Interferon-γ induces combined pyroptotic angiopathy and APOL1 expression in human kidney disease.

Elevated interferon (IFN) signaling is associated with kidney diseases including COVID-19, HIV, and apolipoprotein-L1 (APOL1) nephropathy, but whether IFNs directly contribute to nephrotoxicity remains unclear. Using human kidney organoids, primary endothelial cells, and patient samples, we demonstrate that IFN-γ induces pyroptotic angiopathy in combination with APOL1 expression. Single-cell RNA sequencing, immunoblotting, and quantitative fluorescence-based assays reveal that IFN-γ-mediated expression of APOL1 is accompanied by pyroptotic endothelial network degradation in organoids. Pharmacological blockade of IFN-γ signaling inhibits APOL1 expression, prevents upregulation of pyroptosis-associated genes, and rescues vascular networks. Multiomic analyses in patients with COVID-19, proteinuric kidney disease, and collapsing glomerulopathy similarly demonstrate increased IFN signaling and pyroptosis-associated gene expression correlating with accelerated renal disease progression. Our results reveal that IFN-γ signaling simultaneously induces endothelial injury and primes renal cells for pyroptosis, suggesting a combinatorial mechanism for APOL1-mediated collapsing glomerulopathy, which can be targeted therapeutically.

Factors associated with the use of psychedelics, ketamine and MDMA among sexual and gender minority youths in Canada: a machine learning analysis.

BACKGROUND: Substance use is increasing among sexual and gender minority youth (SGMY). This increase may be due to changes in social norms and socialisation, or due to SGMY exploring the potential therapeutic value of drugs such as psychedelics. We identified predictors of psychedelics, MDMA and ketamine use. METHODS: Data were obtained from 1414 SGMY participants who completed the ongoing longitudinal 2SLGBTQ+ Tobacco Project in Canada between November 2020 to January 2021. We examined the association between 80 potential features (including sociodemographic factors, mental health-related factors and substance use-related factors) with the use of psychedelics, MDMA and ketamine in the past year. Random forest classifier was used to identify the predictors most associated with reported use of these drugs. RESULTS: 18.1% of participants have used psychedelics in the past year; 21.9% used at least one of the three drugs. Cannabis and cocaine use were the predictors most strongly associated with any of these drugs, while cannabis, but not cocaine use, was the one most associated with psychedelic use. Other mental health and 2SLGBTQ+ stigma-related factors were also associated with the use of these drugs. CONCLUSION: The use of psychedelics, MDMA and ketamine among 2SLGBTQ+ individuals appeared to be largely driven by those who used them together with other drugs. Depression scores also appeared in the top 10 factors associated with these illicit drugs, suggesting that there were individuals who may benefit from the potential therapeutic value of these drugs. These characteristics should be further investigated in future studies.

Investigating How Preregistrant Pharmacists Respond in Job Interviews.

OBJECTIVE: To investigate what competencies and attributes preregistrant pharmacists draw upon in job interviews. METHODS: We used a virtual mock job interview assessment asking preregistrant pharmacists to apply for an entry-level pharmacist position. Data were analyzed using a team-based framework analysis using an inductive and deductive approach and mapping responses to the National Competency Standards. RESULTS: A total of 143 interview transcripts were included in the analysis. The top skills mentioned were leadership of self (98.6%) and communication and collaboration (96.5%). Despite graduating from a course with an integrated research curriculum, participants rarely reflected on research skills (31.5%) and no participant discussed any expertise in clinical topics or knowledge of specific professional services. Responses generally lacked specific skills and skills were spoken about broadly without relating to evidence/experience and were often not targeted to the job description. A proposal for educators aligned with competency standards was also developed based on the findings. CONCLUSION: Preregistrant pharmacists perceive experience within the workforce and communication and collaboration as the most desired by employers for entry-level pharmacy positions. Education and research competencies were seen as least useful to the job. There was a disconnect between skills gained in university and translation to practice. Academics could enhance the better preregistrant pharmacists' reflection of the skills and competencies they have developed employability by (1) providing portfolio management from the beginning of the course that collects evidence and maps to competencies; (2) integrating learning opportunities across all competencies; and (3) regular skills coaching/mentoring from practicing pharmacists to ensure students are aware of current needs in the job market.

Prescribing patterns of fall risk-increasing drugs in older adults hospitalized for heart failure.

