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Takotsubo syndrome (TS) is a transient cardiac condition characterized by regional systolic dysfunction, often precipitated by emotional or physical stressors. The pathophysiology of TS is not fully understood, but evidence suggests that it may be influenced by multiple factors. We present a case of TS following a traumatic left humerus fracture in an 82-year-old male patient with hypertension. Diagnosis was confirmed through comprehensive clinical evaluation, identification of ECG abnormalities, echocardiographic findings, and exclusion of other diseases. The patient’s management consisted of β-blockers, aspirin, and supportive care. Despite initial concerns, the patient's clinical course was uneventful, illustrating the various presentations of TS. This case emphasizes that TS can occur as a result of a traumatic event, particularly among older individuals with comorbidities. Early recognition and appropriate management are essential for optimizing outcomes.

IntroductionThe accurate distinction between periprosthetic joint infections (PJI) and aseptic failures (AF) is of paramount importance due to differences in treatment. However, this could be challenging by using the current criteria. Various synovial fluid biomarkers are being assessed to improve the diagnostic accuracy. Myeloperoxidase (MPO), an enzyme contained in the granules of neutrophils, may be a promising biomarker for PJI.MethodsSynovial fluids of 99 patients (n = 65 PJI according to EBJIS criteria; n = 34 AF) were collected in two specialized orthopedic centers. PJI were divided into acute (n = 33) and low-grade (n = 32) according to previously published classification. An activity assay specific for active MPO was performed in each sample. Ability of MPO to correctly discriminate patients with PJI from AF was determined by ROC analysis. The best discriminating cut-off value was determined by calculating the J Youden index. For all analyses, a P value < 0.05 was considered statistically significant.ResultsActive MPO was higher in PJI than AF (P < 0.0001). The ROC analysis revealed a significant area under the curve (AUC: 0.86; 95% CI: 0.78–0.93, P < 0.0001). A cut-off value of 561.9 U/mL, with good sensitivity (0.69) and specificity (0.88), discriminated between AF and PJI (accuracy 75.76%, 95% CI: 66.11–83.81%, positive likelihood ratio 5.88, 95% CI: 2.31–14.98 and negative likelihood ratio 0.35, 95%CI: 0.24–0.51). No difference in MPO levels was found between acute and chronic low-grade PJI.ConclusionThe proposed assay appears to be a reliable and affordable tool for detecting the active MPO in synovial fluid, with promising characteristics of sensitivity and specificity in discriminating both acute and low-grade PJI from AF. Further studies are needed to confirm MPO diagnostic cut-off values and validate their use in the routine clinical practice.

Abstract Background Pediatric chronic intestinal pseudo-obstruction (PIPO) is a rare disease characterized by symptoms and radiological signs suggestive of intestinal obstruction, in the absence of lumen-occluding lesions. It results from an extremely severe impairment of propulsive motility. The intestinal endocrine system (IES) jointly with the enteric nervous system (ENS) regulates secreto-motor functions via different hormones and bioactive messengers/neurotransmitters. The neurotransmitter 5-hydroxytryptamine (5-HT) (or serotonin) is linked to intestinal peristalsis and secretory reflexes. Gut microbiota and its interplay with ENS affect 5-HT synthesis, release, and the subsequent serotonin receptor activation. To date, the interplay between 5-HT and gut microbiota in PIPO remains largely unclear. This study aimed to assess correlations between mucosa associated microbiota (MAM), intestinal serotonin-related genes expression in PIPO. To this purpose, biopsies of the colon, ileum and duodenum have been collected from 7 PIPO patients, and 7 age-/sex-matched healthy controls. After DNA extraction, the MAM was assessed by next generation sequencing (NGS) of the V3-V4 region of the bacterial RNA 16 S, on an Illumina Miseq platform. The expression of genes implicated in serotoninergic pathway (TPH1, SLC6A4, 5-HTR3 and 5-HTR4) was established by qPCR, and correlations with MAM and clinical parameters of PIPO have been evaluated. Results Our results revealed that PIPO patients exhibit a MAM with a different composition and with dysbiosis, i.e. with a lower biodiversity and fewer less connected species with a greater number of non-synergistic relationships, compared to controls. qPCR results revealed modifications in the expression of serotonin-related intestinal genes in PIPO patients, when compared to controls. Correlation analysis do not reveal any kind of connection. Conclusions For the first time, we report in PIPO patients a specific MAM associated to underlying pathology and an altered intestinal serotonin pathway. A possible dysfunction of the serotonin pathway, possibly related to or triggered by an altered microbiota, may contribute to dysmotility in PIPO patients. The results of our pilot study provide the basis for new biomarkers and innovative therapies targeting the microbiota or serotonin pathways in PIPO patients.

