The impact of outpatient versus inpatient management on health-related quality of life outcomes for patients with malignant pleural effusion: the OPTIMUM randomised clinical trial.

BACKGROUND: The principal aim of malignant pleural effusion (MPE) management is to improve health-related quality of life (HRQoL) and symptoms. METHODS: In this open-label randomised controlled trial, patients with symptomatic MPE were randomly assigned to either indwelling pleural catheter (IPC) insertion with the option of talc pleurodesis or chest drain and talc pleurodesis. The primary end-point was global health status, measured with the 30-item European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) at 30 days post-intervention. 142 participants were enrolled from July 2015 to December 2019. RESULTS: Of participants randomly assigned to the IPC (n=70) and chest drain (n=72) groups, primary outcome data were available in 58 and 56 patients, respectively. Global health status improved in both groups at day 30 compared with baseline: IPC (mean difference 13.11; p=0.001) and chest drain (mean difference 10.11; p=0.001). However, there was no significant between-group difference at day 30 (mean intergroup difference in baseline-adjusted global health status 2.06, 95% CI -5.86-9.99; p=0.61), day 60 or day 90. No significant differences were identified between groups in breathlessness and chest pain scores. All chest drain arm patients were admitted (median length of stay 4 days); seven patients in the IPC arm required intervention-related hospitalisation. CONCLUSIONS: While HRQoL significantly improved in both groups, there were no differences in patient-reported global health status at 30 days. The outpatient pathway using an IPC was not superior to inpatient treatment with a chest drain.

PEGylated thrombopoietin mimetic, JNJ­26366821 a novel prophylactic radiation countermeasure for acute radiation injury.

Thrombopoietin (TPO) is the primary regulator of platelet generation and a stimulator of multilineage hematopoietic recovery following exposure to total body irradiation (TBI). JNJ­26366821, a novel PEGylated TPO mimetic peptide, stimulates platelet production without developing neutralizing antibodies or causing any adverse effects. Administration of a single dose of JNJ­26366821 demonstrated its efficacy as a prophylactic countermeasure in various mouse strains (males CD2F1, C3H/HeN, and male and female C57BL/6J) exposed to Co-60 gamma TBI. A dose dependent survival efficacy of JNJ­26366821 (- 24 h) was identified in male CD2F1 mice exposed to a supralethal dose of radiation. A single dose of JNJ­26366821 administered 24, 12, or 2 h pre-radiation resulted in 100% survival from a lethal dose of TBI with a dose reduction factor of 1.36. There was significantly accelerated recovery from radiation-induced peripheral blood neutropenia and thrombocytopenia in animals pre-treated with JNJ­26366821. The drug also increased bone marrow cellularity and megakaryocytes, accelerated multi-lineage hematopoietic recovery, and alleviated radiation-induced soluble markers of bone marrow aplasia and endothelial damage. These results indicate that JNJ­26366821 is a promising prophylactic radiation countermeasure for hematopoietic acute radiation syndrome with a broad window for medical management in a radiological or nuclear event.

Case report: Surgical resection of a retro-hepatic leiomyosarcoma involving atrial reconstruction, cardiopulmonary bypass, ex vivo tumor resection, and liver re-implantation.

