Clinical outcomes of hypomethylating agents plus Venetoclax as frontline treatment in patients 75 years and older with acute myeloid leukemia: Real-world data from eight US academic centers.

Venetoclax (VEN) combined with hypomethylating agents (HMAs) is the standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) unfit for intensive chemotherapy. To date, real-world data published on HMAs plus VEN have been either single-center studies or using community-based electronic databases with limited details on mutational landscape, tolerability, and treatment patterns in elderly patients. Therefore, we conducted a multicenter retrospective study to assess the real-world experience of 204 elderly patients (≥75 years) with newly diagnosed AML treated with HMAs plus VEN from eight academic centers in the United States. Overall, 64 patients achieved complete remission (CR; 38%) and 43 CR with incomplete count recovery (CRi; 26%) for a CR/CRi rate of 64%, with a median duration of response of 14.2 months (95% CI: 9.43, 22.1). Among responders, 63 patients relapsed (59%) with median overall survival (OS) after relapse of 3.4 months (95% CI, 2.4, 6.7). Median OS for the entire population was 9.5 months (95% CI, 7.85-13.5), with OS significantly worse among patients with TP53-mutated AML (2.5 months) and improved in patients harboring NPM1, IDH1, and IDH2 mutations (13.5, 18.3, and 21.1 months, respectively). The 30-day and 60-day mortality rates were 9% and 19%, respectively. In conclusion, HMAs plus VEN yielded high response rates in elderly patients with newly diagnosed AML. The median OS was inferior to that reported in the VIALE-A trial. Outcomes are dismal after failure of HMAs plus VEN, representing an area of urgent unmet clinical need.

Phase I/II Trial of Carboplatin, Nab-paclitaxel, and Pembrolizumab for Advanced Non-Small Cell Lung Cancer: Hoosier Cancer Research Network LUN13-175.

BACKGROUND: Combination chemotherapy and immunotherapy regimens have significantly improved survival for patients with previously untreated advanced non-small cell lung cancer (NSCLC). Improvements in overall survival (OS) in two separate pembrolizumab trials have demonstrated survival improvements over chemotherapy alone, regardless of PD-L1 status. The optimal chemotherapy backbone for combination with immunotherapy is unknown. We hypothesized nab-paclitaxel may be a well-suited platinum partner to use in combination with checkpoint inhibitor therapy for both adenocarcinoma and squamous histology and conducted a phase I/II trial to assess the efficacy of this regimen in advanced NSCLC. METHODS: Adult patients with previously untreated, stage IIIB/IV NSCLC (any histology) with an Eastern Cooperative Oncology Group performance status of 0-1, any PD-L1 expression, and no EGFR mutations or ALK translocations, received carboplatin area under the curve (AUC) 6 day 1, nab-paclitaxel 100 mg/m2 days 1, 8, 15, and pembrolizumab 200 mg day 1 q21 days for 4 cycles followed by maintenance pembrolizumab q3w. Co-primary endpoints were progression-free survival (PFS) and overall response rate (ORR). RESULTS: Forty-six evaluable patients enrolled, 14 in phase I and 32 in phase II, from June 2015 to July 2018 with a median duration of follow-up of 35.4 months. Median time from enrollment to data lock was 42 months. In the ITT population, the ORR was 35%, median PFS was 5.6 months (95% CI, 4.6-8.2), and median OS was 15.4 months (CI, 12.4-28.1). There were no statistical differences in PFS or OS by PD-L1 status. The 2- and 3-year landmark OS rates were 33% and 24%, respectively. CONCLUSION: Carboplatin, nab-paclitaxel, and pembrolizumab are a safe and effective regimen for patients with both squamous and nonsquamous NSCLC. Although this study did not meet the prespecified endpoints, the median and landmark OS results are consistent with durable benefit of this regimen as seen in phase III trials for first-line treatment of advanced NSCLC.

Phase Ib trial of inhaled iloprost for the prevention of lung cancer with predictive and response biomarker assessment.

