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Abstract Background Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann’s procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P

Abstract Psychological characterization of patients affected by Inflammatory Bowel Disease (IBD) focuses on comorbidity with psychiatric disorders, somatization or alexithymia. Whereas IBD patients had higher risk of stable anxiety and depression for many years after the diagnosis of the disease, there is a lack of studies reporting a comprehensive psychosomatic assessment addressing factors of disease vulnerability, also in the long-term. The objective of this investigation is to fill this gap in the current literature. The aims were thus to assess: a) changes between baseline and a 4-year follow-up in psychiatric diagnoses (SCID), psychosomatic syndromes (DCPR), psychological well-being (PWB-I), lifestyle, gastrointestinal symptoms related to IBD and Irritable Bowel Syndrome (IBS)-like symptoms b) stability of psychiatric and psychosomatic syndromes at 4-year follow-up. A total of 111 IBD outpatients were enrolled; 59.5% of them participated at the follow-up. A comprehensive assessment, including both interviews and self-report questionnaires, was provided at baseline and follow-up. Results showed increased psychiatric diagnoses, physical activity, consumption of vegetables and IBS-like symptoms at follow-up. Additionally, whereas psychiatric diagnoses were no longer present and new psychopathological pictures ensued at follow-up, more than half of the sample maintained psychosomatic syndromes (particularly allostatic overload, type A behavior, demoralization) from baseline to follow-up. Long-term presence/persistence of such psychosocial burden indicates the need for integrating a comprehensive psychosomatic evaluation beyond traditional psychiatric nosography in IBD patients. Moreover, since psychosomatic syndromes represent vulnerability factors of diseases, further studies should target subgroups of patients presenting with persistent psychosomatic syndromes and worse course of the disease.

Background/Aim: Prevalence of gastroduodenal endoscopic and histological lesions may modify over time due to different factors. We assessed both macroscopic and histological lesions currently detected at upper endoscopy performed in routine practice. Patients and Methods: Clinical, endoscopic, and histological data of consecutive adult patients referred for upper endoscopy in the 28 participating centres were analysed. Only patients who underwent the first endoscopic examination were considered. Prevalence of erosive/ulcerative lesions, cancers and extensive precancerous lesions in the stomach, and Helicobacter pylori infection was computed. Results: A total of 1,431 patients underwent endoscopy for gastro-oesophageal reflux symptoms (31.5%), dyspepsia (29.4%), or alarm symptoms (18.5%). Erosive oesophagitis or Barrett’s oesophagus was detected in 210 (14.7%) cases, peptic ulcer in 49 (3.4%), and a neoplastic lesion in 17 (1.2%). H. pylori was present in 201 (22.6%) cases, and extensive precancerous lesions on gastric mucosa in 46 (5.6%) patients. Gastric lesions were more prevalent in patients aged ≥50 years (26% vs. 18%; p = 0.001), and peptic ulcers were more frequently detected in patients with H. pylori (9.4% vs. 2.3%; p = 0.001) and in males (5.8% vs. 1.6%; p = 0.001), while neoplastic lesions in patients with alarm symptoms (3.8% vs. 0.6%; p = 0.001). Conclusions: The overall endoscopic lesions were more prevalent in patients aged ≥50 years, peptic ulcer and erosions were more frequent in H. pylori-infected patients, and extensive gastric precancerous lesions were present in less than 6% of cases.

Background: Antimicrobial resistance (AMR) has emerged as a significant challenge to public health, posing a considerable threat to effective disease management on a global scale. The increasing incidence of infections caused by resistant bacteria has led to heightened morbidity and mortality rates, particularly among vulnerable populations. Main text: This review analyzes current strategies and health policies adopted in the European Union (EU) and Italy to manage AMR, presenting an in-depth examination of approaches for containment and mitigation. Factors such as excessive prescriptions, self-medication, and the misuse of antibiotics in livestock contribute to the selection and spread of resistant strains. Furthermore, this review provides a detailed overview of resistance mechanisms, including enzymatic inactivation, reduced permeability, efflux pump activity, and target site protection, with specific examples provided. The review underscores the urgent need to develop new antibiotics and implement diagnostic testing to ensure targeted prescriptions and effectively combat resistant infections. Current estimates indicate that AMR-related infections cause over 60,000 deaths annually in Europe and the United States, with projections suggesting a potential rise to 10 million deaths per year by 2050 if current trends are not reversed. The review also examines existing public health policies in Europe and Italy, focusing on national and regional strategies to combat AMR. These include promoting responsible antibiotic use, improving surveillance systems, and encouraging research and development of new therapeutic options. Conclusions: Finally, the review presents short- and long-term perspectives from the authors, suggesting actionable steps for policymakers and healthcare providers. Ultimately, a coordinated and multidisciplinary approach involving healthcare professionals, policymakers, and the public is essential to mitigate the impact of AMR and ensure the effectiveness of antibiotics for future generations.

