Pre-hospital glycemia as a biomarker for in-hospital all-cause mortality in diabetic patients - a pilot study.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) presents a significant healthcare challenge, with considerable economic ramifications. While blood glucose management and long-term metabolic target setting for home care and outpatient treatment follow established procedures, the approach for short-term targets during hospitalization varies due to a lack of clinical consensus. Our study aims to elucidate the impact of pre-hospitalization and intra-hospitalization glycemic indexes on in-hospital survival rates in individuals with T2DM, addressing this notable gap in the current literature. METHODS: In this pilot study involving 120 hospitalized diabetic patients, we used advanced machine learning and classical statistical methods to identify variables for predicting hospitalization outcomes. We first developed a 30-day mortality risk classifier leveraging AdaBoost-FAS, a state-of-the-art ensemble machine learning method for tabular data. We then analyzed the feature relevance to identify the key predictive variables among the glycemic and routine clinical variables the model bases its predictions on. Next, we conducted detailed statistical analyses to shed light on the relationship between such variables and mortality risk. Finally, based on such analyses, we introduced a novel index, the ratio of intra-hospital glycemic variability to pre-hospitalization glycemic mean, to better characterize and stratify the diabetic population. RESULTS: Our findings underscore the importance of personalized approaches to glycemic management during hospitalization. The introduced index, alongside advanced predictive modeling, provides valuable insights for optimizing patient care. In particular, together with in-hospital glycemic variability, it is able to discriminate between patients with higher and lower mortality rates, highlighting the importance of tightly controlling not only pre-hospital but also in-hospital glycemic levels. CONCLUSIONS: Despite the pilot nature and modest sample size, this study marks the beginning of exploration into personalized glycemic control for hospitalized patients with T2DM. Pre-hospital blood glucose levels and related variables derived from it can serve as biomarkers for all-cause mortality during hospitalization.

Impact of Modified Frailty Index on Readmissions Following Surgery for NSCLC.

BACKGROUND: Analyzing the risk factors that predict readmissions can potentially lead to more individualized patient care. The 11-factor modified frailty index is a valuable tool for predicting postoperative outcomes following surgery. The objective of this study is to determine whether the frailty index can effectively predict readmissions within 90 days after lung resection surgery in cancer patients within a single health care institution. METHODS: Patients who underwent elective pulmonary resection for nonsmall cell lung cancer (NSCLC) between January 2012 and December 2020 were selected from the hospital's database. Patients who were readmitted after surgery were compared to those who were not, based on their data. Propensity score matching was employed to enhance sample homogeneity, and further analyses were conducted on this newly balanced sample. RESULTS: A total of 439 patients, with an age range of 68 to 77 and a mean age of 72, were identified. Among them, 55 patients (12.5%) experienced unplanned readmissions within 90 days, with an average hospital stay of 29.4 days. Respiratory failure, pneumonia, and cardiac issues accounted for approximately 67% of these readmissions. After propensity score matching, it was evident that frail patients had a significantly higher risk of readmission. Additionally, frail patients had a higher incidence of postoperative complications and exhibited poorer survival outcomes with statistical significance. CONCLUSION: The 11-item modified frailty index is a reliable predictor of readmissions following pulmonary resection in NSCLC patients. Furthermore, it is significantly associated with both survival and postoperative complications.

Migration rate using fully covered metal stent in anastomotic strictures after liver transplantation: Results from the BASALT study group.

BACKGROUND AND STUDY AIM: The traditional endoscopic therapy of anastomotic strictures (AS) after orthotopic liver transplantation (OLT) is multiple ERCPs with the insertion of an increasing number of plastic stents side-by-side. Fully covered self-expanding metal stents (cSEMS) could be a valuable option to decrease the number of procedures needed or non-responders to plastic stents. This study aims to retrospectively analyse the results of AS endoscopic treatment by cSEMS and to identify any factors associated with its success. PATIENTS AND METHODS: Ninety-one patients (mean age 55.9 ± 7.6 SD; 73 males) from nine Italian transplantation centres, had a cSEMS positioned for post-OLT-AS between 2007 and 2017. Forty-nine (54%) patients were treated with cSEMS as a second-line treatment. RESULTS: All the procedures were successfully performed without immediate complications. After ERCP, adverse events occurred in 11% of cases (2 moderate pancreatitis and 8 cholangitis). In 49 patients (54%), cSEMSs migrated. After cSEMS removal, 46 patients (51%) needed further endoscopic (45 patients) or radiological (1 patient) treatments to solve the AS. Lastly, seven patients underwent surgery. Multivariable stepwise logistic regression showed that cSEMS migration was the only factor associated with further treatments (OR 2.6, 95% CI 1.0-6.6; p value 0.03); cSEMS implantation before 12 months from OLT was associated with stent migration (OR 5.2, 95% CI 1.7-16.0; p value 0.004). CONCLUSIONS: cSEMS appears to be a safe tool to treat AS. cSEMS migration is the main limitation to its routinary implantation and needs to be prevented, probably with the use of new generation anti-migration stents.

