Resident training in interventional pathology: Ultrasound-guided fine-needle aspiration and rapid on site evaluation-5 years of teaching experience in a single university hospital.

INTRODUCTION: Despite the established role of the interventional pathologist, their diagnostic performance is difficult to establish. At least in Spain training of pathology residents in ultrasound-guided interventional procedures for specimen collection is limited or absent in most institutions. We present our teaching experience in the instruction of ultrasound-guided fine-needle aspiration (FNA) to pathology residents in a tertiary-level hospital. MATERIALS AND METHODS: The training of pathology residents who rotated through the interventional unit of the pathology department and the application of ultrasound-guided FNA and rapid on-site evaluation (U-ROSE) was documented over 5 years. The training period was broken down into learning phases and included the number of ultrasound-guided FNA performed, anatomical location, and their diagnostic performance, among other aspects. RESULTS: Nineteen (19) pathology residents were trained in U-ROSE, and performed a total of 4003 procedures, with a mean of 211 per resident. In 53% of cases only one pass was required for an adequated sample. The specimen was diagnostic in more than 97% of cases. The most frequently sampled anatomical sites were the thyroid gland (n = 2347), followed by lymph node (n = 667), soft tissues (n = 663) and salivary glands (n = 322). CONCLUSION: The results support the training programme followed by pathology residents in learning U-ROSE, which is essential to lay the foundations for the future interventional pathologist.

SingleNucleotide Polymorphisms as Biomarkers of Mepolizumab and Benralizumab Treatment Response in Severe Eosinophilic Asthma.

The most promising treatment options for severe uncontrolled asthma (SUA) have emerged in recent years with the development of monoclonal antibodies for blocking selective targets responsible for the underlying inflammation, such as mepolizumab and benralizumab. However, there is variability in treatment response that is not fully controlled. The variability of the response to mepolizumab and benralizumab could be influenced by single-nucleotide polymorphisms (SNPs), and it would be useful to detect these and use them as predictive biomarkers of response. We conducted a retrospective observational cohort study of 72 Caucasian patients recruited from a tertiary hospital with severe uncontrolled eosinophilic asthma treated with mepolizumab and benralizumab. Polymorphisms in the IL5 (rs4143832, rs17690122), RAD50 (rs11739623, rs4705959), IL1RL1 (rs1420101, rs17026974, rs1921622), GATA2 (rs4857855), IKZF2 (rs12619285), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs569108), and ZNF415 (rs1054485) genes were analyzed by real-time polymerase chain reaction (PCR) using Taqman probes. The response was analyzed after 12 months of treatment. In patients under mepolizumab treatment, a treatment response defined as a reduction in exacerbations was associated with ZNF415 rs1054485-T (p = 0.042; OR = 5.33; 95% CI = 1.06-30.02), treatment response defined as a reduction in oral corticosteroids use was associated with the number of exacerbations in the previous year (p = 0.029; OR = 3.89; 95% CI = 1.24-14.92), and treatment response defined as improvement in lung function was associated with the age at the beginning of biological therapy (p = 0.002; OR = 1.10; 95% CI = 1.04-1.18), FCER1B rs569108-AA (p < 0.001; OR = 171.06; 95% CI = 12.94-6264.11), and FCER1A rs2427837-A (p = 0.021; OR = 8.61; 95% CI = 1.71-76.62). On the other hand, in patients under benralizumab treatment, treatment response, defined as a reduction in exacerbations, was associated with ZNF415 rs1054485-T (p = 0.073; OR = 1.3 × 108; 95% CI = 1.8 × 10-19-NA), FCER1B rs569108-AA (p = 0.050; OR = 11.51; 95% CI = 1.19-269.78), allergies (p = 0.045; OR = 4.02; 95% CI = 1.05-16.74), and sex (p = 0.028; OR = 4.78; 95% CI = 1.22-20.63); and treatment response defined as improvement in lung function was associated with polyposis (p = 0.027; OR = 9.16; 95% CI = 1.58-91.4), IKZF2 rs12619285-AA (p = 0.019; OR = 9.1; 95% CI = 1.7-75.78), IL5 rs4143832-T (p = 0.017; OR = 11.1; 95% CI = 1.9-112.17), and FCER1B rs1441586-C (p = 0.045; OR = 7.81; 95% CI = 1.16-73.45). The results of this study show the potential influence of the studied polymorphisms on the response to mepolizumab and benralizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.

