First Decade of Supportive Services for Veteran Families Program and Homelessness, 2012-2022.

As homelessness remains an urgent public health crisis in the United States, specific programs in the US Department of Veterans Affairs (VA) system may serve as a roadmap for addressing it. We examine lessons learned from the first decade (2012-2022) of the Supportive Services for Veteran Families (SSVF) program, a cornerstone in the VA continuum of homeless services aimed at both preventing homelessness among those at risk and providing rapid rehousing for veterans and their families who are currently experiencing homelessness. Drawing on information from annual reports and other relevant literature, we have identified 3 themes of SSVF that emerged as features to comprehensively deliver support for homeless veterans and their families: (1) responsiveness and flexibility, (2) coordination and integration, and (3) social resource engagement. Using these strategies, SSVF reached nearly three quarters of a million veterans and their families in its first decade, thereby becoming one of the VA's most substantial programmatic efforts designed to address homelessness. We discuss how each feature might apply to addressing homelessness in the general population as well as future research directions. (Am J Public Health. 2024;114(6):610-618. https://doi.org/10.2105/AJPH.2024.307625).

Adaptive pathology: new insights into the physical examination and imaging of the thrower's shoulder and elbow.

Throwing with high velocity requires extremes of glenohumeral external rotation of the abducted arm where particularly high forces in the shoulder and elbow are endured. Repeated throwing leads to dominant-arm bony remodeling of the humerus, glenoid, and elbow, and multiple soft tissue changes that would be considered abnormal. Many of these features are thought to be adaptive and protective. The purpose of this work is to (1) define the concept of adaptive pathology; (2) review the mechanics of the throwing motion; (3) review pertinent physical examination and imaging findings seen in asymptomatic throwers' shoulders and elbows and describe how these changes develop and may be adaptive-allowing the thrower to perform at high levels; and then (4) review the principles of surgical treatment in the throwing athletes, which should focus on reducing symptoms, but not necessarily restoring the thrower's anatomy to normal.

Factors Associated With Humeral Avulsion of Glenohumeral Ligament Lesions in Patients With Anterior Shoulder Instability: An Analysis of the MOON Shoulder Instability Cohort.

Background: Humeral avulsion of the glenohumeral ligament (HAGL) lesions are an uncommon cause of anterior glenohumeral instability and may occur in isolation or combination with other pathologies. As HAGL lesions are difficult to detect via magnetic resonance imaging (MRI) and arthroscopy, they can remain unrecognized and result in continued glenohumeral instability. Purpose: To compare patients with anterior shoulder instability from a large multicenter cohort with and without a diagnosis of a HAGL lesion and identify preoperative physical examination findings, patient-reported outcomes, imaging findings, and surgical management trends associated with HAGL lesions. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients with anterior glenohumeral instability who underwent surgical management between 2012 and 2020 at 11 orthopaedic centers were enrolled. Patients with HAGL lesions identified intraoperatively were compared with patients without HAGL lesions. Preoperative characteristics, physical examinations, imaging findings, intraoperative findings, and surgical procedures were collected. The Student t test, Kruskal-Wallis H test, Fisher exact test, and chi-square test were used to compare groups. Results: A total of 21 HAGL lesions were identified in 915 (2.3%) patients; approximately one-third (28.6%) of all lesions were visualized intraoperatively but not identified on preoperative MRI. Baseline characteristics did not differ between study cohorts. Compared with non-HAGL patients, HAGL patients were less likely to have a Hill-Sachs lesion (54.7% vs 28.6%; P = .03) or an anterior labral tear (87.2% vs 66.7%; P = .01) on preoperative MRI and demonstrated increased external rotation when their affected arm was positioned at 90° of abduction (85° vs 90°; P = .03). Additionally, HAGL lesions were independently associated with an increased risk of undergoing an open stabilization surgery (odds ratio, 74.6 [95% CI, 25.2-221.1]; P < .001). Conclusion: Approximately one-third of HAGL lesions were missed on preoperative MRI. HAGL patients were less likely to exhibit preoperative imaging findings associated with anterior shoulder instability, such as Hill-Sachs lesions or anterior labral pathology. These patients underwent open procedures more frequently than patients without HAGL lesions.

