Pressure injury education for older adults and carers living in community settings: A scoping review.

Older adults are at increased risk of pressure injuries (PIs) due to age-related changes. Traditionally, PI knowledge and education have been delivered in hospitals and residential aged care facilities, however, there remains a critical gap in understanding how PI knowledge on prevention and management is shared with older adults and their carers living in the community. We aimed to describe the nature and characteristics of structured and unstructured PI education programs available to community-dwelling older adults and their carers. As coping review was undertaken. We searched five databases: CINAHL, Medline, Scopus, Cochrane Library and ProQuest from 2009 to August 2023. The review was guided by Arksey and O'Malley's six-step framework and adhered to the PRISMA-ScR guidelines. It included primary peer-reviewed papers published in English, which focus on PI education for older adults and/or their carers living in community settings. Data extraction was organised in a table, and findings presented as a narrative summary. One-hundred and thirty-six papers were screened and four included in the review. Results indicate that consideration was placed on literacy levels and cognitive status of older adults and their carers when designing PI education materials. Educational materials such as leaflets/brochures, in-person training sessions or a combination of both were used. However, duration of these interventions varied, lasting for 1-4 weeks while others were completed over 12 months. Some improvements in PI knowledge such as how to treat PI, dietary requirements and importance of mobility were noted. However, information retention and its translation into effective long-term behaviour change remained unclear. In conclusion, adopting a multifaceted educational approach increases the effectiveness of PI knowledge translation. Continuous education, support and reinforcement on PIs over time are necessary when interacting with older adults and caregivers to ensure long-term management and prevention success. Conversations on PIs should start at the primary care levels when older adults and carers are visiting their GP clinics and accessing support services for other healthcare needs. Understanding older adults' and carers' literacy levels, cognitive status and cultural background can assist clinicians in designing and delivering fit-for-purpose PI educational interventions that are accessible, relatable and effective in promoting knowledge transfer and behaviour change. Carers are vital conduits in the care continuum. These factors will lead to a more informed, collaborative and person-centred approaches to PI management and prevention.

The Mediator CDK8-Cyclin C complex modulates Dpp signaling in Drosophila by stimulating Mad-dependent transcription.

Dysregulation of CDK8 (Cyclin-Dependent Kinase 8) and its regulatory partner CycC (Cyclin C), two subunits of the conserved Mediator (MED) complex, have been linked to diverse human diseases such as cancer. Thus, it is essential to understand the regulatory network modulating the CDK8-CycC complex in both normal development and tumorigenesis. To identify upstream regulators or downstream effectors of CDK8, we performed a dominant modifier genetic screen in Drosophila based on the defects in vein patterning caused by specific depletion or overexpression of CDK8 or CycC in developing wing imaginal discs. We identified 26 genomic loci whose haploinsufficiency can modify these CDK8- or CycC-specific phenotypes. Further analysis of two overlapping deficiency lines and mutant alleles led us to identify genetic interactions between the CDK8-CycC pair and the components of the Decapentaplegic (Dpp, the Drosophila homolog of TGFß, or Transforming Growth Factor-ß) signaling pathway. We observed that CDK8-CycC positively regulates transcription activated by Mad (Mothers against dpp), the primary transcription factor downstream of the Dpp/TGFß signaling pathway. CDK8 can directly interact with Mad in vitro through the linker region between the DNA-binding MH1 (Mad homology 1) domain and the carboxy terminal MH2 (Mad homology 2) transactivation domain. Besides CDK8 and CycC, further analyses of other subunits of the MED complex have revealed six additional subunits that are required for Mad-dependent transcription in the wing discs: Med12, Med13, Med15, Med23, Med24, and Med31. Furthermore, our analyses confirmed the positive roles of CDK9 and Yorkie in regulating Mad-dependent gene expression in vivo. These results suggest that CDK8 and CycC, together with a few other subunits of the MED complex, may coordinate with other transcription cofactors in regulating Mad-dependent transcription during wing development in Drosophila.

The Operational Feasibility of Vaccination Programs Targeting Influenza Risk Groups in the World Health Organization (WHO) African and South-East Asian Regions.

