The p66Shc Redox Protein and the Emerging Complications of Diabetes.

Diabetes mellitus is a chronic metabolic disease, the prevalence of which is constantly increasing worldwide. It is often burdened by disabling comorbidities that reduce the quality and expectancy of life of the affected individuals. The traditional complications of diabetes are generally described as macrovascular complications (e.g., coronary heart disease, peripheral arterial disease, and stroke), and microvascular complications (e.g., diabetic kidney disease, retinopathy, and neuropathy). Recently, due to advances in diabetes management and the increased life expectancy of diabetic patients, a strong correlation between diabetes and other pathological conditions (such as liver diseases, cancer, neurodegenerative diseases, cognitive impairments, and sleep disorders) has emerged. Therefore, these comorbidities have been proposed as emerging complications of diabetes. P66Shc is a redox protein that plays a role in oxidative stress, apoptosis, glucose metabolism, and cellular aging. It can be regulated by various stressful stimuli typical of the diabetic milieu and is involved in various types of organ and tissue damage under diabetic conditions. Although its role in the pathogenesis of diabetes remains controversial, there is strong evidence regarding the involvement of p66Shc in the traditional complications of diabetes. In this review, we will summarize the evidence supporting the role of p66Shc in the pathogenesis of diabetes and its complications, focusing for the first time on the emerging complications of diabetes.

Lipoprotein(a) levels and risk of adverse events after myocardial infarction in patients with and without diabetes.

INTRODUCTION: The aim of this study was to evaluate the association of lipoprotein(a) [Lp(a)] levels with long-term outcome in patients with recent history of myocardial infarction (MI), and to investigate if diabetes may influence this association. METHODS: Consecutive MI patients who underwent urgent/emergent coronary angiography from February 2013 to June 2019 were prospectively collected. The primary outcome was the composite of MI recurrence and all-cause death. The propensity score weighting technique was used to account for covariates potentially influencing the relationship between Lp(a) levels and the study outcomes. RESULTS: The study population consisted of 1018 post-MI patients (median age 63 years). Diabetes was reported in 280 patients (27.5%), who showed lower Lp(a) levels than patients without diabetes (p = 0.026). At a median follow-up of 1121 days, the primary outcome was reported in 182 patients (17.9%). At univariable Cox regression analysis, Lp(a) was associated with the risk of the primary outcome in the overall population and in non-diabetic patients, but not in diabetics. The adjusted Cox regression analysis confirmed the independent association between Lp(a) values and the primary outcome in non-diabetic patients, but not in diabetics.Lp(a) levels > 70 mg/dL were independently associated with the risk of the primary outcome in non-diabetic patients (adjusted HR: 2.839; 95% CI, 1.382-5.832), but not in diabetics. CONCLUSIONS: In this real-world post-MI population, increasing Lp(a) levels were significantly associated with the risk of recurrent MI and all-cause death, and very high Lp(a) serum concentration independently predicted long-term outcome in non-diabetic patients, but not in diabetics.

New approach to implement cancer patient care: The valutazione percorso rete oncologica campana (ValPeROC)-experience from an Italian oncology network.

OBJECTIVE: The primary goal of the Campania Oncology Network (ROC) was to reduce cancer delay and care fragmentation through the establishment of cancer-specific multidisciplinary oncologic groups (GOMs) and diagnostic and therapeutic assistance paths (PDTAs). METHODS: Five cancer centres of the ROC, with their own cancer specific GOM, were selected. In our analysis, we have focused on four neoplasms: lung, colon, ovarian and prostate cancers. The median time for pre-GOM and GOM Times was calculated for each tumour site. Univariate and multivariate logistic regressions were performed to individuate risk factors for pre-GOM and GOM Time. RESULTS: Significant differences were observed for prostate cancer compared to other patients either for pre-GOM or GOM Times. Significant risks were found for ovarian and prostate cancers in pre-GOM time and for prostate cancer in GOM-Time. CONCLUSIONS: This experience will produce knowledge and data to guide decision-making and to manage more effectively the challenges of fighting cancer in Campania region. The Valutazione Percorso Rete Oncologica Campana (ValPeROC) study evaluates, for the first time, the ROC activity, through the analysis of key performance indices. Pre-GOM and GOM Time represent the quality of the entire regional health system and are useful to define models, which can evaluate the performance of the ROC over time.

Multiple regression model to analyze the total LOS for patients undergoing laparoscopic appendectomy.

