The epidemiology of pelvic ring fractures in Qatar.

PURPOSE: This study aimed to determine the incidence of pelvic ring fractures and their associated epidemiological profile in Qatar. METHODS: A retrospective cross-sectional study was performed at the only level I trauma centre in Qatar for patients diagnosed with pelvic ring fractures between January 2016 and December 2018. Age, sex, mechanism of injury, fracture classification and associated characteristics, mode of treatment, associated nerve injuries, and other complications were analyzed. RESULTS: A total of 327 consecutive patients were included, with an average age of 32.6 years. Most of the included patients were males, 85% (279), with a male: female ratio of 6:1. The incidence of pelvic fractures was 3.887/100,000 across the three years. High-speed motor vehicle collisions (MVC) were the most common mechanism of injury (108, 33%), followed by falling from height (105, 32%). Young-Burgess lateral compression (LC) fracture type was the most frequent (224, 68.5%) and was associated with 25% of the entire mortalities. Nine (2.8%) cases were open fractures, and 12% (39) were deemed unstable. Around 29% of cases had associated injuries, with an overall mortality rate of 4.9% (16) observed. Most fractures were treated nonoperatively(n = 283,86.5%). CONCLUSION: This study demonstrated the epidemiology of pelvic fractures in Qatar. MVC and work-related injuries were predominant in a younger cohort compared to the literature. Also, the mortality rate was lower than those reported in the literature. Therefore, well-trained surgeons and specialized trauma centres for treating these injuries are recommended.

Reliability of artificial intelligence in predicting total knee arthroplasty component sizes: a systematic review.

PURPOSE: This systematic review aimed to investigate the reliability of AI predictive models of intraoperative implant sizing in total knee arthroplasty (TKA). METHODS: Four databases were searched from inception till July 2023 for original studies that studied the reliability of AI prediction in TKA. The primary outcome was the accuracy ± 1 size. This review was conducted per PRISMA guidelines, and the risk of bias was assessed using the MINORS criteria. RESULTS: A total of four observational studies comprised of at least 34,547 patients were included in this review. A mean MINORS score of 11 out of 16 was assigned to the review. All included studies were published between 2021 and 2022, with a total of nine different AI algorithms reported. Among these AI models, the accuracy of TKA femoral component sizing prediction ranged from 88.3 to 99.7% within a deviation of one size, while tibial component sizing exhibited an accuracy ranging from 90 to 99.9% ± 1 size. CONCLUSION: This study demonstrated the potential of AI as a valuable complement for planning TKA, exhibiting a satisfactory level of reliability in predicting TKA implant sizes. This predictive accuracy is comparable to that of the manual and digital templating techniques currently documented in the literature. However, future research is imperative to assess the impact of AI on patient care and cost-effectiveness. LEVEL OF EVIDENCE III: PROSPERO registration number: CRD42023446868.

The outcomes of total hip arthroplasty in developmental dysplasia of hip versus osteoarthritis: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to compare the outcomes of total hip arthroplasty (THA) in patients with developmental dysplasia of the hip (DDH) and those with osteoarthritis (OA). METHODS: Four databases were searched from inception till February 2023 for original studies that compared the outcomes of THA in DDH and OA. The primary outcome was the revision rate; the secondary outcomes were dislocation and failure modes (i.e. aseptic loosening, PJI, instability, and periprosthetic fractures), hospital stay and costs. This review was conducted as per PRISMA guidelines, and the risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: A total of 9 observational studies with 575,255 THA (469,224 hips) were included, with a mean age of 50.6 years and 62.1 years for DDH and OA groups, respectively. There was a statistically significant difference in revision rate between DDH and OA patients in favour of OA (OR, 1.66; 95% CI 1.11-2.48; p-value, 0.0251). However, dislocation rate (OR, 1.78, 95% CI 0.58-5.51; p-value, 0.200), aseptic loosening (OR, 1.69; 95% CI 0.26-10.84; p-value, 0.346) and PJI (OR, 0.76; 95% CI 0.56-1.03; p-value, 0.063) were comparable across both groups. CONCLUSION: A higher revision rate following total hip arthroplasty was associated with DDH compared with osteoarthritis. However, both groups had similar dislocation rates, aseptic loosening and PJI. Consideration of confounding factors, such as patient age and activity level, is crucial when interpreting these findings. LEVEL OF EVIDENCE : III. TRIAL REGISTRATION: PROSPERO registration: CRD42023396192.

