Therapeutic Management Research Articles

Innovative Therapeutic Approaches in Congenital Myasthenic Syndromes.

To provide real-word clinical follow-up data on patients carrying variations of congenital myasthenic syndromes (CMS) and who respond to some innovative drugs. Patients recruited from the Neurology Department of the Mustapha Bacha university hospital in Algiers. Treated with innovative drugs, they were monitored and their clinical progress was evaluated on the basis of clinical arguments suggestive of CMSs, but also para clinical arguments (electromyography and genetic study). Six patients carrying different mutations in different genes of CMSs were studied. They had different pathophysiologic profiles (slow or fast channel syndromes, low expressor of receptor). Their therapeutic management was based on innovative drugs, normally indicated in other, non-neurological pathologies. Their outcome was toward a clear clinical improvement. This work relates the interest of proposing treatments (outside of Pyridostigmine) in the management of CMSs. These therapies can greatly modify the prognosis of patients suffering from this orphan disease. This study provides Class IV evidence that for patients with congenital myasthenic syndromes, some innovative treatments are effective.

Inequalities in the Prevention and Treatment of Alzheimer Disease.

Incidence of Alzheimer disease (AD) is going to rise in the next years and to become a health and social emergency. The prevention and the therapeutic management of AD still present unmet needs worldwide. The recent approval of monoclonal antibodies against amyloid β (anti-Aβ mAbs) for AD has increased the level of uncertainty regarding on how such drugs should be administered, to whom, and for how long. Concerns about cost-effectiveness ratios of anti-Aβ mAbs and the need for actual strategies of risk prevention have further dug barriers of inequalities between the national health care systems. Planning research to address questions on the real feasibility of the correct therapeutic management, improving international cooperation on surveillance of risk factors, implementing pathways for timely diagnosis, and effective medical and social support for patients with AD worldwide would be extremely valuable to fight against this upcoming pandemic.

Gastroretentive Raft Forming System for Enhancing Therapeutic Effect of Drug-Loaded Hollow Mesoporous Silica on Gastric Ulcers.

Gastric ulcers are characterized by damage to the stomach lining and are often triggered by substances such as ethanol and non-steroidal anti-inflammatory drugs. Patchouli alcohol (PA) has demonstrated effectiveness in treating gastric ulcers through antioxidative and anti-inflammatory effects. However, the water insolubility of PA and rapid gastric emptying cause low drug concentration and poor absorption in the stomach, resulting in limited treatment efficacy of PA. This study develops an oral gastroretentive raft forming system (GRFDDS) containing the aminated hollow mesoporous silica nanoparticles (NH2-HMSN) for PA delivery. The application of NH2-HMSN can enhance PA-loading capacity and water dispersibility, promoting bio-adhesion to the gastric mucosa and sustained drug release. The incorporation of PA-loaded NH2-HMSN (NH2-HMSN-PA) into GRFDDS can facilitate gastric drug retention and achieve long action, thereby improving therapeutic effects. The results reveal that NH2-HMSN-PA protects the gastric mucosa damage by inhibiting NLRP3-mediated pyroptosis. The GRFDDS, optimized through orthogonal design, demonstrates the gastric retention capacity and sustained drug release, exhibiting significant therapy efficacy in an ethanol-induced acute gastric ulcersmodel and an aspirin-induced chronic gastric ulcersmodel through antioxidation, anti-pyroptosis, and anti-inflammation. This study provides a potential strategy for enhancing druggability of insoluble natural compounds and therapeutic management of gastric ulcers.

Myelin Oligodendrocyte Glycoprotein-Antibody Associated Disease: An Updated Review of the Clinical Spectrum, Pathogenetic Mechanisms and Therapeutic Management

Clinical syndromes associated with antibodies against myelin oligodendrocyte glycoprotein (MOG) are now recognized as a distinct neurological disease entity, and are gaining increasing attention. The pathogenic mechanisms underlying MOG-antibody disease (MOGAD) remain incompletely understood. Case series, facilitated by registries, and observational studies over the past few years have shed increasing light on the clinical aspects and therapeutic approaches of MOGAD. MOGAD may manifest with a variety of clinical syndromes, including acute disseminated encephalomyelitis (ADEM), autoimmune encephalitis, optic neuritis (ON) and transverse myelitis (TM). MOGAD can be either monophasic or relapsing. This review aims to provide a comprehensive updated description of the clinical spectrum, paraclinical features, and prognosis of MOG-antibody disease, as well as summarize its therapeutic considerations. Randomized clinical trials, standardized diagnostic criteria and treatment guidelines are the steps forward.

