Treating traumatized children with intellectual disabilities: Tailoring Trauma-Focused Cognitive Behaviour Therapy for a vulnerable population.

BACKGROUND: Children with intellectual disabilities are at heightened risk for traumatization, though underserved due to silos of care, diagnostic overshadowing, and lack of adapted treatment. Trauma-Focused Cognitive Behavioural Therapy (TF-CBT), an evidence-based childhood trauma therapy, is described with recommended adaptations for use with children who have intellectual disabilities. METHOD: We present a suggested theoretical and clinical guide for treating children with mild to moderate intellectual disabilities. We explicate key functional domains of intellectual disabilities-comprehension, executive functions, and generalization-as the basis for tailoring the treatment model. RESULTS: Therapy recommendations are organized into a heuristic 'matrix' of resources and adaptations to TF-CBT components, based on clinical experience and research literature, illustrated with composite case vignettes. CONCLUSION: Children with intellectual disabilities are a uniquely vulnerable population historically excluded from clinical trauma interventions and research but can respond to adapted care. Considerations for future research and dissemination are discussed.

Exploring the Efficacy of Sotagliflozin on Heart and Kidney Health in Diabetic Patients: A Comprehensive Meta-Analysis.

Evidence for reducing cardiovascular and renal events with sotagliflozin is uncertain among type 2 diabetes mellitus (T2DM) patients. To gather more evidence, this meta-analysis assesses the beneficial effects of sotagliflozin, a dual sodium-glucose cotransporter 1 and 2 inhibitor, in reducing the cardiovascular and renal events in diabetic patients with or without chronic kidney disease (CKD). Scopus, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed were the databases used to search. The studies published from January 1, 2018, to January 30, 2022, were considered. The eligibility of studies was assessed independently. The data were collected in a modified Cochrane data extraction form. The included studies' quality was assessed with the Cochrane risk-of-bias tool. The quality of evidence for renal and cardiovascular outcomes was evaluated using GRADEpro software. The number of events of urgent visits to the hospital and requiring hospitalization was reduced (RR: 0.73; 95% CI: 0.69, 0.78; P value <0.00001). The mortality rate because of cardiovascular events was decreased with sotagliflozin (RR: 0.73; 95% CI: 0.67, 0.80; P value <0.00001). Patients taking sotagliflozin had a drastic decline in the number of deaths due to stroke and non-fatal myocardial infarction. Yet, there is no difference between the groups in terms of changes in mortality due to other causes or the glomerular filtration rate (GFR). Sotagliflozin demonstrated effectiveness in reducing the mortality rate related to heart failure and cardiovascular events when the dose was increased from 200 mg to 400 mg. Despite this, evidence is still needed to prove the renal protective action.

Impact of jail-based methadone or buprenorphine treatment on non-fatal opioid overdose after incarceration.

BACKGROUND: Non-fatal overdose is a leading predictor of subsequent fatal overdose. For individuals who are incarcerated, the risk of experiencing an overdose is highest when transitioning from a correctional setting to the community. We assessed if enrollment in jail-based medications for opioid use disorder (MOUD) is associated with lower risk of non-fatal opioid overdoses after jail release among individuals with opioid use disorder (OUD). METHODS: This was a retrospective, observational cohort study of adults with OUD who were incarcerated in New York City jails and received MOUD or did not receive any MOUD (out-of-treatment) within the last three days before release to the community in 2011-2017. The outcome was the first non-fatal opioid overdose emergency department (ED) visit within 1 year of jail release during 2011-2017. Covariates included demographic, clinical, incarceration-related, and other characteristics. We performed multivariable cause-specific Cox proportional hazards regression analysis to compare the risk of non-fatal opioid overdose ED visits within 1 year after jail release between groups. RESULTS: MOUD group included 8660 individuals with 17,119 incarcerations; out-of-treatment group included 10,163 individuals with 14,263 incarcerations. Controlling for covariates and accounting for competing risks, in-jail MOUD was associated with lower non-fatal opioid overdose risk within 14 days after jail release (adjusted HR=0.49, 95% confidence interval=0.33-0.74). We found no significant differences 15-28, 29-56, or 57-365 days post-release. CONCLUSION: MOUD group had lower risk of non-fatal opioid overdose immediately after jail release. Wider implementation of MOUD in US jails could potentially reduce post-release overdoses, ED utilization, and associated healthcare costs.

