A Meta-Analysis of Success Rates of One-Stage Versus Two-Stage Revisions in Knee Prosthetic Joint Infections.

Prosthetic joint infections (PJIs) pose significant challenges following total joint arthroplasties and cause profound complications. They are associated with significant morbidity and mortality. One-stage revision involves the removal of the infected implant and simultaneous re-implantation of a new prosthesis in a single surgical procedure. The two-stage approach is traditionally more common in the United States and follows a deliberate sequence: the infected implant is first removed, followed by a period of antibiotic therapy, and then a second surgery for implant reinsertion. While two-stage revisions were traditionally considered the gold standard, recent advancements have introduced one-stage revisions as a viable alternative. One-stage revision offers the advantage of being a single procedure, significantly reducing the patient's downtime without a functioning knee. Currently, there has not been a comprehensive exploration of the comparative outcomes between two-stage revisions and one-stage revisions. This systematic review and meta-analysis aimed to assess the outcomes of both one- and two-stage revisions for total knee arthroplasties (TKAs), by utilizing comparison studies as the foundation for analysis. Our search encompassed databases such as MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase, and Cochrane to identify articles examining the comparative efficacy and outcomes of one- and two-stage revision procedures between January 2000 and June 2023. We employed keywords relevant to knee PJIs to identify comparative studies reporting on success rates, reinfection rates, microbiological findings, and other pertinent outcomes. Statistical analysis for this investigation was performed using Review Manager 5.4 (The Cochrane Collaboration, 2020) with a standard significance threshold set at a p-value less than .05. This meta-analysis incorporated six comparison articles and 802 patients. Two-stage revisions (547 patients) were associated with greater success rates (i.e., infection eradication) than one-stage revisions (255 patients) (p = .03). The studies did not suggest a difference in the microbiology of the infections. Two-stage revisions are associated with higher success rates than one-stage revisions in the treatment of knee PJIs. Future randomized controlled trials should evaluate the optimization of the management of these complications.

The STRAT-PARK cohort: A personalized initiative to stratify Parkinson's disease.

The STRAT-PARK initiative aims to provide a platform for stratifying Parkinson's disease (PD) into biological subtypes, using a bottom-up, multidisciplinary biomarker-based and data-driven approach. PD is a heterogeneous entity, exhibiting high interindividual clinicopathological variability. This diversity suggests that PD may encompass multiple distinct biological entities, each driven by different molecular mechanisms. Molecular stratification and identification of disease subtypes is therefore a key priority for understanding and treating PD. STRAT-PARK is a multi-center longitudinal cohort aiming to recruit a total of 2000 individuals with PD and neurologically healthy controls from Norway and Canada, for the purpose of identifying molecular disease subtypes. Clinical assessment is performed annually, whereas biosampling, imaging, and digital and neurophysiological phenotyping occur every second year. The unique feature of STRAT-PARK is the diversity of collected biological material, including muscle biopsies and platelets, tissues particularly useful for mitochondrial biomarker research. Recruitment rate is ∼150 participants per year. By March 2023, 252 participants were included, comprising 204 cases and 48 controls. STRAT-PARK is a powerful stratification initiative anticipated to become a global research resource, contributing to personalized care in PD.

Innovations in Diabetic Macular Edema Management: A Comprehensive Review of Automated Quantification and Anti-vascular Endothelial Growth Factor Intervention.

Diabetic macular edema (DME) poses a significant threat to the vision and quality of life of individuals with diabetes. This comprehensive review explores recent advancements in DME management, focusing on integrating automated quantification techniques and anti-vascular endothelial growth factor (anti-VEGF) interventions. The review begins with an overview of DME, emphasizing its prevalence, impact on diabetic patients, and current challenges in management. It then delves into the potential of automated quantification, leveraging machine learning and artificial intelligence to improve early detection and monitoring. Concurrently, the role of anti-VEGF therapies in addressing the underlying vascular abnormalities in DME is scrutinized. The review synthesizes vital findings, highlighting the implications for the future of DME management. Promising outcomes from recent clinical trials and case studies are discussed, providing insights into the evolving landscape of personalized medicine approaches. The conclusion underscores the transformative potential of these innovations, calling for continued research, collaboration, and integration of these advancements into clinical practice. This review aims to serve as a roadmap for researchers, clinicians, and industry stakeholders, fostering a collective effort to enhance the precision and efficacy of DME management.

