Calcium phosphate nanoclusters modify periodontium remodeling and minimize orthodontic relapse.

Orthodontic relapse is one of the most prevalent concerns of orthodontic therapy. Relapse results in patients' teeth reverting towards their pretreatment positions, which increases the susceptibility to functional problems, dental disease, and substantially increases the financial burden for retreatment. This phenomenon is thought to be induced by rapid remodeling of the periodontal ligament (PDL) in the early stages and poor bone quality in the later stages. Current therapies, including fixed or removable retainers and fiberotomies, have limitations with patient compliance and invasiveness. Approaches using biocompatible biomaterials, such as calcium phosphate polymer-induced liquid precursors (PILP), is an ideal translational approach for minimizing orthodontic relapse. Here, post-orthodontic relapse is reduced after a single injection of high concentration PILP (HC-PILP) nanoclusters by altering PDL remodeling in the early stage of relapse and improving trabecular bone quality in the later phase. HC-PILP nanoclusters are achieved by using high molecular weight poly aspartic acid (PASP, 14 kDa) and poly acrylic acid (PAA, 450 kDa), which resulted in a stable solution of high calcium and phosphate concentrations without premature precipitation. In vitro results show that HC-PILP nanoclusters prevented collagen type-I mineralization, which is essential for the tooth-periodontal ligament (PDL)-bone interphase. In vivo experiments show that the PILP nanoclusters minimize relapse and improve the trabecular bone quality in the late stages of relapse. Interestingly, PILP nanoclusters also altered the remodeling of the PDL collagen during the early stages of relapse. Further in vitro experiments showed that PILP nanoclusters alter the fibrillogenesis of collagen type-I by impacting the protein secondary structure. These findings propose a novel approach for treating orthodontic relapse and provide additional insight into the PILP nanocluster's structure and properties on collagenous structure repair.

Comparison of Outcomes in Pediatric and Adolescent Posterior Cruciate Ligament Injuries With and Without Meniscal Tears: Operative Versus Nonoperative Management.

Background: Despite the posterior cruciate ligament (PCL) being an essential stabilizer of the knee, there is a paucity of data regarding injury management in pediatric patients. Purpose/Hypothesis: The purpose of this study was to evaluate differences in outcomes after operative (OP) versus nonoperative (NOP) management of pediatric isolated (single-ligament) PCL tears. It was hypothesized that managing PCL tears operatively would lead to improved functional outcomes compared with NOP management, especially in the setting of an associated meniscal tear. Study Design: Cohort study; Level of evidence, 3. Methods: Pediatric patients with an isolated PCL injury between 2006 and 2020 were identified and grouped according to whether they had a concomitant meniscal tear (PCL+M) or no meniscal tear (PCL-M). These cohorts were further sorted into OP, NOP, and nonoperative converted to operative (NOP2OP) treatment cohorts. Outcome data collected included Lysholm score, current activity level, and whether the patient returned to sports after treatment. Results: A total of 48 patients (49 knees) met study inclusion criteria (31 male, 18 female; mean age at injury, 15.6 years; age range, 8.3-18.9 years). There were 37 knees in the PCL-M cohort (30 NOP, 2 NOP2OP, and 5 OP) and 12 knees in the PCL+M cohort (4 NOP, 4 NOP2OP, and 4 OP). The mean duration of follow-up was 6.2 years (range, 2.4-15.7 years). The mean Lysholm scores were not significantly different between the OP and NOP knees in either the PCL-M cohort (P = .582) or the PCL+M cohort (P = .570); however, the PCL-M cohort overall had significantly higher scores compared with the PCL+M cohort (92.7 ± 13.0 vs 82.8 ± 18.8, respectively; P = .019). Conclusion: The pediatric patients in this series had similar functional outcomes when managed operatively or nonoperatively for their single-ligament PCL tear. When considering concomitant meniscal injury, the results indicated that children with meniscal injury had a worse outcome than those without a meniscal injury. Shared decision-making with patients and their family should take these results into consideration.

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.

Scoping Review of Interventions and Experiences Increasing Medical Student Interest in Physical Medicine and Rehabilitation.

