High-resolution anatomical imaging of the fetal brain with a reduced field of view using outer volume suppression.

PURPOSE: To achieve high-resolution fetal brain anatomical imaging without introducing image artifacts by reducing the FOV, and to demonstrate improved image quality compared to conventional full-FOV fetal brain imaging. METHODS: Reduced FOV was achieved by applying outer volume suppression (OVS) pulses immediately prior to standard single-shot fast spin echo (SSFSE) imaging. In the OVS preparation, a saturation RF pulse followed by a gradient spoiler was repeated three times with optimized flip-angle weightings and a variable spoiler scheme to enhance signal suppression. Simulations and phantom and in-vivo experiments were performed to evaluate OVS performance. In-vivo high-resolution SSFSE images acquired using the proposed approach were compared with conventional and high-resolution SSFSE images with a full FOV, using image quality scores assessed by neuroradiologists and calculated image metrics. RESULTS: Excellent signal suppression in the saturation bands was confirmed in phantom and in-vivo experiments. High-resolution SSFSE images with a reduced FOV acquired using OVS demonstrated the improved depiction of brain structures without significant motion and blurring artifacts. The proposed method showed the highest image quality scores in the criteria of sharpness, contrast, and artifact and was selected as the best method based on overall image quality. The calculated image sharpness and tissue contrast ratio were also the highest with the proposed method. CONCLUSION: High-resolution fetal brain anatomical images acquired using a reduced FOV with OVS demonstrated improved image quality both qualitatively and quantitatively, suggesting the potential for enhanced diagnostic accuracy in detecting fetal brain abnormalities in utero.

Real-World Assessment of Personalized Approach With Voglibose Fixed-Dose Combination in Type 2 Diabetes Mellitus.

BACKGROUND: Post-prandial hyperglycemia (PPHG) remains a complex aspect in the management of type 2 diabetes mellitus (T2DM) in the Indian population due to uncertainty in the optimal utilization of alpha-glucosidase inhibitors (AGIs) either as standalone therapy or in combination, whether initiated initially or as a sequential therapy. METHODS: This was a post-approval, observational, multicentric clinical study conducted at 50 centers according to principles of the International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use Guideline for Good Clinical Practice (ICH-GCP) and Declaration of Helsinki and local ethics approval. Descriptive and analytical statistics were applied for conclusion and categorical variables using SPSS version 29.0.1.0 (171) (Armonk, NY: IBM Corp.). RESULTS: Protocol analyses of 515 cases revealed baseline demographics as follows: age 57.35±10.04 years, weight 72.86±10.92 kg, and BMI 28.33±6.07 kg/m2. Comorbidities included hypertension (N=169, 32.82%), thyroid disorders (N=99, 19.22%), and heart failure (N=92, 17.86%). Concomitant oral antidiabetics (OADs) prescribed as DPP4i (9.50%), SGLT2i (19.20%), and DPP4i+SGLT2i (7.20%). Study drug reduced glycosylated hemoglobin (HbA1c) by 13.77% (1.25% mean change, p<0.01), fasting blood glucose (FBG) by 23.69% (44.61 mg/dL mean change, p<0.01), post-prandial blood glucose (PPBG) by 24.57% (70.46 mg/dL mean change, p<0.01), and body weight by 4.43% (3.21 kg mean change, p<0.01) over 12 weeks. A total of 161 patients accomplished targeted PPBG of <180 mg/dL (119.13 mg/dL mean change, p<0.01). Regression analysis considering PPBG and HbA1c ≤7.5% showed a weak correlation between them (R-value=0.13, R-squared value=0.02), whereas between PPBG and HbA1c ≤9% yielded moderate positive correlation (R-value=0.53, R-squared value=0.28). There were no adverse events reported or analyzed during the observation period. CONCLUSION: Voglibose fixed-dose combination (FDC) demonstrates significant effectiveness at the initial dosage when started early in the management of T2DM and high PPBG levels. Moreover, it exhibits good tolerability, thereby contributing to higher compliance among Indian patients who consume a high-carbohydrate diet.

Carotid artery calcium score: Definition, classification, application, and limits.

