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Pharmaceuticals (Basel, Switzerland) May 2024The pharmacokinetic (PK) profiles of voriconazole in intensive care unit (ICU) patients differ from that in other patients. We aimed to develop a population...
AIMS
The pharmacokinetic (PK) profiles of voriconazole in intensive care unit (ICU) patients differ from that in other patients. We aimed to develop a population pharmacokinetic (PopPK) model to evaluate the effects of using extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and those of various biological covariates on the voriconazole PK profile.
METHODS
Modeling analyses of the PK parameters were conducted using the nonlinear mixed-effects modeling method (NONMEM) with a two-compartment model. Monte Carlo simulations (MCSs) were performed to observe the probability of target attainment (PTA) when receiving CRRT or not under different dosage regimens, different stratifications of quick C-reactive protein (qCRP), and different minimum inhibitory concentration (MIC) ranges.
RESULTS
A total of 408 critically ill patients with 746 voriconazole concentration-time data points were included in this study. A two-compartment population PK model with qCRP, CRRT, creatinine clearance rate (CL), platelets (PLT), and prothrombin time (PT) as fixed effects was developed using the NONMEM.
CONCLUSIONS
We found that qCRP, CRRT, CL, PLT, and PT affected the voriconazole clearance. The most commonly used clinical regimen of 200 mg q12h was sufficient for the most common sensitive pathogens (MIC ≤ 0.25 mg/L), regardless of whether CRRT was performed and the level of qCRP. When the MIC was 0.5 mg/L, 200 mg q12h was insufficient only when the qCRP was <40 mg/L and CRRT was performed. When the MIC was ≥2 mg/L, a dose of 300 mg q12h could not achieve ≥ 90% PTA, necessitating the evaluation of a higher dose.
PubMed: 38931333
DOI: 10.3390/ph17060665 -
Pharmaceuticals (Basel, Switzerland) May 2024Photodynamic therapy (PDT) is a minimally invasive treatment for several diseases. It combines light energy with a photosensitizer (PS) to destroy the targeted cells or... (Review)
Review
UNLABELLED
Photodynamic therapy (PDT) is a minimally invasive treatment for several diseases. It combines light energy with a photosensitizer (PS) to destroy the targeted cells or tissues. A PS itself is a non-toxic substance, but it becomes toxic to the target cells through the activation of light at a specific wavelength. There are some limitations of PDT, although it has been used in clinical studies for a long time. Two-photon excitation (TPE) and upconversion (UC) for PDT have been recently developed. A TPE nanoparticle-based PS combines the advantages of TPE and nanotechnology that has emerged as an attractive therapeutic agent for near-infrared red (NIR) light-excited PDT, whilst UC is also used for the NIR light-triggered drug release, activation of 'caged' imaging, or therapeutic molecules during PDT process for the diagnosis, imaging, and treatment of cancers.
METHODS
Nine electronic databases were searched, including WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link, SciFinder, and China National Knowledge Infrastructure (CNKI), without any language constraints. TPE and UCNP were evaluated to determine if they had different effects from PDT on cancers. All eligible studies were analyzed and summarized in this review.
RESULTS
TPE-PDT and UCNP-PDT have a high cell or tissue penetration ability through the excitation of NIR light to activate PS molecules. This is much better than the conventional PDT induced by visible or ultraviolet (UV) light. These studies showed a greater PDT efficacy, which was determined by enhanced generation of reactive oxygen species (ROS) and reduced cell viability, as well as inhibited abnormal cell growth for the treatment of cancers.
CONCLUSIONS
Conventional PDT involves Type I and Type II reactions for the generation of ROS in the treatment of cancer cells, but there are some limitations. Recently, TPE-PDT and UCNP-PDT have been developed to overcome these problems with the help of nanotechnology in in vitro and in vivo studies.
