US of the Penis: Beyond Erectile Dysfunction.

High-frequency US, with a linear transducer and gray-scale, color, and spectral Doppler US techniques, is the primary imaging modality for evaluation of the penis. It can allow delineation of anatomy and assessment of dynamic blood flow; it is easily available and noninvasive or minimally invasive; it is cost effective; and it is well tolerated by patients. US assessment after pharmacologic induction of erection is an additional tool in assessing patients with suspected vasculogenic impotence, and also in selected patients with penile trauma and suspected Peyronie disease. Penile injuries, life-threatening infections, and vascular conditions such as priapism warrant rapid diagnosis to prevent long-term morbidities due to clinical misdiagnosis or delayed treatment. US can facilitate a timely diagnosis in these emergency conditions, even at the point of care such as the emergency department, which can facilitate timely treatment. In addition, color and spectral Doppler US are valuable applications in the follow-up of patients treated with endovascular revascularization procedures for vasculogenic erectile dysfunction. Image optimization and attention to meticulous techniques including Doppler US is vital to improve diagnostic accuracy. Radiologists should be familiar with the detailed US anatomy, pathophysiologic characteristics, scanning techniques, potential pitfalls, and US manifestations of a wide spectrum of vascular and nonvascular penile conditions to suggest an accurate diagnosis and direct further management. The authors review a range of common and uncommon abnormalities of the penis, highlight their key US features, discuss differential diagnosis considerations, and briefly review management. ©RSNA, 2024 Supplemental material is available for this article.

How do we ensure a safe ABO recheck process?

BACKGROUND: Collecting a patient's blood in a correctly labeled pretransfusion specimen tube is essential for accurate ABO typing and safe transfusion. Noncompliance with specimen collection procedures can lead to wrong blood in tube (WBIT) incidents with potentially fatal consequences. Recent WBIT events inspired the investigation of how various institutions currently reduce the risk of these errors and ensure accurate ABO typing of patient samples. MATERIALS AND METHODS: This article describes the techniques employed at various institutions across the United States to mitigate the risk of misidentified pretransfusion patient specimens. Details and considerations for each of these measures are provided. RESULTS: Several institutions require the order for an ABO confirmation specimen, if indicated, to be generated from the transfusion medicine (TM) laboratory. Others issue a dedicated collection tube that is available exclusively from the TM service. Many institutions employ barcoding for electronic positive patient identification. Some use a combination of these strategies, depending on the locations or service lines from which the specimens are collected. CONCLUSION: The description of various WBIT mitigation strategies will inform TM services on practices that may be effective at their respective institutions. Irrespective of the method(s) utilized, institutions should continue to monitor and mitigate specimen misidentification errors to promote sustained safe transfusion practices.

How do we operate a large monthly red blood cell exchange program.

BACKGROUND: Red blood cell (RBC) exchange for sickle cell disease presents unique difficulties due to RBC phenotyping, complex antibody work-ups, large number of RBC units required, and vascular access considerations, any of which can delay the procedure. Multidisciplinary coordination and systemic processes ensure that monthly appointments remain on schedule. STUDY DESIGN AND METHODS: A high-volume chronic RBC exchange program is described, highlighting the importance of multidisciplinary coordination and process improvement strategies involving initial referral, vascular access, order sets, and allocation of antigen-negative or phenotypically matched RBCs. RESULTS: Approximately 50 outpatient RBC exchanges are performed each month with an 82% kept-appointment rate. Specific factors for program success include open communication across services and improvements to referrals and standardized order sets. CONCLUSION: A combination of multidisciplinary coordination and process improvement can ensure the success of a high volume RBC exchange program. Frequent communication of upcoming appointments between the referring hematologists, the hemapheresis clinic, transfusion service, and interventional radiology is critical. Advance notice to the immunohematology reference lab of upcoming appointments is needed to allow enough time for allocating antigen-negative RBCs. Order sets can be leveraged to standardize and streamline RBC exchanges. Lastly, numerous mechanisms help patients compensate for the cognitive sequelae of stroke.

A comparison of four leukapheresis methods to harvest an optimal dose of CD34+ cells: A single center experience.

