Evidence for phloem loading via the abaxial bundle sheath cells in maize leaves.

Leaves are asymmetric, with different functions for adaxial and abaxial tissue. The bundle sheath (BS) of C3 barley (Hordeum vulgare) is dorsoventrally differentiated into three types of cells: adaxial structural, lateral S-type, and abaxial L-type BS cells. Based on plasmodesmatal connections between S-type cells and mestome sheath (parenchymatous cell layer below bundle sheath), S-type cells likely transfer assimilates toward the phloem. Here, we used single-cell RNA sequencing to investigate BS differentiation in C4 maize (Zea mays L.) plants. Abaxial BS (abBS) cells of rank-2 intermediate veins specifically expressed three SWEET sucrose uniporters (SWEET13a, b, and c) and UmamiT amino acid efflux transporters. SWEET13a, b, c mRNAs were also detected in the phloem parenchyma (PP). We show that maize has acquired a mechanism for phloem loading in which abBS cells provide the main route for apoplasmic sucrose transfer toward the phloem. This putative route predominates in veins responsible for phloem loading (rank-2 intermediate), whereas rank-1 intermediate and major veins export sucrose from the PP adjacent to the sieve element companion cell complex, as in Arabidopsis thaliana. We surmise that abBS identity is subject to dorsoventral patterning and has components of PP identity. These observations provide insights into the unique transport-specific properties of abBS cells and support a modification to the canonical phloem loading pathway in maize.

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.

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.

Video-based coaching for surgical residents: a systematic review and meta-analysis.

BACKGROUND: Video-based coaching (VBC) is used to supplement current teaching methods in surgical education and may be useful in competency-based frameworks. Whether VBC can effectively improve surgical skill in surgical residents has yet to be fully elucidated. The objective of this study is to compare surgical residents receiving and not receiving VBC in terms of technical surgical skill. METHODS: The following databases were searched from database inception to October 2021: Medline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed. Articles were included if they were randomized controlled trials (RCTs) comparing surgical residents receiving and not receiving VBC. The primary outcome, as defined prior to data collection, was change in objective measures of technical surgical skill following implementation of either VBC or control. A pairwise meta-analyses using inverse variance random effects was performed. Standardized mean differences (SMD) were used as the primary outcome measure to account for differences in objective surgical skill evaluation tools. RESULTS: From 2734 citations, 11 RCTs with 157 residents receiving VBC and 141 residents receiving standard surgical teaching without VBC were included. There was no significant difference in post-coaching scores on objective surgical skill evaluation tools between groups (SMD 0.53, 95% CI 0.00 to 1.01, p = 0.05, I2 = 74%). The improvement in scores pre- and post-intervention was significantly greater in residents receiving VBC compared to those not receiving VBC (SMD 1.62, 95% CI 0.62 to 2.63, p = 0.002, I2 = 85%). These results were unchanged with leave-one-out sensitivity analysis and subgroup analysis according to operative setting. CONCLUSION: VBC can improve objective surgical skills in surgical residents of various levels. The benefit may be most substantial for trainees with lower baseline levels of objective skill. Further studies are required to determine the impact of VBC on competency-based frameworks.

Functional Meta-Analysis of the Proteomic Responses of Arabidopsis Seedlings to the Spaceflight Environment Reveals Multi-Dimensional Sources of Variability across Spaceflight Experiments.

The human quest for sustainable habitation of extraterrestrial environments necessitates a robust understanding of life's adaptability to the unique conditions of spaceflight. This study provides a comprehensive proteomic dissection of the Arabidopsis plant's responses to the spaceflight environment through a meta-analysis of proteomics data from four separate spaceflight experiments conducted on the International Space Station (ISS) in different hardware configurations. Raw proteomics LC/MS spectra were analyzed for differential expression in MaxQuant and Perseus software. The analysis of dissimilarities among the datasets reveals the multidimensional nature of plant proteomic responses to spaceflight, impacted by variables such as spaceflight hardware, seedling age, lighting conditions, and proteomic quantification techniques. By contrasting datasets that varied in light exposure, we elucidated proteins involved in photomorphogenesis and skotomorphogenesis in plant spaceflight responses. Additionally, with data from an onboard 1 g control experiment, we isolated proteins that specifically respond to the microgravity environment and those that respond to other spaceflight conditions. This study identified proteins and associated metabolic pathways that are consistently impacted across the datasets. Notably, these shared proteins were associated with critical metabolic functions, including carbon metabolism, glycolysis, gluconeogenesis, and amino acid biosynthesis, underscoring their potential significance in Arabidopsis' spaceflight adaptation mechanisms and informing strategies for successful space farming.

