Acute coronary occlusion secondary to radiofrequency catheter ablation of a left lateral accessory pathway

A case of asymptomatic acute coronary occlusion secondary to radiofrequency catheter ablation of a left lateral accessory pathway is reported. Due to post-procedural ST modifications of the surface ECG, a coronary angiography was performed which disclosed total occlusion of the first marginal branch of the left circumflex coronary artery. A cute myocardial infarction was confirmed by moderate cardiac enzyme release, abnormal myocardial perfusion scan and mild lateral hypokinesia at echocardiographv. This rare but potentially harmful complication of interventional electrophysiology should be kept in mind and coronary angiography performed immediately when coronary occlusion related to radiofrequency application is suspecte

A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections

Indexación: Scopus.A rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics and reducing the therapeutic arsenal available for treatment of infectious diseases. In the present study, we developed a new class of compounds with antibacterial activity obtained by a simple, two step synthesis and screened the products for in vitro antibacterial activity against ATCC® strains using the broth microdilution method. The compounds exhibited minimum inhibitory concentrations (MIC) of 1⁻32 μg/mL against Gram-positive ATCC® strains. The structure⁻activity relationship indicated that the thiophenol ring is essential for antibacterial activity and the substituents on the thiophenol ring module, for antibacterial activity. The most promising compounds detected by screening were tested against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) clinical isolates. We found remarkable activity against VREF for compounds 7 and 16, were the MIC50/90 were 2/4 µg/mL and 4/4 µg/mL, respectively, while for vancomycin the MIC50/90 was 256/512 µg/mL. Neither compound affected cell viability in any of the mammalian cell lines at any of the concentrations tested. These in vitro data show that compounds 7 and 16 have an interesting potential to be developed as new antibacterial drugs against infections caused by VREF.https://www.mdpi.com/1420-3049/23/7/177

Revealing the dynamic allosteric changes required for formation of the cysteine synthase complex by hydrogen-deuterium exchange MS

CysE and CysK, the last two enzymes of the cysteine biosynthetic pathway, engage in a bienzyme complex, cysteine synthase, with yet incompletely characterized three-dimensional structure and regulatory function. Being absent in mammals, the two enzymes and their complex are attractive targets for antibacterial drugs. We have used hydrogen/deuterium exchange MS to unveil how complex formation affects the conformational dynamics of CysK and CysE. Our results support a model where CysE is present in solution as a dimer of trimers, and each trimer can bind one CysK homodimer. When CysK binds to one CysE monomer, intratrimer allosteric communication ensures conformational and dynamic symmetry within the trimer. Furthermore, a long-range allosteric signal propagates through CysE to induce stabilization of the interface between the two CysE trimers, preparing the second trimer for binding the second CysK with a nonrandom orientation. These results provide new molecular insights into the allosteric formation of the cysteine synthase complex and could help guide antibacterial drug design

Miscarriage following dengue virus 3 infection in the first six weeks of pregnancy of a dengue virus-naive traveller returning from Bali to Italy, April 2016

We report miscarriage following dengue virus (DENV)-3 infection in a pregnant woman returning from Bali to Italy in April 2016. On her arrival, the woman had fever, rash, asthenia and headache. DENV RNA was detected in plasma and urine samples collected the following day. Six days after symptom onset, she had a miscarriage. DENV RNA was detected in fetal material, but in utero fetal infection cannot be demonstrated due to possible contamination by maternal blood

Small Cell Lung Cancer Transformation as a Resistance Mechanism to Osimertinib in Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma: Case Report and Literature Review

Introduction: Small cell lung cancer (SCLC) transformation represents a mechanism of resistance to osimertinib in EGFR-mutated lung adenocarcinoma, which dramatically impacts patients' prognosis due to high refractoriness to conventional treatments. Case Description: We present the case of a patient who developed a SCLC phenotypic transformation as resistance mechanism to second-line osimertinib for T790M-positive EGFR-mutated NSCLC. Our patient received platinum–etoposide doublet following SCLC switch and achieved a modest clinical benefit which lasted 4 months. NGS and IHC analyses for p53 and Rb were performed on subsequent liver biopsies, revealing baseline TP53 mutation and complete absence of p53 and Rb expression. Primary cell cultures were established following a liver biopsy at the time of SCLC transformation, and drug sensitivity assays showed meaningful cell growth inhibition when osimertinib was added to platinum–etoposide compared with control (p < 0.05). A review of the current literature regarding SCLC transformation after failure of osimertinib was performed. Conclusions: Based on retrospective data available to date, platinum–etoposide chemotherapy is the preferred treatment choice in the occurrence of SCLC transformation after osimertinib failure. The extension of osimertinib in combination with chemotherapy in the occurrence of SCLC transformation as resistance mechanism to osimertinib is a matter of debate. The combination of osimertinib and platinum–etoposide was effective in inhibiting cell growth in our primary cell cultures. Clinical studies are needed to further explore this combination in the occurrence of SCLC transformation as a resistance mechanism to osimertinib

