Arthroscopy Association of Canada Position Statement on Opioid Prescription After Arthroscopic Surgery.

Background: Despite the ongoing opioid epidemic, most patients are still prescribed a significant number of opioid medications for pain management after arthroscopic surgery. There is a need for consensus among orthopaedic surgeons and solutions to aid providers in analgesic strategies that reduce the use of opioid pain medications. Purpose: This position statement was developed with a comprehensive systematic review and meta-analysis of exclusively randomized controlled trials (RCTs) to synthesize the best available evidence for managing acute postoperative pain after arthroscopic surgery. Study Design: Position statement. Methods: The Embase, MEDLINE, PubMed, Scopus, and Web of Science databases were searched from inception until August 10, 2022. Keywords included arthroscopy, opioids, analgesia, and pain, and associated variations. We included exclusively RCTs on adult patients to gather the best available evidence for managing acute postoperative pain after arthroscopic surgery. Patient characteristics, pain, and opioid data were extracted, data were analyzed, and trial bias was evaluated. Results: A total of 21 RCTs were identified related to the prescription of opioid-sparing pain medication after arthroscopic surgery. The following recommendations regarding noninvasive, postoperative pain management strategies were made: (1) multimodal oral nonopioid analgesic regimens-including at least 1 of acetaminophen-a nonsteroidal anti-inflammatory drug-can significantly reduce opioid consumption with no change in pain scores; (2) cryotherapy is likely to help with pain management, although the evidence on the optimal method of application (continuous-flow vs ice pack application) is unclear; (3) and (4) limited RCT evidence supports the efficacy of transcutaneous electrical nerve stimulation and relaxation exercises in reducing opioid consumption after arthroscopy; and (5) limited RCT evidence exists against the efficacy of transdermal lidocaine patches in reducing opioid consumption. Conclusion: A range of nonopioid strategies exist that can reduce postarthroscopic procedural opioid consumption with equivalent vocal pain outcomes. Optimal strategies include multimodal analgesia with education and restricted/reduced opioid prescription.

The elusive role of herpesviruses in Alzheimer's disease: current evidence and future directions.

Alzheimer's disease (AD) is the most common cause of dementia. While pathologic hallmarks, such as extracellular beta-amyloid plaques, are well-characterized in affected individuals, the pathogenesis that causes plaque formation and eventual cognitive decline is not well understood. A recent resurgence of the decades-old "infectious hypothesis" has garnered increased attention on the potential role that microbes may play in AD. In this theory, it is thought that pathogens such as viruses may act as seeds for beta-amyloid aggregation, ultimately leading to plaques. Interest in the infectious hypothesis has also spurred further investigation into additional characteristics of viral infection that may play a role in AD progression, such as neuroinflammation, latency, and viral DNA integration. While a flurry of research in this area has been recently published, with herpesviruses being of particular interest, the role of pathogens in AD remains controversial. In this review, the insights gained thus far into the possible role of herpesviruses in AD are summarized. The challenges and potential future directions of herpesvirus research in AD and dementia are also discussed.

Arthroscopic anatomic glenoid reconstruction has a lower rate of recurrent instability compared to arthroscopic Bankart repair while otherwise maintaining a similar complication and safety profile.

