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Background: Computed tomography to body divergence (CTBD) is one of the main barriers to bronchoscopic techniques for the diagnosis of peripherally located lung nodules. Cone-beam CT (CBCT) guidance is being rapidly adopted to correct for this phenomenon and to potentially increase diagnostic outcomes. In this trial, we hypothesized that the addition of mobile CBCT (m-CBCT) could improve the rate of tool in lesion (TIL) and the diagnostic yield of shape-sensing robotic-assisted bronchoscopy (SS-RAB). Methods: This was a prospective, single-arm study, which enrolled patients with peripheral lung nodules of 1–3 cm and compared the rate of TIL and the diagnostic yield of SS-RAB alone and combined with mCBCT. Results: A total of 67 subjects were enrolled, the median nodule size was 1.7 cm (range, 0.9–3 cm). TIL was achieved in 23 patients (34.3%) with SS-RAB alone, and 66 patients (98.6%) with the addition of mCBCT (p < 0.0001). The diagnostic yield of SS-RAB alone was 29.9% (95% CI, 29.3–42.3%) and it was 86.6% (95% CI, 76–93.7%) with the addition of mCBCT (p < 0.0001). There were no pneumothoraxes or any bronchoscopy-related complications, and the median total dose–area product (DAP) was 50.5 Gy-cm2. Conclusions: The addition of mCBCT guidance to SS-RAB allows bronchoscopists to compensate for CTBD, leading to an increase in TIL and diagnostic yield, with acceptable radiation exposure.

ABSTRACTPatients with preexisting autoimmune disease (pAID) are generally excluded from clinical trials for immune checkpoint inhibitors (ICIs) for cancer due to concern of flaring pAID. In this multi-center, retrospective observational study, we compared safety of ICI combination (two ICI agents) versus monotherapy in cancer patients with pAIDs. The primary outcome was time to AEs (immune-related adverse events (irAEs) and/or pAID flares), with progression-free survival (PFS) and overall survival as secondary outcomes. Sixty-four of 133 patients (48%) received ICI combination and 69 (52%) monotherapy. Most had melanoma (32%) and lung cancer (31%). Most common pAIDs were rheumatic (28%) and dermatologic (23%). Over a median follow-up of 15 months (95%CI, 11-18 mo), the cumulative incidence of any-grade irAEs was higher for combination compared to monotherapy (subdistribution hazard ratio (sHR) 2.27, 95%CI 1.35–3.82). No statistically significant difference was observed in high-grade irAEs (sHR 2.31 (0.95–5.66), P = .054) or the cumulative incidence of pAID flares. There was no statistically significant difference for melanoma PFS between combination versus monotherapy (23.2 vs. 17.1mo, P = .53). The combination group was more likely to discontinue or hold ICI, but > 50% of the combination group was still able to continue ICI therapy. No treatment-related deaths occurred. In our cohort with pAIDs, patients had a tolerable toxicity profile with ICI combination therapy. Our results support the use of ICI combination if deemed necessary for cancer therapy in patients with pAIDs, since the ICI toxicities were comparable to monotherapy, able to be effectively managed and mostly did not require ICI interruption.

Abstract Background Oral mucositis (OM) in patients receiving cancer therapy is thus far not well managed with standard approaches. We aimed to assess the safety and effectiveness of methylene blue (MB) oral rinse for OM pain in patients receiving cancer therapy. Methods In this randomized, single-blind phase 2 clinical trial, patients were randomized to one of four arms: MB 0.025%+conventional therapy (CTx) (n = 15), MB 0.05%+CTx (n = 14), MB 0.1%+CTx (n = 15), or CTx alone (n = 16). Intervention groups received MB oral rinse every 6 h for 2 days with outcomes measured at days 1–2; safety was evaluated up to 30 days. The primary outcome measured change in the pain numeric rating scale (0–10) from baseline to day 2. Secondary outcome measured change in oral function burden scores from baseline to day 2, World Health Organization OM grades, morphine equivalent daily doses, and adverse events. The trial was registered with ClinicalTrials.gov ID: NCT03469284. Results Sixty patients (mean age 43, range 22–62 years) completed the study. Compared with those who received CTx alone, those who received MB had a significant reduction of pain scores at day 2 of treatment (mean ± SD); 0.025%: 5.2 ± 2.9, 0.05%: 4.5 ± 2.9, 0.1%: 5.15 ± 2.6) and reduction of oral function burden scores (0.025%: 2.5 ± 1.55, 0.05%: 2.8 ± 1.7, 0.1%: 2.9 ± 1.60). No serious adverse events were noted, but eight patients reported burning sensation of the oral cavity with the first dose, and this caused one patient to discontinue therapy. Conclusions MB oral rinse showed significant pain reduction and improved oral functioning with minimal adverse effects. Trial registration ClinicalTrials.gov ID: NCT03469284.

Background Up to 20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), for which the current standard of care is radiation therapy with or without surgery. There are no prospective data on the safety of stereotactic radiosurgery (SRS) concurrent with immune checkpoint inhibitor therapy for BM. This is the safety cohort of the phase I/II investigator-initiated trial of SRS with nivolumab and ipilimumab for patients with BM from NSCLC.Patients and methods This single-institution study included patients with NSCLC with active BM amenable to SRS. Brain SRS and systemic therapy with nivolumab and ipilimumab were delivered concurrently (within 7 days). The endpoints were safety and 4-month intracranial progression-free survival (PFS).Results Thirteen patients were enrolled in the safety cohort, 10 of whom were evaluable for dose-limiting toxicities (DLTs). Median follow-up was 23 months (range 9.7–24.3 months). The median interval between systemic therapy and radiation therapy was 3 days. Only one patient had a DLT; hence, predefined stopping criteria were not met. In addition to the patient with DLT, three patients had treatment-related grade ≥3 adverse events, including elevated liver function tests, fatigue, nausea, adrenal insufficiency, and myocarditis. One patient had a confirmed influenza infection 7 months after initiation of protocol treatment (outside the DLT assessment window), leading to pneumonia and subsequent death from hemophagocytic lymphohistiocytosis. The estimated 4-month intracranial PFS rate was 70.7%.Conclusion Concurrent brain SRS with nivolumab/ipilimumab was safe for patients with active NSCLC BM. Preliminary analyses of treatment efficacy were encouraging for intracranial treatment response.

