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BACKGROUND: Ibrutinib, a Bruton's tyrosine kinase inhibitor, may have clinical benefit when administered in combination with bendamustine and rituximab and followed by rituximab maintenance therapy in older patients with untreated mantle-cell lymphoma. METHODS: We randomly assigned patients 65 years of age or older to receive ibrutinib (560 mg, administered orally once daily until disease progression or unacceptable toxic effects) or placebo, plus six cycles of bendamustine (90 mg per square meter of body-surface area) and rituximab (375 mg per square meter). Patients with an objective response (complete or partial response) received rituximab maintenance therapy, administered every 8 weeks for up to 12 additional doses. The primary end point was progression-free survival as assessed by the investigators. Overall survival and safety were also assessed. RESULTS: Among 523 patients, 261 were randomly assigned to receive ibrutinib and 262 to receive placebo. At a median follow-up of 84.7 months, the median progression-free survival was 80.6 months in the ibrutinib group and 52.9 months in the placebo group (hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.01). The percentage of patients with a complete response was 65.5% in the ibrutinib group and 57.6% in the placebo group (P = 0.06). Overall survival was similar in the two groups. The incidence of grade 3 or 4 adverse events during treatment was 81.5% in the ibrutinib group and 77.3% in the placebo group. CONCLUSIONS: Ibrutinib treatment in combination with standard chemoimmunotherapy significantly prolonged progression-free survival. The safety profile of the combined therapy was consistent with the known profiles of the individual drugs. (Funded by Janssen Research and Development and Pharmacyclics; SHINE ClinicalTrials.gov number, NCT01776840.).
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Célula do Manto , Adenina/administração & dosagem , Adenina/análogos & derivados , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Progressão da Doença , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/mortalidade , Quimioterapia de Manutenção , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Indução de Remissão , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Análise de SobrevidaRESUMO
PURPOSE: AI has shown promise in automating and improving various tasks, including medical image analysis. Distal humerus fractures are a critical clinical concern that requires early diagnosis and treatment to avoid complications. The standard diagnostic method involves X-ray imaging, but subtle fractures can be missed, leading to delayed or incorrect diagnoses. Deep learning, a subset of artificial intelligence, has demonstrated the ability to automate medical image analysis tasks, potentially improving fracture identification accuracy and reducing the need for additional and cost-intensive imaging modalities (Schwarz et al. 2023). This study aims to develop a deep learning-based diagnostic support system for distal humerus fractures using conventional X-ray images. The primary objective of this study is to determine whether deep learning can provide reliable image-based fracture detection recommendations for distal humerus fractures. METHODS: Between March 2017 and March 2022, our tertiary hospital's PACS data were evaluated for conventional radiography images of the anteroposterior (AP) and lateral elbow for suspected traumatic distal humerus fractures. The data set consisted of 4931 images of patients seven years and older, after excluding paediatric images below seven years due to the absence of ossification centres. Two senior orthopaedic surgeons with 12 + years of experience reviewed and labelled the images as fractured or normal. The data set was split into training sets (79.88%) and validation tests (20.1%). Image pre-processing was performed by cropping the images to 224 × 224 pixels around the capitellum, and the deep learning algorithm architecture used was ResNet18. RESULTS: The deep learning model demonstrated an accuracy of 69.14% in the validation test set, with a specificity of 95.89% and a positive predictive value (PPV) of 99.47%. However, the sensitivity was 61.49%, indicating that the model had a relatively high false negative rate. ROC analysis showed an AUC of 0.787 when deep learning AI was the reference and an AUC of 0.580 when the most senior orthopaedic surgeon was the reference. The performance of the model was compared with that of other orthopaedic surgeons of varying experience levels, showing varying levels of diagnostic precision. CONCLUSION: The developed deep learning-based diagnostic support system shows potential for accurately diagnosing distal humerus fractures using AP and lateral elbow radiographs. The model's specificity and PPV indicate its ability to mark out occult lesions and has a high false positive rate. Further research and validation are necessary to improve the sensitivity and diagnostic accuracy of the model for practical clinical implementation.