OBJECTIVES: The primary purpose of this study was to determine the frequency and type of complications, including subluxation, infection, hardware complication, graft/glenoid fracture, chondrolysis, neurovascular deficits and stiffness following an Arthroscopic Bankart Repair (ABR) or an Arthroscopic Anatomic Glenoid Reconstruction (AAGR) using a distal tibia allograft for recurrent anterior shoulder instability. Secondary purposes were to determine the frank dislocation rate and the associations of post-operative complications with demographic patient factors. METHODS: Demographic and clinical data were reviewed using means ± standard deviations or frequencies in patients with recurrent anterior shoulder instability who underwent either an ABR or an AAGR. Post-operative patient records were analysed to identify any post-operative complications. The numerical variables of the two groups were compared using the independent t-test or Mann-Whitney U test. Categorical variables and complications were tested using the chi-square test, Fisher's exact test, or the two-sided Monte Carlo test with a significance level of 0.05. RESULTS: We included 174 patients in this cohort, with 61.5% of patients receiving ABR and 38.5% receiving AAGR. Most of our patients were male (70.1%) with an average age of 23.41 ± 8.26 years in the ABR group and 29.37 ± 13.54 years in the AAGR group (p = 0.001). The two groups were similar with respect to their post-operative complication rates when excluding frank dislocation (ABR: 11%, AAGR: 12%). The AAGR group had statistically significantly higher rates of hardware removal compared to the ABR group (p = 0.004). The ABR group had 25 post-operative frank dislocations, with none reported in the AAGR cohort (p < 0.001). The total complication rate for each procedure was found to be 35% for ABR and 12% for AAGR. CONCLUSION: AAGR has a comparable safety profile to the ABR when assessing post-operative complications such as subluxation, infection, graft/glenoid fracture, chondrolysis, neurovascular deficits and stiffness. AAGR is superior to ABR with respect to rates of recurrent instability and should be considered as a first-line treatment in certain patients with specific risk factors such as younger age, competitive contact sports participation, and higher number of instability events pre-operatively. LEVEL OF EVIDENCE: Level III.

Challenges in Drug Discovery for Intracellular Bacteria.

Novel drugs are needed to treat a variety of persistent diseases caused by intracellular bacterial pathogens. Virulence pathways enable many functions required for the survival of these pathogens, including invasion, nutrient acquisition, and immune evasion. Inhibition of virulence pathways is an established route for drug discovery; however, many challenges remain. Here, we propose the biggest problems that must be solved to advance the field meaningfully. While it is established that we do not yet understand the nature of chemicals capable of permeating into the bacterial cell, this problem is compounded when targeting intracellular bacteria because we are limited to only those chemicals that can permeate through both human and bacterial outer envelopes. Unfortunately, many chemicals that permeate through the outer layers of mammalian cells fail to penetrate the bacterial cytoplasm. Another challenge is the lack of publicly available information on virulence factors. It is virtually impossible to know which virulence factors are clinically relevant and have broad cross-species and cross-strain distribution. In other words, we have yet to identify the best drug targets. Yes, standard genomics databases have much of the information necessary for short-term studies, but the connections with patient outcomes are yet to be established. Without comprehensive data on matters such as these, it is difficult to devise broad-spectrum, effective anti-virulence agents. Furthermore, anti-virulence drug discovery is hindered by the current state of technologies available for experimental investigation. Antimicrobial drug discovery was greatly advanced by the establishment and standardization of broth microdilution assays to measure the effectiveness of antimicrobials. However, the currently available models used for anti-virulence drug discovery are too broad, as they must address varied phenotypes, and too expensive to be generally adopted by many research groups. Therefore, we believe drug discovery against intracellular bacterial pathogens can be advanced significantly by overcoming the above hurdles.

Arthroscopy Association of Canada Position Statement on Exercise for Knee Osteoarthritis: A Systematic Review of Guidelines.

BACKGROUND: Exercise is widely regarded to improve pain and function in patients with knee osteoarthritis (OA) through building supportive muscle mass, facilitating weight loss, and through the other beneficial effects associated with it. PURPOSE: To explore literature that presents clinical guidelines for the use of exercise in the treatment of knee OA to inform an evidence-based position statement for the Arthroscopy Association of Canada. STUDY DESIGN: Position statement. METHODS: PubMed, MEDLINE, Embase, and Cochrane databases were searched for guidelines commenting on the role of exercise for knee OA. The search was limited to guidelines published in the last 10 years. Articles were screened for relevance, focusing on recently published research with clinical guidelines. Inclusion criteria involved all articles providing clinical guidelines for exercise and knee OA. RESULTS: Eight guidelines were identified. All eight recommended exercise as an important component of treatment for knee OA, with 6/8 strongly recommending it. CONCLUSION: Exercise is an effective and important component of the non-pharmacological management of knee OA. The Arthroscopy Association of Canada strongly recommends the use of exercise in the management of knee OA.

