New Carbothioamide and Carboxamide Derivatives of 3-Phenoxybenzoic Acid as Potent VEGFR-2 Inhibitors: Synthesis, Molecular Docking, and Cytotoxicity Assessment.

INTRODUCTION/BACKGROUND: Because of the well-established link between angiogenesis and tumor development, the use of antiangiogenic therapeutics, such as those targeting VEGFR-2, presents a promising approach to cancer treatment. In the current study, a set of five hydrazine-1-- carbothioamide (compounds 3a-e) and three hydrazine-1-carboxamide derivatives (compounds 4a-c) were successfully synthesized from 3-phenoxybenzoic acid. These compounds were specially created as antiproliferative agents with the goal of targeting cancer cells by inhibiting VEGFR-2 tyrosine kinase. MATERIALS AND METHODS: The new derivatives were synthesized by conventional organic methods, and their structure was versified by IR, 1HNMR, 13CNMR, and mass spectroscopy. In silico investigation was carried out to identify the compounds' target, molecular similarity, ADMET, and toxicity profile. The cytotoxic activity of the prepared compounds was evaluated in vitro against three human cancer cell lines (DLD1 colorectal adenocarcinoma, HeLa cervical cancer, and HepG2 hepatocellular carcinoma). The effects of the leading compound on cell cycle progression and apoptosis induction were investigated by flow cytometry, and the specific apoptotic pathway triggered by the treatment was evaluated by RT-PCR and immunoblotting. Finally, the inhibitory activities of the new compounds against VEGFR-2 was measured. RESULTS: The designed derivatives exhibited comparable binding positions and interactions to the VEGFR-2 binding site to that of sorafenib (a standard VEGFR-2 tyrosine kinase inhibitor), as determined by molecular docking analysis. Compound 4b was the most cytotoxic compound, achieving the lowest IC50 against HeLa cells. Compound 4b, a strong representative of the synthesized series, induced cell cycle arrest at the G2/M phase, increased the proportion of necrotic and apoptotic HeLa cells, and activated caspase 3. The EC50 value of compound 4b against VEGFR-2 kinase activity was comparable to sorafenib's. CONCLUSION: Overall, the findings suggest that compound 4b has a promising future as a starting point for the development of new anticancer drugs.

Synthesis, In Silico Prediction, and In Vitro Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors.

INTRODUCTION: Allosteric inhibition of EGFR Tyrosine Kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies. METHOD: A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR, and HR-mass spectroscopy. Compound S4 had a relatively high pharmacophore-fit score, indicating that it may have biological activity similar to the EGFR allosteric inhibitor reference, and it scored a relatively low ΔG against EGFR TK allosteric site, indicating a high likelihood of drug-receptor complex formation. Compound S4 was cytotoxic to the three cancer cell lines tested, particularly HCT-116 colorectal cancer cells, with an IC50 value comparable to Erlotinib. Compound S4 induced the intrinsic apoptotic pathway in HCT-116 cells by arresting them in the G2/M phase. RESULT: All of the new derivatives, including S4, met the in silico requirements for EGFR allosteric inhibitory activity. CONCLUSION: Compound S4 is a promising EGFR tyrosine kinase allosteric inhibitor that warrants further research.

Synthesis, docking study, and antitumor evaluation of benzamides and oxadiazole derivatives of 3-phenoxybenzoic acid as VEGFR-2 inhibitors.

Current chemotherapeutic agents have several limitations, including lack of selectivity, the development of undesirable side effects, and chemoresistance. As a result, there is an unmet need for the development of novel small molecules with minimal side effects and the ability to specifically target tumor cells. A new series of 3-phenoxybenzoic acid derivatives, including 1,3,4-oxadiazole derivatives (4a-d) and benzamides derivatives (5a-e) were synthesized; their chemical structures were confirmed by Fourier-transform infrared spectroscopy, 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectra; and various physicochemical properties were determined. The antiproliferative activities of the new derivatives were evaluated by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Three compounds (4b, 4c, and 4d) exhibited cytotoxicity against two of the three cell lines tested, five compounds (3, 4a, 5a, 5b, and 5e) were toxic to one cell line, while two compounds (5c and 5d) were not cytotoxic to any of the three cell lines tested in the current study. Based on docking scores, MTT assay findings, and vascular endothelial growth factor receptor 2 (VEGFR-2) kinase activity data, Compound 4d was selected for further biological investigation. Flow cytometry was used to determine the mode of cell death (apoptosis vs. necrosis) and the effect on cell cycle progression. Compound 4d arrested HepG2 hepatocellular carcinoma cells in the G2/M phase and activated both the intrinsic and extrinsic apoptosis pathways. In conclusion, Compound 4d has shown promising results for future research as a potent VEGFR-2 tyrosine kinase inhibitor.

