Recurrent acute myocardial and renal infarction with aplastic anaemia/paroxysmal nocturnal haemoglobinuria syndrome: a case report.

Background: Aplastic anaemia (AA) is known to progress to paroxysmal nocturnal haemoglobinuria (PNH) during treatment, and thrombosis is a characteristic symptom of PNH. This case report investigates a case of repeated and rapidly progressive multiple arterial thrombosis due to PNH. Case Summary: This case is a 24-year-old woman undergoing treatment for AA. She presented with chest pain and underwent emergency coronary angiography. Thrombus occlusion was found in the distal portion of the right coronary artery, acute myocardial infarction was diagnosed and percutaneous coronary intervention was performed. Thrombus aspiration and balloon dilation were performed. Anticoagulants were administered, but chest pain flared up again on Day 9; coronary angiography was performed, indicating that the proximal portion of the right coronary artery had caused occlusion. On Days 9 and 24, she experienced back pain and was diagnosed with renal infarction. Considering that AA had evolved into PNH and intravascular haemolysis and thrombosis appeared, the diagnosis of PNH was made via flow cytometry. Multiple arterial thrombosis due to PNH was diagnosed, and ravulizumab treatment was started, resulting in the improvement of thrombus progression, chest pain, and back pain. Discussion: Thrombosis due to PNH can recur even after the administration of anticoagulants and antiplatelet agents and has been associated with a high fatality rate. The treatment with ravulizumab, a humanized monoclonal antibody against complement C5, helps with the prevention of thrombosis. Furthermore, anti-complement component C5 therapy is very effective in improving rapidly progressive multiple arterial thrombosis resistant to anticoagulants and antiplatelet agents due to PNH.

Brain Functional Alterations in Patients With Benign Paroxysmal Positional Vertigo Demonstrate the Visual-Vestibular Interaction and Integration.

OBJECTIVE: This study aimed to analyze the features of resting-state functional magnetic resonance imaging (rs-fMRI) and clinical relevance in patients with benign paroxysmal positional vertigo (BPPV) that have undergone repositioning maneuvers. METHODS: A total of 38 patients with BPPV who have received repositioning maneuvers and 38 matched healthy controls (HCs) were enrolled in the present study from March 2018 to August 2021. Imaging analysis software was employed for functional image preprocessing and indicator calculation, mainly including the amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), percent amplitude of fluctuation (PerAF), and seed-based functional connectivity (FC). Statistical analysis of the various functional indicators in patients with BPPV and HCs was also conducted, and correlation analysis with clinical data was performed. RESULTS: Patients with BPPV displayed decrease in ALFF, fALFF, and PerAF values, mainly in the bilateral occipital lobes in comparison with HCs. Additionally, their ALFF and fALFF values in the proximal vermis region of the cerebellum increased relative to HCs. The PerAF values in the bilateral paracentral lobules, the right supplementary motor area (SMA), and the left precuneus decreased in patients with BPPV and were negatively correlated with dizziness visual analog scale (VAS) scores 1 week after repositioning (W1). In addition, in the left fusiform gyrus and lingual gyrus, the PerAF values show a negative correlation with dizziness handicap inventory (DHI) scores at initial visit (W0). Seed-based FC analysis using the seeds from differential clusters of fALFF, ALFF, and PerAF showed reductions between the left precuneus and bilateral occipital lobe, the left precuneus and left paracentral lobule, and within the occipital lobes among patients with BPPV. CONCLUSION: The spontaneous activity of certain brain regions in the bilateral occipital and frontoparietal lobes of patients with BPPV was reduced, whereas the activity in the cerebellar vermis was increased. Additionally, there were reductions in FC between the precuneus and occipital cortex or paracentral lobule, as well as within the occipital cortex. The functional alterations in these brain regions may be associated with the inhibitory interaction and functional integration of visual, vestibular, and sensorimotor systems. The functional alterations observed in the visual cortex and precuneus may represent adaptive responses associated with residual dizziness.

Synergistic Integration of Traditional Chinese Medicine and Western Medical Intervention in the Treatment of Brain Abscess: A Case Report.

