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OBJECTIVE: Sepsis is a life-threatening disease resulting from the interaction between pathogen and host response; its dysregulation causes organ dysfunction, high morbidity, and mortality. Despite the increase of septic patients admitted to Internal Medicine wards, data about clinical predictors of mortality in this setting are still lacking. The aim of this study was to evaluate the role of MEDS score and vitamin D as predictors of mortality (28-day and 90-day) in septic patients admitted to the Internal Medicine department. PATIENTS AND METHODS: Prospectively collected clinical data, lab tests including vitamin D, and clinical scores (SIRS, MEDS, SCS, REMS, SOFA, qSOFA) were retrospectively analyzed. Eightyeight microbiologically identified septic patients (median age 75 years old, IQR 65-82 years old; range 37-94 years old) were evaluated. RESULTS: Twenty-three patients (26.1%) died at 28 days, 33 (37.5%) died at 90 days. The logistic regression showed a positive effect of MEDS score (p=0.006; OR 1.24, 95% CI 1.08-1.49), and a negative effect of low vitamin D levels (p=0.008, OR 0.83, 95% CI 0.72-0.94) on mortality. Moreover, the cut-off of 7 points for MEDS score and of 7 ng/ml for vitamin D levels significantly predicted poor prognosis at 28 and 90 days. CONCLUSIONS: MEDS score and vitamin D levels represent independent predictors of mortality in a cohort of Internal Medicine septic patients. Further studies on larger samples are needed to confirm our results and to clarify the pathophysiological mechanisms at the basis of vitamin D deficiency as a predictor of mortality in septic patients. [ABSTRACT FROM AUTHOR]

Catheter-related bloodstream infections (CRBI) represent a frequent complication of immune-compromised hosts with a high mortality rate. In this setting, opportunistic pathogens can create a biofilm on implanted devices, being the source of infection. We provide a mini-review of the literature, starting from the description of two cases of CRBI by opportunistic pathogens in poly-morbid patients, successfully treated by antibiotic lock-therapy. [ABSTRACT FROM AUTHOR]

Ignition and combustion behavior in the second stage of a sequential combustor are investigated numerically at atmospheric pressure for pure CH 4 fueling and for two CH 4 - H 2 fuel blends in 24:1 and 49:1 mass ratios , respectively, using Large Eddy Simulation (LES). Pure CH 4 fueling results in a turbulent propagating flame anchored by the hot gas recirculation zones developed near the inlet of the sequential combustion chamber. As the H 2 content increases, the combustion process changes drastically, with multiple auto-ignition kernels produced upstream of the main flame brush. Analysis of the explosive modes indicates that, for the highest H 2 amount investigated, flame stabilization in the combustion chamber is strongly supported by auto-ignition chemistry. The analysis of fuel decomposition pathways highlights that radicals advected from the first stage flame, in particular OH, induce a rapid fuel decomposition and cause the reactivity enhancement that leads to auto-ignition upstream of the sequential flame. This behavior is promoted by the relatively large mass fraction of OH radicals found in the flow reaching the second stage, which is approximately one order of magnitude greater than it would be at chemical equilibrium. The importance of the out-of-equilibrium vitiated air on the ignition behavior is proven via an additional LES that features weak auto-ignition kernel formation when equilibrium is artificially imposed. It is therefore concluded that parameters affecting the relaxation towards chemical equilibrium of the vitiated flow can have an important influence on the operability of sequential combustors fueled with varying fractions of H 2 blending., Supplementary Information: The online version contains supplementary material available at 10.1007/s10494-024-00540-8., Competing Interests: Conflict of interestThe authors that they have no Conflict of interest as defined by Springer, or other interests that might be perceived to influence the results and/or discussion reported in this paper., (© The Author(s) 2024.)

Competing Interests: The authors declare that they have no conflict of interest.