BACKGROUND: Older adults hospitalized for heart failure (HF) are at risk for falls after discharge. One modifiable contributor to falls is fall risk-increasing drugs (FRIDs). However, the prevalence of FRIDs among older adults hospitalized for HF is unknown. We describe patterns of FRIDs use and examine predictors of a high FRID burden. METHODS: We used the national biracial REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a prospective cohort recruited from 2003-2007. We included REGARDS participants aged ≥ 65 years discharged alive after a HF hospitalization from 2003-2017. We determined FRIDs -cardiovascular (CV) and non-cardiovascular (non-CV) medications - at admission and discharge from chart abstraction of HF hospitalizations. We examined the predictors of a high FRID burden at discharge via modified Poisson regression with robust standard errors. RESULTS: Among 1147 participants (46.5% women, mean age 77.6 years) hospitalized at 676 hospitals, 94% were taking at least 1 FRID at admission and 99% were prescribed at least 1 FRID at discharge. The prevalence of CV FRIDs was 92% at admission and 98% at discharge, and the prevalence of non-CV FRIDs was 32% at admission and discharge. The most common CV FRID at admission (88%) and discharge (93%) were antihypertensives; the most common agents were beta blockers (61% at admission, 75% at discharge), angiotensin-converting enzyme inhibitors (36% vs. 42%), and calcium channel blockers (32% vs. 28%). Loop diuretics had the greatest change in prevalence (53% vs. 72%). More than half of the cohort (54%) had a high FRID burden (Agency for Healthcare Research and Quality (AHRQ) score ≥ 6), indicating high falls risk after discharge. In a multivariable Poisson regression analysis, the factors strongly associated with a high FRID burden at discharge included hypertension (PR: 1.41, 95% CI: 1.20, 1.65), mood disorder (PR: 1.24, 95% CI: 1.10, 1.38), and hyperpolypharmacy (PR: 1.88, 95% CI: 1.64, 2.14). CONCLUSIONS: FRID use was nearly universal among older adults hospitalized for HF; more than half had a high FRID burden at discharge. Further work is needed to guide the management of a common clinical conundrum whereby guideline indications for treating HF may contribute to an increased risk for falls.

A 20-Year Study of Capsular Polysaccharide Seroepidemiology, Susceptibility Profiles, and Virulence Determinants of Klebsiella pneumoniae from Bacteremia Patients in Taiwan.

In this study, we selected bacteremic Klebsiella pneumoniae isolates from the Taiwan Surveillance of Antimicrobial Resistance program. A total of 521 isolates were collected over a period of 2 decades, including 121 from 1998, 197 from 2008, and 203 from 2018. Seroepidemiology showed that the top five capsular polysaccharide types were serotypes K1, K2, K20, K54, and K62, constituting 48.5% of the total isolates, and the respective ratios at each time point have remained similar over the past 2 decades. The antibacterial susceptibility tests showed that K1, K2, K20, and K54 were susceptible to most antibiotics, while K62 was relatively resistant compared to other typeable and nontypeable strains. In addition, six virulence-associated genes, clbA, entB, iroN, rmpA, iutA, and iucA, were predominant in K1 and K2 isolates of K. pneumoniae. In conclusion, serotypes K1, K2, K20, K54, and K62 of K. pneumoniae are the most prevalent serotypes and carry more virulence determinants in bacteremia patients, which may indicate their invasiveness. If further serotype-specific vaccine development is performed, these five serotypes should be included. Since the antibiotic susceptibility profiles were stable over a long duration, empirical treatment may be predicted according to serotype if rapid diagnosis from direct clinical specimens is available, such as PCR or antigen serotyping for serotype K1 and K2. IMPORTANCE This is the first nationwide study to examine the seroepidemiology of Klebsiella pneumoniae using blood culture isolates collected over a period of 20 years. The study found that the prevalence of serotypes remained consistent over the 20-year period, with high-prevalence serotypes associated with invasive types. Nontypeable isolates had fewer virulence determinants than other serotypes. With the exception of serotype K62, the other high-prevalence serotypes were highly susceptible to antibiotics. If rapid diagnosis using direct clinical specimens, such as PCR or antigen serotyping, is available, empirical treatment can be predicted based on serotype, particularly for K1 and K2. The results of this seroepidemiology study could also help the development of future capsule polysaccharide vaccines.

Accuracy of medication histories derived from an Australian cloud-based repository of prescribed and dispensed medication records.