Brain abscess is life-threatening and carries a high risk of mortality. Despite advances in sensitive imaging techniques, effective antimicrobial therapies, and sophisticated surgical procedures, diagnosing and treating brain abscesses remains challenging. Although empirical antimicrobial therapy and neurosurgery are considered primary treatments for brain abscesses, their efficacy is limited by potential side effects including neutropenia development, the need for repeat surgeries, and the risk of new-onset epilepsy. Here, we present a case of a 52-year-old male patient who experienced paroxysmal convulsions accompanied by left-sided limb weakness and numbness for over 2 months. Despite a brain MRI revealing a multilocular cystic lesion in the right frontal lobe, with about 28 mm × 19 mm × 21 mm in size, the patient declined neurosurgical interventions. After completing a 6-week course of antimicrobial therapy, the patient sought traditional Chinese medicine (TCM) treatment. As a result, the patient remained free of paroxysmal convulsions for about 60 days after a 4-month TCM treatment. A follow-up MRI imaging at 8 months showed a reduction in the size of the lesion in the right frontal lobe to 8 mm × 4 mm. To the best of our knowledge, this is the first well-documented case of a brain abscess that was successfully managed with a combination of antimicrobial therapy and TCM. This case report suggests that TCM may provide significant supplementary benefits in managing infections like brain abscesses. However, further evidence from prospective studies is necessary to substantiate the efficacy of Chinese herbal medicine for the treatment of brain abscesses.

Heterozygous KCNJ10 Variants Affecting Kir4.1 Channel Cause Paroxysmal Kinesigenic Dyskinesia.

BACKGROUND: More than 60% of paroxysmal kinesigenic dyskinesia (PKD) cases are of uncertain variants. OBJECTIVE: The aim was to elucidate novel genetic contribution to PKD. METHODS: A total of 476 probands with uncertain genetic causes were enrolled for whole-exome sequencing. A method of case-control analysis was applied to identify the candidate genes. Whole-cell patch-clamp recording was applied to verify the electrophysiological impact of the identified variants. A mouse model with cerebellar heterozygous knockout of the candidate gene was developed via adeno-associated virus injection, and dystonia-like phenotype inducement and rotarod tests were performed. In vivo multiunit electrical recording was applied to investigate the change in neural excitability in knockout mice. RESULTS: Heterozygous variants of potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) clustered in PKD patients were compared with those in the control groups. Fifteen variants were detected in 16 of 522 probands (frequency = 3.07%). Patients with KCNJ10 variants tended to have a milder manifestation compared to those with PRRT2 (proline-rich transmembrane protein 2) variants. KCNJ10 variants partially altered the transmembrane location of inwardly rectifying potassium channel 4.1 (Kir4.1). The Kcnj10 expression is consistent with the natural course of PKD. Variants resulted in different degrees of reduction in cell Kir4.1 currents, and mice with heterozygous conditional knockout of Kcnj10 in the cerebellum presented dystonic posture, together with poor motor coordination and motor learning ability in rotarod tests. The firing rate of deep cerebellar nuclei was significantly elevated in Kcnj10-cKO mice. CONCLUSION: We identified heterozygous variants of KCNJ10 in PKD. Impaired function of Kir4.1 might lead to abnormal neuronal excitability, which attributed to PKD. © 2024 International Parkinson and Movement Disorder Society.

Classification of underlying paroxysmal supraventricular tachycardia types using deep learning of sinus rhythm electrocardiograms.

