Long-term outcomes in advanced anterior skull base malignancy: a single quaternary institution experience.

BACKGROUND: Advanced skull base malignancies are a heterogenous subset of head and neck cancers, and management is often complex. In recent times, there has been a paradigm shift in surgical technique and the advent of novel systemic options. Our goal was to analyse the long-term outcomes of a single quaternary head and neck and skull base service. METHODS: A retrospective review of 127 patients with advanced anterior skull base malignancies that were treated at our institution between 1999 and 2015 was performed. Multiple variables were investigated to assess their significance on 5 and 10-year outcomes. RESULTS: The mean age was 60.9 (± 12.6 SD). Sixty-four percent were males and 36% were females. Ninety percent of patients had T4 disease. Median survival time was 133 months. The 5-year overall survival (OS) was 66.2%, disease-specific survival (DSS) was 74.7%, and recurrence-free survival (RFS) was 65.0%. The 10-year OS was 55.1%, DSS was 72.1%, and RFS was 53.4%. Histological type and margin status significantly affected OS & DSS. CONCLUSION: Surgical management of advanced skull base tumours has evolved over the last few decades at our institution with acceptable survival outcomes and complication rates. Histological diagnosis and margin status are the main predictors of survival. The addition of neoadjuvant systemic agents in current trials may improve outcomes.

Assessment of bronchodilator response in preschoolers: A systematic review.

BACKGROUND: Several techniques can be used to assess bronchodilator response (BDR) in preschool-aged children, including spirometry, respiratory oscillometry, the interrupter technique, and specific airway resistance. However, there has not been a systematic comparison of BDR thresholds across studies yet. METHODS: A systematic review was performed on all studies up to May 2023 measuring a bronchodilator effect in children 2-6 years old using one of these techniques (PROSPERO CRD42021264659). Studies were identified using MEDLINE, Cochrane, EMBASE, CINAHL via EBSCO, Web of Science databases, and reference lists of relevant manuscripts. RESULTS: Of 1224 screened studies, 43 were included. Over 85% were from predominantly European ancestry populations, and only 22 studies (51.2%) calculated a BDR cutoff based on a healthy control group. Five studies included triplicate testing with a placebo to account for the within-subject intrasession repeatability. A relative BDR was most consistently reported by the included studies (95%) but varied widely across all techniques. Various statistical methods were used to define a BDR, with six studies using receiver operating characteristic analyses to measure the discriminative power to distinguish healthy from wheezy and asthmatic children. CONCLUSION: A BDR in 2- to 6-year-olds cannot be universally defined based on the reviewed literature due to inconsistent methodology and cutoff calculations. Further studies incorporating robust methods using either distribution-based or clinical anchor-based approaches to define BDR are required.

Comparison of physiological and behavioral nutrition-related factors in people with and without adolescent idiopathic scoliosis, from cohort data at 8 to 20 years.

Nutrition-related variables including lower body mass index (BMI), lower bone mineral density (BMD), altered body composition and hormone levels have been reported in adolescent idiopathic scoliosis (AIS). The aims of this study were to determine if physiological and behavioral nutrition-related factors differ between people with and without AIS, and to quantify their relationship with AIS, in unbiased cohort sample. BMI, presence of an eating disorder, leptin, adiponectin, BMD, vitamin D, lean mass, and fat mass were compared between those with and without AIS at ages 8, 10, 14, 17, and 20 years, and multiple logistic regression was performed between these variables and AIS. Lower total body BMD (median, 1.0 g/cm2 vs 1.1 g/cm2; p = .03) and lean mass (median, 38.8 kg vs 46.0 kg; p = .04) at age 20 years were observed in those with AIS compared to those without scoliosis. At age 20, the odds of AIS were 3.23 times higher for adolescents with an eating disorder compared to those with no eating disorder (95% CI, 1.02-8.63) when adjusted for BMI. Every 1 kg/m2 increase in BMI decreased the odds of AIS by 0.88 times (95% CI, 0.76-0.98), after adjusting for eating disorder diagnosis. In conclusion, lower BMI in mid-adolescence and presence of eating disorder outcomes, lower BMD, and lower lean mass in late adolescence were associated with the presence of AIS. Current data do not explain the mechanisms for these associations but suggest that serum leptin, adiponectin, and vitamin D are unlikely to be contributing factors. Conclusive determination of the prevalence of eating disorders in AIS will require further studies with larger sample sizes.

Vertebral body tethering for idiopathic scoliosis: a systematic review and meta-analysis.

