Complete Response to Immunotherapy Using Pembrolizumab in a Patient With Conjunctival Squamous Cell Carcinoma With Nodal Metastasis.

A 92-year-old woman presented with a large bulbar conjunctival mass in the OD. She also had a palpable parotid mass which on fine needle aspiration biopsy confirmed to be metastatic squamous cell carcinoma. The conjunctival mass was biopsied to confirm the diagnosis of squamous cell carcinoma with positive programmed cell death ligand 1 expression and a high tumor mutation burden. She was treated with pembrolizumab and had complete resolution of the conjunctival mass and the associated parotid metastasis after just 2 cycles of treatment. This case underscores the promising role of immune checkpoint inhibitors in the treatment of conjunctival squamous cell carcinoma, especially when surgery is associated with significant ocular morbidity, in patients who may not be good surgical candidates, or in patients with metastasis.

cGLRs Join Their Cousins of Pattern Recognition Receptor Family to Regulate Immune Homeostasis.

Pattern recognition receptors (PRRs) recognize danger signals such as PAMPs/MAMPs and DAMPs to initiate a protective immune response. TLRs, NLRs, CLRs, and RLRs are well-characterized PRRs of the host immune system. cGLRs have been recently identified as PRRs. In humans, the cGAS/STING signaling pathway is a part of cGLRs. cGAS recognizes cytosolic dsDNA as a PAMP or DAMP to initiate the STING-dependent immune response comprising type 1 IFN release, NF-κB activation, autophagy, and cellular senescence. The present article discusses the emergence of cGLRs as critical PRRs and how they regulate immune responses. We examined the role of cGAS/STING signaling, a well-studied cGLR system, in the activation of the immune system. The following sections discuss the role of cGAS/STING dysregulation in disease and how immune cross-talk with other PRRs maintains immune homeostasis. This understanding will lead to the design of better vaccines and immunotherapeutics for various diseases, including infections, autoimmunity, and cancers.

Ancient DNA of narrow-headed vole reveal common features of the Late Pleistocene population dynamics in cold-adapted small mammals.

The narrow-headed vole, collared lemming and common vole were the most abundant small mammal species across the Eurasian Late Pleistocene steppe-tundra environment. Previous ancient DNA studies of the collared lemming and common vole have revealed dynamic population histories shaped by climatic fluctuations. To investigate the extent to which species with similar adaptations share common evolutionary histories, we generated a dataset comprised the mitochondrial genomes of 139 ancient and 6 modern narrow-headed voles from several sites across Europe and northwestern Asia covering approximately the last 100 thousand years (kyr). We inferred Bayesian time-aware phylogenies using 11 radiocarbon-dated samples to calibrate the molecular clock. Divergence of the main mtDNA lineages across the three species occurred during marine isotope stages (MIS) 7 and MIS 5, suggesting a common response of species adapted to open habitat during interglacials. We identified several time-structured mtDNA lineages in European narrow-headed vole, suggesting lineage turnover. The timing of some of these turnovers was synchronous across the three species, allowing us to identify the main drivers of the Late Pleistocene dynamics of steppe- and cold-adapted species.

Targeting cGAS/STING signaling-mediated myeloid immune cell dysfunction in TIME.

Myeloid immune cells (MICs) are potent innate immune cells serving as first responders to invading pathogens and internal changes to cellular homeostasis. Cancer is a stage of altered cellular homeostasis that can originate in response to different pathogens, chemical carcinogens, and internal genetic/epigenetic changes. MICs express several pattern recognition receptors (PRRs) on their membranes, cytosol, and organelles, recognizing systemic, tissue, and organ-specific altered homeostasis. cGAS/STING signaling is a cytosolic PRR system for identifying cytosolic double-stranded DNA (dsDNA) in a sequence-independent but size-dependent manner. The longer the cytosolic dsDNA size, the stronger the cGAS/STING signaling activation with increased type 1 interferon (IFN) and NF-κB-dependent cytokines and chemokines' generation. The present article discusses tumor-supportive changes occurring in the tumor microenvironment (TME) or tumor immune microenvironment (TIME) MICs, specifically emphasizing cGAS/STING signaling-dependent alteration. The article further discusses utilizing MIC-specific cGAS/STING signaling modulation as critical tumor immunotherapy to alter TIME.

