Association of Symptomatic Venous Thromboembolism and BMI in Patients Undergoing Sports Medicine Knee Procedures: A Retrospective Case-Control Study.

BACKGROUND: The purpose of this study was to characterize the prevalence of venous thromboembolism (VTE; including deep vein thrombosis [DVT] and pulmonary embolism [PE]) after sports medicine knee procedures by a single surgeon at an academic institution, identify factors associated with increased risk of VTE, and determine risk factor thresholds for beyond which VTE risk is elevated. HYPOTHESIS: We hypothesized that the prevalence of VTE after sports medicine knee procedures is low, but that increasing weight and body mass index (BMI) would be associated with elevated risk. STUDY DESIGN: Retrospective case-control study. LEVEL OF EVIDENCE: Level 3. METHODS: A retrospective case-control study analyzing sports medicine knee surgeries from 2017 to 2020 was conducted using current procedural terminology codes to identify cases. Optimal cutoff points for specific continuous patient characteristics were calculated to determine elevated risk of postoperative VTE. Overall VTE-free survival was assessed using Kaplan-Meier analysis and Cox proportional hazard regression models. RESULTS: Among the 724 eligible patients, there were 13 postoperative VTE events (1.79% prevalence; 12 DVTs, 1 DVT/PE). Increasing weight and BMI were significant risk factors for postoperative VTE (P = 0.03 and P = 0.04, respectively), with weight >94.7 kg and BMI >27.9 kg/m2 associated with elevated risk in male patients and weight >79.1 kg and BMI >28.1 kg/m2 associated with elevated risk for female patients. Cox regression demonstrated a significantly increased risk of postoperative VTE for male patients with BMI ≥27.9 kg/m2. CONCLUSION: Patients who undergo sports medicine knee surgery with increased weight and BMI are at an elevated risk of postoperative VTE. An individualized approach should be considered for chemoprophylaxis in patients with these risk factors. CLINICAL RELEVANCE: Consider chemoprophylaxis in patients with increased weight and BMI who undergo sports medicine knee surgery since they are at an elevated risk of postoperative VTE.

Referred otalgia: Common causes and evidence-based strategies for assessment and management.

OBJECTIVE: To provide family physicians and general otolaryngologists with a practical, evidence-based, and comprehensive approach to the management of patients presenting with suspected referred otalgia. SOURCES OF INFORMATION: The approach described is a review based on the authors' clinical practices along with research and clinical review articles published between 2000 and 2020. MEDLINE and PubMed were searched using the terms otalgia, referred otalgia, and secondary otalgia. Current guidelines for the management of referred otalgia were also reviewed. MAIN MESSAGE: Otalgia is defined as pain localized to the ear. It is one of the most common head and neck presentations in primary care, otolaryngology, and emergency medicine. Secondary otalgia arises from nonotologic pathology and represents nearly 50% of otalgia cases. Otalgia in the absence of other otologic symptoms is highly indicative of a secondary cause. A thorough assessment of patients presenting with referred otalgia requires an understanding of the possible causes of this condition, including dental and oral mucosal pathologies, temporomandibular joint disorders, cervical spine pathology, sinusitis, upper airway infection, and reflux, as well as head and neck malignancy. This paper aims to highlight the most common causes of referred otalgia, their presentations, and initial options for assessment and management. CONCLUSION: The prevalence of referred otalgia makes this an important condition for family physicians to be able to assess, manage, and triage based on patient presentation and examination. Understanding the common causes of referred otalgia will help reduce wait times for specialist assessment and allow ease and speed of access to management options for patients in community clinics.

Otalgie référée: Causes habituelles et stratégies d'évaluation et de prise en charge fondées sur des données probantes.

