Endoscopic or combined management of post-surgical biliary leaks: a two-center recent experience.

BACKGROUND AND AIMS: Post-surgical biliary leaks (PSBL) are one of the most prevalent and significant adverse events emerging after liver or biliary tract surgeries. Endoscopic retrograde cholangiopancreatography (ERCP) alone or combined with another approach (Rendez Vous) as treatment of PSBL obtains optimal outcomes due to the possibility of modifying the resistances in the biliary tree. METHODS: A retrospective double-center study was conducted in two tertiary centers. Consecutive patients who underwent at least one attempt of PSBL correction by ERCP or Rendez Vous procedure between January 2018 and August 2023 were included. The primary outcome was overall endoscopic clinical success. In contrast, the secondary outcomes were hospital stay exceeding five days and endoscopic clinical success with the first endoscopic procedure at the tertiary center. Both univariate and multivariate analyses were used to assess outcomes. RESULTS: 65 patients were included. Patients with one or multiple) leaks had more possibility to achieve the endoscopic clinical success compared to those affected by the association of leaks and stricture (96% vs 67%, p value 0.005). Leaks occurring in the main biliary duct had less probability (67%) to achieve the overall endoscopic clinical success compared to those in the end-to-end anastomosis (90%), in the resection plane or biliary stump (96%) or first or secondary order biliary branches (100%, p value 0.038). A leak-bridging stent positioning had more probability of achieving the endoscopic clinical success than a not leak-bridging stent (91% vs 53%, p value 0.005). CONCLUSIONS: ERCP and Rendez Vous procedures are safe and effective for treating PSBL, regardless of the type of preceding surgery, even if technical or clinical success was not achieved on the first attempt. A stent should be placed, if feasible, leak-bridging to enhance treatment efficacy.

Risk of appendiceal neoplasm in patients with appendix disorders.

The most common appendicular disease is acute appendicitis, with a lifetime risk of 7%-8%. Complicated cases, which can occur in 2%-7% of patients, can significantly impact the severity of the condition and may require different management approaches. Nonoperative management with possible delayed appendectomy has been suggested for selected patients, however, there is a non-negligible risk of missing an underlying malignancy, which is reported to be as high as 11%. Diagnostic work-up is paramount to achieve optimal treatment with good results.

Current therapeutic overview and future perspectives regarding the treatment of psoriasis.

Psoriasis is a chronic inflammatory skin disease affecting millions of people worldwide, characterized by rapid proliferation of keratinocytes, immune cell infiltration, and systemic inflammation. Over time, treatment strategies have evolved significantly from traditional topical therapies and phototherapy to advanced systemic options such as biologics and, more recently, oral small molecule drugs. This review aims to provide an in-depth examination of current psoriasis therapies, with a focus on biologics, oral small molecules, and new and emerging treatments. Several classes of biologic therapies have received regulatory approval for psoriasis, including inhibitors of TNF-α, IL-12/23, IL-17, and IL-23. Biologics have transformed psoriasis care, offering improved disease management and quality of life for patients, with generally favorable safety profiles. However, challenges such as high cost, potential immunogenicity and complexity of administration have sparked interest in alternative treatment options. Oral small molecules, particularly Janus kinase (JAK) inhibitors, have gained attention for their efficacy and ease of use, being orally administered drugs. These drugs mark a shift in therapeutic paradigms by providing an oral option that precisely targets specific signaling pathways. In addition to existing therapies, this review also highlights emerging treatments that could shape the future of psoriasis care, including new small-molecule inhibitors. Early clinical trials suggest that these agents could improve treatment outcomes for psoriasis patients. Current research is increasingly focused on understanding disease recurrence, particularly the influence of tissue-resident memory T cells (TRMs). Avoiding the proliferation of these cells may be crucial in attenuating recurrence. In particular, interleukin-23 (IL-23), produced by CD301b+ cells, has been linked to stimulation of TRM cell proliferation in the skin. This finding highlights that IL-23 inhibitors and treatments targeting CD301b+ cells are promising strategies for maintaining remission and preventing relapse. In summary, the landscape of psoriasis treatments is advancing rapidly, with an increasing focus on personalized, patient-specific therapies. Research is expected to continue to refine and improve therapeutic approaches for this complex disease.

Analysis of prescriptive monitoring regarding the current therapeutic landscape of rheumatoid arthritis: the experience of an Italian local health authority.

