Focused ultrasound therapy in movement disorders: management roadmap toward optimal pathway organization.

MRI-guided focused ultrasound (MRgFUS) lesioning is an innovative, safe and effective treatment which provides an innovative development in the field of minimally invasive stereotactic neurosurgery. Based on the application of focused ultrasound energy under full MR planning and thermal imaging control, unilateral lesioning of the thalamus, subthalamic nucleus, and globus pallidus is indicated for the treatment of movement disorders, including essential tremor, Parkinson's disease, and dystonia. We started to apply this technique in February 2019 for the treatment of patients with movement disorders. The authors developed a diagnostic therapeutic care pathway, which is herewith proposed and applied as an explication of standard clinical practice in use. The project was the result of the application of different methods such as Health Technology Assessment (HTA), Strengths, Weaknesses, Opportunities and Threats analysis (SWOT) and Demin -Plan, Do, Check, Act (PDCA) cycle. The aim of this project was to standardize the MRgFUS diagnostic-therapeutic pathway (DTP), describe its application and the appropriateness of different phases (patient selection, intervention phase and follow-up). Here, we described in detail our experience in the DTP application from 2019 up to now in 610 patients with movement disorders.

Immune Analysis Using Vitreous Optical Coherence Tomography Imaging in Rats with Steroid-Induced Glaucoma.

Glaucoma is a multifactorial pathology involving the immune system. The subclinical immune response plays a homeostatic role in healthy situations, but in pathological situations, it produces imbalances. Optical coherence tomography detects immune cells in the vitreous as hyperreflective opacities and these are subsequently characterised by computational analysis. This study monitors the changes in immunity in the vitreous in two steroid-induced glaucoma (SIG) animal models created with drug delivery systems (microspheres loaded with dexamethasone and dexamethasone/fibronectin), comparing both sexes and healthy controls over six months. SIG eyes tended to present greater intensity and a higher number of vitreous opacities (p < 0.05), with dynamic fluctuations in the percentage of isolated cells (10 µm2), non-activated cells (10-50 µm2), activated cells (50-250 µm2) and cell complexes (>250 µm2). Both SIG models presented an anti-inflammatory profile, with non-activated cells being the largest population in this study. However, smaller opacities (isolated cells) seemed to be the first responder to noxa since they were the most rounded (recruitment), coinciding with peak intraocular pressure increase, and showed the highest mean Intensity (intracellular machinery), even in the contralateral eye, and a major change in orientation (motility). Studying the features of hyperreflective opacities in the vitreous using OCT could be a useful biomarker of glaucoma.

Oxidative Stress and Migraine.

The pathogenesis of migraine is not completely understood, but inflammation and oxidative stress seem to be involved, according to data from an experimental model of the disease. This narrative review summarizes data from studies on oxidative stress markers in migraine patients, case-control association studies on the possible association of candidate genes related to oxidative stress with the risk for migraine, studies showing the presence of oxidative stress in experimental models of migraine, and studies on the efficacy of antioxidant drugs in migraine therapy. Many studies have addressed the value of concentrations of prooxidant and antioxidant substances or the activity of antioxidant enzymes in different tissues (mainly in serum/plasma or in blood cells) as possible biomarkers for migraine, being thiobarbituric acid (TBA) reactive substances (TBARS) such as malonyl dialdehyde acid (MDA) and 4-hydroxynonenal, and nitric oxide (this at least during migraine attacks in patients with migraine with aura (MWA) the most reliable. In addition, the possible usefulness of antioxidant treatment is not well established, although preliminary short-term studies suggest a beneficial action of some of them such as Coenzyme Q10 and riboflavin. Both topics require further prospective, multicenter studies with a long-term follow-up period involving a large number of migraine patients and controls.

Are lead, cadmium and mercury risk factors for resistant hypertension?

