Local cefuroxime tissue concentrations in the hand after single and repeated administration to 16 patients undergoing trapeziectomy: a randomized controlled trial.

BACKGROUND AND PURPOSE:  The duration of antibiotic coverage in hand tissues during surgery is unknown. We investigated the time the free concentration of cefuroxime was above the minimal inhibitory concentration (fT>MIC) of 4 µg/mL in hand tissues after single and repeated administration. METHODS:  In a prospective, unblinded randomized study 16 patients (13 female, age range 51-80 years) underwent trapeziectomy. Microdialysis catheters were placed in the metacarpal bone (primary effect parameter), synovial sheath, and subcutaneous tissue. Patients were randomized to postoperative administration of either intravenous single administration of cefuroxime (1,500 mg) (Group 1, n = 8) or repeated dosing (2 x 1,500 mg) with a 4 h interval (Group 2, n = 8). Samples were taken over 8 h. RESULTS: The fT>MIC of 4 µg/mL was found to be significantly longer in the metacarpal bone in Group 2 compared with Group 1 with a mean difference of 199 min (95% confidence interval 158-239). The same trend was evident in the remaining compartments. A concentration of 4 µg/mL was reached in all compartments in both groups within a mean time of 6 min (range 0-27 min). In Group 1, the mean concentrations decreased below 4 µg/mL between 3 h 59 min and 5 h 38 min. CONCLUSION:  The fT>MIC was longer after repeated administration compared with single administration in all compartments. A single administration of cefuroxime 1,500 mg provided antimicrobial hand tissue coverage for a minimum of 3 h 59 min. Cefuroxime administration in hand surgeries should be done minimum 27 min prior to incision to achieve sufficient coverage in all individuals. Cefuroxime readministration should be considered in hand surgeries lasting longer than 4 h from time of administration.

Incidence of Ischemic Stroke in Individuals With and Without Aortic Valve Stenosis: A Danish Retrospective Cohort Study.

Background and Purpose- Aortic valve stenosis may lead to atrial and ventricular remodeling, predisposes to atrial fibrillation, and may also be an independent risk factor of ischemic stroke. However, information on stroke rates among persons with aortic valve stenosis are sparse. We aimed to determine the incidence rates and relative risks of ischemic stroke in individuals with diagnosed aortic valve stenosis compared with age- and sex-matched controls. Methods- All patients with incident aortic valve stenosis aged >18 years (n=79 310) and age- and sex-matched controls were identified using the Danish nationwide registries (1997-2017). Incidence rates per 1000 person-years (PY) and multivariable adjusted hazard ratios with 95% CIs were reported. Results- In total, 873 373 individuals (median age 77 years, 51.5% men, 9.1% with aortic valve stenosis) were included. Ischemic stroke occurred in 70 205 (8.0%) individuals during 4 880 862 PY of follow-up. Incidence rates of ischemic stroke were 13.3/1000 PY among the controls compared with 30.4/1000 PY in patients with aortic valve stenosis, corresponding to a hazard ratio of 1.31 (95% CI, 1.28-1.34). In all age-groups, the incidence rates and relative risks were significantly increased in patients with aortic valve stenosis compared with controls, but the relative risk was greater for younger individuals (eg, age group, 18-45 years: hazard ratio, 5.94 [95% CI, 4.10-8.36]). In patients with aortic valve stenosis above 65 years of age, the risk of ischemic stroke was markedly lower after aortic valve replacement (30.3 versus 19.6/1000 PY before and after valve replacement). Among people with atrial fibrillation the incidence rate of ischemic stroke was 1.5 times higher when aortic valve stenosis was present (33.0/1000 PY versus 49.9/1000 PY). Conclusions- People with aortic valve stenosis have a significantly increased risk of ischemic stroke compared with age- and sex-matched controls. Future studies are warranted to explore whether antithrombotic therapy may be beneficial in some individuals.

No correlations between radiological angles and self-assessed quality of life in patients with hip dysplasia at 2-13 years of follow-up after periacetabular osteotomy.