INTRODUCTION: Rheumatoid Arthritis (RA) is among the most prevalent chronic inflammatory diseases affecting millions of people with a significant expenditure of resources by National Healthcare Systems. This study aimed to analyze all available treatments exclusively for RA to highlight the costs of each treatment type and raise awareness of the use of biosimilar drugs. METHODS: In an Italian healthcare authority, all prescriptions made for the diagnosis of RA were extracted to verify consumption expressed in Defined Daily Dose (DDD) and the expenditure incurred expressed in euros. Consequently, a grouping into three major drug categories has been performed: anti - tumor necrosis factor alpha agents (TNFα), other injectable formulations, and novel oral formulations. RESULTS: Prescriptions for the second half-year 2022 and 2023 have been analyzed, with a total cost of almost 7 million euros in the sample considered. All pharmaceutical categories showed an increase in consumption, but only anti- TNFα recorded a decrease in costs from 25% in 2022 to 22% in 2023, thanks to the lower cost of the biosimilar drug. CONCLUSION: The costs of RA may represent a significant spending commitment for central governments. As a result, actions are needed to encourage the preferential use of biosimilar drugs.

Laparoendoscopic extraperitoneal surgical techniques for ventral hernias and diastasis recti repair: a systematic review.

PURPOSE: this systematic review aims to classify and summarize the characteristics and outcomes of the different laparoendoscopic extraperitoneal approaches for the repair of ventral hernias and diastasis recti described in the last 10 years. METHODS: a literature search was performed by two reviewers in December 2023 including articles from January 2013, 01 to December 2023, 15. The techniques were selected according to the surgical access site (anterior or posterior to the rectus sheath), the access type (laparoendoscopic, single incision laparoscopic, mini or less open), the main space used to repair the defect (subcutaneous or retromuscular) and the mesh place (onlay, sublay-retromuscular or sublay-preperitoneal) and classified as anterior or posterior approaches. RESULTS: the literature search retrieved 1755 results and 27 articles were included in the study. The studies included 1874 patients, the mean age ranged from 37.8 to 60.2 years. The access site was anterior in 16 cases and posterior in 11 cases. The mesh was positioned onlay in 13 cases and sublay in 13 cases, with only one study using no mesh. Complications were: seroma, ranging from 0.8 to 81%, followed by skin complications (leak, ischemia, necrosis) from 0.8 to 6.4%, surgical site infections and bleeding. Recurrences ranged from 0% to 12,5%, with a mean follow-up from 1 to 24 months. CONCLUSION: this systematic review confirms the presence of several new minimally invasive extraperitoneal techniques for the repair of abdominal wall defects, with different advantages and disadvantages. Further studies, with more extensive follow-up data and wider patient groups, are necessary to define specific indications for each technique.

Therapeutic Advances in Psoriasis: From Biologics to Emerging Oral Small Molecules.

Psoriasis is a persistent, inflammatory condition affecting millions globally, marked by excessive keratinocyte proliferation, immune cell infiltration, and widespread inflammation. Over the years, therapeutic approaches have developed significantly, shifting from conventional topical treatments and phototherapy to more sophisticated systemic interventions such as biologics and, recently, oral small-molecule drugs. This review seeks to present a comprehensive investigation of the existing psoriasis treatment options, focusing on biologic agents, oral small molecules, and emerging treatments. Several categories of biologic treatments have received regulatory approval for psoriasis, including TNF-α, IL-17, IL-12/23, and IL-23 inhibitors. Biologics have revolutionized the treatment of psoriasis. These targeted therapies offer significant improvement in disease control and quality of life, with acceptable safety profiles. However, limitations such as cost, potential immunogenicity, and administration challenges have driven the exploration of alternative treatment modalities. Oral small molecules, particularly inhibitors of Janus kinase (JAK), have emerged as options due to their convenience and efficacy. These agents represent a paradigm shift in the management of the condition, offering oral administration and targeted action on specific signaling pathways. In addition to existing therapies, the review explores emerging treatments that hold promise for the future of psoriasis care. These include innovative small-molecule inhibitors. Early-stage clinical trials suggest these agents may enhance outcomes for psoriasis patients. In conclusion, the therapeutic landscape of psoriasis is rapidly evolving, emphasizing targeted, patient-centered treatments. Ongoing research and development are expected to lead to more personalized and effective management strategies for this complex condition.

