Med Sci (Paris). 2021 May;37(5):491-499. doi: 10.1051/medsci/2021051. Epub 2021 May 18.

ABSTRACT

Neonatal screening for cystic fibrosis has optimised the prognosis for patients allowing very early multidisciplinary care. Over the past 20 years, screening programmes have undergone major international expansion. The performances of the French neonatal cystic fibrosis screening programme, established in 2002, has met European guideline standards, with positive predictive value of 0.31 (against a minimum of 0.30) and sensitivity value of 0.95 (against a minimum of 0.95). It is also important to highlight the very high percentage of sweat tests performed (95.5%), of mutations identified (96.6%), the 9:1 ratio of cystic fibrosis cases to cases of inconclusive diagnosis achieved and the effectiveness of the strategy implemented for the detection of false negative cases. A new organisation for cystic fibrosis neonatal screening has now been established in France. It is vital that effectiveness is maintained throughout the process, from newborn maternity care to diagnosis in cystic fibrosis care centres, and that further knowledge is gained through exhaustive data collection and validation.

PMID:34003095 | DOI:10.1051/medsci/2021051

Med Sci (Paris). 2021 May;37(5):441-456. doi: 10.1051/medsci/2021059. Epub 2021 May 18.

ABSTRACT

Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders ("conditions") then gradually expanded, with a boost in the late 1990's with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40-50 conditions in one blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular genetics techniques. For this survey we collected data from 51 European countries. We report on the developments between 2010 and 2020, and highlight the achievements made during this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe have matured considerably, both in terms of methodology (modernised) and with regards to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. Only by working together can we accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate actions.

PMID:34003089 | DOI:10.1051/medsci/2021059

Cell Death Discov. 2021 May 18;7(1):113. doi: 10.1038/s41420-021-00491-3.

ABSTRACT

Reactive oxygen species (ROS) are essential for neutrophil extracellular trap (NET) formation or NETosis. Nevertheless, how ROS induces NETosis is unknown. Neutrophil activation induces excess ROS production and a meaningless genome-wide transcription to facilitate chromatin decondensation. Here we show that the induction of NADPH oxidase-dependent NETosis leads to extensive DNA damage, and the subsequent translocation of proliferating cell nuclear antigen (PCNA), a key DNA repair protein, stored in the cytoplasm into the nucleus. During the activation of NETosis (e.g., by phorbol myristate acetate, Escherichia coli LPS, Staphylococcus aureus (RN4220), or Pseudomonas aeruginosa), preventing the DNA-repair-complex assembly leading to nick formation that decondenses chromatin causes the suppression of NETosis (e.g., by inhibitors to, or knockdown of, Apurinic endonuclease APE1, poly ADP ribose polymerase PARP, and DNA ligase). The remaining repair steps involving polymerase activity and PCNA interactions with DNA polymerases β/δ do not suppress agonist-induced NETosis. Therefore, excess ROS produced during neutrophil activation induces NETosis by inducing extensive DNA damage (e.g., oxidising guanine to 8-oxoguanine), and the subsequent DNA repair pathway, leading to chromatin decondensation.

PMID:34001856 | DOI:10.1038/s41420-021-00491-3

Ann Am Thorac Soc. 2021 May 17. doi: 10.1513/AnnalsATS.202102-220RL. Online ahead of print.

NO ABSTRACT

PMID:34000224 | DOI:10.1513/AnnalsATS.202102-220RL

Ugeskr Laeger. 2021 May 10;183(19):V12200978.

ABSTRACT

Aquagenic wrinkling of the palms was first described in 1974. This review summarises the present knowledge. Aquagenic wrinkling of the palms is most often associated with cystic fibrosis, but several other associated conditions are described. Patients report of pruritus, pain and discomfort in the palms after contact with water, and excessive wrinkling is visible. The prognosis is good, and symptoms often decrease in adulthood. A positive water exposure test will support the diagnosis, and the patient should be referred for dermatological investigation and genetic test for cystic fibrosis should be offered.

PMID:33998454

Front Microbiol. 2021 Apr 30;12:626715. doi: 10.3389/fmicb.2021.626715. eCollection 2021.