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.

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.

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.

The Use of Rifampin in Total Joint Arthroplasty: A Systematic Review and Meta-Analysis of Comparative Studies.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty (TJA). Rifampin is an antibiotic with the ability to penetrate bacterial biofilms, and thus has been considered as a potentially important adjunct in the prevention and treatment of PJI. The aim of this systematic review is to evaluate and summarize the use of rifampin in TJA, particularly in the context of PJI. METHODS: A literature search of all relevant electronic databases was performed. All comparative studies assessing the use of rifampin in the context of TJA were included. Descriptive data are reported, and a meta-analysis was performed using all studies which compared the addition of rifampin to standard care in treating PJI. RESULTS: A total of 33 studies met inclusion criteria. A meta-analysis of 22 studies comparing the addition of rifampin to standard care for treating PJI found a significant reduction in failure rates (26.0% vs 35.9%; odds ratio 0.61, 95% confidence interval 0.43-0.86). The protective effect of rifampin was maintained in studies which included exchange arthroplasty as a treatment strategy, but not in studies only using an implant retention strategy. Among studies reporting adverse events of rifampin, there was a 20.5% adverse event rate. CONCLUSION: Overall, rifampin appears to confer a protective effect against treatment failure following PJI. This treatment effect is particularly pronounced in the context of exchange arthroplasty. Further high-level evidence is needed to clarify the exact indications and doses of rifampin which can most effectively act as an adjunct in the treatment of PJI. LEVEL OF EVIDENCE: Level III, Systematic Review and Meta-Analysis of Level I-III Studies.

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.

Transcriptome profiling of insulin sensitive tissues from GH deficient mice following GH treatment.

PURPOSE: Most studies that have examined the transcriptional response to GH have been performed with a single tissue. Thus, the current study performed RNASeq across three insulin-sensitive tissues of GH-treated GH deficient (GHKO) mice. METHODS: GHKO mice were injected with recombinant human GH (hGH) or vehicle daily for 5 days and adipose, liver, and muscle tissues were collected 4 h after the final injection. RNA was isolated from the tissues and sequenced. Genes that were differentially expressed between GH and vehicle treatments were further analyzed. Enrichment analysis and topology-aware pathway analysis were performed. RESULTS: GHKO mice treated with hGH had expected phenotypic alterations, with increased body, fat, fluid, liver, and muscle mass, and increased serum IGF-1 and insulin. 55 Genes were differentially expressed in all three tissues, including the canonical GH targets Igf1, Igfals, and Cish. Enrichment analysis confirmed the canonical GH response in select tissues, such as cell proliferation, metabolism, and fibrosis. The JAK/STAT pathway was the only pathway significantly altered in all three tissues. CONCLUSIONS: As expected, GH caused expression changes of many known target genes, although new candidate GH targets were identified. Liver and muscle appear to be more GH sensitive than adipose tissue due to the larger number of DEG and pathways significantly altered, but adipose still has a characteristic GH response. The diversity of changes uncovered in all three tissues after 5 days of GH treatment highlights the multiplicity of GH's effects in its target tissues.

The Fragility of Statistically Significant Findings From Randomized Controlled Trials in Hip and Knee Arthroplasty.