Background Management of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) as therapy for irAEs.Methods We performed a retrospective multicenter study evaluating patients diagnosed with de novo irAEs or flare of pre-existing autoimmune disease following ICI and were treated with anti-IL-6R. Our objectives were to assess the improvement of irAEs as well as the overall tumor response rate (ORR) before and after anti-IL-6R treatment.Results We identified a total of 92 patients who received therapeutic anti-IL-6R antibodies (tocilizumab or sarilumab). Median age was 61 years, 63% were men, 69% received anti-programmed cell death protein-1 (PD-1) antibodies alone, and 26% patients were treated with the combination of anti-cytotoxic T lymphocyte antigen-4 and anti-PD-1 antibodies. Cancer types were primarily melanoma (46%), genitourinary cancer (35%), and lung cancer (8%). Indications for using anti-IL-6R antibodies included inflammatory arthritis (73%), hepatitis/cholangitis (7%), myositis/myocarditis/myasthenia gravis (5%), polymyalgia rheumatica (4%), and one patient each with autoimmune scleroderma, nephritis, colitis, pneumonitis and central nervous system vasculitis. Notably, 88% of patients had received corticosteroids, and 36% received other disease-modifying antirheumatic drugs (DMARDs) as first-line therapies, but without adequate improvement. After initiation of anti-IL-6R (as first-line or post-corticosteroids and DMARDs), 73% of patients showed resolution or change to ≤grade 1 of irAEs after a median of 2.0 months from initiation of anti-IL-6R therapy. Six patients (7%) stopped anti-IL-6R due to adverse events. Of 70 evaluable patients by RECIST (Response Evaluation Criteria in Solid Tumors) V.1.1 criteria; the ORR was 66% prior versus 66% after anti-IL-6R (95% CI, 54% to 77%), with 8% higher complete response rate. Of 34 evaluable patients with melanoma, the ORR was 56% prior and increased to 68% after anti-IL-6R (p=0.04).Conclusion Targeting IL-6R could be an effective approach to treat several irAE types without hindering antitumor immunity. This study supports ongoing clinical trials evaluating the safety and efficacy of tocilizumab (anti-IL-6R antibody) in combination with ICIs (NCT04940299, NCT03999749).

Atelectasis during bronchoscopy under general anesthesia is very common and can have a detrimental effect on navigational and diagnostic outcomes. While the intraprocedural incidence and anatomic location have been previously described, the severity of atelectasis has not. We reviewed chest CT images of patients who developed atelectasis in the VESPA trial (Ventilatory Strategy to Prevent Atelectasis). By drawing boundaries at the posterior chest wall (A), the anterior aspect of the vertebral body (C), and mid-way between these two lines (B), we delineated at-risk lung zones 1, 2, and 3 (from posterior to anterior). An Atelectasis Severity Score System (“ASSESS”) was created, classifying atelectasis as “mild” (zone 1), “moderate” (zones 1–2), and “severe” (zones 1–2–3). A total of 43 patients who developed atelectasis were included in this study. A total of 32 patients were in the control arm, and 11 were in the VESPA arm; 20 patients (47%) had mild atelectasis, 20 (47%) had moderate atelectasis, and 3 (6%) had severe atelectasis. A higher BMI was associated with increased odds (1.5 per 1 unit change; 95% CI, 1.10–2.04) (p = 0.0098), and VESPA was associated with decreased odds (0.05; 95% CI, 0.01–0.47) (p = 0.0080) of developing moderate to severe atelectasis. ASSESS is a simple method used to categorize intra-bronchoscopy atelectasis, which allows for a qualitative description of this phenomenon to be developed. In the VESPA trial, a higher BMI was not only associated with increased incidence but also increased severity of atelectasis, while VESPA had the opposite effect. Preventive strategies should be strongly considered in patients with risk factors for atelectasis who have lesions located in zones 1 and 2, but not in zone 3.

IntroductionThis study examined the role of echocardiographic and cardiac histomorphology parameters in predicting mortality in patients with cardiac AL amyloidosis.MethodsPatients with endomyocardial biopsy-proven cardiac AL amyloidosis treated at MD Anderson Cancer Center between 6/2011 and 6/2020 were identified. Stored echocardiographic images and endomyocardial biopsy samples were processed for myocardial strain analysis and a detailed histomorphology characterization.ResultsOf 43 patients; 44% were women and 63% white. Median age was 65 years; 51% underwent stem cell transplantation (SCT). Thirty patients (70%) died during follow up (median follow up: 4.1 years). Lower LA strain (

BackgroundCarcinoid heart disease (CnHD) is a frequent cause of morbidity and mortality in patients with neuroendocrine tumors and carcinoid syndrome. Although valve replacement surgery appears to decrease all-cause mortality in patients with advanced CnHD, few studies have investigated the outcomes of patients after valve replacement.MethodsWe conducted a multi-institution retrospective registry of patients who received both tricuspid and pulmonic bioprosthetic valve (TV/PV) replacements for advanced CnHD from November 2005 to March 2021. Patients were followed post-operatively with echocardiographic studies every 3 months. Carcinoid valvular heart disease scores were used to monitor valve degeneration. Neuroendocrine tumor treatment, their administration times, and associations with echocardiographic findings were recorded.ResultsOf 87 patients with CnHD, 22 patients underwent simultaneous surgical TV and PV replacement. In 6 patients (27.3%), increased PV Vmax was the first echocardiographic manifestation of valve degeneration in the setting of occult neurohormonal release. Post-operative telotristat ethyl and peptide receptor radionuclide therapy appeared to stabilize PV Vmax. The PV Vmax showed consistent elevation in the entire patient population when compared to baseline, while bioprosthetic TV echocardiographic parameters were relatively unchanged throughout. Post-operative warfarin therapy did not affect the rate of PV degeneration, and no major bleeding was recorded during or after post-operative anticoagulation therapy.ConclusionBioprosthetic valve degeneration is common in CnHD. Monitoring with echocardiographic studies every 3 months, focusing on PV velocities, could identify patients with occult disease that very likely promotes valve degeneration. Novel neuroendocrine tumor therapies may have a beneficial impact on valve degeneration.

