Two-year Opioid Prescription Trends in Local Sanitary Agency Naples 3 South, Campania Region, Italy. Descriptive Analyses and AI-based Translational Perspectives.

Aims: This study delves into the two-year opioid prescription trends in the Local Sanitary Agency Naples 3 South, Campania Region, Italy. The research aims to elucidate prescribing patterns, demographics, and dosage categories within a population representing 1.7% of the national total. Perspectives on artificial intelligence research are discussed. Methods: From the original dataset, spanning from January 2022 to October 2023, we processed multiple variables including demographic data, medications, dosages, drug consumption, and administration routes. The dispensing quantity was calculated as defined daily doses (DDD). Results: The analysis reveals a conservative approach to opioid therapy. In subjects under the age of 20, prescriptions accounted for 2.1% in 2022 and declined to 1.4% in 2023. The drug combination paracetamol/codeine was the most frequently prescribed, followed by tapentadol. Approximately two-thirds of the consumption pertains to oral formulations. Transdermal formulations were 15% (fentanyl 9.8%, buprenorphine 5.1%) in 2022; and 16.6% (fentanyl 10%, buprenorphine 6.6%) in 2023. These data were confirmed by the DDD analysis. The trend analysis demonstrated a significant reduction ( p < 0.001) in the number of prescribed opioids from 2022 to 2023 in adults (40-69 years). The study of rapid-onset opioids (ROOs), drugs specifically used for breakthrough cancer pain, showed higher dosage (>267 mcg) consumption among women, whereas a lower dosage (<133 mcg) was calculated for men. Fentanyl pectin nasal spray accounted for approximately one-fifth of all ROOs. Conclusion: Despite limitations, the study provides valuable insights into prescribing practices involving an important study population. The findings underscore the need for tailored approaches to prescribing practices, recognizing the complexities of pain management in different contexts. This research can contribute to the ongoing discourse on opioid use, advocating for innovative strategies that optimize therapeutic outcomes while mitigating potential risks.

Bridging knowledge gaps: a bibliometric analysis of non-invasive ventilation in palliative care studies.

BACKGROUND: Despite being a useful strategy for providing respiratory support to patients with advanced or terminal illnesses, non-invasive ventilation (NIV) requires in-depth investigation in several key aspects. OBJECTIVES: This bibliometric analysis seeks to comprehensively examine the existing research on the subject. Its goal is to uncover valuable insights that can inform the prediction trajectory of studies, guide the implementation of corrective measures, and contribute to the improvement of research networks. METHODS: A comprehensive review of literature on NIV in the context of palliative care was conducted using the Web of Science core collection online database. The search utilized the key terms "non-invasive ventilation" and "palliative care" to identify the most relevant articles. All data were gathered on November 7, 2023. Relevant information from documents meeting the specified criteria was extracted, and Journal Citation Reports™ 2022 (Clarivate Analytics) served as the data source. The analysis employed literature analysis and knowledge visualization tools, specifically CiteScope (version 6.2.R4) and VOSviewer (version 1.6.20). RESULTS: A dataset with bibliometric findings from 192 items was analyzed. We found a consistent upward of the scientific output trend over time. Guidelines on amyotrophic lateral sclerosis management received the highest number of citations. Most documents were published in top-ranked journals. Less than one-third of the documents pertain to clinical studies, especially retrospective analyses (25%). Key topics such as "decision making", and "communication" were less addressed. CONCLUSIONS: Given the substantial clinical implications, further high-quality studies on this subject are recommended. Encouraging international collaborations is needed. Despite the growing volume of documents in the field, this bibliometric analysis indicates a decline in collaborative networks.

Ethical issues in pain and palliation.