Evidence That Peripheral Leptin Resistance in Omental Adipose Tissue and Liver Correlates with MASLD in Humans.

Leptin regulates lipid metabolism, maximizing insulin sensitivity; however, peripheral leptin resistance is not fully understood, and its contribution to metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. This study evaluated the contribution of the leptin axis to MASLD in humans. Forty-three participants, mostly female (86.04%), who underwent cholecystectomy were biopsied. Of the participants, 24 were healthy controls, 8 had MASLD, and 11 had metabolic dysfunction-associated steatohepatitis (MASH). Clinical and biochemical data and the gene expression of leptin, leptin receptor (LEPR), suppressor of cytokine signaling 3 (SOCS3), sterol regulatory element-binding transcription factor 1 (SREBF1), stearoyl-CoA desaturase-1 (SCD1), and patatin-like phospholipase domain-containing protein 2 (PNPLA2), were determined from liver and adipose tissue. Higher serum leptin and LEPR levels in the omental adipose tissue (OAT) and liver with MASH were found. In the liver, LEPR was positively correlated with leptin expression in adipose tissue, and SOCS3 was correlated with SREBF1-SCD1. In OAT, SOCS3 was correlated with insulin resistance and transaminase enzymes (p < 0.05 for all. In conclusion, we evidenced the correlation between the peripheral leptin resistance axis in OAT-liver crosstalk and the complications of MASLD in humans.

Impact of Anti-IL5 Therapies on Patients with Severe Uncontrolled Asthma and Possible Predictive Biomarkers of Response: A Real-Life Study.

Severe Uncontrolled Asthma (SUA) counts for more than 25% of cases of severe asthma. The main factors that impair the quality of life of these patients are high doses of oral corticosteroids, the presence of exacerbations, and reduced lung function. The objective of this study was to evaluate, in real life, the clinical improvement of patients with SUA treated with anti-interleukin 5 (IL5) therapies: mepolizumab and benralizumab, together with the search for biomarkers associated with the response. We conducted a retrospective observational cohort study that included patients with severe uncontrolled eosinophilic asthma in a tertiary hospital receiving biological therapies. Three types of response were evaluated: improvement in lung function, reduction in exacerbations, and decrease in the use of oral corticosteroids. After 12 months of treatment, significant reductions were found in the number of exacerbations, the use of oral corticosteroids, and blood eosinophil levels for both biological therapies (p < 0.001). Lung function improved, achieving a significant improvement in %FEV1 (p < 0.001), as well as asthma control, with a significant increase in asthma control test (ACT) scores in both therapies. The markers associated with the corticosteroid-saving effect were the low doses of oral corticosteroids and absence of exacerbations for mepolizumab, and higher blood eosinophilia, absence of chronic obstructive pulmonary disease (COPD), and reduction in oral corticosteroid cycles for benralizumab. The greatest improvement in lung function in both therapies was linked to lower previous FEV1 levels and absence of other respiratory diseases. The reduction in exacerbations was associated with absence of exacerbations the previous year for mepolizumab and never smokers for benralizumab. The results of this real-life study confirm the clinical benefit obtained after the introduction of an anti-IL5 biological therapy and the possible predictive biomarkers of response to treatment.

Influence of Genetics on the Response to Omalizumab in Patients with Severe Uncontrolled Asthma with an Allergic Phenotype.

