Evaluating CD1a Immunohistochemistry for Tegumentary Leishmaniasis Diagnosis in the New World: A Focus on Colombia.

INTRODUCTION: Leishmaniasis, a chronic vector-borne disease caused by parasites of the genus Leishmania, presents diagnostic challenges. Conventional diagnostic methods struggle with accurate visualization of these parasites. Immunostaining with CD1a has demonstrated effectiveness in visualizing Leishmania parasites, particularly in the Old World. However, the application of CD1a immunostaining in Colombian leishmaniasis remains unexplored. OBJECTIVE: To determine the utility of CD1a as an immunomarker in detecting chronic forms of tegumentary leishmaniasis. MATERIALS AND METHODS: This proof-of-concept study involved 48 paraffin-embedded samples categorized into 3 groups: moderate-to-high parasite load (n = 15), low load (n = 15), and chronic granulomatous inflammation (n = 13); 5 samples diagnosed with cutaneous histoplasmosis. These samples were stained with the immunomarker CD1a clone EP3622 for comparative analysis. In addition, CD1a immunohistochemistry was compared with 18S rDNA qPCR and hematoxylin-eosin staining to evaluate its performance in relation to these established methods. RESULTS: CD1a immunohistochemistry was positive in 46.51% of the samples evaluated. This immunomarker showed lower sensitivity and negative predictive value than 18S rDNA qPCR and hematoxylin-eosin staining; specificity and negative predictive value were consistent. ROC indicated inferior discrimination for leishmaniasis compared with 18 s rDNA qPCR and hematoxylin-eosin staining. CONCLUSIONS: Immunohistochemistry for CD1a could be a diagnostic support in the detection of chronic forms of tegumentary leishmaniasis.

Evaluation of Muscle Mass and Malnutrition in Patients with Colorectal Cancer Using the Global Leadership Initiative on Malnutrition Criteria and Comparing Bioelectrical Impedance Analysis and Computed Tomography Measurements.

OBJECTIVES: The aim of this investigation was to evaluate the discrepancies between bioelectrical impedance analysis (BIA) and computed tomography (CT) in assessing skeletal muscle mass and identifying low muscle mass in patients with colorectal cancer. METHODS: This study recruited 137 patients with colorectal cancer from February 2028 to December 2023. CT scans were analyzed at the Lumbar 3 vertebral level to determine the area of skeletal muscle, which was then utilized to estimate whole-body skeletal muscle mass. [BIA] was also employed to measure skeletal muscle. Both skeletal muscle mass values [kg] were divided by height2 [m2] to calculate the skeletal muscle index [SMI, kg/m2], denoted as SMI-CT and SMI-BIA, respectively. RESULTS: The median age was 69.8 + 9.5 years, with the sex ratio being 88/49 [male/female]. Whereas more than one-third of the patients were classified as malnourished based on the Global Leadership Initiative on Malnutrition GLIM-CT criteria using L3-SMI [n = 36.5%], fewer patients were classified as malnourished based on GLIM-BIA using SMI-BIA [n = 19.0%]. According to the CT analysis [low SMI-L3], 52 [38.0%] patients were diagnosed as having poor muscle mass, whereas only 18 [13.1%] patients were identified as having low muscle mass using BIA [low SMIBIA]. The measured SMI showed a positive association with SMI-CT in all patients [r = 0.63, p < 0.001]. Using Bland-Altman evaluation, a significant mean bias of 0.45 + 1.41 kg/m2 [95% CI 0.21-0.70; p < 0.001] between SMI-BIA and SMI-CT was reported. Receiver operating characteristic (ROC) curves were generated to detect poor muscle mass using SMI-BIA with CT as the gold standard. The area under the curve (AUC) for SMI-BIA in identifying poor muscle mass was 0.714 (95% CI: 0.624-0.824), with a good cut-off value of 8.1 kg/m2, yielding a sensitivity of 68.3% and a specificity of 66.9%. CONCLUSIONS: BIA generally overestimates skeletal muscle mass in colorectal cancer patients when contrasted to CT. As a result, BIA may underestimate the prevalence of poor muscle mass and malnutrition according to the GLIM criteria in this patient population.

