The cost-effectiveness of osteoporosis medications for preventing periprosthetic fractures following femoral neck fracture indicated hip arthroplasty: a break-even analysis.

Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Our study evaluated the economic viability of treatment in patients following arthroplasty and demonstrates that treatment with oral bisphosphonates can be cost-effective in preventing PPF. INTRODUCTION: Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Although cost-effective in reducing the rate of secondary fragility fracture, the economic viability of osteoporosis treatment in preventing PPF has not been evaluated. Therefore, the purpose of this study is to use a break-even analysis to determine whether and which current osteoporosis medications are cost-effective in preventing PPF following arthroplasty for FNFs. METHODS: Three-year average cost of osteoporosis medication (oral bisphosphonates, estrogen hormonal therapy, intravenous (IV) bisphosphonates, denosumab, teriparatide, and abaloparatide), costs of PPF care, and PPF rates in patients who underwent hip arthroplasty for FNFs without osteoporosis treatment were used to perform a break-even analysis. The absolute risk reduction (ARR) related to osteoporosis treatment and sensitivity analyses were used to evaluate the cost-effectiveness of this intervention and break-even PPF rates. RESULTS: Oral bisphosphonate therapy following arthroplasty for hip fractures would be economically justified if it prevents one out of 56 PPFs (ARR, 1.8%). Given the current cost and incidence of PPF, overall treatment can only be economically viable for PPF prophylaxis if the 3-year costs of these agents are less than $1500. CONCLUSION: The utilization of lower cost osteoporosis medications such as oral bisphosphonates and estrogen hormonal therapy as PPF prophylaxis in this patient population would be economically viable if they reduce the PPF rate by 1.8% and 1.5%, respectively. For IV bisphosphonates and newer agents to be economically viable as PPF prophylaxis in the USA, their costs need to be significantly reduced.

No Difference in Revision Rates up to 10 years Following Total Hip Arthroplasty in Patients Who Had Prior Bariatric Surgery When Compared to Patients Who Had Class III Obesity: A Propensity Matched Analysis.

BACKGROUND: There is no clear research showcasing bariatric surgery's (BS's) impact on long-term surgical complications following total hip arthroplasty (THA). Therefore, this study compared the 10-year cumulative incidence and risk of revision following THA in patients who underwent BS when compared to the general population and class III obesity patients who did not undergo BS. METHODS: Patients who underwent elective THA from 2010 to 2021 were identified using an all-payer claims database. Patients who underwent BS prior to THA were separately matched to a control of the general population and those who had class III obesity (body mass index ≥40) by age, sex, Charlson Comorbidity Index, and diabetes using a 1:4 ratio. Kaplan-Meier analyses generated 10-year cumulative incidence rates, and a Cox proportional hazard ratio (HR) model generated HRs and 95% confidence intervals (CIs). RESULTS: When compared to the general control, patients who have a history of BS had an elevated 10-year risk of all-cause revision (HR 1.31, 95% CI: 1.16 to 1.47, P < .001), prosthetic joint infection (HR: 1.62, CI: 1.30 to 2.04; P < .001), mechanical loosening (HR: 1.20, CI: 1.01 to 1.44; P = .040), and dislocation/instability (HR: 1.35, CI: 1.09 to 1.68; P = .007). There was no difference in the 10-year risk of all-cause revision or other indications for revision in the BS cohort compared to the matched class III obesity cohort (P = .142). CONCLUSIONS: Those who underwent BS before THA had comparable 10-year revision rates when compared to those who had class III obesity and higher rates compared to the general population. This suggests BS may not reduce the 10-year surgical risks associated with obesity when compared to a class III obese surgical population.

Trends in anti-osteoporotic medication utilization following fragility fracture in the USA from 2011 to 2019.