Correlation between anthropometric measurements and graft size in anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to investigate the correlation between anthropometric measurements and graft size in anterior cruciate ligament (ACL) reconstruction. METHODS: A systematic search of Ovid MEDLINE, Embase, and Cochrane Library databases was conducted for observational studies published until March 2023 that reported the relationship between anthropometric data [height, weight, body mass index (BMI), age, gender, thigh length, and circumference] and ACL graft size. Correlation coefficients (COR) and their associated 95% confidence intervals were used as the primary effect size. This review was conducted in line with PRISMA guidelines. RESULTS: A total of 42 observational studies involving 7110 patients were included, with a mean age of 29.8 years. Statistically significant, moderately positive correlations were found between graft size and height (COR: 0.49; 95% CI: 0.41-0.57; p-value: < 0.001), weight (COR: 0.38; 95% CI: 0.31-0.44; p-value: < 0.001), thigh circumference (COR: 0.40; 95% CI: 0.19-0.58; p-value: < 0.001), and thigh length (COR: 0.35; 95% CI: 0.18-0.50; p-value: < 0.001). However, age and gender were insignificantly correlated with graft size (p-value: NS). A subanalysis based on graft type showed a significant positive correlation between height and graft diameter, which was more significant in the peroneus tendon than in hamstring grafts (COR: 0.76 vs. 0.45; p-value: 0.020). CONCLUSION: This study demonstrated a moderate positive correlation between anthropometric measurements (height, weight, thigh circumference, and length) and ACL graft size, along with a weak positive correlation with BMI. Age and gender showed no significant correlation. These findings support the predictability and selection of ACL graft size based on pre-operative patient anthropometric data. LEVEL OF EVIDENCE: Level of Evidence: IV. PROSPERO registration number: CRD42023416044.

Serial SARS-CoV-2 Antibody Titers in Vaccinated Dialysis Patients: Prevalence of Unrecognized Infection and Duration of Seroresponse.

Rationale & Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are likely underdiagnosed, but the degree of underdiagnosis among patients receiving maintenance dialysis is unknown. The durability of the immune response after the third vaccine dose in this population also remains uncertain. This descriptive study tracked antibody levels to (1) assess the rate of undiagnosed infections and (2) characterize seroresponse durability after the third dose. Study Design: Retrospective observational study. Setting & Participants: SARS-CoV-2-vaccinated patients receiving maintenance dialysis through a national dialysis provider. Immunoglobulin G spike antibodies [anti-spike immunoglobulin (Ig) G] titers were assessed monthly after vaccination. Exposures: Two and 3 doses of SARS-CoV-2 vaccine. Outcomes: Undiagnosed and diagnosed SARS-CoV-2 infections; anti-spike IgG titers over time. Analytical Approach: Undiagnosed SARS-CoV-2 infections were identified as an increase in anti-spike IgG titer of ≥100 BAU/mL, not associated with receipt of vaccine or diagnosed SARS-CoV-2 infection (by polymerase chain reaction test or antigen test). In descriptive analyses, anti-spike IgG titers were followed over time. Results: Among 2,703 patients without previous coronavirus disease 2019 (COVID-19) who received an initial 2-dose vaccine series, 271 had diagnosed SARS-CoV-2 infections (3.4 per 10,000 patient-days) and 129 had undiagnosed SARS-CoV-2 infections (1.6 per 10,000 patient-days). Among 1,894 patients without previous COVID-19 who received a third vaccine dose, 316 had diagnosed SARS-CoV-2 infections (7.0 per 10,000 patient-days) and 173 had undiagnosed SARS-CoV-2 infections (3.8 per 10,000 patient-days). In both cohorts, anti-spike IgG levels declined over time. Of the initial 2-dose cohort, 66% had a titer of ≥500 BAU/mL in the first month, with 24% maintaining a titer of ≥500 BAU/mL at 6 months. Of the third dose cohort, 95% had a titer of ≥500 BAU/mL in the first month after the third dose, with 77% maintaining a titer of ≥500 BAU/mL at 6 months. Limitations: The assays used had upper limits. Conclusions: Among patients receiving maintenance dialysis, about 1 in every 3 SARS-CoV-2 infections was undiagnosed. Given this population's vulnerability to COVID-19, ongoing infection control measures are needed. A 3-dose primary mRNA vaccine series optimizes seroresponse rate and durability. Plain-Language Summary: Patients receiving maintenance dialysis have been particularly vulnerable to COVID-19. Using serially measured antibodies, we found that a substantial proportion (about one-third) of SARS-CoV-2 infections among this population had been missed, both among those who had completed a 2-dose vaccine series and among those who had received a third vaccine dose. Such missed infections likely had only mild or minimal symptoms, but this failure to recognize all infections is concerning. Furthermore, vaccines have been effective among patients receiving dialysis, but our study additionally shows that the immune response wanes over time, even after a third dose. There is therefore a role for ongoing vigilance against this highly transmissible infection.

