural residence (P = 0.03, 95% CI = 1.12–10.39) were found to be predictors of anemia for HAART naïve participants. On the other hand, HAART regimen (ZDV/3TC/NVP) (P = 0.019, 95% CI = 0.01–1.24) and the duration of HAART (P = 0.007, 95% CI = 0.003–0.40.24) were found to be predictors of anemia for HAART experienced groups.

Conclusion

The prevalence of anemia in HAART naïve persons was higher than HAART experienced persons. Risk factors for anemia in HAART naïve and HAART experienced HIV positive persons were different. Hence, there is a need for longitudinal study to further explore the causes of HIV associated anemia and the pattern of hemoglobin changes with initiation of HAART.     

Oxygen Generating Biomaterials Preserve Skeletal Muscle Homeostasis under Hypoxic and Ischemic Conditions

Provision of supplemental oxygen to maintain soft tissue viability acutely following trauma in which vascularization has been compromised would be beneficial for limb and tissue salvage. For this application, an oxygen generating biomaterial that may be injected directly into the soft tissue could provide an unprecedented treatment in the acute trauma setting. The purpose of the current investigation was to determine if sodium percarbonate (SPO), an oxygen generating biomaterial, is capable of maintaining resting skeletal muscle homeostasis under otherwise hypoxic conditions. In the current studies, a biologically and physiologically compatible range of SPO (1–2 mg/mL) was shown to: 1) improve the maintenance of contractility and attenuate the accumulation of HIF1α, depletion of intramuscular glycogen, and oxidative stress (lipid peroxidation) that occurred following ∼30 minutes of hypoxia in primarily resting (duty cycle = 0.2 s train/120 s contraction interval <0.002) rat extensor digitorum longus (EDL) muscles in vitro (95% N₂–5% CO₂, 37°C); 2) attenuate elevations of rat EDL muscle resting tension that occurred during contractile fatigue testing (3 bouts of 25 100 Hz tetanic contractions; duty cycle = 0.2 s/2 s = 0.1) under oxygenated conditions in vitro (95% O₂–5% CO₂, 37°C); and 3) improve the maintenance of contractility (in vivo) and prevent glycogen depletion in rat tibialis anterior (TA) muscle in a hindlimb ischemia model (i.e., ligation of the iliac artery). Additionally, injection of a commercially available lipid oxygen-carrying compound or the components (sodium bicarbonate and hydrogen peroxide) of 1 mg/mL SPO did not improve EDL muscle contractility under hypoxic conditions in vitro. Collectively, these findings demonstrate that a biological and physiological concentration of SPO (1–2 mg/mL) injected directly into rat skeletal muscle (EDL or TA muscles) can partially preserve resting skeletal muscle homeostasis under hypoxic conditions.     

Hemoglobin May Contribute to Sex Differences in Mortality among HIV-Infected Persons in Care

Background

Some retrospective studies have found that HIV-infected women have a higher mortality risk than men after adjusting for baseline characteristics, while others have not. Anemia is a known predictor of HIV-related mortality. We assessed whether anemia contributed to the sex difference in mortality in our cohort.

Methods

We conducted a retrospective cohort study among HIV-infected persons in care at the Comprehensive Care Center (Nashville, TN) between 1998 and 2009. Cox proportional hazards models compared time from first clinic visit to death and AIDS-defining events (ADE), adjusted for baseline characteristics with and without baseline hemoglobin.

Results

Of 3,633 persons, 879 (24%) were women. Women had lower median baseline hemoglobin compared to men: 12.4 g/dL (inter-quartile range (IQR) 11.3–13.4) vs. 14.4 (IQR 13.1–15.5), respectively (P<0.001). In multivariable models without hemoglobin, the risk of death was higher among women: hazard ratio (HR) 1.46 (95% confidence interval (CI) 1.17, 1.82; P = 0.001). In multivariable models with hemoglobin, the risk of death in women was diminished and no longer statistically significant: HR 1.2 (95% CI 0.93, 1.55; P = 0.17). The risk of ADE was higher among women in both models, but not statistically significant: HR 1.1 (95% CI 0.85–1.42; P = 0.46) in the model without hemoglobin and 1.11 (95% CI 0.82–1.48; P = 0.50) in the model with hemoglobin. Hemoglobin was a strong predictor of death: HR 0.88 per 1 g/dL increase (95% CI 0.83, 0.93; P<0.001).