The purpose of this study was to determine whether there has been any change in osteoporosis treatment following primary fragility fractures and what agents were being given. The study found an overall low utilization rate with no difference in treatment utilization from 2011 to 2019. PURPOSE: The aim of this study is to describe trends in the utilization of anti-osteoporotic medication after fragility fracture, including changes in the specific types of medications prescribed. METHODS: Patients older than 65 with fragility fractures sustained from 2011 to 2019 were identified in the PearlDiver Patient Records Database. Osteoporosis treatment rate was defined as the rate at which patients were prescribed any of the fourteen most used anti-osteoporotic medications within 1 year of fragility fracture. Fragility fractures were subcategorized by type. Treatment of fragility fractures was further stratified by patient demographics (age and gender) and medication type. RESULTS: This study showed an overall osteoporosis treatment rate of 8.01%, with treatment rates of 6.87% following hip fractures, 6.71% following upper extremity fractures, and 14.38% following vertebral compression fractures (VCF). From 2011 to 2018, there was no change in the overall fragility fracture treatment rate (p = 0.32). Of the three fracture categories analyzed, only the treatment rate for VCFs increased (p = 0.048). Osteoporosis treatment in patients with VCF increased among patients 65-74 years old (p < 0.05) and male patients (p = 0.013). Treatment in patients with upper extremity fractures increased among patients 70-74 years old (p = 0.038). Bisphosphonates were the most frequently prescribed class of medications. Bisphosphonates and denosumab increased in utilization (p = 0.049 and p < 0.001 respectively) while calcitonin utilization decreased (p < 0.001). CONCLUSION: Besides the overall low utilization rate of osteoporosis treatment in patients following fragility fractures, there has been no change in the treatment utilization rate within the past decade. More resources and interventions need to be enforced for all providers managing these patients if we are ever to address the osteoporosis epidemic.

The impact of prior fragility fractures on long-term periprosthetic fracture risk following total knee arthroplasty.

The study found that patients undergoing total knee arthroplasty with prior fragility fracture had increased risk of subsequent fragility fracture and periprosthetic fracture within 8 years postoperatively when compared to those without a prior history. However, these patients were not at increased risk for all-cause revision within this period. PURPOSE: The aim of this study was to characterize the association of prior FFs on long-term risk of secondary fragility fracture (FF), periprosthetic fracture (PPF), and revision TKA. METHODS: Patients at least 50 years of age who underwent elective TKA were identified in the PearlDiver Database. Patients were stratified based on whether they sustained a FF within 3 years prior to TKA (7410 patients) or not (712,954 patients). Demographics and comorbidities were collected. Kaplan Meier analysis was used to observe the cumulative incidence of all-cause revision, PPF, and secondary FF within 8 years of TKA. Cox Proportional hazard ratio analysis was used to statistically compare the risk. RESULTS: In total, 1.0% of patients had a FF within three years of TKA. Of these patients, only 22.6% and 10.9% had a coded diagnosis of osteoporosis and osteopenia, respectively, at time of TKA. The 8-year cumulative incidence of secondary FF and periprosthetic fracture was significantly higher in those with a prior FF (27.5% secondary FF and 1.9% PPF) when compared to those without (9.1% secondary FF and 0.7% PPF). After adjusting for covariates, patients with a recent FF had significantly higher risks of secondary FF (HR 2.73; p < 0.001) and periprosthetic fracture (HR 1.86; p < 0.001) than those without a recent FF. CONCLUSIONS: Recent FF before TKA is associated with increased risk for additional FF and PPF within 8 years following TKA. Surgeons should ensure appropriate management of fragility fracture is undertaken prior to TKA to minimize fracture risk, and if not, be vigilant to identify patients with prior FF or other bone health risk factors who may have undocumented osteoporosis.

The Association of Postoperative Osteoporosis Therapy With Periprosthetic Fracture Risk in Patients Undergoing Arthroplasty for Femoral Neck Fractures.

BACKGROUND: Displaced femoral neck fractures in older adults are generally treated with hip arthroplasty. One concern following hip arthroplasty is the risk for periprosthetic fractures (PPFs). Most patients who have hip fractures are candidates for antiosteoporotic therapy, but the impact of this treatment on PPFs is unknown. Therefore, the primary objective of this study was to evaluate whether patients treated with antiosteoporotic medical therapy had lower odds of PPFs following arthroplasty for hip fracture. METHODS: Patients at least 65 years old who underwent hip arthroplasty for femoral neck fractures from 2010 to 2020 were identified in a national database. Patients were stratified based on whether they initiated antiosteoporotic therapy within 1 year of hip arthroplasty. Minimum follow-up was 1 year, and maximum follow-up was 10.6 years. The primary endpoint was cumulative incidence of PPF as determined using Kaplan-Meier and Cox proportional hazards regression analyses. Overall, 2,026 patients who underwent arthroplasty for femoral neck fracture received antiosteoporotic medications within 1 year following surgery (mean follow up 4.8 years; range 1.0 to 10.6 years) and 33,639 patients did not (mean follow up 4.1 years; range 1.1 to 10.3 years). RESULTS: The 10-year cumulative incidence of PPF for patients treated for osteoporosis was 3.88% compared to 5.92% for those who were untreated (P < .001). Adjusting for covariates, patients who received osteoporosis treatment had a significantly lower risk for PPF than those who were untreated (hazard ratio (HR): 0.663; 95% confidence interval (CI): 0.465-0.861; P = .038). CONCLUSION: The present study suggests that osteoporosis treatment is associated with lower incidence of PPF following hip arthroplasty for femoral neck fractures. Treatment of osteoporosis should be initiated in eligible patients who sustain a femoral neck fracture, especially those who undergo hip arthroplasty.