Comparison of three-dimensional cell culture techniques of dedifferentiated liposarcoma and their integration with future research.

Background: Dedifferentiated liposarcoma is a formidable sarcoma subtype due to its high local recurrence rate and resistance to medical treatment. While 2D cell cultures are still commonly used, 3D cell culture systems have emerged as a promising alternative, particularly scaffold-based techniques that enable the creation of 3D models with more accurate cell-stroma interactions. Objective: To investigate how 3D structures with or without the scaffold existence would affect liposarcoma cell lines growth morphologically and biologically. Methods: Lipo246 and Lipo863 cell lines were cultured in 3D using four different methods; Matrigel® ECM scaffold method, Collagen ECM scaffold method, ULA plate method and Hanging drop method, in addition to conventional 2D cell culture methods. All samples were processed for histopathological analysis (HE, IHC and DNAscope™), Western blot, and qPCR; moreover, 3D collagen-based models were treated with different doses of SAR405838, a well-known inhibitor of MDM2, and cell viability was assessed in comparison to 2D model drug response. Results: Regarding morphology, cell lines behaved differently comparing the scaffold-based and scaffold-free methods. Lipo863 formed spheroids in Matrigel® but not in collagen, while Lipo246 did not form spheroids in either collagen or Matrigel®. On the other hand, both cell lines formed spheroids using scaffold-free methods. All samples retained liposarcoma characteristic, such as high level of MDM2 protein expression and MDM2 DNA amplification after being cultivated in 3D. 3D collagen samples showed higher cell viability after SAR40538 treatment than 2D models, while cells sensitive to the drug died by apoptosis or necrosis. Conclusion: Our results prompt us to extend our investigation by applying our 3D models to further oncological relevant applications, which may help address unresolved questions about dedifferentiated liposarcoma biology.

A review of artificial intelligence-assisted omics techniques in plant defense: current trends and future directions.

Plants intricately deploy defense systems to counter diverse biotic and abiotic stresses. Omics technologies, spanning genomics, transcriptomics, proteomics, and metabolomics, have revolutionized the exploration of plant defense mechanisms, unraveling molecular intricacies in response to various stressors. However, the complexity and scale of omics data necessitate sophisticated analytical tools for meaningful insights. This review delves into the application of artificial intelligence algorithms, particularly machine learning and deep learning, as promising approaches for deciphering complex omics data in plant defense research. The overview encompasses key omics techniques and addresses the challenges and limitations inherent in current AI-assisted omics approaches. Moreover, it contemplates potential future directions in this dynamic field. In summary, AI-assisted omics techniques present a robust toolkit, enabling a profound understanding of the molecular foundations of plant defense and paving the way for more effective crop protection strategies amidst climate change and emerging diseases.

Chemical Pneumonitis and Reactive Airways Dysfunction Syndrome After Fumigation Exposure to Dimethanol and Glutaraldehyde: A Silent Menace Unmasked.

Chemical pneumonitis caused by dimethanol and glutaraldehyde exposure is a serious medical condition that requires prompt and effective treatment. As per a literature search in Google Scholar, PubMed, and Scopus, this is the first instance of chemical pneumonitis caused after fumigation with dimethanol and glutaraldehyde inhalation. This article discusses the factors that can contribute to the development of chemical pneumonitis and outlines the diagnostic and treatment options available to healthcare professionals. By understanding the causes and consequences of dimethanol- and glutaraldehyde-induced chemical pneumonitis, medical professionals can provide better care to their patients and help prevent future cases of this potentially life-threatening condition. This describes a case of a 60-year-old female who presented to the emergency department complaining of acute onset of shortness of breath approximately 48 hours after being exposed to dimethanol and glutaraldehyde while working in intensive care. After 13 days, the patient's symptoms subsided and she was discharged. On follow-up, after 1 month, there was a marked resolution of the initial symptoms.

Recent advances on genome-wide association studies (GWAS) and genomic selection (GS); prospects for Fusarium head blight research in Durum wheat.

