Switching anti-CGRP monoclonal antibodies in chronic migraine: real-world observations of erenumab, fremanezumab and galcanezumab.

OBJECTIVES: The anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP-mAb) are effective in migraine; however, few studies have examined the benefit of switching from one anti-CGRP-mAb to another. In order to better inform clinical practice in this situation, we present our real-world findings of switching anti-CGRP-mAb in chronic migraine. METHODS: Individuals with chronic migraine that switched anti-CGRP-mAb treatment (erenumab, fremanezumab or galcanezumab) due to ineffectiveness or adverse effects were retrospectively identified. Headache diary data before and up to 6 months after anti-CGRP-mAb switch were analysed. Main outcome measures were monthly red days (days with headaches limiting activity or requiring triptans), headache days (days with any kind of headache), triptan use, other analgesic use and headache disability (Headache Impact Test-6 (HIT-6) score) at 3 months. RESULTS: The analysis included 66 instances of switching among 54 individuals. There were non-significant reductions of -1.2 (-2.7, 0.3) red days from baseline at 3 months, with 10 individuals (15%) showing ≥50% improvement and 22 (33%) experiencing a ≥30% improvement. Improvements in headache days, triptan days, other painkiller use and HIT-6 score were non-significant. When individuals that switched due to side effects were excluded from the analysis, significant reductions in headache (Friedman p=0.044) and a trend for improvement in red days (Friedman p=0.083) were observed. With regard to side effects, on 12 occasions these improved or resolved on switching to a different anti-CGRP-mAb, while new symptoms were reported on eight occasions following a switch. CONCLUSION: We recorded modest improvements in headache outcomes, although significant results were only observed in those that switched anti-CGRP-mAb due to ineffectiveness. Switching may therefore be a viable option for these individuals.

Effectiveness and safety profile of greater occipital nerve blockade in cluster headache: a systematic review.

BACKGROUND: Greater occipital nerve (GON) blockade is a short-term preventive therapy for cluster headache (CH). We conducted a systematic review to evaluate the effectiveness and safety of GON blockade in patients with CH. METHODS: On 23 October 2020, we searched MEDLINE, Embase, Embase Classic, PsycINFO, CINAHL, CENTRAL and Web of Science databases from their inception date. Studies included participants with a CH diagnosis who received corticosteroid and local anaesthetic suboccipital region injections. Outcomes were change in the frequency/severity/duration of attacks; proportion of participants responding to treatment, time to attack freedom from an attack, change in attack bout length and/or the presence of adverse effects after GON blockade. Risk of bias was assessed with the Cochrane Risk of Bias V.2.0 (RoB2)/Risk of Bias in Non-randomized Studies - of Interventions (ROBINS- I) tools and a specific tool for case reports/series. RESULTS: Two RCTs, eight prospective and eight retrospective studies, and four case reports were included in the narrative synthesis. Every effectiveness study found a significant response in one or more of frequency/severity/duration of individual attacks or proportion of patients responding to treatment (47.8%-100.0%). There were five instances of potentially irreversible adverse effects. A higher injectate volume and use of concurrent prophylaxis may be associated with an increased likelihood of response. Methylprednisolone may have the best safety profile of available corticosteroids. DISCUSSION: GON blockade is safe and effective for CH prevention. Higher injectate volumes may improve likelihood of response, and the likelihood of serious adverse events may be reduced by using methylprednisolone. PROSPERO REGISTRATION NUMBER: CRD42020208435.

A Workflow Change in Anterior Approach Total Hip Arthroplasty Leads to Improved Accuracy of Biomechanical Reconstruction Without Increased Risk of Complications.