PURPOSE OF REVIEW: Increased public awareness of ethical issues in pain and palliative care, along with patient advocacy groups, put pressure on healthcare systems and professionals to address these concerns.Our aim is to review the ethics dilemmas concerning palliative care in ICU, artificial intelligence applications in pain therapy and palliative care, and the opioids epidemics. RECENT FINDINGS: In this focus review, we highlighted state of the art papers that were published in the last 18 months, on ethical issues in palliative care within the ICU, artificial intelligence trajectories, and how opioids epidemics has impacted pain management practices (see Visual Abstract). SUMMARY: Palliative care in the ICU should involve a multidisciplinary team, to mitigate patients suffering and futility. Providing spiritual support in the ICU is an important aspect of holistic patient care too.Increasingly sophisticated tools for diagnosing and treating pain, as those involving artificial intelligence, might favour disparities in access, cause informed consent problems, and surely, they need prudence and reproducibility.Pain clinicians worldwide continue to face the ethical dilemma of prescribing opioids for patients with chronic noncancer pain. Balancing the need for effective pain relief with the risk of opioid misuse, addiction, and overdose is a very controversial task.

The Role of Globularia alypum Explored Ex Vivo In Vitro on Human Colon Biopsies from Ulcerative Colitis Patients.

The existing literature indicates that Globularia alypum L. (GA) influences inflammation and oxidative stress modulation in rats and in vitro. The present study aims to investigate the effects of this plant in patients with ulcerative colitis (UC) and normal controls. In our experiments, we pretreated colon biopsies from 46 UC patients and normal controls with GA leaves aqueous extract (GAAE) used at two concentrations (50 and 100 µg/mL) for 3 h, followed by Lipopolysaccharides (from Escherichia coli) stimulation. We analyzed the effects on inflammation by studying the cyclo-oxygenase-2, the intercellular adhesion molecule-1, the nuclear factor kappa B, and p38 mitogen-activated protein kinase expression. Moreover, we assessed the levels of interleukin 6, the superoxide dismutase activity, and nitric oxide release in the supernatant of cultures. Our data showed that GAAE influences UC patients and normal controls for most studied markers and enzymes. These results acknowledge, with some scientific evidence, the traditional belief in the anti-inflammatory properties of GA and represent the first demonstration of its effect in a human in vitro model of inflammatory conditions.

KL-6 in ARDS and COVID-19 Patients.

The Acute Respiratory Distress Syndrome (ARDS) is a common, devastating clinical pattern characterized by life-threatening respiratory failure. In ARDS there is an uncontrolled inflammatory response that results in alveolar damage, with the exudation of protein-rich pulmonary-edema fluid in the alveolar space. Although severe COVID-19 lung failure (CARDS) often meets diagnostic criteria of traditional ARDS, additional features have been reported, such as delayed onset, binary pulmonary compliant states, and hypercoagulable profile. Increased levels of Krebs von den Lungen 6 (KL-6, also known as MUC1) have been reported in both ARDS and CARDS. KL-6 is a transmembrane protein expressed on the apical membrane of most mucosal epithelial cells and it plays a critical role in lining the airway lumen. Abnormalities in mucus production contribute to severe pulmonary complications and death from respiratory failure in patients with diseases such as cystic fibrosis, chronic obstructive pulmonary disease, and acute lung injury due to viral pathogens. Nevertheless, it is not clear what role KL-6 plays in ARDS/CARDS pathophysiology. KL-6 may exert anti-inflammatory effects through the intracellular segment, as proven in animal models of ARDS, while its extracellular segment will enter the blood circulation through the alveolar space when the alveolar epithelial cells are damaged. Therefore, changes in plasma KL-6 levels may be useful in ARDS and CARDS phenotyping, and KL-6 might guide future clinical trials in 'personalized medicine' settings.

An overview of the preclinical discovery and development of remdesivir for the treatment of coronavirus disease 2019 (COVID-19).

INTRODUCTION: Remdesivir (RDV) is an inhibitor of the viral RNA-dependent RNA polymerases that are active in some RNA viruses, including the Ebola virus and zoonotic coronaviruses. When severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent of the coronavirus disease 2019 (COVID-19), several investigations have assessed the potential activity of RDV in inhibiting viral replication, giving rise to hope for an effective treatment. AREAS COVERED: In this review, the authors describe the main investigations leading to the discovery of RDV and its subsequent development as an antiviral agent, focusing on the main clinical trials investigating its efficacy in terms of symptom resolution and mortality reduction. EXPERT OPINION: RDV is the most widely investigated antiviral drug for the treatment of COVID-19. This attention on RDV activity against SARS-CoV-2 is justified by promising in vitro studies, which demonstrated that RDV was able to suppress viral replication without significant toxicity. Such activity was confirmed by an investigation in an animal model and by the results of preliminary clinical investigations. Nevertheless, the efficacy of RDV in reducing mortality has not been clearly demonstrated.