BACKGROUND: Influenza vaccination is uncommon in low-resource settings. We evaluated aspects of operational feasibility of influenza vaccination programs targeting risk groups in the World Health Organization (WHO) African (AFR) and South-East Asian (SEAR) Regions. METHODS: We estimated routine immunization and influenza vaccination campaign doses, doses per vaccinator, and cold storage requirements for 1 simulated country in each region using evidence-based population distribution, vaccination schedule, and vaccine volumes. Influenza vaccination targeted persons <5 years, pregnant women, persons with chronic diseases, persons ≥65 years, and healthcare workers (HCW). For the AFR country, we compared vaccine volumes to actual storage capacities. RESULTS: Targeting HCW had a small operational impact, and subsequent findings exclude this group. During 3-month influenza vaccination campaigns, monthly doses delivered in the AFR country increased from 15.0% for ≥65 years to 93.1% for <5 years and in the SEAR country from 19.6% for pregnant women to 145.0% for persons with chronic diseases. National-level cold storage capacity requirements increased in the AFR country from 4.1% for ≥65 years to 20.3% for <5 years and in the SEAR country from 3.9% for pregnant women to 28.8% for persons with chronic diseases. Subnational-level cold storage capacity requirements increased in the AFR country from 5.9% for ≥65 years to 36.8% for <5 years and the SEAR country from 17.6% for pregnant women to 56.0% for persons with chronic diseases. CONCLUSIONS: Influenza vaccination of most risk groups will require substantial increases in doses, doses per vaccinator, and cold storage capacity in countries where infrastructure and resources are limited.

US hospital webpages on atrial fibrillation ablation: A potential source for misinformation.

INTRODUCTION: Atrial fibrillation (AF) ablation is performed worldwide. To attract patients, hospitals frequently have webpages that tout the success of the procedure. The information disseminated to the public via these webpages has not been systematically reviewed. Our objective was to assess accuracy of information delivered to the public on hospital websites in regard to atrial AF ablation. METHODS: From July 2019 to January 2020, we performed a Google search for all US hospitals registered with Medicare to see if they had a webpage describing AF ablation. Resulting hospital webpages were abstracted for data on AF ablation success rates and risks. Success rates over 86%, the highest success rate in the medical literature, were deemed exaggerated. RESULTS: Among 4805 hospitals, 487 had webpages describing AF ablation and 33 discussed success rates of AF ablation. Twelve percentage reported exaggerated success rates, 3% referred to ablation as a cure, and 2.8% referred to ablation as a tool to eliminate AF. Less than 10% of webpages describing AF ablation noted the potential need for a second ablation to achieve the stated success rate and merely 16% mentioned risks of the procedure. One percentage of webpages directly suggested AF ablation could reduce risk of stroke while others indirectly suggested it by discussing cessation of anticoagulation. Two webpages mentioned reduced mortality. CONCLUSION: US hospital webpages rarely discuss AF ablation. When discussed, there were concerning unsubstantiated claims regarding mortality, stroke prevention, and need for medical therapy. This could lead to some patients undergoing AF ablation based on faulty understanding.

Evolution of an Opioid Sparse Pain Management Program for Total Knee Arthroplasty With the Addition of Intravenous Acetaminophen.

BACKGROUND: Perioperative pain management for patients undergoing total knee arthroplasty (TKA) improves patient outcomes and facilitates recovery. In this study, we compared the effects of preoperative oral acetaminophen vs intravenous (IV) acetaminophen administered once intraoperatively and once postoperatively. METHODS: Two standardized, multimodal analgesia protocols were compared in patients undergoing primary, unilateral TKA. The oral acetaminophen cohort (OA) received doses of oral acetaminophen preoperatively and an as-needed basis postoperatively (n = 698). The IV acetaminophen cohort (IA) received 2 doses of IV acetaminophen, one intraoperative and one 6 hours postoperatively, with no oral acetaminophen given (n = 318). No other variables were significantly changed during the study period. RESULTS: The IV acetaminophen group demonstrated less narcotic usage on postoperative day 0 (OA: 13.3 mme [morphine mg equivalents], IA: 6.2 mme, P < .001) and overall usage (OA: 66.1 mme, IA: 48.5 mme, P < .001). Pain scores were statistically and clinically significantly decreased in the immediate postoperative (the first 8 hours) for the IA group (OA: patient-reported pain scores of 4.0; IA: patient-reported pain scores of 2.0, P < .001). Both groups progressed and completed their physical therapy similarly for each postoperative day. Length of stay and percent discharge home were slightly improved in the IA group as well, however did not reach statistical difference. CONCLUSION: An iterative approach to multimodal pain management after TKA led to improvements in narcotic usage, pain scores, and several quality measures. IV acetaminophen is an integral and effective part of our opioid-sparing multimodal pain regimen in TKA.

Vancomycin Powder and Dilute Povidone-Iodine Lavage for Infection Prophylaxis in High-Risk Total Joint Arthroplasty.