Development and Validation of a Short-Form Version of the Western Ontario Shoulder Instability Scale (Short-WOSI).

BACKGROUND: Patient-reported outcome measures (PROMs) have transitioned from primarily being used as research instruments to becoming increasingly used in the clinical setting to assess recovery and inform shared decision-making. However, there is a need to develop validated short-form PROM instruments to decrease patient burden and ease incorporation into clinical practice. PURPOSE: To assess the validity and responsiveness of a shortened version of the Western Ontario Shoulder Instability Index (Short-WOSI) when compared with the full WOSI and other shoulder-related PROM instruments. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: This study was a secondary analysis of data collected as part of an institutional review board-approved, multicenter cohort of 1160 patients undergoing surgical stabilization for shoulder instability. The following PROMs were captured preoperatively and 2 years after surgery: WOSI, American Shoulder and Elbow Surgeons (ASES) score, the Single Assessment Numeric Evaluation (SANE), and 36-Item Health Survey (RAND-36). The cohort was split into 2 data sets: a training set to be used in the development of the Short-WOSI (n = 580) and a test set to be used to assess the validity and responsiveness of the Short-WOSI relative to the full WOSI, ASES, SANE, and RAND-36. RESULTS: The Short-WOSI demonstrated excellent internal consistency before surgery (Cronbach α = .83) and excellent internal consistency at the 2-year follow-up (Cronbach α = .93). The baseline, 2-year, and pre- to postoperative changes in Short-WOSI and WOSI were closely correlated (r > 0.90), with both demonstrating large effect sizes (Short-WOSI = 1.92, WOSI = 1.81). Neither the Short-WOSI nor the WOSI correlated well with the other PROM instruments before (r = 0.21-0.33) or after (r = 0.25-0.38) surgery. The Short-WOSI, WOSI, and SANE scores were more responsive than ASES and RAND-36 scores. CONCLUSION: The 7-item Short-WOSI demonstrated excellent internal consistency and a lack of floor or ceiling effects. The Short-WOSI demonstrated excellent cross-sectional and longitudinal construct validity and was similarly responsive over time as the full WOSI. Neither the Short-WOSI nor WOSI correlated with more general shoulder PROMs, underscoring the advantage of using instability-specific instruments for this population.

Utilizing metformin to prevent metabolic syndrome due to androgen deprivation therapy (ADT): a randomized phase II study of metformin in non-diabetic men initiating ADT for advanced prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) can lead to metabolic syndrome (MS) and is implicated in ADT-resistance. Metformin showed antineoplastic activity through mTOR inhibition secondary AMPK-activation. MATERIALS AND METHODS: To investigate whether metformin mitigated ADT-related MS, we conducted a randomized double-blind phase II trial of metformin 500 mg TID or placebo in non-diabetic patients with biochemically-relapsed or advanced PC due for ADT. Fasting serum glucose, insulin, PSA, metformin, weight and waist circumference (WC) were measured at baseline, week 12 and 28. The primary endpoint was a group of MS metrics. Secondary endpoints include PSA response, safety, serum metformin concentrations and analysis of downstream an mTOR target, phospho-S6-kinase. RESULTS: 36 men were randomized to either metformin or placebo. Mean age was 68.4. Mean weight, WC and insulin levels increased in both arms. At week 12 and 28, no statistical differences in weight, WC or insulin were observed in either arm. No significant difference in percentage of patients with PSA <0.2 at week 28 between metformin (45.5%) vs. placebo (46.7%). Analysis in the metformin-arm showed variable down-regulation of phospho-S6 kinase. CONCLUSIONS: In our small study, metformin added to ADT did not show a reduced risk of ADT-related MS or differences in PSA response.

Nonoperative Treatment of Rotator Cuff Tears.