PURPOSE: Vertebral body tethering (VBT) is a recent procedure to correct and reduce spinal curves in skeletally immature patients with adolescent idiopathic scoliosis (AIS). The purpose of this systematic review and meta-analysis is to determine the expected curve reduction and potential complications for adolescent patients after VBT. METHODS: PubMed, Embase, Google Scholar and Cochrane databases were searched until February 2022. Records were screened against pre-defined inclusion and exclusion criteria. Data sources were prospective and retrospective studies. Demographics, mean differences in Cobb angle, surgical details and complication rates were recorded. Meta-analysis was conducted using a random-effects model. RESULTS: This systematic review includes 19 studies, and the meta-analysis includes 16 of these. VBT displayed a statistically significant reduction in Cobb angle from pre-operative to final (minimum 2 years) measurements. The initial mean Cobb angle was 47.8° (CI 95% 42.9-52.7°) and decreased to 22.2° (CI 95% 19.9-24.5°). The mean difference is - 25.8° (CI 95% - 28.9-22.7) (p < 0.01). The overall complication rate was 23% (CI 95% 14.4-31.6%), the most common complication was tether breakage 21.9% (CI 95% 10.6-33.1%). The spinal fusion rate was 7.2% (CI 95% 2.3-12.1%). CONCLUSION: VBT results in a significant reduction of AIS at 2 years of follow-up. Overall complication rate was relatively high although the consequences of the complications are unknown. Further research is required to explore the reasons behind the complication rate and determine the optimal timing for the procedure. VBT remains a promising new procedure that is effective at reducing scoliotic curves and preventing spinal fusion in the majority of patients. LEVEL OF EVIDENCE: Systematic review of Therapeutic Studies with evidence level II-IV.

Limb salvage surgery reconstructive techniques following long-bone lower limb oncological resection: a systematic review and meta-analysis.

BACKGROUND: Limb salvage surgery (LSS) is now considered the gold standard surgical treatment for lower limb bone sarcomas. However, there is a paucity of literature comparing the various LSS reconstructive options. The aim of this systematic review and meta-analysis was to compare functional outcomes and complications of LSS reconstructive techniques. METHODS: The primary aim of the meta-analysis was to determine functional outcomes from the pooled data utilizing the Musculoskeletal Tumour Society score (MSTS). Comparisons could then made for this outcome between biological and prosthetic, vascularised and non-vascularised, and prosthetic and composite reconstructions. The secondary aim was to compare complication outcomes of each reconstruction. Standardized mean difference (Cohen's d) and odds ratios were estimated using a random effects model. RESULTS: Fourteen studies with a total of 785 patients were included. We found structural failure was 75% less likely to occur in prosthetic reconstruction compared to biological (OR = 0.24; 95% CI: 0.07-0.79; P = 0.02). We did not find any evidence of difference in function (MSTS score) between vascularised verses non-vascularised reconstructions (Cohen's d = -1.14; 95% CI = -3.06 to 0.78; I2  = 87%). Other analyses comparing complications found no difference between the reconstructive groups. CONCLUSION: The study found no correlation between functional outcomes and the type of LSS reconstruction. Structural failure was more likely to occur in biological when compared with prosthetic reconstruction. There was no correlation between the incidence of other complications and the type of LSS technique. This suggests a role for improved approaches to reconstruction methods including bioprinting and bioresorbable devices.