PURPOSE: Wheat is an important cereal crop that is cultivated in different parts of the world. The biotic stresses are the major concerns in wheat-growing nations and are responsible for production loss globally. The change in climate dynamics makes the pathogen more virulent in foothills and tropical regions. There is growing concern about FHB in major wheat-growing nations, and until now, there has been no known potential source of resistance identified in wheat germplasm. The plant pathogen interaction activates the cascade of pathways, genes, TFs, and resistance genes. Pathogenesis-related genes' role in disease resistance is functionally validated in different plant systems. Similarly, Genomewide association Studies (GWAS) and Genomic selection (GS) are promising tools and have led to the discovery of resistance genes, genomic regions, and novel markers. Fusarium graminearum produces deoxynivalenol (DON) mycotoxins in wheat kernels, affecting wheat productivity globally. Modern technology now allows for detecting and managing DON toxin to reduce the risk to humans and animals. This review offers a comprehensive overview of the roles played by GWAS and Genomic selection (GS) in the identification of new genes, genetic variants, molecular markers and DON toxin management strategies. METHODS: The review offers a comprehensive and in-depth analysis of the function of Fusarium graminearum virulence factors in Durum wheat. The role of GWAS and GS for Fusarium Head Blight (FHB) resistance has been well described. This paper provides a comprehensive description of the various statistical models that are used in GWAS and GS. In this review, we look at how different detection methods have been used to analyze and manage DON toxin exposure. RESULTS: This review highlights the role of virulent genes in Fusarium disease establishment. The role of genome-based selection offers the identification of novel QTLs in resistant wheat germplasm. The role of GWAS and GS selection has minimized the use of population development through breeding technology. Here, we also emphasized the function of recent technological developments in minimizing the impact of DON toxins and their implications for food safety.

Neuroimaging Pearls from the MDS Congress Video Challenge. Part 2: Acquired Disorders.

The MDS Video Challenge continues to be the one of most widely attended sessions at the International Congress. Although the primary focus of this event is the presentation of complex and challenging cases through videos, a number of cases over the years have also presented an unusual or important neuroimaging finding related to the case. We reviewed the previous Video Challenge cases and present here a selection of those cases which incorporated such imaging findings. We have compiled these "imaging pearls" into two anthologies. The first focuses on pearls where the underlying diagnosis was a genetic condition. This second anthology focuses on imaging pearls in cases where the underlying condition was acquired. For each case we present brief clinical details along with neuroimaging findings, the characteristic imaging findings of that disorder and, finally, the differential diagnosis for the imaging findings seen.

Brain iron deposition and movement disorders in hereditary haemochromatosis without liver failure: A cross-sectional study.

BACKGROUND AND PURPOSE: Hereditary haemochromatosis (HH) is the most common inherited disorder of systemic iron excess in Northern Europeans. Emerging evidence indicates that brain iron overload occurs in HH. Despite this observation, there is a paucity of literature regarding central neurological manifestations, in particular movement disorders, in HH. The current study documents deep gray matter (DGM) nuclei iron deposition, movement disorders, and clinicoradiological correlations in HH without liver failure. METHODS: This is a cross-sectional study. Consecutive subjects with HFE-haemochromatosis without liver disease were recruited from an outpatient gastroenterology clinic. Age- and sex-matched healthy controls (HCs) were enrolled. Iron content in individual DGM nuclei was measured as mean susceptibility on magnetic resonance imaging using quantitative susceptibility mapping-based regions of interest analysis. Occurrence and phenotype of movement disorders were documented and correlated with patterns of DGM nuclei iron deposition in subjects with HH. RESULTS: Fifty-two subjects with HH and 47 HCs were recruited. High magnetic susceptibility was demonstrated in several DGM nuclei in all HH subjects compared to HCs. Thirty-five subjects with HH had movement disorders. Magnetic susceptibility in specific DGM nuclei correlated with individual movement disorder phenotypes. Serum ferritin, phlebotomy frequency, and duration were poor predictors of brain iron deposition. CONCLUSIONS: Abnormal brain iron deposition can be demonstrated on imaging in all subjects with HH without liver failure. A significant proportion of these subjects manifest movement disorders. Peripheral iron measurements appear not to correlate with brain iron deposition. Therefore, routine neurological examination and quantitative brain iron imaging are recommended in all subjects with HH.