Background: Hospital malnutrition affects nearly 30% of patients in medical wards and correlates with worse outcomes. An early assessment is necessary to stratify the risk of short-term outcomes and mortality. The predictive role of COntrolling NUTritional status (CONUT) score in this context has not yet been elucidated in Western countries. We aimed to test CONUT at admission as a predictive score of hospital outcomes, in an Internal Medicine and Gastroenterology Department of an Italian Tertiary Care University hospital., Methods: We prospectively enrolled patients admitted to our center, stratifying them into the four CONUT classes (normal = 0-1; mild = 2-4; moderate = 5-8; severe = 9-12 points) according to serum albumin (g/dL), total lymphocyte count (/mm 3 ), and total cholesterol (mg/dL); the primary outcome measure was length of stay (LOS) and the secondary one was in-hospital mortality., Results: Out of a total of 203 patients enrolled, 44 (21.7%) patients had a normal status (0-1), 66 (32.5%) had a mild impairment (2-4), 68 (33.5%) had a moderate impairment (5-8), and 25 (12.3%) a severe impairment (9-12). The mean LOS was 8.24 ± 5.75 days; nine patients died. A moderate-severe CONUT correlated with a higher LOS at the univariate [HR 1.86 (95% CI 13.9-3.47); p < 0.0001] and multivariate analysis [HR 1.52 (95% CI 1.10-2.09); p = 0.01]. The CONUT score was also a predictor of mortality, with an AUC of 0.831 (95% CI 0.680-0.982) and with an optimal cut-off at 8.5 points. Nutritional supplementation within 48 h from admission correlated with lower mortality [OR 0.12 (95% CI 0.02-0.56) p = 0.006]., Conclusions: CONUT is a reliable and simple predictor of LOS and in-hospital mortality in medical wards.

Surgery has been regarded as the only curative treatment for patients with small nonfunctional pancreatic neuroendocrine neoplasms (NF-PNENs) less than 2 cm. Due to the significant adverse event rates of surgery, the European Neuroendocrine Tumor Society issued guidelines favoring surveillance for those patients lacking criteria suggestive of an aggressive disease. Despite the above recommendations, a significant proportion of small NF-PNEN patients still undergo surgery. Recently, several studies have reported the safety and effectiveness of EUS-guided radiofrequency ablation (RFA) for the treatment of small NF-PNENs. The experience with EUS-RFA is, however, limited, but published results indicate a potential role as a minimally invasive alternative treatment for these patients, in particular in those in whom further progression is more probable, before they reach the absolute need for surgery. A step-up approach with EUS-RFA followed by surgery for the failure cases can become a valid option to be validated in clinical studies., Competing Interests: None

Competing Interests: Dr. Larghi is a consultant for Boston Scientific Corp. and Pentax Medical. He has also received research support from Medtronic. All other authors declare that they have no conflict of interest.

Background: Refeeding syndrome (RS) is a neglected, potentially fatal syndrome that occurs in malnourished patients undergoing rapid nutritional replenishment after a period of fasting. The American Society for Parenteral and Enteral Nutrition (ASPEN) recently released new criteria for RS risk and diagnosis. Real-life data on its incidence are still limited. Methods: We consecutively enrolled patients admitted to the Internal Medicine and Gastroenterology Unit of our center. The RS risk prevalence and incidence of RS were evaluated according to ASPEN. The length of stay (LOS), mortality, and re-admission rate within 30 days were assessed. Results: Among 203 admitted patients, 98 (48.3%) were at risk of RS; RS occurred in 38 patients (18.7% of the entire cohort). Patients diagnosed with RS had a higher mean LOS (12.5 days ± 7.9) than those who were not diagnosed with RS (7.1 ± 4.2) (p < 0.0001). Nine patients (4.4%) died. Body mass index (OR 0.82; 95% CI 0.69−0.97), RS diagnosis (OR 10.1; 95% CI 2.4−42.6), and medical nutritional support within 48 h (OR 0.12; 95% CI 0.02−0.56) were associated with mortality. Conclusions: RS incidence is high among clinical wards, influencing clinical outcomes. Awareness among clinicians is necessary to identify patients at risk and to support those developing this syndrome.