High-Flow Nasal Cannula for Apneic Oxygenation in Obese Patients for Elective Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Obese patients desaturate rapidly during the apneic period after induction of anesthesia for elective surgery. Administration of oxygen using high-flow nasal cannulae (HFNCs) may prevent desaturation in nonobese patients compared to facemask (FM) preoxygenation. The aim of this meta-analysis was to compare the effectiveness of HFNC to FM preoxygenation techniques in reducing preintubation desaturation in obese patients undergoing elective surgery. METHODS: This study protocol was registered on PROSPERO (CRD42022309391). Adult studies that compared HFNC and FM preoxygenation in obese patients requiring general anesthesia for elective surgery were included. The primary outcome was desaturation resulting in oxygen saturation of <92% from induction of anesthesia until intubation. Secondary outcomes included the lowest arterial oxygen content before intubation expressed in mm Hg, safe apnea time expressed in seconds, the lowest oxygen saturation before intubation expressed as a percentage, patient-reported discomfort, the need for rescue ventilation, and the incidence of aspiration of gastric contents during intubation. Risk of bias was assessed using the Cochrane Collaboration tool. Certainty was assessed following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Six studies including 351 participants were eligible for analysis. There was no difference in odds of oxygen desaturation <92% between HFNC and FM (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.15-1.63; P = .24). The HFNC group had a significantly longer safe apnea time (mean difference [MD], -124.20 with 95% CI, -200.47 to -47.93; P = .001). There was no difference between HFNC and FM in the lowest arterial oxygen content (MD, -23.90; 95% CI, -88.64 to 40.85; P = .47) and the lowest peripheral oxygenation saturation (MD, -0.47 with 95% CI, -5.07 to 4.12; P = .84). HFNC had a lower odd of discomfort than FM (OR, 0.13; 95% CI, 0.03-0.52; P = .004). There was no difference in the odds of aspiration of gastric contents between HFNC and FM (OR, 0.33; 95% CI, 0.01-8.21; P = .50). The risk of bias for our primary and secondary outcomes was low. The GRADE assessment for our primary outcome indicated a low level of certainty. For secondary outcomes, the GRADE assessment indicated a very low certainty for all outcomes except for patient discomfort, which was indicated as a moderate level of certainty. CONCLUSIONS: There may be no difference between HFNC and FM preoxygenation in preventing oxygen desaturation <92% or the lowest oxygen saturation before intubation. Preparation remains important to prevent and manage desaturation during induction of obese patients.

Environmental pathways affecting gene expression (E.PAGE) as an R package to predict gene-environment associations.

The purpose of this study is to manually and semi-automatically curate a database and develop an R package that will act as a comprehensive resource to understand how biological processes are dysregulated due to interactions with environmental factors. The initial database search run on the Gene Expression Omnibus and the Molecular Signature Database retrieved a total of 90,018 articles. After title and abstract screening against pre-set criteria, a total of 237 datasets were selected and 522 gene modules were manually annotated. We then curated a database containing four environmental factors, cigarette smoking, diet, infections and toxic chemicals, along with a total of 25,789 genes that had an association with one or more of gene modules. The database and statistical analysis package was then tested with the differentially expressed genes obtained from the published literature related to type 1 diabetes, rheumatoid arthritis, small cell lung cancer, COVID-19, cobalt exposure and smoking. On testing, we uncovered statistically enriched biological processes, which revealed pathways associated with environmental factors and the genes. The curated database and enrichment tool are available as R packages at https://github.com/AhmedMehdiLab/E.PATH and https://github.com/AhmedMehdiLab/E.PAGE respectively.

Laparoscopic fundoplication versus laparoscopic Roux-en-Y gastric bypass for gastro-oesophageal reflux disease in obese patients: protocol for a randomized clinical trial.

BACKGROUND: Laparoscopic fundoplication (LF) is the standard surgical procedure for the treatment of gastro-oesophageal reflux disease (GORD). Laparoscopic Roux-en-Y gastric bypass (LRYGB) is commonly performed to achieve weight loss in obese patients, but it also has anti-reflux properties. Hence, in the obese population suffering from GORD, LRYGB could be an alternative to LF. The aim of this trial will be to compare LF and LRYGB in an obese population presenting with GORD and being considered for surgery. METHODS: This will be an investigator-initiated randomized clinical trial. The research population will be obese patients (BMI 30-34.9 with waist circumference more than 88 cm (women) or more than 102 cm (men), or BMI 35-40 with any waist circumference) referred to a public hospital for consideration of anti-reflux surgery. The primary aim of the study will be to determine the efficacy of LF compared with LRYGB on subjective and objective control of GORD. Secondary aims include determining early and late surgical morbidity and the side-effect profile of LF compared with LRYGB and to quantify any non-reflux benefits of LRYGB (including overall quality of life) compared with LF. CONCLUSION: This trial will determine whether LRYGB is effective and acceptable as an alternative to LF for the surgical treatment of GORD in obese patients Registration number: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000636752p (https://www.anzctr.org.au/).

Defining the expected 30-day mortality for patients undergoing palliative radiotherapy: A meta-analysis.

