Mortality surrogates in combined pulmonary fibrosis and emphysema.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) with coexistent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may associate with reduced forced vital capacity (FVC) declines compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts. METHODS: Visual emphysema presence (>0% emphysema) scored on computed tomography identified CPFE patients (CPFE/non-CPFE: derivation cohort n=317/n=183, replication cohort n=358/n=152), who were subgrouped using 10% or 15% visual emphysema thresholds, and an unsupervised machine-learning model considering emphysema and interstitial lung disease extents. Baseline characteristics, 1-year relative FVC and diffusing capacity of the lung for carbon monoxide (D LCO) decline (linear mixed-effects models), and their associations with mortality (multivariable Cox regression models) were compared across non-CPFE and CPFE subgroups. RESULTS: In both IPF cohorts, CPFE patients with ≥10% emphysema had a greater smoking history and lower baseline D LCO compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-year D LCO decline showed stronger mortality associations than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials and in subjects subgrouped by ≥15% emphysema and using unsupervised machine learning. Importantly, the unsupervised machine-learning approach identified CPFE patients in whom FVC decline did not associate strongly with mortality. In non-CPFE IPF patients, 1-year FVC declines ≥5% and ≥10% showed strong mortality associations. CONCLUSION: When assessing disease progression in IPF, D LCO decline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients.

Chest radiograph classification and severity of suspected COVID-19 by different radiologist groups and attending clinicians: multi-reader, multi-case study.

OBJECTIVES: To quantify reader agreement for the British Society of Thoracic Imaging (BSTI) diagnostic and severity classification for COVID-19 on chest radiographs (CXR), in particular agreement for an indeterminate CXR that could instigate CT imaging, from single and paired images. METHODS: Twenty readers (four groups of five individuals)-consultant chest (CCR), general consultant (GCR), and specialist registrar (RSR) radiologists, and infectious diseases clinicians (IDR)-assigned BSTI categories and severity in addition to modified Covid-Radiographic Assessment of Lung Edema Score (Covid-RALES), to 305 CXRs (129 paired; 2 time points) from 176 guideline-defined COVID-19 patients. Percentage agreement with a consensus of two chest radiologists was calculated for (1) categorisation to those needing CT (indeterminate) versus those that did not (classic/probable, non-COVID-19); (2) severity; and (3) severity change on paired CXRs using the two scoring systems. RESULTS: Agreement with consensus for the indeterminate category was low across all groups (28-37%). Agreement for other BSTI categories was highest for classic/probable for the other three reader groups (66-76%) compared to GCR (49%). Agreement for normal was similar across all radiologists (54-61%) but lower for IDR (31%). Agreement for a severe CXR was lower for GCR (65%), compared to the other three reader groups (84-95%). For all groups, agreement for changes across paired CXRs was modest. CONCLUSION: Agreement for the indeterminate BSTI COVID-19 CXR category is low, and generally moderate for the other BSTI categories and for severity change, suggesting that the test, rather than readers, is limited in utility for both deciding disposition and serial monitoring. KEY POINTS: • Across different reader groups, agreement for COVID-19 diagnostic categorisation on CXR varies widely. • Agreement varies to a degree that may render CXR alone ineffective for triage, especially for indeterminate cases. • Agreement for serial CXR change is moderate, limiting utility in guiding management.

Project ECHO in Psychiatric Workforce Development: the Example of a Perinatal Mental Health ECHO.

OBJECTIVE: Perinatal mental health and substance use disorders (PMHSUD) often go unrecognized and untreated. This study examined the use of the Project ECHO model to teach obstetric, primary care, and mental health clinicians about screening, diagnosis, and treatment of PMHSUD. METHODS: Participants in 3 years of the University of Washington's Moms' Access Project (MAP) ECHO program (2019-2022) completed pre- and post-program surveys. Nine participants in year 1 completed qualitative interviews. Dedoose was used for qualitative analysis of interviews. RESULTS: Of 136 participants, 62.5% (15/24) completed both pre- and post-surveys in year 1, 56% (28/50) in year 2, and 32.2% (20/62) in year 3. Most respondents agreed or strongly agreed that they were glad to have participated (96.8%; 60/62) and that they had used information learned in the program in treating a patient (95.1%; 58/61). In all years, respondents endorsed increased confidence regarding learning objectives of the program. Qualitative interviews following year 1 yielded themes of hierarchy of competence, motivation versus results of participation, connection, and politics of change: position and practice type. CONCLUSIONS: Findings supported the feasibility, acceptability, and self-reported effectiveness of the ECHO model for workforce development in PMHSUD.