Weight-adjusted waist index predicts metabolic syndrome in Caucasian patients with obesity.

BACKGROUND AND AIMS: the usefulness of the weight-adjusted waist index (WWI) among persons with metabolic syndrome (MS) has not been previously evaluated. The objective of this study was to evaluate the ability of WWI to predict MS in a Caucasian population with obesity. METHODS: we conducted a cross sectional study in 2162 Caucasian patients with obesity. Anthropometric data (weight, height, body mass index [BMI], waist circumference, [WWI]), bioimpedanciometer parameters (total fat mass [FM], skeletal muscle mass [SMM] and skeletal muscle mass index [SMMi]), blood pressure, presence of MS and biochemical parameters were recorded and compared by tertiles of WWI. RESULTS: a total of 1,176 subjects had MS (54.4 %) and 986 did not show MS (45.6 %). Compared with the lowest WWI category Q1 (< 11.24 cm/√kg), the prevalence of MS increased in the logistic regression model adjusted by sex and age in the Q3 group (OR = 2.53, 95 % CI = 1.71-3.23; p = 0.001). In addition, the prevalence of MS was higher in the Q3 group than in Q2 (OR = 1.65, 95 % CI = 1.25-2.17; p = 0.005). Finally, the prevalence of MS in Q2 was higher than in the Q1 group (OR = 1.21, 95 % CI = 1.06-3.11; p = 0.01). The area under the curve (AUC) to assess the ability of WWI to identify MS showed values of 0.811 (0.687-0.871; p = 0.001). The cut-off point according to the Youden index was 11.59, with sensitivity and specificity of 70 % and 93.4 %, respectively. CONCLUSION: we described a good accuracy of WWI to identify MS an independent association between WWI in Caucasian patients with obesity.

Identification of host endotypes using peripheral blood transcriptomics in a prospective cohort of patients with endocarditis.

OBJECTIVES: Host responses to infection are a major determinant of outcome. However, the existence of different response profiles in patients with endocarditis has not been addressed. Our objective was to apply transcriptomics to identify endotypes in patients with infective endocarditis. METHODS: A total of 32 patients with infective endocarditis were studied. Clinical data and blood samples were collected at diagnosis and RNA sequenced. Gene expression was used to identify two clusters (endocarditis endotype 1 [EE1] and endocarditis endotype 2 [EE2]). RNA sequencing was repeated after surgery. Transcriptionally active cell populations were identified by deconvolution. Differences between endotypes in clinical data, survival, gene expression, and molecular pathways involved were assessed. The identified endotypes were recapitulated in a cohort of COVID-19 patients. RESULTS: A total of 18 and 14 patients were assigned to EE1 and EE2, respectively, with no differences in clinical data. Patients assigned to EE2 showed an enrichment in genes related to T-cell maturation and a decrease in the activation of the signal transducer and activator of transcription protein family pathway, with higher counts of active T cells and lower counts of neutrophils. A total of 14 patients (nine in EE1 and five in EE2) were submitted to surgery. Surgery in EE2 patients shifted gene expression toward a EE1-like profile. In-hospital mortality was higher in EE1 (56% vs 14%, P = 0.027), with an adjusted hazard ratio of 12.987 (95% confidence interval 3.356-50). Translation of these endotypes to COVID-19 and non-COVID-19 septic patients yielded similar results in cell populations and outcome. CONCLUSIONS: Gene expression reveals two endotypes in patients with acute endocarditis, with different underlying pathogenetic mechanisms, responses to surgery, and outcomes.

Exploring the Trade-Off between generalist and specialized Models: A center-based comparative analysis for glioblastoma segmentation.

