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1.
JTO Clin Res Rep ; 5(6): 100592, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38827378

ABSTRACT

Introduction: EGFR exon 20 insertion (ex20ins) mutations account for approximately 10% of EGFR mutations in lung adenocarcinoma. Patients with ex20ins mutation do not respond to standard EGFR tyrosine kinase inhibitor therapy. In this work, we analyzed the characteristics, treatment patterns, and outcomes in this subgroup of patients with NSCLC. Methods: The American Society of Clinical Oncology CancerLinQ Discovery data set was queried to identify patients with initial diagnosis of NSCLC between the years 1995 and 2018 and with EGFR ex20ins mutations. Data were extracted on patient demographics, tumor characteristics, treatments, and outcomes, and compared using chi-square and analysis of variance. Kaplan-Meier curves were generated to compare overall survival with log-rank tests. All analyses were performed using Python 3.6 (Python Software Foundation). Results: A total of 357 patients were eligible. Patient characteristics include a median age of 68 years comprising female sex of 54%, White race of 63%, and Black race of 9%. Approximately 62% of total patients had stage 4 disease, and 30% of all patients had brain metastasis. There were 54% of patients who were treated with chemotherapy and 15% with immune checkpoint inhibitors (ICIs). In patients with brain metastasis, 16% were treated with ICI, 18% with targeted therapy, and 59% with chemotherapy. The median survival of the entire group was 23.8 months. Among patients with stage 4 disease (n = 222): 51% were women, 64% were white, 37% had brain metastasis, 18% were treated with ICI, 14% had targeted therapy, and 60% were treated with chemotherapy. Stage 4 patients treated with targeted therapy had better survival compared with those who did not receive targeted therapy (20.6 versus 16.1 mo, p = 0.02). Univariate and multivariate analyses suggested favorable outcomes for patients treated with immunotherapy. Conclusions: EGFR ex20ins mutation represents a unique subset of NSCLC; it is associated with a higher propensity for brain metastases and a relatively modest overall survival. Novel treatment approaches are urgently needed to improve patient outcomes.

2.
World Neurosurg ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38945207

ABSTRACT

BACKGROUND: Craniovertebral junction tumors are challenging due to their unique anatomical location. This study aimed to evaluate the complexities in dealing with such precarious craniovertebral junction extradural lesions over the decade. METHODS: 27 patients of extradural CVJ tumors operated between 2009-2018 were included. The demographic details, neurological status, surgical approach, extent of resection, type of fixation, complications and outcome at final follow-up were recorded for each patient. RESULTS: The mean age of the patients was 39.5 +/- 20 years. Most (17/27) of the patients had involvement of a single level. Clivus was the most common (9/17) involved region followed by atlas (7/17) vertebrae. Majority of the patients (13/27) were operated through the posterior-only approach. About 15 patients (55.5%) had instability or extensive lesions that necessitated posterior fixation. None of the patients underwent anterior fixation. Gross and near total excision were achieved in 10 patients (37%) and 3 patients (11 %) respectively while 14 patients underwent subtotal excision of tumor. On histopathological analysis, clival chordoma (8/27) was found to be the most common pathology followed by giant cell tumor (6/27), plasmacytoma (4/27) and multiple myeloma (2/27). Most patients (13 out of 27) had the same neurological status after the surgery. Six patients (22%) improved post-operatively with decreased weakness and spasticity. Thirteen (48%) patients underwent adjuvant radiotherapy. CONCLUSION: This retrospective study provides valuable insights into managing extradural CVJ tumors and highlights the importance of individualized approaches for optimal outcome.

3.
Proteomics ; : e2400071, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700387

ABSTRACT

Plasma is an abundant source of proteins and potential biomarkers to aid in the detection, diagnosis, and prognosis of human diseases. These proteins are often present at low levels in the blood and difficult to identify and measure due to the large dynamic range of proteins. The goal of this work was to characterize and compare various protein precipitation methods related to how they affect the depth and breadth of plasma proteomic studies. Abundant protein precipitation with perchloric acid (PerCA) can increase protein identifications and depth of plasma proteomic studies. Three acid- and four solvent-based precipitation methods were evaluated. All methods tested provided excellent plasma proteomic coverage (>600 identified protein groups) and detected protein in the low pg/mL range. Functional enrichment analysis revealed subtle differences within and larger changes between the precipitant groups. Methanol-based precipitation outperformed the other methods based on identifications and reproducibility. The methods' performance was verified using eight lung cancer patient samples, where >700 protein groups were measured and proteins with an estimated plasma concentration of ∼10 pg/mL were detected. Various protein precipitation agents are amenable to extending the depth and breadth of plasma proteomes. These data can guide investigators to implement inexpensive, high-throughput methods for their plasma proteomic workflows.

