Archivio Istituzionale della Ricerca- Università degli Studi di Foggia
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From the green revolution to green resilience: Rht genes between productivity and adaptation
No full textLGALS3BP antibody-drug conjugate enhances tumor-infiltrating lymphocytes and synergizes with immunotherapy to restrain neuroblastoma growth
No full textBackground: LGALS3BP, also referred as Gal-3BP, Mac2-BP, or 90 K, is a heavily glycosylated, secreted protein prominently localized at the surface of cancer-derived extracellular vesicles (EVs). Its levels are significantly elevated in various types of cancer, including neuroblastoma, and are generally associated with advanced disease and tumor progression. Our previous research has shown that LGALS3BP is an effective target for ravtansine (DM4)-based Antibody-Drug Conjugate (ADC) therapy in multiple preclinical models. Methods: We assessed total and extracellular vesicles (EVs)-associated LGALS3BP through ELISA assay in serum of a pseudometastatic neuroblastoma model to evaluate the correlation of LGALS3BP levels with tumor dissemination. We employed a syngeneic neuroblastoma mouse model using murine neuroblastoma NXS2 cells overexpressing human LGALS3BP in order to evaluate immunogenic cell death (ICD) induced by anti-LGALS3BP ADC therapy and investigated the nature of the tumor immune infiltrate by cytofluorimetry. Furthermore, we designed a six-arm in vivo experiment to evaluate the efficacy of ADC in combination with an immune check-point inhibitor (ICI) anti-PD-1. Finally, a rechallenge assay was conducted on cured mice to assess the presence of immunological memory. Results: Here, we report that circulating and EVs-associated LGALS3BP levels significantly correlate with neuroblastoma progression and dissemination. Moreover, we show that in the syngeneic NXS2 neuroblastoma model, DM4 treatment induces cell surface expression of ICD markers calreticulin, HSP70, and HSP90, and an increased PD-L1 expression in vitro, followed by enhanced tumor-infiltrating lymphocytes in vivo. Notably, the combination therapy of anti-LGALS3BP-targeting ADC with anti-PD-1 results in a higher inhibition of tumor growth and prolonged survival compared with either agent given alone. Rechallenge assay reveals that mice previously treated and cured with the ADC retain immune memory, suggesting the therapy's ability to induce a durable and protective antitumor immune response. Conclusions: Our findings establish that circulating LGALS3BP is a potential biomarker for liquid biopsy and uncover this protein as a suitable target for therapeutic strategies combining 1959-sss/DM4 ADC with an anti-PD-1 ICI for the treatment of LGALS3BP expressing neuroblastoma
Postcardiotomy extracorporeal membrane oxygenation in patients older than 70 years: Characteristics, outcomes, and variables associated with mortality
No full textObjectives: Age is the main determinant for mortality in patients requiring postcardiotomy extracorporeal membrane oxygenation (PC-ECMO), but strategies to reverse this trend are unknown. This study investigates PC-ECMO outcomes in older patients (≥70 years) compared with younger patients (<70 years). Methods: This retrospective study included patients who required PC-ECMO between 2000 and 2020. Variables independently associated with in-hospital mortality were identified using mixed Cox proportional hazards models. Results: The study included 2057 patients (mean age: 62.3 [first and third quartile: 19-94]; male patients: n = 1213 [59%]): 1376 (67%) were <70 years and 680 (33%) were ≥70 years old. Older patients had more preoperative comorbidities, whereas younger patients had lower cardiac function and more preoperative intubation and vasopressor use. In-hospital mortality was 56.3% (n = 775) and 68.8% (n = 468) in the <70 year and ≥70 year groups, respectively (P < .001). The 7-year postdischarge survival rate was greater for the younger patient group (P < .001). Variables associated with in-hospital mortality in older patients were previous stroke (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.05-1.84), preoperative right ventricular failure (HR, 1.45; 95% CI, 1-2.1), aortic surgery (HR 1.65; 95% CI, 1.2-2.2), and postoperative complications including bleeding (HR 1.24; 95% CI, 1.0-1.5), cardiac arrest (HR, 1.65; 95% CI, 1.3-2.1), and right ventricular failure (HR, 1.29; 95% CI, 1.0-1.6). Conclusions: PC-ECMO mortality is high in older patients. Preoperative factors including previous stroke and right ventricular failure and postoperative factors including bleeding, cardiac arrest, and right ventricular failure should be targeted to reduce in-hospital mortality after appropriate initial selection in older patients
Authors' Response to Nicolò et al.: "A Ventilatory Control Model Explaining the Respiratory Compensation Point"
No full text[no abstract available
Predicting acute kidney injury after endourological treatment of Kidney stones.