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Fraturas Ósseas , Fraturas Distais do Úmero , Humanos , Criança , Inteligência Artificial , Fraturas Ósseas/diagnóstico por imagem , Radiografia , Algoritmos , Estudos RetrospectivosRESUMO
Cancer is characterized by the abnormal development of cells that divide in an uncontrolled manner and further take over the body and destroy the normal cells of the body. Although several therapies are practiced, the demand and need for new therapeutic agents are ever-increasing because of issues with the safety, efficacy and efficiency of old drugs. Several plant-based therapeutics are being used for treatment, either as conjugates with existing drugs or as standalone formulations. Withania somnifera (L.) Dunal is a highly studied medicinal plant which is known to possess immunomodulatory activity as well as anticancer properties. The pivotal role of KAT6A in major cellular pathways and its oncogenic nature make it an important target in cancer treatment. Based on the literature and curated datasets, twenty-six compounds from the root of W. somnifera and a standard inhibitor were docked with the target KAT6A using Autodock vina. The compounds and the inhibitor complexes were subjected to molecular dynamics simulation (50 ns) using Desmond to understand the stability and interactions. The top compounds (based on the docking score of less than -8.5 kcal/mol) were evaluated in comparison to the inhibitor. Based on interactions at ARG655, LEU686, GLN760, ARG660, LEU689 and LYS763 amino acids with the inhibitor WM-8014, the compounds from W. somnifera were evaluated. Withanolide D, Withasomniferol C, Withanolide E, 27-Hydroxywithanone, Withanolide G, Withasomniferol B and Sitoindoside IX showed high stability with the residues of interest. The cell viability of human breast cancer MCF-7 cells was evaluated by treating them with W. Somnifera root extract using an MTT assay, which showed inhibitory activity with an IC50 value of 45 µg/mL. The data from the study support the traditional practice of W. somnifera as an anticancer herb.
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Neoplasias , Plantas Medicinais , Withania , Vitanolídeos , Humanos , Vitanolídeos/farmacologia , Vitanolídeos/metabolismo , Simulação de Acoplamento Molecular , Withania/química , Plantas Medicinais/metabolismo , Extratos Vegetais/química , Simulação de Dinâmica Molecular , Raízes de Plantas/química , Histona AcetiltransferasesRESUMO
Finding structurally similar compounds in compound databases is highly efficient and is widely used in present-day drug discovery methodology. The most-trusted and -followed similarity indexing method is Tanimoto similarity indexing. Epigenetic proteins like histone deacetylases (HDACs) inhibitors are traditionally used to target cancer, but have only been investigated very recently for their possible effectiveness against rheumatoid arthritis (RA). The synthetic drugs that have been identified and used for the inhibition of HDACs include SAHA, which is being used to inhibit the activity of HDACs of different classes. SAHA was chosen as a compound of high importance as it is reported to inhibit the activity of many HDAC types. Similarity searching using the UNPD database as a reference identified aglaithioduline from the Aglaia leptantha compound as having a ~70% similarity of molecular fingerprints with SAHA, based on the Tanimoto indexing method using ChemmineR. Aglaithioduline is abundantly present in the shell and fruits of A. leptantha. In silico studies with aglaithioduline were carried out against the HDAC8 protein target and showed a binding affinity of -8.5 kcal mol. The complex was further subjected to molecular dynamics simulation using Gromacs. The RMSD, RMSF, compactness and SASA plots of the target with aglaithioduline, in comparison with the co-crystallized ligand (SAHA) system, showed a very stable configuration. The results of the study are supportive of the usage of A. leptantha and A. edulis in Indian traditional medicine for the treatment of pain-related ailments similar to RA. Our study therefore calls for further investigation of A. leptantha and A. edulis for their potential use against RA by targeting epigenetic changes, using in vivo and in vitro studies.
