Forage sources in total mixed rations early in life influences performance, metabolites, and behaviour of dairy calves.

The objective of this study was to evaluate effects of forage inclusion and sources on performance, metabolism, and feeding behavior of dairy calves. Forty-eight Holstein calves were blocked and randomly assigned to 1 of 4 dietary treatments according to sex, and body weight (BW) at 28 d of life to determine the effects of feeding forage sources (ensiled and dry), with different quality on performance, metabolites, and behavior. Treatments consisted of a no-forage coarsely ground starter (CON); or total mixed ration containing 7.5% on DM basis of Tifton hay of either medium quality (MH) or low quality (LH); or 10% on DM basis of corn silage (CS). During the first 28 d of life, all calves received 3 L of whole milk twice daily, a commercial pelleted starter and no forage, and water ad libitum. After that, the solid diet was changed to the respective dietary treatments. Calves were gradually weaned from 52 to 56 d of age, and followed for 14 d post-weaning. Individual solid feed and milk intakes were recorded daily, and BW and metabolic indicators of intermediate metabolism were recorded weekly. Behavior was recorded, and the analysis was conducted on wk 7 (preweaning) and 10 (post-weaning). Solid feed intake increased at wk 7 and 8 when MH, LH, and CS were included in TMR; the same results were observed post-weaning. The diets did not affect the average daily gain and body weight, but the feed efficiency increased with the CON diet. The ß-hydroxybutyrate concentration was greater in calves receiving TMR containing forage than CON diet. Furthermore, calves supplemented with forage had a greater rumination time. In conclusion, all forage sources included in the TMR showed feed intake and behavior benefits, reinforcing the need for fiber from forage in pre- and post-weaning diets.

Understanding and Overcoming the Pitfalls in Cytopathological Diagnosis of Hyalinizing Trabecular Tumor of Thyroid.

Hyalinizing trabecular tumor (HTT), a rare low-malignant-potential thyroid neoplasm, is usually treated with conservative surgery. However, cytomorphological diagnosis of HTT is challenging due to the significant overlap of nuclear features with more common malignancies such as papillary thyroid carcinoma (PTC), which usually requires more radical surgical intervention. To avoid unnecessary overtreatment, a precise diagnosis of HTT is therefore essential. Advances in molecular diagnostics provide the opportunity to overcome the limitations of cytological analysis. We present a case of HTT in a 71-year-old male who was initially suspected to be PTC based on cytopathology. However, further molecular analysis revealed PAX8::GLIS3 gene fusion, classifying the lesion as HTT and preventing surgical overtreatment. We discuss the diagnostic pitfall of cytopathology in HTT and suggest using emerging molecular genetic tools to avoid it.

Diagnostic difficulties in non-tuberculous mycobacterial infection in lung transplant recipients.

Despite antimicrobial prophylaxis, 34% to 59% of lung transplant recipients experience severe life-threatening opportunistic infections, sometimes caused by Nontuberculous Mycobacteria (NTM) and Nocardia. Although differentiating these infections is of utmost importance for effective treatment, it can be challenging as they share morphological and growth characteristics. Therefore, culture remains the gold standard for laboratory confirmation. With the aid of novel molecular methods performed on the cultured organisms, diagnosis may be accomplished rapidly and precisely. We present a case of a lung transplant recipient with a pulmonary infection where long, thin, beaded, branching filamentous organisms were seen with Acid-Fast Bacilli (AFB) and Modified Gomori's Methenamine Silver (GMS) stains in bronchoalveolar lavage sample. Cytological characteristics led to the suspicion of a Nocardia species infection. However, culture and the PCR-restriction fragment length polymorphism analysis (PRA) identified M. fortuitum. Additionally, antibiotic resistance was detected, which aided in choosing the appropriate treatment. Therefore, to overcome such diagnostic difficulties to differentiate NTM and Nocardia, a multidisciplinary approach including culture, molecular methods, and cytology is needed to enhance clinical outcomes.

Sinonasal IgG4-related sclerosing disease: A rare entity and challenging diagnosis.

