Optimizing management of sickle cell disease in patients undergoing surgery

Individuals with sickle cell disease (SCD) are likely to be referred for surgery at some point in their lifetime due to a high incidence of musculoskeletal and intrabdominal complications such as avascular necrosis and gallbladder disease. Preoperative optimization is a multidisciplinary process that involves a hematologist with SCD expertise, an anesthesiologist, and the surgical team. The type and risk classification of the surgery, disease severity, medications, baseline hemoglobin, transfusion history, and history of prior surgical complications are often documented. Clinicians should consider perioperative risk assessment that includes determining the patient's functional status and cardiovascular risk and screening for obstructive sleep apnea. Many patients will require preoperative transfusion to reduce the risk of postoperative complications such as acute chest syndrome and vaso-occlusive pain crises. The hematologist should consider the patient's preoperative transfusion requirements and ensure that the surgical team has an appropriate plan for postoperative observation and management. This often includes follow-up laboratory studies, a postoperative pain management plan, and venous thromboembolism prophylaxis. The transfusion plan should be patient-specific and take into account the SCD genotype, baseline hemoglobin, disease severity, risk classification of the surgery, and history of prior surgical complications. In the intraoperative and postoperative period, dehydration, hypothermia, hypotension, hypoxia, and acidosis should be avoided, and incentive spirometry should be utilized to minimize complications such as acute chest syndrome. In this review we discuss preoperative, intraoperative, and postoperative strategies to optimize patients with SCD undergoing surgery.

Use of metformin following a population-level intervention to encourage people with pre-diabetes to enroll in the National Diabetes Prevention Program

IntroductionThe National Diabetes Prevention Program (NDPP) and metformin are interventions to slow progression from pre-diabetes to type 2 diabetes. When coverage for the NDPP was offered by a public research university’s health insurance plan, proactive strategies were used to combat historically low enrollment. Although not specifically targeted by these strategies, metformin use was higher than expected, leading to this evaluation.Research design and methodsWe used insurance enrollment, claims, pharmacy, and laboratory data for 64 131 adult employees, dependents, and retirees to identify individuals with pre-diabetes and invite them to enroll in the NDPP at no out-of-pocket cost. The characteristics of individuals with pre-diabetes who used metformin before and after their invitation were compared with NDPP enrollees.Results8131 individuals with pre-diabetes were identified. Of these, 776 (9.5%) enrolled in a NDPP and 802 (9.9%) used metformin. Metformin users were younger, had higher body mass index, were more likely to have comorbidities, and had higher baseline hemoglobin A1c levels than non-users. Timing of metformin use varied with 107 (13%) discontinuing, 426 (53%) continuing, and 269 (34%) initiating metformin use after their NDPP invitation. Of NDPP enrollees, 13 (2%) discontinued, 56 (7%) continued, and 34 (4%) initiated metformin use when they enrolled.ConclusionsDespite no active encouragement, use of metformin was similar to the rate of enrollment in the NDPP. Metformin use was higher for individuals with higher likelihood of responding. With the proven cost-effectiveness of metformin, targeted strategies to increase metformin use in individuals with pre-diabetes who are likely to respond, but not willing to enroll in a lifestyle intervention, are needed.

Age and baseline creatinine as risk factors for methotrexate nephrotoxicity in children with acute lymphoblastic leukemia in resource-limited countries

Introduction. The search for risk factors for high-dose methotrexate (MTX)–induced nephrotoxicity in children with acute lymphoblastic leukemia (ALL) has been complex in the context of resource-limited countries where serum levels of MTX are not always available. Objective. To analyze the demographic, clinical, and biochemical factors associated with MTX-induced nephrotoxicity in children with ALL. Methodology. Case-control study in children with ALL from a General Hospital in Mexico over a four-year period (2016-2020). Kidney damage was defined with KDIGO criteria and the following variables were analyzed: sex, age, weight, height, creatinine, urea, transaminases, hematic cytometry, vomiting, mucositis, dermatitis, and number of MTX applications. Results: One hundred and eight children were studied, 22 females (38%) and 36 males (62%), ages 1 to14 years. The incidence of nephrotoxicity was 5.8% in 238 events of MTX administration. The children in the group with nephrotoxicity were older (average age 9.5 vs 5, p = 0.036), had higher baseline creatinine (0.5 mg/dL vs 0.4 mg/dL p = 0.006), and had lower baseline hemoglobin (10.1 g/dL vs 11.3 g/dL, p = 0.034). Mucositis was associated with nephrotoxicity with OR 13 95% CI 4-42, p <0.001. A cut-off value for creatinine of 0.44 mg/dL (AUC of 68%) and an age of 8 years (AUC of 64%) were identified for risk of nephrotoxicity. Conclusions: The incidence of MTX nephrotoxicity in children with ALL was 5.8%, with a high association with mucositis. The risk is greater for children older than 8 years and baseline creatinine higher than 0.44 mg/dL.