ABSTRACT

Pseudomonas aeruginosa (Pae) is notorious for its high-level resistance toward clinically used antibiotics. In fact, Pae has rendered most antimicrobials ineffective, leaving polymyxins and aminoglycosides as last resort antibiotics. Although several resistance mechanisms of Pae are known toward these drugs, a profounder knowledge of hitherto unidentified factors and pathways appears crucial to develop novel strategies to increase their efficacy. Here, we have performed for the first time transcriptome analyses and ribosome profiling in parallel with strain PA14 grown in synthetic cystic fibrosis medium upon exposure to polymyxin E (colistin) and tobramycin. This approach did not only confirm known mechanisms involved in colistin and tobramycin susceptibility but revealed also as yet unknown functions/pathways. Colistin treatment resulted primarily in an anti-oxidative stress response and in the de-regulation of the MexT and AlgU regulons, whereas exposure to tobramycin led predominantly to a rewiring of the expression of multiple amino acid catabolic genes, lower tricarboxylic acid (TCA) cycle genes, type II and VI secretion system genes and genes involved in bacterial motility and attachment, which could potentially lead to a decrease in drug uptake. Moreover, we report that the adverse effects of tobramycin on translation are countered with enhanced expression of genes involved in stalled ribosome rescue, tRNA methylation and type II toxin-antitoxin (TA) systems.

PMID:33995291 | PMC:PMC8120321 | DOI:10.3389/fmicb.2021.626715

Saudi Pharm J. 2021 Apr;29(4):291-304. doi: 10.1016/j.jsps.2021.02.005. Epub 2021 Mar 10.

ABSTRACT

In the present study, we have investigated and/or compared the role of glibenclamide, G as cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor, and lubiprostone, L as chloride channel-2 (ClC-2) activator in the 2,4-dinitrobenzene sulfonic acid (DNBS)-induced gastrointestinal inflammation. GI inflammation was induced by intrarectal administration of DNBS. Rats were randomly allocated in 5 groups as sham control, distilled water + DNBS, sulfasalazine (S) + DNBS, G + DNBS, and L + DNBS. All the groups were pre-treated successively for five days before the induction of colitis. One day before and the first four days after DNBS administration various parameters were studied. Later, blood chemistry, colon's gross structure, histology, and the antioxidant load was examined. Pre-treatment with G significantly protected the change induced by DNBS concerning the change in body weight, food intake, diarrhea, occult blood in the feces, wet weight of the colon, and spleen. G because of its anti-inflammatory property down-regulated the neutrophil and WBC count and up-regulated the lymphocyte number. Moreover, G efficiently ameliorates the oxidative stress in the colon and declines the level of myeloperoxidase and malondialdehyde and up-regulated the level of superoxide dismutase and glutathione. Lubiprostone has not shown any promising effects, in fact, it causes an increase in diarrheal frequency. Our findings from this study represent that G has good potential to ameliorate GI inflammation induced by DNBS by its multiple actions including CFTR blockage and reducing the release of inflammatory markers from the MCs, anti-inflammatory and free radical scavenging property.

PMID:33994824 | PMC:PMC8093574 | DOI:10.1016/j.jsps.2021.02.005

Arch Bronconeumol. 2021 Apr 26. doi: 10.1016/j.arbres.2021.04.021. Online ahead of print.

NO ABSTRACT

PMID:33994633 | PMC:PMC8074518 | DOI:10.1016/j.arbres.2021.04.021

Signal Transduct Target Ther. 2021 May 17;6(1):183. doi: 10.1038/s41392-021-00567-7.

ABSTRACT

CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (either viral and host proteins). CK2 is also considered an emerging target for neurological diseases, inflammation and autoimmune disorders, diverse ophthalmic pathologies, diabetes, and obesity. In addition, CK2 activity has been associated with cardiovascular diseases, as cardiac ischemia-reperfusion injury, atherosclerosis, and cardiac hypertrophy. The hypothesis of considering CK2 inhibition for cystic fibrosis therapies has been also entertained for many years. Moreover, psychiatric disorders and syndromes due to CK2 mutations have been recently identified. On these bases, CK2 is emerging as an increasingly attractive target in various fields of human medicine, with the advantage that several very specific and effective inhibitors are already available. Here, we review the literature on CK2 implication in different human pathologies and evaluate its potential as a pharmacological target in the light of the most recent findings.

PMID:33994545 | DOI:10.1038/s41392-021-00567-7

J Med Invest. 2021;68(1.2):59-70. doi: 10.2152/jmi.68.59.

