Epileptic seizure forecasting with wearable-based nocturnal sleep features.

OBJECTIVE: Non-invasive biomarkers have recently shown promise for seizure forecasting in people with epilepsy. In this work, we developed a seizure-day forecasting algorithm based on nocturnal sleep features acquired using a smart shirt. METHODS: Seventy-eight individuals with epilepsy admitted to the Centre hospitalier de l'Université de Montréal epilepsy monitoring unit wore the Hexoskin biometric smart shirt during their stay. The shirt continuously measures electrocardiography, respiratory, and accelerometry activity. Ten sleep features, including sleep efficiency, sleep latency, sleep duration, time spent in non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM), wakefulness after sleep onset, average heart and breathing rates, high-frequency heart rate variability, and the number of position changes, were automatically computed using the Hexoskin sleep algorithm. Each night's features were then normalized using a reference night for each patient. A support vector machine classifier was trained for pseudo-prospective seizure-day forecasting, with forecasting horizons of 16- and 24-h to include both diurnal and nocturnal seizures (24-h) or diurnal seizures only (16-h). The algorithm's performance was assessed using a nested leave-one-patient-out cross-validation approach. RESULTS: Improvement over chance (IoC) performances were achieved for 48.7% and 40% of patients with the 16- and 24-h forecasting horizons, respectively. For patients with IoC performances, the proposed algorithm reached mean IoC, sensitivity and time in warning of 34.3%, 86.0%, and 51.7%, respectively for the 16-h horizon, and 34.2%, 64.4% and 30.2%, respectively, for the 24-h horizon. SIGNIFICANCE: Smart shirt-based nocturnal sleep analysis holds promise as a non-invasive approach for seizure-day forecasting in a subset of people with epilepsy. Further investigations, particularly in a residential setting with long-term recordings, could pave the way for the development of innovative and practical seizure forecasting devices. PLAIN LANGUAGE SUMMARY: Seizure forecasting with wearable devices may improve the quality of life of people living with epilepsy who experience unpredictable, recurrent seizures. In this study, we have developed a seizure forecasting algorithm using sleep characteristics obtained from a smart shirt worn at night by a large number of hospitalized patients with epilepsy (78). A daily seizure forecast was generated following each night using machine learning methods. Our results show that around half of people with epilepsy may benefit from such an approach.

The C-terminal sequences of Bcl-2 family proteins mediate interactions that regulate cell death.

Programmed cell death via the both intrinsic and extrinsic pathways is regulated by interactions of the Bcl-2 family protein members that determine whether the cell commits to apoptosis via mitochondrial outer membrane permeabilization (MOMP). Recently the conserved C-terminal sequences (CTSs) that mediate localization of Bcl-2 family proteins to intracellular membranes, have been shown to have additional protein-protein binding functions that contribute to the functions of these proteins in regulating MOMP. Here we review the pivotal role of CTSs in Bcl-2 family interactions including: (1) homotypic interactions between the pro-apoptotic executioner proteins that cause MOMP, (2) heterotypic interactions between pro-apoptotic and anti-apoptotic proteins that prevent MOMP, and (3) heterotypic interactions between the pro-apoptotic executioner proteins and the pro-apoptotic direct activator proteins that promote MOMP.

Deep learning and explainable artificial intelligence for investigating dental professionals' satisfaction with CAD software performance.