Conclusion

In our study population of HIV-infected persons in care, women had lower baseline hemoglobin, and lower hemoglobin contributed to their higher risk of ADE and death.     

Severe Nocturnal and Postexercise Hypoxia in Children and Adolescents with Sickle Cell Disease

Hypoxia is a common feature in children with sickle cell disease (SCD) that is inconsistently associated with painful crises and acute chest syndrome. To assess the prevalence and risk factors of hypoxia, we recorded daytime, nocturnal, and postexercise pulse oximetry (SpO₂) values in 39 SCD patients with a median age of 10.8 years. Median daytime SpO₂ was 97% (range, 89%–100%), and 36% of patients had daytime hypoxia defined as SpO₂<96%. Median nocturnal SpO₂ was 94.7% (range, 87.7%–99.5%), 50% of patients had nocturnal hypoxia defined as SpO₂≤93%, and 11(37%) patients spent more than 10% of their total sleep time with SpO₂<90%. Median postexercise SpO₂ was 94% (range, 72%–100%) and 44.7% of patients had postexercise hypoxia defined as an SpO₂ decrease ≥3% after a 6-minute walk test. Among patients with normal daytime SpO₂, 35% had nocturnal and 42% postexercise hypoxia. Compared to 9 patients without daytime, nocturnal, or postexercise hypoxia, 25 patients with hypoxia under at least one of these three conditions had greater anemia severity (P = 0.01), lower HbF levels (P = 0.04), and higher aspartate aminotransferase levels (P = 0.03). Males predominated among patients with postexercise hypoxia (P = 0.004). Hypoxia correlated neither with painful crises nor with acute chest syndrome. Of 32 evaluable patients, 6 (18.8%) had a tricuspid regurgitation velocity ≥2.6 m/s, and this feature was associated with anemia (P = 0.044). Median percentage of the predicted distance covered during a 6-minute walk test was 86% [46–120]; the distance was negatively associated with LDH (P = 0.044) and with a past history of acute chest syndrome (P = 0.009). In conclusion, severe episodes of nocturnal and postexercise hypoxia are common in children with SCD, even those with normal daytime SpO₂.     

End Criteria for Reaching Maximal Oxygen Uptake Must Be Strict and Adjusted to Sex and Age: A Cross-Sectional Study

Objective

To describe different end criteria for reaching maximal oxygen uptake (VO_2max) during a continuous graded exercise test on the treadmill, and to explore the manner by which different end criteria have an impact on the magnitude of the VO_2max result.

Methods

A sample of 861 individuals (390 women) aged 20–85 years performed an exercise test on a treadmill until exhaustion. Gas exchange, heart rate, blood lactate concentration and Borg Scale_6–20 rating were measured, and the impact of different end criteria on VO_2max was studied;VO₂ leveling off, maximal heart rate (HR_max), different levels of respiratory exchange ratio (RER), and postexercise blood lactate concentration.

Results

Eight hundred and four healthy participants (93%) fulfilled the exercise test until voluntary exhaustion. There were no sex-related differences in HR_max, RER, or Borg Scale rating, whereas blood lactate concentration was 18% lower in women (P<0.001). Forty-two percent of the participants achieved a plateau in VO₂; these individuals had 5% higher ventilation (P = 0.033), 4% higher RER (P<0.001), and 5% higher blood lactate concentration (P = 0.047) compared with participants who did not reach a VO₂ plateau. When using RER ≥1.15 or blood lactate concentration ≥8.0 mmol•L^–1, VO_2max was 4% (P = 0.012) and 10% greater (P<0.001), respectively. A blood lactate concentration ≥8.0 mmol•L^–1 excluded 63% of the participants in the 50–85-year-old cohort.

Conclusions

A range of typical end criteria are presented in a random sample of subjects aged 20–85 years. The choice of end criteria will have an impact on the number of the participants as well as the VO_2max outcome. Suggestions for new recommendations are given.     