Patella alta is reduced following MPFL reconstruction but has no effect on quality-of-life outcomes in patients with patellofemoral instability.

PURPOSE: The primary purpose of this study was to determine if isolated medial patellofemoral ligament (MPFL) reconstruction for lateral patellofemoral instability altered the patellar height ratio. Secondary purposes were to use disease-specific quality-of-life scores to determine if MPFL reconstruction is as successful in patients with patella alta, compared to those without; and whether the change in the patellar height ratio after MPFL reconstruction is influenced by demographic and clinical factors. METHODS: Demographic and clinical data were collected pre-operatively on 283 patients with recurrent patellofemoral instability. Pre-operative and 6-month post-operative true-lateral radiographs were assessed to determine the patellar height ratio using the Caton-Deschamps index. A Caton-Deschamps index ≥ 1.2 was defined as patella alta. Paired t tests evaluated the effect of MPFL reconstruction on the Caton-Deschamps index. Using a two-sample t test, pre- and 24-month post-operative Banff Patellofemoral Instability Instrument (BPII) scores were assessed for differences in clinical outcomes between patients with and without patella alta. Pearson (for continuous variables) and Spearman rank correlations (for binary/ordinal variables) were calculated to determine the relationship between the patellar height ratio, demographic and pathoanatomic risk factors, and pre- and post-operative BPII scores. RESULTS: Pre- and post-operative true-lateral radiographs were admissible for 229/283 patients (81%) following isolated MPFL reconstruction. A statistically significant difference in the Caton-Deschamps index was evident from pre- to post-operative for the entire cohort (p < 0.001). The mean decrease in ratio was 0.03, and the effect size was 0.27, classified as small. Pre-operatively 52/229 patients (22.7%) demonstrated a Caton-Deschamps index ≥ 1.2, mean = 1.27 (SD = 0.08); post-operatively 21/229 patients (9.2%) demonstrated patella alta, mean = 1.18, (SD = 0.10), p < 0.001 (two-tailed). The mean decrease in the Caton-Deschamps index for patients with pre-operative patella alta was 0.10; the effect size was 0.82, classified as large. Pearson r correlation of patella alta to the pre- and post-operative BPII scores demonstrated no statistically significant relationship. CONCLUSION: This study has demonstrated that treatment of lateral patellofemoral instability with an isolated MPFL reconstruction results in a statistically significant decrease in patellar height ratio, with the effect size being greatest in patients with higher pre-operative Caton-Deschamps indices. In patients that presented with patella alta, normalization of the patellar height ratio occurred in 31/52 (59.6%) of the cases. Pre-operative patella alta was not associated with a statistically significant difference in disease-specific BPII outcome scores at any time point. Given these findings, the utility and results of tibial tubercle distalization in patients with patella alta should be a focus of further research. Level of evidence IV.

Increased litigation burden among tibia, pelvis, and spine fractures: An analysis of 756 fracture-related malpractice cases.