BACKGROUND: The Fragility Index (FI) is a method for evaluating the robustness of statistically significant findings from randomized controlled trials (RCTs) beyond the P value in trials with dichotomous outcomes. The FI is defined as the number of patients in one arm of a trial that would have to have a different outcome to change the results of the trial from statistically significant to nonsignificant. This review assessed the FI in arthroplasty RCTs. METHODS: A systematic search was conducted in MEDLINE, Embase, and Web of Science for RCTs related to primary total joint arthroplasty (TJA) from 2010 to 2020. Trials with a statistically significant dichotomous primary outcome were included. The FI was calculated using Fisher's exact test to determine how many events would need to be reversed to change a study from statistically significant to nonsignificant. RESULTS: A total of 34 RCTs were included. The median sample size was 103 patients (range 24-791). The median FI was 1 (range 0-45), meaning that reversing the outcome of just one patient in either treatment group of each trial would change it from a significant to a nonsignificant result. CONCLUSION: Hip and knee arthroplasty RCTs with statistically significant dichotomous outcomes in TJA are fragile. The median FI in TJA is lower than the FI in any of the other previously reported orthopedic subspecialties. Fragility is another reason to be cautious when conducting or interpreting small trials, and to continue to strive toward large trials to answer important questions in TJA. LEVEL OF EVIDENCE: Level I.

Spaceflight induces novel regulatory responses in Arabidopsis seedling as revealed by combined proteomic and transcriptomic analyses.

BACKGROUND: Understanding of gravity sensing and response is critical to long-term human habitation in space and can provide new advantages for terrestrial agriculture. To this end, the altered gene expression profile induced by microgravity has been repeatedly queried by microarray and RNA-seq experiments to understand gravitropism. However, the quantification of altered protein abundance in space has been minimally investigated. RESULTS: Proteomic (iTRAQ-labelled LC-MS/MS) and transcriptomic (RNA-seq) analyses simultaneously quantified protein and transcript differential expression of three-day old, etiolated Arabidopsis thaliana seedlings grown aboard the International Space Station along with their ground control counterparts. Protein extracts were fractionated to isolate soluble and membrane proteins and analyzed to detect differentially phosphorylated peptides. In total, 968 RNAs, 107 soluble proteins, and 103 membrane proteins were identified as differentially expressed. In addition, the proteomic analyses identified 16 differential phosphorylation events. Proteomic data delivered novel insights and simultaneously provided new context to previously made observations of gene expression in microgravity. There is a sweeping shift in post-transcriptional mechanisms of gene regulation including RNA-decapping protein DCP5, the splicing factors GRP7 and GRP8, and AGO4,. These data also indicate AHA2 and FERONIA as well as CESA1 and SHOU4 as central to the cell wall adaptations seen in spaceflight. Patterns of tubulin-α 1, 3,4 and 6 phosphorylation further reveal an interaction of microtubule and redox homeostasis that mirrors osmotic response signaling elements. The absence of gravity also results in a seemingly wasteful dysregulation of plastid gene transcription. CONCLUSIONS: The datasets gathered from Arabidopsis seedlings exposed to microgravity revealed marked impacts on post-transcriptional regulation, cell wall synthesis, redox/microtubule dynamics, and plastid gene transcription. The impact of post-transcriptional regulatory alterations represents an unstudied element of the plant microgravity response with the potential to significantly impact plant growth efficiency and beyond. What's more, addressing the effects of microgravity on AHA2, CESA1, and alpha tubulins has the potential to enhance cytoskeletal organization and cell wall composition, thereby enhancing biomass production and growth in microgravity. Finally, understanding and manipulating the dysregulation of plastid gene transcription has further potential to address the goal of enhancing plant growth in the stressful conditions of microgravity.

The role of fecal calprotectin in the diagnosis of acute pouchitis following IPAA for ulcerative colitis: a systematic clinical review.