Why and What Happens to Patients Younger Than 60 Years Who Need Revision Total Knee Arthroplasty?

BACKGROUND: With the increasing number of young patients undergoing primary total knee arthroplasty (TKA), there will be an increase in the number of patients who require revision. While the results of TKA in younger patients are well known, there is little information regarding to the outcomes of revision TKA in this population. The purpose of this study was to evaluate the clinical outcomes in patients <60 years of age undergoing aseptic revision TKA. METHODS: We retrospectively reviewed 433 patients undergoing aseptic revision TKA between 2008 and 2019. There were 189 patients <60 years compared to a group of 244 patients >60 years undergoing revision TKA for aseptic failures in terms of implant survivorships, complications, and clinical outcomes. Patients were followed for a mean of 48 months (range, 24 to 149). RESULTS: A total of 28 (14.8%) patients less than 60 years of age required repeat revision compared to 25 (10.2%) 60 years or older (odds ratio (OR) 1.94, 95% confidence interval (CI) 0.73-5.22, P = .187). There were no differences regarding postprocedural Patient-Reported Outcomes Measurement Information System (PROMIS) physical health scores (72.3 ± 13.7 versus 72.0 ± 12.0, P = .66) and PROMIS mental health scores (66.6 ± 17.4 versus 65.8. ± 14.7, P = .72), at an average of 32.9 and 30.7 months, respectively. Postoperative infection occurred in 3 (1.6%) patients <60 years of age, while 12 (4.9%) postoperative infections occurred in patients 60 years or older (OR 0.75, 95% CI 0.06-10.2, P = .83). CONCLUSION: There were no statistically significant differences in clinical outcomes between patients <60 versus > 60 years of age undergoing aseptic revision TKA.

The Association of Prior Fragility Fractures on 8-Year Periprosthetic Fracture Risk Following Total Hip Arthroplasty.

BACKGROUND: Fragility fractures are often the initial clinical presentation of osteoporosis. Patients who have a history of fragility fractures undergoing total hip arthroplasty (THA) have an increased risk of 2-year postoperative complications. However, the association of recent fragility fractures with complications beyond 2 years following THA remains unknown. The purpose of this study was to characterize the association of prior fragility fractures with 8-year risks of revision THA, periprosthetic fracture (PPF), and secondary fragility fracture. METHODS: Patients aged 50 years and more who underwent THA for osteoarthritis were identified in a large national database. Patients were stratified based on whether they sustained a fragility fracture within 3 years prior to THA. There were 18,529 patients who had a prior fragility fracture and 408,753 who did not have a prior fragility fracture. Demographics and comorbidities were collected. Kaplan-Meier and Cox Proportional Hazards analyses were used to observe the cumulative incidences of all-cause revision, PPF, and secondary fragility fracture within 8 years of index surgery. RESULTS: Patients who had recent fragility fracture had significantly higher risks of revision THA (Hazard Ratio [HR] 1.7; P < .001), PPF (HR 2.2; P < .001), and secondary fragility fracture (HR 4.9; P < .001). CONCLUSION: Prior fragility fracture was shown to be a significant risk factor for revision THA, PPF, and secondary fragility fracture within 8 years of THA. Identification of these high-risk patients with an emphasis on preoperative and postoperative bone health optimization may help minimize these complications.

10-Year Cumulative Incidence and Indications for Revision Total Knee Arthroplasty Among Patients Who Have Sickle Cell Disease.