Police Harassment and Psychiatric, Sexual, and Substance Use Risk Among Black Sexual Minority Men and Black Transgender Women in the HIV Prevention Trials 061 Cohort.

BACKGROUND: Black sexual minority men and Black transgender women (BSMM/BTW) experience disproportionate levels of HIV/STI-related risk factors as well as police harassment (PH). PH is linked to psychiatric risk and could play a role in substance use, sexual risk behavior, and HIV/STI risk. METHODS: We used data from the HIV Prevention Trials Network 061(HPTN 061) study to examine associations between PH and HIV/STI-related outcomes. Using PH exposure measured at baseline and 6-month study visits, we examined an ordinal exposure (PH reported at both visits, PH reported at either visit, versus PH reported at neither baseline nor 6 months) and a binary exposure of persistent PH reported at both visits (yes versus no). We estimate risk ratios (RR) for associations between PH and depression, use of alcohol and methamphetamine, multiple partnerships, condomless sex, and syphilis. RESULTS: Persistent PH (binary) was associated with a 20% or greater increase in the risk of depression (RR, 1.26 (1.07, 1.47)) and multiple partnerships (RR, 1.20 (1.05, 1.39)). There was evidence that ordinal PH was associated with elevated risk of alcohol use (RR, 1.17 (1.00, 1.36)); the point estimate for the association between persistent PH and alcohol use was similar but the imprecision was greater (RR, 1.16 (0.95, 1.42)). CONCLUSION: PH may influence not only mental health but also behavioral risks that contribute to HIV/STI among BSMM/BTW, highlighting the potential wide-ranging and downstream effects of PH on health. Further research is required to confirm associations and elucidate pathways through which PH may influence HIV/STI among BSMM/BTW.

Management of Breast Intraductal Papilloma Diagnosed on Core Needle Biopsy: Excision or Follow-up?

Introduction Management of intraductal papillomas (IDPs) diagnosed on core needle biopsy (CNB) remains controversial. We report our experience of IDPs identified on CNB, our institutional rates of upgradation to atypia/malignancy as well as radiologic/pathologic features that may allow selection for surgery as well as those for safe observation. Methods The study is a retrospective review of patient records from 2012 to 2019, at a tertiary care hospital in Pakistan. Data was analyzed using Statistical Package for Social Sciences (SPSS), version 21.0 (IBM Corp., Armonk, NY). Associations between various patient factors were assessed using Pearson's chi-square test. Results This study included a total of 55 female patients with IDPs, with a mean age of 54.67 ± 15.57 years. On CNB, 69.1% (n = 38) of patients had IDP without atypia while 30.9% (n = 17) had IDP with atypia, with single IDPs being the most common lesions on excisional biopsy. Overall, of all CNB-diagnosed IDPs, only 4/55 (7.3%) demonstrated upgradation (3/4 to DCIS, 1/4 showed atypia) on excisional biopsy, and all these upgraded cases had failed to demonstrate atypia on initial CNB. Conclusion CNB-identified cases of IDPs are rarely upgraded on excision and thus routine excision in all cases may be unnecessary. Appropriate patient selection based on radiology-pathology findings should be done. Those with suspicious findings on imaging as well as those that demonstrate atypia on CNB must be excised.

Risk of Potential Invasive Non-Tuberculous Mycobacterial Infection in Major Cardiothoracic Surgeries.

