Predictivity of clinical, laboratory and imaging findings in diagnostic definition of palpable thyroid nodules. A multicenter prospective study

Abstract PURPOSE: To assess the role of clinical, biochemical, and morphological parameters, as added to cytology, for improving pre-surgical diagnosis of palpable thyroid nodules. METHODS: Patients with a palpable thyroid nodule were eligible if surgical intervention was indicated after a positive or suspicious for malignancy FNAC (TIR 4-5 according to the 2007 Italian SIAPEC-IAP classification), or two inconclusive FNAC at a 653 months interval, or a negative FNAC associated with one or more risk factor. Reference standard was histological malignancy diagnosis. Likelihood ratios of malignancy, sensitivity, specificity, negative (NPV), and positive predictive value (PPV) were described. Multiple correspondence analysis (MCA) and logistic regression were applied. RESULTS: Cancer was found in 433/902 (48%) patients. Considering TIR4-5 only as positive cytology, specificity, and PPV were high (94 and 91%) but sensitivity and NPV were low (61 and 72%); conversely, including TIR3 among positive, sensitivity and NPV were higher (88 and 82%) while specificity and PPV decreased (52 and 63%). Ultrasonographic size 653\u2009cm was independently associated with benignity among TIR2 cases (OR of malignancy 0.37, 95% CI 0.18-0.78). In TIR3 cases the hard consistency of small nodules was associated with malignity (OR: 3.51, 95% CI 1.84-6.70, p\u2009<\u20090.001), while size alone, irrespective of consistency, was not diagnostically informative. No other significant association was found in TIR2 and TIR3. CONCLUSIONS: The combination of cytology with clinical and ultrasonographic parameters may improve diagnostic definition of palpable thyroid nodules. However, the need for innovative diagnostic tools is still high

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Colorectal cancer; Emergency surgery; Hartmann’s procedureCàncer de colorectal; Cirurgia d'urgència; Procediment de HartmannCáncer colorrectal; Cirugía de emergencia; Procedimiento de HartmannBackground Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann’s procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions After 100 years since the first Hartmann’s procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment’s choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Juego compulsivo, arritmias y trastornos disautonómicos

Fil: Mitelman, Jorge E. Instituto Universitario de Ciencias de la Salud. Fundación Barceló; Argentina.Fil: Gimenez, Luisa. Instituto Universitario de Ciencias de la Salud. Fundación Barceló; Argentina.Fil: Perrone, Hebe. Instituto Universitario de Ciencias de la Salud. Fundación Barceló; Argentina.Fil: Acuña, Luciano. Instituto Universitario de Ciencias de la Salud. Fundación Barceló; Argentina.Fil: Palacios, Karina. Instituto Universitario de Ciencias de la Salud. Fundación Barceló; Argentina.Fil: Deboli, Alberto. Instituto Universitario de Ciencias de la Salud. Fundación Barceló; Argentina.La ludopatía fue reconocida por la Organización Mundial de la Salud en su clasificación internacional de enfermedades como una alteración progresiva del comportamiento por la cual un individuo siente una incontrolable necesidad de jugar (juegos de azar). Al igual que en otras adicciones, intervendría en el desarrollo de enfermedades cardiovasculares a través del disbalance del sistema nervioso autónomo y la predisposición a presentar arritmias

A Molecular Epidemiology Case Control Study on Pleural Malignant Mesothelioma

Abstract Pleural malignant mesothelioma is an uncommon neoplasm usually associated with asbestos exposure. The increasing incidence of malignant mesothelioma cases involving individuals with low levels of asbestos exposure suggests a complex carcinogenetic process with the involvement of other cofactors. Cytogenetic studies revealed the complexity of the genetic changes involved in this neoplasm reflecting the accumulation of genomic damage. One of the most used methodologies for assessing genomic damage is the cytokinesis-blocked micronucleus test applied in peripheral blood lymphocytes (PBL). This approach allows the detection of chromosomal alterations expressed in binucleated cells after nuclear division in vitro. This marker could provide a tool for assessing genetically determined constitutional differences in chromosomal instability. A biomonitoring study was carried out to evaluate the micronuclei frequency in PBLs of patients with pleural malignant mesothelioma with respect to lung cancer, healthy, and risk controls as a marker of cancer susceptibility in correlation with the presence of SV40. A significant increased micronuclei frequency was observed in patients with malignant mesothelioma in comparison with all the other groups, the mean micronuclei frequency was double in patients with malignant mesothelioma compared with healthy controls, risk controls, and patients with lung adenocarcinoma (median 11.4 binucleated cells with micronuclei/1,000 binucleated cells versus 6.2, 6.1, and 5.1, respectively). Our data indicate that human T lymphocyte samples carry DNA sequences coding for SV40 large T antigen at low prevalence, both in cancer cases and controls. Evidence of cytogenetic damage revealed as micronuclei frequency in mesothelioma cancer patients could be related to exogenous and endogenous cofactors besides asbestos exposure

