Citations

Objective: Symptomatic thumb carpometacarpal (CMC) joint osteoarthritis is common. Early data support selective strengthening of the first dorsal interosseous (FDI) and opponens pollicis (OP) muscles for conservative management with improvement in pain and functional outcomes scores. There are limited biomechanical studies to support such strengthening programs. The purpose of these studies was to quantify the kinematics and joint kinetics at the thumb CMC joint during simulated pinch with selective activation of the FDI and OP muscles. The first study was completed with all ligamentous attachments of the CMC joint intact. The second study was completed with all CMC ligaments released. Hypothesis: Our hypothesis was that increased loads in the FDI and OP result in effects to the joint kinematics and reduce subluxation. Results: Our results from both studies show the OP and FDI act synergistically to center the first metacarpal on the trapezium and reduce subluxation during simulated pinch. The OP is the predominant corrective force but tends to overcorrect if unopposed. The FDI tempers the action of OP and contributes to improved CMC congruency. Conclusion: Our conclusion is these biomechanical data support selective thenar muscle re-education and strengthening programs for conservative management of thumb CMC joint osteoarthritis and pain.

Objective/HypothesisEosinophilic otitis media (EOM) is a variant of chronic otitis media that is characterized by the development of thick mucoid middle ear effusion, adult onset bronchial asthma, sinonasal polyposis, and aspirin sensitivity. EOM is typically refractory to corticosteroid therapy and surgical intervention. Pegylated interferon (PEG‐IFN) has effectively treated hypereosinophilic syndrome in clinical trials; however, the efficacy of this medication for EOM treatment remains undefined.Study DesignRetrospective, case series, tertiary academic center.MethodsA retrospective chart review was performed on EOM patients from 2008–2014. A total of 32 patients met the clinical criteria for EOM according to established diagnostic guidelines. Outcomes of all patients with severe, refractory EOM who initiated PEG‐IFN therapy are reported.ResultsEight patients were treated with pegylated interferon‐α 2a or 2b for refractory EOM. Half of the patients had significant side effects with interferon treatment. Three of these were able to continue at a reduced dosage without side effect reoccurrence, and one patient stopped the medication permanently. Four of eight (50%) patients had a complete clinical response with total resolution of otorrhea and normalization of middle ear mucosa, and were able to discontinue corticosteroid treatment. Two patients attempted to stop PEG‐IFN therapy after prolonged symptom remission and had recurrent otorrhea. Both patients had symptom resolution after PEG‐IFN reinitiation.ConclusionsThese data demonstrate that pegylated interferon‐α 2a and 2b therapy may benefit patients with severe, refractory EOM. Further larger studies with long‐term follow‐up are required to validate these early but promising results.Level of Evidence4. Laryngoscope, 127:1208–1216, 2017

Background— The use of transcatheter aortic valve replacement (TAVR) to treat aortic stenosis in the United States is growing, yet little is known about the variation in procedural outcomes in community practice. We developed a TAVR in-hospital mortality risk model and used it to quantify variation in mortality rates across United States (US) TAVR centers. Methods and Results— We analyzed data from 22 248 TAVR procedures performed at 318 sites participating in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry (November 2011 to October 2014). A Bayesian hierarchical model was developed to estimate hospital-specific risk-adjusted mortality rates adjusting for 40 patient baseline factors. A total of 1130 in-hospital deaths (5.1%) were observed. Reliability-adjusted risk-adjusted mortality rate estimates ranged from 3.4% to 7.7% with an interquartile range of 4.8% to 5.4%. A patient’s predicted odds of dying was 80% higher if treated by a hospital 1 standard deviation above the mean compared with a hospital 1 standard deviation below the mean (odds ratio =1.8; 95% credible interval, 1.4%–2.2%). Conclusions— Risk modeling of TAVR in-hospital mortality revealed variation in risk-adjusted mortality rates during the US early commercial experience. Transcatheter Valve Therapy Registry analyses using this model will support research, feedback reporting, and the identification of factors associated with quality.