Nontuberculous Mycobacteria (NTM) commonly colonise municipal water supplies and cause healthcare-associated outbreaks. Although the infections are rare, they are associated with high mortality.  Aerosolization of NTM from colonised Heater cooler devices causes invasive infections in cardiac surgery patients. These units are widely used in open-chest heart surgery as an essential part of extracorporeal circulation but have been suggested as being a risk for infection.  Water disinfection as well as effective engineering-related mitigation strategies should be designed to decrease the burden of NTM in the hospital water supply. Key Words: Nontuberculous Mycobacteria, Heater cooler devices, Endocarditis, Water, Cardiothoracic surgeries.

Differing radiation exposure in scrub technicians and rotating staff in Cardiac catheterization laboratory: occupation matters.

BACKGROUND: Radiation exposure is a significant hazard associated with invasive Cardiology, with most studies based on primary operator exposure. This prospective, observational study aimed to find out over lead radiation exposure as effective dose acquired by non-physician staff comprising scrub technicians and rotating staff in the cath laboratory. Effective dose (ED) measured per procedure via Raysafe i2®dosimeter badges worn by both rotating staff and scrub technicians over lead aprons along with dose area product (DAP), fluoroscopy time (FT) and procedure time (PT) in minutes was collected prospectively over forty-six invasive Cardiology procedures. RESULTS: This study shows that rotating staff acquire higher ED in comparison with their scrub technician colleagues in diagnostic, interventional and electrophysiology cases. However, a statistically significant difference in radiation exposure of both staff groups was demonstrated in diagnostic and interventional Cardiology procedures, with p values of 0.04 and 0.01, respectively. CONCLUSIONS: These findings highlight occupational role and mobility around fluoroscopic sources as major factors in radiation exposure, which should be addressed within current radiation protection practices.

A comparable risk of extensively drug-resistant typhoid fever in the pediatric cohort during the COVID-19 pandemic.

Objective: The number of extremely drug-resistant (XDR) Salmonella typhi isolates is growing in the northwest of Pakistan, where health-care facilities are already under strain due to the coronavirus disease 2019 (COVID-19) issue. In Khyber Pakhtunkhwa, Pakistan, we currently describe the first widespread appearance of an XDR Salmonella typhi epidemic during the COVID-19 pandemic. This strain of Salmonella typhi is resistant to all first- and second-line drugs and even the third-generation cephalosporin. Methods: Salmonella species isolated from pediatric blood samples shown a high level of resistance to the various antibiotic classes evaluated between November and December 2020. Gender, age, address, and clinical symptoms were among the demographic information that was recorded. A total of 562 blood cultures from symptomatic patients have been collected by the Pathology Laboratory at a tertiary care institution of Rehman Medical Institute, Peshawar. All samples have been processed in accordance with regulatory requirements and incubated in BacT/ALERT 3D. Results: Of the 562 blood samples, 71 included Salmonella typhi, of which 66 (92.9%) and 5 (7%) were multidrug resistant (MDR) and XDR, respectively. Ciprofloxacin (100%), chloramphenicol (100%), ceftriaxone (100%), ampicillin (100%), and cotrimoxazole (93%) were completely resistant to all isolates. Azithromycin and carbapenems were effective against every Salmonella typhi isolate that was MDR or XDR. Males (76%) were more commonly affected than females (24%), and the frequency was substantially higher in children under 15 years of age (88%) than in adults (P = 0.0016). Conclusion: The emergence of XDR Salmonella typhi with a high level of resistance is in fact alarming. Due to the lack of viable treatment alternatives, the current situation necessitates the immediate implementation of efficient preventive measures, such as campaigns for typhoid vaccination and food and water safety.

Characterization of patients with brain metastases referred to palliative care.