Abstract Background Pulmonary embolism (PE) is one of the most common causes of death from cardiovascular disease. Although deep vein thrombosis (DVT) is the leading cause of PE, its prognostic role is unclear. This study investigated the incidence and prognostic value of DVT in predicting in‐hospital mortality (IHM) in patients admitted from the emergency department (ED) for PE. Methods This retrospective cohort study was conducted in the ED of a third‐level university hospital. Patients over 18 years admitted for PE between 1 January 2018 and 31 December 2022 were included. Results Five hundred and thirty patients (mean age 73.13 years, 6% IHM) were included. 69.1% of cases had DVT (36.4% unilateral femoral vein, 3.6% bilateral, 39.1% unilateral popliteal vein, 2.8% bilateral, 45.7% distal vein thrombosis and 7.4% iliocaval involvement). Patients who died in hospital had a higher Pulmonary Embolism Severity Index (PESI) (138.6 vs. 99.65, p II, right ventricular dysfunction, increased blood markers of myocardial damage and involvement of the iliocaval venous axis were independent predictors of IHM on multivariate analysis. Conclusions Although further studies are needed to confirm the prognostic role of DVT at PE, involvement of the iliocaval venous axis should considered to be a sign of a higher risk of IHM and may be a key factor in prognostic stratification.

Sex and gender are fundamental health determinants and their role as modifiers of treatment response is increasingly recognized. Norepinephrine is a cornerstone of septic shock management and its use is based on the highest level of evidence compared to dopamine. The related 2021 Surviving Sepsis Campaign (SCC) recommendation is presumably applicable to both females and males; however, a sex- and gender-based analysis is lacking, thus not allowing generalizable conclusions. This paper was aimed at exploring whether sex- and gender-disaggregated data are available in the evidence supporting this recommendation. For all the studies underpinning it, four pairs of authors, including a woman and a man, extracted data concerning sex and gender, according to the Sex and Gender Equity in Research guidelines. Nine manuscripts were included with an overall population of 2126 patients, of which 43.2% were females. No sex analysis was performed and gender was never reported. In conclusion, the present manuscript highlighted that the clinical studies underlying the SCC recommendation of NE administration in septic shock have neglected the likely role of sex and gender as modifiers of treatment response, thus missing the opportunity of sex- and gender-specific guidelines.

Upper Gastro-Intestinal Bleeding (UGIB) spans from minor bleeding to life-threatening events. Identification of early signs of shock, proper management of hemodynamically unstable patients, and correct risk stratification are essential for an appropriate diagnostic workup and therapy. This case reports a young man admitted to the emergency department with haematemesis. His medical history was unremarkable, without any risk factors for gastrointestinal bleeding. A few hours after admission, further episodes of haematemesis occurred, and the patient's condition rapidly deteriorated to irreversible shock. A contrast-enhanced computed tomography (CECT) revealed morphological features of chronic liver disease and oesophagal varices. The patient underwent upper gastrointestinal endoscopy, confirming oesophagal varices with massive bleeding. Although promptly applied, endoscopic hemostasis was ineffective, and the patient died twenty-four hours after admission. Based on this case, we reviewed the diagnostic and therapeutic approaches for patients with massive UGIB and provided a practical approach to this life-threatening emergency.