Bias Issues in Colorectal Cancer Management: A Review.

Based on census data, over one-third of the US population identifies as a racial or ethnic minority. This group of racial and ethnic minorities is more likely to develop cancer and die from it when compared with the general population of the USA. These disparities are most pronounced in the African American community. Despite overall CRC rates decreasing nationally and within certain racial and ethnic minorities in the USA, there continue to be disparities in incidence and mortality when compared with non-Hispanic Whites. The disparities in CRC incidence and mortality are related to systematic racism and bias inherent in healthcare systems and society. Disparities in CRC management will continue to exist until specific interventions are implemented in the context of each racial and ethnic group. This review's primary aim is to highlight the disparities in CRC among African Americans in the USA. For surgeons, understanding these disparities is formative to creating change and improving the quality of care, centering equity for all patients.

Comparison of the host response to larvicidal and nonlarvicidal treatment of naturally acquired cyathostomin infections in horses.

This study aimed to collect information on local and systemic inflammatory responses, and goblet cell-associated components, following anthelmintic treatment with moxidectin and ivermectin in horses naturally infected with cyathostomin parasites. Thirty-six horses aged 2-5 years of age were randomly allocated to three groups. Group 1 received ivermectin/praziquantel (0.2 mg/kg), Group 2 received moxidectin/praziquantel (0.4 mg/kg) and Group 3 were untreated controls. Tissue samples from the Cecum, Dorsal and Ventral Colons were used for histopathological evaluation and preserved for RNA isolation and gene expression analysis. Whole blood was collected weekly for gene expression analysis as well. The control group had significantly higher inflammation associated with higher larval scores. The treatment groups displayed no differences in larval counts and inflammatory cell populations (p > .05). Mucosal larval counts were positively correlated with goblet cell hyperplasia scores (p = .047). The moxidectin-treated group had a significantly lower expression of IFN-γ (p < .05). The data suggest that removal of cyathostomins reduced the pro-inflammatory response associated with cyathostomin infections. Pro-inflammatory reactions associated with anthelmintic treatment were minimal, but lowest for moxidectin-treated horses. Results suggested that cecum, ventral and dorsal colons responded differently to cyathostomin larvae, which may have implications in the disease process.

Comparing a daily versus weekly titration algorithm in people with type 2 diabetes switching from basal insulin to iGlarLixi in the LixiLan ONE CAN randomized trial.

AIM: To compare the efficacy and safety of a simple daily titration algorithm compared with a weekly dose adjustment of iGlarLixi in people with type 2 diabetes. MATERIALS AND METHODS: LixiLan ONE CAN (NCT03767543), a randomized, 26-week, open-label, multicentre phase 3 trial conducted in Canada, involved 265 people with type 2 diabetes and an HbA1c of ≥7.5% to ≤ 10.5% or less (≥58 to ≤91 mmol/mol) on basal insulin for 6 months or longer. Participants were randomized 1:1 with instructions to self-titrate iGlarLixi daily (1 unit/day) or once weekly (2 or 4 units/week) to a common target fasting plasma glucose of 4.4 to 5.6 mmol/L (79 to 101 mg/dl). The primary objective was to show non-inferiority of the daily versus weekly titration algorithm. RESULTS: At 26 weeks, daily titration of iGlarLixi was not inferior to a weekly titration for both the prespecified primary endpoint of change in HbA1c from baseline (least square [LS] mean change: -1.24% vs. -0.92%, respectively; LS mean difference: 0.32%; 95% CI [0.07, 0.57]; P < .0001) and for the secondary endpoint of change in weight from baseline (LS mean change: -0.22 vs. +0.81 kg, respectively; LS mean difference: 1.03 kg; 95% CI [0.01, 2.06]; P < .0001). Indeed, for both the primary and secondary outcome, the daily titration of iGlarLixi was superior. There were no statistically significant differences in hypoglycaemia incidence between the two titration strategies during the 26-week study. CONCLUSION: A daily titration algorithm for switching basal insulin to iGlarLixi was shown to be non-inferior and superior for glycaemic control and weight compared with weekly titration.