We investigated the design and characterization of a Lab-On-a-Chip (LoC) cell detection system primarily designed to support immunotherapy in cancer treatment. Immunotherapy uses Chimeric Antigen Receptors (CARs) and T Cell Receptors (TCRs) to fight cancer, engineering the response of the immune system. In recent years, it has emerged as a promising strategy for personalized cancer treatment. However, it requires bioreactor-based cell culture expansion and manual quality control (QC) of the modified cells, which is time-consuming, labour-intensive, and prone to errors. The miniaturized LoC device for automated QC demonstrated here is simple, has a low cost, and is reliable. Its final target is to become one of the building blocks of an LoC for immunotherapy, which would take the place of present labs and manual procedures to the benefit of throughput and affordability. The core of the system is a commercial, on-chip-integrated capacitive sensor managed by a microcontroller capable of sensing cells as accurately measured charge variations. The hardware is based on standardized components, which makes it suitable for mass manufacturing. Moreover, unlike in other cell detection solutions, no external AC source is required. The device has been characterized with a cell line model selectively labelled with gold nanoparticles to simulate its future use in bioreactors in which labelling can apply to successfully engineered CAR-T-cells. Experiments were run both in the air—free drop with no microfluidics—and in the channel, where the fluid volume was considerably lower than in the drop. The device showed good sensitivity even with a low number of cells—around 120, compared with the 107 to 108 needed per kilogram of body weight—which is desirable for a good outcome of the expansion process. Since cell detection is needed in several contexts other than immunotherapy, the usefulness of this LoC goes potentially beyond the scope considered here.

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.

Abstract Background The creation of an ileostomy or colostomy is a common surgical event, both in elective and in emergency context. The main aim of stoma creation is to prevent postoperative complications, such as the anastomotic leak. However, stoma-related complications can also occur and their morbidity is not negligible, with a rate from 20 to 70%. Most stomal complications are managed conservatively, but, when this approach is not resolutive, surgical treatment becomes necessary. The aim of this mapping review is to get a comprehensive overview on the incidence, the risk factors, and the management of the main early and late ostomy complications: stoma necrosis, mucocutaneous separation, stoma retraction, stoma prolapse, parastomal hernia, stoma stenosis, and stoma bleeding. Material and methods A complete literature research in principal databases (PUBMED, EMBASE, SCOPUS and COCHRANE) was performed by Multidisciplinary Italian Study group for STOmas (MISSTO) for each topic, with no language restriction and limited to the years 2011–2021. An international expert panel, from MISSTO and World Society of Emergency Surgery (WSES), subsequently reviewed the different issues, endorsed the project, and approved the final manuscript. Conclusion Stoma-related complications are common and require a step-up management, from conservative stoma care to surgical stoma revision. A study of literature evidence in clinical practice for stoma creation and an improved management of stoma-related complications could significantly increase the quality of life of patients with ostomy. Solid evidence from the literature about the correct management is lacking, and an international consensus is needed to draw up new guidelines on this subject.

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.

Cholangiocarcinoma (CCA) is a rare malignancy originating from the biliary tree and is anatomically categorized as intrahepatic (iCCA), perihilar, and extrahepatic or distal. iCCA, the second most prevalent hepatobiliary cancer following hepatocellular carcinoma (HCC), constitutes 5–20 % of all liver malignancies, with an increasing incidence. The challenging nature of iCCA, combined with nonspecific symptoms, often leads to late diagnoses, resulting in unfavorable outcomes. The advanced phase of this neoplasm is difficult to treat with dismal results. Early diagnosis could significantly reduce mortality attributed to iCCA but remains an elusive goal. The identification of biomarkers specific to iCCA and their translation into clinical practice could facilitate diagnosis, monitor therapy response, and potentially reveal novel interventions and personalized medicine. In this review, we present the current landscape of biomarkers in each of these contexts. In addition to CA19.9, a widely recognized biomarker for iCCA, others such as A1BG, CYFRA 21–1, FAM19A5, MMP-7, RBAK, SSP411, TuM2-PK, WFA, etc., as well as circulating tumor DNA, RNA, cells, and exosomes, are under investigation. Advancing our knowledge and monitoring of biomarkers may enable us to improve diagnosis, prognostication, and apply treatments dynamically and in a more personalized manner.

Pancreatic cystic lesions are often asymptomatic, incidentally detected and include a range of entities with varying degrees of concern for malignancy. Among these, intraductal papillary mucinous neoplasms (IPMN) are considered premalignant pancreatic lesions, with a broad pathological spectrum ranging from lesions without dysplasia, which can be managed conservatively, to malignant lesions that require surgical resection. The increasing use of CT and MRI has led to increased recognition of this entity incidentally, with branch-duct IPMN representing the most common subtype and the most challenging lesions in terms of patient management. The main imaging modality involved in diagnosis and surveillance of IPMN is MRI. Radiologists play an important role in the management of patients with IPMN, including lesion detection, characterization, follow-up and prognostication, allowing early MRI identification of features that are concerning for malignancy. The main aim of this pictorial review is to illustrate MRI features of IPMN and to discuss risk stratification scores based on different guidelines, with a main focus on branch-duct IPMN. The secondary aims include the presentation of common and uncommon imaging evolution of BD-IPMN as well as the discussion on current controversies on the appropriate management of IPMN.

A 70-year-old man was admitted to the Emergency Department (ED) for marked asthenia and severe anemia. In addition, a high level of lipase was found. During hospitalization, a locally advanced gastric cancer was diagnosed, with endoscopic evidence of a large polyploid formation originating under the cardias that occupied most of the gastric lumen. A total body CT scan was performed before surgery; the tumor affected the posterior gastric wall, with tenacious infiltration of the pancreatic body. Therefore, we performed a total gastrectomy with esophageal jejunum anastomosis and reconstruction of intestinal continuity according to Roux, distal spleno-pancreatectomy, and cholecystectomy. At histology, a pancreatic acinar cell carcinoma (PACC) with full thickness infiltration of the gastric wall was diagnosed. Acinar cell carcinomas are highly aggressive neoplasms, and surgical resection, when feasible, is the treatment of choice regardless of size, also because the role of neoadjuvant or adjuvant chemo- or radiotherapy remains uncodified.

