Objective
Despite recent advancement recurrent respiratory papillomatosis (RRP) remains a rare but challenging benign airway neoplasm. In recent years there has been significant shifts in incidence ...of this disease due to changes in vaccination and prevention for human papilloma virus (HPV) and its related pathology. This review will highlight the epidemiology, prevention and treatment of RRP.
Methods
The PubMed database was searched using relevant MeSH terms including “recurrent respiratory papillomatosis.” The titles and s were reviewed to assess relevance and unrelated articles were excluded. A full‐text review for select articles was performed, the data and discussions were interpreted and synthesized to create a concise update on the management of RRP.
Results
With the increasing utilization of the 9‐valent and quadrivalent HPV vaccine in Australia, we have seen a significant decrease in the incidence of RRP. Preliminary data in the US shows a similar trend of decreased incidence after implementation of vaccination. Single dose Gardasil in developing countries has shown sustained immunization for at least 7 years. Preliminary clinical trials and retrospective studies have shown the HPV vaccine may have benefit as a treatment method in addition to prevention for HPV related diseases. Bevacizumab (Avastin), a VEGF monoclonal antibody, has shown promise as a systemic treatment for RRP. The Corona Virus Disease 2019 (COVID‐19) pandemic has affected perioperative management of RRP.
Conclusion
RRP continues to decline in incidence since the implementation of HPV vaccination. Advancement in the medical management including Bevacizumab show promise as an additional option for the management of RRP.
Objective:
To critically review the literature on nasal nitric oxide (nNO) and its current clinical and research applicability in the diagnosis and treatment of different sinonasal inflammatory ...diseases, including acute bacterial rhinosinusitis (ABRS), allergic rhinitis (AR), and chronic rhinosinusitis (CRS).
Methods:
A search of the PubMed database was conducted to include articles on nNO and sinonasal diseases from January 2003 to January 2020. All article titles and abstracts were reviewed to assess their relevance to nNO and ABRS, AR, or CRS. After selection of the manuscripts, full-text reviews were performed to synthesize current understandings of nNO and its applications to the various sinonasal inflammatory diseases.
Results:
A total of 79 relevant studies from an initial 559 articles were identified using our focused search and review criteria. nNO has been consistently shown to be decreased in ABRS and CRS, especially in cases with nasal polyps. While AR is associated with elevations in nNO, nNO levels have also been found to be lower in AR cases with higher symptom severity. The obstruction of the paranasal sinuses is speculated to be an important variable in the relationship between nNO and the sinonasal diseases. Treatment of these diseases appears to affect nNO through the reduction of inflammatory disease burden and also mitigation of sinus obstruction.
Conclusion:
nNO has been of increasing interest to researchers and clinicians over the last decade. The most compelling data for nNO as a clinical tool involve CRS. nNO can be used as a marker of ostiomeatal complex patency. Variations in measurement techniques and technology continue to impede standardized interpretation and implementation of nNO as a biomarker for sinonasal inflammatory diseases.
Abstract Background Walking dysfunction is common in multiple sclerosis (MS). The thalamus and basal ganglia seemingly have important associations with walking performance. The contribution of these ...subcortical gray matter (SGM) structures for walking dysfunction is poorly understood in MS. Purpose This study examined associations among volumes of the thalamus and basal ganglia with walking outcomes in MS. Method We enrolled 61 MS patients who underwent brain MRI and completed the 6-minute walk (6 MW) and timed 25-foot walk (T25FW). Volumes of the thalamus, caudate, putamen, and pallidum as well as whole-brain white matter (WM) and gray matter (GM) were calculated from 3D T1-weighted structural brain images. We examined associations using bivariate correlations ( r ) and partial correlations ( pr ) that controlled for age, MS clinical course, and whole-brain WM and GM volumes. We further performed hierarchical linear regression (HLR) for identifying the strongest SGM correlate of walking performance. Results The 6 MW and T25FW correlated significantly with volumes of the thalamus ( r 's = .382 & .383), caudate ( r 's = .388 & .416), pallidum ( r 's = .457 & .457), and putamen ( r 's = .258 & .293) in bivariate correlations. The 6 MW and T25FW remained significantly correlated with caudate ( pr 's = .243 & .312) and pallidum ( pr 's = .321 & .345) volumes in partial correlations. Pallidum volume was the strongest SGM correlate of 6 MW ( β = .39) and T25FW ( β = .40) performance in HLR. Conclusion We provide novel evidence of possible SGM structures, particularly the pallidum and perhaps caudate, as correlates of walking performance in MS.
