Discovery of new antigens for serodiagnosis of visceral leishmaniasis in humans and dogs adds valuable tools to our arsenal.

Surveillance and sustained control of visceral leishmaniasis (VL) require reliable serodiagnostic tools. rK39, the gold standard antigen for VL diagnosis, is limited by its documented poor sensitivity in certain endemic regions, such as East Africa, and by the longevity of its antibodies, making it difficult to distinguish active from cured infections. In a recent publication in mBio, Roberts et al. (A. J. Roberts, H.B. Ong, S. Clare, C. Brandt, et al., mBio 15:e00859-24, 2024, https://doi.org/10.1128/mbio.00859-24) identified new immunogenic Leishmania candidates in dogs and humans. In dogs, combined antigens LdBPK_290790.1 + LdBPK_362700.1 (D4 +D46) distinguished symptomatic from asymptomatic infections. For humans, LdBPK_323600.1 (D36) antigen produced short-lived antibodies and performed well in patient cohorts from Bangladesh and Ethiopia, but not Kenya. This study adds promising new candidates to our serodiagnostic toolbox but highlights the need for more antigen discovery studies that may have to be focused on regional performance.

MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review.

Neurodegenerative diseases (NDs) are characterized by abnormalities within neurons of the brain or spinal cord that gradually lose function, eventually leading to cell death. Upon examination of affected tissue, pathological changes reveal a loss of synapses, misfolded proteins, and activation of immune cells-all indicative of disease progression-before severe clinical symptoms become apparent. Early detection of NDs is crucial for potentially administering targeted medications that may delay disease advancement. Given their complex pathophysiological features and diverse clinical symptoms, there is a pressing need for sensitive and effective diagnostic methods for NDs. Biomarkers such as microRNAs (miRNAs) have been identified as potential tools for detecting these diseases. We explore the pivotal role of miRNAs in the context of NDs, focusing on Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Huntington's disease, and Amyotrophic Lateral Sclerosis. The review delves into the intricate relationship between aging and NDs, highlighting structural and functional alterations in the aging brain and their implications for disease development. It elucidates how miRNAs and RNA-binding proteins are implicated in the pathogenesis of NDs and underscores the importance of investigating their expression and function in aging. Significantly, miRNAs exert substantial influence on post-translational modifications (PTMs), impacting not just the nervous system but a wide array of tissues and cell types as well. Specific miRNAs have been found to target proteins involved in ubiquitination or de-ubiquitination processes, which play a significant role in regulating protein function and stability. We discuss the link between miRNA, PTM, and NDs. Additionally, the review discusses the significance of miRNAs as biomarkers for early disease detection, offering insights into diagnostic strategies.

Application of Next-Generation Sequencing (NGS) Techniques for Selected Companion Animals.

Next-Generation Sequencing (NGS) techniques have revolutionized veterinary medicine for cats and dogs, offering insights across various domains. In veterinary parasitology, NGS enables comprehensive profiling of parasite populations, aiding in understanding transmission dynamics and drug resistance mechanisms. In infectious diseases, NGS facilitates rapid pathogen identification, characterization of virulence factors, and tracking of outbreaks. Moreover, NGS sheds light on metabolic processes by elucidating gene expression patterns and metabolic pathways, essential for diagnosing metabolic disorders and designing tailored treatments. In autoimmune diseases, NGS helps identify genetic predispositions and molecular mechanisms underlying immune dysregulation. Veterinary oncology benefits from NGS through personalized tumor profiling, mutation analysis, and identification of therapeutic targets, fostering precision medicine approaches. Additionally, NGS plays a pivotal role in veterinary genetics, unraveling the genetic basis of inherited diseases and facilitating breeding programs for healthier animals. Physiological investigations leverage NGS to explore complex biological systems, unraveling gene-environment interactions and molecular pathways governing health and disease. Application of NGS in treatment planning enhances precision and efficacy by enabling personalized therapeutic strategies tailored to individual animals and their diseases, ultimately advancing veterinary care for companion animals.

