The role of collaboration in educating the global pediatric anesthesia workforce.

An estimated 1.7 billion children and adolescents do not have access to safe and affordable surgical care, and the vast majority of these are located in low-middle-income countries (LMICs). Pediatric anesthesia, a specialized field that requires a diverse set of knowledge and skills, has seen various advancements over the years and has become well-established in upper-middle and high-income countries. However, in LMICs, due to a multitude of factors including severe workforce shortages, this has not been the case. Collaborations play a vital role in increasing the capacity of pediatric anesthesiology educators and training the pediatric anesthesia workforce. These efforts directly increase access for children who require surgical intervention. Collaboration models can be operationalized through bidirectional knowledge sharing, training, resource allocation, research and innovation, quality improvement, networking, and advocacy. This article aims to highlight a few of these collaborative efforts. Specifically, the role that the World Federation of Societies of Anaesthesiologists, the Safer Anesthesia from Education program, the Asian Society of Pediatric Anaesthesiologists, Pediatric Anesthesia Training in Africa, the Paediatric Anaesthesia Network New Zealand, the Safe Pediatric Anesthesia Network and two WhatsApp™ groups (global ped anesthesia and the Pediatric Difficult Intubation Collaborative) have played in improving anesthesiology care for children.

Children's surgery and the emergency, critical, and operative care resolution: Immediate actions to eliminate disparities in surgery, anesthesia, and perioperative care for all children.

Around 1.7 billion children lack access to surgical care worldwide. To reinvigorate the efforts to address these disparities and support work to address global challenges in surgery, anesthesia, emergency, and critical care, the World Health Assembly passed World Health Organization Resolution World Health Assembly 76.2: Integrated emergency, critical and operative care for universal health coverage and protection from health emergencies (ECO) in 2023. This resolution highlights the integral role of surgery, anesthesia, and perioperative care in health systems. However, understanding how best to operationalize this resolution is challenging. We review the ECO resolution and highlight points that the pediatric surgical and anesthesia community can leverage to advocate for its recommendations for operative care.

Children's surgery and the emergency, critical, and operative care resolution: immediate actions to eliminate disparities in surgical anesthesia and perioperative care for all children.

1.7 billion children lack access to surgical care worldwide. The emergency, critical, and operative care (ECO) resolution represents a call to action to reinvigorate the efforts to address these disparities. We review the ECO resolution and highlight the avenues that may be utilized in advocating for children's surgical care.

Evolution of cisplatin resistance through coordinated metabolic reprogramming of the cellular reductive state.

BACKGROUND: Cisplatin (CDDP) is a mainstay treatment for advanced head and neck squamous cell carcinomas (HNSCC) despite a high frequency of innate and acquired resistance. We hypothesised that tumours acquire CDDP resistance through an enhanced reductive state dependent on metabolic rewiring. METHODS: To validate this model and understand how an adaptive metabolic programme might be imprinted, we performed an integrated analysis of CDDP-resistant HNSCC clones from multiple genomic backgrounds by whole-exome sequencing, RNA-seq, mass spectrometry, steady state and flux metabolomics. RESULTS: Inactivating KEAP1 mutations or reductions in KEAP1 RNA correlated with Nrf2 activation in CDDP-resistant cells, which functionally contributed to resistance. Proteomics identified elevation of downstream Nrf2 targets and the enrichment of enzymes involved in generation of biomass and reducing equivalents, metabolism of glucose, glutathione, NAD(P), and oxoacids. This was accompanied by biochemical and metabolic evidence of an enhanced reductive state dependent on coordinated glucose and glutamine catabolism, associated with reduced energy production and proliferation, despite normal mitochondrial structure and function. CONCLUSIONS: Our analysis identified coordinated metabolic changes associated with CDDP resistance that may provide new therapeutic avenues through targeting of these convergent pathways.

Virtual Human-Delivered Interviews for Patients With Chronic Pain: Feasibility, Acceptability, and a Pilot Randomized Trial of Standard Medical, Psychosocial, and Educational Interviews.