Contemporary Treatment of Intracranial Blood Blister Aneurysms - A Systematic Review.

INTRODUCTION: Blood blister aneurysms (BBAs) are rare aneurysms affecting non-branched points of intracerebral arteries. Due to their small size and fragility, BBAs are prone to rupture, and can be challenging to diagnose and treat. Several treatment options have been suggested yet there is no consensus regarding the best modality to reduce morbidity and mortality. MATERIALS AND METHODS: A systematic review of the literature was conducted searching for articles discussing the treatment of BBAs. Inclusion criteria included: articles published between January 2010 and August 2020, English language, with each paper including at least 15 patients. Studies included required detailed reporting of patient demographics, treatment, and patient outcomes (including complications, recurrence, neurologic functional status, and mortality). RESULTS AND DISCUSSION: A total of 25 studies with 883 patients were included. Most were female (n = 594, 67.3%) and aneurysms were overwhelmingly located in the supraclinoid internal carotid artery (99%). Aneurysms were variable in size and mostly presented with subarachnoid haemorrhage. Endovascular treatment (n = 518, 58.7%) was more common than microsurgery (n = 365, 41.1%) while only 2 patients were managed conservatively. Complications were more common in patients treated microsurgically. Microsurgical procedures had an unfavorable outcome (mRS 4-6, GOS 1-3) rate of 27.8% (n = 100/360) while that of endovascular procedures was 14.7% (n = 70/477). Endovascular procedures had a lower mortality rate than microsurgical interventions (8.4% vs 11%). CONCLUSION: This review demonstrates that endovascular treatment of blood blister aneurysm has reduced morbidity and mortality when compared with microsurgical treatment. Small sample sizes and substantial study heterogeneity makes strong conclusions difficult.

Total Gastrectomy for CDH-1 Mutation Carriers: An Institutional Experience.

BACKGROUND: Gastric cancer is a leading cause of cancer-related death across the world. A subset of gastric cancers demonstrates an inherited genetic predisposition. Individuals with germline mutations in the CDH1 gene incur a lifetime risk for diffuse gastric cancer and benefit from prophylactic gastrectomy. The results for this operative intervention remain relatively undescribed in the literature, despite guidelines supporting its use. METHODS: We present a single-institution series of patients with confirmed CDH1 mutations who underwent gastrectomy. We describe their presenting symptoms, preoperative screening, clinicopathologic features, and outcomes. Focal outcomes of interest are weight loss and postoperative morbidity. RESULTS: Between 2010 and 2018, ten patients with a confirmed CDH1 mutation underwent total gastrectomy with intestinal pouch reconstruction at our institution. Two patients had clinical gastric cancer at the time of their operation at 21 and 60 y of age. Eight patients had prophylactic gastrectomy. All prophylactic patients had undergone prior endoscopic screening without detection of cancer; however, three had occult gastric cancer on pathological examination. Median weight loss after gastrectomy was 10 kg at 6 mo and 11 kg at 1 y. Postoperative morbidity was limited to one anastomotic leak, one hematoma, and one case of pneumonia. All patients remain disease-free with median follow-up of 19 mo. CONCLUSIONS: Total gastrectomy for patients with a CDH1 mutation is a cancer-preventing operation for a high-risk population. For this series, jejunal pouch reconstruction was performed with encouragingly low postoperative morbidity, weight loss, and good subjective function.

Low Frequency of Lymph Node Metastases in Patients in the United States With Early-stage Gastric Cancers That Fulfill Japanese Endoscopic Resection Criteria.