PubMed: 38931331
DOI: 10.3390/ph17060663 -
Nutrients Jun 2024The prevalence of allergic diseases has dramatically increased among children in recent decades. These conditions significantly impact the quality of life of allergic... (Review)
Review
The prevalence of allergic diseases has dramatically increased among children in recent decades. These conditions significantly impact the quality of life of allergic children and their families. Lactoferrin, a multifunctional glycoprotein found in various biological fluids, is emerging as a promising immunomodulatory agent that can potentially alleviate allergic diseases in children. Lactoferrin's multifaceted properties make it a compelling candidate for managing these conditions. Firstly, lactoferrin exhibits potent anti-inflammatory and antioxidant activities, which can mitigate the chronic inflammation characteristic of allergic diseases. Secondly, its iron-binding capabilities may help regulate the iron balance in allergic children, potentially influencing the severity of their symptoms. Lactoferrin also demonstrates antimicrobial properties, making it beneficial in preventing secondary infections often associated with respiratory allergies. Furthermore, its ability to modulate the immune response and regulate inflammatory pathways suggests its potential as an immune-balancing agent. This review of the current literature emphasises the need for further research to elucidate the precise roles of lactoferrin in allergic diseases. Harnessing the immunomodulatory potential of lactoferrin could provide a novel add-on approach to managing allergic diseases in children, offering hope for improved outcomes and an enhanced quality of life for paediatric patients and their families. As lactoferrin continues to capture the attention of researchers, its properties and diverse applications make it an intriguing subject of study with a rich history and a promising future.
Topics: Lactoferrin; Humans; Child; Quality of Life; Hypersensitivity; Anti-Inflammatory Agents; Antioxidants
PubMed: 38931261
DOI: 10.3390/nu16121906 -
Journal of Clinical Medicine Jun 2024: Poor cardiorespiratory fitness poses the highest risk of mortality. Long-COVID-19 survivors exhibit a reduced cardiorespiratory fitness (CRF). While exercise... (Review)
Review
: Poor cardiorespiratory fitness poses the highest risk of mortality. Long-COVID-19 survivors exhibit a reduced cardiorespiratory fitness (CRF). While exercise rehabilitation, such as cardiopulmonary exercise, is used for long-COVID-19 survivors, the effects of exercise on CRF in this population remain inconclusive. In this study, we aim to systematically summarise and synthesise whether exercise rehabilitation improves CRF among long-COVID-19 survivors. : A comprehensive search was performed through PubMed, CINAHL, Embase, Scopus, and the Cochrane Library (since their inception to November 2023) and study reference lists. Studies presenting the effects of exercise rehabilitation on CRF (peak oxygen consumption (VO) and six-minute walk distance (6MWD)) in long-COVID-19 survivors were identified. The standardised mean difference (SMD), mean difference (MD), and 95% confidence interval (CI) were used for analyses. The certainty of evidence was measured using a Grading of Recommendation Assessment, Development and Evaluation approach. : Twelve eligible studies (five RCTs and seven non-RCTs) with 682 participants were analysed. The meta-analysis showed significantly improved 6MWDs (MD 76.47, 95% CI 59.19-93.71, low certainty) and significantly greater 6MWDs (SMD 0.85, 95% CI 0.11-1.59, very low certainty) in the exercise rehabilitation group compared to the control group. A significantly improved 6MWD was found in subgroups of young to middle-aged adults and subgroups of patients who undertook aerobic exercise combined with resistance and respiratory exercise and centre-based training programs. : Exercise rehabilitation is effective for improving CRF, as measured by the 6MWD in long-COVID-19 survivors. Improvements are likely to be more pronounced in specific subgroups of young to middle-aged adults and patients undertaking aerobic exercise combined with resistance and respiratory exercise and centre-based training programs. However, recommendations for clinical practice are limited due to the very low evidence certainty.
PubMed: 38930148
DOI: 10.3390/jcm13123621 -
Journal of Clinical Medicine Jun 2024The efficacy of veno-venous extracorporeal membrane oxygenation (VV-ECMO) as rescue therapy for refractory COVID-19-related ARDS (C-ARDS) is still debated. We describe...