BACKGROUND: Dilute povidone-iodine lavage has been shown to be safe and effective in decreasing acute periprosthetic joint infection (PJI) following total joint arthroplasty (TJA). Vancomycin powder is reported to be effective in preventing infection in spine surgery. We hypothesize that a "vanco-povidone protocol" (VIP) for TJA patients at high risk for infection is safe and will decrease the rate of PJI. METHODS: High-risk TJA patients (body mass index >40, active smokers, American Society of Anesthesiologists ≥3, immunosuppression/diabetes, methicillin-resistant Staphylococcus aureus colonization, revision surgery) utilizing VIP were compared to a high-risk historical cohort not treated with VIP, at a single institution. VIP consisted of dilute povidone-iodine lavage followed by application of vancomycin powder prior to wound closure. Primary endpoint was PJI within 3 months postoperatively. RESULTS: The historical, high-risk control cohort consisted of 3251 patients with a PJI incidence of 1.8%. A total of 1413 subjects received the VIP protocol with a PJI incidence of 1.3%. There was a 27.8% risk reduction when compared to the control group of high-risk subjects not treated with the VIP. There were no medical complications secondary to the use of VIP, no increase in vancomycin-resistant enterococcus or vancomycin-resistant Staph aureus, and no cases of acute renal impairment secondary to application of the local vancomycin. CONCLUSIONS: PJI remains a common complication of TJA, especially in high-risk populations. This study indicates that a protocol of dilute povidone-iodine lavage combined with topical vancomycin powder is safe and may reduce PJI incidence in high-risk TJA patients. Due to low, current PJI rates, a multi-institutional randomized controlled trial is necessary to assess interventions that minimize the risk of PJI. LEVEL OF EVIDENCE: Retrospective Observational Cohort.

Microbial colonization of subscapularis tagging sutures in shoulder arthroplasty: a prospective, controlled study.

BACKGROUND: Reducing intraoperative wound contamination is a critical preventive strategy for reducing the risk of prosthetic joint infection in shoulder arthroplasty. The aim of this study was to investigate the potential microbial colonization of subscapularis tagging sutures during shoulder arthroplasty. METHODS: In this prospective study, 50 consecutive patients undergoing primary shoulder arthroplasty (anatomic or reverse) were enrolled. Patients with revision shoulder arthroplasty and proximal humeral fractures were excluded. Nonabsorbable, braided tagging sutures were placed through the subscapularis tendon prior to tenotomy. A similar nonabsorbable, braided suture (control) was placed in a sterile container on the back table, open to the operating room environment. Subscapularis tagging sutures (experimental specimens) and control sutures were collected prior to subscapularis tenotomy repair and submitted for aerobic and anaerobic cultures. Cultures were held for 21 days to account for extended growth of slow-growing bacteria. RESULTS: A total of 12 of 50 experimental and 16 of 50 control sutures had positive cultures. Staphylococcus epidermidis and Cutibacterium acnes were the 2 most commonly isolated organisms. Active tobacco use (P = .038) and procedure length (P = .03) were significantly associated with positive cultures. No significant association between positive subscapularis tagging suture cultures and positive control cultures was found (P = .551). Patient age, sex, body mass index, and significant medical comorbidities were not significantly associated with positive cultures. DISCUSSION: Subscapularis tagging sutures are a potential source of microbial contaminant in shoulder arthroplasty, and we recommend exchanging the tagging suture with a suture opened immediately prior to subscapularis repair.

Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma.

The majority of diffuse large B-cell lymphoma (DLBCL) tumors contain mutations in histone-modifying enzymes (HMEs), indicating a potential therapeutic benefit of histone deacetylase inhibitors (HDIs), and preclinical data suggest that HDIs augment the effect of rituximab. In this randomized phase 2 study, we evaluated the response rate and toxicity of panobinostat, a pan-HDI administered 30 mg orally 3 times weekly, with or without rituximab, in 40 patients with relapsed or refractory de novo (n = 27) or transformed (n = 13) DLBCL. Candidate genes and whole exomes were sequenced in relapse tumor biopsies to search for molecular correlates, and these data were used to quantify circulating tumor DNA (ctDNA) in serial plasma samples. Eleven of 40 patients (28%) responded to panobinostat (95% confidence interval [CI] 14.6-43.9) and rituximab did not increase responses. The median duration of response was 14.5 months (95% CI 9.4 to "not reached"). At time of data censoring, 6 of 11 patients had not progressed. Of the genes tested for mutations, only those in MEF2B were significantly associated with response. We detected ctDNA in at least 1 plasma sample from 96% of tested patients. A significant increase in ctDNA at day 15 relative to baseline was strongly associated with lack of response (sensitivity 71.4%, specificity 100%). We conclude that panobinostat induces very durable responses in some patients with relapsed DLBCL, and early responses can be predicted by mutations in MEF2B or a significant change in ctDNA level at 15 days after treatment initiation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT01238692).

