The Problem of Home Therapy during COVID-19 Pandemic in Italy: Government Guidelines versus Freedom of Cure?

After starting in late 2019, COVID-19 spread worldwide, and Italy was one of the first Western nations to be seriously affected. At that time, both the virus and the disease were little known and there were no Evidence-Based Medicine indications for treatment. The Italian Health Ministry guidelines claimed that, unless oxygen saturation fell to <92%, no pharmacological treatment was necessary during the first 72 hours, other than on a purely symptomatic basis, preferably with paracetamol. As later confirmed, that delay in therapeutic intervention may have been responsible for numerous hospital admissions and a very high lethality (3.5 %). To try to remedy this situation, several volunteer groups were formed, managing to promptlycure thousands of patients at home with non-steroidal anti-inflammatory drugs and a variety of re-purposed drugs (principally hydroxychloroquine, ivermectin) and supplements (such as antioxidants, polyphenols and vitamin D). Although not documented by any randomized controlled studies, these approaches were nonetheless based on the best available evidence, were aimed at addressing otherwise unmet major needs and produced a significant reduction of hospitalizations, of symptom duration, and a complete recovery from the disease compared with late treatment, according to some retrospective observational studies and the clinical experience of many physicians. A prompt discussion, with a clear and open exchange between healthcare Institutions and the said groups of voluntary physicians, could clarify the most effective approaches to reduce the number of hospitalizations and the lethality of this disease.

Vegetable but not animal protein intake is associated to a better physical performance: a study on a general population sample of adults.

BACKGROUND: The research was conducted in the frame of a population-based, case control study, called Genes Environment Interaction in Respiratory Disease. OBJECTIVE: To assess the association between protein intake and physical performance in a general population sample. DESIGN: Researchers investigated the association between the participants' dietary information and their physical performance using the 6-min walking test and the distance walked in metres (6MWD) as main outcome measure. Information on dietary intake was collected using the validated European Investigation into Cancer and Nutrition food frequency questionnaires (FFQs). Then, daily intake of energy and macronutrients was estimated by means of the NAF software (nutritional analysis of FFQ). Linear regression models were used to evaluate the associations between vegetable, animal and total protein intakes and the 6MWD. The models were adjusted for socio-demographic features, total fats and available carbohydrate intakes. RESULTS: The participants were 223 subjects (57% females) aged between 23 and 68 years. Their mean vegetable and animal proteins intake for gram/kg of body weight/day were, respectively, 0.4 and 0.7. After adjusting for all the potential confounders, there was a significant increase of 20.0 (95% CI 0.8; 39.2) m in the distance walked for an increase in 10 g/day of vegetable proteins and non-significant variations of -1.8 (95% CI -9.3; 5.7) m for an increase in 10 g/day of animal proteins and of 0.5 (95% CI -6.8; 7.7) for an increase in 10 g/day of total proteins. DISCUSSION AND CONCLUSIONS: Our result suggests a positive role of vegetable proteins on physical performance. Whether this result is related to the high protein intake itself or may be a consequence of the other properties of plant-based foods deserves further investigation.

Comparison of imaging-based and pathological dimensions in pancreatic neuroendocrine tumors.

AIM: To establish the ability of magnetic resonance (MR) and computer tomography (CT) to predict pathologic dimensions of pancreatic neuroendocrine tumors (PanNET) in a caseload of a tertiary referral center. METHODS: Patients submitted to surgery for PanNET at the Surgical Unit of the Pancreas Institute with at least 1 preoperative imaging examination (MR or CT scan) from January 2005 to December 2015 were included and data retrospectively collected. Exclusion criteria were: multifocal lesions, genetic syndromes, microadenomas or mixed tumors, metastatic disease and neoadjuvant therapy. Bland-Altman (BA) and Mountain-Plot (MP) statistics were used to compare size measured by each modality with the pathology size. Passing-Bablok (PB) regression analysis was used to check the agreement between MR and CT. RESULTS: Our study population consisted of 292 patients. Seventy-nine (27.1%) were functioning PanNET. The mean biases were 0.17 ± 7.99 mm, 1 ± 8.51 mm and 0.23 ± 9 mm, 1.2 ± 9.8 mm for MR and CT, considering the overall population and the subgroup of non-functioning- PanNET, respectively. Limits of agreement (LOA) included the vast majority of observations, indicating a good agreement between imaging and pathology. The MP further confirmed this finding and showed that the two methods are unbiased with respect to each other. Considering ≤ 2 cm non-functioning-PanNET, no statistical significance was found in the size estimation rate of MR and CT (P = 0.433). PBR analysis did not reveal significant differences between MR, CT and pathology. CONCLUSION: MR and CT scan are accurate and interchangeable imaging techniques in predicting pathologic dimensions of PanNET.