Patient genetic heterogeneities acting as indicators of post-operative pain and opioid requirement in orthopedic surgery: A systematic review.

INTRODUCTION: Orthopedic surgical procedures are expected to increase annually, making it imperative to understand the correlations between patient genetic makeup and post-operative pain levels. METHODS: We performed a systematic literature review using PubMed and Cochrane databases in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 299 articles were initially selected, 20 articles remained after title and abstract review, and nine articles were selected for inclusion upon full text review. RESULTS: Genetic risk factors identified included the A allele of the 5HT2A gene single nucleotide polymorphism, the AA genotype of the ADRB2 gene, the CG genotype of the IL6 gene, the genotypes CT and TT of the NTRK1 gene, genotypes AA and GA of the OPRM gene, and the AA and GA genotypes of the COMT gene. Additional studies in the review discuss statistical significance of other variants of the COMT gene. CONCLUSION: There have been genetic association studies performed on the patient heterogeneity and its relationship on patient pain levels, but more data need to be collected to understand the clinical utility of stratifying patients based on genomic sequence.

Comparison of Contemporary Risk Scores in All Groups of Pulmonary Hypertension: A Pulmonary Vascular Research Institute GoDeep Meta-Registry Analysis.

BACKGROUND: Pulmonary hypertension (PH) is a heterogeneous disease with a poor prognosis. Accurate risk stratification is essential for guiding treatment decisions in pulmonary arterial hypertension (PAH). Although various risk models have been developed for PAH, their comparative prognostic potential requires further exploration. Additionally, the applicability of risk scores in PH groups beyond group 1 remains to be investigated. RESEARCH QUESTION: Are risk scores originally developed for PAH predictive in PH groups 1 through 4? STUDY DESIGN AND METHODS: We conducted a comprehensive analysis of outcomes among patients with incident PH enrolled in the multicenter worldwide Pulmonary Vascular Research Institute GoDeep meta-registry. Analyses were performed across PH groups 1 through 4 and further subgroups to evaluate the predictive value of PAH risk scores, including REVEAL Lite 2, REVEAL 2.0, ESC/ERS 2022, COMPERA 3-strata, and COMPERA 4-strata. RESULTS: Eight thousand five hundred sixty-five patients were included in the study, of whom 3,537 patients were assigned to group 1 PH, whereas 1,807 patients, 1,635 patients, and 1,586 patients were assigned to group 2 PH, group 3 PH, and group 4 PH, respectively. Pulmonary hemodynamics were impaired with median mean pulmonary arterial pressure of 42 mm Hg (33-52 mm Hg) and pulmonary vascular resistance of 7 WU (4-11 WU). All risk scores were prognostic in the entire PH population and in each of the PH groups 1 through 4. The REVEAL scores, when used as continuous prediction models, demonstrated the highest statistical prognostic power and granularity; the COMPERA 4-strata risk score provided subdifferentiation of the intermediate-risk group. Similar results were obtained when separately analyzing various subgroups (PH subgroups 1.1, 1.4.1, and 1.4.4; PH subgroups 3.1 and 3.2; group 2 with isolated postcapillary PH vs combined precapillary and postcapillary PH; patients of all groups with concomitant cardiac comorbidities; and severe [> 5 WU] vs nonsevere PH). INTERPRETATION: This comprehensive study with real-world data from 15 PH centers showed that PAH-designed risk scores possess predictive power in a large PH cohort, whether considered as common to the group or calculated separately for each PH group (1-4) and various subgroups.

Pearls and Pitfalls of an Orthopaedic Mission Trip.