Omalizumab is a monoclonal antibody indicated for the treatment of severe uncontrolled asthma with an allergic phenotype. Its effectiveness could be influenced by clinical variables and single nucleotide polymorphisms (SNPs) in one or more of the genes involved in the mechanism of action and process of response to omalizumab, and these could be used as predictive biomarkers of response. We conducted an observational retrospective cohort study that included patients with severe uncontrolled allergic asthma treated with omalizumab in a tertiary hospital. Satisfactory response after 12 months of treatment was defined as (1) Reduction ≥ 50% of exacerbations or no exacerbations, (2) Improvement of lung function ≥ 10% FEV1, and (3) Reduction ≥ 50% of OCS courses or no OCS. Polymorphisms in the FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs1054485, rs569108), C3 (rs2230199), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), IL1RL1 (rs1420101, rs17026974, rs1921622), and GATA2 (rs4857855) genes were analyzed by real-time polymerase chain reaction (PCR) using TaqMan probes. A total of 110 patients under treatment with omalizumab were recruited. After 12 months of treatment, the variables associated with a reduction in exacerbations were the absence of polyposis (odds ratio [OR] = 4.22; 95% confidence interval [CI] = 0.95-19.63), IL1RL1 rs17026974-AG (OR = 19.07; 95% CI = 1.27-547), and IL1RL1 rs17026974-GG (OR = 16.76; 95% CI = 1.22-438.76). Reduction in oral corticosteroids (OCS) was associated with age of starting omalizumab treatment (OR = 0.95; 95% CI = 0.91-0.99) and blood eosinophil levels > 300 cells/µL (OR = 2.93; 95% CI = 1.01-9.29). Improved lung function showed a relationship to the absence of chronic obstructive pulmonary disease (COPD) (OR = 12.16; 95% CI = 2.45-79.49), FCGR2B rs3219018-C (OR = 8.6; 95% CI = 1.12-117.15), GATA2 rs4857855-T (OR = 15.98; 95% CI = 1.52-519.57) and FCGR2A rs1801274-G (OR = 13.75; 95% CI = 2.14-142.68; AG vs. AA and OR = 7.46; 95% CI = 0.94-89.12; GG vs. AA). Meeting one response criterion was related to FCER1A rs2251746-TT (OR = 24; 95% CI = 0.77-804.57), meeting two to age of asthma diagnosis (OR = 0.93; 95% CI = 0.88-0.99), and meeting all three to body mass index (BMI) < 25 (OR = 14.23; 95% CI = 3.31-100.77) and C3 rs2230199-C (OR = 3; 95% CI = 1.01-9.92). The results of this study show the possible influence of the polymorphisms studied on the response to omalizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.

Effects of Non-Invasive Radiofrequency Diathermy in Pelvic Floor Disorders: A Systematic Review.

Background and Objectives: In recent years, the use of radiofrequency diathermy in pelvic floor disorders has grown proportionally to the interest in this specialty. Despite the common use of this therapy among pelvic floor physiotherapists, little is known about its effects and effectiveness in pelvic floor disorders. For this reason, the aim of the present review is to assess the effects of non-invasive 300 kHz-1 MHz radiofrequency diathermy in the treatment of pelvic floor disorders. Materials and Methods: A literature search was performed in PubMed, Scopus and Web of Science, searching for any type of study that included pelvic floor disorder participants and an experimental group treated with non-invasive nor ablative radiofrequency diathermy. Results: There were a total of 578 studies after removing duplicates. The inclusion and exclusion criteria were applied, resulting in a total of 15 studies, which were methodologically assessed with PEDro and the Newcastle and Ottawa scale. Conclusions: Despite the low quality of most of them, the studies showed improvements in urinary incontinence, pelvic pain conditions, pelvic floor muscles strength and sexual function. These findings must be considered with caution until more randomized clinical trials are performed to solve the biases detected.

The adverse prognostic effect of tumor budding on the evolution of cutaneous head and neck squamous cell carcinoma.

BACKGROUND: Tumor budding is a readily detectable histopathologic feature that has been recognized as an adverse prognostic factor in several human cancers. OBJECTIVE: We sought to assess the correlation of tumor budding with the clinicopathologic features and the prognostic value of tumor budding in cutaneous squamous cell carcinoma (cSCC). METHODS: Forty-nine primary nonmetastatic and 49 primary metastatic cSCCs to regional lymph nodes were retrospectively studied. Statistical analyses were carried out to assess the relationship between tumor budding, clinicopathologic parameters, and patient survival. RESULTS: Tumor budding was observed in 45 cases of 98 (46%). High-intensity budding (≥5 tumor buds) was observed in 20 tumors. Presence of tumor buds was a significant risk factor for nodal metastasis with crude and adjusted hazard ratios (HRs) of 8.92 (95% CI, 4.39-18.1) and 6.93 (95% CI, 3.30-14.5), respectively, and for reduced overall survival time (crude and adjusted HRs of 2.03 [95% CI, 1.26-3.28] and 1.72 [95% CI, 1.05-2.83], respectively). LIMITATIONS: This was a retrospective study limited to cSCCs of the head and neck. Examined tumors were >2 mm thick, and all were from a primary excision. CONCLUSION: These results indicate an increased frequency of nodal metastasis and risk of death in patients with tumor buds.