Efficacy and safety of dronedarone across age and sex subgroups: a post hoc analysis of the ATHENA study among patients with non-permanent atrial fibrillation/flutter.

AIMS: Age and sex may impact the efficacy of antiarrhythmic drugs on cardiovascular outcomes and arrhythmia recurrences in patients with atrial fibrillation (AF). We report on a post hoc analysis of the ATHENA study (NCT00174785), which examined cardiovascular outcomes in patients with non-permanent AF treated with dronedarone vs. placebo. METHODS AND RESULTS: Efficacy and safety of dronedarone were assessed in patients according to age and sex. Baseline characteristics were comparable across subgroups, except for cardiovascular comorbidities, which were more frequent with increasing age. Dronedarone significantly reduced the risk of cardiovascular hospitalization or death due to any cause among patients 65-74 [n = 1830; hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.60-0.83; P < 0.0001] and ≥75 (n = 1925; HR 0.75, 95% CI 0.65-0.88; P = 0.0002) years old and among males (n = 2459; HR 0.74, 95% CI 0.64-0.84; P < 0.00001) and females (n = 2169; HR 0.77, 95% CI 0.67-0.89; P = 0.0002); outcomes were similar for time to AF/AFL recurrence. Among patients aged <65 years (n = 873), cardiovascular hospitalization or death due to any cause with dronedarone vs. placebo was associated with an HR of 0.89 (95% CI 0.71-1.11; P = 0.3). The incidence of all treatment-emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation was comparable among males and females, and increased with increasing age. CONCLUSIONS: These results support the use of dronedarone for the improvement of clinical outcomes among patients aged ≥65 years and regardless of sex.

Predicting malignant pleural effusion during diagnostic pleuroscopy with biopsy: A prospective multicentre study.

BACKGROUND AND OBJECTIVE: Pleuroscopy with pleural biopsy has a high sensitivity for malignant pleural effusion (MPE). Because MPEs tend to recur, concurrent diagnosis and treatment of MPE during pleuroscopy is desired. However, proceeding directly to treatment at the time of pleuroscopy requires confidence in the on-site diagnosis. The study's primary objective was to create a predictive model to estimate the probability of MPE during pleuroscopy. METHODS: A prospective observational multicentre cohort study of consecutive patients undergoing pleuroscopy was conducted. We used a logistic regression model to evaluate the probability of MPE with relation to visual assessment, rapid on-site evaluation (ROSE) of touch preparation and presence of pleural nodules/masses on computed tomography (CT). To assess the model's prediction accuracy, a bootstrapped training/testing approach was utilized to estimate the cross-validated area under the receiver operating characteristic curve. RESULTS: Of the 201 patients included in the study, 103 had MPE. Logistic regression showed that higher level of malignancy on visual assessment is associated with higher odds of MPE (OR = 34.68, 95% CI = 9.17-131.14, p < 0.001). The logistic regression also showed that higher level of malignancy on ROSE of touch preparation is associated with higher odds of MPE (OR = 11.63, 95% CI = 3.85-35.16, p < 0.001). Presence of pleural nodules/masses on CT is associated with higher odds of MPE (OR = 6.61, 95% CI = 1.97-22.1, p = 0.002). A multivariable logistic regression model of final pathologic status with relation to visual assessment, ROSE of touch preparation and presence of pleural nodules/masses on CT had a cross-validated AUC of 0.94 (95% CI = 0.91-0.97). CONCLUSION: A prediction model using visual assessment, ROSE of touch preparation and CT scan findings demonstrated excellent predictive accuracy for MPE. Further validation studies are needed to confirm our findings.

Cytopathology assistance for optimizing interventional diagnostic procedures.