BACKGROUND: Chemokine receptor CXCR4 antagonist plerixafor (Px) as well as high volume (HV) leukapheresis have been shown to reduce hematopoietic stem progenitor cell (HSPC) mobilization failure rates. However, no direct comparisons of such methods currently exists. METHODS AND MATERIALS: We compared the HSPC collection yield based on basal peripheral blood CD34+ cell numbers in patients diagnosed with multiple myeloma or non-Hodgkin's lymphoma undergoing autologous stem cell transplantation in a retrospective chart review. The leukapheresis methods used included HV versus regular volume (RV) with or without Px. There were 116 patients in the study group while the historical control group had 34 patients. RESULTS AND CONCLUSIONS: Control group underwent RV leukapheresis without Px. Addition of Px or HV in the study group failed to display significant improvement in CD34+ cell collection yield; however, when basal CD34+ cell numbers were taken into account, both Px + RV and HV without Px increased CD34+ cell collection yield. The collection failure rates of HV without Px group were comparable to Px + RV when the basal CD34+ cell numbers were over 20/µl. Of interest, multivariate linear regression analysis did not detect any significant difference between HV versus Px + RV or other leukapheresis methods in CD34 yields or collection failure rates from a single collection after controlling for other factors (sex, age, or underlying disease). In multivariate analysis, pre apheresis CD34+ cell number was significantly and positively associated with the CD34+ cell yields from a single apheresis. In our studies, the majority of patients can be rescued without Px by HV alone as a potential cost saving approach. In summary, trend in our studies reflects that both Px and HV are capable of reducing the mobilization failure rates except the poorest mobilizers, which will need to be validated in larger studies.

Restoring carbapenem efficacy: a novel carbapenem companion targeting metallo-ß-lactamases in carbapenem-resistant Enterobacterales.

BACKGROUND: The dissemination of MBLs compromises effective use of many ß-lactams in the treatment of patients with life-threatening bacterial infections. Predicted global increases in the prevalence of MBL-producing carbapenem-resistant Enterobacterales (CRE) are being realized, yielding infections that are untreatable with existing therapies including newly approved ß-lactam/ß-lactamase inhibitor combinations. Developing MBL inhibitors (MBLIs) now is essential to address the growing threat that MBL-producing CRE pose to patients. METHODS: A novel MBLI series was assessed by susceptibility testing and time-kill assays. Target activity and selectivity was evaluated using bacterial NDM, VIM and IMP enzyme assays and human matrix metallopeptidase enzyme assays, respectively, and cytotoxicity was assessed in HepG2 cells. In vivo efficacy of meropenem/MBLI combinations was evaluated in a mouse thigh infection model using an NDM-1-producing Escherichia coli strain. RESULTS: Combination of MBLIs with carbapenems reduced MICs for NDM/IMP/VIM-producing Enterobacterales by up to 128-fold compared with the carbapenems alone. Supplementation of meropenem with the promising compound 272 reduced the MIC90 from 128 to 0.25 mg/L in a panel of MBL-producing CRE clinical isolates (n = 115). Compound 272 restored the bactericidal activity of meropenem and was non-cytotoxic, potentiating the antimicrobial action of meropenem through specific inhibition of NDM, IMP and VIM. In vivo efficacy was achieved in a mouse thigh infection model with meropenem/272 dosed subcutaneously. CONCLUSIONS: We have developed a series of rationally designed MBLIs that restore activity of carbapenems against NDM/IMP/VIM-producing Enterobacterales. This series warrants further development towards a novel combination therapy that combats antibiotic-resistant organisms, which pose a critical threat to human health.

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

Race/ethnicity and underlying disease influences hematopoietic stem/progenitor cell mobilization response: A single center experience.

