Pronator quadratus preserving versus pronator quadratus dissecting approaches in volar plate fixation of distal radius fractures: a systematic review of comparative studies.

PURPOSE: To compare pronator quadratus preserving (PQ-P) approaches with PQ dissecting (PQ-D) approaches in volar plate fixation of distal radius fractures (DRFs). METHODS: Three databases were searched on March 10th, 2024. The authors adhered to the PRISMA and R-AMSTAR guidelines and Cochrane Handbook for Systematic Reviews. Data on demographics, fracture classifications, patient reported outcome measures (PROMs), range of motion, radiographic parameters, and complications were extracted. RESULTS: Thirteen studies with a total of 1007 fractures were included. Two of three studies reported lower DASH scores in the PQ-P group between 6 weeks and 3 months postoperative, however no studies reported lower scores in the PQ-P group after 3 months. Three of three studies reported significantly lower VAS scores at 6 weeks postoperative, however no studies reported significant differences after 6 months. Only one of six studies reported significantly greater flexion, extension, and pronation in the PQ-P group. One of four studies reported greater radial deviation in the PQ-P group, while there were no differences in supination or ulnar deviation. One of ten and one of six studies reported greater volar tilt and ulnar variance or radial length, respectively, in the PQ-P group. CONCLUSION: There is not sufficient evidence supporting the utility of PQ-P approaches over conventional PQ-D approaches for volar plate fixation of DRFs, especially at long-term follow-ups (3+ months). There may be short term benefits with PQ-P approaches, specifically with regards to PROMs in the short-term (< 6 weeks), however there is limited high-quality evidence supporting these findings. LEVEL OF EVIDENCE: Level III.

The Role of Preoperative Opioid Use in Foot and Ankle Surgery: A Systematic Review.

Prescription opioids, particularly for treating musculoskeletal pain, are a significant contributor to the opioid epidemic in North America. There is also evidence to suggest that chronic use of opioids is associated with poor outcomes after orthopedic surgery. However, whether this association is relevant in foot and ankle surgery is still unclear. Accordingly, a systematic review of the literature was undertaken to assess the impact of preoperative opioid use in patients undergoing foot and ankle surgery concerning postoperative pain, complications, and postoperative opioid dependence. Four databases, including EMBASE, MEDLINE, PubMed, and CINAHL, were searched to March 2022 for studies reporting preoperative opioid use and its effect on postoperative outcomes or opioid use after foot and ankle surgery. A total of 22,092 patients were included in the final synthesis of 8 studies. Most of which were level 3 evidence (5 studies). Around 18% of the patients used opioids preoperatively. Preoperative opioid use was associated with more quantities and prolonged use of opioids postoperatively. Two studies showed an increased risk of complications postoperatively in patients who used opioids preoperatively compared to the nonopioid group. Preoperative opioid use in patients undergoing foot and ankle surgeries is associated with increased and prolonged use of opioids postoperatively and may therefore predict the potential for misuse.

Effect of Local Antibiotic Prophylaxis on Postoperative Deep Infection in Fracture Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVES: Despite the use of systemic antibiotic prophylaxis, postoperative infection after fracture surgery remains an issue. The purpose of this systematic review and meta-analysis was to evaluate the effect of locally applied antibiotics on deep infection in fracture surgery in both the open and closed fractures. DATA SOURCES: A comprehensive search of MEDLINE, Embase, and PubMed was performed from the date of inception to April 15, 2021, and included studies in all languages. STUDY SELECTION: Cohort studies were eligible if they investigated the effect on the infection rate of local antibiotic prophylaxis on deep infection after fracture surgery. DATA EXTRACTION: This study was conducted according to the Cochrane Handbook for Systematic Reviews and reported as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials and the Methodological Index for Nonrandomized Studies tool where applicable. DATA SYNTHESIS: An inverse variance random-effects model was the primary analysis model because of the anticipated diversity in the evaluated populations. Univariate models were used when a single outcome was of interest. CONCLUSIONS: The risk of deep infection was significantly reduced when local antibiotics were applied compared with the control group receiving systemic prophylaxis only. This beneficial effect was observed in open fractures but failed to reach statistical significance in closed fractures. This meta-analysis suggests that there may be a significant risk reduction in deep infection rate after fracture surgery when local antibiotics are added to standard systemic prophylaxis, particularly in open fractures. Further high-powered Level I studies are needed to support these findings. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

COVID-19 and the transition to virtual teaching sessions in an orthopaedic surgery training program: a survey of resident perspectives.

