Internal carotid artery fibromuscular dysplasia in arterial hypertension: Management in clinical practice

Fibromuscular dysplasia (FMD) reminds of a rare form of secondary arterial hypertension occurring in young people and involving the renal arteries. FMD may also involve vertebral, subclavian, mesenteric, iliac arteries and carotid arteries. FMD of internal carotid arteries is a rare finding that is frequently incidental and asymptomatic. It usually occurs in middle-aged women and is secondary to media-intima fibrodysplasia. The carotid artery may be elongated or kinked and associated cerebral aneurysms have been reported. Symptoms including transient ischaemic attack or stroke are uncommon and are related to decrease of blood flow or embolization by platelet aggregates. At the onset, differential diagnosis with vasculitis must be placed. Computed tomography or magnetic resonance imaging (MRI) angiography demonstrates bilateral high-grade stenosis with the characteristic "string of beads" pattern. Antiplatelet medication is the accepted therapy for asymptomatic lesions. Graduated endoluminal surgical dilation is an outmoded therapy, no longer used in most medical centres. Current percutaneous angioplasty is the preferred treatment for symptomatic carotid FMD, but no randomized controlled trials comparing this methodology with surgery is available. The management of a case of arterial systemic FMD in a 52-year-old women, diagnosed after a hypertensive crysis, is discussed. Imaging methods disclosed stenoses of carotid arteries, of celiac tripod and of superior mesenteric artery. Because of high risk associated to endovascular surgery, medical therapy was started. In the first year of follow-up, no events have been reported

FFF-based high-throughput sequence shortlisting to support the development of aptamer-based analytical strategies

Aptamers are biomimetic receptors that are increasingly exploited for the development of optical and electrochemical aptasensors. They are selected in vitro by the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure, but although they are promising recognition elements, for their reliable applicability for analytical purposes, one cannot ignore sample components that cause matrix effects. This particularly applies when different SELEX-selected aptamers and related truncated sequences are available for a certain target, and the choice of the aptamer should be driven by the specific downstream application. In this context, the present work aimed at investigating the potentialities of asymmetrical flow field-flow fractionation (AF4) with UV detection for the development of a screening method of a large number of anti-lysozyme aptamers towards lysozyme, including randomized sequences and an interfering agent (serum albumin). The possibility to work in native conditions and selectively monitor the evolution of untagged aptamer signal as a result of aptamer-protein binding makes the devised method effective as a strategy for shortlisting the most promising aptamers both in terms of affinity and in terms of selectivity, to support subsequent development of aptamer-based analytical devices

The R521K polymorphism of EGFR influences the risk of colorectal cancer

In colorectal cancer (CRC) epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and HER4) have been found frequently over-expressed. New therapies directed against EGFR have been developed in many human cancers. Unexpectedly, EGFR alterations could be good prognostic indicators, like in lung cancer, where an EGFR variant in non-smoker female patients is associated with higher survival after surgery and increases the efficiency of therapy based on EGFR inhibitors. The role of the genetic polymorphisms of the EGFR family members in colorectal cancer development has not been completely explored. In our preliminary study, three missense polymorphisms mapping in EGFR family members have been investigated in the peripheral blood of a small Italian sample size of 70 patients and 72 controls to verify if they could be considered CRC susceptibility factors. For the first time, the evidence of genotype association was found for the R521K EGFR polymorphism: the protective effect for this variant allele has been found to reduce the risk for colon cancer onset

The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer: A Multicenter Study

CONTEXT: Despite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP. EVIDENCE SYNTHESIS: We retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis. EVIDENCE ACQUISITION: We included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P < .05). CONCLUSIONS: PSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging

The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer:A Multicenter Study

Context: Despite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP. Evidence Synthesis: We retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis. Evidence Acquisition: We included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P &lt; .01). This held true at multivariable analysis: (HR 6.184, 95% CI: 3.386-11-295; P &lt; .001) whilst no significant results were highlighted for Choline PET/CT. No significant associations for both PET types were found for local progression, BCR, and overall mortality (all P &gt; .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P &lt; .05). Conclusions: PSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging.</p

The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer:A Multicenter Study

Context: Despite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP. Evidence Synthesis: We retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis. Evidence Acquisition: We included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P &lt; .01). This held true at multivariable analysis: (HR 6.184, 95% CI: 3.386-11-295; P &lt; .001) whilst no significant results were highlighted for Choline PET/CT. No significant associations for both PET types were found for local progression, BCR, and overall mortality (all P &gt; .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P &lt; .05). Conclusions: PSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging.</p

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Reingegnerizzazione del percorso medico in urgenza: Sviluppo di modelli di simulazione numerica e ottimizzazione presso il Policlinico Sant'Orsola di Bologna

La complessità dell’ambito sanitario richiede l’uso di metodologie e strumenti per l’analisi quantitativa dei processi, permettendo di garantire una sempre maggiore efficienza nell’utilizzo delle risorse e nella pianificazione. Il tirocinio per tesi svolto presso il Policlinico Sant’Orsola ha avuto come obiettivo migliorare la gestione del flusso dei pazienti da Pronto Soccorso (PS) verso dodici reparti medici, con particolare attenzione alla riduzione di tempi di attesa e sovraffollamento in PS, e supportare il processo decisionale di Bed Management. Il lavoro è stato strutturato in tre fasi e ha incluso lo sviluppo di modelli di simulazione numerica e ottimizzazione che permettono di descrivere il flusso dei pazienti, analizzare lo scenario attuale e valutare proposte di miglioramento. Un primo modello di simulazione ha evidenziato i vantaggi di un’anticipazione della fascia oraria di dimissione dai reparti, in modo da allineare maggiormente le richieste di ricovero da PS con la disponibilità di posti letto. Un’analisi approfondita della domanda da PS ne ha permesso una caratterizzazione sulla base della compatibilità tra la diagnosi di ogni paziente e la vocazione specialistica di ciascun reparto medico analizzato. Integrando il concetto di appropriatezza di ricovero nel modello e simulando l’indirizzamento dei pazienti verso reparti adeguati alle loro necessità cliniche, si sono evidenziate una diminuzione dei tempi di attesa e una netta riduzione del collo di bottiglia tra PS e reparti. La terza fase del lavoro ha comportato l’utilizzo di modelli di programmazione lineare intera per valutare il corretto dimensionamento e la distribuzione ottimale dei posti letto nei reparti analizzati. Il lavoro svolto si pone come base metodologica per promuovere una maggiore standardizzazione nella gestione dei ricoveri e ha permesso di mettere in evidenza i vantaggi dell’utilizzo di metodi della ricerca operativa a supporto del processo decisionale in ambito sanitario