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JAMA Jul 2024
PubMed: 38949806
DOI: 10.1001/jama.2024.6111 -
Medical Physics Jul 2024Measuring non-parametric intravoxel mean diffusivity distributions (MDDs) using magnetic resonance imaging (MRI) is a sensitive method for detecting intracellular...
BACKGROUND
Measuring non-parametric intravoxel mean diffusivity distributions (MDDs) using magnetic resonance imaging (MRI) is a sensitive method for detecting intracellular diffusivity changes during physiological alterations. Histological and molecular glioma classifications are essential for prognosis and treatment, with distinct water diffusion dynamics among subtypes.
PURPOSE
We developed a data-driven approach using a fully connected network (FCN) to enhance the speed and stability of calculating MDDs across varying SNRs, enable tumor microstructural mapping, and test its reliability in identifying MIB-1 labeling index (LI) levels and molecular status of gliomas.
METHODS
An FCN was trained to learn the mapping between the simulated diffusion decay curves and the ground truth MDDs. We performed 5 000 000 simulation curves with various diffusivity components and random SNR . Eighty percent of simulation curves were used for the FCN training, 10% for validation, and the others were external tests for the FCN performance evaluation. In vivo data were collected to evaluate its clinical reliability. One hundred one patients (44 years 14, 67 men) with gliomas and six healthy controls underwent a 3.0 T MRI examination with a spin echo-echo planar imaging (SE-EPI) diffusion-weighted imaging (DWI) sequence. The trained FCN was employed to calculate MDDs of each brain voxel by voxel. We used the Fuzzy C-means algorithm to cluster the MDDs of tumor voxels, facilitating the characterization of distinct glioma tissues. Quantitative assessments were conducted through sectional integrals of the MDDs, demarcated by six bands to derive signal fractions ( ) and diffusivities of the maximum peaks ( ). Cosine similarity scores (CSS) were used for MDD similarity. ANOVA and Mann-Whitney U test were used for difference analysis. Logistic regression and area under the receiver operator characteristic curve (AUC) were used for classification evaluation.
RESULTS
The simulation results showed that the FCN-based MDD approach (FCN-MDD) achieved higher CSS than non-negative least squares-based MDD (NNLS-MDD). For in vivo data, the spectra of ET and NET obtained by FCN-MDD are more distinguishable than NNLS-MDD. Fraction maps delineate the characteristics of different tumor tissues (enhancing and non-enhancing tumor, edema, and necrosis). showed a positive and negative correlation with MIB-1 respectively ( , all ). The AUC of for predicting MIB-1 LI levels was 0.900 (95% CI, 0.826-0.974), versus 0.781 (0.677-0.886) of ADC. The highest AUC of isocitrate dehydrogenase (IDH) mutation status, assessed by a logistic regression model ( ) was 0.873 (95% CI, 0.802-0.944).
CONCLUSION
The proposed FCN-MDD method was more robust to variations in SNR and less reliant on empirically set regularization values than the NNLS-MDD method. FCN-MDD also enabled qualitative and quantitative evaluation of the composition of gliomas.
PubMed: 38949565
DOI: 10.1002/mp.17280 -
Pain Practice : the Official Journal of... Jul 2024Gabapentin, a widely prescribed medication for various neuropathic pain conditions, has demonstrated efficacy in managing diverse neurological disorders. While...
BACKGROUND
Gabapentin, a widely prescribed medication for various neuropathic pain conditions, has demonstrated efficacy in managing diverse neurological disorders. While conventional side effects are well-documented, a growing body of evidence suggests the existence of atypical side effects, necessitating comprehensive exploration. This paper aims to systematically review and summarize the literature on the atypical side effects of gabapentin, shedding light on manifestations beyond the conventional spectrum.
METHODS
A systematic review was conducted, encompassing peer-reviewed articles published up to the knowledge cutoff date in November 2023. Databases, specifically PubMed, were searched for relevant studies, focusing on atypical side effects such as myoclonus, ataxia, pediatric aggression, respiratory depression, pneumonia, pregnancy complications, sleep interference, encephalopathy, peripheral edema, suicidal ideation, dyskinesia, anorgasmia, and myopathy. Inclusion criteria comprised studies with a focus on gabapentin-related atypical side effects, published in recognized journals and involving human subjects.
RESULTS
The review identified a spectrum of atypical side effects associated with gabapentin use, ranging from neurological manifestations like myoclonus and ataxia to behavioral changes such as pediatric aggression and suicidal ideation. Additionally, respiratory complications, pregnancy-related issues, sleep disturbances, and rare complications like encephalopathy and myopathy were observed. Literature synthesis provided insights into the incidence, clinical presentation, and potential mechanisms underlying these atypical side effects.
