Clinical characteristics, management, diagnostic findings, and various etiologies of patients with Kounis syndrome. A systematic review.

BACKGROUND: Kounis syndrome (KS) is defined by the association of acute coronary syndrome secondary to an anaphylactic reaction. KS is often underdiagnosed, and new etiologies have been proposed. AIMS: To synthesize the available evidence on clinical profile, management, diagnosis, and etiologies in patients with KS. METHODS: A search was conducted in the following databases: PubMed, Scopus, EMBASE and Web of Science from inception to March 19th, 2024. Case reports, case series, and observational studies were included. Letters to the editor, editorials, comments, notes, narrative reviews, and systematic reviews were excluded. RESULTS: A total of 190 studies were included (174 case reports, 13 case series, and 3 observational studies, 214 patients). A predominance of male gender was observed (69.63 %). Mean age was 54.4 ± 16.5 years. The most common comorbidities were hypertension (33.64 %), diabetes (16.82 %), and dyslipidemia (16.35 %). The most frequent clinical manifestations were chest pain (66.35 %) and difficulty breathing (34.11 %). Three variants of KS were identified: type I or allergic coronary vasospasm was the most frequent (43.46 %), and type III, the least common (8.88 %). The most frequent etiology was drug use (38.32 %), primarily antibiotics (42.68 %), followed by animal stings or bites (26.17 %). The calculated KS rate was 11.12 per 1000 people. The mortality rate was 7.47 %, and the majority had a favorable outcome (86.92 %) after management. CONCLUSIONS: KS is a complex and underdiagnosed disease that should be considered as a differential diagnosis in acute coronary syndrome associated with an allergic reaction.

Association between frailty and activities of daily living disability in older adults residing in a high-altitude Peruvian Andean community: the Aunqui-Andes study.

BACKGROUND: The prevalence of frailty and activities of daily living (ADL) disability may be higher in high-altitude Andean regions, due to chronic hypoxia, malnutrition, and physical challenges. and their association is relevant. This study aimed to evaluate the association between frailty and ADL disability among older adults residing in the Totos district in Peru during the year 2022. METHODS: A cross-sectional study was conducted in Totos district (mean altitude: 3286 m above sea level), located in Ayacucho, Peru, during 2022. A complete census was employed including residents aged 60 and above. The exposure variable was frailty, defined by fulfilling 3 or more criteria of the Fried phenotype. The outcome variable was ADL disability, defined as a score below 95 on the Barthel index. Generalized linear models with a Poisson family, logarithmic link function, and robust variances were employed to estimate crude prevalence ratios and adjusted prevalence ratios (aPRs), along with their corresponding 95% confidence intervals (CIs). RESULTS: We evaluated 272 older adults with a mean age of 74 years, of whom 59.9% were female, 62.1% were cohabiting or married and 83.1% had not completed primary education. We found that 19.5% were frail, while 51.1% had ADL disability. In the adjusted regression model, we found frailty increased the prevalence of ADL disability (aPR = 1.77; 95%CI: 1.44-2.16; p < 0.001). CONCLUSION: Frailty was associated with an increased prevalence of ADL disability. These findings could contribute to establishing government intervention plans to manage disability and frailty within the high-risk group comprising older adults living at high altitudes.

Preclinical Evaluation of Electronic Health Records (EHRs) to Predict Poor Control of Chronic Respiratory Diseases in Primary Care: A Novel Approach to Focus Our Efforts.

Background/Objectives: Managing chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) within the Spanish Sistema Nacional de Salud (SNS) presents significant challenges, particularly due to their high prevalence and poor disease control rates-approximately 45.1% for asthma and 63.2% for COPD. This study aims to develop a novel predictive model using electronic health records (EHRs) to estimate the likelihood of poor disease control in these patients, thereby enabling more efficient management in primary care settings. Methods: The Seleida project employed a bioinformatics approach to identify significant clinical variables from EHR data in primary care centers in Seville and Valencia. Statistically significant variables were incorporated into a logistic regression model to predict poor disease control in patients with asthma and COPD patients. Key variables included the number of short-acting ß-agonist (SABA) and short-acting muscarinic antagonist (SAMA) canisters, prednisone courses, and antibiotic courses over the past year. Results: The developed model demonstrated high accuracy, sensitivity, and specificity in predicting poorly controlled disease in both asthma and COPD patients. These findings suggest that the model could serve as a valuable tool for the early identification of at-risk patients, allowing healthcare providers to prioritize and optimize resource allocation in primary care settings. Conclusions: Integrating this predictive model into primary care practice could enhance the proactive management of asthma and COPD, potentially improving patient outcomes and reducing the burden on healthcare systems. Further validation in diverse clinical settings is warranted to confirm the model's efficacy and generalizability.