OBJECTIF: Présenter aux médecins de famille et aux otorhinolaryngologistes généraux une approche pratique, exhaustive et fondée sur des données probantes pour la prise en charge des patients chez qui l'on soupçonnne une otalgie référée. SOURCES DE L'INFORMATION: L'approche décrite est une revue qui se fonde sur les pratiques cliniques des auteurs, et sur des articles de recherche et des revues cliniques publiés entre 2000 et 2020. Une recension a été effectuée dans MEDLINE et PubMed à l'aide des expressions en anglais otalgia, referred otalgia et secondary otalgia. Les lignes directrices actuelles sur la prise en charge de l'otalgie référée ont aussi été passées en revue. MESSAGE PRINCIPAL: L'otalgie désigne une douleur localisée à l'oreille. Il s'agit de l'une des présentations liées à la tête et au cou les plus fréquentes en soins primaires, en otorhinolaryngologie et en médecine d'urgence. L'otalgie secondaire découle d'une pathologie non otologique, et près de 50 % des cas d'otalgie lui sont attribuables. L'otalgie sans autres symptômes otologiques évoque fortement une cause secondaire. Une évaluation rigoureuse des patients qui présentent une otalgie référée nécessite une bonne compréhension des causes possibles de ce problème, notamment des pathologies dentaires et des muqueuses buccales, des troubles de l'articulation temporo-mandibulaire, des pathologies de la colonne cervicale, de la sinusite, des infections des voies aériennes supérieures et du reflux, de même que des cancers de la tête et du cou. Cet article a pour but de mettre en évidence les causes les plus fréquentes d'une otalgie référée, leurs caractéristiques, et les options initiales pour l'évaluation et la prise en charge. CONCLUSION: La prévalence de l'otalgie référée fait en sorte qu'il importe que les médecins de famille soient en mesure d'évaluer, de prendre en charge et de trier les patients d'après la présentation et l'examen. Une bonne compréhension des causes courantes de l'otalgie référée aide à réduire le temps d'attente avant une évaluation spécialisée, et permet de faciliter et d'accélérer l'accès par les patients à des options de prise en charge dans les cliniques communautaires.

Exploring Gut Microbiome in Predicting the Efficacy of Immunotherapy in Non-Small Cell Lung Cancer.

We performed various analyses on the taxonomic and functional features of the gut microbiome from NSCLC patients treated with immunotherapy to establish a model that may predict whether a patient will benefit from immunotherapy. We collected 65 published whole metagenome shotgun sequencing samples along with 14 samples from our previous study. We systematically studied the taxonomical characteristics of the dataset and used both the random forest (RF) and the multilayer perceptron (MLP) neural network models to predict patients with progression-free survival (PFS) above 6 months versus those below 3 months. Our results showed that the RF classifier achieved the highest F-score (85.2%) and the area under the receiver operating characteristic curve (AUC) (95%) using the protein families (Pfam) profile, and the MLP neural network classifier achieved a 99.9% F-score and 100% AUC using the same Pfam profile. When applying the model trained in the Pfam profile directly to predict the treatment response, we found that both trained RF and MLP classifiers significantly outperformed the stochastic predictor in F-score. Our results suggested that such a predictive model based on functional (e.g., Pfam) rather than taxonomic profile might be clinically useful to predict whether an NSCLC patient will benefit from immunotherapy, as both the F-score and AUC of functional profile outperform that of taxonomic profile. In addition, our model suggested that interactive biological processes such as methanogenesis, one-carbon, and amino acid metabolism might be important in regulating the immunotherapy response that warrants further investigation.

Tying Small Changes to Large Outcomes: The Cautious Promise in Incorporating the Microbiome into Immunotherapy.

The role of the microbiome in immunology is a rapidly burgeoning topic of study. Given the increasing use of immune checkpoint inhibitor (ICI) therapy in cancers, along with the recognition that carcinogenesis has been linked to dysregulations of the immune system, much attention is now directed at potentiation of ICI efficacy, as well as minimizing the incidence of treatment-associated immune-related adverse events (irAEs). We provide an overview of the major research establishing links between the microbiome to tumorigenesis, chemotherapy and radiation potentiation, and ICI efficacy and irAE development.

Prospective correlation between the patient microbiome with response to and development of immune-mediated adverse effects to immunotherapy in lung cancer.