Towards the development of cost-effective point-of-care diagnostic tools for poverty-related infectious diseases in sub-Saharan Africa.

In this review, we examine the current landscape of point-of-care testing (POCT) diagnostic tools designed for poverty-related infectious diseases (PRIDs) in sub-Saharan Africa (sSA) while delineating key avenues for future advancements. Our analysis encompasses both established and emerging diagnostic methods for PRIDs, addressing the persistent challenges in POCT tool development and deployment, such as cost, accessibility, and reliability. We emphasize recent advancements in POCT diagnostic tools as well as platforms poised to enhance diagnostic testing in sSA. Recognizing the urgency for affordable and widely accessible POCT diagnostic tools to detect PRIDs in sSA, we advocate for a multidisciplinary approach. This approach integrates current and emerging diagnostic methods, explicitly addressing challenges hindering point-of-care (POC) tool development. Furthermore, it recognizes the profound impact of misdiagnosis on public and global health, emphasizing the need for effective tools. To facilitate the successful development and implementation of POCT diagnostic tools in sSA, we propose strategies including the creation of multi-analyte detection POCT tools, the implementation of education and training programs, community engagement initiatives, fostering public-private collaborations, and the establishment of reliable supply chains. Through these concerted efforts, we aim to accelerate the development of POCT in the sSA region, ensuring its effectiveness and accessibility in addressing the diagnostic challenges associated with PRIDs.

Empagliflozin's role in reducing ventricular repolarization heterogeneity: insights into cardiovascular mortality decline from the EMPATHY-HEART trial.

BACKGROUND: The incidence of myocardial infarction (MI) and sudden cardiac death (SCD) is significantly higher in individuals with Type 2 Diabetes Mellitus (T2DM) than in the general population. Strategies for the prevention of fatal arrhythmias are often insufficient, highlighting the need for additional non-invasive diagnostic tools. The T-wave heterogeneity (TWH) index measures variations in ventricular repolarization and has emerged as a promising predictor for severe ventricular arrhythmias. Although the EMPA-REG trial reported reduced cardiovascular mortality with empagliflozin, the underlying mechanisms remain unclear. This study investigates the potential of empagliflozin in mitigating cardiac electrical instability in patients with T2DM and coronary heart disease (CHD) by examining changes in TWH. METHODS: Participants were adult outpatients with T2DM and CHD who exhibited TWH > 80 µV at baseline. They received a 25 mg daily dose of empagliflozin and were evaluated clinically including electrocardiogram (ECG) measurements at baseline and after 4 weeks. TWH was computed from leads V4, V5, and V6 using a validated technique. The primary study outcome was a significant (p < 0.05) change in TWH following empagliflozin administration. RESULTS: An initial review of 6,000 medical records pinpointed 800 patients for TWH evaluation. Of these, 412 exhibited TWH above 80 µV, with 97 completing clinical assessments and 90 meeting the criteria for high cardiovascular risk enrollment. Empagliflozin adherence exceeded 80%, resulting in notable reductions in blood pressure without affecting heart rate. Side effects were generally mild, with 13.3% experiencing Level 1 hypoglycemia, alongside infrequent urinary and genital infections. The treatment consistently reduced mean TWH from 116 to 103 µV (p = 0.01). CONCLUSIONS: The EMPATHY-HEART trial preliminarily suggests that empagliflozin decreases heterogeneity in ventricular repolarization among patients with T2DM and CHD. This reduction in TWH may provide insight into the mechanism behind the decreased cardiovascular mortality observed in previous trials, potentially offering a therapeutic pathway to mitigate the risk of severe arrhythmias in this population. TRIAL REGISTRATION: NCT: 04117763.

Dermatological guide for primary care physicians: full body skin checks, skin cancer detection, and patient education on self-skin checks and sun protection.