Background: Obtaining tachycardia electrocardiograms (ECGs) in patients with paroxysmal supraventricular tachycardia (PSVT) is often challenging. Sinus rhythm ECGs are of limited predictive value for PSVT types in patients without preexcitation. This study aimed to explore the classification of atrioventricular nodal reentry tachycardia (AVNRT) and concealed atrioventricular reentry tachycardia (AVRT) using sinus rhythm ECGs through deep learning. Methods: This retrospective study included patients diagnosed with either AVNRT or concealed AVRT, validated through electrophysiological studies. A modified ResNet-34 deep learning model, pre-trained on a public ECG database, was employed to classify sinus rhythm ECGs with underlying AVNRT or concealed AVRT. Various configurations were compared using ten-fold cross-validation on the training set, and the best-performing configuration was tested on the hold-out test set. Results: The study analyzed 833 patients with AVNRT and 346 with concealed AVRT. Among ECG features, the corrected QT intervals exhibited the highest area under the receiver operating characteristic curve (AUROC) of 0.602. The performance of the deep learning model significantly improved after pre-training, showing an AUROC of 0.726 compared to 0.668 without pre-training (p < 0.001). No significant difference was found in AUROC between 12-lead and precordial 6-lead ECGs (p = 0.265). On the test set, deep learning achieved modest performance in differentiating the two types of arrhythmias, with an AUROC of 0.708, an AUPRC of 0.875, an F1-score of 0.750, a sensitivity of 0.670, and a specificity of 0.649. Conclusion: The deep-learning classification of AVNRT and concealed AVRT using sinus rhythm ECGs is feasible, indicating potential for aiding in the non-invasive diagnosis of these arrhythmias.

Clinical features between paroxysmal and nonparoxysmal atrial fibrillation: a comparative analysis in eastern China.

BACKGROUND: Atrial fibrillation (AF) has emerged as a notable public health issue in China due to the aging population and rapid urbanization. This study aimed to describe the characteristics of patients with AF (paroxysmal and nonparoxysmal) and investigate the association between left ventricular ejection fraction (LVEF) levels and AF subtypes to facilitate early prevention in patients with AF. METHOD: Patients with AF who presented at the cardiology department of the First People's Hospital of Yancheng were recruited in this study. In univariate and multivariate logistic regression analyses, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the relationships between each dependent variable and nonparoxysmal AF. The restricted cubic splines (RCS) curve was employed to explore the linear relationship between LVEF and nonparoxysmal AF on a continuous scale. Subgroup analysis was applied to examine the stability of the results. RESULTS: The study included a total of 2054 patients who were diagnosed with AF. 652 (31.74%) patients had paroxysmal AF, and 1402 (68.26%) had nonparoxysmal AF. Multivariate logistic regression analyses indicated that compared to those with paroxysmal AF, patients with nonparoxysmal AF tended to have a higher prevalence of coronary artery disease, lower levels of LVEF, and an elevated heart rate. Additionally, RCS curves also showed that LVEF was negatively and linearly associated with the nonparoxysmal AF. Furthermore, the association between LVEF and nonparoxysmal AF was stronger among patients with hypertension and obesity (P for interaction < 0.05). CONCLUSIONS: Patients with nonparoxysmal AF have a more advanced AF burden and the transition from paroxysmal to nonparoxysmal AF should be recognized in time, especially to treat the corresponding comorbidities (including hypertension and obesity) more consistently.

Epley's Manoeuvre vs. Semont's Maneuver in Post-Canal Benign Paroxysmal Positional Vertigo: A Comparative Study in a Tertiary Centre.

Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder characterized by brief episodes of vertigo triggered by changes in head position. Epley's manoeuvre and Semont's manoeuvre are widely used canalith repositioning procedures for the treatment of BPPV. This study aimed to compare the effectiveness of these two manoeuvres in treating post-canal BPPV in a cohort of 100 patients. METHODS: This was a prospective, comparative study conducted at a tertiary care hospital. One hundred patients diagnosed with post-canal BPPV were randomized into two groups: Group A (n = 50) underwent the Epley's manoeuvre, and Group B (n = 50) underwent the Semont's manoeuvre. The patients were assessed for the resolution of vertigo and nystagmus immediately after the manoeuvre and at a follow-up visit one week later. The resolution of symptoms was confirmed through Dix-Hallpike test. RESULTS: In Group A, 46 patients (92%) reported complete resolution of vertigo immediately after Epley's manoeuvre, and 47 patients (94%) had no nystagmus on the Dix-Hallpike test at the one-week follow-up. In Group B, 42 patients (84%) reported complete resolution of vertigo immediately after Semont's manoeuvre, and 44 patients (88%) had no nystagmus on the DH test at the one-week follow-up. The difference in effectiveness between the two manoeuvres was not statistically significant (p > 0.05). CONCLUSION: Both Epley's manoeuvre and Semont's manoeuvre are effective in treating post-canal BPPV, with similar success rates. The choice of manoeuvre may depend on patient preference, clinician expertise, and other individual factors. Further studies with larger sample sizes are warranted to validate these findings and explore other potential factors influencing the outcomes of canalith repositioning manoeuvres in BPPV.

