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1.
Exp Gerontol ; 190: 112420, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38588751

ABSTRACT

Sex differences are consistently identified in determining the prevalence, manifestation, and response to therapies in several systemic disorders, including those affecting the cardiovascular (CV), skeletal muscle, and nervous system. Interestingly, such differences are often more noticeable as we age. For example, premenopausal women experience a lower risk of CV disease than men of the same age. While at an advanced age, with menopause, the risk of cardiovascular diseases and adverse outcomes increases exponentially in women, exceeding that of men. However, this effect appears to be reversed in diseases such as pulmonary hypertension, where women are up to seven times more likely than men to develop an idiopathic form of the disease with symptoms developing ten years earlier than their male counterparts. Explaining this is a complex question. However, several factors and mechanisms have been identified in recent decades, including a role for sex hormones, particularly estrogens and their related receptors. Furthermore, an emerging role in these sex differences has also been suggested for ß-adrenergic receptors (ßARs), which are essential regulators of mammalian physiology. It has in fact been shown that ßARs interact with estrogen receptors (ER), providing further demonstration of their involvement in determining sexual differences. Based on these premises, this review article focused on the ß3AR subtype, which shows important activities in adipose tissue but with new and interesting roles in regulating the function of cardiomyocytes and vascular cells. In detail, we examined how ß3AR and ER signaling are intertwined and whether there would be sex- and age-dependent specific effects of these receptor systems.


Subject(s)
Aging , Cardiovascular Diseases , Estrogens , Receptors, Adrenergic, beta-3 , Receptors, Estrogen , Humans , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/physiopathology , Female , Male , Receptors, Adrenergic, beta-3/metabolism , Estrogens/metabolism , Receptors, Estrogen/metabolism , Aging/physiology , Animals , Sex Factors , Cardiovascular System/metabolism , Cardiovascular System/physiopathology , Sex Characteristics , Signal Transduction
2.
Expert Opin Drug Metab Toxicol ; 20(4): 275-292, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38568077

ABSTRACT

INTRODUCTION: Since COVID-19 patients are often polytreated, monitoring drug-drug interaction (DDIs) is necessary. We evaluated whether drugs used after the second COVID-19 pandemic wave were associated with DDI-related adverse events and the role of drug interaction checkers in identifying them. METHODS: The study (PROSPERO-ID: CRD42024507634) included: 1) consulting the drug interaction checkers Drugs.com, Liverpool COVID-19 Interactions, LexiComp, Medscape, and Micromedex; 2) systematic review; 3) reviewed studies analysis; 4) evaluating drug interaction checkers potential to anticipate DDI-related adverse events.The systematic review was performed searching PubMed, Scopus, ScienceDirect, and Cochrane databases from 1 March 2022 to 11 November 2023. Observational studies, and clinical trials were included. Article without reporting direct association between DDIs and adverse events were excluded. The risk of bias was assessed by Newcastle-Ottawa scale. RESULTS: The most frequent DDIs involved nirmatrelvir/ritonavir (N/R) and fluvoxamine. Fifteen studies, including 150 patients and 35 DDI-related outcomes, were analyzed. The most frequent DDIs involved tacrolimus with N/R, resulting in creatinine increase.Eighty percent of reported DDI-related adverse events would have been identified by all drug-interaction checkers, while the remaining 20% by at least 2 of them. CONCLUSIONS: Drug interaction checkers are useful but show inconsistencies. Multiple sources are needed to tailor treatment in the context of COVID-19.


Subject(s)
Antiviral Agents , COVID-19 Drug Treatment , Drug Interactions , Humans , Antiviral Agents/adverse effects , Antiviral Agents/administration & dosage , COVID-19/epidemiology , Drug-Related Side Effects and Adverse Reactions/epidemiology
3.
Mol Cancer ; 23(1): 63, 2024 03 25.
Article in English | MEDLINE | ID: mdl-38528526