Inflammatory breast cancer (IBC) is an aggressive form of primary breast cancer characterized by rapid onset and high risk of metastasis and poor clinical outcomes. The biological basis for the aggressiveness of IBC is still not well understood and no IBC‐specific targeted therapies exist. In this study, we report that lipocalin 2 (LCN2), a small secreted glycoprotein belonging to the lipocalin superfamily, is expressed at significantly higher levels in IBC vs non‐IBC tumors, independently of molecular subtype. LCN2 levels were also significantly higher in IBC cell lines and in their culture media than in non‐IBC cell lines. High expression was associated with poor‐prognosis features and shorter overall survival in IBC patients. Depletion of LCN2 in IBC cell lines reduced colony formation, migration, and cancer stem cell populations in vitro and inhibited tumor growth, skin invasion, and brain metastasis in mouse models of IBC. Analysis of our proteomics data showed reduced expression of proteins involved in cell cycle and DNA repair in LCN2‐silenced IBC cells. Our findings support that LCN2 promotes IBC tumor aggressiveness and offer a new potential therapeutic target for IBC.

BackgroundManagement of coronary artery disease (CAD) is unique and challenging in cancer patients. However, little is known about the outcomes of using BMS or DES in these patients. This study aimed to compare the outcomes of percutaneous coronary intervention (PCI) in cancer patients who were treated with bare metal stents (BMS) vs. drug-eluting stents (DES).MethodsWe identified cancer patients who underwent PCI using BMS or DES between 2013 and 2020. Outcomes of interest were overall survival (OS) and the number of revascularizations. The Kaplan–Meier method was used to estimate the survival probability. Multivariate Cox regression models were utilized to compare OS between BMS and DES.ResultsWe included 346 cancer patients who underwent PCI with a median follow-up of 34.1 months (95% CI, 28.4–38.7). Among these, 42 patients were treated with BMS (12.1%) and 304 with DES (87.9%). Age and gender were similar between the BMS and DES groups (p = 0.09 and 0.93, respectively). DES use was more frequent in the white race, while black patients had more BMS (p = 0.03). The use of DES was more common in patients with NSTEMI (p = 0.03). The median survival was 46 months (95% CI, 34–66). There was no significant difference in the number of revascularizations between the BMS and DES groups (p = 0.43). There was no significant difference in OS between the BMS and DES groups in multivariate analysis (p = 0.26). In addition, independent predictors for worse survival included age > 65 years, BMI ≤ 25 g/m2, hemoglobin level ≤ 12 g/dL, and initial presentation with NSTEMI.ConclusionsIn our study, several revascularizations and survival were similar between cancer patients with CAD treated with BMS and DES. This finding suggests that DES use is not associated with an increased risk for stent thrombosis, and as cancer survival improves, there may be a more significant role for DES.

Xiaoding Hu et al. find that expression of the proteoglycan decorin is decreased in patients with inflammatory breast cancer compared to normal breast tissue and some other types of breast cancer. They demonstrate that decorin acts as a tumor suppressor in cancer cells and human xenograft mouse models by destabilizing the E-cadherin-EGFR signaling axis, and their findings suggest potential therapeutic strategies for this aggressive breast cancer.

AimThis study investigated the factors predicting survival and the recurrence of pericardial effusion (PE) requiring pericardiocentesis (PCC) in patients with cancer.Materials and MethodsWe analyzed the data of patients who underwent PCC for large PEs from 2010 to 2020 at The University of Texas MD Anderson Cancer Center. The time to the first recurrent PE requiring PCC was the interval from the index PCC with pericardial drain placement to first recurrent PE requiring drainage (either repeated PCC or a pericardial window). Univariate and multivariate Fine-Gray models accounting for the competing risk of death were used to identify predictors of recurrent PE requiring drainage. Cox regression models were used to identify predictors of death.ResultsThe study cohort included 418 patients with index PCC and pericardial drain placement, of whom 65 (16%) had recurrent PEs requiring drainage. The cumulative incidences of recurrent PE requiring drainage at 12 and 60 months were 15.0% and 15.6%, respectively. Younger age, anti-inflammatory medication use, and solid tumors were associated with an increased risk of recurrence of PE requiring drainage, and that echocardiographic evidence of tamponade at presentation and receipt of immunotherapy were associated with a decreased risk of recurrence. Factors predicting poor survival included older age, malignant effusion on cytology, non-use of anti-inflammatory agents, non-lymphoma cancers and primary lung cancer.ConclusionAmong cancer patients with large PEs requiring drainage, young patients with solid tumors were more likely to experience recurrence, while elderly patients and those with lung cancer, malignant PE cytology, and non-use of anti-inflammatory agents showed worse survival.

Objectives: To assess the clinical impact of Cardiovascular Magnetic Resonance (CMR) in clinical decision making of cancer patients with a suspected cardiomyopathy in a tertiary cancer center.Background: Cardiomyopathies of diverse etiologies are frequently encountered in a Cardio-Oncology practice. The clinical impact of CMR after a presumptive diagnosis of cardiomyopathy has not been studied in cancer patients.Methods: We reviewed data on cancer patients with presumptive diagnosis of cardiomyopathy who underwent CMR in a tertiary cancer center. The clinical impact of CMR was defined as either change in clinical diagnosis or management post CMR results. Univariate and multivariate logistic regression models were used to assess whether any of the baseline characteristics were predictive of the clinical impact of CMR.Results: A total of 110 consecutive patients were identified. Clinical impact of CMR was seen in 68 (62%) patients. Change in the clinical diagnosis and management was seen in 56 (51%) and 41 (37%) of patients, respectively. The most common change was prevention of endomyocardial biopsy in 26 patients (24%). Overall, patients with higher left ventricular ejection fraction (LVEF) by echocardiography (echo), clinical impact was influenced more by CMR (LVEF of 37.2 ± 12.3% vs. 51.5 ± 11.6%, p < 0.001). Cancer diagnosis of multiple myeloma was associated with change in the management post CMR (adjusted OR of 25.6, 95% CI 4.0–162.4, p = 0.001). Suspicion of infiltrative cardiomyopathy was associated with a higher likelihood of change in diagnosis. Having an LVEF≥40 by echo was associated with change in diagnosis and management by CMR.Conclusions: Utilization of CMR has a significant clinical impact in cancer patients with suspected cardiomyopathy. Patients with cancer diagnosis of multiple myeloma, suspicion of infiltrative cardiomyopathy and those with higher LVEF by echo seem to benefit more from CMR.