BACKGROUND: Literature regarding total knee arthroplasty (TKA) outcomes in sickle cell disease (SCD) is limited. Moreover, 10-year survivorship of SCD implants is unknown. This study aimed to observe 10-year cumulative incidence and indications for revision TKA in patients who did and did not have SCD. METHODS: Patients who underwent primary TKA were identified using a large national database. The SCD patients were matched by age, sex, and a comorbidity index to a control cohort in a 1:4 ratio. The 10-year cumulative incidence rates were determined using Kaplan-Meier survival analyses. Multivariable analyses were conducted using Cox proportional hazard modeling. Chi-squared analyses were conducted to compare indications for revision between cohorts. In total, 1,010 SCD patients were identified, 100,000 patients included in the unmatched control, and 4,020 patients included in the matched control. RESULTS: Compared to the unmatched control cohort, SCD patients exhibited higher 10-year all-cause revision (HR: 1.86; P < .001) with higher proportions of revisions for periprosthetic joint infection (PJI) (P < .001), aseptic loosening (P < .001), and hematoma (P < .001). Compared to the matched control, SCD patients had higher 10-year all-cause revision (Hazard Ratio (HR): 1.39; P = .034) with a higher proportion of revisions for PJI (P = .044), aseptic loosening (P = .003), and hematoma (P = .019). CONCLUSION: Independent of other comorbidities, SCD patients are more likely to undergo revisions for PJI, aseptic loosening, and hematoma compared to patients who do not have SCD. Due to the high-risk of these complications, perioperative and postoperative surgical optimization should be enforced in SCD patients.

Risks of Immunosuppressive Therapy in Patients Undergoing Open Reduction Internal Fixation for Ankle Fractures.

Chronic steroid and immunosuppressant use have been shown to increase the risk for postoperative complications in orthopedic surgery. Further understanding of the risks of immunosuppression is necessary to aid in risk stratification and patient counseling. However, these risks have not yet been explored in ankle fracture patients. Thus, the purpose of this study is to determine whether patients taking immunosuppressives are at an increased risk for morbidity and mortality following open reduction and internal fixation (ORIF) of ankle fractures. Patients undergoing operative treatment for ankle fractures from 2006 to 2018 were identified in the National Surgical Quality Improvement Program database. Patients were categorized based on their use of immunosuppressive medications. Postoperative outcomes assessed included superficial surgical site infections, deep surgical site infections, organ space infections, wound dehiscence, pneumonia, unplanned intubation, pulmonary embolism, urinary tract infection, renal failure, blood transfusion requirement, deep vein thrombosis, sepsis, cardiac arrest, extended length of hospital stay, readmission, reoperation, and mortality. Univariate and multivariate analyses were performed. In total, 10,331 patients underwent operative treatment for ankle fracture. Total 10,153 patients (98.3%) were not taking immunosuppressants and 178 (1.7%) were taking these medications. In multivariate analysis, patients taking immunosuppressants were at increased risk of pulmonary embolism (odds ratio [OR] 4.382; p = .041) and hospital readmission (OR 2.131; p = .021). Use of immunosuppressive medications is an independent risk factor for pulmonary embolism and readmission following ORIF for ankle fractures. Notably, no association with wound complications, infections, or sepsis was identified.

Systematic review of long-term chemotherapy-induced peripheral neuropathy (CIPN) following adjuvant oxaliplatin for colorectal cancer.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is the most common dose-limiting side effect of oxaliplatin. It often persists and can adversely affect quality of life of colorectal cancer (CRC) survivors. This systematic review explored the proportions of patients with persistent CIPN and the reporting methods used. METHODS: MEDLINE, EMBASE, Web of Science and CINAHL were searched up to March 2021 for publications reporting CIPN outcomes following adjuvant oxaliplatin-containing chemotherapy at prespecified timepoints in participants with CRC. Secondary outcomes assessed the tools used to measure CIPN. Two authors reviewed full text publications for eligibility, data extraction and appraisal. Meta-analysis was performed where Common Terminology Criteria for Adverse Events (any grade) was reported at the most frequent timepoints. RESULTS: From 7895 citations identified, 27 studies met the eligibility criteria: six were randomised control trials, and 21 were non-randomised studies. Pooled prevalence of CIPN at 6, 12, 24 and 36 months after chemotherapy were 58%, 45%, 32% and 24% respectively. The average prevalence of CIPN decreased by 26% per year after chemotherapy (pooled RR = 0.74; 95% CI 0.72-0.75). Across all studies, ten separate tools were used as the primary measure of CIPN. Quality appraisal identified open-label design and inadequate reporting of participants lost to follow-up as the main methodological limitations. CONCLUSION: Our summary of reported rates of persistent CIPN indicates substantial long-term toxicity affecting CRC survivors, and will help clinicians estimate CIPN risk and its change over time. The heterogeneity of CIPN measures identified in the review highlights the need for a standardised CIPN assessment.