Peroral endoscopic myotomy (POEM) has gained acceptance as a treatment for achalasia. The aim of this study was to assess symptomatic, quality of life (QoL), and physiological outcomes of POEM using ...standardized methods.
Patients who were planned to undergo POEM were evaluated pre- and postoperatively with timed barium esophagogram (TBE), high-resolution manometry (HRM), the achalasia symptom questionnaire (ASQ) (best score 10, worst score 31), and the short form (SF)-36 (best score 100, worst score 0). Nine patients completed postoperative HRM, TBE, and 48 hours esophageal pH monitoring. A P-value of <.05 was considered statistically significant.
A total of 34 of 37 patients completed the POEM procedure. There was improvement in the ASQ scores and in QoL. HRM integrated relaxation pressures (IRPs) improved from 31.4 ± 10.8 mmHg preoperatively to 12.3 ± 6.7 mmHg postoperatively, and lower esophageal sphincter pressure (LESP) improved from 49.1 ± 16.9 mmHg preoperatively to 23.1 ± 9.4 mmHg postoperatively. Of the 7 patients who were evaluated with 48-hour pH monitoring postoperatively, 5 patients (71%) demonstrated pathological reflux with an average Demeester score of 23.1 ± 19.1. There was a negative linear correlation between LESP change and Demeester scores (r = -0.7, P = .03).
The POEM procedure significantly improves achalasia-related symptoms and improves social functioning. Physiologically, there is reduction in both IRP and LESP. Postoperative pathological reflux is correlated with LESP reduction.
Selective BRAF inhibitors (BRAFi) yield objective responses in 50% of patients with metastatic BRAF V600E mutant melanoma. Adding an MEK inhibitor increases this response rate to 70%. Limited data ...are available on the outcomes of unresectable stage III patients, and it remains unclear whether BRAF-targeted therapy can be utilized as a neoadjuvant strategy. Data on patients with advanced locoregional BRAF V600E mutant melanoma treated with BRAF-targeted therapy at Moffitt Cancer Center were analyzed to determine response rates, subsequent resection rates after tumor downsizing, pathologic responses, and patient survival. Fifteen patients with locoregional disease treated with BRAF-targeted therapy, either BRAFi alone (vemurafenib; 11 patients) or a combination of BRAFi and an MEK inhibitor (dabrafenib plus trametinib or placebo; four patients), were identified. The median age was 50 years; the median follow-up was 25.4 months. The median BRAF-targeted therapy treatment duration was 6.0 months (range 1.2-29.4 months). Response Evaluation Criteria In Solid Tumors-based evaluation demonstrated objective response in 11 patients (73.3%). Six patients underwent resection of the remaining disease after therapy. Pathological analysis showed complete pathologic response (n=2), partial pathologic response (n=2), or no pathologic response (n=2). Four of six patients undergoing surgery have been alive for more than 2 years, including three patients currently free from active disease. No complications attributable to BRAF-targeted therapy were observed in the perioperative period. Dose reduction or discontinuation because of toxicities occurred in 10/15 patients. Neoadjuvant BRAF-targeted therapy may be effective in advanced locoregional BRAF V600E mutant melanoma patients in increasing resectability, yielding pathological responses, and achieving prolonged survival.