ABSTRACT

Vibrio parahaemolyticus is a foodborne bacterium that causes acute gastroenteritis through the consumption of contaminated, raw, or undercooked seafood. Cystic fibrosis transmembrane conductance regulator (CFTR) is a well-characterized chloride channel that regulates several other ion channels and transporters to maintain water homeostasis in the gut lumen. Also, CFTR is a main target of bacterial infection-associated diarrhea. Hence, the aim of this study was to clarify the contribution of CFTR in V. parahaemolyticus-induced diarrhea in a mouse model of intestinal loop fluid accumulation, with CFTR inhibitors and a CFTR knockout model. The results indicated that CFTR plays a critical role in fluid accumulation in response to V. parahaemolyticus infection. We also investigated the inflammatory association in CFTR-mediated V. parahaemolyticus-induced fluid secretion with cyclooxygenase inhibitors and found that fluid accumulation was decreased by inhibition of cyclooxygenase 2 produced by neutrophils. These findings suggest that V. parahaemolyticus-inducing infiltration and activation of neutrophils also participated in CFTR mediated fluid secretion. This study reveals an important relationship between V. parahaemolyticus-induced diarrhea and inflammation in a mouse model. J. Med. Invest. 68 : 59-70, February, 2021.

PMID:33994481 | DOI:10.2152/jmi.68.59

Pancreatology. 2021 May 11:S1424-3903(21)00147-2. doi: 10.1016/j.pan.2021.04.008. Online ahead of print.

ABSTRACT

BACKGROUND: /Objectives: The pathogenesis of hyperglycemia during acute pancreatitis (AP) remains unknown due to inaccessibility of human tissues and lack of animal models. We aimed to develop an animal model to study the mechanisms of hyperglycemia and impaired glucose tolerance in AP.

METHODS: We injected ferrets with intraperitoneal cerulein (50 μg/kg, 9 hourly injections) or saline. Blood samples were collected for glucose (0, 4, 8, 12, 24h); TNF-α, IL-6 (6h); amylase, lipase, insulin, glucagon, pancreatic polypeptide (PP), glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) (24h). Animals underwent oral glucose tolerance test (OGTT), mixed meal tolerance test (MMTT) at 24h or 3 months, followed by harvesting pancreas for histopathology and immunostaining.

RESULTS: Cerulein-injected ferrets exhibited mild pancreatic edema, neutrophil infiltration, and elevations in serum amylase, lipase, TNF-α, IL-6, consistent with AP. Plasma glucose was significantly higher in ferrets with AP at all time points. Plasma glucagon, GLP-1 and PP were significantly higher in cerulein-injected animals, while plasma insulin was significantly lower compared to controls. OGTT and MMTT showed abnormal glycemic responses with higher area under the curve. The hypoglycemic response to insulin injection was completely lost, suggestive of insulin resistance. OGTT showed low plasma insulin; MMTT confirmed low insulin and GIP; abnormal OGTT and MMTT responses returned to normal 3 months after cerulein injection.

CONCLUSIONS: Acute cerulein injection causes mild acute pancreatitis in ferrets and hyperglycemia related to transient islet cell dysfunction and insulin resistance. The ferret cerulein model may contribute to the understanding of hyperglycemia in acute pancreatitis.

PMID:33994067 | DOI:10.1016/j.pan.2021.04.008

Ann Pharm Fr. 2021 May 13:S0003-4509(21)00071-7. doi: 10.1016/j.pharma.2021.05.002. Online ahead of print.

ABSTRACT

BACKGROUND: One diagnosis of cystic fibrosis involves measuring the nasal transepithelial potential difference (NPD) as a complementary technique in the forms of the disease, where the sweat test is non-discriminating. The NPD is measured using solutions with and without chlorides, containing a variety of substances whose activities on nasal mucus membranes are studied or assessed. Among the solutions described in the literature and used in specialized centers, none seems to be best adapted for industrial production for reasons of stability (formulas of the international consensus of Rowe et al. and formulas of Knowles et al.) and/or potential toxicity (formulas of Middleton et al.).

OBJECTIVE(S): Defining new formulas, according to those of the international consensus, with greater physicochemical and microbiological stability Methods: The reformulation tests were conducted on the formulas of Rowe et al., using CHESS® (CHemical Equilibrium of Species and Surfaces) software for modeling aqueous systems that substantially reduced the number of experiments. CHESS® software was first validated using models of ideal and non-ideal solutions. Thereafter, experimentation was carried out for the seek of comparison with theoretical data.