ABSTRACT

Efficient predictive biomarkers are needed for immune checkpoint inhibitor (ICI)-based immunotherapy in non-small cell lung cancer (NSCLC). Testing the predictive value of single nucleotide polymorphisms (SNPs) in programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) has shown contrasting results. Here, we aim to validate the predictive value of PD-L1 SNPs in advanced NSCLC patients treated with ICIs as well as to define the molecular mechanisms underlying the role of the identified SNP candidate. rs822336 efficiently predicted response to anti-PD-1/PD-L1 immunotherapy in advanced non-oncogene addicted NSCLC patients as compared to rs2282055 and rs4143815. rs822336 mapped to the promoter/enhancer region of PD-L1, differentially affecting the induction of PD-L1 expression in human NSCLC cell lines as well as their susceptibility to HLA class I antigen matched PBMCs incubated with anti-PD-1 monoclonal antibody nivolumab. The induction of PD-L1 expression by rs822336 was mediated by a competitive allele-specificity binding of two identified transcription factors: C/EBPß and NFIC. As a result, silencing of C/EBPß and NFIC differentially regulated the induction of PD-L1 expression in human NSCLC cell lines carrying different rs822336 genotypes. Analysis by binding microarray further validated the competitive allele-specificity binding of C/EBPß and NFIC to PD-L1 promoter/enhancer region based on rs822336 genotype in human NSCLC cell lines. These findings have high clinical relevance since identify rs822336 and induction of PD-L1 expression as novel biomarkers for predicting anti-PD-1/PD-L1-based immunotherapy in advanced NSCLC patients.


Subject(s)
B7-H1 Antigen , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Biomarkers , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , CCAAT-Enhancer-Binding Protein-beta/genetics , CCAAT-Enhancer-Binding Protein-beta/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , NFI Transcription Factors/metabolism , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use
4.
J Clin Med ; 13(2)2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38276090

ABSTRACT

This study aimed to assess the main clinical and anamnestic characteristics of adult Cystic Fibrosis (CF) patients and to evaluate the association of frailty with the CF genotyping classification. In an observational cross-sectional study, all ambulatory CF patients over 18 years old who received a diagnosis at the Regional Cystic Fibrosis Center for adults were enrolled and assessed by spirometry for respiratory function, by ADL and IADL for functional status, and by the Study of Osteoporotic Fractures (SOF) Index for frailty. The study population consisted of 139 CF patients (mean age 32.89 ± 10.94 years old, 46% women). Most of the subjects were robust (60.4%). The pre-frail/frail group was more frequently females (p = 0.020), had a lower BMI (p = 0.001), worse respiratory function, a higher number of pulmonary exacerbations/years, cycles of antibiotic therapy, and hospitalization (all p < 0.001) with respect to robust patients. The pre-frail/frail subjects used more drugs and were affected by more CF-related diseases (all p < 0.001). In relation to logistic regression, the best predictor of the pre-frail/frail status was a low FEV1 level. The CF patients show similarities to older pre-frail/frail subjects, suggesting that CF might be considered an early expression of this geriatric syndrome. This finding could help to better define the possible progression of CF, but overall, it could also suggest the usefulness employing of some tools used in the management and therapy of frailty subjects to identify the more severe CF subjects.

5.
J Clin Med ; 12(21)2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37959277

ABSTRACT

Understanding the link between COVID-19 and patient immune characteristics is crucial. We previously demonstrated that high levels of the soluble Programmed Death-Ligand1 (sPD-L1) at the beginning of the infection correlated with low lymphocyte number and high C-reactive protein (CRP), longer length of stay (LOS), and death. This study investigated whether sPD-L1 can be a prognosis biomarker during COVID-19. Severe and non-severe COVID-19 patients were enrolled at the University Hospital of Salerno. During hospitalization, at admission, and after 12-14 days, patients' data were collected, and sPD-L1 levels were measured by enzyme-linked immunosorbent assay. The peripheral lymphocyte number negatively correlated with the time of negativization (p = 0.006), length of stay (LOS) (p = 0.032), and CRP (p = 0.004), while sPD-L1 positively correlated with LOS (p = 0.015). Patients with increased sPD-L1 and lymphocyte number showed a shorter LOS than those with decreased sPD-L1 and lymphocyte number (p = 0.038) and those with increased sPD-L1 and decreased lymphocyte number (p = 0.025). Moreover, patients with increased sPD-L1 and decreased CRP had a shorter LOS than those with increased sPD-L1 and CRP (p = 0.034) and those with decreased sPD-L1 and CRP (p = 0.048). In conclusion, while at an early phase of COVID-19, sPD-L1 promotes an immune escape, later, it might act to dampen an excessive immune response, proving its role in COVID-19 prognosis.

