Prothrombin time predicts steroid response in severe alcohol-related hepatitis.

BACKGROUND AND AIMS: Alcohol-related hepatitis (AH) is the most severe form of acute alcohol-related liver disease. Maddrey's discriminant function ≥32 defines the severe form of AH, which is associated with a high mortality. Steroid therapy represents the main medical treatment that may reduce short-term mortality. Lille score at day 7 assesses the therapeutic response to steroid therapy. At present, no parameters able to predict the response to steroid therapy have been highlighted. The aim of the present study was to evaluate if baseline prothrombin time (BPT) could predict the response to steroid in severe AH (sAH). METHODS: Patients consecutively admitted in two Italian Liver Units, from 2017 to 2022, suffering from sAH were included. Data were collected prospectively. In order to evaluate if BPT could predict steroid response, we assessed the correlation between BPT using the Lille score at day 7. RESULTS: A total of 52 patients received steroid treatment were enrolled in the study. The response to therapy was assessed by Lille score at day 7. Responders were 34 patients (65%), non-responders 18 patients (34%). BPT significantly predicted the steroid response (p < .001). The likelihood of not responding to the steroid therapy was significantly higher in patients with higher BPT (OR = 2.954). CONCLUSIONS: BPT value predicted steroid response in patients with sAH. BPT could quickly identify non-responder patients to steroid therapy, reducing the risk of infections and it could allow the early evaluation for liver transplantation.

Identifying Predictors Associated with Risk of Death or Admission to Intensive Care Unit in Internal Medicine Patients with Sepsis: A Comparison of Statistical Models and Machine Learning Algorithms.

Background: Sepsis is a time-dependent disease: the early recognition of patients at risk for poor outcome is mandatory. Aim: To identify prognostic predictors of the risk of death or admission to intensive care units in a consecutive sample of septic patients, comparing different statistical models and machine learning algorithms. Methods: Retrospective study including 148 patients discharged from an Italian internal medicine unit with a diagnosis of sepsis/septic shock and microbiological identification. Results: Of the total, 37 (25.0%) patients reached the composite outcome. The sequential organ failure assessment (SOFA) score at admission (odds ratio (OR): 1.83; 95% confidence interval (CI): 1.41-2.39; p < 0.001), delta SOFA (OR: 1.64; 95% CI: 1.28-2.10; p < 0.001), and the alert, verbal, pain, unresponsive (AVPU) status (OR: 5.96; 95% CI: 2.13-16.67; p < 0.001) were identified through the multivariable logistic model as independent predictors of the composite outcome. The area under the receiver operating characteristic curve (AUC) was 0.894; 95% CI: 0.840-0.948. In addition, different statistical models and machine learning algorithms identified further predictive variables: delta quick-SOFA, delta-procalcitonin, mortality in emergency department sepsis, mean arterial pressure, and the Glasgow Coma Scale. The cross-validated multivariable logistic model with the least absolute shrinkage and selection operator (LASSO) penalty identified 5 predictors; and recursive partitioning and regression tree (RPART) identified 4 predictors with higher AUC (0.915 and 0.917, respectively); the random forest (RF) approach, including all evaluated variables, obtained the highest AUC (0.978). All models' results were well calibrated. Conclusions: Although structurally different, each model identified similar predictive covariates. The classical multivariable logistic regression model was the most parsimonious and calibrated one, while RPART was the easiest to interpret clinically. Finally, LASSO and RF were the costliest in terms of number of variables identified.

Small nonfunctional pancreatic neuroendocrine neoplasms: Time for a step-up treatment approach?

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.

Sepsis: New Challenges and Future Perspectives for an Evolving Disease-Precision Medicine Is the Way!

Sepsis still remains the leading cause of in-hospital death in the world [...].

Risk of burnout and stress in physicians working in a COVID team: A longitudinal survey.