BACKGROUND & AIMS: In the West, early gastric cancer is increasingly managed with endoscopic resection (ER). This is, however, based on the assumption that the low prevalence and risk of lymph node metastases observed in Asian patients is applicable to patients in the United States. We sought to evaluate the frequency of and factors associated with metastasis of early gastric cancers to lymph nodes, and whether the Japanese ER criteria are applicable to patients in the US. METHODS: We performed a retrospective study of 176 patients (mean age 68.5 years; 59.1% male; 58.5% white) who underwent surgical resection with lymph node dissection of T1 and Tis gastric adenocarcinomas, staged by pathologists, at 7 tertiary care centers in the US from January 1, 1999, through December 31, 2016. The frequency of lymph node metastases and associated risk factors were determined. RESULTS: The mean size of gastric adenocarcinomas was 23.0 ± 16.6 mm-most were located in the lower-third of the stomach (67.0%), invading the submucosa (55.1%), and moderately differentiated (31.3%). Lymphovascular invasion was observed in 18.2% of lesions. Overall, 20.5% of patients had lymph node metastases. Submucosal invasion (odds ratio, 3.9; 95% CI, 1.4-10.7) and lymphovascular invasion (odds ratio, 4.6; 95% CI, 1.8-12.0) were independently associated with increased risk of metastasis to lymph nodes. The frequency of lymph node metastases among patients fulfilling standard and expanded Japanese criteria for ER were 0 and 7.5%, respectively. CONCLUSIONS: The frequency of lymph node metastases among patients with early gastric cancer in a US population is higher than that of published Asian series. However, early gastric cancer lesions that meet the Japanese standard criteria for ER are associated with negligible risk of metastasis to lymph nodes, so ER can be recommended for definitive therapy. Expanded criteria cancers appear to have a higher risk of metastasis to lymph nodes, so ER may be considered for select cases.

Irrigation Versus Suction in Laparoscopic Appendectomy for Complicated Appendicitis: A Meta-analysis.

BACKGROUND: Acute appendicitis is currently one of the most common surgical emergencies. Intra-abdominal abscesses (IAA) are a fearsome complication, which may occur. Irrigation during the appendectomy is one of the factors suggested to affect the rates of IAA. We sought to investigate the evidence regarding the use of irrigation versus suction alone and the development of IAA after laparoscopic appendectomy for complicated appendicitis. METHODS: We searched PubMed, Scopus, Embase, Cochrane, and the Web of Science through November 10, 2017, according to Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. We extracted information of interest, including rates of postoperative (IAA), and performed meta-analysis using random-effects model using the RevMan software. RESULTS: We identified five eligible studies with 2511 patients in total. Use of irrigation overall did not demonstrate significant increase in IAA (odds ratio [OR] = 2.39, 95% confidence interval [CI; 0.49, 11.74], P = 0.28). For the adult subpopulation, the use of irrigation was associated with nonsignificant lower odds of IAAs (OR = 0.42, 95% CI [0.15, 1.16]), whereas in pediatric with nonsignificant higher risk (OR = 2.98, 95% CI [0.25, 35.34]). Performance of irrigation led to the addition of, on average, 7 min to the duration of the operation (mean difference = 7.16, 95% CI [3.23, 11.09], P < 0.001). Irrigation did not affect postoperative length of stay (mean difference = -0.80, 95% CI [-2.30, 0.69], P = 0.29). CONCLUSIONS: Performance of irrigation during laparoscopic appendectomy does not seem to prevent the development of IAA in neither adults nor pediatric patients.

Acute Care Surgery for Transplant Recipients: A National Survey of Surgeon Perspectives and Practices.

BACKGROUND: Transplant recipients are living longer than ever before, and occasionally require acute care surgery for nontransplant-related issues. We hypothesized that while both acute care surgeons (ACS) and transplant surgeons would feel comfortable operating on this unique patient population, both would believe transplant centers provide superior care. METHODS: To characterize surgeon perspectives, we conducted a national survey of ACS and transplant surgeons. Surgeon- and center-specific demographics were collected; surgeon preferences were compared using χ2, Fisher's exact, and Kruskal-Wallis tests. RESULTS: We obtained 230 responses from ACS and 204 from transplant surgeons. ACS and transplant surgeons believed care is better at transplant centers (78% and 100%), and transplant recipients requiring acute care surgery should be transferred to a transplant center (80.2% and 87.2%). ACS felt comfortable operating (97.5%) and performing laparoscopy (94.0%) on transplant recipients. ACS cited transplant medication use as the most important underlying cause of increased surgical complications for transplant recipients. Transplant surgeons felt it was their responsibility to perform acute care surgery on transplant recipients (67.3%), but less so if patient underwent transplant at a different institution (26.5%). Transplant surgeons cited poor transplanted organ resiliency as the most important underlying cause of increased surgical complications for transplant recipients. CONCLUSIONS: ACS and transplant surgeons feel comfortable performing laparoscopic and open acute care surgery on transplant recipients, and recommend treating transplant recipients at transplant centers, despite the lack of supportive evidence. Elucidating common goals allows surgeons to provide optimal care for this unique patient population.

