Mesenchymal stem cells for sensorineural hearing loss: a systematic review of preclinical studies.

Sensorineural hearing loss (SNHL) is the most common form of hearing loss that is routinely treated with hearing aids or cochlear implants. Advances in regenerative medicine have now led to animal studies examining the possibility of restoring injured hair cells with mesenchymal stem/stromal cell (MSC) administration. We conducted a systematic review and meta-analysis to collate the existing preclinical literature evaluating MSCs as a treatment for SNHL and quantify the effect of MSCs on functional hearing. Our protocol was published online on CAMARADES. Searches were conducted in four medical databases by two independent investigators. Twelve studies met inclusion and were evaluated for risk of bias using SYRCLE. Rodent models were commonly used (n = 8, 66%), while auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) were the most frequent measures assessing hearing loss. MSCs were derived from multiple tissue sources, including bone marrow, adipose tissue, and umbilical cord blood and the dose ranged from 4 × 103 to 1 × 107 cells. Treatment with MSCs resulted in an improvement in ABR and DPOAE (mean difference-15.22, + 9.10, respectively). Despite high heterogeneity and multiple "unclear" domains in the risk of bias, this review provides evidence that MSCs may have a beneficial effect in hearing function.

Re-evaluating the Weekend Effect on SAH: A Nationwide Analysis of the Association Between Mortality and Weekend Admission.

OBJECTIVE: Multiple studies have shown worse outcomes in patients admitted for medical and surgical conditions on the weekend. However, past literature analyzing this "weekend effect" on subarachnoid hemorrhage (SAH) found no significant increase in mortality. This study utilizes more recent data to re-evaluate the association between weekend admission and mortality of patients hospitalized for SAH. METHODS: This retrospective cohort study queried the SAH patients in the Nationwide Inpatient Sample (NIS) database who were discharged from 2006 through 2014 during the weekend. RESULTS: Of the 54,703 admissions for SAH identified during the study period, 14,821 (27.1%) occurred over the weekend. Patients admitted over the weekend had a mean age of 59.2 years and were most likely to be female (59.6%), to be white (62.9%), located in the south region of the USA (40.1%), and be admitted to a teaching hospital (74.4%). When compared directly to weekday admissions, patients admitted over the weekend had higher odds of in-hospital mortality (odds ratio 1.07; confidence interval 95%, 1.02-1.12). There was no significant difference shown in the rate patients get surgical clipping versus endovascular coiling (p = 0.28) or the amount of time between admission to procedure for clipping (p = 0.473) or coiling (p = 0.255) on the weekend versus a weekday. CONCLUSION: Based on our findings, the likelihood of the in-hospital mortality was higher for patients admitted over the weekend. However, the characteristics of the study, primarily observational, prevent us arriving at an accurate conclusion about why this occurs; hence, we believe it is an important starting point to consider for future research.

Mesenchymal stem cells and their application to rotator cuff pathology: A meta-analysis of pre-clinical studies.

Background: Rotator cuff injury (RCI) is a leading cause of morbidity in orthopaedics. Advances in regenerative medicine have led to the novel pleiotropic effects of mesenchymal stromal cells (MSCs) as therapeutic agents for RCI. Objective: Conduct a systematic evaluation of available preclinical studies to quantify the effects of MSCs on RCI. Methods: A literature search was performed in PubMed, Scopus, Cochrane, CINAHL, and Google Scholar. At least two independent investigators screened animal studies assessing the therapeutic effects of MSCs on: (i) biomechanical testing, imaging, and/or range-of-motion (primary outcome), and (ii) histologic analyses of wound healing, gene/protein expression of regenerative factors, and safety/long-term outcomes (secondary outcome). Meta-analysis data is reported as standardized mean difference (SMD) with 95% confidence interval (CI). Results: A total of 858 titles and abstracts were screened; 18 studies (n=576) met inclusion criteria. MSC therapy improved ultimate load failure [SMD -0.43 (95% CI -0.65, -0.22), p<0.0001; 15 studies, 28 comparisons], site stiffness [SMD -0.29 (95% CI -0.55, -0.04), p<0.05; 9 studies, 17 comparisons], bone mineral density [SMD -0.77 (95% CI -1.16, -0.38), p<0.0001; 2 studies, 6 comparisons], and stimulated fibrocartilage formation [SMD of -1.37 (95% CI -1.99, -0.74), p<0.0001; 4 studies, 7 comparisons]. Heterogeneity between studies was high and risk of bias was unclear. Conclusion: Administration of MSCs in preclinical models recapitulating RCI improved aspects of shoulder biomechanics, imaging, and collagen formation. Although these findings are promising, future studies should attempt to limit the risk of bias and focus on optimizing MSCs by standardizing methodologies.

Mesenchymal stem cells for sensorineural hearing loss: protocol for a systematic review of preclinical studies.

