Return to work and self-reported swallowing following transoral robotic surgery for early-stage oropharyngeal squamous cell carcinoma: A retrospective cohort study.

BACKGROUND: Treatment de-intensification, including transoral robotic surgery (TORS), may outcomes in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). Early return to work (RTW) improves quality of life in oncology patients. Our objective was to compare the RTW time in OPSCC patients undergoing primary TORS or chemoradiotherapy (CRT). We investigated the role of treatment modality on self-reported swallowing function. METHODS: All patients were adults diagnosed with early-stage (T1-2, N0-2) OPSCC and treated via primary TORS or CRT. We performed 1:1 exact case matching based on tumor stage and subsite. We collected RTW outcomes for all patients. We also reported MD Anderson Dysphagia Index (MDADI) scores up to 24 months from the end of treatment. We performed statistical analyses and comparison of RTW and MDADI outcomes based on treatment group. RESULTS: Overall, 26 patients undergoing primary TORS and 25 undergoing primary CRT were included. We found a significant improvement in RTW in TORS patients compared to CRT (TORS: 54 days (1.8 months), IQR: 30.8; CRT: 164 days (5.4 months), IQR: 109; W=587, p = 9.28e-08) independent of HPV status, tonsillar subsite, and radiotherapy alone. Primary TORS had a 16.2-fold (95 % CI: 5.78-45.5) higher likelihood of returning to work than primary CRT patients. Primary TORS also had better MDADI scores within two years of treatment. CONCLUSIONS: In OPSCC, primary TORS accelerated RTW and improved swallowing when compared to primary CRT. The potential economic advantage of returning to work sooner should be discussed when reviewing treatment options with patients.

High proportion of PD-1 and CD39 positive CD8+ tissue resident T lymphocytes correlates with better clinical outcome in resected human oesophageal adenocarcinoma.

OBJECTIVE: To understand the CD8+ tumour infiltrating lymphocyte (TIL) compartment of oesophageal adenocarcinoma (OAC) with regards to markers of lymphocyte exhaustion, tissue residency and to identify possible reasons behind differential responses to therapy. DESIGN: Tumour samples from 44 patients undergoing curative resection for OAC were assessed by flow cytometry for presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of PD-1 and CD39 positive OAC TILs were sorted, and bulk RNA sequencing undertaken using a modified SmartSeq2 protocol. Flow cytometric assessment of functionality was completed. RESULTS: A higher proportion of antigen experienced CD8+ OAC TILs was associated with improved survival following surgery; while, high double positivity (DP) for PD-1 and CD39 among these TILs also correlated significantly with outcome. These DP TILs possess a minority population which is positive for the markers of exhaustion TIM3 and LAG3. Transcriptomic assessment of the PD-1 and CD39 DP TILs demonstrated enrichment for a tissue resident memory T lymphocyte (TRM) phenotype associated with improved survival in other cancers, reinforced by positivity for the canonical TRM marker CD103 by flow cytometry. This population demonstrated maintained functional capacity both in their transcriptomic profile, and on flow cytometric assessment, as well as preserved proliferative capacity. CONCLUSION: Resected OAC are variably infiltrated by PD-1 and CD39 DP TILs, an abundance of which among lymphocytes is associated with improved survival. This DP population has an increased, but still modest, frequency of TIM3 and LAG3 positivity compared to DN, and is in keeping with a functionally competent TRM phenotype.

Stability study of Nepeta cataria iridoids analyzed by LC/MS.