Background : The management of septic patients hospitalized in Internal Medicine wards represents a challenge due to their complexity and heterogeneity, and a high mortality rate. Among the available prognostic tools, procalcitonin (PCT) is considered a marker of bacterial infection. Furthermore, an association between vitamin D deficiency and poor sepsis-related outcomes has been described. Objectives: To evaluate the prognostic accuracy of two consecutive PCT determinations (Delta-PCT) and of vitamin D levels in predicting mortality in a population of patients with microbiological identified sepsis admitted to Internal Medicine wards. Methods : This is a sub-analysis of a previous prospective study. A total of 80 patients had at least two available consecutive PCT determinations, while 63 had also vitamin D. Delta-PCT was defined as a reduction of PCT > 50% after 48 h, >75% after 72 h, and >85% after 96 h. Mortality rate at 28- and 90-days were considered as main outcome. Results: Mortality rate was 18.7% at 28-days and 30.0% at 90-days. Baseline PCT levels did not differ between survived and deceased patients (28-days: p = 0.525; 90-days: p = 0.088). A significantly higher proportion of survived patients showed Delta-PCT (28-days: p = 0.002; 90-days: p < 0.001). Delta-PCT was associated with a lower 28-days ( p = 0.007; OR = 0.12, 95%CI 0.02-0.46) and 90-days mortality ( p = 0.001; OR = 0.17, 95%CI 0.06-0.48). A significantly higher proportion of deceased patients showed severe vitamin D deficiency (28-days: p = 0.047; 90-days: p = 0.049). Severe vitamin D deficiency was associated with a higher 28-days ( p = 0.058; OR = 3.95, 95%CI 1.04-19.43) and 90-days mortality ( p = 0.054; OR = 2.94, 95%CI 1.00-9.23). Conclusions : Delta-PCT and vitamin D represent two useful tests for predicting prognosis of septic patients admitted to Internal Medicine wards.

Background: and study aims Pancreatic neuroendocrine tumors (pNETs) can be difficult to detect intra-operatively. The aim of this paper is to evaluate the safety and efficacy of preoperative endoscopic ultrasound guided fine needle tattooing (EUS-FNT) to facilitate intra-operative detection of pNETs., Patients and Methods: Sixteen patients with pNETs (8 insulinoma and 8 non-functional pancreatic neuroendocrine tumors) underwent EUS-FNT. The procedure was carried out using the conventional curvilinear EUS. Tattooing was performed by intralesional injection of 1-2 mL of Spot® ink (Spot®, GI Supply, Comp Hill, PA, US) using a standard 22 gauge EUS-FNA needle., Results: All identified pNETs could be tattooed in one session. The procedure was well tolerated in all patients without any complication. The time interval between tattooing and surgery was between 1 and 565 days (mean of 52 days). Nine patients underwent open and seven laparoscopic surgery. The tattooed lesions could be recognized in all but one patient. In one patient, a small hematoma secondary to the EUS-FNT was observed. Pathological examination of the resection specimen showed local R0 resection in all cases, and no interference with the specimen evaluation was encountered., Conclusions: Our results suggest that EUS-guided FNT is a safe and useful method to mark preoperatively small (≤ 2 cm) pNETs.

Competing Interests: Dr. Larghi has received fees for lecture and training from Pentax Medical and Boston Scientific. He has also received research grant from Medtronic.Prof. Costamagna is a consultant for Olympus Medical, Boston Scientific Corp., Cook Medical.

Direct endoscopic necrosectomy (DEN) is a cumbersome, time-consuming procedure that can be necessary in cases of infected pancreatic walled-off necrosis (WON) not responding to endoscopic ultrasound (EUS)- guided drainage only. Until now, DEN has been performed with non-dedicated devices, thus requiring multiple, long-lasting sessions to achieve adequate clearance of necrotic content. These results in prolonged hospital stay, increased costs and have potential consequences for patients who must undergo multiple endoscopic interventions under sedation. We report four cases of DEN performed in patients with WON after EUS-guided drainage with the Endorotor system, a new morcellator device specifically designed to perform the procedure.