Carotid artery stenting: Current state of evidence and future directions.

Both carotid endarterectomy (CEA) and carotid artery stenting (CAS) are common treatments for carotid artery stenosis. Several randomized controlled trials (RCTs) have compared CEA to CAS in the treatment of carotid artery stenosis. These studies have suggested that CAS is more strongly associated with periprocedural stroke; however, CEA is more strongly associated with myocardial infarction. Published long-term outcomes report that CAS and CEA are similar. A reduction in complications associated with CAS has also been demonstrated over time. The symptomatic status of the patient and history of previous CEA or cervical radiotherapy are significant factors when deciding between CEA or CAS. Numerous carotid artery stents are available, varying in material, shape and design but with minimal evidence comparing stent types. The role of cerebral protection devices is unclear. Dual antiplatelet therapy is typically prescribed to prevent in-stent thrombosis, and however, evidence comparing periprocedural and postprocedural antiplatelet therapy is scarce, resulting in inconsistent guidelines. Several RCTs are underway that will aim to clarify some of these uncertainties. In this review, we summarize the development of varying techniques of CAS and studies comparing CAS to CEA as treatment options for carotid artery stenosis.

The 100 most cited articles in the endovascular treatment of thoracic and abdominal aortic aneurysms.

OBJECTIVE: Since the introduction of endovascular technology to treat thoracic and abdominal aortic aneurysms, there has been a global research effort focused on assessing the effectiveness of treatment. A bibliometric analysis is used to identify the scientific impact of an article, impactful authors, institutions, and collaborative groups. Our objective was to identify and to analyze the 100 most cited articles in the field of endovascular treatment of thoracic and abdominal aortic aneurysms. METHODS: We performed a retrospective bibliometric analysis in April 2018. Articles were searched on the Science Citation Index Expanded database using Web of Science to identify the most cited articles in endovascular therapy for thoracic and aortic aneurysms since 1945. Use of selected key terms ("AAA," "aortic aneurysm," "thoracic aneurysm," "abdominal aneurysm," "endovascular," "endoluminal," "stent," "graft," "repair," "EVAR," and "TEVAR") yielded a total of 23,354 articles. The top 100 articles were identified and analyzed to extract relevant information including year of publication, citation count, journal, authorship country of origin, and article type. RESULTS: The earliest articles were published in 1991, with the majority being published in the 2000s (n = 59). The number of citations for the top 100 articles ranged from 151 to 1142, with a median citation count of 212. All articles were cited an average of 22.4 times per year. Almost half (n = 46) of the top 100 articles were published in the Journal of Vascular Surgery. Thirty-nine authors contributed four or more articles, with two being credited on 10 papers to make the list. The majority (n = 62) of the articles arose from the United States, while the United Kingdom contributed 11 articles. There were 7 guidelines and 12 randomized controlled trials, and the majority constituted level III or level IV evidence. CONCLUSIONS: This study provides a comprehensive and informative analysis of the most cited and impactful research undertaken in the field of endovascular treatment of abdominal and thoracic aortic aneurysms. By quantitatively assessing the 100 most cited articles in the field, we recognize the contributions of key authors, institutions, and collaborative groups and develop an understanding of the strengths of past research and the requirements for future global efforts.

Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma.

OBJECTIVE: Recent data supports a significant role for immune checkpoint inhibitors in the treatment of solid tumours. Here, we evaluate gastric and gastro-oesophageal junction (G/GEJ) adenocarcinomas for their expression of programmed death-ligand 1 (PD-L1), infiltration by CD8+ T cells and the relationship of both factors to patient survival. DESIGN: Thirty-four resections of primary invasive G/GEJ were stained by immunohistochemistry for PD-L1 and CD8 and by DNA in situ hybridisation for Epstein-Barr virus (EBV). CD8+ T cell densities both within tumours and at the tumour-stromal interface were analysed using whole slide digital imaging. Patient survival was evaluated according to PD-L1 status and CD8 density. RESULTS: 12% of resections showed tumour cell membranous PD-L1 expression and 44% showed expression within the immune stroma. Two cases (6%) were EBV positive, with one showing membranous PD-L1 positivity. Increasing CD8+ densities both within tumours and immune stroma was associated with increasing percentage of tumour (p=0.027) and stromal (p=0.005) PD-L1 expression. Both tumour and immune stromal PD-L1 expression and high intratumoral or stromal CD8+ T cell density (>500/mm2) were associated with worse progression-free survival (PFS) and overall survival (OS). CONCLUSIONS: PD-L1 is expressed on both tumour cells and in the immune stroma across all stages and histologies of G/GEJ. Surprisingly, we demonstrate that increasing CD8 infiltration is correlated with impaired PFS and OS. Patients with higher CD8+ T cell densities also have higher PD-L1 expression, indicating an adaptive immune resistance mechanism may be occurring. Further characterisation of the G/GEJ immune microenvironment may highlight targets for immune-based therapy.