Abstract Background The incidence of the highly morbid and potentially lethal gangrenous cholecystitis was reportedly increased during the COVID-19 pandemic. The aim of the ChoCO-W study was to compare the clinical findings and outcomes of acute cholecystitis in patients who had COVID-19 disease with those who did not. Methods Data were prospectively collected over 6 months (October 1, 2020, to April 30, 2021) with 1-month follow-up. In October 2020, Delta variant of SARS CoV-2 was isolated for the first time. Demographic and clinical data were analyzed and reported according to the STROBE guidelines. Baseline characteristics and clinical outcomes of patients who had COVID-19 were compared with those who did not. Results A total of 2893 patients, from 42 countries, 218 centers, involved, with a median age of 61.3 (SD: 17.39) years were prospectively enrolled in this study; 1481 (51%) patients were males. One hundred and eighty (6.9%) patients were COVID-19 positive, while 2412 (93.1%) were negative. Concomitant preexisting diseases including cardiovascular diseases (p

CHARGE syndrome (CS) is a rare genetic disease that affects many areas of the body. The aim of the present systematic review was to evaluate the prevalence and types of congenital heart diseases (CHDs) in CS and their impact on clinical outcome. A systematic review from 1981 to September 2022 was conducted. Clinical studies that reported the association between CS and CHDs were identified, including a case report of a rare congenital anomaly of the aortic arch (AA) with persistent fifth aortic arch (PFAA). Demographic, clinical and outcome data were extracted and analyzed. Sixty-eight studies (44 case reports and 24 case series; n=943 CS patients) were included. The prevalence of CHDs was 76.6%, patent ductus arteriosus (PDA) 26%, ventricular (VSD) 21%, atrial septal defects (ASD) 18%, tetralogy of Fallot 11%, aortic abnormalities 24%. PFAA has not been previously reported in CS. Cardiac surgery was performed in more than half of CS patients (150/242, 62%). In-hospital mortality rate was about 9.5% (n=86/900) in case series studies and 12% (n=5/43) in case reports, including cardiovascular (CV) and non-CV causes. CHDs and feeding disorders associated with CS may have a substantial impact on prognosis. CHDs were usually associated with CS and represent important causes of morbidity and mortality. PFAA, although rare, may also be present. The prognosis is highly dependent on the presence of cardiac and non-cardiac developmental abnormalities. Further studies are needed to better identify the main causes of the long-term outcome of CS patients.

The TITAN project aims to improve immunotherapy, targeting the efficiency of methods to obtain genetically engineered T cells. Immunotherapy has achieved great success in clinical trials, but it is currently very expensive in terms of time required for analysis, reagents, and samples. TITAN aims to the continuous sampling of critical quality attributes, in order to quickly recognize deviations from the desired range and take appropriate corrective actions on process parameters for an optimal outcome. To achieve its aims, TITAN is currently developing microfluidic and sensing tools for the accurate and efficient real-time monitoring of the T cells amplification process.

The development of 3D porous nanocarbon composites has improved the performance of piezoresistive sensors. However, the functionalization and surface distribution of nanocarbon may limit conductivity and mechanical stability. In this study, a mechanochemical approach was developed to create an elastomeric/CNTs 3D porous nanocomposite. By changing parameters such as CNT length and polymer amount, different composites with improved piezoresistive properties can be produced for wearables or fluidic devices. The material can withstand compressive stress up to 150 Kpa and has a sensitivity of up to 330 Kpa−1 and a limit of detection of 0.2 Pa and 50 nm for pressure and extension, respectively.

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.

Producing sustainable microfluidic devices on a large scale has become a trend in the biomedical field. However, the transition from laboratory prototyping to large-scale industrial production poses several challenges due to the gap between academia and industry. In this context, prototyping with a mass production approach could be the novel strategy necessary to bridge academic research to the market. Here, the performance of polymer inserts to produce PMMA microfluidic devices using the microinjection moulding process is presented. Inserts were fabricated with an additive manufacturing process: material jetting technology. The importance of the inserts’ orientation on the printing plate in order to produce samples with more uniform thickness and lower roughness has been demonstrated using a flat cavity insert. In addition, preliminary tests were carried out on microstructured inserts with inverted channels of various cross-section shapes (semi-circular or trapezoidal) and widths (200 or 300 µm) in order to investigate the microstructures’ resistance during the moulding cycles. The best geometry was found in the channel with the trapezoidal cross-section with a width equal to 300 µm. Finally, a preliminary microfluidic test was performed to demonstrate the devices’ workability.

