Metformin and the Liver: Unlocking the Full Therapeutic Potential.

Metformin is a highly effective medication for managing type 2 diabetes mellitus. Recent studies have shown that it has significant therapeutic benefits in various organ systems, particularly the liver. Although the effects of metformin on metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis are still being debated, it has positive effects on cirrhosis and anti-tumoral properties, which can help prevent the development of hepatocellular carcinoma. Furthermore, it has been proven to improve insulin resistance and dyslipidaemia, commonly associated with liver diseases. While more studies are needed to fully determine the safety and effectiveness of metformin use in liver diseases, the results are highly promising. Indeed, metformin has a terrific potential for extending its full therapeutic properties beyond its traditional use in managing diabetes.

Untargeted metabolomics provide new insights into the implication of Lactobacillus helveticus strains isolated from natural whey starter in methylglyoxal-mediated browning.

Hard cheeses may occasionally show a brown discolouration during ripening due to multifactorial phenomena that involve bacteria and give rise to pyrazines arising from methylglyoxal. The present work aimed at developing a novel approach to investigate the role of natural starters in browning. To this object, 11 strains of L. helveticus were incubated in a medium containing 10 % rennet casein dissolved in whey, and then growth was monitored by measuring pH and number of genomes/mL. Browning was assessed through CIELab analysis, methylglyoxal production was determined by targeted mass spectrometry, and untargeted metabolomics was used to extrapolate marker compounds associated with browning discoloration. The medium allowed the growth of all the strains tested and differences in colour were observed, especially for strain A7 (ΔE* value 15.92 ± 0.27). Noteworthy, this strain was also the higher producer of methylglyoxal (2.44 µg/mL). Metabolomics highlighted pyrazines and ß-carboline compounds as markers of browning at 42 °C and 16 °C, respectively. Moreover, multivariate statistics pointed out differences in free amino acids and oligopeptides linked to proteolysis, while 1,2-propanediol and S-Lactoylglutathione suggested specific detoxification route in methylglyoxal-producing strains. Our model allowed detecting differences in browning amid strains, paving the way towards the study of individual L. helveticus strains to identify the variables leading to discoloration or to study the interaction between different strains in natural whey starters.

Similarities and differences between myocarditis following COVID-19 mRNA vaccine and multiple inflammatory syndrome with cardiac involvement in children.

Despite the multiple benefits of vaccination, cardiac adverse Events Following COVID-19 Immunization (c-AEFI) have been reported. These events as well as the severe cardiac involvement reported in Multisystem inflammatory syndrome in children (MIS-C) appear more frequent in young adult males. Herein, we firstly report on the inflammatory profiles of patients experiencing c-AEFI in comparison with age, pubertal age and gender matched MIS-C with cardiac involvement. Proteins related to systemic inflammation were found higher in MIS-C compared to c-AEFI, whereas a higher level in proteins related to myocardial injury was found in c-AEFI. In addition, higher levels of DHEAS, DHEA, and cortisone were found in c-AEFI which persisted at follow-up. No anti-heart muscle and anti-endothelial cell antibodies have been detected. Overall current comparative data showed a distinct inflammatory and androgens profile in c-AEFI patients which results to be well restricted on heart and to persist months after the acute event.

Higher Troponin Levels on Admission are associated With Persistent Cardiac Magnetic Resonance Lesions in Children Developing Myocarditis After mRNA-Based COVID-19 Vaccination.