Introduction: Iloprost, a prostacyclin analog, has lung cancerpreventive activity in preclinical models and improved dysplasia in former smokers in a phase IIb trial. Oral iloprost is currently unavailable. We performed a phase Ib trial of inhaled iloprost in former smokers to assess tolerance and compliance. Methods: Participants self-administered nebulized iloprost (5ug) or placebo four (QID) or two (BID) times daily. As QID dose was well tolerated and due to expiration of the placebo, the BID dosing and placebo were eliminated early on in the trial. Bronchoscopy with biopsyat six standard sites was performed at treatment initiation and two months post-iloprost, with exploratory histological analysis. Bulk RNA sequencing, single cell RNA sequencing and an in vitro assay of epithelial progenitor cell iloprost response were performed on a subset of biopsies in an exploratory investigation of response mechanisms and predictive biomarkers. Results and discussion: Thirty-four of a planned 48 participants were recruited to the trial.Inhaled iloprost was well tolerated with no adverse events > grade 2. Compliance was 67% in the QID group. The trial was not powered to detect histologic response and none was found. Bulk RNA sequencing of biopsies pre/post iloprost suggest that iloprost is immunomodulatory and downregulates cell proliferation pathways. Single cell RNA sequencing showed an increase in CD8-positive T cells with upregulation of genes in interferon γ signaling. In vitro iloprost response by epithelial progenitor cells correlated with histologic response with kappa coefficient of 0.81 (95% CI 0.47, 1.0). Inhaled iloprost was well tolerated with suboptimal compliance. Molecular analysis suggested that iloprosthas immunomodulatory and antiproliferative effects.The progenitor cell iloprost response assay may be a promising avenue to develop predictive biomarkers. Clinical trial registration: https://clinicaltrials.gov/study/NCT02237183, identifier NCT02237183.

Combination of pembrolizumab and pelareorep promotes anti-tumour immunity in advanced pancreatic adenocarcinoma (PDAC).

BACKGROUND: We previously reported activity of pelareorep, pembrolizumab and chemotherapy. Patients developed new T-cell clones and increased peripheral T-cell clonality, leading to an inflamed tumour. To evaluate a chemotherapy-free regimen, this study assesses if pelareorep and pembrolizumab has efficacy by inducing anti-tumour immunological changes (NCT03723915). METHODS: PDAC patients who progressed after first-line therapy, received iv pelareorep induction with pembrolizumab every 21-days. Primary objective is overall response rate. Secondary objectives included evaluation of immunological changes within tumour and blood. RESULTS: Clinical benefit rate (CBR) was 42% amongst 12 patients. One patient achieved partial response (PR) and four stable disease (SD). Seven progressed, deemed non-responders (NR). VDAC1 expression in peripheral CD8+ T cells was higher at baseline in CBR than NR but decreased in CBR upon treatment. On-treatment peripheral CD4+ Treg levels decreased in CBR but not in NR. Analysis of tumour demonstrated PD-L1+ cells touching CD8+ T cells, and NK cells were more abundant post-treatment vs. baseline. A higher intensity of PD-L1 in tumour infiltrates at baseline, particularly in CBR vs. NR. Finally, higher levels of soluble (s)IDO, sLag3, sPD-1 observed at baseline among NR vs. CBR. CONCLUSION: Pelareorep and pembrolizumab showed modest efficacy in unselected patients, although potential immune and metabolic biomarkers were identified to warrant further evaluation.

Urologists and Lesbian, Gay, Bisexual, Transgender, or Queer Patients: A Survey-based Study of the Practice Patterns, Attitudes, and Knowledge Base of Urologists Toward Their Lesbian, Gay, Bisexual, Transgender, or Queer Patients.

OBJECTIVE: To assess urologists' attitudes toward treating lesbian, gay, bisexual, transgender, or queer (LGBT) patients and counseling practices during diagnosis and treatment of prostate cancer. METHODS: A 35-question survey was sent to program directors of U.S. urology residency programs. RESULTS: 154 responses met the inclusion criteria. Respondents were primarily male, heterosexual, in academia, representing a range of ages and geography. 54.2% of respondents don't assume patients are heterosexual. While 88% of providers feel comfortable discussing sexual health with LGBTQ patients, 42.9% disagree that knowing sexual orientation is necessary to providing optimal care. 57.8% of respondents don't provide intake forms to indicate sexual orientation and 60.4% don't inquire about sexual orientation during history-taking. A majority (32.7%) reported 1-5 hours of LGBTQ health training. 74.3% believe more training is needed. 74.5% agreed to being listed as an LGBTQ-Friendly Provider currently, 65.8% felt they needed additional training. 63.6% agreed the prostate is a source of sexual pleasure. 55.9% believed it important to assess sexual satisfaction in patients who engage in receptive anal intercourse after prostate cancer treatment. Responses were mixed regarding the timing of resuming receptive anal intercourse after treatment and whether patients are counseled to refrain from anal stimulation before PSA testing. Answers to knowledge questions regarding anal cancer and communication were primarily correct; answers to questions regarding anejaculation and differences in health concerns were mixed. CONCLUSION: Ongoing education is necessary on specific differences between heterosexual and lesbian, gay, bisexual, transgender, or queer (LGBTQ) patient concerns and how to apply this knowledge in order to address the needs of a rapidly aging LGBTQ population.

Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial.

BACKGROUND: Low-intensity pulsed ultrasound with concomitant administration of intravenous microbubbles (LIPU-MB) can be used to open the blood-brain barrier. We aimed to assess the safety and pharmacokinetics of LIPU-MB to enhance the delivery of albumin-bound paclitaxel to the peritumoural brain of patients with recurrent glioblastoma. METHODS: We conducted a dose-escalation phase 1 clinical trial in adults (aged ≥18 years) with recurrent glioblastoma, a tumour diameter of 70 mm or smaller, and a Karnofsky performance status of at least 70. A nine-emitter ultrasound device was implanted into a skull window after tumour resection. LIPU-MB with intravenous albumin-bound paclitaxel infusion was done every 3 weeks for up to six cycles. Six dose levels of albumin-bound paclitaxel (40 mg/m2, 80 mg/m2, 135 mg/m2, 175 mg/m2, 215 mg/m2, and 260 mg/m2) were evaluated. The primary endpoint was dose-limiting toxicity occurring during the first cycle of sonication and albumin-bound paclitaxel chemotherapy. Safety was assessed in all treated patients. Analyses were done in the per-protocol population. Blood-brain barrier opening was investigated by MRI before and after sonication. We also did pharmacokinetic analyses of LIPU-MB in a subgroup of patients from the current study and a subgroup of patients who received carboplatin as part of a similar trial (NCT03744026). This study is registered with ClinicalTrials.gov, NCT04528680, and a phase 2 trial is currently open for accrual. FINDINGS: 17 patients (nine men and eight women) were enrolled between Oct 29, 2020, and Feb 21, 2022. As of data cutoff on Sept 6, 2022, median follow-up was 11·89 months (IQR 11·12-12·78). One patient was treated per dose level of albumin-bound paclitaxel for levels 1 to 5 (40-215 mg/m2), and 12 patients were treated at dose level 6 (260 mg/m2). A total of 68 cycles of LIPU-MB-based blood-brain barrier opening were done (median 3 cycles per patient [range 2-6]). At a dose of 260 mg/m2, encephalopathy (grade 3) occurred in one (8%) of 12 patients during the first cycle (considered a dose-limiting toxicity), and in one other patient during the second cycle (grade 2). In both cases, the toxicity resolved and treatment continued at a lower dose of albumin-bound paclitaxel, with a dose of 175 mg/m2 in the case of the grade 3 encephalopathy, and to 215 mg/m2 in the case of the grade 2 encephalopathy. Grade 2 peripheral neuropathy was observed in one patient during the third cycle of 260 mg/m2 albumin-bound paclitaxel. No progressive neurological deficits attributed to LIPU-MB were observed. LIPU-MB-based blood-brain barrier opening was most commonly associated with immediate yet transient grade 1-2 headache (12 [71%] of 17 patients). The most common grade 3-4 treatment-emergent adverse events were neutropenia (eight [47%]), leukopenia (five [29%]), and hypertension (five [29%]). No treatment-related deaths occurred during the study. Imaging analysis showed blood-brain barrier opening in the brain regions targeted by LIPU-MB, which diminished over the first 1 h after sonication. Pharmacokinetic analyses showed that LIPU-MB led to increases in the mean brain parenchymal concentrations of albumin-bound paclitaxel (from 0·037 µM [95% CI 0·022-0·063] in non-sonicated brain to 0·139 µM [0·083-0·232] in sonicated brain [3·7-times increase], p<0·0001) and carboplatin (from 0·991 µM [0·562-1·747] in non-sonicated brain to 5·878 µM [3·462-9·980] µM in sonicated brain [5·9-times increase], p=0·0001). INTERPRETATION: LIPU-MB using a skull-implantable ultrasound device transiently opens the blood-brain barrier allowing for safe, repeated penetration of cytotoxic drugs into the brain. This study has prompted a subsequent phase 2 study combining LIPU-MB with albumin-bound paclitaxel plus carboplatin (NCT04528680), which is ongoing. FUNDING: National Institutes of Health and National Cancer Institute, Moceri Family Foundation, and the Panattoni family.