Chronobiological variation in takotsubo syndrome: an updated systematic review and meta-analysis.

Takotsubo syndrome (TTS) might exhibit particular chronobiological patterns in its onset, characterized by variations according to time of the day, day of the week, and month of the year. The aim of this study was to fully explore the temporal patterns (circadian, weekly and seasonal) in the onset of TTS. A systematic review and meta-analysis of literature were conducted for studies (2006-2024) reporting the temporal patterns (circadian, weekly and/or seasonal) in the onset of TTS. Among the 4257 studies retrieved, 20 (including 64,567 subjects) fulfilled all eligibility criteria. Data were aggregated used random effects model as pooled risk ratio and the attributable risk (AR). The proportion analysis (including 8 studies; n=853) showed a decreasing pattern of the pooled rates of TTS shifting from the morning to the night (pooled TTS rates: 34.0%; 32.1%; 21.7%; 12.7% in the morning, afternoon, evening and night, respectively). The same pattern was observed stratifying by type of preceding stressful factor or event, considering physical stressors (pooled rates in the morning and night: 37.6% and 9.8%, respectively), and also in case no event could be identified. The pooled rates of TTS onset peaked on Monday and Tuesday (17.3% and 18.4% respectively), then declined during the week, reaching the lowest rates on Friday and Saturday (10.6% and 10.8%, respectively), with no sex differences. TTS onset reached the highest values on summer, and the lowest in winter (27.9% versus 21.7% in summer and winter, respectively). The TTS morning peak based analyses (∼33% of all the registered events) account for a RR of 1.46 (95% CI: 1.38-1.54), the week-based for a RR of 1.26 (1.16-1.35), the season-based for a RR of 1.04 (1.04-1.05). TTS onset exhibits specific chronobiological patterns, characterized by a peak during the morning hours, and on Monday and Tuesday. Differing from other cardiovascular emergencies TTS was more frequent during summer. Further studies are needed to fully understand the underlying pathophysiological mechanisms in order to tailor relative management and preventive strategies.

Upper endoscopy in elderly patients: a multicentre, cross-sectional study.

BACKGROUND: Both macroscopic and histological lesions are frequently detected at upper endoscopy in elderly patients. We assessed the prevalence of main endoscopic and histological alterations in elderly (> 65 years old) patients. METHODS: In this study, clinical, endoscopic and histological features of patients referred for upper endoscopy in clinical practice were retrieved. Both univariate and multivariate analyses were executed. Comparisons with previous data were performed. RESULTS: A total of 1336 underwent upper endoscopy in the 28 participating centres. At endoscopy, at least one macroscopic lesion was present in overall 420 (31.4%) patients. Erosive gastritis (13.3%) and erosive oesophagitis (9.8%) were the most prevalent lesions, whilst Barrett's oesophagus, gastric ulcer, duodenal ulcer and erosive duodenitis were observed in 1.8%, 2%, 1.4% and 3.1% patients, respectively. Nine (0.6%) cases of oesophageal, 25 (1.8%) gastric and 2 (0.1%) duodenal neoplasia were detected. At histology, Helicobacter pylori infection was diagnosed in 99 (15.9%) patients, and extensive precancerous lesions on gastric mucosa were detected in 80 (14.5%) patients. Endoscopic lesions were more frequent in males, at first endoscopy and in those with alarm symptoms and lower during PPI therapy. At multivariate analysis, PPI therapy significantly reduced the probability of finding endoscopic lesions (OR: 0.68, 95% CI: 0.46-0.99; P = 0.04), whilst neoplastic lesions were associated with presence of alarm symptoms (OR: 1.5, 95% CI: 1.1-2.1; P = 0.005). CONCLUSIONS: We found that the frequency of erosive and neoplastic lesions remained high in elderly patients, whilst the prevalence of both H. pylori infection and peptic ulcer was decreased.

High Stability and Low Power Nanometric Bio-Objects Trapping through Dielectric-Plasmonic Hybrid Nanobowtie.