Rotator cuff tears are common with prevalence increasing with age. Diagnosis by physical examination may require a cluster of tests. Although radiographs can be helpful, MRI, MRI arthrography, and ultrasound represent the most used imaging technique to identify rotator cuff tears. Although surgery is sometimes necessary, a large portion of patients may respond to conservative treatment including physical therapy and injections. Physical therapy should include restoring the range of motion, addressing any pectoralis minor or posterior capsule stiffness, and restoring motor control/strength to the scapula and rotator cuff. Other conservative treatments may include nonsteroidal anti-inflammatory drugs, corticosteroid injects, and platelet-rich plasma.

Predictors of Bone Loss in Anterior Glenohumeral Instability.

BACKGROUND: Anterior shoulder instability can result in bone loss of both the anterior glenoid and the posterior humerus. Bone loss has been shown to lead to increased failure postoperatively and may necessitate more complex surgical procedures, resulting in worse clinical outcomes and posttraumatic arthritis. HYPOTHESIS/PURPOSE: The purpose of this study was to investigate predictors of glenoid and humeral head bone loss in patients undergoing surgery for anterior shoulder instability. It was hypothesized that male sex, contact sport participation, traumatic dislocation, and higher number of instability events would be associated with greater bone loss. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A total of 892 patients with anterior shoulder instability were prospectively enrolled in the Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability cohort. The presence and amount of anterior glenoid bone loss and accompanying Hill-Sachs lesions were quantified. Descriptive information and injury history were used to construct proportional odds models for the presence of any bone defect, for defects >10% of the anterior glenoid or humeral head, and for combined bony defects. RESULTS: Anterior glenoid bone loss and Hill-Sachs lesions were present in 185 (20.7%) and 470 (52.7%) patients, respectively. Having an increased number of dislocations was associated with bone loss in all models. Increasing age, male sex, and non-White race were associated with anterior glenoid bone defects and Hill-Sachs lesions. Contact sport participation was associated with anterior glenoid bone loss, and Shoulder Actitvity Scale with glenoid bone loss >10%. A positive apprehension test was associated with Hill-Sachs lesions. Combined lesions were present in 19.4% of patients, and for every additional shoulder dislocation, the odds of having a combined lesion was 95% higher. CONCLUSION: An increasing number of preoperative shoulder dislocations is the factor most strongly associated with glenoid bone loss, Hill-Sachs lesions, and combined lesions. Early surgical stabilization before recurrence of instability may be the most effective method for preventing progression to clinically significant bone loss. Patients should be made aware of the expected course of shoulder instability, especially in athletes at high risk for recurrence and osseous defects, which may complicate care and worsen outcomes. REGISTRATION: NCT02075775 (ClinicalTrials.gov identifier).

Patient Complaints in Orthopedic Surgery: An Analysis Utilizing a Large National Database.

INTRODUCTION: Unsolicited patient complaints (UPCs) about surgeons correlate with surgical complications and malpractice claims. Analysis of UPCs in orthopedics is limited. METHODS: Patient complaint reports recorded at 36 medical centers between January 1, 2015 and December 31, 2018 were coded using a previously validated coding algorithm Patient Advocacy Reporting System. RESULTS: A total of 33,174 physicians had 4 consecutive years of data across the 36 participating medical centers and met other inclusion criteria. CONCLUSIONS: Orthopedists with high numbers of UPCs may benefit from being made aware of their elevated risk status in ways that invite reflection on underlying causes.

Upfront Biology-Guided Therapy in Diffuse Intrinsic Pontine Glioma: Therapeutic, Molecular, and Biomarker Outcomes from PNOC003.