INTRODUCTION: Catnip (Nepeta cataria, L.) has well-documented applications in arthropod repellency because of its bioactive iridoids. Long-term stability of nepetalactones and other iridoids in N. cataria are needed to develop as effective pest repellents. OBJECTIVES: The present work intends to measure iridoid concentration over time in biomass, plant extracts, and extract solution while identifying degradative byproducts under different storage conditions. METHODOLOGY: Samples of desiccated biomass, ethanol extract, and extract in ethanol solution were stored in ambient light or darkness. Through UHPLC-QTOF/MS or UHPLC-QQQ/MS, the concentration of Z,E-nepetalactone, E,Z-nepetalactone, nepetalic acid, and dihydronepetalactone were examined over 2 years and statistically analyzed for determination of best storage practices. Degradation kinetics were applied to each analyte using graphical estimation. With targeted formula searching, degradative byproducts were identified and quantified. RESULTS: Light exposure caused significant decreases in E,Z-nepetalactone concentration in all sample types, while having no effect on Z,E-nepetalactone as it decayed more rapidly. Extract samples lost nepetalactone content faster than biomass or extract solution. Dihydronepetalactone levels were low, but never declined over 2 years. Nepetalic acid increased over some periods, depending on sample type, indicating a relationship between the acid and nepetalactone. Four degradative byproducts-nepetonic acid, dehydronepetalactone, an anhydride, and an ethanolic ester-were identified, with variable responses to light exposure. CONCLUSIONS: Protecting catnip products from light is necessary to preserve nepetalactones, and a discernable difference in nepetalactone isomer stability was discovered. Identifying Nepeta chemotypes rich in dihydronepetalactone may provide more resilient botanicals as starting materials for processing.

Active video games as an adjunct to pulmonary rehabilitation of patients with Chronic Obstructive Pulmonary Disease: a commentary on a systematic review.

Pulmonary rehabilitation is a key evidence-based intervention to improve the outcomes of people living with Chronic Obstructive Pulmonary Disease (COPD). However, there are challenges in delivering pulmonary rehabilitation including reduced referral rates and suboptimal uptake and completion rates. Active video game interventions, when used as an adjunct, may increase the adoption of and access to pulmonary rehabilitation. This commentary summarises and critically appraises a systematic review which investigated the effectiveness of active video games as a supplementary component in the pulmonary rehabilitation of individuals suffering from chronic obstructive pulmonary disease.

Distrust in the Health Care System and Adherence to Direct-Acting Antiviral Therapy among People with Hepatitis C Virus Who Inject Drugs.

This study is a secondary analysis of a randomized clinical trial (October 2013-April 2017) involving 150 People Who Inject Drugs (PWIDs) with hepatitis C virus (HCV) seen in opioid agonist treatment programs in the Bronx, New York, and investigates the impact of distrust in the healthcare system on adherence to Direct-Acting Antivirals (DAAs) HCV treatment therapy among PWIDs. The distrust was scaled on a 9-item instrument and the adherence to DAA medications was measured using electronic blister packs. This study demonstrated a significant inverse relationship between levels of distrust and medication adherence: 71.8 ± 2.2% (se) vs. 77.9 ± 1.8%, p = 0.024 between participants with higher and lower distrust levels. Despite the absence of significant association of distrust with sociodemographic or substance use characteristics, these findings suggest that building trust within the healthcare system is paramount for improving adherence to DAAs among PWIDs. The results call for a healthcare approach that emphasizes trust-building through patient-centered care, sensitivity training, peer support, and health system reform to effectively address the treatment needs of this marginalized population.

Moderate-intensity aerobic exercise training improves CD8+ tumor-infiltrating lymphocytes effector function by reducing mitochondrial loss.

Aerobic exercise training (AET) has emerged as a strategy to reduce cancer mortality, however, the mechanisms explaining AET on tumor development remain unclear. Tumors escape immune detection by generating immunosuppressive microenvironments and impaired T cell function, which is associated with T cell mitochondrial loss. AET improves mitochondrial content and function, thus we tested whether AET would modulate mitochondrial metabolism in tumor-infiltrating lymphocytes (TIL). Balb/c mice were subjected to a treadmill AET protocol prior to CT26 colon carcinoma cells injection and until tumor harvest. Tissue hypoxia, TIL infiltration and effector function, and mitochondrial content, morphology and function were evaluated. AET reduced tumor growth, improved survival, and decreased tumor hypoxia. An increased CD8+ TIL infiltration, IFN-γ and ATP production promoted by AET was correlated with reduced mitochondrial loss in these cells. Collectively, AET decreases tumor growth partially by increasing CD8+ TIL effector function through an improvement in their mitochondrial content and function.

Phosphonodiamidate prodrugs of phosphoantigens (ProPAgens) exhibit potent Vγ9/Vδ2 T cell activation and eradication of cancer cells.

The phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) is an established activator of Vγ9/Vδ2 T cells and stimulates downstream effector functions including cytotoxicity and cytokine production. In order to improve its drug-like properties, we herein report the design, synthesis, serum stability, in vitro metabolism, and biological evaluation of a new class of symmetrical phosphonodiamidate prodrugs of methylene and difluoromethylene monophosphonate derivatives of HMBPP. These prodrugs, termed phosphonodiamidate ProPAgens, were synthesized in good yields, exhibited excellent serum stability (>7 h), and their in vitro metabolism was shown to be initiated by carboxypeptidase Y. These phosphonodiamidate ProPAgens triggered potent activation of Vγ9/Vδ2 T cells, which translated into efficient Vγ9/Vδ2 T cell-mediated eradication of bladder cancer cells in vitro. Together, these findings showcase the potential of these phosphonodiamidate ProPAgens as Vγ9/Vδ2 T cell modulators that could be further developed as novel cancer immunotherapeutic agents.

Trends in using intraoperative parathyroid hormone monitoring during parathyroidectomy: Protocol and rationale for a cross-sectional survey study of North American surgeons.

Hyperparathyroidism is a common endocrine disorder that occurs secondary to abnormal parathyroid gland functioning. Depending on the type of hyperparathyroidism, surgical extirpation of hyperfunctioning parathyroid glands can be considered for disease cure. Intraoperative parathyroid hormone (IOPTH) monitoring improves outcomes in patients undergoing surgery for primary hyperparathyroidism, but studies are needed to characterize its institutional adoption and its role in surgery for secondary and tertiary hyperparathyroidism, as these entities can be difficult to cure. Hence, we will perform a cross-sectional survey study of surgeon rationale, operational details, and barriers associated with IOPTH monitoring adoption across North America. We will utilize a convenience sampling technique to distribute an online survey to head and neck surgeons and endocrine surgeons across North America. This survey will be distributed via email to three North American professional societies (i.e., Canadian Society for Otolaryngologists-Head and Neck Surgeons, American Head and Neck Society, and American Association of Endocrine Surgeons). The survey will consist of 30 multiple choice questions that are divided into three concepts: (1) participant demographics and training details, (2) details of surgical adjuncts during parathyroidectomy, and (3) barriers to adoption of IOPTH. Descriptive analyses and multiple logistic regression will be used to evaluate the impact of demographic, institutional, and training variables on the use of IOPTH monitoring in surgery for all types of hyperparathyroidism and barriers to IOPTH monitoring adoption. Ethics approval was obtained by the Hamilton Integrated Research Ethics Board (2024-17173-GRA). These findings will characterize surgeon and institutional practices with regards to IOPTH monitoring during parathyroid surgery and will inform future trials aimed to optimize the use of IOPTH monitoring in secondary and tertiary hyperparathyroidism.

Reduction of benztropine use duration in acute psychiatry: A quality improvement initiative.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Secondary to the risk of antipsychotic-induced acute dystonia, prophylactic use of benztropine is occasionally warranted but is recommended for no longer than 7 days after initiating an antipsychotic, correlating to the period of highest dystonia risk. Despite the associated increased anticholinergic burden, many clinicians continue to order benztropine for periods exceeding the recommended prophylactic duration. We investigated the reduction of benztropine use duration subsequent to implementation of truncated electronic entry orders to improve benztropine prescribing within an acute psychiatric facility. METHODS: Data were collected for psychiatric inpatients admitted between January and June 2020 who were prescribed scheduled benztropine. In a quality improvement initiative implemented in April 2022, electronic orders for benztropine were modified from a 180-day to a 7-day duration, with subsequent postintervention data collection. The primary outcomes included a change in the duration of benztropine use for any indication in the hospital, and a change in the percentage of patients meeting predetermined "unnecessary use" criteria. Secondary analyses included the percentage of patients with discharge prescriptions for scheduled benztropine (either for prophylaxis or for other indications) in the pre- and postintervention periods. RESULTS: 73 pre- and 77 postintervention individual patients/encounters were included. Following the intervention, in-hospital duration of benztropine use for any indication decreased from a median of 14 days to a median of 7.5 days (P < 0.05), and appropriate use increased by 92.9%. The percentage of patients with prescriptions for scheduled benztropine decreased from 67.1% in the preintervention group to 29.9% in the postintervention group. CONCLUSION: Decreased benztropine use duration, by means of truncated order entry sentences, during inpatient psychiatric admissions, appears feasible regardless of dual antipsychotic or first-generation antipsychotic use, and may reduce the rates of benztropine prescriptions written for discharge.