INTRODUCTION: In the current paper, the "carotid artery calcium score" method is presented with the target to offer a metric method to quantify the amount of calcification in the carotid artery. MODEL AND DEFINITION: The Volume of Interest (VOI) should be extracted and those voxels, with a Hounsfield Unit (HU) value ≥130, should be considered. The total weight value is determined by calculating the sum of the HU attenuation values of all voxels with values ≥130 HU. This value should be multiplied by the conversion factor ("or voxel size") and divided by a weighting factor, the attenuation threshold to consider a voxel as calcified (and therefore 130 HU): this equation determines the Carotid Artery Calcium Score (CACS). RESULTS: In order to provide the demonstration of the potential feasibility of the model, the CACS was calculated in 131 subjects (94 males; mean age 72.7 years) for 235 carotid arteries (in 27 subjects, unilateral plaque was present) considered. The CACS value ranged from 0.67 to 11716. A statistically significant correlation was found (rho value = 0.663, p value = .0001) between the CACS in the right and left carotid plaques. Moreover, a statistically significant correlation between the age and the total CACS was present (rho value = 0.244, p value = .005), whereas no statistically significant difference was found in the distribution of CACS by gender (p = .148). The CACS was also tested at baseline and after contrast and no statistically significant difference was found. CONCLUSION: In conclusion, this method is of easy application, and it weights at the same time the volume and the degree of calcification in a unique parameter. This method needs to be tested to verify its potential utility, similar to the coronary artery calcium score, for the risk stratification of the occurrence of cerebrovascular events of the anterior circulation. Further studies using this new diagnostic tool to determine the prognostic value of carotid calcium quantification are needed.

Study of Glycemic Variability in Well-controlled Type 2 Diabetic Patients Using Continuous Glucose Monitoring System.

INTRODUCTION: The world has changed tremendously for patients suffering from diabetes mellitus with the development of cutting-edge technologies like continuous glucose monitoring and flash glucose monitoring systems. Now, the details of constant fluctuations of glucose in their blood can be monitored not only by medical professionals but also by patients, and this is called glycemic variability (GV). Traditional metrics of glycemic control measurement, such as glycated hemoglobin (HbA1c), fail to reflect various short-term glycemic changes like postprandial hyperglycemia and hypoglycemic episodes, paving the way to the occurrence of various diabetic complications even in asymptomatic, well-controlled diabetic patients. This need for advanced management of diabetes and effective monitoring of these swings in blood glucose can be met by using a continuous glucose monitoring system (CGMS). AIM AND OBJECTIVE: To evaluate the extent of GV in well-controlled type 2 diabetes mellitus (T2DM) patients using a flash CGMS and to assess the correlation between GV and HbA1c. MATERIALS AND METHODS: A hospital-based prospective observational study was carried out from May 2020 to Oct 2021 at the Department of Medicine, SMS Hospital, Jaipur, Rajasthan (India), after approval from the Ethics Committee of the institution. A total of 30 patients with well-controlled T2DM (HbA1c was ≥6.5, but ≤7.5) were included in the study using simple random techniques after written informed consent from patients. Patients were studied for glycemic excursions over a period of 7 days by using FreeStyle® Libre Pro™, which is a flash glucose monitoring system. The CGM sensor was attached to the left upper arm of the patient on day 0 and removed on day 7. The data recorded in the sensor was then retrieved using pre-installed computer software and analyzed using standard CGM metrics like standard deviation (SD), percentage coefficient of variation (%CV), time above range (TAR), time below range (TBR), and time in range (TIR), out of which %CV was used to quantify GV. %CV has been used to cluster patients into four cohorts from best to worst, namely: best/low CV ≤ 10%, intermediate CV from 10 to 20%, high CV from 20 to 30%, and very high CV of >30%. Scatterplots are used to establish correlations between various parameters. RESULT: Data from a total of 30 patients were analyzed using CGMS and thus used for calculating standard CGM metrics; glucose readings every 15 minutes were recorded consecutively for 7-day periods, making it a total of 672 readings for each patient. Interpreting the CGM data of all 30 patients, the following results were found: the mean blood glucose of all cases is 134.925 ± 22.323 mg/dL, the mean SD of blood glucose of all cases is 35.348 ± 9.388 mg/dL, the mean of %CV of all cases is 26.376 ± 6.193%. CGM parameters of time are used in the form of percentages, and the following results were found: the mean of TAR, TBR, and TIR is 14.425 ± 13.211, 5.771 ± 6.808, and 82.594 ± 12.888%, respectively. Clustering the patients into cohorts, the proportion of patients exhibiting best/low %CV (10%) is 0, intermediate %CV (10-20%) is 16.67% (five out of 30 patients), high %CV (20-30%) is 50% (15 out of 30 patients) and very high %CV (>30%) is 33.33% (10 out of 30 patients). Also, there is no significant correlation found between HbA1c and %CV (ρ = 0.076, p-value = 0.690); a significant negative correlation was found between %CV and TIR (ρ = -0.604, p < 0.001S); a positive correlation of %CV with TAR and TBR is significant (ρ = 0.816, p-value of <0.001). CONCLUSION: Using a flash CGMS device and considering %CV as the parameter and primary measure of GV, the study demonstrated the overall instability of a person's glycemic control, making note of unrecognized events of hypoglycemia and hyperglycemia in asymptomatic well-controlled T2DM patients, revealing the overall volatile glycemic control. The most important finding of this study is that even those diabetics who are considered well-controlled experience a great degree of GV as assessed by CGM-derived metrics. This study also demonstrated that there is no significant correlation between HbA1c and GV, suggesting that patients may not have optimal control of their diabetes despite having "normal HbA1c" values; hence, GV can be considered an HbA1c-independent danger factor, having more harmful effects than sustained hyperglycemia in the growth of diabetic complications. So, by using CGM-derived metrics, the measurement of GV has the potential to complement HbA1c data. In this manner, a more comprehensive assessment of glycemic excursions can be provided for better treatment decisions, thereby facilitating optimal glycemic control, which is essential for reducing overall complications and promoting good quality of life.