BACKGROUND: COVID-19 has had a tremendous impact on medical education. Due to concerns of the virus spreading through gatherings of health professionals, in-person conferences and rounds were largely cancelled. The purpose of this study is the evaluate the implementation of an online educational curriculum by a major Canadian orthopaedic surgery residency program in response to COVID-19. METHODS: A survey was distributed to residents of a major Canadian orthopaedic surgery residency program from July 10th to October 24th, 2020. The survey aimed to assess residents' response to this change and to examine the effect that the transition has had on their participation, engagement, and overall educational experience. RESULTS: Altogether, 25 of 28 (89%) residents responded. Respondents generally felt the quality of education was superior (72%), their level of engagement improved (64%), and they were able to acquire more knowledge (68%) with the virtual format. Furthermore, 88% felt there was a greater diversity of topics, and 96% felt there was an increased variety of presenters. Overall, 76% of respondents felt that virtual seminars better met their personal learning objectives. Advantages reported were increased accessibility, greater convenience, and a wider breadth of teaching faculty. Disadvantages included that the virtual sessions felt less personal and lacked dynamic feedback to the presenter. CONCLUSIONS: Results of this survey reveal generally positive attitudes of orthopaedic surgery residents about the transition to virtual learning in the setting of an ongoing pandemic. This early evaluation and feedback provides valuable guidance on how to grow this novel curriculum and bring the frontier of virtual teaching to orthopaedic education long-term.

Reverse Total Shoulder Arthroplasty Is the Most Cost-effective Treatment Strategy for Proximal Humerus Fractures in Older Adults: A Cost-utility Analysis.

BACKGROUND: Proximal humerus fractures are the second-most common fragility fracture in older adults. Although reverse total shoulder arthroplasty (RTSA) is a promising treatment strategy for proximal humerus fractures with favorable clinical and quality of life outcomes, it is associated with much higher, and possibly prohibitive, upfront costs relative to nonoperative treatment and other surgical alternatives. QUESTIONS/PURPOSES: (1) What is the cost-effectiveness of open reduction internal fixation (ORIF), hemiarthroplasty, and RTSA compared with the nonoperative treatment of complex proximal humerus fractures in adults older than 65 years from the perspective of a single-payer Canadian healthcare system? (2) Which factors, if any, affect the cost-effectiveness of ORIF, hemiarthroplasty, and RTSA compared with nonoperative treatment of proximal humerus fractures including quality of life outcomes, cost, and complication rates after each treatment? METHODS: This cost-utility analysis compared RTSA, hemiarthroplasty, and ORIF with the nonoperative management of complex proximal humerus fractures in adults older than 65 years over a lifetime time horizon from the perspective of a single-payer healthcare system. Short-term and intermediate-term complications in the 2-year postoperative period were modeled using a decision tree, with long-term outcomes estimated through a Markov model. The model was initiated with a cohort of 75-year-old patients who had a diagnosis of a comminuted (three- or four-part) proximal humerus fractures; 90% of the patients were women. The mean age and gender composition of the model's cohort was based on a systematic review conducted as part of this analysis. Patients were managed nonoperatively or surgically with either ORIF, hemiarthroplasty, or RTSA. The three initial surgical treatment options of ORIF, hemiarthroplasty, and RTSA resulted in uncomplicated healing or the development of a complication that would result in a subsequent surgical intervention. The model reflects the complications that result in repeat surgery and that are assumed to have the greatest impact on clinical outcomes and costs. Transition probabilities and health utilities were derived from published sources, with costs (2020 CAD) sourced from regional costing databases. The primary outcome was the incremental cost-utility ratio, which was calculated using expected quality-adjusted life years (QALYs) gained and costs. Sensitivity analyses were conducted to explore the impact of changing key model parameters. RESULTS: Based on both pairwise and sequential analysis, RTSA was found to be the most cost-effective strategy for managing complex proximal humerus fractures in adults older than 65 years. Compared with nonoperative management, the pairwise incremental cost-utility ratios of hemiarthroplasty and RTSA were CAD 25,759/QALY and CAD 7476/QALY, respectively. ORIF was dominated by nonoperative management, meaning that it was both more costly and less effective. Sequential analysis, wherein interventions are compared from least to most expensive in a pairwise manner, demonstrated ORIF to be dominated by hemiarthroplasty, and hemiarthroplasty to be extendedly dominated by RTSA. Further, at a willingness-to-pay threshold of CAD 50,000/QALY, RTSA had 66% probability of being the most cost-effective treatment option. The results were sensitive to changes in the parameters for the probability of revision RTSA after RTSA, the treatment cost of RTSA, and the health utilities associated with the well state for all treatment options except ORIF, although none of these changes were found to be clinically realistic based on the existing evidence. CONCLUSION: Based on this economic analysis, RTSA is the preferred treatment strategy for complex proximal humerus fractures in adults older than 65 years, despite high upfront costs. Based on the evidence to date, it is unlikely that the parameters this model was sensitive to would change to the degree necessary to alter the model's outcome. A major strength of this model is that it reflects the most recent randomized controlled trials evaluating the management of this condition. Therefore, clinicians should feel confident recommending RTSA for the management of proximal humerus fractures in adults older than 65 years, and they are encouraged to advocate for this intervention as being a cost-effective practice, especially in publicly funded healthcare systems wherein resource stewardship is a core principle. Future high-quality trials should continue to collect both clinical and quality of life outcomes using validated tools such as the EuroQOL-5D to reduce parameter uncertainty and support decision makers in understanding relevant interventions' value for money. LEVEL OF EVIDENCE: Level III, economic and decision analysis.