Genotype Characterization and MiRNA Expression Profiling in Usher Syndrome Cell Lines.

Usher syndrome (USH) is an inherited disorder characterized by sensorineural hearing loss (SNHL), retinitis pigmentosa (RP)-related vision loss, and vestibular dysfunction. USH presents itself as three distinct clinical types, 1, 2, and 3, with no biomarker for early detection. This study aimed to explore whether microRNA (miRNA) expression in USH cell lines is dysregulated compared to the miRNA expression pattern in a cell line derived from a healthy human subject. Lymphocytes from USH patients and healthy individuals were isolated and transformed into stable cell lines using Epstein-Barr virus (EBV). DNA from these cell lines was sequenced using a targeted panel to identify gene variants associated with USH types 1, 2, and 3. Microarray analysis was performed on RNA from both USH and control cell lines using NanoString miRNA microarray technology. Dysregulated miRNAs identified by the microarray were validated using droplet digital PCR technology. DNA sequencing revealed that two USH patients had USH type 1 with gene variants in USH1B (MYO7A) and USH1D (CDH23), while the other two patients were classified as USH type 2 (USH2A) and USH type 3 (CLRN-1), respectively. The NanoString miRNA microarray detected 92 differentially expressed miRNAs in USH cell lines compared to controls. Significantly altered miRNAs exhibited at least a twofold increase or decrease with a p value below 0.05. Among these miRNAs, 20 were specific to USH1, 14 to USH2, and 5 to USH3. Three miRNAs that are known as miRNA-183 family which are crucial for inner ear and retina development, have been significantly downregulated as compared to control cells. Subsequently, droplet digital PCR assays confirmed the dysregulation of the 12 most prominent miRNAs in USH cell lines. This study identifies several miRNA signatures in USH cell lines which may have potential utility in Usher syndrome identification.

A Newly Validated HPLC-DAD Method for the Determination of Ricinoleic Acid (RA) in PLGA Nanocapsules.

The assessment of ricinoleic acid (RA) incorporated into polymeric nanoparticles is a challenge that has not yet been explored. This bioactive compound, the main component of castor oil, has attracted attention in the pharmaceutical field for its valuable anti-inflammatory, antifungal, and antimicrobial properties. This work aims to develop a new and simple analytical method using high-performance liquid chromatography with diode-array detection (HPLC-DAD) for the identification and quantification of ricinoleic acid, with potential applicability in several other complex systems. The method was validated through analytical parameters, such as linearity, limit of detection and quantification, accuracy, precision, selectivity, and robustness. The physicochemical properties of the nanocapsules were characterized by dynamic light scattering (DLS) to determine their hydrodynamic mean diameter, polydispersity index (PDI), and zeta potential (ZP), via transmission electron microscopy (TEM) and quantifying the encapsulation efficiency. The proposed analytical method utilized a mobile phase consisting of a 65:35 ratio of acetonitrile to water, acidified with 1.5% phosphoric acid. It successfully depicted a symmetric peak of ricinoleic acid (retention time of 7.5 min) for both the standard and the RA present in the polymeric nanoparticles, enabling the quantification of the drug loaded into the nanocapsules. The nanocapsules containing ricinoleic acid (RA) exhibited an approximate size ranging from 309 nm to 441 nm, a PDI lower than 0.2, ζ values of approximately -30 mV, and high encapsulation efficiency (~99%). Overall, the developed HPLC-DAD procedure provides adequate confidence for the identification and quantification of ricinoleic acid in PLGA nanocapsules and other complex matrices.

Association between papillary thyroid cancer and primary aldosteronism in individuals with hypertension.