OBJECTIVES: To analyze a series of claims from a large national malpractice insurer associated with fracture care to understand what parameters are associated with claims, defense costs, and paid indemnity. DESIGN: Review of claims in fracture care settings from a national database; case series. SETTING: Database draws from insured pool of 400,000 medical malpractice cases from 400 healthcare entities across the country, representing 165,000 physicians; both academic and private. PATIENTS/PARTICIPANTS: Fracture care patients bringing legal suit. MAIN OUTCOME MEASUREMENTS: Cost of legal proceedings and indemnity, ICD-9 codes, and contributing causes toward claims. RESULTS: A total of 756 fracture claims were asserted between 2005 and 2014 regarding fracture care within the database; 70% were brought for inaccurate, missed, or delayed diagnosis, while 22% addressed medical treatment and 8% were for surgical management. Orthopaedics was the primary service in 22%. Total cost (expenses and indemnity) to orthopaedic providers totaled $13.1MM (million). The most common claim against orthopaedics was for fractures of the tibia and fibula (11.4%). Impact factor (IF) analysis (as described by Matsen) of indemnity in these cases reveals 3 fracture regions of highest indemnity burden: fractures of the tibia and fibula (IF: 1.86, 11.4%), pelvis (IF: 1.77, 6.6%), and spine (IF 1.33, 6.6%). Analysis of contributing factors identifies the category of clinical judgement as the most common category (62%). Other common factors include patient noncompliance (31%), communication (28%), technical skill (17%), clinical systems (11%), and documentation (10%). The single most common specific cause of a claim in orthopaedic fracture care was misinterpretation of diagnostic imaging (25%). CONCLUSION: This study is the first of its kind to identify fractures of the tibia and fibula as high risk for litigation against orthopaedic providers and provides general counseling of legal pitfalls in fracture care. Finally, we are able to identify the act of patient assessment as a key issue in over half of all fracture-related claims against orthopaedic providers. Providers in general and specialty settings can use this information to help guide their treatment and care ownership decisions in the care of patients with fractures. LEVEL OF EVIDENCE: Economic - Level III.

Analysis of the Clinical Outcome of Arthrographic Steroid Injection for the Treatment of Adhesive Capsulitis.

BACKGROUND: Idiopathic adhesive capsulitis is a condition of uncertain etiology characterized by pain and decreased shoulder range of motion (ROM) that occurs without a known intrinsic disorder. Many treatments have been advocated, yet the best option remains unclear. The purpose of this study was to determine if arthrographic injection of the shoulder joint with steroid and local anesthetic results in decreased pain and increased shoulder function in a cohort of patients with idiopathic adhesive capsulitis. METHODS: This is a retrospective case series of patients who were treated with an arthrographic steroid and local anesthetic injection for adhesive capsulitis. The injections were all given by the same musculoskeletal radiologist using image guidance, and the patients were all from the same surgeon's practice. Patients were evaluated with the Shoulder Pain and Disability Questionnaire (SPADI) and Constant Shoulder Score and their shoulder ROM was tested. Descriptive statistics in the form of counts, percentages, means and standard deviations were used, as well as parametric and non-parametric tests. RESULTS: Thirty-three shoulders in 25 patients were examined. The average length of follow-up was 17 months. Sixty-nine percent of the cohort continued to complain of some shoulder pain in the post-injection follow-up clinic, however, their pain had improved from 8.8/10 pre-injection to 2.2/10 post-injection (p=0.01). The average score of the SPADI Pain, SPADI Disability and Constant Score were 36, 31 and 64, respectively. CONCLUSION: All patients who received an arthrographic injection using steroid and local anesthetic reported improved pain and mobility. In addition, those who had tried other treatment modalities felt that the injection had been the most beneficial.

Flow cytometry and real-time quantitative PCR as tools for assessing plasmid persistence.

The maintenance of a plasmid in the absence of selection for plasmid-borne genes is not guaranteed. However, plasmid persistence can evolve under selective conditions. Studying the molecular mechanisms behind the evolution of plasmid persistence is key to understanding how plasmids are maintained under nonselective conditions. Given the current crisis of rapid antibiotic resistance spread by multidrug resistance plasmids, this insight is of high medical relevance. The conventional method for monitoring plasmid persistence (i.e., the fraction of plasmid-containing cells in a population over time) is based on cultivation and involves differentiating colonies of plasmid-containing and plasmid-free cells on agar plates. However, this technique is time-consuming and does not easily lend itself to high-throughput applications. Here, we present flow cytometry (FCM) and real-time quantitative PCR (qPCR) as alternative tools for monitoring plasmid persistence. For this, we measured the persistence of a model plasmid, pB10::gfp, in three Pseudomonas hosts and in known mixtures of plasmid-containing and -free cells. We also compared three performance criteria: dynamic range, resolution, and variance. Although not without exceptions, both techniques generated estimates of overall plasmid loss rates that were rather similar to those generated by the conventional plate count (PC) method. They also were able to resolve differences in loss rates between artificial plasmid persistence assays. Finally, we briefly discuss the advantages and disadvantages for each technique and conclude that, overall, both FCM and real-time qPCR are suitable alternatives to cultivation-based methods for routine measurement of plasmid persistence, thereby opening avenues for high-throughput analyses.

