Outcomes of patients with indolent lymphoma treated with bendamustine plus rituximab compared to rituximab plus CVP or CHOP chemoimmunotherapy in Ontario.

Bendamustine (B) with rituximab (R) has become the preferred regimen for patients with indolent lymphoma in Ontario, Canada, compared to R with cyclophosphamide, vincristine, prednisone (CVP) or cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). We conducted a propensity-matched retrospective cohort population-based study of patients treated with R-CVP/CHOP from 2005 to 2012 and patients treated with BR from 2013 to 2018. The primary outcome was 5-year overall survival (OS), and secondary outcomes included toxicities and healthcare utilization. The 5-year OS for patients treated with BR (n = 2023) and R-CVP/CHOP (n = 2023) was 80% and 75% respectively. Treatment with BR was associated with improved OS (HR 0.79, 95% CI 0.69-0.91). During the first 9 months, patients treated with BR versus R-CVP/CHOP had a higher number of admissions for infection (22% compared to 17%, p < 0.01) and a higher number of mean ED visits (mean 1.01 ± 1.68 visits vs. 0.85 ± 1.51 visits, p < 0.01). This trend persisted for 3 years. The adjusted 5-year OS for patients 75 years and older did not differ based on treatment regimen (55.5% for BR vs. 55.4% for R-CVP/CHOP). Our study supports the use of BR for patients with indolent lymphoma requiring treatment but suggests increased risk of certain toxicities warranting careful patient selection.

Ovarian cancer incidence and death in average-risk women undergoing bilateral salpingo-oophorectomy at benign hysterectomy.

BACKGROUND: Opportunistic bilateral salpingo-oophorectomy is often offered to patients undergoing benign hysterectomy to prevent ovarian cancer, but the magnitude of risk reduction obtained with bilateral salpingo-oophorectomy in this population remains unclear and must be weighed against potential risks of ovarian hormone deficiency. OBJECTIVE: This study aimed to quantify the relative and absolute risk reduction in ovarian cancer incidence and death associated with bilateral salpingo-oophorectomy at the time of benign hysterectomy. STUDY DESIGN: We performed a population-based cohort study of all adult women (≥20 years) undergoing benign hysterectomy from 1996 to 2010 in Ontario, Canada. Patients with ovarian pathology, previous breast or gynecologic cancer, or evidence of genetic susceptibility to malignancy were excluded. Inverse probability of treatment-weighted Fine-Gray subdistribution hazard models were used to quantify the effect of bilateral salpingo-oophorectomy on ovarian cancer incidence and death while accounting for competing risks and adjusting for demographic characteristics, gynecologic conditions, and comorbidities. Analyses were performed in all women and specifically in women of postmenopausal age (≥50 years) at the time of hysterectomy. RESULTS: We identified 195,282 patients (bilateral salpingo-oophorectomy, 24%; ovarian conservation, 76%) with a median age of 45 years (interquartile range, 40-51 years). Over a median follow-up of 16 years (interquartile range, 12-20 years), 548 patients developed ovarian cancer (0.3%), and 16,170 patients (8.3%) died from any cause. Bilateral salpingo-oophorectomy was associated with decreased ovarian cancer incidence (hazard ratio, 0.23; 95% confidence interval, 0.14-0.38; P<.001) and decreased ovarian cancer death (hazard ratio, 0.30; 95% confidence interval, 0.16-0.57; P<.001). At 20 years follow-up, the weighted cumulative incidences of ovarian cancer were 0.08% and 0.46% with bilateral salpingo-oophorectomy and ovarian conservation, respectively, yielding an absolute risk reduction of 0.38% (95% confidence interval, 0.32-0.45; number needed to treat, 260). After restricting to women aged ≥50 years at hysterectomy, the absolute risk reduction was 0.62% (95% confidence interval, 0.47-0.77; number needed to treat, 161). CONCLUSION: Bilateral salpingo-oophorectomy resulted in a significant absolute reduction in ovarian cancer among women undergoing benign hysterectomy. Population-average risk estimates derived in this study should be balanced against other potential implications of bilateral salpingo-oophorectomy to inform practice guidelines, patient decision-making, and surgical management.