Many physicians chose to pursue years of rigorous medical training because of an innate desire to care for others, which often translates into volunteering in their local communities. Some physicians take this a step further by contributing their time and skills to global health delivery through medical mission trips. The need is apparent: a 40-year discrepancy in average life span, 36 deaths versus 4 deaths per 1,000 births in low-income versus high-income countries, and over 70% of preventable pediatric deaths occurring in solely 15 countries. In addition, a remarkable gap exists in the access of care and resources, with the world's poorest countries receiving only 4% of surgical services. Orthopaedic missions are seldom because the cost and complexity of these trips supersede many other specialties. However, the care that orthopaedic surgery can provide restores an individual's function, allowing them to increase productivity in their personal lives and in their community. Addressing this disparity in health care is a great first step, but studies have shown that mission trips may have some serious downfalls. We aim to discuss these downfalls and provide recommendations to mitigate them.

New Indole-6-Carboxylic Acid Derivatives as Multi-Target Antiproliferative Agents: Synthesis, in Silico Studies, and Cytotoxicity Evaluation.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are commonly overexpressed in cancers making them appealing targets for cancer therapeutics. Two groups of indole-6-carboxylic acid derivatives, hydrazone derivatives targeting EGFR and oxadiazole derivatives targeting VEGFR-2, were synthesized and characterized using FT-IR, 1 H-NMR, 13 CNMR, and HR-MS techniques. Binding patterns to potential molecular targets were studied using molecular docking and compared to standard EGFR and VEGFR-2 inhibitors. The newly synthesized compounds were cytotoxic to the three cancer cell lines tested (HCT-116, HeLa, and HT-29 cell lines) as evaluated by the MTT assay. Compound 3 b (EGFR-targeting) and compound 6 e (VEGFR-2-targeting) possessed the highest antiproliferation activity, were cancer-selective, arrested cancer cells in the G2/M phase, induced the extrinsic apoptosis pathway, and had the highest EGFR/VEGFR-2 enzyme inhibitory activity, respectively. The structure-activity relationships of the new compounds showed that the presence of an aryl or heteroaryl fragment attached to a linker is required for the anti-tumor activity. In conclusion, the findings of the current study suggest that compounds 3 b and 6 e are promising cytotoxic agents that act by inhibiting EGFR and VEGFR-2 tyrosine kinases, respectively.

Bone marrow aspirate concentrate chondroplasty to delaying need for total knee arthroplasty: a retrospective review of a veteran cohort.

Aim: Osteoarthritis (OA) is a highly prevalent and costly condition, rooted in cartilaginous defects. Despite various causes, the inability for chondrocytes to regenerate prohibits these lesions from self-healing. Debridement commonly provides symptomatic relief but does not target the underlying disease process, necessitating investigation into possible treatments. Intraosseous and intraarticular bone marrow aspirate concentrate (BMAC) injection is a new promising therapy aimed at repairing these cartilage defects. Methods/materials: We retrospectively reviewed patients who underwent BMAC chondroplasty and examined the efficacy in delaying need for further intervention. Results: Only 5 of 23 procedures (21.7%) required postoperative intervention within the 2-year follow-up period. Only one request for total knee arthroplasty was made, but the procedure has not been done. Conclusion: This study demonstrates that BMAC chondroplasty may be an efficacious method to delay need for total knee arthroplasty.

InSpace Balloon for the Management of Massive Irreparable Rotator Cuff Tears: A Systematic Review and Meta-Analysis.

Background: The best course of action for massive irreparable rotator cuff tears (MIRCTs) is not universally agreed upon. Numerous surgical techniques have been discussed. The implantation of a biodegradable spacer into the subacromial area has been documented since 2012 by several authors. The implantation method is touted as being simpler, repeatable, and less invasive than other solutions that are now available. The purpose of this systematic review and meta-analysis, being the first of its kind, was to evaluate the literature to see the efficacy of InSpace balloon (ISB) implantation in the management of MIRCTs. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, and with 2 researchers assessing and analyzing each study separately, an extensive electronic search of the literature was conducted in the PubMed database from 1961 until July 27, 2022. Results: Fourteen studies were included in this systematic review and three in the meta-analysis. Eleven out of fourteen studies favored ISB use for MIRCTs, while only three were against its use. All spacers were arthroscopically implanted in the subacromial space. Three studies were included in the meta-analysis. The differences in the compared outcomes were statistically insignificant. Conclusions: A controversy about the use of ISB remains in patients with MIRCTs. Both good and bad outcomes were reported. However, the majority of patients had good clinical outcomes across several grading scales, radiographic evidence of improved impingement, and self-report that they would redo the procedure in hindsight. To draw more solid conclusions and have statistically significant results in the meta-analysis, more randomized controlled trials and comparative studies comparing this device to other treatments are needed.