INTRODUCTION: Inherent variations between inter-center data can undermine the robustness of segmentation models when applied at a specific center (dataset shift). We investigated whether specialized center-specific models are more effective compared to generalist models based on multi-center data, and how center-specific data could enhance the performance of generalist models within a particular center using a fine-tuning transfer learning approach. For this purpose, we studied the dataset shift at center level and conducted a comparative analysis to assess the impact of data source on glioblastoma segmentation models. METHODS & MATERIALS: The three key components of dataset shift were studied: prior probability shift-variations in tumor size or tissue distribution among centers; covariate shift-inter-center MRI alterations; and concept shift-different criteria for tumor segmentation. BraTS 2021 dataset was used, which includes 1251 cases from 23 centers. Thereafter, 155 deep-learning models were developed and compared, including 1) generalist models trained with multi-center data, 2) specialized models using only center-specific data, and 3) fine-tuned generalist models using center-specific data. RESULTS: The three key components of dataset shift were characterized. The amount of covariate shift was substantial, indicating large variations in MR imaging between different centers. Glioblastoma segmentation models tend to perform best when using data from the application center. Generalist models, trained with over 700 samples, achieved a median Dice score of 88.98%. Specialized models surpassed this with 200 cases, while fine-tuned models outperformed with 50 cases. CONCLUSIONS: The influence of dataset shift on model performance is evident. Fine-tuned and specialized models, utilizing data from the evaluated center, outperform generalist models, which rely on data from other centers. These approaches could encourage medical centers to develop customized models for their local use, enhancing the accuracy and reliability of glioblastoma segmentation in a context where dataset shift is inevitable.

Long-Term Risks of Benign and Malign Complications after Endoscopic Sphincterotomy in the Management of Benign Biliopancreatic Pathology: A Cohort Study.

BACKGROUND:  Endoscopic retrograde cholangiopancreatography (ERCP) is the preferred technique for treating pathologies of the bile duct. It has been suggested that this procedure, combined with sphincterotomy, may influence the subsequent development of long-term complications. The main objective of this study was to determine the long-term complications of biliopancreatic disease after ERCP and their potential association with the development of biliopancreatic neoplasms. METHODS:  This retrospective cohort study included 576 patients who underwent ERCP (referred to as index ERCP) with sphincterotomy for benign biliary disease, with a minimum follow-up period of more than 2 years. RESULTS:  The incidence of long-term benign and neoplastic pathologies after ERCP was analyzed. The most common findings were recurrence of choledocholithiasis in 70 patients (12.1%), cholangitis "sine materia" in 27 patients (4.7%), and acute pancreatitis in 8 patients (1.4%). Eight patients (1.4%) developed hepatobiliopancreatic neoplasms, including 4 cases of pancreatic neoplasms (0.7%), 1 cholangiocarcinoma (0.2%), 1 ampulloma (0.2%), and 2 intrahepatic neoplasms (0.3%). Multivariate analysis revealed that factors such as age over 50 years, previous biliary surgery, diversion of the bile duct (BD) to the digestive tract, dilation of the BD, stent placement, biopsy, and cholecystectomy were factors associated with an increased risk of long-term benign complications. CONCLUSION:  Endoscopic retrograde cholangiopancreatography with sphincterotomy is associated with an increased long-term risk of subsequent benign biliopancreatic disease. However, our data do not allow us to establish a direct relationship with the development of biliopancreatic neoplasms.

Prevalence of transthyretin cardiac amyloidosis in patients with heart failure with preserved ejection fraction: the PRACTICA study.

