Global quantification and distribution of antibiotic resistance genes in oceans and seas: Anthropogenic impacts and regional variability.

The global spread of antibiotic resistance genes (ARGs) in the marine environment poses a significant threat to public health and natural ecosystems. This study quantified and analysed the distribution and co-occurrence patterns of ARGs in a wide range of oceans and high seas, including the Atlantic, Arctic and Indian Ocean, the Mediterranean Sea and the Persian Gulf. Focusing on beta-lactamases (blaOXA-48, blaCTX-M-1 group, and blaTEM), sulfonamides (sul1) and tetracycline (tetA), our results showed that sul1 was ubiquitous, indicating widespread dissemination. Notably, the Mediterranean Sea exhibited higher levels of multiple ARGs in single samples, suggesting significant anthropogenic impact. Interestingly, the Arctic Ocean, particularly around the Svalbard Islands, also showed the presence of multiple ARGs, highlighting the pervasive occurrence of antibiotic resistance in remote areas. We employed two clustering approaches to explore ARG patterns, primarily focusing on identifying geographic trends and differences in ARG abundance. Additionally, we investigated potential sources of contamination, including proximity to wastewater treatment plants, ports, marine traffic, and currents. These findings clearly demonstrate that antibiotic resistance gene contamination is widespread across diverse marine environments, with significant regional variations. This underscores the urgent need for tailored intervention strategies and global collaboration to mitigate the spread of ARGs and manage their complex dynamics in marine ecosystems.

Comorbidity and in-hospital mortality in peritoneal dialysis patients: data of the Emilia Romagna region of Italy.

OBJECTIVE: Kidney failure increases in-hospital mortality (IHM); however, comorbidity is crucial for predicting mortality in dialysis patients. Our aim was to evaluate the impact of comorbidity, assessed by modified Elixhauser index (mEI), Charlson Comorbidity Index (CCI), and age-adjusted CCI, on IHM in a cohort of peritoneal dialysis patients admitted to hospitals of the Emilia Romagna region (ERR) of Italy. PATIENTS AND METHODS: All hospital admissions of peritoneal dialysis patients recorded between 2007 and 2021 in the ERR database were analyzed. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) was used for detecting diagnoses and procedures, and the inclusion criterion was code 5498. Comorbidity burden was evaluated by three different scores, and hemodialysis (HD) treatment need was considered. IHM was our outcome. RESULTS: During the 15 years of the study, 3,242 hospitalized peritoneal dialysis patients (62.7% males) were evaluated. Mean age was 62.8±20.6 years, 9.6% underwent HD, and IHM was 5.9% (n=192). IHM mortality was stable throughout the study period. Deceased subjects were older, were hospitalized longer, had a higher comorbidity burden, and had a higher percentage of HD treatment needs than survivors. Age, male sex, comorbidity burden, and HD treatment were predictors of IHM. Receiver operating characteristics (ROC) analysis confirmed the impact of comorbidity burden on IHM, especially when age was considered. CONCLUSIONS: We conclude that in male, elderly hospitalized peritoneal dialysis patients with failing dialysis technique, comorbidity burden should be considered being a predictor of IHM.

The Effect of Crackers Enriched with Camelina Sativa Oil on Omega-3 Serum Fatty Acid Composition in Older Adults: A Randomized Placebo-Controlled Pilot Trial.

BACKGROUND: Camelina sativa oil is one of the richest dietary sources of omega-3, with polyunsaturated fatty acids amounts of over 50%, linolenic acid content of around 40-45%, and linoleic acid of about 15%. Moreover, this oil is a valuable source of antioxidants which provide oxidative stability. All those features raise interest in considering Camelina oil as an alternative and sustainable oil source providing stable omega-3-rich emulsions for functional food production. OBJECTIVES: The present study aimed to investigate the effects of Camelina oil-enriched crackers on serum omega-3 concentration, inflammatory markers and serum lipid profile. DESIGN: Randomized placebo-controlled pilot trial. SETTING: Research and Development Center (Complife Italia s.r.l.). PARTICIPANTS: Sixty-six free-living older volunteers (aged≥65 years). INTERVENTION: Older adults were enrolled and randomly assigned to one of two groups: the camelina group or the placebo group. Subjects consumed daily 35 g of crackers (Camelina enriched crackers or placebo ones) twice daily for 12 weeks. MEASUREMENTS: Serum polyunsaturated fatty acid profile, inflammatory status and serum lipid panel parameters were recorded pre and post-intervention. RESULTS: In the camelina group, alpha-linolenic acid serum concentration was significantly higher (p<0.01) compared to the placebo group at the end of the study. Concerning inflammatory plasma markers, a significant mean pro-inflammatory interleukin-18 plasma concentration decrease in the placebo group compared to the camelina one was observed (p<0.05). No significant differences in other mean inflammatory markers concentrations post-intervention were noted in either group. Lastly, examining the change in lipid profile, it is noteworthy that a higher reduction of total cholesterol, low-density lipoprotein and triglycerides in the camelina group post-intervention, despite the lack of statistical significance. CONCLUSION: Camelina oil significantly elevated the serum alpha-linolenic acid concentration with no significant changes in inflammatory markers and lipid profile.