Introduction: Leiomyosarcomas (LMS) involving the inferior vena cava (IVC) is a clinically rare entity, accounting for approximately 0.5% of all adult sarcomas. Case presentation: A 67-year-old male presented to the emergency department with mild back and lower abdominal pain. During the workup, a computed tomography scan without contrast showed an area of decreased attenuation within the liver adjacent to the intrahepatic IVC. Magnetic resonance imaging confirmed the involvement of the retro-hepatic IVC; biopsy confirmed the diagnosis of LMS. Given the location of the involvement of the retro-hepatic IVC, liver explantation was deemed necessary for adequate tumor resection. The superior extension of the tumor toward the heart necessitated Cardio-Pulmonary (CPB). The patient successfully underwent a complex surgical procedure involving liver explantation with ex vivo back-table resection of the retro-hepatic LMS, replacement of the retro-hepatic vena cava with a ringed Gore-Tex graft, liver re-implantation, and hepatic vein-atrial reconstruction under cardiopulmonary bypass. There were no intraoperative or post-op complications. Discussion: The role of vascular reconstruction of the IVC varies depending on the level and extent of the tumor, with options ranging from primary repair, ligation, or reconstruction dictated. Surgical resection with negative margins remains the treatment of choice due to the lack of efficacy of adjuvant therapies. Importantly, liver explantation offers a chance for complete surgical resection and reconstruction. Similarly, the complex nature of the tumor necessitated a pioneering approach involving direct hepato-atrial venous anastomosis. Conclusion: To the best of our knowledge, this is the first reported case in which the hepatic veins were anastomosed directly to the right atrium while also replacing the native vena cava with a separate graft.

Mitigation of total body irradiation-induced mortality and hematopoietic injury of mice by a thrombopoietin mimetic (JNJ-26366821).

The threat of a nuclear attack has increased in recent years highlighting the benefit of developing additional therapies for the treatment of victims suffering from Acute Radiation Syndrome (ARS). In this work, we evaluated the impact of a PEGylated thrombopoietin mimetic peptide, JNJ-26366821, on the mortality and hematopoietic effects associated with ARS in mice exposed to lethal doses of total body irradiation (TBI). JNJ-26366821 was efficacious as a mitigator of mortality and thrombocytopenia associated with ARS in both CD2F1 and C57BL/6 mice exposed to TBI from a cobalt-60 gamma-ray source. Single administration of doses ranging from 0.3 to 1 mg/kg, given 4, 8, 12 or 24 h post-TBI (LD70 dose) increased survival by 30-90% as compared to saline control treatment. At the conclusion of the 30-day study, significant increases in bone marrow colony forming units and megakaryocytes were observed in animals administered JNJ-26366821 compared to those administered saline. In addition, enhanced recovery of FLT3-L levels was observed in JNJ-26366821-treated animals. Probit analysis of survival in the JNJ-26366821- and saline-treated cohorts revealed a dose reduction factor of 1.113 and significant increases in survival for up to 6 months following irradiation. These results support the potential use of JNJ-26366821 as a medical countermeasure for treatment of acute TBI exposure in case of a radiological/nuclear event when administered from 4 to 24 h post-TBI.

A Multicenter Study of Patient Acceptability of the IBD Disk Tool and Patient-Reported Disabilities.

BACKGROUND: IBD, both Crohn's disease and ulcerative colitis, is associated with significant functional disability. Gastrointestinal symptoms alone are not the sole purpose of the interaction between patients and providers. In order to ascertain patients' disabilities, we utilized the recently developed IBD Disk to help determine their functional concerns and initiate relevant conversation. We aimed to ascertain patient acceptability and their major disabilities. PATIENTS AND METHODS: In this multicenter study, IBD patients at their outpatient visit were given the paper version of the IBD Disk. Patients were asked to score their level of disability for each item of the IBD Disk. The completed scores were then shared with their healthcare provider to act as a focus of discussion during the consultation. Patients and clinicians were also asked to provide informal qualitative feedback as to the benefits of the IBD Disk and areas for improvement. RESULTS: A total of 377 (female 60%) patients completed the questionnaires over the study period. Patient acceptability scored on a 0-10 Likert scale was excellent. All patients scored all domains of disability. Sleep, energy, and joint pain were the highest scoring domains of the IBD Disk, scoring higher than digestive symptoms. Clinicians and patients agreed that the IBD Disk allowed for ease of communication about disability symptoms and relevance to their day-to-day functioning. CONCLUSION: The IBD Disk is a novel easy-to-use tool to assess the functional disability of patients. We next plan to utilize it in the form of an electronic app internationally and in relation to treatment commencement and escalation.