BACKGROUND: During anterior approach total hip arthroplasty (THA), the femur may be an impediment for acetabular access, pushing reamers proximally and consequently altering the hip center. In an effort to address this, the senior author changed the surgical workflow from acetabulum first (AF) to femur first (FF). The objective of this study was to compare the precision of biomechanical hip reconstruction and clinical outcomes between the FF and AF techniques. METHODS: This is a retrospective, case-control study of 267 anterior THAs (132 AF and 135 FF). A normal, contralateral hip was used to determine the native biomechanical parameters. Using a calibrated software program, radiographic measurements were performed to calculate the hip center position, femoral offset, global offset, and leg length of the operative and native hips using 2-week postoperative anteroposterior pelvis radiographs. Demographics, operative information, hemoglobin change, and complication data were obtained. Functional outcomes were assessed with the Hip Dysfunction and Osteoarthritis Outcome Score for Joint Replacement survey at 1 year postoperatively. RESULTS: The groups exhibited similar demographic characteristics. The FF group demonstrated significantly more accurate and more precise reconstruction of horizontal and vertical hip centers, femoral offset, and leg length. There was no significant difference in operative time, hemoglobin change, complication rate, or Hip Disability and Osteoarthritis Outcome Score, Joint Replacement scores between groups. CONCLUSIONS: The FF technique allowed for more accurate and precise reconstruction of the hip center, leg length, and offset in THA than the AF workflow. Furthermore, the FF approach demonstrated no significant differences in complication rate or blood loss, nor in clinical outcomes. LEVEL OF EVIDENCE: Therapeutic Study Level III.

Achieving a Balanced Knee in Robotic TKA.

Total knee arthroplasty (TKA) surgery with manual instruments provides a quantitatively balanced knee in approximately 50% of cases. This study examined the effect of combining robotics technology with real-time intra-operative sensor feedback on the number of quantitatively balanced cases in a consecutive series of 200 robotic-assisted primary TKAs. The robotics platform was used to plan the implant component position using correctable poses in extension and a manual, centrally pivoting the balancer in flexion, prior to committing to the femoral cuts. During the initial trialing, the quantitative state of balance was assessed using an instrumented tibial tray that measured the intra-articular loads in the medial and lateral compartments. These sensor readings informed a number of surgical corrections, including bone recuts, soft-tissue corrections, and cement adjustments. During initial trialing, a quantitatively balanced knee was achieved in only 65% of cases. After performing the relevant soft-tissue corrections, bone recuts, and cement adjustments, 87% of cases ended balanced through the range of motion. Meanwhile, this resulted in a wide range of coronal alignment conditions, ranging from 6° valgus to 9° varus. It is therefore concluded that gaps derived from robotics navigation are not indicative for a quantitatively balanced knee, which was only consistently achieved when combining the robotics platform with real-time feedback from intra-operative load sensors.

The Actis and Corail Femoral Stems Provide for Similar Clinical and Radiographic Outcomes in Total Hip Arthroplasty.

BACKGROUND: The introduction of new devices for total hip arthroplasty (THA) offers surgeons the ability to address deficits in the portfolio. However, once introduced, data regarding the performance of devices is not publicly available until their use is widespread. PURPOSE/QUESTIONS: The objective of this study was to compare the clinical and radiographic performance, including patient reported outcomes and radiographic evidence of osseointegration, subsidence, and stress shielding, of the newer Actis femoral component to the Corail stem (DePuy Synthes, Warsaw, IN, USA), which has an extensive clinical history. METHODS: This short-term, retrospective cohort study was a single surgeon series of 330 anterior approach THAs, consisting of 165 cases using the Actis stem and 165 cases using the Corail stem. Both devices were cementless, titanium, tapered, hydroxyapatite-coated stems. They differed in geometry, neck choices, broach philosophy, and collar availability. Data was obtained for 1 year following THA. Functional outcomes were measured with the Hip Dysfunction and Osteoarthritis Outcome Score for Joint Replacement (HOOS, JR.) survey. Complications were recorded from patient charts, and radiographic analysis was performed for signs of osseointegration, subsidence, and stress shielding. RESULTS: The groups shared similar demographic characteristics except the Actis population was younger with fewer women. The complication rate did not significantly vary, and no patient required revision within the first year. Radiographically, one patient in each group demonstrated subsidence. No cases exhibited radiolucent lines, and the prevalence of stress shielding at 1 year was comparable. HOOS, JR. scores did not significantly vary at 8 weeks or 1 year. CONCLUSION: The Actis stem does not carry an increased risk of device-related complications compared with the Corail implant. Although aspects of bone remodeling differed between groups, Actis achieved radiographic signs of bone ingrowth at the 1-year mark and performed well clinically, with equivalent patient reported outcome scores to the Corail stem.