BACKGROUND: Lead (Pb), cadmium (Cd) and mercury (Hg) are toxic trace elements that represent a public health problem as risk factors for cardiovascular disease and hypertension (HT) and could also contribute to the development of resistant hypertension (rHT) AIMS: To compare the blood concentrations of Pb, Cd and Hg in subjects with resistant and non-resistant HT and to define whether there is a relationship between its levels and rHT. METHODS: Cross-sectional study. Subjects aged ≥ 21 to ≤ 80 years with a body mass index < 40 kg/m2 were recruited on a discretionary basis from October 2001 to October 2004 in a hypertension unit of a tertiary hospital amongst those sent to the hypertension unit by their family physician. Resistant hypertension was defined according to the American Heart Association (AHA) criteria. Whole blood concentrations of Cd, Pb and Hg were measured by electrothermal atomic absorption spectrometry. RESULTS: 46 out of 73 included subjects (63%) suffered from rHT. Blood Pb median: HT 3.9 (IQR 2.7-5.2) vs. rHT 3.6 (IQR 2.8-6.0) µg/dL (p=0.941). Blood Cd median: HT 0.07 (IQR 0.07-0.80) vs. rHT 0.30 (IQR 0.07-0.65) µg/L (p=0.681). Blood Hg median: HT 7.9 (IQR 5.8-12.9) vs. rHT 7.3 (IQR 4.6-13.3) µg/L (p=0.611). Considering the 75th percentile of each element (Pb: 5.55 µg/dL, Cd: 0.75 µg/L, Hg: 13.15 µg/L), a multiple logistic regression analysis (adjusted for age, BMI, diabetes mellitus, clearance of creatinine and only for Cd the smoking habit) showed an OR = 3.44 (0.84-14.10, p=0.086) for Pb, OR = 1.80 (0.39-8.24, p=0.451), for Cd and OR = 2.31 (0.59-9.14, p=0.232) for Hg. Moreover, the stratified analyses showed that men with Pb ≥5.55 µg/dL have a 14 times higher risk of suffering from rHT (p=0.026). Interestingly, a 9-fold increased risk was found for non-obese subjects with elevated Pb levels, above 5.55 µg/dL (p=0.029). Also in men, the probability of suffering from rHT was more than 7 times higher if Cd levels were ≥ 0.75 µg/L (p=0.076). Most smokers had higher Cd levels, with a high risk of suffering from rHT (ORa 12.6 (0.8-200.2), p=0.072). CONCLUSION: A higher blood Pb levels, defined by the 75th percentile (Pb ≥ 5.55 µg/dL), is associated with a greater risk of suffering from rHT and to a lesser extent in the case of Cd and Hg.

Corrigendum to "Laponite for biomedical applications: An ophthalmological perspective" [Mater. Today Bio 24 (2024) 100935].

[This corrects the article DOI: 10.1016/j.mtbio.2023.100935.].

A rare case of hepatoid gastric adenocarcinoma.

Hepatoid gastric adenocarcinoma (HGA) is a rare subtype of gastric cancer. It usually presents with non-specific digestive tract symptoms and is usually diagnosed in advanced stages. It has radiological and histological similarities to hepatocarcinoma (HCC), and serum elevation of alpha-fetoprotein (AFP) is characteristic, as is positive staining for this marker on immunohistochemistry. Given the low incidence and poor prognosis of this type of tumour, it is essential to make a correct differential diagnosis and to initiate early surgical treatment in localised stages and systemic treatment in those where the disease is disseminated. In this context, we present the case of a GHA diagnosed this year in our centre.

Developments in pharmacogenetics, pharmacogenomics, and personalized medicine.

The development of Pharmacogenetics and Pharmacogenomics in Western Europe is highly relevant in the worldwide scenario. Despite the usually low institutional support, many research groups, composed of basic and clinical researchers, have been actively working for decades in this field. Their contributions made an international impact and paved the way for further studies and pharmacogenomics implementation in clinical practice. In this manuscript, that makes part of the Special Issue entitled Spanish Pharmacology, we present an analysis of the state of the art of Pharmacogenetics and Pharmacogenomics research in Europe, we compare it with the developments in Spain, and we summarize the most salient contributions since 1988 to the present, as well as recent developments in the clinical application of pharmacogenomics knowledge. Finally, we present some considerations on how we could improve translation to clinical practice in this specific scenario.