SIRT1 is a critical regulator of K562 cell growth, survival, and differentiation.

Inhibition of histone deacetylases (HDACi) has emerged as a promising approach in the treatment of many types of cancer, including leukemias. Among the HDACs, Class III HDACs, also known as sirtuins (SIRTs), are unique in that their function is directly related to the cell's metabolic state through their dependency on the co-factor NAD(+). In this study, we examined the relation between SIRTs and the growth, survival, and differentiation of K562 erythroleukemia cells. Using a mass spectrometry approach we previously developed, we show that SIRT expression and deacetylase activity in these cells changes greatly with differentiation state (undifferentiated vs. megakaryocytic differentiation vs. erythroid differentiation). Moreover, SIRT1 is crucially involved in regulating the differentiation state. Overexpression of wildtype (but not deacetylase mutant) SIRT1 resulted in upregulation of glycophorin A, ~2-fold increase in the mRNA levels of α, γ, ε, and ζ-globins, and spontaneous hemoglobinization. Hemin-induced differentiation was also enhanced by (and depended on) higher SIRT1 levels. Since K562 cells are bipotent, we also investigated whether SIRT1 modulation affected their ability to undergo megakaryocytic (MK) differentiation. SIRT1 was required for commitment to the MK lineage and subsequent maturation, but was not directly involved in polyploidization of either K562 cells or an already-MK-committed cell line, CHRF-288-11. The observed blockage in commitment to the MK lineage was associated with a dramatic decrease in the formation of autophagic vacuoles, which was previously shown to be required for K562 cell MK commitment. Autophagy-associated conversion of the protein LC3-I to LC3-II was greatly enhanced by overexpression of wildtype SIRT1, further suggesting a functional connection between SIRT1, autophagy, and MK differentiation. Based on its clear effects on autophagy, we also examined the effect of SIRT1 modulation on stress responses. Consistent with results of prior studies, we found that SIRT1 silencing modestly promoted drug-induced apoptosis, while overexpression was protective. Furthermore, pan-SIRT inhibition mediated by nicotinamide pre-treatment substantially increased imatinib-induced apoptosis. Altogether, our results suggest a complex role for SIRT1 in regulating many aspects of K562 cell state and stress response. These observations warrant further investigation using normal and leukemic primary cell models. We further suggest that, ultimately, a well-defined mapping of HDACs to their substrates and corresponding signaling pathways will be important for optimally designing HDACi-based therapeutic approaches.

Applications of MALDI Mass Spectrometry in Clinical Chemistry.

BACKGROUND: MALDI-TOF mass spectrometry (MS) is set to make inroads into clinical chemistry because it offers advantages over other analytical platforms. These advantages include low acquisition and operating costs, ease of use, ruggedness, and high throughput. When coupled with innovative front-end strategies and applied to important clinical problems, it can deliver rapid, sensitive, and cost-effective assays. CONTENT: This review describes the general principles of MALDI-TOF MS, highlights the unique features of the platform, and discusses some practical methods based upon it. There is substantial potential for MALDI-TOF MS to make further inroads into clinical chemistry because of the selectivity of mass detection and its ability to independently quantify proteoforms. SUMMARY: MALDI-TOF MS has already transformed the practice of clinical microbiology and this review illustrates how and why it is now set to play an increasingly important role in in vitro diagnostics in particular, and clinical chemistry in general.

Megakaryocyte Polyploidization and Proplatelet Formation in Low-Attachment Conditions.