INTRODUCTION AND OBJECTIVES: Transthyretin cardiac amyloidosis (ATTR-CA) is a frequent cause of heart failure with preserved ejection fraction (HFpEF). This study sought to determine the prevalence of ATTR-CA among HFpEF patients in a multicenter nationwide study. METHODS: Consecutive ambulatory or hospitalized patients aged ≥ 50 years with HFpEF and left ventricle hypertrophy ≥ 12mm were studied at 20 Spanish hospitals. Screening for cardiac amyloidosis was initiated according to the usual clinical practice of each center. Positive scintigraphs were centrally analyzed. RESULTS: 422 patients were included, of whom 387 underwent further screening for cardiac amyloidosis. A total of 65 patients (16.8%) were diagnosed with ATTR-CA, none below 75 years. There was an increase of prevalence with age. Of them, 60% were male, with a mean age of 85.3±5.2 years, mean left ventricle ejection fraction of 60.3±7.6% and a mean maximum left ventricle wall thickness of 17.2 [12-25] mm. Most of the patients were New York Heart Association class II (48.4%) or III (46.8%). Besides being older than non-ATTR-CA patients, ATTR-CA patients had higher median NT-proBNP levels (3801 [2266-7132] vs 2391 [1141-4796] pg/mL; P=.003). There was no statistical difference in the prevalence of ATTR-CA by sex (19.7% for men and 13.8% for women, P=.085). A ∼7% (4/56) of the patients exhibited a genetic variant (ATTRv). CONCLUSIONS: This multicenter nationwide study found a prevalence of 16.8%, confirming that ATTR-CA is a significant contributor to HFpEF in male and female patients with left ventricle hypertrophy and more than 75 years.

Tattoos: risks and complications, clinical and histopathological approach

Abstract Background Skin modification through tattoos is as old as humanity itself. However, this trend is on the rise, and with the use of different types of pigments and application practices, both cutaneous and systemic complications can arise. Adverse reactions can be grouped into five classes: inflammatory, infectious, neoplastic, aesthetic, and miscellaneous. On histopathology, inflammatory reactions can exhibit a lichenoid pattern or present as spongiotic dermatitis, granulomatous reactions, pseudolymphoma, pseudoepitheliomatous hyperplasia, or scleroderma/morphea-like changes. This article reviews tattoo complications, including their clinical and histopathological characteristics. Methods An open search was conducted on PubMed using the terms "tattoo", "complications", and "skin". No limits were set for period, language, or publication type of the articles. Results Reactions to tattoos are reported in up to 67% of people who get tattooed, with papulonodular and granulomatous reactions being the most common. Some neoplastic complications have been described, but their causality is still debated. Any pigment can cause adverse reactions, although red ink is more frequently associated with them. Patients with pre-existing dermatoses may experience exacerbation or complications of their diseases when getting tattoos; therefore, this procedure is not recommended for this patient group. Conclusions Dermatological consultation is recommended before getting a tattoo, as well as a histopathological examination in case of complications. In patients who develop cutaneous inflammatory reactions following tattooing, additional studies are recommended to investigate systemic diseases such as sarcoidosis, pyoderma gangrenosum, atopic dermatitis, and neoplasms. It is important for physicians to be trained in providing appropriate care in case of complications.

Quality of Life and Psychological Changes in Bariatric Surgery: An Observational Study.

INTRODUCTION: Candidates for bariatric surgery may have psychiatric disorders that must be evaluated. The aim of this study was to describe the psychological state and quality of life (QoL) of patients with obesity awaiting bariatric surgery prior to surgical procedure and 1 year after surgery. METHODS: A longitudinal retrospective observational study was carried out in 71 patients awaiting bariatric surgery. Anthropometric data were collected, and the following were evaluated before and 1 year after the intervention: 44 patients were evaluated to rule out personality disorder, using the Salamanca Questionnaire of Personality Disorders; eating disorder, with the Bulimia Test of Edinburgh (BITE); depression, using the Beck Depression Inventory (BDI); and 71 patients were evaluated QoL, with the "36-Item Short Form Health Survey" (SF-36). RESULTS: A total of 34.1% (n = 15) of patients presented personality disorder (group B most frequent). A total of 31.8% (n = 14) obtained scores suggesting anomalous food behavior (6.8%, n = 3 severe). According to the BDI, 43.2% (n = 19) showed low mood prior to the intervention. Lower scores were obtained when evaluating QoL for physical functioning (physical function: 56.81 ± 24.9; physical problems: 66.76 ± 37.64). One year after the intervention, QoL improved in those patients who underwent the sleeve gastrectomy (SG). CONCLUSIONS: Patients with bariatric surgery more frequently presented with type B and C personalities. One year after bariatric surgery, an improvement in QoL test was observed. Patients who underwent SG technique showed better mean scores than those after biliopancreatic diversion.