Preparing the Frontlines: Delivering Special Pathogen Training to Maryland Hospital Staff.

Healthcare workers (HCWs) at community hospitals, also known as frontline hospitals (FLHs), may encounter patients with possible infectious diseases, including those caused by high-consequence pathogens such as Zaire ebolavirus. We created and piloted a 1-day, in-person, didactic and skills training program to determine the feasibility and acceptability of implementing an educational program to enhance the knowledge and skills needed to respond when a patient with a potential high-consequence pathogen presents to an FLH. The Maryland Department of Health queried all 104 state FLHs to identify their interest in participating in the pilot training program. HCWs from 12 (75%) of the 16 interested FLHs participated in the program before it was interrupted by the COVID-19 pandemic. In addition to pathogen-specific training based on the Identify, Isolate, and Inform framework, we provided skills training in the proper use of personal protective equipment, spill cleanup, and removal of an incapacitated HCW from an isolation area. We conducted a paired pretraining and posttraining knowledge assessment and measured a significant learning gain among 135 participants (2-tailed t test, P<.05). Over 95% of the participants reported that the training was relevant to their daily work and the clinical simulations and reference material were useful and appropriate for their learning level. Findings from this pilot program demonstrated the feasibility and acceptability of a 1-day combined didactic and skills training program focused on high-consequence pathogens. We plan to reengage the original FLHs and add regional FLHs in an updated training effort based on our findings.

The macular retinal ganglion cell layer as a biomarker for diagnosis and prognosis in multiple sclerosis: A deep learning approach.

PURPOSE: The macular ganglion cell layer (mGCL) is a strong potential biomarker of axonal degeneration in multiple sclerosis (MS). For this reason, this study aims to develop a computer-aided method to facilitate diagnosis and prognosis in MS. METHODS: This paper combines a cross-sectional study of 72 MS patients and 30 healthy control subjects for diagnosis and a 10-year longitudinal study of the same MS patients for the prediction of disability progression, during which the mGCL was measured using optical coherence tomography (OCT). Deep neural networks were used as an automatic classifier. RESULTS: For MS diagnosis, greatest accuracy (90.3%) was achieved using 17 features as inputs. The neural network architecture comprised the input layer, two hidden layers and the output layer with softmax activation. For the prediction of disability progression 8 years later, accuracy of 81.9% was achieved with a neural network comprising two hidden layers and 400 epochs. CONCLUSION: We present evidence that by applying deep learning techniques to clinical and mGCL thickness data it is possible to identify MS and predict the course of the disease. This approach potentially constitutes a non-invasive, low-cost, easy-to-implement and effective method.

Upregulation in Inflammation and Collagen Expression in Perirenal but Not in Mesenteric Adipose Tissue from Diabetic Munich Wistar Frömter Rats.

Perirenal adipose tissue (PRAT) surrounding the kidney is emerging as a player and novel independent risk factor in diabetic kidney disease (DKD); DKD is a complication of diabetes and is a major cause of increased cardiovascular (CV) risk and CV mortality in affected patients. We determined the effect of diabetes induction on (i) kidney and CV damage and (ii) on the expression of proinflammatory and profibrotic factors in both the PRAT and the mesenteric adipose tissue (MAT) of Munich Wistar Frömter (MWF) rats. The 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF-C) or a high-fat/high-sucrose diet for 6 weeks together with low-dose streptozotocin (15 mg/kg i.p.) at the start of dietary exposure (MWF-D). Phenotyping was performed at the end of treatment through determining water intake, urine excretion, and oral glucose tolerance; use of the homeostatic model assessment-insulin resistance index (HOMA-IR) evidenced the development of overt diabetes manifestation in MWF-D rats. The kidney damage markers Kim-1 and Ngal were significantly higher in MWF-D rats, as were the amounts of PRAT and MAT. A diabetes-induced upregulation in IL-1, IL-6, Tnf-α, and Tgf-ß was observed in both the PRAT and the MAT. Col1A1 was increased in the PRAT but not in the MAT of MWF-D, whereas IL-10 was lower and higher in the PRAT and the MAT, respectively. Urinary albumin excretion and blood pressure were not further increased by diabetes induction, while heart weight was higher in the MWF-D. In conclusion, our results show a proinflammatory and profibrotic in vivo environment in PRAT induced by diabetes which might be associated with kidney damage progression in the MWF strain.