6.
Open Med (Wars) ; 18(1): 20230822, 2023.
Article in English | MEDLINE | ID: mdl-37900963

ABSTRACT

The aim of this retrospective cohort study is to understand if and how much the preventive self-isolation approach might have been a valid model to avoid care-related infection, not only from COVID-19 but also from other non-viral infectious diseases. From March to May 2020, the healthcare and management staff of the Villa Santa Maria long-term care facilities, located in the village of Montenero di Bisaccia (Campobasso, Molise, Italy), decided to carry out a preventive self-isolation plan to safeguard the residents from SARS-CoV-2. The impact on other infectious diseases was evaluated by analyzing the antibiotic therapies prescription trend among the inpatients. Our data showed that although self-isolation protected residents and caregivers from SARS-CoV-2, it can also be associated with mobility reduction, leading to an increase in bedridden pathologies, namely, pressure ulcers and pressure sores. The simultaneous isolation of residents and caregivers in the same location significantly reduced any outside influence as a cause of possible infections.

7.
J Clin Med ; 12(17)2023 Sep 03.
Article in English | MEDLINE | ID: mdl-37685798

ABSTRACT

Oxidative stress, a condition induced by an excessive amount of free radicals, such as reactive oxygen species (ROS), shows several gender-related differences in basal cellular redox state and antioxidant responses. Crenotherapy with sulfureous mineral water can improve the cellular redox state. In this retrospective observational study, gender-related differences in the efficacy of sulfureous crenotherapy in decreasing oxidant species were investigated. Seventy-eight patients, stratified by sex, with osteoarthritis or degenerative joint disease and Vulgar psoriasis who have received a cycle of sulfureous mud-bath therapy + sulfureous hydropinotherapy were enrolled. Plasma concentration of oxidant species and clinical outcomes were measured at baseline and at the end of treatment. After 2 weeks of sulfureous crenotherapy, a significant amelioration of clinical outcomes and a significant reduction of oxidant species were observed in both sexes, more marked in females than in males (p = 0.0001 and p = 0.04, respectively). For patients with high oxidant species at baseline, females showed a greater reduction in itching compared to males (-95% vs. -50%), while men had a higher amelioration in pain and morning stiffness (-45% vs. -32%, and -50% vs. -37%, respectively). In conclusion, sulfureous crenotherapy can be a valuable strategy to improve cellular redox state in both sexes.

8.
Int J Mol Sci ; 24(15)2023 Jul 27.
Article in English | MEDLINE | ID: mdl-37569440

ABSTRACT

Estrogen deficiency is a major cause of loss of postmenopausal bone mineral density (BMD). This study aimed to evaluate the effects of equol and resveratrol on bone turnover biomarkers in postmenopausal women. Sixty healthy postmenopausal women were randomly assigned to receive 200 mg fermented soy containing 10 mg equol and 25 mg resveratrol or a placebo for 12 months. Whole-body BMD and bone turnover biomarkers, such as deoxypyridinoline (DPD), tartrate-resistant acid phosphatase 5b (TRACP-5b), osteocalcin, and bone-specific alkaline phosphatase (BAP), were measured at baseline and after 12 months of treatment. At the end of treatment, DPD, osteocalcin, and BAP significantly improved in the active group (p < 0.0001 for all) compared to the placebo group. Conversely, TRACP-5b levels were unaffected by supplementation (p = 0.051). Statistically significant changes in the concentrations of DPD (p < 0.0001), osteocalcin (p = 0.0001), and BAP (p < 0.0001) compared to baseline were also identified. Overall, the intervention significantly increased BMD measured in the whole body (p = 0.0220) compared with the placebo. These data indicate that the combination of equol and resveratrol may positively modulate bone turnover biomarkers and BMD, representing a potential approach to prevent age-related bone loss in postmenopausal women.