Perineural Invasion of Cranial Nerves in Cutaneous Squamous Cell Carcinoma: Unraveling Its Complexities, Diagnostic Challenges, and Multifaceted Treatment Approaches.

Cutaneous squamous cell carcinoma is the second most common neoplasm among non-melanoma skin cancers. When associated with perineural invasion of the cranial nerves, with clinical features often observed in trigeminal and facial nerves due to their cutaneous extension, it may lead to a worse prognosis. This paper introduces a rare case of an 81-year-old male, with a history of a moderately differentiated invasive carcinoma of the left frontal region with perineural invasion on the left trigeminal cranial nerve. The case underscores the aggressive nature of the intraneural infiltration by squamous cell carcinoma and the challenges in managing such advanced malignancies.

Endovascular stenting using a sagittal sinus approach for sigmoid sinus wall dehiscence related to intractable pulsatile tinnitus: a case series.

BACKGROUND: Sigmoid sinus wall dehiscence can lead to pulsatile tinnitus with a significant decrease in quality of life, occasionally leading to psychiatric disorders. Several surgical and endovascular procedures have been described for resolving dehiscence. Within endovascular procedures, the sagittal sinus approach could be a technical alternative for tracking and accurate stent positioning within the sigmoid sinus when the jugular bulb anatomy is unfavorable. CASE PRESENTATION: A retrospective case series of three patients with pulsatile tinnitus due to sigmoid sinus wall dehiscence without intracranial hypertension was reviewed from January 2018 to January 2022. From the participants enrolled, the median age was 50.3 years (range 43-63), with 67% self-identifying as female and 33% as male. They self-identified as Hispanic. Sigmoid sinus dehiscence was diagnosed using angiotomography, and contralateral transverse sinus stenosis was observed in all patients. Patients underwent surgery via a navigated endovascular sagittal sinus approach for sigmoid sinus stenting. No neurological complications were associated with the procedure. Pulsatile tinnitus improved after the procedure in all patients. CONCLUSIONS: Superior sagittal sinus resection for sigmoid sinus wall stenting is a safe and effective technique. Pulsatile tinnitus due to sigmoid sinus wall dehiscence could be treated using the endovascular resurfacing stenting technique. However, further research is needed to evaluate the potential benefit of contralateral stenting for removing sinus dehiscence when venous stenosis is detected. However, resurfacing sigmoid sinus wall dehiscence results in symptomatic improvement.

Combined open maxillectomy and endoscopic endonasal resection of a giant V2 trigeminal schwannoma.

BACKGROUND: Trigeminal schwannoma is a rare type of tumor that arises from the Schwann cells of the trigeminal nerve. METHOD: We present a case of a patient with a giant V2 trigeminal schwannoma with painful swelling in the left maxilla. A complete resection using a combined open maxillectomy and endoscopic endonasal approach was performed. CONCLUSION: This case highlights the importance of a multidisciplinary approach to perform a combined open and endoscopic approach for safe resection while preserving adequate speech and swallowing.

The prognostic relevance of a gene expression signature in MRI-defined highly vascularized glioblastoma.