BACKGROUND: Whether race/ethnicity plays a role in hematopoietic stem/progenitor cells (HSPC) mobilization in autologous donors has not been studied. We hypothesize that donor characteristic including race/ethnicity, age, sex, body mass index, and diagnostic groups influences HSPC mobilization. Diagnostic groups include healthy allogeneic donors, autologous multiple myeloma (MM) and non-MM donors. STUDY DESIGN AND METHODS: Here, we conducted a single-center retrospective study in 64 autologous patients and 48 allogeneic donors. Autologous donors were patients diagnosed with MM or non-MM. All donors were grouped as African American (AA), White (W), or "Other"(O). RESULTS: Multivariate analysis demonstrated diagnostic group differences for CD34+ cell yields between race/ethnicity. Specifically, non-MM patients had the lowest CD34+ cell yields in AA and O, but not in W. For pre-apheresis peripheral blood (PB) CD34+ cell numbers, race/ethnicity had a significant effect both in bivariate and multivariate analyses. Non-MM patients had the lowest, and AA patients had the highest PB CD34+ cells. The results support the view that past therapies used in MM are likely more conducive of recovery of HSPC. CONCLUSIONS: Our study shows that race/ethnicity and diagnostic group differences influenced CD34+ cell mobilization response across donor types. Interestingly, autologous MM donors with the aid of plerixafor displayed comparable CD34 yields to allogeneic donors. Even though both MM and non-MM donors received plerixafor, non-MM donors had significantly lower CD34 yields among AA and O donors but not in W donors. Larger studies would be required to validate the role of diagnostic groups and race/ethnicity interactions.

Diagnostic Ultrasound Services During the Coronavirus Disease (COVID-19) Pandemic.

OBJECTIVE. Nosocomial transmission of coronavirus disease (COVID-19) to frontline health care workers is well known, and health care workers may inadvertently become vectors for onward transmission. Ultrasound (US) service providers are at significant risk because scanning usually requires prolonged close patient contact. The bulky US equipment may also facilitate fomite transmission of disease. With increasing use of point-of-care and portable diagnostic US services, the risk is substantial. CONCLUSION. Our experience and protocols may help service providers with their own effective response against COVID-19.

Red blood cell exchange to avoid intubating a COVID-19 positive patient with sickle cell disease?

As the COVID-19 pandemic continues to claim lives across the globe, insufficient data exists regarding the optimal treatment. It is well known that patients 55 years of age or older and patients with certain chronic diseases are at higher risk of severe illness, including acute respiratory distress syndrome and death. A potentially fatal pulmonary complication of sickle cell disease, acute chest syndrome, can be precipitated by acute infections, including respiratory viruses. We report the case of a patient with sickle cell disease (HbSC) who developed COVID-19 pneumonia and acute chest syndrome who was treated with emergent red blood cell exchange in order to avoid endotracheal intubation.

Comparison of blur and magnification effects on stereopsis: overall and meridional, monocularly- and binocularly-induced.

PURPOSE: To determine whether monocularly- and binocularly-induced spherical and meridional blur and aniseikonia had similar effects on stereopsis thresholds. METHODS: Twelve participants with normal binocular vision viewed McGill modified random dot stereograms to determine stereoacuities in a four-alternative forced-choice procedure. Astigmatism was induced by placing trial lenses in front of the eyes. Twenty-three conditions were used, consisting of zero (no lens), +1 D and +2 D spheres and cylinders at axes 180, 45 and 90 in front of the right eye, and the following binocular combinations of both lens powers: R × 180/L × 180, R × 45/L × 45, R × 90/L × 90, R sphere/L sphere, R × 180/L × 90, R × 45/L × 135, R × 90/L × 180. Aniseikonia was induced by placing magnifying lenses in front of the eyes. Twenty-three conditions were used, consisting of zero, 6% and 12% overall magnification and both magnifications at axes 180, 45 and 90 in front of the right eye only, and the following binocular combinations using 3% and 6% lenses: R × 90/L × 90, R × 45/L × 45, R × 180/L × 180, R overall/L overall, R × 90/L × 180, R × 45/L × 135, and R × 180/L × 90. RESULTS: Stereopsis losses for binocular blur effects with parallel axes (non-anisometropic) were the same as for monocular blur effects of the same axes, and these were strongly dependent on axis (spherical blur and ×90 had the greatest effects). Binocular blur effects with orthogonal axes had greater effects than with parallel axes, with the axis combination of the former having no effect (e.g. R × 90/L × 180 was similar to R × 45/L × 135). For induced aniseikonia, splitting the magnifications between the eyes improved stereopsis slightly, and the effects were not dependent on axis. CONCLUSION: Binocular blur affects stereopsis similarly to monocular meridional blur if axes in the two eyes are parallel, whereas the effect is greater if the axes are orthogonal. In meridional aniseikonia, splitting magnification between the right and left lenses produces a small improvement in stereopsis that is independent of axis direction and right/left combination.