Folliculitis Decalvans: A Review of Current Treatment Modalities

Background: Folliculitis decalvans (FD) is a rare subtype of neutrophilic cicatricial alopecia, firstly described by Quinquad in 1888, as inflammatory scalp disease usually affecting young adults. The exact etiopathology of the disease is not fully understood, however the presence of Staphylococcus aureus, dysfunction of the host’s immune response, genetic factors, previous trauma of the scalp, as well as Epidermal Growth Factor Receptor inhibitors (EGFRi) use seem to play a role. Clinically, FD presents with scarring alopecic patches with follicular pustules, crusts and tufted hair. Objectives: As the full etiology of the disease is unknown and most data in the literature is based on retrospective date, therapeutic management is not precisely established. The objective of this review is to describe therapeutic options, as well as highlighting potential new therapeutic modalities reported in the literature. Limitations: Because FD is a rare disease, the main limitation is lack of randomized control trials, evaluating therapeutic modalities. Methods: An exhaustive search of references related to FD published in PubMed between 2017 and 2024 was undertaken, using the search term: "folliculitis decalvans". Articles with large patient cohorts and reviews were included, as well as case reports and case series, that reported novel treatment approaches for FD.Conclusions: The management of FD poses a challenge. Systemic antibiotics, particularly rifampicin and clindamycin, are considered the first-line agents and are commonly used in combination with local therapies. Systemic isotretinoin yields sustained remission in some cases, while biological agents exhibit promise in managing severe FD. Novel therapeutic modalities, incorporating, among others, botulinum toxin A injections, Platelet-Rich-Plasma (PRP), or surgical procedures, necessitate randomized double-blind trials to evaluate their safety and efficacy.

PULMONARY HYPERTENSION AND CONGENITAL HEART DISEASE: THE CLINIC BEYOND THE EVIDENCE

Abstract Eisenmenger syndrome (ES), first described by Victor Eisenmenger, was defined by Paul Wood in pathophysiologic terms as “pulmonary hypertension (PH) at systemic level, caused by a high pulmonary vascular resistance (PVR), with reversed or bidirectional shunt at aorto–pulmonary, ventricular, or atrial level.” It represents the most severe hemodynamic phenotype of pulmonary arterial hypertension (PAH) in association with congenital heart disease (CHD) and develops in the presence of large, unrepaired atrial or ventricular septal defects, arterial shunts, or complex forms of CHD. Although therapeutic management has rapidly advanced in recent years, these patients were not included in randomized controlled trials for specific pulmonary arterial hypertension drugs, except for bosentan. However, in clinical practice we apply treatment strategies combining drugs targeting multiple pathobiological pathways. The clinical case we describe is that of a 44–year–old patient, suffering from Down syndrome, with ES due to subaortic VSD and a a patency of Botallo duct, followed in our PH clinic of the "Ruggi D‘Aragona" University Hospital for about 9 years. The patient, on dual therapy with Macitentan 10 mg and Sildenafil 60 mg, was in the intermediate–high risk class, stationary. During the last two checks, there was a progressive worsening of the hemodynamic parameters, walking distance of only 100 meters, with SpO2 at baseline 90% and desaturation during the 6mwt. On cardiac color Doppler ultrasound evidence of TAPSE 18 mm, PAPS 100 mmHg, RAA 20 cm²; TAPSE/PAPS 0.18. The patient presented in WHO class 3. The only RCTs currently available concern the use of bosentan, but in clinical practice, initial monotherapy with an endothelin receptor antagonist or a phosphodiesterase type 5 inhibitor for symptomatic patients is proposed. Reassess and consider escalation to a double combination therapy in case of clinical worsening or inadequate clinical response. Consider uptitration with the addition of prostanoids when inadequate response and timely assess the eligibility for transplantation. For our patient therefore, in consideration of the impossibility of surgery, although there is little evidence on prospective observational studies based on cohorts of a few patients, we added selexipag 200 ug x 2/day to titrate therapy.This case opens the door to still unclear scenarios in which unfortunately the only weapon available remains the clinician‘s judgment and experience.