OBJECTIVE: Seminal advances in virtual human (VH) technology have introduced highly interactive, computer-animated VH interviewers. Their utility for aiding in chronic pain care is unknown. We developed three interactive telehealth VH interviews-a standard pain-focused, a psychosocial risk factor, and a pain psychology and neuroscience educational interview. We then conducted a preliminary investigation of their feasibility, acceptability, and efficacy. We also experimentally compared a human and a computer-generated VH voice. METHODS: Patients ( N = 94, age = 22-78 years) with chronic musculoskeletal pain were randomly assigned to the standard ( n = 31), psychosocial ( n = 34), or educational ( n = 29) VH interview and one of the two VH voices. Acceptability ratings included patient satisfaction and expectations/evaluations of the VH interview. Outcomes assessed at baseline and about 1-month postinterview were pain intensity, interference, emotional distress, pain catastrophizing, and readiness for pain self-management. Linear mixed-effects models were used to test between- and within-condition effects. RESULTS: Acceptability ratings showed that satisfaction with the VH and telehealth format was generally high, with no condition differences. Study attrition was low ( n = 5). Intent-to-treat-analyses showed that, compared with the standard interview, the psychosocial interview yielded a significantly greater reduction in pain interference ( p = .049, d = 0.43) and a marginally greater reduction in pain intensity ( p = .054, d = 0.36), whereas the educational interview led to a marginally greater yet nonsignificant increase in readiness for change ( p = .095, d = 0.24), as well as several significant improvements within-condition. Results did not differ by VH voice. CONCLUSIONS: Interactive VH interviewers hold promise for improving chronic pain care, including probing for psychosocial risk factors and providing pain-related education.

The retention and bioavailability of phytochemicals in the manufacturing of baked snacks.

There is a growing body of evidence supporting the role that phytochemicals play in reducing the risk of various chronic diseases. Although there has been a rise in health products marketed as being "supergrains," "superfood," or advertising their abundance in antioxidants, these food items are often limited to powdered blends, dried fruit, nuts, or seeds, rarely intercepting the market of baked snacks. This is in part due to the still limited understanding of the impact that different industrial processes have on phytochemicals in a complex food matrix and their corresponding bioavailability. This review brings together the current data on how various industrial dehydration processes influence the retention and bioaccessibility of phytochemicals in baked snacks. It considers the interplay of molecules in an intricate snack matrix, limitations of conventional technologies, and constraints with consumer acceptance preventing wider utilization of novel technologies. Furthermore, the review takes a holistic approach, encompassing each stage of production-discussing the potential for inclusion of by-products to promote a circular economy and the proposal for a shift in agriculture toward biofortification or tailored growing of crops for their nutritional and post-harvest attributes.

Delivery of Safe Pediatric Anesthesia Care in the First 8000 days: Realities, Challenges, and Solutions in Low- and Middle-Income Countries.

BACKGROUND: Worldwide, perioperative mortality has declined over the past 50 years, but the reduction is skewed toward high-income countries (HICs). Currently, pediatric perioperative mortality is much higher in low- and middle-income countries (LMICs) compared to HICs, despite studied cohorts being predominantly low-risk. These disparities must be studied and addressed. METHODS: A narrative review of the literature was undertaken to identify contributing factors and potential knowledge gaps. Interventions aimed at alleviating the outcomes disparities are discussed, and recommendations are made for future directions. RESULTS AND CONCLUSIONS: There is a lack of adequately trained pediatric anesthesia providers in LMICs, and the number must be bolstered by making such training available. Essential anesthesia medications and equipment, in pediatric-appropriate sizes, are often not available; neither are essential infrastructure items. Perioperative staff are underprepared for emergent situations that may arise and simulation training may help to ameliorate this. The global anesthesia community has implemented several solutions to address these issues. The World Federation of Societies of Anaesthesiologists (WFSA) and Global Initiative for Children's Surgery have published standards that outline essential items for the provision of safe perioperative pediatric care. Several short educational courses have been developed and introduced in LMICs that either specifically address pediatric patients, or contain a pediatric component. The WFSA also maintains a collection of discrete tutorials for educational purposes. Finally, in Africa, large-scale, prospective data collection is underway to examine pediatric perioperative outcomes. More work needs to be done, though, to improve perioperative outcomes for pediatric patients in LMICs.