Treatment decision-making among patients with metastatic prostate cancer: Impact of decision locus of control on functional outcomes and decision satisfaction.

BACKGROUND: Shared decision-making (SDM) for metastatic prostate cancer (mPC) engages patients in the decision-making process and may be associated with better outcomes relative to physician- or patient-directed decision-making. We assessed the association between decision locus of control (DLOC) and patient-reported quality of life (QOL), functional outcomes, and decision satisfaction among mPC patients. METHODS: After a clinic visit in which a treatment decision was made (baseline), mPC patients completed DLOC and QOL surveys. QOL was re-assessed at 2- and 4-months post-baseline. Mean scores for each QOL dimension (physical, emotional, cognitive, social, and role functioning) were compared by DLOC group using mixed effects models. Patient preferences for DLOC and provider communication techniques were similarly collected via survey. RESULTS: Median age of participants (N = 101) was 69 years (range: 49-92); most were White (80%) and married (82%). 62% reported using SDM. At baseline, there were no differences in QOL dimensions between DLOC groups. At 4 months, patient-directed (p = 0.01) and SDM (p = 0.03) were associated with better physical functioning than physician-directed decision-making, and there was an indication of potentially greater decision satisfaction among patients who reported patient-directed (p = 0.06) or SDM (p = 0.10). SDM was the most reported preferred DLOC. CONCLUSION: mPC patients reporting SDM had better physical functioning at 4 months than physician- or patient-directed decision-making, suggesting measurable benefit from patient involvement in decision-making. Future investigations of these associations in larger, more diverse populations can further clarify these previously unmeasured benefits of patient engagement in treatment decisions.

Efficacy and safety of sonographer discretion to terminate a venous duplex ultrasound for diagnosis of deep vein thrombosis in coronavirus disease 2019 patients.

OBJECTIVE: Sonographers performing venous duplex ultrasound (VDUS) of patients with coronavirus disease 2019 (COVID-19) have an increased risk of exposure owing to their close contact with these patients for an extended period. The objective of the present study was to evaluate the efficacy of a modified COVID-19 VDUS protocol to reduce sonographer exposure to COVID-19 patients. METHODS: We performed a single-center retrospective review. Patients who had undergone VDUS under the modified COVID-19 protocol between March 1, 2020, and June 30, 2020, with a confirmed or presumed COVID-19 diagnosis at the VDUS were included. The modified COVID-19 protocol was defined as the ability of the sonographer to terminate the examination on detection of an acute deep vein thrombosis (DVT). The primary outcome measures were the number of anatomic deep venous segments recorded by the sonographer, which was used as a surrogate measure for sonographer exposure time, and the number of acute DVTs found on follow-up examinations in segments not visualized at the index VDUS. RESULTS: A total of 160 lower extremity VDUS (LEVDUS) scans and 72 upper extremity VDUS (UEVDUS) scans were performed using the modified COVID-19 protocol. The index VDUS had found an acute DVT for 44 of 160 patients (27.5%) who had undergone LEVDUS and 26 of 72 (36.6%) who had undergone UEVDUS. On follow-up imaging, 7 of 38 LEVDUS scans (17.9%) and 1 of 10 UEVDUS scans (10%) had demonstrated a new acute DVT. Malignancy and surgery 30 days before imaging were significantly associated with acute lower extremity DVT, and mechanical ventilation and extracorporeal membrane oxygenation were associated with acute upper extremity DVT. On the index VDUS, the average was 10.6 of 12 total visualized segments on LEVDUS and 6.4 of 10 total segments on UEVDUS. Of the index VDUS scans, 35.6% of the LEVDUS and 78.6% of the UEVDUS scans had been abbreviated. The index VDUS scans that were positive for acute DVT had had significantly fewer visualized segments for both lower (8.4 vs 11.5; P < .0001) and upper (4.2 vs 7.6) extremities (P < .0001). On the follow-up examinations, only one of eight new acute DVTs had been found in a patient whose index VDUS had been abbreviated and the corresponding segment not assessed. These findings did not affect the patient's clinical course. CONCLUSIONS: The modified COVID-19 VDUS protocol reduced sonographers' potential exposure time to COVID-19. Additionally, the clinical efficacy was maintained, with no missed DVTs, despite the abbreviation of the VDUS examinations.