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Artrite Reumatoide , Inibidores de Histona Desacetilases , Humanos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/química , Amidas , Simulação de Dinâmica Molecular , Epigênese Genética , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Simulação de Acoplamento Molecular , Histona Desacetilases/genética , Proteínas RepressorasRESUMO
BACKGROUND: The unprecedented drought and frequent occurrence of pathogen infection in rice is becoming more due to climate change. Simultaneous occurrence of stresses lead to more crop loss. To cope up multiple stresses, the durable resistant cultivars needs to be developed, by identifying relevant genes from combined biotic and abiotic stress exposed plants. RESULTS: We studied the effect of drought stress, bacterial leaf blight disease causing Xanthomonas oryzae pv. oryzae (Xoo) pathogen infection and combined stress in contrasting BPT5204 and TN1 rice genotypes. Mild drought stress increased Xoo infection irrespective of the genotype. To identify relevant genes that could be used to develop multi-stress tolerant rice, RNA sequencing from individual drought, pathogen and combined stresses in contrasting genotypes has been developed. Many important genes are identified from resistant genotype and diverse group of genes are differentially expressed in contrasting genotypes under combined stress. Further, a meta-analysis from individual drought and Xoo pathogen stress from public domain data sets narrowed- down candidate differentially expressed genes. Many translation associated genes are differentially expressed suggesting their extra-ribosomal function in multi-stress adaptation. Overexpression of many of these genes showed their relevance in improving stress tolerance in rice by different scientific groups. In combined stress, many downregulated genes also showed their relevance in stress adaptation when they were over-expressed. CONCLUSIONS: Our study identifies many important genes, which can be used as molecular markers and targets for genetic manipulation to develop durable resistant rice cultivars. Strategies should be developed to activate downregulated genes, to improve multi-stress tolerance in plants.
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Oryza , Xanthomonas , Secas , Regulação da Expressão Gênica de Plantas , Oryza/genética , Oryza/microbiologia , Transcriptoma , Xanthomonas/genéticaRESUMO
Terminalia chebula Retz. forms a key component of traditional folk medicine and is also reported to possess antihepatitis C virus (HCV) and immunomodulatory activities. However, information on the intermolecular interactions of phytochemicals from this plant with HCV and human proteins are yet to be established. Thus, by this current study, we investigated the HCV NS3/4A inhibitory and host immune-modulatory activity of phytocompounds from T. chebula through in silico strategies involving network pharmacology and structural bioinformatics techniques. To start with, the phytochemical dataset of T. chebula was curated from biological databases and the published literature. Further, the target ability of the phytocompounds was predicted using BindingDB for both HCV NS3/4A and other probable host targets involved in the immune system. Further, the identified targets were docked to the phytochemical dataset using AutoDock Vina executed through the POAP pipeline. The resultant docked complexes with significant binding energy were subjected to 50 ns molecular dynamics (MD) simulation in order to infer the stability of complex formation. During network pharmacology analysis, the gene set pathway enrichment of host targets was performed using the STRING and Reactome pathway databases. Further, the biological network among compounds, proteins, and pathways was constructed using Cytoscape 3.6.1. Furthermore, the druglikeness, side effects, and toxicity of the phytocompounds were also predicted using the MolSoft, ADVERpred, and PreADMET methods, respectively. Out of 41 selected compounds, 10 were predicted to target HCV NS3/4A and also to possess druglike and nontoxic properties. Among these 10 molecules, Chebulagic acid and 1,2,3,4,6-Pentagalloyl glucose exhibited potent HCV NS3/4A inhibitory activity, as these scored a lowest binding energy (BE) of -8.6 kcal/mol and -7.7 kcal/mol with 11 and 20 intermolecular interactions with active site residues, respectively. These findings are highly comparable with Asunaprevir (known inhibitor of HCV NS3/4A), which scored a BE of -7.4 kcal/mol with 20 key intermolecular interactions. MD studies also strongly suggest that chebulagic acid and 1,2,3,4,6-Pentagalloyl glucose as promising leads, as these molecules showed stable binding during 50 ns of production run. Further, the gene set enrichment and network analysis of 18 protein targets prioritized 10 compounds and were predicted to potentially modulate the host immune system, hemostasis, cytokine levels, interleukins signaling pathways, and platelet aggregation. On overall analysis, this present study predicts that tannins from T. chebula have a potential HCV NS3/4A inhibitory and host immune-modulatory activity. However, further experimental studies are required to confirm the efficacies.