Micro and nano-scale manipulation of living matter is crucial in biomedical applications for diagnostics and pharmaceuticals, facilitating disease study, drug assessment, and biomarker identification. Despite advancements, trapping biological nanoparticles remains challenging. Nanotweezer-based strategies, including dielectric and plasmonic configurations, show promise due to their efficiency and stability, minimizing damage without direct contact. Our study uniquely proposes an inverted hybrid dielectric-plasmonic nanobowtie designed to overcome the primary limitations of existing dielectric-plasmonic systems, such as high costs and manufacturing complexity. This novel configuration offers significant advantages for the stable and long-term trapping of biological objects, including strong energy confinement with reduced thermal effects. The metal's efficient light reflection capability results in a significant increase in energy field confinement (EC) within the trapping site, achieving an enhancement of over 90% compared to the value obtained with the dielectric nanobowtie. Numerical simulations confirm the successful trapping of 100 nm viruses, demonstrating a trapping stability greater than 10 and a stiffness of 2.203 fN/nm. This configuration ensures optical forces of approximately 2.96 fN with an input power density of 10 mW/µm2 while preserving the temperature, chemical-biological properties, and shape of the biological sample.

The challenge of antimicrobial resistance (AMR): current status and future prospects.

Antimicrobial resistance (AMR) represents a critical global threat, compromising the effectiveness of antibacterial drugs as bacteria adapt and survive exposure to many classes of these drugs. This phenomenon is primarily fueled by the widespread overuse and misuse of antibacterial drugs, exerting selective pressure on bacteria and promoting the emergence of multi-resistant strains. AMR poses a top-priority challenge to public health due to its widespread epidemiological and economic implications, exacerbated not only by the diminishing effectiveness of currently available antimicrobial agents but also by the limited development of genuinely effective new molecules. In addressing this issue, our research aimed to examine the scientific literature narrating the Italian situation in the common European context of combating AMR. We sought to delineate the current state of AMR and explore future prospects through an analysis of strategies to counter antibacterial drug resistance. Adopting the "One Health" model, our objective was to comprehensively engage diverse sectors, integrate various disciplines, and propose programs, policies, and regulations. This narrative review, based on PubMed research related to antibiotic resistance, emphasizes the urgent need for a coordinated and proactive approach at both national and European levels to mitigate the impact of AMR and pave the way for effective strategies to counter this global health challenge.

Application of the 2016 ASE-EACVI Criteria for the Assessment of Diastolic Function in Arterial Hypertension.

INTRODUCTION: No data are available on the diagnostic algorithms recommended by guidelines for the assessment of diastolic dysfunction (DD) in patients with arterial hypertension. AIM: To fill this gap, we evaluated diastolic function in hypertensive patients with and without LVH matched with healthy subjects by applying 2016 American Society of Echocardiography-European Association of Cardiovascular Imaging Guidelines for the evaluation of LV diastolic function. METHODS: 717 healthy and hypertensives with normal LV ejection fraction and with and without LV hypertrophy (LVH), matched 1:1:1 from two prospective registries, represented the study population. RESULTS: By applying algorithm A, indeterminate pattern was found in 0.4% of healthy, in 6.3% of hypertensives without LVH, and in 21% with LVH (overall p < 0.05 vs. healthy). DD was absent in healthy, however present in 2 and 8% of hypertensives without and with LVH (p = 0.06 and p = 0.001 vs. healthy, respectively). By applying algorithm B, no cases of indeterminate pattern were found. DD was observed in 2.9% of healthy, 7 and 10.5% of hypertensives without and with LVH (p < 0.05 vs. healthy). CONCLUSIONS: The use of algorithm A should be limited only to truly normal subjects, whereas algorithm B should be applied to all patients with hypertension, even without comorbidities and irrespective of LVH.

The use of new antibacterial drugs against infections caused by multidrug-resistant Gram-negative bacteria: an Italian real-world evidence study in a Lombardy hospital.