Can Multimodal Pain Management in TKA Eliminate Patient-controlled Analgesia and Femoral Nerve Blocks?

BACKGROUND: TKA pain management protocols vary widely with no current consensus on a standardized pain management regimen. Multimodal TKA pain management protocols aim to address pain control, facilitate functional recovery, and maintain patient satisfaction. QUESTIONS/PURPOSES: (1) Did changes to our pain management protocol, specifically adding liposomal bupivacaine, eliminating patient-controlled analgesia (PCA), and discontinuing femoral nerve blocks (FNBs), affect narcotic consumption after TKA? (2) Did these changes to our pain management protocols affect patient-reported pain scores? (3) Does the use of an immediate postoperative PCA affect rapid rehabilitation and functional recovery? (4) How did changes to our pain management regimen affect discharge disposition and pain-related Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores? METHODS: We retrospectively analyzed an institutional arthroplasty database between September 2013 and September 2015 containing 1808 patients who underwent primary TKA. Departmental pain management protocols were compared in 6-month periods as the protocol changed. All patients received a multimodal pain management protocol including preoperative oral medications, spinal or general anesthesia, a short-acting intraoperative pericapsular injection, and continued postoperative oral narcotics for breakthrough pain. From September 2013 to April 2014, all patients received an intraoperative FNB and a PCA for the first 24 hours postoperatively (Cohort 1). From May 2014 to October 2014, a periarticular injection of liposomal bupivacaine was added to the protocol and FNBs were discontinued (Cohort 2). After April 2015, PCA was eliminated (Cohort 3). No other major changes were made to the TKA pain management pathways. Narcotic use, pain scores on 8-hour intervals, physical therapy milestones, and discharge disposition were compared. RESULTS: Total narcotic use was the least in Cohort 3 (Cohort 3: 66 ± 54 morphine milligram equivalents versus Cohort 2: 82 ± 72 versus Cohort 1: 96 ± 62; p < 0.001). There was an increase in pain score immediately after surgery in Cohort 3 (4.0 ± 3.5 versus 1.2 ± 2.2 versus 1.2 ± 2.5, post hoc analysis of Cohort 2 versus 3: mean difference 2.6, 95% confidence interval [CI] 2.2-3.0; p < 0.001); however, it was not different for the remainder of the hospital stay. Patients who did not receive PCA reached functional milestones for both gait and stairs faster by postoperative day 1 (47% [328 of 698] versus 30% [158 of 527] versus 16% [93 of 583], p < 0.001; Cohort 3 versus 2: odds ratio 2.1, 95% CI 1.6-2.6; p < 0.001). Discharge to home occurred more frequently (84% [583 of 698] versus 78% [410 of 527] versus 72% [421 of 583], p = 0.010) in Cohort 3. There were no differences in pain-related HCAHPS scores across all cohorts. CONCLUSIONS: Discontinuing PCAs and FNBs from our multimodal TKA pain management protocols and adding liposomal bupivacaine resulted in fewer narcotics consumed with no difference in pain control and faster functional recovery while maintaining high HCAHPS scores relating to pain. LEVEL OF EVIDENCE: Level III, therapeutic study.

Periarticular Soft Tissue Envelope Size and Postoperative Wound Complications Following Total Knee Arthroplasty.

BACKGROUND: Periprosthetic joint infection following total knee arthroplasty (TKA) is a serious complication often related to obesity which leads to poor patient outcomes and increased resource utilization. A periarticular soft tissue index (PASTI) may help predict postoperative wound complications than BMI alone. METHODS: Three hundred seventy-six TKA patients with a preoperative, lateral knee X-ray radiograph and 1 year of follow up were analyzed. We used 2 pairs of soft tissue and bony measurements, one referencing the femur and the other the tibia. A high PASTI was defined as a ratio >3.0. Minor complications involved clinical interventions related to the surgical wound. Major complications involved return to the operating room. RESULTS: More minor complications occurred in high PASTI for both tibial (20.9% vs 6.4%; odds ratio 3.89, 95% confidence interval 1.94-7.79, P < .001) and femoral measurements (15.3% vs 7.2%; odds ratio 2.09, 95% confidence interval 1.06-4.15, P = .013). Major complications were also more frequent in high PASTI, though not statistically significant. The proportion of obesity (BMI > 30) in both minor (12.4% vs 7.7%, P = .140) and major complications (2.8% vs 3.3%, P = .788) was not statistically different. CONCLUSION: More wound complications occurred in patients with high PASTI, while no difference was seen using BMI. BMI has traditionally approximated patient size, but does not describe variations in body habitus. PASTI is a more reliable and direct way to assess the periarticular soft tissue envelope size, which is associated with postoperative wound complications in the knee.