Association between Single Nucleotide Polymorphisms Related to Vitamin D Metabolism and the Risk of Developing Asthma.

Asthma is a chronic non-communicable disease that affects all age groups. The main challenge this condition poses is its heterogeneity. The role of vitamin D in asthma has aroused great interest, correlating low vitamin D levels and polymorphisms in the genes involved in its metabolic pathway with the risk of asthma. The aim of this study was to evaluate the influence of 13 single nucleotide polymorphisms (SNPs) related to the vitamin D metabolism on the susceptibility to asthma. An observational case-control study was performed, including 221 patients with asthma and 442 controls of Caucasian origin from southern Spain. The SNPs CYP24A1 (rs6068816, rs4809957), CYP27B1 (rs10877012, rs4646536, rs703842, rs3782130), GC (rs7041), CYP2R1 (rs10741657) and VDR (ApaI, BsmI, FokI, Cdx2, TaqI) were analyzed by real-time PCR, using TaqMan probes. The logistic regression model adjusted for body mass index revealed that in the genotype model, carriers of the Cdx2 rs11568820-AA genotype were associated with a higher risk of developing asthma (p = 0.005; OR = 2.73; 95% CI = 1.36-5.67; AA vs. GG). This association was maintained in the recessive model (p = 0.004). The haplotype analysis revealed an association between the ACTATGG haplotype and higher risk of asthma for the rs1544410, rs7975232, rs731236, rs4646536, rs703842, rs3782130 and rs10877012 genetic polymorphisms (p = 0.039). The other SNPs showed no effect on risk of developing asthma. The Cdx2 polymorphism was significantly associated with the susceptibility of asthma and could substantially act as a predictive biomarker of the disease.

Impact of Omalizumab in Patients with Severe Uncontrolled Asthma and Possible Predictive Biomarkers of Response: A Real-Life Study.

Most patients with asthma can control their symptoms with a basic standard of medical care and with maintenance and rescue medication. However, between 5% and 10% of asthmatics worldwide do not achieve control of their symptoms and have recurrent exacerbations and respiratory difficulties. The objective of the study was the real-life evaluation of the clinical improvement of patients with severe eosinophilic asthma treated with omalizumab, together with the search for biomarkers associated with the response. An observational retrospective cohort study was conducted that included patients with severe uncontrolled allergic asthma being treated with omalizumab. Three types of response were evaluated: lower use of oral corticosteroids, improvement in lung function, and reduction in exacerbations. A total of 110 patients under treatment with omalizumab were included, with a mean age of 48 ± 16 years. After 12 months had elapsed, significant reductions were found in the number of exacerbations, use of oral cortico-steroids and doses of inhaled corticosteroids (p < 0.001). Lung function and asthma control improved significantly (p < 0.001; p = 0.004) and eosinophil levels were significantly reduced (p = 0.004). Low scores in the Asthma Control Test were associated with the oral corticosteroid-saving effect; lower previous FEV1 levels and absence of chronic obstructive pulmonary disease (COPD) were related to improvement in lung function, and prior FEV1 values higher than 80% and absence of gastroesophageal reflux disease (GERD) with a reduction in exacerbations. The results of this study confirm the clinical benefit obtained after the introduction of omalizumab and the possible predictive biomarkers of response to the treatment.

Pleural metastasis from pulmonary primary signet-ring squamous cell carcinoma. Case report and literature review.