SARS-CoV-2 caused a surge in antibiotic consumption causing a silent pandemic inside the pandemic. A retrospective analysis of Italian data in the first half of 2022.

BACKGROUND: The phenomenon of antibiotic resistance shows no sign of stopping, despite global policies to combat it that have been in place for several years. The risk of forms of pathogenic microorganisms that are increasingly resistant to common antibiotics has led health authorities around the world to pay greater attention to the phenomenon. The worrying situation, has led to further recommendations from the World Health Organization (WHO) and national recommendations in Italy through the new National Plan against Antibiotic Resistance 2022-2025 (PNCAR 2022-2025). AIM: This manuscript aims to raise the awareness of all health professionals to follow what is suggested by regulatory agencies and scientific societies. METHOD: We conducted a retrospective study of antibiotic pharmacoutilization in Italy, in the Campania region at the Azienda Sanitaria Locale (ASL) Napoli 3 Sud, on consumption in the first half of 2022 in a population of more than 1 million people. RESULT: The results indicate that consumption, based on defined daily doses (DDDs), is above the national average. Probably the COVID-19 pandemic has influenced this growth in prescriptions. CONCLUSIONS: Our study suggests an informed and appropriate use of antibiotics, so as to embark on a virtuous path in the fight against antibiotic resistance.

Association between microbiota and immune response to Sars-CoV-2 infection.

In recent times, the key role of the human microbiota in the body's response to infectious diseases has been increasingly demonstrated. The human microbiota is the set of symbiotic microorganisms which coexist with the human organism without harming it. However, diseases related to the microbiota occur and are being studied, and numerous publications suggest that altered microbiota composition is implicated in psychiatric diseases, chronic inflammatory diseases, and some viral infections. On the other hand, the role of the human microbiota in the host immune response to viral infections is not entirely clear. Metabolites or components produced by the microbiota are the main mediators of microbiota-host interactions that influence host immunity. It has been shown that in patients with COVID-19 and post-acute COVID-19 syndrome (PACS), the microbiota is significantly altered. In this brief review, we examine the associations between the role of the microbiota in response to COVID-19 infection in terms of molecular biology and clinical relevance. We finally discuss the mechanisms by which metabolites produced by the microbiota modulate host immune responses to SARS-CoV-2 infection.

Gilteritinib as treatment for extra-medullary relapse of FLT3-ITD acute myeloid leukemia FLT3-ITD, after allogeneic haematopoietic stem cell transplantation.

Case of a patient with acute myeloid leukemia (AML) positive for mutations in both genes NPM1 and FLT3-ITD who underwent two allogeneic haematopoietic stem cell transplants (HSCT); the second allograft one was followed by extramedullary relapse (granulocytic sarcoma of right breast), with blast cells positive for FLT3-ITDmutation.  Treatment with Gilteritinib, a second generation selective oral type I FLT3 inhibitor, was started after the second HSCT with complete regression of breast granulocytic sarcoma in absence of hematological and extra hematologic toxicity. We conclude that Gilteritinib can represent an effective therapy for extra hematologic relapse, with acceptable toxicity and outpatient management.

Phenotyping congestion in patients with acutely decompensated heart failure with preserved and reduced ejection fraction: The Decongestion duRing therapY for acute decOmpensated heart failure in HFpEF vs HFrEF- DRY-OFF study.