Background Infective endocarditis (IE) is more common in patients with cancer as compared with the general population. Due to an immunocompromised state, the need for invasive procedures, hypercoagulability and the presence of indwelling catheters, patients with cancer are particularly predisposed to the development of IE.Objectives Limited information exists about IE in patients with cancer. We aimed to evaluate the characteristics of patients with cancer and IE at our tertiary care centre, including a comparison of the microorganisms implicated and their association with mortality.Methods A retrospective chart review of patients with cancer who had echocardiography for suspicion of endocarditis was conducted. A total of 56 patients with a confirmed diagnosis of cancer and endocarditis, based on the modified Duke criteria, were included in the study. Baseline demographics, risk factors for developing IE, echocardiography findings, microbiology and mortality data were analysed.Results Following the findings of vegetations by echocardiography, the median survival time was 8.5 months. Staphylococcus aureus was the most common organism identified as causing endocarditis. The mitral and aortic valves were the most commonly involved sites of endocarditis. Patients with S. aureus endocarditis (SAE) had a significantly poorer survival when compared with patients without SAE (p=0.0217) over the 12-month period from diagnosis of endocarditis.Conclusions Overall survival of patients with cancer and endocarditis is poor, with a worse outcome in patients with SAE.

Background: Patients with previously irradiated metastatic epidural spinal cord compression (MESCC) who are not surgical candidates are at high risk of neurologic deterioration due to disease in the setting of limited treatment options. We seek to establish the feasibility of using salvage spine stereotactic radiosurgery (SSRS) allowing for spinal cord dose constraint relaxation as the primary management of MESCC in inoperable patients monitoring for radiation related toxicity and radiographic local control (LC). Methods: Inoperable patients with previously irradiated MESCC were enrolled on this prospective Phase 1 single institution protocol. Single fraction SSRS was delivered to a prescription dose of 18 Gy. Spinal cord constraint relaxation was performed incrementally from an initial allowable Dmax cohort of 8 Gy to 14 Gy in the final planned cohort. Patients were monitored every 3 months with follow-up visits and MRI scans. Results: The trial was closed early due to slow accrual. From 2011 to 2014, 11 patients were enrolled of which 9 patients received SSRS. Five patients were in the 8 Gy cord Dmax cohort and 4 in the 10 Gy cord Dmax cohort.The median overall survival (OS) was 11.9 months (95% CI 7.1, 22 months). Of the 9 patients treated with SSRS, 1 died prior to post-SSRS evaluation. Of the remaining 8 patients, 5 experienced a local failure. Three of the five were treated with surgery while two received systemic therapy. Two of the five failures ultimately resulted in loss of neurologic function. The median LC was 9.1 months (95%CI 4.8, 20.1 months). With a median clinical follow-up of 6.8 months, there were no cases of RM. Conclusions: Despite the limited life expectancy in this high-risk cohort of patients, strategies to optimize LC are necessary to prevent neurologic deterioration. Larger prospective trials exploring optimal dose/fractionation and cord constraints are required.

Abstract Background Frailty is a syndrome characterized by weakness, slow gait, weight loss, exhaustion, and low activity. We sought to determine whether frailty was associated with age or stage in newly diagnosed patients with pancreatic ductal adenocarcinoma (PDAC), and determine its association with survival. Methods Consecutive patients with newly diagnosed PDAC of all stages underwent baseline assessment. Frailty (per Fried criteria) was defined as having three or more abnormalities in: grip strength, gait speed, weight loss, self‐reported exhaustion, or self‐reported physical activity. Baseline clinicodemographic characteristics, anatomic stage, performance status, and laboratory markers of prognosis were included. The association between baseline characteristics, frailty, and survival was determined. The associations of individual frailty measures with age, stage, comorbidities, and performance status were examined. Body composition was measured from computed tomographic images using SliceOMatic software. Results Of 150 patients enrolled, 8 were excluded because they did not have PDAC on final diagnosis. The median age was 65 years (range, 32‐89). Seventy‐nine patients (55.6%) were sarcopenic, and 36 (25.4%) were frail. Frailty was associated with increasing comorbidities (P = 0.03) and worse performance status (P

Abstract Background Fatigue is distressing and affects quality of life (QoL) among patients with myelodysplastic syndrome (MDS), aplastic anemia (AA), and paroxysmal nocturnal hemoglobinuria (PNH). Limited data exist on the impact of fatigue, QoL, and related symptoms in these patients. Objective Prospectively assess fatigue (functional assessment of cancer therapy‐anemia [FACT‐An]); QoL (FACT‐An subscales); pain (brief pain inventory); and depression, anxiety, and stress (depression anxiety stress scale‐21) and strategies used to manage these symptoms in patients with MDS, AA, and PNH. Methods Surveys were administered via the AA and MDS International Foundation website and database from October 2014 through April 2015 in a cross‐sectional study. Results were summarized using descriptive statistics. Results Of 303 patients, 145 (48%) had MDS, 84 (28%) had AA, and 74 (24%) had PNH; 31 (10%) had >1 diagnosis. The mean age was 57 years, 200 (66%) were female, and 195 (92%) were white. The mean fatigue scores were 25 (range 1‐52) for the whole cohort, 28 for AA, 25 for MDS, and 24 for PNH (P = 0.117); these are all considered severe level. The mean QoL score was 68 (range 10‐104) for the whole cohort, 67 for AA, 69 for MDS, and 67 for PNH (P = 0.821). The ranges for stress were normal; pain and depression, mild; and anxiety, moderate. The most common management strategies perceived as helpful for fatigue in the past month were preserving energy, physical activity, and naps. Conclusions Many patients with MDS, AA, and PNH report severe fatigue. The helpfulness of fatigue management strategies may impact patients’ continued use; whether these strategies are beneficial and decrease fatigue levels needs more study.