Signet-ring cells are morphologically defined by the presence of a large intracytoplasmic vacuole that compresses and displaces the nucleus to the periphery. In most cases, these cells are associated with adenocarcinomas of various locations, and with non-epithelial neoplasms. To date, less than 20 cases of squamous cell carcinoma with signet-ring morphology have been described, mainly located on the skin. We present the case of a 73-year-old male with pleural effusion and a left lower lobe mass. The cytological study of the pleural effusion allowed the diagnosis of metastasis of squamous cell carcinoma, signet-ring cell variant. The treatment of lung cancer in advanced stages requires a precise diagnosis that allows the best therapy to be offered to the patient, depending on the clinical stage and the positivity of the biomarkers, among others. Our patient died 18 months after the initial diagnosis.

Amyloid goiter diagnosis by ultrasound-guided fine needle aspiration performed by interventional pathologist.

Amyloid goiter (AG) (primary or secondary) is extremely rare. An abdominal fat pad core needle biopsy (CNB) is the diagnostic gold standard for secondary amyloidosis. Although CNB is useful to detect amyloid infiltration of a specific organ, fine-needle aspiration (FNA) is proven to be the best diagnostic method for thyroid disorders. Guidelines recommend an ultrasound-guided FNA (US-FNA) whenever possible. This procedure is usually performed by various interventional specialists, including pathologists, who perform the procedure in addition to validating the adequacy of the sample. We report a rare case of AG diagnosed using US-FNA performed by a pathologist in a 39-year-old patient with systemic amyloidosis. US-FNA performed by pathologists is a proven, less-invasive, and cost-effective tool that ensures acquisition of adequate specimens and reduces nondiagnostic rates of this procedure to ensure timely cytological diagnosis.

[Minimally invasive percutaneous musculoskeletal biopsy performed by Interventional Pathologist for myopathy study. Twenty years of experience]. / Biopsia percutánea muscular mínimamente invasiva realizada por patólogo intervencionista en el estudio de miopatías. Veinte años de experiencia.

INTRODUCTION: Muscle biopsy plays a major role in the final diagnosis of myopathies. Open muscle biopsy is the benchmark procedure, although minimally invasive percutaneous muscle biopsy (MIPMB) has demonstrated comparable diagnostic performance at a lower cost and can be carried out by interventional pathologists. MATERIALS AND METHODS: Muscle biopsies performed from 1997 to 2017 were reviewed and classified according to the type of procedure, whether carried out by an interventional pathologist or another specialist, the diagnosis and the effectiveness of the procedure. RESULTS: 738 muscle biopsies were performed; 32% were open biopsies and 68% MIPMB carried out by pathologist. The muscle most often biopsied was the femoral quadriceps and the most frequent diagnosis was inflammatory myopathies. In only 39 cases (20 open biopsies and 19 MIPMB) was there insufficient tissue for diagnosis. CONCLUSIONS: Muscle biopsy proved highly effective as a diagnostic tool as 90% yielded adequate tissue samples. The results obtained with MIPMB performed by interventionist pathologists were comparable to those of open muscle biopsy.

Ultrasound-Guided Fine-Needle Aspiration of Superficial Lymphadenopathy Performed by Interventional Pathologists: The Applicability of the Sydney System from 2 Years of Experience and 363 Cases.

INTRODUCTION: The Sydney system proposal for the study and reporting of lymphadenopathy by fine-needle aspiration (FNA) constitutes one of the first attempts to standardize this procedure. Here, we review its applicability. MATERIALS AND METHODS: A retrospective study in which all ultrasound-guided FNAs (USFNAs) of superficial lymphadenopathy (palpable or not) performed by interventional pathologists in 2 specialized hospital centers were quantified over 2 years. The procedure was systematized, and the diagnoses were reclassified according to the Sydney system categories. RESULTS: We analyzed 363 USFNAs of lymphadenopathies. The distribution of cases by categories was as follows: insufficient (n = 13; 3.58%), benign (n = 208; 57.30%), atypia of uncertain significance (n = 7; 1.93%), suspicious (n = 21; 5.79), and malignant (n = 114; 31.40%). The risks of malignancy calculated for categories I, II, III, IV, and V were 27%, 3%, 50%, 100%, and 100%, respectively. CONCLUSION: The implementation of the Sydney system allows the systematization and standardization of the lymph node FNA methodology, with increased efficacy and efficiency. Assimilating the recommendations enables the qualification of the diagnostic procedure.