Haploidentical Peripheral Blood Stem Cell Transplantation Demonstrates Stable Engraftment in Adults with Sickle Cell Disease.

We report on the screening and development of haploidentical hematopoietic stem cell transplantation (HSCT) for adult patients with clinically aggressive sickle cell disease (SCD) at our institution. Of 50 adult SCD patients referred for HSCT between January 2014 and March 2017, 20% were denied by insurance. Of 41 patients initially screened, 10% lacked an available haploidentical donor, 29% had elevated donor-specific antibodies (DSAs), and 34% declined to proceed to HSCT. All 10 patients who were transplanted received peripheral blood stem cells. The initial 2 were conditioned with alemtuzumab/total body irradiation (TBI) 3 Gy followed by post-transplant cyclophosphamide and failed to engraft. The next 8 patients received the regimen developed at Johns Hopkins University with TBI 3 Gy. Granulocyte colony-stimulating factor was administered from day +12 in those with HbS < 30%. All 8 patients engrafted with a median time to neutrophil >.5 × 109/L of 22 days (range, 18 to 23). One patient subsequently lost the graft, and 7 (87.5%) maintained >95% donor cell chimerism at 1-year post-HSCT. Two patients developed acute graft-versus-host disease (GVHD) of at least grade II. One had chronic GVHD and died >1 year after HSCT of unknown causes. With a median follow-up of 16 months (range, 11 to 29), 7 patients (87.5%) are alive. Our findings suggest that limited insurance coverage, high rate of DSAs, and patient declining HSCT may limit the availability of haploidentical HSCT in adult SCD patients. The modified Hopkins regimen used here demonstrates high engraftment and low morbidity rates and should be tested in larger, multicenter, prospective clinical trials.

Red blood cell alloimmunization in sickle cell disease: assessment of transfusion protocols during two time periods.

BACKGROUND: Prevention of red blood cell (RBC) alloimmunization in patients with sickle cell disease (SCD) focuses on phenotypic RBC matching. We assessed alloimmunization among transfused patients with SCD after implementing leukoreduction and prophylactic antigen matching (PAM). STUDY DESIGN AND METHODS: Retrospective review of transfusion and medical records for SCD patients 18 months to 81 years of age was performed covering two 5-year periods: Period 1, no PAM, occasional leukoreduction, and Period 2, consistent leukoreduction and extended PAM (Rh, Kell, S, Fy, Jk) for patients already alloimmunized. Patients transfused in Period 1 were excluded from Period 2. RESULTS: A total of 293 patients were transfused in Period 1 and 183 in Period 2. Median time between first sample and last type and screen after transfusion was 2.12 years in Period 1 and 1.03 years in Period 2. Initial alloimmunization prevalence was lower in Period 2 (26.2%) versus Period 1 (37.5%) and after subsequent transfusions in Period 2 (23.8%) versus Period 1 (45.7%), although without significant difference after adjusting for number of units transfused, percentage of leukoreduced RBCs, sex, and age. Alloimmunized patients received more nonleukoreduced RBCs in Period 1 than nonalloimmunized. Patients transfused during inflammatory conditions were not significantly more likely to become alloimmunized. CONCLUSIONS: The prevalence of initial and subsequent RBC alloimmunization in Period 2 was lower than that in Period 1; however, overall prevalence remained high. We recommend leukoreduced, hemoglobin S-negative Rh and Kell PAM RBCs for transfusion of patients with SCD. Component and recipient factors affecting alloimmunization should be studied further.

Nonmyeloablative Stem Cell Transplantation with Alemtuzumab/Low-Dose Irradiation to Cure and Improve the Quality of Life of Adults with Sickle Cell Disease.