Clinical biomarkers in soft tissue sarcoma A comprehensive review of current soft tissue sarcoma biomarkers.

Soft tissue sarcomas (STS) are a heterogeneous group of tumors that arise from mesenchymal tissue. Investigation at the molecular level has been challenging due to the rarity of STS and the number of histologic subtypes. However, recent research has provided new insight into potential genomic, proteomic, and immunological biomarkers of STS. The identification of biomarkers can improve diagnosis, prognosis, and prediction of recurrence and treatment response. This review provides an understanding of biomarkers, discussing the current status of biomarker research in STS.

Evaluating newer generation intraocular lens calculation formulas in manual versus femtosecond laser-assisted cataract surgery.

AIM: To determine the refractive accuracy of the Haigis, Barrett Universal II (Barrett), and Hill-radial basis function 2.0 (Hill-RBF) intraocular lens (IOL) power calculations formulas in eyes undergoing manual cataract surgery (MCS) and refractive femtosecond laser-assisted cataract surgery (ReLACS). METHODS: This was a REB-approved, retrospective interventional comparative case series of 158 eyes of 158 patients who had preoperative biometry completed using the IOL Master 700 and underwent implantation of a Tecnis IOL following uncomplicated cataract surgery using either MCS or ReLACS. Target spherical equivalence (SE) was predicted using the Haigis, Barrett, and Hill-RBF formulas. An older generation formula (Hoffer Q) was included in the analysis. Mean refractive error (ME) was calculated one month postoperatively. The lens factors of all formulas were retrospectively optimized to set the ME to 0 for each formula across all eyes. The median absolute errors (MedAE) and the proportion of eyes achieving an absolute error (AE) within 0.5 diopters (D) were compared between the two formulas among MCS and ReLACS eyes, respectively. RESULTS: Of the 158 eyes studied, 64 eyes underwent MCS and 94 eyes underwent ReLACS. Among MCS eyes, the MedAE did not differ between the formulas (P=0.59), however among ReLACS eyes, Barrett and Hill-RBF were more accurate (P=0.001). Barrett and Hill-RBF were both more likely to yield AE<0.5 D among both groups (P<0.001). CONCLUSION: The Barrett and Hill-RBF formula lead to greater refractive accuracy and likelihood of refractive success when compare to Haigis in eyes undergoing ReLACS.

Links between mitochondrial retrograde response and mitophagy in pathogenic cell signalling.

Preservation of mitochondrial quality is paramount for cellular homeostasis. The integrity of mitochondria is guarded by the balanced interplay between anabolic and catabolic mechanisms. The removal of bio-energetically flawed mitochondria is mediated by the process of mitophagy; the impairment of which leads to the accumulation of defective mitochondria which signal the activation of compensatory mechanisms to the nucleus. This process is known as the mitochondrial retrograde response (MRR) and is enacted by Reactive Oxygen Species (ROS), Calcium (Ca2+), ATP, as well as imbalanced lipid and proteostasis. Central to this mitochondria-to-nucleus signalling are the transcription factors (e.g. the nuclear factor kappa-light-chain-enhancer of activated B cells, NF-κB) which drive the expression of genes to adapt the cell to the compromised homeostasis. An increased degree of cellular proliferation is among the consequences of the MRR and as such, engagement of mitochondrial-nuclear communication is frequently observed in cancer. Mitophagy and the MRR are therefore interlinked processes framed to, respectively, prevent or compensate for mitochondrial defects.In this review, we discuss the available knowledge on the interdependency of these processes and their contribution to cell signalling in cancer.

Non-invasive Transcranial Electrical Stimulation in Movement Disorders.

Dysfunction within large-scale brain networks as the basis for movement disorders is an accepted hypothesis. The treatment options for restoring network function are limited. Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation are now being studied to modify the network. Transcranial electrical stimulation (tES) is also a portable, cost-effective, and non-invasive way of network modulation. Transcranial direct current stimulation and transcranial alternating current stimulation have been studied in Parkinson's disease, dystonia, tremor, and ataxia. Transcranial pulsed current stimulation and transcranial random noise stimulation are not yet studied enough. The literature in the use of these techniques is intriguing, yet many unanswered questions remain. In this review, we highlight the studies using these four potential tES techniques and their electrophysiological basis and consider the therapeutic implication in the field of movement disorders. The objectives are to consolidate the current literature, demonstrate that these methods are feasible, and encourage the application of such techniques in the near future.