PURPOSE: PNOC003 is a multicenter precision medicine trial for children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG). PATIENTS AND METHODS: Patients (3-25 years) were enrolled on the basis of imaging consistent with DIPG. Biopsy tissue was collected for whole-exome and mRNA sequencing. After radiotherapy (RT), patients were assigned up to four FDA-approved drugs based on molecular tumor board recommendations. H3K27M-mutant circulating tumor DNA (ctDNA) was longitudinally measured. Tumor tissue and matched primary cell lines were characterized using whole-genome sequencing and DNA methylation profiling. When applicable, results were verified in an independent cohort from the Children's Brain Tumor Network (CBTN). RESULTS: Of 38 patients enrolled, 28 patients (median 6 years, 10 females) were reviewed by the molecular tumor board. Of those, 19 followed treatment recommendations. Median overall survival (OS) was 13.1 months [95% confidence interval (CI), 11.2-18.4] with no difference between patients who followed recommendations and those who did not. H3K27M-mutant ctDNA was detected at baseline in 60% of cases tested and associated with response to RT and survival. Eleven cell lines were established, showing 100% fidelity of key somatic driver gene alterations in the primary tumor. In H3K27-altered DIPGs, TP53 mutations were associated with worse OS (TP53mut 11.1 mo; 95% CI, 8.7-14; TP53wt 13.3 mo; 95% CI, 11.8-NA; P = 3.4e-2), genome instability (P = 3.1e-3), and RT resistance (P = 6.4e-4). The CBTN cohort confirmed an association between TP53 mutation status, genome instability, and clinical outcome. CONCLUSIONS: Upfront treatment-naïve biopsy provides insight into clinically relevant molecular alterations and prognostic biomarkers for H3K27-altered DIPGs.

Targeting aberrant replication and DNA repair events for treating breast cancers.

The major limitations of DNA-targeting chemotherapy drugs include life-threatening toxicity, acquired resistance and occurrence of secondary cancers. Here, we report a small molecule, Carbazole Blue (CB), that binds to DNA and inhibits cancer growth and metastasis by targeting DNA-related processes that tumor cells use but not the normal cells. We show that CB inhibits the expression of pro-tumorigenic genes that promote unchecked replication and aberrant DNA repair that cancer cells get addicted to survive. In contrast to chemotherapy drugs, systemic delivery of CB suppressed breast cancer growth and metastasis with no toxicity in pre-clinical mouse models. Using PDX and ex vivo explants from estrogen receptor (ER) positive, ER mutant and TNBC patients, we further demonstrated that CB effectively blocks therapy-sensitive and therapy-resistant breast cancer growth without affecting normal breast tissue. Our data provide a strong rationale to develop CB as a viable therapeutic for treating breast cancers.

Techno-economic and sustainability analysis of siloxane removal from landfill gas used for electricity generation.

A technoeconomic analysis (TEA) and life cycle assessment (LCA) was conducted on the use of landfill gas (LFG) for electricity generation using an internal combustion engine. This study provides insights that can guide LFG waste to energy (WTE) operators on decisions concerning installation of contaminant removal from LFG for electricity generation. Four scenarios were analyzed; the first (Scenario 1) was a facility with a single siloxane removal unit (SREU) sized for 6 months of continuous use, the second (Scenario 2) was a facility with parallel SREUs sized for one month of use, the third (Scenario 3) was a facility with no SREU, and the fourth was a facility that flared all LFG captured. The TEA revealed that the chiller cost was over 50% the total purchase cost of the LFG pre-treatment system. When the complete LFG to electricity process was analyzed, the internal combustion engine had the highest percentage of total capital investment and the total annual cost. For the base case, it became economically beneficial to install a SREU at facilities with LFG flowrates greater than ∼2000 m3/h. Sensitivity analysis showed that at a base case of 1700 m3/h, LFG (50% CH4), and 50 mg/m3 D4, the net income of facilities in Scenarios 1 to 3 became positive at an electricity sales price greater than 5.5 cents/kWh. LCA revealed that Scenario 2 had the greatest CO2 emission reduction. Scenario 3 is observed to save less CO2 emissions as biogas flowrate increases due to frequent engine shutdowns. Although there are differences in the global warming potential (GWP 100) for Scenarios 1 to 3, with Scenario 2 being the best and Scenario 3 being the worst, the differences are very small. For this reason, economics alone are sufficient in decision making.

Factors Associated With Shoulder Activity Level at Time of Surgery and at 2-Year Follow-up in Patients Undergoing Shoulder Stabilization Surgery.