BACKGROUND: Only few studies have described patients' health-related quality of life (QoL) after periacetabular osteotomy (PAO). Thus, there is a lack of data on the self-assessed outcome of patients operated with PAO, and none of the existing studies correlate the results from Medical Outcomes Short Form-36 questionnaire (SF-36) with the radiological parameters. PURPOSE: To investigate the health-related QoL for patients with hip dysplasia operated with PAO and to investigate whether QoL is associated with the acetabular angles or hypermobility. MATERIAL AND METHODS: Out of 388 patients, 228 patients (mean age, 40.5 years; mean follow-up, 7.1 years) returned the SF-36 and Beighton questionnaires. The patient's QoL was compared to reference data from a Danish population. Center-edge (CE) and acetabular index (AI) angles were measured before and after PAO and the association with the patients' QoL was tested with logistic regression. RESULTS: For both men and women the postoperative SF-36 score was significantly lower than for the reference data for a Danish population, especially for those dimensions concerning physical health. No association was found between the patients' CE or AI angles before or after PAO and their subsequent QoL. Significant associations were found between both Physical Component Score (PCS) and physical function (PF) and follow-up time after the operation. The adjusted OR for a PCS ≥ 50 was 0.87 (95% CI 0.76-0.99) and for a PF ≥ 85 0.81 (95% CI 0.71-0.91). No association between hyper mobility and PCS, PF, or bodily pain (BP) was found. CONCLUSION: The physical components of QoL in patients undergoing PAO are significantly lower than the Danish population used as reference. Furthermore, the results suggest that physical function after PAO decreases with longer follow-up time. Neither the acetabular angles nor hypermobility is associated with the physical components of QoL.

Conditioning techniques and ischemic reperfusion injury in relation to on-pump cardiac surgery.

OBJECTIVES: The objective was to investigate the potential protective effects of two conditioning methods, on myocardial ischemic and reperfusion injury in relation to cardiac surgery. DESIGN: Totally 68 patients were randomly assigned to either a control group (n = 23), a remote ischemic preconditioning (RIPC) group (n = 23) or a glucagon-like peptide-1 (GLP-1) analogue group (n = 22). The RIPC protocol consisted of three cycles of upper limb ischemia. The GLP-1 analogue protocol consisted of intravenous infusion with exenatide. The primary endpoint was postoperative cardiac enzyme release. The other secondary endpoints were metabolic parameters related to myocardial ischemia, measured using microdialysis technique, as well as other operative- and postoperative data. RESULTS: Postoperative cardiac enzyme release indicated a possible beneficial effect of the interventions, but the difference did not reach statistical significance. RIPC showed a trend toward lower levels (p = 0.07). We managed to establish a functional myocardial microdialysis model, but we were unable to demonstrate clear protective effects. CONCLUSIONS: We were in this prospective randomized proof-of-concept trial, unable to show distinct protective effects of the studied conditioning methods. However, this trial can hopefully contribute to generate a productive discussion concerning limitations and future use of cardiac conditioning as well as microdialysis technique.

Is cup positioning challenged in hips previously treated with periacetabular osteotomy?

After periacetabular osteotomy (PAO), some patients develop osteoarthritis with need of a total hip arthroplasty (THA). We evaluated the outcome of THA following PAO and explored factors associated with inferior cup position and increased polyethylene wear. Follow-up were performed 4 to 10 years after THA in 34 patients (38 hips) with previous PAO. Computer analysis evaluated cup position and wear rates. No patient had dislocations or revision surgery. Median scores were: Harris hip 96, Oxford hip 38 and WOMAC 78. Mean cup anteversion and abduction angles were 22° (range 7°-43°) and 45° (range 28°-65°). Outliers of cup abduction were associated with persisting dysplasia (CE <25°). THA after PAO can produce excellent clinical results. Persisting acetabular dysplasia following PAO may lead surgeons to place the acetabular component in excessive cup abduction, and this tendency should be recognized at the time of the PAO.

The role of the acetabular labrum in hip dysplasia. A literature overview.

A periacetabular osteotomy (PAO) is the preferred joint preserving treatment for young adults with symptomatic hip dysplasia and no osteoarthritis. In symptomatic dysplasia of the hip, there is labral pathology in up to 90% of cases. However, no consensus exists as to whether a labral tear should be treated before the periacetabular osteotomy (PAO), treated simultaneously with the PAO, or left alone and only treated if symptoms persist after the PAO. This review is an update of aspects of labral anatomy and function, the etiology of labral tears in hip dysplasia, and diagnostic assessment of labral tears, and we discuss treatment strategies for coexisting labral tears and hip dysplasia.

Identification of wild-type transthyretin cardiac amyloidosis in patients with carpal tunnel syndrome surgery (CACTuS).