Corrigendum: Gamma Tocotrienol Protects Mice From Targeted Thoracic Radiation Injury.

[This corrects the article DOI: 10.3389/fphar.2020.587970.].

Venting issues.

Introduction: A 65-year-old woman with type 3 intestinal failure secondary to scleroderma of the gut (limited cutaneous sclerosis (centromere positive) and rheumatoid arthritis (anti-cyclic citrullinated peptide (CCP) and rheumatoid factor positive)) on home parenteral nutrition since 2011 underwent a venting PEG replacement in 2015 for intractable vomiting due to gut dysmotility and small bowel bacterial overgrowth, poorly responding to cyclical antibiotics. An endoscopy was undertaken for planned PEG review for consideration of elective replacement (figure 1).Figure 1Initial endoscopy.Based on this endoscopy, her case was discussed at a multidisciplinary team meeting and the anaesthetic risk of laparotomy to remove the PEG was deemed too high (previous endoscopic PEG exchange under sedation had been poorly tolerated due to tube removal through the oesophagus (possibly affected by scleroderma), and necessitated anaesthesia). Therefore, it was decided to insert a new venting PEG endoscopically alongside the previous buried PEG (cut short and clamped) with the plan to remove the old one at a later date. QUESTIONS: What is shown during the initial endoscopy?What is shown during follow-up endoscopy?

Rare case of plasmablastic myeloma diagnosed on lung biopsy.

Plasmablastic myeloma is a rare variant of multiple myeloma characterised by neoplastic proliferation of single clone of plasma cells producing monoclonal immunoglobulins. A 60-year-old man presented to hospital with a 6-week history of chest pain, back pain, leg weakness and numbness. Imaging revealed a 75 mm left lobular lung mass with chest wall invasion, metastatic bony and soft-tissue deposits and spinal cord compression at T5 level. Lung biopsy, for suspected metastatic lung cancer, surprisingly showed features of plasmablastic myeloma. Protein electrophoresis demonstrated 2 g/L of IgG lambda paraproteinaemia and an increase in lambda light chains with reduced kappa/lambda ratio of 0.01. Bone marrow biopsy did not show evidence of infiltration by disease. The patient received radiotherapy to the spine; responded to third-line chemotherapy and received autologous stem cell transplant. This case adds to the rare causes of lung mass and is the first reported case of plasmablastic myeloma diagnosed on lung biopsy.

Gene networks determine predisposition to AMD.

PURPOSE: AMD genetic studies have revealed various genetic loci as causal to AMD pathology. We have described the genetic complexity of Indian AMD by describing the interaction of genotypes and subsequent changes in protein expression under the influence of environmental factors. This can be utilized to enhance the diagnostic and therapeutic efficacy in AMD patients. DESIGN: Genotype association was studied in 464 participants (AMD =277 & controls = 187) for eight genetic variants and their corresponding protein expression METHODS: SNP analysis and protein expression analysis was carried out in AMD and controls in tandem with longitudinal assessment of protein levels during the course of AMD pathology. ANCOVA and contrast analysis were used to examine the genotypic interactions and corresponding alterations in protein levels. In order to identify the important genetic variants Logistic Regression (LR) modeling was carried out and to authenticate the model Area under the Receiver Operating Characteristic curve (AUROC) were also computed. RESULTS: We have found genetic variants of rs5749482 (TIMP-3), rs11200638 (HTRA1), rs769449 (APOE) and rs6795735 (ADAMTS9) to be associated with AMD, concomitant with significant alterations of studied proteins levels. Analysis also revealed that the genetic interaction between APOE-HTRA1 genotypes and changes in LIPC levels (>6 pg/ug) by one unit change in SNP, play a crucial role in AMD. LR model suggested that the seven factors (including both genetic and environmental) can be utilized to predict the AMD cases with 88% efficacy and 95.6% AUROC. CONCLUSION: Results suggest that diagnostic and therapeutic strategy for Indian AMD must include estimation of genetic interaction and concomitant changes in expression levels of proteins under influence of environmental factors.