Potential strategies for supporting mental health and mitigating the risk of burnout among healthcare professionals: insights from the COVID-19 pandemic.

Healthcare professionals (HCPs) experienced prolonged stressful conditions during the coronavirus disease 2019 pandemic, and the global situation (particularly in the United Kingdom) meant that they continue to sustain mental stress related to the subsequent cost-of-living and healthcare budgeting crises. The psychological toll on HCPs may lead to increased staff attrition, adversely impacting the quality of patient care and work security. To help mitigate this psychological impact, the current evidence is strongly supportive of healthcare providers consistently adopting programmes fostering improvement in coping and resilience, facilitating healthy lifestyle, and allocating some resources for therapeutic strategies (e.g. cognitive behavioural therapy-based strategies and other strategies specified to trauma-related issues) which can be delivered by trained professionals. We stress that some approaches are not a one-size-fits-all strategy, and we also highlight the need to encourage treatment-seeking among those who need it. These strategies are highly relevant to healthcare employers and policymakers to support all HCPs in settings marked by prolonged periods of stress. The investment in these strategies are expected not only to reduce staff attrition in the long-term, but are likely to add to the cost-effectiveness of overall healthcare budgetary allocation.

Nitrodopamine modified MnO2 NS-MoS2QDs hybrid nanocomposite for the extracellular and intracellular detection of glutathione.

We have developed a highly sensitive and reliable fluorescence resonance energy transfer (FRET) probe using nitro-dopamine (ND) and dopamine (DA) coated MnO2 nanosheet (ND@MnO2 NS and DA@MnO2 NS) as an energy acceptor and MoS2 quantum dots (QDs) as an energy donor. By employing surface-modified MnO2 NS, we can effectively reduce the fluorescence intensity of MoS2 QDs through FRET. It can reduce MnO2 NS to Mn2+ and facilitate the fluorescence recovery of the MoS2 QDs. This ND@MnO2 NS@MoS2 QD-based nanoprobe demonstrates excellent sensitivity to GSH, achieving an LOD of 22.7 nM in an aqueous medium while exhibiting minimal cytotoxicity and good biocompatibility. Moreover, our sensing platform shows high selectivity to GSH towards various common biomolecules and electrolytes. Confocal fluorescence imaging revealed that the nanoprobe can image GSH in A549 cells. Interestingly, the ND@MnO2 NS nanoprobe demonstrates no cytotoxicity in living cancer cells, even at concentrations up to 100 µg mL-1. Moreover, the easy fabrication and eco-friendliness of ND@MnO2 NS make it a rapid and simple method for detecting GSH. We envision the developed nanoprobe as an incredible platform for real-time monitoring of GSH levels in both extracellular and intracellular mediums, proving valuable for biomedical research and clinical diagnostics.

Reduction in Constitutively Activated Auditory Brainstem Microglia in Aging and Alzheimer's Disease.

Background: Alzheimer's disease (AD) pathology is considered to begin in the brainstem, and cerebral microglia are known to play a critical role in AD pathogenesis, yet little is known about brainstem microglia in AD. Translocator protein (TSPO) PET, sensitive to activated microglia, shows high signal in dorsal brainstem in humans, but the precise location and clinical correlates of this signal are unknown. Objective: To define age and AD associations of brainstem TSPO PET signal in humans. Methods: We applied new probabilistic maps of brainstem nuclei to quantify PET-measured TSPO expression over the whole brain including brainstem in 71 subjects (43 controls scanned using 11C-PK11195; 20 controls and 8 AD subjects scanned using 11C-PBR28). We focused on inferior colliculi (IC) because of visually-obvious high signal in this region, and potential relevance to auditory dysfunction in AD. We also assessed bilateral cortex. Results: TSPO expression was normally high in IC and other brainstem regions. IC TSPO was decreased with aging (p = 0.001) and in AD subjects versus controls (p = 0.004). In cortex, TSPO expression was increased with aging (p = 0.030) and AD (p = 0.033). Conclusions: Decreased IC TSPO expression with aging and AD-an opposite pattern than in cortex-highlights underappreciated regional heterogeneity in microglia phenotype, and implicates IC in a biological explanation for strong links between hearing loss and AD. Unlike in cerebrum, where TSPO expression is considered pathological, activated microglia in IC and other brainstem nuclei may play a beneficial, homeostatic role. Additional study of brainstem microglia in aging and AD is needed.