Quality of Life Evaluation in Patients with Paroxysmal Atrial Fibrillation.

BACKGROUND: To estimate quality of life (QoL) in patients with paroxysmal atrial fibrillation (AF) using the SF-36 Health Status Survey. MATERIALS AND METHODS: In a single-center study involving 6,630 patients, we defined a group of 97 patients having an incidental finding of atrial fibrillation (AF). The control group included 99 patients from the same primary cohort, but without paroxysmal AF. The two study groups matched closely in anthropometric parameters and comorbidity. All patients underwent standard laboratory and instrumental research methods. In the primary visit, at the time of AF detection, we evaluated the patients QoL using the classical SF-36 Health Status Survey. At the second visit (6±0.5 months follow-up) and third visit (12±0.5 months follow-up), we re-evaluated the QoL using the SF-36 Health Status Survey. RESULTS: The absolute majority (95/97; 98%) of patients of the main group had a special variant of extrasystoles, namely the early atrial "P on T" type (versus 4.0% incidence in the control group) [OR 846 (382;187,000)]. The main group showed a significantly greater frequency of supraventricular extrasystoles. At the 1st visit, there was no group differences in QoL scores between the main and control groups (p>0.05). However, at 6 and 12 months follow-up, metrics of physical and mental health differed significantly between groups stratified by low and high QoL (p<0.05). The asymptomatic patients with paroxysmal AF and high compliance in oral anticoagulant therapy showed higher physical activity and social functioning. CONCLUSIONS: Paroxysmal AF in asymptomatic patients is a predictor for declining QoL during 12 months follow-up in patients with cardiovascular pathology. The paroxysmal AF patients who had high compliance of oral anticoagulant therapy proved to have improved physical activity and social functioning.

Utility of smart watch in expediting diagnosis of cold drink-triggered atrial fibrillation: a case report.

BACKGROUND: Patients presenting to the emergency department with recent palpitations are a diagnostic challenge when the arrhythmia and its symptoms have resolved prior to arrival. Newer smart watch technology, adept at detecting atrial fibrillation, can assist in the diagnostic evaluation of transitory palpitations. We report a case of cold drink-triggered atrial fibrillation whose diagnosis would not have been possible without the assistance of the patient's smart watch. CASE PRESENTATION: A middle-aged man without cardiac history developed sudden rapid, irregular palpitations with shortness of breath while drinking a glass of cold juice. He activated his smart watch with 1-lead electrocardiography technology which detected rapid atrial fibrillation. He sought medical care, but while waiting, his symptoms-then 90 min in duration-spontaneously resolved. His initial diagnostic evaluation documented only sinus rhythm, as did several follow-up evaluations with cardiology the next several weeks. Had it not been for his smart watch, the etiology of his transitory palpitations would have remained undiagnosed. His physicians encouraged trigger avoidance. In the following months, he avoided rapid ingestion of cold drink, taking instead small sips. The atrial fibrillation has not recurred. CONCLUSIONS: The case illustrates the valuable contribution of smart watch technology in the diagnostic evaluation of patients with short-lived palpitations. The case also educates clinicians about cold drink and food as a trigger of paroxysmal atrial fibrillation. This trigger, like alcohol, can be modified. Cold drink trigger avoidance has been reported by patients to reduce atrial fibrillation recurrence and is a low-risk, cost-effective strategy that is often successful.