Infection Control Practices and Outcomes of Endoscopy Units in the Lombardy Region of Italy: A Survey From the Italian Society of Digestive Endoscopy During COVID-19 Spread.

GOALS: The present survey from the Italian Society of Digestive Endoscopy (SIED-Società Italiana di Endoscopia Digestiva) was aimed at reporting infection control practice and outcomes at Digestive Endoscopy Units in a high-incidence area. BACKGROUND: Lombardy was the Italian region with the highest coronavirus disease-2019 (COVID-19) prevalence, at the end of March 2020 accounting for 20% of all worldwide deaths. Joint Gastro-Intestinal societies released recommendations for Endoscopy Units to reduce the risk of the contagion. However, there are few data from high-prevalence areas on adherence to these recommendations and on their efficacy. METHODS: A survey was designed by the Lombardy section of SIED to analyze (a) changes in activity and organization, (b) adherence to recommendations, (c) rate of health care professionals' (HCP) infection during the COVID-19 outbreak. RESULTS: In total, 35/61 invited centers (57.4%) participated; most modified activities were according to recommendations and had filtering face piece 2/filtering face piece 3 and water-repellent gowns available, but few had negative-pressure rooms or provided telephonic follow-up; 15% of HCPs called in sick and 6% had confirmed COVID-19. There was a trend (P=0.07) toward different confirmed COVID-19 rates among endoscopists (7.9%), nurses (6.6%), intermediate-care technicians (3.4%), and administrative personnel (2.2%). There was no correlation between the rate of sick HCPs and COVID-19 incidence in the provinces and personal protective equipment availability and use, whereas an inverse correlation with hospital volume was found. CONCLUSIONS: Adherence to recommendations was rather good, though a minority were able to follow all recommendations. Confirmed COVID-19 seemed higher among endoscopists and nurses, suggesting that activities in the endoscopy rooms are at considerable viral spread risk.

COVID-19 inpatients with gastrointestinal onset: sex and care needs' differences in the district of Ferrara, Italy.

BACKGROUND: COVID-19 is characterized by interstitial pneumonia, but a presentation of the disease with digestive symptoms only may occur. This work was aimed at evaluating: (1) the prevalence of presentation with digestive symptoms only in our cohort of COVID-19 inpatients; (2) differences between patients with and without gastrointestinal onset; (3) differences among males and females with gastrointestinal presentation; (4) outcomes of the groups of subjects with and without gastrointestinal onset. METHOD: We retrospectively divided the patients hospitalized with COVID-19 into two groups: (1) the one with digestive symptoms (DSG) and (2) the other without digestive symptoms (NDSG). We compared the subjects of DSG with those of NDSG and males with females in the DSG group only, in terms of demographics (age, sex), inflammation and organ damage indexes, length of stay, in-hospital and 100-day mortality. RESULTS: The prevalence of gastrointestinal symptoms at presentation was 12.5%. The DSG group showed a prevalence of females, and these tended to a shorter hospital stay; DSG patients were younger and with a higher load of comorbidities, but no differences concerning inflammation and organ damage indexes, need for intensification of care, in-hospital and 100-day mortality were detected. Among DSG patients, males were younger than females, more comorbid, with higher serum CRP and showed a longer length of hospital stay. Survival functions of DSG patients, in general, are more favourable than those of NDSG if adjusted for sex, age and comorbidities. CONCLUSIONS: (1) The prevalence of gastrointestinal presentation among hospitalized COVID-19 patients was 12.5%; (2) DSG patients were on average younger, more comorbid and with a prevalence of females, with a shorter hospital stay; (3) in the DSG group, males had a higher Charlson Comorbidity Score and needed a longer hospital stay; (4) DSG subjects seem to survive longer than those of the NDSG group.