Antitumor activity of the new tyrphostin briva against BRAFV600E-mutant colorectal carcinoma cells.

Because of a reduced sensitivity of BRAF-mutant colorectal cancers to BRAF inhibitor treatment when compared with BRAF-mutant melanoma, it is essential to develop efficient drugs to cope with this disease. The new 2-(4-bromophenyl)-3-arylacrylonitrile compound Briva was prepared in one step from commercially available starting compounds. Briva and two known thiophene analogs (Thio-Iva and Thio-Dam) were tested for their cytotoxic activity against various tumor cell lines including colorectal and breast cancer cells. The antitumor activities of the test compounds were assessed in vitro via the MTT assay, DAPI staining of nuclei, RT-PCR and immunoblotting, wound healing, clonogenic assay, collagen I adhesion assay, and kinase inhibition assays. A selective activity of Briva was observed against BRAFV600E-mutant HT-29 and COLO-201 colorectal carcinoma (CRC) cells. Briva caused inhibition of HT-29 clonogenic tumor growth and was found to induce cytotoxicity by activating the intrinsic apoptosis pathway. In addition, Briva reduced HT-29 cell adhesion and migration. Kinase inhibition experiments revealed that Briva inhibits VEGFR2. Thus, Briva can be considered as a promising antitumor compound against BRAFV600E-mutant colon carcinoma by targeting VEGFR2 tyrosine kinase and consequently reducing cell adhesion and metastasis formation.

Sub-chondroplasty Reduces Pain, Improves Function and Delays the Conversion to Arthroplasty in Patients with Advanced Knee Osteoarthritis: A Stratified Meta-analysis and Quality Assessment.

There is an ongoing interest in alternatives to total knee arthroplasty, as a means to delay inevitable replacement. A possible, minimally invasive, alternative is a sub-chondroplasty, involving interosseous injection of bone substitute materials such as calcium phosphate (CaPo4), platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC) or Injectable demineralized bone matrix (iDBM) into the subchondral bone. Eleven clinical trials were found, investigating the effectiveness of sub-chondroplasties performed using CaPo4, PRP, BMAC, and iDBM. A non-stratified and stratified meta-analysis of the included studies were conducted to test for confounding variables across the trials. Non-stratified analysis, regardless of injectable type, revealed a significant improvement in the average Visual Analog Scale (VAS) score and postoperative Knee Injury and Osteoarthritis Outcome Score (KOOS) in patients post sub-chondroplasty, as compared to baseline. This analysis demonstrates that the sub-chondroplasty procedure reduces pain, improves function, and has lower risk of conversion to arthroplasty. (Journal of Surgical Orthopaedic Advances 32(2):065-074, 2023).

Effects of embryonic thermal manipulation on the immune response to post-hatch Escherichia coli challenge in broiler chicken.