Fatal Neutropenic Enterocolitis in a Young Female After the First Round of Eculizumab for Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder characterized by glycosylphosphatidylinositol (GPI)-linked membrane protein deficiency, leading to hemolytic anemia and thrombosis. A subset of patients develop severe neutropenia, predisposing them to neutropenic enterocolitis (NEC). We present a case of fatal NEC following eculizumab therapy in a 31-year-old female with PNH. She presented with abdominal pain, fever, and neutropenia post-eculizumab. Despite aggressive management, including antibiotics and supportive care, she developed septic shock complicated by bacteremia, multiorgan failure, and two episodes of cardiac arrest, leading to severe lactic acidosis and ultimately progressing to brain death. The etiology of NEC in PNH patients remains multifactorial, involving immunocompromised and treatment-related factors. This case underscores the challenges in managing NEC and highlights the importance of early recognition and intervention in high-risk patients.

New- and early-onset benign paroxysmal positional vertigo after otologic surgery.

PURPOSE: To determine the frequency and clinical features of new- and early-onset benign paroxysmal positional vertigo (BPPV) after different otologic surgical operations with and without surgical drilling. METHODS: All unilateral otologic operations performed at the otolaryngology clinic of a tertiary university hospital between January 2021 and May 2023 were screened, and 437 adult cases were included in the study. Of these patients, those who were diagnosed with BPPV within the first month postoperatively were examined. RESULTS: The overall incidence of BPPV after otologic operations was 2.28% (10 out of 437 patients). This incidence was 3% (8/266 patients) in cases where a drill was used and 1.16% (2/171 patients) in those where a drill was not used. There was no significant difference between the two groups (p > 0.05). Clinical symptoms related to BPPV appeared on average in 13.3 ± 6.8 (range: 3-25) days following surgery and presented as canalolithiasis. All cases involved the posterior semicircular canal (SCC) on the operated side. In addition, one patient with a cochlear implant had involvement of both the posterior and lateral SCCs. All patients responded well to repositioning maneuvers during follow-up. CONCLUSION: Otologic surgery, especially operations involving drilling, is a potential risk factor for the development of BPPV. Postoperative BPPV, primarily presenting as canalolithiasis in the posterior SCC on the operated side, can be effectively managed with repositioning maneuvers. Clinicians should be vigilant for BPPV in patients experiencing vertigo/dizziness within four weeks following otologic surgery.

Gray matter structural alterations of cortico-striato-thalamo-cortical loop in familial Paroxysmal Kinesigenic Dyskinesia.

Background: Previous studies have indicated that patients with Paroxysmal Kinesigenic Dyskinesia (PKD) exhibit reduced gray matter volume in certain brain regions within the cortico-striato-thalamo-cortical (CSTC) loop. However, a comprehensive investigation specifically targeting the CSTC loop in PKD has never been conducted. Objectives: To provide evidence for the involvement of the CSTC loop in the pathogenesis of PKD from the perspective of structural alterations, this study carried out a surface-based morphometry (SBM), voxel-based morphometry (VBM), and structural covariance networks (SCN) combined analysis in familial PKD patients. Methods: A total of 8 familial PKD patients and 10 healthy family members were included in the study and underwent Brain MRI examinations. Based on 3D T1 MPRAGE data, neuroimaging metrics of cortical thickness from SBM, subcortical nuclei volume from VBM, and covariance coefficient from SCN were used to systematically investigate the brain structural alterations along the CSTC loop of PKD patients. Results: A significant decrease in the average cortical thickness of the left S1 region in the PKD group was observed. The volumes of subcortical nuclei, including the thalamus, putamen, and globus pallidus were reduced, with a pronounced effect observed in the bilateral putamen. And the structural covariance connection between the left putamen and the left globus pallidus was significantly strengthened. Conclusions: The study confirms the involvement of the CSTC loop in the pathogenesis of PKD from the perspective of structural alterations, and the findings may provide potential targets for objective diagnosis and therapeutic monitoring of PKD.