The efficacy of veno-venous extracorporeal membrane oxygenation (VV-ECMO) as rescue therapy for refractory COVID-19-related ARDS (C-ARDS) is still debated. We describe the cohort of C-ARDS patients treated with VV-ECMO at our ECMO center, focusing on factors that may affect in-hospital mortality and describing the time course of lung mechanics to assess prognosis. We performed a prospective observational study in the intensive care unit at the "Città della Salute e della Scienza" University Hospital in Turin, Italy, between March 2020 and December 2021. Indications and management of ECMO followed the Extracorporeal Life Support Organization (ELSO) guidelines. The 60-day in-hospital mortality was particularly high (85.4%). Non-survivor patients were more frequently treated with non-invasive ventilatory support and steroids before ECMO (95.1% vs. 57.1%, = 0.018 and 73.2% vs. 28.6%, = 0.033, respectively), while hypertension was the only pre-ECMO factor independently associated with in-hospital mortality (HR: 2.06, 95%CI: 1.06-4.00). High rates of bleeding (85.4%) and superinfections (91.7%) were recorded during ECMO, likely affecting the overall length of ECMO (18 days, IQR: 10-24) and the hospital stay (32 days, IQR: 24-47). Static lung compliance was lower in non-survivors ( = 0.031) and differed over time ( = 0.049), decreasing by 48% compared to initial values in non-survivors. Our data suggest the importance of considering NIS among the common ECMO eligibility criteria and changes in lung compliance during ECMO as a prognostic marker.
PubMed: 38930073
DOI: 10.3390/jcm13123545 -
Journal of Clinical Medicine Jun 2024: This study evaluated early childhood comorbidities of cerebral palsy (CP) in low birth weight (LBW) children and assessed the impact of maternal bio-psychosocial...
The Prevalence and Risk Analysis of Cerebral Palsy and Other Neuro-Psychological Comorbidities in Children with Low Birth Weight in Taiwan: A Nationwide Population-Based Cohort Study.
: This study evaluated early childhood comorbidities of cerebral palsy (CP) in low birth weight (LBW) children and assessed the impact of maternal bio-psychosocial factors on CP risk in preterm infants of varying birth weights (BWs). : Data from 15,181 preterm infants (2009-2013) and 151,810 controls were analyzed using Taiwan's National Health Insurance Research Database. CP prevalence and LBW-associated comorbidities were examined, and odds ratios (ORs) were calculated. : This study confirmed increasing prematurity and LBW rates in Taiwan, with LBW infants showing higher CP prevalence. Significant maternal risk factors included age extremes (<20 and >40 years). LBW infants exhibited higher risks for respiratory, circulatory, nervous system, and psycho-developmental comorbidities compared with controls, with the lowest BW having even higher ORs. Maternal factors such as family income, the number of hospital admissions, and length of hospital stay were remarkably correlated with BW and subsequent complications. Each additional gestational week crucially reduced the risk of complications in premature infants. : LBW infants are at a higher risk for CP and various comorbidities, with maternal bio-psychosocial factors playing a critical role. Addressing these factors in prenatal care and interventions is essential to improve outcomes for premature infants.
PubMed: 38930008
DOI: 10.3390/jcm13123480 -
Journal of Clinical Medicine Jun 2024Severe asthma often remains uncontrolled despite optimized inhaled treatment. The rise of biologic therapy in severe asthma represented a major advance for the disease...