Background and Aim: Thermal manipulation (TM), exposure to mild heat shock during embryogenesis, which is a critical developmental period of broiler chickens, improves tissue stability, oxidative stress response, and immune response during heat stress. Thermal manipulation could be more cost-effective than other methods to boost the immune response. This study aimed to evaluate the impact of TM during embryogenesis, concomitant with an Escherichia coli challenge, on body weight (BW), body temperature (Tb), and splenic mRNA expression of cytokines (Interleukin [IL]-1ß, IL-2, IL-6, IL-8, IL-12, IL-15, IL-16, IL-18, and interferon [IFN]-γ) in poultry. Materials and Methods: A total of 740 fertile eggs were procured from a certified Ross broiler breeder. The eggs were divided into two incubation groups: the control and TM groups. The eggs in the control group were kept at 37.8°C air temperature and 56% relative humidity (RH) during incubation; eggs of the TM group were incubated under standard conditions, except for embryonic days 10-18, during which they were incubated at 39°C and 65% RH for 18 h daily. On the 7th day of incubation, eggs with dead embryos were excluded. After hatching was complete, each group was further subdivided into saline-treated or E. coli-challenged groups. The E. coli (serotype 078 with the dose of 1.5 × 105 colony-forming unit/mL) challenge was performed when the birds were 20 days old. Body weight and Tb measurements were taken on post-hatch days 20, 21, 23, and 25. Splenic mRNA expression of cytokines (IL-1ß, IL-2, IL-6, IL-8, IL-12, IL-15, IL-16, IL-18, and IFN-γ) was analyzed by real-time quantitative polymerase chain reaction. Results: Following the E. coli challenge, the TM-treated group's body performance parameters (BW and Tb) were significantly increased compared with the control group. Body weight was higher in the TM group than in the control group (p < 0.05); Tb was lower in the TM group than in the control group (p < 0.05). The mRNA levels of IL and IFN-γ were more stable and moderately induced in the TM group compared with the control group. Thermal manipulation altered the basal mRNA levels of ILs and IFN-γ and changed their expression dynamics after the E. coli challenge. Conclusion: Thermal manipulation during embryogenesis could boost the immune system response to E. coli.

Frailty and Pre-Frailty in the Setting of Total Joint Arthroplasty: A Narrative Review.

Background: Total joint arthroplasties are among the most common surgical procedures performed in the United States. Although numerous safeguards are in place to optimize patient health and safety pre-, intra-, and postoperatively, patient frailty is often incompletely assessed or not assessed at all. Frailty has been shown to increase rates of adverse events and length of stay. We discuss the impact of frailty on patient outcomes and healthcare economics as well as provide widely accepted models to assess frailty and their optimal usage. Methods: Several databases were searched using the keywords "frailty," "TJA," "THA," "frailty index," "frailty assessment," and "frailty risk." A total of 45 articles were used in this literature review. Results: It is estimated that nearly half of patients over the age of 85 meet criteria for frailty. Frailty in surgical patients has been shown to increase total costs as well as length of stay. Additionally, increased rates of numerous adverse events are associated with increased frailty. Conclusions: The literature demonstrates that frailty poses increased risk of adverse events, increased length of stay, and increased cost. There are several models that accurately assess frailty and can feasibly be implemented into preoperative screening.

Comprehensive description of the prevalence, serological and clinical characteristics, and visceral involvement of systemic sclerosis (scleroderma) in a large cohort from the United Arab Emirates Systemic Sclerosis Registry.

Systemic sclerosis is an autoimmune condition characterized by a wide range of clinical presentations. Registries may serve to expand understanding about systemic sclerosis and aid in patient care and follow-up. The objective of this study was to analyze the prevalence of systemic sclerosis in a large cohort from the United Arab Emirates Systemic Sclerosis Registry and find the significant similarities and differences between the different subsets. All scleroderma patients in the United Arab Emirates were included in this multicenter national retrospective analysis. Data on demographics, comorbidities, serological characteristics, clinical aspects, and treatment were collected and analyzed, highlighting the most common traits identified. A total of 167 systemic scleroderma patients from diverse ethnic backgrounds were enrolled. Overall, 54.5% (91/167) of the patients were diagnosed with diffuse cutaneous systemic sclerosis, and 45.5% (76/167) with limited cutaneous systemic sclerosis. The prevalence of systemic sclerosis was 1.66 per 100,000 for the total registry and 7.78 per 100,000 for United Arab Emirates patients. Almost all patients in the diffuse cutaneous systemic sclerosis and limited cutaneous systemic sclerosis groups tested positive for the immunofluorescence antinuclear antibody. Antibodies against Scl-70 were significantly more associated with diffuse cutaneous systemic sclerosis, whereas anticentromere antibodies were significantly more associated with the limited cutaneous systemic sclerosis group (p < 0.001). Sclerodactyly, shortness of breath, and digital ulcers were more common in diffuse cutaneous systemic sclerosis patients compared with the limited cutaneous systemic sclerosis subtype in terms of clinical symptoms and organ involvement. Telangiectasia was much more common in the limited cutaneous systemic sclerosis group. Furthermore, diffuse cutaneous systemic sclerosis patients had more lung fibrosis (interstitial lung disease) than limited cutaneous systemic sclerosis patients (70.5% vs 45.7%), and pulmonary arterial hypertension was twice as common in limited cutaneous systemic sclerosis patients as it was in diffuse cutaneous systemic sclerosis patients. Local registries are paramount to understanding the clinical/serological characteristics of scleroderma. This study emphasizes the importance of raising disease awareness and distinguishing between the various systemic sclerosis subsets to implement patient-tailored strategies for early detection, better management, and higher quality of care.