Early-life stress is associated with a preponderance of habitual responding in a novel instrumental avoidance learning paradigm.

There is substantial evidence linking early-life stress (ELS) to negative health outcomes in adulthood, including addiction. However, the neurocognitive and behavioral mechanisms through which ELS increases these risks remain unclear. To address this gap in knowledge, we developed a novel instrumental learning paradigm to explore the effects of ELS on the balance of habitual versus goal-directed learning. Habits efficiently reproduce repetitive behaviors but are inflexible whenreward contingencies related to those behaviors change. Persisting in performing a response after its outcome has been devalued is the hallmark of habitual behavior in instrumental learning. Participants with a history of higher ELS were significantly more likely to make habitual responses in this instrumental avoidance learning paradigm than individuals with a history of lower ELS. Logistic regression analysis showed that ELS is significantly related to habitual responding over and above the effects of retrospective socioeconomic status, trait and state anxiety, depression and recent levels of stress. Analysis of the differential impacts of the type of ELS suggested that these effects are largely driven by experiences of physical neglect.

Clinical Utility of the Personality Assessment Inventory in Predicting Symptom Change and Clinical Outcome in an Inpatient Chemical Dependency Rehabilitation Unit.

Newly admitted inpatients in a 28-day chemical dependency rehabilitation unit completed the Personality Assessment Inventory (PAI) at admission and measures of clinical symptomatology (Symptom Checklist-90-Revised) and clinical outcome (Schwartz Outcome Scale-10) at admission and discharge. PAI drug and alcohol scale scores were clinically elevated in this inpatient sample. Modest elevations were found on scales measuring stress, depression, and antisocial and borderline features. Lower scores on most PAI clinical scales were associated with greater symptom reduction and improved psychological well-being, while controlling for pretreatment levels. Multivariate analysis controlling for contributions of clinical scales measuring borderline, depressive, and antisocial traits, as well as pretreatment outcome measures, demonstrated that the PAI Suicidal Ideation and Treatment Rejection scales were significant individual predictors of symptom reduction and improved psychological well-being, respectively, although the treatment scales as a group failed to incrementally contribute to prediction. Overall, the results support the clinical utility of using the PAI to predict clinical improvement among inpatients treated for substance use disorders.

Does It Matter: Total Hip Arthroplasty or Lumbar Spinal Fusion First? Preoperative Sagittal Spinopelvic Measurements Guide Patient-Specific Surgical Strategies in Patients Requiring Both.

