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3d printing is capable of providing dose individualization for pediatric medicines and translating the precision medicine approach into practical application. In pediatrics, dose individualization and preparation of small dosage forms is a requirement for successful therapy, which is frequently not possible due to the lack of suitable dosage forms. For precision medicine, individual characteristics of patients are considered for the selection of the best possible API in the most suitable dose with the most effective release profile to improve therapeutic outcome. 3d printing is inherently suitable for manufacturing of individualized medicines with varying dosages, sizes, release profiles and drug combinations in small batch sizes, which cannot be manufactured with traditional technologies. However, understanding of critical quality attributes and process parameters still needs to be significantly improved for this new technology. To ensure health and safety of patients, cleaning and process validation needs to be established. Additionally, adequate analytical methods for the in-process control of intermediates, regarding their printability as well as control of the final 3d printed tablets considering any risk of this new technology will be required. The PolyPrint consortium is actively working on developing novel polymers for fused deposition modeling (FDM) 3d printing, filament formulation and manufacturing development as well as optimization of the printing process, and the design of a GMP-capable FDM 3d printer. In this manuscript, the consortium shares its views on quality aspects and measures for 3d printing from drug-loaded filaments, including formulation development, the printing process, and the printed dosage forms. Additionally, engineering approaches for quality assurance during the printing process and for the final dosage form will be presented together with considerations for a GMP-capable printer design., (© 2021. The Author(s).)

Objectives: Our study aimed to evaluate the usefulness of Vitamin D3 (VitD3) among patients hospitalized for COVID-19. The primary endpoint was to evaluate the difference in survival rates between patients receiving and not VitD3. The secondary endpoints were to evaluate clinical outcomes, such as needing non-invasive ventilation (NIV), ICU transfer, and laboratory findings (inflammatory parameters). Methods: We conducted a retrospective, monocentric matched-cohort study, including patients attending our ward for COVID-19. Patients were divided into two groups depending on VitD3 administration (Group A) or not (Group B) among patients with low VitD levels (defined as blood levels < 30 ng/mL), which depended on physicians’ judgment. Our internal protocol provides VitD3 100,000 UI/daily for two days. Findings: 58 patients were included in Group A, and 58 in Group B. Patients were matched for age, sex, comorbidities, COVID-19-related symptoms, PaO2/FiO2 ratio, blood exams, and medical treatments. Regarding the principal endpoint, there was a statistically significant difference between the two groups in survival rates [Group A vs. Group B = 3 vs. 11 (p = 0.042)]. When considering secondary endpoints, Group A patients were less likely to undergo NIV [Group A vs. Group B = 12 vs. 23 (p = 0.026)] and showed an improvement in almost all inflammatory parameters. Conclusions: The link between VitD3 deficiency and the clinical course of COVID-19 during hospitalization suggests that VitD3 level is a useful prognostic marker. Considering the safety of supplementation and the low cost, VitD3 replacement should be considered among SARS-CoV-2 infected patients needing hospitalization.

Background: According to the international guidelines, patients affected by interstitial lung disease with unusual clinical presentation and radiological findings that are not classic for usual interstitial pneumonia end up meeting criteria for surgical lung biopsy, preferably performed with video-assisted thoracic surgery. The growing appeal of non-intubated thoracic surgery has shown the benefits in several different procedures, but the strict selection criteria of candidates are often considered a limitation to this approach. Although several authors define obesity as a contraindication for non-intubated thoracoscopic surgery, the assessment of obesity as a dominant risk factor represents a topic of debate when minor tubeless procedures such as lung biopsy are considered. Our study aims to investigate the impact of obesity on morbidity and mortality in non-intubated lung biopsy patients with interstitial lung disease, analyzing the efficacy and safeness of this procedure., Materials and Methods: The study group of 40 obese patients consecutively collected from 202 patients who underwent non-intubated lung biopsy was compared with overweight and normal-weight patients, according to their body mass index. Post-operative complications were identified as the primary endpoint. The other outcomes explored were the early 30-day mortality rate and intraoperative complications, length of surgery, post-operative hospitalization, patient's pain feedback, and diagnostic yield., Results: The overall median age of the patients was 67.4 years (60, 73.5). No 30-day mortality or significant differences in terms of post-operative complications ( P = 0.93) were noted between the groups. The length of the surgery was moderately longer in the group of obese patients ( P = 0.02). The post-operative pain rating scale was comparable among the three groups ( P = 0.45), as well as the post-operative length of stay ( P = 0.96). The diagnosis was achieved in 99% of patients without significant difference between groups ( P = 0.38)., Conclusion: Our analysis showed the safety and efficacy of surgical lung biopsy with a non-intubated approach in patients affected by lung interstitiopathy. In the context of perioperative risk stratification, obesity would not seem to affect the morbidity compared to normal-weight and overweight patients undergoing this kind of diagnostic surgical procedure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cherchi, Ferrari, Guerrera, Grimaldi, Pinna-Susnik, Murenu, Rosboch, Lybéris, Ibba, Balsamo, Saderi, Fois, Ruffini and Sotgiu.)

