Pirfenidone and Nintedanib in idiopathic pulmonary fibrosis: Real-life experience in an Italian referral centre.

BACKGROUND: Idiopathic pulmonary fibrosis has a median survival time after diagnosis of 2-5 years. The main goal of treating IPF is to stabilize or reduce the rate of disease progression. Nintedanib and Pirfenidone have been a breakthrough in the management of IPF. Here we evaluated the effectiveness of Pirfenidone and Nintedanib in a population of IPF patients diagnosed in the last 12 months at Florence ILD Referral Centre. METHODS: In the last 12 months, 82 IPF patients (66 male, mean age 78.3±23.8 years) were diagnosed and started antifibrotic therapy with Pirfenidone or Nintedanib. Their clinical and functional details were analyzed retrospectively at time 0 and after 6 and 12 months of therapy. RESULTS: The median age of the patients treated with Nintedanib was higher than that of the Pirfenidone group (p<0.0001). The most common symptoms at disease onset were exertional dyspnoea and dry cough with no differences between the two groups (p<0.05). All IPF patients manifested bibasal crackles at the time of diagnosis. No significant differences in FVC, FEV1, TLC and DLCO were found at time 0 or after 6 months between patients treated with Pirfenidone and Nintedanib (p>0.05). After 1 year, lung function test parameters of patients treated with Pirfenidone had remained stable from baseline. DISCUSSION: This study emphasizes that both antifibrotic drugs appeared to be a good therapeutic choice in terms of functional stabilization, also in older patients.

Is there room for luminal-basal urothelial cell population quantification? / ¿Hay lugar para la cuantificación de la población de células uroteliales luminales basales?

PURPOSE: Three cell layers compose the urothelium: basal, intermediate and luminal ("umbrella cells") and different diseases might arise from different cell populations. The aim of this study is to analyze the quantification ability of such cell populations by using four different protocols. METHODS: Twenty male rats (Wistar) were randomized in four groups of five animals: scraping, enzymatic 30, 45 and 60minutes. The cells were isolated, analyzed by flow cytometer and data processed by BD FACSDIVA™ software. RESULTS: The urothelium was separated in two cell populations that are different in size and complexity. The group that showed more efficiency in cells dissociation and cells separation was enzymatic protocol 45minutes. CONCLUSIONS: Enzymatic protocol 45minutes was able to isolate urothelial cell populations and might be explored as potential prognostic tool, patient selection and therapeutic target in urothelial diseases. Future studies should validate the potential clinical application to the proposed rational of luminal-basal paradigm in the urothelial cancer as hope for individualized approach.

Manejo del síndrome de abstinencia alcohólica en los pacientes críticos / Management of the syndrome of alcohol withdrawal in critical patients

El manejo del síndrome de abstinencia alcohólica es un desafío en los pacientes críticos. Con frecuencia, se desconocen los antecedentes de consumo de alcohol o este dato es incompleto, lo que limita la identificación de quienes pueden desarrollar este síndrome. El cese abrupto del consumo de alcohol coloca a estos pacientes en alto riesgo de sufrir síndrome de abstinencia alcohólica grave. Típicamente, las benzodiacepinas son consideradas las drogas de primera línea para el manejo de estos casos. Sin embargo, si el paciente progresa a un estado más grave con convulsiones o delirium tremens, puede ser necesario administrar medicación adyuvante a las benzodiacepinas, como el propofol o la dexmedetomidina, o emplear estas últimas drogas como terapias alternativas en aquellos que no responden a las benzodiacepinas. La aparición de convulsiones representa un fuerte factor de riesgo para la progresión a un síndrome de abstinencia alcohólica grave, con el desarrollo posterior de delirium tremens hasta en el 30% de los casos. El delirium tremens es el cuadro más grave y ocurre en el 5-20% de los pacientes con este síndrome, con una mortalidad hasta del 25% sin tratamiento y que se reduce al 0-1% con tratamiento. Es importante conocer el antecedente del consumo de alcohol para evitar el síndrome de abstinencia alcohólica o tratar rápidamente sus síntomas más graves, y mejorar la supervivencia de estos pacientes.(AU)