AIMS: Wild-type transthyretin cardiac amyloidosis (ATTRwt) is an infiltrative cardiomyopathy with a poor prognosis. The condition is associated with carpal tunnel syndrome (CTS), which often precedes the ATTRwt diagnosis by several years. The aim of the study was (i) to screen patients with a recent history of CTS for ATTRwt using red flags, (ii) to determine whether patients with screened ATTRwt had less advanced disease compared with patients with clinical ATTRwt, and (iii) to assess the sensitivity and specificity of known red flags in ATTRwt. METHODS AND RESULTS: Patients aged ≥60 years at the time of CTS surgery were invited for screening. Red flags were defined as elevated biomarker levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) or cardiac troponin, an electrocardiogram pattern associated with ATTRwt, left ventricular hypertrophy (LVH), and impaired longitudinal strain with apical sparring. All patients with a red flag were referred for a diagnostic scintigraphy. Patients with ATTRwt diagnosed by screening were compared with patients with clinical ATTRwt (n = 51) matched by age, gender, and CTS surgery. Among the 120 enrolled subjects (mean age 74.5 years, 90% male), the suspicion of ATTR was raised in 67 (55.8%), and 10 (8.3%) were diagnosed with ATTRwt. Patients identified with ATTRwt were predominantly asymptomatic and had mildly elevated NT-proBNP, mildly increased LVH, preserved left ventricular ejection fraction, and systolic longitudinal function, which differed significantly from clinical ATTRwt controls (P < 0.001). CONCLUSIONS: The study found an ATTRwt prevalence of 8.3% in a population of age and gender-selected patients with a recent history of CTS. The identified patients with ATTRwt had less structural and functional cardiac involvement than clinical ATTRwt controls.

Clinical characteristics and prognostic implications of orthopedic ligament disorders in patients with wild-type transthyretin amyloidosis cardiomyopathy.

BACKGROUND: Wild-type transthyretin amyloidosis (ATTRwt) is associated with multiple ligament disorders (LD) such as carpal tunnel syndrome (CTS), lumbar spinal stenosis (LSS), and spontaneous tendon rupture (STR). No studies have investigated the prevalence of these LD in the same cohort of ATTRwt patients. Furthermore, the clinical characteristics and prognostic implications of such disorders have not been studied. METHODS: From 2017 to 2022, 206 consecutive patients with ATTRwt were diagnosed and followed prospectively to the time of death or the censoring date of September 1st, 2022. Patients with and without LD were compared, and the presence of LD was used along with the baseline clinical, biochemical, and echocardiographic characteristics to predict hospitalization with worsening heart failure and death. RESULTS: CTS surgery was performed in 34 % of the patients, 8 % were treated for LSS, and 10 % had experienced an STR. The median follow-up time was 706 days (312-1067). Hospitalization with worsening heart failure occurred more frequently in patients with LD compared to patients without LD (p = 0.035). Presence of LD or surgery for CTS were found to be independent predictors of worsening heart failure with a hazard ratio of 2.0 (p = 0.01). The mortality was comparable between patients with and without LD (p = 0.10). CONCLUSION: Orthopedic disorders are prevalent in ATTRwt cardiomyopathy, and presence of LD was an independent predictor of hospitalization with worsening heart failure.

What factors predict failure 4 to 12 years after periacetabular osteotomy?

BACKGROUND: The goal of periacetabular osteotomy (PAO) is to delay or prevent osteoarthritic development in dysplastic hips. However, it is unclear whether the surgical goals are achieved and if so in which patients. This information is essential to select appropriate patients for a durable PAO that achieves its goals. QUESTIONS/PURPOSES: We therefore (1) determined hip survival rates; (2) determined how many preserved hips were functionally unsuccessful after PAO; and (3) identified demographic, clinical, and radiographic factors predicting failure after PAO. METHODS: We retrospectively reviewed 316 patients (401 hips) who had PAO between December 1998 and May 2007. We evaluated radiographic parameters of dysplasia and osteoarthritis and obtained WOMAC scores. Through inquiry to the National Registry of Patients, we identified conversions to THA. Risk factors for conversion to THA were assessed. Minimum followup was 4 years (mean, 8 years; range, 4-12 years). RESULTS: The overall Kaplan-Meier hip survival rate was 74.8% at 12.4 years. A WOMAC pain score of 10 or more, suggesting clinical failure, was observed in 13% of preserved hips at last followup. Higher age, preoperative Tönnis grade of 2, incongruent hip, postoperative joint space width of 3 mm or less, and postoperative center-edge angle of less than 30° or more than 40° predicted conversion to THA. CONCLUSIONS: PAO preserved three of four hips with most functioning well at 4- to 12-year followup. When planning surgery, surgeons should attempt to achieve hip congruence and a center-edge angle of between 30° to 40° to improve the durability of PAO. LEVEL OF EVIDENCE: Level II, prognostic study. See Instructions for Authors for a complete description of levels of evidence.