Practice variation in bilateral salpingo-oophorectomy at benign abdominal hysterectomy: a population-based study.

BACKGROUND: Bilateral salpingo-oophorectomy at benign hysterectomy is not recommended in premenopausal women who are in the premenopausal stage because of its potential associations with increased all-cause mortality and cardiovascular disease; however, contemporary practice patterns are unknown. OBJECTIVE: This study aimed to quantify between-surgeon variation in bilateral salpingo-oophorectomy and identify surgeon and patient characteristics associated with bilateral salpingo-oophorectomy to evaluate current quality of care and identify targets for knowledge translation and future research. STUDY DESIGN: We conducted a population-based retrospective cross-sectional study of adult women (≥20 years) undergoing benign abdominal hysterectomy from 2014 to 2018 in Ontario, Canada. Hierarchical multivariable logistic regression models, stratified by age group (<45, 45-54, ≥55 years), were used to model between-surgeon variation after multivariable adjustment for patient and surgeon characteristics. Cases of bilateral salpingo-oophorectomy were classified as potentially appropriate or potentially avoidable based on the presence or absence of diagnostic indications. RESULTS: Of 44,549 eligible women, 17,797 (39.9%) underwent concurrent bilateral salpingo-oophorectomy, and 26,752 (60.1%) did not. In all three age strata, the individual surgeon providing care was one of the strongest factors influencing whether patients received bilateral salpingo-oophorectomy (median odds ratio, 2.00-2.53). Surgeons accounted for more than 22% of the residual observed variation in bilateral salpingo-oophorectomy in women aged 45-54 years compared with 16% and 14% of the residual observed variation in bilateral salpingo-oophorectomy in women aged <45 and ≥55 years, respectively. Non-gynecologic patient factors, such as obesity (odds ratio, 1.33; 95% confidence interval, 1.17-1.52; P<.001) and residing in low-income regions (odds ratio, 1.34; 95% confidence interval, 1.16-1.55; P<.001), were also associated with bilateral salpingo-oophorectomy. Approximately 40% of patients who underwent bilateral salpingo-oophorectomy had no indication for the procedure in their discharge records. CONCLUSION: Marked between-surgeon variation in bilateral salpingo-oophorectomy rates, even after adjusting for patient case mix, suggests ongoing uncertainty in practice. Stronger evidence-based guidelines on the risks and benefits of salpingo-oophorectomy as women age are needed, particularly focusing on perimenopausal women.

Early Surgical Complications of Total Hip Arthroplasty in Patients With Morbid Obesity: Propensity-Matched Cohort Study of 3683 Patients.

BACKGROUND: The aim of this study is to determine whether the high risk of surgical complications within 1 year of total hip arthroplasty (THA) is due to associated comorbidities or morbid obesity alone as measured by body mass index (BMI ≥ 40 kg/m2). METHODS: Population-based retrospective cohort study was conducted of all adults in Ontario undergoing primary THA for osteoarthritis (2012-2018). All patients were followed for 1 year. Outcomes were compared among matched groups (hypertension, diabetes, chronic obstructive pulmonary disease, frailty, congestive heart failure, coronary artery disease, asthma, and Charlson score). Primary outcome measure was major surgical complications within 1 year (composite of deep infection requiring surgery, dislocation requiring closed or open reduction, and revision surgery). RESULTS: A total of 3683 patients with morbid obesity were matched and had a significantly greater risk of major complications within 1-year (132 [3.6%] vs 54 [1.5%]; hazard ratio [HR] 2.54, 95% confidence interval [CI]; 1.98-3.25). This included greater risk for deep infection requiring surgery (100 [2.8%] vs 26 [0.7%]; HR 3.85, 95% CI; 2.70-45.48) and revision arthroplasty (86 [2.4%] vs 34 [0.9%]; HR 2.61, 95% CI; 1.92-3.55). Operative time was also longer with a median 116 (99-138) vs 102 (87-121) minutes. There were no significant differences in hospital stay, cost of acute care episode, or medical complications. CONCLUSION: Patients' large body habitus seems to contribute to the increased risk of surgical complications within 1-year of THA. Future research is needed to identify ways of mitigating surgical complications such as centralizing care for this complex group of patients in specialist centers.

