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Background: Anterior labrum periosteal sleeve avulsion (ALPSA) lesion of the shoulder is defined as a labral avulsion with an intact periosteum of the glenoid neck resulting in medial malattachment of the labrum, which is both nonanatomic and nonfunctional. It is relatively rare compared with Bankart lesions, and its results are usually reported in combination with other anterior labroligamentous lesions in the literature. Purpose: To (1) assess the size and scope of the literature on ALPSA lesions, (2) highlight the importance of this lesion, and (3) distinguish between ALPSA and Bankart lesions in diagnostic and treatment strategies. Study Design: Scoping review; Level of evidence, 4. Methods: The PubMed, Scopus, Embase, and Google Scholar databases were searched with the keywords "ALPSA,""anterior labrum periosteal sleeve avulsion,""anterior labral periosteal sleeve avulsion," and "anterior labroligamentous periosteal sleeve avulsion" lesion. Duplicate articles and those that did not meet the inclusion criteria were excluded, resulting in the identification of 42 relevant articles. Their references were analyzed for further data curation. Results: This scoping review demonstrated that ALPSA lesions are difficult to clinically identify. Magnetic resonance angiography in the adduction internal rotation position is the most sensitive and specific imaging modality for identification. Optimal views are the anterosuperior portal for accurate identification and the anteroinferior portal for surgical repair during arthroscopy. Treatment begins with correctly identifying the labrum, in contradistinction to dense reactive fibrous tissue, and reattaching the labrum to the correct anatomic glenoid footprint. Chronic lesions with bone loss require either bone block or soft tissue augmentation procedures. Conclusion: There is paucity of exclusive literature on ALPSA lesions. It is important to distinguish this lesion from the Bankart lesion as it is associated with worse outcomes. The higher failure rates of ALPSA lesion repair indicate that the current repair techniques require further refinement to improve the outcomes to the standard of Bankart lesions.
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Management of prepatellar hematomas can be difficult, and recurrences or persistent oozing are common. Endoscopic-assisted management of these hematomas has not been reported. We present the case of a 44-year-old lady with traumatic prepatellar hematoma who was managed with the evacuation of the hematoma assisted by endoscopic visualization and debridement. She recovered completely within three weeks and remained asymptomatic on the last follow-up at six months. Endoscopic visualization of the hematoma cavity is a useful adjunct to managing prepatellar hematomas, with the potential to identify and control sources of future concerns in wound healing.
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Ranjith K.The objective of this study was to compare the efficacy, safety, pharmacokinetics, and immunogenicity of a proposed bevacizumab biosimilar (DRL_BZ) with the innovator Avastin (reference medicinal product [RMP]) in patients with nonresectable metastatic colorectal cancer (mCRC) over a period of 9 months and advanced nonsquamous non-small cell lung cancer (NSCLC) over 6 months. The study was planned as a randomized, double-blind trial. In part A, a total of 117 mCRC patients were intended to receive 5 mg/kg of bevacizumab every 2 weeks along with mFOLFOX6 chemotherapy for a maximum of 18 cycles. In part B, 60 NSCLC patients were to receive 15 mg/kg of bevacizumab every 3 weeks along with pemetrexed and carboplatin for the initial four cycles, followed by pemetrexed for another four cycles. The primary endpoint was the progression-free survival rate at 6 months (PFS6) in both subparts. The anticipated sample size was 106 evaluable mCRC patients to achieve 85% statistical power for concluding noninferiority with a margin of half the difference (18.8%) between DRL_BZ and Avastin, along with a pilot study involving 60 evaluable NSCLC patients. Safety comparison included assessing adverse events (AEs), infusion reactions, and lab abnormalities. Immunogenicity comparison involved the incidence of antidrug antibodies (ADAs) and neutralizing antibodies (NAbs). Pharmacokinetic comparison was planned after the first and fourth dosing cycles of treatment in 24 NSCLC patients. The PFS6 for mCRC patients treated with DRL_BZ and RMP was 57.8% and 50% respectively, with a difference in efficacy of 7.8 (-8.7, 23.7). The PFS9 was 31.1% and 22.9%, with a difference of 8.2% (-6.9%, 22.9%). The objective response rate (ORR) for DRL_BZ and RMP was 28.8% and 22.4%, while the disease control rate (DCR) was 44.2% and 37.9% respectively. For NSCLC patients, the PFS6 was 44% and 45%, showing a difference of -1.0 (-4.2, 22.1). The ORR was 41.4% and 48.1%, and the DCR was 62.1% and 63%. The frequency, type, and severity of AEs were similar in both indications. Blood levels during the first and fourth dosing cycles exhibited comparable values. All NSCLC patients tested negative for ADA, while no mCRC patients on DRL_BZ tested positive for ADA. Low incidences of ADA (8%) and NAbs (4.0%) were reported in patients on RMP. Overall, the efficacy, safety, immunogenicity, and pharmacokinetic parameters of DRL_BZ and RMP were found to be comparable. Clinical Trial Registration For BZ-01-002: CTRI/2016/01/006481.