Objectives: To describe the rare presentation, imaging and histological findings, and treatments in patients with IgG4-related disease (IgG4-RD) and diagnostic pitfalls and difficulties. Methods: Cases of sinonasal IgG4-RD were retrieved, and clinicopathological features were reviewed. Results: Seven cases of sinonasal IgG4-RD were identified over an 11-year period, including four males and three females, with an age range of 19-66 years (median 58 years). Patients presented with symptoms related to the mass effect of the lesions or the destructive nature of the disease including fullness, swelling, obstruction, and pain. Serum IgG and IgG4 levels, IgG/IgG4 ratios, storiform fibrosis, obliterative phlebitis, and plasma cell infiltration were seen in varying proportions. Bony erosion and tissue inflammation were present in some cases. Conclusion: Sinonasal IgG4-RD is exceedingly rare among other IgG4-RD and varied in its clinical presentation thus posing as a clinically difficult disease to diagnosis. Proper clinical, pathological, and immunohistopathological analysis is required for accurate diagnosis. Such disease should be considered in all cases of similar presentation to those in this study.Level of Evidence: 4.

A 65-Year-Old Woman With Intractable Cough.

CASE PRESENTATION: A 65-year-old woman was referred for a second opinion regarding a 7-month history of a persistent, progressive, nonproductive cough. Her cough occurred several times a minute, causing a significant impact on her daily activities. She denied fever, chills, weight loss, chest pain, wheezing, symptoms of gastroesophageal reflux, or postnasal drip. She was a never smoker with no history of asthma, allergies, sinus disease, or dermatitis. She had never taken an angiotensin-converting enzyme inhibitor. Her medical history included rheumatoid arthritis, for which she was treated with methotrexate for 3 years. She denied any occupational or environmental exposures. She was previously treated with a short-acting ß-agonist, inhaled corticosteroid/long-acting ß-agonist, montelukast, nasal steroids, a proton pump inhibitor, gabapentin, and azithromycin without relief. She also received codeine, which provided mild relief.

Rapid SARS-CoV-2 diagnosis using disposable strips and a metal-oxide-semiconductor field-effect transistor platform.

The SARS-CoV-2 pandemic has had a significant impact worldwide. Currently, the most common detection methods for the virus are polymerase chain reaction (PCR) and lateral flow tests. PCR takes more than an hour to obtain the results and lateral flow tests have difficulty with detecting the virus at low concentrations. In this study, 60 clinical human saliva samples, which included 30 positive and 30 negative samples confirmed with RT-PCR, were screened for COVID-19 using disposable glucose biosensor strips and a reusable printed circuit board. The disposable strips were gold plated and functionalized to immobilize antibodies on the gold film. After functionalization, the strips were connected to the gate electrode of a metal-oxide-semiconductor field-effect transistor on the printed circuit board to amplify the test signals. A synchronous double-pulsed bias voltage was applied to the drain of the transistor and strips. The resulting change in drain waveforms was converted to digital readings. The RT-PCR-confirmed saliva samples were tested again using quantitative PCR (RT-qPCR) to determine cycling threshold (Ct) values. Ct values up to 45 refer to the number of amplification cycles needed to detect the presence of the virus. These PCR results were compared with digital readings from the sensor to better evaluate the sensor technology. The results indicate that the samples with a range of Ct values from 17.8 to 35 can be differentiated, which highlights the increased sensitivity of this sensor technology. This research exhibits the potential of this biosensor technology to be further developed into a cost-effective, point-of-care, and portable rapid detection method for SARS-CoV-2.

El sodio como excipiente de medicamentos y su potencial relación con la elevación de la presión arterial / Sodium as a drug excipient and its potential relationship with blood pressure elevation