Jogo compulsivo, arritmias e transtornos disautonômicos

INTRODUCCION: La ludopatía fue reconocida por la Organización Mundial de la Salud en su clasificación internacional de enfermedades como una alteración progresiva del comportamiento por la cual un individuo siente una incontrolable necesidad de jugar (juegos de azar). Al igual que en otras adicciones, intervendría en el desarrollo de enfermedades cardiovasculares a través del disbalance del sistema nervioso autónomo y la predisposición a presentar arritmias. OBJETIVOS: 1) Evaluar la respuesta cardiovascular al stress simulado o provocado mediante videojuegos competitivos. 2) Prevalencia de arritmias en jugadores compulsivos. 3) Evaluar la asociación entre la presencia de arritmias y disautonomía mediante Holter. 4) Detectar asociación entre ludopatía y disautonomía. MATERIAL Y MÉTODOS: En un estudio observacional, transversal, se incluyó una población de individuos adictos al juego de cartas (n=62), varones (42) y mujeres (20) con edades comprendidas entre los 42 a 61 años (51,7 ± 9.2). Como grupo control (juego ocasional), fueron incluidas 60 personas (46 varones), edades 39 a 50 años (46.6 ± 5.1). Para ser incluidos debían ser ambulatorios sin factores de riesgo que requiriesen ningún tipo de tratamiento y firmar el consentimiento escrito. Se llevó una ficha de entrevista, hoja de orientación (diagnóstico psiquiátrico DSM IV), diagnóstico situacional (ludopatía). (South Oaks Gambling Screen SOGS) A todos ellos se les realizó examen clínico completo, análisis de laboratorio, electrocardiograma de 12 derivaciones y Holter de 24 horas. Resultados En el grupo ludópata, la alteración disautonómica fue significativamente más frecuente cuando se compara con controles (pDISCUSION: La alteración simpática en los ludópatas (arousal, trastorno neurobiológico) es una complicación en la cual la disautonomía sería el origen de isquemia silente y predeciría un riesgo aumentado en la morbilidad y mortalidad cardiovascular por arritmias que se presentarían en jugadores compulsivos. La utilización de nuevas herramientas diagnósticas para detectar precozmente disautonomía permitirían evitar las complicaciones y consecuencias severas. mediante la aplicación de un tratamiento integral tanto psicológico como biológico