A 20–YEAR FOLLOW–UP OF SUCCESSFUL SURGICAL MANAGEMENT OF DOUBLE–OUTLET RIGHT VENTRICLE WITH PULMONARY STENOSIS: A CASE REPORT

Abstract A 25–year–old man, suffering from worsening exertional dyspnea for 4 months, was referred to our Cardiology Unit. The patient was previously diagnosed with a late diagnosis of double outlet right ventricle (DORV), as well as pulmonary stenosis, VSD, and right–sided aortic arch for which he underwent a first surgical procedure around the age of 2 involving an intersternal anastomosis through a left lateral thoracotomy approach. A second intervention took place 2 years later for a radical correction of the anomaly through a median sternotomy. The patient had sporadic follow–up since then. A baseline ECG was performed, showing evidence of sinus rhythm, normal AV with a bifid P wave in lead II, slight RAD, incomplete RBBB, and asymmetric negative T waves from V1 to V3 and in aVL, and biphasic T waves in V4–V5. We performed an echocardiogram which showed: a dilated RA, a normal–sized LA, an apparently intact interatrial septum without evident shunts; a normal sized LV; EF 60%; a moderately dilated, hypertrophic and hypertrabeculated RV; FAC 33%; normal aortic flow; a minimal MR; a massive residual pulmonary insufficiency; a moderate TR; a dilatated pulmonary trunk; a normal–sized and collapsible IVC upon inspiration; PAPs of 70 mmHg; no pericardial effusion. A maximal exercise stress test appeared to be normal throughout. However, due to the severe pulmonary hypertension he was referred to our PH centre. While these patients are commonly affected by residual early or late left ventricular outflow tract obstruction, fortunately our patient was not. DORV is a relatively common congenital heart defect characterized by an abnormal connection between the ventricles and arteries, in which both the aorta and the pulmonary trunk are connected completely or predominantly to the right ventricle. The anatomical spectrum of this anomaly is quite large, and it can be associated with the presence of a VSD that often extends towards one or both of the arterial valves, allowing the flow of blood from the left ventricle to the aorta. An accurate diagnosis through echocardiography or CMR is essential in order to guide the surgical repair and the appropriate therapeutic approach for individuals affected by this anomaly. A successful surgical correction of DORV is essential, but it is important to be aware of the potential complications of post–operative PH (especially in patients with preoperative PH), which necessitates close surveillance and appropriate therapeutic management.

Allele-Specific Suppression of Variant MHC With High-Precision RNA Nuclease CRISPR-Cas13d Prevents Hypertrophic Cardiomyopathy.

Familial hypertrophic cardiomyopathy has severe clinical complications of heart failure, arrhythmia, and sudden cardiac death. Heterozygous single nucleotide variants (SNVs) of sarcomere genes such as MYH7 are the leading cause of this type of disease. CRISPR-Cas13 (clustered regularly interspaced short palindromic repeats and their associated protein 13) is an emerging gene therapy approach for treating genetic disorders, but its therapeutic potential in genetic cardiomyopathy remains unexplored. We developed a sensitive allelic point mutation reporter system to screen the mutagenic variants of Cas13d. On the basis of Cas13d homology structure, we rationally designed a series of Cas13d variants and obtained a high-precision Cas13d variant (hpCas13d) that specifically cleaves the MYH7 variant RNAs containing 1 allelic SNV. We validated the high precision and low collateral cleavage activity of hpCas13d through various in vitro assays. We generated 2 HCM mouse models bearing distinct MYH7 SNVs and used adenovirus-associated virus serotype 9 to deliver hpCas13d specifically to the cardiomyocytes. We performed a large-scale library screening to assess the potency of hpCas13d in resolving 45 human MYH7 allelic pathogenic SNVs. Wild-type Cas13d cannot distinguish and specifically cleave the heterozygous MYH7 allele with SNV. hpCas13d, with 3 amino acid substitutions, had minimized collateral RNase activity and was able to resolve various human MYH7 pathological sequence variations that cause hypertrophic cardiomyopathy. In vivo application of hpCas13d to 2 hypertrophic cardiomyopathy models caused by distinct human MYH7 analogous sequence variations specifically suppressed the altered allele and prevented cardiac hypertrophy. Our study unveils the great potential of CRISPR-Cas nucleases with high precision in treating inheritable cardiomyopathy and opens a new avenue for therapeutic management of inherited cardiac diseases.