BACKGROUND: The expected 30-day mortality rate for patients treated with palliative radiationisnotestablished. The primary objective of this study is todefinetheproportion of patientswith advanced cancerwho diewithin 30-daysofpalliative radiotherapy(PR). Additionally, we explored the short term survival of patient subgroups undergoing PR treatment. METHODS: We searched MEDLINE, CINAHL, Embase and Cochrane Database of Systematic Reviews from January 1st 1980 to June 26, 2020. We included PUBMED's related search and reference lists to further identify articles. A meta-analysis of these research studies and reviews was performed. Published and unpublished English language randomized controlled trials, observational or prospective studies, and systematic reviews that reported 30-day mortality for patients with advanced cancer who received PR were eligible. Data extraction was done by two independent authors and included study quality indicators. To improve distribution and variance, all proportions were transformed using logit transformation. A random-effects model was used to pool data, using Der Simonian and Laird method of estimation where possible and appropriate. RESULTS: The data from 42 studies contributing 88,516 patients with advanced cancer who received PR were evaluated. The summary proportion of mortality in patients with advanced cancer within 30 days of receiving PR was 16% (95% CI = 14% to 18%). We found substantial heterogeneity in our data (I2 = 98.76%, p < 0.001), hence we applied subgroup analysis to identify potential moderating factors. We found a higher 30-day mortality rate after PR in the following groups: multiple treatment sites (QM(1) = 9.54, p = 0.002), hepatobiliary primary (QM(1) = 24.20, p < 0.001), inpatient status (QM(1) = 92.27, p < 0.001), Eastern Cooperative Oncology Group performance status (ECOG) 3-4 (QM(1) = 8.70, p = 0.003), United States (U.S.) patients (QM(1) = 28.70, p < 0.001) among others. CONCLUSIONS: We found that 16% of patients with advanced cancer receiving PR die within 30 days of treatment. Our findingcan be used asabenchmarktoestablishaglobal quality metric for radiation oncology practice audits.

Direct oral anticoagulants for cancer-associated venous thromboembolisms: a systematic review and network meta-analysis.

BACKGROUND: Several recent randomised controlled trials (RCT) have investigated the use of direct oral anticoagulants (DOAC) in the treatment of malignancy-associated venous thromboembolism (VTE). AIMS: This meta-analysis combines all RCT data to determine the risks of recurrent VTE and bleeding with DOAC in patients with malignancy-associated VTE compared with low-molecular-weight heparin (LMWH). METHODS: The study followed PRISMA guidelines. MEDLINE, EMBASE and CENTRAL were systematically searched from inception to 1 April 2020. References of reviews and relevant conference proceedings were searched by hand. Two authors independently evaluated study eligibility, extracted data and assessed risk of bias. Direct and indirect meta-analyses were performed. RESULTS: In four RCT with low risk of bias (2907 patients), high certainty evidence suggested that DOAC had a 37% reduction in risk of recurrent VTE compared with LMWH (direct pooled risk ratio (RR) 0.63; 95% confidence interval (CI) 0.44-0.91; I2 = 28%). No significant difference was observed in the risk of major bleeding with DOAC compared with LMWH (RR 1.31; 95% CI 0.83-2.07; I2 = 22%; moderate certainty evidence), including in patients in gastrointestinal and genitourinary malignancy. An increased risk of combined major or clinically relevant non-major bleeding was seen with DOAC (RR 1.52; 95% CI 1.09-2.12; I2 = 51%; low certainty evidence). Apixaban had the highest probability of being ranked the most effective and least bleeding risk among the DOAC. CONCLUSION: DOAC are effective in treating malignancy associated VTE; however, caution is required in patients with high risk of bleeding. Apixaban had lower risk of bleeding compared to other DOAC in this population.

A retrospective analysis of the investigative practices of acute limb ischaemia presenting with an unknown aetiology.

BACKGROUND: Acute limb ischaemia (ALI) is a limb and life-threatening condition with significant morbidity. There are currently no consensus recommendations for the investigative practices to determine the aetiology of ALI presenting without a known aetiology. We undertook a detailed analysis of all investigations performed to identify an underlying precipitant in those with unexplained ALI and formulated a suggested diagnostic algorithm for the evaluation of unexplained ALI. METHODS: ALI cases presenting to a tertiary referral centre over a 3-year period were reviewed, and known aetiologies, and investigations undertaken to determine the underlying aetiology of unexplained ALI were obtained. RESULTS: Unexplained ALI was found in 27 of 222 patients (12%), of which 21 (78%) had a cause for ALI established after further investigations. Six patients had no cause identified despite extensive work-up. Most patients with unexplained ALI had a cardioembolic source identified as the underlying cause (62%), and this included atrial fibrillation, infective endocarditis, cardiac myxoma and intra-cardiac thrombus. Other causes of unexplained ALI were detected by computed tomography (CT) imaging and included newly diagnosed significant atherosclerotic disease (19%), embolism from isolated proximal large vessel thrombus (10%) and metastatic malignancy (10%). There were no cases attributed to inherited thrombophilias, myeloproliferative neoplasms or anti-phospholipid syndrome. CONCLUSION: Among patients with unexplained ALI, the majority had a cardioembolic source highlighting the importance of comprehensive cardiac investigations. A subset of patients had alternative causes identified on CT imaging. These data support the use of a collaborative and integrative diagnostic algorithm in the evaluation of unexplained ALI.