RESULTS: CHESS® software using models of ideal and non-ideal solutions were validated. The experimentation confirmed the theoretical data, and new formulas were assessed on the basis of their physicochemical (pH, content, Osmolality) and microbiological stability.

CONCLUSION: The new formulas defined here guarantee excellent physicochemical and microbiological stability of diagnostic solutions, indispensable criteria for harmonizing and comparing results from different specialized centers using NPD measurements. These new formulas are applicable to the harmonization approach of techniques for measuring nasal transepithelial potential difference.

PMID:33992643 | DOI:10.1016/j.pharma.2021.05.002

Curr Hypertens Rev. 2021 May 10. doi: 10.2174/1573402117666210511012609. Online ahead of print.

ABSTRACT

BACKGROUND: The prevalence of fungal infections has been increasing in recent years. Cystic fibrosis (CF) is a genetic disorder that affects organs such as the intestines, liver, pancreas, and especially the lungs.

INTRODUCTION: Fungal pathogens are becoming a challenge in CF. Advanced medical science is associated with longer life expectancy in some patient groups.

METHOD: A review was conducted on studies found on such online databases as Google Scholar, PubMed, and Scopus. Internet-based searches were performed on these databases for cystic fibrosis, respiratory infections, and fungal infection profiling to identify all relevant studies published between 2010 and 2020.

RESULT: Fungal pathogens most frequently isolated from the respiratory tract include the Aspergillus genus, the Candida genus, Scedosporium apiospermum, and the Rasamsonia genus. In cystic fibrosis, these organisms usually colonize the respiratory and intestinal tracts and cause hypersensitivity responses and invasive diseases.

CONCLUSION: Fungus-patient interactions are complicated and depend on various factors. Moreover, the emergence of drug-resistant species is a serious health issue, and the development of new treatments is crucial.

PMID:33992058 | DOI:10.2174/1573402117666210511012609

Mycopathologia. 2021 May 15. doi: 10.1007/s11046-021-00547-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Fungal infection and sensitization are common in chronic respiratory patient populations such as bronchiectasis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) and are often associated with prolonged antifungal therapy (Hohmann et al. in Clin Infect Dis 15:939-940, 2010; Vissichelli et al. in Infect Prev Pract 1:100029, 2019), morbidity, and mortality. Although the use of antifungal stewardship (AFS) is increasing within an invasive fungal disease setting, its use and impact within a chronic respiratory setting have not been defined.

METHODS: A systematic literature review was conducted using PRISMA guidelines to evaluate the use of antifungal stewardship within a chronic respiratory care setting. Three databases have been searched, Medline via Ovid, Embase and GlobalHealth, for papers published between 1949 and 2020.

RESULTS: The initial search identified 987 papers from Medline, 1761 papers from Embase, and 481 papers from GlobalHealth. Only 28 papers met the criteria for inclusion in this systematic literature review. The included studies were subjected to CASP and GRADE assessments to rank their quality and applicability. Only two studies were focussed on Aspergillus species infection.

CONCLUSION: Although antifungal stewardship is increasing, its applications are still limited in chronic respiratory care settings despite the prolonged requirement for antifungal therapy and high antimicrobial resistance.

PMID:33991279 | DOI:10.1007/s11046-021-00547-z

Pediatr Pulmonol. 2021 May 15. doi: 10.1002/ppul.25464. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple-breath inert gas washout (MBW) is a sensitive technique to assess lung volumes and ventilation inhomogeneity in infancy. Poor agreement amongst commercially available setups and a lack of transparency in the underlying algorithms for the computation of infant MBW outcomes currently limit the widespread application of MBW as a surveillance tool in early lung disease.

METHODS: We determined all computational steps in signal processing and the calculation of MBW outcomes in the current infant WBreath/Exhalyzer D setup (Exhalyzer D device, Eco Medics AG; WBreath software version 3.28.0, ndd Medizintechnik AG; Switzerland). We developed a revised WBreath version based on current consensus guidelines and compared outcomes between the current (3.28.0) and revised (3.52.3) WBreath version. We analyzed 60 visits from 40 infants with cystic fibrosis (CF) and 20 healthy controls at six weeks and one year of age.