Short-term outcomes vary by surgical approach in total hip arthroplasty: a network meta-analysis.

BACKGROUND: The direct anterior approach (DAA) has increased in popularity in recent years. Proponents cite its muscle-sparing approach and purported reduction in pain and improvement in function when compared to the traditional surgical approaches. There remains controversy surrounding the validity of these claims. The objective of this study was to compare the common total hip surgical approaches in terms of pain scores, functional outcomes, opioid use and complications within the first 12 weeks postoperatively. METHODS: A network meta-analysis of randomized controlled trials (RCT) comparing postoperative outcomes of different surgical approaches in primary THA up to 12 weeks was performed. PubMed, MEDLINE, Embase, Web of Science and SCOPUS were systematically searched from inception to May 2020. Outcomes included pain scores, functional outcome scores, length of stay (LOS), complications and opioid consumption. RESULTS: Twenty-five RCTs (n = 2339) were included. The DAA demonstrated statistically significant improvement in Harris Hip Scores at 6 weeks when compared to the posterior and direct lateral approaches. The DAA reduced pain scores on postoperative day 2 and at 2 weeks compared to the direct lateral approach. The anterolateral approach was found to have a significantly shorter LOS compared to the other major surgical approaches. The differences in functional outcomes or pain scores did not surpass conventional cutoffs for a minimal clinically important difference. CONCLUSION: The DAA led to functional improvements at 6 weeks compared to the posterior and direct lateral approaches and reduced postoperative pain compared to the direct lateral approach. However, these improvements failed to reach clinical significance. All major surgical approaches led to large improvements in function by 12 weeks with relatively low complication rates. Whether a short-term statistically significant improvement in function is sufficiently patient important to recommend DAA as a standard remains uncertain.

Posterior mesorectal thickness as a predictor of increased operative time in rectal cancer surgery: a retrospective cohort study.

BACKGROUND: In rectal cancer surgery, larger mesorectal fat area has been shown to correlate with increased intraoperative difficulty. Prior studies were mostly in Asian populations with average body mass indices (BMIs) less than 25 kg/m2. This study aimed to define the relationship between radiological variables on pelvic magnetic resonance imaging (MRI) and intraoperative difficulty in a North American population. METHODS: This is a single-center retrospective cohort study analyzing all patients who underwent low anterior resection (LAR) or transanal total mesorectal excision (TaTME) for stage I-III rectal adenocarcinoma from January 2015 until December 2019. Eleven pelvic magnetic resonance imaging measures were defined a priori according to previous literature and measured in each of the included patients. Operative time in minutes and intraoperative blood loss in milliliters were utilized as the primary indicators of intraoperative difficulty. RESULTS: Eighty-three patients (39.8% female, mean age: 62.4 ± 11.6 years) met inclusion criteria. The mean BMI of included patients was 29.4 ± 6.2 kg/m2. Mean operative times were 227.2 ± 65.1 min and 340.6 ± 78.7 min for LARs and TaTMEs, respectively. On multivariable analysis including patient, tumor, and MRI factors, increasing posterior mesorectal thickness was significantly associated with increased operative time (p = 0.04). Every 1 cm increase in posterior mesorectal thickness correlated with a 26 min and 6 s increase in operative time. None of the MRI measurements correlated strongly with BMI. CONCLUSION: As the number of obese rectal cancer patients continues to expand, strategies aimed at optimizing their surgical management are paramount. While increasing BMI is an important preoperative risk factor, the present study identifies posterior mesorectal thickness on MRI as a reliable and easily measurable parameter to help predict operative difficulty. Ultimately, this may in turn serve as an indicator of which patients would benefit most from pre-operative resources aimed at optimizing operative conditions and postoperative recovery.