Systolic Anterior Motion (SAM) Complicating Mitral Valve Repair: Current Concepts of Intraoperative and Postoperative Management.

Mitral valve repair is the gold standard for treatment of degenerative mitral regurgitation, such as that caused by leaflet prolapse, flail or annular dilatation. A variety of surgical techniques allow surgeons to achieve a high rate of success with mitral valve repair, even in complex cases, and mitral valve repair is associated with better long-term outcomes than valve replacement. However, in the setting of mitral valve surgical repair, systolic anterior motion (SAM) is a complication that determines the dynamic anterior movement of the mitral valve towards the interventricular septum during systole, and creates a left ventricular outflow tract obstruction associated with residual mitral regurgitation. Awareness of risk factors for SAM influences operative planning for repair. Predictors of SAM are known and can be definitively evaluated with intraoperative transesophageal echocardiography, but SAM still complicates mitral valve repair and, if untreated, negatively impacts short-term and long-term outcomes. A stepwise approach in SAM correction is advocated, consisting of medical therapy with aggressive volume-loading and beta-adrenoceptor blockade, but severe or persistent SAM requires surgical revision with a second cross-clamping or a redo procedure. The correct choice of surgical technique requires a deep understanding of the anatomical substrate of SAM, as SAM can be due to different mechanisms that require tailored surgical correction to avoid ineffective or potentially dangerous procedures. This paper reviews the mechanisms and predictors of SAM and summarizes the current concepts of intraoperative and postoperative SAM management.

Pressure ulcers in cardiac surgery: Few clinical studies, difficult risk assessment, and profound clinical implications.

Pressure ulcers (PUs) are a common complication after cardiac surgery, with almost one third of patients suffering from PUs during hospitalisation. Because of the burden that PUs exert on both the patients and the health care system, prevention is of utmost importance. The first step in successful prevention, however, includes the identification of the main features that render patients prone to PU development. Cardiac surgery population is not adequately addressed in current clinical trials and studies. Few studies focused specifically on cardiac surgery patients, but the majority included cardiac surgery patients within a heterogeneous population of acute or critical care patients. Therefore, additional research is warranted to understand the unique risk profile of patients undergoing cardiac surgery. Intraoperative risk factors that affect tissue tolerance have not been thoroughly investigated but are likely to play an important role, which might explain the epidemiology of a PU. Further research is also needed to better comprehend the risk of PUs among cardiac surgery patients and to design effective and tailored preventative measures with the help of newer tools for risk assessment.

Celiac Disease Diagnosis Without Biopsy: Is a 10× ULN Antitransglutaminase Result Suitable for a Chemiluminescence Method?

OBJECTIVES: 2012 European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines allow to establish a celiac disease diagnosis without duodenal biopsy in symptomatic pediatric patients with antitissue transglutaminase (anti-tTG) titers >10 times the upper limit of normal. For some years now, new chemiluminescence immunoassays have been made available: it is important to establish the clinical performance of anti-tTG and to determine the cut-off best suited to predict Marsh ≥2 to avoid gastrointestinal endoscopy not only in children, but also in the adult population. METHODS: A total of 2565 patients performed duodenal biopsy from July 2012 to September 2016; we selected all the patients who had undergone QUANTA Flash anti-tTG immunoglobulin A (IgA) within -3 months of duodenal biopsy and before the start of gluten-free diet. A total of 827 patients fulfilled the criteria for selection. RESULTS: Using a cut-off of 20 chemiluminescent unit (CU; area under the curve: 0.995), sensitivity, specificity, positive, and negative predictive value were 98.2%, 98.4%, 97.9%, and 98.6%, respectively. For the correlation with Marsh ≥2, in the pediatric population, positive predictive values (PPV) were 92.1%, 99%, and 100% at 200 CU (10×), 560 CU (28×), and 1000 CU (50×), respectively. In the adult population PPV was 94.2%, 98.2%, and 100% at 200 CU (10×), 350 CU (15×), and 400 CU (20×). CONCLUSIONS: Sensitivity, specificity, positive, and negative predictive value of QUANTA Flash h-tTG IgA were excellent. The cut-off providing an optimized PPV for histological lesions compatible for celiac disease (Marsh ≥2) for the QUANTA Flash h-tTG IgA is 350 CU (15×) in adult and 560 CU (28×) in children.