Objective: The relationship between chronic rhinosinusitis, asthma and allergic rhinitis is well known, but only recently has the scientific community started to evaluate these as different manifestations of a common pathogenic phenomenon, considering them as a unified airway disease., Methods: Twenty-two patients with chronic rhinosinusitis treated with endoscopic sinus surgery (ESS) were included in the study. Sino-nasal assessment questionnaire (SNAQ) investigating subjective evaluation of sino-nasal state was administered to patients, while objective evaluations included nasal endoscopy, sinonasal CT, skin prick tests, nasal cytology, spirometry, bronchodilator responsiveness testing and sputum eosinophil count. All tests were performed before surgery. Two months after surgery, SNAQ questionnaire, nasal endoscopy, spirometry and bronchodilator responsiveness testing were repeated., Results: All patients had significant improvement of subjective status: mean SNAQ score decreased in all from 99.31 to 16.04. Mean Forced Expiratory Volume in the 1 st second (FEV 1 ) significantly improved after surgery from 3.23 to 3.45 L/s., Conclusions: ESS achieved a beneficial effect on upper and lower airway status in patients with chronic rhinosinusitis with or without lower airway diseases., (Copyright © 2021 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Introduction: The early identification of factors that predict the length of hospital stay (HS) in patients affected by coronavirus desease (COVID-19) might assist therapeutic decisions and patient flow management., Methodology: We collected, at the time of admission, routine clinical, laboratory, and imaging parameters of hypoxia, lung damage, inflammation, and organ dysfunction in a consecutive series of 50 COVID-19 patients admitted to the Respiratory Disease and Infectious Disease Units of the University Hospital of Sassari (North-Sardinia, Italy) and alive on discharge., Results: Prolonged HS (PHS, >21 days) patients had significantly lower PaO2/FiO2 ratio and lymphocytes, and significantly higher Chest CT severity score, C-reactive protein (CRP) and lactic dehydrogenase (LDH) when compared to non-PHS patients. In univariate logistic regression, Chest CT severity score (OR = 1.1891, p = 0.007), intensity of care (OR = 2.1350, p = 0.022), PaO2/FiO2 ratio (OR = 0.9802, p = 0.007), CRP (OR = 1.0952, p = 0.042) and platelet to lymphocyte ratio (OR = 1.0039, p = 0.036) were significantly associated with PHS. However, in multivariate logistic regression, only the PaO2/FiO2 ratio remained significantly correlated with PHS (OR = 0.9164; 95% CI 0.8479-0.9904, p = 0.0275). In ROC curve analysis, using a threshold of 248, the PaO2/FiO2 ratio predicted PHS with sensitivity and specificity of 60% and 91%, respectively (AUC = 0.780, 95% CI 0.637-0.886 p = 0.002)., Conclusions: The PaO2/FiO2 ratio on admission is independently associated with PHS in COVID-19 patients. Larger prospective studies are needed to confirm this finding., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 Angelo Zinellu, Andrea De Vito, Valentina Scano, Panagiotis Paliogiannis, Vito Fiore, Giordano Madeddu, Ivana Maida, Elisabetta Zinellu, Arduino Aleksander Mangoni, Luigi Benedetto Arru, Ciriaco Carru, Sergio Babudieri, Pietro Pirina, Alessandro Giuseppe Fois.)

Idiopathic pulmonary fibrosis (IPF) is an aggressive pulmonary disease which shares several molecular, pathophysiological and clinical aspects with lung cancer, including high mortality rates. The antifibrotic drugs Nintedanib and Pirfenidone have recently been introduced in clinical practice for the treatment of IPF. Nintedanib is also used for the treatment of several malignancies, including non-small cell lung cancer (NSCLC) in combination with Docetaxel, while Pirfenidone showed some anti-neoplastic effects in preclinical studies. On the other hand, novel targeted agents and immunotherapies have been introduced in the last decade for the treatment of NSCLC, and some of them showed anti-fibrotic properties in recent studies. These evidences, based on the common pathophysiological backgrounds of IPF and lung cancer, make possible the mutual or combined use of anti-fibrotic and anti-neoplastic drugs to treat these highly lethal diseases. The aim of the present review is to depict the current scientific landscape regarding the repurposing of anti-neoplastic drugs in IPF and anti-fibrotic drugs in lung cancer, and to identify future research perspectives on the topic., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The first European case series are detecting a very high frequency of chemosensitive disorders in COVID-19 patients, ranging between 19.4% and 88%., Methods: Olfactory and gustatory function was objectively tested in 72 COVID-19 patients treated at University Hospital of Sassari., Results: Overall, 73.6% of the patients reported having or having had chemosensitive disorders. Olfactory assessment showed variable degree hyposmia in 60 cases and anosmia in two patients. Gustatory assessment revealed hypogeusia in 33 cases and complete ageusia in one patient. Statistically significant differences in chemosensitive recovery were detected based on age and distance from the onset of clinical manifestations., Conclusion: Olfactory and gustatory dysfunctions represent common clinical findings in COVID-19 patients. Otolaryngologists and head-neck surgeons must by now keep this diagnostic option in mind when evaluating cases of ageusia and nonspecific anosmia that arose suddenly and are not associated with rhinitis symptoms., (© 2020 Wiley Periodicals, Inc.)