Treatment of essential tremor: current status.

Essential tremor is the most common cause of tremor involving upper limbs, head and voice. The first line of treatment for limb tremor is pharmacotherapy with propranolol or primidone. However, these two drugs reduce the tremor severity by only half. In medication refractory and functionally disabling tremor, alternative forms of therapy need to be considered. Botulinum toxin injections are likely efficacious for limb, voice and head tremor but are associated with side effects. Surgical interventions include deep brain stimulation; magnetic resonance-guided focused ultrasound and thalamotomy for unilateral and deep brain stimulation for bilateral procedures. Recent consensus classification for essential tremor has included a new subgroup, 'Essential tremor plus', who have associated subtle neurological 'soft signs', such as dystonic posturing of limbs and may require a different treatment approach. In this review, we have addressed the current management of essential tremor with regard to different anatomical locations of tremor as well as different modalities of treatment.

Botulinum Toxin Induced Atrophy: An Uncharted Territory.

Botulinum neurotoxins (BoNTs) produce local chemo-denervation by cleaving soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE) proteins. Botulinum neurotoxins are therapeutically indicated in several neurological disorders and have been in use for three decades. The long-term efficacy, safety, and side effects of BoNTs have been well documented in the literature. However, the development of muscle atrophy following chronic exposure to BoNTs has not received sufficient attention. Muscle atrophy is not only cosmetically distressing, but also has an impact on future injections. An extensive literature search was conducted on atrophy and mechanisms of atrophy. Five hundred and four relevant articles in the English language were reviewed. This review revealed the surprising lack of documentation of atrophy within the literature. In addition, as demonstrated in this review, the mechanisms and the clinical factors that may lead to atrophy have also been poorly studied. However, even with this limited information it is possible to indicate factors that could modify the clinical approach to botulinum toxin injections. This review highlights the need for further study of atrophy following BoNT injections.

Botulinum toxin in Meige's syndrome: A video-based case series.

CONTEXT: Despite being the most common cause of cranial dystonia, Meige's syndrome remains a rare clinical entity. Characterized by blepharospasm and orofacial dystonia, patients suffering from Meige's syndrome benefit from the injection of botulinum toxin (BTX). AIMS: As the majority of the studies tend to discuss Meige's syndrome with blepharospasm patients, there is a paucity of case-based studies dealing exclusively with this syndrome. Hence, we intended to characterize and define the evolution of this syndrome and objectively determine the response of the patients suffering from this entity to BTX therapy. MATERIALS AND METHODS: Eight patients with Meige's syndrome who had never been injected with BTX in the past were evaluated at our movement disorder clinic using a structured questionnaire. Videotaping of abnormal movements was done for 5 minutes before the BTX injection and at a 1-month follow-up. All patients received electromyography-guided injection of BTX and the dosage was decided using clinical evaluation. Their demography, clinical features, and treatment response to BTX were analyzed using the "Burke-Fahn-Marsden dystonia rating scale" (BFMDRS) before injection and at a 1-month follow-up. RESULTS: The peak age of symptom onset was 46.4 years with a male: female ratio of 1:1. The average duration of symptoms was 6.43 years. Majority of the patients (6/8) manifested their disease with blepharospasm, including five patients who had clonic blepharospasm. Lingual dystonia (6/8) and pharyngeal involvement (4/8) were commonly noted. Sensory tricks were present in all, with placement of the fingers over eyelids being the commonest trick (7/8). The average BTX dose administered was 51.58 units, and the peak onset of relief was noted at 8.62 days after the injection. The duration of the effect lasted for 82.5 days on an average. Only one patient reported mild weakness of the muscles of mastication following BTX injection. The average BFMDRS improved from the preprocedural score of 25.06 to 13.12 following the BTX injection. CONCLUSIONS: In this series exclusively dealing with Meige's syndrome patients, tongue involvement was found to be very common (6/8, 75%), and the response to the first dose of BTX treatment was found to be excellent without the occurrence of any major side effects.