The Capnography Project.

Capnography is an essential tool used in the monitoring of patients during anesthesia and in critical care which, while required in most high-income countries, is unavailable in many low- and middle-income countries. Launched in 2020, the Smile Train-Lifebox Capnography Project aimed to find a "capnography solution" for resource-poor settings. The project was specifically interested in a capnography device that would meet the needs of the Smile Train partner hospitals to help monitor children requiring airway or cleft surgery. Project advisory and technical groups were formed and included representation from anesthesia practitioners from a balanced representation from all level of income countries, technical experts in capnography, and representatives from the Global Capnography Project (GCAP), the University of California at San Francisco Center for Health Equity in Surgery & Anesthesia (CHESA), and the World Federation of Societies of Anaesthesiologists (WFSA). Built upon the WFSA minimum capnometer specifications, a human centered design approach was used to develop a Target Product Profile. Seven manufacturers submitted 13 devices for consideration and 3 devices were selected for the testing phase. Each of these devices was evaluated for build quality, and clinical and usability performance. Based on the findings from the overall testing process, a combined capnography and pulse oximetry device by Zug Medical Systems was chosen. To accompany the new Smile Train-Lifebox capnograph, an international team of experienced anesthesiologists and educators came together to develop the necessary education materials. These materials were piloted in Ethiopia, subsequently modified, and endorsed by the education team. The device is now ready for distribution, with the accompanying education package, to the Smile Train network and beyond. In addition, a study is being planned to measure the impact of capnography introduction into operating rooms in resource-constrained settings.

REV7 Monomer Is Unable to Participate in Double Strand Break Repair and Translesion Synthesis but Suppresses Mitotic Errors.

Rev7 is a regulatory protein with roles in translesion synthesis (TLS), double strand break (DSB) repair, replication fork protection, and cell cycle regulation. Rev7 forms a homodimer in vitro using its HORMA (Hop, Rev7, Mad2) domain; however, the functional importance of Rev7 dimerization has been incompletely understood. We analyzed the functional properties of cells expressing either wild-type mouse Rev7 or Rev7K44A/R124A/A135D, a mutant that cannot dimerize. The expression of wild-type Rev7, but not the mutant, rescued the sensitivity of Rev7-/- cells to X-rays and several alkylating agents and reversed the olaparib resistance phenotype of Rev7-/- cells. Using a novel fluorescent host-cell reactivation assay, we found that Rev7K44A/R124A/A135D is unable to promote gap-filling TLS opposite an abasic site analog. The Rev7 dimerization interface is also required for shieldin function, as both Rev7-/- cells and Rev7-/- cells expressing Rev7K44A/R124A/A135D exhibit decreased proficiency in rejoining some types of double strand breaks, as well as increased homologous recombination. Interestingly, Rev7K44A/R124A/A135D retains some function in cell cycle regulation, as it maintains an interaction with Ras-related nuclear protein (Ran) and partially rescues the formation of micronuclei. The mutant Rev7 also rescues the G2/M accumulation observed in Rev7-/- cells but does not affect progression through mitosis following nocodazole release. We conclude that while Rev7 dimerization is required for its roles in TLS, DSB repair, and regulation of the anaphase promoting complex, dimerization is at least partially dispensable for promoting mitotic spindle assembly through its interaction with Ran.

Inhibition of nonsense-mediated decay rescues p53ß/γ isoform expression and activates the p53 pathway in MDM2-overexpressing and select p53-mutant cancers.