BACKGROUND: Aldosterone excess chronically induces oxidative stress and cell proliferation. Previously, a single study investigated primary aldosteronism (PA) in patients with papillary thyroid cancer (PTC), albeit without a matched control group. METHODS: We conducted a propensity score matched case-control study to investigate the association between PA and PTC in individuals with arterial hypertension (HT). PA was investigated in 137 patients with PTC and HT. The control group included 137 (1:1) age, sex-, and body mass index (BMI)-matched individuals with HT. We conducted a secondary analysis in which the controls were also matched according to HT stage. RESULTS: The prevalence of PA was 29.20% (95% confidence interval [CI], 21.91%-37.68%) in the PTC group and 20.44% (95% CI, 14.22%-28.35%) in the controls not matched for HT stage (p = 0.093). Although the PA prevalence was similar in both groups, the frequency of severe HT (stage III or resistant) was significantly lower in the PTC group (23%) compared to the hypertensive controls (73%, p < 0.001). After matching the controls by HT stage, the prevalence of PA in the PTC group was significantly higher compared to the hypertensive controls (9.56%; 95% CI, 5.39%-16.1%, p < 0.0001). In the multivariable analysis, PTC was independently associated with PA in both unmatched hypertensive individuals (odds ratio [OR] 4.74; 95% CI, 2.26-10.55; p< 0.001) and in those matched for HT stage (OR 5.88, 95% CI, 2.79-13.37; p< 0.001). CONCLUSION: PTC was an independent variable associated with a diagnosis of PA in hypertensive individuals. Therefore, we propose the association between PTC and HT as a new recommendation for PA screening regardless of HT severity.

Kidney transplantation outcomes: Is it possible to improve when good results are falling down?

Famure et al describe that close to 50% of their patients needed early or very early hospital readmissions after their kidney transplantation. As they taught us the variables related to those outcomes, we describe eight teaching capsules that may go beyond what they describe in their article. First two capsules talk about the ideal donors and recipients we should choose for avoiding the risk of an early readmission. The third and fourth capsules tell us about the reality of cadaveric donors and recipients with comorbidities, and the way transplant physicians should choose them to maximize survival. Fifth capsule shows that any mistake can result in an early readmission, and thus, in poorer outcomes. Sixth capsule talks about economic losses of early readmissions, cost-effectiveness of transplantation, and how to improve outcomes and reduce costs by managing a risky patient-portfolio. Seventh capsule argues about knowing your risk behavior to better manage your portfolio; and Eighth capsule about the importance of the center experience in transplanting complex patients. We finish with some lessons of the importance of the transplantation process and the collaboration with other disciplines in order to prevent the conditions that lead to early readmissions.

Donor hepatectomy time and liver transplantation outcomes: An opportunity that cannot be dismissed.

The probability of developing primary dysfunction (PD) is a function of the probability of ischemia/reperfusion (I/R) injury. The probability of I/R injury in turn, is a function of several donor and transplantation process variables, among which is ischemia time. Custodio et al studied the duration of a special type of warm ischemia and showed, contrary to what is known, that a longer duration is not statistically different from a shorter one in PD development. This finding opens the door to the unforeseen opportunity of training fellows in performing hepatectomies, since the duration will not jeopardize liver transplant outcomes, albeit with some precautions.

Association between Subclinical Hypothyroidism and Glycemic Control in Older Adults in a Medical Center in Peru.

Objective: To determine whether there is an association between subclinical hypothyroidism and glycemic control in older adults who received care at the "Centro Médico Naval" from 2010 to 2015. Methods: This retrospective analytical study analyzed a secondary database of the care of elderly in the study hospital. The sample was comprised of 1,385 older adults. To detect an association between variables, the Poisson regression with robust variance was used at a significance level of 95%. The analyses were carried out with the STATA 16 program. Results: Of the elderly 45.6% were between 71 and 80 years old; 58.4% were women and 43.8% had a normal body mass index. There was evidence of inadequate glycemic control in 8.1% and subclinical hypothyroidism in 15.2% of the elderly patients. Subclinical hypothyroidism was more frequent in the inadequate glycemic control vs. adequate glycemic control populations (41.1% vs. 13.0%). In the multivariance analysis, subclinical hypothyroidism (aPR = 2.22 95% CI [1.47-3.36]) was independent factor associated with inadequate glycemic control (p < 0.001). Conclusions: A significant association was detected between subclinical hypothyroidism and inadequate glycemic control in older adults who presented at the "Centro Médico Naval" from 2010 to 2015.