SHAPE analysis of the 5' end of the Mason-Pfizer monkey virus (MPMV) genomic RNA reveals structural elements required for genome dimerization.

Earlier genetic and structural prediction analyses revealed that the packaging determinants of Mason Pfizer monkey virus (MPMV) include two discontinuous core regions at the 5' end of its genomic RNA. RNA secondary structure predictions suggested that these packaging determinants fold into several stem-loops (SLs). To experimentally validate this structural model, we employed selective 2' hydroxyl acylation analyzed by primer extension (SHAPE), which examines the flexibility of the RNA backbone at each nucleotide position. Our SHAPE data validated several predicted structural motifs, including U5/Gag long-range interactions (LRIs), a stretch of single-stranded purine (ssPurine)-rich region, and a distinctive G-C-rich palindromic (pal) SL. Minimum free-energy structure predictions, phylogenetic, and in silico modeling analyses of different MPMV strains revealed that the U5 and gag sequences involved in the LRIs differ minimally within strains and maintain a very high degree of complementarity. Since the pal SL forms a helix loop containing a canonical "GC" dyad, it may act as a RNA dimerization initiation site (DIS), enabling the virus to package two copies of its genome. Analyses of wild-type and pal mutant RNAs revealed that disruption of pal sequence strongly affected RNA dimerization. However, when in vitro transcribed trans-complementary pal mutants were incubated together showed RNA dimerization was restored authenticating that the pal loop (5'-CGGCCG-3') functions as DIS.

Structural basis of genomic RNA (gRNA) dimerization and packaging determinants of mouse mammary tumor virus (MMTV).

BACKGROUND: One of the hallmarks of retroviral life cycle is the efficient and specific packaging of two copies of retroviral gRNA in the form of a non-covalent RNA dimer by the assembling virions. It is becoming increasingly clear that the process of dimerization is closely linked with gRNA packaging, and in some retroviruses, the latter depends on the former. Earlier mutational analysis of the 5' end of the MMTV genome indicated that MMTV gRNA packaging determinants comprise sequences both within the 5' untranslated region (5' UTR) and the beginning of gag. RESULTS: The RNA secondary structure of MMTV gRNA packaging sequences was elucidated employing selective 2'hydroxyl acylation analyzed by primer extension (SHAPE). SHAPE analyses revealed the presence of a U5/Gag long-range interaction (U5/Gag LRI), not predicted by minimum free-energy structure predictions that potentially stabilizes the global structure of this region. Structure conservation along with base-pair covariations between different strains of MMTV further supported the SHAPE-validated model. The 5' region of the MMTV gRNA contains multiple palindromic (pal) sequences that could initiate intermolecular interaction during RNA dimerization. In vitro RNA dimerization, SHAPE analysis, and structure prediction approaches on a series of pal mutants revealed that MMTV RNA utilizes a palindromic point of contact to initiate intermolecular interactions between two gRNAs, leading to dimerization. This contact point resides within pal II (5' CGGCCG 3') at the 5' UTR and contains a canonical "GC" dyad and therefore likely constitutes the MMTV RNA dimerization initiation site (DIS). Further analyses of these pal mutants employing in vivo genetic approaches indicate that pal II, as well as pal sequences located in the primer binding site (PBS) are both required for efficient MMTV gRNA packaging. CONCLUSIONS: Employing structural prediction, biochemical, and genetic approaches, we show that pal II functions as a primary point of contact between two MMTV RNAs, leading to gRNA dimerization and its subsequent encapsidation into the assembling virus particles. The results presented here enhance our understanding of the MMTV gRNA dimerization and packaging processes and the role of structural motifs with respect to RNA-RNA and possibly RNA-protein interactions that might be taking place during MMTV life cycle.