An experimental study of the heterogeneity and anisotropy of porcine meniscal ultimate tensile strength.

Characterizing the ultimate tensile strength (UTS) of the meniscus is critical in studying knee damage and pathology. This study aims to determine the UTS of the meniscus with an emphasis on its heterogeneity and anisotropy. We performed tensile tests to failure on the menisci of six month old Yorkshire pigs at a low strain rate. Specimens from the anterior, middle and posterior regions of the meniscus were tested in the radial and circumferential directions. Then the UTS was obtained for each specimen and the data were analyzed statistically, leading to a comprehensive view of the variations in porcine meniscal strength. The middle region has the highest average strength in the circumferential (43.3 ± 4.7 MPa) and radial (12.6 ± 2.2 MPa) directions. This is followed by the anterior and posterior regions, which present similar average values (about 34.0MPa) in circumferential direction. The average strength of each region in the radial direction is approximately one-fourth to one-third of the value in the circumferential direction. This study is novel as it is the first work to focus on the experimental methods to investigate the heterogeneity and anisotropy only for porcine meniscus.

Socioeconomic Status, Length of Stay, and Postoperative Complications in Oral Cavity Squamous Cell Carcinoma.

Background: Despite universal healthcare in Canada, low socioeconomic status (SES) has been associated with worse survival in oral cavity squamous cell carcinoma (OCSCC) patients. However, the relationship between SES and outcomes during the acute postoperative period is poorly defined. Hamilton, Ontario, presents a unique population with widely varying SES within the same geography. The objective of this study was to examine the relationship between SES, length of hospital stay (LOHS), and postoperative complications in OCSCC. Methods: Newly diagnosed OCSCC patients receiving primary surgical treatment from 2010 to 2014 were identified within a prospectively collected database. Inclusion criteria included age >18 years old, pathological diagnosis of oral cavity cancer, and primary surgical treatment with curative intent. Patients were excluded if they were undergoing palliative treatment or had previous head and neck surgery/radiotherapy. Postal codes were used to identify neighborhood-level socioeconomic variables via 2011 Canada Census data. Income quartiles were defined from groups of neighboring municipalities based on Canada Census definitions. Demographic, social, pathological, staging, and treatment data were collected through chart review. Results: One hundred and seventy-four patients were included in the final analysis. OCSCC patients with lower SES were more likely to be younger (P = .041), male (P = .040), have significant tobacco and alcohol use (P = .001), higher Charlson Comorbidity Index (CCI; P = .014), lower levels of education (P = .001), and have lower employment levels (P = .001). Lower SES patients had higher clinical tumor (P = .006) and clinical nodal (P = .004) staging and were more likely to receive adjuvant therapy (P = .001) and G-tubes (P = .001). Multivariable regression analysis showed that low SES was a statistically significant predictor of postoperative complications [ß 2.50 (95% confidence interval (CI) 0.200, 3.17); P = .014] and LOHS [ß 2.03 (95% CI 1.06, 2.99); P = .0001]. Tobacco and alcohol use, clinical tumor, and nodal stage, CCI, and planned adjuvant therapy were also statistically significant predictors of postoperative complications and LOHS (P < .05). Conclusion: Patients with lower SES have more advanced OCSCC disease with increased comorbidities that owes itself to more acute postoperative complications and LOHS within this study population. Patients with low SES should be identified as patients that require more support during their cancer treatment.

Interactions between microsporidia and other members of the microbiome.