PURPOSE: Total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is commonly performed for patients with refractory ulcerative colitis (UC). Pouchitis occurs in 20-50% of these patients. Fecal calprotectin is a biomarker that correlates well with the pouchitis disease activity index. However, its role in the diagnosis and management of acute pouchitis has not been thoroughly defined. The aim of this study is to review previously established cut-off values and contextualize the clinical utility of fecal calprotectin. METHODS: Search of Medline, EMBASE, CENTRAL, and PubMed was performed. Articles were eligible if they measured fecal calprotectin in the setting of pouchitis in patients who underwent TPC with IPAA for UC. Risk of bias of the included studies was evaluated with the QUADAS-2. RESULTS: From 117 relevant citations, seven studies with 256 patients (44.8% female, 39.88 years) met inclusion criteria. The pooled prevalence of pouchitis was 42%. The derived fecal calprotectin cut-off values ranged from 56 to 494 µg/g. The corresponding sensitivities and specificities ranged from 57 to 100% and 38 to 92%, respectively. The area under the curve was reported in three studies and ranged from 0.832 to 0.840. CONCLUSION: Fecal calprotectin may be a reliable diagnostic tool for acute pouchitis in patients following TPC with IPAA for UC. The high sensitivity of fecal calprotectin for detection of pouchitis makes it a valuable test for ruling out pouchitis. When used in conjunction with other biomarkers, the high specificity offers value in ruling in pouchitis. However, given the complexity of this disease process, relying solely on biomarkers for diagnosis is currently unreasonable.

ALS blood expression profiling identifies new biomarkers, patient subgroups, and evidence for neutrophilia and hypoxia.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a debilitating disease with few treatment options. Progress towards new therapies requires validated disease biomarkers, but there is no consensus on which fluid-based measures are most informative. METHODS: This study analyzed microarray data derived from blood samples of patients with ALS (n = 396), ALS mimic diseases (n = 75), and healthy controls (n = 645). Goals were to provide in-depth analysis of differentially expressed genes (DEGs), characterize patient-to-patient heterogeneity, and identify candidate biomarkers. RESULTS: We identified 752 ALS-increased and 764 ALS-decreased DEGs (FDR < 0.10 with > 10% expression change). Gene expression shifts in ALS blood broadly resembled acute high altitude stress responses. ALS-increased DEGs had high exosome expression, were neutrophil-specific, associated with translation, and overlapped significantly with genes near ALS susceptibility loci (e.g., IFRD1, TBK1, CREB5). ALS-decreased DEGs, in contrast, had low exosome expression, were erythroid lineage-specific, and associated with anemia and blood disorders. Genes encoding neurofilament proteins (NEFH, NEFL) had poor diagnostic accuracy (50-53%). However, support vector machines distinguished ALS patients from ALS mimics and controls with 87% accuracy (sensitivity: 86%, specificity: 87%). Expression profiles were heterogeneous among patients and we identified two subgroups: (i) patients with higher expression of IL6R and myeloid lineage-specific genes and (ii) patients with higher expression of IL23A and lymphoid-specific genes. The gene encoding copper chaperone for superoxide dismutase (CCS) was most strongly associated with survival (HR = 0.77; P = 1.84e-05) and other survival-associated genes were linked to mitochondrial respiration. We identify a 61 gene signature that significantly improves survival prediction when added to Cox proportional hazard models with baseline clinical data (i.e., age at onset, site of onset and sex). Predicted median survival differed 2-fold between patients with favorable and risk-associated gene expression signatures. CONCLUSIONS: Peripheral blood analysis informs our understanding of ALS disease mechanisms and genetic association signals. Our findings are consistent with low-grade neutrophilia and hypoxia as ALS phenotypes, with heterogeneity among patients partly driven by differences in myeloid and lymphoid cell abundance. Biomarkers identified in this study require further validation but may provide new tools for research and clinical practice.

Effect of Depression Interventions in Patients Undergoing Total Joint Arthroplasty Without a Formal Diagnosis of Depression: A Systematic Review.

PURPOSE: Depression is a notable contributor to suboptimal outcomes after total joint arthroplasty (TJA). We conducted a systematic review of comparative studies to review the available evidence of interventions that affected depression scores and/or outcomes for patients undergoing TJA. METHODS: EMBASE, Ovid MEDLINE, PubMed, and Scopus were reviewed systematically from inception until November 15, 2022. Studies that were relevant for this review included comparative studies between patients who received an intervention within 3 months before or after their primary total hip or knee arthroplasty procedure. The interventions included a wide range of modalities, which were grouped into psychotherapy, enhanced perioperative support, and pharmacotherapy. Other interventions included physiotherapy techniques with a psychological focus, art/music-based therapy, occupational therapy support, and educational interventions. Meta-analysis was conducted for psychotherapy and enhanced support. RESULTS: The final systematic review consisted of 28 relevant studies, most of which were randomized controlled trials. A total of 3,702 patients, with a mean age of 66 years, were considered, of whom 59% were female. Most of the studies reported a notable reduction in depressive symptoms and/or scores based on the interventions being analyzed. At 3 months postoperatively, psychotherapy and enhanced support both resulted in markedly better depression and function scores compared with control subjects, with psychotherapy additionally improving pain scores. CONCLUSIONS: Overall, a wide range of interventions aimed at psychological optimization of patients undergoing TJA can improve depressive symptoms, pain, and function, even in the absence of a formal diagnosis of depression. Specifically, cognitive-based psychotherapy and enhanced perioperative support had the best evidence. Routine pharmacotherapy plays a limited role, if any, in the care of TJA. Additional efforts to develop pragmatic, evidence-based, and reproducible interventions are warranted to continue to optimize outcomes in TJA patients.