AIMS: To evaluate pulmonary and intravascular congestion at admission and repeatedly during hospitalization for acute decompensated heart failure (ADHF) in HFrEF and HFpEF patients using lung (LUS) and inferior vena cava (IVC) ultrasound. METHODS AND RESULTS: Three-hundred-fourteen patients (82±9 years; HFpEF =172; HFrEF=142) admitted to Internal Medicine wards for ADHF were enrolled in a multi-center prospective study. At admission HFrEF presented higher indexes of pulmonary and intravascular congestion (LUS-score: 0.9 ±â€¯0.4 vs 0.7 ±â€¯0.4; p<0.01; IVC end-expiratory diameter: 21.6 ±â€¯5.1 mm vs 20±5.5 mm, p<0.01; IVC collapsibility index 24.4 ±â€¯17.4% vs 30.9 ±â€¯21.1% p<0.01) and higher Nt-proBNP values (8010 vs 3900 ng/l; p<0.001). At discharge, HFrEF still presented higher B-scores (0.4 ±â€¯4 vs 0.3 ±â€¯0.4; p = 0.023), while intravascular congestion improved to a greater extent, thus IVC measurements were similar in the two groups. No differences in diuretic doses, urine output, hemoconcentration, worsening renal function were found. At 90-days follow up HF readmission/death did not differ in HFpEF and HFrEF (28% vs 31%, p = 0,48). Residual congestion was associated with HF readmission/death considering the whole population; while intravascular congestion predicted readmission/death in the HFrEF, no association between sonographic indexes and the outcome was found in HFpEF. CONCLUSIONS: Serial assessment of pulmonary and intravascular congestion revealed a higher burden of fluid overload in HFrEF and, conversely, a greater reduction in intravascular venous congestion with diuretic treatment. Although other factors beyond EF could play a role in congestion/decongestion patterns, our data may be relevant for further phenotyping HF patients, considering the importance of decongestion optimization in the clinical approach.

COVID-19 vaccines and decreased transmission of SARS-CoV-2.

A massive COVID-19 vaccination campaign is underway worldwide. Epidemiological data from studies indicate excellent efficacy and safety profile for COVID-19 vaccines. However, there are few data from studies on the effect of decreasing the probability of infection of vaccinated subjects compared to unvaccinated subjects. In this short communication, we describe some evidence on this important and current topic providing useful personal reflections.

Scientific Hypothesis for Treatment of COVID-19's Lung Lesions by Adjusting ACE/ACE2 Imbalance.

In March 2019 began the global pandemic COVID-19 caused by the new Coronavirus SARS-CoV-2. The first cases of SARS-CoV-2 infection occurred in November-19 in Wuhan, China. The preventive measures taken did not prevent the rapid spread of the virus to all countries around the world. To date, there are about 2.54 million deaths, effective vaccines are in clinical trials. SARS-CoV-2 uses the ACE-2 protein as an intracellular gateway. ACE-2 is a key component of the Renin Angiotensin (RAS) system, a key regulator of cardiovascular function. Considering the key role of ACE-2 in COVID-19 infection, both as an entry receptor and as a protective role, especially for the respiratory tract, and considering the variations of ACE-2 and ACE during the stages of viral infection, it is clear the important role that the pharmacological regulation of RAS and ACE-2 can assume. This biological knowledge suggests different pharmacological approaches to treat COVID-19 by modulating RAS, ACE-2 and the ACE/ACE2 balance that we describe in this article.

Pharmacological approach for the reduction of inflammatory and prothrombotic hyperactive state in COVID-19 positive patients by acting on complement cascade.

The novel Coronavirus SARS-CoV-2 is the viral pathogen responsible for the ongoing global pandemic, COVID-19 (Coronavirus disease 2019). To date, the data recorded indicate 1.62 Mln deaths and 72.8 Mln people infected (WHO situation report Dec 2020). On December 27, the first anti-COVID-19 vaccinations started in Europe. There are no direct antivirals against SARS-CoV-2. Understanding the pathophysiological and inflammatory/immunological processes of SARS-CoV-2 infection is essential to identify new drug therapies. In the most severe COVID-19 cases, an unregulated immunological/inflammatory system results in organ injury that can be fatal to the host in some cases. Pharmacologic approaches to normalize the unregulated inflammatory/immunologic response is an important therapeutic solution. Evidence associates a non-regulation of the "complement system" as one of the causes of generalized inflammation causing multi-organ dysfunction. Serum levels of a complement cascade mediator, factor "C5a", have been found in high concentrations in the blood of COVID-19 patients with severe disease. In this article we discuss the correlation between complement system and COVID-19 infection and pharmacological solutions directed to regulate.

Pharmacological agents to therapeutic treatment of cardiac injury caused by Covid-19.