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The traditional plicae of the knee have been updated recently with reports of new variants in the coronal plane. We report another variant, an extended medial coronal plane plica (EMCPP), previously unreported, in a 70-year-old lady with osteoarthritis of the knee and a loose body. The preoperative symptoms after the excision of the plica and loose body were temporarily relieved for 11 months before she underwent total knee arthroplasty (TKA) for associated osteoarthritis. Excision of the EMCPP could resolve symptoms, but resultant internal scarring or the plica itself could cause difficulty in exposure during TKA.
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Purpose: The aim of the present systematic review was to quantitatively synthesize the best literature evidence regarding osteoarthritis developing after anterior cruciate ligament reconstruction (ACLR), including only studies with a follow-up duration of at least 20 years. Material and Methods: A systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines on four electronic databases (PubMed, Scopus, EMBASE and Cochrane Library). The outcome measures extracted from the studies were failure rate, subsequent knee surgery on the same knee, radiographic development of osteoarthritis measured with Kellgren-Lawrence, International Knee Documentation Committee (IKDC) radiographic score and Ahlbäck classification. The health of both the ACLR knee and the contralateral knee was compared. Results: A total of 1552 patients were included in the study, of which 1290 (83.11%) were operated on using a patellar tendon graft, 190 (12.24%) with hamstrings, 27 (1.73%) with an iliotibial band and 45 (2.89%) with patellar tendon plus a ligament augmentation device (LAD). The mean age at the time of surgery was 25.18 ± 1.91 years, and the mean follow-up time was 23.34 ± 2.56 years. Analysing IDKC Score at final follow-up, ACLR Group showed a higher degree of OA compared with contralateral healthy knee (p < 0.01), but only 33.2% (324/976) of the patients showed a moderate to severe degree (Grade C or D) of osteoarthritis, while for Kellgren-Lawrence, ACLR Group showed a higher degree of OA compared with contralateral healthy knee (p < 0.01), but only 28.9% (196/678) of the patients showed a moderate to severe degree (Grade III or IV) of osteoarthritis. In total, 1552 patients were registered, 155 reruptures (9.98%) and a total of 300 (19.3%) new surgeries, of which 228 meniscectomy (14.69%), 21 (1.35%) knee arthroplasty and 17 (1.09%) hardware removal were recorded. Conclusions: ACL reconstruction appears to result in mild osteoarthritis in the long term in most of the patients and only less than 33.2% develop a moderate to severe degree of knee OA according to IKDC radiographic score. A slight degree of osteoarthritis appears to be present in ACLR knees compared with contralateral healthy knees. Level of Evidence: Level IV.