Therapy-related myeloid neoplasms with normal karyotype show distinct genomic and clinical characteristics compared to their counterparts with abnormal karyotype.

Therapy-related myeloid neoplasms (t-MNs) are a complication of treatment with cytotoxic chemotherapy and/or radiation therapy. The majority of t-MNs show chromosomal abnormalities associated with myelodysplastic syndrome (MDS) or KMT2A rearrangements and are characterized by poor clinical outcomes. A small but substantial subset of patients have normal karyotype (NK) and their clinical characteristics and mutational profiles are not well studied. We retrospectively studied patients diagnosed with t-MN at three institutions and compared the mutational profile and survival data between t-MNs with NK and t-MNs with abnormal karyotype (AK). A total of 204 patients with t-MN were identified including 158 with AK and 46 with NK. NK t-MNs, compared to AK, were enriched for mutations in TET2 (p < 0.0001), NPM1 (p < 0.0001), ASXL1 (p = 0.0003), SRSF2 (p < 0.0001), RUNX1 (p = 0.0336) and STAG2 (p = 0.0099) and showed a significantly lower frequency of TP53 mutations (p < 0.0001). Overall survival (OS) was significantly lower in AK t-MNs as compared to NK cases (p = 0.0094). In our study, NK t-MNs showed a significantly better OS, a higher prevalence of MN-associated mutations and a lower frequency of TP53 mutations compared to their AK counterparts. The distinct clinical and mutational profile of NK t-MNs merits a separate classification.

Treatment Decision-Making in Metastatic Prostate Cancer: Perceptions of Locus of Control Among Patient, Caregiver, and Physician Triads.

BACKGROUND: Multiple treatments for metastatic prostate cancer have similar efficacy, leaving patients with complicated treatment choices. Shared decision-making can facilitate difficult treatment decisions, but the extent to which this is used for metastatic prostate cancer is unknown. We assessed patient, caregiver, and physician perceptions of decision locus of control (shared decision-making vs physician- or patient-directed decisions) and the degree of agreement between groups. METHODS: Triads of patients, caregivers, and physicians completed surveys of decision-making practices after a clinic visit in which a decision occurred. To evaluate the degree of agreement for decision locus of control, we used the quadratic-weighted kappa coefficient (κ). We used relative frequencies to evaluate which knowledge learned and treatment factors were most strongly endorsed by patients as informing and influencing their treatment decision-making, respectively. RESULTS: Fifty triads participated, with median patient age of 72 years. A majority of patients, caregivers, and physicians reported shared decision-making (66%, 56%, and 52%, respectively). Patients and physicians demonstrated minimal agreement about decision locus of control (44%, κ=0.35 [SD = 0.52]), but caregiver reports were not statistically significantly associated with physician and patient reports (38%, κ=0.23, [SD = 0.28]), p=0.055; 44%, κ=0.34 [SD = 1.98], p=0.14). Treatment efficacy was the most common patient-reported factor influencing treatment decisions (44%). CONCLUSION: This study characterized metastatic prostate cancer patients', caregivers', and physicians' experiences and communication preferences for treatment decision-making. Patients and physicians had greater agreement in decision locus of control compared with caregivers, yet patient-physician agreement was minimal. Metastatic prostate cancer patients report being influenced by information about treatment efficacy and clear next steps, and a desire for patient-friendly language and an invitation to be as involved in decision making at their preferred level. Emphasizing these may increase agreement in decision locus of control between all participants in the decision-making process.

TRUE-Bolivia: Trauma Responders Unifying to Empower Communities in Santa Cruz, Bolivia.