Based in part on the results of randomized controlled trials (RCTs) that suggest a beneficial effect over alternative treatment options, the use of platelet-rich plasma (PRP) for the management of ...knee osteoarthritis (OA) is widespread and increasing. However, the extent to which these studies are vulnerable to slight variations in the outcomes of patients remains unknown.
To evaluate the statistical fragility of conclusions from RCTs that reported outcomes of patients with knee OA who were treated with PRP versus alternative nonoperative management strategies.
Systematic review and meta-analysis; Level of evidence, 2.
All RCTs comparing PRP with alternative nonoperative treatment options for knee OA were identified. The fragility index (FI) and reverse FI were applied to assess the robustness of conclusions regarding the efficacy of PRP for knee OA. Meta-analyses were performed to determine the minimum number of patients from ≥1 trials included in the meta-analysis for which a modification on the event status would change the statistical significance of the pooled treatment effect.
In total, this analysis included outcomes from 1993 patients with a mean ± SD age of 58.0 ± 3.8 years. The mean number of events required to reverse significance of individual RCTs (FI) was 4.57 ± 5.85. Based on random-effects meta-analyses, PRP demonstrated a significantly higher rate of successful outcomes when compared with hyaluronic acid (
= .002; odds ratio OR, 2.19; 95% CI, 1.33-3.62), as well as higher rates of patient-reported symptom relief (
= .019; OR, 1.55; 95% CI, 1.07-2.24), not requiring a reintervention after the initial injection treatment (
= .002; OR, 2.17; 95% CI, 1.33-3.53), and achieving the minimal clinically important difference (MCID) for pain improvement (
= .007; OR, 6.19; 95% CI, 1.63-23.42) when compared with all alternative nonoperative treatments. Overall, the mean number of events per meta-analysis required to change the statistical significance of the pooled treatment effect was 8.67 ± 4.50.
Conclusions drawn from individual RCTs evaluating PRP for knee OA demonstrated slight robustness. On meta-analysis, PRP demonstrated a significant advantage over hyaluronic acid as well as improved symptom relief, lower rates of reintervention, and more frequent achievement of the MCID for pain improvement when compared with alternative nonoperative treatment options. Statistically significant pooled treatment effects evaluating PRP for knee OA are more robust than approximately half of all comparable meta-analyses in medicine and health care. Future RCTs and meta-analyses should consider reporting FIs and fragility quotients to facilitate interpretation of results in their proper context.
Supervised learning is the most common form of machine learning utilized in medical research. It is used to predict outcomes of interest or classify positive and/or negative cases with a known ground ...truth. Supervised learning describes a spectrum of techniques, ranging from traditional regression modeling to more complex tree boosting, which are becoming increasingly prevalent as the focus on “big data” develops. While these tools are becoming increasingly popular and powerful, there is a paucity of literature available that describe the strengths and limitations of these different modeling techniques. Typically, there is no formal training for health care professionals in the use of machine learning models. As machine learning applications throughout medicine increase, it is important that physicians and other health care professionals better understand the processes underlying application of these techniques. The purpose of this study is to provide an overview of commonly used supervised learning techniques with recent case examples within the orthopedic literature. An additional goal is to address disparities in the understanding of these methods to improve communication within and between research teams.
OSA is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent upper airway obstruction and hypoxia, hallmarks of OSA, have been shown in animal models to ...induce substantial changes to the gut microbiota composition, and subsequent transplantation of fecal matter to other animals induced changes in BP and glucose metabolism.
Does OSA in adults associate with the composition and functional potential of the human gut microbiota?
We used respiratory polygraphy data from up to 3,570 individuals 50 to 64 years of age from the population-based Swedish Cardiopulmonary bioimage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia, and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, onsite anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register.
We found that all three OSA parameters were associated with lower diversity of species in the gut. Furthermore, in multivariable-adjusted analysis, the OSA-related hypoxia parameters were associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsella aerofaciens. The latter species was also independently associated with increased systolic BP. Furthermore, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Finally, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively.
OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.
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