Treatment of Concurrent Depression and Its Effect on Outcomes After Total Joint Arthroplasty: A Systematic Review of Comparative Studies.

PURPOSE: There is a growing body of evidence suggesting that patients with a diagnosis of depression suffer worse outcomes after total joint arthroplasty (TJA) procedures. It is unclear whether depression treatment is a modifiable risk factor that can be targeted to improve suboptimal outcomes. We conducted a systematic review to understand the role that various interventions have on outcomes of TJA in patients with diagnosed depression (PDDs). METHODS: PubMed, Ovid MEDLINE, Scopus, and EMBASE were searched systematically from inception until November 2022. Studies of PDDs who underwent TJA that compared any intervention/treatment of depression with a control group and reported pain, functional outcomes, depression scores, and/or revision rates after TJA were relevant for this review. RESULTS: Ten relevant studies were included in the final systematic review, with a total of 33,501 patients included. Two studies reported lower revision rates for patients receiving selective serotonin reuptake inhibitor treatment and psychotherapy. Two studies showed no difference in functional outcomes for patients receiving pharmacologic treatment. One study reported improved functional outcomes for patients receiving cognitive behavioral therapy and another reported improved postoperative functional outcomes for patients receiving alprazolam. CONCLUSION: Interventions targeted at PDDs may improve short-term pain and functional outcomes, and there may be an association between selective serotonin reuptake inhibitor use and implant survival. The current literature is limited and inconclusive, with important gaps in understanding regarding the optimization and treatment of this modifiable risk factor. Surgeons should consider depression treatment as a method to improve outcomes in this cohort.

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.

Management of Very Distal Ulna Fractures: A Systematic Review.

OBJECTIVES: To synthesize all-cause complications and reoperations data, and secondary clinical, functional, and radiographic outcomes after the management of very distal ulna fractures (VDUFs) either nonoperatively or operatively. DATA SOURCES: MEDLINE, Embase, and Web of Science were searched for English-language articles from inception to February 17, 2022. STUDY SELECTION: Studies reporting the nonoperative or operative management of VDUFs were eligible for inclusion. VDUFs were defined as either being Q2-Q5 distal ulna fractures using the OTA/AO Comprehensive Classification of Fractures for distal ulna fractures associated with distal radius fractures or being amenable to characterization by the classification system for ulnar head, neck and metaphyseal fractures by Biyani et al. DATA EXTRACTION: Two reviewers independently extracted data from included studies. Study validity was assessed using the methodological index for nonrandomized studies. DATA SYNTHESIS: Seventeen studies (512 VDUFs) were included for analysis. There were 209, 237, and 66 fractures in the nonoperative, open reduction internal fixation (ORIF), and distal ulna resection groups, respectively. Descriptive statistics including weighted mean values, standard deviations, and 95% confidence intervals were calculated. CONCLUSIONS: The treatment of VDUFs with nonoperative management, ORIF, or distal ulna resection may all be acceptable treatment options in specific patient populations. Nonoperative management of VDUFs is a promising treatment strategy even for complex fracture patterns in patients 65 years of age or older. Despite higher reoperation rates, ORIF may be considered for the younger, high-demand patient. Distal ulna resection presents with very favorable functional outcomes in patients 65 years of age or older presenting with a complex VDUF with the lowest reoperation rate across all groups. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.