Objetivos: Conocer la composición cuantitativa de sodio en las formas farmacéuticas efervescentes y en soluciones de analgésicos, suplementos de calcio y mucolíticos utilizadas crónicamente; evaluar en qué proporción se tiene en cuenta el potencial riesgo a la hora de prescribir estos medicamentos a pacientes hipertensos y analizar si la toma de estas formas farmacéuticas por la población hipertensa se acompañaba de una descompensación de los valores de presión arterial (PA). Métodos: Se calculó el porcentaje de hipertensos tratados con paracetamol, calcio y acetilcisteína efervescentes (bicarbonato y carbonato sódico) en 10 Centros de Atención Primaria. Se realizó un estudio de cohortes retrospectivo con grupo control (ajustado por edad y género) en uno de los centros; seguimiento de un año. Las variables estudiadas fueron: PA sistólica (PAS) y diastólica (PAD) pre-post inicio del tratamiento con las formas farmacéuticas efervescentes, considerando clínicamente relevantes incrementos >5 mmHg; intensificación del tratamiento antihipertensivo.Resultados: Un 7,7% (rango: 5,4%-9,9%) de pacientes hipertensos se trataron con los medicamentos efervescentes estudiados. El porcentaje de hipertensos que mostraron un aumento de PAS relevante fue significativamente superior en el grupo tratado con medicamentos efervescentes en comparación al del grupo control: 35,9% (IC 95% 27,2%-44,6%) vs. 18,8% (IC 95% 12,7%-24,8%) y también respecto a la intensificación del tratamiento antihipertensivo, 46,6% (IC 95% 37,5%-55,6%) vs. 30% (IC 95% 22,9%-37,1%).Conclusiones: La sensibilización al potencial efecto adverso es muy variable. Los medicamentos efervescentes que incluyen carbonato-bicarbonato de sodio pueden incrementar la PA. El uso de las formas farmacéuticas efervescentes, especialmente en pacientes de riesgo, debe evitarse. (AU)

Aim: To know the quantitative composition of sodium in effervescent pharmaceutical forms and in solutions of analgesics, calcium supplements and mucolytics used chronically; to evaluate in what proportion the potential risk is taken into account when prescribing these drugs to hypertensive patients and to analyze whether the taking of these pharmaceutical forms by the hypertensive population was accompanied by a decompensation of blood pressure (BP) values.Methods: The percentage of hypertensive patients treated with effervescent paracetamol, calcium and acetylcysteine (bicarbonate and sodium carbonate) in 10 Primary Care Centers was calculated. A retrospective cohort study with a control group (adjusted for age and gender) was carried out in one of the centers. The follow-up was one year. The study variables were systolic (SBP) and diastolic (DBP) pre-post initiation of treatment with effervescent preparations, considering clinically relevant increases >5 mmHg; intensification of antihypertensive treatment.Results: 7.7% (range 5.4%-9.9%) of hypertensive patients were treated with the study effervescent drugs. The percentage of hypertensive patients who showed a relevant increase in SBP was significantly higher in the group treated with effervescent drugs compared to the control group: 35.9% (95% CI 27.2%-44.6%) vs. 18.8% (95% CI 12.7%-24.8%) and also regarding the intensification of antihypertensive treatment, 46.6% (95% CI 37.5%-55.6%) vs. 30% (95% CI 22.9%-37.1%).Conclusions: Sensitivity to the potential adverse effect is highly variable. Effervescent medications that include sodium carbonate-bicarbonate can increase BP. The use of effervescent pharmaceutical forms, especially in patients at risk, should be avoided. (AU)

Ensayos clínicos con medicamentos registrados en España sobre COVID-19: situación casi dos años después de la declaración de pandemia / Clinical trials with COVID-19 registered medicines in Spain: situation almost two years after pandemic declaration

JUSTIFICACIÓN: la COVID-19 es una enfermedad causada por el virus SARS-CoV-2, detectado en diciembre de 2019. Poco después, en marzo de 2020, fue considerada pandemia por la OMS. Dicha pandemia ha supuesto un aumento de la investigación a la vez que un entorno de incertidumbre que favorece la desinformación, evidenciado la necesidad de información detallada, confiable, accesible y regularmente actualizada. OBJETIVOS: Caracterizar los ensayos clínicos con medicamentos sobre la COVID-19 registrados en España hasta diciembre de 2021. MATERIAL Y MÉTODOS: se realizó un estudio observacional descriptivo de tipo transversal sobre los ensayos clínicos con medicamentos relacionados con la COVID-19 (diciembre de 2021). La fuente de datos fue el Registro Español de estudios clínicos (REec) en el que se aplicó como filtro la palabra clave “COVID-19”. Las variables de estudio fueron: promotor, población (participantes), ámbito de estudio, estado del estudio, centro-s, tipo de tratamiento, fase del ensayo e identificación de los medicamentos ensayados. Se creó un grupo interdisciplinar de trabajo constituido por profesionales de la salud y de otros ámbitos. El registro de los datos se realizó mediante una hoja Excel, clasificando la información para su posterior análisis. RESULTADOS Y DISCUSIÓN: se cuantificaron un total de 196 ensayos clínicos con medicamentos. 148 presentan un promotor nacional y los 48 restantes un promotor internacional. La fuente de financiación principal de los ensayos clínicos proviene de instituciones privadas (n=116). (AU)

