•This study investigates the temporal trends and significance of a positive/equivocal cytology (CP) in the absence of visible disease recurrence after trimodal therapy for muscle-invasive bladder ...cancer.•CP is common, occurring in approximately a third of patients at first follow-up.•CP does not preclude subsequent negative cytology as the probability of having negative cytology after CP was 57% at the 6-month follow-up and the mean time-to-negative cytology was 3.2 months.•Persistence of positive cytology may be associated with adverse recurrence and survival outcomes.
Urine cytology and cystoscopy are routinely employed during follow-up of patients after trimodal therapy (TMT) for muscle-invasive bladder cancer (MIBC). The significance of positive or equivocal cytology without visible disease recurrence on cystoscopy during follow-up is unknown, and studies informing outcomes in this scenario are lacking. This study aims to investigate the temporal trends of positive/equivocal cytology in the absence of visible disease recurrence and the association with bladder cancer recurrence and survival outcomes.
One hundred and twenty-nine patients with available post-TMT cytology data and negative cystoscopy from a single academic institution between 2002 and 2017 with a median follow-up of 3.4 (range 0.1–14.2) years were analyzed. Cytology results, first post-TMT cytology positive/equivocal (CP) and negative (CN), were evaluated for association with disease recurrence and survival. Kaplan. Meier and competing risks methods were used to assess time-to-negative cytology in CP patients with ≥2 interval post-TMT cytology results (n = 33), time-to-recurrence, and disease-specific mortality (DSM) stratified by first post-TMT cytology result.
At first follow-up (6–8 weeks post-TMT completion), CP was observed in 41 (32%) and CN in 88 (68%) of patients. With further follow-up of CP patients with ≥2 interval post-TMT cytology results, the probability of developing negative cytology was 57% (95% CI 42, 77) at 6 months post-TMT, and the median time-to-negative cytology was 3.2 months (95% CI 2.99, 5.80). The median time-to-recurrence was reduced in CP patients compared to CN (24.3 vs. 78.1 months, p = 0.1), corresponding with an apparent increase in the cumulative incidence of recurrence rate at 3 years in the CP vs. CN group (62% vs. 42%, p = 0.1). No significant difference was observed in the 3-year DSM rates. On univariable analysis, the hazards of recurrence and DSM for patients with CP were 1.5 (95% CI 0.9, 2.5, p = 0.1) and 2.1 (95% CI 0.9, 4.7, p = 0.07) respectively.
This is the first study to investigate the significance of a positive/equivocal cytology without visible disease following TMT for MIBC. Positive cytology is common and does not preclude subsequent negative cytology supporting a watchful waiting approach rather than proceeding immediately to biopsy. However, cytology that remains positive at subsequent follow-up may be associated with adverse recurrence and survival outcomes.
Patients with metastatic non-small cell lung cancer (NSCLC) experience significant morbidity with dyspnea being a common symptom with a prevalence of 70%. The objective of this study was to determine ...factors associated with a moderate-to-severe dyspnea score based on the Edmonton Symptom Assessment System (ESAS), as well as resultant patterns of intervention and factors correlated to intervention receipt.
Using health services administrative data, we conducted a population-based study of all patients diagnosed with metastatic NSCLC treated from January 2007 to September 2018 in the province of Ontario. The primary outcomes of interest are the prevalence of moderate-to-severe dyspnea scores, and the receipt of dyspnea-directed intervention. Differences in baseline characteristic between moderate-to-severe dyspnea and low dyspnea score cohorts were assessed by comparative statistics. Predictors of intervention receipt for patients with moderate-to-severe dyspnea scores were estimated using multivariable modified Poisson regression.
The initial study cohort included 13,159 patients diagnosed with metastatic NSCLC and of these, 9,434 (71.7%) reported a moderate-to-severe dyspnea score. Compared to patients who did not report moderate-to-severe dyspnea scores, those who reported a moderate-to-severe dyspnea score were more likely to complete a greater number of ESAS surveys, be male, have a higher Elixhauser comorbidity index (ECI) score, and receive subsequent systemic therapy after diagnosis. Most patients with a moderate-to-severe dyspnea score received intervention (96%), of which the most common were palliative care management (87%), thoracic radiotherapy (56%) and thoracentesis (37%). Multivariable regression identified older patients to be less likely to undergo pleurodesis. Thoracentesis was less common for patients living in rural and non-major urban areas, lower income areas, and earlier year of diagnosis. Receipt of thoracic radiotherapy was less common for older patients, females, those with ECI ≥4, patients living in major urban areas, and those with later year of diagnosis. Finally, palliative care referrals were less frequent for patients with ECI ≥4, age 60-69, residence outside of major urban areas, earlier year of diagnosis, and lower income areas.