Introduction: The emergence and spread of drug-resistant pathogens due to the improper use of antibiotics have become increasingly apparent in recent years. Objective: This retrospective comparative analysis aimed to assess and compare antibiotic prescription trends in Italy across two different regions based on geographic area and healthcare structure. One region represents a large hospital institution, while the other represents a populous local Italian health agency. The study also examined the impact of documented antibiotic stewardship programs and efforts to promote responsible antibiotic use at all levels, in alignment with international goals. Antibiotic consumption data were collected from the Umberto I Polyclinic Hospital and the ASL Napoli 3 South Local Health Agency. Methods: To compare consumption between regions, a standardized comparison using the Defined Daily Dose (DDD) was employed. The internal management system of each healthcare facility records all prescriptions and drug dispensations, and these data were extrapolated for this retrospective study. Results: A comparative assessment between the first half of 2022 and 2023 (January–June) highlighted a significant increase in beta-lactam antibiotic consumption, showing a twofold rise compared to the previous year’s term. Regarding prescription averages, there was a noticeable increase of +29.00% in hospitalizations and +28.00% in hospital discharges within the ASL Napoli 3 South. Conversely, at Policlinico Umberto I, there was a marginal increase of +1.60% in hospitalizations and a decrease of −7.40% in hospital discharges. Conclusions: The study offers valuable insights into expenditure patterns and antibiotic consumption, underscoring the need for enhanced prescribing practices and awareness campaigns to address the issue of antibiotic resistance. The findings stress the importance of implementing international guidelines to combat the growing threat of antibiotic resistance and ensure the effective management of infectious diseases.

Contamination of cell cultures can result in a significant loss of precious biological material, particularly in long-term processes including amplification of chimeric antigen receptors (CAR)-T cells and differentiation of patient-derived stem cells, for therapeutic purposes. Bacterial contamination can also lead to more complex conditions such as sepsis which can cause morbidity and mortality, despite strict controls and good laboratory/manufacturing practices in the manipulation of complex biological samples such as blood used in autologous and allogeneic stem cells transplantation.The current standard method to identify biological risk is the set-up of microbial cultures, which can be time consuming with the likelihood of wasting large amounts of reagents in the event of contamination.Real-Time Polymerase Chain Reaction (qPCR) is a molecular method able to detect biological agents in a highly sensitive and specific way and in a short time. However, qPCR assays require complex DNA/RNA purification steps and expensive benchtop instruments, which may not always be available.This paper reports an extraction-free and low-volume protocol for qPCR in a standard instrument, which has been demonstrated to be effective on both Gram-positive (Gram+) and Gram-negative (Gram-) bacteria. Detection has been obtained from spiked cell culture samples, reaching a limit of detection (LOD) of 1 colony forming unit (CFU)/ml. To demonstrate the high potential of this optimized procedure, the same samples were also tested on a Point-Of-Care platform, which includes a cartridge with micro-chambers and a compact instrument, capable of performing qPCR with the same efficiency. Staphylococcus aureus (Gram+) was selected as the target for a proof of concept, achieving a LOD of 1 CFU/ml also on the portable device. The availability of these results paves the way for a simplified protocol for DNA extraction and amplification.

Purpose The new coronavirus, called SARS-CoV-2, is responsible for the recent global pandemic COVID-19. The status of the global pandemic COVID-19 is currently underway, and the virus has caused about 1.11 million deaths. Several SARS-CoV-2 vaccines are in phase 3 clinical trials. Pending the availability of safe and effective vaccines, pharmacological treatments are experimental and aimed at avoiding the most serious complications of the infection. Methods This article explores and describes the scientific evidence in the literature and the scientific pharmacological and molecular rationale to consider drugs that modulate the RAS system as therapeutic agents that if administered appropriately can help the host organism to fight SARS-CoV-2 infection. Results It is known from the 2003 SARS epidemic that the critical receptor for SARS-CoV entry into host cells is the angiotensin 2 conversion enzyme (ACE2), the strain involved in the current SARS-CoV-2 epidemic is similar to the SARS-CoV strain involved in the 2002-2003 SARS epidemic. ACE-2 is part of the RAS system, the modulation of this enzyme could be of therapeutic efficacy. Conclusion Depending on pharmacological knowledge, and epidemiological evidence in the literature based on current knowledge of the mechanism of penetration of SARS-CoV-2 in cells, and the role of ACE-2 in the inflammatory state of infection, therapeutic treatments that modulate RAS could be a weapon to fight COVID-19 infection.

Circulating tumor cells (CTCs) have emerged as pivotal biomarkers with significant predictive and prognostic implications in solid tumors. Their presence in peripheral blood offers a non-invasive window into the dynamic landscape of cancer progression and treatment response. This narrative literature review synthesizes the current state of knowledge surrounding the multifaceted role of CTCs in predicting clinical outcomes and informing prognosis across a spectrum of solid tumor malignancies. This review delves into the evolving landscape of CTC-based research, emphasizing their potential as early indicators of disease recurrence, metastatic potential, and therapeutic resistance. Moreover, we have underscored the dynamic nature of CTCs and their implications for personalized medicine. A descriptive and critical analysis of CTC detection methodologies, their clinical relevance, and their associated challenges is also presented, with a focus on recent advancements and emerging technologies. Furthermore, we examine the integration of CTC-based liquid biopsies into clinical practice, highlighting their role in guiding treatment decisions, monitoring treatment efficacy, and facilitating precision oncology. This review highlights the transformative impact of CTCs as predictive and prognostic biomarkers in the management of solid tumors by promoting a deeper understanding of the clinical relevance of CTCs and their role in advancing the field of oncology.