Dermatological conditions and skin cancers are common health concerns that require early detection and intervention. Primary care physicians play a crucial role in recognizing these conditions and serving as the first line of defense against skin cancers. This guide provides a systematic approach to conducting thorough skin examinations and enhancing understanding of common presentations of precancerous and cancerous lesions. We emphasize the importance of performing annual full-body skin exams to facilitate early detection and management of skin conditions, including a step-by-step, systematic protocol for conducting these exams, comprising preparing the patient, documenting findings, educating the patient, and considering biopsy or referral for suspicious lesions. Furthermore, we explore the atypical features of skin lesions that raise clinical suspicion and warrant further investigation. We describe the characteristics of common skin cancers, such as basal cell carcinoma, squamous cell carcinoma, and melanoma. We stress the importance of patient education on self-skin checks and sun protection measures. By incorporating the knowledge and skills presented in this guide, primary care physicians can confidently perform thorough full-body skin checks, identify common dermatological findings and early signs of skin cancers, and provide comprehensive care to patients. This will help ensure optimal outcomes in dermatological health.

The Evaluation of a 5-miRNA Panel in Patients with Periodontitis Disease.

INTRODUCTION: Side by side with tooth decay, periodontitis remains one of the most common oral diseases and is increasingly recognized as a serious public health concern worldwide. OBJECTIVES: The present study aims at comparing the levels of 5 specific miRNAs (miR-29b-3p, miR-34a-5p, miR-155-5p, miR-181a-5p, and miR-192-5p) in patients with periodontal disease and healthy controls. METHODS: The pathogenic mechanism is related to the activation of immune response and significant alteration of coding and noncoding genes, including miRNA. The study includes 50 subjects (17 with periodontal disease and 33 healthy controls) with a mean age of 45.3 y. In both periodontitis patients and healthy controls, a panel of 5 miRNAs (miR-29b-3p, miR-34a-5p, miR-155-5p, miR-181a-5p, and miR-192-5p) is examined by determining their expression levels with quantitative reverse transcription polymerase chain reaction. RESULTS: The periodontitis patients express high levels of all the investigated miRNAs. Receiver operating characteristic curve analysis shows an area under the curve (AUC) of 0.69 to 0.74 for individual transcripts with the highest AUC value observed for miR-192, followed by miR-181a. CONCLUSIONS: The study indicates that the 5-miRNA panel can be used as biomarker for periodontitis. In this way, all implantology procedures and treatment options for patients diagnosed with periodontitis can be improved for better long-term results, predictability, and follow-up frequency. KNOWLEDGE TRANSFER STATEMENT: The discovery of a miRNA panel as a potential biomarker for periodontitis offers major opportunities for practical application. Our study can improve diagnostic accuracy; researchers can develop new theories on molecular mechanisms and biomarker discovery.

Sella turcica bridging as a potential diagnostic tool for dental anomalies: A retrospective cross-sectional study at university dental hospital.

BACKGROUND: A lateral cephalogram is an essential diagnostic record for an orthodontist. It is used for diagnosis and treatment planning. This can be a prediction tool as well for developing anomalies of the skeletal, dental, and soft tissues of the head and neck. The sella turcica (ST), being a central landmark for cephalometric assessment, has great importance in itself as a diagnostic parameter to predict certain dental problems related to its bridging. AIM OF THE STUDY: 1. To assess and compare the shape, size, and bridging of ST in subjects of Taif with different skeletal classifications. 2. To find whether there is any association between dental anomalies and sella turcica bridging (STB). MATERIALS AND METHODS: The study obtained ethical approval from the research ethics committee of Taif University with application no. 44-354 and with no. HAO-02-T-1 dated June 4, 2023. The study involved 87 study samples, divided as follows: a. Group 1: 49 control records. b. Group 2: 38 case records with STB. RESULTS: The results of our study were promising in relation to STB and the occurrence of dental anomalies in both the case and the control with the frequencies of occurrence being 46.94% and 36.84%, respectively. It was found that the percentage of distribution was more among class I malocclusions and least in class III. It is imperative that impaction (13.8%) is the most associated anomaly, followed by ectopic eruption (11.5%). Supernumerary teeth and gemination were the least associated with STB, and only 1% of the cases showed an association. Statistically significant associations were found for all types of dental anomalies as a result of distribution among cases and controls. CONCLUSION: Orthodontists commonly employ lateral cephalograms as a regular practice to aid in diagnosis and treatment planning. Furthermore, these cephalograms can serve as predictive tools for dental anomalies. Detecting skeletal abnormalities at an early stage can provide insight into the likelihood of future dental anomalies, enabling clinicians to implement preventive measures accordingly.