Background: Clostridioides difficile infection (CDI) is a risk factor for bloodstream infection (BSI). Fecal microbiota transplantation (FMT) is more effective than antibiotics in treating recurrent CDI, but its efficacy in preventing CDI-related BSI is uncertain., Objective: To assess incidence of primary BSI in patients with recurrent CDI treated with FMT versus antibiotics., Design: Prospective cohort study. Patients treated with FMT and those treated with antibiotics were matched on propensity score., Setting: Single academic medical center., Patients: 290 inpatients with recurrent CDI (57 patients per treatment in matched cohort)., Intervention: FMT or antibiotics., Measurements: The primary outcome was primary BSI within 90 days. Secondary outcomes were length of hospitalization and overall survival (OS) at 90 days., Results: Of the 290 patients, 109 were treated with FMT and 181 received antibiotics. Five patients in the FMT group and 40 in the antibiotic group developed BSI. Because of differences in the patients treated with FMT versus antibiotics in many baseline characteristics, including number of recurrences and CDI severity, comparative analyses were limited to the matched cohort. Risk for BSI was 23 percentage points (95% CI, 10 to 35 percentage points) lower in the FMT group; the FMT group also had 14 fewer days of hospitalization (CI, 9 to 20 fewer days) and a 32-percentage point increase in OS (CI, 16 to 47 percentage points) compared with the antibiotic group., Limitation: Nonrandomized study with potential for unmeasured or residual confounding; limited generalizability of the propensity score-matched cohort., Conclusion: In a propensity score-matched cohort, patients with recurrent CDI treated with FMT were less likely to develop primary BSI., Primary Funding Source: None.

Sepsis represents a global health problem in terms of morbidity, mortality, social and economic costs. Although usually managed in Intensive Care Units, sepsis showed an increased prevalence among Internal Medicine wards in the last decade. This is substantially due to the ageing of population and to multi-morbidity. These characteristics represent both a risk factor for sepsis and a relative contra-indication for the admission to Intensive Care Units. Although there is a lack of literature on the management of sepsis in Internal Medicine, the outcome of these patients seems to be gradually improving. This is due to Internists' increased adherence to guidelines and "bundles". The routine use of SOFA score helps physicians in the definition of septic patients, even if the optimal score has still to come. Point-of-care ultrasonography, lactates, procalcitonin and beta-d-glucan are of help for treatment optimization. The purpose of this narrative review is to focus on the management of sepsis in Internal Medicine departments, particularly on crucial concepts regarding diagnosis, risk assessment and treatment. Key Messages Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The prevalence of sepsis is constantly increasing, affecting more hospital patients than any other disease. At least half of patients affected by sepsis are admitted to Internal Medicine wards. Adherence to guidelines, routine use of clinical and lab scores and point-of-care ultrasonography are of help for early recognition of septic patients and treatment optimization.

Intralobar pulmonary sequestration is an uncommon congenital lung anomaly which consists of a mass of normal lung tissue not connected to the normal tracheobronchial tree and supplied by an anomalous systemic artery. Carbohydrate antigen 19-9 (CA 19-9) is widely accepted as a tumour marker for biliary, pancreatic and gastrointestinal cancer. However, CA 19-9 may also be increased in patients with benign disease. We describe the case of a 56-year-old woman with intralobar pulmonary sequestration who underwent unnecessary and extensive diagnostic abdominal examinations because of an increase in CA 19-9 serum levels., Learning Points: Knowledge of pulmonary sequestration causing increased serum CA 19-9 is important for the internist because it can help in the differential diagnosis even with neoplastic disease.Such awareness can also decrease the use of antibiotics.Familiarity with the condition can reduce the number of invasive examinations performed to exclude neoplasms of the gastrointestinal tract., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests.