BACKGROUND: Patients undergoing shoulder stabilization surgery have been shown to have elevated activity levels. Factors associated with shoulder activity in this patient population at baseline and after surgery are unknown. HYPOTHESIS: Patient-specific variables are associated with shoulder activity level at baseline and at 2-year follow-up in a cohort of patients undergoing shoulder stabilization surgery. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Patients undergoing shoulder stabilization surgery were prospectively enrolled. As part of the data collection process, patients completed a previously validated Shoulder Activity Scale. A regression analysis was performed to assess the association of patient characteristics with baseline and 2-year follow-up shoulder activity levels. RESULTS: A total of 764 (n = 612 men, n = 152 women) out of 957 patients (80%) undergoing shoulder stabilization surgery with a median age of 25 years had baseline and 2-year follow-up data and were included in the current analysis. The baseline shoulder activity level was associated with race ( P < .0001) and preoperative duration of instability (P < .0001). At 2 years, 52% of the cohort had returned to the same or higher activity level after surgery. Predictors of higher shoulder activity level at 2-year follow-up included higher baseline activity level (P < .0001), male sex (P < .0001), younger age (P = .004), higher body mass index (BMI) (P = .03), more dislocations (P = .03), nonsmokers (P = .04), and race (P = .04). CONCLUSION: A longer duration of preoperative symptoms was associated with a lower baseline activity in this cohort. High baseline preoperative shoulder activity, younger age, male sex, higher BMI, number of dislocations, and nonsmoking status predicted higher shoulder activity 2 years after shoulder stabilization surgery. REGISTRATION: NCT02075775 (ClinicalTrials.gov identifier).

Obesity and sex influence fatty infiltration of the rotator cuff: the Rotator Cuff Outcomes Workgroup (ROW) and Multicenter Orthopaedic Outcomes Network (MOON) cohorts.

BACKGROUND: Fatty infiltration (FI) is one of the most important prognostic factors for outcomes after rotator cuff surgery. Established risk factors include advancing age, larger tear size, and increased tear chronicity. A growing body of evidence suggests that sex and obesity are associated with FI; however, data are limited. METHODS: We recruited 2 well-characterized multicenter cohorts of patients with rotator cuff tears (Multicenter Orthopaedic Outcomes Network [MOON] cohort [n = 80] and Rotator Cuff Outcomes Workgroup [ROW] cohort [n = 158]). We used multivariable logistic regression to evaluate the relationship between body mass index (BMI) and the presence of FI while adjusting for the participant's age at magnetic resonance imaging, sex, and duration of shoulder symptoms, as well as the cross-sectional area of the tear. We analyzed the 2 cohorts separately and performed a meta-analysis to combine estimates. RESULTS: A total of 27 patients (33.8%) in the Multicenter Orthopaedic Outcomes Network (MOON) cohort and 57 patients (36.1%) in the Rotator Cuff Outcomes Workgroup (ROW) cohort had FI. When BMI < 25 kg/m2 was used as the reference category, being overweight was associated with a 2.37-fold (95% confidence interval [CI], 0.77-7.29) increased odds of FI and being obese was associated with a 3.28-fold (95% CI, 1.16-9.25) increased odds of FI. Women were 4.9 times (95% CI, 2.06-11.69) as likely to have FI as men. CONCLUSIONS: Among patients with rotator cuff tears, obese patients had a substantially higher likelihood of FI. Further research is needed to assess whether modifying BMI can alter FI in patients with rotator cuff tears. This may have significant clinical implications for presurgical surgical management of rotator cuff tears. Sex was also significantly associated with FI, with women having higher odds of FI than men. Higher odds of FI in female patients may also explain previously reported early suboptimal outcomes of rotator cuff surgery and higher pain levels in female patients as compared with male patients.

A phase 1/2 clinical trial of the nitric oxide synthase inhibitor L-NMMA and taxane for treating chemoresistant triple-negative breast cancer.