Outcomes of drain versus no drain in total knee arthroplasty: a retrospective cohort study.

PURPOSE: The use of suction drains in total knee arthroplasty (TKA) remains controversial. The aim of this study is to compare the outcomes of patients who received suction drains versus those who did not, focusing on blood loss, blood transfusion need, and length of hospital stay. METHODS: A retrospective observational cohort study was conducted at a tertiary hospital between January 1, 2015, and December 30, 2019, and included 262 patients who underwent unilateral non-traumatic primary TKA and were over 18 years old. The Institutional Review Board (IRB) approved the study (MRC-02-20-278). RESULTS: A total of 262 patients were included, with an age range of 47 to 91 years. Most of the included patients were females, 74.4% (195). Hypertension was the most frequent risk factor, 67.6%, followed by diabetes. Of 262 patients, 156 (59.5%) received a drain. The drain group had significantly longer hospital stay, 30% longer tourniquet time, greater haemoglobin and haematocrit drops, higher count of transfused packed RBC units, and lower use of anticoagulants. Moreover, tranexamic acid (TXA) use (n = 106) in surgery reduced hospital stays, tourniquet time, drain output, and increased pre- and postoperative haemoglobin and hematocrit levels compared to no TXA group (n = 156) (p < 0.05, z-score reported). CONCLUSIONS: This study found that patients who received a drain had longer hospital stays and greater blood loss and transfusion rates compared to those who did not. The use of TXA in surgery was associated with improved outcomes and reduced overall complications.

Functions for platelet factor 4 (PF4/CXCL4) and its receptors in fibroblast-myofibroblast transition and fibrotic failure of arteriovenous fistulas (AVFs).

BACKGROUND: Over 60% of End Stage Renal Disease (ESRD) patients are relying on hemodialysis (HD) to survive, and the arteriovenous fistula (AVF) is the preferred vascular access method for HD. However approximately half of all newly created AVF fail to mature and cannot be used without a salvage procedure. We have recently demonstrated an association between AVF maturation failure and post-operative fibrosis, while our RNA-seq study also revealed that veins that ultimately failed during AVF maturation had elevated levels of platelet factor 4 (PF4/CXCL4). However, a link between these two findings was yet to be established. METHODS: In this study, we investigated potential mechanisms between PF4 levels and fibrotic remodeling in veins. We compared the local expression of PF4 and fibrosis marker integrin ß6 (ITGB6) in veins that successfully underwent maturation with that in veins that ultimately failed to mature. We also measured the changes of expression level of α-smooth muscle actin (αSMA/ACTA2) and collagen (Col1/COL1A1) in venous fibroblasts upon various treatments, such as PF4 pharmacological treatment, alteration of PF4 expression, and blocking of PF4 receptors. RESULTS: We found that PF4 is expressed in veins and co-localizes with αSMA. In venous fibroblasts, PF4 stimulates expression of αSMA and Col1 via different pathways. The former requires integrins αvß5 and α5ß1, while chemokine receptor CXCR3 is needed for the latter. Interestingly, we also discovered that the expression of PF4 is associated with that of ITGB6, the ß subunit of integrin αvß6. This integrin is critical for the activation of the major fibrosis factor TGFß, and overexpression of PF4 promotes activation of the TGFß pathway. CONCLUSIONS: These results indicate that upregulation of PF4 may cause venous fibrosis both directly by stimulating fibroblast differentiation and expression of extracellular matrix (ECM) molecules and indirectly by facilitating the activation of the TGFß pathway.