Suplementación de la vitamina D: Análisis de las presentaciones y dosificaciones disponibles en España, China, Ecuador y Colombia / Vitamin D supplementation: Analysis of presentations and dosages available in Spain, China, Ecuador and Colombia

JUSTIFICACIÓN: en la actualidad, están aumentando las notificaciones de reacciones adversas graves asociadas a la vitamina D que parecen relacionarse con errores de prescripción y el uso de suplementos a dosis altas. OBJETIVOS: describir los medicamentos de vitamina D monocomponente (colecalciferol y calcifediol) comercializados en China, Colombia, Ecuador y España, y realizar un análisis comparativo entre los diferentes países. MATERIAL Y MÉTODOS: estudio transversal descriptivo (enero 2022) a nivel internacional. Se obtuvo la información a través de las bases de datos de las agencias reguladoras de cada país: NMPA (China), INVIMA (Colombia), ARCSA (Ecuador) y CIMA de la AEMPS (España), de acceso público a través de Internet. RESULTADOS Y DISCUSIÓN: se contabilizó un total de 51 medicamentos, de los cuales 31 (60,8 %) se comercializan en España, 10 (19,6 %) en Ecuador, 6 (11,8 %) en Colombia y 4 (7,8 %) en China. Se encontró un número mayor de presentaciones disponibles para la población adulta de los suplementos de colecalciferol que para la población pediátrica en España y Ecuador. Respecto a calcifediol, en los cuatro países existen menos presentaciones comercializadas para la población adulta y China es el único país que comercializa calcifediol para la población pediátrica. Respecto a las formas farmacéuticas disponibles (solución oral, ampollas y cápsulas/comprimidos), Colombia lidera el número de presentaciones en solución oral (33 %), seguido de España (30 %) y Ecuador (10 %), mientras que en China no se encuentra disponible esta forma farmacéutica y sí en ampollas (China un 50%, seguido de Colombia con un 33 %). (AU)

Ensayos clínicos con medicamentos registrados en España sobre la covid-19: Estudio comparativo de los años 2020 y 2021 / Clinical trials with covid-19 registered medicines in Spain: A comparative study of the years 2020 and 2021

JUSTIFICACIÓN: la situación sanitaria actual debido a la pandemia por la COVID-19 ha puesto en evidencia la importancia de la investigación, desarrollo e innovación (I+D+i) de los países, dada la repercusión en la mejora en salud y calidad de vida. OBJETIVOS: realizar un análisis comparativo de los ensayos clínicos con medicamentos relacionados con la COVID-19 registrados en España en 2020 y 2021. MATERIAL Y MÉTODOS: estudio observacional, descriptivo y transversal, con dos fechas de corte: 27 de octubre de 2020 y 21 de diciembre de 2021. La fuente de información fue la base de datos pública Registro Español de estudios clínicos (REec), utilizando el término “COVID-19” en el apartado de búsqueda avanzada. Las variables de estudio fueron: promotor, número de centros participantes, ámbito, estado del estudio, fase, número, género y edad de los voluntarios. El análisis de los datos se realizó mediante una hoja Excel, clasificando toda la información para su posterior análisis. RESULTADOS/DISCUSIÓN: en octubre de 2020 había 127 ensayos clínicos con medicamentos relacionados con la COVID-19 (75 en estado de reclutamiento, 11 finalizado el reclutamiento, 8 iniciados, 25 no iniciados y 8 finalizados) y en diciembre de 2021 había 196 (64, 36, 0, 35 y 61, respectivamente), por tanto, se observó un incremento del 54,3 % en el número de estudios un año después. El promotor mayoritario continuó siendo nacional (80,3 % en 2020 y 75,5 % en 2021), aumentando el patrocinio privado (49,6 % en 2020 frente al 59,2 % en 2021) frente al público. El ámbito de estudio principal siguió siendo la eficacia y seguridad de los medicamentos ensayados para la COVID-19, dado que alrededor del 80 % incluyeron estas características entre sus objetivos primarios en los dos años analizados. (AU)