Rhabdoid tumor predisposition syndrome: A historical review of treatments and outcomes for associated pediatric malignancies.

Rhabdoid tumor predisposition syndrome (RTPS) is a rare disorder associated with malignant rhabdoid tumor of the kidney (RTK), atypical teratoid rhabdoid tumor (ATRT), and/or other extracranial, extrarenal rhabdoid tumors (EERT), and these pediatric malignancies are difficult to treat. Presently, most of the information regarding clinical manifestations, treatment, and outcomes of rhabdoid tumors comes from large data registries and case series. Our current understanding of treatments for patients with rhabdoid tumors may inform how we approach patients with RTPS. In this manuscript, we review the genetic and clinical features of RTPS and, using known registry data and clinical reports, review associated tumor types ATRT, RTK, and EERT, closing with potential new approaches to treatment. We propose collaborative international efforts to study the use of SMARC (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin)-targeting agents, high-dose consolidative therapy, and age-based irradiation of disease sites in RTPS.

Healthcare utilization and clinical characteristics of genetic epilepsy in electronic health records.

Understanding the clinical characteristics and medical treatment of individuals affected by genetic epilepsies is instrumental in guiding selection for genetic testing, defining the phenotype range of these rare disorders, optimizing patient care pathways and pinpointing unaddressed medical need by quantifying healthcare resource utilization. To date, a matched longitudinal cohort study encompassing the entire spectrum of clinical characteristics and medical treatment from childhood through adolescence has not been performed. We identified individuals with genetic and non-genetic epilepsies and onset at ages 0-5 years by linkage across the Cleveland Clinic Health System. We used natural language processing to extract medical terms and procedures from longitudinal electronic health records and tested for cross-sectional and temporal associations with genetic epilepsy. We implemented a two-stage design: in the discovery cohort, individuals were stratified as being 'likely genetic' or 'non-genetic' by a natural language processing algorithm, and controls did not receive genetic testing. The validation cohort consisted of cases with genetic epilepsy confirmed by manual chart review and an independent set of controls who received negative genetic testing. The discovery and validation cohorts consisted of 503 and 344 individuals with genetic epilepsy and matched controls, respectively. The median age at the first encounter was 0.1 years and 7.9 years at the last encounter, and the mean duration of follow-up was 8.2 years. We extracted 188,295 Unified Medical Language System annotations for statistical analysis across 9659 encounters. Individuals with genetic epilepsy received an earlier epilepsy diagnosis and had more frequent and complex encounters with the healthcare system. Notably, the highest enrichment of encounters compared with the non-genetic groups was found during the transition from paediatric to adult care. Our computational approach could validate established comorbidities of genetic epilepsies, such as behavioural abnormality and intellectual disability. We also revealed novel associations for genitourinary abnormalities (odds ratio 1.91, 95% confidence interval: 1.66-2.20, P = 6.16 × 10-19) linked to a spectrum of underrecognized epilepsy-associated genetic disorders. This case-control study leveraged real-world data to identify novel features associated with the likelihood of a genetic aetiology and quantified the healthcare utilization of genetic epilepsies compared with matched controls. Our results strongly recommend early genetic testing to stratify individuals into specialized care paths, thus improving the clinical management of people with genetic epilepsies.

Embracing Exoscope in the Arsenal of Spine Surgeons in the Low- and Middle-Income Countries.

