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Sickle cell disease (SCD) patients are at a four- to 100-fold increased risk for thrombosis compared with the general population, although the mechanisms and risk factors are not clear. We investigated the incidence and predictors for thrombosis in a retrospective, longitudinal cohort of 1193 pediatric and adult SCD patients treated at our institution between January 2008 and December 2017. SCD diagnosis and thrombotic complications were identified using International Classification of Diseases coding and verified through medical chart review. Clinical and laboratory data were extracted from the medical records. With a median follow-up of 6.4 years, 208 (17.4%) SCD patients experienced 352 thrombotic events (64 strokes, 288 venous thromboembolisms [VTE]). Risk factors for stroke included older age and HbSS/Sβ0-genotype and a lower hemoglobin (Hb) F% in the subset of HbSS/Sβ0-genotype patients (P < .05). VTE risk was independently associated with lower estimated glomerular filtration rate, hydroxyurea (HU) use, HbSS/Sβ0 genotype, and higher white blood cell (WBC) counts and Hb (P ≤ .03). Two thrombomodulin gene variants previously associated with thrombosis in the general African American population, THBD rs2567617 (minor allele frequency [MAF] 0.25; odds ratio [OR], 1.5; P = .049) and THBD rs1998081 (MAF, 0.24; OR, 1.5; P = .059), were associated with thrombosis in this cohort. In summary, thrombotic complications are common, and several traditional and SCD-specific risk factors are associated with thrombotic risk. Future studies integrating clinical, laboratory, and genetic risk factors may improve our understanding of thrombosis and guide intervention practices in SCD.

Sickle cell disease (SCD) patients are at a four- to 100-fold increased risk for thrombosis compared with the general population, although the mechanisms and risk factors are not clear. We investigated the incidence and predictors for thrombosis in a retrospective, longitudinal cohort of 1193 pediatric and adult SCD patients treated at our institution between January 2008 and December 2017. SCD diagnosis and thrombotic complications were identified using International Classification of Diseases coding and verified through medical chart review. Clinical and laboratory data were extracted from the medical records. With a median follow-up of 6.4 years, 208 (17.4%) SCD patients experienced 352 thrombotic events (64 strokes, 288 venous thromboembolisms [VTE]). Risk factors for stroke included older age and HbSS/Sβ0-genotype and a lower hemoglobin (Hb) F% in the subset of HbSS/Sβ0-genotype patients (P< .05). VTE risk was independently associated with lower estimated glomerular filtration rate, hydroxyurea (HU) use, HbSS/Sβ0genotype, and higher white blood cell (WBC) counts and Hb (P≤ .03). Two thrombomodulin gene variants previously associated with thrombosis in the general African American population, THBDrs2567617 (minor allele frequency [MAF] 0.25; odds ratio [OR], 1.5; P= .049) and THBDrs1998081 (MAF, 0.24; OR, 1.5; P= .059), were associated with thrombosis in this cohort. In summary, thrombotic complications are common, and several traditional and SCD-specific risk factors are associated with thrombotic risk. Future studies integrating clinical, laboratory, and genetic risk factors may improve our understanding of thrombosis and guide intervention practices in SCD.

Frailty is a multi-system syndrome of decreased physiologic reserve that has been shown to strongly and independently predict morbidity and mortality. Frailty is prevalent in patients living with kidney disease and occurs earlier in individuals with kidney disease as compared to the general population. In this comprehensive review, we aim to advance the clinical and research applications of frailty in kidney disease populations. Specifically, we clarify the definition of frailty and address its common misconceptions; review the mechanisms and epidemiology of frailty in kidney disease; discuss challenges and limitations in frailty measurement; and provide updated evidence related to risk factors for frailty, its associated adverse outcomes, and interventions. We further add to the literature in this topic by highlighting potential applications of frailty measurement in care of patients with kidney disease and conclude with our recommendations for future research related to this important syndrome.