BACKGROUND: Acute pericarditis/myocarditis is a rare complication of the mRNA-based vaccines and although mostly self-limiting, long-term sequelae remain unclear. METHODS: We enrolled all patients admitted to the emergency department between September 2021 and February 2022 meeting the CDC work case definition, with symptoms onset after mRNA-based COVID-19 vaccine. Alternative virologic causes were excluded. Clinical data, laboratory values, cardiologic evaluation, electrocardiogram (ECG), and echocardiogram (ECHO) were collected on admission, at discharge, and during follow-up in all patients. Cardiac Magnetic Resonance (CMR) was performed only in those with signs consistent with myocarditis. RESULTS: We observed 13 patients (11M and 2F), median age 15 years, affected by acute pericarditis/myocarditis after COVID-19 mRNA vaccination (11 after Comirnaty® and 2 after Spikevax®). Symptoms'onset occurred at a median of 5 days (range, 1 to 41 days) after receiving mRNA vaccine (13 Prizer 2 Moderna): 4 patients (31%) after the 1st dose, 6 (46%) after the 2nd, and 3 (23%) after 3rd dose. Increased levels of high-sensitive troponin T (hsTnT) (median 519,5 ng/mL) and N-terminal-pro hormone BNP (NT-proBNP) (median 268 pg/mL) and pathognomonic ECG and ECHO abnormalities were detected. On admission, 7 of 13 (54%) presented with myopericarditis, 3 (23%) with myocarditis, and 3 (23%) with pericarditis; CMR was performed in 5 patients upon pediatric cardiologist prescription and findings were consistent with myocarditis. At 12 weeks of follow-up, all but one patient (92%), still presenting mild pericardial effusion at ECHO, were asymptomatic with normal hsTnT and NT-proBNP levels and ECG. On CMR 6 of 9 patients showed persistent, although decreased, myocardial injury. Higher hsTnT levels on admission significantly correlated with persistent CMR lesions. CONCLUSION: Evidence of persistent CMR lesions highlights the need for a close and standardized follow-up for those patients who present high hsTnT levels on admission.

A rare case of sudden death due to endomyocardial fibrosis in Italy: A differential diagnosis with other causes of restrictive cardiomyopathy.

A 45-years-old Indonesian woman was admitted to the hospital with nausea, vomiting, abdominal pain and tachyarrhythmia. Atrial fibrillation was found at ECG, blood tests showed mild hepatic function alterations. Radiological exams showed bilateral pleural effusions, ascites, hepatomegaly. Systolic and diastolic functions of the left ventricle were found to be strongly compromised at US. Physical conditions and laboratory results worsened rapidly, followed by multi organ failure. Death occurred 28 hours after admission. An autopsy was performed to clarify the cause of death and investigated medical malpractice. External examination showed jaundice skin and at internal examination bilateral pleural and pericardial effusions, ascites, mild cardiomegaly, ventricular endocardial fibrosis, a thrombus in tight junction to the left ventricular wall and hepatic necrosis were observed. Histological investigations revealed a massive endomyocardial fibrosis, detected through Azan-Mallory and Verhoef-Van-Gieson stain, and confirmed the presence of hepatic and renal necrosis. Toxicological and microbiological investigations were negative. The cause of death was a global cardiac dysfunction caused by a restrictive cardiomyopathy in an Indonesian woman affected by an undiagnosed and asymptomatic endomyocardial fibrosis. In this case, autopsy and histopathological investigations were fundamental to diagnose an occult endomyocardial fibrosis, which is an idiopathic disorder of tropical and subtropical regions of the world. The not common incidence of this disease in our country and its unusual clinical onset were at first perceived as a medical malpractice from the relatives. Consequently, the clinical aspects of the case intertwine with the medicolegal implications concerning the undiagnosed disease and the causality with the patient's death.

Two Pediatric Cases of Multisystem Inflammatory Syndrome with Overlapping Neurological Involvement Following SARS-CoV-2 Vaccination and Unknown SARS-CoV2 Infection: The Importance of Pre-Vaccination History.

The SARS-CoV-2 vaccine roll-out has been successful around the world. However, there are increasing concerns about adverse events. We report two pediatric cases of Multisystem-Inflammatory-Syndrome (MIS-C) with neurological involvement that occurred after SARS-CoV-2 vaccination and unknown recent SARS-CoV-2 infection. Brain magnetic resonance revealed mild-encephalopathy with reversible-splenial-lesion in both cases and complete resolution within 4 weeks. In conclusion, this report aims to describe rare emerging clinical entities that can help pediatricians to make an early diagnosis and to provide appropriate treatment. Multisystem-Inflammatory-Syndromes following COVID-19 vaccination remain rare events. When a history of a recent contact with SARS-CoV-2 is present, a careful evaluation by the clinicians in charge of immunization activities is suggested prior to proceeding with the vaccination.

Pediatric Hospitalization for Varicella in an Italian Pediatric Hospital: How Much Does It Cost?