Total body fat and central fat mass independently predict insulin resistance but not hyperandrogenemia in women with polycystic ovary syndrome.

CONTEXT/OBJECTIVE: Obesity is a common feature of women with polycystic ovary syndrome (PCOS). The aim of this study was to assess the role of body fat on insulin resistance and androgen excess in these subjects. PATIENTS/DESIGN: One hundred sixteen consecutive Caucasian women with PCOS, diagnosed by the Rotterdam criteria, underwent accurate assessment of clinical, anthropometric, hormonal, and metabolic features. In particular, total fat mass and fat distribution were assessed by dual-energy x-ray absorptiometry, serum-free T by liquid chromatography mass spectrometry and equilibrium dialysis and insulin sensitivity by the glucose clamp technique. RESULTS: Total fat mass and truncal fat were significantly higher in insulin-resistant than in insulin-sensitive PCOS subjects (+89% and +127%, respectively, both P < .001), and both tended to be higher in hyperandrogenemic than in normoandrogenemic women (+22% and +28%, respectively, P = .087 and P = .090). All parameters of adiposity correlated inversely with insulin sensitivity (P < .001) and directly with serum-free T (P ≤ .001). A statistically significant inverse relationship was observed between insulin sensitivity and serum-free T concentrations (r = -0.527, P < .001). In a multiple regression analysis, either total fat mass or truncal fat, in addition to serum-free T and age, were independent predictors of insulin sensitivity. However, insulin sensitivity, but not total fat mass or truncal fat, was an independent predictor of free T concentrations. CONCLUSIONS: These data suggest that body fat contributes to determining insulin resistance in PCOS women. However, the association between body fat and hyperandrogenism seems to be to a large extent explained by insulin resistance.

The TNF-family cytokine TL1A inhibits proliferation of human activated B cells.

Death receptor (DR3) 3 is a member of the TNFR superfamily. Its ligand is TNF-like ligand 1A (TL1A), a member of the TNF superfamily. TL1A/DR3 interactions have been reported to modulate the functions of T cells, NK, and NKT cells and play a crucial role in driving inflammatory processes in several T-cell-dependent autoimmune diseases. However, TL1A expression and effects on B cells remain largely unknown. In this study, we described for the first time that B cells from human blood express significant amounts of DR3 in response to B cell receptor polyclonal stimulation. The relevance of these results has been confirmed by immunofluorescence analysis in tonsil and spleen tissue specimens, which showed the in situ expression of DR3 in antigen-stimulated B cells in vivo. Remarkably, we demonstrated that TL1A reduces B-cell proliferation induced by anti-IgM-antibodies and IL-2 but did not affect B-cell survival, suggesting that TL1A inhibits the signal(s) important for B-cell proliferation. These results revealed a novel function of TL1A in modulating B-cell proliferation in vitro and suggest that TL1A may contribute to homeostasis of effector B-cell functions in immune response and host defense, thus supporting the role of the TL1A/DR3 functional axis in modulating the adaptive immune response.

The early psoriatic arthritis screening questionnaire: a simple and fast method for the identification of arthritis in patients with psoriasis.