[Local anaesthesia and steroid blockades for carpal tunnel syndrome in pregnancy].

The possible impact on the foetus must always be taken into account, whenever non-conservative strategies are considered in pregnancy. As to carpal tunnel syndrome, surgery is usually reserved for severe cases, or when steroid blockades have been insufficient. If only pharmacological considerations are taken into account, surgery with local anaesthetics may however be preferred over blockades. While especially lidocaine is considered quite safe in pregnancy, a foetal risk cannot be ruled out for the synthetic glucocorticoids. Moreover, the duration of exposure is considerably shorter. These issues are summarized and discussed in this review.

Role of neutrophils in response to Bordetella pertussis infection in mice.

Pertussis is an acute respiratory disease caused by the bacterium Bordetella pertussis, for which humans are the only known reservoir. During infection, B. pertussis releases several toxins, including pertussis toxin (PT) and adenylate cyclase toxin (ACT), which have both been shown to play roles in promoting bacterial growth during early infection in a mouse model. Furthermore, in vitro and in vivo studies suggest that PT and ACT affect neutrophil chemotaxis and/or function, thereby altering the innate immune response. In this study we depleted animals of neutrophils to investigate whether neutrophils play a protective role during B. pertussis infection in mice. In addition, by infection with toxin-deficient strains, we investigated whether neutrophils are the main targets for PT and/or ACT activity in promoting bacterial growth. Surprisingly, we found no role for neutrophils during B. pertussis infection in naïve mice. However, in previously infected (immune) mice or in mice receiving immune serum, we observed a significant role for neutrophils during infection. Furthermore, in this immune mouse model our evidence indicates that neutrophils appear to be the main target cells for ACT, but not for PT.

Clostridium histolyticum as first-line treatment of Dupuytren's disease.

INTRODUCTION: The optimal minimal invasive treatment for Dupuytren's contractures (DC) remains debated. The aim of this study was to evaluate the effect of Clostridium histo-lyticum collagenase after 1-4 years of follow-up. The out-comes of this study were 1) overall improvements in degrees from baseline to follow-up; 2) contraction recurrence defined as an extension deficit above 20°, and 3) Hurst endpoint defined as an extension deficit below 5°. METHODS: All patients treated with C. histolyticum collagen-ase at the Regional Hospital Horsens from 2013 to 2016 with a minimum of one year of follow-up due to DC were included. The range of motion of the affected finger joint was measured before and immediately after injection and at follow-up. Specific information regarding known co-morbidities to DC was acquired. RESULTS: A total of 112 metacarpophalangeal (MCP) and 47 proximal interphalangeal (PIP) joints were included. Total improvement in the range of motion for MCP and PIP joints were 43° and 16°, respectively. The recurrence rate was 9% for MCP joints and 70% for PIP joints. 73% of MCP joints and 9% of PIP joints achieved the Hurst endpoint. 92% of the patients were willing to repeat treatment. CONCLUSIONS: Collagenase is a viable first-line treatment for MCP joint contractures. However, results are inferior in the PIP joint. FUNDING: This work was supported by the The Scientific Foundation of Horsens Regional Hospital (grant number 00.06-G01-1-17). TRIAL REGISTRATION: ClinicalTrials ID NCT03331926.

Mortality associated with cardiovascular drugs in patients with chronic obstructive pulmonary disease and right-sided heart failure - A danish nationwide registry-based study.