PURPOSE: This study aimed to examine the satisfaction of dental professionals, including dental students, dentists, and dental technicians, with computer-aided design (CAD) software performance using deep learning (DL) and explainable artificial intelligence (XAI)-based behavioral analysis concepts. MATERIALS AND METHODS: This study involved 436 dental professionals with diverse CAD experiences to assess their satisfaction with various dental CAD software programs. Through exploratory factor analysis, latent factors affecting user satisfaction were extracted from the observed variables. A multilayer perceptron artificial neural network (MLP-ANN) model was developed along with permutation feature importance analysis (PFIA) and the Shapley additive explanation (Shapley) method to gain XAI-based insights into individual factors' significance and contributions. RESULTS: The MLP-ANN model outperformed a standard logistic linear regression model, demonstrating high accuracy (95%), precision (84%), and recall rates (84%) in capturing complex psychological problems related to human attitudes. PFIA revealed that design adjustability was the most important factor impacting dental CAD software users' satisfaction. XAI analysis highlighted the positive impacts of features supporting the finish line and crown design, while the number of design steps and installation time had negative impacts. Notably, finish-line design-related features and the number of design steps emerged as the most significant factors. CONCLUSIONS: This study sheds light on the factors influencing dental professionals' decisions in using and selecting CAD software. This approach can serve as a proof-of-concept for applying DL-XAI-based behavioral analysis in dentistry and medicine, facilitating informed software selection and development.

Outcome of emergency neurosurgery in patients with refractory and super-refractory status epilepticus: a systematic review and individual participant data meta-analysis.

Background: Refractory (RSE) and super-refractory status epilepticus (SRSE) are serious neurological conditions requiring aggressive management. Beyond anesthetic agents, there is a lack of evidence guiding management in these patients. This systematic review and individual participant data meta-analysis (IPDMA) seeks to evaluate and compare the currently available surgical techniques for the acute treatment of RSE and SRSE. Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Individual Participant Data (PRISMA-IPD). Only patients who underwent surgery while in RSE and SRSE were included. Descriptive statistics were used to compare various subgroups. Multivariable logistic regression models were constructed to identify predictors of status epilepticus (SE) cessation, long-term overall seizure freedom, and favorable functional outcome (i.e., modified Rankin score of 0-2) at last follow-up. Results: A total of 87 studies including 161 participants were included. Resective surgery tended to achieve better SE cessation rate (93.9%) compared to non-resective techniques (83.9%), but this did not reach significance (p = 0.071). Resective techniques were also more likely to achieve seizure freedom (69.1% vs. 34.4%, p = <0.0001). Older age at SE (OR = 1.384[1.046-1.832], p = 0.023) was associated with increased likelihood of SE cessation, while longer duration of SE (OR = 0.603[0.362-1.003], p = 0.051) and new-onset seizures (OR = 0.244[0.069-0.860], p = 0.028) were associated with lower likelihood of SE cessation, but this did not reach significance for SE duration. Only shorter duration of SE prior to surgery (OR = 1.675[1.168-2.404], p = 0.0060) and immediate termination of SE (OR = 3.736 [1.323-10.548], p = 0.014) were independently associated with long-term seizure status. Rates of favorable functional outcomes (mRS of 0-2) were comparable between resective (44.4%) and non-resective (44.1%) techniques, and no independent predictors of outcome were identified. Conclusion: Our findings suggest that emergency neurosurgery may be a safe and effective alternative in patients with RSE/SRSE and may be considered earlier during the disease course. However, the current literature is limited exclusively to small case series and case reports with high risk of publication bias. Larger clinical trials assessing long-term seizure and functional outcomes are warranted to establish robust management guidelines.

Evaluation of Dihydroartemisinin-Piperaquine Efficacy and Molecular Markers in Uncomplicated Falciparum Patients: A Study across Binh Phuoc and Dak Nong, Vietnam.