The placenta as the window to congenital heart disease.

PURPOSE OF REVIEW: There is an increasing recognition that structural abnormalities and functional changes in the placenta can have deleterious effects on the development of the fetal heart. This article reviews the role of the placenta and the potential impact of placental insufficiency on fetuses with congenital heart disease. RECENT FINDINGS: The fetal heart and the placenta are directly linked because they develop concurrently with shared regulatory and signaling pathways. Placental disease is more common in pregnancies carrying a fetus with congenital heart disease and the fetal response to placental insufficiency may lead to the postnatal persistence of cardiac remodeling. The mechanisms underlying this placental-fetal axis of interaction potentially include genetic factors, oxidative stress, chronic hypoxia, and/or angiogenic imbalance. SUMMARY: The maternal-placental-fetal circulation is critical to advancing our understanding of congenital heart disease. We must first expand our ability to detect, image, and quantify placental insufficiency and dysfunction in utero. Elucidating the modifiable factors involved in these pathways is an exciting opportunity for future research, which may enable us to improve outcomes in patients with congenital heart disease.

Chemical exposures from upholstered furniture with various flame retardant technologies.

Upholstered furniture is often manufactured with polyurethane foam (PUF) containing flame retardants (FRs) to prevent the risk of a fire and/or to meet flammability regulations, however, exposure to certain FRs and other chemicals have been linked to adverse health effects. This study developed a new methodology for evaluating volatile organic compound (VOC) and FR exposures to users of upholstered furniture by simulating use of a chair in a controlled exposure chamber and assessing the health significance of measured chemical exposure. Chairs with different fire-resistant technologies were evaluated for VOC and FR exposures via inhalation, ingestion, and dermal contact exposure routes. Data show that VOC exposure levels are lower than threshold levels defined by the US and global indoor air criteria. Brominated FRs were not detected from the studied chairs. The organophosphate FRs added to PUF were released into the surrounding air (0.4 ng/m3 ) and as dust (16 ng/m2 ). Exposure modeling showed that adults are exposed to FRs released from upholstered furniture mostly by dermal contact and children are exposed via dermal and ingestion exposure. Children are most susceptible to FR exposure/dose (2 times higher average daily dose than adults) due to their frequent hand to mouth contact.

Understanding and managing the complex balance between bleeding and thrombosis following cardiopulmonary bypass in paediatric cardiac surgical patients.

Bleeding in the perioperative period of congenital heart surgery with cardiopulmonary bypass is associated with increased morbidity and mortality both from the direct effects of haemorrhage as well as the therapies deployed to restore haemostasis. Perioperative bleeding is complex and multifactorial with both patient and procedural contributions. Moreover, neonates and infants are especially at risk. The objective of this review is to summarise the evidence regarding bleeding management in paediatric surgical patients and identify strategies that might facilitate appropriate bleeding management while minimising the risk of thrombosis. We will address the use of standard and point-of-care tests, and the role of contemporary coagulation factors and other novel drugs.

Preoperative estimated glomerular filtration rate is a marker for postoperative complications following aseptic revision total hip arthroplasty.

INTRODUCTION: Revision total hip arthroplasty (rTHA) is increasingly performed but may carry a high rate of complication. This aim of the study was to determine if a decreased eGFR increases risks of postoperative complications following rTHA. METHODS: A retrospective cohort study using the American College of Surgeons National Quality Improvement Program Database was conducted. Patients undergoing rTHA between 2007 and 2014 were identified and stratified by glomerular filtration rates (eGFR): eGFR > 125 mL/min, eGFR 90-125 mL/min, eGFR 60-90 mL/min, eGFR 30-60 mL/min, and eGFR < 30 mL/min. The incidence of postoperative adverse events within 30 days, including cardiac, pulmonary, renal, septic, thromboembolic, urinary tract, and wound complications, blood transfusion, death, length of stay > 7 days, and unplanned return to the operating room, was assessed. The complication rates following rTHA were assessed with univariate and multivariate analysis with a significance set at p < 0.05. RESULTS: In total, 8898 revision THA procedures were included for analysis. 28.4% of patients that underwent rTHA developed a complication following surgery. Following adjustment, an eGFR of less than 30 mL/min independently increased the odds of any complication (OR 1.447; 95% C.I. 1.010-2.074; p = 0.044), cardiac complications (OR 3.344; 95% C.I. 1.040-10.752; p = 0.043), blood transfusion (O.R. 1.623; 95% C.I. 1.122-2.352; p = 0.010), and extended length of stay (O.R. 2.392; 95% C.I. 1.526-3.759; p < 0.001) when compared to normal renal function. CONCLUSIONS: Diminished eGFR of less than 30 mL/min increased the odds of total complications, cardiac complications, blood transfusions, and extended length of stay compared to normal renal function.