Severe asthma often remains uncontrolled despite optimized inhaled treatment. The rise of biologic therapy in severe asthma represented a major advance for the disease management. However, correct phenotyping and monitoring of severe asthma patients is key to the success of targeted biologic therapy. We present the case of a 63-year-old female, never a smoker, diagnosed with asthma at the age of 45 and associated persistent mild rhinitis, without other notable comorbidities. She was prescribed medium-dose ICS/LABA, administered inconstantly in the first years after the diagnosis, with poor overall control of the disease. After several exacerbation episodes, treatment compliance improved, but the control of the disease remained poor despite adding an antileukotriene. In January 2019, she presented an exacerbation episode requiring treatment with oral corticosteroids (OCS) and she was afterwards put on high-dose ICS/LABA and continued the antileukotriene. She was referred for a skin allergy test, which revealed mild sensitization to Dermatophagoides pteronyssinus and farinae, with a total IgE level of 48.3 IU/mL. The blood eosinophil level was 270 cells/mm. The lung function was variable, going from mild impairment to severe fixed obstruction during exacerbations. Despite optimized inhaled treatment, good adherence and inhaler technique, and allergen avoidance strategies, asthma control was not achieved, and she continued to experience severe episodes of exacerbation requiring OCS. In October 2019, she was initiated on biologic therapy with omalizumab, which allowed asthma control to be achieved and maintained for 18 months, with preserved lung function, good symptom control, no exacerbations and slightly elevated blood eosinophil level (340-360 cells/mm). In April 2021, she started experiencing exacerbation episodes requiring OCS (three episodes within 6 months), with a progressive increase in blood eosinophil level (up to 710 cells/mm), and progressive deterioration of asthma control and lung function, despite continuation of previous therapy. A specific IgE test against Aspergillus was negative, and total IgE level was 122.4 IU/mL. In December 2021, the patient was switched from omalizumab to benralizumab. Asthma control was again achieved, lung function improved significantly and the patient did not experience any other exacerbation episodes up until today, which allowed for a reduction in ICS dose. Intriguingly, a relapsing eosinophilia was also noted under anti-IL5-R treatment prior to the dose administration, but with preserved asthma control. This case underscores the pivotal role of meticulous phenotyping in severe asthma management on one side, and careful monitoring of patient evolution and possible side effects of treatment on the other side. By showcasing how diverse inflammatory pathways can coexist within a single patient and impact treatment outcomes, it highlights the necessity of tailored biologic therapy for sustained control.
PubMed: 38929930
DOI: 10.3390/jcm13123402 -
Life (Basel, Switzerland) May 2024Features of cardiovascular autonomic regulation in infants are poorly studied compared with adults. However, the clinical significance of autonomic dysfunction in...
BACKGROUND
Features of cardiovascular autonomic regulation in infants are poorly studied compared with adults. However, the clinical significance of autonomic dysfunction in infants is very high. The goal of our research was to study the temporal and frequency-dependent features, as well as low-frequency synchronization in cardiovascular autonomic regulation in full-term vs. preterm newborns, based on the analysis of their heart rate variability (HRV) and photoplethysmographic waveform variability (PPGV).
METHODS
The study included three groups of newborns: 64 full-term newborns (with a gestational age at birth of 37-40 weeks) with a physiological course of the neonatal adaptation; 23 full-term newborns (with a gestational age at birth of 37-40 weeks) with a pathological course of the neonatal adaptation; and 17 preterm newborns (with a postconceptional age of 34 weeks or more). We conducted spectral analysis of HRV and PPGV, along with an assessment of the synchronization strength between low-frequency oscillations in HRV and in PPGV (synchronization index). We employed several options for the boundaries of the high-frequency (HF) band: 0.15-0.40 Hz, 0.2-2 Hz, 0.15-0.8 Hz, and 0.24-1.04 Hz.
RESULTS
Preterm newborns had higher heart rate, RMSSD, and PNN50 values relative to both groups of full-term newborns. Values of SDNN index and synchronization index (S index) were similar in all groups of newborns. Differences in frequency domain indices of HRV between groups of newborns depended on the considered options of HF band boundaries. Values of frequency domain indices of PPGV demonstrated similar differences between groups, regardless of the boundaries of considered options of HF bands and the location of PPG signal recording (forehead or leg). An increase in sympathetic influences on peripheral blood flow and a decrease in respiratory influences were observed along the following gradient: healthy full-term newborns → preterm newborns → full-term newborns with pathology.