BACKGROUND: Though the gut microbiome has been associated with efficacy of immunotherapy (ICI) in certain cancers, similar findings have not been identified for microbiomes from other body sites and their correlation to treatment response and immune related adverse events (irAEs) in lung cancer (LC) patients receiving ICIs. METHODS: We designed a prospective cohort study conducted from 2018 to 2020 at a single-center academic institution to assess for correlations between the microbiome in various body sites with treatment response and development of irAEs in LC patients treated with ICIs. Patients must have had measurable disease, ECOG 0-2, and good organ function to be included. Data was collected for analysis from January 2019 to October 2020. Patients with histopathologically confirmed, advanced/metastatic LC planned to undergo immunotherapy-based treatment were enrolled between September 2018 and June 2019. Nasal, buccal and gut microbiome samples were obtained prior to initiation of immunotherapy +/- chemotherapy, at development of adverse events (irAEs), and at improvement of irAEs to grade 1 or less. RESULTS: Thirty-seven patients were enrolled, and 34 patients were evaluable for this report. 32 healthy controls (HC) from the same geographic region were included to compare baseline gut microbiota. Compared to HC, LC gut microbiota exhibited significantly lower α-diversity. The gut microbiome of patients who did not suffer irAEs were found to have relative enrichment of Bifidobacterium (p = 0.001) and Desulfovibrio (p = 0.0002). Responders to combined chemoimmunotherapy exhibited increased Clostridiales (p = 0.018) but reduced Rikenellaceae (p = 0.016). In responders to chemoimmunotherapy we also observed enrichment of Finegoldia in nasal microbiome, and increased Megasphaera but reduced Actinobacillus in buccal samples. Longitudinal samples exhibited a trend of α-diversity and certain microbial changes during the development and resolution of irAEs. CONCLUSIONS: This pilot study identifies significant differences in the gut microbiome between HC and LC patients, and their correlation to treatment response and irAEs in LC. In addition, it suggests potential predictive utility in nasal and buccal microbiomes, warranting further validation with a larger cohort and mechanistic dissection using preclinical models. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03688347 . Retrospectively registered 09/28/2018.

Quality Indicators for the Diagnosis and Management of Sudden Sensorineural Hearing Loss.

OBJECTIVE: Sudden sensorineural hearing loss (SSNHL) is an ideal entity for quality indicator (QI) development, providing treatment challenges resulting in variable or substandard care. The American Academy of Otolaryngology-Head and Neck Surgery recently updated their SSNHL guidelines. With SSNHL demonstrating a large burden of illness, this study sought to leverage the updated guidelines and develop QIs that support quality improvement initiatives at an individual, institutional, and systems level. METHODS: Candidate indicators (CIs) were extracted from high-quality SSNHL guidelines that were evaluated using the Appraisal of Guidelines for Research and Evaluation II tool. Each CI and its supporting evidence were summarized and reviewed by a nine-member expert panel based on validity, reliability, and feasibility of measurement. Final QIs were selected from CIs using the modified RAND Corporation-University of California, Los Angeles appropriateness methodology. RESULTS: Fifteen CIs were identified after literature review. After the first round of evaluations, the panel agreed on 11 candidate indicators as appropriate QIs with 2 additional CIs suggested for consideration. An expert panel meeting provided a platform to discuss areas of disagreement before final evaluations. The expert panel subsequently agreed upon 11 final QIs as appropriate measures of high-quality care for SSNHL. CONCLUSION: The 11 proposed QIs from this study are supported by evidence and expert consensus, facilitating measurement across a wide breadth of quality domains. With the recently updated SSNHL guidelines, and a greater focus on quality improvement opportunities, these QIs may be used by healthcare providers for targeted quality improvement initiatives.

Building an Otoscopic screening prototype tool using deep learning.

BACKGROUND: Otologic diseases are often difficult to diagnose accurately for primary care providers. Deep learning methods have been applied with great success in many areas of medicine, often outperforming well trained human observers. The aim of this work was to develop and evaluate an automatic software prototype to identify otologic abnormalities using a deep convolutional neural network. MATERIAL AND METHODS: A database of 734 unique otoscopic images of various ear pathologies, including 63 cerumen impactions, 120 tympanostomy tubes, and 346 normal tympanic membranes were acquired. 80% of the images were used for the training of a convolutional neural network and the remaining 20% were used for algorithm validation. Image augmentation was employed on the training dataset to increase the number of training images. The general network architecture consisted of three convolutional layers plus batch normalization and dropout layers to avoid over fitting. RESULTS: The validation based on 45 datasets not used for model training revealed that the proposed deep convolutional neural network is capable of identifying and differentiating between normal tympanic membranes, tympanostomy tubes, and cerumen impactions with an overall accuracy of 84.4%. CONCLUSION: Our study shows that deep convolutional neural networks hold immense potential as a diagnostic adjunct for otologic disease management.