Inactivation of p53 is present in almost every tumor, and hence, p53-reactivation strategies are an important aspect of cancer therapy. Common mechanisms for p53 loss in cancer include expression of p53-negative regulators such as MDM2, which mediate the degradation of wildtype p53 (p53α), and inactivating mutations in the TP53 gene. Currently, approaches to overcome p53 deficiency in these cancers are limited. Here, using non-small cell lung cancer and glioblastoma multiforme cell line models, we show that two alternatively spliced, functional truncated isoforms of p53 (p53ß and p53γ, comprising exons 1 to 9ß or 9γ, respectively) and that lack the C-terminal MDM2-binding domain have markedly reduced susceptibility to MDM2-mediated degradation but are highly susceptible to nonsense-mediated decay (NMD), a regulator of aberrant mRNA stability. In cancer cells harboring MDM2 overexpression or TP53 mutations downstream of exon 9, NMD inhibition markedly upregulates p53ß and p53γ and restores activation of the p53 pathway. Consistent with p53 pathway activation, NMD inhibition induces tumor suppressive activities such as apoptosis, reduced cell viability, and enhanced tumor radiosensitivity, in a relatively p53-dependent manner. In addition, NMD inhibition also inhibits tumor growth in a MDM2-overexpressing xenograft tumor model. These results identify NMD inhibition as a novel therapeutic strategy for restoration of p53 function in p53-deficient tumors bearing MDM2 overexpression or p53 mutations downstream of exon 9, subgroups that comprise approximately 6% of all cancers.

Inhibition of the Phosphatidylinositol-3 Kinase Pathway Using Bimiralisib in Loss-of-Function NOTCH1-Mutant Head and Neck Cancer.

BACKGROUND: PI3K/mTOR inhibition leads to apoptosis of NOTCH1-mutant head and neck squamous cell carcinoma (HNSCC) cells. We tested the efficacy of the PI3K/mTOR inhibitor bimiralisib in patients with NOTCH1-mutant HNSCC. METHODS: Patients with recurrent/metastatic NOTCH1-mutant HNSCC who had progressed during chemotherapy and immunotherapy received bimiralisib until unacceptable toxicity or progression. To assess whether NOTCH1 mutations can be detected in blood, we measured circulating tumor DNA (ctDNA). To assess activated NOTCH1 protein levels, we quantitated cleaved NOTCH1 (cl-NOTCH) by immunohistochemistry. RESULTS: Eight patients were treated, and 6 were evaluable for response. The objective response rate was 17%. For all 8 patients, median progression-free and overall survival was 5 and 7 months, respectively. Bimiralisib was well tolerated, with expected hyperglycemia. Pharmacokinetic values were consistent with published studies. NOTCH1 mutations were detected in 83.3% of ctDNA. Staining for tumor cl-NOTCH1 was negative. The trial closed early due to sponsor insolvency. CONCLUSION: Although the trial was small, outcomes with bimiralisib were better than the historical standard of care; Results will need to be confirmed in a larger trial. The lack of cl-NOTCH1 was consistent with loss-of-function mutations and validated our mutation function algorithm. The ability to detect NOTCH1 mutations in blood will help future studies. (ClinicalTrials.gov Identifier: NCT03740100).

Management of patients with a persistently elevated PSA after radical prostatectomy: a narrative review.

INTRODUCTION: The management of the postoperative biological relapse of prostate cancer is most often based on salvage radiotherapy (SRT) with or without the addition of a variable duration of hormone therapy (HT). The indications for SRT +/- HT are established in the setting of a rising PSA level after a period where an undetectable PSA was achieved. However, in case of detectable PSA immediately after radical prostatectomy, the treatment options and prognosis are still unclear. MATERIALS AND METHODS: We conducted a narrative review based on an analysis of the literature focusing on articles targeting the population of patients with postoperative persistently detectable PSA level. Case reports, original articles, clinical trials, and published reviews were studied for this purpose. CONCLUSION: This article will describe current management of patients with detectable PSA immediately after radical prostatectomy, notably the contribution of modern imaging and new treatment options involving the combination of RT and HT.

Imetelstat in intermediate-2 or high-risk myelofibrosis refractory to JAK inhibitor: IMpactMF phase III study design.