The inducible nitric oxide signaling (iNOS) pathway is associated with poor prognosis in triple-negative breast cancer (TNBC). Prior studies using in vivo models showed that inhibition of the iNOS signaling pathway using the pan-NOS inhibitor NG-monomethyl-l-arginine (L-NMMA) reduced tumor growth and enhanced survival in patients with TNBC. Here, we report a first-in-class phase 1/2 trial of L-NMMA combined with taxane for treating patients with chemorefractory, locally advanced breast cancer (LABC) or metastatic TNBC. We also examined immune cell correlates of chemotherapy response. 35 patients with metastatic TNBC were recruited: 15 in the phase 1 trial and 24 in the phase 2 trial (including 4 recommended phase 2 dose patients from the phase 1 trial). The overall response rate was 45.8% (11 of 24): 81.8% (9 of 11) for patients with LABC and 15.4% (2 of 13) for patients with metastatic TNBC. Among the patients with LABC, three patients had a pathological complete response at surgery (27.3%). Grade ≥3 toxicity was noted in 21% of patients; however, no adverse events were attributed to L-NMMA. Immune cells analyzed by CyTOF indicated that chemotherapy nonresponders showed greater expression of markers associated with M2 macrophage polarization and increased concentrations of circulating IL-6 and IL-10 cytokines. In contrast, chemotherapy responders showed an increase in CD15+ neutrophils in blood, as well as a decrease in arginase (a marker of protumor N2 neutrophils) in tumor biopsies obtained at the end of treatment. L-NMMA combined with taxane warrants further investigation in larger clinical studies of patients with breast cancer.

Consensus statement on the treatment of massive irreparable rotator cuff tears: a Delphi approach by the Neer Circle of the American Shoulder and Elbow Surgeons.

BACKGROUND: Management of massive irreparable rotator cuff tears (MIRCTs) remains controversial owing to variability in patient features and outcomes contributing to a lack of unanimity in treatment recommendations. The purpose of this study was to implement the Delphi process using experts from the Neer Circle of the American Shoulder and Elbow Surgeons to determine areas of consensus regarding treatment options for a variety of MIRCTs. METHODS: A panel of 120 shoulder surgeons were sent a survey regarding MIRCT treatments including arthroscopic débridement and partial cuff repair, graft augmentation, reverse shoulder arthroplasty (RSA), superior capsular reconstruction (SCR), and tendon transfer. An iterative Delphi process was then conducted with a first-round questionnaire consisting of 13 patient factors with the option for open-ended responses to identify important features influencing the treatment of MIRCTs. The second-round survey sought to determine the importance of patient factors related to the 6 included treatment options. A third-round survey asked participants to classify treatment options for 60 MIRCT patient scenarios as either preferred treatment, acceptable treatment, not acceptable/contraindicated, or unsure/no opinion. Patient scenarios were declared to achieve consensus for the preferred and not acceptable/contraindicated categories when at least 80% of the survey respondents agreed on a response, and a 90% threshold was required for the acceptable treatment category, defined by an acceptable treatment or preferred treatment response. RESULTS: Seventy-two members agreed to participate and were deemed to have the requisite expertise to contribute based on their survey responses regarding clinical practice and patient volume. There were 20 clinical scenarios that reached 90% consensus as an acceptable treatment, with RSA selected for 18 scenarios and arthroscopic débridement and/or partial repair selected for 2. RSA was selected as the singular preferred treatment option in 8 scenarios. Not acceptable/contraindicated treatment options reached consensus in 8 scenarios, of which, 4 related to SCR, 3 related to RSA, and 1 related to partial repair with graft augmentation. CONCLUSION: This Delphi process exhibited significant consensus regarding RSA as a preferred treatment strategy in older patients with pseudoparesis, an irreparable subscapularis, and dynamic instability. In addition, the process identified certain unacceptable treatments for MIRCTs such as SCR in older patients with pseudoparesis and an irreparable subscapularis or RSA in young patients with an intact or reparable subscapularis without pseudoparesis or dynamic instability. The publication of these scenarios and areas of consensus may serve as a useful guide for practitioners in the management of MIRCTs.