Oncological outcomes post transoral robotic surgery (TORS) for HPV-associated oropharyngeal squamous cell carcinoma, a single-centre retrospective Australian study.

We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year period. A retrospective case series review was performed of patients undergoing primary surgical treatment for HPV-associated OPSCC through the St. Vincent's Head and Neck Cancer service from 2011 to 2022. The primary outcomes were to investigate complete resection of the primary tumour, rates of recurrence, and survival analysis. Secondary outcomes included complications, rates of adjuvant therapy, sites of recurrence and rates of percutaneous endoscopic gastrostomy (PEG). 184 patients underwent TORS-based therapy with neck dissection, and guideline-directed adjuvant therapy for HPV-associated OPSCC. Our median follow-up was 46 months. The positive margin rate on final histopathology analysis was 10.9%. Adjuvant therapy was indicated in 85 patients (46%). The local recurrence rate was 10.9% with the majority (80%) of patients recurring in the first 3 years since treatment. The disease-specific survival at 3 years was 98.6% and at 5 years was 94.4%. The 3-year and 5-year OS for the cohort was 96.7% and 92.5%, respectively. The presence of extranodal extension and positive margins were associated with increased risk of recurrence, whereas adjuvant therapy was found to be a protective factor for both overall recurrence and survival. Major complications occurred in 12 patients (6.5%), resulting in one death. This study has demonstrated that primary surgical therapy for HPV-associated OPSCC is a safe and effective treatment modality with low local recurrence and complication rates, and overall survival benefits.

Efficacy of preemptive analgesia treatments for the management of postoperative pain: a network meta-analysis.

BACKGROUND: Preemptive analgesia may improve postoperative pain management, but the optimal regimen is unclear. This study aimed to compare the effects and adverse events of preemptive analgesia on postoperative pain and opioid consumption. METHODS: In this network meta-analysis, 19 preemptive analgesia regimens were compared. Two authors independently searched databases, selected studies, and extracted data. Primary outcomes were the intensity of postoperative pain and opioid consumption. Secondary outcomes included the time to first analgesia rescue and incidence of postoperative nausea or vomiting (PONV). RESULTS: In total, 188 studies were included (13 769 subjects). Ten of 19 regimens reduced postoperative pain intensity compared with placebo, with mean differences 100-point scale ranging from -4.79 (95% confidence interval [CI]: -8.61 to -0.96.) for gabapentin at 48 h to -21.99 (95% CI: -36.97 to -7.02) for lornoxicam at 6 h. Eight regimens reduced opioid consumption compared with placebo, with mean differences ranging from -0.48 mg (95% CI: -0.89 to -0.08) i.v. milligrams of morphine equivalents (IMME) for acetaminophen at 12 h to -2.27 IMME (95% CI: -3.07 to -1.46) for ibuprofen at 24 h. Five regimens delayed rescue analgesia from 1.75 (95% CI: 0.59-2.91) h for gabapentin to 7.35 (95% CI: 3.66-11.04) h for epidural analgesia. Five regimens had a lower incidence of PONV compared with placebo, ranging from an odds ratio of 0.22 (95% CI: 0.11-0.42) for ibuprofen to 0.59 (95% CI: 0.40-0.87) for pregabalin. CONCLUSIONS: Use of preemptive analgesia reduces postoperative pain, opioid consumption, and postoperative nausea or vomiting, and delays rescue analgesia. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021232593.

Resveratrol for Weight Loss in Obesity: An Assessment of Randomized Control Trial Designs in ClinicalTrials.gov.

Resveratrol is a polyphenol that may improve weight loss outcomes in obese individuals. However, assessing the effectiveness of resveratrol supplementations as an appropriate intervention for weight loss in obesity across randomized control trials (RCTs) has been complicated by variability in their design. This study aims to evaluate design elements across RCTs of resveratrol interventions in obesity with weight loss as an end-point outcome, as recorded in ClinicalTrials.gov. We found discrepancies in participant inclusion criteria (sample size, age ranges, sex, BMI, medical conditions), interventional design (delivery modalities, dosages, duration) and primary outcomes measured (anthropomorphic, blood biomarkers). We identified a near three-fold variation in study sample size, two-fold variation in minimum inclusion age, five modalities of therapeutic resveratrol delivery with interventional durations ranging from two weeks to six months. Weight loss was only identified as a primary outcome in three of the seven studies evaluated. In conclusion, heterogeneity in trial design using resveratrol suggests that weight-loss-related outcomes are difficult to interpret and cross-validate. Indeed, conclusions drawn from human studies have been inconsistent, which may be attributed to study design heterogeneity including major differences in sample population, age, sex, BMI, underlying health conditions and end-point measures.

A single-cell tumor immune atlas for precision oncology.