Chemokine receptor PET imaging: Bridging molecular insights with clinical applications.

Chemokine receptors are important components of cellular signaling and play a critical role in directing leukocytes during inflammatory reactions. Their importance extends to numerous pathological processes, including tumor differentiation, angiogenesis, metastasis, and associations with multiple inflammatory disorders. The necessity to monitor the in vivo interactions of cellular chemokine receptors has been driven the recent development of novel positron emission tomography (PET) imaging agents. This imaging modality provides non-invasive localization and quantitation of these receptors that cannot be provided through blood or tissue-based assays. Herein, we provide a review of PET imaging of the chemokine receptors that have been imaged to date, namely CXCR3, CXCR4, CCR2, CCR5, and CMKLR1. The quantification of these receptors can aid in understanding various diseases, including cancer, atherosclerosis, idiopathic pulmonary fibrosis, and acute respiratory distress syndrome. The development of specific radiotracers targeting these receptors will be discussed, including promising results for disease diagnosis and management. However, challenges persist in fully translating these imaging advancements into practical therapeutic applications. Given the success of CXCR4 PET imaging to date, future research should focus on clinical translation of these approaches to understand their role in the management of a wide variety of diseases.

Biosensing of Alpha-Fetoprotein: A Key Direction toward the Early Detection and Management of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is currently one of the most prevalent cancers worldwide. Associated risk factors include, but are not limited to, cirrhosis and underlying liver diseases, including chronic hepatitis B or C infections, excessive alcohol consumption, nonalcoholic fatty liver disease (NAFLD), and exposure to chemical carcinogens. It is crucial to detect this disease early on before it metastasizes to adjoining parts of the body, worsening the prognosis. Serum biomarkers have proven to be a more accurate diagnostic tool compared to imaging. Among various markers such as nucleic acids, circulating genetic material, proteins, enzymes, and other metabolites, alpha-fetoprotein (AFP) is a protein marker primarily used to diagnose HCC. However, current methods need a large sample and carry a high cost, among other challenges, which can be improved using biosensing technology. Early and accurate detection of AFP can prevent severe progression of the disease and ensure better management of HCC patients. This review sheds light on HCC development in the human body. Afterward, we outline various types of biosensors (optical, electrochemical, and mass-based), as well as the most relevant studies of biosensing modalities for non-invasive monitoring of AFP. The review also explains these sensing platforms, detection substrates, surface modification agents, and fluorescent probes used to develop such biosensors. Finally, the challenges and future trends in routine clinical analysis are discussed to motivate further developments.

Systematic analysis of ocular features and responses of cultured spotted wolffish (Anarhichas minor).