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Antivirais/farmacologia , Hepacivirus/enzimologia , Serina Proteases/química , Serina Proteases/metabolismo , Taninos/farmacologia , Terminalia/química , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Antivirais/efeitos adversos , Antivirais/química , Benzopiranos/farmacologia , Domínio Catalítico , Simulação por Computador , Glucosídeos/farmacologia , Hepacivirus/efeitos dos fármacos , Taninos Hidrolisáveis/farmacologia , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Farmacologia em Rede , Extratos Vegetais/farmacologia , Ligação Proteica , Conformação Proteica , Taninos/efeitos adversos , Taninos/química , Proteínas não Estruturais Virais/antagonistas & inibidoresAssuntos
Ensaios Clínicos como Assunto/estatística & dados numéricos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linfoma de Célula do Manto/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Terapia de Salvação , Adenina/análogos & derivados , Seguimentos , Humanos , Linfoma de Célula do Manto/patologia , Recidiva Local de Neoplasia/patologia , Piperidinas , Prognóstico , Taxa de SobrevidaRESUMO
Plants evolved several acquired tolerance traits for drought stress adaptation to maintain the cellular homeostasis. Drought stress at the anthesis stage in rice affects productivity due to the inefficiency of protein synthesis machinery. The effect of translational mechanisms on different pathways involved in cellular tolerance plays an important role. We report differential responses of translation-associated mechanisms in rice using polysome bound mRNA sequencing at anthesis stage drought stress in resistant Apo and sensitive IR64 genotypes. Apo maintained higher polysomes with 60 S-to-40 S and polysome-to-monosome ratios which directly correlate with protein levels under stress. IR64 has less protein levels under stress due to defective translation machinery and reduced water potential. Many polysome-bound long non-coding RNAs (lncRNA) were identified in both genotypes under drought, influencing translation. Apo had higher levels of N6-Methyladenosine (m6A) mRNA modifications that contributed for sustained translation. Translation machinery in Apo could maintain higher levels of photosynthetic machinery-associated proteins in drought stress, which maintain gas exchange, photosynthesis and yield under stress. The protein stability and ribosome biogenesis mechanisms favoured improved translation in Apo. The phytohormone signalling and transcriptional responses were severely affected in IR64. Our results demonstrate that, the higher translation ability of Apo favours maintenance of photosynthesis and physiological responses that are required for drought stress adaptation.
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Resistência à Seca , Oryza , Oryza/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fotossíntese , Secas , Polirribossomos/metabolismo , Estresse Fisiológico/genéticaRESUMO
Metatarsal fractures pose significant challenges in orthopedic practice, necessitating effective treatment methods to ensure optimal patient outcomes. This comprehensive review focuses on intramedullary Kirschner wire fixation as a promising intervention for metatarsal fractures. Beginning with an overview of metatarsal fractures and the imperative for effective treatments, the review delves into intramedullary fixation's definition, historical background, advantages, and disadvantages. Indications for its use in metatarsal fractures are discussed, providing a foundation for understanding its application. The surgical technique section outlines critical aspects, including patient selection criteria and preoperative planning. Before presenting a detailed step-by-step procedure for intramedullary Kirschner wire fixation, anesthesia considerations are explored. Emphasizing precision, fluoroscopic guidance, and meticulous postoperative care, this section provides insights for surgeons and healthcare practitioners. Considerations for rehabilitation follow, addressing postoperative care, expected recovery timelines, and physical therapy recommendations. Early mobilization, weight-bearing guidelines, and a structured rehabilitation program play pivotal roles in recovery. In the conclusion, key findings are summarized, highlighting the efficacy of intramedullary Kirschner wire fixation, its advantages, and recommendations for clinical practice. Additionally, areas for future research are identified, guiding further exploration and refinement of this surgical approach. This review is valuable for clinicians, researchers, and healthcare practitioners involved in metatarsal fracture management, contributing to the evolution of treatment strategies and improving patient care.