The screening and early diagnosis of diseases are crucial for a patient’s treatment to be successful and to improve their survival rate, especially for cancer. The development of non-invasive analytical methods able to detect the biomarkers of pathologies is a critical point to define a successful treatment and a good outcome. This study extensively reviews the electrochemical methods used for the development of biosensors in a liquid biopsy, owing to their ability to provide a rapid response, precise detection, and low detection limits. We also discuss new developments in electrochemical biosensors, which can improve the specificity and sensitivity of standard analytical procedures. Electrochemical biosensors demonstrate remarkable sensitivity in detecting minute quantities of analytes, encompassing proteins, nucleic acids, and circulating tumor cells, even within challenging matrices such as urine, serum, blood, and various other body fluids. Among the various detection techniques used for the detection of cancer biomarkers, even in the picogram range, voltammetric sensors are deeply discussed in this review because of their advantages and technical characteristics. This widespread utilization stems from their ability to facilitate the quantitative detection of ions and molecules with exceptional precision. A comparison of each electrochemical technique is discussed to assist with the selection of appropriate analytical methods.

Abstract Therapeutic treatment of severe COVID-19 infection involves the administration of multiple pharmacologic agents to reduce the risk of serious complications; this may result in drug interactions and possible adverse reactions and induced cardiotoxicity. The risk–benefit ratio associated with the use of medications to treat COVID-19 should be carefully monitored. In addition, the severe COVID-19 patient may experience cardiac damage, and alteration of normal cardiac electrophysiology function. Severe COVID-19 with cardiac involvement and the risk of drug-induced adverse reactions may cause cardiac arrhythmias, including long qt syndrome, which in some cases may lead to sudden death. In this short review we briefly review the pharmacological agents used to treat severe COVID-19 with increased risk of causing long qt forms.

Rapid prototyping methods for the design and fabrication of polymeric labs-on-a-chip are on the rise, as they allow high degrees of precision and flexibility. For example, a microfluidic platform may require an optimization phase in which it could be necessary to continuously modify the architecture and geometry; however, this is only possible if easy, controllable fabrication methods and low-cost materials are available. In this paper, we describe the realization process of a microfluidic tool, from the computer-aided design (CAD) to the proof-of-concept application as a capture device for circulating tumor cells (CTCs). The entire platform was realized in polymethyl methacrylate (PMMA), combining femtosecond (fs) laser and micromilling fabrication technologies. The multilayer device was assembled through a facile and low-cost solvent-assisted method. A serpentine microchannel was then directly biofunctionalized by immobilizing capture probes able to distinguish cancer from non-cancer cells without labeling. The low material costs, customizable methods, and biological application of the realized platform make it a suitable model for industrial exploitation and applications at the point of care.

Abstract Few studies have investigated psychosocial characteristics and lifestyle behaviors of participants at programs for secondary prevention of colorectal cancer (CRC). This study aimed, through a comprehensive psychosomatic assessment based on clinimetric principles, to evaluate psychosocial characteristics and lifestyle behaviors in participants at CRC secondary prevention program, and to investigate the associations between these variables and endoscopic outcomes. In this cross-sectional study, the first 150 consecutive asymptomatic participants at the CRC prevention program who resulted positive to fecal occult blood test (FOBT) and were thus referred to colonoscopy, underwent a psychosomatic assessment including psychiatric diagnoses (DSM-5), psychosomatic syndromes (DCPR-R), psychological distress, psychological well-being and lifestyle behaviors. Whereas only 5.3% of the sample showed at least one DSM-5 diagnosis, 51.3% showed at least one DCPR syndrome, such as allostatic overload, alexithymia, Type A behavior, and demoralization. Patients affected by psychosomatic syndromes presented with significantly higher psychological distress, lower psychological well-being and unhealthy lifestyle behaviors, such as tobacco smoking and unhealthy diet, in comparison with patients without DCPR syndromes. Among endoscopic outcomes, the presence of adenomas was significantly associated with DCPR irritable mood. In a clinical context of secondary prevention addressing asymptomatic patients with positive FOBT, a comprehensive psychosomatic assessment may provide relevant clinical information for those patients who present certain psychosomatic syndromes associated with high psychological distress, impaired psychological well-being, unhealthy lifestyle behaviors and colorectal precancerous lesions. The results of the present study indicate a road to the practice of “preventive” medicine at CRC screening program.

Abstract Background The global pandemic COVID-19 caused by the new coronavirus SARS-CoV-2 has already caused about 1.4 million deaths, and to date, there are no effective or direct antiviral vaccines. Some vaccines are in the last stages of testing. Overall mortality rates vary between countries, for example, from a minimum of 0.05% in Singapore to a maximum of 9.75 in Mexico; however, mortality and severity of COVID-19 are higher in the elderly and in those with comorbidities already present such as diabetes, hypertension, and heart disease. Main text Recent evidence has shown that an underlying liver disease can also be a risk factor, and SARS-CoV-2 itself can cause direct or indirect damage to liver tissue through multisystem inflammation generated especially in the more severe stages. In the current pandemic, liver dysfunction has been observed in 14–53% of patients with severe COVID-19. In addition, drugs administered during infection may be an additional factor of liver damage. The mechanism of cellular penetration of the virus that occurs by viral entry is through the receptors of the angiotensin 2 conversion enzyme (ACE-2) host that are abundantly present in type II pneumocytes, heart cells, but also liver cholangiocytes. Conclusion In this manuscript, we describe the clinical management aimed at preserving the liver or reducing the damage caused by COVID-19 and anti-COVID-19 drug treatments.

Abstract Purpose This study was a quality-control study of resting and exercise Doppler echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork. Methods All participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S’), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e’) and left ventricular ejection fraction (LVEF) were measured. Results The accuracy of 19 investigators for all variables ranged from 99.7 to 100%. ICC was > 0.90 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e’ = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S’ = 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%. Conclusions When performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation.