PURPOSE: In this study, we aimed to assess the clinical characteristics, reasons for referral, and outcomes of patients with brain metastases (BM) referred to the supportive care center. METHODS: Equal numbers of patients with melanoma, breast cancer, and lung cancer with (N = 90) and without (N = 90) BM were retrospectively identified from the supportive care database for study. Descriptive statistics were used to analyze demographic, disease, and clinical data. Kaplan Meier method was used to evaluate survival outcomes. RESULTS: While physical symptom management was the most common reason for referral to supportive care for both patients with and without BM, patients with BM had significantly lower pain scores on ESAS at time of referral (p = 0.002). They had greater interaction with acute care in the last weeks of life, with higher rates of ICU admission, emergency room visits, and hospitalizations after initial supportive care (SC) visit. The median survival time from referral to Supportive Care Center (SCC) was 0.90 years (95% CI 0.73, 1.40) for the brain metastasis group and 1.29 years (95% CI 0.91, 2.29) for the group without BM. CONCLUSIONS: Patients with BM have shorter survival and greater interaction with acute care in the last weeks of life. This population also has distinct symptom burdens from patients without BM. Strategies to optimize integration of SC for patients with BM warrant ongoing study.

Jail-based medication for opioid use disorder and patterns of reincarceration and acute care use after release: A sequence analysis.

BACKGROUND: Treatment with methadone and buprenorphine medications for opioid use disorder (MOUD) during incarceration may lead to better community re-entry, but evidence on these relationships have been mixed. We aimed to identify community re-entry patterns and examine the association between in-jail MOUD and a pattern of successful reentry defined by rare occurrence of reincarceration and preventable healthcare utilization. METHODS: Data came from a retrospective, observational cohort study of 6066 adults with opioid use disorder who were incarcerated in New York City jails and released to the community during 2011-14. An outcome was community re-entry patterns identified by sequence analysis of 3-year post-release reincarceration, emergency department visits, and hospitalizations. An exposure was receipt of in-jail MOUD versus out-of-treatment (42 % vs. 58 %) for the last 3 days before discharge. The study accounted for differences in baseline demographic, clinical, behavioral, housing, and criminal legal characteristics between in-jail MOUD and out-of-treatment groups via propensity score matching. RESULTS: This study identified five re-entry patterns: stability (64 %), hospitalization (23 %), delayed reincarceration (7 %), immediate reincarceration (4 %), and continuous incarceration (2 %). After addressing confounding, 64 % and 57 % followed the stability pattern among MOUD and out-of-treatment groups who were released from jail in 2011, respectively. In 2012-14, the prevalence of following the stability pattern increased year-by-year while a consistently higher prevalence was observed among those with in-jail MOUD. CONCLUSIONS: Sequence analysis helped define post-release stability based on health and criminal legal system involvement. Receipt of in-jail MOUD was associated with a marker of successful community re-entry.

Associations Between Incarceration History and Risk of Hypertension and Hyperglycemia: Consideration of Differences among Black, Hispanic, Asian and White Subgroups.

BACKGROUND: Studies have shown that adults with a history of incarceration have elevated cardiovascular (CVD) risk. Research on racial/ethnic group differences in the association between incarceration and CVD risk factors of hypertension and hyperglycemia is limited. OBJECTIVE: To assess racial/ethnic group differences in the association between incarceration and hypertension and hyperglycemia. DESIGN: We performed a secondary data analysis using the National Longitudinal Survey of Adolescent to Adult Health (Add Health). Using modified Poisson regression, we estimated the associations between lifetime history of incarceration reported during early adulthood with hypertension and hyperglycemia outcomes measured in mid-adulthood, including incident diagnosis. We evaluated whether associations varied by self-reported race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, and Asian). PARTICIPANTS: The analytic sample included 4,015 Add Health respondents who self-identified as non-Hispanic White, Non-Hispanic Black, Hispanic, and Asian, and provided incarceration history and outcome data. MAIN MEASURES: Outcome measures included (1) hypertension (2) systolic blood pressure ≥ 130 mmHg, and (3) hyperglycemia. KEY RESULTS: In non-Hispanic Black and non-Hispanic White participants, there was not evidence of an association between incarceration and measured health outcomes. Among Hispanic participants, incarceration was associated with hyperglycemia (Adjusted Risk Ratio (ARR): 2.1, 95% Confidence Interval (CI): 1.1-3.7), but not with hypertension risk. Incarceration was associated with elevated systolic blood pressure (ARR: 3.1, CI: 1.2-8.5) and hypertension (ARR: 1.7, CI: 1.0-2.8, p = 0.03) among Asian participants, but not with hyperglycemia risk. Incarceration was associated with incident hypertension (ARR 2.5, CI 1.2-5.3) among Asian subgroups. CONCLUSIONS: Our findings add to a growing body of evidence suggesting that incarceration may be linked to chronic disease outcomes. Race/ethnic-specific results, while limited by small sample size, highlight the need for long-term studies on incarceration's influence among distinct US groups.