Alcohol withdrawal syndrome (AWS) is a well-known and a challenging condition occurring in critically ill patients. Frequently, history of alcohol abuse is unknown when the patient is admitted to the intensive care unit, limiting the identification of those who could develop AWS. The abrupt cessation of a heavy or constant drinking put these patients in high risk of suffering from this syndrome in its severe form. Typically, benzodiazepines are considered the first line of treatment. However, if clinical conditions progress to epileptic seizures or delirium tremens or are refractory to benzodiazepines, adjuvant drugs like propofol or dexmedetomidine might be an option to control the severe symptoms. Delirium tremens can occur in up to 30% of patients; it is the most severe picture with a mortality of 25% without treatment and that can be reduced to almost 0-1% with treatment. It is important to appropriately identify alcohol abuse in order to avoid the early clinical manifestations of AWS or rapidly treat its most severe symptoms and improve survival.(AU)

Increased dose-intensity of gemcitabine in advanced non small cell lung cancer (NSCLC): a multicenter phase II study in elderly patients from the "polmone toscano group" (POLTO).

Gemcitabine is usually administered at a planned dose-intensity (DI) from 750 to 800 mg/m2/week. Preclinical data have suggested a possible dose-response relationship of gemcitabine. A multicenter phase II study was conducted to evaluate the activity in terms of no progression rate (complete responses+partial responses+stable diseases) of gemcitabine administered at an increased DI (1000 mg/m2/week) in elderly advanced non-small-cell lung cancer (NSCLC) patients. Secondary endpoints were to evaluate tolerability, progression free survival and overall survival. Elderly (age>or=70 years) chemo-naive advanced NSCLC patients, ECOG PS 0-2, were treated with intravenous gemcitabine 1500 mg/m2 intravenous (30 min infusion) on days 1 and 8 every 21 days for four courses. One hundred and twenty-two patients with a median age of 75 years (range 70-84) entered the study. The following grade 3 (NCI-CTC) haematological toxicities were reported (percent of patients): neutropenia 2.4%, thrombocytopenia 1.6%, anaemia 2.4%. No grades 3-4 non-haematological toxicities were observed. Among 111 evaluable patients 52 (46.8%) no progressions, 17 (15.3%) partial responses (WHO criteria), 35 (31.5%) stable diseases and 59 (53.2%) progressions were observed. Median time to progression was 3.2 months and median duration of survival was 5.4 months. The overall 1-year survival rate was 27%. Although increased dose-intensity of gemcitabine in elderly NSCLC patients is feasible without severe toxicities, this does not seem to be associated with an increased activity and efficacy in comparison to standard gemcitabine regimens with lower dose-intensities.

Recurrent spontaneous breast hematoma: report of a case and review of the literature.

BACKGROUND: Breast hematomas are common after traumas, surgeries, or contusions. They are rarely spontaneous, but they can occur spontaneously in patients with hematologic disease or with coagulation disorders. MATERIAL AND METHODS: The authors report a clinical case of a 48-year-old female with a 27-year history of paroxysmal nocturnal hemoglobinuria who underwent mammography screening because of a painless palpable moveable node in the upper inner quadrant of the right breast. RESULTS: Mammography showed a partially defined heterogeneous node of 35 mm without microcalcifications in the upper inner quadrant of the right breast which, associated with the clinical features, seemed to be an hematoma. Further mammography and ultrasound after 45 days showed retrocession of the lesion, and another mammography obtained after 60 days was normal. Seventy-five days after the first episode, the patient complained of another node with a skin bruise in the upper outer quadrant of the same breast, which seemed to be a recurrent hematoma. Two months later the mammography obtained was normal. CONCLUSION: Breast hematoma must be thought of as a differential diagnosis for a breast node, regardless of previous trauma or hematologic disorders.