A prognostic index for risk stratification for acute heart failure and death in subjects with ischemic cardiomyopathy and cardiac defibrillator.

To propose a clinical prognostic index for death and heart failure in patients with ischemic cardiomyopathy implanted with an ICD. This prospective study included 192 consecutive patients (age 68 ± 10) recruited from 2004 to 2009 and implanted with an ICD for MADIT II criteria. All patients performed 24-h ambulatory blood pressure monitoring after discharge and common haematological samples. The prognostic index (PI) was built according to the formula: 120 - age + mean 24 h systolic blood pressure--(creatinine 9 10). Other variables were assessed: EF, haemoglobin concentration, mean 24 h heart rate and diastolic blood pressure, sodium level, pacing mode and diabetes. Non-arrhythmic cardiac death and new hospitalizations for heart failure during 1-year follow-up were the combined end point. A total of 48 events (25%) occurred during the follow-up: 7 cardiac deaths and 41 hospitalizations for acute heart failure. Cox proportional hazards model showed that PI was the only predictor of events (HR = 0.96; CI 95% 0.944­0.976, p < 0.0001). ROC curve showed that PI best cut-off was 144, with AUC 0.79, p < 0.0001; sensitivity 77%, specificity 74%, positive predictive value 50%, negative predictive value 90%. PI was predictive of events in a clinical setting where EF had no predictive value. PI works according to the rule ''the lower the worse''. The high negative predictive value (90%) of PI allows to identify subjects at lower risk for death and heart failure. PI can be a practical tool to stratify risk in ischemic cardiomyopathy.

Decision support systems for environmental management: a case study on wastewater from agriculture.

Dealing with spatial decision problems means combining and transforming geographical data (input) into a resultant decision (output), interfacing a Geographical Information System (GIS) with Multi-Criteria Decision Analysis (MCDA) methods. The conventional MCDA approach assumes the spatial homogeneity of alternatives within the case study area, although it is often unrealistic. On the other side, GIS provides excellent data acquisition, storage, manipulation and analysis capabilities, but in the case of a value structure analysis this capability is lower. For these reasons, several studies in the last twenty years have given attention to MCDA-GIS integration and to the development of Spatial Decision Support Systems (SDSS). Hitherto, most of these applications are based only on a formal integration between the two approaches. In this paper, we propose a complete MCDA-GIS integration with a plurality of MCDA methodologies, grouped in a suite. More precisely, we considered an open-source GIS (GRASS GIS 6.4) and a modular package including five MCDA modules based on five different methodologies. The methods included are: ELECTRE I, Fuzzy set, REGIME analysis, Analytic Hierarchy Process and Dominance-based Rough Set Approach. Thanks to the modular nature of the package, it is possible to add new methods without modifying the existing structure. To present the suite, we applied each module to the same case study, making comparisons. The strong points of the MCDA-GIS integration we developed are its open-source setting and the user friendly interface, both thanks to GRASS GIS, and the use of raster data. Moreover, our suite is a genuine case of perfect integration, where the spatial nature of criteria is always present.

Assessing Rural Sustainable Development potentialities using a Dominance-based Rough Set Approach.

Rural Development is a priority in Europe and it is supported by specific, financial programmes. At the same time, sustainability is the key word for the European Union to construct programmes and policies for all human activities. However, measuring sustainability of rural areas is not easy, due to their particular features. The improvement of knowledge on sustainability in rural areas is important to build long term policies and strategies for those territories. The objective of this study is the development of a decision support system based on the Dominance-based Rough Set Approach (DRSA), to assess the level of Rural Sustainable Development in specific areas. We used DRSA to analyze the level of sustainability of the 92 municipalities of the Region of Umbria, Italy. The results were synthesized in a final ranking, taking into account the equilibrium and the integration between development and sustainability of each municipality. DRSA showed a high potential in the context of management or planning, and for supporting Decision Makers. DRSA is able to give a ranking as well as an explanation of the main factors driving sustainable development in rural areas.

Dyslipidemia, Cholangitis and Fatty Liver Disease: The Close Underexplored Relationship: A Narrative Review.