Gamma Tocotrienol Protects Mice From Targeted Thoracic Radiation Injury.

Radiation injury will result in multiorgan dysfuntion leading to multiorgan failure. In addition to many factors such as radiation dose, dose rate, the severity of the injury will also depend on organ systems which are exposed. Here, we report the protective property of gamma tocotrienol (GT3) in total as well as partial body irradiation (PBI) model in C3H/HeN male mice. We have carried out PBI by targeting thoracic region (lung-PBI) using Small Animal Radiation Research Platform, an X-ray irradiator with capabilities of an image guided irradiation with a variable collimator with minimized exposure to non-targeted tissues and organs. Precise and accurate irradiation of lungs was carried out at either 14 or 16 Gy at an approximate dose rate of 2.6 Gy/min. Though a low throughput model, it is amenable to change the field size on the spot. No damage to other non-targeted organs was observed in histopathological evaluation. There was no significant change in peripheral blood counts of irradiated mice in comparison to naïve mice. Femoral bone marrow cells had no damage in irradiated mice. As expected, damage to the targeted tissue was observed in the histopathological evaluation and non-targeted tissue was found normal. Regeneration and increase of cellularity and megakaryocytes on GT3 treatment was compared to significant loss of cellularity in saline group. Peak alveolitis was observed on day 14 post-PBI and protection from alveolitis by GT3 was noted. In irradiated lung tissue, thirty proteins were found to be differentially expressed but modulated by GT3 to reverse the effects of irradiation. We propose that possible mode of action of GT3 could be Angiopoietin 2-Tie2 pathway leading to AKT/ERK pathways resulting in disruption in cell survival/angiogenesis.

Surveillance strategy of Barrett's esophagus in the Asian region with particular reference to its locoregional epidemiology.

Barrett's esophagus (BE) is a premalignant condition associated with the development of esophageal adenocarcinoma (EAC). Over the past decade, BE and its associated neoplasia has increased in prevalence globally. Current surveillance guidelines aimed to detect and treat BE-associated dysplasia early in the hope of improving the morbidity and mortality of the condition. However, due to the lack of long-term data and the proven benefit that surveillance actually improves mortality from EAC, the guidelines of the United States and Europe are slightly different. This review will focus on discussing the surveillance strategy for BE appropriate for the Asian region, taking into account the unique epidemiologic features of this disease in the Asian region.

Dysregulated Cardiac IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity.

Acute exposure to ionizing radiation leads to Hematopoietic Acute Radiation Syndrome (H-ARS). To understand the inter-strain cellular and molecular mechanisms of radiation sensitivity, adult males of two strains of minipig, one with higher radiosensitivity, the Gottingen minipig (GMP), and another strain with comparatively lower radiosensitivity, the Sinclair minipig (SMP), were exposed to total body irradiation (TBI). Since Insulin-like Growth Factor-1 (IGF-1) signaling is associated with radiation sensitivity and regulation of cardiovascular homeostasis, we investigated the link between dysregulation of cardiac IGF-1 signaling and radiosensitivity. The adult male GMP; n = 48, and SMP; n = 24, were irradiated using gamma photons at 1.7-2.3 Gy doses. The animals that survived to day 45 after irradiation were euthanized and termed the survivors. Those animals that were euthanized prior to day 45 post-irradiation due to severe illness or health deterioration were termed the decedents. Cardiac tissue analysis of unirradiated and irradiated animals showed that inter-strain radiosensitivity and survival outcomes in H-ARS are associated with activation status of the cardiac IGF-1 signaling and nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated induction of antioxidant gene expression. Our data link H-ARS with dysregulation of cardiac IGF-1 signaling, and highlight the role of oxidative stress and cardiac antioxidant response in radiation sensitivity.