CONCLUSION
This comprehensive review highlights the diverse range of atypical side effects associated with gabapentin use, expanding beyond conventional knowledge. Healthcare practitioners must be cognizant of these manifestations, recognizing their potential impact on patient well-being. As clinical decision-making relies on a thorough understanding of a medication's side effect profile, this review contributes to enhancing awareness and fostering informed practices in the prescription and management of gabapentin. Further research is warranted to elucidate the mechanisms and risk factors associated with these atypical side effects, refining our understanding of gabapentin's safety profile.
PubMed: 38949515
DOI: 10.1111/papr.13400 -
Journal of Visualized Experiments : JoVE Jun 2024Lung transplantation is hampered by the lack of suitable donors. Previously, donors that were thought to be marginal or inadequate were discarded. However, new and...
Lung transplantation is hampered by the lack of suitable donors. Previously, donors that were thought to be marginal or inadequate were discarded. However, new and exciting technology, such as ex vivo lung perfusion (EVLP), offers lung transplant providers extended assessment for marginal donor allografts. This dynamic assessment platform has led to an increase in lung transplantation and has allowed providers to use donors that were previously discarded, thus expanding the donor pool. Current perfusion techniques use cellular or acellular perfusates, and both have distinct advantages and disadvantages. Perfusion composition is critical to maintaining a homeostatic environment, providing adequate metabolic support, decreasing inflammation and cellular death, and ultimately improving organ function. Perfusion solutions must contain sufficient protein concentration to maintain appropriate oncotic pressure. However, current perfusion solutions often lead to fluid extravasation through the pulmonary endothelium, resulting in inadvertent pulmonary edema and damage. Thus, it is necessary to develop novel perfusion solutions that prevent excessive damage while maintaining proper cellular homeostasis. Here, we describe the application of a polymerized human hemoglobin (PolyhHb)-based oxygen carrier as a perfusate and the protocol in which this perfusion solution can be tested in a model of rat EVLP. The goal of this study is to provide the lung transplant community with key information in designing and developing novel perfusion solutions, as well as the proper protocols to test them in clinically relevant translational transplant models.
Topics: Animals; Rats; Lung Transplantation; Hemoglobins; Perfusion; Lung; Humans; Oxygen; Blood Substitutes; Male; Organ Preservation Solutions
PubMed: 38949382
DOI: 10.3791/66702 -
Clinical Ophthalmology (Auckland, N.Z.) 2024To compare the efficacy of intravitreal injections of Conbercept combined with dexamethasone (DEX) for macular edema (ME) following central retinal vein occlusion (CRVO).
BACKGROUND
To compare the efficacy of intravitreal injections of Conbercept combined with dexamethasone (DEX) for macular edema (ME) following central retinal vein occlusion (CRVO).
METHODS
This was a prospective, single-masked, randomised, controlled clinical trial. Patients with ME following CRVO were randomised into groups to receive intravitreal injections of 0.5 mg Conbercept plus 0.2 mg DEX or 0.5 mg Conbercept alone on day 0 followed by repeat injections as indicated. The primary outcome measure was the change in best-corrected visual acuity (BCVA) from baseline to month 12. Secondary outcome measures included decrease in central retinal thickness (CRT), injection frequency and interval and percentage of patients who gained more than 15 ETDRS letters or achieved a CRT of < 250 μm at month 12.
RESULTS
33 males (51%) and 32 females (49%) were initially recruited with an average age of 56.64 ± 13.88 years. Patients in the Conbercept and Conbercept + DEX groups gained an average of 14.55 ± 19.19 and 14.88 ± 17.68 ETDRS letters, respectively, at months 12 ( = 4.221, = 0.000; and = 4.834, = 0.000) with no significant difference between the two groups ( = 0.071, = 0.943). In the Conbercept group, the mean reduction in CRT from baseline to month 12 was 435.26 ± 293.37 μm ( = 8.261, = 0.000) compared to 431.36 ± 294.55 ( = 8.413, = 0.000) in the Conbercept + DEX group. There was no significant difference between the two groups ( = 0.053, = 0.958). The Conbercept + DEX group received fewer intravitreal injections. No major complications occurred.
CONCLUSION
Conbercept, alone or with DEX, can improve BCVA and reduce CRT in ME following CRVO without serious adverse events. The treatment interval was longer in the Conbercept + DEX group.
TRIAL REGISTRATION
The study was registered with the Chinese Clinical Trial Registry at 5 July 2017. (http://www.chictr.org.cn, 05/07/2017 Registration Number: ChiCTR-INR-17011877).