SARS-CoV-2 is responsible for the 2019 coronavirus disease (COVID-19), a global pandemic that began in March 2020 and is currently in progress. To date, COVID-19 has caused about 935,000 deaths in more than 200 countries. The respiratory system is most affected by injuries caused by COVID-19, but other organs may be involved, including the cardiovascular system. SARS-CoV-2 penetrates host cells through the angiotensin 2 conversion enzyme (ACE-2). ACE-2 is expressed not only in the lungs, but also in other organs, including the cardiovascular system. Several studies have found that a good percentage of patients with severe COVID-19 have cardiac lesions, including myocardial fibrosis, edema and pericarditis. Pathological remodeling of the extracellular matrix caused by viral infection leads to myocardial fibrotic lesions. These fibrotic scars can cause cardiac dysfunction, reducing the ejection fraction caused by the presence of stiffened myocardial matrix, or cardiac arrhythmias that cause an alteration in the electrical conduction system of the heart. These cardiac dysfunctions can cause death. It is therefore essential to identify cardiac involvement early in order to act with appropriate therapeutic treatments. In this review, we describe what is known about cardiac injury from COVID-19, highlighting effective pharmacological therapeutic solutions to combat cardiac injury, particularly cardiac fibrosis, caused by COVID-19.

KRD (carfilzomib and lenalidomide plus dexamethasone) for the treatment of relapsed or refractory multiple myeloma in the real-life: a retrospective survey in 123 patients.

From April 2016, carfilzomib, in combination with lenalidomide and dexamethasone (KRD), became available for use in the daily practice in Italy for patients with relapsed or refractory multiple myeloma (RRMM). We performed a retrospective survey at 14 different institutions from Southern Italy in order to evaluate patient characteristics and treatment results from an unselected series of patients treated accordingly so far. One hundred and twenty-three consecutive patients were included, with a median of 2 previous lines of therapy (range 1-9) and a median age of 63 years (range 39-82). At the time of analysis, median number of courses administered is 11 (range 1-34), and all patients are evaluable for response. Overall response rate including complete remission, very good partial remission, and partial remission is 85%. After a median follow-up of 27 months, median overall and progression-free survival are 33 and 23 months, respectively. Sixty-three patients are alive and between them, 45 (37%) are in continuous remission. Sixty patients have died (49%), mainly from progressive disease. There were 6 treatment-related deaths (5% of the whole patient population). Overall, hematological and non-hematological toxicity were manageable, mostly on outpatient basis. Arterial hypertension has been observed in 43 cases (35%) but did not lead to treatment interruption. Our data demonstrate that in real life, KRD is highly effective and well tolerated in the majority of patients with RRMM.

The Influence of Medial Comminution in the Treatment Choice of Radial Head Fracture.

INTRODUCTION: The aim of our retrospective study was to investigate the role of the medial side involvement in the treatment choice of radial head fractures. MATERIALS AND METHODS: We searched the databases of our institutions for the surgical procedures diagnosed as "fracture of the radial head" and for the procedures related to "prosthesis of the radial head" and "osteosynthesis of the radial head" in the period from May 2014 to October 2017. The fractures were first classified according to the Mason classification . We then allocated the patients into three study groups according to the site of the fracture, either the medial or lateral side of the radial head : Group A, with an isolated lateral fracture of the radius head; Group B1, with a medial fracture of the radius head with two medial fragments; and Group B2, with a medial fracture of the radius head with multiple medial fragments. We performed a multivariate analysis to identify statistically significant correlation between the pre-operative classifications of Mason and our study, the type of surgical procedure, and the clinical outcome. RESULTS: Mayo Elbow Performance (MEP) scores determined at the final follow-up of the study (mean 16.6 months, range 12-26 months) was excellent in 17 patients (4 in Group A, 6 in Group B1 and 7 in Group B2), and good in 12 patients (3 in Group A, 7 in Group B1, and 2 in Group B2). One patient showed a poor result in MEP score probably because of an infection and implant removal. CONCLUSION: Regarding medial fractures of the radial head, our study showed satisfactory results with a radial head prosthesis for comminuted or multifragmentary radial head fractures. For surgeons with advanced elbow fracture expertise, osteosynthesis could be attempted in a fracture pattern that involved only two medial fragments.

Italian guidelines for the surgical management of enteral stomas in adults.