Resolution of Unexplained Iron Deficiency Following Successful Eradication of Helicobacter Pylori in Children

Background: Evidence is needed to inform whether Helicobacter pylori (HP) treatment is beneficial in children with refractory iron deficiency. We aimed to assess association between successful HP eradication and resolution of unexplained iron deficiency. Methods: Medical records of children diagnosed with HP infection (based on histopathology) and without significant upper gastrointestinal source of blood loss, were retrospectively reviewed for presence of iron deficiency. Among those with non-anemic iron deficiency (NAID) or iron deficiency anemia (IDA), hemoglobin, ferritin and C-reactive protein (CRP) levels were compared prior and 6-9 months’ post successful HP eradication. Patients with overt bleeding or subsequent iron supplement therapy post HP diagnosis were excluded. Predictors of resolution of iron deficiency following HP eradication were assessed. Results: Among 60 included children (median age 14.8, IQR12.3-16; 62% males), symptoms of anemia were observed in 20%. A total of 21 (35%) had IDA while the remainder 65% had NAID. Following successful HP eradication, 60% of these 60 patients normalized their iron status. There were significant improvements in both hemoglobin and ferritin following HP eradication with hemoglobin increasing from 12.3g/dL to 13.0 g/dL (P<0.001), and ferritin increasing from 6.3μg/l to 15.1 μg/l (P<0.001). In multivariate logistic regression that assessed sex, ethnicity, baseline hemoglobin, anemia or GI symptoms, previous iron therapy, and time from diagnosis to eradication, older age was the only factor associated with resolution of anemia following HP eradication: (OR 1.65, 95% CI 1.16-2.35, P = 0.005).Conclusion: Successful HP eradication could be helpful in improving iron status among children with refractory NAID or IDA. Older age may predict this outcome. Screening for HP should be considered in the workup of refractory IDA or NAID.

Hb Levels and Sex Differences in Relation to Short-Term Outcomes in Patients With Acute Myocardial Infarction

Background: Women had worse outcomes after acute myocardial infarction (AMI), and physiologically, women had lower hemoglobin values. We examined whether there were sex-related differences in the relationship between hemoglobin levels and adverse outcomes in patients with acute myocardial infarction.Method: We conducted a post-hoc analysis of data from the Acute Coronary Syndrome Quality Improvement in Kerala (ACS-QUIK) Study. We explored the relationship between baseline hemoglobin level and 30-days adverse outcomes by logistic regression model, generalized additive model (GAM) and two-piecewise linear regression model. We used multiple imputation, based on five replications and a chained equation approach method in the R multiple imputation procedure, to account for missing data. The primary outcome were 30-day major adverse cardiovascular events (MACEs) defined as death, reinfarction, stroke, and major bleeding. The secondary outcomes were 30-day major bleeding, 30-day stroke and 30-day cardiovascular death (CVD death).Results: Twenty thousand, five hundred fifty-nine patients with AMI were included in our analysis. Baseline hemoglobin level was associated with major bleeding [OR: 0.74, 95%CI (0.60, 0.92) P &lt; 0.01], CVD death [OR: 0.94, 95%CI (0.90, 0.99) P &lt; 0.01], and MACEs [OR: 0.95, 95%CI (0.92, 0.99) P &lt; 0.01]. There was no significant relationship between baseline hemoglobin level and stroke incidence in both men [OR: 1.02, 95%CI (0.90, 1.14) P = 0.77] and women [OR: 1.15, 95%CI (0.96, 1.37) P = 0.18]. Baseline hemoglobin level was associated with major bleeding [OR: 0.71, 95%CI (0.58, 0.85) P &lt; 0.01] in male patients, however we did not find the same relationship in female patients [OR: 0.89, 95%CI (0.56, 1.41) P = 0.61]. GAM and two-piecewise linear regression model showed the relationships of hemoglobin level with major bleeding, CVD death, and MACEs were non-linear (non-linear P &lt; 0.05), and the threshold value were 13, 14.8, and 14.3 g/dL for MACEs and CVD death, respectively.Conclusion: Baseline hemoglobin level was one of the independent predictors of prognosis in South Asia patients with acute myocardial infarction. Moreover, its impact on prognosis was largely different depending on the patients' sex.

Comparison of Bleeding Rates between Oral Anticoagulants in Combination with Dual Antiplatelet Therapy (Triple Therapy) in a Real-World Cohort

Background: Triple antithrombotic therapy including an anticoagulant, P2Y12 inhibitor, and aspirin increases bleed risk up to 27%. The components of this regimen can vary, which may impact bleed risk. Objective: To compare the safety of various triple antithrombotic regimens. Methods: An Institutional Review Board approved retrospective cohort study was conducted from 2014 to 2017. Patients admitted to a large urban health system on triple therapy were evaluated for inclusion. The primary outcome compared rates of International Society of Thrombosis and Hemostasis major and clinically relevant nonmajor bleeding during index admission or within 90 days in patients receiving warfarin, rivaroxaban, or apixaban; aspirin; and a P2Y12 inhibitor. A multivariable logistic regression assessed the association between bleeding, antithrombotic use, and relevant confounding variables. Results: Three hundred and seventy-two patients were included: 238 patients received warfarin, 63 received rivaroxaban, and 71 received apixaban. Forty-five patients (12.1%) experienced a bleed, 25 of which (55.6%) were major. The rate of bleeding was 12.2% (n = 29) with warfarin, 14.3% (n = 9) with rivaroxaban, and 9.9% (n = 7) with apixaban ( P = .7335). The use of prasugrel versus clopidogrel (OR 4.35, 95% CI 1.20-15.72; P = .025) and admission hemoglobin less than 12 mg/dL (OR 2.54, 95% CI 1.28-5.04; P = .008) were identified as risk factors associated with bleeding in the model. Conclusion: In patients on triple antithrombotic therapy, choice of oral anticoagulant did not impact bleeding rates, but use of prasugrel and a low baseline hemoglobin were associated with increased bleed rates which warrants further investigation.