Factors associated with loss to follow-up in outpatient parenteral antimicrobial therapy: A retrospective cohort study.

We assessed factors associated with increased risk to loss of follow-up with infectious diseases staff in OPAT patients. Discharge to subacute healthcare facilities is strongly associated with loss to follow-up. We did not identify sociodemographic disparities. Poor communication between OPAT providers and subacute healthcare facilities remains a serious issue.

Utility of self-report antiretroviral adherence for predicting HIV viral load among persons who inject drugs in Hai Phong Vietnam: assessing differences by methamphetamine use.

ABSTRACTIn resource-limited settings, alternatives to HIV viral load testing may be necessary to monitor the health of people living with HIV. We assessed the utility of self-report antiretroviral therapy (ART) to screen for HIV viral load among persons who inject drugs in Hai Phong Vietnam, and consider differences by recent methamphetamine use. From 2016 to 2018 we recruited PWID through cross sectional surveys and collected self-report ART adherence and HIV viral load to estimate sensitivity, specificity, positive and negative predictive values (PPV, NPV) and likelihood ratios (LR+, LR-) for self-reported ART adherence as a screening test for HIV viral load. We used three HIV viral load thresholds: < 1000, 500 and 250 copies/mL; laboratory-confirmed HIV viral load was the gold standard. Among 792 PWID recruited, PPV remained above 90% regardless of recent methamphetamine use with slightly higher PPV among those not reporting recent methamphetamine use. The results remained consistent across all three HIV viral load thresholds. Our findings suggest that when HIV viral load testing is not possible, self-reported ART adherence may inform decisions about how to prioritize HIV viral load testing among PWID. The high PPV values suggest self-reported high ART adherence indicates likely HIV viral suppression, irrespective of methamphetamine use.

Impact of Decarceration Plus Alcohol, Substance Use, and Mental Health Screening on Life Expectancies of Black Sexual Minority Men and Black Transgender Women Living With HIV in the United States: A Simulation Study Based on HPTN 061.

BACKGROUND: Given the disproportionate rates of incarceration and lower life expectancy (LE) among Black sexual minority men (BSMM) and Black transgender women (BTW) with HIV, we modeled the impact of decarceration and screening for psychiatric conditions and substance use on LE of US BSMM/BTW with HIV. METHODS: We augmented a microsimulation model previously validated to predict LE and leading causes of death in the US with estimates from the HPTN 061 cohort and the Veteran's Aging Cohort Studies. We estimated independent associations among psychiatric and substance use disorders, to simulate the influence of treatment of one condition on improvement on others. We used this augmented simulation to estimate LE for BSMM/BTW with HIV with a history of incarceration under alternative policies of decarceration (ie, reducing the fraction exposed to incarceration), screening for psychiatric conditions and substance use, or both. RESULTS: Baseline LE was 61.3 years. Reducing incarceration by 25%, 33%, 50%, and 100% increased LE by 0.29, 0.31, 0.53, and 1.08 years, respectively, versus no reductions in incarceration. When reducing incarceration by 33% and implementing screening for alcohol, tobacco, substance use, and depression, in which a positive screen triggers diagnostic assessment for all psychiatric and substance use conditions and linkage to treatment, LE increased by 1.52 years compared with no screening or decarceration. DISCUSSION: LE among BSMM/BTW with HIV is short compared with other people with HIV. Reducing incarceration and improving screening and treatment of psychiatric conditions and substance use could substantially increase LE in this population.