Real-World Safety of Niraparib for Maintenance Treatment of Ovarian Cancer in Canada.

Niraparib was recently funded in Canada for the maintenance treatment of ovarian cancer following platinum-based chemotherapy. However, the drug's safety profile in the real world remains uncertain. We conducted a cohort study to describe the patient population using niraparib and the proportion that experienced adverse events between June 2019 and December 2022 in four Canadian provinces (Ontario, Alberta, British Columbia [BC], and Quebec). We used administrative data and electronic medical records from Ontario Health, Alberta Health Services, and BC Cancer, and registry data from Exactis Innovation. We summarized baseline characteristics using descriptive statistics and reported safety outcomes using cumulative incidence. We identified 514 patients receiving niraparib. Mean age was 67 years and most were initiated on a daily dose of 100 or 200 mg/day. Grade 3/4 anemia, neutropenia, and thrombocytopenia occurred in 11-16% of the cohort. In Ontario, the three-month cumulative incidence of grade 3/4 thrombocytopenia was 11.6% (95% CI, 8.3-15.4%), neutropenia was 7.1% (95% CI, 4.6-10.4%), and anemia was 11.3% (95% CI, 8.0-15.2%). Cumulative incidences in the remaining provinces were similar. Initial daily dose and proportions of hematological adverse events were low in the real world and may be related to cautious prescribing and close monitoring by clinicians.

Access to hip arthroplasty and rates of complications in different socioeconomic groups : a review of 111,000 patients in a universal healthcare system.

AIMS: Total hip arthroplasty (THA) is one of the most successful surgical procedures. The objectives of this study were to define whether there is a correlation between socioeconomic status (SES) and surgical complications after elective primary unilateral THA, and investigate whether access to elective THA differs within SES groups. METHODS: We conducted a retrospective, population-based cohort study involving 202 hospitals in Ontario, Canada, over a 17-year period. Patients were divided into income quintiles based on postal codes as a proxy for personal economic status. Multivariable logistic regression models were then used to primarily assess the relationship between SES and surgical complications within one year of index THA. RESULTS: Of 111,359 patients who underwent elective primary THA, those in the lower SES groups had statistically significantly more comorbidities and statistically significantly more postoperative complications. While there was no increase in readmission rates within 90 days, there was a statistically significant difference in the primary and secondary outcomes including all revisions due (with a subset of deep wound infection and dislocation). Results showed that those in the higher SES groups had proportionally more cases performed than those in lower groups. Compared to the highest SES quintile, the lower groups had 61% of the number of hip arthroplasties performed. CONCLUSION: Patients in lower socioeconomic groups have more comorbidities, fewer absolute number of cases performed, have their procedures performed in lower-volume centres, and ultimately have higher rates of complications. This lack of access and higher rates of complications is a "double hit" to those in lower SES groups, and indicates that we should be concentrating efforts to improve access to surgeons and hospitals where arthroplasty is routinely performed in high numbers. Even in a universal healthcare system where there are no penalties for complications such as readmission, there seems to be an inequality in the access to THA. Cite this article: Bone Joint J 2022;104-B(5):589-597.

Incidence and Predictors of Mental Health Outcomes Among Survivors of Adolescent and Young Adult Cancer: A Population-Based Study Using the IMPACT Cohort.