Incidence of neutropenia in breast cancer patients with administration of mecapegfilgrastim.

e24070 Background: Neutropenia is the frequently observed adverse events for breast cancer patients under chemotherapy. Prophylactic administration of mecapegfilgrastim could reduce the incidence of grade 3/4 neutropenia/febril neutropenia(FN). The effectiveness of mecapegfilgrastim in breast cancer patients and different subgroups were explored. Methods: Patients with breast cancer and tolerable of mecapegfilgrastim were prospectively enrolled in a real-world study. All the patients received mecapegfilgrastim prophylacticly at least in chemotherapy cycle one. The incidence of grade 3/4 neutropenia/febril neutropenia in all patients and subgroups were presented. Results: 322 eligible patients were enrolled. The median age was fifty one years. The ECOG performace score was 0 – 1. In total, 752 chemothrapy cycles were conducted. Grade 3/4 neutropenia occurred in 44 (5.9 %) cycles, grade 4 neutropenia occurred in 16 (2.1 %) cycles. FN were reported in 4 (1.2 %) patients. The incidence of grade 3/4 neutropenia were stratificated by age group (≥65, ＜65), chemotherapy history, radiotherapy history, baseline absolute white blood cell count (≥4.0 ×109/L, ＜4.0 ×109/L), baseline absolute neutrophil count (≥2.0 ×109/L, ＜2.0 ×109/L), baseline hemoglobin level (≥110 g/L, ＜110 g/L) and chemotherapy regimens (High risk of FN, intermediate risk of FN). The results showed that patients with baseline hemoglobin of ≥110 g/L and ＜110 g/L had grade 3/4 neutropenia of 5% and 14.8 % respectively (P = 0.017). Patients treated with high FN risk chemotherapy and intermediate FN risk chemotherapy had grade 3/4 neutropenia of 0.9 % and 8.9 % respectively (P = 0.003). No significant difference of incidence of grade 3/4 neutropenia between other subgroups were found. Patients treated with cyclophosphamide and epirubicin (AC, classified as intermediate risk of FN by investigator) had grade 3/4 neutropenia of 15.4 %; Patients treated with cyclophosphamide, docetaxel and epirubicin (TAC, classified as high risk of FN by investigator) had grade 3/4 neutropenia of 14.3 %; Patients treated with docetaxel monotherapy (classified as intermediate risk of FN by investigator) had grade 3/4 neutropenia of 4.9 %. Conclusions: Prophylactic administration of mecapegfilgratim reduced the incidence of grade 3/4 neutropenia/febril neutropenia. Baseline hemoglobin level and specific chemotherapy regimen could be a useful prognostic facots for neutropenic events after administered mecapegfilgrastim.

Survival of HIV/AIDS patients treated under ART follow-up at the University hospital, northwest Ethiopia

Introduction The survival of HIV/AIDS patients on antiretroviral therapy (ART) is determined by a number of factors, including economic, demographic, behavioral, and institutional factors. Understanding the survival time and its trend is crucial to developing policies that will result in changes. The aim of this study was to compare the survival estimates of different subgroups and look into the predictors of HIV/AIDS patient survival. Methods A retrospective cohort study of HIV/AIDS patients receiving ART at the University of Gondar teaching hospital was carried out. To compare the survival of various groups, a Kaplan-Meier survival analysis was performed. The Cox proportional hazards model was used to identify factors influencing HIV/AIDS patient survival rates. Results In the current study, 5.91% of the 354 HIV/AIDS patients under ART follow-up were uncensored or died. Age (HR = 1.051) and lack of formal education (HR = 5.032) were associated with lower survival rate, whereas family size of one to two (HR = 0.167), three to four (HR = 0.120), no alcoholic consumption (HR = 0.294), no smoking and chat use (HR = 0.101), baseline weight (HR = 0.920), current weight (HR = 0.928), baseline CD4 cell count (HR = 0.990), baseline hemoglobin (HR = 0.800), and no TB diseases were associated with longer survival rate. Conclusions Fewer deaths were reported in a study area due to high patient adherence, compared to previous similar studies. Age, educational status, family size, alcohol consumption, tobacco and chat usage, baseline and current weight, baseline CD4 cell count, baseline hemoglobin, and tuberculosis (TB) diseases were all significant predictors of survival of HIV/AIDS patients.