Background: The vascular heterogeneity of glioblastomas (GB) remains an important area of research, since tumor progression and patient prognosis are closely tied to this feature. With this study, we aim to identify gene expression profiles associated with MRI-defined tumor vascularity and to investigate its relationship with patient prognosis. Methods: The study employed MRI parameters calculated with DSC Perfusion Quantification of ONCOhabitats glioma analysis software and RNA-seq data from the TCGA-GBM project dataset. In our study, we had a total of 147 RNA-seq samples, which 15 of them also had MRI parameter information. We analyzed the gene expression profiles associated with MRI-defined tumor vascularity using differential gene expression analysis and performed Log-rank tests to assess the correlation between the identified genes and patient prognosis. Results: The findings of our research reveal a set of 21 overexpressed genes associated with the high vascularity pattern. Notably, several of these overexpressed genes have been previously implicated in worse prognosis based on existing literature. Our log-rank test further validates that the collective upregulation of these genes is indeed correlated with an unfavorable prognosis. This set of genes includes a variety of molecules, such as cytokines, receptors, ligands, and other molecules with diverse functions. Conclusions: Our findings suggest that the set of 21 overexpressed genes in the High Vascularity group could potentially serve as prognostic markers for GB patients. These results highlight the importance of further investigating the relationship between the molecules such as cytokines or receptors underlying the vascularity in GB and its observation through MRI and developing targeted therapies for this aggressive disease.

Spinal Cord Syndrome Due to Extramedullary Epithelioid Hemangioendothelioma of the Thoracic Spine: A Case Report and Literature Review.

We report a 48-year-old male patient with spinal epithelioid hemangioendothelioma in T3 and T4 who began with symptoms of paresthesia in the lower limbs and distal weakness of the right lower limb, back pain, increased limitation in walking, urinary incontinence, and constipation. A safe maximum resection was performed, finding residual disease during the PET/CT scan, so it was decided to treat with radiotherapy, and there was a good response to this treatment. A literature review of epithelioid hemangioendothelioma of the thoracic spine was done which showed a mean age of presentation of 41 years and a male-female ratio of 1:0.53. The main symptom was pain, which was present in 100% of the patients, and wide surgery was performed in 56.8% of the patients, intralesional surgery in 31.8%, and biopsy in 11.4%. A total of 46.6% of patients received radiation therapy, and only 6.6% received chemotherapy. The patients had an average follow-up of 38 months. We recommend that extension studies such as PET/CT scans be performed after surgical resection. This can serve as a follow-up with hemangioendothelioma epithelioma patients about metastatic disease or residual disease that will guide us in giving adjuvant treatments, such as radiotherapy or chemotherapy, for better control of the disease.

Evaluation of [18F]fluoroestradiol and ChRERα as a gene expression PET reporter system in rhesus monkey brain.

Positron emission tomography (PET) reporter systems are a valuable means of estimating the level of expression of a transgene in vivo. For example, the safety and efficacy of gene therapy approaches for the treatment of neurological and neuropsychiatric disorders could be enhanced via the monitoring of exogenous gene expression levels in the brain. The present study evaluated the ability of a newly developed PET reporter system [18F]fluoroestradiol ([18F]FES) and the estrogen receptor-based PET reporter ChRERα, to monitor expression levels of a small hairpin RNA (shRNA) designed to suppress choline acetyltransferase (ChAT) expression in rhesus monkey brain. The ChRERα gene and shRNA were expressed from the same transcript via lentivirus injected into monkey striatum. In two monkeys that received injections of viral vector, [18F]FES binding increased by 70% and 86% at the target sites compared with pre-injection, demonstrating that ChRERα expression could be visualized in vivo with PET imaging. Post-mortem immunohistochemistry confirmed that ChAT expression was significantly suppressed in regions in which [18F]FES uptake was increased. The consistency between PET imaging and immunohistochemical results suggests that [18F]FES and ChRERα can serve as a PET reporter system in rhesus monkey brain for in vivo evaluation of the expression of potential therapeutic agents, such as shRNAs.