BACKGROUND: The aim of this study is to assess the efficacy of the TRUE-Bolivia (Trauma Responders Unifying to Empower Communities Bolivia) trauma first responder course at improving participant confidence in first responder abilities and increasing knowledge of trauma response skills. METHODS: Participants attended the 4-h TRUE-Bolivia course at the municipal department of urban transportation and universities and medical schools in Santa Cruz, Bolivia and completed a demographic survey and pre- and post-course knowledge assessments. All participants who attended the full course and completed both knowledge assessments were included in the study, with 453 people attending at least one portion of the course and 329 completing the full course and assessments. RESULTS: A majority of participants were men, had completed high school or attended university, and worked or trained in the fields of transportation or medicine. Participant ratings of confidence on a 5-point Likert scale improved from a median of 3 (interquartile range [IQR] 2) before the course to 5 (IQR 1) after the course (P < 0.01). The median number of correct answers on the pre-course nine-question knowledge assessment was 3 (IQR 3), improving to 7 (IQR 3) on the post-course assessment (P < 0.01). All demographic groups demonstrated improvements in scores from the pre- to post-test. Female gender, higher education level, a background in medicine, and prior training in first aid were associated with higher pre- and post-test scores. CONCLUSIONS: The TRUE-Bolivia course increased knowledge of first responder skills and improved confidence in these abilities in participants from a variety of backgrounds. Further study is needed to determine the long-term skill utilization by participants and the course's impact on local trauma morbidity and mortality.

Real-world application of autologous hematopoietic stem cell transplantation in 507 patients with multiple sclerosis.

OBJECTIVE: To investigate the results of real-world application of non-myeloablative autologous HSCT for multiple sclerosis (MS). METHODS: Between July 2003 and October 2019 at a single center (Northwestern University), 414 patients with relapsing remitting MS (RRMS) and 93 patients with newly diagnosed secondary progressive MS (SPMS) underwent non-myeloablative HSCT. RESULTS: There was one treatment-related death (0.19%) due to hospital-acquired legionella pneumonia, and one patient developed neutropenic bacteremia (Klebsiella pneumonia) without sepsis. Overall 5-year survival was 98.8%. Post HSCT secondary autoimmune diseases (2nd ADs) were idiopathic thrombocytopenia (ITP) and hypo or hyperthyroidism. ITP was highest with alemtuzumab (14%) and 0 to 2.8% for the non-alemtuzumab regimens. After HSCT, 16 patients developed hypothyroidism (3.5%) and 15 developed hyperthyroidism / Grave's disease (3.3%). Relapse free survival (RFS) at 5 years for RRMS and SPMS was 80.1% and 98.1%, respectively, while progression free survival (PFS) at 4 years for RRMS and SPMS was 95% versus 66%, respectively. For patients with RRMS, the EDSS significantly improved (p < 0.0001) at each follow-up from a pre-HSCT mean of 3.87 to 2.51, 2.50, 2.41, 2.33, and 2.19 at 1, 2, 3, 4, and 5 years, respectively. For SPMS, the EDSS improved significantly only at 1 year but not thereafter. For SPMS, the mean baseline EDSS of 5.09 changed post-HSCT to 4.85 (p = 0.04), 4.88 (p = 0.2), 4.92 (p = .27), 4.72 (p = 0.07), and 4.2 (p = 0.21) at 1, 2, 3, 4, 5 years, respectively. CONCLUSION: In patients with RRMS, autologous non-myeloablative HSCT is an effective one-time therapy, while HSCT appears of less benefit for newly diagnosed SPMS.

Direct oral anticoagulants decrease treatment failure for acute lower extremity deep venous thrombosis.