The microbiome is the collection of microbes that are associated with a host. Microsporidia are intracellular eukaryotic parasites that can infect most types of animals. In the last decade, there has been much progress to define the relationship between microsporidia and the microbiome. In this review, we cover an increasing number of reports suggesting that microsporidia are common components of the microbiome in both invertebrates and vertebrates. These microsporidia infections can range from mutualistic to pathogenic, causing several physiological phenotypes, including death. Infection with microsporidia often causes a disruption in the normal microbiome, with both increases and decreases of bacterial, fungal, viral, and protozoan species being observed. This impact on the microbiome can occur through upregulation and downregulation of innate immunity as well as morphological changes to tissues that impact interactions with these microbes. Other microbes, particularly bacteria, can inhibit microsporidia and have been exploited to control microsporidia infections. These bacteria can function through regulating immunity, secreting anti-microsporidia compounds, and, in engineered versions, expressing double-stranded RNA targeting microsporidia genes. We end this review by discussing potential future directions to further understand the complex interactions between microsporidia and the other members of the microbiome.

Analysis, treatment modality and demographic characteristics of urolithiasis patients visiting Korle-Bu Teaching Hospital in Ghana.

Background: Globally urolithiasis is on the rise and gradually becoming a public health concern due to the associated complications. This study reviewed the demographic characteristics, the chemical composition of stones, treatment modality and duration of hospitalisation of urolithiasis patients at Korle-Bu Teaching Hospital, Accra, Ghana. Materials and Methods: This was a retrospective study conducted between March 2019 and April 2022. Data from consecutive patients treated for urolithiasis were used for this study. Data on demographic characteristics, stones chemical composition, urine factors, urolithiasis treatment modality and duration of hospital stay after therapy were collated and analysed using descriptive and inferential approaches. Results: The age of the patients ranged from 2 to 75 years with a mean of 45 (±13.4). The predominant age group for stone formation was 30-39 years - 52(26.3%). Urolithiasis was common among patients in the formal employment sector: 81(40.9%). All stones had two or more chemical compositions, with the combination of calcium oxalate monohydrate, calcium oxalate dihydrate and uric acid being the predominant stone type: 88(57.5%). Ureteroscopy with semi-rigid and Percutaneous nephrolithotomy were the predominant treatment modalities: 105(53.0%) and 74(37.4%), respectively. Escherichia coli was responsible for most urinary tract infections in urolithiasis patients 8(4.0%) and the least duration of hospital stay after the procedure was associated with the use of semi-rigid ureteroscope as the treatment modality with a median duration of 2 days (1-2 days) with P < 0.0001. Conclusions: Urolithiasis was predominant among professionals in the formal sector. All stones were mixed with Calcium oxalate monohydrate, calcium oxalate dihydrate, and uric acid combination being the majority. Ureteroscopy with semi-rigid and percutaneous nephrolithotomy were the common treatment modality.

Commentary on packing vs non-packing of pilonidal sinus cavities after incision and drainage.

Pilonidal sinus disease (PSD) manifests as an inflammatory skin condition typically emerging within the anal cleft. The prevalence of this disease varies in high income countries. This disease is associated with significant physical and psychosocial distress. Surgery is an option for managing PSD; yet, surgical methods vary, and a universally accepted gold standard approach is lacking, leading to current practices that are diverse and subject to ongoing debate. One such point of contention revolves around the decision to use packing or opt for a non-packing approach following surgery. Mohamedahmed et al (2021) conducted a systematic review to evaluate the comparative outcomes of packing versus non-packing of an abscess cavity following incision and drainage of cutaneous abscess on any part of the body. This commentary aims to critically appraise the methods used within the review by Mohamedahmed et al (2021) and expand upon the findings in the context of treatment and management of PSD.

Corrigendum: Non-invasive methods to assess muscle function in dogs: a scoping review.

[This corrects the article DOI: 10.3389/fvets.2023.1116854.].

Pain and diet: A summary of the evidence for the role of diet modification in chronic pain.

Chronic pain constitutes a significant burden to patients and healthcare systems. For many patients, the only option is to attempt to manage their pain within their daily lives. Here, we review evidence provided by three systematic reviews for the effect of diet and diet supplements on patients' experience of chronic pain.

Muscle function assessment of the hindlimbs in healthy dogs using acoustic myography.