Nitric oxide, gravity response, and a unified schematic of plant signaling.

Plant signaling components are often involved in numerous processes. Calcium, reactive oxygen species, and other signaling molecules are essential to normal biotic and abiotic responses. Yet, the summation of these components is integrated to produce a specific response despite their involvement in a myriad of response cascades. In the response to gravity, the role of many of these individual components has been studied, but a specific sequence of signals has not yet been assembled into a cohesive schematic of gravity response signaling. Herein, we provide a review of existing knowledge of gravity response and differential protein and gene regulation induced by the absence of gravity stimulus aboard the International Space Station and propose an integrated theoretical schematic of gravity response incorporating that information. Recent developments in the role of nitric oxide in gravity signaling provided some of the final contextual pillars for the assembly of the model, where nitric oxide and the role of cysteine S-nitrosation may be central to the gravity response. The proposed schematic accounts for the known responses to reorientation with respect to gravity in roots-the most well studied gravitropic plant tissue-and is supported by the extensive evolutionary conservation of regulatory amino acids within protein components of the signaling schematic. The identification of a role of nitric oxide in regulating the TIR1 auxin receptor is indicative of the broader relevance of the schematic in studying a multitude of environmental and stress responses. Finally, there are several experimental approaches that are highlighted as essential to the further study and validation of this schematic.

Operative management of colonic diverticular disease in the setting of immunosuppression: A systematic review and meta-analysis.

BACKGROUND: Immunosuppressed patients with diverticular disease are at higher risk of postoperative complications, however reported rates have varied. The aim of this study is to compare postoperative outcomes in immunosuppressed and immunocompetent patients undergoing surgery for diverticular disease. METHODS: Medline, EMBASE, and CENTRAL were searched. Articles were included if they compared immunosuppressed and immunocompetent patients undergoing surgery for diverticular disease. RESULTS: From 204 citations, 11 studies with 2,977 immunosuppressed patients and 780,630 immunocompetent patients were included. Mortality was greater in immunosuppressed patients compared to immunocompetent patients for emergent surgery (RR 1.91, 95%CI 1.24-2.95, p < 0.01), but not elective surgery (RR 1.70, 95%CI 0.14-20.47, p = 0.68). Morbidity was greater in immunosuppressed patients compared to immunocompetent patients for elective surgery (RR 2.18, 95%CI 1.02-4.65, p = 0.04), but not emergent surgery (RR 1.40, 95%CI 0.68-2.90, p = 0.37). CONCLUSIONS: Increased consideration for elective operation may preclude the need for emergent surgery and the associated increase in postoperative mortality.

Growth Hormone Upregulates Melanocyte-Inducing Transcription Factor Expression and Activity via JAK2-STAT5 and SRC Signaling in GH Receptor-Positive Human Melanoma.