PURPOSE: Risk and predictors of long-term mental health outcomes in survivors of adolescent and young adult (AYA) cancers are poorly characterized. Mental health is consequently neglected in long-term follow-up. METHODS: We identified all AYA in Ontario, Canada age 15-21 years when diagnosed with one of six common cancers between 1992-2012 using a population-based database, and compared them with matched controls. Linkage to provincial healthcare data allowed analysis of rates of outpatient (family physician and psychiatrist) visits for psychiatric indications and time to severe psychiatric events (emergency room visit, hospitalization, and suicide). Demographic-, disease-, and treatment-related predictors of adverse outcomes, including treatment setting (adult v pediatric), were examined. RESULTS: Among 2,208 survivors and 10,457 matched controls, 5-year survivors experienced higher rates of outpatient mental health visits than controls (671 visits per 1,000 person-years v 506; adjusted rate ratio [RR] 1.3; 95% CI, 1.1 to 1.5; P = .006). Risk of a severe psychiatric episode was also increased among survivors (adjusted hazard ratio [HR], 1.2; 95% CI, 1.1 to 1.4, P = .008). Risk of a psychotic disorder-associated severe event was doubled in survivors (HR, 2.0, 95% CI, 1.3 to 2.4; P = .007) although absolute risk remained low (15-year cumulative incidence 1.7%; 95% CI, 1.0 to 2.7). In multivariable analysis, survivors treated in adult centers experienced substantially higher outpatient visit rates compared with those treated in pediatric settings (RR 1.8; 95% CI, 1.0 to 3.1; P = .04). CONCLUSION: Survivors of AYA cancer are at substantially increased risk of adverse mental health outcomes, with those treated in adult centers at particular risk. Although absolute incidence was low, survivors were at increased risk of psychotic disorder-associated severe events. Long-term mental health surveillance is warranted, as is research into effective interventions during or after cancer treatment.

Association of Surgical Experience With Risk of Complication in Total Hip Arthroplasty Among Patients With Severe Obesity.

Importance: Severe obesity is a risk factor for major early complications after total hip arthroplasty (THA). Objective: To determine the association between surgeon experience with THA in patients with severe obesity and risk of complications. Design, Setting, and Participants: This retrospective population-based cohort study was performed in Ontario, Canada, from April 1, 2007, to March 31, 2017, with data analysis performed from March 2020 to January 2021. A cohort of patients who received a primary THA for osteoarthritis and who also had severe obesity (body mass index [calculated as weight in kilograms divided by height in meters squared] ≥40) at the time of surgery was defined. These patients were identified using the Canadian Institute for Health Information Discharge Abstract Database and physician claims from the Ontario Health Insurance Plan. Generalized estimating equations were used to determine the association between overall THA and severe obesity-specific THA surgeon volume and the occurrence of complications after controlling for potential confounders. The study hypothesized that surgeon experience specific to patients with severe obesity could further reduce the risk of complications. Exposures: Primary THA. Main Outcomes and Measures: Complications were considered as a composite outcome (revision, infection requiring surgery, or dislocation requiring reduction), within 1 year of surgery. This was defined before the study, as was the study hypothesis. Results: A total of 4781 eligible patients was identified. The median age was 63 (interquartile range [IQR], 56-69) years, and 3050 patients (63.8%) were women. Overall, 186 patients (3.9%) experienced a surgical complication within 1 year of surgery. The median overall THA surgeon volume was 70 (IQR, 46-106) cases/y, whereas the median obesity-specific surgeon volume was 5 (IQR, 2-9) cases/y. After controlling for patient and hospital factors, greater obesity-specific THA surgeon volume (adjusted odds ratio per additional 10 cases, 0.65 [95% CI, 0.47-0.89]; P = .007), but not greater overall THA surgeon volume (adjusted odds ratio per 10 additional cases, 0.97 [95% CI, 0.93-1.02]; P = .24), was associated with a reduced risk of complication. Conclusions and Relevance: Increased surgeon experience performing THA in patients with severe obesity was associated with fewer major surgical complications. These findings suggest that surgeon experience is required to mitigate the unique anatomical challenges posed by surgery in patients with severe obesity. Referral pathways for patients with severe obesity to surgeons with high obesity-specific THA volume should be considered.