Timing of surgery following neoadjuvant chemoradiation in rectal cancer: a retrospective analysis from an academic medical center.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) has been shown to achieve decreased local recurrence (LR) with lower toxicity in rectal cancer patients, but data confirming the optimal timing of surgery following this therapy is less robust. METHODS: The University of Iowa Cancer Registry was queried to identify all patients with stages II-III rectal cancer who received nCRT and surgery from 2000 through 2012. Primary endpoints were time interval to surgery (TI), and overall survival (OS). Secondary endpoints included pathologic outcomes, perioperative morbidities and postoperative complications. Patient characteristics and treatment regimens were compared. Univariate Cox proportional hazard models were used to study the association between TI and OS. Associations of TI with secondary endpoints were tested using Chi-square tests of association. RESULTS: Eighty-seven patients presented with stages II-III rectal cancer. Mean TI was 9.92 weeks. There was no significant association between TI and OS when comparing <8 to ≥8 weeks (P=0.23) or when considering the interval as a continuous variable (P=0.85). Increased LOS [median 7.00 days, P=0.05, HR 1.03 (1.00-1.06)] did correlate with worse survival outcomes. Delaying surgery beyond 8 weeks was associated with increased risk for wound infection (P=0.05). CONCLUSIONS: OS was not influenced by longer intervals between nCRT and surgery. Delaying surgery beyond 8 weeks was associated with increased risk for wound infection.

Acute Flare of Bullous Pemphigus With Pembrolizumab Used for Treatment of Metastatic Urothelial Cancer.

In the past decade, the resurgence of immunotherapy has changed the landscape of cancer therapy. Checkpoint inhibitors targeting cytotoxic T-lymphocyte antigen-4, programmed death-1 on lymphocytes, and programmed death ligand-1 on tumors cells are currently utilized in the management of several cancers. These agents are double-edged sword with the positive effect being robust antitumor response but on the other side they can throttle up the normal immunologic homeostasis in a negative way, leading to adverse autoimmune toxicities. These adverse toxicities are frequent if patients have active autoimmune disorders. Here, we report a rare case of quiescent bullous pemphigoid which flared after initiation of pembrolizumab, a programmed death ligand-1 inhibitor.

Identification of altered protein abundances in cholesteatoma matrix via mass spectrometry-based proteomic analysis.

BACKGROUND: Cholesteatoma are cyst-like structures lined with a matrix of differentiated squamous epithelium overlying connective tissue. Although epithelium normally exhibits self-limited growth, cholesteatoma matrix erodes mucosa and bone suggesting changes in matrix protein constituents that permit destructive behaviour. Differential proteomic studies can measure and compare the cholesteatoma proteome to normal tissues, revealing protein alterations that may propagate the destructive process. METHODS: Human cholesteatoma matrix, cholesteatoma-involved ossicles, and normal middle ear mucosa, post-auricular skin, and non-involved ossicles were harvested. These tissues were subjected to multiplex peptide labeling followed by liquid chromatography and tandem mass spectrometry analysis. Relative protein abundances were compared and evaluated for ontologic function and putative involvement in cholesteatoma. RESULTS: Our methodology detected 10 764 peptides constituting 1662 unique proteins at 95 % confidence or greater. Twenty-nine candidate proteins were identified in soft tissue analysis, with 29 additional proteins showing altered abundances in bone samples. Ontologic functions and known relevance to cholesteatoma are discussed, with several candidates highlighted for their roles in epithelial integrity, evasion of apoptosis, and immunologic function. CONCLUSION: This study produced an extensive cholesteatoma proteome and identified 58 proteins with altered abundances contributing to disease pathopathysiology. As well, potential biomarkers of residual disease were highlighted. Further investigation into these proteins may provide useful options for novel therapeutics or monitoring disease status.

Evidence-based practice: management of adult sensorineural hearing loss.

Sensorineural hearing loss is a complex disease state influenced by genetics, age, noise, and many other factors. This article reviews our current knowledge regarding the causes of sensorineural hearing loss and reviews the more challenging clinical presentations of sensorineural hearing loss. We have reviewed the latest medical literature in an attempt to provide an evidence-based strategy for the assessment and management of sudden sensorineural hearing loss, rapidly progressive sensorineural hearing loss, and asymmetric/unilateral sensorineural hearing loss.

Systematic review and meta-analysis of the risk factors for sudden sensorineural hearing loss in adults.