No full textIntroduction and Objective:
Postoperative acute kidney injury (AKI) can occur after Percutaneous Nephrolithotomy
(PCNL). This study aimed to assess AKI incidence after standard and mini-PCNL and
identify associated risk factors.
Methods:
A retrospective analysis of prospectively collected data from 1,398 patients undergoing
PCNL (2005-2024) at a single institution was carried out. Only patients with renal stones
into bilaterally anatomically normal kidneys were included. AKI was defined by KDIGO
criteria as at least a ≥1.5-fold or ≥0.3 mg/dL increase in baseline serum creatinine (sCr)
within 72 hours postoperatively. Multivariable logistic regression analyzed predictors of
AKI.
Results:
AKI occurred in 153 (10.9%) patients, classified as stage I, II, and III in 8.0%, 2.0%, and
0.9%, respectively. Major complications increased with AKI severity, notably infections
and bleeding requiring angioembolization, leading to AKI patients having a longer
postoperative hospital stay. Independent predictors included older age (OR 1.05 per
year; 95%CI 1.03–1.07), female gender (OR 1.66; 95%CI 1.14–2.43), baseline eGFR
(U-shaped relationship: linear term OR 0.50 per 10-unit increase; 95%CI 0.36–0.68,
quadratic term OR 1.06 per 10-unit increase; 95%CI 1.04–1.08), larger tract size >22
Ch (OR 2.29; 95%CI 1.53–3.44), surgical time (OR 1.01 per minute; 95%CI 1.01–1.01),
intraoperative hemoglobin loss (OR 1.16 per g/dL; 95%CI 1.05–1.29), minor
complications (Clavien grade 1–2, OR 2.29; 95% CI 1.49–3.51), and major
complications (Clavien grade≥3, OR 6.08; 95% CI 3.57–10.35).
Conclusion:
AKI following PCNL significantly affects postoperative morbidity and hospitalization.
Risk factors include age, gender, baseline renal function, sheath size, surgical time,
hemoglobin loss, and postoperative complications. Given the potential negative effects
of AKI, urologists should be aware and pay attention to the non-negligible incidence of
such event after PCNL, particularly in patients “at risk
Disproportionate vs. Proportionate Secondary Mitral Regurgitation: A Long-Term Pilot Analysis After Mitral Valve Surgery
No full text: Objectives: The treatment of secondary mitral regurgitation (MR) is still controversial. In 2019, a new conceptual framework was introduced, distinguishing between patients with a degree of MR "proportionate" to the left ventricular (LV) dilatation and patients in whom the severity of MR is "disproportionate" to the LV dilatation. The aim of this study was to compare the long-term outcome of patients with disproportionate vs. proportionate secondary MR who underwent mitral valve (MV) surgery. Methods: From January 2012 to June 2022, 96 patients with a preoperative diagnosis of pure secondary MR and LV dysfunction underwent MV surgery. The patients were divided in two groups, disproportionate vs. proportionate MR, according to echocardiographic parameters. A 5.2 (3.5-7.5) years complete clinical and echocardiographic follow-up was performed. Results: In the study period, 61 patients with disproportionate and 35 patients with proportionate MR underwent surgical MV repair or MV replacement. The thirty-day outcome was comparable in the two groups. At long-term follow-up, mortality was 5% in the disproportionate group vs. 11% in the proportionate group (p = 0.2), and cardiovascular mortality was 3% vs. 9%, respectively (0.5). Rehospitalization for heart failure was 6% vs. 20% (p = 0.04), and the rate of patients with New York Heart Association (NYHA) functional class ≥ III was 8% vs. 26%, respectively (p = 0.01). LV volumes were significantly higher in the proportionate group, thus presenting a lower LV ejection fraction (p < 0.001 and p = 0.03, respectively). No cases of recurrent MR have been observed. Conclusions: In this first exploratory analysis, patients with disproportionate secondary MR seem to present a possible benefit in terms of mortality and cardiovascular mortality, although not ones reaching statistical significance. Nevertheless, significant advantages were observed in terms of rehospitalization for heart failure, clinical status and symptoms, LV volumes, and LV function. Among patients referred to cardiac surgery, identifying the subset of patients with functional MR, who may obtain more significant advantages from surgery, seems relevant for patient selection, risk stratification, and to predict long-term outcomes