BACKGROUND: The rapid growth in the complexity of services and stringent quality requirements present a challenge to all healthcare facilities, especially from an economic perspective. The goal is to implement different strategies that allows to enhance and obtain health processes closer to standards. The Length Of Stay (LOS) is a very useful parameter for the management of services within the hospital and is an index evaluated for the management of costs. In fact, a patient's LOS can be affected by a number of factors, including their particular condition, medical history, or medical needs. To reduce and better manage the LOS it is necessary to be able to predict this value. METHODS: In this study, a predictive model was built for the total LOS of patients undergoing laparoscopic appendectomy, one of the most common emergency procedures. Demographic and clinical data of the 357 patients admitted at "San Giovanni di Dio e Ruggi d'Aragona" University Hospital of Salerno (Italy) had used as independent variable of the multiple linear regression model. RESULTS: The obtained model had an R2 value of 0.570 and, among the independent variables, the significant variables that most influence the total LOS were Age, Pre-operative LOS, Presence of Complication and Complicated diagnosis. CONCLUSION: This work designed an effective and automated strategy for improving the prediction of LOS, that can be useful for enhancing the preoperative pathways. In this way it is possible to characterize the demand and to be able to estimate a priori the occupation of the beds and other related hospital resources.

Overcrowding analysis in emergency department through indexes: a single center study.

INTRODUCTION: Overcrowding in the Emergency Department (ED) is one of the major issues that must be addressed in order to improve the services provided in emergency circumstances and to optimize their quality. As a result, in order to help the patients and professionals engaged, hospital organizations must implement remedial and preventative measures. Overcrowding has a number of consequences, including inadequate treatment and longer hospital stays; as a result, mortality and the average duration of stay in critical care units both rise. In the literature, a number of indicators have been used to measure ED congestion. EDWIN, NEDOCS and READI scales are considered the most efficient ones, each of which is based on different parameters regarding the patient management in the ED. METHODS: In this work, EDWIN Index and NEDOCS Index have been calculated every hour for a month period from February 9th to March 9th, 2020 and for a month period from March 10th to April 9th, 2020. The choice of the period is related to the date of the establishment of the lockdown in Italy due to the spread of Coronavirus; in fact on 9 March 2020 the Italian government issued the first decree regarding the urgent provisions in relation to the COVID-19 emergency. Besides, the Pearson correlation coefficient has been used to evaluate how much the EDWIN and NEDOCS indexes are linearly dependent. RESULTS: EDWIN index follows a trend consistent with the situation of the first lockdown period in Italy, defined by extreme limitations imposed by Covid-19 pandemic. The 8:00-20:00 time frame was the most congested, with peak values between 8:00 and 12:00. on the contrary, in NEDOCS index doesn't show a trend similar to the EDWIN one, resulting less reliable. The Pearson correlation coefficient between the two scales is 0,317. CONCLUSION: In this study, the EDWIN Index and the NEDOCS Index were compared and correlated in order to assess their efficacy, applying them to the case study of the Emergency Department of "San Giovanni di Dio e Ruggi d'Aragona" University Hospital during the Covid-19 pandemic. The EDWIN scale turned out to be the most realistic model in relation to the actual crowding of the ED subject of our study. Besides, the two scales didn't show a significant correlation value.

Adipose Tissue Secretion Pattern Influences ß-Cell Wellness in the Transition from Obesity to Type 2 Diabetes.

The dysregulation of the ß-cell functional mass, which is a reduction in the number of ß-cells and their ability to secure adequate insulin secretion, represents a key mechanistic factor leading to the onset of type 2 diabetes (T2D). Obesity is recognised as a leading cause of ß-cell loss and dysfunction and a risk factor for T2D. The natural history of ß-cell failure in obesity-induced T2D can be divided into three steps: (1) ß-cell compensatory hyperplasia and insulin hypersecretion, (2) insulin secretory dysfunction, and (3) loss of ß-cell mass. Adipose tissue (AT) secretes many hormones/cytokines (adipokines) and fatty acids that can directly influence ß-cell function and viability. As this secretory pattern is altered in obese and diabetic patients, it is expected that the cross-talk between AT and pancreatic ß-cells could drive the maintenance of the ß-cell integrity under physiological conditions and contribute to the reduction in the ß-cell functional mass in a dysmetabolic state. In the current review, we summarise the evidence of the ability of the AT secretome to influence each step of ß-cell failure, and attempt to draw a timeline of the alterations in the adipokine secretion pattern in the transition from obesity to T2D that reflects the progressive deterioration of the ß-cell functional mass.