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Diabetes is a chronic metabolic disorder characterized by elevated levels of glucose in the blood. This causes small nerve polyneuropathy resulting in diabetic foot ulcers. A diabetic foot ulcer is an open sore or wound that develops as a result of chronic diabetes. Indocyanine green angiography (ICGA) near-infrared (NIR) can provide real-time visualization of blood flow within the microvasculature of the underlying organ. Here, we discuss a 63-year-old patient who came with a diabetic foot ulcer over his right great toe. His blood glucose level was 208 mg/dl. He drinks alcohol occasionally and smokes regularly. The tissue perfusion of his right foot was checked using the indocyanine green dye, after which orthopedic surgeons were consulted, and the gangrenous part was amputated.
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Soft tissue angiofibroma is a pathology consisting of a benign fibrous vascularized tumor that mimics low-grade sarcoma. Such tumors frequently arise in the extremities, more commonly in the lower extremities, presenting as a slow-growing, painless swelling. Females are more commonly affected than males. We present the case of a 42-year-old male with a slow-growing, painless mass on the extensor aspect of his left foot. Differential diagnoses considered were soft tissue fibrosarcoma, liposarcoma, and sebaceous cysts. Surgical excision of the tumor was done, and upon histopathology, there were multiple lobules with well-circumscribed, alternating areas of collagenous and myxoid tissues. There was a prominent small vascular network with uniformly arranged spindle cells consisting of pale eosinophil-rich cytoplasm and small ovoid nuclei, fine chromatin, and an indistinct nucleolus. There are not many reported cases of this clinical entity, and every new case reported brings light to the pathology and progression of this tumor. Understanding this pathology is necessary since it mimics many other skin and soft tissue tumors.
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Synovial chondromatosis is a rare and benign disorder that involves the synovial lining of joints, synovial sheaths and bursae. The synovial layer of the joint is affected by a metaplastic process which in turn converts it into cartilagenous tissue. Eventually, it gets dislodged and transformed into a loose body in the large joints. We report the case of a 24-year-old young athlete who presented with complaints of painful movements and restriction of joint movements associated with a growing deformity in the right knee joint. This case report aims to describe a rare synovial pathology that necessitated arthroscopic synovectomy and diagnostic arthroscopy to treat, particularly in younger individuals. The atypical feature, in this case, was metaplastic development from the peripheral joint capsule attached to the surrounding cartilage, which, to the extent that the authors are aware, has only been documented in one instance in the record. Magnetic resonance imaging (MRI) was performed which demonstrated evidence of the joint effusion, synovial hypertrophy and a loose calcific body just anterior of the distal femoral condyle causing pressure over the patellar tendon anteriorly as well as a hyper-dense cyst in the popliteal region. Treatment often requires partial or complete synovectomy with either an arthroscopic or open approach.