Subject(s)
Osteoporosis, Postmenopausal , Postmenopause , Humans , Female , Equol/pharmacology , Resveratrol/pharmacology , Resveratrol/therapeutic use , Tartrate-Resistant Acid Phosphatase , Osteocalcin , Bone Density , Alkaline Phosphatase/therapeutic use , Biomarkers , Bone Remodeling , Osteoporosis, Postmenopausal/drug therapy
9.
Aging Clin Exp Res ; 35(9): 1823-1834, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37340168

ABSTRACT

Accumulating evidence suggests that fatty acids (FAs) play an essential role in regulating skeletal muscle mass and function throughout life. This systematic review and meta-analysis aimed to examine the relationship between dietary or circulatory levels of monounsaturated FAs (MUFAs) and sarcopenia in observational studies. A comprehensive literature search was performed in three databases (PubMed, Scopus, and Web of Science) from inception until August 2022. Of 414 records, a total of 12 observational studies were identified for this review. Ten studies were meta-analysed, comprising a total of 3704 participants. The results revealed that MUFA intake is inversely associated with sarcopenia (standardized mean difference = - 0.28, 95% CI - 0.46 to - 0.11; p < 0.01). Despite the limited number of studies, our results suggest that lower MUFA intake is associated with a higher risk of sarcopenia. However, the available evidence is still insufficient and further investigations are needed to demonstrate this relationship.


Subject(s)
Fatty Acids, Monounsaturated , Sarcopenia , Humans , Fatty Acids , Diet , Observational Studies as Topic
10.
Pharmaceuticals (Basel) ; 16(5)2023 May 18.
Article in English | MEDLINE | ID: mdl-37242544

ABSTRACT

Vascular aging is linked to reduce NO bioavailability, endothelial dysfunction, oxidative stress, and inflammation. We previously showed that a 4-week treatment of middle-aged Wistar rats (MAWRs, 46 weeks old) with Moringa oleifera seed powder (MOI, 750 mg/kg/day) improved vascular function. Here, we investigated the involvement of SIRT1 in MOI-induced vascular improvement. MAWRs were treated with a standard or MOI-containing diet. Young rats (YWR, 16 weeks old) were the controls and received a standard diet. The hearts and aortas were harvested to evaluate SIRT1 and FOXO1 expression via Western blot and/or immunostaining, SIRT1 activity via a fluorometric assay, and oxidative stress using the DHE fluorescent probe. In the hearts and aortas, SIRT1 expression, reduced in MAWRs compared to YWRs, was enhanced in MOI MAWRs. In the hearts, SIRT1 activity did not differ between YWRs and MAWRs, whereas it was increased in MOI MAWRs compared with them. In the aortas, SIRT1 activity decreased in MAWRs, and it was similar in the MOI MAWRs and YWRs. FOXO1 expression increased in the nuclei of MAWR aortas compared to YWR and was reversed in MOI MAWRs. Interestingly, MOI treatment normalized oxidative stress enhanced in MAWRs, in both the heart and aorta. These results demonstrate the protective role of MOI against cardiovascular dysfunction due to aging via enhanced SIRT1 function and subsequently reduced oxidative stress.

11.
J Pers Med ; 13(2)2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36836568

ABSTRACT

More than two years after the onset of the COVID-19 pandemic, healthcare providers are facing an emergency within an emergency, the so-called long COVID or post-COVID-19 syndrome (PCS). Patients diagnosed with PCS develop an extended range of persistent symptoms and/or complications from COVID-19. The risk factors and clinical manifestations are many and various. Advanced age, sex/gender, and pre-existing conditions certainly influence the pathogenesis and course of this syndrome. However, the absence of precise diagnostic and prognostic biomarkers may further complicate the clinical management of patients. This review aimed to summarize recent evidence on the factors influencing PCS, possible biomarkers, and therapeutic approaches. Older patients recovered approximately one month earlier than younger patients, with higher rates of symptoms. Fatigue during the acute phase of COVID-19 appears to be an important risk factor for symptom persistence. Female sex, older age, and active smoking are associated with a higher risk of developing PCS. The incidence of cognitive decline and the risk of death are higher in PCS patients than in controls. Complementary and alternative medicine appears to be associated with improvement in symptoms, particularly fatigue. The heterogeneous nature of post-COVID symptoms and the complexity of patients with PCS, who are often polytreated due to concomitant clinical conditions, suggest a holistic and integrated approach to provide useful guidance for the treatment and overall management of long COVID.