BACKGROUND: Obtaining accurate medication histories at transitions of care is challenging, but important for patient safety. Prescription exchange services (PES) securely transfer electronic prescription and dispensing records between prescribers and pharmacies, which is potentially useful data for determining medication histories. AIM: To evaluate the accuracy of PES-derived medication histories. METHODS: Prospective observational study, at two Australian tertiary-referral health services. A convenience sample of adult inpatients was recruited. The main outcome measure was: proportion of patients with ≥1 errors in their PES-derived pre-admission medication histories, compared with gold-standard best-possible medication histories, including prescribed and non-prescribed medications, obtained by pharmacists using multiple sources including patient/carer interview. RESULTS: Of 154 patients (median age 76 years; interquartile range (IQR) 64-84 years; median 10.0 pre-admission medications; IQR 6.0-14.0), 153 (99.4%) had ≥1 errors in their PES-derived medication history (median 6.0 errors per patient; IQR 4.0-9.0). Excluding when-required medications, 146 (94.8%) patients had >1 errors (median 4.0 errors per patient; IQR 2.0-6.0). Omission was the most common error, affecting 549 (33.3%) of 1648 current medications (median 3.0; IQR 1.0-5.0 per patient); 396 (72.1%) omissions were over-the-counter medicines. Dose-regimen errors affected 276 (25.1%) of 1099 current medications captured in PES-derived medication histories (median 1.0 error per patient; IQR 0.0-3.0). Commission errors (medications in PES-derived histories that were not current) affected 224 (16.9%) of 1323 medications (median 1.0 error per patient; IQR 1.0-2.0). CONCLUSIONS: Medication histories derived solely from a cloud-based medication record repository had a high error rate compared with patients' actual medication use. Like all medication history sources, data from cloud-based repositories need to be verified with additional sources including the patient and/or their carer.

Home Milrinone in Pediatric Hospice Care of Children with Heart Failure.

CONTEXT: The symptom profile of children dying from cardiac disease, especially heart failure, differs from those with cancer and other non-cardiac conditions. Treatment with vasoactive infusions at home may be a superior therapy for symptom control for these patients, rather than traditional pain and anxiety management with morphine and benzodiazepines. OBJECTIVES: We report our experience using outpatient milrinone in children receiving hospice care for end-stage heart failure. METHODS: Retrospective review of a contemporary cohort of all patients at Lucile Packard Children's Hospital, Stanford who were discharged on intravenous milrinone and hospice care between 2008 and 2021. Clinical data, including cardiac diagnosis, milrinone dose and route of administration, total milrinone days, symptoms reported, rehospitalization rates, concurrent therapies and complications were analyzed. RESULTS: Among 8 patients, median duration of home milrinone infusion was 191 (33, 572) days with the longest support duration 1,054 days. All (100%) patients were also receiving diuretics at the time of death. Five (63%) were receiving no other pain control medications until the active phase of dying. From milrinone initiation to last outpatient assessment, a reduction in the number of patients reporting respiratory discomfort, abdominal pain, weight loss/lack of appetite, and fatigue was observed. Six (75%) died at home. CONCLUSION: We used milrinone with oral diuretics effectively for symptom control in children with heart failure on palliative care. Our experience was that this combination can be used safely in the outpatient setting for long-term use without the addition of opiates, benzodiazepines, or supplemental oxygen in most cases.

Subcutaneous Treprostinil Improves Surgical Candidacy for Next Stage Palliation in Single Ventricle Patients With High-Risk Hemodynamics.

Single ventricle (SV) patients with pulmonary vascular disease (SV-PVD) are considered poor surgical candidates for Glenn or Fontan palliation. Given limited options for Stage 1 (S1) and Stage 2 (S2) SV patients with SV-PVD, we report on the use of subcutaneous treprostinil (TRE) to treat SV-PVD in this population. This single-center, retrospective cohort study examined SV patients who were not candidates for subsequent surgical palliation due to SV-PVD and were treated with TRE. The primary outcome was ability to progress to the next surgical stage; secondary outcomes included changes in hemodynamics after TRE initiation. Between 3/2014 and 8/2021, 17 SV patients received TRE for SV-PVD: 11 after S1 and 6 after S2 (median PVR 4.1 [IQR 3.2-4.8] WU*m2 and 5.0 [IQR 1.5-6.1] WU*m2, respectively). Nine of 11 (82%) S1 progressed to S2, and 2 (18%) underwent heart transplant (HTx). Three of 6 (50%) S2 progressed to Fontan, 1 underwent HTx and 2 are awaiting Fontan on TRE. TRE significantly decreased PVR in S1 patients with median post-treatment PVR of 2.0 (IQR 1.5-2.6) WU*m2. TRE can allow for further surgical palliation in select pre-Fontan patients with SV-PVD, obviating the need for HTx. Improvement in PVR was significant in S1 patients and persisted beyond discontinuation of therapy for most patients.