Background and Objectives: Malaria continues to be a significant global health challenge. The efficacy of artemisinin-based combination therapies (ACTs) has declined in many parts of the Greater Mekong Subregion, including Vietnam, due to the spread of resistant malaria strains. This study was conducted to assess the efficacy of the Dihydroartemisinin (DHA)-Piperaquine (PPQ) regimen in treating uncomplicated falciparum malaria and to conduct molecular surveillance of antimalarial drug resistance in Binh Phuoc and Dak Nong provinces. Materials and Methods: The study included 63 uncomplicated malaria falciparum patients from therapeutic efficacy studies (TES) treated following the WHO treatment guidelines (2009). Molecular marker analysis was performed on all 63 patients. Methods encompassed Sanger sequencing for pfK13 mutations and quantitative real-time PCR for the pfpm2 gene. Results: This study found a marked decrease in the efficacy of the DHA-PPQ regimen, with an increased rate of treatment failures at two study sites. Genetic analysis revealed a significant presence of pfK13 mutations and pfpm2 amplifications, indicating emerging resistance to artemisinin and its partner drug. Conclusions: The effectiveness of the standard DHA-PPQ regimen has sharply declined, with rising treatment failure rates. This decline necessitates a review and possible revision of national malaria treatment guidelines. Importantly, molecular monitoring and clinical efficacy assessments together provide a robust framework for understanding and addressing detection drug resistance in malaria.

Association between Bacteroides fragilis and Fusobacterium nucleatum infection and colorectal cancer in Vietnamese patients.

BACKGROUND: Colorectal cancer (CRC) is a significant global health concern, and understanding the role of specific bacterial infections in its development and progression is of increasing interest. This cross-sectional study investigated the associations between Bacteroides fragilis (B. fragilis) and Fusobacterium nucleatum (F. nucleatum) infections and Vietnamese CRC patients. METHODS: 192 patients with either polyps or CRC at varying stages were recruited from May 2017 to December 2020. Real-time PCR assessed infection rates and bacterial loads in CRC tissues. RESULTS: B. fragilis infection was notably higher in CRC tissues (51.6 %) than polyps (9.4 %), with a fivefold higher relative load. Positive associations were found in stages II and III, indicating a fivefold increase in CRC progression risk. F. nucleatum infection rates were significantly higher in CRC tissues (55.2 %) than in polyps (10.5 %). In stage II, the infection rate exceeded that in adjacent tissues. The relative load of F. nucleatum was higher in stage III than in stages I and II. Positive F. nucleatum patients had a 3.2 times higher risk of CRC progression. CONCLUSION: These findings suggest associations between loading of F. nucleatum or/and B. fragilis with the advanced stages of CRC.

Urchin-like CoP3/Cu3P heterostructured nanorods supported on a 3D porous copper foam for high-performance non-enzymatic electrochemical dopamine sensors.

In this study, we developed a high-performance non-enzymatic electrochemical sensor based on urchin-like CoP3/Cu3P heterostructured nanorods supported on a three-dimensional porous copper foam, namely, CoP3/Cu3P NRs/CF, for the detection of dopamine. Benefiting from the promising intrinsic catalytic activities of CoP3 and Cu3P, urchin-like microsphere structures, and a large electrochemically active surface area for exposing numerous accessible catalytic active sites, the proposed CoP3/Cu3P NRs/CF shows extraordinary electrochemical response towards the electrocatalytic oxidation of dopamine. As a result, the CoP3/Cu3P NRs/CF sensing electrode has a broad detection window (from 0.2 to 2000 µM), low detection limit (0.51 µM), high electrochemical sensitivity (0.0105 mA µM-1 cm-2), excellent selectivity towards dopamine in the coexistence of some interfering species, and good stability for dopamine determination. More importantly, the CoP3/Cu3P NRs/CF catalyst also exhibits excellent catalytic activity, sensitivity, and selectivity for dopamine detection under simulated human body conditions at a physiological pH of 7.25 (0.1 M PBS) at 36.6 °C.

Investigating demic versus cultural diffusion and sex bias in the spread of Austronesian languages in Vietnam.