Dyspnea is a prevalent symptom amongst patients with metastatic NSCLC. Subpopulations of patients with moderate-to-severe dyspnea scores were in which inequities may exist in access to care that require further attention and evaluation.
(1) Background: The COVID-19 pandemic has created challenges for college athletes as they return to sport and campus life. Emerging literature highlights some of these challenges, but no studies have ...used a primarily qualitative approach to assess the impact of the pandemic on college athletes. The purpose of this study was to better understand factors affecting college athletes' return to sport and campus life amidst the COVID-19 pandemic. (2) Methods: Semi-structured interviews were conducted with varsity athletes who participated in the 2020-2021 season at a single university. Qualitative analysis was performed using the Strauss and Corbin method to derive codes, categories, and themes. Additionally, Athletic Coping Skills Inventory-28 (ACSI-28) scores were recorded and analyzed using descriptive statistics. (3) Results: A total of 20 student athletes were interviewed, revealing that confidence and motivation, increased stress and anxiety, and adaptive coping strategies were common themes affecting their experiences returning to sport and campus life. Results from the ACSI-28 showed an average score of 49.5 and a range of 24-66. (4) Conclusions: Semi-structured interviews revealed factors impacting return to sport and student life. These findings can help inform how to better support college athletes throughout the remainder of the current pandemic and moving forward.
Purpose To determine whether 400 mg of celecoxib administered 1 hour before hip arthroscopy surgery would reduce pain, provide reduction in overall narcotic consumption, and lead to more rapid ...discharge from recovery rooms. Methods Ninety-eight patients were randomized to either the celecoxib group (n = 50) or the placebo group (n = 48). An a priori power analysis was done set to detect a difference of 0.50 on the visual analog scale (VAS), based on the senior author's preference. The number of patients planned for recruitment was rounded up to 100 to allow for flexibility in the study. Inclusion criteria were any patient at least 18 years old who underwent hip arthroscopy surgery performed by the senior author. All patients had less than Tönnis grade 2 arthritis. Exclusion criteria were allergy to sulfa-based drugs, prior adverse reaction to celecoxib, or patients who were on chronic narcotics for whom alternative pain management regimens were arranged before surgery. Randomization was performed on a 1:1 basis in blocks of 10 using sealed envelopes stating celecoxib or placebo. One hour before surgery, all patients received either 400 mg celecoxib or placebo. Patients were evaluated using a VAS preoperatively, immediately postoperatively, and at 1 and 2 hours postoperatively. Time from the operating room to “ready for discharge” and number of morphine equivalents of narcotic medication required in the postanesthesia care unit were recorded. Results Age and preoperative VAS were similar between the celecoxib and placebo control group, with average ages of 34.2 ± 11.9 and 35.8 ± 11.6 ( P = .27) and preoperative VAS of 2.1 ± 2.06 and 2.3 ± 1.98 ( P = .29), respectively. The celecoxib group had 26 females and 24 males, whereas the placebo group had 29 females and 19 males ( P = .42). The most common surgical procedures were labral repair (31 patients in the celecoxib group and 29 patients in the placebo group), and labral repair with acetabular osteoplasty (13 patients in the celecoxib group and 11 patients in the placebo group). There were no significant differences in procedures performed between the 2 groups ( P > .05). At 1 hour postoperatively, patients who received celecoxib had a lower pain score that was statistically significant compared with the placebo group (4.6 vs 5.4, P = .03). There was a significant difference in discharge time between patients who received celecoxib and the control group (152.9 minutes vs 172.9 minutes, P = .04). There was no significant difference found in morphine equivalents consumed in the postanesthesia care unit between the 2 groups (15.3 vs 15.4, P = .48). Conclusions A preoperative dose of 400 mg of celecoxib led to statistically significantly reduced patient-reported pain on the VAS in the acute postoperative period after hip arthroscopy surgery, though the difference is not likely clinically significant. There was a significantly shorter time to discharge in patients who received celecoxib versus placebo. Level of Evidence Level I, randomized controlled trial.