Medicina interna perioperatoria - Il paziente chirurgico complesso: il ruolo dell’internista nell’ospedale snello, a misura del paziente, organizzato per intensità di cure

Perché l’internista è necessario nella gestione dei pazienti complessi candidati ad intervento chirurgico F. Gilioli, G. Chesi La medicina interna nell’assistenza del paziente chirurgico complesso M. Fabbri, S. Galli, A. Morettini Il paziente cardiopatico G. Chesi, F. Gilioli Il paziente con broncopneumopatia cronica ostruttiva M. Candela Il paziente diabetico L. Morbidoni La chirurgia nel grande anziano: rischi e opportunità A. Greco, M. Greco, G. D’Onofrio, G. Paroni, D. Sancarlo, M. Lauriola, D. Seripa Il paziente candidato ad intervento chirurgico a rischio trombo-embolico R. Re, M. Campanini Concetto di Ospedale snello, hospitalist e di co-management I. Stefani, A. Mazzone L’internista nel reparto di Ortopedia: il percorso del paziente ricoverato per frattura prossimale di femore R. Nardi, M. Mazzetti, C. Marchetti L’internista nel reparto di neurochirurgia C. Cicognani, S. Zaccaroni L’internista nel reparto di ostetricia A. Maina, V. Donvito, L. Balbi L’internista nel Centro Trapianti di fegato L. Fontanella, M. Imparato La gestione del dolore post-operatorio in ambito internistico M. Bosco, R. Bertè, G. Civardi La sindrome da rialimentazione R. Risicato, G. Scanelli, L. Tramontano, U. Politti Terapia infusionale pre-intra-post-operatoria: solamente un problema dell’anestesista? F. Sgambato, G. Pinna, S. Prozzo, E. Sgambato Il paziente ad elevato rischio emorragico: valutazione e management A.M. Pizzini, I. Iori La gestione perioperatoria o periprocedurale della terapia anticoagulante-antiaggregante in elezione e in urgenza A. Fontanella, R. Re Le complicanze mediche e gli eventi avversi indesiderabili più frequenti nel paziente internistico complesso operato M. Silingardi Pazienti chirurgici ricoverati in Medicina Interna: i pazienti a rischio, selezione delle priorità e delle emergenze urgenze e pianificazione dell’assistenza P. Gnerre, M. Gambacorta, A. Percivale Qualità, indicatori ed audit come strumento di miglioramento nell’assistenza del paziente complesso in chirurgia S. De Carli, A. Montagnani Quali proposte ed evidenze per nuovi modelli organizzativi in cui l’internista può assumere un ruolo fondamentale? A. Fontanella, M. Campanin

L’appropriatezza nella gestione dell’iperglicemia nel paziente ospedalizzato: schemi di orientamento

Clinical governance e appropriatezza nel management dell’iperglicemia in ospedale I numeri del diabete  Nel mondo   In Italia Il diabete nella real life ospedaliera L’appropriatezza nella gestione dell’iperglicemia nella fase del ricovero in ospedale  L’appropriatezza nella definizione della terapia insulinica e degli obiettivi glicemici     Perché sospendere gli ipoglicemizzanti orali?      Distinzione fra paziente critico e acuto non critico      Paziente critico      Paziente acuto non critico      Schema basal bolus      Schema basal plus      Transizione dalla somministrazione endovena alla somministrazione sottocute      Perché no sliding scale?      Obiettivi glicemici      L’appropriatezza nella somministrazione dell’insulina sottocute     Vantaggi in termini di costi      Considerazioni riassuntive sull’impiego del sistema siringa/flacone     Considerazioni riassuntive sull’impiego degli iniettori a penna     Aree di miglioramento     Appropriatezza del trattamento con le penne pre-riempite in ospedale     L’appropriatezza nella gestione dell’iperglicemia nel paziente in terapia cortisonica     Come comportarsi?      L’appropriatezza nella gestione dell’iperglicemia nel paziente candidato al trattamento chirurgico     Cosa deve fare l’internista?     Dopo l’intervento chirurgico ed il rientro in reparto     L’appropriatezza nella rilevazione e nel trattamento delle ipoglicemie      Definizione     Prevalenza nelle Unità Operative di Medicina Interna     Fattori di rischio     Esiti      Prevenzione      Trattamento     L’appropriatezza nella gestione dell’iperglicemia nella fase della dimissione     Conclusioni     Appendix     Bibliografia 