A better understanding of unique anatomical and functional features of the visual systems of teleost fish could provide key knowledge on how these systems influence the health and survival of these animals in both wild and culture environments. We took a systematic approach to assess some of the visual systems of spotted wolffish (Anarhichas minor), a species of increasing importance in North Atlantic aquaculture initiatives. The lumpfish (Cyclopterus lumpus) was included in these studies in a comparative manner to provide reference. Histology, light and electron microscopy were used to study the spatial distribution and occurrence of cone photoreceptor cells and the nature of the retinal tissues, while immunohistochemistry was used to explore the expression patterns of two photoreceptor markers, XAP-1 and XAP-2, in both species. A marine bacterial infection paradigm in lumpfish was used to assess how host-pathogen responses might impact the expression of these photoreceptor markers in these animals. We define a basic photoreceptor mosaic and present an ultrastructural to macroscopic geographical configuration of the retinal pigment tissues in both animals. Photoreceptor markers XAP-1 and XAP-2 have novel distribution patterns in spotted wolffish and lumpfish retinas, and exogenous pathogenic influences can affect the normal expression pattern of XAP-1 in lumpfish. Live tank-side ophthalmoscopy and spectral domain optical coherence tomography (SD-OCT) revealed that normal cultured spotted wolffish display novel variations in the shape of the retinal tissue. These two complementary imaging findings suggest that spotted wolffish harbour unique ocular features not yet described in marine teleosts and that visual function might involve specific retinal tissue shape dynamics in these animals. Finally, extensive endogenous biofluorescence is present in the retinal tissues of both animals, which raises questions about how these animals might use retinal tissue in novel ways for visual perception and/or communication. This work advances fundamental knowledge on the visual systems of two economically important but now threatened North Atlantic teleosts and provides a basic foundation for further research on the visual systems of these animals in health versus disease settings. This work could also be useful for understanding and optimizing the health and welfare of lumpfish and spotted wolffish in aquaculture towards a one health or integrative perspective.

The diagnostic performance of GeneXpert MTB/RIF in tuberculosis meningitis: A multicentre accuracy study.

OBJECTIVES: To evaluate the performance of GeneXpert MTB/RIF (Xpert) for tuberculous meningitis (TBM) and to identify additional indicators to improve diagnostic accuracy. METHODS: An accuracy study was conducted. During 2011-2019, 243 TBM with 140 non-TBM in three TB-designated facilities in China were enrolled. Microbiological evidence of M tuberculosis (Mtb) in CSF was used as the reference. Additional indicators were identified by Boosted-Classification and Regression Tree (CART), the improvement of diagnostic performance was evaluated by ROC. RESULTS: The diagnostic sensitivity of Xpert was 71.1 % for definite TBM, and 5.5 % for probable/possible TBM. The positive rate of Xpert was improved with cerebrospinal fluid (CSF) increasing volume and was associated with CSF color (yellow). The additional indicators obtained by CART were CSF lactate and glucose and increased the sensitivity to 96.1 % (definite TBM) and 84.6 % (probable/possible TBM). CONCLUSIONS: The diagnostic performance of Xpert was satisfactory in definite TBM and would significantly be improved by the additional use of CSF lactate and glucose.

Validez de herramientas diagnósticas en pacientes pediátricos hospitalizados con diagnóstico presuntivo de dengue en un Hospital de Referencia de Paraguay / Validity of diagnostic tools in pediatric patients hospitalized with a presumptive diagnosis of dengue in a Reference Hospital in Paraguay

Introducción: El dengue es la enfermedad arboviral más común en los seres humanos. Un diagnóstico temprano y preciso del dengue puede respaldar el manejo clínico, la vigilancia y el control de la enfermedad y es fundamental, por ello en el diagnóstico del dengue es importante contar con pautas clínicas y epidemiológicas que permitan la identificación oportuna y una conducta terapéutica adecuada. Objetivos: Evaluar la validez de herramientas diagnósticas en pacientes pediátricos hospitalizados con diagnóstico presuntivo de dengue en un Hospital de Referencia de Paraguay durante los años de 2012 a 2020. Materiales y métodos: Estudio analítico de tipo observacional, retrospectivo correspondientes a pacientes pediátricos (0 a 18 años) internados en el Hospital de Referencia de Paraguay el periodo enero 2012 a julio 2020 con diagnostico presuntivo de dengue al ingreso. Se realizó́ un análisis bivariado relacionando las frecuencias de 20 grupos de criterios diagnósticos combinados y 3 criterios diagnósticos aislados (OMS 2009, nexo epidemiológico y antigenemia NS1 para dengue) con el gold standard de diagnóstico que fue la conversión serológica. Resultados: Participaron del estudio 342 sujetos. EL 44% tenía edad escolar y 70% tenía 5 años o más. El 52,76% (191) fueron masculinos. Se encontraron desnutrición y sobrepeso en el 13% y 2%, respectivamente. La combinación de proteína C reactiva con plaquetopenia se encontró́ en 0.45% de los pacientes sin dengue y en el 6% de los pacientes con diagnóstico final de dengue (p=0.004). Conclusión: Este resultado aporta la alternativa de uso de una combinación sencilla de exámenes de laboratorio que puede replicarse en salas de urgencias como en salas de internación en un primer contacto con pacientes febriles con sospecha de fiebre dengue.