Osteoid osteoma of the wrist: Recent advances.

Osteoid osteoma is a benign bone tumor usually arising in the diaphysis and metaphysis of the long bones, with male predominance (sex ratio, 2:1). Despite being the most common bone tumor in the wrist, it is still an atypical location for this lesion. The usual presentation is pain that is exacerbated at night and relieved by aspirin or non-steroidal anti-inflammatory drugs. This presentation is not always the case in the wrist, which leads to numerous differential diagnoses and often a delay in definitive diagnosis and treatment. Various imaging modalities can confirm the presence of the tumor and guide the surgical approach. Resection is the gold-standard, with radiofrequency gaining popularity in recent years.

The First Pulmonary Hypertension Registry in the United Arab Emirates (UAEPH): Clinical Characteristics, Hemodynamic Parameters with Focus on Treatment and Outcomes for Patients with Group 1-PH.

BACKGROUND: The aim of this study is to present the first United Arab Emirates pulmonary hypertension registry of patients' clinical characteristics, hemodynamic parameters and treatment outcomes. METHOD: This is a retrospective study describing all the adult patients who underwent a right heart catheterization for evaluation of pulmonary hypertension (PH) between January 2015 and December 2021 in a tertiary referral center in Abu Dhabi, United Arab Emirates. RESULTS: A total of 164 consecutive patients were diagnosed with PH during the five years of the study. Eighty-three patients (50.6%) were World Symposium PH Group 1-PH; nineteen patients (11.6%) were Group 2-PH due to left heart disease; twenty-three patients (14.0%) were Group 3-PH due to chronic lung disease; thirty-four patients (20.7%) were Group 4-PH due to chronic thromboembolic lung disease, and five patients (3.0%) were Group 5-PH. Among Group 1-PH, twenty-five (30%) had idiopathic, twenty-seven (33%) had connective tissue disease, twenty-six (31%) had congenital heart disease, and five patients (6%) had porto-pulmonary hypertension. The median follow-up was 55.6 months. Most of the patients were started on dual then sequentially escalated to triple combination therapy. The 1-, 3- and 5-year cumulative probabilities of survival for Group 1-PH were 86% (95% CI, 75-92%), 69% (95% CI, 54-80%) and 69% (95% CI, 54-80%). CONCLUSIONS: This is the first registry of Group 1-PH from a single tertiary referral center in the UAE. Our cohort was younger with a higher percentage of patients with congenital heart disease compared to cohorts from Western countries but similar to registries from other Asian countries. Mortality is comparable to other major registries. Adopting the new guideline recommendations and improving the availability and adherence to medications are likely to play a significant role in improving outcomes in the future.

Identifying and Addressing Burnout in the Orthopaedic Surgeon.

Throughout the career of a physician, they are subjected to long working hours, high stress, life and death situations, risk of malpractice, significant financial debt, and an increasing bureaucratic load. This, in turn, has led to significant rates of burnout and potential suicidal ideation. Suicide prevalence has increased roughly 30% over the past 2 decades, with surgeon suicide rates reaching as high as 3x that of the general cohort. Orthopedic surgeons are most severely affected, composing 28.2% of physician suicides and seeing one third of their suicides from 2003 to 2017 occurring in the last 2 years alone. We provide the latest data and the current trends in orthopedic burnout and suicide rates, delve into the possible inciting factors driving their increase, and provide recommendations to identify their early signs and mitigate progression.