Toxin-like peptides in plasma, urine and faecal samples from COVID-19 patients.

Background: SARS-CoV-2 that causes COVID-19 disease and led to the pandemic currently affecting the world has been broadly investigated. Different studies have been performed to understand the infection mechanism, and the involved human genes, transcripts and proteins. In parallel, numerous clinical extra-pulmonary manifestations co-occurring with COVID-19 disease have been reported and evidence of their severity and persistence is increasing. Whether these manifestations are linked to other disorders co-occurring with SARS-CoV-2 infection, is under discussion. In this work, we report the identification of toxin-like peptides in COVID-19 patients by application of the Liquid Chromatography Surface-Activated Chemical Ionization - Cloud Ion Mobility Mass Spectrometry.   Methods: Plasma, urine and faecal samples from COVID-19 patients and control individuals were analysed to study peptidomic toxins' profiles. Protein precipitation preparation procedure was used for plasma, to remove high molecular weight proteins and efficiently solubilize the peptide fraction; in the case of faeces and urine, direct peptide solubilization was employed.   Results: Toxin-like peptides, almost identical to toxic components of venoms from animals, like conotoxins, phospholipases, phosphodiesterases, zinc metal proteinases, and bradykinins, were identified in samples from COVID-19 patients, but not in control samples.  Conclusions: The presence of toxin-like peptides could potentially be connected to SARS-CoV-2 infection. Their presence suggests a possible association between COVID-19 disease and the release in the body of (oligo-)peptides almost identical to toxic components of venoms from animals. Their involvement in a large set of heterogeneous extra-pulmonary COVID-19 clinical manifestations, like neurological ones, cannot be excluded. Although the presence of each individual symptom is not selective of the disease, their combination might be related to COVID-19 by the coexistence of the panel of the here detected toxin-like peptides. The presence of these peptides opens new scenarios on the aetiology of the COVID-19 clinical symptoms observed up to now, including neurological manifestations.

Presepsin as a biomarker in perioperative medicine.

Presepsin is the soluble fragment of CD14, a multifunctional glycoprotein expressed on the surface of innate immune cells. In healthy individuals, presepsin is present in very low concentrations with reference values ranging from 60 to 382 pg/mL. Several studies have shown that presepsin is a valuable biomarker for sepsis diagnosis in adults. Only lately, presepsin has been evaluated for prediction and early detection of neonatal sepsis and septic shock. Elevated plasma presepsin concentration has also been reported in patients undergoing cardiac and non-cardiac surgery and it has further been evaluated as a potential independent predictor of perioperative cardiovascular complications and mortality. Combined cardiac and inflammatory biomarker evaluation may offer additive predictive information, but further investigations in large populations are required to determine presepsin diagnostic and prognostic value, in order to personalize therapy and reduce surgical patients' morbidity and mortality.

Myocardial injury after non-cardiac surgery: a perioperative affair?

Myocardial injury after non-cardiac surgery (MINS) is a rather new nosological entity and an unfortunately common perioperative complication. The diagnostic criteria for MINS, also indicated as isolated myocardial injury (IMI), are an elevated postoperative high sensitivity troponin T (hsTnT level ranging between 20 and 65 ng/L with an absolute change of at least 5 ng/L or hsTnT level >65 ng/L), in absence of symptoms and/or EKG findings suggestive of ischemia and without a non-ischemic etiology causing troponin elevation. MINS does not fulfill the universal definition of myocardial infarction even if it is related to ischemic causes and it is independently associated with 30-day postoperative mortality and complications. Nevertheless, mortality at 30 days in MINS patients has been calculated up to 10% and it increases exponentially as a function of peak postoperative troponin concentration. Physician and researchers should discriminate MINS from perioperative myocardial infarction and from not ischemic troponin increases. In the postoperative period, the possibility of missing the diagnosis of an acute coronary syndrome for the paucity of clinical symptoms or because physician failed to evaluate a postoperative EKG recording should always be considered. Physiopathology of MINS is not yet well defined: current hypotheses are surrogated from perioperative myocardial infarction studies. Up to now there are not specific treatments for MINS, even if antithrombotic therapy is under evaluation. Treatment decisions should be tailored to the individual case; potential benefits of troponin screening include a cardiology consultation and consequently, improved patients' information to promote lifestyle changes and enhanced therapy.