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Introduction: The impact of female biological sex on the development of heart failure with preserved ejection fraction (HFpEF) and its associated kidney disease and vascular endothelial dysfunction is still controversial. Whether females are protected from HFpEF and associated complications is not well established. Previous studies report conflicting prevalence between genders. We hypothesize that female mice are unprotected from HFpEF and its associated kidney disease and vascular endothelial dysfunction. Methods: Eight-week-old female mice were divided into four groups: control groups receiving a standard diet and water for either 5 or 16 weeks, and HFpEF groups fed a high-fat diet (HFD, Rodent Diet With 60 kcal% Fat) and N [w]-nitro-l-arginine methyl ester (L-NAME - 0.5 g/L) in the drinking water for 5 or 16 weeks. Various measurements and assessments were performed, including echocardiography, metabolic and hypertensive evaluations, markers of heart and kidney injury, and assessment of vascular endothelial function. Results: Female mice with HFD and L-NAME developed HFpEF at 5 weeks, evidenced by increased E/E' ratio, reduced cardiac index, left ventricular mass, and unchanged ejection fraction. After 16 weeks, HFpEF worsened. Metabolic disorders, hypertension, lung wet/kidney weight increase, exercise intolerance, and cardiac/renal injury markers were observed. Vascular endothelial dysfunction was associated with ER stress and fibrosis induction. Conclusions: We found that female mice are susceptible to the development of HFpEF and its associated kidney disease and vascular endothelial dysfunction. Our data support the concept that the female sex does not protect from HFpEF and its associated kidney disease and vascular endothelial dysfunction when disease risk factors are present.
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Background: As information on the meniscus accumulates in PubMed, it is possible to evaluate the trends in research on the topic over time. Purpose: To evaluate the major trends in meniscus-related publications in PubMed from the earliest publication to the present day. Study Design: Cross-sectional study. Methods: PubMed was searched on January 3, 2023, using the search strategy "menisc *"[All Fields] AND ("knee"[MeSH Terms] OR "knee"[All Fields] OR "knee joint"[MeSH Terms] OR ("knee"[All Fields] AND "joint"[All Fields]) OR "knee joint"[All Fields]) AND 1900/01/01:2022/12/31[Date - Publication]. This retrieved 15,569 human and animal studies. We determined the top 10 meniscus-related publications in terms of overall citations and citations per year, as well as the top 10 authors, journals, countries, and institutions of cited publications on the meniscus. In addition, we performed word-cloud analyses based on meniscus-related terms from different periods (before 1981, before 2000, after 2005, and in the past 5 years [2018-2022]), including the year of first appearance and the number of publications featured. Results: Since the first recorded publication on the meniscus in 1928, there was a steady growth in the number of articles until 2005, when there was an upsurge in publications from 254 in 2005 to 955 in 2022. Noyes was the author with the most citations (n = 3314), and a 2006 study by Caplan and Dennis had the most citations per year (n = 125). Arthroscopy published the most articles on the meniscus with 1118, whereas the Journal of Cellular Biochemistry had the most citations per article with 125.69. The most published countries and institutes were the United States and the Hospital for Special Surgery, respectively. Word-cloud analysis of article titles showed that "meniscectomy" had become less prominent, and "root,""ramp,""transplantation," and "slope" had become more prominent. Conclusion: There has been an upsurge in publications on the meniscus since 2005, with word-cloud analysis indicating shifting interests in meniscus-related research.
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Objective: Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease due to macro- and microvascular dysfunction. This study aimed to investigate the potential involvement of plasmacytoid dendritic cells (pDCs) in T2D-related vascular dysfunction. Approach and results: pDCs were isolated from db/db and control mice. It was found that pDCs from db/db mice impaired endothelial cell eNOS phosphorylation in response to ATP and decreased vascular endothelium-dependent relaxation compared to pDCs from control mice. Moreover, isolated CD4+ cells from control mice, when stimulated overnight with high glucose and lipids, and isolated pDCs from db/db mice, display elevated levels of ER stress, inflammation, and apoptosis markers. Flow cytometry revealed that pDC frequency was higher in db/db mice than in controls. In vivo, the reduction of pDCs using anti-PDCA-1 antibodies in male and female db/db mice for 4 weeks significantly improved vascular endothelial function and eNOS phosphorylation. Conclusion: pDCs may contribute to vascular dysfunction in T2D by impairing endothelial cell function. Targeting pDCs with anti-PDCA-1 antibodies may represent a promising therapeutic strategy for improving vascular endothelial function in T2D patients. This study provides new insights into the pathogenesis of T2D-related vascular dysfunction and highlights the potential of immunomodulatory therapies for treating this complication. Further studies are warranted to explore the clinical potential of this approach.