Background and Objectives: Cancer and coronary artery disease (CAD) often coexist. Compared to quantitative coronary angiography (QCA), fractional flow reserve (FFR) has emerged as a more reliable method of identifying significant coronary stenoses. We aimed to assess the specific management, safety and outcomes of FFR-guided percutaneous coronary intervention (PCI) in cancer patients with stable CAD. Materials and Methods: FFR was used to assess cancer patients that underwent coronary angiography for stable CAD between September 2008 and May 2016, and were found to have ≥50% stenosis by QCA. Patients with lesions with an FFR > 0.75 received medical therapy alone, while those with FFR ≤ 0.75 were revascularized. Procedure-related complications, all-cause mortality, nonfatal myocardial infarction, or urgent revascularizations were analyzed. Results: Fifty-seven patients with stable CAD underwent FFR on 57 lesions. Out of 31 patients with ≥70% stenosis as measured by QCA, 14 (45.1%) had an FFR ≥ 0.75 and lesions were reclassified as moderate and did not receive PCI nor DAPT. Out of 26 patients with p = 0.03). Conclusions: Further studies are needed to define the optimal therapeutic approach for cancer patients with CAD. Using an FFR cut-off point of 0.75 to guide PCI translates into fewer interventions and can facilitate cancer care. There was an overall reduction in mortality in patients that received a stent, suggesting increased resilience to cancer therapy and progression.

Background: Pericardiocentesis is an important diagnostic and therapeutic tool for cancer-associated pericardial effusion. Limited safety and outcomes data exists regarding the management of malignancy-related pericardial effusion in patients with thrombocytopenia.Objectives: Our study aimed to analyze prognostic factors and overall survival (OS) after pericardiocentesis in thrombocytopenic cancer patients.Methods and Results: A retrospective review of 136 thrombocytopenic cancer patients who underwent primary percutaneous pericardiocentesis was performed. Degree of thrombocytopenia was classified by platelet count recorded on day of pericardiocentesis: 75–149 × 103 cells/μL (41%); 50–74 × 103 cells/μL (10%); 25–49 × 103 cells/μL (24%);

BackgroundCOVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP.Patients and MethodsPatients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed.ResultsCCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex.ConclusionsCommon cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.

Patients with cancer and aortic stenosis (AS) are exposed to several factors that could accelerate the progression of AS. This study aimed to determine the cumulative incidence of AS progression and associated factors in these patients. This retrospective cohort study included patients with cancer, mild or moderate AS and at least two echocardiograms 6 months apart between 1996 and 2016 at MD Anderson Cancer Center. AS progression was defined by an increase in mean gradient of 20 mmHg or peak velocity of 2 m/s by spectral Doppler echocardiography or as requiring aortic valve replacement. Univariate and multivariable Fine-Gray models to account for the competing risk of death were used. One hundred and two patients were included and median follow-up was 7.3 years. Overall, 30 patients (29%) developed AS progression, while 48 (47%) died without it. Yearly rate of mean gradient change was 4.9 ± 3.9 mmHg and yearly rate of peak velocity change was 0.23 ± 0.29 m/s for patients who developed AS progression. In the univariate analysis, coronary artery disease (CAD), dyspnea, prevalent cyclophosphamide and beta-blocker use were associated with AS progression. In multivariable analysis, CAD and prevalent cyclophosphamide use for the time interval of more than 3 years of follow-up remained significantly associated with increased cumulative incidence of AS progression. In conclusion, patients with mild or moderate AS and cancer are more likely to die before having AS progression. AS progression is associated with CAD and prevalent cyclophosphamide use.

BACKGROUND:Radiologic severity may predict adverse outcomes after lower respiratory tract infection (LRI). However, few studies have quantified radiologic severity of LRIs. We sought to evaluate whether a semi-quantitative scoring tool, the Radiologic Severity Index (RSI), predicted mortality after parainfluenza virus (PIV)-associated LRI. METHODS:We conducted a retrospective review of consecutively-enrolled adult patients with hematologic malignancy or hematopoietic stem cell transplantation and with PIV detected in nasal wash who subsequently developed radiologically-confirmed LRI. We measured RSI (range 0-72) in each chest radiograph during the first 30 days after LRI diagnosis. We used extended Cox proportional hazards models to identify factors associated with mortality after onset of LRI with all-cause mortality as our failure event. RESULTS:After adjustment for patient characteristics, each 1-point increase in RSI was associated with an increased hazard of death (HR 1.13, 95% confidence interval [CI] 1.05-1.21, p = 0.0008). Baseline RSI was not predictive of death, but both peak RSI and the change from baseline to peak RSI (delta-RSI) predicted mortality (odds ratio for mortality, peak: 1.11 [95%CI 1.04-1.18], delta-RSI: 1.14 [95%CI 1.06-1.22]). A delta-RSI of ≥19.5 was 89% sensitive and 91% specific in predicting 30-day mortality. CONCLUSIONS:We conclude that the RSI offers precise, informative and reliable assessments of LRI severity. Progression of RSI predicts 30-day mortality after LRI, but baseline RSI does not. Our results were derived from a cohort of patients with PIV-associated LRI, but can be applied in validated in other populations of patients with LRI.