MULTIDISCIPLINARY APPROACH TO A DIFFICULT CASE OF ACUTE HEART FAILURE DUE TO POSSIBILE ISOLATED CARDIAC SARCOIDOSIS

Abstract Background Cardiac sarcoidosis (CS) is a rare, infiltrative cardiomyopathy that results from granulomatous inflammation affecting the heart with high morbidity and mortality. It is usually associated with a systemic (i.e. pulmonary) involvement, but lone heart involvement has been described. Even with extensive multidisciplinary evaluation making a firm diagnosis is difficult, especially in case of isolated CS where the endomyocardial biopsy (EBM) diagnostic yield is low (20–30%). Case Description A 71–year–old patient, heavy smoker with no previously known diseases, was admitted with a 3–month history of dyspnea. On admission he showed typical features of heart failure with reduced ejection fraction (HFrEF). A coronary angiography excluded coronary artery disease, while echocardiography (TTE), cardiac magnetic resonance (CMR), and positron emission tomography (FDG–PET) showed a pattern consistent with a non–ischemic dilated cardiomyopathy with reduction in systolic function, and signs of active inflammation (highly suspected CS). Two electroanatomic mapping driven EBM were made but no clear histological signs of CS (i.e., granulomatous inflammation) were detected. The patient was treated with corticosteroids and HFrEF optimal medical therapy (sacubitril/valsartan, mineralocorticoid receptor antagonists, beta–blockers, dapagliflozin) and a temporary wearable defibrillator (LifeVest) was applied. At 2–month follow–up, despite a moderate improvement in the systolic function and HF symptoms, after a multidisciplinary discussion, considering the extensive left ventricle scar, inflammatory involvement, and the presence of multiple non–sustained ventricular tachycardia, a permanent cardioverter–defibrillator (ICD) was implanted. Conclusion This case highlights how, even with (repeated) extensive multidisciplinary evaluation (TTE, CRM, FGD–PET, EBM), a definitive diagnosis of isolated CS often remains presumptive. The presence of an experienced cardiomyopathy team (HF specialists, cardiac imager, electrophysiologists, internal medicine doctor) can help in the diagnostic–therapeutic management of these patients with inflammatory heart disease.

Systematic review of risk factors, prognosis, and management of colorectal signet-ring cell carcinoma.

Colorectal signet-ring cell carcinoma (CSRCC) is a rare clinical entity which accounts for approximately 1% of all colorectal cancers. Although multiple studies concerning this specific topic have been published in the past decades, the pathogenesis, associated risk factors, and potential implications on treatment are still poorly understood. Besides the low incidence, historically confusing histological criteria have resulted in confusing data. Nevertheless, the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis, highlight the actual interest to synthesize the known literature regarding CSRCC. To provide an updated overview of risk factors, prognosis, and management of CSRCC. A literature search in the MEDLINE/PubMed database was conducted with the following search terms used: 'Signet ring cell carcinoma' and 'colorectal'. Studies in English language, published after January 1980, were included. Studies included in the qualitative synthesis were evaluated for content concerning epidemiology, risk factors, and clinical, diagnostic, histological, and molecular features, as well as metastatic pattern and therapeutic management. If possible, presented data was extracted in order to present a more detailed overview of the literature. In total, 67 articles were included for qualitative analysis, of which 54 were eligible for detailed data extraction. CSRCC has a reported incidence between 0.1%-2.4% and frequently presents with advanced disease stage at the time of diagnosis. CSRCC is associated with an impaired overall survival (5-year OS: 0%-46%) and a worse stage-corrected outcome compared to mucinous and not otherwise specified adenocarcinoma. The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised. Surgery is the mainstay of treatment, although the rates of curative resection in CSRCC (21%-82%) are lower compared to those in other histological types. In case of peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients. CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation. As such, diagnostic modalities and therapeutic approach should be tailored accordingly.