In assessing individual cardiovascular risk, dyslipidemia is known for emerging as a pivotal factor significantly contributing to major cardiovascular events. However, dyslipidemic patients frequently present with concurrent medical conditions, each with varying frequencies of occurrence; cholangitis, whether acute or chronic, and hepatic steatosis, along with associated conditions, are strongly associated with specific forms of dyslipidemia, and these associations are reasonably well elucidated. Conversely, evidence linking biliary disease to hepatic steatosis is comparatively scant. This narrative review aims to bridge this gap in knowledge concerning the interplay between dyslipidemia, cholangitis, and hepatic steatosis. By addressing this gap, clinicians can better identify patients at heightened risk of future major cardiovascular events, facilitating more targeted interventions and management strategies. The review delves into the intricate relationships between dyslipidemia and these hepatic and biliary clinical conditions, shedding light on potential mechanisms underlying their associations. Understanding these complex interactions is crucial for optimizing cardiovascular risk assessment as well and devising tailored treatment approaches for patients with dyslipidemia and associated hepatic disorders. Moreover, elucidating these connections empowers clinicians with the knowledge needed to navigate the multifaceted landscape of cardiovascular risk assessment and management effectively. By exploring the intricate relationships between dyslipidemia, cholangitis, and hepatic steatosis (without forgetting the possible clinical consequences of hepatic steatosis itself), this review not only contributes to the existing body of knowledge but also offers insights into potential avenues for further research and clinical practice. Thus, it serves as a valuable resource for healthcare professionals striving to enhance patient care and outcomes in the context of cardiovascular disease and associated hepatic conditions.

Update on Classic and Novel Approaches in Metastatic Triple-Negative Breast Cancer Treatment: A Comprehensive Review.

Triple-negative breast cancer (TNBC) accounts for almost 15% of all diagnosed breast cancers and often presents high rates of relapses and metastases, with generally poor prognosis despite multiple lines of treatment. Immunotherapy has radically changed the approach of clinicians towards TNBC in the last two to three years, even if targeted and specific therapeutic options are still missing; this unmet need is further justified by the extreme molecular and clinical heterogeneity of this subtype of breast cancer and by the weak response to both single-agent and combined therapies. In March 2023, the National Comprehensive Cancer Network (NCCN), the main association of cancer centers in the United States, released the last clinical practice guidelines, with an update on classic and novel approaches in the field of breast cancer. The purpose of this comprehensive review is to summarize the latest findings in the setting of metastatic TNBC treatment, focusing on each category of drugs approved by the Food and Drug Administration (FDA) and included in the NCCN guidelines. We also introduce part of the latest published studies, which have reported new and promising molecules able to specifically target some of the biomarkers involved in TNBC pathogenesis. We searched the PubMed and Scopus databases for free full texts reported in the literature of the last 5 years, using the words "triple-negative breast cancer" or "TNBC" or "basal-like". The articles were analyzed by the authors independently and double-blindly, and a total of 114 articles were included in the review.

A rare case of jejunal Vanek's tumor causing intussusception in an adult: a case report and comprehensive literature overview.

Inflammatory fibroid polyp, or Vanek's tumor, is an uncommon benign small bowel tumor and a rare cause of intussusception in adults. This case involves a 62-year-old man with persistent abdominal pain, diagnosed with jejunoileal intussusception. A 4 cm inflammatory fibroid polyp was discovered during surgery, leading to distal jejunal resection. Despite the rarity of adult intussusceptions, they should be considered in abdominal pain diagnoses. The optimal management approach, whether en bloc resection or initial reduction with limited resection, remains debated.

The Impact of GLP-1 RAs and DPP-4is on Hospitalisation and Mortality in the COVID-19 Era: A Two-Year Observational Study.

Novel antidiabetic drugs have the ability to produce anti-inflammatory effects regardless of their glucose-lowering action. For this reason, these molecules (including GLP-1 RAs and DPP-4is) were hypothesized to be effective against COVID-19, which is characterized by cytokines hyperactivity and multiorgan inflammation. The aim of our work is to explore the potential protective role of GLP-1 RAs and DPP-4is in COVID-19 (with the disease intended to be a model of an acute stressor) and non-COVID-19 patients over a two-year observation period. Retrospective and one-versus-one analyses were conducted to assess the impact of antidiabetic drugs on the need for hospitalization (in both COVID-19- and non-COVID-19-related cases), in-hospital mortality, and two-year mortality. Logistic regression analyses were conducted to identify the variables associated with these outcomes. Additionally, log-rank tests were used to plot survival curves for each group of subjects, based on their antidiabetic treatment. The performed analyses revealed that despite similar hospitalization rates, subjects undergoing home therapy with GLP-1 RAs exhibited significantly lower mortality rates, even over a two-year period. These individuals demonstrated improved survival estimates both within hospital and non-hospital settings, even during a longer observation period.