Association of bilateral salpingo-oophorectomy with all cause and cause specific mortality: population based cohort study.

OBJECTIVES: To determine if bilateral salpingo-oophorectomy, compared with ovarian conservation, is associated with all cause or cause specific death in women undergoing hysterectomy for non-malignant disease, and to determine how this association varies with age at surgery. DESIGN: Population based cohort study. SETTING: Ontario, Canada from 1 January 1996 to 31 December 2015, and follow-up to 31 December 2017. PARTICIPANTS: 200 549 women (aged 30-70 years) undergoing non-malignant hysterectomy, stratified into premenopausal (<45 years), menopausal transition (45-49 years), early menopausal (50-54 years), and late menopausal (≥55 years) groups according to age at surgery; median follow-up was 12 years (interquartile range 7-17). EXPOSURES: Bilateral salpingo-oophorectomy versus ovarian conservation. MAIN OUTCOMES MEASURES: The primary outcome was all cause death. Secondary outcomes were non-cancer and cancer death. Within each age group, overlap propensity score weighted survival models were used to examine the association between bilateral salpingo-oophorectomy and mortality outcomes, while adjusting for demographic characteristics, gynaecological conditions, and comorbidities. To account for comparisons in four age groups, P<0.0125 was considered statistically significant. RESULTS: Bilateral salpingo-oophorectomy was performed in 19%, 41%, 69%, and 81% of women aged <45, 45-49, 50-54, and ≥55 years, respectively. The procedure was associated with increased rates of all cause death in women aged <45 years (hazard ratio 1.31, 95% confidence interval 1.18 to 1.45, P<0.001; number needed to harm 71 at 20 years) and 45-49 years (1.16, 1.04 to 1.30, P=0.007; 152 at 20 years), but not in women aged 50-54 years (0.83, 0.72 to 0.97, P=0.018) or ≥55 years (0.92, 0.82 to 1.03, P=0.16). Findings in women aged <50 years were driven largely by increased non-cancer death. In secondary analyses identifying a possible change in the association between bilateral salpingo-oophorectomy and all cause death with advancing age at surgery, the hazard ratio gradually decreased during the menopausal transition and remained around 1 at all ages thereafter. CONCLUSION: In this observational study, bilateral salpingo-oophorectomy at non-malignant hysterectomy appeared to be associated with increased all cause mortality in women aged <50 years, but not in those aged ≥50 years. While caution is warranted when considering bilateral salpingo-oophorectomy in premenopausal women without indication, this strategy for ovarian cancer risk reduction does not appear to be detrimental to survival in postmenopausal women.

Factors associated with emergency department presentation after total joint arthroplasty: a population-based retrospective cohort study.

BACKGROUND: Unplanned visits to the emergency department after total joint arthroplasty are far more common than unplanned readmissions. Our objectives were to characterize the prevalence of presentation to an emergency department for any reason after total joint arthroplasty and to identify risk factors for such visits. METHODS: Using health administrative databases, we conducted a population-based retrospective cohort study of adults (19-89 yr of age) who received their first primary elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) procedure for arthritis between April 2011 and March 2016 in Ontario. We made univariate comparisons between patients who presented to the emergency department within 30 days of surgery and those who did not in. We determined differences in use of health care services between groups by comparing the change in use in the year before and after surgery between patients who presented to the emergency department and those who did not. We developed logistic regression models for the occurrence of an emergency department visit using backward variable elimination. RESULTS: We identified 42 273 total hip recipients and 70 725 total knee recipients, of whom 5640 (13.3%) and 11 224 (15.9%), respectively, presented to the emergency department within 30 days of surgery. Fewer than 1% of these patients required admission, and nearly half (45%) went to a different institution from where they had their surgery. Among both THA and TKA recipients, patients who presented to the emergency department had a net increase in their median annual health care costs (THA: $501, TKA: $682), compared to a net decrease for the cohort as a whole. Factors associated with increased risk of an emergency visit included increased patient age, male sex, rural residence and various comorbidities. Predictive regression models showed poor discriminative ability for both THA (C-statistic 0.57) and TKA (C-statistic 0.58) recipients. INTERPRETATION: One in 7 patients presented to the emergency department within 30 days of THA or TKA. Some may conceivably have been managed remotely, and very few required readmission. There is a crucial need for strategies to minimize these events.