INTRODUCTION: Impaired muscle function is a frequent consequence of musculoskeletal disorders in dogs. Musculoskeletal disorders, especially stifle joint diseases, are common in dogs and assessment of muscle function in dogs is clinically relevant. Acoustic myography (AMG) is a non-invasive method to assess muscle activity. Quantifying muscle function in normal dogs could help identify clinically relevant changes in dogs with orthopaedic disease and allow targeted interventions to improve recovery in these. The objectives of the study were to characterize hindlimb muscle function in healthy dogs using AMG and to investigate the repeatability and reproducibility of AMG in dogs. METHODS: Healthy dogs (15-40 kg) without musculoskeletal disorders were recruited and screened for eligibility to participate in the study. The muscle activity in four hindlimb muscles related to the stifle was assessed using AMG. The degree of symmetry between the hindlimbs in these dogs was investigated and the reliability of AMG was evaluated. RESULTS AND CONCLUSIONS: The study population comprised 21 dogs. Reference intervals and symmetry indices for AMG scores of the hindlimb muscles were identified, with highest variability for the E-scores. For all AMG-scores, same-day variation was lower than between days variation, and both were lowest for S- and T-scores. Further investigation is needed to establish if AMG can enable discrimination between dogs with altered muscle function and healthy dogs.

Autosomal dominant polycystic kidney disease with ectopic unilateral multicystic kidney: a case report.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder and the fourth cause of death of end-stage renal disease. The disease has a prevalence of 1:400-1:1000 accounting for 10% of patients on dialysis. In most ADPKD patients, bilateral kidneys are similarly affected, with numerous fluid-filled cysts arising from different nephron segments. Only a few cases of ADPKD with ectopic unilateral multicystic kidney have been reported. It has been observed that the deterioration of their kidney function seemed to be quicker than their age- and sex-matched controls and siblings especially when the ectopic kidney is dysplastic. CASE PRESENTATION: We report a case of a 46-year-old Ghanaian male patient who presented with left flank pain and hematuria with high BP and deranged renal function. Abdominal ultrasonography showed both kidneys to be larger than normal and had multiple cysts of varying sizes with the right kidney located in the right iliac fossa. Follow up Abdominopelvic computer tomographic scan (CT-Scan) without contrast showed enlarged kidneys with the renal parenchyma replaced by innumerable cyst of varying sizes. The right kidney was ectopically located in the right aspect of the pelvis. A diagnosis of ADPKD with right pelvic ectopic multicystic kidney was made. He was put on antihypertensives, analgesia for the left flank pain and to have follow up at the urology and nephrology departments. CONCLUSION: In most ADPKD patients, bilateral kidneys are similarly affected. Only a few cases of ADPKD with ectopic unilateral multicystic kidney have been reported. It has been observed that the deterioration of their kidney function seemed to be quicker than their age- and sex-matched controls and siblings especially when the ectopic kidney is dysplastic.

Effect of center of rotation of angulation-based levelling osteotomy on instantaneous center of rotation ex vivo.

Cranial cruciate ligament rupture is a common cause of femorotibial instability in dogs. Despite numerous techniques being described for achieving joint stabilization, no consensus exists on the optimal management strategy. This ex vivo study utilized the path of the instantaneous center of rotation (ICR) to compare normal, pathological and treated joints. Fluoroscopic recordings of seven limbs from a previous study of canine stifle joint stability following center of rotation of angulation-based levelling osteotomy (CBLO) with and without hamstring loading were analyzed using least-squares approximation of the ICR and estimation of percentage gliding (vs. rolling) to determine if alterations in ICR path and gliding caused by CCL transection and following meniscal release could be normalized by CBLO. In intact joints, the ICR path was located mid-condyle, but this shifted significantly proximally and caudally following CCL transection and medial meniscal release (p < 0.007, p < 0.04). Hamstring loading resulted in qualitative and some quantitative improvements in joint movement based on percentage gliding movement analysis. The ICR path after CBLO remained significantly different to the intact location with or without a hamstring load (p < 0.02, p < 0.04), potentially consistent with CBLO aims of mild residual instability. CBLO resulted in percentage gliding characteristics not significantly different to intact joints (p > 0.08). Qualitative improvements in ICR path and percentage gliding quantities and variability suggest that hamstring loading positively influences joint biomechanics and that further investigation of this role ex vivo and clinically is warranted.