Servicio profesional farmacéutico asistencial de indicación farmacéutica. Uso de protocolos en la farmacia comunitaria / Professional pharmaceutical care service for pharmaceutical indication. Use of protocols in community pharmacy

JUSTIFICACIÓN: para poder realizar correctamente el servicio profesional farmacéutico asistencial de indicación farmacéutica es fundamental contar con protocolos de actuación para los distintos trastornos o sintomatologías menores, adaptados y de fácil aplicación en la práctica diaria de la farmacia comunitaria. El registro de este servicio de atención farmacéutica es totalmente necesario para demostrar su impacto en la población, en la profesión farmacéutica y en la sostenibilidad del sistema público de salud español. OBJETIVOS: el objetivo principal fue conocer y analizar la aplicabilidad de los protocolos y los métodos de registro del servicio profesional farmacéutico asistencial de indicación farmacéutica en las farmacias comunitarias españolas. MATERIAL Y MÉTODOS: estudio descriptivo-analítico. Revisión y selección bibliográfica hasta enero de 2020 en Pubmed, Google Académico y páginas webs de asociaciones/sociedades científicas/profesionales relacionadas con la atención farmacéutica, entre ellas la Sociedad Española de Farmacia Clínica, Familiar y Comunitaria (SEFAC) y de grupos universitarios. Palabras clave: indicación farmacéutica, atención farmacéutica, pharmaceutical care y community pharmacy Spain. Variables analizadas: diseño del estudio, número de farmacias participantes, localización, periodo de estudio, cómo se utilizan y registran los protocolos, limitaciones, aplicabilidad y efectividad. RESULTADOS Y DISCUSIÓN: se seleccionaron 17 artículos para su análisis, el 47,2 % descriptivos y el 46,8 % analíticos. El número de farmacias participantes oscilaba entre 1 y 876 farmacias. La duración de los estudios también fue muy variable (rango: 6 días – 10 meses). El 76,5 % especificaron el método de registro. Se registraron variables del paciente, del motivo de la consulta y de la intervención farmacéutica, mayoritariamente en soporte papel. Solo un 23,5 % de los estudios mencionaban la aplicabilidad y la efectividad de los protocolos. (AU)

Leiomyosarcoma of the Nasal Cavity and Paranasal Sinuses: A Case Report and Comprehensive Review of the Literature.

Sinonasal leiomyosarcoma (LMS) is a rare and aggressive mesenchymal tumor with smooth muscle differentiation. The sinonasal tract is an unusual primary site for LMS, as scant smooth muscle exists in this location, with only 75 cases reported in the English literature including the case presented herein. Sinonasal LMS is considered an aggressive head and neck tumor with significant potential for recurrence and metastasis. Since recurrence is high and the potential for late metastasis exists, lifelong follow-up in these patients would be beneficial, especially among those with previous history of RB.

The CRTC1-MAML2 fusion is the major oncogenic driver in mucoepidermoid carcinoma.