No Difference in Outcomes Between Short and Longer-Stay Total Joint Arthroplasty with a Discharge Home: A Propensity Score-Matched Analysis Involving 46,660 Patients.

BACKGROUND: Outcomes following total hip arthroplasty (THA) and total knee arthroplasty (TKA) with a short length of hospital stay have been reported; however, most studies have not accounted for an inherent patient selection bias and discharge disposition. The purpose of this study was to utilize a propensity score to match and compare the outcomes of patients undergoing THA or TKA with short and longer lengths of stay with a discharge directly home. METHODS: An administrative database from Ontario, Canada, which has a single-payer health-care system, was retrospectively reviewed to identify patients who underwent THA or TKA from 2008 to 2016. Patients were subsequently stratified into 2 groups based on their length of stay: short length of stay (≤2 days; thereafter referred to as short stay) and longer length of stay (>2 days; thereafter referred to as longer stay). Using a propensity score, patients who underwent short-stay THA or TKA were matched to patients who underwent longer-stay THA or TKA. Matching was based on 15 demographic, medical, and surgical factors. Our primary outcomes included postoperative complications, health-care utilization (readmission and emergency department presentation), and health-care costs. RESULTS: Overall, 89,656 TKAs (14,645 short stays and 75,011 longer stays) and 52,610 THAs (9,426 short stays and 43,184 longer stays) were included in this study. Patients who underwent short-stay THA or TKA were significantly more likely (p < 0.05) to be younger, male, healthier, and from a higher socioeconomic status and to have undergone the procedure with a higher-volume surgeon. Over 95% of short-stay cases were successfully matched to longer-stay cases, and we found no significant difference in complications, health-care utilization, and costs between patients on the basis of the length of stay. CONCLUSIONS: Patients undergoing short-stay THA or TKA with a discharge home were more likely to be younger, healthy, male patients from a higher socioeconomic status. Higher-volume surgeons are also more likely to perform short-stay THA or TKA. These characteristics confirm the previously held belief that a selection bias exists when comparing cohorts based on time to discharge. When comparing matched cohorts of patients who underwent short-stay and longer-stay THA or TKA, we observed no difference in outcomes, suggesting that a short stay with a discharge home in the appropriately selected patient is safe following THA or TKA. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Surgical duration is associated with an increased risk of periprosthetic infection following total knee arthroplasty: A population-based retrospective cohort study.

BACKGROUND: Total knee arthroplasty (TKA) is one the most common elective procedures in the world. Post-operative infection is one of its most devastating complications, often necessitating multiple additional surgeries. We aimed to describe the relationship between surgical duration and risk of deep infection following primary elective TKA. METHODS: In this cohort study we analyses primary TKAs done between 2009 and 2016 in Ontario, Canada. We utilized restricted cubic splines to identify a threshold of surgical duration that was associated with an increased risk for infection requiring surgery. Patients with a 'short' duration of surgery were matched to those with a 'long' duration on patient age (±3 years), patient sex, severe obesity (BMI > 40), the primary surgeon, the hospital and the type of anesthetic. FINDINGS: In 92,343 primary TKAs, the median surgical duration was 106 min. We identified a cut-point of 100 min that was associated with an increased risk for infection. Subsequently, 17,815 TKA recipients with a 'long' procedure length were matched to those with a 'short' procedure length. 'Long' procedures had a higher rate of deep infection (1.1% versus 0.6%, p < 0.0001). This was equal to a relative risk of 1.81 (p < 0.0001). INTERPRETATION: In a cohort of TKA recipients, we found that procedure lengths longer than 100 min were associated with a significantly increased risk of deep infection requiring surgery. This time threshold serves a useful time-point to identify patients that require closer surveillance.