Acteoside and isoacteoside alleviate renal dysfunction and inflammation in lipopolysaccharide-induced acute kidney injuries through inhibition of NF-κB signaling pathway.

Acute kidney injury (AKI) is a sudden loss of renal function with a high mortality rate and inflammation is thought to be the underlying cause. The phenylpropanoid components acteoside (ACT) and isoacteoside (ISO), which were isolated from Cistanche deserticola Y.C.Ma, have been reported to have preventive effects against kidney disorders. This study aimed to investigate the anti-inflammatory properties and protective mechanisms of ACT and ISO. In this investigation, kidney function was assessed using a semi-automatic biochemical analyzer, histopathology was examined using Hematoxylin-Eosin staining and immunohistochemistry, and the concentration of inflammatory cytokines was assessed using an enzyme-linked immunosorbent assay (ELISA) test. In addition, using Western blot and q-PCR, the expression of proteins and genes connected to the NF-κB signaling pathway in mice with lipopolysaccharide (LPS)-induced AKI was found. The findings showed that under AKI intervention in LPS group, ACT group and ISO group, the expression of Rela (Rela gene is responsible for the expression of NFκB p65 protein) and Tlr4 mRNA was considerably elevated (P<0.01), which led to a significant improvement in the expression of MyD88, TLR4, Iκ-Bɑ and NF-κB p65 protein (P<0.001). The levels of Alb, Crea and BUN (P<0.001) increased along with the release of downstream inflammatory factors such as IL-1β, IL-6, Cys-C, SOD1 and TNF-α (P<0.001). More importantly, the study showed that ISO had a more favorable impact on LPS-induced AKI mice than ACT. In conclusion, by inhibiting NF-κB signaling pathway, ACT and ISO could relieve renal failure and inflammation in AKI, offering a fresh possibility for the therapeutic management of the condition.

Hereditary angioedema: current therapeutic management and future approaches.

The aim of this review is to provide an account of the focus of therapeutic strategies for hereditary angioedema (HAE), give a brief overview of those used in the past and set aside and toughly discuss those currently available as first line. Further research is ongoing and the future therapeutic approaches that are still in different phases of study will be reviewed as well. In the last two decades, major research advancements on HAE pathophysiology and management were made and numerous novel therapeutic options are now available. Compared to the past, drugs available nowadays are more effective, well tolerated, and possibly have a more convenient administration route. Moreover, numerous other drugs with innovative mechanisms of action are under development. HAE is a rare genetic disease that if not promptly treated, it can lead to death from asphyxiation. Furthermore, due to its disfiguring and painful manifestations, HAE implies an important burden on the quality of life. Recently, following great research progresses on HAE therapy, evidence-based guidelines on HAE management were released. The therapeutic landscape of HAE is still under florid development, and it is possible novel treatments will remarkably revolutionize HAE management in the future.

Therapeutic Management of Primary Atrophic Rhinitis (Ozene): About 4 Cases.

Objective: To study the clinical characteristics and therapeutic means of primary atrophic rhinitis. Method: We present 4 cases of atrophic rhinitis caused by Klebsiella ozaenae observed in our hospital over a period of 5 years. Results: All patients presented the clinical triad: mucosal atrophy, presence of crusts, and cacosmia. Treatment was medical in 3 patients and surgical in 1 patient. We used rifampicin and sulfamethoxazole as antibiotics as well as trimethoprim for a period of 4 months. The surgical treatment consisted of recalibration of the nasal cavities by placing 2 silicone sticks in the subperiosteum. The evolution was marked by obstruction and cacosmia in 3 out of 4 patients. Conclusion: The treatment of primary atrophic rhinitis poses a problem for the clinician in terms of means and therapeutic effectiveness given that it is a chronic pathology requiring regular monitoring.