OBJECTIVE: Optimal medical therapy for acute lower extremity deep venous thrombosis (DVT) remains an enigma. While clinical trials demonstrate non-inferiority with an oral anti-Xa inhibitor, or direct oral anticoagulant (DOAC), versus combined low-molecular weight heparin (LMWH) and oral vitamin K antagonist (VKA), the most effective regimen remains to be determined. METHODS: This study is a single-center retrospective cohort study from October 2014 to December 2015 of patients with a diagnosis of acute DVT and subsequent serial lower extremity venous duplex. Demographics, medical history, medications, serial ultrasound findings, as well as the primary anticoagulant used for treatment were collected and analyzed by two independent data extractors. Treatment failure was defined as any new DVT or progression of an existing DVT within 3 months of diagnosis of the index clot. Risk factors for treatment failure were assessed using standard odds ratios and Fischer's exact test. RESULTS: Among 496 patients with an acute lower extremity DVT, 54% (n = 266) were men, mean age was 61 years, 35% (n = 174) involved the popliteal or more proximal segments, and 442 had documentation of the primary treatment for DVT: 20% (n = 90) received nothing; 20% (n = 92) received an oral VKA; 34% (n = 149) received a DOAC; 20% (n = 90) received LMWH; and 5% (n = 21) received another class of anticoagulant. Within 3 months, 21% (n=89 out of 427) had treatment failure defined as any new DVT or progression of prior DVT. Patients treated with a DOAC were less likely to experience treatment failure when compared with any other treatment (odds ratio 0.43; 95% confidence intervals [0.23, 0.79]; p = 0.0069) and when compared with traditional oral VKA (OR 0.44; 95% CI [0.21, 0.92]; p = 0.029). None of prior history of DVT, pulmonary embolism, thrombophilia, renal insufficiency, hepatic insufficiency, cancer, or antiplatelet therapy correlated with treatment failure. Treatment outcome did not correlate with being on any anticoagulation versus none (p = 0.74), nor did it correlate with the duration of treatment (<3 months versus ≥3 months) (p = 0.42). Proximal and distal DVTs showed no difference in treatment failure (19% versus 22%, respectively; p = 0.43). CONCLUSION: In summary, the use of a DOAC for acute lower extremity DVT yielded better overall outcomes and fewer treatment failures at 3 months as compared to traditional oral VKA therapy based on serial duplex imaging.

Association between quality of life and patient-reported complications from surgery and radioiodine in early-stage thyroid cancer survivors: A matched-pair analysis.

BACKGROUND: Remnant radioiodine ablation is discouraged in low-risk differentiated thyroid cancer because it confers no survival advantage. The impact of remnant radioiodine ablation on health-related quality of life in these patients is not well described. We hypothesized remnant radioiodine ablation is associated with lower health-related quality of life in early-stage differentiated thyroid cancer survivors. METHODS: A retrospective matched-pair analysis was conducted in stage I differentiated thyroid cancer survivors recruited from a thyroid cancer support group. Respondents self-reported via online survey. Dysphonia and dysphagia were reported via Likert scale. Health-related quality of life was evaluated using Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item profile. Respondents who received remnant radioiodine ablation were matched for age, sex, race, and years since diagnosis with respondents who did not receive remnant radioiodine ablation. PROMIS t-scores were compared between remnant radioiodine ablation and nonremnant radioiodine ablation groups, and among those with or without surgical complications. RESULTS: One hundred and twenty-two pairs were matched. There was no significant difference in incidence of self-reported hypocalcemia, infection, dysphonia, or dysphagia between remnant radioiodine ablation and no remnant radioiodine ablation groups. There was no significant difference in mean PROMIS t-scores. Of respondents reporting normal preoperative voice and swallowing, there were no significant differences in postprocedural outcomes or PROMIS scores. Regardless of remnant radioiodine ablation treatment, those with surgical complications of hypocalcemia, dysphonia, or dysphagia reported worse PROMIS scores across multiple domains. Remnant radioiodine ablation-associated xerostomia was associated with worse PROMIS scores across multiple domains. CONCLUSION: This is the first study to use PROMIS measures to evaluate the association between remnant radioiodine ablation and health-related quality of life in early-stage differentiated thyroid cancer survivors treated surgically. Surgical and remnant radioiodine ablation-associated complications were associated with significantly worse PROMIS scores across multiple domains.

Cardiac safe hematopoietic stem cell transplantation for systemic sclerosis with poor cardiac function: a pilot safety study that decreases neutropenic interval to 5 days.

We compared three fludarabine-based regimens for systemic sclerosis patients with a high-risk cardiac phenotype that according to EBMT criteria would be a contraindication for a high-dose cyclophosphamide (200 mg/kg) transplant regimen. All three regimens included fludarabine, ATG, and cyclophosphamide (60 mg/kg), while two regimens also included rituximab with or without IVIG. Treatment related mortality (TRM) was 2.4%. The mean number of days of neutropenia (ANC < 500) was 5.2, the mean number of platelet and red blood cell transfusions was 0.3 and 1.85, respectively. Skin score, forced vital capacity (FVC), and total lung capacity (TLC) improved with all three regimens. For patients whose regimen did not include rituximab versus those that included rituximab, 1-year overall relapse rate was higher 36% (5/14) versus 3.6% (1 of 28) (p = 0.01), secondary autoimmune diseases were higher 21% (3/14) versus 0% (0/28) (p = 0.03), and upper respiratory tract infections were higher 28% (4/14) versus 3.6% (1/28) (p = 0.04). In this safety study, a fludarabine-based regimen was relatively safe with a TRM of 2.4% and a neutropenic interval of only 5.2 days in systemic sclerosis patients with a high-risk cardiac phenotype. The addition of rituximab decreased 1-year relapse rate, risk of late secondary autoimmune diseases, and upper-respiratory tract infections.