Herein, we review the components of Rapid On-Site Evaluation (ROSE) and the mechanics of Fine Needle Aspiration (FNA) to prepare cytopathologists to assist radiologists in optimizing their diagnostic procedures. The performance of FNA differs among proceduralists (interventional radiologists, general radiologists, bronchoscopists, endoscopists, surgeons, and clinicians), organ systems, diseases, and cancer types. The discussion is necessarily broad. Although practiced, professional aspects of ROSE interaction are not typically discussed in the literature. The target audience is primarily trainees and pathologists in an early stage of their career, but we hope that some ideas may be of general benefit. The information presented in this article is partially derived from experience in a busy tertiary care center with active ROSE services.

Geographical variation in age and growth of the endemic Australian sciaenid Atractoscion atelodus.

Growth rates and other age-related population characteristics are essential parameters underpinning management of a stock. This is the first study to estimate length-at-age of Atractoscion atelodus (family Sciaenidae) in New South Wales (NSW), despite the species being exploited since the 1940s. The aim of the current study was to quantify the age-based biological characteristics of A. atelodus and in particular: (a) validate the use of sagittal otoliths to quantify age; (b) estimate the growth rates and longevity of males and females; (c) examine geographical variation in age and growth; (d) document the age composition in commercial landings and (e) estimate mortality rates. A. atelodus is relatively fast growing, reaching 40 cm fork length (LF ) in the first year of life and living to at least 14 years. Growth was significantly different between sexes, with modelled asymptotic lengths of females (L∞  = 84.6 cm LF ) greater than males (L∞  = 69.0 cm LF ). Growth rates were also significantly different between northern and southern populations. Fish sampled from the southern region were younger and faster growing than those sampled in the northern region, supporting the counter-gradient growth theory and the influence of upwelling providing greater nutrient and food availability. The commercial fishery was predominantly based on young fish <3 years. with few (c. 5%) greater than 5 years. Fishing mortality estimates (F = 0.42) were similar to natural mortality estimates (M = 0.44). The age-based parameters estimated in the present study suggest that A. atelodus should be relatively resilient to fishing; nonetheless, the sizes and ages in landings are indicative of a stock heavily fished. The fishery is experiencing truncated age distributions and appears to be largely recruitment driven, increasing susceptibility to overexploitation. Determining geographical differences in growth rates of a population has important implications when considering impacts of anthropogenic drivers such as global warming and overexploitation and is important to determine in managing exploited fish populations.

Using their heads - A novel, collaborative approach between industry and scientists to monitor a commercial mullet fishery as a result of COVID-19 restrictions.

The COVID-19 global pandemic-related restrictions during 2020 severely impacted the Australian seafood industry, including essential scientific monitoring to support stock assessment and to demonstrate sustainability. Here we detail a novel, collaborative monitoring program between scientists and the seafood industry to generate length and age compositions that were representative of one of the largest, most valuable, and controversial fisheries along eastern Australia, the pre-spawning ocean run fishery for Sea Mullet Mugil cephalus that is predominantly a roe fishery. The standard approach to monitoring this fishery has been to base trained scientific staff at the major processing facility for M. cephalus, where they access whole fish from entire catches to generate representative length and age compositions during the peak season, April to May. Covid-19 restrictions prevented this approach for 2020 in eastern Australia. In recognition that in addition to the high-value roe, all components of the female fish are utilized (heads and guts for bait, bodies for human consumption), a multi-stage, spatially stratified sampling design was investigated. Female heads were retained from randomly selected catches from each of the three major fishing zones and transported to the New South Wales Department of Primary Industries fish laboratory based in Sydney. Head lengths (HLs) were measured and converted to Fork Lengths (FLs) using a HL to FL relationship. The resulting fish length compositions from each catch were subsequently combined based on: (i) relative catch size of females within an ocean zone, and; (ii) the relative reported landings of females in each ocean fishing zone. Otoliths were randomly collected from heads sampled from each ocean zone and used to estimate age. The resulting ocean zone to age matrix was combined with the relative reported landings of female fish in each ocean fishing zone to generate a total female age composition for the fishery. The estimated age composition of females were typical in being mainly between ages 3 and 6, with a strong presence of 4-year olds. This stronger cohort was present as 3-year olds in 2018/19 and 5-year olds in 2020/21, thus providing confidence that our sampling was representative of the fishery. The study reinforces the positive outcomes that can be generated through co-management between scientists and the seafood industry.