5.
Neuropharmacology ; 251: 109942, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38570066

ABSTRACT

Epilepsy is a neurological disorder characterised by unprovoked, repetitive seizures caused by abnormal neuronal firing. The Wnt/ß-Catenin signalling pathway is involved in seizure-induced neurogenesis, aberrant neurogenesis, neuroinflammation, and hyperexcitability associated with epileptic disorder. Wnt/ß-Catenin signalling is crucial for early brain development processes including neuronal patterning, synapse formation, and N-methyl-d-aspartate receptor (NMDAR) regulation. Disruption of molecular networks such as Wnt/ß-catenin signalling in epilepsy could offer encouraging anti-epileptogenic targets. So, with a better understanding of the canonical Wnt/-Catenin pathway, we highlight in this review the important elements of Wnt/-Catenin signalling specifically in Mesial Temporal Lobe Epilepsy (MTLE) for potential therapeutic targets.


Subject(s)
Epilepsy, Temporal Lobe , Epilepsy , Humans , Epilepsy, Temporal Lobe/chemically induced , beta Catenin/metabolism , Neuroinflammatory Diseases , Epilepsy/metabolism , Neurogenesis , Catenins/metabolism , Hippocampus/metabolism
6.
Expert Opin Ther Targets ; 28(4): 283-294, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38629385

ABSTRACT

INTRODUCTION: Epilepsy is a chronic neurological condition characterized by a persistent propensity for seizure generation. About one-third of patients do not achieve seizure control with the first-line treatment options, which include >20 antiseizure medications. It is therefore imperative that new medications with novel targets and mechanisms of action are developed. AREAS COVERED: Clinical studies and preclinical research increasingly implicate Non-receptor tyrosine kinases (nRTKs) in the pathogenesis of epilepsy. To date, several nRTK members have been linked to processes relevant to the development of epilepsy. Therefore, in this review, we provide insight into the molecular mechanisms by which the various nRTK subfamilies can contribute to the pathogenesis of epilepsy. We further highlight the prospective use of specific nRTK inhibitors in the treatment of epilepsy deriving evidence from existing literature providing a rationale for their use as therapeutic targets. EXPERT OPINION: Specific small-molecule inhibitors of NRTKs can be employed for the targeted therapy as already seen in other diseases by examining the precise molecular pathways regulated by them contributing to the development of epilepsy. However, the evidence supporting NRTKs as therapeutic targets are limiting in nature thus, necessitating more research to fully comprehend their function in the development and propagation of seizures.


Subject(s)
Anticonvulsants , Drug Development , Epilepsy , Molecular Targeted Therapy , Protein Kinase Inhibitors , Protein-Tyrosine Kinases , Humans , Epilepsy/drug therapy , Epilepsy/physiopathology , Animals , Anticonvulsants/pharmacology , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/metabolism
7.
Methods Mol Biol ; 2761: 57-66, 2024.
Article in English | MEDLINE | ID: mdl-38427229

ABSTRACT

The objective of this chapter is to provide an overview of the methods used to investigate the connectivity and structure of the nervous system. These methods allow neuronal cells to be categorized according to their location, shape, and connections to other cells. The Golgi-Cox staining gives a thorough picture of all significant neuronal structures found in the brain that may be distinguished from one another. The most significant characteristic is its three-dimensional integrity since all neuronal structures may be followed continuously from one part to the next. Successions of sections of the brain's neurons are seen with the Golgi stain. The Golgi method is used to serially segment chosen brain parts, and the resulting neurons are produced from those sections.