Prospective cohort study to evaluate the accuracy of sleep measurement by consumer-grade smart devices compared with polysomnography in a sleep disorders population.

OBJECTIVES: Consumer-grade smart devices are now commonly used by the public to measure waking activity and sleep. However, the ability of these devices to accurately measure sleep in clinical populations warrants more examination. The aim of the present study was to assess the accuracy of three consumer-grade sleep monitors compared with gold standard polysomnography (PSG). DESIGN: A prospective cohort study was performed. SETTING: Adults undergoing PSG for investigation of a suspected sleep disorder. PARTICIPANTS: 54 sleep-clinic patients were assessed using three consumer-grade sleep monitors (Jawbone UP3, ResMed S+ and Beddit) in addition to PSG. OUTCOMES: Jawbone UP3, ResMed S+ and Beddit were compared with gold standard in-laboratory PSG on four major sleep parameters-total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO) and sleep efficiency (SE). RESULTS: The accelerometer Jawbone UP3 was found to overestimate TST by 28 min (limits of agreement, LOA=-100.23 to 157.37), with reasonable agreement compared with gold standard for TST, WASO and SE. The doppler radar ResMed S+ device underestimated TST by 34 min (LOA=-257.06 to 188.34) and had poor absolute agreement compared with PSG for TST, SOL and SE. The mattress device, Beddit underestimated TST by 53 min (LOA=-238.79 to 132) on average and poor reliability compared with PSG for all measures except TST. High device synchronisation failure occurred, with 20% of recordings incomplete due to Bluetooth drop out and recording loss. CONCLUSION: Poor to moderate agreement was found between PSG and each of the tested devices, however, Jawbone UP3 had relatively better absolute agreement than other devices in sleep measurements compared with PSG. Consumer grade devices assessed do not have strong enough agreement with gold standard measurement to replace clinical evaluation and PSG sleep testing. The models tested here have been superseded and newer models may have increase accuracy and thus potentially powerful patient engagement tools for long-term sleep measurement.

Systematic Review and Meta-Analysis of Inflammatory Bowel Disease Adverse Events with Anti-Interleukin 17A Agents and Tumor Necrosis Factor Inhibitors in Rheumatic Disease and Skin Psoriasis.

INTRODUCTION: The aim of this work is to perform a systematic review and meta-analysis of anti-tumor necrosis factor (anti-TNF) and anti-interleukin-17 (anti-IL-17) trials for spondyloarthritis, psoriatic arthritis, and psoriasis comparing rates of inflammatory bowel disease (IBD) events compared to placebo. METHODS: MEDLINE, EMBASE, and The Cochrane Library were searched for double-blind, randomized placebo-controlled anti-TNF and anti-IL-17 trials of included diseases. Inflammatory bowel disease events from the RCT period were pooled and meta-analyzed using statistical methods suitable for low-event-rate meta-analysis (Peto's, Mantel-Haenszel, hypergeometric-normal model, and Shuster-Guo-Skyler). When observed data were insufficient, we performed an exploratory sensitivity analysis to compare methods. RESULTS: We identified 9551 original papers, and included 96 publications: 65 anti-TNF and 31 anti-IL-17 trials, containing 21 new and 12 flare IBD events in 28,209 participants. New IBD on anti-IL-17 occurred 0.23/100 patient-years (PY) in psoriasis, 0.61/100 PY in PsA and 1.63/100 PY in spondyloarthritis, rates similar to observational cohorts, and less commonly on anti-TNF (0/100 PY, 0/100 PY, 0.32/100 PY, respectively). No evidence of difference between groups was found, with wide CI from many pooled counts of zero, especially in placebo arms. CONCLUSIONS: IBD events were rare, occurring at rates similar to biologic-naive groups. We could not find statistically significant differences in risk of new or recurrent IBD between treatment and control groups using selected meta-analytical methods for low event rate scenarios. Meta-analyses of this topic require more IBD events, ideally without pooling heterogeneous groups. Larger, thoroughly reported trials with systematic and detailed safety reporting are required to improve risk estimation and to make accurate inferences.