Optimizing Preoperative Chronic Pain Management in Elective Spine Surgery Patients: A Narrative Review of Outcomes with Opioid and Adjuvant Pain Therapies.

¼ Chronic preoperative opioid use negatively affects outcomes after spine surgery, with increased complications and reoperations, longer hospital stays, decreased return-to-work rates, worse patient-reported outcomes, and a higher risk of continued opioid use postoperatively.¼ The definition of chronic opioid use is not consistent across studies, and a more specific and consistent definition will aid in stratifying patients and understanding their risk of inferior outcomes.¼ Preoperative weaning periods and maximum dose thresholds are being established, which may increase the likelihood of achieving a meaningful improvement after surgery, although higher level evidence studies are needed.¼ Spinal cord stimulators and intrathecal drug delivery devices are increasingly used to manage chronic back pain and are equivalent or perhaps even superior to opioid treatment, although few studies exist examining how patients with these devices do after subsequent spine surgery.¼ Further investigation is needed to determine whether a true mechanistic explanation exists for spine-related analgesia related to spinal cord stimulators and intrathecal drug delivery devices.

Defining Operative Indications in Lisfranc Injuries: A Systematic Review.

OBJECTIVE: The aim of this review was to determine operative indications for Lisfranc injuries. METHODS: A systematic review using a MEDLINE literature search was performed using the index "Lisfranc Injury" from 1980 onward using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines where applicable. Inclusion criteria were all clinical studies reporting on the management of Lisfranc injuries obtained via the search index, including case reports, review articles, cohort studies, and randomized trials. Non-English-language articles, inaccessible articles, those not relevant to the management of Lisfranc injuries (biomechanical, cadaveric, and technique articles), and those that did not explicitly state operative indications (vague or absent indications) were excluded. RESULTS: After identifying 737 studies, the full text of 391 studies was reviewed, and 58 reports providing explicit operative indications were included in the final analysis. Fifty-one (81.1%) studies provided diastasis cutoffs varying ≥2 mm (35/58; 60.4%), ≥1 mm (13; 22.4%), and ≥3 mm (3; 5.2%); the diastasis location was most commonly unspecified (31/58; 53.5%) or varied between combinations of metatarsal, tarsal, cuboid, and cuneiform bones (20/58; 27.6%). Specific imaging criteria for surgery included an avulsion fracture or fleck sign (3/58; 5.2%), arch height loss (3/58; 5.2%), and a tear on magnetic resonance imaging (5; 8.6%). The 11 (19%) studies defining operative indications in terms of classification schemes used the Nunley and Vertullo (8/58; 13.8%), Myerson (2; 3.5%), and Buehren (1; 1.7%) systems. Twenty-one (36.2%) studies provided multiple operative indications. CONCLUSION: The most common Lisfranc operative indications among the limited reporting studies varied from a 1- to 3-mm diastasis across several locations. It is imperative for operative indications to be reported with an increased frequency and in a homogenous fashion to guide the clinical management of these subtle injuries. LEVELS OF EVIDENCE: Level IV; systematic Review.

Contemporary Review: An Overview of the Utility of Patient-Reported Outcome Measurement Information System (PROMIS) in Foot and Ankle Surgery.

Patient-Reported Outcome Measurement Information System (PROMIS) has favorable psychometric and administrative properties in orthopaedic clinical research. It facilitates clinically meaningful data collection while minimizing administration time and survey fatigue and improving compliance. PROMIS is a critical component of patient-centered care and shared decision making, as it provides enhanced communication and engagement between patients and providers. As a validated instrument, it may also aid in measuring value-based health care quality. The goal of the current work is to provide an overview of PROMIS metrics used in orthopaedic foot and ankle, including advantages and disadvantages compared to legacy scales and PROMIS's applicability in specific foot and ankle conditions based on psychometric properties. We provide a review of the literature regarding the utilization of PROMIS as an outcome measure for specific foot and ankle procedures and conditions.

A systematic review of the patient reported outcome measures utilized in level 1 randomized controlled trials involving achilles tendon ruptures.