Introduction: Dengue is the most common arboviral disease in humans. An early and accurate diagnosis of dengue can support the clinical management, surveillance and control of the disease and is essential, therefore in the diagnosis of dengue it is important to have clinical and epidemiological guidelines that allow timely identification and appropriate therapeutic conduct. Objectives: To evaluate the validity of diagnostic tools in pediatric patients hospitalized with a presumptive diagnosis of dengue in a Reference Hospital in Paraguay during the years 2012 to 2020. Materials and methods: Analytical study of case and control type, observational, longitudinal, retrospective corresponding to pediatric patients (0 to 18 years) admitted to the Reference Hospital of Paraguay from January 2012 to July 2020 with a presumptive diagnosis of dengue at income. A bivariate analysis was performed relating the frequencies of 20 groups of combined diagnostic criteria and 3 isolated diagnostic criteria (WHO 2009, epidemiological link and NS1 antigenemia for dengue) with the gold standard of diagnosis, which was serological conversion. Results: 342 subjects participated in the study. 44% were school age and 70% were 5 years old or older. 52.76% (191) were male. Malnutrition and overweight were found in 13% and 2%, respectively. The combination of C-reactive protein with thrombocytopenia was found in 0.45% of patients without dengue and in 6% of patients with a final diagnosis of dengue (p=0.004). Conclusion: This result provides the alternative of using a simple combination of laboratory tests that can be replicated in emergency rooms and inpatient wards in a first contact with febrile patients with suspected dengue fever.

Antimicrobial De-Escalation in Critically Ill Patients.

Antimicrobial de-escalation (ADE) is defined as the discontinuation of one or more antimicrobials in empirical therapy, or the replacement of a broad-spectrum antimicrobial with a narrower-spectrum antimicrobial. The aim of this review is to provide an overview of the available literature on the effectiveness and safety of ADE in critically ill patients, with a focus on special conditions such as anti-fungal therapy and high-risk categories. Although it is widely considered a safe strategy for antimicrobial stewardship (AMS), to date, there has been no assessment of the effect of de-escalation on the development of resistance. Conversely, some authors suggest that prolonged antibiotic treatment may be a side effect of de-escalation, especially in high-risk categories such as neutropenic critically ill patients and intra-abdominal infections (IAIs). Moreover, microbiological documentation is crucial for increasing ADE rates in critically ill patients with infections, and efforts should be focused on exploring new diagnostic tools to accelerate pathogen identification. For these reasons, ADE can be safely used in patients with infections, as confirmed by high-quality and reliable microbiological samplings, although further studies are warranted to clarify its applicability in selected populations.

Circulating miR-16-5p, miR-92a-3p and miR-451a are biomarkers of lung cancer in Tunisian patients.

Lung cancer is one of the most common type of cancer and, despite significant advances in screening and diagnosis approaches, a large proportion of patients at diagnosis still present advanced stages of the disease with distant metastasis and bad prognosis. Finding and validating biomarkers of lung cancer is therefore essential. Such studies are often conducted on European, American and Asian populations and the relevance of these biomarkers in other populations remains less clear. In that prospect, we investigated the expression level of seven microRNAs, chosen from the medical literature (miR-16-5p, miR-92a-3p, miR-103a-3p, miR-375-3p, miR-451a, miR-520-3p and miR-let-7e-5p), in the blood of Tunisian lung cancer patients, treated or not by chemotherapy, and healthy control individuals. We found that high expression levels of circulating miR-16-5p, miR-92a-3p and miR-451a in the plasma of untreated patients discriminate them from healthy control individuals. In addition, miR-16-5p and miR-451a expression levels are significantly reduced in the plasma of chemotherapy-treated patients compared to untreated patients. Our results confirmed previous work in other populations worldwide and provide further evidence that circulating miR-16-5p, miR-92a-3p and miR-451a potentially regulate key pathways involved in the initiation and progression of cancer.