¿Será realmente una verdadera comunicación interventricular? / Could it really be a true ventricular septal defect?

Ventricular septal defect (VSD) is one of the most common congenital defects. It has a wide variety of clinical spectrum of presentation depending on the location and size of the defect. Generally, small restrictive VSDs present spontaneous closure during follow-up. A clinical case is presented with suspected persistent perimembranous VSD, with described intraoperative anatomical findings of aneurysmal cribriform membrane, ruling out VSD.

La comunicación interventricular (CIV) es uno de los defectos congénitos más comunes. Tiene una amplia variedad de espectro clínico de presentación dependiendo de la localización y tamaño del defecto. Por lo general, en los CIV restrictivos pequeños presentan un cierre espontáneo durante el seguimiento. Se presenta un caso clínico con sospecha de CIV perimembranosa persistente, con hallazgos anatómicos intraoperatorios descritos de membrana cribiforme aneurismática descartandose CIV.

Endocarditis Infecciosa: una mirada desde la semiología, a propósito de un caso / Infectious Endocarditis: a View from Semiology, case report

Infective endocarditis (IE) is an infection of the inner lining of the heart, especially the heart valves, and carries high morbidity and mortality. It can manifest itself acutely or subacutely, the latter being more insidious. Diagnosis is challenging, especially in early stages, requiring high clinical suspicion using modified Duke criteria. Treatment involves antimicrobials and in certain cases cardiac surgery is essential. The clinical case presents a patient with a history of aortic valve replacement, who develops acute symptoms. Although the diagnosis of endocarditis is achieved, a por physical examination delays starting optimal treatment. Early diagnosis is crucial to avoid adverse outcomes. Post-hospital discharge follow-up is essential to identify possible long-term complications.

La endocarditis infecciosa es una infección del revestimiento interno del corazón, especialmente de las válvulas cardíacas, con alta morbimortalidad. Se manifiesta como aguda o subaguda, siendo esta última más insidiosa. El diagnóstico es desafiante, especialmente en etapas tempranas, requiriendo sospecha clínica en pacientes con fiebre, factores de riesgo cardiacos o no cardiacos y el uso de los criterios de Duke- International Society of Cardiovascular Infectious Diseases. El tratamiento implica antimicrobianos y en ciertos casos es imprescindible la cirugía cardiaca. Se presenta un caso clínico de un paciente con antecedentes de reemplazo valvular aórtico, que desarrolla síntomas agudos. Aunque se logra el diagnóstico de endocarditis, un examen físico poco exhaustivo causa retraso en el inicio del tratamiento óptimo. Un diagnóstico temprano es crucial para evitar resultados adversos. Es esencial la vigilancia estrecha post alta hospitalaria debido a complicaciones a largo plazo.

Role of rs2282679 in 25-hydroxyvitamin D levels and insulin resistance after a sleeve gastrectomy.

BACKGROUND & AIMS: Some studies have reported links between 25-hydroxyvitamin D levels and the presence of obesity and some genetic variants. The aim of our design was to evaluate the effects of rs2282679 genetic variant of CG gene on 25-hydroxyvitamin D levels, weight loss and metabolic parameters after a robotic sleeve gastrectomy in premenopausal females with obesity. METHODS: 76 participants were enrolled. 25-hydroxyvitamin D levels, biochemical evaluation and anthropometric parameters were registered before surgery and after 3, 6 and 12 months follow up. Genotype of rs2282679 CG gene was evaluated. RESULTS: The improvements in anthropometric parameters, blood pressure and lipid profile were similar in both genotypes (TT vs TG + GG). Basal insulin levels and HOMA-IR were greater in G allele carriers than non-carriers (Delta: 6.7 ± 1.2 mUI/L; p = 0.01) and (Delta: 1.3 ± 0.1 units; p = 0.02). 25-hydroxyvitamin D levels were lower in G allele carriers than non-carriers (Delta: 8.1 ± 1.1 ng/dl; p = 0.03). The levels of insulin and HOMA-IR remained greater in G allele carriers than non-carriers throughout all the visits. The levels of 25-hydroxyvitamin D remained lower in G allele carriers than non-G allele. The average level of 25-hydroxyvitamin D at 12 months in non-G allele carriers were above 30 ng/dl (36.0 ± 3.1 ng/dl) and the level in G allele carriers were below (24.9 ± 4.9 ng/dl). CONCLUSIONS: rs 2282679 (GC) was related with low 25 hydroxyvitamin D levels and insulin resistance. In addition, the presence of G allele produced a decrease in the improvement of 25-hydroxyvitamin D levels and insulin resistance after weight loss during 12 months.