Allogeneic hematopoietic stem cell transplantation (HSCT) is rarely performed in adult patients with sickle cell disease (SCD). We utilized the chemotherapy-free, alemtuzumab/total body irradiation 300 cGy regimen with sirolimus as post-transplantation immunosuppression in 13 high-risk SCD adult patients between November 2011 and June 2014. Patients received matched related donor (MRD) granulocyte colony-stimulating factor-mobilized peripheral blood stem cells, including 2 cases that were ABO incompatible. Quality-of-life (QoL) measurements were performed at different time points after HSCT. All 13 patients initially engrafted. A stable mixed donor/recipient chimerism was maintained in 12 patients (92%), whereas 1 patient not compliant with sirolimus experienced secondary graft failure. With a median follow-up of 22 months (range, 12 to 44 months) there was no mortality, no acute or chronic graft-versus-host disease (GVHD), and no grades 3 or 4 extramedullary toxicities. At 1 year after transplantation, patients with stable donor chimerism have normalized hemoglobin concentrations and improved cardiopulmonary and QoL parameters including bodily pain, general health, and vitality. In 4 patients, sirolimus was stopped without rejection or SCD-related complications. These results underscore the successful use of a chemotherapy-free regimen in MRD HSCT for high-risk adult SCD patients and demonstrates a high cure rate, absence of GVHD or mortality, and improvement in QoL including the applicability of this regimen in ABO mismatched cases (NCT number 01499888).

Critical Role of Alpha-Toxin and Protective Effects of Its Neutralization by a Human Antibody in Acute Bacterial Skin and Skin Structure Infections.

Methicillin-resistant Staphylococcus aureus (MRSA) causes large-scale epidemics of acute bacterial skin and skin structure infections (ABSSSI) within communities across the United States. Animal models that reproduce ABSSSI as they occur in humans are urgently needed to test new therapeutic strategies. Alpha-toxin plays a critical role in a variety of staphylococcal infection models in mice, but its role in the pathogenesis of ABSSSI remains to be elucidated in rabbits, which are similar to humans in their susceptibility to S. aureus superantigens and certain bicomponent pore-forming leukocidins. We report here a new rabbit model of ABSSSI and show that those infected with a mutant deficient in expression of alpha-toxin (Δhla) developed a small dermonecrotic lesion, whereas those infected with isogenic USA300 MRSA wild-type or complemented Δhla strains developed ABSSSI that mimic the severe infections that occur in humans, including the large central dermonecrotic core surrounded by erythema, induration, and marked subcutaneous hemorrhage. More importantly, immunoprophylaxis with MEDI4893*, an anti-alpha-toxin human monoclonal antibody, significantly reduced the severity of disease caused by a USA300 wild-type strain to that caused by the Δhla mutant, indicating that this toxin could be completely neutralized during infection. Thus, this study illustrates a potential high standard for the development of new immunotherapeutic agents in which a toxin-neutralizing antibody provides protection to the same degree achieved with a toxin gene knockout. When MEDI4893* was administered as adjunctive therapy with a subtherapeutic dose of linezolid, the combination was significantly more efficacious than either agent alone in reducing the severity of ABSSSI.

Red blood cell alloimmunization in sickle cell disease: listen to your ancestors.

Red blood cell (RBC) alloimmunization occurs in approximately 30% of transfused sickle cell disease patients compared to 2-5% of all transfusion recipients. Because RBC transfusion is an important part of therapy in sickle cell disease, the need for additional antigen matching once alloimmunization occurs is problematic and leads to therapeutic limitations. Thus, identification of risk factors would benefit this patient population. Genome-wide analyses, in particular, methods which take into account genetic ancestry such as admixture mapping, could identify molecular markers which could be used to identify immune responders to transfusion.

SARS-CoV-2 rapidly evolves lineage-specific phenotypic differences when passaged repeatedly in immune-naïve mice.