Neuropathic ankle fractures.

A 65-year-old diabetic female presented with a 3-week history of a left swollen foot after a minor inversion injury and was found to have a minimally displaced fibular fracture. Despite casting and strict instructions to remain non-weight bearing, the patient continued to bear weight and later developed a significantly more displaced fracture with a draining ulcer. This injury eventually required a tibiotalocalcaneal arthrodesis using a retrograde hindfoot nail. Neuropathy and neuropathic fractures can be devastating complications of diabetes and thus require early diagnosis and intervention because they may result in significant morbidity for the patient. Thorough assessment involving imaging, a complete history and physical examination, and tools such as a 129 Hz tuning fork and the 10 g Semmes-Weinstein monofilament are paramount to establishing an accurate initial diagnosis. These tactics aid in future follow-up of the patient's injury and can be employed in both the clinic and the emergency department. Although management remains controversial for neuropathic ankle fractures because both conservative and surgical treatment regimens have high complication rates, open reduction and internal fixation continues to be the treatment of choice once closed reduction has been attempted and fails. Education is essential because diabetic patients have compromised pain and pressure sensation, which can lead to injuries and subsequent complications of which they are simply unaware. Physicians must be diligent when evaluating the diabetic foot and be explicit when providing instructions to these patients because preventing these injuries and their complications is the best patient care available.

Metal to ligand charge transfer induced DNA photobinding in a Ru(II)-Pt(II) supramolecule using red light in the therapeutic window: a new mechanism for DNA modification.

The Ru(II)-Pt(II) supramolecular complex, [(Ph(2)phen)(2)Ru(dpp)PtCl(2)](2+), displays a new mechanism for DNA modification: photobinding through a (3)MLCT excited state. Gel shift analysis, selective DNA precipitation, and DNA melting point experiments support efficient covalent DNA binding following visible light excitation.

Convalescent cultures for control of shigellosis outbreaks.

BACKGROUND: A shigellosis outbreak in the St Louis, Missouri metropolitan area. OBJECTIVE: To evaluate the utility of a second convalescent stool culture following an initial negative convalescent stool culture among persons excluded from work or childcare for shigellosis. METHODS: An observational study of 219 shigellosis cases. Laboratory-confirmed shigellosis patients who are required to submit 2 negative convalescent stool cultures before returning to childcare facilities or work and who submitted at least 1 culture were included in the study. Univariate and multivariable logistic regression analyses were performed to evaluate potential risk factors for a convalescent stool culture being positive. RESULTS: Of 308 persons, 219 (71%) submitted at least 1 convalescent stool culture, and 164 (53%) submitted 2 negative convalescent stool cultures. Among 172 cases with > or =2 follow-up cultures, the probability that the second test result would agree with the first test result was 7% for a "positive" initial stool culture, and 100% for a "negative" stool culture. When adjusted for age, sex, and child care attendance, treated case-patients who had Shigella organisms in the first convalescent culture were more likely to have had stool collected <48 hours after the treatment completion and were more likely to have been treated with trimethoprim-sulfamethoxazole. CONCLUSIONS: Compliance is poor with statutes requiring serial negative stool cultures among certain populations with shigellosis. Absence of Shigella species in the first convalescent stool culture of patients recovering from shigellosis appears to be an adequate measure of bacteriologic cure; however, the health impacts of requiring any convalescent cultures during shigellosis outbreaks remain unclear.