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This comprehensive review examines the intricate relationship between genetic variations in collagen-encoding genes and their implications in intervertebral disc degeneration (IVDD). Intervertebral disc degeneration is a prevalent spinal condition characterized by structural and functional changes in intervertebral discs (IVDs), and understanding its genetic underpinnings is crucial for advancing diagnostic and therapeutic strategies. The review begins by exploring the background and importance of collagen in IVDs, emphasizing its role in providing structural integrity. It then delves into the significance of genetic variations within collagen-encoding genes, categorizing and discussing their potential impact on disc health. The methods employed in studying these variations, such as genome-wide association studies (GWASs) and next-generation sequencing (NGS), are also reviewed. The subsequent sections analyze existing literature to establish associations between genetic variations and IVDD, unraveling molecular mechanisms linking genetic factors to disc degeneration. The review concludes with a summary of key findings, implications for future research and clinical practice, and a reflection on the importance of understanding genetic variations in collagen-encoding genes to diagnose and treat IVDD. The insights gleaned from this review contribute to our understanding of IVDD and hold promise for the development of personalized interventions based on individual genetic profiles.
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A rare benign bone condition called monostotic fibrous dysplasia (MFD) is characterized by the growth of fibrous tissue in place of a normal bone. It may lead to deformity in the affected bone, pain, and a pathologic fracture due to bone weakness. Hereunder, a case report of MFD in a 17-year-old male adolescent presenting to the hospital with localized bone pain and swelling in his right tibia is presented. After clinical examination and radiographic imaging, a provisional diagnosis of benign osteolytic lesion was considered. A magnetic resonance imaging (MRI) scan of the leg suggested the possibility of fibrous dysplasia or adamantinoma. The patient was managed with an intralesional curettage of the dysplastic bone and packing the cavity with blocks of a synthetic bone. The excised material was sent for histopathology, which established the diagnosis of fibrous dysplasia.
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This comprehensive review explores the mechanical and anatomical axis approaches in total knee replacement (TKR) surgery, addressing the ongoing debate within the orthopedic community. Emphasizing the significance of TKR in alleviating knee-related disorders, this review underscores the pivotal role of accurate alignment in achieving optimal surgical outcomes. The purpose is to navigate the divide between the well-established mechanical axis approach, focusing on a straight-line alignment, and the anatomical axis approach, aligning with natural knee landmarks. The analysis delves into the advantages, disadvantages, and clinical implications of each approach, offering a nuanced perspective on their efficacy. The conclusion emphasizes a patient-centric approach, recommending the adoption of hybrid strategies and the incorporation of emerging technologies for enhanced precision. The future of TKR aligns with personalized medicine, leveraging advancements in computer-assisted navigation, robotics, and patient-specific implants. Ongoing professional development and interdisciplinary collaboration are crucial for surgeons, and as the field evolves, innovations in artificial intelligence, imaging, and 3D printing are expected to shape the trajectory of TKR alignment approaches.
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Periprosthetic fractures (PPF) of the femur in connection with total hip arthroplasty are becoming common and also frequently challenging to repair. Such patients typically are frail, elderly, and have osteoporosis. Owing to a scarcity of research there are no clear strategies for its effective management. However, the Vancouver classification may help in facilitating treatment decisions. For fractures around a loose femoral prosthesis (types B2 and B3), revision using a modular uncemented long stem, with or without additional fracture fixation, has been known to provide a reliable outcome. It is prudent to treat osteoporosis for fracture healing and to prevent further fractures. In this case report, we share our experience with the use of an uncemented modular long femoral stem prosthesis with a cerclage wiring technique for the management of Vancouver type B3 PPF of the left femur in a 63-year-old male patient. Revision arthroplasty using a long stem prosthesis with a cerclage wiring technique can provide better fixation, stability, and functional outcomes for the patient.