BACKGROUND: Varicella is a common pediatric infection. Even if it generally has a benign course, it may complicate and require hospitalization. The aim of our study was to estimate the acute hospitalization cost (AHC) for varicella in the acute phase in a pediatric population. METHODS: We calculated the AHC of pediatric patients admitted for varicella at Bambino Gesù Children Hospital, Rome, Italy, from 1 November 2005 to 1 November 2020. RESULTS: In the study period, 825 pediatric patients affected by varicella were hospitalized. The mean hospitalization cost was EUR 4015.35 (range from EUR 558.44 to EUR 42,608.00). Among patients, 55% were unvaccinable due to either their age or their immunosuppression status. They would benefit from herd immunity, reducing the overall AHC by EUR 182,196,506. Since the introduction of the compulsory vaccination against varicella in Italy, we observed a significant reduction in AHC cost of 60.6% in 2019 and of 93.5% in 2020. Finally, from the beginning of the COVID-19 pandemic, we documented a decline of 81.2% and 76.9% in varicella hospitalization, compared to 2018 and 2019, respectively. CONCLUSIONS: Varicella AHC is an important economic and health assessment point and can be useful for improving preventive strategies.

A case report on potential postmortem redistribution of furanyl fentanyl and 4-ANPP.

Fatal intoxications due to accidental or voluntary intake of synthetic opioids represent an actual emerging issue. We report a case where we have analyzed furanyl fentanyl and its metabolite 4-anilino-N-phenetyl-piperidine (4-ANPP) in blood, urine, gastric content, bile and cerebrospinal fluid. In this case, a 53-year-old man was found dead at home with a needle still inserted in a vein; a plastic bag containing a white powder (later identified as a furanyl fentanyl-based product) was discovered in the room. Biological samples were collected during autopsy and extracted/purified onto a SPE cartridge before instrumental analysis. Qualitative and quantitative analyses were performed by LC-MS/MS on peripheral and cardiac blood, urine, cerebrospinal fluid (CSF), bile and gastric content. Furanyl fentanyl was identified and quantified in all the biological fluids collected. Interestingly, gastric content revealed an unexpected high amount of furanyl fentanyl; yet, cardiac blood and femoral blood provided significantly different concentrations (11.8 and 2.7 ng/g respectively). The concentration of furanyl fentanyl in CSF was similar to that measured in femoral blood (2.6 ng/mL), thus confirming that CSF could be a good alternative biological fluid whenever a postmortem redistribution is suspected. Concentrations of 93.5, 50.4, 171.7, 41.9, 10.2 ng/mL(g) were measured for 4-ANPP in cardiac blood, femoral blood, urine, bile and cerebrospinal fluid, respectively. The outcomes from the presented case report suggest that the two substances have been not only injected intravenously, but probably also ingested by the man. Fentanyl derivative and its precursor seemed to undergo an extensive postmortem redistribution.

Pediatric meningococcocal meningitis in the acute phase: how much does it cost?

BACKGROUND: Meningococcal meningitis (MM) is known to be responsible of high cost for the Public Health Administration. Aim of the work is to calculate the costs for the hospitalization of pediatric patients affected by MM. METHODS: We calculate the costs for the hospitalization of pediatric patients affected by MM in the acute phase (HAP) over a nine year period. We performed a MEDLINE search to verify the cost of MM HAP reported in other studies. RESULTS: At Bambino Gesù Children Hospital, the median cost of HAP was of 12,604 euro (range from 9203 to 35,050 euro). Comparing our data with the previous studies, we find out similar results of approximately 16,750 euro (range 12,000-20,000 euro). DISCUSSION: Despite the relative rarety of the disease, MM is associated to direct high cost of HAP. CONCLUSIONS: Hospital costs are an important end-point in health economic evaluation of the disease and may be useful to policy makers and health economists to understand the potential benefit of improving meningococcal vaccination programmes.

Radiology of Mummies.

In the past, autoptic examinations were usually performed for research. This type of examination, for obvious reasons, did not appeal to paleopathologists as these procedures potentially damaged the finds destined to musealization. Since the discovery of X-ray, radiology has been used to study mummies as a noninvasive technique. The radiology of mummies allows us to discover pathologies, to elaborate on the type of ritual mummification for the artificial embalming, to comprehend the diagenetic process that guaranteed a natural mummification, or to conclude anthropological identification. We present a review on the latest studies on mummies that have shown that the radiological approach has been essential to conduct research.

Biomechanical analysis of a femur fracture in osteoarchaeology: Reconstruction of pathomechanics, treatment and gait.