Clinical characteristics and management of paroxysmal nocturnal haemoglobinuria in Latin America: a narrative review.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, complement-associated, haematological disorder. The level of knowledge about the disease and its management varies around the world. This narrative review provides an overview of available clinical data on PNH in Latin America (LATAM). A search of the PubMed, EMBASE and LILACS/IBECS databases to February 2023, and addition of author-known articles, yielded 24 relevant published articles, the majority (n = 15) from Brazil. Fourteen articles were full papers; 10 were conference abstracts. The prevalence of PNH in Brazil is estimated at 1:237,000 inhabitants. Among blood samples sent for flow cytometry screening for suspected PNH in Brazil and Colombia, 14 - 30% were positive. There is suggestion that disease subtypes may differ among LATAM populations, with classical PNH more common in Brazilian patients and PNH with aplastic anaemia more common in Mexican patients. Median age at diagnosis of PNH ranged from 24 to 41 years. Common symptoms included fatigue, haemoglobinuria, and abdominal pain, although the symptom profile varied by subtype. Three available studies indicated that eculizumab was effective at reducing haemolysis, improving anaemia, and reducing the risk of thrombosis in patients with PNH with intravascular haemolysis. A consensus document from the Brazilian Association of Hematology, Hemotherapy and Cell Therapy RBC and Iron Committee provides guidance on identifying and managing PNH patients, including appropriate selection of patients for eculizumab. Additional data on the epidemiology, natural history and outcomes of patients with PNH in LATAM countries are needed to better understand the disease and its management throughout the region.

One Haemolytic Anaemia May Hide Another: Paroxysmal Nocturnal Haemoglobinuria Masquerading As Plasmodium Falciparum Infection.

Background: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, genetic and acquired haematologic disease that causes complement-mediated intravascular haemolytic anaemia, thrombosis and bone marrow failure. Case description: A 27-year-old migrant patient attended the emergency department in a context of fever and chills over the previous few days as well as chronic fatigue, dyspnoea and chest pain. His medical history included chronic anaemia and erectile dysfunction. Initial biology showed a haemoglobin of 6.3 g/dl, platelets of 25,000/µl, total leucocytes of 3,500/µl with 1,500 neutrophils. B12 vitamin, folic acid, ferritin and thyroid stimulating hormone were normal. Lactate dehydrogenase levels were high and haptoglobin was non-measurable. C-reactive protein was 46.1 mg/l. A thick blood smear revealed Plasmodium falciparum infection with 0.1% parasitaemia. The patient was treated with an oral combination of artemether and lumefantrine. Three weeks later, the patient consulted the infectious disease department given the lack of clinical improvement. The cytopenias worsened, and lactate dehydrogenase (LDH) and reticulocytes increased. Tests for schistocytes, a thick blood smear for malaria and a direct Coombs test were negative; a myelogram was reassuring. An abdominal, pelvic and thoracic CT scan showed a mild hepatomegaly with no focal lesion and no splenomegaly or adenomegaly. A 12-colour flow cytometry unveiled a PNH clone on 90.9545% of neutrophils and 80.7371% of monocytes. Discussion: PNH patients can be vulnerable to parasites infection (such as P. falciparum) as it may trigger breakthrough haemolysis through uncontrolled resurgence of activity of the complement system. In our patient, P. falciparum infection was a confounding factor, as it commonly causes haemolytic anaemia and thrombocytopenia, and patients living in malaria-endemic regions can carry low parasitaemia while being slightly symptomatic or asymptomatic. LEARNING POINTS: Plasmodium falciparum infection can cause breakthrough haemolysis in patients with paroxysmal nocturnal haemoglobinuria.Low P. falciparum parasitemia in patients living in malaria-endemic regions is not always significant as these patients often carry acquired immunity.Patients from malaria-endemic regions presenting with severe sickness and low P. falciparum parasitemia must be assessed for other diseases, as it cannot explain heavy illness.Patients presenting with haemolytic anaemia, no schistocytes, a negative direct Coombs test and other unexplained cytopenia such as thrombocytopenia/neutropenia and other unexplained clinical manifestations such as dyspnoea, chest pain or erectile dysfunction should be assessed for paroxysmal nocturnal haemoglobinuria.