Perioperative risks of bariatric surgery among patients with and without history of solid organ transplant.

Bariatric surgery is effective among patients with previous transplant in limited case series. However, the perioperative safety of bariatric surgery in this patient population is poorly understood. Therefore, we assessed the safety of bariatric surgery among previous-transplant patients using a database that captures >92% of all US bariatric procedures. All primary, laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass procedures between 2017 and 2018 were identified from the MBSAQIP dataset. Patients with previous transplant (n = 610) were compared with patients without previous transplant (n = 321 447). Primary outcomes were 30 day readmissions, surgical complications, medical complications, and death. Multivariable logistic regression with predictive margins was used to compare outcomes. Previous transplant patients experienced higher incidence of readmissions (8.0% vs 3.5%), surgical complications (5.0% vs 2.7%), and medical complications (4.3% vs 1.5%). There was no difference in incidence of death (0.2% vs 0.1%). Among individual complications, there no statistical differences in intraabdominal leak, unplanned reoperation, myocardial infarction, or infectious complications. Baseline estimated glomerular filtration rate was found to be a strong moderator of primary outcomes, with the highest risk of complications occurring at the lowest baseline estimated glomerular filtration rate. Given the many long-term benefits of bariatric surgery among patients with previous transplant, our findings should not preclude this patient population from operative consideration.

Dilated cardiomyopathy in children: moving beyond traditional pharmacologic therapy.

PURPOSE OF REVIEW: Dilated cardiomyopathy (DCM) is a rare myocardial disorder characterized by a dilated left ventricle and systolic dysfunction. Globally, it affects around 1 in every 100 000 children. The prognosis is generally poor, with 40% either failing traditional medical therapy within the first 2 years or requiring a heart transplant. This article will address the basic cause, epidemiology, pathobiology, and historical treatment approach of DCM and introduce novel contemporary medical and surgical strategies that may reduce the need for heart transplantation. RECENT FINDINGS: In the last 15 years, there has been a significant emphasis on identifying alternative treatment strategies in managing the child with a DCM and heart failure symptoms. New therapies have evolved to help bridge these critically ill children to transplant or have these therapeutic modalities serve as end-points in themselves. Thus subsequently, we will highlight contemporary as well as novel medical and procedural therapies that are being used for the treatment of pediatric DCM. SUMMARY: The child with a DCM and severe left ventricular dysfunction has a number of options available beyond simple diuretics and afterload reduction. Novel pacing strategies and mechanical assist device may provide not only a more stable clinical bridge environment but also may actually serve as an endpoint itself.

The microbiome of the infertile male.

PURPOSE OF REVIEW: Contrary to historic dogma, many tissues and organs in the human body contain a resident population of bacteria, fungi, and viruses collectively known as the microbiome. The microbiome plays a role in both homeostatic symbiosis and also pathogenic dysbiosis in a wide array of diseases. Our understanding of the relationship between the microbiome and male factor infertility is in its infancy but is slowly evolving. RECENT FINDINGS: Recent literature indicates that semen (and likely the testis) is not sterile and contains a distinct microbiome, and these changes in its composition are associated with alterations in semen quality and fertility status. Preliminary investigation indicates that manipulating the human microbiome may have implications in improving semen parameters and fertility. SUMMARY: In this review, we describe relationships between the microbiome and the genitourinary system, discuss the prior work on the relationship among bacteriospermia, leukocytospermia and male factor infertility, and summarize the current literature utilizing 16s rRNA-based next-generation sequencing on the seminal and testicular microbiome. We explore the specific microbial taxa implicated in various aspects of spermatic dysfunction and introduce preliminary evidence for therapeutic approaches to alter the microbiome and improve fertility status.

Sex Differences in Osteoarthritis Pathogenesis: A Comprehensive Study Based on Bioinformatics.