Imetelstat, a first-in-class telomerase inhibitor, demonstrated meaningful clinical benefit including a robust symptom response rate and potential overall survival benefit in IMbark, a phase II study in intermediate-2 or high-risk myelofibrosis (MF) patients who have relapsed after or are refractory to JAK inhibitors. We describe the rationale and design for the phase III trial, IMpactMF (NCT04576156), an open-label evaluation of imetelstat versus best available therapy, excluding JAK inhibitors, in MF patients refractory to JAK inhibitor. Imetelstat 9.4 mg/kg is administered as an intravenous infusion every 21 days. Primary objective is to assess overall survival. Secondary objectives include symptom and spleen responses, progression-free survival, clinical response assessment, bone marrow fibrosis reduction, safety and pharmacokinetics. Biomarker, cytogenetics and mutation analyses will be performed.

Imetelstat is a new type of treatment being studied in patients with myelofibrosis (MF). Encouraging clinical benefits were seen in a phase II clinical trial of imetelstat in higher risk MF. This article discusses the ongoing phase III trial, called IMpactMF. IMpactMF is comparing imetelstat to best available therapy (BAT) in MF patients not responding to a specific type of treatment, a JAK inhibitor. Imetelstat is an intravenous infusion, given every 21 days. This study will determine if patients who receive imetelstat live longer than patients who are given BAT. It will also collect information on additional outcomes, including safety. Trial Registration Number: NCT04576156 (ClinicalTrials.gov).

Evaluation of Open Access Websites for Anesthesia Education.

BACKGROUND: While the prevalence of free, open access medical education resources for health professionals has expanded over the past 10 years, many educational resources for health care professionals are not publicly available or require fees for access. This lack of open access creates global inequities in the availability and sharing of information and may have the most significant impact on health care providers with the greatest need. The extent of open access online educational websites aimed for clinicians and trainees in anesthesiology worldwide is unknown. In this study, we aimed to identify and evaluate the quality of websites designed to provide open access educational resources for anesthesia trainees and clinicians. METHODS: A PubMed search of articles published between 2009 and 2020, and a Startpage search engine web search was conducted in May 2021 to identify websites using the following inclusion criteria: (1) contain educational content relevant for anesthesia providers or trainees, (2) offer content free of charge, and (3) are written in the English language. Websites were each scored by 2 independent reviewers using a website quality evaluation tool with previous validity evidence that was modified for anesthesia (the Anesthesia Medical Education Website Quality Evaluation Tool). RESULTS: Seventy-five articles and 175 websites were identified; 37 websites met inclusion criteria. The most common types of educational content contained in the websites included videos (66%, 25/37), text-based resources (51%, 19/37), podcasts (35%, 13/37), and interactive learning resources (32%, 12/37). Few websites described an editorial review process (24%, 9/37) or included opportunities for active engagement or interaction by learners (30%,11/37). Scores by tertile differed significantly across multiple domains, including disclosure of author/webmaster/website institution; description of an editorial review process; relevancy to residents, fellows, and faculty; comprehensiveness; accuracy; disclosure of content creation or revision; ease of access to information; interactivity; clear and professional presentation of information; and links to external information. CONCLUSIONS: We found 37 open access websites for anesthesia education available on the Internet. Many of these websites may serve as a valuable resource for anesthesia clinicians looking for self-directed learning resources and for educators seeking to curate resources into thoughtfully integrated learning experiences. Ongoing efforts are needed to expand the number and improve the existing open access websites, especially with interactivity, to support the education and training of anesthesia providers in even the most resource-limited areas of the world. Our findings may provide recommendations for those educators and organizations seeking to fill this needed gap to create new high-quality educational websites.

Novel Systemic Treatment Modalities Including Immunotherapy and Molecular Targeted Therapy for Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common cancers worldwide. More than half of patients with HNSCC eventually experience disease recurrence and/or metastasis, which can threaten their long-term survival. HNSCCs located in the oral cavity and larynx are usually associated with tobacco and/or alcohol use, whereas human papillomavirus (HPV) infection, particularly HPV16 infection, is increasingly recognized as a cause of oropharyngeal HNSCC. Despite clinical, histologic, and molecular differences between HPV-positive and HPV-negative HNSCCs, current treatment approaches are the same. For recurrent disease, these strategies include chemotherapy, immunotherapy with PD-1-inhibitors, or a monoclonal antibody, cetuximab, that targets epidermal growth factor; these therapies can be administered either as single agents or in combination. However, these treatment strategies carry a high risk of toxic side effects; therefore, more effective and less toxic treatments are needed. The landscape of HNSCC therapy is changing significantly; numerous clinical trials are underway to test novel therapeutic options like adaptive cellular therapy, antibody-drug conjugates, new targeted therapy agents, novel immunotherapy combinations, and therapeutic vaccines. This review helps in understanding the various developments in HNSCC therapy and sheds light on the path ahead in terms of further research in this field.