New insights on the Jacobsite mineral from Bahia and related synthetic manganese-ferrite nanoparticles.

Jacobsite is a relatively rare mineral of composition MnFe2O4, found in Urandi (Bahia State) in Brazil. It is also a common species in the deep-sea manganese nodules, attracting the interest of many mineral-extracting companies. Because of its spinel constitution similar to magnetite, Jacobsite is commonly called a manganese-ferrite. However, the manganese/iron content may vary substantially according to its origin, demanding specific studies in each case. The Jacobsite mineral inspired our laboratory synthesis of the analogous manganese ferrite nanoparticles. The direct synthesis by the coprecipitation method has not been successful; however, it can be carried in the presence of citrate ions, yielding strongly magnetic nanoparticles, with a maximum magnetization of 45.6 emu.g1. Although they were structurally identical to Jacobsite, the mineral from Bahia exhibited a rather weak magnetism, because it involves a ferrimagnetic coupling. For this reason, the synthetic method seems to provide a better way of obtaining strongly magnetic manganese ferrites. These magnetic nanoparticles have been investigated in detail, including their interaction with diatoms, providing interesting magnetic bio-silicate carriers in drug delivery.

Wine Volatilome as Affected by Tartaric Stabilization Treatments: Cold Stabilization, Carboxymethylcellulose and Metatartaric Acid.

The primary cause of bottled wine sediment is tartrate crystal precipitation. To prevent this, wines undergo a stabilization process before bottling. The most commonly used method is cold stabilization, which induces the precipitation of tartrate crystals that are then removed, thereby eliminating the excess ions that cause instability in wine. Another approach to tartaric stabilization is using enological stabilizers with a colloid protective effect, which prevents the formation of tartrate crystals. The most commonly used tartaric stabilizers are sodium carboxymethylcellulose (CMC) and metatartaric acid. However, both have drawbacks: they are semi-synthetic products, and metatartaric acid degrades over time, losing its stabilizing effect. This study aims to compare the effects of cold stabilization, stabilization with CMC, and metatartaric acid on the chemical composition, particularly the volatilome, of white, rosé, and red wines. Cold stabilization significantly impacted the wine volatilome, especially in white and rosé wines, by decreasing total alcohols and increasing total esters. It also reduced the color intensity of rosé and red wines by lowering monomeric anthocyanins. In contrast, enological stabilizers had minimal impact on the wines' phenolic composition, chromatic characteristics, and volatilome. The sensory impact of cold stabilization is complex; it can potentially enhance the aroma of white and rosé wines by increasing ester VOCs and decreasing higher alcohols, but it negatively affects the color of rosé and red wines.

Analysis of Neuroradiologic Findings in Idiopathic Intracranial Hypertension-A Population-Based Study.

BACKGROUND: Idiopathic intracranial hypertension (IIH) has been associated with several MRI features. We assessed types of MRI findings and clinical-radiologic correlations in patients with IIH from one hospital system. METHODS: A retrospective chart review of IIH and control patients was conducted. Brain MRI/magnetic resonance venogram features were enumerated and assessed for correlation with body mass index (BMI) and lumbar puncture opening pressure (LPOP). Sensitivity, specificity, positive predictive value (PPV), and likelihood ratios (LRs) were calculated for each MRI sign. Significance was set at P < 0.05. RESULTS: One hundred one patients diagnosed with IIH, and 119 control patients had complete files and were included. Patients with IIH were predominantly female (92.8% vs 59.7%; P = <0.001), younger (30.6 years vs 46.4 years; P < 0.001), and more obese (mean BMI = 35.2 vs 29.3; P < 0.001) than controls. Mean (SD) number of MRI findings was 2.21 (1.8) in IIH and 0.6 (1.2) in controls; (P < 0.001). Vertical nerve tortuosity (44.1%; P < 0.001), TVSS (37.8%; P < 0.001), sheath expansion (36.0%; P < 0.001), globe flattening (22.5%; P < 0.001), slit ventricles (18.9%; P < 0.001), optic disc protrusion (9.9%; P = 0.007), and complete empty sella (12.6%; P < 0.042) were observed more in patients with IIH than control patients. In the IIH group, mean (SD) LPOP was 33.6 (11.11) cmH2O and weakly correlated with number of MRI findings (rho = 0.182, P = 0.057). TVSS (sensitivity 37.84%; confidence interval [CI] 29.3%-47.2%, specificity 98.32%; CI 93.5%-99.6%) had the highest PPV (95.45%) and positive LR (22.51) for IIH diagnosis. CONCLUSIONS: These results are consistent with IIH predominance in young, obese females. In patients with IIH, the number of MRI findings exceeded controls and positively correlated with LPOP. TVSS was most predictive of IIH.