No effective systemic treatment is available for patients with unresectable, recurrent, or metastatic mucoepidermoid carcinoma (MEC), the most common salivary gland malignancy. MEC is frequently associated with a t(11;19)(q14-21;p12-13) translocation that creates a CRTC1-MAML2 fusion gene. The CRTC1-MAML2 fusion exhibited transforming activity in vitro; however, whether it serves as an oncogenic driver for MEC establishment and maintenance in vivo remains unknown. Here, we show that doxycycline-induced CRTC1-MAML2 knockdown blocked the growth of established MEC xenografts, validating CRTC1-MAML2 as a therapeutic target. We further generated a conditional transgenic mouse model and observed that Cre-induced CRTC1-MAML2 expression caused 100% penetrant formation of salivary gland tumors resembling histological and molecular characteristics of human MEC. Molecular analysis of MEC tumors revealed altered p16-CDK4/6-RB pathway activity as a potential cooperating event in promoting CRTC1-MAML2-induced tumorigenesis. Cotargeting of aberrant p16-CDK4/6-RB signaling and CRTC1-MAML2 fusion-activated AREG/EGFR signaling with the respective CDK4/6 inhibitor Palbociclib and EGFR inhibitor Erlotinib produced enhanced antitumor responses in vitro and in vivo. Collectively, this study provides direct evidence for CRTC1-MAML2 as a key driver for MEC development and maintenance and identifies a potentially novel combination therapy with FDA-approved EGFR and CDK4/6 inhibitors as a potential viable strategy for patients with MEC.

Proliferative Verrucous Leukoplakia: An Expert Consensus Guideline for Standardized Assessment and Reporting.

The many diverse terms used to describe the wide spectrum of changes seen in proliferative verrucous leukoplakia (PVL) have resulted in disparate clinical management. The objective of this study was to produce an expert consensus guideline for standardized assessment and reporting by pathologists diagnosing PVL related lesions. 299 biopsies from 84 PVL patients from six institutions were selected from patients who had multifocal oral leukoplakic lesions identified over several years (a minimum follow-up period of 36 months). The lesions demonstrated the spectrum of histologic features described in PVL, and in some cases, patients developed oral cavity squamous cell carcinoma (SCC). An expert working group of oral and maxillofacial and head and neck pathologists reviewed microscopic features in a rigorous fashion, in combination with review of clinical photographs when available. The working group then selected 43 single slide biopsy cases for whole slide digital imaging (WSI) review by members of the consensus conference. The digital images were then reviewed in two surveys separated by a washout period of at least 90 days. Five non-PVL histologic mimics were included as controls. Cases were re-evaluated during a consensus conference with 19 members reporting on the cases. The best inter-observer diagnostic agreement relative to PVL lesions were classified as "corrugated ortho(para)hyperkeratotic lesion, not reactive" and "SCC" (chi-square p = 0.015). There was less than moderate agreement (kappa < 0.60) for lesions in the "Bulky hyperkeratotic epithelial proliferation, not reactive" category. There was ≥ moderate agreement (> 0.41 kappa) for 35 of 48 cases. This expert consensus guideline has been developed with support and endorsement from the leadership of the American Academy of Oral and Maxillofacial Pathology and the North American Society of Head and Neck Pathologists to recommend the use of standardized histopathologic criteria and descriptive terminology to indicate three categories of lesions within PVL: (1) "corrugated ortho(para)hyperkeratotic lesion, not reactive;" (2) "bulky hyperkeratotic epithelial proliferation, not reactive;" and (3) "suspicious for," or "squamous cell carcinoma." Classification of PVL lesions based on a combination of clinical findings and these histologic descriptive categories is encouraged in order to standardize reporting, aid in future research and potentially guide clinical management.

Continuous Scan Strategy (CSS): A Novel Technique to Improve the Accuracy of Intraoral Digital Impressions.

PURPOSE: To present the results obtained with the "Continuous Scan Strategy" (CSS), a direct intraoral scanning technique based on the connection of the implant scan bodies (SBs) with thermoplastic resin. METHODS: 40 patients were restored with 45 long-span monolithic implant-supported zirconia restorations (10 partial prostheses [PP] and 35 full arches [FA]) fabricated via a full-digital workflow after the capture of an intraoral impression (Trios3®) using the CSS technique. The primary outcomes were the marginal adaptation and passive fit of the superstructures, checked at T0 (intraoral try-in of polyurethane or metal replica of the final prosthesis) and T1 (delivery of the final zirconia restoration). The secondary outcomes, registered at T2 (2 years after the delivery of the final prosthesis), were implant survival, prosthetic success, and complications. A throughout statistical analysis was performed. RESULTS: At T0, 40/45 replicas demonstrated a perfect passive fit and adaptation. At T1, one prosthesis had fractured, and at T2, an additional prosthesis had fractured and one had chipped. The implant survival rate was 100%. The prosthetic success was 93.3%. CONCLUSIONS: CSS seems to represent a viable option for capturing accurate intraoral digital impressions for the fabrication of precise long-span implant-supported restorations.

