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Diabetes mellitus and its complications are a known public health problem nowadays. Diabetic nephropathy is one of the main complications and the result of multiple mechanisms, including: activation of the renin-angiotensin-aldosterone system, formation of advanced glycation end products and chronic inflammation that led to glomerular and tubulo-interstitial damage producing mesangial expansion and glomerulosclerosis, which finally results in chronic kidney disease. Early detection of diabetic nephropathyis essential for adequate intervention to stop, or at least sloww down its progression. Multiple markers have been described, not only the classic ones such as serum creatinine, urea, and albuminuria, but at this point also novel biomarkers such as neutrophil gelatinase-associated lipocalin, tumor necrosis factor 1 receptor and monocyte chemoattractant protein-1, among others. The aim of this article was to provide an update review of the role of biomarkers in the diagnosis of diabetic nephropathy.

Lipschütz ulcer is a non-sexually transmitted genital lesion of unknown etiology, which presents as a painful vulvar ulcer. Lipschütz ulcers have been described in most continents. This is the first case reported in Peru and South America. We present the case of a 33-year-old female patient with a Lipschütz ulcer after being vaccinated with the second dose of the AstraZeneca COVID-19 vaccine. She reported having had only one sexual partner in her lifetime. Laboratory results were negative for herpes simplex 2, Cytomegalovirus, Toxoplasma gondii, Epstein-Barr virus, and syphilis. The patient received symptomatic treatment. Ten days after the onset, the patient was significantly better during follow-up. This case report displays a potential adverse effect of the AstraZeneca COVID-19 vaccine as a Lipschütz ulcer triggered by the host humoral immune response. However, further research is needed to establish the causal relationship between these two.

Introduction: Lung biopsy in asthmatic patients is justified in case of atypical presentations of asthma, when other differential diagnoses, such as hypersensitivity pneumonitis or eosinophilic granulomatosis with polyangiitis, could be possible or for research purposes., Aim: We aim to describe the utility and the safety of TBLC (transbronchial lung cryobiopsy) in asthmatic patients, providing data on the pathological changes occurring in the airways and in the lung parenchyma., Methods: We reviewed asthmatic patients that underwent TBLC, that eventually had only a final diagnosis of asthma., Results: Three patients were detected. TBLC described pathological abnormalities in peribronchiolar and alveolar spaces already well identified with SLB (surgical lung biopsy); the pathological information provided could be useful to better understand the pathobiology of the disease. Finally, we had no complications, confirming a satisfactory safety profile of TBLC., Conclusion: We suggest the potential role of TBLC in asthmatic patients: its safety and its acceptable diagnostic accuracy lead to consider this procedure instead of SLB when histological changes in lung parenchyma are needed for the differential diagnosis. Furthermore, TLBC could be useful for research in the pathobiology of asthma and severe asthma., Competing Interests: Since it is a retrospective analysis, no ethical committee approval was required.All patients gave the consent to treat their data anonimously.The authors declare that they have no competing interests. RP is a member of the Editorial Board of Multidisciplinary Respiratory Medicine.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Due to the increasing role of endosonography [endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and esophageal ultrasound-guided fine needle aspiration (EUS-FNA)] in the diagnosis of several lung diseases, the knowledge of technical aspects is mandatory to optimize the success of the procedure. Among those technicalities related to the procedure, the choice of a needle over another one-either in terms of dimension and type-may have a role in the diagnostic process, especially in some diseases such as lymphoproliferative disorders. In this review, we analyze the current knowledge about the biopsy needle for endosonography, providing also some hints for the future., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Several documents and guidelines provide recommendations for effective management of COPD patients. However, there is often a significant imbalance between recommended treatment of COPD patients and the actual care provided both in primary care and specialty setting. This imbalance could result in a significant negative impact on patients' health status and quality of life, leading to increased hospitalisations and health resource utilisation in COPD patients METHODS: MISTRAL was an observational, longitudinal, prospective cohort study, designed to assess the overall pharmacological approach of COPD in routine clinical practice in Italy. Eligible patients were divided into two cohorts based on their exacerbation history in the year prior to the enrolment, frequent exacerbators (FEs; ≥2 exacerbations), and non-frequent exacerbators (NFEs; ≤1 exacerbation). The primary objective was to assess adherence to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 treatment recommendations in FEs and NFEs at baseline and follow-up visits RESULTS: Of the 1489 enrolled patients, 1468 (98.6%; FEs, 526; NFEs, 942) were considered evaluable for analyses. At baseline, 57.8% of patients were treated according to GOLD 2011 recommendations; a greater proportion of FEs were treated according to GOLD recommendations, compared with NFEs patients at baseline (77.1% versus 46.7%; P < 0.0001), and all study visits. At baseline, GOLD group D patients were the most adherent (81.2%) to treatment recommendations, while group A patients were the least adherent (30.3%) at baseline, attributed mainly to overuse of inhaled corticosteroids in less severe GOLD groups. Triple therapy with long-acting muscarinic antagonist (LAMA) + long-acting β 2 -agonist/inhaled corticosteroid (LABA/ICS) was the most frequent prescribed treatment at all study visits, irrespective of patient's exacerbation history. Changes in treatment were more frequent in FEs versus NFEs CONCLUSIONS: The Mistral study reports a scarce adherence to the GOLD 2011 treatment recommendations in routine clinical practice in Italy. The adherence was particularly low in less severe, non-frequent exacerbating patients mostly for ICS overuse, and was higher in high-risk, frequent exacerbating COPD patients., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The LDA-1/2 method evaluates ionization potentials as the energy of the highest occupied molecular orbitals (HOMOs) at half occupation. It has proven to be a viable approach for calculating band gaps of semiconductors. To address its accuracy for finite systems, we apply LDA-1/2 to the atoms and molecules of the GW100 test set. The obtained HOMO energies are validated against CCSD(T) data and the G 0 W 0 approach of many-body perturbation theory. The accuracy of LDA-1/2 and G 0 W 0 is found to be the same, where the latter is computationally much more involved. To get insight into the benefits and limitations of the LDA-1/2 method, we analyze the impact of each assumption made in deriving the methodology.