Differential Study of Retinal Thicknesses in the Eyes of Alzheimer's Patients, Multiple Sclerosis Patients and Healthy Subjects.

Multiple sclerosis (MS) and Alzheimer's disease (AD) cause retinal thinning that is detectable in vivo using optical coherence tomography (OCT). To date, no papers have compared the two diseases in terms of the structural differences they produce in the retina. The purpose of this study is to analyse and compare the neuroretinal structure in MS patients, AD patients and healthy subjects using OCT. Spectral domain OCT was performed on 21 AD patients, 33 MS patients and 19 control subjects using the Posterior Pole protocol. The area under the receiver operating characteristic (AUROC) curve was used to analyse the differences between the cohorts in nine regions of the retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL) and outer nuclear layer (ONL). The main differences between MS and AD are found in the ONL, in practically all the regions analysed (AUROCFOVEAL = 0.80, AUROCPARAFOVEAL = 0.85, AUROCPERIFOVEAL = 0.80, AUROC_PMB = 0.77, AUROCPARAMACULAR = 0.85, AUROCINFERO_NASAL = 0.75, AUROCINFERO_TEMPORAL = 0.83), and in the paramacular zone (AUROCPARAMACULAR = 0.75) and infero-temporal quadrant (AUROCINFERO_TEMPORAL = 0.80) of the GCL. In conclusion, our findings suggest that OCT data analysis could facilitate the differential diagnosis of MS and AD.

Assisted reproductive technology in France: The reproductive rights of LGBT people.

BACKGROUND: In 2021, France authorized ART with sperm donor for female couples and single women. OBJECTIVES: We summarize here the possibilities of ART among LGBT people in France to date, pointing out the main restrictions for LGBT reproductive rights, requiring future legislative changes. RESULTS: Despite the latest modification of the French bioethics laws which notably opens ART to female couples, French legislation still excludes most LGBT people from parenthood through ART, especially gay men and transgender people in most cases. Surrogacy, ROPA, co-parenting and directed sperm donation are banned. CONCLUSIONS: Legalize ROPA and overcome gender issues for trans people are necessary. A French model of surrogacy is to be considered.

The Use of Fissios App© as a Complement to a Face-to-Face Respiratory Physiotherapy Program versus an Attendance-Only Face-to-Face Physiotherapy Program in Patients Scheduled for Thoracic Surgical Procedures Reduces the Risk of Developing Postoperative Pulmonary Complications-A Quasi-Experimental Study.

Postoperative pulmonary complications (PPCs) increase the hospital length of stay (LOS) and the cost of healthcare associated with surgical procedures. Strategies to reduce PPCs begin before surgery and continue in the postoperative period. Fissios App© is a smartphone application that contains perioperative medical advice and a structured respiratory physiotherapy program. The objective was to implement the use of this app in a group of patients scheduled for a thoracic surgical procedure and determine its efficacy in reducing PPCs. This was a quasi-experimental study in which all patients attended a face-to-face respiratory physiotherapy program, and the intervention group used Fissios App© as a complement. We prospectively recorded the postoperative evolution of both groups, analyzed the categorical differences and quantitative variables, and created a binary logistic regression model. We recruited 393 patients (131 intervention and 262 control). The intervention group had a lower incidence of PPCs (12.2% versus 24% in the control group, p = 0.006), a shorter LOS (a median of 3 days (IQR = 2-5) versus 4 days (IQR = 3-6, p = 0.001) in the control group), and a reduction in the risk of developing PPCs by 63.5% (OR: 0.365, 95% CI: 0.17-0.78). The use of Fissios App© improved the clinical outcomes after surgery and reduced the probability of developing PPCs.