The Effects of Body Mass Index on Pain Control With Liposomal Bupivacaine in Hip and Knee Arthroplasty.

BACKGROUND: There is evidence to suggest that liposomal bupivacaine (LB) is an effective component of a multimodal pain regimen for total joint arthroplasty (TJA). Obesity has been associated with chronic pain following TJA. This study assessed whether early postoperative pain is affected by body mass index (BMI), and whether the standard LB dose has similar effects on obese vs nonobese patients. METHODS: A retrospective analysis of 2629 primary TJA over a 12-month period was conducted, with LB used in half of this group. Patients were further classified as nonobese (BMI < 30) or obese (BMI ≥ 30). Pain scores and narcotic use were recorded. Independent-sample t-tests were used for continuous variables and chi-squared analyses for categorical variables. A multivariate regression analysis was performed. RESULTS: Significantly less narcotic was required on postoperative days (POD) 0 and 1 in patients receiving LB compared to those who did not in both obese and nonobese patient groups. On POD 2, obese and nonobese patients had an increase in narcotic requirement, which was significant in obese patients. A regression analysis found that on POD 0 and POD 1, lack of LB use, obesity, and younger age were independently associated with increased narcotic use. CONCLUSION: While narcotic requirement of obese and nonobese patients decreased on POD 0 and POD 1 with initiation of LB at our institution, all patients demonstrated increased narcotic requirement on POD 2 which was statistically and clinically significant in obese patients. Further studies are needed to determine the optimal pain regimen in the growing obese population undergoing TJA.

Vancomycin Povidone-Iodine Protocol Improves Survivorship of Periprosthetic Joint Infection Treated With Irrigation and Debridement.

BACKGROUND: Irrigation and debridement with modular component and liner exchange (IDLE) is a low morbidity procedure for treatment of periprosthetic joint infection (PJI) with reported failure rates exceeding 50%. Dilute povidone-iodine lavage has been shown to be safe and effective in decreasing acute PJI in primary total joint arthroplasty. Vancomycin powder has also shown to be effective in preventing infection in spine surgery. We hypothesize that a vancomycin povidone-iodine protocol (VIP) used in conjunction with IDLE can increase infection-free survivorship after acute PJI. METHODS: This is a single institution retrospective review of all PJIs treated with IDLE and VIP since March 2014. A consecutive matched control group of patients treated with IDLE for PJI for 2 years prior to March 2014 was also included for analysis. Primary outcome was failure, defined as return to operating room for an infection-related problem. Secondary outcome was chronic suppression with antibiotics at final follow-up. Minimum follow-up was 1 year. RESULTS: A total of 36 patients in the VIP group and 38 patients in control group were identified. In the VIP group, 16.7% (6/36) failed at final follow-up compared to 37% failure rate (14/38) in the control group (P < .05). Three patients in the VIP group were on chronic antibiotic suppression at final follow-up. There were no medical complications secondary to the VIP. CONCLUSIONS: The VIP group demonstrated a significant reduction in reinfection and failure rate following IDLE. The authors believe that a VIP is an effective adjunct for treating PJI with irrigation and debridement.

Prevalence of Neurocognitive Dysfunction and Its Effects on Postoperative Outcomes in Total Joint Arthroplasty.