Microbial load and antibiotic resistance in raw beef preparations from northwest Spain.

Beef preparations (meatballs, minced meat, hamburgers, white sausages, and red sausages) from northwest Spain were tested. Microbial counts ranged from 0.70 ± 0.00 log10 cfu/g (enterococci) to 9.57 ± 0.37 log10 cfu/g (psychrotrophs). In 73.3% of cases, total aerobic counts were higher than the microbiological limits set for the end of the manufacturing process in the European Union (EU Regulation 2073/2005). Forty Escherichia coli isolates were tested against thirteen clinically important antibiotics (disk diffusion method; CLSI). Three of the strains (7.5%) were susceptible to all the antibiotics, four (10.0%) showed resistance or reduced susceptibility to one antibiotic, and 33 (82.5%) were multiresistant (with resistance or reduced susceptibility to between two and eight antibiotics), with an average of 1.85 resistances per strain. The highest rates of resistance were observed for two antimicrobials widely used on cattle farms (cefalotin and tetracycline). The findings in this research emphasize the need to correctly handle beef preparations with the aim of reducing risks to consumers.

Is asthma in the elderly different? Functional and clinical characteristics of asthma in individuals aged 65 years and older.

BACKGROUND: The prevalence of chronic diseases in the elderly (> 65 years), including asthma, is growing, yet information available on asthma in this population is scarce.Our objective is to determine the differential clinical and functional characteristics of the population > 65 years old with asthma included in the Integrated Research Programs of Asthma Databank of the Spanish Society of Pneumology and Thoracic Surgery (www.bancodatosasma.com). METHODS: Retrospective comparative descriptive study of demographic, clinical and functional variables for 1713 patients with asthma categorized into 3 age groups as follows: adults aged < 65 years (A), younger elderly aged 65-74 years (B) and older elderly aged ≥75 years (C). RESULTS: Predominant features of elderly patients with asthma (N = 471) were the female sex, fewer smokers, greater obesity, poorer lung function, and lower values of nitric oxide in exhaled air (p < 0.01). The most frequently associated comorbidity was gastroesophageal reflux. The highest doses of inhaled corticosteroids were by group A (60.8%). For the sample overall, 23.2% (N = 398) were being treated with omalizumab and 8.2% (N = 140) were corticosteroid-dependent (10.6% in group B). The highest percentage of patients receiving antileukotriene agents was in group B (42.9%). CONCLUSIONS: Asthma in adults aged> 65 is more severe and associated with greater comorbidity, which would indicate the need for a more integrated and multidimensional approach to asthma treatment for these patients.

Predictive Model for Anxiety and Depression in Spanish Patients with Stable Chronic Obstructive Pulmonary Disease.

INTRODUCTION: The association between chronic obstructive pulmonary disease (COPD) and anxiety and depression is not yet completely characterized, and differences between countries may exist. We used a predictive model to assess this association in a Spanish population. PATIENTS AND METHOD: Prospective transversal descriptive study of 204 patients with stable COPD. Concomitant anxiety or depression were diagnosed by psychiatric assessment, using the diagnostic criteria of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). Sociodemographic, clinical and lung function parameters were analyzed. RESULTS: In total, 36% of stable COPD patients had psychiatric comorbidities, but 76% were unaware of their diagnosis. Nineteen percent had a pure anxiety disorder, 9.8% had isolated depression, and 7.3% had a mixed anxiety-depression disorder. Predictive variables in the multivariate analysis were younger age, higher educational level, lack of home support, higher BODE index, and greater number of exacerbations. The ROC curve of the model had an AUC of 0.765 (P<0.001). CONCLUSIONS: In COPD, concomitant psychiatric disorders are significantly associated with sociodemographic factors. Anxiety disorders are more common than depression. Patients with more severe COPD, according to BODE, younger patients and those with a higher educational level have a greater risk of being diagnosed with anxiety or depression in a structured psychiatric interview. In our population, most patients with psychiatric comorbidities remain unidentified.