Objective According to the 2019 European Society of Cardiology (ESC) guidelines on pulmonary embolism (PE), prognosis is calculated using the Pulmonary Embolism Severity Index (PESI), a complex score with debated validity, or simplified PESI (sPESI). We have developed and validated a new risk score for in-hospital mortality (IHM) of patients with PE in the emergency department. Methods This retrospective, dual-center cohort study was conducted in the emergency departments of two third-level university hospitals. Patients aged >18 years with a contrast-enhanced computed tomography-confirmed PE were included. Clinical variables and laboratory tests were evaluated blindly to IHM. Multivariable logistic regression was performed to identify the new score’s predictors, and the new score was compared with the PESI, sPESI, and shock index. Results A total of 1,358 patients were included in this study: 586 in the derivation cohort and 772 in the validation cohort, with a global 10.6% of IHM. The PATHOS scores were developed using independent variables to predict mortality: platelet count, age, troponin, heart rate, oxygenation, and systolic blood pressure. The PATHOS score showed good calibration and high discrimination, with an area under the receiver operating characteristics curve of 0.83 (95% confidence interval [CI], 0.77–0.89) in the derivation population and 0.74 (95% CI, 0.68–0.80) in the validation cohort, which is significantly higher than the PESI, sPESI, and shock index in both cohorts (P

Background: Renowned since ancient times for its medical properties, liquorice is nowadays mainly used for flavoring candies or soft drinks. Continuous intake of large amounts of liquorice is a widely known cause of pseudo-hyperaldosteronism leading to hypertension and hypokalemia. These manifestations are usually mild, although in some cases may generate life-threatening complications, i.e., arrhythmias, muscle paralysis, rhabdomyolysis, and coma. In addition, liquorice has an important estrogenic-like activity. Methods: We summarized the current knowledge about liquorice and reviewed 104 case reports in both the English and Italian languages from inception to June 2023 concerning complications due to an excess of liquorice intake. Results: In contrast to most published data, female sex and old age do not appear to be risk factors. However, hypertension and electrolyte imbalance (mainly hypokalemia) are prevalent features. The detection of glycyrrhetinic acid in blood is very uncommon, and the diagnosis is essentially based on an accurate history taking. Conclusions: Although there is not a significant mortality rate, liquorice toxicity often requires hospitalization and therefore represents a significant health concern. Major pharmaceutical drug regulatory authorities should solicit public awareness about the potentially dangerous effects caused by excessive use of liquorice.

The aim of this study was to investigate whether the presence of Staphylococcus aureus (SA) producing the Panton–Valentine leukocidin (PVL) affects the outcome of Prosthetic Joint Infection (PJI). Patients with acute and chronic PJI sustained by SA were prospectively enrolled at the orthopedic unit of “Casa di Cura Santa Maria Maddalena”, from January 2019 to October 2021. PJI diagnosis was reached according to the diagnostic criteria of the International Consensus Meeting on PJI of Philadelphia. Synovial fluid obtained via joint aspirations was collected in order to isolate SA. The detection of PVL was performed via real-time quantitative PCR (RT-qPCR). The outcome assessment was performed using the criteria of the Delphi-based International Multidisciplinary Consensus. Twelve cases of PJI caused by SA were included. Nine (75%) cases were acute PJI treated using debridement, antibiotic and implant retention (DAIR); the remaining three (25%) were chronic PJI treated using two-stage (n = 2) and one-stage revision (n = 1), respectively. The SA strains that tested positive for PVL genes were 5/12 (41.6%,). Treatment failure was documented in three cases of acute PJI treated using DAIR, all supported by SA–PVL strains (p < 0.045). The remaining two cases were chronic PJI treated with a revision arthroplasty (one and two stage, respectively), with a 100% eradication rate in a medium follow-up of 24 months. Although a small case series, our study showed a 100% failure rate in acute PJI, probably caused by SA PVL-producing strains treated conservatively (p < 0.04). In this setting, toxin research should guide radical surgical treatment and targeted antibiotic therapy.