Detecting Structural Changes in the Choroidal Layer of the Eye in Neurodegenerative Disease Patients through Optical Coherence Tomography Image Processing.

PURPOSE: To evaluate alterations of the choroid in patients with a neurodegenerative disease versus healthy controls, a custom algorithm based on superpixel segmentation was used. DESIGN: A cross-sectional study was conducted on data obtained in a previous cohort study. SUBJECTS: Swept-source optical coherence tomography (OCT) B-scan images obtained using a Triton (Topcon, Japan) device were compiled according to current OSCAR IB and APOSTEL OCT image quality criteria. Images were included from three cohorts: multiple sclerosis (MS) patients, Parkinson disease (PD) patients, and healthy subjects. Only patients with early-stage MS and PD were included. METHODS: In total, 104 OCT B-scan images were processed using a custom superpixel segmentation (SpS) algorithm to detect boundary limits in the choroidal layer and the optical properties of the image. The algorithm groups pixels with similar structural properties to generate clusters with similar meaningful properties. MAIN OUTCOMES: SpS selects and groups the superpixels in a segmented choroidal area, computing the choroidal optical image density (COID), measured as the standard mean gray level, and the total choroidal area (CA), measured as px2. RESULTS: The CA and choroidal density (CD) were significantly reduced in the two neurodegenerative disease groups (higher in PD than in MS) versus the healthy subjects (p < 0.001); choroidal area was also significantly reduced in the MS group versus the healthy subjects. The COID increased significantly in the PD patients versus the MS patients and in the MS patients versus the healthy controls (p < 0.001). CONCLUSIONS: The SpS algorithm detected choroidal tissue boundary limits and differences optical density in MS and PD patients versus healthy controls. The application of the SpS algorithm to OCT images potentially acts as a non-invasive biomarker for the early diagnosis of MS and PD.

Late recurrence of lobular breast carcinoma presented as gastric metastasis.

A 81-year-old woman with a history of mild chronic heart failure and invasive lobular breast carcinoma pT2N0M0 diagnosed in 2009 and treated by mastectomy, chemotherapy, radiotherapy and adjuvant endocrine therapy with letrozole until 2016. Since then the patient has been disease-free. She presented to the Emergency Room in April 2023 due to severe postprandial epigastric pain and a 7 kg weight loss in the last 3 months. Abdominal computed tomography was performed showing thickening of the gastric antrum and proximal duodenum walls, peritoneal implants and ascites that suggested primary gastric tumor or lymphoma as the first possibility. An endoscopic ultrasound was schedule, performing a biopsy of the gastric lesion and placing a Hot-Axios® stent. The sample showed infiltration by lobular breast carcinoma CK7 (+), CK20 (-), CDX2 (-), GATA3 (+) GCDFP15 (+) RE (+) RP (-) HER2 (-). Treatment with capecitabine was started, with which it continues currently.

The OSCAR-MP Consensus Criteria for Quality Assessment of Retinal Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVES: Optical coherence tomography angiography (OCTA) is a noninvasive high-resolution imaging technique for assessing the retinal vasculature and is increasingly used in various ophthalmologic, neuro-ophthalmologic, and neurologic diseases. To date, there are no validated consensus criteria for quality control (QC) of OCTA. Our study aimed to develop criteria for OCTA quality assessment. METHODS: To establish criteria through (1) extensive literature review on OCTA artifacts and image quality to generate standardized and easy-to-apply OCTA QC criteria, (2) application of OCTA QC criteria to evaluate interrater agreement, (3) identification of reasons for interrater disagreement, revision of OCTA QC criteria, development of OCTA QC scoring guide and training set, and (4) validation of QC criteria in an international, interdisciplinary multicenter study. RESULTS: We identified 7 major aspects that affect OCTA quality: (O) obvious problems, (S) signal strength, (C) centration, (A) algorithm failure, (R) retinal pathology, (M) motion artifacts, and (P) projection artifacts. Seven independent raters applied the OSCAR-MP criteria to a set of 40 OCTA scans from people with MS, Sjogren syndrome, and uveitis and healthy individuals. The interrater kappa was substantial (κ 0.67). Projection artifacts were the main reason for interrater disagreement. Because artifacts can affect only parts of OCTA images, we agreed that prior definition of a specific region of interest (ROI) is crucial for subsequent OCTA quality assessment. To enhance artifact recognition and interrater agreement on reduced image quality, we designed a scoring guide and OCTA training set. Using these educational tools, 23 raters from 14 different centers reached an almost perfect agreement (κ 0.92) for the rejection of poor-quality OCTA images using the OSCAR-MP criteria. DISCUSSION: We propose a 3-step approach for standardized quality control: (1) To define a specific ROI, (2) to assess the occurrence of OCTA artifacts according to the OSCAR-MP criteria, and (3) to evaluate OCTA quality based on the occurrence of different artifacts within the ROI. OSCAR-MP OCTA QC criteria achieved high interrater agreement in an international multicenter study and is a promising QC protocol for application in the context of future clinical trials and studies.