Clostridium difficile: What is the risk?

INTRODUCTION: Clostridium difficile infections (CDIs) are rising among pediatric patients in the community and hospital setting. Children undergoing transplants and bowel surgery are at a higher risk, while renal surgery has a lower risk. We hypothesize children undergoing pediatric urologic procedures are uncommonly diagnosed with postoperative CDI. OBJECTIVE: To study CDI in pediatric patients undergoing urologic surgery and identify associated perioperative factors. STUDY DESIGN: The American College of Surgeons National Surgical Quality Improvement Program Pediatric data file was queried for children undergoing surgery with pediatric urology or urology between 2015 and 2017. Data points included patient demographics (age, gender, race, ASA classification), surgery performed, and perioperative outcomes (operative time, admission status, length of stay, complications, readmission, and reoperation). Students T-test and Chi-square analyses were applied to detect differences between those with CDI and those without CDI. RESULTS: Of the 27,193 patients undergoing urologic surgery, 36 (0.13%) were diagnosed with CDI. The surgeries are presented in the Summary Figure. Patients with CDI were more likely to be female (50% vs 28%, p = 0.003) than those without. There was no difference in mean age or race. Children with CDI had higher ASA classifications (p < 0.001). Their mean operative times were longer (156.1 ± 19.6 vs 105.2 ± 0.6 min, p < 0.001), as were their mean lengths of stay (4.6 ± 0.8 vs 1.3 ± 0.0 days, p < 0.001). CDI patients were more likely to have other complications (29% vs 6%, p < 0.001). Among patients with CDI, 19.4% experienced concomitant infectious complications. There was no difference in reoperation rate, but more patients with CDI required readmission (56% vs 4%, p < 0.001). A third of children with CDI had undergone vesicoureteral reflux correction, comprising 0.3% of the included procedures. Over 11% of children with CDI had undergone nephrectomy, comprising 1.1% of the included procedures for the highest rate. DISCUSSION: CDI are uncommon following pediatric urologic procedures. No patients undergoing inguinal or scrotal cases developed CDI, while only one patient developed CDI after penile surgery. Our study does have several important limitations: we are unable to provide clinical information about the exact diagnoses, CDI risk factors such as antibiotic usage or comorbid conditions, and the number of patients who were tested for CDI. CONCLUSION: While pediatric urologists are unlikely to encounter postoperative CDI, when they occur, they are associated with longer lengths of stay, increased readmission rates, and an increased rate of non-CDI complications.

Cross-protection induced by highly conserved outer membrane proteins (Omps) in mice immunized with OmpC of Salmonella Typhi or OmpK36 of Klebsiella pneumoniae.

BACKGROUND/PURPOSE: Outer membrane proteins (Omps) are a family of proteins that are highly conserved throughout the evolution of Enterobacteriaceae. Previous studies using sequence comparisons have found a high degree of sequence homology between OmpK36 of Klebsiella pneumoniae and OmpC of Salmonella enterica serovar Typhi. Whether highly conserved OmpC can be directly extrapolated as a common vaccine candidate against K. pneumoniae or other Enterobacteriaceae remains to be verified. METHODS: OmpK36 and OmpC were purified and used to immunize BALB/c mice. After immunization, five mice from each group were injected intraperitoneally with a cell suspension of K. pneumoniae or S. Typhi, and the mice were monitored daily for 14 days to measure the severity of illness and assess their survival. RESULTS: Cross-reacting OmpK36 and OmpC antibodies were identified in the mice immunized with OmpK36 or OmpC. No cross-protection was observed in the mice immunized with OmpC in the presence of K. pneumoniae infection. CONCLUSION: Although a high degree of similarity was observed for the amino acid sequences between OmpK36 and OmpC, our results suggested that no cross-protection occurred in the mice challenged with other species.

Respiratory and nonrespiratory COVID-19 complications in patients with obesity: recent developments.