ABSTRACT: Increasing medical student exposure to physical medicine and rehabilitation is an important factor for future growth of the field. Therefore, it is important to determine which types of interventions during medical school have the greatest impact on medical students' decision to pursue a career in physical medicine and rehabilitation. The purpose of this study is to perform a scoping review of the current literature that has analyzed how different interventions and experiences impact medical school students' decision to pursue a career in physical medicine and rehabilitation. A systematic and comprehensive search strategy was implemented across five different journal databases and yielded 18 articles meeting the inclusion criteria. Most studies analyzing specific interventions looked only at presurvey and postsurvey comparisons of the immediate impact of the intervention on interest in physical medicine and rehabilitation, and few looked at longitudinal outcomes, such as match characteristics. The most frequently cited factor that was shown to positively impact interest in physical medicine and rehabilitation was early exposure. Participating in clinical rotations also had a positive impact but was most effective when combined with early exposure. This review highlights the need for national recommendations for integrating physical medicine and rehabilitation into all 4 yrs of medical education.

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 Menière's Disease.

OBJECTIVE: Menière's disease (MD) is a clinical disorder that often provides challenges in diagnosis and management. High-quality evidence to guide care providers is sparse, which can result in significant practice variations. Quality indicators (QIs) are one method that can be used to standardize and measure accepted care practices to improve healthcare quality and patient outcomes. Here, we developed practical, high-yield QIs that serve to measure and inform the quality of care provided to patients with MD. STUDY DESIGN: Modified RAND Corporation University of California, Los Angeles appropriateness methodology for QI development. SETTING: Multicenter nine-member expert panel. PATIENTS: NA. INTERVENTIONS: NA. MAIN OUTCOME MEASURE: Final QIs deemed appropriate measures of quality care with agreement by the expert panel. RESULTS: Twenty-seven candidate indicators were identified after literature review. After the first round of evaluations, the panel agreed on three candidate indicators as appropriate QIs. A subsequent expert panel meeting provided a platform to discuss disagreements. Two agreed-upon QIs were revised during this discussion before final evaluations. The expert panel ultimately agreed upon five QIs as appropriate measures of high-quality care after completing final evaluations and reviewing updated literature. The five quality indicators measure audiometric documentation, minimization of electrocochleography, use of intratympanic dexamethasone, use of intratympanic gentamycin, and rate of labyrinthectomy/vestibular neurectomy in refractory MD patient. CONCLUSIONS: This study proposes five QIs that cover key aspects of care for MD, such as accurate diagnosis and management options including initial destructive therapies. These QIs can serve multiple purposes, the most important of which is to galvanize quality improvement initiatives.

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.

Otoscopic diagnosis using computer vision: An automated machine learning approach.

OBJECTIVE: Access to otolaryngology is limited by lengthy wait lists and lack of specialists, especially in rural and remote areas. The objective of this study was to use an automated machine learning approach to build a computer vision algorithm for otoscopic diagnosis capable of greater accuracy than trained physicians. This algorithm could be used by primary care providers to facilitate timely referral, triage, and effective treatment. METHODS: Otoscopic images were obtained from Google Images (Google Inc., Mountain View, CA), from open access repositories, and within otolaryngology clinics associated with our institution. After preprocessing, 1,366 unique images were uploaded to the Google Cloud Vision AutoML platform (Google Inc.) and annotated with one or more of 14 otologic diagnoses. A consensus set of labels for each otoscopic image was attained, and a multilabel classifier architecture algorithm was trained. The performance of the algorithm on an 89-image test set was compared to the performance of physicians from pediatrics, emergency medicine, otolaryngology, and family medicine. RESULTS: For all diagnoses combined, the average precision (positive predictive value) of the algorithm was 90.9%, and the average recall (sensitivity) was 86.1%. The algorithm made 79 correct diagnoses with an accuracy of 88.7%. The average physician accuracy was 58.9%. CONCLUSION: We have created a computer vision algorithm using automated machine learning that on average rivals the accuracy of the physicians we tested. Fourteen different otologic diagnoses were analyzed. The field of medicine will be changed dramatically by artificial intelligence within the next few decades, and physicians of all specialties must be prepared to guide that process. LEVEL OF EVIDENCE: NA Laryngoscope, 130:1408-1413, 2020.

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.