Objectives: The use of synthetic cannabimimetics (SC; "spice" drugs) is increasing, especially among teenagers and young adults. In parallel with this, the number of studies describing intoxication episodes associated with psychotic symptoms in SC users is growing. We present both a systematic review of the related literature and a case report, which seems to highlight the existence of a possible association between SC use and psychosis., Methods: Some 223 relevant studies were here identified and reviewed. Out of these, 120 full text articles were assessed for eligibility, and 41 were finally included in the systematic review., Results: According to the available data from the studies here identified, SC's average age of users was 22.97 years, and the male/female ratio was 3.16:1. SC compounds most often reported in studies using biological specimen analysis were JWH-018, JWH-073, JWH-122, CP-47,497, and JWH-250. Mounting evidence seemed to suggest that psychotic symptoms such as hallucinations and delusions may occur in acute/chronic SC users., Conclusions: Although a clear causal link may not be here identified, the available evidence suggests that SC can trigger the onset of acute psychosis in vulnerable individuals and/or the exacerbation of psychotic episodes in those with a previous psychiatric history., (Copyright © 2013 John Wiley & Sons, Ltd.)

Growth factor-induced signaling by receptor tyrosine kinases (RTKs) plays a central role in embryonic development and in pathogenesis and, hence, is tightly controlled by several regulatory proteins. Recently, Sprouty, an inhibitor of Drosophila development-associated RTK signaling, has been discovered. Subsequently, four mammalian Sprouty homologues (Spry-1-4) have been identified. Here, we report the functional characterization of two of them, Spry-1 and -2, in endothelial cells. Overexpressed Spry-1 and -2 inhibit fibroblast growth factor- and vascular endothelial growth factor-induced proliferation and differentiation by repressing pathways leading to p42/44 mitogen-activating protein (MAP) kinase activation. In contrast, although epidermal growth factor-induced proliferation of endothelial cells was also inhibited by Spry-1 and -2, activation of p42/44 MAP kinase was not affected. Biochemical and immunofluorescence analysis of endogenous and overexpressed Spry-1 and -2 reveal that both Spry-1 and -2 are anchored to membranes by palmitoylation and associate with caveolin-1 in perinuclear and vesicular structures. They are phosphorylated on serine residues and, upon growth factor stimulation, a subset is recruited to the leading edge of the plasma membrane. The data indicate that mammalian Spry-1 and -2 are membrane-anchored proteins that negatively regulate angiogenesis-associated RTK signaling, possibly in a RTK-specific fashion.

Although the function of vascular endothelial growth factor in the induction of tumor angiogenesis is well understood, the role of a second group of angiogenic factors, the fibroblast growth factors (FGFs), remains elusive. We used a recombinant adenovirus expressing soluble FGF receptor (AdsFGFR) to interfere with FGF function in tumor angiogenesis. AdsFGFR repressed endothelial cell proliferation in vitro and inhibited tumor angiogenesis in an ex vivo bioassay, in which endothelial cells were cocultured with angiogenic tumor biopsies in a collagen gel. Moreover, AdsFGFR repressed tumor angiogenesis and hence tumor growth in vivo in allograft transplantation experiments. Whereas adenoviral expression of a soluble form of VEGF receptor 1 (AdsFlt) predominantly affected the initiation of tumor angiogenesis, soluble FGF receptor (sFGFR) appeared to impair the maintenance of tumor angiogenesis. The combination of sFGFR and soluble Flt exhibited a synergistic effect in the repression of tumor growth. Finally, i.v. injection of AdsFGFR resulted in a dramatic repression of tumor growth in a transgenic mouse model of pancreatic beta cell carcinogenesis. Similar to control infections with AdsFlt, tumor-associated vessel density was decreased, indicating that the expression of sFGFR impaired tumor angiogenesis. These data indicate that FGFs play a critical role in tumor angiogenesis.

Consumers' and family members' involvement was indispensable to create social support networks promoted by the comprehensive mental health services resulting from the closure and subsequent complete reconversion of the mental hospital in Trieste. Despite long term consumers' disabilities and the families' heavy burden the individuals' positive skills and resources can be, and indeed are, 'valorized'. Mutual help groups, social clubs and solidarity initiatives in the community were the outcome of the individual consumer's active daily involvement in the service therapeutic programmes and of stimulation of social and communication skills. The service considers these forms of supported self-organisation of consumers and family members as new instruments for further deinstitutionalisation and demedicalisation of therapeutic and rehabilitative practices, for the overcoming of social isolation and learning of coping strategies from the mutual experience.