Lichen Sclerosus (LS) is a chronic inflammatory skin disease with unknown etiology. In pediatric age the main disease “lichenlinked” is the phimosis in male. This is a retrospective study that reports the experience of our clinic and review of the literature. We included all patients affected by pathological phimosis, treated by circumcision between January 2015 and May 2020, older than 6 years old and with an histopathological diagnosis of lichen sclerosus. The aim was to identify prognostic factors based on histological report to plan the clinical management of patients. Statistical analysis was done. We included 207 patients. The mean age of children was 9,78 years (5-18 years, DS±3.29). Based on the histological features we divided patients in 2 groups: early lesions (70/207, 34%) and advanced (137/207, 66%). In term of complications lichen linked we considered meatal stenosis that needed of urethral dilatations. We included 7 patients (7/207, 3,4%). We report P value Statistical Significance in many aspects. An early diagnosis of LS and surgical treatment of foreskin are essential to prevent early and late complications in children. The size of sample is a limit of the study but results encourage our management.

Fungal infections, named mycosis, can cause severe invasive and systemic diseases that can even lead to death. In recent years, epidemiological data have recorded an increase in cases of severe fungal infections, caused mainly by a growing number of immunocompromised patients and the emergence of fungal pathogenic forms that are increasingly resistant to antimycotic drug treatments. Consequently, an increase in the incidence of mortality due to fungal infections has also been observed. Among the most drug-resistant fungal forms are those belonging to the Candida and Aspergillus spp. Some pathogens are widespread globally, while others are endemic in some areas only. In addition, some others may represent a health threat for some specific subpopulations and not for the general public. In contrast to the extensive therapeutic armamentarium available for the antimicrobial chemotherapeutic treatment of bacteria, for fungal infections there are only a few classes of antimycotic drugs on the market, such as polyenes, azoles, echinocandins, and a few molecules are under trial. In this review, we focused on the systemic mycosis, highlighted the antifungal drug compounds available in the pipeline, and analyzed the main molecular mechanisms for the development of antifungal resistance to give a comprehensive overview and increase awareness on this growing health threat.

The Liquid Biopsy (LB) is an opportunity for non-invasive diagnosis and prognosis of various diseases. To date, it isn't possible to consider that tissue biopsy can represent a pathology entirety. Then, body fluids are rich in a large number and variety of biomarkers and they can provide information about several diseases. • Recently, other biological fluids, easy to be collected are rising for their significant content of biomarkers and for the possibility to collect and manipulate them without the intervention of medical staff. • The management of biological fluids requires suitable storage methods. Temperature, storage time and physical stresses due to sample handling can lead to chemical and physical changes that may induce sample degradation and incorrect analysis. • The reliability of a diagnostic or screening test depends on its sensitivity and specificity. As the liquid biopsy is a 'snapshot' of a pathophysiological condition, it is crucial that its components do not degrade due to the improper handling of the body fluid.In this review, some handling methods of Saliva, Urine, Stool, Seminal Fluid, Tears and Sweat samples will be described, as well as protocols to facilitate the analysis of metabolites, nucleic acids, proteins and Extracellular Vesicles (EVs) from those unusual body fluids.

Carbon dioxide (CO2)-laser processing of glasses is a versatile maskless writing technique to engrave micro-structures with flexible control on shape and size.In this study, we present the fabrication of hundreds of microns quartz micro-channels and micro-holes by pulsed CO2-laser ablation with a focus on the great potential of the technique in microfluidics and biomedical applications. After discussing the impact of the laser processing parameters on the design process, we illustrate specific applications. First, we demonstrate the use of a serpentine microfluidic reactor prepared by combining CO2-laser ablation and post-ablation wet etching to remove surface features stemming from laser-texturing that are undesirable for channel sealing. Then, cyclic olefin copolymer micro-pillars are fabricated using laser-processed micro-holes as molds with high detail replication. The hundreds of microns conical and square pyramidal shaped pillars are used as templates to drive 3D cell assembly. Human Umbilical Vein Endothelial Cells are found to assemble in a compact and wrapping way around the micro-pillars forming a tight junction network. These applications are interesting for both Lab-on-a-Chip and Organ-on-a-Chip devices.

The global pandemic SARS-CoV-2 (COVID-19) is causing thousands of deaths worldwide and is one of the greatest health challenges ever faced in human history. SARS-CoV-2 infection can cause fatal lung injuries caused by a generalized inflammatory state associated with multi-organ dysfunction. In this context, it is essential to recognize the factors that increase the risk of viral infection. People with pre-existing conditions, such as diabetes, are at greater risk of complications and death caused by COVID-19. Old age, possible chronic drug therapies, kidney failure, hyperglycemia, and heart disease, are predictive factors of a bad outcome for the diabetic patient. The regulation of glycemia and the adoption of appropriate measures are critical aspects to be taken into consideration for the diabetic patient in this pandemic period, especially in the patient with ongoing infection. In the latter, the use of drugs used to fight COVID-19 infection, such as antivirals or immunomodulants, must be well controlled to avoid possible drug interactions and major complications. People with diabetes fall into the category of the fragile and at-risk population, and if a COVID-19 infection is also ongoing, the patient must be managed optimally, trying to fight the virus but also without neglecting homeostasis and glycemic control. This analysis highlights the current knowledge and challenges for the prevention and management of patients with diabetes and COVID-19 infection.