BACKGROUND Osteoarthritis (OA) is a common disorder in the elderly. OA influences the daily life of patients and has become a worldwide health problem. It is still unclear whether the pathogenesis mechanism is different between males and females. This study investigated the differentially expressed genes (DEGs) and explored the different signaling pathways of OA between males and females. MATERIAL AND METHODS Data sets of GSE55457, GSE55584, and GSE12021 were retrieved from Gene Expression Omnibus to conduct DEGs analysis. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology term was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) bioinformatics tool. The protein interaction network was constructed in Cytoscape 3.7.2. qRT-PCR was then performed to validate the expression of hub genes in OA patients and healthy people. RESULTS In total, 4 co-upregulated and 10 co-downregulated genes were identified. We found that enriched pathways were different between males and females. BCL2L1, EEF1A1, EEF2, HNRNPD, and PABPN1 were considered as hub genes in OA pathogenesis in males, while EEF2, EEF1A1, RPL37A, FN1 were considered as hub genes in OA pathogenesis in females. Consistent with the bioinformatics analysis, the qRT-PCR analysis also showed that the gene expression of BCL2L1, HNRNPD, and PABPN1 was significantly lower in male OA patients. In contrast, EEF2, EEF1A1, and RPL37A were significantly lower in female OA patients. CONCLUSIONS The DEGs identified may be involved in different OA disease progression mechanisms between males and females, and they are considered as treatment targets or prognosis markers for males and females. The pathogenesis mechanism is sex-dependent.

Ivabradine as a stabilising anti-arrhythmic agent for multifocal atrial tachycardia.

Multifocal atrial tachycardia has certain electrocardiographic similarities to atrial fibrillation. The mechanism of atrial fibrillation is heterogenous but in some cases may arise from a single ectopic driver with fibrillatory conduction to the rest of the atria. This has led to the speculation that multifocal atrial tachycardia may have a similar mechanistic unifocal site that disperses through the atrium in a fibrillatory pattern. Ivabradine has been reported to be efficacious in an adult with paroxysmal atrial fibrillation as well as in children with junctional or ectopic atrial tachycardias. This is the first report of successfully using ivabradine, a novel anti-arrhythmic If blocking agent, to convert multifocal atrial tachycardia in a 5-month-old critically ill infant to a pattern indicating a single ectopic atrial focus. This allowed the patient's single atrial focus to be ablated with return to sinus rhythm and decannulation from ventriculoarterial extracorporeal membrane oxygenation. This case suggests that multifocal atrial tachycardia may arise from a single automatic focus with downstream fibrillatory conduction to the atria.

Prior Knee Arthroscopy Is Associated With Increased Risk of Revision After Total Knee Arthroplasty.

BACKGROUND: Knee arthroscopy (KA) is frequently performed to provide improved joint function and pain relief. However, outcomes following total knee arthroplasty (TKA) after prior KA are not fully understood. The purpose of this study is to determine the relationship between prior KA within 2 years of TKA on revision rates after TKA. METHODS: Data were collected from the Humana insurance database using the PearlDiver Patient Records Database from 2006 to 2017. Subjects were identified using Current Procedural Terminology and International Classification of Diseases procedure codes to identify primary TKA. Patients were stratified into 2 groups based upon a history of prior KA. Univariate and multivariate analyses were conducted to determine association between KA and outcomes at 2-year postoperative period. RESULTS: In total, 138,019 patients were included in this study, with 3357 (2.4%) patients receiving a KA before TKA and 134,662 (97.6%) patients who did not. The most common reason for KA was osteoarthritis (40.0%), followed by medial tear of the meniscus (26.0%) and chondromalacia (21%.0). After adjustment, prior KA was associated with increased revision rate (odds ratio [OR], 1.392; P = .003), postoperative stiffness (OR, 1.251; P = .012), periprosthetic joint infection (OR, 1.326; P < .001), and aseptic loosening (OR, 1.401; P = .048). CONCLUSION: Prior KA is significantly associated with increased 2-year TKA revision rate. The most common etiology for arthroscopy was osteoarthritis. The results of the study, showing that arthroscopy before TKA substantially increases the rates of revision, PJI, aseptic loosening, and stiffness, lend further credence to the idea that patients may be better served by nonsurgical management of their degenerative pathology until they become candidates for TKA. Subjecting this population to arthroscopy appears to offer limited benefit at the cost of poorer outcomes when they require arthroplasty in the future. LEVEL OF EVIDENCE: Level III therapeutic study.