BACKGROUND AND AIMS: The COVID-19 pandemic represents a source of stress and potential burnout for many physicians. This single-site survey aimed at assessing perceived stress and risk to develop burnout syndrome among physicians operating in COVID wards. METHODS: This longitudinal survey evaluated stress and burnout in 51 physicians operating in the COVID team of Gemelli Hospital, Italy. Participants were asked to complete the Maslach Burnout Inventory (MBI) and the Perceived Stress Questionnaire on a short run (PSQs) (referring to the past 7 days) at baseline (T0) and then for four weeks (T1-T4). Perceived Stress Questionnaire on a long run (PSQl) (referring to the past 2 years) was completed only at T0. RESULTS: Compared with physicians board-certified in internal medicine, those board-certified in other disciplines showed higher scores for the Emotional Exhaustion (EE) score of the MBI scale (P < .001). Depersonalisation (DP) score showed a reduction over time (P = .002). Attending physicians scored lower than the resident physicians on the DP scale (P = .048) and higher than resident physicians on the Personal Accomplishment (PA) scale (P = .04). PSQl predicted higher scores on the EE scale (P = .003), DP scale (P = .003) and lower scores on the PA scale (P < .001). PSQs showed a reduction over time (P = .03). Attending physicians had a lower PSQs score compared with the resident physicians (P = .04). CONCLUSIONS: Medical specialty and clinical position could represent risk factors for the development of burnout in a COVID team. In these preliminary results, physicians board-certified in internal medicine showed lower risk of developing EE during the entire course of the study.

Neutropenic Enterocolitis and Sepsis: Towards the Definition of a Pathologic Profile.

Background: Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a nosological entity that is difficult to diagnose and whose pathogenesis is not fully known to date. Initially described in pediatric patients with leukemic diseases, it has been gradually reported in adults with hematological malignancies and non-hematological conditions, such as leukemia, lymphoma, multiple myeloma, aplastic anemia, and also myelodysplastic syndromes, as well as being associated with other immunosuppressive causes such as AIDS treatment, therapy for solid tumors, and organ transplantation. Therefore, it is associated with high mortality due to the rapid evolution in worse clinical pictures: rapid progression to ischemia, necrosis, hemorrhage, perforation, multisystem organ failure, and sepsis. Case report: A case report is included to exemplify the clinical profile of patients with NE who develop sepsis. Literature Review: To identify a specific profile of subjects affected by neutropenic enterocolitis and the entity of the clinical condition most frequently associated with septic evolution, a systematic review of the literature was conducted. The inclusion criteria were as follows: English language, full-text availability, human subjects, and adult subjects. Finally, the papers were selected after the evaluation of the title and abstract to evaluate their congruity with the subject of this manuscript. Following these procedures, 19 eligible empirical studies were included in the present review. Conclusions: Despite the recent interest and the growing number of publications targeting sepsis and intending to identify biomarkers useful for its diagnosis, prognosis, and for the understanding of its pathogenesis, and especially for multi-organ dysfunction, and despite the extensive research period of the literature review, the number of publications on the topic "neutropenic enterocolitis and sepsis" appears to be very small. In any case, the extrapolated data allowed us to conclude that the integration of medical history, clinical and laboratory data, radiological imaging, and macroscopic and histological investigations can allow us to identify a specific pathological profile.

Delta-Procalcitonin and Vitamin D Can Predict Mortality of Internal Medicine Patients with Microbiological Identified Sepsis.

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.

Sarilumab use in severe SARS-CoV-2 pneumonia.

BACKGROUND: Interleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia. METHODS: 53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead. FINDINGS: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO2/FiO2:146(IQR:120-212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO2/FiO2: 112(IQR:100-141.5)].Within the medical wards, 7(17·9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89·7% of medical inpatients significantly improved (46·1% after 24 h, 61·5% after 3 days), 70·6% were discharged from the hospital and 85·7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64·2% were discharged from ICU to the ward and 35·8% were still alive at the last follow-up. Overall mortality rate was 5·7%. INTERPRETATION: IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical outcome and good safety.

New Strategies for Treatment of Sepsis.

Sepsis represents a major global health concern and is one of the most feared complications for hospitalized patients, being the cause, directly or indirectly, of about half of all hospital deaths. According to the last definition, sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and defined septic shock as a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to significantly increase mortality. Sepsis is a time-dependent disease and requires a prompt recognition and a standardized treatment. The Special Issue "New Strategies for Treatment of Sepsis" has been thought to connect the experience of physicians involved in the diagnosis, management, and treatment of sepsis at every stage of disease, from emergency departments to general and intensive wards. The focus will be pointed on new approaches to this syndrome, such as early recognition based on clinical features and biomarkers, management in non-ICUs, non-invasive treatment strategies, including non-antimicrobial agents, and, of course, invasive approaches. This Special Issue will highlight the many different facets of sepsis, seen through the eyes of different specialists. We hope to spread the knowledge of a new blueprint for treatment.

Make Mission Impossible Feasible: The Experience of a Multidisciplinary Team Providing Treatment for Alcohol Use Disorder to Homeless Individuals.