Huntington's disease is an inherited and incurable neurodegenerative disorder caused by an abnormal polyglutamine (polyQ) expansion in huntingtin (encoded by HTT). PolyQ length determines disease ...onset and severity, with a longer expansion causing earlier onset. The mechanisms of mutant huntingtin-mediated neurotoxicity remain unclear; however, mitochondrial dysfunction is a key event in Huntington's disease pathogenesis. Here we tested whether mutant huntingtin impairs the mitochondrial fission-fusion balance and thereby causes neuronal injury. We show that mutant huntingtin triggers mitochondrial fragmentation in rat neurons and fibroblasts of individuals with Huntington's disease in vitro and in a mouse model of Huntington's disease in vivo before the presence of neurological deficits and huntingtin aggregates. Mutant huntingtin abnormally interacts with the mitochondrial fission GTPase dynamin-related protein-1 (DRP1) in mice and humans with Huntington's disease, which, in turn, stimulates its enzymatic activity. Mutant huntingtin-mediated mitochondrial fragmentation, defects in anterograde and retrograde mitochondrial transport and neuronal cell death are all rescued by reducing DRP1 GTPase activity with the dominant-negative DRP1 K38A mutant. Thus, DRP1 might represent a new therapeutic target to combat neurodegeneration in Huntington's disease.
Purpose
Multi-ligament knee injuries are a serious consequence of knee dislocation with a poorly evaluated post-operative complication profile due to low incidence. The aim of this study is to assess ...the risk of adverse post-operative events associated with operative management of multi-ligament knee injuries.
Methods
The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients undergoing surgical procedures for multi-ligament knee injuries from 2006 to 2016 using Current Procedural Terminology codes. We evaluated data on patient demographics and used a propensity score algorithm to adjust for baseline differences in these patients and developed univariate and multivariate logistic regression models to assess effects on minor and severe 30-day post-operative complications.
Results
We identified 444 patients in this database who underwent multi-ligament knee reconstructions between 2006 and 2016. After propensity matching, minor and major adverse post-operative events were more frequent in patients with multi-ligament knee injuries (1.4% vs 0.2%,
p
< 0.001 and 2.7% vs 1.1%,
p
= 0.002, respectively). Patients with multi-ligament knee injuries experienced a 55-fold increase risk of need for transfusion (
p
< 0.001) and a fivefold increased risk of pulmonary embolism (
p
= 0.025), with most occurring in bicruciate reconstructions (Schenck Classification KD-III and KD-IV injuries).
Conclusion
The surgical management of multi-ligament knee injuries confers significant increased risk of 30-day post-operative minor or severe adverse event over arthroscopic ACL reconstruction. These patients are most at risk for post-operative blood transfusion requirement, and pulmonary embolism, with patient’s undergoing surgery for bicruciate ligament injuries at particularly high risk of complication.
Level of evidence
IV.
To use the American College of Surgeons National Surgical Quality Improvement Program database to determine whether body mass index (BMI) is associated with 30-day postoperative complications ...following arthroscopic surgery.
Cases of elective knee, hip, and shoulder arthroscopy were identified. A retrospective comparative analysis was conducted, and the overall rates of morbidity, mortality, readmission, reoperation, and venothromboembolism (VTE) were compared using univariate analyses and binary logistic regressions to ascertain the adjusted effect of BMI, with and without diabetes, on morbidity, readmission, reoperation, and VTE.
There were 141,335 patients who met the criteria. The most common complications were deep vein thrombosis (0.27%), superficial surgical site infection (0.17%), urinary tract infection (0.13%), and pulmonary embolism (0.11%). Obesity class III with diabetes was a risk factor for morbidity (odds ratio OR = 1.522; 95% confidence interval CI, 1.101-2.103) and readmission (OR = 2.342; 95% CI, 1.998-2.745) following all procedures, while obesity class I was protective toward reoperation (OR = 0.687, 95% CI, 0.485-0.973). Underweight patients were at higher risk for morbidity following shoulder arthroscopy (OR = 3.776; 95% CI, 1.605-8.883), as were the class I obese (OR = 1.421; 95% CI, 1.010-1.998) and class II obese (OR = 1.726, 95% CI, 1.159-2.569). BMI did not significantly affect morbidity following knee arthroscopy. VTE risk factors included being overweight (OR = 1.474; 95% CI, 1.088-1.996) or diabetic with class I obesity (OR = 1.469; 95% CI, 1.027-2.101).
Arthroscopic procedures are safe with very low complication rates. However, underweight and class I and class II obese patients are at higher risk for morbidity following shoulder arthroscopy, and diabetic patients with class III obesity are at higher risk for morbidity and readmission following all arthroscopy. Because BMI is a modifiable risk factor, these patients should be evaluated carefully before being considered for outpatient arthroscopic surgery.
Level III, retrospective comparative study.
Background:
Orthopaedic surgeons have a responsibility to develop responsible opioid practices. Growing evidence has helped define an optimal number of opioids to prescribe after surgical procedures, ...but little evidence-based guidance exists to support specific practice patterns to decrease opioid utilization.
