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.
Purpose
Pulmonary Embolism (PE) is the third leading cause of cardiovascular death, following myocardial infarction and stroke. The latest European Society of Cardiology (ESC) guidelines on PE ...recommend short-term prognostic stratification based on right ventricular (RV) overload detected by transthoracic echocardiography (TTE) or contrast-enhanced chest CT. The aim of the study is to find out which of the signs of right ventricular dysfunction best predicts in-hospital mortality (IHM).
Methods
This is a monocentric, retrospective study including adult patients admitted from the emergency department with a c-e cCT confirmed diagnosis of PE between January 2018 and December 2022 who underwent a TTE within 48 h.
Results
509 patients (median age 76 years IQR 67–84) were included, with 7.1% IHM. At univariate analysis, RV/LV ratio > 1 (OR 2.23, 95% CI 1.1–4.5), TAPSE < 17 mm (OR 4.73, 95% CI 2.3–9.8), the D-shape (OR 3.73, 95% CI 1.71–8.14), and LVEF < 35% (OR 5.78, 95% CI 1.72–19.47) resulted significantly correlated with IHM. However, at multivariate analysis including also haemodynamic instability, PESI class > II, and abnormal hs-cTnI levels, only LVEF < 35% (OR 5.46, 95% CI 1.32–22.61) resulted an independent predictor of IHM.
Conclusion
Despite the recognised role of TTE in the early management of patients with circulatory shock and suspected PE, signs of RV dysfunction have been shown to be poor predictors of IHM, whereas severely reduced LVEF is an independent risk factor for in-hospital death.
The Q Allele Variant (GLN 121 ) of Membrane Glycoprotein PC-1 Interacts With the Insulin Receptor and Inhibits Insulin Signaling More Effectively Than the
Common K Allele Variant (LYS 121 )
Benedetta ...V. Costanzo 1 ,
Vincenzo Trischitta 2 ,
Rosa Di Paola 2 ,
Daniela Spampinato 1 ,
Antonio Pizzuti 2 3 ,
Riccardo Vigneri 1 and
Lucia Frittitta 1
1 Institute of Internal Medicine, Endocrine and Metabolic Diseases, University of Catania, Ospedale Garibaldi, Catania
2 Division and Research Unit of Endocrinology, Scientific Institute, Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo
(Foggia)
3 Institute of Neurological Diseases, Ospedale Policlinico Istituto Ricovero e Cura a Carattere Scientifico, Milan, Italy
Abstract
When overexpressed, the membrane glycoprotein PC-1 may play a role in human insulin resistance through the inhibition of insulin
receptor (IR) autophosphorylation. A PC-1 variant (K 121 Q, with lysine 121 replaced by glutamine) is also associated with whole-body insulin resistance when not overexpressed. To
better understand the effects of the Q allele on IR function and downstream signaling, we transfected cultured cells with
cDNAs for either the Q or the K alleles. In human MCF-7 cells, the Q allele was severalfold more effective ( P < 0.05–0.01) than the K allele in reducing insulin stimulation of IR autophosphorylation, insulin receptor substrate-1 phosphorylation,
phosphatidylinositol 3-kinase activity, glycogen synthesis, and cell proliferation. Similar data on IR autophosphorylation
inhibition were also obtained in mouse R − /hIR and human HEK 293 cell lines. In transfected MCF-7 cells, 125 I-labeled insulin binding and IR content were unchanged, and PC-1 overexpression did not influence IGF-1 stimulation of IGF-1
receptor autophosphorylation. Both the Q and K alleles directly interacted with the IR, as documented by coimmunoprecipitation
assays. This interaction was greater for the Q allele than for the K allele ( P < 0.01), suggesting that direct PC-1–IR interactions are important for the PC-1 inhibitory effect on insulin signaling. In
conclusion, the Q allele has stronger inhibitory activity on IR function and insulin action than the more common K allele,
and this is likely a consequence of the intrinsic characteristics of the molecule, which more strongly interacts with the
IR.