In vitro-derived platelets (PLTs), which could provide an alternative source of PLTs for patient transfusions, are formed from polyploid megakaryocytes (MKs) that extend long cytoplasmic projections, termed proplatelets (proPLTs). In this study, we compared polyploidization and proPLT formation (PPF) of MKs cultured on surfaces that either promote or inhibit protein adsorption and subsequent cell adhesion. A megakaryoblastic cell line exhibited increased polyploidization and arrested PPF on a low-attachment surface. Primary human MKs also showed low levels of PPF on the same surface, but no difference in ploidy. Importantly, both cell types exhibited accelerated PPF after transfer to a surface that supports attachment, suggesting that pre-culture on a non-adhesive surface may facilitate synchronization of PPF and PLT generation in culture.

Mass spectrometry and 3-nitrotyrosine: strategies, controversies, and our current perspective.

Reactive-nitrogen species (RNS) such as peroxynitrite (ONOO(-)), that is, the reaction product of nitric oxide ((•)NO) and superoxide (O2(-•)), nitryl chloride (NO2Cl) and (•)NO2 react with the activated aromatic ring of tyrosine to form 3-nitrotyrosine. This modification, which has been known for more than a century, occurs to both the free form of the amino acid (i.e., soluble/free tyrosine) and to tyrosine residues covalently bound within the backbone of peptides and proteins. Nitration of tyrosine is thought to be of biological significance and has been linked to health and disease, but determining its role has proved challenging. Several key questions have been the focus of much of the research activity: (a) to what extent is free/soluble tyrosine nitrated in biological tissues and fluids, and (b) are there specific site(s) of nitration within peptides/proteins and to what extent (i.e., stoichiometry) does this modification occur? These issues have been addressed in a wide range of sample types (e.g., blood, urine, CSF, exhaled breath condensate and various tissues) and a diverse array of physiological/pathophysiological scenarios. The accurate determination of nitrated tyrosine is, however, a stumbling block. Despite extensive study, the extent to which nitration occurs in vivo, the specificity of the nitration reaction, and its importance in health and disease, remain unclear. In this review, we highlight the analytical challenges and discuss the approaches adopted to address them. Mass spectrometry, in combination with either gas chromatography (GC-MS, GC-MS/MS) or liquid chromatography (LC-MS/MS), has played the central role in the analysis of 3-nitrotyrosine and tyrosine-nitrated biological macromolecules. We discuss its unique attributes and highlight the role of stable-isotope labeled 3-nitrotyrosine analogs in both accurate quantification, and in helping to define the biological relevance of tyrosine nitration. We show that the application of sophisticated mass spectrometric techniques is advantageous if not essential, but that this alone is by no means a guarantee of accurate findings. We discuss the important analytical challenges in quantifying 3-nitrotyrosine, possible workarounds, and we attempt to make sense of the disparate findings that have been reported so far.

Extended-release naltrexone and harm reduction counseling for chronically homeless people with alcohol dependence.

BACKGROUND: Abstinence-based alcohol interventions are minimally desirable to and effective for chronically homeless individuals with alcohol dependence who have multimorbidity and high publicly funded service utilization and associated costs. Lower-barrier, patient-centered combined pharmacobehavioral interventions may more effectively treat this population. Harm reduction counseling involves a nonjudgmental, empathic style and patient-driven goal setting that requires neither abstinence nor use reduction. Extended-release naltrexone (XR-NTX), a monthly injectable formulation of an opioid receptor antagonist, reduces craving, is safe and effective for active drinkers, and may thereby support harm reduction goal setting. The aims of this 12-week, single-arm pilot were to initially document some aspects of feasibility, acceptability, and alcohol outcomes following XR-NTX administration and harm reduction counseling for chronically homeless individuals with alcohol dependence. METHODS: Participants were currently/formerly chronically homeless, alcohol-dependent individuals (N = 31) from 2 community-based agencies in the US Pacific Northwest. Measures included self-reported alcohol craving, quantity/frequency, problems, and biomarkers (ethyl glucuronide [EtG], liver transaminases). XR-NTX and harm reduction counseling were administered monthly over the 3-month treatment course. RESULTS: Of the 45 individuals approached, 43 were interested in participation. The first injection was received by 31 participants, and 24 complied with all study procedures. Participants reported the treatment was acceptable. Participants evinced decreases in alcohol craving (33%), typical (25%) and peak (34%) use, frequency (17%), problems (60%), and EtG from the baseline to the 12-week follow-up (Ps < .05). CONCLUSIONS: XR-NTX and harm reduction counseling are promising means of supporting reductions in alcohol use and alcohol-related harm among chronically homeless, alcohol-dependent individuals.