OBJECTIVE: Dermatologists usually see patients with psoriasis before arthritis develops, making them well placed to diagnose early PsA (ePsA). This study aimed to develop a rapid and robust screening questionnaire for predicting PsA in patients with psoriasis referred to a specialized joint dermatology-rheumatology combined clinic. METHODS: In all, 228 psoriasis patients naïve to DMARD treatment were administered two screening questionnaire: the new Early ARthritis for Psoriatic patients (EARP) questionnaire and the existing Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire. The diagnostic accuracy of the two questionnaires for the diagnosis of ePsA was compared by receiving operating characteristics curves. RESULTS: After psychometric analysis, a simplified questionnaire of 10 items was found to have good internal reliability (Cronbach's α = 0.83) and was much faster and simpler to administer than the PASE. Both the EARP and PASE questionnaires presented similar receiving operating characteristics curves (specificity 91.6 and 67.2 and sensitivity 85.2 and 90.7, respectively) in identifying ePsA patients by using the cut-off value of 3 for EARP-10 and the standard cut-off value of 44 for PASE. The CASPAR criteria for PsA were present in 61 (26.7%) of the patients at clinical presentation and in 32.9% at 1-year follow-up, and the EARP score of ≥3 correlated with clinically determined arthropathy by a rheumatologist. CONCLUSION: The EARP questionnaire is simple and fast to administer and proved robust for the identification of PsA in the dermatological setting. Dermatologists should consider the EARP for patients attending clinics, as it correlates well with early PsA diagnosis.

Effects of high-dilutions in behavioural models: a commentary on critical issues, from reproducibility to plausibility / Efeitos de altas diluições em modelos comportamentais: comentários sobre temas críticos, da reprodutibilidade a plausibilidade / Efectos de las altas diluciones em modelos comportamentales: comentários respecto a temas críticos, da reprodutibilidad a la plausibilidad

As part of a rigorous investigation into the effects of Gelsemium sempervirens on laboratory mice, we performed two complete series of experiments and published three scientific papers. A recent commentary has, however, called into question the reproducibility and validity of these findings. In this article we discuss the major issues raised by this critique within the framework of methodological aspects and the interpretation of results of high-dilution and homeopathic research. The charge of non-reproducibility is shown to be unfounded, because a same homeopathic medicine displayed the same direction of effects in two well-validated models (light-dark and open-), albeit with nonlinear patterns. The double-blind protocols and statistics by means of ANOVA were performed appropriately and the difference between dilutions of Gelsemium (5cH, 7cH, 9cH and 30cH with variations according to model) and placebo was statistically highly significant. Our investigations brought to light some problems related with the lack of activity of buspirone and diazepam (conventional anxiolytic drugs used as control) on some behavioural parameters, suggesting that Gelsemium may have broader action, and raising doubts as to the reliability of benzodiazepines as positive controls for homeopathic treatments. Concerning the plausibility of experiments in this , disputed on the grounds of alleged lack of dose-response effect, we note that the latter is not at all uncommon, and can be accounted for by a host of possible reasons. In conclusion, our research line showed reproducible and consistent effects of Gelsemium in laboratory mice.

Como parte da investigação rigorosa sobre os efeitos do Gelsemium sempervirens em camundongos de laboratório, realizamos dois conjuntos completos de experimentos o que deu origem a três artigos sobre o tema. Porém, uma crítica recentemente publicada questionou a reprodutibilidade e validade desses resultados. Neste artigo, discutimos os pontos principais levantados pelos críticos, com base em aspectos metodológicos e a interpretação de resultados de pesquisas em altas diluições e homeopatia. Mostramos que a crítica sobre a não reprodutibilidade é infundada porque um mesmo medicamento sempre gerou efeitos na mesma direção, em dois modelos bem validados (claro-escuro e campo aberto), embora com padrões não-lineares. Os protocolos duplo-cegos e a estatística ANOVA foram devidamente realizados e as diferenças estatísticas entre as diluições de Gelsemiun semprevirens (5cH, 7cH, 9cH e 30cH, com variações de acordo com o modelo) e o placebo foram altamente significativa. Nossas pesquisas trouxeram a tona alguns problemas relacionados com a atividade da buspirona e diazepam (drogas anxiolíticas convencionais usadas como controle) em alguns parâmetros comportamentais, sugerindo que Gelsemiun pode ter uma ação mais ampla, levantando dúvidas sobre o uso de benzodiazepinas como controle positivo para tratamentos homeopáticos. Em relação a plausividade dos experimentos nessa area e a alegada falta de efeito dose-resposta, notamos que estas não são de todo incomuns, e podem ser explicadas por uma série de possíveis razões. Em conclusão, nossa linha de pesquisa mostrou reprodutibilidade e efeitos consistentes, para os efeitos do Gelsemiun em camundongos de laboratório.