PubMed: 38948340
DOI: 10.2147/OPTH.S448671 -
World Journal of Transplantation Jun 2024In this editorial, we talk about a compelling case focusing on posterior reversible encephalopathy syndrome (PRES) as a complication in patients undergoing liver...
In this editorial, we talk about a compelling case focusing on posterior reversible encephalopathy syndrome (PRES) as a complication in patients undergoing liver transplantation and treated with Tacrolimus. Tacrolimus (FK 506), derived from , is a potent immunosuppressive macrolide. It inhibits T-cell transcription by binding to FK-binding protein, and is able to amplify glucocorticoid and progesterone effects. Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES. PRES presents with various neurological symptoms alongside elevated blood pressure, and is primarily characterized by vasogenic edema on neuroimaging. While computed tomography detects initial lesions, magnetic resonance imaging, especially the Fluid-Attenuated Inversion Recovery sequence, is superior for diagnosing cortical and subcortical edema. Our discussion centers on the incidence of PRES in solid organ transplant recipients, which ranges between 0.5 to 5 +ACU-, with varying presentations, from seizures to visual disturbances. The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES. Radiographically evident in the parietal and occipital lobes, PRES underlines the need for heightened vigilance among healthcare providers. This editorial emphasizes the importance of early recognition, accurate diagnosis, and effective management of PRES to optimize outcomes in liver transplant patients. The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks, underlining the necessity for careful monitoring and intervention strategies in this patient population.
PubMed: 38947962
DOI: 10.5500/wjt.v14.i2.91146 -
ACS Omega Jun 2024The genus is a leading source of a wide range of structurally diverse metabolites with significant pharmacological implications. The present study investigated...
The genus is a leading source of a wide range of structurally diverse metabolites with significant pharmacological implications. The present study investigated metabolite profiling, pharmacological investigation, anticancer potential, and molecular docking analysis of the stem part of (AHS). The metabolite profiling of the AHS extract was experimentally examined using LC-MS/MS-orbitrap in both modes (ESI/ESI) and GC-MS in EI mode. The MTT model was used to study the anticancer potential, while the animal model was used to study the anti-inflammatory and antinociceptive activities. The MOE software was used for the molecular docking study. A total of 118 novel and previously known metabolites, among 44 metabolites (26 in ESI positive mode and 18 in ESI negative mode) in the MeOH extract, while 74 metabolites (46 in ESI and 28 in ESI mode) were identified in the -hexane extract via LCMS/MS. The identified metabolites include 24 phenolic compounds, 18 alkaloids, 10 flavonoids, 24 terpenoids, 2 coumarins, 2 lignans, and 38 other fatty acids and organic compounds. The major bioactive metabolites identified were hordenine, hernagine, formononetin, chrysin, -methylhernagine, guineesine, shogaol, kauralexin, colneleate, zerumbone, medicarpin, boldine, miraxinthin-v, and lariciresinol-4-O-glucoside. Furthermore, the GC-MS study helped in the identification of volatile and nonvolatile chemical constituents based on the mass spectrum and retention indices. The methanol extract significantly inhibited tumor progression in H9c2 and MDCK cancer cells with IC values of 186.39 and 199.63 μg/mL. In comparison, the positive control aconitine exhibited potent IC values (132.32 and 141.58 μg/mL) against H9c2 and MDCK cell lines. The anti-inflammatory (carrageenan-induced hind paw edema) and antinociceptive (acetic acid-induced writhing) effects were significantly dose-dependent, ( < 0.001) and ( < 0.05), respectively. In addition, a molecular docking study was conducted on identified ligands against the anti-inflammatory enzyme (COX-2) (PDB ID: 5JVZ) and the cancer enzyme ADAM10 (PDB ID: 6BDZ) which confirmed the anti-inflammatory and anticancer effects in an model. Among all ligands, L2, L3, and L7 exhibit the most potent potential for inhibiting COX-2 inflammation with binding energies of -7.3424, -7.0427, and -8.3562 kcal/mol. Conversely, against ADAM10 cancer protein, ligands L1, L4, L6, and L7, with binding energies of -8.0650, -7.7276, -7.0454, and -7.2080 kcal/mol, demonstrated notable effectiveness. Overall, the identified metabolites revealed in this AHS research study hold promise for discovering novel possibilities in the disciplines of chemotaxonomy and pharmacology.
PubMed: 38947854
DOI: 10.1021/acsomega.3c09668 -
Cancer Innovation Jun 2024Immune checkpoint inhibitors (ICI) are increasingly used in the first-line treatment of malignant tumors. There is increasing recognition of their cardiotoxicity and,...
