Abdominal Surgical Procedures in Adult Patients With Cystic Fibrosis: What Are the Risks?
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ABSTRACT:
SUBMITTER: Hite MA
PROVIDER: S-EPMC9259049 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Practitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharmacokinetics of amikacin in adults with cystic fibrosis may increase the efficacy and safety of therapy. This study was aimed to establish the population pharmacokinetics of amikacin in adults with cystic fibrosis. We used serum concentration data obtained during routine therapeutic drug monitoring and explored the influence of patient covariates on drug disposition. We performed a retrospective chart review to collect the amikacin dosing regimens, serum amikacin concentrations, blood sampling times, and patient characteristics for adults with cystic fibrosis admitted for treatment of acute pulmonary exacerbations. Amikacin concentrations were retrospectively collected for 49 adults with cystic fibrosis, and 192 serum concentrations were available for analysis. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling with the first-order conditional estimation method. A two-compartment model with first-order elimination best described amikacin pharmacokinetics. Creatinine clearance and weight were identified as significant covariates for clearance and the volume of distribution, respectively, in the final model. Residual variability was modeled using a proportional error model. Typical estimates for clearance, central and peripheral volumes of distribution, and intercompartmental clearance were 3.06 liters/h, 14.4 liters, 17.1 liters, and 0.925 liters/h, respectively. The pharmacokinetics of amikacin in individuals with cystic fibrosis seems to differ from those in individuals without cystic fibrosis. However, further investigations are needed to confirm these results and, thus, the need for variations in amikacin dosing. Future pharmacodynamic studies will potentially establish the optimal amikacin dosing regimens for the treatment of acute pulmonary exacerbations in adult patients with CF.
| S-EPMC6153835 | biostudies-other
Project description:Cystic fibrosis (CF), the most common lethal autosomal recessive disorder among Caucasians, is caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride channel gene. Despite significant advances in the management of CF patients, novel disease-related biomarkers and therapies must be identified. We performed serum proteomics profiling in CF patients (n = 28) and healthy subjects (n = 10) using the 2D-DIGE MALDI-TOF proteomic approach. Out of a total of 198 proteins identified, 134 showed a statistically significant difference in abundance and a 1.5-fold change (ANOVA, p < 0.05), including 80 proteins with increased abundance and 54 proteins with decreased abundance in CF patients. A multiple reaction monitoring-mass spectrometry analysis of six differentially expressed proteins identified by a proteomic approach (DIGE-MALD-MS) showed a significant increase in C3 and CP proteins and a decrease in APOA1, Complement C1, Hp, and RBP4proteins compared with healthy controls. Fifteen proteins were identified as potential biomarkers for CF diagnosis. An ingenuity pathway analysis of the differentially regulated proteins indicates that the central nodes dysregulated in CF subjects involve pro-inflammatory cytokines, ERK1/2, and P38 MAPK, which are primarily involved in catalytic activities and metabolic processes. The involved canonical pathways include those related to FXR/RXR, LXR/RXR, acute phase response, IL12, nitric oxide, and reactive oxygen species in macrophages. Our data support the current efforts toward augmenting protease inhibitors in patients with CF. Perturbations in lipid and vitamin metabolism frequently observed in CF patients may be partly due to abnormalities in their transport mechanism.
| S-EPMC7582405 | biostudies-literature
Project description:This multi-center study will compare multi-target DNA and quantitative FIT stool-based testing to colonoscopy in individuals with Cystic Fibrosis (CF) undergoing colon cancer screening with colonoscopy. The primary endpoint is detection of any adenomas, including advanced adenomas and colorectal cancer (CRC).
| 2726863 | ecrin-mdr-crc
Project description:BACKGROUND:Few studies have suggested the potential role of respiratory viruses in cystic fibrosis (CF) exacerbation, but their real impact is probably underestimated. METHOD:Sixty-four sputum samples collected from 46 adult patients were included in the study: 33 samples were collected during exacerbation of CF, and 31 during the stable phase. After extraction, nucleic acids were tested for the presence of respiratory viruses. When rhinovirus (HRV) was detected, the 5'UTR and VP4/2 regions were sequenced, and phylogenetically analyzed. The characteristics of patients in exacerbation and stable phase were compared. RESULTS:Viruses were found in 25% of samples. The HRV viruses were the most frequently detected followed by coronaviruses. Only the HRV detection was significantly associated with the occurrence of CF pulmonary exacerbation (p<0.027). Characterization of 5'UTR and VP4/2 regions of the HRV genome specified that HRV-A, -B, -C were detected. All HRV-C were recombinant HRV-Ca. CONCLUSIONS:HRV were the most frequently detected viruses; their detection was significantly associated with the occurrence of an exacerbation. The reality of viral recombination between HRV was demonstrated in CF patients for the first time, raising the role of viruses in lung microbiota. Further studies are now warranted to decipher virus impact in CF.
| S-EPMC7108260 | biostudies-literature
Project description:Sweat plays a crucial role in thermo-regulation and skin health and potentially antimicrobial defense. Its composition is highly dynamic and its homeostasis involves a fine tuning of metabolic pathways. In-depth profiling of sweat protein composition will increase our understanding of skin disorders. Cystic Fibrosis (CF) is associated with high NaCl sweat concentration due to the absence of the CFTR protein. Patients with CF (pwCF) often display aquagenic palmoplantar keratodermia, a rare skin disorder characterized by skin wrinkling with oedema and whitish papules on the palms and/or soles, the pathophysiology of which is unknown. We report an in-depth analysis of the human sweat proteome of pwCF patients in comparison with that of healthy subjects (S).