The persistence of SARS-CoV-2 despite the development of vaccines and a degree of herd immunity is partly due to viral evolution reducing vaccine and treatment efficacy. Serial infections of wild-type (WT) SARS-CoV-2 in Balb/c mice yield mouse-adapted strains with greater infectivity and mortality. We investigate if passaging unmodified B.1.351 (Beta) and B.1.617.2 (Delta) 20 times in K18-ACE2 mice, expressing the human ACE2 receptor, in a BSL-3 laboratory without selective pressures, drives human health-relevant evolution and if evolution is lineage-dependent. Late-passage virus causes more severe disease, at organism and lung tissue scales, with late-passage Delta demonstrating antibody resistance and interferon suppression. This resistance co-occurs with a de novo spike S371F mutation, linked with both traits. S371F, an Omicron-characteristic mutation, is co-inherited at times with spike E1182G per Nanopore sequencing, existing in different within-sample viral variants at others. Both S371F and E1182G are linked to mammalian GOLGA7 and ZDHHC5 interactions, which mediate viral-cell entry and antiviral response. This study demonstrates SARS-CoV-2's tendency to evolve with phenotypic consequences, its evolution varying by lineage, and suggests non-dominant quasi-species contribution.

Effect of risedronate on bone in renal transplant recipients.

Bisphosphonates may prevent or treat the bone loss promoted by the immunosuppressive regimens used in renal transplantation. Risedronate is a commonly used third-generation amino-bisphosphonate, but little is known about its effects on the bone health of renal transplant recipients. We randomly assigned 42 new living-donor kidney recipients to either 35 mg of risedronate weekly or placebo for 12 months. We obtained bone biopsies at the time of renal transplant and after 12 months of protocol treatment. Treatment with risedronate did not affect bone mineral density (BMD) in the overall cohort. In subgroup analyses, it tended to preserve BMD in female participants but did not significantly affect the BMD of male participants. Risedronate did associate with increased osteoid volume and trabecular thickness in male participants, however. There was no evidence for the development of adynamic bone disease. In summary, further study is needed before the use of prophylactic bisphosphonates to attenuate bone loss can be recommended in renal transplant recipients.

Angiotensin II Type 1 Receptor Antibody-Mediated Kidney Rejection Unresponsive to Treatment.

Allograft rejection is a significant cause of renal transplant failure which needs prompt diagnosis and treatment for graft salvage. Angiotensin II type 1 receptor antibody-mediated rejection (AT1R-AMR) is increasingly being identified as the etiology of antibody-mediated rejection in kidney transplant recipients with allograft rejection but without detectable human leukocyte antigen (HLA) antibodies. While some reports have suggested that AT1R-AMR may be refractory to standard therapy, others have reported improvement or stabilization of graft function. We present two patients in which anti-rejection therapy including therapeutic plasma exchange was unable to salvage the allograft.

Hemolysis dictates monocyte differentiation via two distinct pathways in sickle cell disease vaso-occlusion.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by painful vaso-occlusive crises (VOC) and chronic hemolysis. The mononuclear phagocyte system is pivotal to SCD pathophysiology, but the mechanisms governing monocyte/macrophage differentiation remain unknown. This study examined the influence of hemolysis on circulating monocyte trajectories in SCD. We discovered that hemolysis stimulated CSF-1 production, partly by endothelial cells via Nrf2, promoting classical monocyte (CMo) differentiation into blood patrolling monocytes (PMo) in SCD mice. However, hemolysis also upregulated CCL-2 through IFN-I, inducing CMo transmigration and differentiation into tissue monocyte-derived macrophages. Blocking CMo transmigration by anti-P selectin antibody in SCD mice increased circulating PMo, corroborating that CMo-to-tissue macrophage differentiation occurs at the expense of CMo-to-blood PMo differentiation. We observed a positive correlation between plasma CSF-1/CCL-2 ratios and blood PMo levels in patients with SCD, underscoring the clinical significance of these two opposing factors in monocyte differentiation. Combined treatment with CSF-1 and anti-P selectin antibody more effectively increased PMo numbers and reduced stasis compared with single-agent therapies in SCD mice. Altogether, these data indicate that monocyte fates are regulated by the balance between two heme pathways, Nrf2/CSF-1 and IFN-I/CCL-2, and suggest that the CSF-1/CCL-2 ratio may present a diagnostic and therapeutic target in SCD.