Adipose Tissue Dysfunction and Obesity-Related Male Hypogonadism.

Obesity is a chronic illness associated with several metabolic derangements and comorbidities (i.e., insulin resistance, leptin resistance, diabetes, etc.) and often leads to impaired testicular function and male subfertility. Several mechanisms may indeed negatively affect the hypothalamic-pituitary-gonadal health, such as higher testosterone conversion to estradiol by aromatase activity in the adipose tissue, increased ROS production, and the release of several endocrine molecules affecting the hypothalamus-pituitary-testis axis by both direct and indirect mechanisms. In addition, androgen deficiency could further accelerate adipose tissue expansion and therefore exacerbate obesity, which in turn enhances hypogonadism, thus inducing a vicious cycle. Based on these considerations, we propose an overview on the relationship of adipose tissue dysfunction and male hypogonadism, highlighting the main biological pathways involved and the current therapeutic options to counteract this condition.

Impact of Dysfunctional Adipose Tissue Depots on the Cardiovascular System.

Obesity with its associated complications represents a social, economic and health problem of utmost importance worldwide. Specifically, obese patients carry a significantly higher risk of developing cardiovascular disease compared to nonobese individuals. Multiple molecular mechanisms contribute to the impaired biological activity of the distinct adipose tissue depots in obesity, including secretion of proinflammatory mediators and reactive oxygen species, ultimately leading to an unfavorable impact on the cardiovascular system. This review summarizes data relating to the contribution of the main adipose tissue depots, including both remote (i.e., intra-abdominal, hepatic, skeletal, pancreatic, renal, and mesenteric adipose fat), and cardiac (i.e., the epicardial fat) adipose locations, on the cardiovascular system. Finally, we discuss both pharmacological and non-pharmacological strategies aimed at reducing cardiovascular risk through acting on adipose tissues, with particular attention to the epicardial fat.

Clinical conditions and echocardiographic parameters associated with mortality in COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a recently recognized viral infective disease which can be complicated by acute respiratory stress syndrome (ARDS) and cardiovascular complications including severe arrhythmias, acute coronary syndromes, myocarditis and pulmonary embolism. The aim of the present study was to identify the clinical conditions and echocardiographic parameters associated with in-hospital mortality in COVID-19. METHODS: This is a multicentre retrospective observational study including seven Italian centres. Patients hospitalized with COVID-19 from 1 March to 22 April 2020 were included into study population. The association between baseline variables and risk of in-hospital mortality was assessed through multivariable logistic regression and competing risk analyses. RESULTS: Out of 1401 patients admitted at the participating centres with confirmed diagnosis of COVID-19, 226 (16.1%) underwent transthoracic echocardiography (TTE) and were included in the present analysis. In-hospital death occurred in 68 patients (30.1%). At multivariable analysis, left ventricular ejection fraction (LVEF, P < .001), tricuspid annular plane systolic excursion (TAPSE, P < .001) and ARDS (P < .001) were independently associated with in-hospital mortality. At competing risk analysis, we found a significantly higher risk of mortality in patients with ARDS vs those without ARDS (HR: 7.66; CI: 3.95-14.8), in patients with TAPSE ≤17 mm vs those with TAPSE >17 mm (HR: 5.08; CI: 3.15-8.19) and in patients with LVEF ≤50% vs those with LVEF >50% (HR: 4.06; CI: 2.50-6.59). CONCLUSIONS: TTE might be a useful tool in risk stratification of patients with COVID-19. In particular, reduced LVEF and reduced TAPSE may help to identify patients at higher risk of death during hospitalization.

Comprehensive Analysis of Combinatorial Pharmacological Treatments to Correct Nonsense Mutations in the CFTR Gene.

Cystic fibrosis (CF) is caused by loss of function of the CFTR chloride channel. A substantial number of CF patients carry nonsense mutations in the CFTR gene. These patients cannot directly benefit from pharmacological correctors and potentiators that have been developed for other types of CFTR mutations. We evaluated the efficacy of combinations of drugs targeting at various levels the effects of nonsense mutations: SMG1i to protect CFTR mRNA from nonsense-mediated decay (NMD), G418 and ELX-02 for readthrough, VX-809 and VX-445 to promote protein maturation and function, PTI-428 to enhance CFTR protein synthesis. We found that the extent of rescue and sensitivity to the various agents is largely dependent on the type of mutation, with W1282X and R553X being the mutations most and least sensitive to pharmacological treatments, respectively. In particular, W1282X-CFTR was highly responsive to NMD suppression by SMG1i but also required treatment with VX-445 corrector to show function. In contrast, G542X-CFTR required treatment with readthrough agents and VX-809. Importantly, we never found cooperativity between the NMD inhibitor and readthrough compounds. Our results indicate that treatment of CF patients with nonsense mutations requires a precision medicine approach with the design of specific drug combinations for each mutation.