Upper Esophageal Sphincter and Esophageal Motility Pathology on Manometry in Retrograde Cricopharyngeal Dysfunction.

OBJECTIVE: There exists a paucity of data regarding the mechanism and manometric findings in retrograde cricopharyngeal dysfunction (RCPD). In this study, we aimed to compare esophageal physiologic findings between patients with RCPD compared to an asymptomatic cohort. STUDY DESIGN: Case-control study. SETTING: Tertiary Care Center. METHODS: Esophageal high-resolution impedance manometry was completed preoperatively in patients diagnosed with RCPD. Manometric data were compared between the RCPD and asymptomatic cohorts. A 2:1 age-sex-matched asymptomatic cohort was used as the control group. Treatment response was assessed among the RCPD cohort. RESULTS: Thirty-nine patients are included: 13 RCPD [mean age: 31.1 (SD: 12.6) years, female sex: 11 (85%)] and 26 asymptomatic [mean age: 32.1 (SD: 1.5) years, female sex: 22 (85%)]. The RCPD cohort, compared to the asymptomatic cohort, exhibited significantly greater upper esophageal sphincter (UES) length [4.5 (SD: 0.7) vs 3.7 (0.9) cm, P = .01] and higher UES basal pressures [91.9 (35.0) vs 49.7 (25.5) mm Hg, P = .002]. Patients with RCPD demonstrated higher rates of ineffective swallows [70.0% (31.6%) vs 15.4% (21.6%), P < .001] and incomplete bolus clearance [81% (22.0%) vs 21.8% (30.0%), P < .001]. All patients who underwent cricopharyngeal botulinum injections experienced initial improvement of symptoms with 3 patients requiring repeat intervention. CONCLUSION: RCPD is associated with a longer UES, elevated UES basal pressures, and an increased incidence of ineffective esophageal motility. This study is the first to compare preoperative manometry results among patients with RCPD to those of an asymptomatic cohort, providing insights into the mechanism of RCPD.

Ultrasound muscle assessment for sarcopenia detection in inflammatory bowel disease: A prospective study.

BACKGROUND: Sarcopenia is prevalent in patients with inflammatory bowel disease (IBD) and impacts surgical and therapeutic outcomes; thus, effective diagnostic tools are needed to assess muscle mass and function in this population. METHODS: 153 consecutive patients were included, 100 in the training cohort and 53 in the study cohort. Three superficial muscles (rectus femoris = RF, rectus abdominis = RA, and biceps brachii = BB) were selected for the detection of sarcopenia using muscle ultrasound (US). The training cohort consisted of consecutive patients with or without IBD and was used to evaluate the feasibility and inter- and intra-observer variability of the US measurement. The study cohort consisted of only IBD patients and served to test US diagnostic accuracy. In the latter, muscle US, bioelectrical impedance analysis (BIA), and magnetic resonance imaging (MRI) were used to measure muscle parameters. RESULTS: Sarcopenia prevalence in IBD patients was 50%. Muscle US showed excellent inter-rater and intra-rater reliability (ICC >0.95) and a good diagnostic accuracy in detecting sarcopenia compared to BIA with area under the receiver operating characteristic curve (AUROC) values of 80% and 85% for RA and BB thickness, respectively. Moreover, an Ultrasound Muscle Index (USMI) was defined as the sum of the RA, BB, and RF thickness divided by the square of the patient's height, resulting in an AUROC of 81%. Muscle thresholds for sarcopenia were detected, with RA and USMI values correlated with the highest positive (84.3%) and negative (99%) predictive values, respectively. Additionally, the agreement between the US and MRI measurements of RA was excellent (ICC 0.96). CONCLUSIONS: The findings of this study emphasize the potential of muscle US as a reliable diagnostic tool for assessing sarcopenia in IBD patients. This research has significant implications for disease management in IBD patients and underscores the need for further investigations to validate these findings in larger cohorts.