Introduction: Although pleural effusion (PE) can be caused by several pathologies like congestive heart failure, infections, malignancies, and pulmonary embolism, it is also a common finding in chronic kidney disease (CKD). Diagnostic thoracentesis is of limited value in the differential diagnosis, and the role of more invasive investigations like medical thoracoscopy (MT) is still unclear., Aim: To evaluate the usefulness of MT in unexplained PE in CKD., Materials and Methods: In the electronic database of our Institution, we retrospectively searched for patients with CKD who underwent MT for unexplained PE between January 2008 and August 2016., Results: Ten patients were included in the present study. The average age was 72.4 years, the male:female ratio 9:1 and the average blood creatinine value 5.96 mg/dL. The average follow-up was 18 months.A thoracentesis showed an exudate was found in 9 patients and in 1 case pleural fluid characteristics were not recorded for technical reasons; in none of them the cytologic or microbiological analyses were considered diagnostic.The clinical suspicion was a neoplastic (5) or an infectious disease (5). In 4 patients with recurrent PE, MT was performed to obtain talc pleurodesis.No immediate procedure-related complications were recorded; 1 patient developed empyema after 2 months. In 6 cases final diagnosis was chronic uremic pleuritis, hydrothorax in 2, and chronic lymphocytic pleurisy in 2., Conclusions: MT represents a safe and effective diagnostic and therapeutic procedure in patients with CKD, that itself is a common cause of exudative effusion, and those patients may not require MT.

It has long been known that the local density approximation and the generalized gradient approximation do not furnish reliable band gaps, and one needs to go beyond these approximations to reliably describe these properties. Among alternatives are the use of hybrid functionals (HSE03 and HSE06 being popular), the GW approximation or the recently proposed LDA-1/2 method. In this work, we compare rigorously the performance of these four methods in describing the band gaps of alloys, employing the generalized quasi-chemical approach to treat the disorder of the alloy and to obtain judiciously the band gap for the entire compositional range. Zincblende InGaAs and InGaN were chosen as prototypes due to their importance in optoelectronic applications. The comparison between these four approaches was guided both by the agreement between the predicted band gap and the experimental one, and by the demanded computational effort (time and memory). We observed that the HSE06 method provided the most accurate results (in comparison with experiments), whereas, surprisingly, the LDA-1/2 method gave the best compromise between accuracy and computational resources. Due to its low computational cost and good accuracy, we decided to double the supercell used to describe the alloys, and employing LDA-1/2 we observed that the bowing parameter changed remarkably, only agreeing with the measured one for the larger supercell, where LDA-1/2 plays an important role.