Jogo compulsivo, arritmias e transtornos disautonômicos

INTRODUCCION: La ludopatía fue reconocida por la Organización Mundial de la Salud en su clasificación internacional de enfermedades como una alteración progresiva del comportamiento por la cual un individuo siente una incontrolable necesidad de jugar (juegos de azar). Al igual que en otras adicciones, intervendría en el desarrollo de enfermedades cardiovasculares a través del disbalance del sistema nervioso autónomo y la predisposición a presentar arritmias. OBJETIVOS: 1) Evaluar la respuesta cardiovascular al stress simulado o provocado mediante videojuegos competitivos. 2) Prevalencia de arritmias en jugadores compulsivos. 3) Evaluar la asociación entre la presencia de arritmias y disautonomía mediante Holter. 4) Detectar asociación entre ludopatía y disautonomía. MATERIAL Y MÉTODOS: En un estudio observacional, transversal, se incluyó una población de individuos adictos al juego de cartas (n=62), varones (42) y mujeres (20) con edades comprendidas entre los 42 a 61 años (51,7 ± 9.2). Como grupo control (juego ocasional), fueron incluidas 60 personas (46 varones), edades 39 a 50 años (46.6 ± 5.1). Para ser incluidos debían ser ambulatorios sin factores de riesgo que requiriesen ningún tipo de tratamiento y firmar el consentimiento escrito. Se llevó una ficha de entrevista, hoja de orientación (diagnóstico psiquiátrico DSM IV), diagnóstico situacional (ludopatía). (South Oaks Gambling Screen SOGS) A todos ellos se les realizó examen clínico completo, análisis de laboratorio, electrocardiograma de 12 derivaciones y Holter de 24 horas. Resultados En el grupo ludópata, la alteración disautonómica fue significativamente más frecuente cuando se compara con controles (pDISCUSION: La alteración simpática en los ludópatas (arousal, trastorno neurobiológico) es una complicación en la cual la disautonomía sería el origen de isquemia silente y predeciría un riesgo aumentado en la morbilidad y mortalidad cardiovascular por arritmias que se presentarían en jugadores compulsivos. La utilización de nuevas herramientas diagnósticas para detectar precozmente disautonomía permitirían evitar las complicaciones y consecuencias severas. mediante la aplicación de un tratamiento integral tanto psicológico como biológico

Persistent Dystrophin Protein Restoration 90 Days after a Course of Intraperitoneally Administered Naked 2′OMePS AON and ZM2 NP-AON Complexes in mdx Mice

In Duchenne muscular dystrophy, the exon-skipping approach has obtained proof of concept in animal models, myogenic cell cultures, and following local and systemic administration in Duchenne patients. Indeed, we have previously demonstrated that low doses (7.5 mg/Kg/week) of 2 -O-methyl-phosphorothioate antisense oligoribonucleotides (AONs) adsorbed onto ZM2 nanoparticles provoke widespread dystrophin restoration 7 days after intraperitoneal treatment in mdx mice. In this study, we went on to test whether this dystrophin restoration was still measurable 90 days from the end of the same treatment. Interestingly, we found that both western blot and immunohistochemical analysis (up to 7% positive fibres) were still able to detect dystrophin protein in the skeletal muscles of ZM2-AON-treated mice at this time, and the level of exon-23 skipping could still be assessed by RT real-time PCR (up to 10% of skipping percentage). In contrast, the protein was undetectable by western blot analysis in the skeletal muscles of mdx mice treated with an identical dose of naked AON, and the percentage of dystrophin-positive fibres and exon-23 skipping were reminiscent of those of untreated mdx mice. Our data therefore demonstrate the long-term residual efficacy of this systemic low-dose treatment and confirm the protective effect nanoparticles exert on AON molecules

Persistent Dystrophin Protein Restoration 90 Days after a Course of Intraperitoneally Administered Naked 2′OMePS AON and ZM2 NP-AON Complexes in mdx Mice

In Duchenne muscular dystrophy, the exon-skipping approach has obtained proof of concept in animal models, myogenic cell cultures, and following local and systemic administration in Duchenne patients. Indeed, we have previously demonstrated that low doses (7.5 mg/Kg/week) of 2  -O-methyl-phosphorothioate antisense oligoribonucleotides (AONs) adsorbed onto ZM2 nanoparticles provoke widespread dystrophin restoration 7 days after intraperitoneal treatment in mdx mice. In this study, we went on to test whether this dystrophin restoration was still measurable 90 days from the end of the same treatment. Interestingly, we found that both western blot and immunohistochemical analysis (up to 7% positive fibres) were still able to detect dystrophin protein in the skeletal muscles of ZM2-AON-treated mice at this time, and the level of exon-23 skipping could still be assessed by RT real-time PCR (up to 10% of skipping percentage). In contrast, the protein was undetectable by western blot analysis in the skeletal muscles of mdx mice treated with an identical dose of naked AON, and the percentage of dystrophin-positive fibres and exon-23 skipping were reminiscent of those of untreated mdx mice. Our data therefore demonstrate the long-term residual efficacy of this systemic low-dose treatment and confirm the protective effect nanoparticles exert on AON molecules

Exon Skipping-Mediated Dystrophin Reading Frame Restoration for Small Mutations

n/