BACKGROUND: The prevalence of neurocognitive dysfunction (NCD) and its effects on postoperative outcomes have not been well characterized following total joint arthroplasty (TJA) population. This study aims at better understand this relationship. METHODS: Patients were evaluated for neurocognitive function using the grooved pegboard test for the dominant (PEG-D) and nondominant hand (PEG-N), and the Rey Auditory Verbal Learning Test (RAVLT). The patient scores for each test was compared to age-controlled normative values in order to identify NCD. Baseline characteristics and postoperative outcomes were then compared amongst the two cohorts. RESULTS: Ninety-nine consecutive patients were prospectively enrolled. Nearly 54% were identified as neurocognitively deficient on at least 1 of the 3 tests (31% by RAVLT, 21% by PEG-D, and 30% by PEG-N). There was a statistically significant prevalence of NCD in patients older than 60 years when compared to normative controls for RAVLT (P < .001). Patients with depression or an American Society of Anesthesiologist score of 3 were 5 times as likely to have NCD, while patients with a body mass index between 20-30 kg/m2 were 5 times less likely to have NCD. Furthermore, patients identified as NCD preoperatively were significantly more likely to be transferred to the intensive care unit (48% vs 14%) and fail physical therapy (64% vs 17%), respectively. CONCLUSION: NCD is highly prevalent within total joint arthroplasty candidates and may be correlated with higher body mass index, American Society of Anesthesiologist scores, and rates of depression. The condition predisposes patients to suboptimal postoperative outcomes including increased intensive care unit admissions and prolonged rehabilitation.

Pain Control and Functional Milestones in Total Knee Arthroplasty: Liposomal Bupivacaine versus Femoral Nerve Block.

BACKGROUND: Although pain management after total knee arthroplasty (TKA) affects rehabilitation, length of stay, and functional outcomes, pain management for patients undergoing TKA has yet to be standardized. Femoral nerve blocks (FNBs) are commonly used as an adjunct; however, these can result in transient quadriceps weakness and have been associated with in-hospital falls. Periarticular infiltration of liposomal bupivacaine has been recently introduced as a long-acting analgesic that can be administered without affecting motor function. QUESTIONS/PURPOSES: (1) Does periarticular liposomal bupivacaine compared with FNB result in improved pain control as measured by pain scores and narcotic consumption? (2) How do liposomal bupivacaine and FNB compare in terms of gait and stairclimbing milestones and the proportion of patients who experienced a fall in the hospital? METHODS: Between September 2013 and October 2014, a retrospective analysis was conducted involving 24 surgeons who performed a total of 1373 unilateral, primary TKAs. From September 2013 to April 2014, the routine approach to TKA pain management pathway consisted of preoperative administration of oral analgesics, intraoperative anesthesia (preferred spinal or general), an ultrasound-guided FNB, intraoperative analgesic cocktail injection, patient-controlled analgesia, and oral and IV narcotics for pain as needed. A total of 583 patients were included in this study group. Starting May 2014, FNBs were discouraged and there was department-wide adoption of liposomal bupivacaine. Liposomal bupivacaine became routinely used in all patients undergoing TKA with no other changes made to the multimodal analgesia protocol at that time, and 527 patients in this study group were compared with the FNB cohort. Chart review on a total of 1110 patients was conducted by a research assistant who was not participating in patient care. During the inpatient stay, pain scores during 8-hour intervals, narcotic use, and physical therapy milestones were compared. RESULTS: With the numbers available, we detected no clinically important difference in pain scores throughout the hospital stay; however, patients treated with liposomal bupivacaine consumed very slightly less narcotics overall (96 ± 62 versus 84 ± 73 eq mg of morphine; [95% confidence interval, 11-13 mg]; p = 0.004) through postoperative Day 2 of inpatient hospitalization. Seventy-seven percent (406 of 527) of patients receiving liposomal bupivacaine achieved their gait milestones of clearing 100 feet of ambulation versus 60% (349 of 583) of patients receiving FNB (p < 0.001) before discharge. Likewise, 94% (497 of 527) of patients receiving liposomal bupivacaine completed stairs compared with 73% (427 of 583) of patients receiving FNB (p < 0.001). Patients who received liposomal bupivacaine were less likely to experience a fall during the hospital stay than were patients treated with FNB (3 of 527 [0.6%] versus 12 of 583 [2%]; p = 0.03). CONCLUSIONS: In the absence of strong data supporting FNB over liposomal bupivacaine, we have modified our TKA pain management protocols by adopting liposomal bupivacaine in lieu of FNBs, facilitating rapid rehabilitation while providing adequate pain control. LEVEL OF EVIDENCE: Level III, therapeutic study.

Two-stage revision for infected shoulder arthroplasty.