Growth hormone (GH) facilitates therapy resistance in the cancers of breast, colon, endometrium, and melanoma. The GH-stimulated pathways responsible for this resistance were identified as suppression of apoptosis, induction of epithelial-to-mesenchymal transition (EMT), and upregulated drug efflux by increased expression of ATP-binding cassette containing multidrug efflux pumps (ABC-transporters). In extremely drug-resistant melanoma, ABC-transporters have also been reported to mediate drug sequestration in intracellular melanosomes, thereby reducing drug efficacy. Melanocyte-inducing transcription factor (MITF) is the master regulator of melanocyte and melanoma cell fate as well as the melanosomal machinery. MITF targets such as the oncogene MET, as well as MITF-mediated processes such as resistance to radiation therapy, are both known to be upregulated by GH. Therefore, we chose to query the direct effects of GH on MITF expression and activity towards conferring chemoresistance in melanoma. Here, we demonstrate that GH significantly upregulates MITF as well as the MITF target genes following treatment with multiple anticancer drug treatments such as chemotherapy, BRAF-inhibitors, as well as tyrosine-kinase inhibitors. GH action also upregulated MITF-regulated processes such as melanogenesis and tyrosinase activity. Significant elevation in MITF and MITF target gene expression was also observed in mouse B16F10 melanoma cells and xenografts in bovine GH transgenic (bGH) mice compared to wild-type littermates. Through pathway inhibitor analysis we identified that both the JAK2-STAT5 and SRC activities were critical for the observed effects. Additionally, a retrospective analysis of gene expression data from GTEx, NCI60, CCLE, and TCGA databases corroborated our observed correlation of MITF function and GH action. Therefore, we present in vitro, in vivo, and in silico evidence which strongly implicates the GH-GHR axis in inducing chemoresistance in human melanoma by driving MITF-regulated and ABC-transporter-mediated drug clearance pathways.

Could calgranulins and advanced glycated end products potentiate acromegaly pathophysiology?

Growth hormone (GH) exerts a diverse set of effects across many tissues including fat, muscle, bone, kidney, heart, and liver. GH is also a diabetogenic hormone in that it inhibits the actions of insulin. Acromegaly, a condition traditionally characterized by increased levels of growth hormone secretion as a result of pituitary adenoma, results in increased tissue growth, lipolysis, and can result in patients with hyperglycemia and hyperinsulinemia. While current treatment modalities have greatly improved prognoses for most patients, a significant number present clinical symptoms of acromegaly with elevated levels of IGF-1 in the absence of increased GH levels, a phenomenon known as micromegaly. This condition presents a challenge to most currently used treatments since the high circulating IGF-1 levels are independent of elevated levels of GH. It has been previously shown that advanced glycation end products (AGE) can stimulate IGF-1 secretion by human monocytes in vitro, demonstrating a possible mechanism for increased IGF-1 levels. To further investigate AGE/GH/IGF-1 interaction, we have reanalyzed a publicly available RNAseq dataset from subcutaneous adipose tissue of patients with acromegaly. S100A1, a member of the calgranulin family of proteins and ligand of the AGE receptor, was shown to be significantly upregulated in patients with acromegaly. These findings identify an important consideration that may help explain the counterintuitive nature of micromegaly, while simultaneously providing new insight into the role of GH in diabetic, inflammatory, and immune pathologies.

Transcriptomics Identifies Modules of Differentially Expressed Genes and Novel Cyclotides in Viola pubescens.

Viola is a large genus with worldwide distribution and many traits not currently exemplified in model plants including unique breeding systems and the production of cyclotides. Here we report de novo genome assembly and transcriptomic analyses of the non-model species Viola pubescens using short-read DNA sequencing data and RNA-Seq from eight diverse tissues. First, V. pubescens genome size was estimated through flow cytometry, resulting in an approximate haploid genome of 455 Mbp. Next, the draft V. pubescens genome was sequenced and assembled resulting in 264,035,065 read pairs and 161,038 contigs with an N50 length of 3,455 base pairs (bp). RNA-Seq data were then assembled into tissue-specific transcripts. Together, the DNA and transcript data generated 38,081 ab initio gene models which were functionally annotated based on homology to Arabidopsis thaliana genes and Pfam domains. Gene expression was visualized for each tissue via principal component analysis and hierarchical clustering, and gene co-expression analysis identified 20 modules of tissue-specific transcriptional networks. Some of these modules highlight genetic differences between chasmogamous and cleistogamous flowers and may provide insight into V. pubescens' mixed breeding system. Orthologous clustering with the proteomes of A. thaliana and Populus trichocarpa revealed 8,531 sequences unique to V. pubescens, including 81 novel cyclotide precursor sequences. Cyclotides are plant peptides characterized by a stable, cyclic cystine knot motif, making them strong candidates for drug scaffolding and protein engineering. Analysis of the RNA-Seq data for these cyclotide transcripts revealed diverse expression patterns both between transcripts and tissues. The diversity of these cyclotides was also highlighted in a maximum likelihood protein cladogram containing V. pubescens cyclotides and published cyclotide sequences from other Violaceae and Rubiaceae species. Collectively, this work provides the most comprehensive sequence resource for Viola, offers valuable transcriptomic insight into V. pubescens, and will facilitate future functional genomics research in Viola and other diverse plant groups.