Sepsis is a time-dependent and life-threating condition related to macro- and micro-circulatory impairment leading to anaerobic metabolism and lactate increase. We assessed the prognostic accuracy of capillary lactates (CLs) vs. serum ones (SLs) on 48-h and 7-day mortality in patients with suspected sepsis. This observational, prospective, single-centre study was conducted between October 2021 and May 2022. Inclusion criteria were: (i) suspect of infection; (ii) qSOFA ≥ 2; (iii) age ≥ 18 years; (iv) signed informed consent. CLs were assessed with LactateProTM2®. 203 patients were included: 19 (9.3%) died within 48 h from admission to the Emergency Department, while 28 (13.8%) within 7 days. Patients deceased within 48 h (vs. survived) had higher CLs (19.3 vs. 5 mmol/L, p < 0.001) and SLs (6.5 vs. 1.1 mmol/L, p = 0.001). The best CLs predictive cut-off for 48-h mortality was 16.8 mmol/L (72.22% sensitivity, 94.02% specificity). Patients within 7 days had higher CLs (11.5 vs. 5 mmol/L, p = 0.020) than SLs (2.75 vs. 1.1 mmol/L, p < 0.001). The multivariate analysis confirmed CLs and SLs as independent predictors of 48-h and 7-day mortality. CLs can be a reliable tool for their inexpensiveness, rapidity and reliability in identifying septic patients at high risk of short-term mortality.

Coronavirus Disease 2019 (COVID-19) is a life-threatening disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus which was first reported in late 2019 in China, from where it then spread worldwide [...]

Celiac disease (CD) is an autoimmune disorder caused by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms (e.g., diarrhea, bloating, and chronic abdominal pain), CD may also present with a broad spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. The etiopathology of bone lesions in CD is multifactorial and other conditions, rather than mineral and vitamin D malabsorption, may affect skeletal health, especially those related to the endocrine system. Here, we describe CD-induced osteoporosis in an attempt to enlighten new and less-known aspects, such as the influence of the intestinal microbiome and sex-related differences on bone health. This review describes the role of CD in the development of skeletal alterations to provide physicians with an updated overview on this debated topic and to improve the management of osteoporosis in CD.

Secretory IgA (sIgA), which may play an important role in the early defense against SARS-CoV-2 infection, were detected in the eye of COVID-19 patients. However, an evaluation of the sIgA response in the tears of vaccinated or non-vaccinated COVID-19 subjects is still lacking. Aimed at characterizing sIgA mucosal immunity in the eye, this study analyzed tear samples from 77 COVID-19 patients, including 63 vaccinated and 14 non-vaccinated subjects. The groups showed similar epidemiological features, but as expected, differences were observed in the percentage of asymptomatic/pauci-symptomatic subjects in the vaccinated vs. non-vaccinated cohort (46% and 29% of the total, respectively). Consistent with this, ocular sIgA values, evaluated by a specific quantitative ELISA assay, were remarkably different in vaccinated vs. non-vaccinated group for both frequency (69.8% vs. 57.1%, respectively) and titer (1372.3 U/mL vs. 143.7 U/mL, respectively; p = 0.01), which was significantly differently elevated depending on the type of administered vaccine. The data show for the first time significant differences of available vaccines to elicit sIgA response in the eye and suggest that quantitative tear-based sIgA tests may potentially serve as a rapid and easily accessible biomarker for the assessment of the development of a protective mucosal immunity toward SARS-CoV-2.

Background: Since 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) has caused millions of deaths worldwide and is the second most serious pandemic after the Spanish flu. Despite SARS-CoV-2 infection having a dominant effect on morbidity and life-threatening outcomes, the role of bacterial co-infection in patients with COVID-19 is poorly understood. The present study aimed to verify the existence of bacterial co-infections and their possible role as cofactors worsening COVID-19-related clinical manifestations. Methods: All patients with suspected SARS-CoV-infection, hospitalised in COVID-19 wards at the Sant’Anna University Hospital of Ferrara, were retrospectively included in this single-centre study and their specific bacterial serologies were assessed. Univariate and logistic regression analyses were performed. Results: A total of 1204 individual records were retrieved. Among them, 959 were excluded because of a negative nasopharyngeal swab or missing data; of the eligible 245 patients, 51 were co-infected. Compared to patients with SARS-CoV-2 infection alone, those with Chlamydia pneumoniae or Mycoplasma pneumoniae co-infections had worse respiratory/radiological features and more intensive care unit admissions. However, the co-infection did not result in a higher mortality rate. Conclusions: The present study, comparing clinical, laboratory and radiological findings between patients with COVID-19 vs. those with co-infections (C. pneumoniae or M. pneumoniae) showed that, on admission, these features were worse in co-infected patients, although the mortality rate did not differ between the two groups.