Inflammatory breast cancer (IBC) is an aggressive form of primary breast cancer characterized by rapid onset and high risk of metastasis and poor clinical outcomes. The biological basis for the aggressiveness of IBC is still not well understood and no IBC-specific targeted therapies exist. In this study, we report that lipocalin 2 (LCN2), a small secreted glycoprotein belonging to the lipocalin superfamily, is expressed at significantly higher levels in IBC vs non-IBC tumors, independently of molecular subtype. LCN2 levels were also significantly higher in IBC cell lines and in their culture media than in non-IBC cell lines. High expression was associated with poor-prognosis features and shorter overall survival in IBC patients. Depletion of LCN2 in IBC cell lines reduced colony formation, migration, and cancer stem cell populations in vitro and inhibited tumor growth, skin invasion, and brain metastasis in mouse models of IBC. Analysis of our proteomics data showed reduced expression of proteins involved in cell cycle and DNA repair in LCN2-silenced IBC cells. Our findings support that LCN2 promotes IBC tumor aggressiveness and offer a new potential therapeutic target for IBC. [ABSTRACT FROM AUTHOR]

Rationale: When stereotactic ablative radiotherapy is an option for patients with non-small cell lung cancer (NSCLC), distinguishing between N0, N1, and N2 or N3 (N2j3) disease is important. Objectives: To develop a prediction model for estimating the probability of N0, N1, and N2j3 disease. Methods: Consecutive patients with clinical-radiographic stage T1 to T3, N0 to N3, and M0 NSCLC who underwent endobronchial ultrasound-guided staging from a single center were included. Multivariate ordinal logistic regression analysis was used to predict the presence of N0, N1, or N2j3 disease. Temporal validation used consecutive patients from 3 years later at the same center. External validation used three other hospitals. Measurements and Main Results: In the model development cohort (n = 633), younger age, central location, adenocarcinoma, and higher positron emission tomography-computed tomography nodal stage were associated with a higher probability of having advanced nodal disease. Areas under the receiver operating characteristic curve (AUCs)were 0.84 and 0.86 for predictingN1 or higher (vs. N0) disease and N2j3 (vs.N0 orN1) disease, respectively. Model fit was acceptable (Hosmer-Lemeshow, P = 0.960; Brier score, 0.36). In the temporal validation cohort (n = 473), AUCs were 0.86 and 0.88. Model fit was acceptable (Hosmer-Lemeshow, P = 0.172; Brier score, 0.30). In the external validation cohort (n = 722), AUCs were 0.86 and 0.88 but required calibration (Hosmer-Lemeshow, P,0.001; Brier score, 0.38). Calibration using the general calibrationmethod resulted in acceptable model fit (Hosmer-Lemeshow, P = 0.094; Brier score, 0.34). Conclusions: This prediction model can estimate the probability of N0, N1, and N2j3 disease in patients with NSCLC. The model has the potential to facilitate decision-making in patients with NSCLC when stereotactic ablative radiotherapy is an option. [ABSTRACT FROM AUTHOR]

Background: Previous studies have not evaluated the prevalence and specific risk factors for the development of left ventricular (LV) thrombus in patients with severely reduced left ventricular dysfunction due to chemotherapy‐related cardiomyopathy. We sought to evaluate the prevalence and potential markers of LV thrombus in this patient population. Methods: From January 2009 to December 2013, patients with chemotherapy‐related severe LV dysfunction (LV ejection fraction [LVEF] ≤ 30%) identified from MD Anderson Cancer Center database were reviewed. Patient characteristics and echocardiographic parameters were analyzed to determine potential risk factors for LV thrombus. Results: A total of 121 patients met inclusion criteria (age 54.8 ± 15.2 years; female 63.6%; LVEF 26.3 ± 4%). LV thrombus was present in 9 patients (7.4%). Patients with LV thrombus have significantly lower LVEF compared to those without (18.7 ± 3.8% vs 26.9 ± 3.4%, P < .0001). Prevalence of LV thrombus increased as LVEF decreased and was the highest in patients with LVEF < 20%. By univariate analysis, decreased LVEF, particularly LVEF < 20% (OR 36.30, 95% CI 7.35–179.25, P < .0001) and restrictive LV filling pattern (OR 18.13, 95% CI 4.17–78.89, P = .0001) were associated with presence of LV thrombus. Conclusion: In patients with severely reduced LV systolic function due to chemotherapy‐induced cardiomyopathy, LV thrombus was found in 7.4% of subjects. Severely decreased LVEF (<20%) and restrictive LV filling pattern were associated with the presence of LV thrombus. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diaphragm muscle weakness and atrophy are consequences of prolonged mechanical ventilation. Our purpose was to determine whether thickness of the diaphragm (TDI) changes over time after intubation and whether the degree of change affects clinical outcome. METHODS: For this prospective, longitudinal observational study, we identified subjects who required mechanical ventilation and measured their TDI by ultrasonography. TDI was measured at baseline and repeated 72 h later and then weekly until the subject was either liberated from mechanical ventilation, was referred for tracheostomy, or died. The analysis was designed to determine whether baseline TDI and change in TDI affect extubation outcome. RESULTS: Of the 57 subjects who underwent both diaphragm measurements at 72 h, 16 died, 33 were extubated, and 8 underwent tracheostomy. Only 14 subjects received mechanical ventilation for 1 week, and 2 subjects received mechanical ventilation for 2 and 3 weeks. Females had significantly thinner baseline TDI (P = .008). At 72 h, TDI had decreased in 84% of subjects. We found no significant association between the rate of thinning and sex (P = .68), diagnosis of COPD (P = .36), current smoking (P = .85), or pleural effusion (P = .83). Lower baseline TDI was associated with higher likelihood of extubation: 12.5% higher for every 0.01-cm decrease in TDI (hazard ratio 0.875, 95% CI 0.80-0.96, P = .003). For every 0.01-cm decrease in TDI at 72 h, the likelihood of extubation increased by 17% (hazard ratio 0.83, 95% CI 0.70-0.99, P = .041). CONCLUSIONS: Although most of the subjects showed evidence of diaphragm thinning, we were unable to find a correlation with outcome of extubation failure. In fact, the thinner the diaphragm at baseline and the greater the extent of diaphragm thinning at 72 h, the greater the likelihood of extubation. Thickening ratio or other measurement may be a more reliable indicator of diaphragm dysfunction and should be explored. [ABSTRACT FROM AUTHOR]