Neuraxial Anesthesia Significantly Reduces 30-Day Venous Thromboembolism Rate and Length of Hospital Stay in Primary Total Hip Arthroplasty: A Stratified Propensity Score-Matched Cohort Analysis.

BACKGROUND: General anesthesia (GA) has been the commonly used protocol for total hip arthroplasty (THA); however, neuraxial anesthesia (NA) has been increasingly performed. Our purpose was to compare NA and GA for 30-day postoperative outcomes in United States veterans undergoing primary THA. METHODS: A large veteran's database was utilized to identify patients undergoing primary THA between 1999 and 2019. A total of 6,244 patients had undergone THA and were included in our study. Of these, 44,780 (79.6%) had received GA, and 10,788 (19.2%) had received NA. Patients receiving NA or GA were compared for 30-day mortalities, cardiovascular, respiratory, and renal complications, and wound infections and hospital lengths of stay (LOS). Propensity score matching, multivariate regression analyses, and subgroup analyses by American Society of Anesthesiology classification were performed to control for selection bias and patient baseline characteristics. RESULTS: Upon propensity-adjusted multivariate analyses, NA was associated with decreased risks for deep venous thrombosis (odds ratio [OR] = 0.63; 95% CI = 0.4-0.9; P = .02), any respiratory complication (OR = 0.63; 95% CI = 0.5-0.9; P = .003), unplanned reintubation (OR = 0.51; 95% CI = 0.3-0.9; P = .009), and prolonged LOS (OR = 0.78; 95% CI = 0.72-0.84; P < .001). Subgroup analyses by American Society of Anesthesiology classes showed NA decreased 30-day venous thromboembolism rate in low-risk (class I/II) patients and decreased respiratory complications in high-risk (class III/IV) patients. CONCLUSION: Using a patient cohort obtained from a large national database, NA was associated with reduced risk of 30-day adverse events compared to GA in patients undergoing THA. Postoperative adverse events were decreased with NA administration with similar decreases observed across all patient preoperative risk levels. NA was also associated with a significant decrease in hospital LOS.

The risk of hospital readmission, revision, and intra- and postoperative complications between direct anterior versus posterior approaches in primary total hip arthroplasty: a stratified meta-analysis and a probability based cost projection.

INTRODUCTION: This study presents stratified meta-analysis and projected cost per case analysis of direct anterior approach (DAA) versus posterior approach (PA) in total hip arthroplasty (THA) to determine the best surgical approach and guarantee hip joint longevity. METHODS: Several online databases were searched for clinical trials comparing DAA and PA in primary THA. The stratified analysis was conducted to test for confounding and biases across the different types of included trials. The average cost and probability were used to determine projected added costs of medical and surgical management for complications. RESULTS: 30 clinical trials included 11,562 patients who underwent THA. Almost 50% of these patients performed DAA. As compared to PA, both non-stratified and stratified analyses demonstrated that DAA has a significant higher incidence of the overall intra- and postoperative complications (non-stratified, OR 1.64; p = 0.003) (stratified, OR 4.12; p = 0.005), nerve injury (non-stratified, OR 22.0; p < 0.00001) (stratified, OR 0.28; p < 0.00001), higher rate of revision surgery (non-stratified; OR 1.54; p = 0.01) (stratified, OR 7.37; p = 0.006), and higher incidence of surgical wound complications (non-stratified; OR 1.67; p = 0.002) as compared to PA following primary THA. In addition, DAA demonstrated higher trends of incidence (non-statistically significant) of femur fracture (Non-stratified, OR 1.32, p = 0.10) and thrombo-embolic complications (Retrospective studies, OR 1.39, p = 0.69). However, PA demonstrated higher trends of incidence (non-statistically significant) of hip joint dislocation, as compared to DAA. (Stratified RCTs, OR 0.63, p = 0.65]. Collectively, this amounts a $421,068.68 surplus in DAA complication costs. CONCLUSIONS: PA may provide a more lucrative, safer approach to those undergoing THA given its comparable postoperative outcomes, reduced complication rates, and lower overall cost relative to DAA.