Risk of endocarditis among patients with coagulase-negative Staphylococcus bacteremia.

Coagulase-negative staphylococci (CoNS) are currently considered typical microorganisms causing infective endocarditis (IE) in patients with prosthetic valves. The objective was to determine variables associated with IE in patients with CoNS bacteremia. We performed an analysis of the clinical characteristics of patients with CoNS bacteremia admitted to a university hospital in Madrid (Spain) from 2021 to December 2022 according to the occurrence of IE. This study is an evaluation of a bacteremia registry. During the study period, 106 patients with CoNS bacteremia were detected. In 85 patients an echocardiogram was performed during hospital admission to rule out IE. Among them, 12 episodes were detected that met IE criteria (14.2%). Of the 6 patients with heart valve prostheses, 5 patients (83.3%) had IE (p < 0.001). Patients with IE more frequently had positive blood cultures more than 12 h after the first draw (58.3% versus 13.4%; p < 0.001). There was a tendency to associate community-acquired bacteremia and to that all blood culture bottles obtained were positive with an increased risk of IE (p = 0.091 and p = 0,057, respectively). Attributable mortality to infection was higher in patients with IE relative to all other patients (16.7% vs. 0%; p = 0.033). The multivariable analysis included having valve prosthesis and persistent bacteremia for more than 12 h. Both were independently associated with IE: valve prosthesis OR 38.6 (95% CI 5.8-258; p < 0.001) and persistent bacteremia OR 2.6 (95% CI 1.1-6.8; p = 0.046). In conclusion, a high percentage of cases of CoNS bacteremia may be due to IE. Some of the variables related to a higher risk of IE, such as having a valvular prosthesis or presenting positive blood cultures for more than 12 h, should lead to rule out or confirm the presence of IE by performing echocardiography.

Automatic Segmentation of Retinal Layers in Multiple Neurodegenerative Disorder Scenarios.

Retinal Optical Coherence Tomography (OCT) allows the non-invasive direct observation of the central nervous system, enabling the measurement and extraction of biomarkers from neural tissue that can be helpful in the assessment of ocular, systemic and Neurological Disorders (ND). Deep learning models can be trained to segment the retinal layers for biomarker extraction. However, the onset of ND can have an impact on the neural tissue, which can lead to the degraded performance of models not exposed to images displaying signs of disease during training. We present a fully automatic approach for the retinal layer segmentation in multiple neurodegenerative disorder scenarios, using an annotated dataset of patients of the most prevalent NDs: Alzheimer's disease, Parkinson's disease, multiple sclerosis and essential tremor, along with healthy control patients. Furthermore, we present a two-part, comprehensive study on the effects of ND on the performance of these models. The results show that images of healthy patients may not be sufficient for the robust training of automated segmentation models intended for the analysis of ND patients, and that using images representative of different NDs can increase the model performance. These results indicate that the presence or absence of patients of ND in datasets should be taken into account when training deep learning models for retinal layer segmentation, and that the proposed approach can provide a valuable tool for the robust and reliable diagnosis in multiple scenarios of ND.