Background: (Buccalin ®) is a Bacterial Lysates (BL) that belongs to a family of immune-stimulators, developed more than 30 years ago and it still has a role in the prophylaxis of Recurrent Respiratory Tract Infections (RRTI). However, original studies were conducted with an approach that does not seem to be aligned with the present methodologies. In addition, concomitant therapies substantially improved in the last decades. These two reasons strongly suggested to update our knowledge on the capacity of this bacterial lysate (Buccalin ®) to reduce the number of days with infectious episodes in patients with RRTI., Methods: A double blind, placebo-controlled, randomized, multicentre study was programmed (EudraCT code: 2011-005187-25). The reduction of the number of days with infectious episodes (IE) was the primary endpoint. Secondary endpoints were the number of IE, the use of concomitant drugs, the efficacy on signs and symptoms of RRTI and the safety of the drug. Patients were treated according to the registered schedule and were followed up for a period of 6 months., Results: From a cohort of 188 patients eligible for the study, 90 were included in the active group and 88 in the placebo group. The study was completed in 170 patients. A significant reduction of the number of days with IE was observed (6.57 days in the active group and 7.47 in the placebo group). Secondary endpoints were only partially achieved. No virtual adverse events related to the treatment were recorded., Conclusion: The administration of bacterial lysate (Buccalin ®) in patients with RRTI had the capacity to significantly reduce the number of days with IE in a multicentre, randomized, placebo controlled, clinical study. The treatment was safe. Of note, all patients were free to be treated with the best concomitant therapies. In these conditions, the positive results observed demonstrated that this bacterial lysate has maintained its capacity of reducing the days with infections in patients with RRTI, also in association to the concomitant therapies available nowadays.

The most recent guidelines define COPD in a multidimensional way, nevertheless the diagnosis is still linked to the limitation of airflow, usually measured by the reduction in the FEV1/FVC ratio below 70%. However, the severity of obstruction is not directly correlated to symptoms or to invalidity determined by COPD. Thus, besides respiratory function, COPD should be evaluated based on symptoms, frequency and severity of exacerbations, patient's functional status and health related quality of life (HRQoL). Therapy is mainly aimed at increasing exercise tolerance and reducing dyspnea, with improvement of daily activities and HRQoL. This can be accomplished by a drug-induced reduction of pulmonary hyperinflation and exacerbations frequency and severity. All guidelines recommend bronchodilators as baseline therapy for all stages of COPD, and long-acting inhaled bronchodilators, both beta-2 agonist (LABA) and antimuscarinic (LAMA) drugs, are the most effective in regular treatment in the clinically stable phase. The effectiveness of bronchodilators should be evaluated in terms of functional (relief of bronchial obstruction and pulmonary hyperinflation), symptomatic (exercise tolerance and HRQoL), and clinical improvement (reduction in number or severity of exacerbations), while the absence of a spirometric response is not a reason for interrupting treatment, if there is subjective improvement in symptoms. Because LABA and LAMA act via different mechanisms of action, when administered in combination they can exert additional effects, thus optimizing (i.e. maximizing) sustained bronchodilation in COPD patients with severe airflow limitation, who cannot benefit (or can get only partial benefit) by therapy with a single bronchodilator. Recently, a fixed combination of ultra LABA/LAMA (indacaterol/glycopyrronium) has shown that it is possible to get a stable and persistent bronchodilation, which can help in avoiding undesirable fluctuations of bronchial calibre.