Bempegaldesleukin (BEMPEG; NKTR-214) efficacy as a single agent and in combination with checkpoint-inhibitor therapy in mouse models of osteosarcoma.

Survival of patients with relapsed/refractory osteosarcoma has not improved in the last 30 years. Several immunotherapeutic approaches have shown benefit in murine osteosarcoma models, including the anti-programmed death-1 (anti-PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) immune checkpoint inhibitors. Treatment with the T-cell growth factor interleukin-2 (IL-2) has shown some clinical benefit but has limitations due to poor tolerability. Therefore, we evaluated the efficacy of bempegaldesleukin (BEMPEG; NKTR-214), a first-in-class CD122-preferential IL-2 pathway agonist, alone and in combination with anti-PD-1 or anti-CTLA-4 immune checkpoint inhibitors in metastatic and orthotopic murine models of osteosarcoma. Treatment with BEMPEG delayed tumor growth and increased overall survival of mice with K7M2-WT osteosarcoma pulmonary metastases. BEMPEG also inhibited primary tumor growth and metastatic relapse in lungs and bone in the K7M3 orthotopic osteosarcoma mouse model. In addition, it enhanced therapeutic activity of anti-CTLA-4 and anti-PD-1 checkpoint blockade in the DLM8 subcutaneous murine osteosarcoma model. Finally, BEMPEG strongly increased accumulation of intratumoral effector T cells and natural killer cells, but not T-regulatory cells, resulting in improved effector:inhibitory cell ratios. Collectively, these data in multiple murine models of osteosarcoma provide a path toward clinical evaluation of BEMPEG-based regimens in human osteosarcoma.

Phase 1 trial of ADI-PEG20 plus cisplatin in patients with pretreated metastatic melanoma or other advanced solid malignancies.

BACKGROUND: Arginine depletion interferes with pyrimidine metabolism and DNA damage-repair pathways, and pairing arginine deiminase pegylated with 20,000-molecular-weight polyethylene glycol (ADI-PEG20) with platinum enhances cytotoxicity in vitro and in vivo in arginine auxotrophs. METHODS: This single-centre, Phase 1 trial was conducted using a 3 + 3 dose escalation designed to assess safety, tolerability and determine the recommended Phase 2 dose (RP2D) of ADI-PEG20. RESULTS: We enrolled 99 patients with metastatic argininosuccinate synthetase 1 (ASS1) deficient malignancies. We observed no dose-limiting toxic effects or treatment-related mortality. Three percent of patients discontinued treatment because of toxicity. After treatment, 5% (5/99) of patients had partial responses, and 41% had stable disease. The median progression-free and overall survival durations were 3.62 and 8.06 months, respectively. Substantial arginine depletion and citrulline escalation persisted in most patients through weeks 24 and 8, respectively. Tumour responses were associated with anti-ADI-PEG20 antibody levels at weeks 8 and 16 (p = 0.031 and p = 0.0357, respectively). CONCLUSION: Concurrently administered ADI-PEG20 and cisplatin had an acceptable safety profile and had shown antitumour activity against metastatic ASS1-deficient solid tumours. Further evaluation of this treatment combination is warranted.

Outcomes of the First Virtual General Surgery Certifying Exam of the American Board of Surgery.

OBJECTIVE: To Study the Outcomes of the First Virtual General Surgery Certifying Exam of the American Board of Surgery. SUMMARY OF BACKGROUND DATA: The ABS General Surgery CE is normally an in-person oral examination. Due to the COVID-19 outbreak, the ABS was required to reschedule these. After 2 small pilots, the CE's October administration represented the first large-scale remote virtual exam. The purpose of this report is to compare the outcomes of this virtual and the previous in-person CEs. METHODS: CE candidates were asked to provide feedback on their experience via a survey. The passing rate was compared to the 1025 candidates who took the 2019-2020 in-person CEs. RESULTS: Of the 308 candidates who registered for the virtual CE, 306 completed the exam (99.4%) and 188 completed the survey (61.4%). The majority had a very positive experience. They rated the virtual CE as very good/excellent in security (90%), ease of exam platform (77%), audio quality (71%), video quality (69%), and overall satisfaction (86%). Notably, when asked their preference, 78% preferred the virtual exam. There were no differences in the passing rates between the virtual or in-person exams. CONCLUSIONS: The first virtual CE by the ABS was completed using available internet technology. There was high satisfaction, with the majority preferring the virtual platform. Compared to past in-person CEs, there was no difference in outcomes as measured by passing rates. These data suggest that expansion of the virtual CE may be desirable.