BACKGROUND
Immune checkpoint inhibitors (ICI) are increasingly used in the first-line treatment of malignant tumors. There is increasing recognition of their cardiotoxicity and, in particular, their potential to lead to myocarditis. Cardiovascular magnetic resonance (CMR) can quantify pathological changes, such as myocardial edema and fibrosis. The purpose of this systematic review and meta-analysis was to examine the evidence for the roles of CMR in predicting prognosis in ICI-associated myocarditis.
METHODS
PubMed, Cochrane Library, and Web of Science databases were searched until October 2023 for published works investigating the relationship between CMR parameters and adverse events in patients with ICI-associated myocarditis. The analysis included studies reporting the incidence of late gadolinium enhancement (LGE), T1 values, T2 values, and CMR-derived left ventricular ejection fraction (LVEF). Odds ratios (OR) and weighted mean differences (WMD) were combined for binary and continuous data, respectively. Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies.
RESULTS
Five cohort studies were included (average age 65-68 years; 25.4% female). Of these, four studies were included in the meta-analysis of LGE-related findings. Patients with major adverse cardiovascular events (MACE) had a higher incidence of LGE compared with patients without MACE (OR = 4.18, 95% CI: 1.72-10.19, = 0.002). A meta-analysis, incorporating data from two studies, showed that patients who developed MACE exhibited significantly higher T1 value (WMD = 36.16 ms, 95% CI: 21.43-50.89, < 0.001) and lower LVEF (WMD = - 8.00%, 95% CI: -13.60 to -2.40, = 0.005). Notably, T2 value (WMD = -0.23 ms, 95% CI: -1.86 to -1.39, = 0.779) was not associated with MACE in patients with ICI-related myocarditis.
CONCLUSIONS
LGE, T1 value, and LVEF measured by CMR imaging have potential prognostic value for long-term adverse events in patients with ICI-related myocarditis.
PubMed: 38947756
DOI: 10.1002/cai2.109 -
Cureus May 2024Carcinoid syndrome is a rare condition resulting from neuroendocrine tumors (NETs) that secrete vasoactive substances like serotonin. This report describes the case of a...
Carcinoid syndrome is a rare condition resulting from neuroendocrine tumors (NETs) that secrete vasoactive substances like serotonin. This report describes the case of a 61-year-old man with a history of chronic obstructive pulmonary disease (COPD) and hypertension who presented with new-onset angioedema, loss of consciousness, and a fall. He had been treated for COPD exacerbations during ER visits without improvement and was unaware of a prior mesenteric carcinoid tumor diagnosis from 2012. The next emergency evaluation revealed significant airway and facial edema necessitating intubation. Imaging and biopsy identified a well-differentiated grade 1 NET with extensive liver metastases. Laboratory tests showed elevated levels of serum serotonin, chromogranin A, and 24-hour urine 5-hydroxyindoleacetic acid (5-HIAA). Post-discharge, a PET scan confirmed metastatic lesions primarily in the liver and small bowel, with an unresectable mesenteric mass. The patient was treated with lanreotide and became symptom-free. This case underscores the need to consider carcinoid syndrome in patients with COPD presenting with unexplained respiratory symptoms, as timely diagnosis and treatment can significantly enhance patient outcomes.
PubMed: 38947683
DOI: 10.7759/cureus.61321 -
Cureus May 2024Fat embolism syndrome is a common occurrence after orthopedic trauma and surgery. Cerebral fat embolism (CFE) may arise after fat globules enter the arterial...
Fat embolism syndrome is a common occurrence after orthopedic trauma and surgery. Cerebral fat embolism (CFE) may arise after fat globules enter the arterial circulation. The neurological manifestations of CFE vary and generally carries a favorable outcome. A small number of reports exist regarding patients with CFE who experienced severe neurological deficits and significant edema on radiographic studies, and subsequently underwent decompressive hemicraniectomy (DHC), some of which had full neurological recoveries. Here, we present the case of a 21-year-old male who presented after a motorcycle accident with multiple orthopedic injuries, who after fixation did not awake from anesthesia. The patient was ultimately found to have cerebral fat emboli, and developed significant edema and swelling. The patient underwent DHC with subsequent cranioplasty and returned to his neurological baseline seven months after his initial injury. DHC for CFE has been described in a few cases with some patients have had substantive recoveries, including the present case. This case emphasizes the importance of promptly recognizing and reversing elevated intracranial pressures and the possibility of promising recoveries.
PubMed: 38947672
DOI: 10.7759/cureus.61338