Lung cancer is the most common cancer in the world today, in terms of both incidence and mortality. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers, and the majority of people diagnosed with NSCLC have locally advanced or metastatic disease. Treatment algorithms have rapidly changed in the last 10 years because of the introduction of new chemotherapeutic and targeted agents in clinical practice. SUN is a 1-year longitudinal observational multicenter study that has consecutively enrolled patients affected by stage IIIB or IV NSCLC with the aim to describe the pattern of care and evolving approaches in the treatment of advanced NSCLC. 987 consecutive NSCLC patients were enrolled between January 2007 and March 2008 at the 74 participating centers throughout Italy and a 12-month follow-up was performed. Cyto-histological diagnosis was performed mainly by broncoscopy with only 24% by CT-scan guided fine-needle aspiration biopsy. 91.4% of the patients received a first-line medical treatment and 8.6% supportive care only. Median age of patients receiving first-line treatment was 66 years. First-line chemotherapy consisted of a single agent in 20% of patients and combination chemotherapy in 80%. The most frequently used chemotherapy regimens were cisplatin plus gemcitabine and carboplatin plus gemcitabine. Median survival of patients receiving first-line chemotherapy was 9.1 months. 32% percent of patients received a second-line treatment that consisted of chemotherapy in 71% of cases and erlotinib in 29%. Overall third-line treatment was given to 7.3% of patients. These results showed a pattern of care for advanced NSCLC that reflects the current clinical practice in Italy at the study time with a high adherence to the International guidelines by the Italian Oncologists., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Docking techniques and the HINT (Hydropathic Interaction) program were used to explain interactions of aflatoxin B(1) and ochratoxin A with beta- and gamma-cyclodextrins. The work was aimed at designing a chemosensor to identify very low concentrations of these mycotoxins by exploiting the affinity of the cyclodextrin cavity for many small organic molecules. Actually, the inclusion of the fluorescent portion of these toxins into the cavity may lower the quenching effect of the solvent, thus enhancing the luminescence. HINT is a 'natural' force field, based on experimentally determined LogP(octanol/water) values, that is able to consider both enthalpic and entropic contributions to the binding free energy with an unified approach. HINT is normally applied to predict the DeltaG degrees of binding for protein-ligand, protein-protein, and protein-DNA interactions. The leading forces in biomolecular processes are the same as those involved in organic host-guest inclusion phenomena, therefore we applied this methodology for the first time to cyclodextrin complexes. The results allowed us to explain spectroscopic data in absence of available crystallographic or NMR structural data.

Oxidative stress caused by airway inflammation is increased in chronic obstructive pulmonary disease (COPD) and may account for the progressive deterioration of structure and function of the respiratory tract observed in this disease. Antioxidant defences of the respiratory tract may be overwhelmed by the oxidant burden in COPD and possibly restored with antioxidant therapy. The level of hydrogen peroxide (H(2)O(2)) concentration in exhaled air condensate (EAC) is a valuable tool for assessing and monitoring oxidative stress. This study aimed to verify the effect of 2-month oral N-acetylcysteine (NAC) treatment compared to placebo on the H(2)O(2) content in EAC of 55 clinically stable COPD patients (48 males), mean age 65.93+/-9.3 years. After clinical examination, pulmonary function tests, and collection of EAC for the basal (T0) assay of H(2)O(2), patients were randomly allocated to group A (usual therapy plus oral NAC 600 mg b.i.d. for 2 months) or group B (usual therapy plus placebo b.i.d. for 2 months). H(2)O(2) assay in EAC was repeated at 15 (T15), 30 (T30), and 60 (T60) days after the start of therapy in each group. All patients were non-smokers or ex smokers for at least 5 years and the two groups were comparable in terms of demographic, respiratory function, and EAC data at baseline. The H(2)O(2) level in EAC of group A was significantly decreased at T15 (1.00+/-0.38 SD microM; p=0.003), T30 (0.91+/-0.44 microM; p=0.007), and T60 (0.83+/-0.41 microM; p=0.000) compared to T0 (1.28+/-0.61 microM). No significant decrease in H(2)O(2) of group B was found at any time point. We conclude that oral NAC 600 mg b.i.d. for 2 months rapidly reduces the oxidant burden in airways of stable COPD patients.

Chronic persistent cough (CPC) is a common symptom generally caused by postnasal drip syndrome (PND), bronchial asthma (A), chronic bronchitis (CB), and gastro-oesophageal reflux (GOR). The purpose of this study was to confirm the value of a testing protocol for determining the causes of CPC in adult patients and for evaluating the outcome of its specific therapy. Ninety-two patients with unexplained CPC were sent to our Department between January 1994 and June 1996. The mean (+/- SE) duration of cough was 32.7 (+/- 4.5) months. We studied these patients (number) by applying an anatomical protocol, according to which clinical evaluation they underwent: chest (92) and sinus (90) radiography, spirometry (92), methacholine inhalation challenge (88), skin prick tests (67), oesophagoscopy (28), prolonged oesophageal pH monitoring (14), and bronchoscopy (49), as needed. The results of the standardized specific therapy refer to 87 patients because 5 patients were lost to follow-up. Thus, CPC was due to: sinusitis or chronic rhinitis plus PND in 56% of patients, CB in 18%, A in 14%, GOR in 5%, PND and GOR in 6%, A and GOR in 1%. The cough went away in 79/87 patients after specific treatment, based on the diagnostic findings, giving a success rate of 91%. The results of the present study confirm previous findings indicating that one or more causes of chronic persistent cough can be found, and that an elevated success rate of therapy was reached when an anatomic diagnostic protocol was used.