Case report: Tissue positivity for SARS-CoV-2 in a preterm born infant death of thrombosis: possible intrauterine transmission.

Intrauterine transmission of SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) is still matter of debate among scientists and there is limited information concerning this aspect of research. This could lead to severe complications of the growing fetus and, theoretically, of the newborn as well. We report the case of a male infant of 1,100 grams, born at 27th week of gestation to a SARS-CoV-2 mother, tested negative for viral detection at delivery. He was immediately admitted to neonatal Intensive Care Unit (ICU) for severe complications, where he died after 37 days by pulmonary embolism and thrombosis of the superior vena cava. After autopsy, SARS-CoV-2 N-protein and Spike RBD were detected in several tissues, particularly in the esophagus, stomach, spleen, and heart, with a significantly higher H-Score than the placenta. In conclusion, immunohistochemical analysis demonstrated SARS-CoV-2 NP and Spike RBD positivity in different tissues suggesting a possible intrauterine transmission. Newborn thrombo-embolism could be a complication of SARS-CoV-2 infection as observed in adult patients.

Rapid Assessment of COVID-19 Mortality Risk with GASS Classifiers.

Risk prediction models are fundamental to effectively triage incoming COVID-19 patients. However, current triaging methods often have poor predictive performance, are based on variables that are expensive to measure, and often lead to hard-to-interpret decisions. We introduce two new classification methods that can predict COVID-19 mortality risk from the automatic analysis of routine clinical variables with high accuracy and interpretability. SVM22-GASS and Clinical-GASS classifiers leverage machine learning methods and clinical expertise, respectively. Both were developed using a derivation cohort of 499 patients from the first wave of the pandemic and were validated with an independent validation cohort of 250 patients from the second pandemic phase. The Clinical-GASS classifier is a threshold-based classifier that leverages the General Assessment of SARS-CoV-2 Severity (GASS) score, a COVID-19-specific clinical score that recently showed its effectiveness in predicting the COVID-19 mortality risk. The SVM22-GASS model is a binary classifier that non-linearly processes clinical data using a Support Vector Machine (SVM). In this study, we show that SMV22-GASS was able to predict the mortality risk of the validation cohort with an AUC of 0.87 and an accuracy of 0.88, better than most scores previously developed. Similarly, the Clinical-GASS classifier predicted the mortality risk of the validation cohort with an AUC of 0.77 and an accuracy of 0.78, on par with other established and emerging machine-learning-based methods. Our results demonstrate the feasibility of accurate COVID-19 mortality risk prediction using only routine clinical variables, readily collected in the early stages of hospital admission.