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The outbreak of COVID-19 was seen first in Wuhan, China, on December 31, 2019. Following this, the virus has emerged, mutated, and spread to all parts of the world, taking many lives. Scientists and healthcare workers all over the world have been involved in developing vaccines and drugs to prevent the deadly virus from spreading. In this review article, we focus on how the human body responds to immune responses by producing antibodies against our immune system and serum levels in different age groups. Few studies are being considered, which include data collected from adults in the UK community, health workers from Oxfordshire, studies from the UK, healthcare workers at a university healthcare center in Turkey, and lastly, non-seropositive and seronegative healthcare workers in the USA children's hospital, respectively, and their responses to the goal. In addition to focusing on this study and its results, we also discuss the role of different vaccines and their development and antibody responses in the body due to natural and post-vaccine infections that include both doses in humans. We focus mainly on immunoglobulin M (IgM) and immunoglobulin G (IgG) levels in the serum produced by plasma cells, as they are involved in the first line of defense against the disease. With the development of effective vaccines and their production, trial, and market distribution to needy people, there are certain prospects for slowing down the progression of the virus, reducing mortality, and preventing re-infection in humans. However impactful and beneficial these vaccines have proven, they also carry a certain amount of danger to the people taking them. We also discuss in this article certain infrequent hematological and cardiovascular complications of the vaccine and their effect on the population.
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Malaria and tuberculosis remain highly prevalent infectious diseases and continue to cause significant burden worldwide. Endemic regions largely overlap, and co-infections are expected to occur frequently. Surprisingly, malaria-tuberculosis co-infection is relatively understudied. Malaria has long been known to have immunomodulatory effects, for example resulting in reduced vaccination responses against some pathogens, and it is conceivable that this also plays a role if co-infection occurs. Data from animal studies indeed suggest clinically important effects of malaria-tuberculosis co-infection on the immune responses with potential consequences for the pathophysiology and clinical course of both infections. Specifically, rodent studies consistently show reduced control of mycobacteria during malaria infection. Although the underlying immunological mechanisms largely remain unclear, an altered balance between pro- and anti-inflammatory responses may play a role. Some observations in humans also support the hypothesis that malaria infection skews the immune responses against tuberculosis, but data are limited. Further research is needed to unravel the underlying immunological mechanisms and delineate possible implications of malaria-tuberculosis co-infection for clinical practice.
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Kohler's disease is characterized by osteochondritis of the navicular bone due to various factors like the lack of blood supply and late ossification of the bone. In particular, it is a disease of the pediatric age group, which has male preponderance. It may present with bony pain unilaterally or, at times, be asymptomatic and diagnosed accidentally. Clinical presentation and radiological investigations are the mainstay of diagnosis. This self-limiting condition requires only symptomatic conservative management. A surgical approach is not yet indicated. One such case of bilateral Kohler's disease is presented in this report. Here, we discuss the disease's presentation, examination, treatment, and prognosis.
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Orthopedic surgeries, ranging from joint replacements to fracture fixations, are integral procedures that enhance the quality of life for countless individuals. Effective postoperative pain management is crucial in ensuring optimal patient recovery and satisfaction. This comprehensive review analyzes the diverse array of analgesic modalities employed in orthopedic practice for postoperative pain relief. The review systematically explores the pharmacological landscape of analgesics commonly used in orthopedic settings, including opioids, non-steroidal anti-inflammatory drugs, acetaminophen, and adjuvant medications. Emphasis is placed on their mechanisms of action, efficacy profiles, and potential adverse effects. Special attention is given to the evolving role of multimodal analgesia, which combines various agents to achieve synergistic pain control while minimizing individual drug-related complications. Furthermore, the review addresses the emerging trends and advancements in postoperative analgesia within orthopedics, such as integrating regional anesthesia techniques, peripheral nerve blocks, and novel pharmacological agents. A critical evaluation of evidence-based practices and recent clinical trials is incorporated to guide practitioners in making informed decisions regarding postoperative pain management. Consideration is also given to the individualized nature of pain experiences and the importance of patient-centric approaches. The review underscores the significance of tailoring analgesic regimens based on patient characteristics, surgical procedures, and potential complications, fostering a personalized and effective pain management strategy. In conclusion, this comprehensive review is valuable for orthopedic practitioners, anesthetists, and healthcare professionals involved in postoperative care. By synthesizing current knowledge and highlighting evolving trends, the review contributes to the ongoing dialogue on optimizing pain management strategies in orthopedic practice, ultimately improving patient outcomes and satisfaction.