This narrative review summarizes recent reports to provide an updated understanding of the multiorgan effects of SARS-CoV-2 infection in obese individuals. A PubMed search of 528 primary articles was performed, with inclusion based on novelty, relevance and redundancy. Obesity confers an increased risk for hospitalization, intensive care unit admission, severe pneumonia, intubation and acute kidney injury in COVID-19 patients. Obesity is also associated with higher levels of inflammatory and thrombotic markers. However, the associations between obesity and mortality or cardiac injury in COVID-19 patients remain unclear. Obesity is a risk factor for several respiratory and nonrespiratory COVID-19 complications. Future work is needed to further explore these relationships and optimize the management of obese COVID-19 patients.

Complications of rabbit anti-thymocyte globulin induction immunosuppression in HIV-infected kidney transplant recipients.

Background: Kidney transplantation in HIV-infected individuals with end-stage kidney disease is associated with improved survival compared to dialysis. Rabbit anti-thymocyte globulin (rATG) induction in HIV-infected kidney transplant recipients has been associated with a lower risk of acute rejection, but data on the rates of de novo malignancy and BK viremia in these patients is lacking. Methods: We performed a single-center retrospective cohort study of adult HIV-infected individuals who underwent kidney transplantation with rATG induction between January 2006 and December 2016. The primary outcome was the development of de novo malignancy. Secondary outcomes included the development of BK viremia, infections requiring hospitalization, HIV progression, biopsy-proven acute rejection, and patient and allograft survival. Results: Twenty-seven HIV-infected individuals with end-stage kidney disease received deceased (n=23) or living (n=4) donor kidney transplants. The cumulative rate of malignancy at five years was 29%, of whom 29% died because of advanced malignancy. BK viremia was detected in six participants (22%), of whom one had biopsy-proven BK virus-associated nephropathy and all of whom cleared the BK viremia. Five-year acute rejection rates, patient survival and death-censored allograft survival were 17%, 85% and 80% respectively. Conclusion: rATG induction in HIV-infected kidney transplant recipients was associated with a low risk of acute rejection, but a potentially higher risk of de novo malignancies and BK viremia in this cohort. Screening strategies to closely monitor for BK virus infection and malignancy post-transplantation may improve outcomes in HIV-infected kidney transplant recipients receiving rATG induction.

Immunosuppression considerations in simultaneous organ transplant.

Solid organ transplantation is a life-saving procedure for patients in the end stage of heart, lung, kidney, and liver failure. For patients with more than one failing organ, simultaneous organ transplantation has emerged as a viable treatment option. Immunosuppression strategies and outcomes for simultaneous organ transplant recipients have been reported, but often involve limited populations. Transplanting dual organs poses challenges in terms of balancing immunosuppression with immunologic risk and allograft damage from surgical complications. Furthermore, transplanting certain organs can impose considerations on the management of immunosuppression. For example, liver allografts may confer immunologic privilege and lower rates of rejection of other allografts. This review article evaluates immunosuppression strategies for simultaneous kidney-pancreas, liver-kidney, heart-kidney, heart-liver, heart-lung, lung-liver, and lung-kidney transplants. To date, no comprehensive review exists to address immunosuppressive strategies in simultaneous organ transplant populations. Our review summarizes the available literature and provides evidence-based recommendations regarding immunosuppression strategies in simultaneous organ transplant recipients.

Syndromic Wilms tumor: a review of predisposing conditions, surveillance and treatment.

Predisposing syndromes associated with an increased risk of Wilms tumor (WT) are responsible for 9-17% of all cases of the malignancy. Due to an earlier age at WT diagnosis and an increased incidence of bilateral and metachronous disease, management of syndromic WT warrants a distinct approach from that of non-syndromic WT. This review of English-language manuscripts about WT focuses on the most common syndromes, surveillance protocols and current treatment strategies. Highlighted syndromes include those associated with WT1, such as WAGR (Wilms-Aniridia-Genitourinary-mental Retardation), Denys-Drash syndrome (DDS), and Frasier syndrome, 11p15 defects, such as Beckwith-Wiedemann syndrome (BWS), among others. General surveillance guidelines include screening renal or abdominal ultrasound every 3-4 months until the age of 5 or 7, depending on the syndrome. Further, some of the predisposing conditions also increase the risk of other malignancies, such as gonadoblastoma and hepatoblastoma. With promising results for nephron-sparing surgery in bilateral non-syndromic WT, there are increasing reports and recommendations to pursue nephron-sparing for these patients who are at greater risk of bilateral, metachronous lesions. In addition to the loss of renal parenchyma from malignancy, many patients are at risk of developing renal insufficiency as part of their syndrome. Although there may be some increase in the complication rate, recurrence free survival seems equivalent. Some conditions require specialized approaches to adjuvant therapy, as their syndrome may make them especially susceptible to side effects.