Protective Effects of Home T2DM Treatment with Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Co-transporter-2 Inhibitors Against Intensive Care Unit Admission and Mortality in the Acute Phase of the COVID-19 Pandemic: A Retrospective Observational Study in Italy.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a relevant risk factor for severe forms of COVID-19 (SARS coronavrus 2 [SARS-CoV-2] disease 2019), and calls for caution because of the high prevalence of T2DM worldwide and the high mortality rates observed in patients with T2DM who are infected with SARS-CoV-2. People with T2DM often take dipeptidyl peptidase-4 inhibitors (DPP-4is), glucagon-like peptide-1 receptor agonists (GLP-1ras), or sodium-glucose co-transporter-2 inhibitors (SGLT-2is), all of which have clear anti-inflammatory effects. The study aimed to compare (i) the severity and duration of hospital stay between patients with T2DM categorized by pre-hospitalization drug class utilization and (ii) the COVID-19-related death rates of those three groups. METHODS: We designed an observational, retrospective, multi-center, population-based study and extracted the hospital admission data from the health care records of 1916 T2DM patients over 18 years old who were previously on GLP-1ra, SGLT-2i, or DPP-4i monotherapy and were hospitalized for COVID-19 (diagnosis based on ICD.9/10 codes) between January 2020 and December 2021 in 14 hospitals throughout Italy. We analyzed general data, pre-admission treatment schedules, date of admission or transfer to the intensive care unit (ICU) (i.e., the index date; taken as a marker of increased COVID-19 disease severity), and death (if it had occurred). Statistics analyzed the impact of drug classes on in-hospital mortality using propensity score logistic regressions for (i) those admitted to intensive care and (ii) those not admitted to intensive care, with a random match procedure used to generate a 1:1 comparison without diabetes cohort replacement for each drug therapy group by applying the nearest neighbor method. After propensity score matching, we checked the balance achieved across selected variables if a balance was ever achieved. We then used propensity score matching between the three drug classes to assemble a sample in which each patient receiving an SGLT-2i was matched to one on a GLP-1ra, and each patient on a DPP-4i was matched to one on a GLP-1ra, adjusting for covariates. We finally used GLP-1ras as references in the logistic regression. RESULTS: The overall mortality rate (MR) of the patients was 14.29%. The MR in patients with COVID was 53.62%, and it was as high as 42.42% in the case of associated T2DM, regardless of any glucose-lowering therapy. In those on DPP-4is, there was excess mortality; in those treated with GLP-1ras and SGLT-2is, the death rate was significantly lower, i.e., almost a quarter of the overall mortality observed in COVID-19 patients with T2DM. Indeed, the odds ratio (OR) in the logistic regression resulted in an extremely high risk of in-hospital death in individuals previously treated with DPP-4is [incidence rate (IR) 4.02, 95% confidence interval (CI) 2.2-5.7) and only a slight, nonsignificantly higher risk in those previously treated with SGLT-2is (IR 1.42, 95% CI 0.6-2.1) compared to those on GLP-1ras. Moreover, the longer the stay, the higher the death rate, which ranged from 22.3% for ≤ 3-day stays to 40.3% for 4- to 14-day stays (p < 0.01 vs. the former) and 77.4% for over-14-day stays (p < 0.001 vs. both the others). DISCUSSION: Our data do not support a protective role of DPP-4is; indeed, this role has already been questioned due to previous observations. However, the data do show a strong protective effect of SGLT-2is and GLP-1ras. Beyond lowering circulating glucose levels, those two drug classes were found to exert marked anti-phlogistic effects: SGLT-2is increased adiponectin and reduced urate, leptin, and insulin concentrations, thus positively affecting overall low-grade inflammation, and GLP-1ras may also greatly help at the lung tissue level, meaning that their extra-glycemic effects extend well beyond those acknowledged in the cardiovascular and renal fields. CONCLUSIONS: The aforedescribed observational clinical data relating to a population of Italian inpatients with T2DM suggest that GLP-1ras and SGLT-2is can be considered antidiabetic drugs of choice against COVID-19, and might even prove beneficial in the event of any upcoming pandemic that has life-threatening effects on the pulmonary and cardiovascular systems.

Acute Esophageal Necrosis as a Rare Complication of Metabolic Acidosis in a Diabetic Patient: A Case Report.

BACKGROUND Acute esophageal necrosis, or Gurvits syndrome, is a rare clinical process often secondary to a systemic low-flow state. It can be caused by several medical conditions, and it is thought to arise from a combination of impaired mucosal barrier and chemical and ischemic insults to the esophagus. Acute esophageal necrosis usually presents with severe complications due to delayed diagnosis and only rarely has surgical indications. We present a case of Gurvits syndrome, presumably triggered by metabolic acidosis in a diabetic patient. CASE REPORT A 61-year-old man with history of hypertension and type 2 diabetes mellitus treated with metformin, canagliflozin, glimepiride, and pioglitazone came to our attention with persistent vomiting, odynophagia, chest pain after each meal, and progressive weight loss. Arterial blood analysis showed mild metabolic acidosis, while the first esophagogastroduodenoscopy performed revealed a circumferential black appearance of the esophageal mucosa, as in concentric necrosis of the distal esophagus with possible fungal superinfection. Brushing cytology confirmed the infection by Candida spp. and the patient was treated with intravenous fluconazole. The second esophagogastroduodenoscopy, performed after 2 weeks, showed almost complete healing of the esophageal mucosa; in this case, biopsy confirmed mucosal ischemia and necrosis, without showing deep impairment of the mucosa by fungal agents. CONCLUSIONS Due to its high lethality, often caused by the underlying medical diseases, acute esophageal disease should be considered in the differential diagnosis of digestive symptoms, even without upper gastrointestinal bleeding. Prompt diagnosis and treatment of contextual collateral conditions can help clinicians to avoid the worst outcomes of the disease. Among the causative factors of metabolic acidosis leading to esophageal necrosis we recognized metformin and dapagliflozin.