Patterns of speciation in a parapatric pair of Saturnia moths as revealed by target capture.

The focus of this study has been to understand the evolutionary relationships and taxonomy of a widely distributed parapatric species pair of wild silk moths in Europe: Saturnia pavonia and Saturnia pavoniella (Lepidoptera: Saturniidae). To address species delimitation in these parapatric taxa, target enrichment and mtDNA sequencing was employed alongside phylogenetic, admixture, introgression, and species delimitation analyses. The dataset included individuals from both species close to and farther away from the contact zone as well as two hybrids generated in the lab. Nuclear markers strongly supported both S. pavonia and S. pavoniella as two distinct species, with hybrids forming a sister group to S. pavoniella. However, the Maximum Likelihood (ML) tree generated from mtDNA sequencing data presented a different picture, showing both taxa to be phylogenetically intermixed. This inconsistency is likely attributable to mitonuclear discordance, which can arise from biological factors (e.g., introgressive hybridization and/or incomplete lineage sorting). Our analyses indicate that past introgressions have taken place, but that there is no evidence to suggest an ongoing admixture between the two species, demonstrating that the taxa have reached full postzygotic reproductive isolation and hence represent two distinct biological species. Finally, we discuss our results from an evolutionary point of view taking into consideration the past climatic oscillations that have likely shaped the present dynamics between the two species. Overall, our study demonstrates the effectiveness of the target enrichment approach in resolving shallow phylogenetic relationships under complex evolutionary circumstances and that this approach is useful in establishing robust and well-informed taxonomic delimitations involving parapatric taxa.

Comparison of Clinical Outcomes of Calcified and Non-Calcified Coronary Artery Lesion Intervention Under IVUS Guidance.

OBJECTIVE: To evaluate the clinical results of intravascular ultrasound (IVUS)-guided intervention for calcified coronary artery lesions. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Medicine, The Aga Khan University Hospital, Karachi, from January 2013 to January 2020. METHODOLOGY: A cohort of 134 consecutive patients who underwent intravascular ultrasonography-guided assessment of coronary arteries were included. Patients were divided into two groups: those with coronary artery calcification (CAC, n=77) and those without (non-CAC, n=57). The two groups were compared for their clinical characteristics, management, in-hospital events, follow-up, and major adverse cardiovascular events (MACEs). RESULTS: The mean follow-up duration was 40.3 ± 30.1 months. Most of the patients were male (n=97, 72.3%), and the mean age was 63.1 ± 12.9 years. In the CAC group, age was the most common risk factor, followed by dyslipidaemia (n=68, 88%), hypertension (n=64, 83%), and Diabetes mellitus (n=44, 57%). CAC group patients were more commonly presented with acute coronary syndrome (n=59, 76.6%), had prior PCI (n=40, 52%), had more LM disease (n=34, 44%, p=0.005), and a significant number of prior stent-ISR (n=27, 35%, p=0.024). Those who had CAC had higher MACE. CONCLUSION: Patients with CAC had more co-morbidities and commonly presented with acute coronary syndrome. MACEs frequency was recorded higher in the CAC group although the results were not statistically significant. KEY WORDS: Coronary artery calcification, Intravascular imaging, Coronary artery disease, Target vessel revascularisation, Percutaneous coronary intervention.

Commodifying Vaccines to Curtail Antibiotic Resistance Impact in Malaria Endemic Countries.