Rationale: Estimating the probability of finding N2 or N3 (prN2/3) malignant nodal disease on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with non-small cell lung cancer (NSCLC) can facilitate the selection of subsequent management strategies.Objectives: To develop a clinical prediction model for estimating the prN2/3.Methods: We used the AQuIRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) registry to identify patients with NSCLC with clinical radiographic stage T1-3, N0-3, M0 disease that had EBUS-TBNA for staging. The dependent variable was the presence of N2 or N3 disease (vs. N0 or N1) as assessed by EBUS-TBNA. Univariate followed by multivariable logistic regression analysis was used to develop a parsimonious clinical prediction model to estimate prN2/3. External validation was performed using data from three other hospitals.Measurements and Main Results: The model derivation cohort (n = 633) had a 25% prevalence of malignant N2 or N3 disease. Younger age, central location, adenocarcinoma histology, and higher positron emission tomography-computed tomography N stage were associated with a higher prN2/3. Area under the receiver operating characteristic curve was 0.85 (95% confidence interval, 0.82-0.89), model fit was acceptable (Hosmer-Lemeshow, P = 0.62; Brier score, 0.125). We externally validated the model in 722 patients. Area under the receiver operating characteristic curve was 0.88 (95% confidence interval, 0.85-0.90). Calibration using the general calibration model method resulted in acceptable goodness of fit (Hosmer-Lemeshow test, P = 0.54; Brier score, 0.132).Conclusions: Our prediction rule can be used to estimate prN2/3 in patients with NSCLC. The model has the potential to facilitate clinical decision making in the staging of NSCLC. [ABSTRACT FROM AUTHOR]

Background: The goal of this study was to evaluate the effectiveness of the American Orthopaedic Association's Own the Bone secondary fracture prevention program in the United States.Methods: The objective of this quality improvement cohort study was dissemination of Own the Bone and implementation of secondary prevention (osteoporosis pharmacologic and bone mineral density [BMD] test recommendations). The main outcome measures were the number of sites implementing Own the Bone and implementation of secondary prevention, i.e., orders for BMD testing and/or pharmacologic treatment. The 177 sites participating in the program were academic and community hospitals, orthopaedic surgery groups, and a health system; data were obtained from the first 125 sites utilizing its registry, between January 1, 2010, and March 31, 2015. It included all patients, aged 50 years or older, presenting with fragility fractures (n = 23,132) who were enrolled in the Own the Bone web-based registry. The interventions were education, development of program elements, dissemination, implementation, and evaluation of the Own the Bone program at participating sites.Results: A growing number of institutions implemented Own the Bone (14 sites in 2005-2006 to 177 sites in 2015). After consultation, 53% of patients had a BMD test ordered and/or pharmacologic therapy for osteoporosis.Conclusions: The Own the Bone intervention has succeeded in improving the behaviors of medical professionals in the areas of osteoporosis treatment and counseling, BMD testing, initiation of pharmacotherapy, and coordination of care for patients who have experienced a fragility fracture. [ABSTRACT FROM AUTHOR]

Background: Advances in treatment of sarcoma patients has prolonged survival but has led to increased disease- or treatment-related complications resulting in greater number of admissions to the intensive care unit (ICU). Survival and long-term outcome information about such critically ill patients with sarcoma is unknown. Methods: The primary objective of the study was to determine the ICU and post-ICU survival rates of critically ill sarcoma patients. Secondary objectives included determining the modifiable and non-modifiable predictors of poor survival. We performed a retrospective chart review of sarcoma patients admitted to the ICU at The University of Texas MD Anderson Cancer Center between January 1, 2005, and December 31, 2012. Main outcome measures were ICU mortality, in-hospital mortality and 1, 2, and 6-month survival rates. Covariates such as histological diagnosis, disease characteristics, chemotherapy use, Charlson comorbidity index, Sequential Organ Failure Assessment (SOFA) scores, and clinical findings leading to ICU admission were analyzed for their effects on survival. Results: We identified 172 admissions over the 8-year study period hat met our inclusion criteria. The study population was 45.9% males with a median age of 52 years. The most common sarcoma subgroups were high-grade unclassified sarcoma (25%) and bone tumors (17.4%). The ICU mortality rate was 23.3% (95% confidence interval [CI], 16.9-29.6%), and an additional 6.4% of patients died before hospital discharge (95% CI, 22.9-37.1%). 6-month OS rates were 41%. The median SOFA scores on admission were 6 (inter quartile range (IQR), 3.5-9) in ICU survivors and 10 (IQR, 6.5-14) in ICU non-survivors. Increase in SOFA scores ≥6 led to poor outcomes (ICU survival 13.3%, OS 6.7%). Charlson comorbidity index (HR 1.139, 95% CI 1.023-1.268, p = 0.02) and discharge SOFA scores (HR 1.210, 95% CI 1.141-1.283, p < 0.0001) correlated with overall survival. Conclusions: Our results suggest that patients that are admitted to the ICU for respiratory failure, cardiac arrest, septic shock, acute renal failure or acidosis and also have a high SOFA score with subsequent worsening in the ICU have poor prognosis. Based on the retrospective data which needs further validation we can recommend that judicious approach should be taken in patients with predictors of poor survival before subjecting them to aggressive treatment. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the effects of pre-reducing Sb-doped SnO2 (ATO) electrodes in viologen-anchored TiO2 (VTO) nanostructure-based electrochromic devices. We find that by pre-reducing an ATO electrode, the operating voltage of a VTO nanostructure-based electrochromic device can be lowered; consequently, such a device can be operated more stably with less hysteresis. Further, we find that a pre-reduction of the ATO electrode does not affect the coloration efficiency of such a device. The aforementioned effects of a pre-reduction are attributed to the fact that a pre-reduced ATO electrode is more compatible with a VTO nanostructure-based electrochromic device than a non-pre-reduced ATO electrode, because of the initial oxidized state of the other electrode of the device, that is, a VTO nanostructure- based electrode. The oxidation state of a pre-reduced ATO electrode plays a very important role in the operation of a VTO nanostructure-based electrochromic device because it strongly influences charge movement during electrochromic switching. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection can be reactivated during lymphoma chemotherapy, specifically with rituximab. In 2008, the Centers for Disease Control and Prevention and, in 2010, the American Society of Clinical Oncology made recommendations that anyone who received cytotoxic or immunosuppressive therapy should be tested for serologic markers of HBV infection. In our study, we wanted to determine the screening rates for HBV infection at our institution and if simply adding a checkbox onto the rituximab order would improve HBV screening. We performed a retrospective chart review of two cohorts of lymphoma patients at Scott & White Health Clinic. Cohort 1 included patients from 1993 to 2008. Cohort 2 included patients who received rituximab after an institutionwide protocol (rituximab order checkbox) was initiated in 2011. A total of 452 patients treated for lymphoma were reviewed. Only 15 of the 404 Cohort 1 patients received HBV screening (3.7%; 95% confidence interval, 2.1%-6.1%). Screening rates were statistically higher if baseline liver laboratory values were elevated (P < 0.0001). HBV was also checked more frequently if patients' liver function tests became elevated while on chemotherapy, 85.7% (12/14). Of the 48 patients in Cohort 2, 33 patients (68.7%) received HBV screening. No patients in either cohort had a positive HBV surface antigen or developed reactivation of HBV during chemotherapy. The addition of a checkbox on the rituximab order form significantly increased our screening for HBV infection in lymphoma patients initiating chemotherapy. [ABSTRACT FROM AUTHOR]