The influence of paraventricular nucleus of the hypothalamus soluble guanylate cyclase on autonomic and neuroendocrine responses to acute restraint stress in rats.

The paraventricular nucleus of the hypothalamus (PVN) regulates physiological and behavioural responses evoked by stressful stimuli, but the local neurochemical and signalling mechanisms involved are not completely understood. The soluble guanylate cyclase (sGC) within the PVN is implicated in autonomic and cardiovascular control in rodents under resting conditions. However, the involvement of PVN sGC-mediated signalling in stress responses is unknown. Therefore, we investigated the role of sGC within the PVN in cardiovascular, autonomic, neuroendocrine, and local neuronal responses to acute restraint stress in rats. Bilateral microinjection of the selective sGC inhibitor ODQ (1 nmol/100 nl) into the PVN reduced both the increased arterial pressure and the drop in cutaneous tail temperature evoked by restraint stress, while the tachycardia was enhanced. Intra-PVN injection of ODQ did not alter the number of Fos-immunoreactive neurons in either the dorsal cap parvocellular (PaDC), ventromedial (PaV), medial parvocellular (PaMP), or lateral magnocelllular (PaLM) portions of the PVN following acute restraint stress. Local microinjection of ODQ into the PVN did not affect the restraint-induced increases in plasma corticosterone concentration. Taken together, these findings suggest that sGC-mediated signalling in the PVN plays a key role in acute stress-induced pressor responses and sympathetically mediated cutaneous vasoconstriction, whereas the tachycardiac response is inhibited. Absence of an effect of ODQ on corticosterone and PVN neuronal activation in and the PaV and PaMP suggests that PVN sGC is not involved in restraint-evoked hypothalamus-pituitary-adrenal (HPA) axis activation and further indicates that autonomic and neuroendocrine responses are dissociable at the level of the PVN.

[Severe asthma: Pathophysiology, diagnosis, and treatment]. / Asma grave: fisiopatología, diagnóstico y tratamiento.

Severe asthma is an entity with a complex diagnosis, requiring an adequate differential diagnosis and identification of endotypes for a correct approach and therapeutic process. In the present review, we show a synthesis of the current literature on the diagnosis, pathophysiology, and management of severe asthma, having critically analyzed the evidence in search engines such as Medline, Scopus, and Embase.

El asma grave es una enfermedad compleja, que requiere un enfoque y diagnóstico diferencial ordenado e identificación de endotipos para el correcto abordaje y tratamiento. El tratamiento farmacológico cuenta cada vez con más moléculas a disposición del personal médico para el control efectivo de los síntomas. Esta revisión muestra una síntesis de la bibliografía actual acerca del diagnóstico, fisiopatología y tratamiento del asma grave, mediante la lectura crítica previa de la evidencia científica en buscadores como Medline, Scopus y Embase.

Sleep disorder syndromes of post-acute sequelae of SARS-CoV-2 (PASC) / Long Covid.