Management of Hypothyroidism in Internal Medicine: Patient Profile and Effects of an Educational Programme in the Cluster-Randomized FADOI TIAMO Study.

Background and aims: There is still limited knowledge regarding the clinical profile and appropriateness of treatment in patients with hypothyroidism hospitalized in Internal Medicine (IM) Departments in Italy. The aim of this study is to evaluate: 1) the characteristics of patients and possible deviations from national and international clinical practice recommendations (CPRs) in evidence-based guidelines (EBGs); 2) the improvement of patient management by means of a standardized educational programme (EP). Methods: A nationwide multicentre study, comprising two replications of a retrospective survey (phases 1 and 3) with an intervening EP (phase 2) in half of the centres and no EP in the other half, was conducted. The EP was based on outreach visits. Centres were assigned to the two arms of the study, labelled the training group (TG) and control group (CG) respectively, by cluster randomization. Four EBGs and 39 CPRs provided the basis on which 22 treatment management indicators were identified (7 referring to the time of hospital admission, 15 to post-admission). Results: The 21 participating centres recruited 587 hospitalized patients with hypothyroidism, 421 of which were females (71.7%, mean age 74.1 + 14.4 yrs): 318 in phase 1 and 269 in phase 3. The cause of hypothyroidism was unknown in 282 patients (48%). Evaluation at the time of admission identified satisfactory adherence to CPRs (>50%) for 63.6% of the indicators. In the phase 3, TG centres showed significant improvement vs CG in 4 of the 15 post-admission indicators, while 1 out of 15 was significantly worse. Conclusions: The EP based on outreach visits significantly improved some indicators in the management of patients with hypothyroidism, with specific reference to appropriateness of TSH dosage and levothyroxine (LT4) treatment modality. Clinical trial registration: ClinicalTrials.gov, identifier NCT05314790

L-serine biosynthesis in the human central nervous system: Structure and function of phosphoserine aminotransferase

Organisms from all kingdoms of life synthesize L-serine (L-Ser) from 3-phosphoglycerate through the phosphorylated pathway, a three-step diversion of glycolysis. Phosphoserine aminotransferase (PSAT) catalyzes the intermediate step, the pyridoxal 5′-phosphate-dependent transamination of 3-phosphohydroxypyruvate and L-glutamate to O-phosphoserine (OPS) and α-ketoglutarate. PSAT is particularly relevant in the central nervous system of mammals because L-Ser is the metabolic precursor of D-serine, cysteine, phospholipids, and nucleotides. Several mutations in the human psat gene have been linked to serine deficiency disorders, characterized by severe neurological symptoms. Furthermore, PSAT is overexpressed in many tumors and this overexpression has been associated with poor clinical outcomes. Here, we report the detailed functional and structural characterization of the recombinant human PSAT. The reaction catalyzed by PSAT is reversible, with an equilibrium constant of about 10, and the enzyme is very efficient, with a kcat/Km of 5.9 × 106 M−1 s−1, thus contributing in driving the pathway towards the products despite the extremely unfavorable first step catalyzed by 3-phosphoglycerate dehydrogenase. The 3D X-ray crystal structure of PSAT was solved in the substrate-free as well as in the OPS-bound forms. Both structures contain eight protein molecules in the asymmetric unit, arranged in four dimers, with a bound cofactor in each subunit. In the substrate-free form, the active site of PSAT contains a sulfate ion that, in the substrate-bound form, is replaced by the phosphate group of OPS. Interestingly, fast crystal soaking used to produce the substrate-bound form allowed the trapping of different intermediates along the catalytic cycle