Partial Rescue of F508del-CFTR Stability and Trafficking Defects by Double Corrector Treatment.

Deletion of phenylalanine at position 508 (F508del) in the CFTR chloride channel is the most frequent mutation in cystic fibrosis (CF) patients. F508del impairs the stability and folding of the CFTR protein, thus resulting in mistrafficking and premature degradation. F508del-CFTR defects can be overcome with small molecules termed correctors. We investigated the efficacy and properties of VX-445, a newly developed corrector, which is one of the three active principles present in a drug (Trikafta®/Kaftrio®) recently approved for the treatment of CF patients with F508del mutation. We found that VX-445, particularly in combination with type I (VX-809, VX-661) and type II (corr-4a) correctors, elicits a large rescue of F508del-CFTR function. In particular, in primary bronchial epithelial cells of CF patients, the maximal rescue obtained with corrector combinations including VX-445 was close to 60-70% of CFTR function in non-CF cells. Despite this high efficacy, analysis of ubiquitylation, resistance to thermoaggregation, protein half-life, and subcellular localization revealed that corrector combinations did not fully normalize F508del-CFTR behavior. Our study indicates that it is still possible to further improve mutant CFTR rescue with the development of corrector combinations having maximal effects on mutant CFTR structural and functional properties.

Development and Improvement of an Effective Method for Air and Surfaces Disinfection with Ozone Gas as a Decontaminating Agent.

Background and objectives: Ozone has been one of the most investigated and discussed sanitization methods. This paper reports a procedure to sanitize air hospital environments, in particular chirurgical surgery rooms that require high levels of disinfection. The purpose of this work was the development and implementation of a cleansing and sanitizing procedure for critical clinical settings with ozone, to prevent hospital infections by the elimination of all toxic and harmful microorganisms in the air, and ensure safe use for operators and patients. Materials and Methods: The protocol for the study involved a structured selection of a representative environment of healthcare structures such as high, medium, and low-risk settings in air and examples of hospital furniture. Results: The concentration of ozone was measured during sanitization treatment and the estimation of the total microbial count in the air and on different surfaces before and after the sanitization operations was performed. The results demonstrated a significant reduction in the microbial count that always fell below the threshold value. Conclusions: Currently, there are no air treatment strategies available for inactivating airborne organisms during hospital outbreaks, which is most probably due to the lack of approved protocols.

TRPV4 and purinergic receptor signalling pathways are separately linked in airway epithelia to CFTR and TMEM16A chloride channels.

KEY POINTS: Eact is a putative pharmacological activator of TMEM16A. Eact is strongly effective in recombinant Fischer rat thyroid (FRT) cells but not in airway epithelial cells with endogenous TMEM16A expression. Transcriptomic analysis, gene silencing and functional studies in FRT cells reveal that Eact is actually an activator of the Ca2+ -permeable TRPV4 channel. In airway epithelial cells TRPV4 and TMEM16A are expressed in separate cell types. Intracellular Ca2+ elevation by TRPV4 stimulation leads to CFTR channel activation. ABSTRACT: TMEM16A is a Ca2+ -activated Cl- channel expressed in airway epithelial cells, particularly under conditions of mucus hypersecretion. To investigate the role of TMEM16A, we used Eact, a putative TMEM16A pharmacological activator. However, in contrast to purinergic stimulation, we found little effect of Eact on bronchial epithelial cells under conditions of high TMEM16A expression. We hypothesized that Eact is an indirect activator of TMEM16A. By a combination of approaches, including short-circuit current recordings, bulk and single cell RNA sequencing, intracellular Ca2+ imaging and RNA interference, we found that Eact is actually an activator of the Ca2+ -permeable TRPV4 channel and that the modest effect of this compound in bronchial epithelial cells is due to a separate expression of TMEM16A and TRPV4 in different cell types. Importantly, we found that TRPV4 stimulation induced activation of the CFTR Cl- channel. Our study reveals the existence of separate Ca2+ signalling pathways linked to different Cl- secretory processes.