Landmark Series on Disparities in Surgical Oncology: Melanoma.

BACKGROUND: Although the lifetime risk of melanoma is disproportionately higher in whites, blacks have a poorer overall survival with an absolute survival difference of 25%. Significant progress has been made in melanoma treatment in the past decade; however, these successes may not be available or accessible to all segments of the population. METHODS: In this review, we highlight important studies in melanoma as well as informative retrospective studies from databases and nonmelanoma cancers where appropriate. RESULTS: There are no level I evidence-based studies on disparities in melanoma, and most likely there will never be, but the studies presented herein and clinical experience demonstrate that disparities in clinical outcomes from melanoma exists. CONCLUSIONS: By becoming aware of the disparities, we can help mitigate them by engagement, education, and corrective and empowering actions through awareness campaigns, appropriate clinical trial design, encouraging participation in clinical trials, increasing the diversity of providers, and advocacy.

Impact of electrical cardioversion on quality of life for patients with symptomatic persistent atrial fibrillation: Is there a treatment expectation effect?

It is assumed that electrical cardioversion (ECV) improves the quality of life (QoL) of patients with atrial fibrillation (AF) by restoring sinus rhythm (SR). OBJECTIVE: We examined the effect of ECV and rhythm status on QoL of patients with symptomatic persistent AF in a randomized controlled trial. METHOD: The elective cardioversion for prevention of symptomatic atrial fibrillation trial examined the efficacy of dronedarone around the time of ECV in maintaining SR. Quality of life was measured with the University of Toronto Atrial Fibrillation Severity Scale. The primary outcome was the change in AF symptom severity (∆AFSS) score over 6 months (0-35 points, with higher scores reflecting worse QoL and a minimal clinically important difference defined as ∆AFSS ≥3 points). Multivariable linear regression was performed to identify factors associated with changes in QoL. RESULTS: We included 148 patients with complete AFSS scores at baseline and 6 months. Over 6 months, QoL improved irrespective of rhythm status (ΔAFSS scores for patients who (i) maintained SR; (ii) had AF relapse after successful ECV; and (iii) had unsuccessful ECV were -6.8 ±â€¯6.4 points, -4.1 ±â€¯6.2 points, and -4.0 ±â€¯5.8 points respectively, P < .01 for all subgroups). After adjustment of baseline covariates, maintenance of SR was associated with QoL improvement (ΔAFSS: -3.8 points, 95% CI: -6.0 to -1.6 points, P < .01). CONCLUSIONS: Maintenance of SR was associated with clinically relevant improvement in patients' QoL at 6 months. Patients with AF recurrence had a small but still relevant improvement in their QoL, potentially due to factors other than sinus rhythm.

A proposal for pathologic processing of breast implant capsules in patients with suspected breast implant anaplastic large cell lymphoma.

Breast implant anaplastic large cell lymphoma is an entity recently recognized by the World Health Organization. The tumor arises around textured-surface breast implants and is usually confined to the surrounding fibrous capsule. Currently, there are no recommendations for handling and sampling of capsules from patients with suspected breast implant anaplastic large cell lymphoma without a grossly identifiable tumor. We analyzed complete capsulectomies without distinct gross lesions from patients with breast implant anaplastic large cell lymphoma. The gross appearance of the capsules as well as the presence, extent and depth of tumor cells on the luminal side and number of sections involved by lymphoma were determined by review of routine stains and CD30 immunohistochemistry. We then used a mathematical model that included the extent of tumor cells and number of positive sections to calculate the minimum number of sections required to identify 95% of randomly distributed lesions. We identified 50 patients with breast implant anaplastic large cell lymphoma who had complete capsulectomies. The implants were textured in all 32 (100%) cases with available information. Anaplastic large cell lymphoma was found in 44/50 (88%) capsules; no tumor was found in six (12%) patients who had lymphoma cells only in the effusion. The median number of sections reviewed was 20 (range, 2-240), the median percentage of sections involved by tumor was 6% (range, 0-90%), and the median percentage of sections involved by lymphoma was 10% (range, 0-90%). Invasion deep into or through the capsule was identified in 18/50 (36%) patients. In patients with breast implant anaplastic large cell lymphoma without a grossly identifiable tumor we identified a spectrum of involvement and we propose a protocol for handling, sampling and reporting these cases. The number of sections to exclude the presence of lymphoma with more than 95% certainty was supported by a mathematic rationale.