Biochemical Analysis of Congenital Hypogonadotropic Hypogonadism in the Context of Male Infertility: A Comprehensive Review

Background: Male infertility encompasses various etiologies, with Congenital Hypogonadotropic Hypogonadism (CHH) standing out as a significant factor. CHH arises from multiple systems, including genetic abnormalities and hormonal imbalances that impair reproductive capabilities. Objective: This review aims to dissect the biochemical underpinnings of CHH and evaluate its impact on male infertility, highlighting the complexities in its diagnosis and therapeutic management. Methods: The analysis involved a review of current literature on the genetic causes and hormonal disruptions associated with CHH. Diagnostic criteria were assessed based on biochemical markers and clinical symptoms. Treatment efficacy was evaluated through outcomes of hormone replacement therapy, surgical interventions, and assisted reproductive technologies. Results: The majority of CHH patients treated with hormone replacement therapy demonstrated improved sexual maturation and fertility, with approximately 70% achieving spermatogenesis. Surgical interventions corrected anatomical defects in 90% of cases, while assisted reproductive technologies resulted in successful pregnancies in 60% of treated individuals. Conclusion: CHH significantly affects male reproductive health, influencing testicular development and endocrine function. Advances in diagnostic and treatment strategies have enhanced management outcomes, but ongoing research is essential for developing more targeted therapies.

Lissencephaly, Pachygyrias, Band Heterotopias, RELN Pathway, and ARX Mutations (Incomplete Neuron Migration)

AbstractLissencephaly (LIS) is a group of malformations of cortical development consisting of a defective neuronal migration that results in lack of formation of the normal cerebral convolutions. It includes a spectrum of defect with varying degrees of severity, from agyria and pachygyria to subcortical band heterotopia. The etiopathogenesis of LIS includes both genetic and environmental factors. Although nongenetic forms of LIS have been reported, genetic causes are certainly more frequent and to date 19 LIS-SBH-associated genes have been identified. Most common mutations involve LIS1, DCX, ARX, and RELN genes. Clinically affected individuals present with early hypotonia, which can progress to limb spasticity, seizures, and psychomotor retardation. Convulsive episodes usually appear early (first months of life) and include infantile spasms, akinetic or myoclonic seizures, up to the development of complex epileptic syndromes, including atypical absences, myoclonia, and partial or tonic–clonic seizures. Several clinical entities are associated with classical LIS, including the following: isolated lissencephaly sequence (ILS); Miller–Dieker syndrome (MDS; OMIM 247200); subcortical band heterotopia (OMIM 300067); X-linked LIS with abnormal genitalia; and LIS with cerebellar hypoplasia. Diagnosis primarily depends on genetic and neuroimaging. Magnetic resonance imaging (MRI) is the gold standard, and it detects the presence of thick cortical cortex, its location, and the layers' architecture. Based on neuroimaging, it is possible to distinguish six subtypes of gyral malformations. Clinical and therapeutic management of these patients is challenging, considering the necessity to face drug-resistant epilepsy, intellectual disability, spasticity, and dysphagia and feeding problems. At the present moment, no gene-specific treatment for LIS is available.

Identification of circRNA–miRNA–mRNA regulatory network associated to the autism spectrum disorder in children through integrated bioinformatics analysis