Multinational transfusion practices and outcomes in haematology patients admitted to the intensive care unit
No full textBackground and Objectives: The number of critically ill patients with haematological conditions is increasing, yet transfusion practices in this population remain poorly defined. This study aimed to compare transfusion strategies in critically ill patients with versus without haematological conditions. Study Design and Methods: This international, prospective observational substudy of the International Point Prevalence Study of Intensive Care Unit [ICU] Transfusion Practices (InPUT) evaluated transfusion use in ICU patients with and without haematological conditions, including benign or malignant diseases or a history of stem cell transplantation. Outcomes included use of red blood cells (RBCs), platelets, plasma, haemostatic interventions, transfusion indications and thresholds. Results: Of 3643 ICU patients, 131 (3.6%) had a haematological condition. These patients were more likely to receive RBC (odds ratio [OR] 1.58, 95% confidence interval [CI] 1.09–2.29) and platelet transfusions (OR 8.32, 95% CI 5.09–13.6), primarily due to low haemoglobin rather than physiological triggers. Platelet thresholds were lower (median 23 × 109/L vs. 64 × 109/L) compared to non-haematology patients. Both platelet and plasma transfusions were more frequently administered prophylactically rather than for active bleeding. Haemostatic interventions were more often used in haematology patients, at higher doses and typically without viscoelastic testing. Transfused haematology patients had higher 28-day mortality and longer ICU stays. Conclusion: ICU patients with haematological conditions receive transfusions differently, particularly regarding platelet and plasma use. These findings underscore the need for prospective studies to define optimal transfusion thresholds in this growing and vulnerable patient population, although the study's limited sample size and lack of diagnostic granularity may affect interpretation
Detection of Chlamydia trachomatis, Neisseria gonorrhoeae and Ureaplasma urealyticum in symptomatic and asymptomatic subjects
No full textReligione, democrazia e sicurezza nell’era digitale
No full textNegli ultimi vent’anni lo sviluppo della tecnologia digitale ha cambiato la vita e la società umana:
da un lato, ha promosso lo sviluppo economico, la partecipazione democratica e i diritti
fondamentali; dall’altro, è stata impiegata come strumento di controllo da attori pubblici e privati
per condurre operazioni di sorveglianza individuale e di massa, di sottrazione di dati personali, di
dossieraggio, di propaganda, disinformazione e censura; a certe latitudini, queste tendenze hanno
addirittura determinato l’emersione di forme di “autoritarismo digitale” in cui l’estensione
dell’impiego di questi strumenti consente di controllare e reprimere il dissenso di minoranze
religiose e/o politiche. La religione ha rappresentato talvolta il bersaglio e talaltra il movente che ha
giustificato l’intrusività digitale. Anche in questo campo, infatti il rapporto tra religione e sicurezza
è stato declinato all’insegna del modello competitivo post-9/11, che considera la sicurezza e la
libertà come conflittuali o, addirittura inversamente proporzionali: lo testimonia l’“eccezionalismo
della sorveglianza” occidentale rivolto alle comunità musulmane e l’autoritarismo digitale di Cina
esponenzialmente impiegato nello Xinjiang; d’altro canto, in Iran, come in altri paesi, è stata la
religione a utilizzare tali mezzi per reprimere il dissenso. La minaccia per le democrazie
costituzionali, invece, viene anche da intermediari digitali che amministrano il discorso pubblico e
libertà fondamentali online. In materia di regolazione digitale, dunque, neppure il diritto può dirsi
immune dal paradosso della modernizzazione, ciò che rende (forse) necessaria l’individuazione di
nuove soluzioni che superino il modello “tecno-libertario” della Section 230 CDA e non corrano al
contempo il rischio della iper-regolazione emersa di recente nel modello “liberal-regolatorio”
europeo, che rischia di violare le stesse libertà che vorrebbe tutelate, anche alla luce
dall’esponenziale diffusione dell’IA che minaccia conseguenze astrattamente pari a quelle di una
catastrofe nucleare