Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19.

Importance: Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective: To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings. Exposures: Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO). Main Outcomes and Measures: The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm. Results: The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79). Conclusions and Relevance: This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm. Trial Registration: ClinicalTrials.gov Identifier: NCT04354701.

Development and evaluation of a bladder Cancer specific survivorship care plan by patients and clinical care providers: a multi-methods approach.

BACKGROUND, CONTEXT AND PURPOSE: In spite of the mixed evidence for their impact, survivorship Care Plans (SCPs) are recommended to enhance quality of care for cancer survivors. Data on the feasibility of SCPs in bladder cancer (BC) is sparse. Using a mixed-methods approach, this study describes the iterative development, acceptability and feasibility of BC specific SCP (BC-SCP) in clinical settings. METHODS: In Phase I, we developed the BC-SCP. In Phase II, we conducted four focus groups with 19 patients and 15 providers to examine its acceptability and usability challenges. Data analyses using the Atlas.ti program, informed refinement of the BC-SCP. In Phase III, we conducted feasibility testing of the refined BC-SCP with 18 providers from 12 health-centers. An encounter survey was completed after each assessment to examine the feasibility of the BC-SCP. Chi-square and Fisher Exact tests were used for comparative analyses. RESULTS: During phase I, we observed high patient and provider acceptability of the BC-SCP and substantial engagement in improving its content, design, and structure. In Phase II, providers completed 59 BC-SCPs. Mean time for BC-SCP completion was 12.3 min. Providers reported that BC-SCP content was clear, did not hamper clinic flow and was readily completed with easy-to-access information. Comparative analyses to examine differences in SCP completion time by patient clinico-demographic characteristics and provider type revealed no significant differences. CONCLUSIONS: Our BC-SCP has clinical relevance, and can be used in an active practice setting. However, considerable progress will be necessary to achieve implementation of and sharing the BC-SCP with patients and care providers, particularly within the electronic medical record. In summary, BC-SCPs are essential to improve the follow up care of BC survivors. Clinical resources are required to ensure appropriate implementation of BC-SCPs. TRIAL REGISTRATION: Study HUM00056082.

Dose-related impacts of imidacloprid oral intoxication on brain and liver of rock pigeon (Columba livia domestica), residues analysis in different organs.

Available data regarding Imidacloprid (IMI) insecticide hazards to birds are still being scare. Our study aimed to investigate toxic impacts of IMI oral gavage by different dose levels on the brain and liver of Rock pigeon (Columba livia domestica). Forty mature male birds were divided equally into four groups. A control group (C) was orally dosed Mazola corn oil and other three groups; the low dose (LD), the medium dose (MD), and the high dose (HD) groups were orally dosed IMI in Mazola corn oil by three dose levels corresponding to 1/15th, 1/10th, 1/5th IMI oral LD50 respectively. IMI exposure induced a significant decrease in serum levels of glutathione (GSH), superoxide dismutase (SOD) enzyme activity. On the other hand; malondialdehyde (MDA) levels were elevated. The levels of serum total protein, albumin, globulin, and A/G ratio showed a non-significant changes in all IMI dosed groups except levels of total protein in the HD IMI dosed group showed a significant decrease compared to the C group. Serum levels of alanine aminotransferase (ALT), lactate dehydrogenase (LDH), uric acid, plasma tumor necrosis factor α (TNFα) and plasma acetylcholinesterase (AChEs) enzyme activities showed a significant dose related increase in all IMI exposed groups compared to the C group; except the levels of ALT, LDH, and uric acid showed a non significant decrease in the LD IMI dosed group only. Residues of IMI were detected in the pectoral muscles, liver, brain, and kidney of all dosed rock pigeon. Moreover; pectoral muscles were the highest tissue for IMI residues detection. This is the first study reports accumulation of IMI in tissues other than crop, liver, and kidney of rock pigeon including brain and muscles. Moreover, the examined brain and liver tissues of all IMI dosed groups showed dosed related alterations in their structural and ultra-structural morphology. It is concluded that IMI oral administration to pigeon induced oxidative stress and detrimental effects in brain and liver of exposed pigeons. Additionally; IMI bio-accumulated in different organs being muscles is the highest tissues for IMI residues, thus monitoring of IMI residues in food is very essential.

Survival benefit of neoadjuvant versus adjuvant radiotherapy in lymph node positive esophageal cancer: a population based analysis.

BACKGROUND: The impact of radiotherapy on the survival of patients with locally advanced esophageal cancer (EC) is presently insufficiently explored. Thus, using data from the Surveillance, Epidemiology, and End Results (SEER) Registry, this study aimed to compare the survival rates of patients with lymph node (LN) positive EC who received curative resection and were treated by neoadjuvant and adjuvant radiotherapy (RT), respectively. METHODS: Retrospectively collected data from the SEER database using all 18 SEER registries on patients that underwent esophagectomy for EC was evaluated. All patients with LN positive pathology who received either neoadjuvant or adjuvant RT and curative intent esophagectomy from 2004 to 2007 were included. A comparison of 5-year relative survival outcome among groups categorized by sex, race, age, histology, and tumor size was performed. RESULTS: A total of 933 patients were evaluated; 636 (69%) and 297 (31%) received RT in neoadjuvant and adjuvant setting respectively. Their overall 5-year relative survival rates were 32.8% (95% CI: 28.7-36.9) and 26.5% (95% CI: 21-32.3) (P=0.058). Patients in the neoadjuvant RT group who underwent curative resection for squamous cell carcinoma (SCC) of EC had an improved 5-year relative survival rate of 43.4% (95% CI: 32.5-53.8) compared to 26.5% (95% CI: 15.4-38.9) measured for the adjuvant RT group (P=0.03). The results further revealed a significant increase in the 5-year relative survival rates for stage T3 and Tx when RT was given in neoadjuvant setting compared to adjuvant RT group (T3 28.5% vs. 20.2%, P=0.011; Tx 46.3% vs. 8.9%, P=0.021). When the patients were grouped according to race, sex or age, or based on the timing of radiation relative to surgery, in the other histological or T stage groups, there were no statistically significant differences in the 5-year survival rates. CONCLUSIONS: Compared to adjuvant radiotherapy, neoadjuvant radiotherapy results in a better 5-year relative survival in patients with squamous cell neoplasms and/or T3, Tx stage disease.

Ameliorative effect of flaxseed oil against thiacloprid-induced toxicity in rats: hematological, biochemical, and histopathological study.

The present study was carried out to evaluate the hematological, biochemical, and histopathological changes due to thiacloprid toxicity, and the potential protective role of flaxseed oil in male Wistar albino rats. Subacute thiacloprid intoxication induced a significant increase in RBCs, Hb, PCV, and WBCs count, and bone marrow micronucleus (MN) formation. Moreover, there was a significant increase in serum biochemical parameters related to hepatic injury: alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Serum total protein and albumin levels were significantly reduced. Thiacloprid increases tumor necrosis factor-alpha (TNF-α) and interleukine-2(IL-2). There was a significant decrease in glutathione-S-transferase, while the lipid peroxidation (MDA) and cytochrome P450 activity were significantly increased. Flaxseed oil coadministration partially retrieved the changes in all studied parameters. Thiacloprid induced histopathological liver damage, which was minimized as a result of flaxseed oil treatment. In general, it was concluded that, flaxseed oil able to protect against thiacloprid-induced hepatoxicity.