Austronesian (AN) is the second-largest language family in the world, particularly widespread in Island Southeast Asia (ISEA) and Oceania. In Mainland Southeast Asia (MSEA), groups speaking these languages are concentrated in the highlands of Vietnam. However, our knowledge of the spread of AN-speaking populations in MSEA remains limited; in particular, it is not clear if AN languages were spread by demic or cultural diffusion. In this study, we present and analyze new data consisting of complete mitogenomes from 369 individuals and 847 Y-chromosomal single nucleotide polymorphisms (SNPs) from 170 individuals from all five Vietnamese Austronesian groups (VN-AN) and five neighboring Vietnamese Austroasiatic groups (VN-AA). We found genetic signals consistent with matrilocality in some, but not all, of the VN-AN groups. Population affinity analyses indicated connections between the AN-speaking Giarai and certain Taiwanese AN groups (Rukai, Paiwan, and Bunun). However, overall, there were closer genetic affinities between VN-AN groups and neighboring VN-AA groups, suggesting language shifts. Our study provides insights into the genetic structure of AN-speaking communities in MSEA, characterized by some contact with Taiwan and language shift in neighboring groups, indicating that the expansion of AN speakers in MSEA was a combination of cultural and demic diffusion.

Pain reflects the informational value of nociceptive inputs.

ABSTRACT: Pain perception and its modulation are fundamental to human learning and adaptive behavior. This study investigated the hypothesis that pain perception is tied to pain's learning function. Thirty-one participants performed a threat conditioning task where certain cues were associated with a possibility of receiving a painful electric shock. The cues that signaled potential pain or safety were regularly changed, requiring participants to continually establish new associations. Using computational models, we quantified participants' pain expectations and prediction errors throughout the task and assessed their relationship with pain perception and electrophysiological responses. Our findings suggest that subjective pain perception increases with prediction error, that is, when pain was unexpected. Prediction errors were also related to physiological nociceptive responses, including the amplitude of nociceptive flexion reflex and electroencephalography markers of cortical nociceptive processing (N1-P2-evoked potential and gamma-band power). In addition, higher pain expectations were related to increased late event-related potential responses and alpha/beta decreases in amplitude during cue presentation. These results further strengthen the idea of a crucial link between pain and learning and suggest that understanding the influence of learning mechanisms in pain modulation could help us understand when and why pain perception is modulated in health and disease.

Neuron Derived Cytokine Interleukin-34 Controls Developmental Microglia Function.

Neuron-microglia interactions dictate the development of neuronal circuits in the brain. However, the factors that support and broadly regulate these processes across developmental stages are largely unknown. Here, we find that IL34, a neuron-derived cytokine, is upregulated in development and plays a critical role in supporting and maintaining neuroprotective, mature microglia in the anterior cingulate cortex (ACC) of mice. We show that IL34 mRNA and protein is upregulated in neurons in the second week of postnatal life and that this increase coincides with increases in microglia number and expression of mature, homeostatic markers, e.g., TMEM119. We also found that IL34 mRNA is higher in more active neurons, and higher in excitatory (compared to inhibitory) neurons. Genetic KO of IL34 prevents the functional maturation of microglia and results in an anxiolytic phenotype in these mice by adulthood. Acute, low dose blocking of IL34 at postnatal day (P)15 in mice decreased microglial TMEM119 expression and increased aberrant microglial phagocytosis of thalamocortical synapses within the ACC. In contrast, viral overexpression of IL34 early in life (P1-P8) caused early maturation of microglia and prevented microglial phagocytosis of thalamocortical synapses during the appropriate neurodevelopmental refinement window. Taken together, these findings establish IL34 as a key regulator of neuron-microglia crosstalk in postnatal brain development, controlling both microglial maturation and synapse engulfment.

Enhancing corrosion resistance of mild steel in hydrochloric acid with Chiquita banana sap extract.