BackgroundAutism spectrum disorder (ASD) is a complex neurological disability with multifactorial etiology. ASD is described by behavior, speech, language, and communication defects. CircRNA is a type of ceRNA that plays an important role in modulating microRNAs (miRNA) in several disorders. However, the potential role of the circRNA/miRNA/mRNA regulatory network in the pathogenesis of ASD is not fully understood. Therefore, this study aimed to create a circRNA/miRNA/mRNA network associated with ASD to cast light on the pathogenesis of ASD.MethodsCircRNA expression profile data were recruited from Gene Expression Omnibus datasets, and the differentially expressed circRNAs (DEcircRNAs) were identified. Then, miRNAs modulated by these circRNAs were predicted and overlapped with differentially expressed miRNAs. Next, the potentially involved genes were identified by overlapping predicted targets, and differentially expressed genes. The enrichment analysis was performed, and a PPI network was projected. Subsequently, ten key genes were selected from the network. Furthermore, a circRNA/miRNA/mRNA regulatory network was constructed, and probable molecules and drugs with potential anti-ASD effects were predicted.Results11 DEcircRNAs and 8 miRNAs regulated by 4 circRNAs were identified as being significantly involved. Subsequently, gene enrichment analysis of 71 overlapped mRNA regulated by these miRNAs showed that they are mostly associated with hippocampal synaptogenesis, neurogenesis, and axon guidance. Additionally, two high-score compounds, GSK3β inhibitor (SB216763) and dexamethasone, and three drugs (haloperidol, nystatin, paroxetine) were confirmed as potential therapeutic options for ASD.ConclusionThe results of this study may help gain deeper insight into the pathogenesis of the circRNA/miRNA/mRNA regulatory network in ASD, providing potential therapeutic management options.

Multi-organ clinical ultrasound as a complement to the diagnostic process in an internal medicine consultation.

Evaluating outpatient cases in internal medicine consultations presents a significant diagnostic challenge. Ultrasound can be a highly useful tool in assessment and decision-making. A prospective observational study was conducted on a cohort of patients attending an internal medicine rapid assessment clinic. Eighty patients were prospectively recruited. A medical consultation was conducted as per usual clinical practice, followed by a POCUS evaluation; collecting pulmonary, cardiac, and abdominal data. All findings were analyzed and recorded, particularly those that were significant or altered the initial diagnosis, subsequent tests, or treatment. Significant ultrasound findings were found in 37.5% of the patients. Of all ultrasound scans, the most clinically relevant were in the heart region (31.9%), followed by the abdomen (26%). These findings led to a change in overall management in 27.5% of patients. Using logistic regression, a model was developed to estimate the presence of clinically relevant findings with an area under the curve (AUC) of 0.78 (95% CI 0.66-0.89; p < 0.001) with 80% Sensitivity and 66% Specificity. The systematic and standardized incorporation of clinical ultrasound in internal medicine consultations contributes to decision-making, can provide significant findings that allow for modifications in clinical suspicion and therapeutic management.

Microbiological findings in infective endocarditis, event predictor and prognostic value

Abstract Funding Acknowledgements None. Introduction In infective endocarditis, microbial isolation can be related to the prognosis of the disease. Identify the cause of endocarditis can help decide further management appropriate. Our purpose was to evaluate the most frequent microbiological findings in our healthcare area, as well as their association with prognostic determinants. Material and Methods Retrospective, observational, single-center study*. Based on a registry of patients diagnosed with infective endocarditis during the years 2016-2022 in a reference hospital with cardiac surgery. Patients with infective endocarditis were analyzed according to their type of microbial isolation, observing the microbial epidemiology and comparing these groups according to their baseline characteristics (age, sex, risk factors), the different therapeutic management in each group (type of antibiotic treatment used, surgical intervention, surgical indication etc.) and compared the groups according to the frequency of different prognostic determinants and events (Reinfection, Embolism, Shock, Mortality, local complications, etc.). To analyze the differences in events between different groups of microorganisms, the Chi square statistic of Homogeneity was used, and a significance level of p&amp;lt;0.05 was established. Results 162 patients were analyzed for an average of 66 years. The rate of positive blood cultures was 93%. The most frequently isolated microorganisms were, Figure 1. Patients who suffered from S. aureus endocarditis (with a mean age also of 66±10 years) had a higher prevalence of pacemaker infections and were complicated by septic shock more frequently (43%, p&amp;lt;0.01) than patients with other types of microorganism isolation. However, we did not have high surgery rates, and we did not observe significant differences in terms of recurrence or mortality, despite being a very virulent microorganism. On the other hand, S.Epidermidis (which is associated with early prosthetic valve endocarditis) is the microorganism most closely related with abscesses, fistulas or other perivalvular involvements (34%, p=0.04), in relation to endocarditis after valve surgery. This group also appears to have a greater tendency, although not significant, to cause AV blocks. Furthermore, S.Epidermidis was the group of patients that most frequently underwent surgery (62% p&amp;lt;0.001) Figure 2. Conclusions In this study, we have observed a higher frequency of isolation of E. feacalis, with significant differences in comparison to other series, and a significantly higher number of recurrences in comparison to other microorganisms. S. aureus is the microorganism most linked to shock, but it is also the one with the lowest number of undergone surgeries, despite being comparable populations. In valve prosthetic endocarditis, S. epidermidis was the most frequent pathogen isolated, and was more frequently associated with perivalvular involvement and the need for surgery.

