Citations

Abstract Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two‐sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low‐density lipoprotein [LDL] and high‐density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels ( P < 5 × 10 −8 ) were identified as instrumental variables, and assessed using genome‐wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non‐endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non‐endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non‐endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non‐endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.

Background Bronchopleural fistula (BPF) is a dreaded complication of pulmonary resection. For high-risk patients, bronchial stump coverage with vascularized tissue has been recommended. The goal of this study was to report our experience with intrathoracic muscle transposition for bronchial stump coverage. Methods A retrospective review of all patients who underwent intrathoracic muscle flap transposition as a prophylactic measure at our institution between 1990 and 2010 was conducted. Demographics, surgical characteristics, and complication rates were abstracted and analyzed. Results A total of 160 patients were identified. The most common lung resections performed were pneumonectomy (n = 69, 43%) and lobectomy (n = 60, 38%). A total of 168 flaps were used where serratus anterior was the most common flap (n = 136, 81%), followed by intercostal (n = 14, 8%), and latissimus dorsi (n = 12, 7%). Ten patients (6%) developed BPF, and empyema occurred in 13 patients (8%). Median survival was 20 months, and operative mortality occurred in 7 patients (4%). Conclusions Reinforcement of the bronchial closure with vascularized muscle is a viable option for potentially decreasing the incidence of BPF in high-risk patients. Further randomized studies are needed to determine the efficacy of this technique for BPF prevention.

Background Lymphedema treatment is an ongoing challenge. It impacts quality of life due to pain, loss of range of motion of the extremity, and repeated episodes of cellulitis. Different modalities have been used to evaluate lymphedema; some are more error-prone and some are more invasive. However, these measurements are poorly standardized, and intrarater and interrater reliabilities are difficult to achieve. This pilot study aims to assess the feasibility of ultrasound vibroelastography for assessing patients with extremity lymphedema via measuring shear wave speeds of subcutaneous tissues. Methods Patients with clinical and lymphoscintigraphic diagnosis of secondary lymphedema in the extremities without prior surgical treatment were included. A 0.1-s harmonic vibration was generated at three frequencies (100, 150, and 200 Hz) by the indenter of a handheld shaker on the skin. An ultrasound probe was used for noninvasively capturing of wave propagation in the subcutaneous tissue. Wave speeds were measured in the subcutaneous tissues of both the control and affected extremities. Results A total of 11 female patients with secondary lymphedema in the extremities were enrolled in this study. The magnitudes of the wave speeds of the region of interest in the subcutaneous tissue at lymphedema sites in the upper extremity (3.9 ± 0.17 m/s, 5.96 ± 0.67 m/s, and 7.41 ± 1.09 m/s) were statistically higher than those of the control sites (2.1 ± 0.27 m/s, 2.93 ± 0.57 m/s, and 3.56 ± 0.76 m/s) at 100, 150, and 200 Hz (P < 0.05), and at 100 and 200 Hz (P < 0.05) between lymphedema (4.33 ± 0.35 m/s, 4.17 ± 1.00 m/s, and 4.56 ± 0.37 m/s) and controls sites (2.48 ± 0.43 m/s, 2.77 ± 0.55 m/s, and 3.06 ± 0.29 m/s) in the lower extremity. Conclusions These preliminary data suggest that ultrasound vibroelastography may be useful in the evaluation of secondary lymphedema and can be a valuable tool to noninvasively track treatment progress.

Abstract Background: Fibromyalgia (FM) is a common chronic pain condition that seriously affects the quality of patient lives. Its etiology, pathogenesis, and treatment still remain uncertain. Dietary supplements have been widely trialed for symptom relief for FM. The review aims to synthesize the previous literature publications to assess the impact of herbs and dietary supplements on FM patients. Methods: We will conduct a literature search in the following databases PubMed, MEDLINE, EMBASE, Cochrane Library, Scopus, and Global Health from database inception to December 2019. Clinical studies published in the English language that used human participants and address the efficacy, safety, and acceptability of herbs and dietary supplements on individuals with FM will be included. The risk of bias and quality assessment of each trial will be evaluated. If trials are enough, a meta-analysis will be conducted using software RevMan5.3, Cochrane Collaboration. Result: Our review will be the first attempt to facilitate evidence-based management using herbs and dietary supplements to treat patients with FM. Conclusion: The findings may provide a framework for future research and clinic practice in FM management. PROSPERO registration number: CRD42020149941

Objective: Laser acupuncture has become increasingly attractive in clinical practice, especially for patients with needle phobias well as elderly people and children. However, literature concerning the safety of laser acupuncture has been limited. This systematic review synthesizes the current available literature on the safety of laser acupuncture. Methods: Ovid MEDLINE, ® Epub Ahead of Print, In-Process & Other Non-Indexed Citations Daily, Ovid Embase, Scopus, and EBM Reviews—Cochrane Central Register of Controlled Trials databases were searched for available randomized controlled trials (RCTs) on laser acupuncture. Safety data were extracted from the included studies. Adverse events (AEs) data were extracted and assessed in terms of severity and causality. Results: Of 737 articles, 21 RCTs were included. The majority of these RCTs reported that laser acupuncture was safe, without AEs; 6 trials reported AEs (including tingling, pain flare-ups, and transient fatigue). All AEs were mild and resolved spontaneously within 24 hours. The causal relationship between AEs and laser acupuncture was felt to be “certain” in 4 studies, “probable” in 1 study, and “possible” in 1 study. AEs were collected and monitored by evaluation methods in 7 trials: 5 with AE questionnaires, 1 with a checklist, and 1 with oral reports. Conclusions: Laser acupuncture appears to be a safe therapy associated with few mild and transient AEs. However, given the heterogeneity of current studies, large, well-designed placebo-controlled RCTs with rigorous evaluation methods are needed to assess the safety of laser acupuncture more completely.