Health-Related Quality of Life After Cytoreductive Surgery/HIPEC for Mucinous Appendiceal Cancer: Results of a Multicenter Randomized Trial Comparing Oxaliplatin and Mitomycin.

BACKGROUND: This study evaluated health-related quality of life (HRQOL) using patient-reported outcomes in subjects with mucinous appendiceal neoplasms who underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as part of a randomized trial comparing mitomycin with oxaliplatin. METHODS: In this prospective multicenter study, 121 mucinous appendiceal cancer patients, with evidence of peritoneal dissemination who underwent CRS, were randomized to receive mitomycin (divided 40 mg) or oxaliplatin (200 mg/m2) for HIPEC. The Functional Assessment of Cancer Therapy Neurotoxicity (FACT-G/NTX) questionnaire was utilized to assess HRQOL. The Trial Outcome Index (TOI) is a summary index responsive to changes in physical/functional outcomes. Repeated measures mixed models with an unstructured variance matrix were applied to assess changes in HRQOL longitudinally. RESULTS: Baseline questionnaire compliance was 95.9%. Baseline physical well-being (PWB) was independently associated with overall survival (hazard ratio 0.79, 95% confidence interval 0.66-0.96; p = 0.017). The TOI was significantly lower in the mitomycin group compared with the oxaliplatin arm at 12 weeks (p = 0.044; score difference 6.35) and 24 weeks after surgery (p = 0.049; score difference 5.61). At 12 weeks after surgery, declines from baseline were significant in the TOI (p = 0.004; score decline 8.99), PWB (p < 0.001; score decline 2.83), and FWB (p < 0.001; score decline 3.42) in the mitomycin group but not the oxaliplatin group. CONCLUSIONS: Compared with mitomycin, HIPEC perfusion with oxaliplatin results in significantly better physical and functional outcomes. With similar survival outcomes and complication rates, oxaliplatin should be considered as the chemoperfusion agent of choice in mucinous appendiceal cancer patients undergoing CRS/HIPEC.

Cytokine and goblet cell gene expression in equine cyathostomin infection and larvicidal anthelmintic therapy.

AIMS: The role of the immune response to cyathostomin infections in horses remains unknown. Intestinal goblet cell hyperplasia has previously been noted as a component in cyathostomin infection; however, the function is unclear. The goal of this study was to evaluate the local and systemic gene expression to cyathostomin infections following larvicidal treatment and explore their relation to goblet cells. METHODS AND RESULTS: Thirty-six ponies with naturally acquired cyathostomin infections were randomly allocated into three groups: fenbendazole-treated (10 mg/kg PO 5 days), moxidectin-treated (0.4 mg/kg PO once) and untreated control. Whole blood from all horses was collected weekly, and tissue samples from the large intestine collected during necropsy at 2 and 5 weeks post-treatment (WPT). Gene expression of interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-22, IFN-γ, resistin-like molecule beta (RELM-ß), Mucin 2 (MUC2) and tumour necrosis factor (TNF)-α was measured using qRT-PCR. There were statistically significant linear correlations between luminal worm burdens and MUC2 (r = -.2358) and RELM-ß (r = -.2261). CONCLUSION: This suggests an active role of immune system post-treatment in parasite expulsion, specifically in goblet cells, and that the organs respond differently to treatment and the larvae themselves. This may have implications in the disease process and treatment.