Imaging of neuroendocrine tumors of the gastrointestinal tract : Value of (hybrid) imaging diagnostics in radiology

Neuroendocrine tumors (NET) represent aheterogeneous group of rare tumors that predominantly arise in the gastrointestinal tract. At the time of initial diagnosis, the NET has already spread locoregionally in about half of the patients, and 27% of patients have already developed distant metastases. Since this plays acrucial role in therapy planning, accurate diagnostic imaging is important. Due to its high temporal and spatial resolution (multiphasic including arterial phase), computed tomography (CT) plays adecisive role in primary staging and follow-up care, while magnetic resonance imaging (MRI) with its excellent soft tissue contrast offers advantages in the assessment of parenchymal organs in the upper abdomen. Somatostatin receptor (SSR) positron emission tomography (PET) provides additional functional information that not only helps to detect the primary tumor and distant metastases, but also has asignificant influence on therapeutic management in atheranostic approach. Hybrid imaging using SSR-PET/CT has proven to be particularly effective in the detection of NET. Compared to conventional imaging, it provides additional information in 68% of patients, which has asignificant impact on clinical management. Imaging of NET requires the combined use of various methods such as ultrasound, CT, MRI, and PET/CT to enable accurate diagnosis and effective treatment planning. SSR-PET/CT is avaluable tool for the accurate staging of neuroendocrine tumors of the gastrointestinal tract, especially with small metastases, while MRI with hepatocyte-specific contrast agent and diffusion-weighted imaging is useful for the specific assessment of liver metastases.

The echocardiographic pulmonary to left atrial ratio: A noninvasive variable for the hemodynamic classification of pulmonary hypertension in dogs.

Hemodynamic classification of pulmonary hypertension (PH) has important clinical implications. However, only a few echocardiographic variables have been used to hemodynamically classify PH in dogs. To evaluate the echocardiographic pulmonary to left atrial ratio index (ePLAR) in dogs with PH. Forty-six dogs with intermediate to high probability of PH. Cross-sectional study. Variables were compared between dogs with precapillary PH [PrePH (n = 24)] vs postcapillary PH [PostPH (n = 22)], and with combined PH [CombPH (n = 14)] vs isolated PH [IsoPH (n = 8)] using the t-, Mann-Whitney, Pearson's Chi, or Fisher's exact test. The receiver operating characteristic curve and Youden index were used to identify the optimal ePLAR cutoff value to differentiate among the groups, intraclass correlation coefficients (ICC) were used to determine the reliability of measurements. The mean (SD) ePLAR of the PrePH was higher than that of the PostPH group [0.36 (0.13) vs 0.26 (0.09), respectively; P = .005]. The median (interquartile range) ePLAR of the CombPH was higher than that of the IsoPH subgroup [0.29 (0.24-0.38), vs 0.20 (0.16-0.23), respectively; P = .001]. The best cutoff value of ePLAR for identifying IsoPH was <0.245 [AUC at cutoff point = 0.86; sensitivity (95% confidence interval [CI]) = 0.71 (0.47-0.95); specificity (95% CI) = 1 (0.76-1)]. The ICC analysis indicated a high degree of reliability. ePLAR can be considered a valid noninvasive variable to hemodynamically classify PH in dogs with an intermediate to high probability of PH. Assessment of ePLAR can be useful in the therapeutic management of PH in dogs.