Subject(s)
Dendrites , Dendritic Spines , Dendritic Spines/physiology , Dendrites/physiology , Neurons/physiology , Temporal Lobe , Silver Staining , Hippocampus
8.
Methods Mol Biol ; 2761: 67-79, 2024.
Article in English | MEDLINE | ID: mdl-38427230

ABSTRACT

Cytokines have the potential to be the ideal biomarkers to track the onset and progression of immune-mediated diseases, study the development of novel therapeutic strategies, and they can serve as outcome parameters due to their crucial role in the regulation of immune and inflammatory responses. It is vital to keep track of the entire cytokine spectrum due to the complex interactions, pleiotropic effects, and redundancy in the cytokine network. The multiplex immunoassay (MIA) is, therefore, the best method for achieving that goal. This chapter addresses the key methodological processes of this technique, such as sample preparation, antibody coupling to beads, and assay procedure.


Subject(s)
Antibodies , Cytokines , Humans , Immunoassay/methods , Brain , Extracellular Space , Biomarkers
9.
Int J Lab Hematol ; 46(3): 515-522, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38357712

ABSTRACT

BACKGROUND: Altered T-cell repertoire with an aberrant T-cell activation and imbalance of the Th17/Treg cells has been reported in acquired aplastic anemia (aAA). miRNAs are well known to orchestrate T-cell activation and differentiation, however, their role in aAA is poorly characterized. The study aimed at identifying the profile of miRNAs likely to be involved in T-cell activation and the Th17/Treg-cell imbalance in aAA, to explore newer therapeutic targets. METHODS: Five milliliters peripheral blood samples from 30 patients of aAA and 15 healthy controls were subjected to flow cytometry for evaluating Th17- and Treg-cell subsets. The differential expression of 7 selected miRNAs viz; hsa-miR-126-3p, miR-146b-5p, miR-155-5p, miR-16, miR-17, miR-326, and miR-181c was evaluated in the PB-MNCs. Expression analysis of the miRNAs was performed using qRT-PCR and fold change was calculated by 2-ΔΔCt method. The alterations in the target genes of deregulated miRNAs were assessed by qRT-PCR. The targets studied included various transcription factors, cytokines, and downstream proteins. RESULTS: The absolute CD3+ lymphocytes were significantly elevated in the PB of aAA patients when compared with healthy controls (p < 0.0035), however, the CD4:CD8 ratio was unperturbed. Th17: Treg-cell ratio was altered in aAA patients (9.1 vs. 3.7%, p value <0.05), which correlated positively with disease severity and the PNH positive aAA. Across all severities of aAA, altered expression of the 07 miRNAs was noted in comparison to controls; upregulation of miR-155 (FC-2.174, p-value-0.0001), miR-146 (FC-2.006, p-value-0.0001), and miR-17 (FC-3.1, p-value-0.0001), and downregulation of miR-126 (FC-0.329, p-value-0.0001), miR-181c (FC-0.317, p-value-0.0001), miR-16 (FC-0.348, p-value-0.0001), and miR-326 (FC-0.334, p-value-0.0001). Target study for these miRNAs revealed an increased expression of transcription factors responsible for Th1 and Th17 differentiation (T-bet, RORϒt, IL-17, IL-6, and IFN-ϒ), T-cell activation (NFκB, MYC, and PIK3R2), downregulation of FOX-P3, and other regulatory downstream molecules like SHIP-1, ETS-1, IRAK-1, TRAF-6, and PTEN. CONCLUSION: The study for the first time highlights the plausible role of different miRNAs in deregulating the Th17/Treg-cell imbalance in aAA, and comprehensively suggest the role of altered NF-kB and mTOR pathways in aAA. The axis may be actively explored for development of newer therapeutic targets in aAA.