Hypothesis:
After knee arthroscopic surgery with partial meniscectomy, patients who were provided a prescription for opioids and instructed to only fill the prescription if absolutely necessary for pain control would take fewer opioids than patients with opioids automatically included as part of a multimodal approach to pain control prescribed at discharge.
Study Design:
Randomized controlled trial; Level of evidence, 2.
Methods:
Patients undergoing arthroscopic partial meniscectomy were provided multimodal pain control with aspirin, acetaminophen, and naproxen and randomized to receive oxycodone as either included with their multimodal pain medications (group 1) or given an optional prescription to fill (group 2). Patients were contacted at time points up to 1 month after surgery to assess opioid utilization and medication side effects. The mean number of tablets utilized was the primary outcome measure, with a 50% reduction defined as a successful outcome.
Results:
A total of 105 patients were initially enrolled, and 95 (91%; 48 in group 1 and 47 in group 2) successfully completed the study. There was no significant reduction in the number of tablets utilized between groups 1 and 2 (3.5 vs 4.5, respectively; P = .45), days that opioids were required (2.2 vs 3.2, respectively; P = .20), or postoperative pain at any time point. The group with the option to fill their prescription had significantly fewer unused tablets remaining than the group with opioids included as part of the multimodal pain control regimen (75% of potentially prescribed tablets vs 82% of prescribed tablets; P < .001). Overall, 37% of patients did not require any opioids after surgery, and 86% used ≤8 tablets.
Conclusion:
Patients required a minimal number of opioids after knee arthroscopic surgery with partial meniscectomy. There was no difference in the number of tablets utilized whether the opioid prescription was included in a multimodal pain control regimen or patients were given an option to fill the prescription. Offering optional opioid prescriptions in the setting of a multimodal approach to pain control can significantly reduce the number of unused opioids circulating in the community.
Registration:
NCT03876743 (ClinicalTrials.gov identifier)
Calcific tendinitis is a relatively common shoulder disorder, with 7%-17% of individuals with shoulder pain having rotator cuff calcium deposits. Several nonoperative interventions, extracorporeal ...shockwave therapy (ESWT) and ultrasonography-guided needling (UGN), and surgical techniques have been described to treat calcific tendonitis with satisfactory outcomes. Clinical guidelines are lacking for surgical excision in cases refractory to nonoperative treatment. Several arthroscopic and open operative techniques have been described to treat calcific tendonitis with satisfactory clinical outcomes. The purpose of this systematic review of randomized controlled trials is to compare outcomes and complications of nonoperative vs. operative management of chronic calcific tendinitis of the rotator cuff, to provide evidence-based treatment guidelines for practitioners.
EMBASE, PubMed, and OVID MEDLINE were searched from database inception until February 20, 2022, for randomized controlled trials reporting outcomes related to operative or nonoperative management for calcific tendonitis of the shoulder. Clinical outcomes including pain on visual analog scale (VAS), Constant-Murley Shoulder Outcome Score (CMS), and resolution of calcific deposits were evaluated. Continuous data at last follow-up was pooled into mean differences using a random effects model for meta-analysis.
A total of 27 studies (2212 nonoperative patients and 140 operative patients) met the final inclusion criteria. Pooled mean difference in VAS for ESWT was –3.83 (95% confidence interval CI −5.38, −2.27); P < .001), compared to −4.83 (95% CI −5.44, −4.22; P < .001) for UGN, and −4.65 (95% CI −5.47, −3.82; P < .001) for the operative interventions. Pooled mean difference in CMS score after ESWT was 18.30 (95% CI 10.95, 25.66; P < .001) compared to 22.01 (95% CI 8.17, 35.84; P = .002) for UGN, and 38.35 (95% CI 31.68, 45.02; P < .001) for the operative interventions. Eighty-five percent of patients receiving operative and 67% of patients receiving UGN management had complete radiographic resolution of calcific deposit.
Surgical treatment of chronic calcific tendonitis of the rotator cuff results in larger improvement in functional outcome scores and comparable pain reduction to nonoperative interventions, particularly UGN. Both operative and nonoperative treatment modalities are likely to have clinically significant improvements in function and pain, and thus it is reasonable to trial UGN and ESWT as first-line treatment. Cost-effectiveness analyses will be needed to support one treatment over the other. High-quality randomized controlled trials directly comparing nonoperative interventions to operative interventions in patients prior to failing conservative treatment are needed to establish high-quality evidence-based guidelines.
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