BACKGROUND: Exoscope (EX) is a device that combines the convenience of an endoscope with the image clarity of an operating microscope (OM) to fill the void between the two. This study aims to compare the 2-dimensional EX with OM in spine surgeries and to explore its utility and feasibility in small and peripheral hospitals of low- and middle-income countries. METHODS: Eighty-two patients with intradural spinal tumors (extramedullary and intramedullary) aged more than 18 years were included between August 2021 and August 2023. Patients with other spinal pathologies were excluded. After each exoscopic surgery, the operating surgeon and assistant had to answer a questionnaire. Postoperatively, outcomes were measured as the length of hospital stay, cerebrospinal fluid leak, and number of reoperations. RESULTS: Thirty-seven patients were included in the OM group and 45 patients were included in the EX group. In 62%-67% of cases, the overall image quality of the EX was comparable to OM and in 29%-38% of cases, it was superior to the OM. The preparation and installation of the EX were much easier and better than the OM in 93%-100% of the cases. Maneuvering surgical instruments and workflow in the operating theater was much more convenient in the EX group (95%-100% of the cases). Ergonomics was far better in the EX group than in the OM group. CONCLUSIONS: Spine surgeons can embrace the benefits of EX and increase their range of surgeries to be performed at the small operation theater setup in low-middle income developing countries.

Remote Associations Between Tau and Cortical Amyloid-ß Are Stage-Dependent.

Background: Histopathologic studies of Alzheimer's disease (AD) suggest that extracellular amyloid-ß (Aß) plaques promote the spread of neurofibrillary tau tangles. However, these two proteinopathies initiate in spatially distinct brain regions, so how they interact during AD progression is unclear. Objective: In this study, we utilized Aß and tau positron emission tomography (PET) scans from 572 older subjects (476 healthy controls (HC), 14 with mild cognitive impairment (MCI), 82 with mild AD), at varying stages of the disease, to investigate to what degree tau is associated with cortical Aß deposition. Methods: Using multiple linear regression models and a pseudo-longitudinal ordering technique, we investigated remote tau-Aß associations in four pathologic phases of AD progression based on tau spread: 1) no-tau, 2) pre-acceleration, 3) acceleration, and 4) post-acceleration. Results: No significant tau-Aß association was detected in the no-tau phase. In the pre-acceleration phase, the earliest stage of tau deposition, associations emerged between regional tau in medial temporal lobe (MTL) (i.e., entorhinal cortex, parahippocampal gyrus) and cortical Aß in lateral temporal lobe regions. The strongest tau-Aß associations were found in the acceleration phase, in which tau in MTL regions was strongly associated with cortical Aß (i.e., temporal and frontal lobes regions). Strikingly, in the post-acceleration phase, including 96% of symptomatic subjects, tau-Aß associations were no longer significant. Conclusions: The results indicate that associations between tau and Aß are stage-dependent, which could have important implications for understanding the interplay between these two proteinopathies during the progressive stages of AD.

Use of Genomics to Develop Novel Therapeutics and Personalize Hypertension Therapy.

Hypertension is a prevalent public health problem, contributing to >10 million deaths annually. Though multiple therapeutics exist, many patients suffer from treatment-resistant hypertension or try several medications before achieving blood pressure control. Genomic advances offer mechanistic understanding of blood pressure variability, therapeutic targets, therapeutic response, and promise a stratified approach to treatment of primary hypertension. Cyclic guanosine monophosphate augmentation, aldosterone synthase inhibitors, and angiotensinogen blockade with silencing RNA and antisense therapies are among the promising novel approaches. Pharmacogenomic studies have also been done to explore the genetic bases underpinning interindividual variability in response to existing therapeutics. A polygenic approach using risk scores is likely to be the next frontier in stratifying responses to existing therapeutics.

Multi-Echo Complex Quantitative Susceptibility Mapping and Quantitative Blood Oxygen Level-Dependent Magnitude (mcQSM + qBOLD or mcQQ) for Oxygen Extraction Fraction (OEF) Mapping.

Oxygen extraction fraction (OEF), the fraction of oxygen that tissue extracts from blood, is an essential biomarker used to directly assess tissue viability and function in neurologic disorders. In ischemic stroke, for example, increased OEF can indicate the presence of penumbra-tissue with low perfusion yet intact cellular integrity-making it a primary therapeutic target. However, practical OEF mapping methods are not currently available in clinical settings, owing to the impractical data acquisitions in positron emission tomography (PET) and the limitations of existing MRI techniques. Recently, a novel MRI-based OEF mapping technique, termed QQ, was proposed. It shows high potential for clinical use by utilizing a routine sequence and removing the need for impractical multiple gas inhalations. However, QQ relies on the assumptions of Gaussian noise in susceptibility and multi-echo gradient echo (mGRE) magnitude signals for OEF estimation. This assumption is unreliable in low signal-to-noise ratio (SNR) regions like disease-related lesions, risking inaccurate OEF estimation and potentially impacting clinical decisions. Addressing this, our study presents a novel multi-echo complex QQ (mcQQ) that models realistic Gaussian noise in mGRE complex signals. We implemented mcQQ using a deep learning framework (mcQQ-NET) and compared it with the existing QQ-NET in simulations, ischemic stroke patients, and healthy subjects, using identical training and testing datasets and schemes. In simulations, mcQQ-NET provided more accurate OEF than QQ-NET. In the subacute stroke patients, mcQQ-NET showed a lower average OEF ratio in lesions relative to unaffected contralateral normal tissue than QQ-NET. In the healthy subjects, mcQQ-NET provided uniform OEF maps, similar to QQ-NET, but without unrealistically high OEF outliers in areas of low SNR, such as SNR ≤ 15 (dB). Therefore, mcQQ-NET improves OEF accuracy by more accurately reflecting realistic Gaussian noise in complex mGRE signals. Its enhanced sensitivity to OEF abnormalities, based on more realistic biophysics modeling, suggests that mcQQ-NET has potential for investigating tissue variability in neurologic disorders.