Gender Differences in Physician Burnout: Driving Factors and Potential Solutions.

Introduction Burnout among physicians has reached an epidemic level, with substantially higher rates among women. In this brief report, the authors evaluate recent literature to identify major factors leading to gender differences in physician burnout. Methods The authors review data on gender within each of the key drivers of burnout, including workload and job demands, efficiency and resources, control and flexibility, organizational culture and values, social support and community at work, work-life integration, and meaning at work. Results Women physicians face a higher workload, spending more time in electronic health records, and more time per patient. Women physicians also receive fewer resources and report less control over their workload and schedules. Organizational culture factors, such as a lack of women in leadership roles, compensation disparities, lower rates of career advancement and academic promotion, as well as gender bias, microaggressions, and harassment, also play a key role in gender disparities in burnout. Disproportionate responsibilities outside of work, including childcare and elder care, contribute to less satisfaction with work-life integration. Additionally, women physicians report lower self-compassion and perceived appreciation. These factors ultimately lead to decreased professional fulfillment and higher burnout rates among women physicians. Finally, the authors present proposals to address each of these factors at an organizational level, to effectively address the high burnout rate among women physicians. Conclusion Burnout among women physicians is substantially higher compared to men and stems from multiple factors. It is crucial for organizations to evaluate the gender differences within each burnout driver and develop sustainable strategies to reduce disparities.

Trauma and orthopaedic surgery response at the world's largest sporting event: an analysis of the FIFA World Cup Qatar 2022.

PURPOSE: The purpose of this study is to analyse the impact of the FIFA World Cup Qatar 2022 on the Orthopaedic Surgery department at Hamad Medical Corporation and its response to the challenges posed by the world's largest sporting event. METHODS: A retrospective analysis was conducted on the epidemiology, crisis management plan, and training program adaptations at the Orthopaedic Surgery department during the World Cup. Descriptive analysis of the number and types of surgeries performed, patient demographics, and the disaster preparedness plan were performed. RESULTS: During the tournament period (November-December 2022), 706 patients (4.22% football fans) were operated on, with an average age of 44 ± 17 years. Most patients were males, 67%. Of the 706 patients, 60.33% were emergency cases, 38.24% were elective, 1.27% were limb-saving, and one life-saving procedure was performed, comparable to pre-tournament numbers. The patients were of 77 different nationalities, reflecting the diverse background of Qatar's population and the international fanbase of the tournament. CONCLUSIONS: This analysis provides valuable insights for future mega sporting events and highlights the importance of crisis management and training program adaptation for optimal patient care and resident training advancement. The findings demonstrate the crucial role of the Orthopaedic Surgery Department in responding to the challenges posed by large-scale events.

Epidemiology of proximal humerus fractures in Qatar.