BACKGROUND: The optimal medical treatment in patients with chronic obstructive pulmonary disease (COPD) and right-sided heart failure (RHF) is unknown. We aimed to estimate the risks of all-cause mortality associated with the current clinical use of various cardiovascular drugs in this patient-group. METHODS: We followed all patients with registered COPD and RHF (defined as a diagnosis of pulmonary hypertension plus use of loop-diuretics) for the risk of all-cause mortality (Jan 1, 1995 to Dec 31, 2015) using the Danish nationwide administrative registries. The association between mortality and claimed prescriptions for cardiovascular drugs was assessed by multivariable Cox regression models. RESULTS: 5991 patients (mean age 74 ±â€¯standard deviation 10 years, 51% women) were included. Of these, 1440 (24%) used beta-blockers, 2149 (36%) renin-angiotensin system inhibitors [RASi], 1340 (22%) oral anticoagulants, 1376 (23%) calcium channel blockers, 1194 (20%) statins, 1824 (30%) spironolactone, and 2099 (35%) low-dose aspirin. During an average follow-up of 2.2 years (±standard deviation 2.8, min-max 0-19.6 years), 5071 (85%) died, corresponding to a mortality rate of 38 per 100 person-years (95% confidence interval 37-39). Compared to no use, beta-blockers were associated with adjusted hazards ratio 0.90 (95% confidence interval 0.84-0.98), RASi 0.92 (0.86-0.98), calcium channel blockers 0.86 (0.80-0.92), spironolactone 1.17 (1.10-1.24), statins 0.85 (0.78-0.92), oral anticoagulants 0.87 (0.79-0.95), and aspirin 0.99 (0.93-1.05). Propensity-score matched analyses and inverse-probability-weighted models yielded similar results. CONCLUSION: Several cardiovascular drugs may be associated with lowered mortality in COPD and RHF. Given the grave prognosis, randomized clinical trials are warranted to test this hypothesis.

Outcomes associated with dual antiplatelet therapy after myocardial infarction in patients with aortic stenosis.

BACKGROUND: Acquired loss of the largest von Willebrand factor multimers is a common hemostatic disturbance in patients with aortic valve stenosis (AS), resulting in impaired platelet adhesion and increased bleeding risk. AS is also associated with atherosclerosis and myocardial infarction (MI). Our aim was to study the clinical outcomes associated with AS in MI patients treated with dual antiplatelet therapy (DAPT) in a nationwide hospital-based register study. METHODS: Based on nationwide hospital discharge registers from Sweden (2005-2010) and Denmark (2005-2015), we calculated 1-year incidence rates and hazard ratios of bleeding, recurrent MI, and all-cause mortality in MI patients with and without AS treated with DAPT. Results from both countries were also combined in a meta-analysis. RESULTS: We included 50,460 MI patients from Sweden and 50,307 MI patients from Denmark, of which 3% had AS. The bleeding rates (per 100 person-years) in Sweden and Denmark were 3.2 and 3.3 among patients without AS vs. 9.2 and 8.3 among patients with AS. All-cause mortality rates were 7.1 vs. 28.7 in Sweden and 5.8 vs. 30.7 in Denmark among patients without and with AS, respectively. Patients with AS had an increased risk of bleeding, recurrent MI and all-cause mortality. Combined results from both countries were similar for bleeding (hazard ratio 1.59 [0.98-2.59]), recurrent MI (1.78 [1.25-2.54]), and all-cause mortality (1.76 [1.26-2.47]). CONCLUSION: AS was associated with an increased risk of bleeding, recurrent MI and mortality after MI when treated with DAPT. Individualized selection of antiplatelet therapy may be warranted in this high-risk population.

High frequency of labral pathology in symptomatic borderline dysplasia: a prospective magnetic resonance arthrography study of 99 patients.

Labral pathology is seen in both dysplastic and borderline dysplastic hips. Periacetabular osteotomy (PAO) is the treatment of choice for dysplasia. However, some authors have suggested that borderline dysplastic hips with concurrent labral pathology should be treated arthroscopically. The purpose of this study was to investigate the frequency of labral pathology between dysplastic and borderline dysplastic hips, whether centre-edge (CE) angle is associated with labral pathology, and finally if pain and labral pathology are associated. Ninety-nine symptomatic patients (104 hips) scheduled for PAO were examined. Five patients were excluded due to complaints from multiple joints and four failed to show at 2-year follow-up. Five patients did not fill out questionnaires preoperatively. Hips were characterized as dysplastic (CE angle <20°) and borderline dysplastic (CE angle 20° ≤ 25°). A magnetic resonance arthrography was performed, and labral pathology was classified according to the Czerny classification. Association with the CE angle, the acetabular index (AI) and preoperative WOMAC pain score was tested by multiple linear regression. There was no significant difference in frequency of labral pathology when comparing the two groups. Across the cohort, 86 of 99 patients had labral pathology. The CE angle was associated with increasing severity of labral pathology, whereas the AI angle and preoperative pain were not associated with labral pathology. Decreased lateral coverage adversely loads the labrum, predisposing it to tears. We advocate reorienting the biomechanical forces through PAO, not arthroscopic treatment. Level of pain was not associated with labral pathology, suggesting that labral pathology may not alone explain the dysplastic pain complex.