Effectiveness and safety of Liriope Tuber (Liriopis seu Ophiopogonis Tuber, Maidong) included traditional herbal medicine for patients with paroxysmal atrial fibrillation: A systematic review, meta-analysis, and network analysis.

Background: Conventional medicine (CM) for paroxysmal atrial fibrillation (PAF) have limitations and side effects. Integrative approaches, including traditional herbal medicines like Liriope Tuber, are being explored for potential benefits, although evidence remains limited. Methods: In April 2023, a literature search was conducted across nine databases, focusing on randomized controlled trials assessing the effects of Liriope Tuber in traditional herbal medicine (LTHM) on PAF. The risk of bias was evaluated using Version 2 of the Cochrane risk-of-bias tool for randomized trials. A random-effects model was employed for the meta-analysis. Results: A total of 43 studies with 3,743 participants were included. The meta-analysis indicated that adding LTHM to CM reduced PAF frequency (SMD = -0.99, 95 % CI = -1.40 to -0.57, I² = 88 %, N = 16, n = 1266), left atrium diameter (LAD) (MD = -2.39 mm, 95 % CI = -3.09 to -1.68), P-wave dispersion (Pd) (MD = -6.41 ms, 95 % CI = -8.44 to -4.37), high sensitive C-Reactive Protein (hs-CRP) (MD = -1.10 mg/l, 95 % CI = -1.73 to -0.47), and improved left ventricular ejection fraction (LVEF) (MD = 4.71 %, 95 % CI = 3.17 to 6.25). Thirty-four studies raised concerns about bias, with eight showing high risk. Certainty of evidence was rated as "low" for PAF frequency, LAD, Pd, hs-CRP, and LVEF. Conclusion: LTHM combined with CM may reduce PAF frequency. However, due to the complexity of interventions, with Liriope Tuber being only one component of the regimen, high risk of bias, substantial heterogeneity, and indirectness, interpretations should be cautious. Study registration: PROSPERO (ID: CRD42023477926).

Doxophylline With Paroxysmal Supraventricular Tachycardia: A Case Report.

Purpose: We report a case of a patient experiencing paroxysmal supraventricular tachycardia after infusing doxophylline. Methods: Clinical evaluations and the electrocardiogram were performed by specialists. Findings: Our patient felt palpitations and chest distress after intravenous Doxophylline. The electrocardiogram showed paroxysmal supraventricular tachycardia. There was no evidence to prove that there was any problem with his heart, liver, and kidney. According to the Naranjo Adverse Drug Reaction probability scale, paroxysmal supraventricular tachycardia has a probable relationship with Doxophylline. Implications: The paroxysmal supraventricular tachycardia is a rare but reasonable adverse reaction of Doxophylline, which should be paid more attention.

Iptacopan Efficacy and Safety to Treat Paroxysmal Nocturnal Hemoglobinuria (PNH): A Systematic Review and Meta-Analysis.

Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon blood condition caused by complement-mediated hemolysis. In early clinical studies, iptacopan, an oral factor B inhibitor, showed promise in treating PNH. This systematic review aimed to compile information on the effectiveness and safety of iptacopan for PNH. A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. The Medline, Embase, PubMed, and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies that evaluated iptacopan for PNH. The primary efficacy outcomes were hemoglobin and lactate dehydrogenase (LDH) changes. A fixed-effects model was used for the meta-analysis. Six studies (three prospective cohorts, two RCTs, and one non-randomized trial) were included, comprising 197 patients. Iptacopan therapy significantly increased hemoglobin levels (mean differences (MD) = 12.98 g/L; 95% CI: 11.82-14.13; p < 0.0001) and decreased LDH (MD = -83.55 IU/L; 95% CI: -83.77 to -83.34; p < 0.0001). Subgroup analyses revealed more significant hemoglobin increases in European vs. Asian populations, studies with baseline Hb > 10 g/dL vs. < 10 g/dL, and studies lasting > 24 weeks vs. ≤ 24 weeks. LDH decreases were more pronounced in studies with baseline LDH > 500 IU/L vs. < 500 IU/L. The incidence of adverse events ranged from 66% to 90%, with the most common being headache, nasopharyngitis, and diarrhea. Serious adverse events occurred in 0-20% of patients across studies. Only one patient withdrew because adverse effects were reported across all studies. Preliminary data support iptacopan's effectiveness in improving hemoglobin levels and lowering hemolysis in PNH, both as a monotherapy and in combination with usual treatment. The safety profile appears to be excellent, with a minimal incidence of major adverse events and treatment discontinuation. Further studies are needed to validate the effectiveness and safety of larger, longer-term trials. Iptacopan is a viable oral therapy option for PNH.