RESULTS: Investigation into the algorithms in WBreath 3.28.0 revealed discrepancies from current consensus guidelines, which resulted in a potential overestimation of functional residual capacity (FRC) and underestimation of lung clearance index (LCI). We developed a revised WBreath version (3.52.3), which overall resulted in 6.7% lower FRC (mean (SD) -1.78 (0.99) mL/kg) and 14.1% higher LCI (1.11 (0.57) TO) than WBreath version 3.28.0.

CONCLUSION: Comprehensive investigation into the signal processing and algorithms used for analysis of MBW measurements improves the transparency and robustness of infant MBW data. The revised software version calculates outcomes according to consensus guidelines. Future work is needed to validate and compare outcomes between infant MBW setups. This article is protected by copyright. All rights reserved.

PMID:33991038 | DOI:10.1002/ppul.25464

Ital J Pediatr. 2021 May 14;47(1):112. doi: 10.1186/s13052-021-01060-1.

ABSTRACT

BACKGROUND: The sweat chloride test (ST) is the gold standard for cystic fibrosis (CF) diagnosis in symptomatic patients, within the newborn screening and in the follow-up of CF patients during molecular therapies. However, false positives have been reported in patients with different diseases. We describe and discuss 4 cases due to different clinical conditions in which we recorded false positive ST, and the test remained altered for a period of varying length.

CASES PRESENTATION: Case 1: Eight months old female child suffering from constipation, recurrent vomiting and failure to thrive, family history of recurrent pancreatitis without mutations in the PRSS1 and SPINK1 genes. Both ST and fecal elastase were altered although no CFTR gene mutations were found. Due to rapid clinical deterioration, celiac disease was suspected and diagnosed by laboratory tests and intestinal biopsy. After 2 weeks of gluten-free diet ST and fecal elastase normalized. Case 2: 14 months old male suffering from bilateral renal dysplasia, episodes of metabolic alkalosis, recurrent respiratory infections and recurrent vomiting. The child had more ST positives, but no CFTR mutations were found. During follow-up, he developed sensorineural hearing loss and an atrial septic defect was found. Finally, a diagnosis of Klinefelter was made, but the ST normalized several years later. Case 3 and 4: Two boys with stubborn constipation and fecal occlusion treated with Poly Ethylene Glycol (PEG) with salts showed pathological ST. The test returned normal a few days after stopping treatment.

CONCLUSIONS: We hypotesized the possible causes of ST alteration in these conditions: in celiac disease it could be due to a transient dysregulation of the aquaporins, rapidly reversed by the diet; in Klinefelter, it may be due to stable pubertal hypoandrogenism; while, the PEG formulation itself contains salts that can temporarily alter ST.

PMID:33990208 | DOI:10.1186/s13052-021-01060-1

Sleep Med. 2021 Apr 22;83:21-25. doi: 10.1016/j.sleep.2021.04.019. Online ahead of print.

ABSTRACT

PURPOSE: In our study we aimed to analyze sleep variability and activity in patients with cystic fibrosis (CF) during their hospital stay.

METHODS: Forty-three CF patients were recruited and have been divided into two subgroups: exacerbated (n = 18) and non-exacerbated (n = 25). During the course of their hospital stay we used VitaLog, a minimal-impact biomotion device, in order to determine total sleep time (TST), time in bed (TIB), sleep efficiency (SE) and intra patient standard deviation (IPSD) of TST.

RESULTS: TST was 5.1 h ± 1.5 h and ranged from 0.6h to 7.9 h.TIB was 17.7 h ± 3.8 h and ranged from 5.6h to 23.9 h. SE was 70.0% ± 17.0% and ranged from 13.6% to 98.5%. TST was higher in non-exacerbated patients (5.3 h ± 1.4 h vs. 4.8 h ± 1.6 h, p = 0.008) whereas TIB was lower in non-exacerbated patients (17.0 h ± 3.7 h vs. 18.5 h ± 3.8 h, p = 0.002). We also found that SE was better in non-exacerbated patients (73.1% ± 14.6% vs. 66.6% ± 18.8%, p = 0.002). Furthermore, we observed that IPSD of TST was higher in exacerbated patients (1.3 h ± 0.5 h vs. 0.9 h ± 0.4 h, p = 0.004).