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Osteoporosis and sarcopenia are major health issues which are going to have a significant impact in an aging global population. Osteoporosis, which reduces bone density and increases fracture risk, and sarcopenia, which causes muscle loss and strength loss, have a complicated risk profile with consequences that go beyond bone and muscle health. This chapter illuminates the complex link between osteoporosis and sarcopenia, including overlapping causes, clinical consequences, and new treatments. This chapter covers bone and muscle biology, age-related changes that cause osteoporosis and sarcopenia, and the importance of physical exercise and diet in their prevention and management. It also discusses clinical evaluation methods, risk assessment and diagnostic criteria for early diagnosis and intervention. Novel therapies and continuing research in the management of osteoporosis and sarcopenia are also discussed. Medications, exercise, and nutrition can promote bone and muscle health. This chapter aims to explore the recent concepts by elucidating the complex relationship between osteoporosis and sarcopenia and advocating for integrated care paradigms.
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Background: Osteoporosis, also called the silent disease, affects the elderly with a significant contribution to their morbidity and mortality through fragility fractures. Most nations have developed their own guidelines on managing this condition. Clinical Practice Guidelines (CPGs) are the highest quality evidence documents on a particular topic prepared by expert panels. CPGs offer standardised recommendations on a particular topic. Methods: We looked at the CPGs of nations in the last five years and present the results of this review here. This review is divided into Risk assessment, prevention, diagnosis, Non pharmacological and pharmacological management with information from major CPGs only. Results: Most CPGs agree on the broad principles of assessment , core risk factors, prevention and management with some finer differences in subtle aspects of assessment and management. There are differences in the use of screening tools based on the population numbers and affordability between nations. FRAX has been advocated for the screening with or without DEXA. Most CPGs use DEXA for confirmation of diagnosis. Intervention is based on FRAX scoring. Intervention thresholds vary. We discuss non-pharmacological management included diet and nutrition, calcium and Vitamin D, Exercise and physiotherapy, lifestyle changes and falls prevention. Pharmacological management included aspects of using different medications and their indications. The key agents recommended include Bisphosphonates, Teriparatide, Denosumab, SERMs, Hormone Replacement Therapy, and other agents including any drug holidays and duration of therapy. Conclusions: This review identified some key recommendations from CPGs from multiple nations in each of the above given aspects of osteoporosis.
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Background: Osteoporosis is a disease of the bones leading to decreased bone mineral density, leading to fragility fractures. This article is an overview of osteoporosis, osteomalacia and fragility fractures and serves as an introductory article for this special issue on osteoporosis. Methods: This is a short, comprehensive account of the given conditions with concepts and a review from the recent literature. The authors provide relevant references from the literature in the bibliography. The sections herein have also been deliberated in the meetings of experts of osteoporosis. Results: An overview of osteoporosis, osteomalacia and fragility fractures is provided, including definitions and summaries of aetiology, pathophysiology, diagnosis, prevention, and management. A detailed account of some of these topics will be provided in subsequent chapters. Conclusion: Osteoporosis is a silent disease with the potential to cause significant morbidity and mortality if not detected early. It is important to differentiate from and diagnose associated osteomalacia to provide accurate therapy. It is also important to identify the type of fragility fractures and initiate treatment for bone strengthening to prevent subsequent fractures.
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BACKGROUND: Integrated addiction treatment in HIV clinics is associated with improved outcomes, yet it is offered inconsistently and with variable models of care. We sought to evaluate the impact of Implementation Facilitation ("Facilitation") on clinician and staff preference for provision of addiction treatment in HIV clinics with on-site resources (all trained or designated on-site specialist) versus outside resources (outside specialist or refer out). METHODS: From July 2017 to July 2020, surveys assessed clinician and staff preferences for addiction treatment models during control (ie, baseline), intervention, evaluation, and maintenance phases in 4 HIV clinics in the Northeast United States. RESULTS: During the control phase, among 76 respondents (response rate, 58%), the proportions who preferred treatment with on-site resources for opioid use disorder (OUD), alcohol use disorder (AUD), and tobacco use disorder (TUD) were 63%, 55%, and 63%, respectively. Compared with control, there were no significant differences in preferred model during the intervention and evaluation phases except for AUD where there was an increased preference for treatment with on-site resources in the intervention versus control phase. Compared with control, during the maintenance phase, a higher proportion of clinicians and staff preferred providing addiction treatment with on-site resources versus outside resources: OUD, 75% (odds ratio [OR; 95% confidence interval {CI}], 1.79 [1.06-3.03]); AUD, 73% (OR [95% CI], 2.23 [1.36-3.65]), and TUD, 76% (OR [95% CI], 1.88 [1.11-3.18]). CONCLUSIONS: The findings from this study lend support for "Facilitation" as a strategy to enhance clinician and staff preference for integrated addiction treatment in HIV clinics with on-site resources.