Manipulation of the Phytochemical Profile of Tenderstem® Broccoli Florets by Short Duration, Pre-Harvest LED Lighting.

Light quality has been reported to influence the phytochemical profile of broccoli sprouts/microgreens; however, few studies have researched the influence on mature broccoli. This is the first study to investigate how exposing a mature glasshouse grown vegetable brassica, Tenderstem® broccoli, to different light wavelengths before harvest influences the phytochemical content. Sixty broccoli plants were grown in a controlled environment glasshouse under ambient light until axial meristems reached >1 cm diameter, whereupon a third were placed under either green/red/far-red LED, blue LED, or remained in the original compartment. Primary and secondary spears were harvested after one and three weeks, respectively. Plant morphology, glucosinolate, carotenoid, tocopherol, and total polyphenol content were determined for each sample. Exposure to green/red/far-red light increased the total polyphenol content by up to 13% and maintained a comparable total glucosinolate content to the control. Blue light increased three of the four indole glucosinolates studied. The effect of light treatments on carotenoid and tocopherol content was inconclusive due to inconsistencies between trials, indicating that they are more sensitive to other environmental factors. These results have shown that by carefully selecting the wavelength, the nutritional content of mature broccoli prior to harvest could be manipulated according to demand.

Outcomes of patients with oropharyngeal squamous cell carcinoma treated with induction chemotherapy followed by concurrent chemoradiation compared with those treated with concurrent chemoradiation.

BACKGROUND: Induction chemotherapy (IC) has been associated with a decreased risk of distant metastasis in locally advanced head and neck squamous cell carcinoma. However, its role in the treatment of oropharyngeal squamous cell carcinoma (OPSCC) is not well established. METHODS: The outcomes of patients with OPSCC treated with IC followed by concurrent chemoradiation (CRT) were compared with the outcomes of those treated with CRT alone. The primary outcome was overall survival (OS), and the secondary end points were the times to locoregional and distant recurrence. RESULTS: In an existing database, 585 patients met the inclusion criteria: 137 received IC plus CRT, and 448 received CRT. Most patients were positive for human papillomavirus (HPV; 90.9%). Patients receiving IC were more likely to present with a higher T stage, a higher N stage, and low neck disease. The 3-year OS rate was significantly lower in patients receiving IC (75.7%) versus CRT alone (92.9%). In a multicovariate analysis, receipt of IC (adjusted hazard ratio [aHR], 3.4; P < .001), HPV tumor status (aHR, 0.36; P = .002), and receipt of concurrent cetuximab (aHR, 2.7; P = .002) were independently associated with OS. The risk of distant metastasis was also significantly higher in IC patients (aHR, 2.8; P = .001), whereas an HPV-positive tumor status (aHR, 0.44; P = .032) and completion of therapy (aHR, 0.51; P = .034) were associated with a lower risk of distant metastasis. In HPV-positive patients, IC remained associated with distant metastatic progression (aHR, 2.6; P = .004) but not OS. CONCLUSIONS: In contrast to prior studies, IC was independently associated with worse OS and a higher risk of distant metastasis in patients with OPSCC. Future studies are needed to validate these findings.

Conditional survival among patients with oropharyngeal cancer treated with radiation therapy and alive without recurrence 5 years after diagnosis.