BACKGROUND: In patients requiring both total hip arthroplasty (THA) and lumbar spinal fusion (LSF), consideration of preoperative sagittal spinopelvic measurements can aid in the prediction of postfusion compensatory changes in pelvic tilt (PT) and inform adjustments to traditional THA cup anteversion. This study aims to identify relationships between spinopelvic measurements and post-THA hip instability and to determine if procedure order reveals a difference in hip dislocation rate. METHODS: Patients at a single practice site who received both THA and LSF between 2005 and 2015 (292: 158 = LSF prior to THA, 134 = THA prior to LSF) were retrospectively reviewed for incidents of THA instability. Those with complete radiograph series (89) had their sagittal (standing) spinopelvic profiles measured preoperatively, immediately postoperatively, and 3 months, 6 months, 1 year, 1.5 years, and 2 years postoperatively. Measured parameters included lumbar lordosis (LL), pelvic incidence (PI), PT, and sacral slope (SS). RESULTS: No significant differences in dislocation rates between operative order groups were elicited (7/73 LSF first, 4/62 THA first; Z = 0.664, P = .509). Compared to nondislocators, dislocators had lower LL (-10.9) and SS (-7.8), and higher PT (+4.3) and PI-LL (+7.3). Additional risk factors for dislocation included sacral fusion (relative risk [RR] = 3.0) and revision fusion (RR = 2.7) . Predictive power of the model generated through multiple regression to characterize individual profiles of post-LSF PT compensation based on perioperative measurements was most significant at 1 year (R2 = 0.565, F = 0.000456, P = .028) and 2 years (R2 = 0.741, F = 0.031, P = .001) postoperatively. CONCLUSION: In performing THA after LSF, it is theoretically ideal to proceed with THA at a postfusion interval of at least 1 year, beyond which further compensatory PT change is minimal. However, the order of surgical procedure revealed no statistical difference in hip instability rates. In cases characterized by large PI-LL mismatch (larger or less predictable compensation profiles) or large SS or LL loss (considerably atypical muscle recruitment), consideration of full functional anteversion range between sitting and standing positions to account for abnormalities not appreciated with standing radiographic assessment alone may be warranted.

Survivorship of the Modular Femoral Revision Stem.

The geriatric population represents a rapidly growing segment of society with prolonged life expectancies and more active lifestyles. Many of these patients have already undergone primary total hip arthroplasty (THA) and are presenting with aseptic loosening, polyethylene wear, osteolysis, or periprosthetic fractures. Therefore, the demand for hip revision procedures is expected to grow. Currently, there are many modular implant options available for use in complicated revision THA. Early results of modular femoral revision systems are promising for the treatment of the deficient femur in complex revision THA. The objective of this study was to evaluate component survivorship of a modular femoral revision system in revision THA. A retrospective review was conducted using electronic health records of patients who underwent revision THA performed by 1 of 3 surgeon investigators from 2010 through 2014. The authors included all patients who underwent a revision THA using a specific modular femoral revision system. The authors evaluated component survivorship and time to re-revision THA. Fifty-one revision THAs were included. Seven patients required a second revision THA (13.7%; 95% confidence interval, 4%-23%). Mean time to re-revision THA was 4.88±3.9 months. Kaplan-Meier survivorship using re-revision for any reason was 86.3% at 60 months. This study showed excellent component survivorship of the specific modular femoral revision system in revision THA. [Orthopedics. 2019; 42(5):294-298.].

Are Patients More Satisfied With a Balanced Total Knee Arthroplasty?

BACKGROUND: Patient-reported outcome measures are increasingly recognized as an important tool in quantifying the clinical success of arthroplasty surgery. The aim of this study is to measure post-operative joint awareness and satisfaction in patients with and without a quantitatively balanced knee following primary total knee arthroplasty (TKA). METHODS: In this multi-center study, a total of 318 eligible patients were assigned to one of the 2 patient groups: sensor-guided TKA or surgeon-guided TKA. In the sensor-guided group, quantitative balancing was performed according to intercompartmental tibiofemoral load measurements measured by an instrumented tibial trial component. In contrast, for the surgeon-guided group, the knees were balanced according to the surgeons' standard manual techniques while blinding the surgeon to the sensor measurements. Patients were blinded to their allocation and filled out the validated Forgotten Joint Score and 2011 Knee Society Satisfaction questionnaires at 6 weeks and 6 months. For the purposes of this study, the subjects were pooled and stratified by their state of soft tissue balance, based on the mediolateral load differential through the range of motion. RESULTS: In the surgeon-guided group, approximately 50% of the cases yielded a quantitatively balanced knee. Significantly more balanced knees were observed in the sensor-guided group (84.0%). More importantly, for both outcome measures, the balanced group of patients reported significantly better outcomes scores. CONCLUSION: This demonstrates that using sensor feedback during knee arthroplasty surgery results in a more reproducible procedure, resulting in a higher percentage of balanced patients who in turn demonstrate superior clinical outcomes compared to unbalanced patients.