COVID-19 emerged in late 2019 in China and quickly spread across the globe, causing over 521 million cases of infection and 6.26 million deaths to date. After 2 years, numerous advances have been made. First of all, the preventive vaccine, which has been implemented in record time, is effective in more than 95% of cases. Additionally, in the diagnostic field, there are numerous molecular and antigenic diagnostic kits that are equipped with high sensitivity and specificity. Real Time-PCR-based assays for the detection of viral RNA are currently considered the gold-standard method for SARS-CoV-2 diagnosis and can be used efficiently on pooled nasopharyngeal, or oropharyngeal samples for widespread screening. Moreover, additional, and more advanced molecular methods such as droplet-digital PCR (ddPCR), clustered regularly interspaced short palindromic repeats (CRISPR) and next-generation sequencing (NGS), are currently under development to detect the SARS-CoV-2 RNA. However, as the number of subjects infected with SARS-CoV-2 continuously increases globally, health care systems are being placed under increased stress. Thus, the clinical laboratory plays an important role, helping to select especially asymptomatic individuals who are actively carrying the live replicating virus, with fast and non-invasive molecular technologies. Recent diagnostic strategies, other than molecular methods, have been adopted to either detect viral antigens, i.e., antigen-based immunoassays, or human anti-SARS-CoV-2 antibodies, i.e., antibody-based immunoassays, in nasal or oropharyngeal swabs, as well as in blood or saliva samples. However, the role of mucosal sIgAs, which are essential in the control of viruses entering the body through mucosal surfaces, remains to be elucidated, and in particular the role of the immune response in counteracting SARS-CoV-2 infection, primarily at the site(s) of virus entry that appears to be promising.

Background: Since 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a rapidly spreading pandemic. The present study aims to compare a modified quick SOFA (MqSOFA) score with the NEWS-2 score to predict in-hospital mortality (IHM), 30-days mortality and recovery setting. Methods: All patients admitted from March to October 2020 to the Emergency Department of St. Anna Hospital, Ferrara, Italy with clinically suspected SARS-CoV-2 infection were retrospectively included in this single-centre study and evaluated with the MqSOFA and NEWS-2 scores. Statistical and logistic regression analyses were applied to our database. Results: A total of 3359 individual records were retrieved. Among them, 2716 patients were excluded because of a negative nasopharyngeal swab and 206 for lacking data; thus, 437 patients were eligible. The data showed that the MqSOFA and NEWS-2 scores equally predicted IHM (p < 0.001) and 30-days mortality (p < 0.001). Higher incidences of coronary artery disease, congestive heart failure, cerebrovascular accidents, dementia, chronic kidney disease and cancer were found in the deceased vs. survived group. Conclusions: In this study we confirmed that the MqSOFA score was non-inferior to the NEWS-2 score in predicting IHM and 30-days mortality. Furthermore, the MqSOFA score was easier to use than NEWS-2 and is more suitable for emergency settings. Neither the NEWS-2 nor the MqSOFA scores were able to predict the recovery setting.

Takotsubo syndrome (TTS) is a clinical syndrome characterized by transient left ventricular dysfunction, ischemic electrocardiographic changes, and minimal release of myocardial enzymes without obstructive coronary artery disease. This syndrome that mimics an acute myocardial infarction is prevalent among female patients and is regarded as a benign medical condition. The precise pathophysiological mechanism of TTS is complex and not completely understood, but specific emotional or physical events precipitate this syndrome that represents a typical condition characterized by interactions between cardiovascular and neuropsychological diseases. In addition, many different neurological disorders, such as stroke, subarachnoid bleeding, head injury, epilepsy, and bacterial meningitis, have directly or indirectly related to TTS; unfortunately, these acute neurological diseases represented the cause of death in patients nominated for organ donation and in particular for the heart donor. This article reviews the relationship between TTS and solid organ transplantation; in particular, this article highlights the possible mechanisms underlying the induction of TTS in pre- and post-transplantation phases and in heart-transplant patients.