Lean thinking to improve emergency department throughput at AORN Cardarelli hospital.

BACKGROUND: Throughout the world, emergency departments (ED) are characterized by overcrowding and excessive waiting times. Furthermore, the related delays significantly increase patient mortality and make inefficient use of resources to the detriment of the satisfaction of employees and patients. In this work, lean thinking is applied to the ED of Cardarelli Hospital of Naples with the aim of increasing patient flow, improving the processes that contribute to facilitating the flow of patients through the various stages of medical treatment and eliminating all bottlenecks (queue) as well as all activities that generate waste. METHODS: This project was performed at National Hospital A.O.R.N. A. Cardarelli of Naples. The historical times of access to the ED were analysed from January 2015 to June 2015, for a total of 16,563 records. Subsequently, starting in November 2015, corrective actions were implemented according to the Lean Approach. Data collected after the introduced improvements were collected from April 2016 to June 2016 and compared to those collected during the starting period. RESULTS: The results acquired before application of the Lean Thinking strategy illustrated the as-is process with its drawbacks. An analysis of the non-added value activities was performed to identify the procedures that need to be improved. After implementation of the corrective actions, we observed a positive increase in the performance of the ED, quantified as percentages of hospitalized patients according to triage codes and waiting times. CONCLUSION: This work demonstrates the applicability of Lean Thinking to ED processes and its effectiveness in terms of increasing the efficiency of services and reducing waste (waiting times).

Type 2 Diabetes and Alzheimer's Disease: The Emerging Role of Cellular Lipotoxicity.

Type 2 diabetes (T2D) and Alzheimer's diseases (AD) represent major health issues that have reached alarming levels in the last decades. Although growing evidence demonstrates that AD is a significant comorbidity of T2D, and there is a ~1.4-2-fold increase in the risk of developing AD among T2D patients, the involvement of possible common triggers in the pathogenesis of these two diseases remains largely unknown. Of note, recent mechanistic insights suggest that lipotoxicity could represent the missing ring in the pathogenetic mechanisms linking T2D to AD. Indeed, obesity, which represents the main cause of lipotoxicity, has been recognized as a major risk factor for both pathological conditions. Lipotoxicity can lead to inflammation, insulin resistance, oxidative stress, ceramide and amyloid accumulation, endoplasmic reticulum stress, ferroptosis, and autophagy, which are shared biological events in the pathogenesis of T2D and AD. In the current review, we try to provide a critical and comprehensive view of the common molecular pathways activated by lipotoxicity in T2D and AD, attempting to summarize how these mechanisms can drive future research and open the way to new therapeutic perspectives.

Pharmacological potentiators of the calcium signaling cascade identified by high-throughput screening.

Pharmacological modulators of the Ca2+ signaling cascade are important research tools and may translate into novel therapeutic strategies for a series of human diseases. We carried out a screening of a maximally diverse chemical library using the Ca2+-sensitive Cl- channel TMEM16A as a functional readout. We found compounds that were able to potentiate UTP-dependent TMEM16A activation. Mechanism of action of these compounds was investigated by a panel of assays that looked at intracellular Ca2+ mobilization triggered by extracellular agonists or by caged-IP3 photolysis, PIP2 breakdown by phospholipase C, and ion channel activity on nuclear membrane. One compound appears as a selective potentiator of inositol triphosphate receptor type 1 (ITPR1) with a possible application for some forms of spinocerebellar ataxia. A second compound is instead a potentiator of the P2RY2 purinergic receptor, an activity that could promote fluid secretion in dry eye and chronic obstructive respiratory diseases.

Impact of SARS-CoV-2 Positivity on Delivery Outcomes for Pregnant Women between 2020 and 2021: A Single-Center Population-Based Analysis.

Despite the existing body of evidence, there is still limited knowledge about the impact of SARS-CoV-2 positivity on delivery outcomes. We aimed to assess the impact of SARS-CoV-2 infection in women who gave birth at the University Hospital "Federico II" of Naples, Italy, between 2020 and 2021. We conducted a retrospective single-center population-based observational study to assess the differences in the caesarean section and preterm labor rates and the length of stay between women who tested positive for SARS-CoV-2 and those who tested negative at the time of labor. We further stratified the analyses considering the time period, dividing them into three-month intervals, and changes in SARS-CoV-2 as the most prevalent variant. The study included 5236 women with 353 positive cases. After vaccination availability, only 4% had undergone a complete vaccination cycle. The Obstetric Comorbidity Index was higher than 0 in 41% of the sample. When compared with negative women, positive ones had 80% increased odds of caesarean section, and it was confirmed by adjusting for the SARS-CoV-2 variant. No significant differences were found in preterm birth risks. The length of stay was 11% higher in positive cases but was not significant after adjusting for the SARS-CoV-2 variant. When considering only positive women in the seventh study period (July-September 2021), they had a 61% decrease in the odds of receiving a caesarean section compared to the fourth (October-December 2020). Guidelines should be implemented to improve the safety and efficiency of the delivery process, considering the transition of SARS-CoV-2 from pandemic to endemic. Furthermore, these guidelines should aim to improve the management of airborne infections in pregnant women.