OBJECTIVE: This study aimed to investigate the epidemiological characteristics and treatment options of proximal humerus fractures at a level one trauma center and to compare our data with the current literature. METHODS: A retrospective review was conducted on all patients diagnosed and treated for proximal humerus fractures at Hamad General Hospital, a level one trauma center, between January 2018 and December 2019. Age, gender, mechanism of injury, fracture classification, mode of treatment, implant type, length of hospital stay, associated injuries and complications were analyzed. RESULTS: A total of 190 patients with a mean age of 52.4 years were included; 56.8% were males. The incidence of proximal humerus fracture was 4.1/100,000 per year. Falling from a standing height was the most common cause of injury (50.5%). Additionally, Neer's two-part fracture was found to be the most common type (n = 132, 69%). Forty-one patients (21.3%) had other associated injuries. Most fractures were treated nonoperatively with an arm sling (n = 138, 72.6%). CONCLUSION: In summary, the incidence of proximal humerus fractures during the two-year study period was found to be 4.1 per 100,000 persons per year. Our results showed a lower incidence of proximal humerus fractures with a predominance of males and younger patients in Qatar's population compared to females and older patients in the developed countries. Our results may contribute to the development of effective strategies for preventing and treating proximal humerus fractures, and can provide important data for further high-level clinical research. LEVEL OF EVIDENCE: IV.

The Transcriptomics of the Human Vein Transformation After Arteriovenous Fistula Anastomosis Uncovers Layer-Specific Remodeling and Hallmarks of Maturation Failure.

Introduction: The molecular transformation of the human preaccess vein after arteriovenous fistula (AVF) creation is poorly understood. This limits our ability to design efficacious therapies to improve maturation outcomes. Methods: Bulk RNA sequencing (RNA-seq) followed by paired bioinformatic analyses and validation assays were performed in 76 longitudinal vascular biopsies (veins and AVFs) from 38 patients with stage 5 chronic kidney disease or end-stage kidney disease undergoing surgeries for 2-stage AVF creation (19 matured, 19 failed). Results: A total of 3637 transcripts were differentially expressed between veins and AVFs independent of maturation outcomes, with 80% upregulated in fistulas. The postoperative transcriptome demonstrated transcriptional activation of basement membrane and interstitial extracellular matrix (ECM) components, including preexisting and novel collagens, proteoglycans, hemostasis factors, and angiogenesis regulators. A postoperative intramural cytokine storm involved >80 chemokines, interleukins, and growth factors. Postoperative changes in ECM expression were differentially distributed in the AVF wall, with proteoglycans and fibrillar collagens predominantly found in the intima and media, respectively. Interestingly, upregulated matrisome genes were enough to make a crude separation of AVFs that failed from those with successful maturation. We identified 102 differentially expressed genes (DEGs) in association with AVF maturation failure, including upregulation of network collagen VIII in medial smooth muscle cells (SMCs) and downregulation of endothelial-predominant transcripts and ECM regulators. Conclusion: This work delineates the molecular changes that characterize venous remodeling after AVF creation and those relevant to maturation failure. We provide an essential framework to streamline translational models and our search for antistenotic therapies.

Hyaluronan Inhibition as a Therapeutic Target for Diabetic Kidney Disease: What Is Next?

Diabetic kidney disease (DKD) is the leading cause of CKD and ESKD in the United States and worldwide. Pharmacotherapy and lifestyle modifications for glycemia, dyslipidemia, and BP control have shown success in slowing the progression of DKD. Traditional treatments, such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and more recently the use of sodium-glucose cotransporter 2 inhibitors, nonsteroidal selective mineralocorticoid receptor antagonists, such as finerenone, and glucagon-like peptide 1 receptor agonists, have led to added benefits on various outcomes. However, significant residual risk for DKD progression remains despite the current standard-of-care approaches. Arteriolar hyalinosis (AH) is among the key findings seen on kidney biopsies of patients with DKD. It results from the excessive accumulation of hyaluronan (HA) in the arterioles. AH has not been targeted specifically by any of the therapeutic methods currently being used. We discuss in this manuscript the potential use of a selective therapy targeting AH and the increased total renal HA deposits using a HA synthesis inhibitor in DKD.