A G-C-rich palindromic structural motif and a stretch of single-stranded purines are required for optimal packaging of Mason-Pfizer monkey virus (MPMV) genomic RNA.

During retroviral RNA packaging, two copies of genomic RNA are preferentially packaged into the budding virus particles whereas the spliced viral RNAs and the cellular RNAs are excluded during this process. Specificity towards retroviral RNA packaging is dependent upon sequences at the 5' end of the viral genome, which at times extend into Gag sequences. It has earlier been suggested that the Mason-Pfizer monkey virus (MPMV) contains packaging sequences within the 5' untranslated region (UTR) and Gag. These studies have also suggested that the packaging determinants of MPMV that lie in the UTR are bipartite and are divided into two regions both upstream and downstream of the major splice donor. However, the precise boundaries of these discontinuous regions within the UTR and the role of the intervening sequences between these dipartite sequences towards MPMV packaging have not been investigated. Employing a combination of genetic and structural prediction analyses, we have shown that region "A", immediately downstream of the primer binding site, is composed of 50 nt, whereas region "B" is composed of the last 23 nt of UTR, and the intervening 55 nt between these two discontinuous regions do not contribute towards MPMV RNA packaging. In addition, we have identified a 14-nt G-C-rich palindromic sequence (with 100% autocomplementarity) within region A that has been predicted to fold into a structural motif and is essential for optimal MPMV RNA packaging. Furthermore, we have also identified a stretch of single-stranded purines (ssPurines) within the UTR and 8 nt of these ssPurines are duplicated in region B. The native ssPurines or its repeat in region B when predicted to refold as ssPurines has been shown to be essential for RNA packaging, possibly functioning as a potential nucleocapsid binding site. Findings from this study should enhance our understanding of the steps involved in MPMV replication including RNA encapsidation process.

Optimal packaging of FIV genomic RNA depends upon a conserved long-range interaction and a palindromic sequence within gag.

The feline immunodeficiency virus (FIV) is a lentivirus that is related to human immunodeficiency virus (HIV), causing a similar pathology in cats. It is a potential small animal model for AIDS and the FIV-based vectors are also being pursued for human gene therapy. Previous studies have mapped the FIV packaging signal (ψ) to two or more discontinuous regions within the 5' 511 nt of the genomic RNA and structural analyses have determined its secondary structure. The 5' and 3' sequences within ψ region interact through extensive long-range interactions (LRIs), including a conserved heptanucleotide interaction between R/U5 and gag. Other secondary structural elements identified include a conserved 150 nt stem-loop (SL2) and a small palindromic stem-loop within gag open reading frame that might act as a viral dimerization initiation site. We have performed extensive mutational analysis of these sequences and structures and ascertained their importance in FIV packaging using a trans-complementation assay. Disrupting the conserved heptanucleotide LRI to prevent base pairing between R/U5 and gag reduced packaging by 2.8-5.5 fold. Restoration of pairing using an alternative, non-wild type (wt) LRI sequence restored RNA packaging and propagation to wt levels, suggesting that it is the structure of the LRI, rather than its sequence, that is important for FIV packaging. Disrupting the palindrome within gag reduced packaging by 1.5-3-fold, but substitution with a different palindromic sequence did not restore packaging completely, suggesting that the sequence of this region as well as its palindromic nature is important. Mutation of individual regions of SL2 did not have a pronounced effect on FIV packaging, suggesting that either it is the structure of SL2 as a whole that is necessary for optimal packaging, or that there is redundancy within this structure. The mutational analysis presented here has further validated the previously predicted RNA secondary structure of FIV ψ.