BACKGROUND: Periprosthetic shoulder infections (PSIs) are challenging to treat and often result in significant patient morbidity. Without a standardized treatment protocol, PSIs are often managed similarly to periprosthetic hip and knee infections. Because 2-stage revision is the gold standard for treating periprosthetic hip and knee infections, we performed a case series and literature review to determine its effectiveness in PSIs. METHODS: We identified 19 patients (14 men) from our institution who were treated with a 2-stage revision after presenting with a PSI. Mean patient age was 63 ± 9 years, and average body mass index was 30.8 ± 5.8. The average time from the index arthroplasty to treatment was 40 months, 8 of 13 positive cultures were Propionibacterium acnes, and 9 of 19 patients had multiple shoulder operations before presenting with infection. Minimum follow-up for all patients was 2 years. RESULTS: After a mean follow-up of 63 months (range, 25-184 months), 15 of 19 patients in our study were successfully treated for PSI. Average postoperative American Shoulder and Elbow Surgeons (ASES) Shoulder Assessment score was 69 (range, 32-98) and average postoperative forward elevation was significantly increased from 58° to 119° (P < .001). The incidence of recurrent infection was 26%. The rate of noninfection complications was 16%, for a total complication rate of 42%. CONCLUSION: In patients with PSIs, especially those with intractable, chronic infections, a 2-stage revision represents a viable treatment option for eradicating infection and restoring function. However, it is important to recognize the risk of recurrent infection and postoperative complications in this challenging patient population.

Multiplex Droplet Digital PCR Quantification of Recurrent Somatic Mutations in Diffuse Large B-Cell and Follicular Lymphoma.

BACKGROUND: A plethora of options to detect mutations in tumor-derived DNA currently exist but each suffers limitations in analytical sensitivity, cost, or scalability. Droplet digital PCR (ddPCR) is an appealing technology for detecting the presence of specific mutations based on a priori knowledge and can be applied to tumor biopsies, including formalin-fixed paraffin embedded (FFPE) tissues. More recently, ddPCR has gained popularity in its utility in quantifying circulating tumor DNA. METHODS: We have developed a suite of novel ddPCR assays for detecting recurrent mutations that are prevalent in common B-cell non-Hodgkin lymphomas (NHLs), including diffuse large B-cell lymphoma, follicular lymphoma, and lymphoplasmacytic lymphoma. These assays allowed the differentiation and counting of mutant and wild-type molecules using one single hydrolysis probe. We also implemented multiplexing that allowed the simultaneous detection of distinct mutations and an "inverted" ddPCR assay design, based on employing probes matching wild-type alleles, capable of detecting the presence of multiple single nucleotide polymorphisms. RESULTS: The assays successfully detected and quantified somatic mutations commonly affecting enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) (Y641) and signal transducer and activator of transcription 6 (STAT6) (D419) hotspots in fresh tumor, FFPE, and liquid biopsies. The "inverted" ddPCR approach effectively reported any single nucleotide variant affecting either of these 2 hotspots as well. Finally, we could effectively multiplex hydrolysis probes targeting 2 additional lymphoma-related hotspots: myeloid differentiation primary response 88 (MYD88; L265P) and cyclin D3 (CCND3; I290R). CONCLUSIONS: Our suite of ddPCR assays provides sufficient analytical sensitivity and specificity for either the invasive or noninvasive detection of multiple recurrent somatic mutations in B-cell NHLs.

Preventing Hospital Readmissions and Limiting the Complications Associated With Total Joint Arthroplasty.

Total joint arthroplasty is a highly successful surgical procedure for patients who have painful arthritic joints. The increasing prevalence of total joint arthroplasty is generating substantial expenditures in the American healthcare system. Healthcare payers, specifically the Centers for Medicare and Medicaid Services, currently target total joint arthroplasty as an area for healthcare cost-savings initiatives, which has resulted in increased scrutiny surrounding orthopaedic care, health resource utilization, and hospital readmissions. Identifying the complications associated with total hip and total knee arthroplasty that result in readmissions will be critically important for predictive modeling and to decrease the number of readmissions after total joint arthroplasty. In addition, improving perioperative optimization, providing seamless episodic care, and intensifying posthospital coordination of care may decrease the number of unnecessary hospital readmissions. Identified modifiable risk factors that substantially contribute to poor clinical outcomes after total joint arthroplasty include morbid obesity; poorly controlled diabetes and nutritional deficiencies; Staphylococcus aureus colonization; tobacco use; venous thromboembolic disease; cardiovascular disease; neurocognitive, psychological, and behavioral problems; and physical deconditioning and fall risk. Both clinical practice and research will be enhanced if defined total joint arthroplasty complications are standardized and stratification schemes are used to identify high-risk patients. Subsequently, clinical intervention will be warranted to address modifiable risk factors before proceeding with total joint arthroplasty.

Risk-Stratified Venous Thromboembolism Prophylaxis After Total Joint Arthroplasty: Aspirin and Sequential Pneumatic Compression Devices vs Aggressive Chemoprophylaxis.