Celiac disease (CD) and non-celiac gluten/wheat sensitivity (NCG/WS) are the two most frequent conditions belonging to gluten-related disorders (GRDs). Both these diseases are triggered and worsened by gluten proteins ingestion, although other components, such as amylase/trypsin inhibitors (ATI) and fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), seem to be involved in the NCG/WS onset. Therefore, the only effective treatment to date is the long-life adherence to a strictly gluten-free diet. Recently, increasing attention has been paid to the intestinal barrier, a dynamic system comprising various components, which regulate the delicate crosstalk between metabolic, motor, neuroendocrine and immunological functions. Among the elements characterizing the intestinal barrier, the microbiota plays a key role, modulating the gut integrity maintenance, the immune response and the inflammation process, linked to the CD and NCG/WS outbreak. This narrative review addresses the most recent findings on the gut microbiota modulation induced by the gluten-free diet (GFD) in healthy, CD and NCG/WS patients.

We report a case of a 53-year old man admitted because of fever (38.5°C) and atypical chest pain. He also complained of epigastric pain spread to left hypochondrium and exacerbated by breathing. In his past medical history, Hodgkin’s lymphoma, gastric MALToma (oncologic follow-up only), hypothyroidism, and hypertension are recorded. Fifteen days prior actual hospital admission, the patient underwent angioplasty with stenting due to a ST elevation myocardial infarction. Moreover, he was enrolled in the experimental clinical double-blind trial GEMINI-ACS [1], designed to compare the safety of rivaroxaban vs aspirin in addition to either clopidogrel or ticagrelor. Thus, his complete therapy included also ticagrelor, bisoprolol, perindopril, levothyroxine, pantoprazole, and atorvastatin. At the time of admission chest X-ray showed bilateral pleural effusion. Blood chemistry panel showed moderate anemia, increase of inflammatory indexes, in particular fibrinogen 1057 mg/dl (normal range 150-400 mg/dl), C-reactive-protein 17.6 mg/dl (normal range

Background: Chronic constipation (CC) is a severe symptom in Parkinson's disease (PD), with an unclear pathogenesis. Abnormalities of the enteric nervous system (ENS) and/or intestinal epithelial barrier (IEB) may be pathophysiologically relevant in PD patients with CC. We investigated possible molecular changes of the IEB in PD/CCs compared with CCs and controls., Methods: Twelve PD/CCs (2 female, age range 51-80 years), 20 CCs (15 female, age range 27-78 years), and 23 controls (11 female, age range 32-74 years) were enrolled. Ten PD/CCs and 10 CCs were functionally characterized by anorectal manometry (AM) and transit time (TT). Colon biopsies were obtained and assessed for gene and protein expression, and localization of IEB tight junction markers claudin-4 (CLDN4), occludin-1 (OCCL-1), and zonula occludens-1 (ZO-1) by RT-qPCR, immunoblot and immunofluorescence labeling., Results: PD/CCs were clustered in 2 functional categories: patients with delayed TT and altered AM (60%), and a second group showing only modifications in AM pattern (40%). Gene expression of CLDN4, OCCL-1 and ZO-1 was higher in PD/CCs than controls (P<0.05). Conversely, PD/CCs showed a trend to decrease (P>0.05) in CLDN4 and OCCL-1 protein levels than controls, whereas ZO-1 protein was comparable. In PD/CCs compared with controls, decreasing tendency of vasoactive intestinal polypeptide mRNA, protein and immunoreactive fiber density were observed, although the difference was not statistically significant., Conclusion: Transit and anorectal dysfunctions in PD/CCs are associated with difference in ZO-1, OCCL-1 and CLDN4 expression, thus supporting the role of an altered IEB as a contributory mechanism to possible neuronal abnormalities., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)