Personality profiles of patients with alcohol use disorder and opioid use disorder in an inpatient treatment setting.

The present study aimed to compare personality profiles of alcohol use disorder and opioid use disorder patients in an inpatient chemical dependency rehabilitation unit using a multidimensional personality inventory, the Personality Assessment Inventory (PAI). Ninety-six patients meeting DSM-IV-TR diagnoses for alcohol use or opioid use disorders completed the PAI at admission. Results revealed largely normative patterns across most PAI scales, though alcohol use disorder patients showed clinically elevated scores on Alcohol Problems and Drug Problems, and opioid use disorder patients showed clinical elevations on Antisocial Features, Borderline Features, and Drug Problems. Opioid use disorder patients showed, on average, significantly higher scores than alcohol use disorder patients on Borderline Features, Antisocial Features, Drug Problems, and Suicidal Ideation. Alcohol use disorder patients showed significantly higher scores than opioid use disorder patients only on Alcohol Problems. Discriminant function analysis (DFA) showed discriminability between patient groups using the PAI clinical scales and treatment scales, highlighting higher levels of disturbed functioning among opioid use disorder patients with respect to clinical syndromes, especially borderline features, antisocial features, suicidal ideation, and anxiety. These findings underscore the need to tailor treatment recommendations to distinctive patterns of personality pathology, especially among opioid use disorder patients.

Is it safe? Outpatient total joint arthroplasty with discharge to home at a freestanding ambulatory surgical center.

BACKGROUND: Total joint arthroplasty (TJA) is trending toward shorter hospitalizations; as a result, there are many ambulatory surgical centers (ASCs) starting to perform outpatient TJA. However, there are limited studies examining the safety of outpatient TJA in the freestanding ASC setting. This study aims to evaluate 30-day and 90-day complication rates in patients who underwent outpatient TJA at a freestanding, independent ASC with direct discharge to home. METHODS: A retrospective cohort review using health records was performed on the first 115 TJAs performed between August 2015 and March 2017 by one of the 4 orthopedic surgeons. Before the first TJA, the ASC had developed a multidisciplinary TJA pathway. RESULTS: Of the 115 TJAs, 37 (32%) were total hip arthroplasties (THAs), 53 (46%) total knee arthroplasties (TKAs), and 25 (22%) unicompartmental knee arthroplasties, with a mean age of 57 ± 7 years and body mass index of 30 ± 5 kg/m2. There were no intraoperative or direct ASC-related complications. There was 1 instance (0.9%) of a postoperative minimally displaced intertrochanteric femur fracture after THA due to a fall treated nonoperatively complication within 30 days of surgery. Of the 90-day complication events, there were 2 patients (2%) with postoperative arthrofibrosis of the knee after TKA requiring manipulation under anesthesia, 1 postoperative patellar tendon rupture during therapy after TKA requiring surgical repair and 1 delayed hematogenous infection after international travel after THA requiring 2-staged exchange. CONCLUSIONS: Outpatient TJA with discharge to home at a freestanding, independent ASC is a safe option after development of a multidisciplinary TJA pathway.

Effects of oral Akkermansia muciniphila supplementation in healthy dogs following antimicrobial administration.