BACKGROUND: Patient Reported Outcome Measures (PROMs) are utilized in level 1 randomized controlled trials involving Achilles tendon ruptures. However, the characteristics of these PROMs and current practices has not yet been reported. We hypothesize that there will be heterogeneous PROM usage in this context. METHODS: A PubMed and Embase systematic review was performed including all dates up to July 27th, 2022, assessing Achilles tendon ruptures in level 1 studies using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines where applicable. Inclusion criteria were all randomized controlled clinical studies involving Achilles tendon injuries. Studies that: (1) were not level 1 evidence (including editorial, commentary, review, or technique articles), (2) omitted outcome data or PROMs, (3) included injuries aside from Achilles tendon ruptures, (4) involved non-human or cadaveric subjects, (5) were not written in English, and (6) were duplicates were excluded. Demographics and outcome measures were assessed in the studies included for final review. RESULTS: Out of 18,980 initial results, 46 studies were included for final review. The average number of patients per study was 65.5. Mean follow up was 25 months. The most common study design involved comparing two different rehabilitation interventions (48 %). Twenty different outcome measures were reported including the Achilles tendon rupture score (ATRS) (48 %), followed by the American Orthopedic Foot and Ankle score Ankle-Hindfoot score (AOFAS-AH) (46 %), the Leppilahti score (20 %), and the RAND-36/Short Form (SF) - 36/SF-12 scores (20 %). An average of 1.4 measures were reported per study. CONCLUSION: Significant heterogeneity exists in PROM usage among level 1 studies involving Achilles tendon ruptures, which prevents meaningful interpretation of these data across multiple studies. We advocate for usage of at least the disease-specific Achilles Tendon Rupture score and a global, quality of life (QOL) survey such as the SF-36/12/RAND-36. Future literature should provide more evidence-based guidelines for PROM usage in this context. LEVEL OF EVIDENCE: Level IV; Systematic Review.

Comparison of Psychometric Properties of Patient-Reported Outcomes Measurement Information System With Traditional Outcome Metrics in Spine Surgery.

OBJECTIVE: Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to address certain shortcomings of traditional, or legacy patient-reported outcome measures (PROMs). Because the use of PROMIS across orthopedic populations continues to increase, the purpose of this study was to provide a comprehensive overview of the use and validation of PROMIS in spine surgery. METHODS: PubMed and Google Scholar were searched for relevant articles reporting on the use and validation of PROMIS in spine surgery. The PROMIS formats and individual domains used by investigators were noted. Additionally, psychometric properties reported in validation studies were evaluated. RESULTS: Both individual studies and systematic reviews have demonstrated the convergent validity of PROMIS domains, reporting moderate-to-strong correlations with legacy measures in a variety of spine patient populations. Across spine surgery patient populations, PROMIS instruments are consistently efficient, demonstrating decreased question burden compared with legacy PROMs. PROMIS domains overall exhibit responsiveness comparable with legacy measures, and the normalization of PROMIS scores to a general population allows for broad coverage, resulting in acceptable floor and ceiling effects. Despite the many strengths of PROMIS, there remain some populations where PROMIS is not suited to be used in isolation. CONCLUSIONS: PROMIS is widely used as an outcome measure in spine surgery and has been validated in a range of patient populations. Although PROMIS domains cannot fully replace legacy measures in spine patients, they can be used in certain settings to provide an efficient and psychometrically sound PROM.

Favorable Patient-Reported Outcomes and High Return to Sport Rates Following Hip Arthroscopy in Adolescent Athletes: A Systematic Review.

PURPOSE: The purpose of this systematic review is to synthesize the existing literature surrounding hip arthroscopy in the adolescent athlete population to determine patient-reported outcomes, return to sport rates, complications, and reoperations associated with this intervention. METHODS: A systematic literature review was performed using PubMed (MEDLINE), Cochrane Library, and Embase according to PRISMA guidelines. Studies were included if they were published in English with greater than 2 participants, contained patients aged 10-19 years old or classified as "high school athletes" or "middle school athletes," and reported postoperative patient-reported outcomes and return to sport. Patient-reported outcomes (PROs) and their associated P values were recorded. Finally, return-to-sport outcomes and sports played were also extracted from the included studies. Weighted kappa was used to assess inter-reviewer agreement. RESULTS: Eleven studies included in the final analysis, resulting in 344 patients and 408 hips were analyzed by this review. Patient-reported outcomes (PROs) were reported in all studies. The modified Harris Hip Score (mHHS) was used in all but 1 study. Six of the 11 studies reported a 100% return-to-sport rate, for a total of 98/98 athletes returning to sport. Fabricant et al. did note that a majority of athletes who returned to sport were able to do so at a subjective "nearly normal" level. Only 4 of the studies reported complications, with the majority being transient neuropraxias. CONCLUSIONS: Adolescent athletes who undergo hip arthroscopy demonstrate favorable postoperative patient-reported outcome scores, high rates of return to sport, and an overall low complication rate. The heterogeneity in both surgical methodology and outcome measures used for evaluation and treatment leads to continued ambiguity with regard to the optimal method for managing adolescent athletes with hip pathology. LEVEL OF EVIDENCE: V, systematic review of Level II-V studies.

Pan-enteric neuropathy and dysmotility are present in a mouse model of short-segment Hirschsprung disease and may contribute to post-pullthrough morbidity.