INTRODUCTION: COVID-19 infection has resulted in a high prevalence of a post-infectious syndrome, known as post-acute sequelae of SARS-CoV-2 (PASC) or "Long COVID". PASC is a heterogeneous disease with a high prevalence of sleep disturbances, varying from an insomnia disorder to excessive daytime sleepiness. METHODS: Patients seen in the Covid Survivorship Program at the Beth Israel Deaconess Medical Center Boston, USA, were screened for sleep disorders as part of a comprehensive multi-system evaluation. Those who screened positive were referred for a comprehensive sleep evaluation in a dedicated COVID-19-Sleep clinic, followed by diagnostic sleep testing and treatment. This report summarizes patients who completed an American Academy of Sleep Medicine (AASM) accredited facility-based diagnostic evaluation. International Classification of Sleep Disorders 3rd Edition-Revised criteria were met for all diagnoses. RESULTS: In 42 patients with PASC, five categories of sleep disorder syndromes were observed following a sleep clinic evaluation, including obstructive sleep apnea, chronic insomnia disorder, primary hypersomnia, REM behavior disorder (RBD), and new onset circadian phase delay. Seven patients met criteria for idiopathic hypersomnia, and two had narcolepsy type 2. RBD patients were infected in three different waves; circadian disturbance patients were all infected in the winter wave of 2020/21, and the primary hypersomnolence group occurred during all waves, predominantly the initial wave of 2020. A peculiar form of insomnia was a persistent loss of sleep regularity. CONCLUSIONS: Specific sleep symptoms/syndromes are reported in this select group of patients with PASC/Long Covid. As new onset sleep complaints are prevalent in PASC, we recommend a complete clinical and investigative sleep evaluation for persistent severe sleep symptoms following COVID-19 infection.

Unexpected Rasburicase-Induced Hemolysis in a Patient With Normal Glucose-6-Phosphate Dehydrogenase Activity.

Tumor lysis syndrome (TLS) presents significant challenges in oncology, primarily due to metabolic complications such as hyperuricemia, which can lead to acute kidney injury. Rasburicase, a recombinant urate oxidase, is frequently employed to manage hyperuricemia in TLS patients. However, its use is an absolute contraindication in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to the risk of hemolysis. In this case, the patient developed hemolytic anemia post-rasburicase administration even though she had normal G6PD activity, which was confirmed on two separate occasions, including during an acute episode and 3 months later. This case is unique as it documents hemolytic anemia induced by rasburicase in a patient without G6PD deficiency, challenging current understandings of the drug's safety profile. It suggests the need for caution and thorough screening before rasburicase use, even in patients considered low risk for G6PD deficiency. The report highlights the importance of close monitoring for adverse effects and the potential for alternative mechanisms of rasburicase-induced hemolysis.

Development of a unified method for the determination of legacy and metabolites of current pesticides in serum for exposure assessment.

The use of pesticides is often regarded as a fundamental aspect of conventional agriculture. However, these compounds have gained recognition as some of the oldest and most widely employed xenobiotic contaminants, necessitating effective strategies for human biomonitoring. In this context, a method was developed for the determination of 16 legacy organochlorine pesticides, 6 metabolites of current pesticides (2,4-D, malathion, parathion, fipronil, pyraclostrobin, cypermethrin, permethrin, cyfluthrin), and 1 triazine herbicide (atrazine) in serum. Samples were prepared with water, formic acid, acetonitrile, and ultrasound irradiation, followed by solid-phase extraction with Oasis Prime HLB. Subsequently, metabolites from current pesticides underwent derivatization using MTBSTFA with 1% TBDMSCl for analysis via gas chromatography-tandem mass spectrometry (GC-MS/MS), employing an SLB-5MS fused silica capillary column. Analytical curves were generated with limits of quantification from 0.3 to 4.0 ng.mL-1. Accuracy ranged from 69 to 124%, and the coefficient of variation from 2 to 28%. Moreover, determining 1-(4-chlorophenyl)-1H-pyrazol-3-ol was suggested as a biomarker for pyraclostrobin biomonitoring. This analytical approach facilitated the determination of both legacy and metabolites of current pesticides in the same serum sample, presenting an interesting and cost-effective option for large cohorts, and multi-omics studies that evaluate time-dependent biomarkers in blood samples, thereby enabling biomonitoring within the same matrix. Furthermore, a proof-of-concept involving 10 volunteers demonstrated exposure to 9 pesticides at mean concentrations measured in ng mL-1, consistent with findings from various biomonitoring initiatives.