OBJECTIVE To measure effects of oral Akkermansia muciniphila administration on systemic markers of gastrointestinal permeability and epithelial damage following antimicrobial administration in dogs. ANIMALS 8 healthy adult dogs. PROCEDURES Dogs were randomly assigned to receive either A muciniphila (109 cells/kg; n = 4) or vehicle (PBS solution; 4) for 6 days following metronidazole administration (12.5 mg/kg, PO, q 12 h for 7 d). After a 20-day washout period, the same dogs received the alternate treatment. After another washout period, experiments were repeated with amoxicillin-clavulanate (13.5 mg/kg, PO, q 12 h) instead of metronidazole. Fecal consistency was scored, a quantitative real-time PCR assay for A muciniphila in feces was performed, and plasma concentrations of cytokeratin-18, lipopolysaccharide, and glucagon-like peptides were measured by ELISA before (T0) and after (T1) antimicrobial administration and after administration of A muciniphila or vehicle (T2). RESULTS A muciniphila was detected in feces in 7 of 8 dogs after A muciniphila treatment at T2 (3/4 experiments) but not at T0 or T1. After metronidazole administration, mean change in plasma cytokeratin-18 concentration from T1 to T2 was significantly lower with vehicle than with A muciniphila treatment (-0.27 vs 2.4 ng/mL). Mean cytokeratin-18 concentration was lower at T1 than at T0 with amoxicillin-clavulanate. No other significant biomarker concentration changes were detected. Probiotic administration was not associated with changes in fecal scores. No adverse effects were attributed to A muciniphila treatment. CONCLUSIONS AND CLINICAL RELEVANCE Detection of A muciniphila in feces suggested successful gastrointestinal transit following oral supplementation in dogs. Plasma cytokeratin-18 alterations suggested an effect on gastrointestinal epithelium. Further study is needed to investigate effects in dogs with naturally occurring gastrointestinal disease.

Epidemiology, Microbiological Diagnosis, and Clinical Outcomes in Pyogenic Vertebral Osteomyelitis: A 10-year Retrospective Cohort Study.

BACKGROUND: Pyogenic vertebral osteomyelitis (PVO) is rising in incidence, but optimal methods of investigation and duration of antibiotic therapy remain controversial. METHODS: We conducted a single-center retrospective cohort study of PVO at an Australian teaching hospital. We included all adults with a first episode of PVO between 2006 and 2015. PVO was defined based on the presence of prespecified clinical and radiological criteria. The main exposures of interest were investigation strategy and antibiotic treatment. The main outcome measures were duration of hospital admission, mortality during index admission, symptom resolution during index admission, and attributable readmission within 2 years. RESULTS: Of 129 included patients, 101 (78%) had a causative organism identified. Patients with an identified pathogen were more likely to be febrile (75% compared with 29%, P < .001) and had a higher mean admission C-reactive protein (207 vs 54, P < .001) compared with patients without an identified pathogen. However, they were less likely to experience an adverse outcome (death or attributable readmission within 2 years; adjusted odds ratio, 0.36; 95% confidence interval, 0.13-0.99; P = .04). Open biopsy of vertebral tissue had a higher diagnostic yield (70%) than fine needle aspirate (41%) or core biopsy (30%). Despite receiving a median of 6 weeks of intravenous antibiotics, only 15% of patients had a full recovery on discharge from index admission. CONCLUSIONS: Clinical outcomes for patients with PVO were poor. Obtaining a microbiological diagnosis is associated with a better outcome. However, prospective and randomized studies are essential to establishing optimal investigation and treatment pathways.

Polymorphic Phase Control of RDX-Based Explosives.

The polymorphic phase of 1,3,5-trinitro-1,3,5-triazine (RDX) was examined as a function of mass loading, solvent, and sample deposition technique. When RDX was deposited at a high mass loading, the vibrational modes in the obtained Raman spectra were indicative of concomitant polymorphism as both the α-RDX and ß-RDX phases were present. At low mass loadings, only ß-RDX was observed regardless of solvent when using the drop cast crystallization method. However, α-RDX (the thermodynamically stable polymorphic phase observed with visible quantities of the explosive) was observed when RDX deposits were dry transferred. Observation of α-RDX was independent of the initial mass loading or the initial deposition solvent when using the dry transfer methodology. These data indicate that the use of the dry transfer preparation method can be used to successfully prepare RDX-based test articles with the α-RDX phase regardless of the solvent used to initially dissolve the RDX, the initial deposition technique, or the mass loading.