Abstract Background Timing and adequacy of peritoneal source control are the most important pillars in the management of patients with acute peritonitis. Therefore, early prognostic evaluation of acute peritonitis is paramount to assess the severity and establish a prompt and appropriate treatment. The objectives of this study were to identify clinical and laboratory predictors for in-hospital mortality in patients with acute peritonitis and to develop a warning score system, based on easily recognizable and assessable variables, globally accepted. Methods This worldwide multicentre observational study included 153 surgical departments across 56 countries over a 4-month study period between February 1, 2018, and May 31, 2018. Results A total of 3137 patients were included, with 1815 (57.9%) men and 1322 (42.1%) women, with a median age of 47 years (interquartile range [IQR] 28–66). The overall in-hospital mortality rate was 8.9%, with a median length of stay of 6 days (IQR 4–10). Using multivariable logistic regression, independent variables associated with in-hospital mortality were identified: age > 80 years, malignancy, severe cardiovascular disease, severe chronic kidney disease, respiratory rate ≥ 22 breaths/min, systolic blood pressure < 100 mmHg, AVPU responsiveness scale (voice and unresponsive), blood oxygen saturation level (SpO2) < 90% in air, platelet count < 50,000 cells/mm3, and lactate > 4 mmol/l. These variables were used to create the PIPAS Severity Score, a bedside early warning score for patients with acute peritonitis. The overall mortality was 2.9% for patients who had scores of 0–1, 22.7% for those who had scores of 2–3, 46.8% for those who had scores of 4–5, and 86.7% for those who have scores of 7–8. Conclusions The simple PIPAS Severity Score can be used on a global level and can help clinicians to identify patients at high risk for treatment failure and mortality.

Vitamin D promotes kidney calcium reabsorption and regulates calcium and phosphate metabolism, as well as the intestinal absorption of calcium and phosphorus and bone mineralization events. Vitamin D is also known for its immunomodulatory properties. It has been shown in the literature that the active form of vitamin D, 1,25-dihydroxyvitamin D, performs multiple functions in the adaptive and innate immune system, as well as acting on the endothelial membrane. Recent evidence shows that vitamin D is a negative endocrine modulator of the renin–angiotensin system (RAS), with protection from diseases leading to lung damage, such as pneumonia caused by various pathogens. Vitamin D support associated with the use of antibiotics could be crucial to counteract these infectious diseases.

The possibility of fabricating micrometric pore size membranes is gaining great interest in many applications, from studying cell signaling, to filtration. Currently, many technologies are reported to fabricate such microsystems, the choice of which depends strictly on the substrate material and on the final application. Here, we demonstrate the capability with a single femtosecond laser source and experimental setup to fabricate micromembranes both on polymeric and multilayer metallic substrate, without the need for moulds, mask, and complex facilities. In particular, the flexibility of laser drilling was exploited to obtain microfilters with pore size of 8 and 18 µm in diameter, on metallic and polymeric substrate, respectively, and controlled distribution. For evaluating the possibility to use such laser-fabricated membranes into biological assay, their biocompatibility has been investigated. To this aim, as a proof of concept, we tested the two materials into viability tests. The culture of mammalian cells on these microfabricated membranes were studied showing their compatibility with cells.

The COVID-19 global pandemic has caused about 4,30 Mln deaths. Recently the first vaccines have been licensed, representing the most powerful weapon available to stop the pandemic. The COVID-19 viral infection in the most severe cases can cause severe lung lesions with the presence of fibrotic tissue. Even among cured individuals, the presence of pulmonary fibrotic tissue may be the major cause of long-term complications of COVID-19 requiring antifibrotic therapeutic treatment even in the post-COVID-19 infection phase to accelerate the healing process and fully recover lung function. This article reviews the fibrogenic mechanism of SARS-CoV-2-induced viral damage and the antifibrotic treatments indicated to treat sequelae post COVID-19 infection.

We present a very rare case of gastric duplication treated with complete excision with two surgical procedures. We decided to report our case to share our experience that confirm the difficult of preoperative/intraoperative diagnosis of gastric duplication in a pediatric patient. Finally we reviewed the literature to date.

The global pandemic caused by COVID-19 has caused more than 1 million deaths worldwide. Some vaccines in clinical trials have reached stage 3. In the meantime, the understanding of the biological and pathophysiological mechanisms of Sars-CoV2 infection is still unclear, such as the role that ACE-2 and DPP-IV may play in patients with diabetes related to COVID-19. The individual with diabetes is a known COVID-19 risk patient. Probably the pharmacological regulation of the RAS system and of ACE-2 on the one hand, and of the incretin system and DPP-IV on the other, could represent a therapeutic route of fundamental importance to reduce the risk of Sars-CoV-2 infection or of serious complications caused by infection.

Glyphozines also called SGLT2 inhibitors, are a new class of agents that inhibit reabsorption of glucose in the kidney, in proximal tubules, and therefore lower blood sugar. They act by inhibiting sodiumglucose transport protein 2 (SGLT2). Glyphozines are used in the treatment of type II diabetes mellitus. In studies with canagliflozin, a member of this class, the medication was found to enhance blood sugar control as well as reduce body weight and systolic and diastolic blood pressure. In addition to regulate blood glucose, recent studies have shown that glyphozines have important positive cardiovascular benefits, such as weight loss, decreased volaemia and PA, reduced triglycerides, natriuresis and improved endothelial wall dysfunction. Clinical studies have shown reduction in deaths from cardiovascular events among diabetic patients treated with glyphozines. At the moment these drugs are being studied for an extension of the therapeutic indication also for cardiovascular diseases such as heart failure. In this review, we discuss the class of SGLT2 inhibitors in the treatment of diabetes, and studies focused on their possible role in the treatment of cardiac disease.