In vitro and ex vivo delivery of tailored siRNA-nanoliposomes for E2F1 silencing as a potential therapy for colorectal cancer.

Tailored developed nanoliposomes loaded with a siRNA against the transcription factor E2F1 (siE2F1), were produced and delivered to human colorectal adenocarcinoma cell lines and to intestinal human biopsies. siE2F1 loaded nanoliposomes were produced through a dedicated ultrasound assisted technique producing particles with about 40nm size (Small Unilamellar Vesicles, SUVs) and 100% siRNA encapsulation efficiency. Compared to other production methods, the one proposed here can easily produce particles in the nanometric scale by suitable ultrasonic duty cycle treatments. Furthermore, SUVs have a high degree of size homogeneity, a relevant feature for uniform delivery behaviour. siE2F1-loaded SUVs demonstrated a very low cytotoxicity in cells when compared to a commercial transfection agent. Moreover, SUVs loaded with siE2F1 were effective in the down regulation of the target in cultured colon carcinoma cells and in the consequent reduction of cell growth. Finally, a remarkable uptake and target silencing efficiencies were observed in cultured human biopsy of colonic mucosa. In conclusion, whereas further studies in more complex models are required, the siE2F1-SUVs generated have the potential to contribute to the development of novel effective inflammatory bowel diseases-associated colorectal cancer therapies for a future personalized medicine.

Cyclin D1 Gene Silencing by siRNA in Ex Vivo Human Tissue Cultures.

BACKGROUND: Short interfering RNAs (siRNAs) are double-stranded RNA molecules able to specifically targeting genes products responsible for human diseases. Cyclin D1 (CyD1) is a cell cycleregulatory molecule, up-regulated at sites of inflammation in several tissues. CyD1 is a very interesting potential target in lung and colon inflammatory diseases. OBJECTIVE: The aim of this paper was testing CyD1 expression in human lung and colon tissues after the application of an inflammatory stimulus, and verifying its gene silencing by using siRNA for CyD1 (siCyD1). METHOD: Colon and pulmonary biopsies were treated with siCyD1 by using two different transfection carriers: a) invivofectamine and b) ad hoc produced nanoliposomes. After 24 hours of incubation with nanoliposomes encapsulating siRNA or invivofectamine-CyD1siRNA, in presence or absence of ECLPS, we analysed the protein expression of CyD1 through Western-Blotting. RESULTS: After EC-LPS treatment, in both colon and pulmonary biopsies, an overexpression of CyD1was found (about 64% and 40% respectively). Invivofectamine-CyD1 siRNA reduced the expression of CyD1 approximately by 46% compared to the basal condition, and by around 65% compared to EC-LPS treated colon samples. In lung, following in vivo fectamine siRNA silencing in the presence of EC-LPS, no reduction was observed. Ad hoc nanoliposomes were able to enter colon and lung tissues, but CyD1 silencing was reported in 2 colon samples out of 4 and no efficacy was demonstrated in the only lung sample we studied. CONCLUSION: The silencing of Cyclin D1 expression in vitro "organ culture" model is possible. Our preliminary results encourage further investigations, using different siRNA concentrations delivered by nanoliposomes.

siRNA Delivery for Control of Cyclin D1 and E2F1 Expression in Crohn's Disease.