Highlights on Fluorine-containing Drugs Approved by U.S. FDA in 2023.

Fluorine continues to show its potential applications in drug discovery and development, as reflected by twelve drugs being fluorinated out of the fifty-five approved by the FDA in 2023. This concise review highlights the discovery of each of these fluorine-containing drugs in the past year, including its brand name, date of approval, composition, sponsors, indication, and mechanism of action. The relevant future trend is also briefly discussed.

Advancing Personalized Medicine by Analytical Means: Selection of Three Metabolites That Allows Discrimination between Glaucoma, Diabetes, and Controls.

This paper aimed at devising an intelligence-based method to select compounds that can distinguish between open-angle glaucoma patients, type 2 diabetes patients, and healthy controls. Taking the concentration of 188 compounds measured in the aqueous humour (AH) of patients and controls, linear discriminant analysis (LDA) was used to identify the right combination of compounds that could lead to accurate diagnosis. All possibilities, using the leave-one-out approach, were considered through ad hoc programming and in silico massive data production and statistical analysis. Our proof of concept led to the selection of four molecules: acetyl-ornithine (Ac-Orn), C3 acyl-carnitine (C3), diacyl C42:6 phosphatidylcholine (PC aa C42:6), and C3-DC (C4-OH) acyl-carnitine (C3-DC (C4-OH)) that, taken in combination, would lead to a 95% discriminative success. 100% success was obtained with a non-linear combination of the concentration of three of these four compounds. By discarding younger controls to adjust by age, results were similar although one control was misclassified as a diabetes patient. Methods based on the consideration of individual clinical chemical parameters have limitations in the ability to make a reliable diagnosis, stratify patients, and assess disease progression. Leveraging human AH metabolomic data, we developed a procedure that selects a minimal number of metabolites (3-5) and designs algorithms that maximize the overall accuracy evaluating both positive predictive (PPV) and negative predictive (NPV) values. Our approach of simultaneously considering the levels of a few metabolites can be extended to any other body fluid and has potential to advance precision medicine. Artificial intelligence is expected to use algorithms that use the concentration of three to five molecules to correctly diagnose diseases, also allowing stratification of patients and evaluation of disease progression. In addition, this significant advance shifts focus from a single-molecule biomarker approach to that of an appropriate combination of metabolites.

Assessment and diagnostic methods of internal nasal valve: Systematic review and meta-analysis.

Background: Accurate methods are needed to evaluate the anatomy of the internal nasal valve (INV), yet there is currently no ideal measurement technique. Our systematic review aims to establish a comprehensive INV assessment tool, compare different INV diagnostic tools, and establish the most ideal measurement technique for the evaluation of the INV. Methods: A systematic review and meta-analysis were conducted following the PRISMA guidelines, and the study was recorded in PROSPERO under reference number CRD42023407950. A systematic search was performed in PubMed, MEDLINE, The Cochrane Library (Cochrane Databases of Systematic Reviews), and the Cochrane Register of Controlled Trials (CENTRAL) for studies assessing INV that were conducted between 1996 and 2023. Result: Of the 421 total database searches, 23 studies were found, covering a total of 974 patients (6 studies assessed the accuracy of different diagnostic methods, with 2 of these studies comparing two different diagnostic modalities, and 17 studies measured INV angle). Based on the STROBE tool for quality appraisal the mean score was 16.92 ± ± 2.29, indicating a moderate quality. When comparing INV angle values from preoperative and postoperative records as obtained from CT readings, results showed no significant differences between the pre- and postoperative values (MD = -1.8, 95% CI, -4.8 to 1.2, p = .227). Conclusion: Acoustic rhinometry has the highest accuracy, followed by rhinomanometry then CT scan then endoscopy. Meta-analysis showed no significant differences between the pre- and postoperative values and a significant heterogeneity in the reported INV angle values across studies.