Subject(s)
Anemia, Aplastic , Lymphocyte Activation , MicroRNAs , T-Lymphocytes, Regulatory , Th17 Cells , Humans , MicroRNAs/genetics , Th17 Cells/immunology , Th17 Cells/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Anemia, Aplastic/immunology , Anemia, Aplastic/genetics , Male , Female , Adult , Middle Aged , Gene Expression Regulation , Aged , Adolescent
10.
Biomed Phys Eng Express ; 10(2)2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38241730

ABSTRACT

Low-grade gliomas (LGGs) are a heterogeneous group of tumors with an average 10-year survival rate of 40%-55%. Current treatment options include chemotherapy, radiotherapy, and gross total resection (GTR) of the tumor. The extent of resection (EOR) plays an important role in improving surgical outcomes. However, the major obstacle in treating low-grade gliomas is their diffused nature and the presence of residual cancer cells at the tumor margins post resection. Cold Atmospheric Plasma (CAP) has shown to be effective in targeted killing of tumor cells in various glioma cell lines without affecting non-tumor cells through Reactive Oxygen and Nitrogen Species (RONS). However, no study on the effectiveness of CAP has been carried out in LGG tissues till date. In this study, we applied helium-based CAP on tumor tissues resected from LGG patients. Our results show that CAP is effective in promoting RONS accumulation in LGG tissues when CAP jet parameters are set at 4 kV voltage, 5 min treatment time and 3 lpm gas flow rate. We also observed that CAP jet is more effective in thinner slice preparations of tumor as compared to thick tumor samples. Our results indicate that CAP could prove to be an effective adjunct therapy in glioma surgery to target residual cancer cells to improve surgical outcome of patients with low-grade glioma.


Subject(s)
Brain Neoplasms , Glioma , Plasma Gases , Humans , Brain Neoplasms/therapy , Reactive Oxygen Species , Oxygen , Reactive Nitrogen Species , Neoplasm, Residual , Treatment Outcome , Glioma/therapy
11.
Childs Nerv Syst ; 40(4): 1239-1244, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38032484

ABSTRACT

PURPOSE: Epilepsy surgery for pediatric drug-resistant epilepsy has been shown to improve seizure control, enhance patient and family QoL, and reduce mortality. However, diagnostic tools and surgical capacity are less accessible worldwide. The International Society Pediatric Neurosurgery (ISPN) has established a Pediatric Epilepsy Surgery Interest Group (PESIG), aiming to enhance global collaboration in research and educational aspects. The goals of this manuscript are to introduce PESIG and analyze geographical differences of epilepsy surgery and technology availability. METHODS: PESIG was established (2022) following an ISPN executive board decision. Using a standardized form, we surveyed the PESIG members, collecting and analyzing data regarding geographical distribution, and availability of various epilepsy treatment-related technologies. RESULTS: Two hundred eighty-two members registered in PESIG from 70 countries, over 6 continents, were included. We categorized the countries by GDP as follows: low, lower-medium, upper-medium, and high income. The most commonly available technology was vagus nerve stimulation 68%. Stereoelectroencephalography was available for 58%. North America had statistically significant greater availability compared to other continents. Europe had greater availability compared to Africa, Asia, and South (Latin) America. Asia had greater availability compared to Africa. High-income countries had statistically significant greater availability compared to other income groups; there was no significant difference between the other income-level subgroups. CONCLUSION: There is a clear discrepancy between countries and continents regarding access to epilepsy surgery technologies. This strengthens the need for collaboration between neurologists and neurosurgeons from around the world, to enhance medical education and training, as well as to increase technological availability.


Subject(s)
Epilepsy , Neurosurgery , Humans , Child , Neurosurgery/education , Quality of Life , Public Opinion , Neurosurgical Procedures , Epilepsy/surgery
12.
Proteomics Clin Appl ; 18(1): e2300006, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37650339

ABSTRACT

PURPOSE: Plasma is an abundant source of protein biomarkers. Mass spectrometry (MS) is an effective means to measure a large number of proteins in a single run. The recent development of data-independent acquisition with parallel accumulation and serial fragmentation (diaPASEF) on a trapped ion mobility spectrometer (TIMS) affords deep proteomic coverage with short liquid chromatography gradients. In this work, we utilized a process optimization approach, design of experiments (DoE), to maximize precursor identification for a plasma proteomic diaPASEF workflow. EXPERIMENTAL DESIGN: A partial factorial design was used to screen 11 sample preparation factors and six diaPASEF MS acquisition factors. Selected factors were optimized using the response surface method. RESULTS: Three important sample preparation factors and the two important MS acquisition factors were identified in the screening experiments and were selected for separate optimization experiments. The optimal parameters were compared to our standard plasma proteomics workflows using either a 1-h or overnight trypsin digestion. The optimized method outperformed the 1-h digestion, and it was similar in performance to the overnight digestion, however, the optimized method could be completed in a day. CONCLUSION AND CLINICAL RELEVANCE: We have used DoE to report an optimized plasma proteomics workflow for diaPASEF, however, established methods are already highly optimized, and resources may be better spent on running samples than comprehensive optimization.