Comparison of the Effect of Two Different Handling Conditions at Slaughter in Saliva Analytes in Pigs.

In this report, different handling conditions at slaughterhouse were studied to assess changes in salivary biomarkers. For this purpose, finishing pigs were divided into two groups, one in which handling was improved to minimize stress (Group A, n = 24, transported and stabled at the slaughterhouse at low density without mixing with unfamiliar animals throughout the whole process) and another one in which animals had a more stressful handling process (Group B, n = 24, transported and stabled at high density with unfamiliar animals). Saliva samples were taken the day before transport to the slaughterhouse at 8:00 a.m. (B0) and 12:00 a.m. (B4), and the day of slaughter just after unloading animals at the slaughterhouse at approximately 8:00 a.m. (S0) and after 4 h of lairage at approximately 12:00 a.m. (S4). Group B showed significantly higher cortisol, total esterase activity, oxytocin, adenosine deaminase and haptoglobin levels than the Group A at both S0 and S4 sampling times, and higher levels of calprotectin and creatine kinase at S4 sampling time. This report indicates that differences in the way in which the pigs are handled at the slaughterhouse can lead to changes in salivary biomarkers and opens the possibility of the use of biomarker at slaughter to monitor handling conditions.

DCLK1-Mediated Regulation of Invadopodia Dynamics and Matrix Metalloproteinase Trafficking Drives Invasive Progression in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a major health concern due to its high mortality from poor treatment responses and locoregional tumor invasion into life sustaining structures in the head and neck. A deeper comprehension of HNSCC invasion mechanisms holds the potential to inform targeted therapies that may enhance patient survival. We previously reported that doublecortin like kinase 1 (DCLK1) regulates invasion of HNSCC cells. Here, we tested the hypothesis that DCLK1 regulates proteins within invadopodia to facilitate HNSCC invasion. Invadopodia are specialized subcellular protrusions secreting matrix metalloproteinases that degrade the extracellular matrix (ECM). Through a comprehensive proteome analysis comparing DCLK1 control and shDCLK1 conditions, our findings reveal that DCLK1 plays a pivotal role in regulating proteins that orchestrate cytoskeletal and ECM remodeling, contributing to cell invasion. Further, we demonstrate in TCGA datasets that DCLK1 levels correlate with increasing histological grade and lymph node metastasis. We identified higher expression of DCLK1 in the leading edge of HNSCC tissue. Knockdown of DCLK1 in HNSCC reduced the number of invadopodia, cell adhesion and colony formation. Using super resolution microscopy, we demonstrate localization of DCLK1 in invadopodia and colocalization with mature invadopodia markers TKS4, TKS5, cortactin and MT1-MMP. We carried out phosphoproteomics and validated using immunofluorescence and proximity ligation assays, the interaction between DCLK1 and motor protein KIF16B. Pharmacological inhibition or knockdown of DCLK1 reduced interaction with KIF16B, secretion of MMPs, and cell invasion. This research unveils a novel function of DCLK1 within invadopodia to regulate the trafficking of matrix degrading cargo. The work highlights the impact of targeting DCLK1 to inhibit locoregional invasion, a life-threatening attribute of HNSCC.