BACKGROUND: Risk of recurrence among patients with oropharyngeal cancer (OPC) who survive 5 years is low. The goal of this study was to assess long-term survival of patients with OPC alive without recurrence 5 years after diagnosis. METHODS: This study included newly diagnosed patients with OPC, who had been treated with radiation and were alive without recurrence 5 years after diagnosis. Overall survival (OS) probabilities beyond 5 years were estimated using the Kaplan-Meier method. Factors associated with OS were determined using Bayesian piecewise exponential survival regression. Standardized mortality ratios for all-cause death were estimated controlling for study year, age, and sex in the US general population. RESULTS: Among 1699 patients, the additional 2-year, 5-year, and 10-year OS probabilities were 94%, 83%, and 63%, respectively, and were lower than those in the general population. Patients who were older, were current or former smokers, had other than tonsil or base of tongue tumors, or had T4 tumors had a higher risk of death. Patients who had base of tongue tumors and had received intensity-modulated radiation therapy (IMRT) or lower-radiation doses had a lower risk of death. Standardized mortality ratios were higher among current and heavy smokers and lower among recipients of IMRT and lower radiation doses. CONCLUSIONS: In this large cohort, long-term survival among patients with OPC was good but lower than predicted for the general population. Patients treated with IMRT and those with less tobacco exposure had better outcomes.

Prognostic significance of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in patients with oropharyngeal cancer treated with radiotherapy.

BACKGROUND: This study aimed to evaluate the prognostic value of pre-treatment NLR in patients with oropharyngeal cancer. METHODS: Patients who completed definitive radiotherapy (RT) for oropharyngeal cancer and had blood counts taken pre-RT from 2002 to 2013 were included. NLR was calculated as total neutrophil/lymphocytes. Survival rates were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were conducted with linear and Cox regression methods. NLR was analysed posteriori and dichotomised on the discovered median. RESULTS: Eight hundred and forty-eight patients were analysed. The median pre-RT NLR was 3. Patients with NLR of <3 had improved overall survival (OS) than those with NLR ≥ 3 (5-year OS 85 vs 74%, p < 0.0001). OS differences remained significant when stratified according to HPV status (HPV-positive p = 0.011; HPV-negative p = 0.003). Freedom from any recurrence (FFR), locoregional control (LRC) and freedom of distant recurrence (FDR) were better in those with NLR < 3. The negative impact of elevated pre-RT NLR on OS (HR = 1.64, p = 0.001), FFR (HR = 1.6, p = 0.006) and LRC (HR = 1.8, p = 0.005) remained significant on multivariable analysis. CONCLUSIONS: Pre-RT NLR is an independent prognostic factor in patients with oropharyngeal cancer regardless of HPV status. Patients with lower NLR had more favourable OS and disease control.

Delivering Essential Surgical Care for Lower-limb Musculoskeletal disorders in the Low-Resource Setting.

BACKGROUND: Mismatched surgeon-anesthesiologist ratios often exist in low-resource settings making safe emergency essential surgical care challenging. This study is an audit of emergency essential procedures performed for lower-limb (LL) musculoskeletal disorders (MSD) when an anesthesiologist was unavailable. It aims to identify strategies for safe anesthesia. METHODS: A 5-year retrospective audit of emergency essential LL orthopedic procedures performed at remote mission hospital in Central India was performed. Out of necessity, a regional anesthesia (RA) protocol was developed in collaboration with anesthesiologists familiar with the setting. The incidence of intraoperative surgical and perioperative anesthesia complications when RA was administered by a surgeon was evaluated. RESULTS: During this period, 766 emergency essential LL MSDs procedures were performed. An anesthesiologist was available for only 6/766. RA was administered by a surgeon for 283/766. This included spinal anesthesia (SA) for 267/283 patients, peripheral nerve blocks for 16/283. Local infiltration and/or sedation was administered to 477/766. There were 17 intraoperative surgical complications. Anesthesia-related complications included 37/267 patients who required multiple attempts to localize subarachnoid space and SA failure in 9/267 patients all of whom had successful re-administration. Additional sedation and infiltration of local anesthetic was required in 5/267 patients. CONCLUSION: Remote pre-anesthesia consultation for high-risk patients, local surgeon-anesthesiologist networking, protocol-guided management, and dedicated short duration of training in anesthesia may be considered as an alternative for delivering RA for emergency essential surgery for LL MSDs due to unavailability of anesthesiologists.