12.
Geroscience ; 45(2): 781-796, 2023 04.
Article in English | MEDLINE | ID: mdl-36449220

ABSTRACT

Long-lived individuals (LLIs) are considered an ideal model to study healthy human aging. Blood fatty acid (FA) profile of a cohort of LLIs (90-111 years old, n = 49) from Sicily was compared to adults (18-64 years old, n = 69) and older adults (65-89 years old, n = 54) from the same area. Genetic variants in key enzymes related to FA biosynthesis and metabolism were also genotyped to investigate a potential genetic predisposition in determining the FA profile. Gas chromatography was employed to determine the FA profile, and genotyping was performed using high-resolution melt (HRM) analysis. Blood levels of total polyunsaturated FA (PUFA) and total trans-FA decreased with age, while the levels of saturated FA (SFA) remained unchanged. Interestingly, distinctively higher circulatory levels of monounsaturated FA (MUFA) in LLIs compared to adults and older adults were observed. In addition, among LLIs, rs174537 in the FA desaturase 1/2 (FADS1/2) gene was associated with linoleic acid (LA, 18:2n-6) and docosatetraenoic acid (DTA, 22:4n-6) levels, and the rs953413 in the elongase of very long FA 2 (ELOVL2) was associated with DTA levels. We further observed that rs174579 and rs174626 genotypes in FADS1/2 significantly affect delta-6 desaturase (D6D) activity. In conclusion, our results suggest that the LLIs have a different FA profile characterized by high MUFA content, which indicates reduced peroxidation while maintaining membrane fluidity.


Subject(s)
Fatty Acids, Monounsaturated , Fatty Acids , Humans , Aged , Aged, 80 and over , Fatty Acids, Monounsaturated/analysis , Fatty Acids, Monounsaturated/metabolism
13.
Eur J Sport Sci ; 23(1): 134-142, 2023 Jan.
Article in English | MEDLINE | ID: mdl-34694208

ABSTRACT

ABSTRACTThe aim of this study was to examine the association between biomarkers of polyunsaturated fatty acids (PUFA), such as omega-3 (ω-3) index and arachidonic acid (AA; 20:4 ω-6)/eicosapentaenoic acid (EPA; 20:5ω-3) ratio (AA/EPA), and the prevalence of running-related injuries (RRI) in a cohort of recreational runners. We performed a retrospective, observational study of 275 non-elite runners (mean age: 41.20 ± 12.47 years) who were not supplemented with ω-3 fatty acids. The training characteristics and RRI were recorded over a period of 12 months through a self-reported questionnaire. Using whole blood samples collected by finger prick, PUFA were quantified by gas chromatography and ω-3 index and AA/EPA ratio measured. A total of 191 RRI cases were reported, with an injury prevalence rate of 50.9% in the overall population. The injured runners ran a significantly greater weekly distance than uninjured subjects (53.54 ± 25.27 km/week; p = 0.007). In a multivariate regression analysis, the lowest number of RRI was associated with higher values of ω-3 index (ß = - 0.237; 95% CI - 0.308 to - 0.164; R2 = 0.172; p < 0.0001), while a higher AA/EPA ratio was correlated with higher number of RRI (ß = 0.019; 95% CI 0.007-0.031; R2 = 0.038; p = 0.003). This study identifies ω-3 index and AA/EPA ratio as potential parameters associated with the risk of RRI. Future research is needed to confirm these results and apply specific nutritional strategies to successfully modify these biochemical variables.Trial registration: ISRCTN.org identifier: ISRCTN12847156..