The corrosion of metals is still a huge challenge for various industries, and the pursuit of effective treatments ensures environmental sustainability. In this study, we utilized Chiquita banana sap-water extract (BSWE) to prevent mild steel from electrochemical corrosion in a 0.1 M HCl at room temperature. Corrosion resistance was assessed using various electrochemical methodologies, combining with surface characterization techniques. The results showed a high level of effectiveness when the corrosion current density decreased from 3292.67 µA cm-2 (for the sample immerged in the blank solution) to 187.33 µA cm-2 after 24 hours of immersion in the solution containing BSWE at a 2000 ppm concentration, equivalent to corrosion efficiency of 94.32%. Surface characterization revealed diminished corrosion on the inhibited steel surface due to the formation of a protective layer. X-ray photoelectron spectroscopy results demonstrated the presence of BSWE ingredients combining with iron oxides and hydroxides to form a smooth protective layer. Furthermore, theoretical calculations also indicated that the addition of BSWE can reduce steel surface damage when exposing to corrosive environment. The inhibitor based on banana sap extract can be referred to as a sustainable protective coating since it is biodegradable, abundantly available in banana plants and free of other harmful substances.

Lightweight Biobased Polyurethane Composites Derived from Liquefied Polyol Reinforced by Biomass Sources with High Mechanical Property and Enhanced Fire-Resistance Performance.

Lightweight biobased insulation polyurethane (BPU) composite foams with high fire-resistance efficiency are interested in building effective energy and low environmental impact today. This study focuses on manufacturing lightweight BPU from liquefied bamboo polyols and biomass resources, including rice husk and wood flour. Then, they are combined with three flame retardant (FR) additives, such as aluminum diethyl phosphinate, aluminum trihydroxide, and diammonium phosphate, to improve their fire resistance performance. The physicochemical properties, microstructure, thermal stability, mechanical properties, and flame-retardant properties of the BPU composites are characterized to optimize their compromise properties. The results showed that composites with optimized FRs achieved UL94 V-0 and those with nonoptimized FRs reached UL94 HB. The limiting oxygen index exhibited that the fire resistance of BPU composites could increase up to 21-37% within FR additives. In addition, the thermal stability of BPU composites was significantly improved in a temperature range of 300-700 °C and the compressive strength of the BPU composites was also enhanced with the presence of FRs. The scanning electron microscopy observation showed an influence of FRs on the morphology and cell size of the BPU composites. The bio-PU-derived samples in this study showed significantly low thermal conductivity values, demonstrating their remarkable thermal insulation effectiveness.

Staged Versus Concomitant TAVI and PCI for the Treatment of Coexisting Aortic Stenosis and Coronary Artery Disease.

Aortic stenosis (AS) is one of the most common valvular pathologies. Severe coronary artery disease (CAD) often coexists with AS. Transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) have been established as alternatives to open surgical interventions. The data on the timing for the treatment of the 2 conditions are scarce and depend on multiple factors. This review compares the clinical outcomes of the concomitant versus staged PCI and TAVI for the treatment of AS and CAD. A systematic, electronic search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines to identify relevant articles that compared outcomes of the staged versus concomitant approaches for the TAVI and PCI. Seven studies were included involving 3745 patients. We found no statistically significant difference in primary outcomes such as 30-day mortality [odds ratio (OR) = 0.78; 95% confidence interval (CI): 0.39-1.57] and secondary outcomes including length of hospital stay (mean difference = -4.74, 95% CI: -10.96 to 1.48), new-onset renal failure (OR = 0.83, 95% CI: 0.22-3.13), cerebrovascular accidents (OR = 1.28, 95% CI: 0.64-2.57), and intraoperative blood loss (OR = 0.83, 95% CI: 0.32-2.12). New pacemaker insertion was statistically significant in favor of the concomitant approach (OR = 0.78, 95% CI: 0.63-0.96). This analysis suggests that while the 2 approaches are largely comparable in terms of most outcomes, patients at risk of requiring a pacemaker postprocedure may benefit from a concomitant approach. In conclusion, concomitant TAVI + PCI approach is nonsuperior to the staged approach for the treatment of CAD and AS. This review calls for robust trials in the field to further strengthen the evidence.

Detection of focal to bilateral tonic-clonic seizures using a connected shirt.