2023-03-11 | PXD032894 | Pride
Project description:Abdominal symptoms are a hallmark of Cystic fibrosis (CF). Yet, their association with morphological abnormalities of different abdominal organs is still poorly understood. Aim was therefore to relate these symptoms, assessed with a questionnaire, to findings in abdominal ultrasound (US). In 114 CF patients of all ages, findings in US considering seventeen specific parameters were related to abdominal symptoms compiled with our novel CF-specific 26-modal symptom score (CFAbd-Score). US abnormalities were detected in 95% of the patients. Most frequent findings were pancreatic lipomatosis (88%), liver steatosis (37%), hepatomegaly (31%), and thickened bowel walls (23%). Highest burden of GI-symptoms was clearly associated with pancreatic lipomatosis (p?=?0.036). In detail, patients revealing this pathology reported higher rates of abdominal pain (p?=?0.018), flatulence (p?=?0.006), heartburn (p?=?0.04), and reflux of stomach content (p?=?0.006). Patients with pancreatic sufficiency had less US-findings (p?=?0.033), which in turn was associated with lower rates of abdominal symptoms. The majority of them were carriers of class IV-VI or G551D mutations. Our approach gives new insights regarding the underestimated multi-organ abdominal involvement in CF. The new score can be of high interest e.g. as a complementary tool to assess the gastrointestinal effects of promising novel CF therapeutics.
| S-EPMC5727223 | biostudies-literature
Project description:Retained respiratory tract (RT) secretions, infection, and exuberant inflammatory responses are core abnormalities in cystic fibrosis (CF) lung disease. Factors contributing to the destructive CF airway inflammatory processes remain incompletely characterized. The pro-oxidative inflammatory CF RT milieu is known to contain enzymatically and nonenzymatically produced regulatory lipid mediators, a panel of structurally defined oxidized metabolites of polyunsaturated fatty acids known to play a role in pathology related to inflammation. Using an extraction protocol that maximizes recoveries of sputum-spiked deuterated standards, coupled with an LC/MS/MS detection system, this study presents a metabolomic method to assess a broad spectrum of regulatory lipid mediators in freshly obtained sputum from CF patients. A broad range of both proinflammatory and anti-inflammatory lipid mediators was detected, including PGE2, PGD2, TXB2, LTB4, 6-trans-LTB4, 20-OH-LTB4, 20-COOH-LTB4, 20-HETE, 15-HETE, 11-HETE, 12-HETE, 8-HETE, 9-HETE, 5-HETE, EpETrEs, diols, resolvin E1, 15-deoxy-PGJ2, and LXA4. The vast majority of these oxylipins have not been reported previously in CF RT secretions. Whereas direct associations of individual proinflammatory lipid mediators with compromised lung function (FEV-1) were observed, the relationships were not robust. However, multiple statistical analyses revealed that the regulatory lipid mediators profile taken in aggregate proved to have a stronger association with lung function in relatively stable outpatient adult CF patients. Our data reveal a relative paucity of the anti-inflammatory lipid mediator lipoxin A4 in CF sputum. Patients displaying detectable levels of the anti-inflammatory lipid mediator resolvin E1 demonstrated a better lung function compared to those patients with undetectable levels. Our data suggest that comprehensive metabolomic profiling of regulatory lipid mediators in CF sputum should contribute to a better understanding of the molecular mechanisms underlying CF RT inflammatory pathobiology. Further studies are required to determine the extent to which nutritional or pharmacological interventions alter the regulatory lipid mediators profile of the CF RT and the impact of potential modulations of RT regulatory lipid mediators on the clinical progression of CF lung disease.