Background Since 1972, patients with large nasal perforations, who were symptomatic, and who were not candidates for surgery, had the option of custom prosthetic closure at Mayo Clinic. Although septal prostheses have helped many patients, 27% of pre-1982 patients chose not to keep the prosthesis in place. Two-dimensional computed tomography (CT) sizing resulted in more of the patients choosing to retain the prosthesis. The introduction of three-dimensional (3-D) printing to the sizing process offered the potential of further improved retention by refinement in prosthesis fit. Objective To describe the fabrication of nasal septal prostheses by using 3-D printing for sizing and to compare the retention rate of 3-D-sized prostheses with those that used previous sizing methods. Methods Twenty-one consecutive patients who had placement of septal prostheses sized by using 3-D printed templates were studied. CT image data were used to print 3-D templates of the exact shape of the patient's septal perforation, and medical-grade silastic prostheses were fabricated to fit. In four cases, the 3-D printed template allowed preoperative surgical simulation. Metrics collected included prosthesis retention; symptoms, including intranasal crusting and epistaxis; and previous prosthetic closure failures. Results Twenty of the twenty-one patients had improvement in symptoms. The mean diameter of the perforations was 2.4 cm; the mean closure time by the end of the study period was 2.2 years. All but two patients chose to keep their prosthesis in place, for a retention rate of 90%. Seven patients with successful closure had failed previously with prior prosthesis sized without the current 3-D printing methodology. This 90% retention rate exceeded the previous rates before the introduction of 3-D sizing. Conclusion Sizing done by 3-D printing for prosthetic closure of nasal septal perforations resulted in a higher retention rate in helping patients with these most-challenging nasal septal perforations.

Background Whereas insurance status has been previously associated with care patterns, little is currently known about the association between Medicaid insurance and the clinical characteristics, treatment, or outcomes of patients with atrial fibrillation ( AF ). Methods and Results We used data from adults with AF enrolled in the Outcomes Registry for Better Informed Treatment of AF ( ORBIT ‐ AF ), a national outpatient registry conducted at 176 community, multispecialty sites. The primary outcome of interest was the proportion of patients prescribed any oral anticoagulation ( OAC ; warfarin or novel oral anticoagulants [ NOAC ]). Secondary outcomes of interest included the proportion of patients prescribed NOAC s (dabigatran or rivaroxaban); time in therapeutic range ( TTR ) for warfarin users, all‐cause mortality, stroke/systemic embolism, and major bleed. Of 10 133 patients, N=470 (4.6%) had Medicaid insurance. Medicaid patients were similarly likely to receive OAC at baseline (72.8% vs 76.3%; unadjusted P =0.079), but less likely to receive NOAC at baseline or follow‐up (12.1% vs 16.3%; unadjusted P =0.019). After risk adjustment, Medicaid status was associated with lower use of OAC at baseline among patients with high stroke risk (odds ratio [ OR ]=0.68; 95% CI =0.49, 0.94), but was not associated with OAC use overall ( OR =0.82; 95% CI =0.61, 1.09). Among warfarin users, median TTR was lower among Medicaid patients (60% vs 68%; P <0.0001; adjusted TTR difference, −2.9; 95% CI =−5.7, −0.2; P =0.04). Use of an NOAC over 2 years of follow‐up was not statistically different by insurance. Compared with non‐Medicaid patients, Medicaid patients had higher unadjusted rates of mortality, stroke/systemic embolism, and major bleeding; however, these differences were attenuated following adjustment for clinical characteristics. Conclusions In a contemporary AF cohort, use of OAC overall and use of NOAC s were not significantly lower among Medicaid patients relative to others. However, among warfarin users, Medicaid patients spent less time in therapeutic range compared with those with other forms of insurance.