AIM: People experiencing homelessness are often excluded from treatment programs for alcohol use disorder (AUD). The goal of this study was to describe the impact of a multidisciplinary treatment program on alcohol consumption and social reintegration in individuals with AUD experiencing homelessness. METHODS: Thirty-one individuals with AUD experiencing homelessness were admitted to an inpatient unit for 5-6 days for clinical evaluation and to treat potential alcohol withdrawal syndrome. A group of volunteers, in collaboration with the Community of Sant'Egidio, provided social support aimed to reintegrate patients. After inpatient discharge, all patients were followed as outpatients. Alcohol intake (number drinks/day), craving and clinical evaluation were assessed at each outpatient visit. Biological markers of alcohol use were evaluated at enrollment (T0), at 6 months (T1) and 12 months (T2). RESULTS: Compared with T0, patients at T1 showed a significant reduction in alcohol consumption [10 (3-24) vs 2 (0-10); P = 0.015] and in γ-glutamyl-transpeptidase [187 (78-365) vs 98 (74-254); P = 0.0021]. The reduction in alcohol intake was more pronounced in patients with any housing condition [10 (3-20) vs 1 (0-8); P = 0.008]. Similarly, compared with T0, patients at T2 showed significant reduction in alcohol consumption [10 (3-24) vs 0 (0-15); P = 0.001], more pronounced in patients with any housing condition [10 (3-20) vs 0 (0-2); P = 0.006]. Moreover, at T2 patients showed a significant reduction in γ-glutamyl-transpeptidase [187 (78-365) vs 97 (74-189); P = 0.002] and in mean cell volume [100.2 (95-103.6) vs 98.3 (95-102); P = 0.042]. CONCLUSION: Patients experiencing homelessness may benefit from a multidisciplinary treatment program for AUD. Strategies able to facilitate and support their social reintegration and housing can improve treatment outcomes.

The use of procalcitonin for the management of sepsis in Internal Medicine wards: current evidence.

Procalcitonin (PCT) is a circulating polypeptide produced in response to bacterial infections. Studies conducted in the Intensive Care Unit (ICU) setting have demonstrated its utility as a biomarker of bacterial infection and sepsis. Thus, PCT is widely used to distinguish between sepsis and SIRS, and to guide antibiotic therapy. At present sepsis represents a frequent diagnosis among patients admitted to internal medicine (IM) departments. Basing on the knowledge derived from ICU studies, the use of PCT has become routine in non-intensive wards, contributing to improve the management of sepsis. However, some differences between the two populations of patients - the IM being older, affected by multiple chronic comorbidities and lacking of invasive monitoring - could limit the generalizability of ICU results. Most of the studies on PCT conducted in the IM setting have focused on chronic obstructive pulmonary disease, pneumonia and sepsis. Although PCT represents one of the best biomarker available in routine clinical practice, there are uncertainties on the optimal cut-offs to be used for starting or discontinuing antibiotic treatment in patients with suspected bacterial infection or sepsis, for predicting outcome and on the role of PCT variations during antibiotic treatment. Moreover, several diseases can produce an elevation of PCT levels, thus producing false positive results. This represents a narrative review summarizing current evidences on PCT for the management of sepsis in an Internal Medicine wards, highlighting differences with ICU, with a special focus on the role of PCT variations as predictor of outcomes in non-ICU wards.

Baclofen for the Treatment of Alcohol Use Disorder in Patients With Liver Cirrhosis: 10 Years After the First Evidence.

Alcohol Use Disorder (AUD) is a chronic and relapsing condition characterized by harmful alcohol intake and behavioral-cognitive changes. AUD is the most common cause of liver disease in the Western world. Alcohol abstinence is the cornerstone of therapy in alcoholic patients affected with liver disease. Medical recommendations, brief motivational interventions and psychosocial approach are essential pieces of the treatment for these patients; however, their efficacy alone may not be enough to achieve total alcohol abstinence. The addition of pharmacological treatment could improve clinical outcomes in AUD patients. Moreover, pharmacological treatments for AUD are limited in patients with advanced liver disease, since impaired liver function affects drugs metabolism and could increase the risk of drugs-related hepatotoxicity. At present, only baclofen has been tested in RCTs in patients with advanced liver disease. This medication was effective to reduce alcohol intake, to promote alcohol abstinence and to prevent relapse in AUD patients affected by liver cirrhosis. In addition, the drug showed a safe profile in these patients. In this review, clinical studies about efficacy and safety of baclofen administration in patients with AUD and advanced liver disease will be reviewed. Open question about the most appropriate dose of the drug, duration of the treatment and need of additional studies will also be discussed.

Sepsis in Internal Medicine wards: current knowledge, uncertainties and new approaches for management optimization.

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.