OBJECTIVE: This study was undertaken to develop and evaluate a machine learning-based algorithm for the detection of focal to bilateral tonic-clonic seizures (FBTCS) using a novel multimodal connected shirt. METHODS: We prospectively recruited patients with epilepsy admitted to our epilepsy monitoring unit and asked them to wear the connected shirt while under simultaneous video-electroencephalographic monitoring. Electrocardiographic (ECG) and accelerometric (ACC) signals recorded with the connected shirt were used for the development of the seizure detection algorithm. First, we used a sliding window to extract linear and nonlinear features from both ECG and ACC signals. Then, we trained an extreme gradient boosting algorithm (XGBoost) to detect FBTCS according to seizure onset and offset annotated by three board-certified epileptologists. Finally, we applied a postprocessing step to regularize the classification output. A patientwise nested cross-validation was implemented to evaluate the performances in terms of sensitivity, false alarm rate (FAR), time in false warning (TiW), detection latency, and receiver operating characteristic area under the curve (ROC-AUC). RESULTS: We recorded 66 FBTCS from 42 patients who wore the connected shirt for a total of 8067 continuous hours. The XGBoost algorithm reached a sensitivity of 84.8% (56/66 seizures), with a median FAR of .55/24 h and a median TiW of 10 s/alarm. ROC-AUC was .90 (95% confidence interval = .88-.91). Median detection latency from the time of progression to the bilateral tonic-clonic phase was 25.5 s. SIGNIFICANCE: The novel connected shirt allowed accurate detection of FBTCS with a low false alarm rate in a hospital setting. Prospective studies in a residential setting with a real-time and online seizure detection algorithm are required to validate the performance and usability of this device.

Feasibility of middle colic artery as a landmark for superior mesenteric artery - first approach in laparoscopic pancreatoduodenectomy: a prospective study.

BACKGROUND: SMA-first approach in pancreatoduodenectomy (PD) has been widely applied in open surgery as well as laparoscopy. Finding the superior mesenteric artery (SMA), inferior pancreatoduodenal artery (IPDA), first jejunal artery (J1A) has become a great challenge in laparoscopic PD (LPD). Meanwhile, exposing the midde colic artery (MCA) might be a feasible approach to determine SMA, IPDA, and J1A. Our study aims to find the anatomical correlation between MCA and SMA, IPDA, J1A, especially in SMA-first approach LPD from the left. METHODS: Uncontrolled clinical trial with 33 patients undergoing LPD had preoperative contrast abdominal CT scan to analyze the anatomical relevance between MCA and SMA, J1A, IPDA. The operation was performed starting with exposing MCA in advance to find SMA, J1A and IPDA. The data was analyzed by SPSS 25.0. RESULTS: 90.9% of MCA started at 12-3 o'clock from SMA, the mean distance from the SMA root to the MCA and J1A was 56.4 mm and 37.4 mm, respectively. The distance between SMA and J1A was 19 mm. 72.7% J1A started at 9-12 o'clock, 69.7% J1A and IPDA had a common trunk. 78.8% IPDA started at 3-6 o'clock. 100% of the cases had J1A controlled intraoperatively, 81.8% for IPDA when approached from the left, 3% had MCA injury. The mean time to approach from the left was 98 min, median blood loss was 100 ml. CONCLUSION: Exposing MCA first helps determine SMA, J1A and IPDA safely, efficiently and faciliates SMA-first approach LPD from the left and complete dissection of the mesopancreas and lymph nodes.

Measuring Vision at Home in 2023.