Purpose: To present our experience of cases of pulmonary sarcoidosis with atypical HRCT patterns found during 2016 focusing on the differential diagnosis to contribute to the difficult role of the radiologist in the disease identification and to help the clinicians to reach the diagnosis., Materials and Methods: The HRCT examinations of 47 patients with sarcoidosis were studied retrospectively. All patients had a histopathological confirm of the disease. 29 (61.7%) show a typical pulmonary pattern and 18 (38.3%) an atypical pattern. The latter were evaluated by three experienced radiologists dedicated to thoracic disease to radiologically define the predominant pattern of presentation., Results: In the 18 patients (38.3%) with atypical sarcoidosis, the following parenchymal patterns were observed: four patients (22.2%) had interstitial fibrotic alterations, three patients (16.6%) with reticular pattern with inter-intralobular septal thickening, two patients (11.1%) with small-airway involvement with mosaic oligoemia, two patients (11.1%) with pleural involvement (pneumothorax and pleural plaques), one patient (5.5%) with fibrocystic changes, 1 (5.5%) with halo-sign, 1 (5.5%) with diffuse bilateral ground-glass opacities, and 1 (5.5%) with isolated lung mass; in addition, three patients (16.6%) with atypical lymph node pattern were also found., Conclusions and Discussion: The atypical pulmonary alterations found in CT examination can be confused with other lung diseases and they are always a challenge even for the most experienced radiologist. In our experience, cases with atypical pulmonary sarcoidosis patterns evaluated in the study are consistent with similar cases described in the literature, both in lymph node and atypical parenchymal involvement. All the atypical characteristics of the work should alert the radiologist to consider sarcoidosis among the possible differential diagnoses, always correlating the results of the computed tomography examination with appropriate clinical-laboratory evaluations.

The Martin-Puplett interferometer (MPI) is a differential Fourier transform spectrometer that measures the difference between spectral brightness at two input ports. This unique feature makes the MPI an optimal zero instrument, able to detect small brightness gradients embedded in a large common background. In this paper, we experimentally investigate the common-mode rejection achievable in the MPI at millimeter wavelengths, and discuss the use of the instrument to measure the spectrum of cosmic microwave background anisotropy.

Background: Pulmonary tuberculosis (TB), a highly contagious infectious disease, is a significant public health problem all over the world and remains an important cause of preventable death in the adult population. Endobronchial TB is an unusual form of thoracic TB that may be complicated by tracheobronchial stenosis, and bronchoesophageal fistula formation is a very rare complication. Tubercular lymphadenitis can also lead to fistula formation through a process of caseum necrosis and opening of a fistula between the bronchus and oesophagus., Case Report: We report an uncommon case of thoracic TB in an immunocompetent 73-year-old Caucasian man who presented several problems: bronchoesophageal fistula, endobronchial TB, and mediastinal lymphadenopathy in the absence of contemporary parenchymal consolidation. Furthermore, he presented a normal chest radiograph and mostly unclear and non-specific symptoms at onset., Conclusions: We emphasize the need for a better knowledge of this illness and awareness that it may have an unusual presentation. In these cases, diagnosis and proper treatment can be delayed, with severe complications for the patient. Pulmonary TB remains a real diagnostic challenge: a normal chest radiograph and nonspecific symptoms do not allow us to exclude this persistent infectious disease.

N-acetyl-L-cysteine (NAC) is a therapeutic drug widely used as mucolytic agent in the treatment of respiratory diseases. Recently it has been proposed that NAC administration may modify the plasma levels of low molecular weight thiols (LMW) like cysteine, homocysteine and glutathione, though it has been still debated if their plasma concentration increases or decreases during the therapy. Therefore research calls for methods able to analyze simultaneously NAC and the other plasma LMW thiols in order to evaluate if NAC is able to modify plasma thiols concentration and in particular to reduce homocysteine levels in hyperhomocysteinemia. In this paper we present a new capillary electrophoresis method that allows a baseline separation of plasma NAC from the physiological thiols. The proposed method has been utilized to measure the drug and the physiological LMW thiols in NAC administered chronic obstructive broncho-pneumopathy (COPB) disease patients.

Anti TNF-alpha drugs seem to be the new frontier of Rheumatoid Arthritis (RA) therapy. The association infliximab methotrexate has been approved for the treatment of RA not responding to the classic therapy, but the short clinical experience in using antiTNF-alpha molecules brings to segnalation of new risks or adverse events. We describe a case of a patient, treated for many years with classic RA therapy, which developed a refractory anemia after treatment with association infliximab-methotrexate.