Evidence in inflammatory bowel diseases (IBD) supports a connection between inflammation and cancer due to the alteration of the cell cycle with loss of control at the G1/S checkpoint. In this study, we analyze the expression and modulation of CyD1 and E2F1 in colon explants from Crohn's disease (CD) patients. We used ex vivo culture of colon explants from 4 CD patients and 2 healthy controls, stimulated with lipopolysaccharide from Escherichia Coli (EC-LPS). Commercial siRNAs for CyD1 and E2F1 inhibition were encapsulated in Invivofectamine® and in purposely produced nanoliposomal vectors to silencing CyD1 and E2F1 expression. Western blot analysis was used to investigate the effect of siRNA on CyD1, E2F1 and cyclooxygenase 2 (COX-2) expression. In CD patients colon explants, CyD1 and E2F1 increased after the inflammatory stimulus but siRNA silencing attenuated their expression and controlled the COX-2 expression too. These data represent a prelimiary exploration of in vitro siRNA use.

siRNA Delivery for Control of Cyclin D1 and E2F1 Expression in Crohn's Disease.

Evidence in inflammatory bowel diseases (IBD) supports a connection between inflammation and cancer due to the alteration of the cell cycle with loss of control at the G1/S checkpoint. In this study, we analyze the expression and modulation of CyD1 and E2F1 in colon explants from Crohn's disease (CD) patients. We used ex vivo culture of colon explants from 4 CD patients and 2 healthy controls, stimulated with lipopolysaccharide from Escherichia Coli (EC-LPS). Commercial siRNAs for CyD1 and E2F1 inhibition were encapsulated in Invivofectamine® and in purposely produced nanoliposomal vectors to silencing CyD1 and E2F1 expression. Western blot analysis was used to investigate the effect of siRNA on CyD1, E2F1 and cyclooxygenase 2 (COX-2) expression. In CD patients colon explants, CyD1 and E2F1 increased after the inflammatory stimulus but siRNA silencing attenuated their expression and controlled the COX-2 expression too. These data represent a prelimiary exploration of in vitro siRNA use.

The use of sugammadex for bariatric surgery: analysis of recovery time from neuromuscular blockade and possible economic impact.

BACKGROUND: Neuromuscular block (NMB) monitoring and use of reversal agents accelerate the recovery time and improve the workflow in the operating room. We aimed to compare recovery times after sugammadex or neostigmine administration, and estimate the time spent in operating theater and the possible economic impact of a faster recovery, in morbidly obese patients undergoing bariatric surgery. METHODS: We conducted a retrospective study that analyzed data from records of morbidly obese patients (body mass index >40 kg/m(2)) undergoing elective laparoscopic bariatric surgery in which sugammadex or neostigmine were used to reverse NMB. Patients were divided in two groups: group 1 (sugammadex group [SUG]) received rocuronium and sugammadex for reversal and group 2 (neostigmine group [NEO]) received either rocuronium or cisatracurium and neostigmine. Data are presented as mean (standard deviation). RESULTS: Compared with NEO, SUG group showed shorter times to achieve train-of-four ratio of 0.9 (P<0.05) and an Aldrete score of 10 (P<0.05), a higher cost (€146.7 vs €3.6 [P<0.05]), plus a remarkable less duration of operating theater occupancy (P<0.05). Sugammadex cost accounted for 2.58% of the total cost per surgery, while neostigmine cost accounted for 0.06%. Total time saved in SUG group was 19.4 hours, which could be used to perform 12 extra laparoscopic sleeve gastrectomies. CONCLUSION: Reversal from NMB was significantly faster with sugammadex than with neostigmine. Although sugammadex was substantially more expensive, duration of operating theater occupancy was reduced with potentially workflow increase or personnel reduced cost.

Update on transfusion solutions during surgery: review of hydroxyethyl starches 130/0.4.

OBJECTIVES: Restoration of circulation is crucial in the surgical patient management. Colloids and crystalloids are widely used for blood volume therapy. We reviewed recent trials to evaluate efficacy and safety of hydroxyethyl starch (HES) 130/0.4 during surgery. MATERIAL AND METHODS: A subjective, not systematic, review of literature was performed. Papers were searched to answer questions about efficacy of HES, its impact on coagulation and inflammation and its effects on pulmonary mechanics and renal function. CONCLUSIONS: HES 130/0.4 is effective for volume therapy and is less expensive than human albumin. Its effects on coagulation and renal function are manageable; it may ameliorate pulmonary permeability and reduce inflammation.