In paleopathology, biomechanics allows us to investigate traumas in ancient skeletal remains. The aim of our current research is to reconstruct pathomechanics, treatment and gait of an individual from a Late Medieval femur with evident bone callus. In particular, to reconstruct the dynamic of the trauma that caused the injury and the adopted therapeutic measures, taking into account medical knowledges of that time. The femur was recovered during the archaeological investigation in the Sanctuary of Sacro Monte, Varese (Northern Italy). Classical physical anthropological methods and CT scans were used for macroscopic and radiological measurements of the bone. Finally, the reconstruction of the static and dynamic functional outcomes of the lesion were performed by Observation Gait Analysis (OGA) procedure. The femur shows an important callus at the middle third proximal of the shaft. The antemortem fracture was oblique and caused by a direct trauma probably related to occupational activities. The alignment of the segments in the frontal plane lead us to assume that the fracture was treated and the femur was immobilized with splints. The overlap and the angle of the segments indicate that the subject was not submitted to traction or fracture reduction. Good bone remodeling and consolidation of the fracture suggest that the subject had gradually led to the resumption of load and walking, although with important effects on posture and movement. The use of the OGA allows us to highlight the subject's kind of gait after healing.

To Save a Corpse from Decomposition - the Purpose of Petrification in the Second Half of the 19th Century.

We present this interesting note on the petrification of corpses, published in 1890 in the Italian Journal of Natural Sciences. After a brief review of the oldest forms of embalming, the author, Michele Martone, presents petrification as the only way to obtain the perfect conservation of the corpse. CONCLUSION: This scientific note presents some considerations regarding the constant search of humanity to arrest, if not the death of a person, the decomposition of their body.

Unusual case of traumatic carotid artery dissection occurred during a work-related activity. A case report.

Carotid artery dissection secondary to cervical blunt trauma is a rare and potentially life-threatening condition that can cause a variety of clinical presentations, including stroke, headache, neck pain, tinnitus, Horner syndrome and cranial neuropathies and is associated with long-term sequelae. We report a case of a 49-year-old industrial vehicles mechanic who was projected to the ground by the explosion of the tire of a heavy truck he was inflating. In the following hours he presented various neurological signs and symptoms and was admitted to the Emergency Department. During hospitalization the patient underwent clinical and instrumental investigations with AngioCT and MR finding of left internal carotid artery dissection in correspondence of its cervical segment and three acute ischemic lesions in the left temporal, parietal and occipital lobes. Medical management was successful and the patient was discharged from the hospital three weeks after the admission but he wasn't able to get back to work due to neurological sequelae. This case report illustrates that traumatic carotid artery dissection, although rare, should be considered in patients who present neurological symptoms after an explosion, can meet the criteria for a work-related injury and may lead to a permanent decrease in the ability to work.

A case of Paget from a Northern Italy medieval necropolis.

An excavation conducted in 2002 by the Lombardy Archaeological Heritage in the St. Giulio Church (Cassano Magnago-Northern Italy) revealed an adult skeleton with an important alteration of the left femur. The femur, longer than the contralateral, exhibited an expansion of the full diaphysis; the surface was coarsened and porous. In cross section, it appeared that almost all the cortical bone had been converted into cancellous bone. Macroscopic and radiological alterations are suggestive of the monostotic form of Paget's disease, a chronic disorder, characterized by focal areas of excessive osteoclastic bone resorption followed by a secondary increase in osteoblastic bone formation. Differential diagnosis is complex for Paget's disease, requiring histological analysis, which revealed a thickened and disorganized trabecular pattern with thick cement lines. Such features, resembling to a mosaic pattern, are typical of Paget's disease.

A foetal tile from an archaeological site: anthropological investigation of human remains recovered in a medieval cemetery in Northern Italy.

BACKGROUND: The recovery of foetal remains is very sporadic in archaeology, especially due the scarce degree of bone mineralisation. This paper presents the singular archaeological discovery of a foetal tile preserving the bone remains, object of our anthropological examination. MATERIALS AND METHODS: The foetal tile was discovered during an archaeological excavation in a medieval site (Northern Italy). The tile was analysed by CT scan and later, human remains were anthropologically examined. RESULTS: The archaeological investigation revealed a special ritual destined to foetuses while forensic anthropological analysis allowed estimating the gestational age near to 21-24 weeks.

Correction to: Neuropsychological and internalizing problems in acute central nervous system infections: a 1 year follow-up.

CORRECTION: The original article [1] contained an error mistakenly carried forward by the Production department handling this article whereby all authors' names were incorrectly inverted. The original article has now been corrected to reflect the correct names of all authors.