ABSTRACT Understanding how some HIV-infected cells resist the cytotoxicity of HIV replication is crucial to enabling HIV cure efforts. HIV killing of CD4 T cells that replicate HIV can involve HIV protease-mediated cleavage of procaspase 8 to generate a fragment (Casp8p41) that directly binds and activates the mitochondrial proapoptotic protein BAK. Here, we demonstrate that Casp8p41 also binds with nanomolar affinity to the antiapoptotic protein Bcl-2, which sequesters Casp8p41 and prevents apoptosis. Further, we show that central memory CD4 T cells (T CM ) from HIV-infected individuals have heightened expression of BCL-2 relative to procaspase 8, possibly explaining the persistence of HIV-infected T CM despite generation of Casp8p41. Consistent with this hypothesis, the selective BCL-2 antagonist venetoclax induced minimal killing of uninfected CD4 T cells but markedly increased the death of CD4 T cells and diminished cell-associated HIV DNA when CD4 T cells from antiretroviral therapy (ART)-suppressed HIV patients were induced with αCD3/αCD28 to reactivate HIV ex vivo . Thus, priming CD4 T cells from ART suppressed HIV patients with a BCL-2 antagonist, followed by HIV reactivation, achieves reductions in cell-associated HIV DNA, whereas HIV reactivation alone does not. IMPORTANCE HIV infection is incurable due to a long-lived reservoir of HIV + memory CD4 T cells, and no clinically relevant interventions have been identified that reduce the number of these HIV DNA-containing cells. Since postintegration HIV replication can result in HIV protease generation of Casp8p41, which activates BAK, causing infected CD4 T cell death, we sought to determine whether this occurs in memory CD4 T cells. Here, we demonstrate that memory CD4 T cells can generate Casp8p41 and yet are intrinsically resistant to death induced by diverse stimuli, including Casp8p41. Furthermore, BCL-2 expression is relatively increased in these cells and directly binds and inhibits Casp8p41's proapoptotic effects. Antagonizing BCL-2 with venetoclax derepresses this antagonism, resulting in death, preferentially in HIV DNA containing cells, since only these cells generate Casp8p41. Thus, BCL-2 antagonism is a clinically relevant intervention with the potential to reduce HIV reservoir size in patients.

OBJECT Endoscopic approaches to the anterior craniocervical junction are increasing in frequency. Choice of oral versus endoscopic endonasal approach to the odontoid often depends on the relationship of the C1–2 complex to the hard palate. However, it is not known how this relevant anatomy changes with age. We hypothesize that there is a dynamic relationship of C-2 and the hard palate, which changes with age, and potentially affects the choice of surgical approach. The aim of this study was to characterize the relationship of C-2 relative to the hard palate with respect to age and sex. METHODS Emergency department billing and trauma records from 2008 to 2014 were reviewed for patients of all ages who underwent cervical or maxillofacial CT as part of a trauma evaluation for closed head injury. Patients who had a CT scan that allowed adequate visualization of the hard palate, opisthion, and upper cervical spine (C-1 and C-2) were included. Patients who had cervical or displaced facial/skull base fractures, a history of rheumatoid arthritis, or craniofacial anomalies were excluded. The distance from McGregor's palatooccipital line to the midpoint of the inferior endplate of C-2 (McL–C2) was measured on midsagittal CT scans. Patients were grouped by decile of age and by sex. A 1-way ANOVA was performed with each respective grouping. RESULTS Ultimately, 483 patients (29% female) were included. The mean age was 46 ± 24 years. The majority of patients studied were in the 2nd through 8th decades of life (85%). Significant variation was found between McL–C2 and decile of age (p < 0.001) and sex (p < 0.001). The mean McL–C2 was 27 mm in the 1st decade of life compared with the population mean of 37 mm. The mean McL–C2 was also noted to be smaller in females (mean difference 4.8 mm, p < 0.0001). Both decile of age (p = 0.0009) and sex (p < 0.0001) were independently correlated with McL–C2 on multivariate analysis. CONCLUSIONS The relationship of C-2 and the hard palate significantly varies with respect to age and sex, descending relative to the hard palate a full centimeter on average in adulthood. These findings may have relevance in determining optimal surgical approaches for addressing pathology involving the anterior craniocervical junction.