Patients affected with chronic obstructive pulmonary disease (COPD) undergo frequent exacerbations of their illness characterized by increased cough and expectoration. The precise aetiology of these episodes often remains unknown. In the absence of clinical or radiographic signs of pneumonia, bacterial or viral cultures of sputum usually provide little useful information. Thus, we performed fibreoptic bronchoscopy using a protected specimen brush (PSB) to obtain uncontaminated secretions for culture from 56 patients with COPD, 16 with stable clinical conditions and 40 affected with exacerbations of the disease. The aim of our study was to evaluate bronchial microbial flora by quantitative aerobic and anaerobic culture of each specimen. Twenty five subjects (45%), 4 (16%) in stable state and 21 (84%) with COPD exacerbations, had specimens which gave rise to significant bacterial growth (> 10(3) colony forming units.mL-1). The predominant bacteria were Streptococcus pneumoniae (in 10 cases) and alpha-haemolytic streptococci (in 6 cases); other bacteria found were coagulase-negative staphylococci and Branhamella catarralis in (2 cases each), and Proteus mirabilis, Haemophilus influenzae, Pseudomonas aeruginosa, Aerococcus viridans and Chromobacterium violaceum (each in a single case only). Although significant bacterial growth was more frequently found in patients with chronic obstructive pulmonary disease exacerbations and in those with a higher degree of bronchial inflammation, the differences between the two groups of patients were not statistically significant. Nevertheless, the results obtained in our study confirm the validity of and the need for reliable sampling methods (like the protected specimen brush) to demonstrate significant bacterial colonization of the airways in chronic obstructive pulmonary disease patients.

The objective of this study was to verify whether the assay of carcinoembryonic antigen (CEA) in bronchoalveolar lavage fluid (BALF) can increase the sensitivity and specificity of serum CEA for the diagnosis of lung cancer. We examined 72 subjects, 53 males and 19 females, 18 affected with peripheral lung cancer (10 adenocarcinoma, 6 squamous cell carcinoma, 1 small cell lung cancer, 1 adenosquamous carcinoma), 19 with acute pneumonia, 14 with chronic obstructive pulmonary disease (COPD), 6 with interstitial lung disease (ILD), and 15 healthy subjects. CEA was assayed in blood and in BALF using microparticle enzyme immunoassay (MEIA) (IMX Abbott). The mean serum CEA value in the lung cancer group did not differ from that in each group of non-neoplastic subjects, neither was it different from that in healthy subjects. The mean BALF CEA in patients with lung cancer, pneumonia, and COPD was significantly increased compared with that in healthy subjects, whereas there was no difference between the three groups of patients. The ratio of BALF CEA was not significantly different in the three groups of patients. There were no differences according to the histological type of the tumour (adenocarcinoma or squamous cell carcinoma). Based on the results in healthy subjects, the upper limits of normal were defined for serum CEA, BALF CEA, and CEA/albumin ratio. Thus, the sensitivity of BALF CEA in detecting lung cancer (50%) was higher than that of serum CEA (33%), although clinically not useful. In addition, BALF CEA had only 59% specificity compared to 100% of serum CEA. The diagnostic accuracy was 79% for serum CEA and 56% for BALF CEA.(ABSTRACT TRUNCATED AT 250 WORDS)

A 65 year old man presented with exacerbation of the chronic bronchitis from which he had been suffering for several years. A chest X-ray revealed disatelectatic pulmonary zones. Bronchoscopy showed numerous nodules, beginning at the mid-trachea and extending into the major bronchi. Histological examination of the biopsy specimens demonstrated well-differentiated cartilaginous tissue, consistent with tracheobronchopathia osteochondroplastica.

A 61 year old man presented with chronic bronchitis, which he had been suffering from for many years, and reported the recent onset of polyuria with polydipsia. A chest X-ray showed a peripheral pulmonary nodule in the right lower lobe, that was diagnosed as small cell lung cancer following histological examination of the pulmonary tissue specimen, obtained with transbronchial biopsy. After establishing the central origin of the diabetes insipidus, its cause was revealed by magnetic resonance imaging of the brain, that demonstrated metastasis to the hypothalamic-neurohypophyseal area.