Pertussis toxin inhibits early chemokine production to delay neutrophil recruitment in response to Bordetella pertussis respiratory tract infection in mice.

Pertussis is an acute respiratory disease of humans caused by the bacterium Bordetella pertussis. Pertussis toxin (PT) plays a major role in the virulence of this pathogen, including important effects that it has soon after inoculation. Studies in our laboratory and other laboratories have indicated that PT inhibits early neutrophil influx to the lungs and airways in response to B. pertussis respiratory tract infection in mice. Previous in vitro and in vivo studies have shown that PT can affect neutrophils directly by ADP ribosylating G(i) proteins associated with surface chemokine receptors, thereby inhibiting neutrophil migration in response to chemokines. However, in this study, by comparing responses to wild-type (WT) and PT-deficient strains, we found that PT has an indirect inhibitory effect on neutrophil recruitment to the airways in response to infection. Analysis of lung chemokine expression indicated that PT suppresses early neutrophil recruitment by inhibiting chemokine upregulation in alveolar macrophages and other lung cells in response to B. pertussis infection. Enhancement of early neutrophil recruitment to the airways in response to WT infection by addition of exogenous keratinocyte-derived chemokine, one of the dominant neutrophil-attracting chemokines in mice, further revealed an indirect effect of PT on neutrophil chemotaxis. Additionally, we showed that intranasal administration of PT inhibits lipopolysaccharide-induced chemokine gene expression and neutrophil recruitment to the airways, presumably by modulation of signaling through Toll-like receptor 4. Collectively, these results demonstrate how PT inhibits early inflammatory responses in the respiratory tract, which reduces neutrophil influx in response to B. pertussis infection, potentially providing an advantage to the pathogen in this interaction.

Current use of beta-blockers in patients with coronary artery disease.

Beta-blockers have long comprised a cornerstone in the symptomatic treatment of ischemic heart disease and in the secondary prevention of myocardial infarction and heart failure. The majority of studies underlying the evidence of a beneficial effect of beta-blockers on outcomes were conducted more than 25 years ago. In a contemporary era where treatment strategies and secondary prophylactic therapy have undergone several changes, the continued role of beta-blockers in ischemic heart disease has been questioned, especially in the absence of heart failure or a recent myocardial infarction. In summary, few randomized clinical trials are available on the effect of beta-blockers in the reperfusion era, especially on hard endpoints. Likewise, the results of numerous observational studies and meta-analysis are conflicting, emphasizing the need for additional large-scale randomized clinical trials to evaluate the role of beta-blocker therapy in current clinical practice.

Association of Timing of Aortic Valve Replacement Surgery After Stroke With Risk of Recurrent Stroke and Mortality.