Introduction: The ability to measure a patient's visual acuity at home (HVA) is by far the most desired remote telemedicine capability sought by ophthalmologists. Methods: A systematic literature review was done using Pubmed to search for publications from 2010 to 2022 in English reporting on 10 studies that compared a patient's HVA to the clinic visual acuity (CVA). Results: Approaches to measuring HVA included using a phone-based application, a physical chart, a computer, and a website. The most accurate of these was the use of personal computers (COMPlog, Macustat, Web based test) at home with a bias of 1 letter. The most accessible and reliable was the use of a printable visual acuity chart, available in the public domain, which had adifference between HVA and CVA of 1 to 3.5 letters. Phone apps (Verana Vision) and stand-alone websites (Farsight.com) both had a greater mean difference of about 6 letters, respectively,with a moderate correlation coefficient. Discussion: Overall, all three methodologies demonstrated a good negative predictive value demonstrating their potential use as an effective screening tool to flag drastic vision decline between clinic visits.

HLA alleles associated with susceptibility and severity of the COVID-19 in Vietnamese.

The diversity of clinical manifestations in COVID-19 has been observed not only among individuals but also among various populations in globally. HLA molecules play a central role in physiology, protective immunity, and deleterious, disease-related autoimmune reactivity or overreaction. This study exploited the association between HLA frequencies and SARS-CoV-2 susceptibility and disease severity among the Vietnamese cohort (159 patients and 52 controls). A significant difference in frequency of both HLA class I and II in mild, moderate, and severe/fatal COVID-19 patients and negative exposure individuals - the controls were observed. Regarding SARS-CoV-2 sensitivity, HLA-A*03:01, 30:01, HLA-DQA1*01:02, DRB1*15:01, and DRB5*02:02 presented higher frequency in the control group compared with infected patients but DRB1 09:01 frequency was higher in infected patients. Regarding COVID-19 severity, HLA-F*01:01, 01:03 and DPA1*01:03 and 02:01, DPB1*04:01, DQA1*01:02, and DQB1*05:02 alleles were detected with higher frequency in severe patients but DOB*01:01, DRB1*05:01 and 09:01 had a significantly higher frequency in the mild group than remaining groups. Surprisingly, HLA-DQA1*01:02 and DRB1*09:01 alleles were identified with both inversely potential roles in protective function and severe risk. The obtained data herein will contribute to explore on the role of host genetic background in the pathology of COVID-19 disease.

Concentration of voxelotor in sickle cell disease can be estimated using electrophoresis and high-performance liquid chromatography.

OBJECTIVES: Voxelotor can increase hemoglobin levels in patients living with sickle cell disease (SCD). A clinician who is monitoring voxelotor response may want to know whole-blood voxelotor concentration, but this cannot be measured in most clinical settings. However, voxelotor has been demonstrated to cause "peak splitting" in common methods of hemoglobin measurement such as capillary zone electrophoresis (CZE) and high-performance liquid chromatography (HPLC). We hypothesized that we could use the size of the peak split to estimate the whole-blood concentration. METHODS: Blood from people with SCD was dosed with known concentrations of voxelotor, and multiparameter regression was used to derive the relationship of voxelotor concentration to the degree of peak splitting observed. To validate these equations, 21 patients started on voxelotor at 1500 mg/d had blood samples drawn at days 0, 14, 30, and 60. Samples were sent out for gold standard voxelotor concentration testing. The derived equations were then used to calculate voxelotor concentration. RESULTS: Calculated concentrations correlated strongly with measured concentrations for both CZE (R2 = 0.83, P < .001) and HPLC (R2 = 0.76, P < .001). Voxelotor concentration also had a significant effect on increases in hemoglobin (R2 = 0.40, P < .001). CONCLUSIONS: Thus, peak splitting CZE and HPLC can be used to estimate voxelotor concentration.

Transcatheter Edge-to-Edge Mitral Valve Repair in a Patient With Anderson-Fabry Disease.

Severe degenerative mitral regurgitation (DMR) is one cardiac manifestation of the multiorgan metabolic enzyme disorder Anderson-Fabry Disease (AFD). Although DMR is normally managed surgically, many patients with AFD are unsuitable for this. We present the first case of mitral transcatheter edge-to-edge repair in a patient with AFD.