Subject(s)
Proteomics , Tandem Mass Spectrometry , Tandem Mass Spectrometry/methods , Workflow , Proteomics/methods , Biomarkers , Proteome/analysis
13.
J Thorac Oncol ; 19(1): 94-105, 2024 01.
Article in English | MEDLINE | ID: mdl-37595684

ABSTRACT

INTRODUCTION: With global adoption of computed tomography (CT) lung cancer screening, there is increasing interest to use artificial intelligence (AI) deep learning methods to improve the clinical management process. To enable AI research using an open-source, cloud-based, globally distributed, screening CT imaging data set and computational environment that are compliant with the most stringent international privacy regulations that also protect the intellectual properties of researchers, the International Association for the Study of Lung Cancer sponsored development of the Early Lung Imaging Confederation (ELIC) resource in 2018. The objective of this report is to describe the updated capabilities of ELIC and illustrate how this resource can be used for clinically relevant AI research. METHODS: In this second phase of the initiative, metadata and screening CT scans from two time points were collected from 100 screening participants in seven countries. An automated deep learning AI lung segmentation algorithm, automated quantitative emphysema metrics, and a quantitative lung nodule volume measurement algorithm were run on these scans. RESULTS: A total of 1394 CTs were collected from 697 participants. The LAV950 quantitative emphysema metric was found to be potentially useful in distinguishing lung cancer from benign cases using a combined slice thickness more than or equal to 2.5 mm. Lung nodule volume change measurements had better sensitivity and specificity for classifying malignant from benign lung nodules when applied to solid lung nodules from high-quality CT scans. CONCLUSIONS: These initial experiments revealed that ELIC can support deep learning AI and quantitative imaging analyses on diverse and globally distributed cloud-based data sets.


Subject(s)
Deep Learning , Emphysema , Lung Neoplasms , Humans , Lung Neoplasms/pathology , Artificial Intelligence , Early Detection of Cancer , Lung/pathology , Emphysema/pathology
14.
Int J Biol Macromol ; 258(Pt 1): 128838, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38128798

ABSTRACT

Pseudomonas aeruginosa is one of the leading causes of opportunistic infections such as chronic wound infection that could lead to multiple organ failure and death. Gallium (Ga3+) ions are known to inhibit P. aeruginosa growth and biofilm formation but require carrier for localized controlled delivery. Lactoferrin (LTf), a two-lobed protein, can deliver Ga3+ at sites of infection. This study aimed to develop a Ga-LTf complex for the treatment of wound infection. The characterisation of the Ga-LTf complex was conducted using differential scanning calorimetry (DSC), Infra-Red (FTIR) and Inductive Coupled Plasma Optical Emission Spectrometry (ICP-OES). The antibacterial activity was assessed by agar disc diffusion, liquid broth and biofilm inhibition assays using the colony forming units (CFUs). The healing capacity and biocompatibility were evaluated using a P.aeruginosa infected wound in a rat model. DSC analyses showed thermal transition consistent with apo-lactoferrin; FTIR confirmed the complexation of gallium to lactoferrin. ICP-OES confirmed the controlled local delivery of Ga3+. Ga-LTf showed a 0.57 log10 CFUs reduction at 24 h compared with untreated control in planktonic liquid broth assay. Ga-LTf showed the highest antibiofilm activity with a 2.24 log10 CFUs reduction at 24 h. Furthermore, Ga-LTf complex is biocompatible without any adverse effect on brain, kidney, liver and spleen of rats tested in this study. Ga-LTf can be potentially promising novel therapeutic agent to treat pathogenic bacterial infections.