BACKGROUND: Venous thromboembolism (VTE) is a major concern after total joint arthroplasty (TJA). We evaluated a risk-stratified prophylaxis protocol for patients undergoing TJA. METHODS: A total of 2611 TJA patients were retrospectively studied. Patients treated with an aggressive VTE chemoprophylaxis protocol were compared with patients treated with a risk-stratified protocol utilizing aspirin and sequential pneumatic compression devices (SPCDs) for standard-risk patients and targeted anticoagulation for high-risk patients. RESULTS: We found equivalence in terms of VTE prevention between the 2 cohorts. There was a decrease in adverse events and readmissions among the risk-stratified cohort, although this did not reach statistical significance. A statistically significant reduction in costs (P < .001) was experienced with the use of aspirin/SPCDs compared with aggressive anticoagulation agents within the risk-stratified cohort. CONCLUSION: The use of aspirin/SPCDs in a risk-stratified TJA population is a safe and cost-effective method of VTE prophylaxis.

Liposomal Bupivacaine as an Adjunct to Postoperative Pain Control in Total Hip Arthroplasty.

BACKGROUND: Although pain management affects rehabilitation, length of stay, and functional outcome, an optimized pain management protocol has yet to be standardized. Opioids are the primary agent used to control acute postoperative pain; however, they are associated with a wide range of side effects. Liposomal bupivacaine (LB), a long-acting analgesic agent administered intraoperatively, has been introduced as a new modality to control pain for up to 72 hours after operation without affecting motor function. METHODS: Six hundred eighty-six primary total hip arthroplasty (THA) patients, who received the standard THA pain management protocol, were compared to a cohort of 586 primary THA patients, who were treated with an additional intraoperative injection of LB. All other pain management parameters and standard of care were identical. Statistical significance was set at P ≤ .05. RESULTS: Although patient-reported pain scores were statistically similar, the LB cohort demonstrated a significant decrease in total narcotic use (P < .001), specifically up to postoperative day 2 (P = .016). Physical therapy milestones were significantly achieved to a greater degree (P < .001) in the LB cohort. Operation time and hospital cost were unaffected (P = .072 and .811, respectively); however, the LB cohort exhibited a decrease in length of stay by 0.31 days (P < .001) and improvement in discharge disposition to home (P = .017). CONCLUSION: LB is a valuable adjunct to our THA pain management protocol, as we strive to achieve improved patient outcomes, reductions in length of stay, and enhanced quality of THA care.

Histone deacetylase inhibitor entinostat in combination with a retinoid downregulates HER2 and reduces the tumor initiating cell population in aromatase inhibitor-resistant breast cancer.

Resistance to aromatase inhibitors (AIs) involves increased HER2. One mechanism by which HER2 may mediate resistance is through expansion of the tumor initiating cell (TIC) population. This study investigates whether combining all-trans retinoic acid (ATRA) and histone deacetylase inhibitor entinostat (ENT) can inhibit TICs and HER2 in AI-resistant cells and tumors. Modulation of cell viability and HER2 expression were assessed in AI-resistant cells treated with ATRA + ENT. Letrozole-resistant LTLT-Ca cells treated with ATRA + ENT were assayed for changes in TIC characteristics, such as TIC markers (BCRP, ALDH, and BMI-1), side population (SP), and mammosphere formation. Xenograft tumors of MCF-7Ca cells made resistant to letrozole were treated with ATRA, ATRA + letrozole, ATRA + ENT, or ATRA + ENT + letrozole. Resulting tumors were assayed for changes in TIC characteristics. Patient samples taken pre- and post-AI treatment were analyzed for changes in ERα and HER2 protein expression. Treatment with ATRA + ENT reduced HER2 expression and viability (P < 0.001) in AI-resistant cells, as well as decreased SP (P < 0.0001), mammosphere formation (P < 0.01), and expression of TIC molecular markers (P < 0.01) in LTLT-Ca. A reduction in tumor growth rate was observed in mice treated with ENT + ATRA + letrozole when compared to mice treated with single agents (P < 0.0001) or ENT + ATRA (P = 0.02). Decreased TIC characteristics, including mammosphere formation (P < 0.05), were observed in tumors from the triple combination. An increase in HER2 and downregulation in ERα protein expression was observed in patients upon resistance to AI (P < 0.005). These studies indicate that the combination of ATRA and ENT inhibits the TIC population of AI-resistant cells and may be effective in reducing tumor recurrence.