Background and Aims Alcoholic hepatitis (AH) is diagnosed by clinical criteria, although several objective scores facilitate risk stratification. Extracellular vesicles (EVs) have emerged as biomarkers for many diseases and are also implicated in the pathogenesis of AH. Therefore, we investigated whether plasma EV concentration and sphingolipid cargo could serve as diagnostic biomarkers for AH and inform prognosis to permit dynamic risk profiling of AH subjects. Approach and Results EVs were isolated and quantified from plasma samples from healthy controls, heavy drinkers, and subjects with end‐stage liver disease (ESLD) attributed to cholestatic liver diseases and nonalcoholic steatohepatitis, decompensated alcohol‐associated cirrhosis (AC), and AH. Sphingolipids were quantified by tandem mass spectroscopy. The median plasma EV concentration was significantly higher in AH subjects (5.38 × 1011/mL) compared to healthy controls (4.38 × 1010/mL; P < 0.0001), heavy drinkers (1.28 × 1011/mL; P < 0.0001), ESLD (5.35 × 1010/mL; P < 0.0001), and decompensated AC (9.2 × 1010/mL; P < 0.0001) disease controls. Among AH subjects, EV concentration correlated with Model for End‐Stage Liver Disease score. When EV counts were dichotomized at the median, survival probability for AH subjects at 90 days was 63.0% in the high‐EV group and 90.0% in the low‐EV group (log‐rank P value = 0.015). Interestingly, EV sphingolipid cargo was significantly enriched in AH when compared to healthy controls, heavy drinkers, ESLD, and decompensated AC (P = 0.0001). Multiple sphingolipids demonstrated good diagnostic and prognostic performance as biomarkers for AH. Conclusions Circulating EV concentration and sphingolipid cargo signature can be used in the diagnosis and differentiation of AH from heavy drinkers, decompensated AC, and other etiologies of ESLD and predict 90‐day survival permitting dynamic risk profiling.

11011 Background: CMB305 (C) is an immunotherapy designed to generate an anti-NY-ESO-1 immune response (IR). C consists of a dendritic cell-targeting lentiviral vector encoding NY-ESO-1 gene (LV305), and a TLR-4 agonist NY-ESO-1 recombinant protein plus GLA-SE (G305). A Phase 1 study demonstrated C is safe, generates IR and conveys a median overall survival (mOS) of 23.7 months (15.5, not reached [NR]) for soft tissue sarcomas & 29.2 months (12.2, NR) for synovial sarcoma (SS) (ESMO 2018). We evaluated efficacy and safety of C and atezolizumab (A) vs A alone in NY-ESO-1+ SS and myxoid round cell liposarcoma (MRCL). Methods: A prospective randomized open label phase 2 study of C (LV305 Intradermal Days 0, 14, 42, 70 + G305 Intramuscular Days 28, 56, 84 then q 6wk up to one year (yr)) + A (1200mg IV q3wk) vs A alone in advanced NY-ESO-1+ SS/MRCL. Primary endpoints of OS and progression-free survival (PFS); secondary endpoints of safety, IR, and response rate and post hoc analysis by line of therapy. Results: 88 patients (pts) were enrolled and dosed. Arm C+A: median age 48 yrs, 73% SS, 98% relapsed metastatic, 73% ≥2 prior lines chemotherapy; Arm A: 47 yrs, 67% SS, 84% relapsed metastatic, 53% ≥2 prior lines chemotherapy. Most treatment-related adverse events (TRAE) Grade 1/2, no treatment related deaths. Summary of clinical outcomes. Conclusions: Despite no major differences in PFS and OS between the treatment arms (Arm C+A had more advanced disease and more prior lines of chemotherapy), Arm A +C achieved PRs, a higher level of anti-NY-ESO-1 IR, and pts with IR had numerically superior outcomes. Moreover, the clinical benefit of C+A in earlier lines of therapy warrant further study. Clinical trial information: NCT02609984. [Table: see text]

Abstract Purpose: Genomic alterations in DNA damage repair (DDR) genes other than BRCA may confer synthetic lethality with PARP inhibition in metastatic castration-resistant prostate cancer (mCRPC). To test this hypothesis, the phase II TRITON2 study of rucaparib included patients with mCRPC and deleterious non-BRCA DDR gene alterations. Patients and Methods: TRITON2 enrolled patients who had progressed on one or two lines of next-generation androgen receptor–directed therapy and one taxane-based chemotherapy for mCRPC. Key endpoints were investigator-assessed radiographic response per modified RECIST/PCWG3 and PSA response (≥50% decrease from baseline). Results: TRITON2 enrolled 78 patients with a non-BRCA DDR gene alteration [ATM (n = 49), CDK12 (n = 15), CHEK2 (n = 12), and other DDR genes (n = 14)]. Among patients evaluable for each endpoint, radiographic and PSA responses were observed in a limited number of patients with an alteration in ATM [2/19 (10.5%) and 2/49 (4.1%), respectively], CDK12 [0/10 (0%) and 1/15 (6.7%), respectively], or CHEK2 [1/9 (11.1%) and 2/12 (16.7%), respectively], including no radiographic or PSA responses in 11 patients with confirmed biallelic ATM loss or 11 patients with ATM germline mutations. Responses were observed in patients with alterations in the DDR genes PALB2, FANCA, BRIP1, and RAD51B. Conclusions: In this prospective, genomics-driven study of rucaparib in mCRPC, we found limited radiographic/PSA responses to PARP inhibition in men with alterations in ATM, CDK12, or CHEK2. However, patients with alterations in other DDR-associated genes (e.g., PALB2) may benefit from PARP inhibition. See related commentary by Sokolova et al., p. 2439