Subject(s)
Gallium , Rats , Animals , Gallium/chemistry , Gallium/metabolism , Gallium/pharmacology , Pseudomonas aeruginosa , Lactoferrin/metabolism , Anti-Bacterial Agents/pharmacology , Biofilms
15.
bioRxiv ; 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38105935

ABSTRACT

Transition metals like Zn are essential for all organisms including bacteria, but fluctuations of their concentrations in the cell can be lethal. Organisms have thus evolved complex mechanisms for cellular metal homeostasis. One mechanistic paradigm involves pairs of transcription regulators sensing intracellular metal concentrations to regulate metal uptake and efflux. Here we report that Zur and ZntR, a prototypical pair of regulators for Zn uptake and efflux in E. coli , respectively, can coordinate their regulation through DNA, besides sensing cellular Zn 2+ concentrations. Using a combination of live-cell single-molecule tracking and in vitro single-molecule FRET measurements, we show that unmetallated ZntR can enhance the unbinding kinetics of Zur from DNA by directly acting on Zur-DNA complexes, possibly through forming heteromeric ternary and quaternary complexes that involve both protein-DNA and protein-protein interactions. This 'through-DNA' mechanism may functionally facilitate the switching in Zn uptake regulation when bacteria encounter changing Zn environments; it could also be relevant for regulating the uptake-vs.-efflux of various metals across different bacterial species and yeast.

17.
Metabolomics ; 19(12): 94, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37975930

ABSTRACT

INTRODUCTION: Idiopathic acquired aplastic anemia (AA) is a bone marrow failure disorder where aberrant T-cell functions lead to depletion of hematopoietic stem and progenitor cells in the bone marrow (BM) microenvironment. T-cells undergo metabolic rewiring, which regulates their proliferation and differentiation. Therefore, studying metabolic variation in AA patients may aid us with a better understanding of the T-cell regulatory pathways governed by metabolites and their pathological engagement in the disease. OBJECTIVE: To identify the differential metabolites in BM plasma of AA patients, AA follow-up (AAF) in comparison to normal controls (NC) and to identify potential disease biomarker(s). METHODS: The study used 1D 1H NMR Carr-Purcell-Meiboom-Gill (CPMG) spectra to identify the metabolites present in the BM plasma samples of AA (n = 40), AAF (n = 16), and NC (n = 20). Metabolic differences between the groups and predictive biomarkers were identified by using multivariate analysis and receiver operating characteristic (ROC) module of Metaboanalyst V5.0 tool, respectively. RESULTS: The AA and AAF samples were well discriminated from NC group as per Principal Component analysis (PCA). Further, we found significant alteration in the levels of 17 metabolites in AA involved in amino-acid (Leucine, serine, threonine, phenylalanine, lysine, histidine, valine, tyrosine, and proline), carbohydrate (Glucose, lactate and mannose), fatty acid (Acetate, glycerol myo-inositol and citrate), and purine metabolism (hypoxanthine) in comparison to NC. Additionally, biomarker analysis predicted Hypoxanthine and Acetate can be used as a potential biomarker. CONCLUSION: The study highlights the significant metabolic alterations in the BM plasma of AA patients which may have implication in the disease pathobiology.


Subject(s)
Anemia, Aplastic , Bone Marrow , Humans , Bone Marrow/metabolism , Bone Marrow/pathology , Anemia, Aplastic/metabolism , Anemia, Aplastic/pathology , Metabolomics , Magnetic Resonance Spectroscopy , Biomarkers , Acetates , Hypoxanthines
18.
J Craniovertebr Junction Spine ; 14(3): 259-267, 2023.
Article in English | MEDLINE | ID: mdl-37860028