a-pY, antiphosphotyrosine
ECL, enhanced chemiluminescence
ELISA, enzyme-linked immunosorbent assay
IGF-1-R, IGF-1 receptor
IR, insulin receptor
IRS-1, IR substrate-1
PI 3-kinase, phosphatidylinositol 3-kinase
PNTP, p-nitrophenyl thymidine 5′-monophosphate
TK, tyrosine kinase
Footnotes
Address correspondence and reprint requests to Dr. Lucia Frittitta, Endocrinologia, Ospedale Garibaldi, Piazza S. M. Gesù,
95123 Catania, Italy. E-mail: segmeint{at}mbox.unict.it .
B.V.C. and V.T. contributed equally to this work.
Received for publication 9 March 2000 and accepted in revised form 3 January 2001.
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.
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.
An increased tissue content of PC-1, an inhibitor of insulin receptor signaling, may play a role in insulin resistance. Large scale prospective studies to test this hypothesis are difficult to carry ...out because of the need for tissue biopsies. The aim of this study was to investigate whether PC-1 is measurable in human plasma and whether its concentration is related to insulin sensitivity. A soluble PC-1, with mol wt and enzymatic activity similar to those of tissue PC-1, was measurable in human plasma by a specific enzyme-linked immunosorbent assay and was inversely correlated to skeletal muscle PC-1 content (r = -0.5; P < 0.01). The plasma PC-1 concentration was decreased (P < 0.05) in insulin-resistant (22.7 +/- 3.0 ng/mL; n = 25) compared to insulin-sensitive (36.7 +/- 4.5; n = 25) nondiabetic subjects and was correlated negatively with the waist/hip ratio (r = -0.48; P < 0.001) and mean blood pressure (r = -0.3; P < 0.05) and positively with high density lipoprotein/total cholesterol (r = 0.38; P < 0.01) and both the M value and the plasma free fatty acid level decrement at clamp studies (r = 0.28; n = 50; P = 0.05 and r = 0.43; n = 22; P < 0.05, respectively). A plasma PC-1 concentration of 19 ng/mL or less identified a cluster of insulin resistance-related alterations with 75% accuracy. In conclusion, PC-1 circulates in human plasma, and its concentration is related to insulin sensitivity. This may help to plan studies aimed at understanding the role of PC-1 in insulin resistance.
When overexpressed, the membrane glycoprotein PC-1 may play a role in human insulin resistance through the inhibition of insulin receptor (IR) autophosphorylation. A PC-1 variant (K121Q, with lysine ...121 replaced by glutamine) is also associated with whole-body insulin resistance when not overexpressed. To better understand the effects of the Q allele on IR function and downstream signaling, we transfected cultured cells with cDNAs for either the Q or the K alleles. In human MCF-7 cells, the Q allele was severalfold more effective (P < 0.05-0.01) than the K allele in reducing insulin stimulation of IR autophosphorylation, insulin receptor substrate-1 phosphorylation, phosphatidylinositol 3-kinase activity, glycogen synthesis, and cell proliferation. Similar data on IR autophosphorylation inhibition were also obtained in mouse R-/hIR and human HEK 293 cell lines. In transfected MCF-7 cells, 125I-labeled insulin binding and IR content were unchanged, and PC-1 overexpression did not influence IGF-1 stimulation of IGF-1 receptor autophosphorylation. Both the Q and K alleles directly interacted with the IR, as documented by coimmunoprecipitation assays. This interaction was greater for the Q allele than for the K allele (P < 0.01), suggesting that direct PC-1-IR interactions are important for the PC-1 inhibitory effect on insulin signaling. In conclusion, the Q allele has stronger inhibitory activity on IR function and insulin action than the more common K allele, and this is likely a consequence of the intrinsic characteristics of the molecule, which more strongly interacts with the IR.
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