Rampant and prevalent deployment of an efficient malaria vaccine in Pakistan, together with basic control and preventive measures, could significantly decrease the economic and healthcare burden caused by drug-resistant malaria. Moreover, RTS, S/AS01 vaccine has attained a much-needed breakthrough after decades of growth, as an innovative vaccine for malaria in Phase III clinical trials, and presently undergoing implementation studies. So far Gavi, WHO, and other stakeholders are contemplating on the practical issues, risk-benefit, and cost-effectiveness in resource-limited settings of vaccine implementation capacity. Imminent advances, like using a delayed as well as enhanced protection, divided schedule for dosing, and alternate adjuvants are likely to attain the vital goal of eradication of malaria. Vaccination is a potentially critical component of efforts to arrest the development and dissemination of antimicrobial resistance; though little is known about the impact vaccination may have within low-and-middle-income countries. Key Words: Antimicrobial resistance, Malaria, Vaccine.

Age Differences in the Associations Between Incarceration and Subsequent Substance Use, Sexual Risk-Taking, and Incident STI Among Black Sexual Minority Men and Black Transgender Women in the HIV Prevention Trials 061 Cohort.

Incarceration can lead to different risk behaviors often due to increased distress and disruption of social networks. It is not well known, however, how these associations may differ by age. In this study, we measure age differences in longitudinal associations between incarceration and substance use, sex risk, and sexually transmitted infection (STI) among Black sexual minority men and Black transgender women (BSMM/BTW). We recruited BSMM/BTW from 2009 to 2011 that were part of the HIV Prevention Trials Network 061 study. We compared those less than 30 years old (n = 375) to those 30 years old or greater (n = 794) examining substance use, sex risk, and STI infection stratified by age. Logistic regression with inverse probability weighting was used for the statistical analysis. Approximately 59% of the sample reported incarceration history. In adjusted analysis, incarceration was more strongly associated with alcohol use and stimulant use among older individuals as was sexual risk behaviors including buying and selling sex. Concurrent partnerships were associated with the younger age groups. STI incidence was associated with younger individuals while associations with HIV infection were similar for the two age groups. Understanding differences in substance use and STI risk among age cohorts is imperative to the design and implementation of re-entry programs. Younger BSMM/BTW participating in re-entry support programs may benefit in particular from HIV/STI prevention and care efforts, while post-release substance abuse treatment and harm reduction programs should target older individuals with continued substance abuse.

The cross-talk between macrophages and tumor cells as a target for cancer treatment.

Macrophages represent an important component of the innate immune system. Under physiological conditions, macrophages, which are essential phagocytes, maintain a proinflammatory response and repair damaged tissue. However, these processes are often impaired upon tumorigenesis, in which tumor-associated macrophages (TAMs) protect and support the growth, proliferation, and invasion of tumor cells and promote suppression of antitumor immunity. TAM abundance is closely associated with poor outcome of cancer, with impediment of chemotherapy effectiveness and ultimately a dismal therapy response and inferior overall survival. Thus, cross-talk between cancer cells and TAMs is an important target for immune checkpoint therapies and metabolic interventions, spurring interest in it as a therapeutic vulnerability for both hematological cancers and solid tumors. Furthermore, targeting of this cross-talk has emerged as a promising strategy for cancer treatment with the antibody against CD47 protein, a critical macrophage checkpoint recognized as the "don't eat me" signal, as well as other metabolism-focused strategies. Therapies targeting CD47 constitute an important milestone in the advancement of anticancer research and have had promising effects on not only phagocytosis activation but also innate and adaptive immune system activation, effectively counteracting tumor cells' evasion of therapy as shown in the context of myeloid cancers. Targeting of CD47 signaling is only one of several possibilities to reverse the immunosuppressive and tumor-protective tumor environment with the aim of enhancing the antitumor response. Several preclinical studies identified signaling pathways that regulate the recruitment, polarization, or metabolism of TAMs. In this review, we summarize the current understanding of the role of macrophages in cancer progression and the mechanisms by which they communicate with tumor cells. Additionally, we dissect various therapeutic strategies developed to target macrophage-tumor cell cross-talk, including modulation of macrophage polarization, blockade of signaling pathways, and disruption of physical interactions between leukemia cells and macrophages. Finally, we highlight the challenges associated with tumor hypoxia and acidosis as barriers to effective cancer therapy and discuss opportunities for future research in this field.