The outcomes of total hip replacement in osteonecrosis versus osteoarthritis: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to compare the outcomes of THA in patients with osteonecrosis (ON) and those with osteoarthritis (OA). METHODS: Four databases were searched from inception till December 2022 for original studies that compared the outcomes of THA in ON and OA. The primary outcome was the revision rate; the secondary outcomes were dislocation and Harris hip score. This review was conducted in line with PRISMA guidelines, and the risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: A total of 14 observational studies with 2,111,102 hips were included, with a mean age of 50.83 ± 9.32 and 55.51 ± 8.95 for ON and OA groups, respectively. The average follow-up was 7.25 ± 4.6 years. There was a statistically significant difference in revision rate between ON and OA patients in favour of OA (OR: 1.576; 95%CI: 1.24-2.00; p-value: 0.0015). However, dislocation rate (OR: 1.5004; 95%CI: 0.92-2.43; p-value: 0.0916) and Haris hip score (HHS) (SMD: - 0.0486; 95%CI: - 0.35-0.25; p-value: 0.6987) were comparable across both groups. Further sub-analysis adjusting for registry data also showed similar results between both groups. CONCLUSION: A higher revision rate, periprosthetic fracture and periprosthetic joint infection following total hip arthroplasty were associated with osteonecrosis of the femoral head compared with osteoarthritis. However, both groups had similar dislocation rates and functional outcome measures. This finding should be applied in context due to potential confounding factors, including patient's age and activity level.

Open versus closed intramedullary nailing of femur shaft fractures in adults: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to compare the outcomes of open- versus closed-reduction and intramedullary nailing (IMN) of adult femur shaft fractures. METHODS: Four databases were searched from inception until July 2022 for original studies that compared the outcomes of IMN following open-reduction versus closed-reduction technique. The primary outcome was the union rate; the secondary outcomes were time to union, nonunion, malalignment, revision, and infection. This review was conducted in line with PRISMA guidelines. RESULTS: A total of 12 studies with 1299 (1346 IMN cases) patients were included, with a mean age of 32.3 ± 3.25. The average follow-up was 2.3 ± 1.45 years. There was a statistically significant difference in union rate (OR, 0.66; 95% CI, 0.45-0.97; p-value, 0.0352), nonunion (OR, 2.06; 95% CI, 1.23-3.44; p-value, 0.0056), and infection rate (OR, 1.94; 95% CI, 1.16-3.25; p-value, 0.0114) between the open-reduction and closed-reduction groups in favour of the latter. However, malalignment was significantly higher in the closed-reduction group (OR, 0.32; 95% CI, 0.16-0.64; p-value, 0.0012), whereas time to union and revision rates were similar (p = NS). CONCLUSION: This study showed that closed-reduction and IMN had more favourable union rate, nonunion, and infection rates than the open-reduction group, yet malalignment was significantly less in the open-reduction group. Moreover, time to union and revision rates were comparable. However, these results must be interpreted in context due to confounding effects and the lack of high-quality studies.

Serial SARS-CoV-2 antibody titers in vaccinated dialysis patients: prevalence of unrecognized infection and duration of seroresponse.

Rationale & Objective: SARS-CoV-2 infections are likely underdiagnosed, but the degree of underdiagnosis among maintenance dialysis patients is unknown. Durability of the immune response after third vaccine doses in this population also remains uncertain. This study tracked antibody levels to 1) assess the rate of undiagnosed infections and 2) characterize seroresponse durability after third doses. Study Design: Retrospective observational study. Setting & Participants: SARS-CoV-2 vaccinated patients receiving maintenance dialysis through a national dialysis provider. Immunoglobulin G spike antibodies (anti-spike IgG) titers were assessed monthly following vaccination. Exposures: Two and three doses of SARS-CoV-2 vaccine. Outcomes: Undiagnosed and diagnosed SARS-CoV-2 infections; anti-spike IgG titers over time. Analytical Approach: "Undiagnosed" SARS-CoV-2 infections were identified as an increase in anti-spike IgG titer of ≥ 100 BAU/mL, not associated with receipt of vaccine or "diagnosed" SARS-CoV-2 infection (by PCR or antigen test). In descriptive analyses, anti-spike IgG titers were followed over time. Results: Among 2660 patients without prior COVID-19 who received an initial two-dose vaccine series, 371 (76%) SARS-CoV-2 infections were diagnosed and 115 (24%) were undiagnosed. Among 1717 patients without prior COVID-19 who received a third vaccine dose, 155 (80%) SARS-CoV-2 infections were diagnosed and 39 (20%) were undiagnosed. In both cohorts, anti-spike IgG levels declined over time. Of the initial two-dose cohort, 66% had a titer ≥ 500 BAU/mL in the first month, with 23% maintaining a titer ≥ 500 BAU/mL at six months. Of the third dose cohort, 95% had a titer ≥ 500 BAU/mL in the first month after the third dose, with 76% maintaining a titer ≥ 500 BAU/mL at six months. Limitations: Assays used had upper limits. Conclusions: Among maintenance dialysis patients, 20-24% of SARS-CoV-2 infections were undiagnosed. Given this population's vulnerability to COVID-19, ongoing infection control measures are needed. A three-dose primary mRNA vaccine series optimizes seroresponse rate and durability.