BACKGROUND: Worldwide, stomas represent a medical and social problem. Data from the literature on stoma management are extensive but not homogeneous. In Italy, no guidelines exist for this topic. Thus, clear and comprehensive clinical guidelines based on evidence-based data and best practice are need. In 2018, the Multidisciplinary Italian Study group for STOmas, called MISSTO, was founded. The aim was to elaborate guidelines for practice management of enteral and urinary stomas in adults. METHODS: A systematic review of the literature was performed using PubMed, National Guideline Clearinghouse, and other databases. The research included guidelines, systematic reviews, meta-analyses, randomized clinical trials, cohort studies, and case reports. Five main topics were identified: "stoma preparation", "stoma creation", "stoma complications", "stoma care", and "stoma reversal". The systematic review was performed for each topic, and studies were evaluated according to the GRADE system, AGREE II tool. RESULTS: Recommendations were elaborated in the form of statements with an established grade of recommendation for each statement. For low levels of scientific evidence statements, a consensus conference composed of expert members of the major Italian scientific societies in the field of stoma management and care was held. After discussing, correcting, validating, or eliminating the statements by the experts, the final version of the guidelines was elaborated and prepared for publication. This manuscript is focused on statements on the surgical management of enteral stomas. CONCLUSIONS: These guidelines are the first Italian guidelines on multidisciplinary management of enteral stomas with the aim of assisting surgeons during stoma management and care.

Elderly psoriatic patients under biological therapies: an Italian experience.

BACKGROUND: The number of elderly patients with psoriasis is steadily increasing in the Western world; nevertheless, they are frequently excluded from biological clinical trials and described as a high-risk group for adverse events. Thus, there is lack of information concerning safety and effectiveness of available treatments for psoriasis in the elderly, particularly about new biological systemic drugs. OBJECTIVE: Our aim was to describe our experience with all biological therapies currently used in the elderly (>65 years) psoriatic patients. METHODS: A retrospective multicentric review of clinical records of all psoriatic patient aged 65 years or older actually receiving biological drugs (etanercept, adalimumab, infliximab, golimumab, certolizumab pegol, ustekinumab or secukinumab) was undertaken. RESULTS: Our study population included 266 elderly psoriatic patients actually receiving any biological therapy (adalimumab 31.2%, ustekinumab 28.9%, etanercept 20.3%, secukinumab 15%, infliximab 3%, golimumab 1% and certolizumab pegol 0.6%). The PASI score at the baseline (week 0) ranged from 4 to 54; mean ± SD, 16.5 ± 7.1, which changed after biological administration to 3.7 ± 8 at week 16, 1.6 ± 2.1 at week 28 and 1.2 ± 2.1 at week 52. Among 266 elderly psoriatic patients, 25 adverse events were reported during the observation period. The most frequent events were infections with 12 (48%) reports, followed by malignancies with four (16%) reports. CONCLUSIONS: To date, our study represents the widest experience on the use of biological drugs in elderly psoriatic patients. We found that all biologics for psoriasis showed a great efficacy also in elderly people, and the rate and the type of adverse effects were similar to the younger patients. In conclusion, the age alone should not limit our therapeutic options. Further observational study using multiple data sources is needed to evaluate long-term effectiveness and safety for elderly psoriatic patients.

Therapeutic targeting of membrane-associated GRP78 in leukemia and lymphoma: preclinical efficacy in vitro and formal toxicity study of BMTP-78 in rodents and primates.

Translation of drug candidates into clinical settings requires demonstration of preclinical efficacy and formal toxicology analysis for filling an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA). Here, we investigate the membrane-associated glucose response protein 78 (GRP78) as a therapeutic target in leukemia and lymphoma. We evaluated the efficacy of the GRP78-targeted proapoptotic drug bone metastasis targeting peptidomimetic 78 (BMTP-78), a member of the D(KLAKLAK)2-containing class of agents. BMTP-78 was validated in cells from patients with acute myeloid leukemia and in a panel of human leukemia and lymphoma cell lines, where it induced dose-dependent cytotoxicity in all samples tested. Based on the in vitro efficacy of BMTP-78, we performed formal good laboratory practice toxicology studies in both rodents (mice and rats) and nonhuman primates (cynomolgus and rhesus monkeys). These analyses represent required steps towards an IND application of BMTP-78 for theranostic first-in-human clinical trials.

Imaging-Guided Preoperative Localization of Intra-Abdominal Local Recurrences of Colorectal Cancer Using the Harpoon Technique.

BACKGROUND AND AIMS: Intra-abdominal local recurrences of colorectal cancer can be difficult to localize and excise because they are not easily visible or palpable. MATERIALS AND METHODS: We report on our experience using the computed tomography-guided harpoon technique to locate and resect these nodules in seven patients. RESULTS: No complications were recorded during the procedures. Six nodes were malignant and all margins were tumor free. CONCLUSIONS: Harpoon placement for intra-abdominal local recurrences of colorectal cancer is a feasible and useful technique that provides direct localization and complete excision of lesions.