Increased canonical NF-kappaB signaling specifically in macrophages is sufficient to limit tumor progression in syngeneic murine models of ovarian cancer.

BACKGROUND: New treatment options for ovarian cancer are urgently required. Tumor-associated macrophages (TAMs) are an attractive target for therapy; repolarizing TAMs from M2 (pro-tumor) to M1 (anti-tumor) phenotypes represents an important therapeutic goal. We have previously shown that upregulated NF-kappaB (NF-κB) signaling in macrophages promotes M1 polarization, but effects in the context of ovarian cancer are unknown. Therefore, we aimed to investigate the therapeutic potential of increasing macrophage NF-κB activity in immunocompetent mouse models of ovarian cancer. METHODS: We have generated a transgenic mouse model, termed IKFM, which allows doxycycline-inducible overexpression of a constitutively active form of IKK2 (cIKK2) specifically within macrophages. The IKFM model was used to evaluate effects of increasing macrophage NF-κB activity in syngeneic murine TBR5 and ID8-Luc models of ovarian cancer in two temporal windows: 1) in established tumors, and 2) during tumor implantation and early tumor growth. Tumor weight, ascites volume, ascites supernatant and cells, and solid tumor were collected at sacrifice. Populations of macrophages and T cells within solid tumor and/or ascites were analyzed by immunofluorescent staining and qPCR, and soluble factors in ascitic fluid were analyzed by ELISA. Comparisons of control versus IKFM groups were performed by 2-tailed Mann-Whitney test, and a P-value < 0.05 was considered statistically significant. RESULTS: Increased expression of the cIKK2 transgene in TAMs from IKFM mice was confirmed at the mRNA and protein levels. Tumors from IKFM mice, regardless of the timing of doxycycline (dox) administration, demonstrated greater necrosis and immune infiltration than control tumors. Analysis of IKFM ascites and tumors showed sustained shifts in macrophage populations away from the M2 and towards the anti-tumor M1 phenotype. There were also increased tumor-infiltrating CD3+/CD8+ T cells in IKFM mice, accompanied by higher levels of CXCL9, a T cell activating factor secreted by macrophages, in IKFM ascitic fluid. CONCLUSIONS: In syngeneic ovarian cancer models, increased canonical NF-κB signaling in macrophages promoted anti-tumor TAM phenotypes and increased cytotoxic T cell infiltration, which was sufficient to limit tumor progression. This may present a novel translational approach for ovarian cancer treatment, with the potential to increase responses to T cell-directed therapy in future studies.

Single-cell RNA sequencing uncovers heterogenous transcriptional signatures in macrophages during efferocytosis.

Efferocytosis triggers cellular reprogramming, including the induction of mRNA transcripts which encode anti-inflammatory cytokines that promote inflammation resolution. Our current understanding of this transcriptional response is largely informed from analysis of bulk phagocyte populations; however, this precludes the resolution of heterogeneity between individual macrophages and macrophage subsets. Moreover, phagocytes may contain so called "passenger" transcripts that originate from engulfed apoptotic bodies, thus obscuring the true transcriptional reprogramming of the phagocyte. To define the transcriptional diversity during efferocytosis, we utilized single-cell mRNA sequencing after co-cultivating macrophages with apoptotic cells. Importantly, transcriptomic analyses were performed after validating the disappearance of apoptotic cell-derived RNA sequences. Our findings reveal new heterogeneity of the efferocytic response at a single-cell resolution, particularly evident between F4/80+ MHCIILO and F4/80- MHCIIHI macrophage sub-populations. After exposure to apoptotic cells, the F4/80+ MHCIILO subset significantly induced pathways associated with tissue and cellular homeostasis, while the F4/80- MHCIIHI subset downregulated these putative signaling axes. Ablation of a canonical efferocytosis receptor, MerTK, blunted efferocytic signatures and led to the escalation of cell death-associated transcriptional signatures in F4/80+ MHCIILO macrophages. Taken together, our results newly elucidate the heterogenous transcriptional response of single-cell peritoneal macrophages after exposure to apoptotic cells.