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Alcoolismo , Comportamento Aditivo , Infecções por HIV , Transtornos Relacionados ao Uso de Opioides , Humanos , New EnglandRESUMO
Background: The purpose of this study is to present a comprehensive overview of the ethical issues and the processes involved in research and publishing in India. The study examines the present ethical norms, guidelines, frameworks and developments in India, providing insights into the nation's current status of research and recommendations for publication. This document will be a useful starting point and reference document for those embarking on research and publication in Orthopaedics in India. Materials: A survey of the literature was done, which included scholarly papers, reports, rules, and policies pertaining to Indian publishing norms and research ethics. the document starts with a general introduction to ethics, followed by the evolution of ethics in research and the current International as well as Indian codes of ethics. Subsequently, the discussion is divided into two broad headings of ethics in research and ethics in publishing. Under each heading, there are many specific areas in orthopaedics that would require the application of a unique set of ethics. These areas are discussed separately as subheadings. Results and Discussion: The review draws attention to the complexity of ethical issues in Indian and international research and publishing in orthopaedics. Where available, specific guidelines about the topic in India or international guidelines are discussed. The importance of informed consent, data integrity, plagiarism, authorship disputes, and conflicts of interest are only a few of the key results. It is obvious that ethical norms and regulations, such as those offered by the University Grants Commission (UGC), the Indian Council of Medical Research (ICMR), and the Council of Publication Ethics (COPE) are crucial in determining how research is conducted and how papers are published. The types of studies discussed include research in humans and animals, research with stem cells, metal implants and devices, orthobiologics, Artificial Intelligence, Robotics, computer modelling, virtual reality, 3D printing and bioprinting, tissue banking and data management. The roles of different personnel in research and publications are discussed. Conclusions: Ethics in research and publishing play a crucial role in establishing the authority and standard of scholarly work in India. This study underlines the key concepts of ethics that guide various types of studies and the publication process. It also highlights the requirement for frameworks and guidelines for certain unique areas of research in orthopaedics.
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Purpose: To improve the clinical outcomes of anterior cruciate ligament reconstruction (ACLR), there have been attempts to reproduce anatomic reconstruction by modifying the single-bundle (SB) and double-bundle (DB) techniques. Although DB ACLR restores better rotational control compared to SB ACLR, it is still debatable whether there are higher clinical outcomes in favor of DB ACLR. We aimed to study the trends of publications on SB and DB ACLR techniques over the last 20 years. Methods: For this bibliometric study, we performed a PubMed search on 31/05/2022 with a well-defined search strategy. The articles were downloaded into Excel software, and citations were determined from the iCite website for PubMed. The analysis was performed using SPSS software version 28.0.1. Data mining was performed using Orange software, Mac version 3.32.0, from the titles of all articles and each group of SB and DB ACLR. The output is presented as word clouds. Results: A total of 10,530 publications were identified, of which 9699 publications (92.1%) pertained to SB-ACLR and 831 publications (7.9%) to DB-ACLR. There was a steady increase in the publications on SB-ACLR until 2012, followed by a steep increase that peaked in 2021. The highest number of publications on DB-ACLR was in 2012 (n = 76; 9.1%). The mean citations per year for SB-ACLR and DB-ACLR were 2.87 ± 4.31 and 2.74 ± 3.17, respectively. The most prolific journals publishing on this topic were Knee Surgery Sports Traumatology Arthroscopy, American Journal of Sports Medicine, and Arthroscopy. The top three articles that received the maximum number of citations were from Japanese authors. Conclusion: The number of publications related to SB-ACLR was significantly higher than that related to DB-ACLR in the last 20 years. The publications related to DB-ACLR have decreased in the recent past, after reaching a peak in 2012. The citations per year of SB-ACLR and DB-ACLR were similar.