Assessment of the quality of patient information sheets and informed consent forms for clinical trials at a hospital neurology service.

BACKGROUND AND PURPOSE: Clinical trials (CTs) aimed at vulnerable groups, such as patients with mental disorders, create ethical complexity. The patient information sheet (PIS) should provide all of the information about the CT that is relevant to the subject's decision to participate. After being informed, the subject will decide freely whether to take part in the CT and will read and sign the informed consent form (ICF). The objective was to assess the quality of PISs/ICFs from a hospital neurology service. The assessment was made using validated and reliable checklists of the information included in the PISs/ICFs of CTs with medicinal products. METHODS: The study comprised analyses of compliance with the checklists of 21 PISs and ICFs reviewed/approved during 2016-2017 by a medicinal research ethics committee. RESULTS: All PISs/ICFs were from multicenter CTs sponsored by pharmaceutical companies in different therapeutic areas, mainly Parkinson's (52.4%) and Alzheimer's (38.1%) diseases. The PISs from the neurology service demonstrated good compliance (≥80%) with the checklist, whereas ICFs should be improved. Sponsors omitted some relevant information, such as the study title or that the participant be informed of any information arising from the research that may be relevant to the subject's health, although this information may be in the PIS. CONCLUSIONS: The PISs/ICFs of CTs of medicinal products that are currently used need improvement. PISs and ICFs should be separate documents for each CT. In particular, the PISs/ICFs should consider the criteria related to the decision of participants, protect their rights and ensure that the information received is complete.

Benign lesions of the mediastinum: A review with emphasis on cytology and small biopsy specimens.

This review focuses on the diagnosis of select benign processes, ranging from reactive entities to heterotopic tissues to neoplasms, which may occur in the mediastinum. Currently, the mediastinum can be evaluated and biopsied with endoscopic procedures. Therefore, cytopathology specimens, fine needle aspirations, and small biopsies play an important role in the diagnosis of these lesions. In this review, an emphasis is given to relevant clinical presentations, histologic and cytologic findings, differential diagnoses, ancillary testing, and interpretation. Pitfalls are reviewed and discussed in each section. It is important for both surgical pathologists and cytopathologists to be familiar with these entities and their cytologic and histologic features that may be helpful in reaching a diagnosis.

Inter-observer Variability in the Diagnosis of Proliferative Verrucous Leukoplakia: Clinical Implications for Oral and Maxillofacial Surgeon Understanding: A Collaborative Pilot Study.

The use of diverse terminology may lead to inconsistent diagnosis and subsequent mistreatment of lesions within the proliferative verrucous leukoplakia (PVL) spectrum. The objectives of this study were: (a) to measure inter-observer variability between a variety of pathologists diagnosing PVL lesions; and (b) to evaluate the impact of diverse terminologies on understanding, interpretation, and subsequent treatment planning by oral and maxillofacial surgeons (OMFS). Six oral pathologists (OP) and six head and neck pathologists (HNP) reviewed 40 digitally scanned slides of PVL-type lesions. Inter-observer agreement on diagnoses was evaluated by Fleiss' kappa analysis. The most commonly used diagnostic terminologies were sent to ten OMFS to evaluate their resulting interpretations and potential follow-up treatment approaches. The overall means of the surgeons' responses were compared by Student t test. There was poor inter-observer agreement between pathologists on the diagnosis of PVL lesions (κ = 0.270), although there was good agreement (κ = 0.650) when diagnosing frankly malignant lesions. The lowest agreement was in diagnosing verrucous hyperplasia (VH) with/without dysplasia, atypical epithelial proliferation (AEP), and verrucous carcinoma (VC). The OMFS showed the lowest agreement on identical categories of non-malignant diagnoses, specifically VH and AEP. This study demonstrates a lack of standardized terminology and diagnostic criteria for the spectrum of PVL lesions. We recommend adopting standardized criteria and terminology, proposed and established by an expert panel white paper, to assist pathologists and clinicians in uniformly diagnosing and managing PVL spectrum lesions.