ABSTRACT

Background: Lumbar discectomy is performed for symptomatic lumbar disc herniation and is one of the most widely performed spinal surgical procedures worldwide in a variety of ways. This survey aimed at providing an overview/perspective of different practice patterns and the impact of lumbar discectomy on axial back pain with or without sciatica. Methods: An online survey was performed using the application "Google Forms." The link to the questionnaire was distributed to neurosurgeons through personal E-mail and social media platforms. Results: We received 333 responses. The largest percentage of responses across five continents was from Asia (66.97%, n = 223). The mean age of the respondents was 40.08 ± 10.5 years. A total of 66 respondents (20%) had a spine practice of 7%-90%, and 28 respondents had a spine practice of 90%-100% (8.4%). The number of respondents who practiced microscopic discectomy using a tubular retractor (n = 143 respondents, 42.9%) was nearly equal to the number of respondents who practiced open discectomy (n = 142 respondents, 42.6%). An almost equal proportion of respondents believed discectomy does not help in relieving axial back pain. Only 20.4% (n = 68) of respondents recommend bed rest for a longer duration postoperatively. Conclusions: Our survey revealed that only 22.2% of spine surgeons recommended discectomy in patients with radiological disc herniation with axial back pain alone and preferred a minimally invasive method of discectomy. Almost half of them believed discectomy to be ineffective for axial low back pain and only a few recommended prolonged bed rest postoperatively.

19.
Ann Med Surg (Lond) ; 85(10): 5223-5227, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37811049

ABSTRACT

Introduction and importance: Most dengue infections are asymptomatic, and some of them develop haemorrhagic manifestations with or without shock. However, dengue can sometimes present with very rare complications like pyomyositis. Case presentation: A healthy 27-year-old male, presented with a 2-day fever, confirmed to be dengue through a positive non-structural protein 1 test. Despite initial symptomatic management, his condition worsened and he was hospitalized. Leucocyte and platelet counts dropped to the lowest value on the seventh day of illness, followed by the gradual development of chest pain, persistent fever, and severe limb pain. Radiographic evaluation revealed pleural effusion, and multiple intramuscular haematomas complicated by pyomyositis. Pleural effusion resolved on its own. Pyomyositis resolved with 6 weeks of appropriate antibiotics and aspiration of pus. Clinical discussion: Dengue infection, caused by a dengue virus transmitted through Aedes mosquitoes, is a significant public health concern in many parts of the world. Dengue haemorrhagic fever is a severe form of dengue infection characterized by vascular leakage, thrombocytopenia, and bleeding manifestations. Although musculoskeletal manifestations are common in dengue fever, the occurrence of multiple muscle haematomas and pyomyositis as complications of Dengue haemorrhagic fever is rare. Drainage or aspiration of pus combined with the antibiotics according to the pus culture and sensitivity report is the management strategy. Conclusion: Prolonged fever with severe musculoskeletal pain and focal tenderness on examination in a dengue patient, warrant radiographic testing (ultrasonography or MRI) considering the differentials of haematoma, myositis, or pyomyositis.

20.
J Chem Neuroanat ; 133: 102329, 2023 11.
Article in English | MEDLINE | ID: mdl-37659616

ABSTRACT

Status Epilepticus (SE) is a distributed network disorder, which involves the hippocampus and extra-hippocampal structures. Epileptogenesis in SE is tightly associated with neurogenesis, plastic changes and neural network reorganization facilitating hyper-excitability. On the other hand, dendritic spines are known to be the excitatory synapse in the brain. Therefore, dendritic spine dynamics could play an intricate role in these network alterations. However, the exact reason behind these structural changes in SE are elusive. In the present study, we have investigated the aforementioned hypothesis in the lithium-pilocarpine treated rat model of SE. We have examined cytoarchitectural and morphological changes using hematoxylin-eosin and Golgi-Cox staining in three different brain regions viz. CA1 pyramidal layer of the dorsal hippocampus, layer V pyramidal neurons of anterior temporal lobe (ATL), and frontal neocortex of the same animals. We observed macrostructural and layer-wise alteration of the pyramidal layer mainly in the hippocampus and ATL of SE rats, which is associated with sclerosis in the hippocampus. Sholl analysis exhibited partial dendritic plasticity in apical and basal dendrites of pyramidal cells as compared to the saline-treated weight-/age-matched control group. These findings indicate that region-specific alterations in dendritogenesis may contribute to the development of independent epileptogenic networks in the hippocampus, ATL, and frontal neocortex of SE rats.


Subject(s)
Neocortex , Status Epilepticus , Rats , Animals , Pilocarpine/toxicity , Lithium/toxicity , Disease Models, Animal , Hippocampus , Status Epilepticus/chemically induced , Temporal Lobe
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