OBJECTIVES/HYPOTHESIS: To review the medical literature evidence of potential risk factors for sudden sensorineural hearing loss (SSNHL) in the adult general population. STUDY DESIGN: Systematic review of prospective and retrospective studies; meta-analysis of case-controlled studies. METHODS: Three researchers independently reviewed MEDLINE (January 1, 1950-November 30, 2010), Embase (January 1, 1980-November 30, 2010), and Evidence-Based Medicine Reviews databases in addition to conducting a manual reference search. Randomized controlled trials, prospective cohort studies, consecutive/nonconsecutive case series, and retrospective reviews in which a clear definition of SSNHL was stated were included in the study. Researchers individually extracted data regarding patient information and the presumed risk factors. Discrepancies were resolved by mutual consensus. RESULTS: Twenty-two articles met the inclusion criteria. Cardiovascular risk factors (smoking, increased alcohol consumption) appeared to be associated with a higher risk of developing SSNHL. A low level of serum folate may also be implicated as a risk factor. Factor V Leiden and MTHFR gene polymorphisms were found to occur more frequently in patients with SSNHL in several studies, suggesting these inherited prothrombophilic mutations could be independent risk factors of SSNHL. CONCLUSIONS: Acquired and inherited cardiovascular risk factors appeared to be associated with an increased risk of developing SSNHL.

Systematic review of the evidence for the etiology of adult sudden sensorineural hearing loss.

OBJECTIVES/HYPOTHESIS: To determine the evidence for different etiologies of sudden sensorineural hearing loss (SSNHL) identified by clinical diagnostic tests in the adult population. STUDY DESIGN: Systematic literature review. METHODS: Review of MEDLINE (1950-October 2009), EMBASE (1980-October 2009), and EBM Review databases in addition to manual reference search of identified papers. Randomized controlled trials, prospective cohort studies, and retrospective reviews of consecutive patients in which a clear definition of SSNHL was stated and data from consecutive patients were reported with respect to etiology of hearing loss. Three researchers independently extracted data regarding patient demographic information, diagnostic tests employed, and the identified presumed etiologies. Discrepancies were resolved by mutual consensus. RESULTS: : Twenty-three articles met the inclusion criteria. The first group of papers searched for different etiologies among patients with SSNHL. Multiple etiologies were identified, including viral infection, vascular impairment, autoimmune disease, inner ear pathology, and central nervous system anomalies. The diagnosis for the majority of patients remained idiopathic. The second group of papers evaluated SSNHL patients with specific diagnostic tests such as autoimmune markers, hemostatic parameters, and diagnostic imaging. CONCLUSIONS: The suspected etiologies for patients suffering sudden sensorineural hearing loss included idiopathic (71.0%), infectious disease (12.8%), otologic disease (4.7%), trauma (4.2%), vascular or hematologic (2.8%), neoplastic (2.3%), and other causes (2.2%). Establishment of a direct causal link between SSNHL and these etiologies remains elusive. Diagnostic imaging is a useful method for identification of temporal bone or intracranial pathology that can present with SSNHL as a primary symptom.

Bone that best matches the properties of the mandible.

OBJECTIVE: The main advantage of primary oromandibular reconstruction using free vascularized bone-containing flaps is improved oral function from (1) the maintenance of mandibular and soft tissue architecture and (2) dental rehabilitation through osseointegrated implants. Bone dimensions, volume, quality, and the ability of the bone to withstand masticatory forces are important factors in achieving successful osseointegration. Previous studies have objectively examined the dimensions of bones used in oromandibular reconstruction, but few have addressed their biomechanical properties. The purpose of this study was to compare the dimensional and biomechanical properties of the bones commonly used in oromandibular reconstruction with those of the mandible. METHODS: Eleven formalin-fixed cadavers were used. The mandibles, fibulae, iliac crests, scapulae, clavicles, second metatarsals, radii, and anterior ribs were harvested. Measurements of the dimensions of the bones were made with calipers at multiple sites. Three-point break strength and screw pulling force tests were then performed on all of the bones. RESULTS: The fibulae, iliac crests, and clavicles had dimensions that best matched those of the mandible. The three-point break strength and screw pulling force tests were consistently the highest for the mandibles and fibulae, followed by the clavicles, scapulae, iliac crests, metatarsals, radii, and ribs, in that order. CONCLUSIONS: The fibula is the bone that best matches the properties of the mandible.