Como parte de una rigurosa investigación de los efectos de Gelsemium sempervirens en ratones de laboratorio, realizamos dos series completas de experimentos y publicamos tres artículos científicos. Sin embargo, un comentario reciente critica la reproductibilidad y validad de nuestros resultados. En este artículo discutimos los aspectos principales de esta crítica en relación a los aspectos metodológicos e interpretativos de la investigación en homeopatía y altas diluciones. La acusación de falta de reproductibilidad carece de fundamentos, pues los efectos de un mismo medicamento homeopático mostraron una misma dirección en dos modelos bien validados (luz/oscuridad y campo abierto), empero, con respuestas no lineares. Los protocolos doble ciego y cálculos estadísticos mediante ANOVA fueron ejecutados correctamente y la diferencia entre diluciones de Gelsemium (5cH, 7cH, 9cH y 30cH según el modelo) y placebo fueron notablemente significativas. Nuestra rigurosa investigación evidenció problemas relacionados con la inactividad de buspirona y diazepam (drogas ansiolíticas convencionales utilizadas como control) en algunos parámetros conductuales, lo que indica que Gelsemium puede tener una acción más amplia y que la confiabilidad de las benzodiazepinas como controles positivos de tratamientos homeopáticos debe ser cuestionada. Con respecto a la plausibilidad de los experimentos en este campo, cuestionados con base en la supuesta ausencia de efecto dosis-respuesta, recordamos que no se trata de nada poco común y que puede ser explicada por innúmeros factores. Concluyendo, nuestra línea de investigación demostró que Gelsemium causa efectos reproducibles y consistentes en ratones de laboratorio.

Effect of addition of FLT-3 ligand and megakaryocyte growth and development factor on hemopoietic cells in serum-free conditions.

The aim of this study was to clarify the mechanisms that regulate hematopoietic cell expansion in vitro by identifying defined culture conditions. We report the results of experiments with CD34(+) cells from cord blood (CB, n = 13), bone marrow (BM, n = 4), and mobilized peripheral blood stem cells (PBSC, n = 5) using two combinations of cytokines: (A) granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3), interleukin-6 (IL-6), stem cell factor (SCF), erythropoietin (EPO), insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (FGF-b) and (B) combination A plus FLT3 ligand (FL) and megakaryocyte growth and development factor (PEG rhMGDF). Cultures of immunoselected CD34(+) cells were performed in serum-free liquid medium without serum substitutes. The area under the curve (AUC) obtained by plotting the logarithm of the total number of viable cells, CD34(+) cells, and CFC per well, toward the week of culture was used as an index of cell expansion. With CB, a significant difference was obtained between the two combinations of cytokines with regard to the total number of viable cells, GM-CFC, and CD34(+) cells. The difference between the two combinations of cytokines obtained with BM was significant with respect to the total number of viable cells and CD34(+) cells but not for the erythroid and myeloid progenitors. When CD34(+) cells from peripheral blood stem cells (PBSC) were cultured in presence of the two combinations of cytokines, the difference in terms of AUC was not statistically significant. Our data indicate additional effects in terms of proliferation and expansion of hematopoietic cells in serum-free conditions when FL and polyethylene glycol (PEG) rhMGDF are included in culture and suggest a differential activity of these cytokines on cells from different hematopoietic sources.