Importance: Timing of surgical aortic valve replacement (SAVR) in patients with aortic valve stenosis and previous stroke for the risk of recurrent stroke is insufficiently investigated. Objective: To evaluate the association of time elapsed between previous stroke and SAVR with the risk of recurrent perioperative stroke, major adverse cardiovascular events (MACE), and mortality among patients with aortic valve stenosis. Design, Setting, and Participants: This cohort study using data from Danish administrative registries included all patients with aortic valve stenosis older than 18 years who underwent SAVR between 1996 and 2014 (n = 14 030). Patients who received simultaneous mitral, tricuspid, or pulmonary valve surgery and patients with endocarditis 1 year prior to surgery were excluded. Data were analyzed from March 2017 to January 2018. Exposures: Time elapsed between prior stroke and SAVR (<3 months, 3-<12 months, ≥12 months, and no prior stroke). Main Outcomes and Measures: Thirty-day risks of MACE, ischemic stroke, and all-cause mortality reported as absolute events and multivariable adjusted odds ratios with 95% confidence intervals. Restricted cubic spline regression models were additionally applied on the subgroup with prior stroke. Results: Of the 14 030 included patients, 616 patients (190 [30.8%] women; mean [SD] age, 72.0 [9.1] years) with prior stroke underwent surgery, and 13 414 (4837 [36.1%] women; mean [SD] age, 69.8 [10.8] years) without prior stroke underwent surgery. The absolute risk of ischemic stroke was significantly increased in patients with stroke less than 3 months prior to surgery compared with patients with no prior stroke (18.4% [37 of 201] vs 1.2% [160 of 13 219]; odds ratio, 14.69; 95% CI, 9.69-22.27). Likewise, compared with patients without stroke, patients with stroke less than 3 months prior surgery were at significantly increased risk of MACE (23.3% [53 of 227] vs 5.7% [768 of 13 414]; odds ratio, 4.57; 95% CI, 3.24-6.44) but not all-cause mortality (6.8% [50 of 730] vs 3.6% [374 of 10 370]; odds ratio, 1.45; 95% CI, 0.83-2.54). Spline analyses supported a declining risk over time, reaching nadir after 2 to 4 months. Conclusions and Relevance: Previous stroke is a major risk factor of recurrent ischemic stroke and MACE in patients undergoing SAVR, especially if time elapsed between previous stroke and surgery is less than 3 months.

Next-generation sequencing of AV nodal reentrant tachycardia patients identifies broad spectrum of variants in ion channel genes.

Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of regular paroxysmal supraventricular tachycardia. This arrhythmia affects women twice as frequently as men, and is often diagnosed in patients <40 years of age. Familial clustering, early onset of symptoms and lack of structural anomaly indicate involvement of genetic factors in AVNRT pathophysiology. We hypothesized that AVNRT patients have a high prevalence of variants in genes that are highly expressed in the atrioventricular conduction axis of the heart and potentially involved in arrhythmic diseases. Next-generation sequencing of 67 genes was applied to the DNA profile of 298 AVNRT patients and 10 AVNRT family members using HaloPlex Target Enrichment System. In total, we identified 229 variants in 60 genes; 215 missenses, four frame shifts, four codon deletions, three missense and splice sites, two stop-gain variants, and one start-lost variant. Sixty-five of these were not present in the Exome Aggregation Consortium (ExAC) database. Furthermore, we report two AVNRT families with co-segregating variants. Seventy-five of 284 AVNRT patients (26.4%) and three family members to different AVNRT probands had one or more variants in genes affecting the sodium handling. Fifty-four out of 284 AVNRT patients (19.0%) had variants in genes affecting the calcium handling of the heart. We furthermore find a large proportion of variants in the HCN1-4 genes. We did not detect a significant enrichment of rare variants in the tested genes. This could be an indication that AVNRT might be an electrical arrhythmic disease with abnormal sodium and calcium handling.

Outcome after arthroscopic labral surgery in patients previously treated with periacetabular osteotomy: a follow-up study of 43 patients.

To identify factors predicting failure after hip arthroscopy in patients with previous periacetabular osteotomy (PAO) defined as a conversion to total hip replacement (THR) and to evaluate the patient reported outcome scores. Of 55 hips treated with hip arthroscopy after PAO from Aug 2008 to 2012 at Aarhus University Hospital, 43 hips were included (median age: 36.1 yrs, range 16.3-56.9 yrs). Indications were unacceptable pain, a positive FABER and impingement test and signs of labral damage on MR-arthrography. Outcomes were evaluated with mHHS and HOS. Failure was defined as conversion to a THR. Nine hips were converted to a THR. Kaplan-Meier survival rate was 52.8% (95% CI, 10%-83.8%) at 6.5 years follow-up. Statistically significant predictors of failure: joint space width after PAO <3.0 mm and Tönnis grade of 2. Fourteen hips needed revision hip arthroscopy. Labral damage was present in 84% of the hips. In 42% of the hips cartilage lesions of Becks grade >3 were found. Mean mHHS and HOS were 65.7 and 68.8 respectively at follow-up. A NRS pain score of >3 in rest and during activity were present in respectively, 43% and 62% of the patients. Hip arthroscopy after PAO demonstrated limited clinical benefit with no decrease in pain levels and 21% of patients needing reoperation to THR. Radiographic signs of joint degeneration after PAO are predictors of faiElure. Further studies are needed to clarify what role hip arthroscopy should play in this patient group.