CONCLUSION: In general, in CF patients TST was short and SE poor during the night. Furthermore, in the course of their hospital stay patients showed low activity. In exacerbated patients sleep quality was lower compared to non-exacerbated patients.

PMID:33990062 | DOI:10.1016/j.sleep.2021.04.019

Biosens Bioelectron. 2021 May 9;187:113313. doi: 10.1016/j.bios.2021.113313. Online ahead of print.

ABSTRACT

The abnormal levels of trypsin in biological fluids can cause some acute illnesses, such as acute pancreatitis, cystic fibrosis and malnutrition. In this paper, we report the development of an integrated liquid crystal (LC) sensing device for simple, rapid and sensitive detection of trypsin assisted by the surfactant-embedded smart hydrogel. The gelatin hydrogel mixed with CTAB is added into the side channel of the LC sensing device. In the presence of trypsin, the gelatin hydrogel is decomposed, which triggers instant release of CTAB into the aqueous solution. The CTAB molecules are then captured by the LCs and form CTAB monolayers at the aqueous/LC interface, which leads to change of the LC images from the bright to the dark appearance under the crossed polarizers. The integrated LC sensing device has a remarkable detection limit of 3.4 × 10-5 mg/mL. It is successfully employed to single-step detection of trypsin in human serum within 30 min. The integrated LC sensing device with use of the surfactant-embedded hydrogel takes advantages of single-step detection, high portability, remarkable sensitivity and fast response time, which provides a new perspective to facilitate development of user-friendly LC-based sensors.

PMID:33989909 | DOI:10.1016/j.bios.2021.113313

Biotechnol Appl Biochem. 2021 May 14. doi: 10.1002/bab.2193. Online ahead of print.

ABSTRACT

Prostate cancer is one of the predominant cancers affecting men and has been widely reported. In the past, various therapies and drugs have been proposed to treat prostate cancer. Among these treatments, gene therapy has been considered to be an optimal and widely applicable treatment. Furthermore, due to the increased specificity of gene sequence complementation, the targeted delivery of complementary gene sequences may represent a useful treatment in certain instances. Various gene therapies, including tumor suppressor gene therapy, suicide gene therapy, immunomodulation gene therapy and anti-oncogene therapies, have been established to treat a wide range of diseases, such as cardiac disease, cystic fibrosis, HIV/AIDS, diabetes, hemophilia and cancers. To this end, several gene-therapy clinical trials at various phases are underway. This overview describes the developments and progress in gene therapy, with a special focus being placed on prostate cancer. Prostate cancer is one of the predominant cancers in men and widely reported. Gene therapy is applicable to treat due to higher specificity of gene sequence. Gene complementation & targeted delivery were desired in several instances. Several studies are under various clinical phase trials and elucidated the developments & progresses with gene therapy in prostate cancer. This article is protected by copyright. All rights reserved.

PMID:33988271 | DOI:10.1002/bab.2193

Acta Biomed. 2021 May 12;92(2):e2021164. doi: 10.23750/abm.v92i2.11261.

ABSTRACT

BACKGROUND AND AIM: In patients with cystic fibrosis (CF) non-invasive ventilation (NIV) improves lung mechanics and gas exchange, and decreases the work of breathing. Domiciliary NIV is mainly used in hypercapnic patients with severe disease, because it counteracts the progression of lung functional impairment and it is often used as a useful "bridge" to lung transplantation. However, to date, there are no standardized criteria to indicate the effect of a precocious starting of NIV in patients with functional ventilation inhomogeneity without hypercapnia. In this pilot study we assessed whether an early NIV treatment might influence functional and clinical outcomes in CF patients.

METHODS: Six normocapnic CF patients were treated for one year with NIV. At baseline and after 1 year of NIV treatment, arterial gas analysis, spirometry, MBW to derive LCI, nocturnal cardio-respiratory polygraphy (PG), and Pittsburgh Sleep Quality Index (PSQI) were perfomed in all enrolled patients.

RESULTS: After one year, despite spirometric and LCI values remain statistically not modified, the number of infectious exacerbations was reduced by 50%.

CONCLUSIONS: These results suggest that nocturnal NIV improves clinical conditions of stable CF patients. Finally, we suggest that this procedure can be useful to counteract the progression of lung disease even in normocapnic patients.

PMID:33988138 | DOI:10.23750/abm.v92i2.11261