Rationale: Investigators have postulated that mediastinal granulomatous inflammation is associated with prolonged overall survival in patients with cancer.Objectives: We sought to determine whether mediastinal granulomatous inflammation affects overall survival in patients with a history of treated cancer.Methods: Patients with a history of treated cancer who underwent endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) for evaluation of mediastinal or hilar lymphadenopathy were grouped based on whether they had mediastinal granulomatous inflammation or benign mediastinal lymphadenopathy without granulomas. Overall survival from the date of EBUS-TBNA to cancer-related death or to last follow-up in patient groups was compared.Measurements and Main Results: We reviewed the records of 106 patients (44 with mediastinal granulomatous inflammation and 62 with benign mediastinal lymphadenopathy). The 3-year survival rate was 90% overall and 93 and 88% in patients with mediastinal granulomatous inflammation and benign mediastinal lymphadenopathy, respectively (P=0.40). After multivariate adjustment, whether patients had mediastinal granulomatous inflammation or benign mediastinal lymphadenopathy did not significantly affect the risk of cancer death (mediastinal granulomatous inflammation to benign mediastinal lymphadenopathy hazard ratio, 1.27; P=0.76).Conclusions: These results suggest that patients who develop mediastinal granulomatous inflammation after cancer treatment do not have an increased overall survival when compared with patients who develop benign mediastinal lymphadenopathy. EBUS-TBNA is warranted for patients with treated cancer who develop mediastinal and/or hilar lymphadenopathy to avoid erroneous upstaging or misdiagnosis of cancer recurrence that would lead to suboptimal management. [ABSTRACT FROM AUTHOR]

Non--ST-segment elevation myocardial infarctions (NSTEMI) are common and cause significant morbidity and mortality. Following evidence-based medicine (EBM) guidelines is one way to ensure that these patients are cared for appropriately. This pilot study examined data from patients with NSTEMI to assess both documentation quality and use of EBM across multiple teams. Medical records were reviewed for significant differences in documentation quality in areas including history and physical exam, treatment, and inpatient mortality. While total documentation quality and mortality were not significantly different between groups, cardiology teams adhered to evidence-based recommendations more often than other teams. [ABSTRACT FROM AUTHOR]

This article describes a new electrochromic device (ECD) designed to achieve improved black color and long-term bistability. We achieved these improvements by fabricating a double-layered nanostructure of two different electrochromic materials stacked in layers on a single electrode. The fabricated ECD maintains 90% of the light transmittance of the colored state even after 1 h if powered off in the colored state. To achieve an improved black, green and blue viologens were successively immobilized in the bottom and top layers of materials on an electrode. The green viologens are initially colored at low voltage, and the purple viologens become colored when the voltage increases. This is because the reduction potential of the green viologens is less than that of purple viologens. Finally, an improved black color is obtained through a mixture of the two colors. [ABSTRACT FROM AUTHOR]

The article discusses updated estimates of the adjusted effectiveness of the seasonal influenza vaccine in the U.S. as of February 2013. Data is based on children and adults enrolled in the U.S. Influenza Vaccine Effectiveness (Flu VE) Network during December 3, 2012 to January 19, 2013. The overall vaccine effectiveness (VE) rate against influenza A and B virus infections linked to medically attended acute respiratory illness is mentioned.

The objective of this study was to compare the results of total thyroidectomy (TT) for hyperthyroidism secondary to Graves' disease (GD) with TT for other benign thyroid diseases to determine if TT should be considered more often as first-line therapy for GD. Seven hundred eighty patients underwent TT for benign disease: 203 for GD, 56 for other hyperthyroidisms, and 521 for other benign diseases from March 1, 2003, to December 31, 2009. The perioperative results of these three groups were compared for demographics, blood loss, operative time, complications, and hospitalization. There were no significant differences among the three groups except the patients with GD were more likely to be younger (42 vs 56 vs 57 years; P < 0.001), have more blood loss (154 vs 99 vs 110 mL; P = 0.05), and were more likely to develop permanent hypoparathyroidism (1.0 vs 1.8 vs 0%; P = 0.03) when compared with other causes of hyperthyroidism and other benign thyroid diseases. Permanent recurrent laryngeal nerve injury did not occur in the GD group (0 vs 0 vs 0.4% nerves at risk; P = 0.69) with transient recurrent laryngeal nerve injury occurring in 1.7 versus 2.7 versus 3.1 per cent nerves at risk (P = 0.35). The lack of a euthyroid state preoperatively had no influence on surgical outcomes or complications. Eighty percent of the TTs for GD were done as same-day outpatient procedures. TT offers a safe, low-risk, and rapid cure for GD to justifiably be considered as a reasonable first-line therapy in selected patients with Graves' hyperthyroidism. [ABSTRACT FROM AUTHOR]