Osteoarthritis: a narrative review of molecular approaches to disease management.

Osteoarthritis (OA) is a chronic, progressive degenerative whole joint disease that affects the articular cartilage, subchondral bone, ligaments, capsule, and synovium. While it is still believed to be a mechanically driven disease, the role of underlying co-existing inflammatory processes and mediators in the onset of OA and its progression is now more appreciated. Post-traumatic osteoarthritis (PTOA) is a subtype of OA that occurs secondary to traumatic joint insults and is widely used in pre-clinical models to help understand OA in general. There is an urgent need to develop new treatments as the global burden is considerable and expanding. In this review, we focus on the recent pharmacological advances in the treatment of OA and summarize the most significant promising agents based on their molecular effects. Those are classified here into broad categories: anti-inflammatory, modulation of the activity of matrix metalloproteases, anabolic, and unconventional pleiotropic agents. We provide a comprehensive analysis of the pharmacological advances in each of these areas and highlight future insights and directions in the OA field.

The role of cerclage wiring in the management of subtrochanteric and reverse oblique intertrochanteric fractures: a meta-analysis of comparative studies.

PURPOSE: Subtrochanteric and reverse oblique intertrochanteric fractures are challenging and often difficult to reduce. While intramedullary nailing (IMN) is considered the standard treatment, achieving anatomic reduction prior to fixation is essential. This study aimed to assess the impact of cerclage wiring with IMN on the outcomes and complication rate in treating subtrochanteric and reverse oblique intertrochanteric fractures. METHODS: This meta-analysis was conducted in line with PRISMA guidelines. The primary outcome was the time to union. The secondary outcomes were operative time, blood loss, quality of reduction, reduction alignment (if in varus), complications and reoperations. PubMed, Cochrane, Web of Science and Google Scholar were searched till July 2021. Articles that compared intramedullary nailing (IMN) versus intramedullary nailing and cerclage wiring (IMN-C) in the treatment of subtrochanteric and reverse oblique intertrochanteric fractures were included. The risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: This meta-analysis included 415 patients with subtrochanteric and reverse oblique intertrochanteric fracture from six comparative studies. Our findings showed that IMN-C was significantly associated with higher mean duration of surgery and blood loss. However, IMN-C had significantly lower mean time to union compared to IMN alone. In addition, IMN-C had lower pooled prevalence of varus reduction and overall complications. CONCLUSION: This study showed that the use of cerclage wiring is associated with lower time to union, lower prevalence of varus reduction and overall complications. Therefore, cerclage wiring augmentation is a safe technique with low complication rate and may be advised whenever open reduction is needed in the management of subtrochanteric and reverse oblique intertrochanteric fractures.

ASDIN white paper: Management of cephalic arch stenosis endorsed by the American Society of Diagnostic and Interventional Nephrology.