| S-EPMC3412514 | biostudies-literature
Project description:Adults with cystic fibrosis (CF) frequently harbor Staphylococcus aureus, which is increasingly antibiotic resistant. Telavancin is a once-daily rapidly bactericidal antibiotic active against methicillin-, linezolid-, and ceftaroline-resistant S. aureus Because CF patients experience alterations in pharmacokinetics, the optimal dose of telavancin in this population is unknown. Adult CF patients (n?=?18) admitted for exacerbations received 3 doses of telavancin 7.5?mg/kg of body weight (first 6 patients) or 10?mg/kg (final 12 patients) every 24?h (q24h). Population pharmacokinetic models with and without covariates were fitted using the nonparametric adaptive grid algorithm in Pmetrics. The final model was used to perform 5,000-patient Monte Carlo simulations for multiple telavancin doses. The best fit was a 2-compartment model describing the volume of distribution of the central compartment (Vc ) as a multiple of total body weight (TBW) and the volume of distribution of the central compartment scaled to total body weight (V ?) normalized by the median observed value (Vc ?=?V ??×?TBW/52.1) and total body clearance (CL) as a linear function of creatinine clearance (CRCL) (CL?=?CLNR?+?CL??×?CRCL), where CLNR represents nonrenal clearance and CL? represents the slope term on CRCL to estimate renal clearance. The mean population parameters were as follows: V ?, 4.92? ± 0.76 liters?·?kg-1; CLNR, 0.59? ± 0.30 liters?·?h-1; CL?, 5.97?×?10-3 ± 1.24?×?10-3; Vp (volume of the peripheral compartment), 3.77? ± 1.41 liters; Q (intercompartmental clearance), 4.08? ± 2.17 liters?·?h-1 The free area under the concentration-time curve (fAUC) values for 7.5 and 10?mg/kg were 30? ± 4.6 and 52? ± 12?mg?·?h/liter, respectively. Doses of 7.5?mg/kg and 10?mg/kg achieved 76.5% and 100% probability of target attainment (PTA) at a fAUC/MIC threshold of >215, respectively, for MIC of ?0.12?mg/liter. The probabilities of reaching the acute kidney injury (AKI) threshold AUC (763?mg?·?h?·?liter-1) for these doses were 0% and 0.96%, respectively. No serious adverse events occurred. Telavancin 10?mg/kg yielded optimal PTA and minimal risk of AKI, suggesting that this FDA-approved dose is appropriate to treat acute pulmonary exacerbations in CF adults. (The clinical trial discussed in this study has been registered at ClinicalTrials.gov under identifier NCT03172793.).
| S-EPMC7187619 | biostudies-literature
Project description:Air travel may imply a health hazard for patients with cystic fibrosis (CF) due to hypobaric environment in the aircraft cabin. The objective was to identify pre-flight variables, which might predict severe hypoxaemia in adult CF patients during air travel.Thirty adult CF-patients underwent pre-flight evaluation with spirometry, arterial oxygen tension (PaO2), pulse oximetry (SpO2) and cardiopulmonary exercise testing (CPET) at sea level (SL). The results were related to the PaO2 obtained during a hypoxia-altitude simulation test (HAST) in which a cabin altitude of 2438 m (8000 ft) was simulated by breathing 15.1% oxygen.Four patients fulfilled the criteria for supplemental oxygen during air travel (PaO2 HAST < 6.6 kPa). While walking slowly during HAST, another eleven patients dropped below PaO2 HAST 6.6 kPa. Variables obtained during CPET (PaO2 CPET, SpO2 CPET, minute ventilation/carbon dioxide output, maximal oxygen uptake) showed the strongest correlation to PaO2 HAST.Exercise testing might be of value for predicting in-flight hypoxaemia and thus the need for supplemental oxygen during air travel in CF patients. Trial registration The study is retrospectively listed in the ClinicalTrials.gov Protocol Registration System: NCT01569880 (date; 30/3/2012).
| S-EPMC5292785 | biostudies-literature
Project description:BackgroundBronchiectasis is associated with morbidity, low exercise capacity and poor quality of life. There is a paucity of data on exercise capacity using cardiopulmonary exercise test (CPET) in non-cystic fibrosis (CF) bronchiectasis. Our aim was to compare exercise capacity using CPET in CF and non-CF bronchiectasis patients.MethodsCross-sectional retrospective/prospective controlled study assessing CPET using cycle ergometer. Exercise parameters and computed tomography (CT) findings were compared. Results: Hundred two patients with bronchiectasis and 88 controls were evaluated; 49 CF (age 19.7 ± 9.7 y/o, FEV1%predicted 70.9 ± 20.5%) and 53 non-CF (18.6 ± 10.6 y/o, FEV1%predicted 68.7 ± 21.5%). Peak oxygen uptake (peak [Formula: see text]) was similar and relatively preserved in both groups (CF 1915.5±702.0; non-CF 1740±568; control 2111.0±748.3 mL/min). Breathing limitation was found in the two groups vs. control; low breathing reserve (49% in CF; 43% non-CF; 5% control) and increased [Formula: see text] (CF 31.4±4.1, non-CF 31.7±4.1 and control 27.2 ± 2.8). Oxygen pulse was lower in the non-CF; whereas a linear relationship between peak [Formula: see text] vs. FEV1 and vs. FVC was found only for CF. CT score correlated with [Formula: see text] and negatively correlated with [Formula: see text] and post exercise oxygen saturation (SpO2).ConclusionsCPET parameters may differ between CF and non-CF bronchiectasis. However, normal exercise capacity may be found unrelated to the etiology of the bronchiectasis. Anatomical changes in CT are associated with functional finding of increased [Formula: see text] and decreased SpO2. Larger longitudinal studies including cardiac assessment are needed to better study exercise capacity in different etiologies of non-CF bronchiectasis.Trial registrationClinicalTrials.gov, registration number: NCT03147651.
| S-EPMC6563963 | biostudies-literature