Awareness of individual goals, preferences, and priorities of persons with severe congenital haemophilia A for a tailored shared decision-making approach to liver-directed gene therapy. A practical guideline.

In clinical medicine, shared decision making (SDM) is a well-recognized strategy to enhance engagement of both patients and clinicians in medical decisions. The success of liver-directed gene therapy (GT) to transform severe congenital haemophilia A (HA) from an incurable to a curable disease has launched a shift beyond current standards of treatment. However, GT acceptance remains low in the community of HA persons. We argue for both persons with haemophilia (PWH) and specialists in HA care including clinicians, as needing SDM-oriented educational programs devoted to GT. Here, we provide an ad hoc outline to implement education to SDM and tailor clinician information on GT to individual PWHs. Based on routine key components of SDM: patient priorities; recommendations based on individual risk reduction; adverse effects; drug-drug interactions; alternatives to GT; and ongoing re-assessment of the objectives as risk factors (and individual priorities) change, this approach is finalized to exploit efficacious communication.

Novel tricyclic pyrrolo-quinolines as pharmacological correctors of the mutant CFTR chloride channel.

F508del, the most frequent mutation in cystic fibrosis (CF), impairs the stability and folding of the CFTR chloride channel, thus resulting in intracellular retention and CFTR degradation. The F508del defect can be targeted with pharmacological correctors, such as VX-809 and VX-445, that stabilize CFTR and improve its trafficking to plasma membrane. Using a functional test to evaluate a panel of chemical compounds, we have identified tricyclic pyrrolo-quinolines as novel F508del correctors with high efficacy on primary airway epithelial cells from CF patients. The most effective compound, PP028, showed synergy when combined with VX-809 and VX-661 but not with VX-445. By testing the ability of correctors to stabilize CFTR fragments of different length, we found that VX-809 is effective on the amino-terminal portion of the protein that includes the first membrane-spanning domain (amino acids 1-387). Instead, PP028 and VX-445 only show a stabilizing effect when the second membrane-spanning domain is included (amino acids 1-1181). Our results indicate that tricyclic pyrrolo-quinolines are a novel class of CFTR correctors that, similarly to VX-445, interact with CFTR at a site different from that of VX-809. Tricyclic pirrolo-quinolines may represent novel CFTR correctors suitable for combinatorial pharmacological treatments to treat the basic defect in CF.

A LC-MS/MS based methodology for the environmental monitoring of healthcare settings contaminated with antineoplastic agents.

Background: Adverse health events associated with the exposure of healthcare workers to antineoplastic drugs are well documented in literature and are often related to the chemical contamination of work surfaces. It is therefore crucial for healthcare professionals to validate the efficiency of safety procedures by periodic biological and environmental monitoring activities where the main methodological limitations are related to the complexity, in terms of chemical-physical features and chemical-biological stability, of the drugs analyzed. Materials and methods: Here we describe the evaluation and application of a UHPLC-MS/MS based protocol for the environmental monitoring of hospital working areas potentially contaminated with methotrexate, iphosphamide, cyclophosphamide, doxorubicin, irinotecan, and paclitaxel. This methodology was used to evaluate working areas devoted to the preparation of chemotherapeutics and combination regimens at the University Hospital "San Giovanni di Dio e Ruggi d'Aragona" in Salerno (Italy). Results: Our analyses allowed to uncover critical aspects in both working protocols and workspace organization, which highlighted, among others, cyclophosphamide and iphosphamide contamination. Suitable adjustments adopted after our environmental monitoring campaign significantly reduced the exposure risk for healthcare workers employed in the unit analyzed. Conclusion: The use of sensitive analytical approaches such as LC-MS/MS coupled to an accurate wiping procedure in routine environmental monitoring allows to effectively improve chemical safety for exposed workers.