CONCLUSIONS
Differences in frequency domain indices of autonomic regulation between the studied groups of newborns depended on the boundaries of the considered options of the HF band. Frequency domain indices of PPGV revealed significantly more pronounced differences between groups of newborns than analogous HRV indicators. An increase in sympathetic influences on peripheral blood flow and a decrease in respiratory influences were observed along the following gradient: healthy full-term newborns → preterm newborns → full-term newborns with pathology.
PubMed: 38929659
DOI: 10.3390/life14060675 -
Medicina (Kaunas, Lithuania) Jun 2024Preterm-born children are susceptible to problems of adaptation in the early neonatal period, as well as the emergence of consequences due to the immaturity of the... (Review)
Review
Preterm-born children are susceptible to problems of adaptation in the early neonatal period, as well as the emergence of consequences due to the immaturity of the respiratory, cardiovascular, and especially cerebrovascular systems. The authors searched PubMed, Scopus, the Cochrane Library, and Web of Science for articles that were available in their entirety and published in English between 1990 and 2024 in peer-reviewed journals using keywords relevant to the manuscript topic. Analyzing the requested studies and manuscripts, adequate articles describing the stated problem were used. The last trimester of pregnancy is the most important period in brain development. Brain growth is at its most intense, and nerve cells are created, multiply, and migrate, creating numerous connections between them and receptors. During this period, the baby is protected from the influence of external environmental factors. When a baby is born, it leaves its protected environment and very often requires intensive treatment to survive. In these circumstances, the immature nervous system, which is in a sensitive stage of development, is overloaded with numerous external stimuli, continuous light, noise, inappropriate positioning, and repeated painful reactions due to necessary diagnostic and therapeutic procedures and the unavoidable absence of the mother and the family, which cause stress that threatens proper programmed development. Minimally invasive therapeutic procedures and the presence of parents during hospitalization play a significant role in reducing the consequences for a premature child.
Topics: Humans; Infant, Newborn; Premature Birth; Female; Pregnancy; Infant, Premature
PubMed: 38929631
DOI: 10.3390/medicina60061014 -
Medicina (Kaunas, Lithuania) Jun 2024: Prolidase deficiency (PD) is a rare, life-threatening, genetically determined disease with an incidence of 1-2 cases per 1 million births. The disease inhibits... (Observational Study)
Observational Study
: Prolidase deficiency (PD) is a rare, life-threatening, genetically determined disease with an incidence of 1-2 cases per 1 million births. The disease inhibits collagen synthesis, which leads to organ and systems failure, including hepato- and splenomegaly, immune disorders, chronic ulcerative wounds, respiratory infections, and pulmonary fibrosis. The complexity of the problems associated with this disease necessitates a comprehensive approach and the involvement of an interdisciplinary team. The objective was to present the treatment and care plan, as well as complications of PD, in a young woman following admission to an intensive care unit (ICU). : A retrospective observational single-case study. : A 26-year-old woman with PD was hospitalized in the ICU for acute respiratory failure. The presence of difficult-to-heal extensive leg ulcers and the patient's immunocompromised condition resulted in the development of sepsis with multiple organ failure (respiratory and circulatory, liver and kidney failure). Complex specialized treatment consisting of wound preparation, limb amputation, the minimization of neuropathic pain, mechanical ventilation, renal replacement therapy, circulatory stabilization, and the prevention of complications of the disease and of therapy were applied. On the 83rd day of hospitalization, the patient expired. : Despite the use of complex treatment and care, due to the advanced nature of the disease and the lack of therapies with proven efficacy, treatment was unsuccessful. There is a need for evidence-based research to develop effective treatment guidelines for PD.
Topics: Humans; Female; Adult; Multiple Organ Failure; Intensive Care Units; Sepsis; Prolidase Deficiency; Retrospective Studies; Fatal Outcome
PubMed: 38929623
DOI: 10.3390/medicina60061006