30-day Morbidity and Mortality after Cholecystectomy for Benign Gallbladder Disease (AMBROSE): A Prospective, International Collaborative Cohort Study.

OBJECTIVE: This study aimed to assess 30-day morbidity and mortality rates following cholecystectomy for benign gallbladder disease and identify the factors associated with complications. SUMMARY BACKGROUND DATA: Although cholecystectomy is common for benign gallbladder disease, there is a gap in the knowledge of the current practice and variations on a global level. METHODS: A prospective, international, observational collaborative cohort study of consecutive patients undergoing cholecystectomy for benign gallbladder disease from participating hospitals in 57 countries between January 1 and June 30, 2022, was performed. Univariate and multivariate logistic regression models were used to identify preoperative and operative variables associated with 30-day postoperative outcomes. RESULTS: Data of 21,706 surgical patients from 57 countries were included in the analysis. A total of 10,821 (49.9%), 4,263 (19.7%), and 6,622 (30.5%) cholecystectomies were performed in the elective, emergency, and delayed settings, respectively. Thirty-day postoperative complications were observed in 1,738 patients (8.0%), including mortality in 83 patients (0.4%). Bile leaks (Strasberg grade A) were reported in 278 (1.3%) patients and severe bile duct injuries (Strasberg grades B-E) were reported in 48 (0.2%) patients. Patient age, ASA physical status class, surgical setting, operative approach and Nassar operative difficulty grade were identified as the five predictors demonstrating the highest relative importance in predicting postoperative complications. CONCLUSION: This multinational observational collaborative cohort study presents a comprehensive report of the current practices and outcomes of cholecystectomy for benign gallbladder disease. Ongoing global collaborative evaluations and initiatives are needed to promote quality assurance and improvement in cholecystectomy.

Carotid stenosis and cryptogenic stroke.

OBJECTIVES: Cryptogenic stroke represents a type of ischemic stroke with an unknown origin, presenting a significant challenge in both stroke management and prevention. According to the Trial of Org 10,172 in Acute Stroke Treatment criteria, a stroke is categorized as being caused by large artery atherosclerosis only when there is >50% luminal narrowing of the ipsilateral internal carotid artery. However, nonstenosing carotid artery plaques can be an underlying cause of ischemic stroke. Indeed, emerging evidence documents that some features of plaque vulnerability may act as an independent risk factor, regardless of the degree of stenosis, in precipitating cerebrovascular events. This review, drawing from an array of imaging-based studies, explores the predictive values of carotid imaging modalities in the detection of nonstenosing carotid plaque (<50%), that could be the cause of a cerebrovascular event when some features of vulnerability are present. METHODS: Google Scholar, Scopus, and PubMed were searched for articles on cryptogenic stroke and those reporting the association between cryptogenic stroke and imaging features of carotid plaque vulnerability. RESULTS: Despite extensive diagnostic evaluations, the etiology of a considerable proportion of strokes remains undetermined, contributing to the recurrence rate and persistent morbidity in affected individuals. Advances in imaging modalities, such as magnetic resonance imaging, computed tomography scans, and ultrasound examination, facilitate more accurate detection of nonstenosing carotid artery plaque and allow better stratification of stroke risk, leading to a more tailored treatment strategy. CONCLUSIONS: Early detection of nonstenosing carotid plaque with features of vulnerability through carotid imaging techniques impacts the clinical management of cryptogenic stroke, resulting in refined stroke subtype classification and improved patient management. Additional research is required to validate these findings and recommend the integration of these state-of-the-art imaging methodologies into standard diagnostic protocols to improve stroke management and prevention.

Legacy benefits of blood pressure treatment on cardiovascular events are primarily mediated by improved blood pressure variability: the ASCOT trial.