The tumor immune microenvironment is a main contributor to cancer progression and a promising therapeutic target for oncology. However, immune microenvironments vary profoundly between patients, and biomarkers for prognosis and treatment response lack precision. A comprehensive compendium of tumor immune cells is required to pinpoint predictive cellular states and their spatial localization. We generated a single-cell tumor immune atlas, jointly analyzing published data sets of >500,000 cells from 217 patients and 13 cancer types, providing the basis for a patient stratification based on immune cell compositions. Projecting immune cells from external tumors onto the atlas facilitated an automated cell annotation system. To enable in situ mapping of immune populations for digital pathology, we applied SPOTlight, combining single-cell and spatial transcriptomics data and identifying colocalization patterns of immune, stromal, and cancer cells in tumor sections. We expect the tumor immune cell atlas, together with our versatile toolbox for precision oncology, to advance currently applied stratification approaches for prognosis and immunotherapy.

Aberrant Zip14 expression in muscle is associated with cachexia in a Bard1-deficient mouse model of breast cancer metastasis.

Nearly 80% of advanced cancer patients are afflicted with cachexia, a debilitating syndrome characterized by extensive loss of muscle mass and function. Cachectic cancer patients have a reduced tolerance to antineoplastic therapies and often succumb to premature death from the wasting of respiratory and cardiac muscles. Since there are no available treatments for cachexia, it is imperative to understand the mechanisms that drive cachexia in order to devise effective strategies to treat it. Although 25% of metastatic breast cancer patients develop symptoms of muscle wasting, mechanistic studies of breast cancer cachexia have been hampered by a lack of experimental models. Using tumor cells deficient for BARD1, a subunit of the BRCA1/BARD1 tumor suppressor complex, we have developed a new orthotopic model of triple-negative breast cancer that spontaneously metastasizes to the lung and leads to systemic muscle deterioration. We show that expression of the metal-ion transporter, Zip14, is markedly upregulated in cachectic muscles from these mice and is associated with elevated intramuscular zinc and iron levels. Aberrant Zip14 expression and altered metal-ion homeostasis could therefore represent an underlying mechanism of cachexia development in human patients with triple-negative breast cancer. Our study provides a unique model for studying breast cancer cachexia and identifies a potential therapeutic target for its treatment.

Modulation of airway epithelial antiviral immunity by fungal exposure.

Multiple pathogens, such as bacteria, fungi, and viruses, have been frequently found in asthmatic airways and are associated with the pathogenesis and exacerbation of asthma. Among these pathogens, Alternaria alternata (Alt), a universally present fungus, and human rhinovirus have been extensively studied. However, their interactions have not been investigated. In the present study, we tested the effect of Alt exposure on virus-induced airway epithelial immunity using live virus and a synthetic viral mimicker, double-stranded RNA (dsRNA). Alt treatment was found to significantly enhance the production of proinflammatory cytokines (e.g., IL-6 and IL-8) induced by virus infection or dsRNA treatment. In contrast to this synergistic effect, Alt significantly repressed type I and type III IFN production, and this impairment led to elevated viral replication. Mechanistic studies suggested the positive role of NF-κB and mitogen-activated protein kinase pathways in the synergism and the attenuation of the TBK1-IRF3 pathway in the inhibition of IFN production. These opposite effects are caused by separate fungal components. Protease-dependent and -independent mechanisms appear to be involved. Thus, Alt exposure alters the airway epithelial immunity to viral infection by shifting toward more inflammatory but less antiviral responses.

Effect of a milk formula containing probiotics on the fecal microbiota of asian infants at risk of atopic diseases.

The fecal microbiota of 37 infants with (n = 20) or without (n = 17) probiotic administration was evaluated on D 3, and at 1, 3, and 12 mo by fluorescence in situ hybridization-flow cytometry (FISH-FC), PCR, and bacteriological culture methods. They represent consecutive subjects of an ongoing double-blind, placebo-controlled trial on a probiotic formula (LGG and Bifidobacterium longum) administered during the first 6 mo of life. Despite varying composition in each baby, there was a general bacterial colonization pattern in the first year. Bifidobacteria increased markedly (p = 0.0003) with a parallel decrease in Enterobacteriaceae (p < 0.001) and Bacteroides-Prevotella (p = 0.005) populations. Eubacterium rectale-Clostridium coccoides (p < 0.001) and Atopobium (p = 0.039) groups also gradually increased. This overall pattern was unaffected by probiotic administration (p > 0.05). B. longum (p = 0.005) and Lactobacillus rhamnosus (p < 0.001) were detected more frequently in probiotic group during supplementation, but no difference after supplementation had ceased (p > 0.05). Cultured lactic acid bacteria were also more numerous in the probiotic-administered babies during treatment period (log CFU/g 8.4 versus 7.4; p = 0.035). Our results indicate that supplemented strains could be detected but did not persist in the bowel once probiotic administration had ceased.