The Impact of Perioperative Arterial Infarct on Recurrence, Functional Outcomes, and Survival in Glioblastoma Patients.

Background: Perioperative infarcts are a known complication that can occur during the resection of glioblastoma (GBM). Recent studies suggest that gross total and even "supra-total" resections may be associated with an increased survival but the rate of complications, including perioperative ischemia, may increase with these more aggressive resection strategies. However, little is known about the impact that perioperative infarcts have on survival, functional outcomes, and tumor recurrence patterns. Our study attempted to quantify and characterize the functional consequences of a perioperative infarct, as well as risk factors associated with occurrence. Methods: Seventy-three patients with a diagnosis of GBM and perioperative ischemia by MRI were identified from the electronic medical record system. We obtained demographic, prognostic, and stroke risk factor data. Infarct volumes were calculated from diffusion-weighted MRI scans, and subjects were segregated into an infarct cohort or a control cohort based on whether the identified lesion appeared to be an infarct in an arterial distribution or instead appeared to be expected postoperative changes. A multivariate statistical analysis was performed on the dataset. Results: Median age was 58.6 years, median post-op KPS (Karnofsky Performance Status) was 90, and median extent of resection (based on MRI) was 97.8%. Overall, perioperative arterial infarcts were uncommon (2.0%), did not have a statistically significant impact on survival (17.9 vs. 18.9 months), did not worsen neurologic function, and did not alter the pattern of recurrence. Conclusion: Perioperative arterial infarcts were uncommon in our patients despite aggressive resection and when present had no impact on survival or neurologic function. Given the clear benefit of maximal tumor resection, the risk of perioperative infarct should not deter maximal safe resection.

The Comorbidity-Polypharmacy Score is an Objective and Practical Predictor of Outcomes and Mortality after Vascular Surgery.

BACKGROUND: The comorbidity-polypharmacy score (CPPS) was developed to quantify the severity of comorbidities of patients with geriatric trauma. CPPS is the sum of the number of medications and comorbidities, and is thus objective, user-friendly, and potentially adaptable to many clinical situations. We sought to understand if CPPS associates with outcomes and mortality after common vascular surgery procedures. METHODS: This is a retrospective single-center study. A total of 466 patients who underwent carotid endarterectomy, infrainguinal bypass, percutaneous lower extremity revascularization, or endovascular abdominal aortic aneurysm repair at a single medical center were included. CPPS were classified as mild, moderate, severe, and morbid based on scores of 0-7, 8-15, 15-21, and ≥21, respectively. End points were reinterventions, 30-day readmission, and mortality. We used chi-squared tests to analyze differences in categorical variables; Kruskal-Wallis tests to analyze differences in continuous variables; Kaplan-Meier estimation and Cox proportional hazard modeling to examine survival data; and receiver operator characteristic (ROC) curve analyses to assess sensitivity and specificity. RESULTS: The mean preoperative CPPS was 14.1 ± 6.1. Higher CPPS were associated with longer hospital and postoperative length of stay (P < 0.001). Severe and morbid CPPS categories had higher rates of ICU admission, reintervention, and 30-day readmission which did not reach statistical significance after correction for multiple comparisons. CPPS was independently associated with 1- and 5-year mortality in a multivariable Cox model (hazard ratio = 2.2, 95% confidence interval: 1.3-3.3). ROC analysis revealed C-statistics of 0.81 and 0.72 for 1-year and 5-year all-cause mortality, respectively (P < 0.001). CONCLUSIONS: CPPS is a simple and pragmatic clinical tool for quantifying risk of postoperative outcomes and mortality after common vascular surgery procedures. Further investigation is needed to validate the use of CPPS in enhancing existing predictors of patient outcomes and in serving as an adjunctive tool for determining resource allocation and discharge planning in patients who underwent vascular surgery.