BACKGROUND AND AIMS: Visit-to-visit systolic blood pressure variability (BPV) is an important predictor of cardiovascular (CV) outcomes. The long-term effect of a period of blood pressure (BP) control, but with differential BPV, is uncertain. Morbidity and mortality follow-up of UK participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure-Lowering Arm has been extended for up to 21 years to determine the CV impact of mean systolic blood pressure (SBP) control and BPV during the trial, and amongst those allocated to amlodipine- and atenolol-based treatment. METHODS: Eight thousand five hundred and eighty hypertensive participants (4305 assigned to amlodipine ± perindopril-based and 4275 to atenolol ± diuretic-based treatment during the in-trial period (median 5.5 years) were followed for up to 21 years (median 17.4 years), using linked hospital and mortality records. A subgroup of participants (n = 2156) was followed up 6 years after the trial closure with a self-administered questionnaire and a clinic visit. In-trial mean SBP and standard deviation of visit-to-visit SBP as a measure of BPV, were measured using >100 000 BP measurements. Cox proportional hazard models were used to estimate the risk [hazard ratios (HRs)], associated with (i) mean with SBP and BPV during the in-trial period, for the CV endpoints occurring after the end of the trial and (ii) randomly assigned treatment to events following randomization, for the first occurrence of pre-specified CV outcomes. RESULTS: Using BP data from the in-trial period, in the post-trial period, although mean SBP was a predictor of CV outcomes {HR per 10 mmHg, 1.14 [95% confidence interval (CI) 1.10-1.17], P < .001}, systolic BPV independent of mean SBP was a strong predictor of CV events [HR per 5 mmHg 1.22 (95% CI 1.18-1.26), P < .001] and predicted events even in participants with well-controlled BP. During 21-year follow-up, those on amlodipine-based compared with atenolol-based in-trial treatment had significantly reduced risk of stroke [HR 0.82 (95% CI 0.72-0.93), P = .003], total CV events [HR 0.93 (95% CI 0.88-0.98), P = .008], total coronary events [HR 0.92 (95% CI 0.86-0.99), P = .024], and atrial fibrillation [HR 0.91 (95% CI 0.83-0.99), P = .030], with weaker evidence of a difference in CV mortality [HR 0.91 (95% CI 0.82-1.01), P = .073]. There was no significant difference in the incidence of non-fatal myocardial infarction and fatal coronary heart disease, heart failure, and all-cause mortality. CONCLUSIONS: Systolic BPV is a strong predictor of CV outcome, even in those with controlled SBP. The long-term benefits of amlodipine-based treatment compared with atenolol-based treatment in reducing CV events appear to be primarily mediated by an effect on systolic BPV during the trial period.

Investigating the phenology and interactions of competitive plant species co-occurring with invasive Lantana camara in Indian Himalayan Region.

Invasive plant species are considered one of the significant drivers of habitat loss, leading to biodiversity loss. They have also been observed to alter the local ecology, resulting in a decline of native flora. The management of invasive species is widely recognised as one of the most severe challenges to biodiversity conservation. The International Union for Conservation of Nature (IUCN) considers Lantana camara, as one of the ten worst weeds. Over time, native and indigenous species may evolve to co-exist or compete with invasive species, reducing invader fitness. It is observed that species competition fluctuates throughout environmental gradients, life phases, and abundances. Hence, competition outcome is very context-dependent. To address this challenge, we conducted a comprehensive study in three phases: we identified native species coexisting with Lantana in their natural habitats in the Doon Valley (Phase I) and documented the phenotypic traits of selected coexisting species using the Landmark BBCH (Biologische Bun-desantalt, Bundessortenamt und Chemische Industrie) scale, revealing the phenological growth patterns of selected co-existing species (Phase II). This was followed by conducting pot (Phase IIIa) and field (Phase IIIb) experiments to study the interactions between them. Notably, Justicia adhatoda, Broussonetia papyrifera, Pongamia pinnata, Urtica dioica and Bauhinia variegata demonstrated promising results in both pot and field conditions. Furthermore, after the mechanical removal of Lantana and prior to the plantation in the field experiments, four native grass species were introduced using the seed ball method. Among these, Pennisetum pedicellatum and Sorghum halpense exhibited prompt regeneration and effectively colonised the field, densely covering the cleared area. The study provides a comprehensive management plan for the restoration of Lantana affected areas through competition using native species. This study utilizes phenological assessment for native plant selection using reclamation from native grasses and proposes a management plan for combating invasive Lantana.

Hyperventilation Induced Seizures in Focal Epilepsy: Two Cases and a Review of Literature.