DCM-Related Tropomyosin Mutants E40K/E54K Over-Inhibit the Actomyosin Interaction and Lead to a Decrease in the Number of Cycling Cross-Bridges

Two DCM mutants (E40K and E54K) of tropomyosin (Tm) were examined using the thin-filament extraction/reconstitu­tion technique. The effects of the Ca²⁺, ATP, phos­phate (Pi), and ADP concentrations on isometric tension and its transients were studied at 25°C, and the results were com­pared to those for the WT protein. Our results indicate that both E40K and E54K have a significantly lower T _HC (high Ca²⁺ ten­sion at pCa 4.66) (E40K: 1.21±0.06 T _a, ±SEM, N = 34; E54K: 1.24±0.07 T _a, N = 28), a significantly lower T _LC (low- Ca²⁺ tension at pCa 7.0) (E40K: 0.07±0.02 T _a, N = 34; E54K: 0.06±0.02 T _a, N = 28), and a significantly lower T _act (Ca²⁺ activatable tension) (T _act = T _HC–T_LC, E40K: 1.15±0.08 T _a, N = 34; E54K: 1.18±0.06 T _a, N = 28) than WT (T _HC = 1.53±0.07 T _a, T _LC = 0.12±0.01 T _a, T _act = 1.40±0.07 T _a, N = 25). All tensions were normalized to T _a ( = 13.9±0.8 kPa, N = 57), the ten­sion of actin-filament reconstituted cardiac fibers (myocardium) under the standard activating conditions. The Ca²⁺ sensitivity (pCa₅₀) of E40K (5.23±0.02, N = 34) and E54K (5.24±0.03, N = 28) was similar to that of the WT protein (5.26±0.03, N = 25). The cooper­a­tivity increased significantly in E54K (3.73±0.25, N = 28) compared to WT (2.80±0.17, N = 25). Seven kinetic constants were deduced using sinusoidal analysis at pCa 4.66. These results enabled us to calculate the cross-bridge distribution in the strongly attached states, and thereby deduce the force/cross-bridge. The results indicate that the force/cross-bridge is ∼15% less in E54K than WT, but remains similar to that of the WT protein in the case of E40K. We conclude that over-inhibition of the actomyosin interaction by E40K and E54K Tm mutants leads to a decreased force-generating ability at systole, which is the main mechanism underlying the early pathogenesis of DCM.     

Aprotinin May Increase Mortality in Low and Intermediate Risk but Not in High Risk Cardiac Surgical Patients Compared to Tranexamic Acid and ε-Aminocaproic Acid – A Meta-Analysis of Randomised and Observational Trials of over 30.000 Patients

Background

To compare the effect of aprotinin with the effect of lysine analogues (tranexamic acid and ε-aminocaproic acid) on early mortality in three subgroups of patients: low, intermediate and high risk of cardiac surgery.

Methods and Findings

We performed a meta-analysis of randomised controlled trials and observational with the following data sources: Medline, Cochrane Library, and reference lists of identified articles. The primary outcome measure was early (in-hospital/30-day) mortality. The secondary outcome measures were any transfusion of packed red blood cells within 24 hours after surgery, any re-operation for bleeding or massive bleeding, and acute renal dysfunction or failure within the selected cited publications, respectively.Out of 328 search results, 31 studies (15 trials and 16 observational studies) included 33,501 patients. Early mortality was significantly increased after aprotinin vs. lysine analogues with a pooled risk ratio (95% CI) of 1.58 (1.13–2.21), p<0.001 in the low (n = 14,297) and in the intermediate risk subgroup (1.42 (1.09–1.84), p<0.001; n = 14,427), respectively. Contrarily, in the subgroup of high risk patients (n = 4,777), the risk for mortality did not differ significantly between aprotinin and lysine analogues (1.03 (0.67–1.58), p = 0.90).

Conclusion

Aprotinin may be associated with an increased risk of mortality in low and intermediate risk cardiac surgery, but presumably may has no effect on early mortality in a subgroup of high risk cardiac surgery compared to lysine analogues. Thus, decisions to re-license aprotinin in lower risk patients should critically be debated. In contrast, aprotinin might probably be beneficial in high risk cardiac surgery as it reduces risk of transfusion and bleeding complications.