For some patients with SARS-CoV-2, the worst clinical damage is not caused by the virus itself, but by an overactive inflammatory state. In fact, in some people the immune system goes into overdrive and launches a large-scale assault on the tissue known as cytokine storm. This excessive inflammatory/immune reaction can damage tissue and eventually kill people. Evidence shows that blocking such cytokine storms can be effective and trials are underway to test drugs that act by reducing cytokine response, such as tocilizumab and sarilumab which bind interleukin 6 (IL-6), or anikinra which is the interleukin 1 receptor antagonist (IL-1). However, other drugs that block the cytokine cascade can also be considered. In this article we describe the scientific and molecular motivation for the use of drugs that act by modulating the hyperactive inflammatory system in severe patients suffering from SARS-CoV-2, considering in particular an old drug that has been in use for many years for other therapeutic indications such as colchicine, and that could be favourable to its use, with low cost and good tolerability.

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Abstract Background The effectiveness trial “Stress echo (SE) 2020” evaluates novel applications of SE in and beyond coronary artery disease. The core protocol also includes 4-site simplified scan of B-lines by lung ultrasound, useful to assess pulmonary congestion. Purpose To provide web-based upstream quality control and harmonization of B-lines reading criteria. Methods 60 readers (all previously accredited for regional wall motion, 53 B-lines naive) from 52 centers of 16 countries of SE 2020 network read a set of 20 lung ultrasound video-clips selected by the Pisa lab serving as reference standard, after taking an obligatory web-based learning 2-h module (http://se2020.altervista.org). Each test clip was scored for B-lines from 0 (black lung, A-lines, no B-lines) to 10 (white lung, coalescing B-lines). The diagnostic gold standard was the concordant assessment of two experienced readers of the Pisa lab. The answer of the reader was considered correct if concordant with reference standard reading ±1 (for instance, reference standard reading of 5 B-lines; correct answer 4, 5, or 6). The a priori determined pass threshold was 18/20 (≥ 90%) with R value (intra-class correlation coefficient) between reference standard and recruiting center) > 0.90. Inter-observer agreement was assessed with intra-class correlation coefficient statistics. Results All 60 readers were successfully accredited: 26 (43%) on first, 24 (40%) on second, and 10 (17%) on third attempt. The average diagnostic accuracy of the 60 accredited readers was 95%, with R value of 0.95 compared to reference standard reading. The 53 B-lines naive scored similarly to the 7 B-lines expert on first attempt (90 versus 95%, p = NS). Compared to the step-1 of quality control for regional wall motion abnormalities, the mean reading time per attempt was shorter (17 ± 3 vs 29 ± 12 min, p

Abstract Background Acute appendicitis (AA) is the most common surgical disease, and appendectomy is the treatment of choice in the majority of cases. A correct diagnosis is key for decreasing the negative appendectomy rate. The management can become difficult in case of complicated appendicitis. The aim of this study is to describe the worldwide clinical and diagnostic work-up and management of AA in surgical departments. Methods This prospective multicenter observational study was performed in 116 worldwide surgical departments from 44 countries over a 6-month period (April 1, 2016–September 30, 2016). All consecutive patients admitted to surgical departments with a clinical diagnosis of AA were included in the study. Results A total of 4282 patients were enrolled in the POSAW study, 1928 (45%) women and 2354 (55%) men, with a median age of 29 years. Nine hundred and seven (21.2%) patients underwent an abdominal CT scan, 1856 (43.3%) patients an US, and 285 (6.7%) patients both CT scan and US. A total of 4097 (95.7%) patients underwent surgery; 1809 (42.2%) underwent open appendectomy and 2215 (51.7%) had laparoscopic appendectomy. One hundred eighty-five (4.3%) patients were managed conservatively. Major complications occurred in 199 patients (4.6%). The overall mortality rate was 0.28%. Conclusions The results of the present study confirm the clinical value of imaging techniques and prognostic scores. Appendectomy remains the most effective treatment of acute appendicitis. Mortality rate is low.

In this period of global pandemic caused by SARS-Cov-2, it is of paramount importance to recognize all risk factors that may increase the likelihood of infection. In addition to the risk factors known as pre-existing diseases and old age, risk factors could be drug treatments for chronic diseases, such as immunomodulating drugs that can alter immune defences and response to infectious agents. Antibodies that inhibit tumor necrosis factor (TNF) such as adalimumab infliximab etanercept and golimumab have been used for over 20 years in severe cases of autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease or ankylosing spondylitis. Due to their mechanism of action they reduce inflammation and can stop the progression of the disease by inhibiting a key factor of inflammation such as TNF. In this article we want to examine the possible correlation between therapy with TNF inhibitors and the increased risk of SARS-CoV-2 infection, and the possible paradoxical therapeutic efficacy in patients with ongoing infection, especially in phase two and three. We express our opinion on this very complex and sensitive topic which is the subject of discussion among physicians and experts, based on current knowledge of the literature.

Recently, the attention paid to self-care tests and the need for easy and large-scale screenings of a high number of people has dramatically increased [...]