Subject(s)
Fatty Acids, Omega-3 , Running , Humans , Adult , Middle Aged , Retrospective Studies , Fatty Acids, Omega-6 , Biomarkers
14.
J Chemother ; 35(5): 383-396, 2023 Sep.
Article in English | MEDLINE | ID: mdl-36102273

ABSTRACT

Remdesivir (RDV) is a broad-spectrum antiviral drug, now approved by Regulatory Agencies for COVID-19 treatment. RDV is associated with improvements in clinical outcomes, but no conclusive studies have shown an effect in reducing mortality. This study aimed to carry out a systematic review with meta-analysis to investigate whether RDV can significantly modify the outcome of COVID-19 patients evaluating its effects on mortality, length of stay, time to clinical improvement and need for oxygen supplementation. No significant improvement in terms of survival in patients treated with standard therapy (ST)+RDV as compared to ST alone (P = 0.24) was found. The duration of oxygen support was significantly lower in patients treated with ST + RDV compared with ST alone (P = 0.03). Further investigations should be planned to assess the real impact of RDV in the management of COVID-19 patients.


Subject(s)
COVID-19 , Humans , COVID-19 Drug Treatment , Antiviral Agents/therapeutic use
15.
Life (Basel) ; 12(12)2022 Dec 19.
Article in English | MEDLINE | ID: mdl-36556504

ABSTRACT

Microgravity exposure causes several physiological and psychosocial alterations that challenge astronauts' health during space flight. Notably, many of these changes are mostly related to physical inactivity influencing different functional systems and organ biology, in particular the musculoskeletal system, dramatically resulting in aging-like phenotypes, such as those occurring in older persons on Earth. In this sense, sarcopenia, a syndrome characterized by the loss in muscle mass and strength due to skeletal muscle unloading, is undoubtedly one of the most critical aging-like adverse effects of microgravity and a prevalent problem in the geriatric population, still awaiting effective countermeasures. Therefore, there is an urgent demand to identify clinically relevant biological markers and to underline molecular mechanisms behind these effects that are still poorly understood. From this perspective, a lesson from Geroscience may help tailor interventions to counteract the adverse effects of microgravity. For instance, decades of studies in the field have demonstrated that in the older people, the clinical picture of sarcopenia remarkably overlaps (from a clinical and biological point of view) with that of frailty, primarily when referred to the physical function domain. Based on this premise, here we provide a deeper understanding of the biological mechanisms of sarcopenia and frailty, which in aging are often considered together, and how these converge with those observed in astronauts after space flight.

16.
Pharmaceuticals (Basel) ; 15(11)2022 Nov 10.
Article in English | MEDLINE | ID: mdl-36355560

ABSTRACT

Hand-Foot syndrome (HFS) and diarrhoea are dose-limiting Adverse Drug Reactions (ADRs) of capecitabine-based chemotherapy. Four polymorphisms in the dihydropyrimidine dehydrogenase (DPYD) gene, encoding the DPD enzyme responsible for the metabolism of fluoropyrimidines, such as capecitabine, are strongly associated with severe ADRs, and their screening should be performed before starting treatment. Moreover, capecitabine-related toxicity may worsen due to drug-drug and drug-supplement interactions. Here we investigated factors responsible for severe HFS and diarrhoea presented by two patients, non-carriers of the recommended DPYD single nucleotide polymorphisms (SNPs) but carriers of other genetic variants suggested to increase the risk of capecitabine-related ADRs. Through careful therapy recognition, we demonstrated that, unbeknownst to the oncologists, the patients were taking folic acid during the treatment with capecitabine at a dosage higher than 2000 mg/m2, which is the maximum tolerated dose when folate is administered. To resolve the ADRs, the therapy had to be drastically changed. In one case, dose reduction of capecitabine and discontinuation of lipid-lowering agents were carried out. In the other case, discontinuation of capecitabine and folic acid and capecitabine re-administration were performed after a month. Genetic and environmental factors should be considered good predictors of severe capecitabine-related toxicity. Medication reconciliation should be encouraged to avoid the harmful consequences of inappropriate treatments.