PURPOSE: Hirschsprung disease (HSCR) is characterized by distal intestinal aganglionosis. While surgery is lifesaving, gastrointestinal (GI) motility disorders persist in many patients. Our objective was to determine whether enteric nervous system (ENS) abnormalities exist in the ganglionated portions of the GI tract far proximal to the aganglionic region and whether these are associated with GI dysmotility. METHODS: Using Ednrb-null mice, a model of HSCR, immunohistochemical analysis was performed to evaluate quantitatively ENS structure in proximal colon, small intestine, and stomach. Gastric emptying and intestinal transit were measured in vivo and small and large bowel contractility was assessed by spatiotemporal mapping ex vivo. RESULTS: Proximal colon of HSCR mice had smaller ganglia and decreased neuronal fiber density, along with a marked reduction in migrating motor complexes. The distal small intestine exhibited significantly fewer ganglia and decreased neuronal fiber density, and this was associated with delayed small intestinal transit time. Finally, in the stomach of HSCR mice, enteric neuronal packing density was increased and gastric emptying was faster. CONCLUSIONS: ENS abnormalities and motility defects are present throughout the ganglionated portions of the GI tract in Ednrb-deficient mice. This may explain the GI morbidity that often occurs following pull-through surgery for HSCR.

Enteric neuronal cell therapy reverses architectural changes in a novel diphtheria toxin-mediated model of colonic aganglionosis.

Hirschsprung disease (HSCR) is characterized by absence of the enteric nervous system (ENS) in the distal bowel. Despite removal of the aganglionic segment, gastrointestinal (GI) problems persist. Cell therapy offers potential treatment but use of genetic models is limited by their poor survival. We have developed a novel model of aganglionosis in which enteric neural crest-derived cells (ENCDCs) express diphtheria toxin (DT) receptor. Local DT injection into the colon wall results in focal, specific, and sustained ENS ablation without altering GI transit or colonic contractility, allowing improved survival over other aganglionosis models. Focal ENS ablation leads to increased smooth muscle and mucosal thickness, and localized inflammation. Transplantation of ENCDCs into this region leads to engraftment, migration, and differentiation of enteric neurons and glial cells, with restoration of normal architecture of the colonic epithelium and muscle, reduction in inflammation, and improved survival.

Intraganglionic macrophages: a new population of cells in the enteric ganglia.

The enteric nervous system shares embryological, morphological, neurochemical, and functional features with the central nervous system. In addition to neurons and glia, the CNS includes a third component, microglia, which are functionally and immunophenotypically similar to macrophages, but a similar cell type has not previously been identified in enteric ganglia. In this study we identify a population of macrophages in the enteric ganglia, intermingling with the neurons and glia. These intraganglionic macrophages (IMs) are highly ramified and express the hematopoietic marker CD45, major histocompatibility complex (MHC) class II antigen, and chB6, a marker specific for B cells and microglia in avians. These IMs do not express antigens typically associated with T cells or dendritic cells. The CD45+ /ChB6+ /MHCII+ signature supports a hematopoietic origin and this was confirmed using intestinal chimeras in GFP-transgenic chick embryos. The presence of green fluorescent protein positive (GFP+) /CD45+ cells in the intestinal graft ENS confirms that IMs residing within enteric ganglia have a hematopoietic origin. IMs are also found in the ganglia of CSF1RGFP chicken and CX3CR1GFP mice. Based on the expression pattern and location of IMs in avians and rodents, we conclude that they represent a novel non-neural crest-derived microglia-like cell population within the enteric ganglia.

The emergence of extracellular vesicles in urology: fertility, cancer, biomarkers and targeted pharmacotherapy.

Extracellular vesicles (EV) are small membrane-bound vesicles enriched in a selective repertoire of mRNA, miRNA, proteins and cell surface receptors from parental cells and are actively involved in the transmission of inter and intracellular signals. Cancer cells produce EV that contain cargo including DNA, mRNA, miRNA and proteins that allow EV to create epigenetic changes in target cells both locally and systemically. Cancer-derived EV play critical roles in tumorigenesis, cancer cell migration, metastasis, evasion of host immune defense, chemoresistance, and they promote a premetastatic niche favourable to micrometastatic seeding. Their unique molecular profiles acquired from originator cells and their presence in numerous body fluids, including blood and urine, make them promising candidates as biomarkers for prostate, renal and bladder cancers. EV may ultimately serve as targets for therapy and as platforms for personalized medicine in urology. As urologic malignancy comprises 28% of new solid tumour diagnoses and 15% of cancer-related deaths, EV-related research is rapidly emerging and providing unique insights into disease progression. In this report, we review the current literature on EV in the setting of genitourinary fertility and malignancy.