We report two cases of temporo-perisylvian epilepsy with habitual seizures consistently inducible by hyperventilation (HV). One case was non-lesional, while the other was a lesional temporo-perisylvian epilepsy. Both underwent surgical resection and were seizure-free or nearly seizure-free thereafter. We discuss the pathophysiological changes evoked by HV in healthy brains, and those with generalized and focal epilepsy. We provide a comprehensive and critical review of the literature on the role of HV in focal epilepsy. We suggest HV should be considered an activation method for patients with focal epilepsy during epilepsy monitoring unit admissions and may help in the localization of the epileptogenic network/zone.

Predictors of therapeutic response following thalamic neuromodulation for drug-resistant pediatric epilepsy: A systematic review and individual patient data meta-analysis.

We sought to perform a systematic review and individual participant data meta-analysis to identify predictors of treatment response following thalamic neuromodulation in pediatric patients with medically refractory epilepsy. Electronic databases (MEDLINE, Ovid, Embase, and Cochrane) were searched, with no language or data restriction, to identify studies reporting seizure outcomes in pediatric populations following deep brain stimulation (DBS) or responsive neurostimulation (RNS) implantation in thalamic nuclei. Studies featuring individual participant data of patients with primary or secondary generalized drug-resistant epilepsy were included. Response to therapy was defined as >50% reduction in seizure frequency from baseline. Of 417 citations, 21 articles reporting on 88 participants were eligible. Mean age at implantation was 13.07 ± 3.49 years. Fifty (57%) patients underwent DBS, and 38 (43%) RNS. Sixty (68%) patients were implanted in centromedian nucleus and 23 (26%) in anterior thalamic nucleus, and five (6%) had both targets implanted. Seventy-four (84%) patients were implanted bilaterally. The median time to last follow-up was 12 months (interquartile range = 6.75-26.25). Sixty-nine percent of patients achieved response to treatment. Age, target, modality, and laterality had no significant association with response in univariate logistic regression. Until thalamic neuromodulation gains widespread approval for use in pediatric patients, data on efficacy will continue to be limited to small retrospective cohorts and case series. The inherent bias of these studies can be overcome by using individual participant data. Thalamic neuromodulation appears to be a safe and effective treatment for epilepsy. Larger, prolonged prospective, multicenter studies are warranted to further evaluate the efficacy of DBS over RNS in this patient population where resection for curative intent is not a safe option.

Recent advances and controversial issues in the optimal management of asymptomatic carotid stenosis.

OBJECTIVE: The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. We updated our 2021 Expert Review and Position Statement, focusing on recent advances in the diagnosis and management of patients with AsxCS. METHODS: A systematic review of the literature was performed up to August 1, 2023, using PubMed/PubMed Central, EMBASE and Scopus. The following keywords were used in various combinations: "asymptomatic carotid stenosis," "carotid endarterectomy" (CEA), "carotid artery stenting" (CAS), and "transcarotid artery revascularization" (TCAR). Areas covered included (i) improvements in best medical treatment (BMT) for patients with AsxCS and declining stroke risk, (ii) technological advances in surgical/endovascular skills/techniques and outcomes, (iii) risk factors, clinical/imaging characteristics and risk prediction models for the identification of high-risk AsxCS patient subgroups, and (iv) the association between cognitive dysfunction and AsxCS. RESULTS: BMT is essential for all patients with AsxCS, regardless of whether they will eventually be offered CEA, CAS, or TCAR. Specific patient subgroups at high risk for stroke despite BMT should be considered for a carotid revascularization procedure. These patients include those with severe (≥80%) AsxCS, transcranial Doppler-detected microemboli, plaque echolucency on Duplex ultrasound examination, silent infarcts on brain computed tomography or magnetic resonance angiography scans, decreased cerebrovascular reserve, increased size of juxtaluminal hypoechoic area, AsxCS progression, carotid plaque ulceration, and intraplaque hemorrhage. Treatment of patients with AsxCS should be individualized, taking into consideration individual patient preferences and needs, clinical and imaging characteristics, and cultural, ethnic, and social factors. Solid evidence supporting or refuting an association between AsxCS and cognitive dysfunction is lacking. CONCLUSIONS: The optimal management of patients with AsxCS should include BMT for all individuals and a prophylactic carotid revascularization procedure (CEA, CAS, or TCAR) for some asymptomatic patient subgroups, additionally taking into consideration individual patient needs and preference, clinical and imaging characteristics, social and cultural factors, and the available stroke risk prediction models. Future studies should investigate the association between AsxCS with cognitive function and the role of carotid revascularization procedures in the progression or reversal of cognitive dysfunction.