Background:Colorectal surgery is associated with a high risk of surgical site infections (SSIs), with an incidence ranging from 16.9% to 20%, and SSIs are associated with significant morbidity and mortality, prolonged length of hospitalization, and increased health care costs. Staphylococcal decolonization is an attempt to alter the microbiome to prevent staphylococcal and other skin flora from accessing the surgical site, and This practice effectively reduces SSIs in orthopedic, neurologic, and cardiac surgeries. A staphylococcal decolonization protocol was enacted in colorectal surgeries at our institution beginning in October 2016. We compared patient outcomes between patients who did and did not undergo preoperative staphylococcal decolonization. Methods:All patients undergoing nonemergent NHSN-defined colorectal procedures from July 2015 until June 2019 at a tertiary-care medical center were included in this retrospective study. Staphylococcal decolonization was performed using chlorhexidine 2% body wash solution, mupirocin nasal ointment, and chlorhexidine 0.12% oral rinse all twice daily for 5 days prior to surgery. All SSIs were defined by NSHN criteria. The primary outcome was SSI, and secondary outcomes were superficial wound infection (SIP) and organ-space infection (IAB). Predictive variables included decolonization status (yes or no), age, gender, body mass index, procedure duration, American Society of Anesthesiologists (ASA) score, diabetes, smoking, and surgical oncology service. Surgical antimicrobial prophylaxis with cefazolin and metronidazole OR cefoxitin, and chlorhexidine skin preparation were standard throughout the study period. Univariate analysis was performed using a χ2or ttest. Multivariable logistic regression was performed to control for all clinically important variables above. All statistical analyses were done using SAS version 9.4 software (Cary, NC). Results:In total, 1,139 patients underwent nonemergent colorectal surgery from July 2015 to June 2019. There were 74 SSIs: 42 IABs and 32 SIPs. Decolonization was performed in 332 of 1,139 cases (29%). There was no difference in overall SSIs between those decolonized and not decolonized (P= .50). However, SIPs were reduced in the group receiving decolonization: 1.2% (4 of 332) versus 3.5% (28 of 807) (P= .04. When controlling for known SSI risk factors, those not receiving decolonization remained at increased risk of SIPs (OR, 3.79; 95% CI, 1.14–12.61; P= .03. Conclusions:Staphylococcal decolonization may prevent a subset of SSIs in patients undergoing colorectal surgery.Funding:NoneDisclosures:Michelle Doll reports a research Grant from Molnlycke Healthcare.

Thrombomodulin (THBD) is a transmembrane protein that regulates endothelial function by 1) binding thrombin and inhibiting its interaction with fibrinogen, 2) augmenting protein C activation, and 3) down-regulating complement activation by inactivating C3a and C5a (PMID 29866818). Reduced THBD function has been implicated in several vasculopathies (PMID 29866818). Oxidative damage increases cleaved non-functional THBD in circulation and increased circulating non-functional THBD predicts the severity of organ damage in thrombotic microangiopathies (PMID 11190905). Vascular endothelial dysfunction is a hallmark feature of sickle cell disease (SCD) that leads to acute and chronic organ damage and may, in part, be mediated by hemolysis (PMID 28248201). Hemolysis leads to release of cell-free hemoglobin which may lead to vasculopathy through consumption of NO, activation of TLR4 pathways, and direct oxidative damage. We investigated whether decreased THBD activity may be implicated in the pathophysiology of SCD vasculopathy in endothelial cells, transgenic sickle mice, and in a prospective cohort of patients with sickle cell anemia.

Gordeuk: Novartis: Consultancy, Honoraria, Research Funding; Emmaus: Consultancy, Honoraria; Global Blood Therapeutics: Consultancy, Honoraria, Research Funding; Modus Therapeutics: Consultancy, Honoraria; Pfizer: Research Funding; Inctye: Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Ironwood: Research Funding; Imara: Research Funding. Saraf:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding.

No relevant conflicts of interest to declare.

Sickle cell anemia (SCA) is an inherited red blood cell disorder that leads to hemoglobin polymerization when it deoxygenates. Lung function abnormalities are observed in up to 90% of adults with SCA (PMID: 16556694) and both the prevalence (PMID: 20644948) and rate of FEV1 decline (PMID: 18383325) are greater in SCA adults compared to the general population. Furthermore, low FEV1 is an independent predictor of early mortality in SCA (PMID: 26261241). Understanding the risk factors and mechanisms for abnormal lung function, which can impact blood oxygen and pH levels, is especially important in SCA.

Sickle cell disease (SCD) is an inherited red blood cell disorder that leads to vaso-occlusion, endothelial damage, and activation of pro-coagulant pathways. Recent studies have demonstrated that thrombotic episodes occur at a 3- to 100-fold higher rate (PMID: 17000225, 22417249) in SCD versus non-SCD populations but the risk factors for thrombosis are not clear.

No relevant conflicts of interest to declare.

Sickle cell disease (SCD) is an inherited erythrocyte disorder characterized by chronic hemolysis and vasculopathy. Females have reduced levels of hemolysis compared to males in both the general population (Jordan A et al, Vox Sang2016) as well as in SCD (Kanias T et al, Transfusion2016). This phenomenon may be due to the effects of gender on hemoglobin (Hb) F levels (Dover GJ et al, Blood1992), red blood cell membrane stability (Jordan A et al, Vox Sang2016), and nitric oxide (NO) bioavailability (Gladwin MT et al, Circulation2003). We wished to confirm reduced hemolysis in SCD females and whether this would be associated with reduced hemolytic complications, some of which are associated with mortality. Finally, we wished to see if there were suggestions of improved survival in females compared to males with SCD.