Infections caused by multidrug-resistant (MDR) bacteria are typically associated with high morbidity and mortality, especially in vulnerable individuals such as patients with prolonged hospitalizations, immunocompromised individuals, and the elderly. This study aimed to provide post-marketing surveillance results concerning the prevalence of antibiotic resistance against Gram-negative bacteria through the collaboration of a multidisciplinary team. Patients involved have been treated with new antibacterial drugs, in particular ceftazidime/avibactam (C/A), meropenem/vaborbactam (M/V), cefiderocol, and ceftolozane/tazobactam (C/T). The most resistant bacterial species were Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. Italian Drug Agency (AIFA) monitoring records for inpatients have been collected and analyzed, assessing the characteristics of the patients involved. Adverse drug reactions (ADRs) and drugs involved have been reported using a descriptive analytical approach. All data have been collected retrospectively from patient's medical records and entered into an electronic case report form (CRF). Among the 104 treated patients, Klebsiella spp. accounted for 50.1% of infections, Pseudomonas aeruginosa for 32.7%, Acinetobacter baumannii for 3%, and other bacterial species for 1.92% configuring polymicrobial infections. Regarding treatment outcomes, healing was achieved in 61 (58.6%) patients, 23 (22.1%) patients died, 8 (7.7%) patients discontinued empirical therapy, and 3 (2.9%) patients were lost to follow-up. Despite the introduction of new antibacterial drugs active against Gram-negative bacteria is improving the clinical scenario, it is crucial that the use of new antibacterial drugs be implemented by appropriate antimicrobial stewardship, surveillance programs, and monitoring efforts to prevent further spread of resistance. This study showed that the new antibiotics have good efficacy against MDR bacteria and cause negligible side effects.

Innovative Drug Modalities for the Treatment of Advanced Prostate Cancer.

Prostate cancer, a prevalent malignancy affecting the prostate gland, is a significant global health concern. Androgen-deprivation therapy (ADT) has proven effective in controlling advanced disease, with over 50% of patients surviving at the 10-year mark. However, a diverse spectrum of responses exists, and resistance to ADT may emerge over time. This underscores the need to explore innovative treatment strategies for effectively managing prostate cancer progression. Ongoing research endeavors persist in unraveling the complexity of prostate cancer and fostering the development of biologic and innovative approaches, including immunotherapies and targeted therapies. This review aims to provide a valuable synthesis of the dynamic landscape of emerging drug modalities in this context. Interestingly, the complexities posed by prostate cancer not only present a formidable challenge but also serve as a model and an opportunity for translational research and innovative therapies in the field of oncology.

Covid-19 psychological distress: Analysis of antipsychotic drugs' use in an Italian population sample.

BACKGROUND: The current pandemic, in addition to putting a strain on healthcare systems and global economies, has exacerbated psychiatric problems and undermined the mental health of many individuals. In an Italian cohort, this phenomenon has been assessed through a retrospective study aimed at evaluating the consumption and costs of antipsychotic drugs between 2020 and 2022. METHODS: All dispensations made in local pharmacies accessible to the public have been extracted from a database called 'Sistema Tessera Sanitaria', which covers a population of approximately one million people residents in the ASL Napoli 3 Sud. Consumption data expressed in defined daily dose (DDD) and expenditure data expressed in Euro have been extrapolated. RESULTS: The results in the years 2020-2021 were relatively consistent, with consumption and expenditure decreasing slightly from 2020 to 2021. In 2022, the results showed a decrease in consumption and expenditure (2,706,951.07 DDD and €1,700,897.47) representing the reduced accessibility of patients to the healthcare facilities due to the pandemic. However, it should be noted that the antipsychotic drug aripiprazole showed an upward trend, registering an increase in consumption. CONCLUSION: Despite expectations of increased consumption of antipsychotic medications, real-world evidence indicated a different phenomenon, with the pandemic seemingly not affecting the consumption of these drugs. The difficulty in accessing care and medical appointments has probably influenced this data, masking the therapeutic needs of citizens. It will be necessary to assess in the coming years, as normal clinical activity resumes, whether there will be a growing consumption of these medications, which represent one of the main expenditure categories for the National Healthcare System.

Antimicrobial Resistance in Gonorrhea.

Antimicrobial resistance is a global public health emergency. The World Health Organization recently highlighted the growing number of new sexually transmitted infections such as gonorrhea, syphilis, and Chlamydia, which are resistant to common antibiotics. The phenomenon is also on the rise due to increasing intercontinental travel. Emerging antibiotic-resistant strains of gonorrhea are particularly associated with international spread from Southeast Asian travelers. Infection with Neisseria gonorrhoeae can cause a wide spectrum of associated diseases such as dermatitis, arthritis and septic arthritis, and pelvic inflammatory disease, and can even lead to serious health consequences for the individual. Natural infection confers no immunity, and vaccination is not available currently, although in several countries, it has been reported that the antimeningococcal vaccine may protect against gonorrhea. Implementing all necessary preventive measures is crucial, as well as appropriate and timely diagnostic methods and effective antimicrobial therapeutic treatments in the correct modalities to avoid the increase of forms of gonorrhea that are resistant to common antibiotics and difficult to eradicate.

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.