BACKGROUND: Sensorineural hearing loss (SNHL) is the most common form of hearing impairment and is characterized by a loss of receptor hair cells and/or spiral ganglion neurons. Regenerative stem cell therapy could potentially restore normal hearing and slow the progression of hearing loss in patients. Preclinical animal studies have demonstrated that mesenchymal stem cells (MSCs) could be a promising new therapy for this condition. These findings have prompted investigators to begin human clinical trials to assess the safety and efficacy of MSCs for the treatment of SNHL. The objective of the proposed systematic review is to examine the efficacy of MSCs as a therapy for SNHL in animal models. METHODS: We will include preclinical animal studies of SNHL in which MSCs are administered, and outcomes are compared against MSC-naïve controls. The primary outcome will include audiologic tests that are routinely used in experimental studies of hearing loss, such as auditory brainstem response (ABR) and distortion product otoacoustic emissions testing (DPOAE). Secondary outcomes will include histology, microscopy, gene protein expression, and behavioral responses of animals. Electronic searches of MEDLINE via PubMed, Scopus, ScienceDirect, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) will be performed. Search results will be screened independently and in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias and publication bias will be assessed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk of bias tool and Funnel Plots/Egger's regression tests, respectively. DISCUSSION: This systematic review will provide a summary of the efficacy of MSC therapy in animal models of SNHL, utilizing functional hearing assessment as a primary outcome. Findings from this review are important because they can elucidate research gaps that should be addressed in future preclinical studies and in turn can be translated into clinical studies. SYSTEMATIC REVIEW REGISTRATION: CAMARADES ( http://www.dcn.ed.ac.uk/camarades/ ).

Healthcare disparities among orthopedic trauma patients in the USA: socio-demographic factors influence the management of calcaneus fractures.

BACKGROUND: Socio-demographic factors have been suggested to contribute to differences in healthcare utilization for several elective orthopedic procedures. Reports on disparities in utilization of orthopedic trauma procedures remain limited. The purpose of our study is to assess the roles of clinical and socio-demographic variables in utilization of operative fixation of calcaneus fractures in the USA. METHODS: The National Inpatient Sample (NIS) dataset was used to analyze all patients from 2005 to 2014 with closed calcaneal fractures. Multivariate logistic regression analyses were performed to evaluate the impact of clinical and socio-demographic variables on the utilization of surgical versus non-surgical treatment. RESULTS: A total of 17,156 patients with closed calcaneus fractures were identified. Operative treatment was rendered in 7039 patients (41.03%). A multivariate logistic regression demonstrated multiple clinical and socio-demographic factors to significantly influence the utilization of surgical treatment including age, gender, insurance status, race/ethnicity, income, diabetes, peripheral vascular disease, psychosis, drug abuse, and alcohol abuse (p <  0.05). In addition, hospital size and hospital type (teaching versus non-teaching) showed a statistically significant difference (p <  0.05). CONCLUSIONS: Besides different clinical variables, we identified several socio-demographic factors influencing the utilization of surgical treatment of calcaneus fractures in the US patient population. Further studies need to identify the specific patient-related, provider-related, and system-related factors leading to these disparities.

Validity of the Hispanic version of the American Academy of Orthopaedic Surgeons Foot and Ankle Outcomes Questionnaire in patients with traumatic foot and ankle injuries.

BACKGROUND: Hispanics represent the largest minority group in the United States and are projected to represent 29% of the US population by 2060. Enrolling Hispanic patients in clinical outcome trials is critical to study a representative sample of the general population. Lack of translated and validated survey tools has been identified as a major barrier to enrolling Spanish speaking patients. The purpose of this validation study was to study the correlation between the Spanish translation of the American Academy of Orthopaedic Surgeons Foot and Ankle Outcomes questionnaire (AAOS-FAOQ) and the Spanish versions of the Foot Function Index (FFI) and the Foot Health Status Questionnaire (FHSQ) in Hispanics from Mexican lineage with traumatic foot and ankle injuries. METHODS: A cross-sectional validation study in 36 Hispanic patients from Mexican lineage with foot and ankle injuries was performed. The Hispanic version of the AAOS-FAOQ and the Spanish translations of the FAOQ, FHSQ, FFI, and the Short-Form 36 questionnaire (SF-36) were distributed among all patients. Subsequent statistical analysis correlating the Hispanic version of the AAOS-FAOQ to the FFI, FHSQ, and SF-36 was performed. Additional analysis on the Hispanic AAOS-FAOQ included test-retest reliability and internal consistency. RESULTS: The Hispanic AAOS-FAOQ Global Foot and Ankle subscale showed statistically significant (P < .05) correlations with 5 of 8 subscales of the FHSQ, the FFI, and the Physical Component Summary subscale of the SF-36. The AAOS-FAOQ Global Foot & Ankle Scale also demonstrated a test-retest reliability of 0.736 and a strong internal consistency. CONCLUSIONS: This study further validates AAOS-FAOQ in Mexican Hispanics by showing strong correlations with the validated Spanish versions of the FFI and FHSQ.