Brachiocephalic arteriovenous fistulas (AVF) makeup approximately one third of prevalent dialysis vascular accesses. The most common cause of malfunction with this access is cephalic arch stenosis (CAS). The accepted requirement for treatment of a venous stenosis lesion is ⩾50% stenosis associated with hemodynamically abnormalities. However, the correlation between percentage stenosis and a clinically significant decrease in access blood flow (Qa) is low. The critical parameter is the absolute minimal luminal diameter (MLD) of the lesion. This is the parameter that exerts the key restrictive effect on Qa and results in hemodynamic and functional implications for the access. CAS is the result of low wall shear stress (WSS) resulting from the effects of increased blood flow and the unique anatomical configuration of the CAS. Decrease in WSS has a linear relationship to increased blood flow velocity and neointimal hyperplasia exhibits an inverse relationship with WSS. The result is a stenotic lesion. The presence of downstream venous stenosis causes an inflow-outflow mismatch resulting in increased pressure within the access. Qa in this situation may be decreased, increased, or within a normal range. Over time, the increased intraluminal pressure can result in marked aneurysmal changes within the AVF, difficulties with cannulation and the dialysis treatment, and ultimately, increasing risk of access thrombosis. Complete characterization of the lesion both hemodynamically and anatomically should be the first step in developing a strategy for management. This requires both access flow measurement and angiographic imaging. Patients with CAS present a relatively broad spectrum as relates to both of these parameters. These data should be used to determine whether primary treatment of CAS should be directed toward the anatomical lesion (small MLD and low Qa) or the pathophysiology (large MLD and high Qa).

CMS ESRD quality incentive program has not improved patient dialysis vascular access.

PURPOSE: Over 468,000 patients in the United States use hemodialysis to manage End Stage Renal Disease (ESRD). The purpose of this study was to determine whether the dialysis access Clinical Performance Measures (CPMs) of Centers for Medicare & Medicaid Services (CMS) ESRD Quality Incentive Program (QIP) have increased arteriovenous fistula (AVF) rates and decreased long-term tunneled hemodialysis catheter (TDC) rates among hemodialysis patients in United States. METHODS: Retrospective observational study: evaluated reported AVF and long-term TDC rates of 4804 dialysis facilities which reported dialysis access data as part of the ESRD QIP from Payment Year (PY) 2014-2020. Facilities were also sorted by specific additional criteria to examine disparities in dialysis access. RESULTS: Mean AVF rates of included facilities increased from 63.7% in PY 2014 to 67.2% in PY 2016 (p < 0.05), did not change in PY 2017 (p > 0.05), and declined significantly in PY 2018-2020 to 64.1% in PY 2020, near AVF rates at the inception of program. Long-term TDC rates decreased from 10.4% in PY 2014 to 9.88% in PY 2015 (p < 0.05), then increased in PY 2015-PY 2020 to rates higher than at the inception of program, at 11.8% in PY 2020 (p < 0.05). Facilities serving majority Black ZIP Code Tabulation Areas (ZCTAs) or ZCTAs with median income <$45,000 achieved significantly lower AVF rates (p < 0.05) with no significant difference in long-term TDC rates (p > 0.05). AVF rates correlated positively and long-term TDC rates correlated negatively with star rating of facilities (p < 0.05). CONCLUSION: As one of the first financial QIPs in healthcare, the ESRD QIP has not achieved the stated goals of the CMS to increase AVF access rates above 68% and reduce long-term TDC clinical rates below 10%. Systemic disparities in race, geographic region, economic status, healthcare access, and education of providers and patients prevent successful attainment of goal metrics.

The anatomical sources of neointimal cells in the arteriovenous fistula.

Neointimal cells are an elusive population with ambiguous origins, functions, and states of differentiation. Expansion of the venous intima in arteriovenous fistula (AVF) is one of the most prominent remodeling processes in the wall after access creation. However, most of the current knowledge about neointimal cells in AVFs comes from extrapolations from the arterial neointima in non-AVF systems. Understanding the origin of neointimal cells in fistulas may have important implications for the design and effective delivery of therapies aimed to decrease intimal hyperplasia (IH). In addition, a broader knowledge of cellular dynamics during postoperative remodeling of the AVF may help clarify other transformation processes in the wall that combined with IH determine the successful remodeling or failure of the access. In this review, we discuss the possible anatomical sources of neointimal cells in AVFs and their relative contribution to intimal expansion.