17.
J Pers Med ; 12(10)2022 Sep 25.
Article in English | MEDLINE | ID: mdl-36294717

ABSTRACT

Vitamin K antagonists (VKAs) are used in the prophylaxis and treatment of thromboembolic disorders. Despite a high efficacy, their narrow therapeutic window and high response variability hamper their management. Several patients experience fluctuations in dose−response and are at increased risk of over- or under-anticoagulation. Therefore, it is essential to monitor the prothrombin time/international normalized ratio to determine the so-called stable dose and to adjust the dosage accordingly. Three polymorphisms, CYP2C9∗2, CYP2C9∗3 and VKORC1-1639G>A, are associated with increased sensitivity to VKAs. Other polymorphisms are associated with a request for a higher dose and VKA resistance. We described the clinical cases of two patients who were referred to the Clinical Pharmacology and Pharmacogenetics Unit of the University Hospital of Salerno for pharmacological counseling. One of them showed hypersensitivity and the other one was resistant to VKAs. A systematic review was performed to identify randomized clinical trials investigating the impact of pharmacogenetic testing on increased sensitivity and resistance to VKAs. Although international guidelines are available and information on the genotype-guided dosing approach has been included in VKA drug labels, VKA pharmacogenetic testing is not commonly required. The clinical cases and the results of the systematically reviewed RCTs demonstrate that the pharmacogenetic-based VKA dosing model represents a valuable resource for reducing VKA-associated adverse events.

18.
Healthcare (Basel) ; 10(9)2022 Sep 19.
Article in English | MEDLINE | ID: mdl-36141412

ABSTRACT

Crenotherapy is recognized as being effective in patients with osteoarthritis of the spine, but to date there is no indication if it is effective for patients who are overweight or obese. The aim of this study is to evaluate the efficacy of sulphurous crenotherapy on pain and disability in overweight/obese subjects affected by chronic low back pain from spine osteoarthritis. Forty-three patients (63 ± 8.8 years) affected by chronic low back pain from lumbar spine osteoarthritis were enrolled in this study. Subjects were treated with 2 weeks of sulphurous creno-treatments. Subjective pain was measured by a numerical rating scale score (NRS), and functional mobility of the lumbar spine was measured using the Oswestry Disability Index (ODI) before and after crenotherapy. Both crenotherapy groups (normal weight: A1; overweight/obese: A2) experienced significantly improved NRS and ODI scores (A1: p < 0.001 and p = 0.001; A2: p = 0.001 and p = 0.001). At end of the treatment, significant improvements were observed as a result of the crenotherapy in overweight/obese subjects in terms of pain reduction measured with NRS (p = 0.03) and in terms of function mobility of the lumbar spine measured with ODI (p = 0.006). This study highlights the beneficial effect of sulphurous crenotherapy on the painful symptomatology and disability in both normal weight and overweight/obese patients suffering from chronic low back pain associated with lumbar spine osteoarthritis.

20.
J Clin Med ; 11(15)2022 Jul 29.
Article in English | MEDLINE | ID: mdl-35956030

ABSTRACT

AIM: "Antimicrobial stewardship" (AMS) is defined as a healthcare-system-wide approach to promoting and monitoring the judicious use of antimicrobials to preserve their future effectiveness. Therefore, we structured an observational study to monitor the hospital trend of antibiotic consumption and related expenditure before the COVID-19 pandemic and to evaluate how much AMS could affect this trend. METHODS: The research covered the antibiotic prescriptions at the University Hospital (U.H.) "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy, comparing data on the therapies prescribed from 1 January to 31 December 2017 (27,384 patients) with those collected during the same period in 2019 (27,047 patients). RESULTS: Unlike national data, our results highlighted a decreasing trend in the consumption of antibiotics that did not concern only carbapenems and fluoroquinolones, but also the third-generation cephalosporins. Noteworthily, there was also a reduction in 2019 compared with 2017 in the consumption of colistin, an antibiotic towards which an increase in bacterial resistance in animals has been found nationally. In agreement with the national data, our research confirms a trend of an increase (+3.7%) in the total antibiotic consumption corresponding to more than 26% and 29% reductions in the total and therapy per-day costs, respectively. CONCLUSIONS: The results show a positive impact of the AMS at the University Hospital "San Giovanni di Dio e Ruggi d'Aragona".

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