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BACKGROUND: Studies have shown that the quantification of circulating clonal plasma cells (cCPCs) in peripheral blood using flow cytometry could be used as a prognostic predictor of poor outcome in multiple myeloma (MM). METHODS: In 66 newly diagnosed MM, cCPCs were quantified (cCPC%) and analysed for association with outcome and survival. Single-tube combined surface (CD45/CD19/CD138/CD38/CD56/CD27/CD81 as per availability) and cytoplasmic (kappa/lambda) staining was done using pre-titrated volumes of antibodies. In 26 patients, repeat cCPC% was assessed post-induction therapy. For association studies, treatment response has been taken as good (VGPR and above) and poor (PR and below). All statistical analyses were performed with SPSS software version 16.0. RESULTS: There was no significant association between cCPC% at baseline with staging (p = 0.43), ß2 -microglobulin (p = 0.27) and albumin (p = 0.08). There was a significant difference between the pre-induction and post-induction cCPC% (p = 0.0001). The patients were segregated using a cut-off of ≥0.197 and <0.197 based on the median values of baseline cCPC%. The post-induction outcome was available for 47 patients among whom 33 (70%) had VGPR and above. There was a significant association between higher cCPC% at baseline with poor treatment response (p = 0.008). The median OS in the study patients was 42 (CI 28.14-43.03) months and the median PFS was 39 (CI 28.49-49.04) months. Higher cCPC% showed a lower median PFS (30 vs. 39 months) and OS (35 vs. 41 months) compared to lower cCPC% though it was not statistically significant. CONCLUSION: Flow cytometric baseline cCPC% in newly diagnosed MM was associated with poor treatment response and survival.
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Mieloma Múltiplo , Humanos , Plasmócitos , Prognóstico , Citometria de Fluxo , Antígenos CD19RESUMO
Introduction: The neonate exposed to opioids in utero faces a constellation of withdrawal symptoms postpartum commonly called neonatal opioid withdrawal syndrome (NOWS). The incidence of NOWS has increased in recent years due to the opioid epidemic. MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in gene regulation. Epigenetic variations in microRNAs (miRNAs) and their impact on addiction-related processes is a rapidly evolving area of research. Methods: The Illumina Infinium Methylation EPIC BeadChip was used to analyze DNA methylation levels of miRNA-encoding genes in 96 human placental tissues to identify miRNA gene methylation profiles as-sociated with NOWS: 32 from mothers whose prenatally opioid-exposed infants required pharmacologic management for NOWS, 32 from mothers whose prenatally opioid-exposed infants did not require treat-ment for NOWS, and 32 unexposed controls. Results: The study identified 46 significantly differentially methylated (FDR p-value ≤ 0.05) CpGs associated with 47 unique miRNAs, with a receiver operating characteristic (ROC) area under the curve (AUC) ≥0.75 including 28 hypomethylated and 18 hypermethylated CpGs as potentially associated with NOWS. These dysregulated microRNA methylation patterns may be a contributing factor to NOWS pathogenesis. Conclusion: This is the first study to analyze miRNA methylation profiles in NOWS infants and illustrates the unique role miRNAs might have in diagnosing and treating the disease. Furthermore, these data may provide a step toward feasible precision medicine for NOWS babies as well.
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Authorship in scientific manuscripts indicates intellectual contribution of individuals to a research project and authors play a key role in the research and dissemination of results of a research project. It is important for authors to follow guidelines on authorship and submission of manuscripts and to agree on the order of authorship before beginning the project. Criteria for authorship, roles and responsibilities of authors, author metrics and misconduct of authors and their consequences are discussed in this editorial. Properly assigning authorship ensures transparency, accountability, and fairness in the scientific community.