Differential Inhibitory Receptor Expression on T Cells Delineates Functional Capacities in Chronic Viral Infection.

Inhibitory receptors have been extensively described for their importance in regulating immune responses in chronic infections and cancers. Blocking the function of inhibitory receptors such as PD-1, CTLA-4, 2B4, Tim-3, and LAG-3 has shown promise for augmenting CD8 T cell activity and boosting pathogen-specific immunity. However, the prevalence of inhibitory receptors on CD4 T cells and their relative influence on CD4 T cell functionality in chronic HIV infection remains poorly described. We therefore determined and compared inhibitory receptor expression patterns of 2B4, CTLA-4, LAG-3, PD-1, and Tim-3 on virus-specific CD4 and CD8 T cells in relation to their functional T cell profile. In chronic HIV infection, inhibitory receptor distribution differed markedly between cytokine-producing T cell subsets with, gamma interferon (IFN-γ)- and tumor necrosis factor alpha (TNF-α)-producing cells displaying the highest and lowest prevalence of inhibitory receptors, respectively. Blockade of inhibitory receptors differentially affected cytokine production by cells in response to staphylococcal enterotoxin B stimulation. CTLA-4 blockade increased IFN-γ and CD40L production, while PD-1 blockade strongly augmented IFN-γ, interleukin-2 (IL-2), and TNF-α production. In a Friend retrovirus infection model, CTLA-4 blockade in particular was able to improve control of viral replication. Together, these results show that inhibitory receptor distribution on HIV-specific CD4 T cells varies markedly with respect to the functional subset of CD4 T cells being analyzed. Furthermore, the differential effects of receptor blockade suggest novel methods of immune response modulation, which could be important in the context of HIV vaccination or therapeutic strategies.IMPORTANCE Inhibitory receptors are important for limiting damage by the immune system during acute infections. In chronic infections, however, their expression limits immune system responsiveness. Studies have shown that blocking inhibitory receptors augments CD8 T cell functionality in HIV infection, but their influence on CD4 T cells remains unclear. We assessed the expression of inhibitory receptors on HIV-specific CD4 T cells and their relationship with T cell functionality. We uncovered differences in inhibitory receptor expression depending on the CD4 T cell function. We also found differences in functionality of CD4 T cells following blocking of different inhibitory receptors, and we confirmed our results in a Friend virus retroviral model of infection in mice. Our results show that inhibitory receptor expression on CD4 T cells is linked to CD4 T cell functionality and could be sculpted by blockade of specific inhibitory receptors. These data reveal exciting possibilities for the development of novel treatments and immunotherapeutics.

Alarmingly High Rate of Implant Fractures in One Modular Femoral Stem Design: A Comparison of Two Implants.

BACKGROUND: Reports of implant fracture at the modular junction have been seen in modular neck designs, stem-sleeve modular femoral stems, and diaphyseal engaging bi-body modular stems. To date, however, there has never been a direct comparison between 2 different implant designs from the same modular family. The purpose of this study is to compare the rate of implant failure of 2 such stem-sleeve modular femoral stem designs, the S-ROM and Emperion, to further identify factors which increase the risk of this mode of failure. METHODS: A retrospective, single surgeon, review of our institutional database was performed to compare the 2 groups of patients. RESULTS: A total of 1168 total hip arthroplasty procedures were included in our analysis, 547 (47%) with Emperion and 621 (53%) with S-ROM. Eight (1.5%) fractures in 7 patients occurred in the Emperion group compared to 1 (0.2%) fracture in the S-ROM group (P = .015). CONCLUSION: The precise cause of the stem fractures in our study remains unknown and is likely multifactorial. Given the unexpectedly high rate of catastrophic implant failures in the form of stem fracture at the stem-sleeve junction, we recommend more judicious use of modularity in primary total hip arthroplasty.