Navigating the Complement Pathway to Optimize PNH Treatment with Pegcetacoplan and Other Currently Approved Complement Inhibitors.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and potentially life-threatening hematologic disorder caused by a somatic mutation in a relevant portion of hematopoietic stem cells. Mutation of the phosphatidylinositol glycan biosynthesis class A (PIGA) gene prevents the expression of cell-surface proteins, including the complement regulatory proteins CD55 and CD59. With decreased or a lack of CD55 and CD59 expression on their membranes, PNH red blood cells become susceptible to complement-mediated hemolysis (symptoms of which include anemia, dysphagia, abdominal pain, and fatigue), leading to thrombosis. State-of-the-art PNH treatments act by inhibiting the dysregulated complement at distinct points in the activation pathway: late at the C5 level (C5 inhibitors, eculizumab, ravulizumab, and crovalimab), centrally at the C3 level (C3/C3b inhibitors and pegcetacoplan), and early at the initiation and amplification of the alternative pathway (factor B inhibitor, iptacopan; factor D inhibitor, danicopan). Through their differing mechanisms of action, these treatments elicit varying profiles of disease control and offer valuable insights into the molecular underpinnings of PNH. This narrative review provides an overview of the mechanisms of action of the six complement inhibitors currently approved for PNH, with a focus on the C3/C3b-targeted therapy, pegcetacoplan.

[Contribution of the Ibero-American Academy of Neuropediatrics to the knowledge of self-limited epilepsy in infants]. / Aporte de la Academia Iberoamericana de Neuropediatría al conocimiento de la epilepsia autolimitada del lactante.

Since the first presentation at the IV Iberoamerican Academy of Neuropediatrics Congress in 1995, our group has studied self-limited infantile epilepsy (SeLIE), both familial and non-familial, corroborating that they belong to the same entity due to their clinical and electroencephalographic characteristics and excellent prognosis. Associations were found with paroxysmal dyskinesias and migraine, as well as with hemiplegic migraine, episodic ataxia and intellectual disability in atypical cases. Mutations in PRRT2 are the main cause of SeLIE, however, other genes, such as SCN2A, KCNQ2-3 and SCN8A, have been recognized. Drugs for focal seizures that act on sodium channels are indicated. In emergencies, during cluster seizures, the use of benzodiazepines is important. In this publication, we review our contribution in SeLIE from our first report to the present and review the existing literature on the subject.

Desde la primera presentación en el IV Congreso de la Academia Iberoamericana de Neurología Pediátrica en 1995, nuestro grupo ha estudiado las epilepsias autolimitadas del lactante (EAL), tanto familiares y no familiares, corroborando que pertenecen a una misma entidad por sus características clínicas, electroencefalográficas y excelente pronóstico. Se encontraron asociaciones con discinesias paroxísticas y migraña, como también con la migraña hemipléjica, la ataxia episódica y la discapacidad intelectual en casos atípicas. Las mutaciones en PRRT2 son la principal causa de EAL. Sin embargo, otros genes, como SCN2A, KCNQ2-3 y SCN8A, han sido reconocidos. Los fármacos para las crisis focales que actúan sobre los canales de sodio son los indicados. En emergencias, durante las convulsiones agrupadas, es importante el uso de benzodiacepinas. En esta publicación, hacemos un recorrido de nuestro aporte en EAL desde nuestra primera contribución hasta la actualidad y además realizamos una revisión de la literatura existente sobre el tema.