Characterization of mouse spinal cord vascular network by means of synchrotron radiation X-ray phase contrast tomography

High resolution Synchrotron-based X-ray Phase Contrast Tomography (XPCT) allows the simultaneous detection of three dimensional neuronal and vascular networks without using contrast agents or invasive casting preparation. We show and discuss the different features observed in reconstructed XPCT volumes of the ex vivo mouse spinal cord in the lumbo-sacral region, including motor neurons and blood vessels. We report the application of an intensity-based segmentation method to detect and quantitatively characterize the modification in the vascular networks in terms of reduction in experimental visibility. In particular, we apply our approach to the case of the experimental autoimmune encephalomyelitis (EAE), i.e. human multiple sclerosis animal model

Conversion to secondary progressive multiple sclerosis: patient awareness and needs. results from an online survey in Italy and Germany

Background: Few studies have investigated the experiences of patients around the conversion to secondary progressive multiple sclerosis (SPMS). ManTra is a mixed-method, co-production research project conducted in Italy and Germany to develop an intervention for newly-diagnosed SPMS patients. In previous project actions, we identified the needs and experiences of patients converting to SPMS via literature review and qualitative research which involved key stakeholders.Aims: The online patient survey aimed to assess, on a larger and independent sample of recently-diagnosed SPMS patients: (a) the characteristics associated to patient awareness of SPMS conversion; (b) the experience of conversion; (c) importance and prioritization of the needs previously identified.Methods: Participants were consenting adults with SPMS since <= 5 years. The survey consisted of three sections: on general and clinical characteristics; on experience of SPMS diagnosis disclosure (aware participants only); and on importance and prioritization of 33 pre-specified needs.Results: Of 215 participants, those aware of their SPMS diagnosis were 57% in Italy vs. 77% in Germany (p = 0.004). In both countries, over 80% of aware participants received a SPMS diagnosis from the neurologist; satisfaction with SPMS disclosure was moderate to high. Nevertheless, 28-35% obtained second opinions, and 48-56% reported they did not receive any information on SPMS. Participants actively seeking further information were 63% in Germany vs. 31% in Italy (p < 0.001).Variables independently associated to patient awareness were geographic area (odds ratio, OR 0.32, 95% CI 0.13-0.78 for Central Italy; OR 0.21, 95% CI 0.08-0.58 for Southern Italy [vs. Germany]) and activity limitations (OR 7.80, 95% CI 1.47-41.37 for dependent vs. autonomous patients).All pre-specified needs were scored a lot or extremely important, and two prioritized needs were shared by Italian and German patients: "physiotherapy" and "active patient care involvement." The other two differed across countries: "an individualized health care plan" and "information on social rights and policies" in Italy, and "psychological support" and "cognitive rehabilitation" in Germany.Conclusions: Around 40% of SPMS patients were not aware of their disease form indicating a need to improve patient-physician communication. Physiotherapy and active patient care involvement were prioritized in both countries

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 < .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

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Aspetti ecografici prenatali e sviluppo neurocognitivo in pazienti affetti da sindrome del cuore sinistro ipoplasico

La presente tesi rappresenta il frutto di un'attivita' di ricerca svolta presso l'Unita' Operativa di Ostetricia e Medicina dell'Eta'Prenatale in collaborazione con la Cardiologia Pediatrica e dell'Eta' Evolutiva, Azienda Policlinico Sant' Orsola-Malpighi, Universita' di Bologna. L'obiettivo del presente lavoro consiste nella valutazione dello sviluppo neurocognitivo di pazienti affetti da sindrome del cuore sinistro ipoplasico. La sindrome del cuore sinistro ipoplasico include un gruppo eterogeneo di malformazioni cardiache complesse, caratterizzate da una severa ipoplasia delle sezioni cardiache di sinistra, ventricolo sinistro e outflow ventricolare sinistro, che non riescono a supportare la circolazione cardiaca sistemica. Rappresenta una delle principali cause di mortalita' perinatale per malformazioni. Grazie al miglioramento della chirurgia cardiaca relativa a tale patologia abbiamo assistito negli ultimi anni ad un aumento della sopravvivenza di questi pazienti ed alla comparsa di dati emergenti riguardanti la presenza di alterazioni del neurosviluppo. In questo studio abbiamo eseguito, in collaborazione con personale specializzato in psicologia dell'eta' evolutiva, una valutazione qualitativa dello sviluppo neurocognitivo di 27 pazienti nati tra il 1990 ed il 2016 presso l'Ostetricia dell' Ospedale Sant' Orsola di Bologna od afferenti al Reparto di Cardiochirurgia e Cardiologia Pediatrica per l'intervento chirurgico ed il successivo follow up evidenziando la presenza di alterazioni in un numero consistente di essi. In secondo luogo lo scopo dello studio consiste nell' evidenziare l'eventuale presenza di segni ecografici prenatali indicatori di outcome prognostico negativo della patologia stessa. Abbiamo raccolto i dati di 24 donne che hanno eseguito una diagnostica prenatale presso gli ambulatori di ecocardiografia fetale dell'Ospedale Sant' Orsola di Bologna tra il 2007 ed il 2016 con una diagnosi di sindrome del cuore sinistro ipoplasico e che hanno portato a termine la gravidanza con espletamento del parto presso la nostra struttura. Sono state inoltre consultate tutte le cartelle ostetriche di queste donne e raccolti i dati, le cartelle neonatali e cardiologiche dei figli cosi come quelle ambulatoriali per la valutazione del follow up anche a lungo termine: di questi attualmente 7 risultano viventi e 17 deceduti. Abbiamo elaborato un database confrontando i dati ecografici prenatali di questi due gruppi di pazienti ( vivi / deceduti ) evidenziando l'associazione con quadri ecografici piu' gravi nei pazienti successivamente deceduti

The Independent Authorities. A study related to their independence and to their normative powers.

openQuando si parla di autorità amministrative indipendenti, l’attenzione è focalizzata solamente sulle due parole chiave “amministrative” e “indipendenti”, rischiando di intendere tali organismi quali una parte esterna all’ordinamento in cui operano ed incaricati di funzioni totalmente sottratte al Governo. Con questa tesi, invece, si vogliono riportare in esame le authorities alla luce dei loro poteri normativi e della loro indipendenza che, come si vedrà, offrono la possibilità di intendere tali enti come importanti ed efficienti articolazioni dell’intero apparato giuridico, e non strutture estranee allo stesso. Con lo scopo teorico di svincolare le authorities dalle catene del tradizionalismo giuridico e di affidarle ad un contesto sempre più innovativo dettato dai dogmi europei, lo studio volgerà dapprima uno sguardo alle radici storiche del fenomeno, per poi proseguire con degli approfondimenti sui temi dell’indipendenza, della legittimità costituzionale e dei poteri normativi, terminando con l’esame esemplificativo delle modalità di azione di una delle autorità più importanti nel panorama italiano, ANAC

RUOLO DELL'AUTOIMMUNITA' ANTITIROIDEA IN DONNE INFERTILI:IPOTESI FOLLICOLARE

L'autoimmunità antitiroidea ( TAI )è il disturbo autoimmune più comune, colpisce il 5-20% delle donne in età fertile. La TAI è la causa principale di disfunzione tiroidea ma può essere presente anche in donne con funzione tiroidea normale. Le pazienti con anticorpi antitiroidei, anche in presenza di eutiroidismo, hanno un rischio aumentato di aborto spontaneo. La presenza di autoimmunità antitiroidea è relazionata ai ripetuti fallimenti di impianto dell'embrione e gli anticorpi antitiroide possono essere considerati come markers indipendenti di fallimento di tecniche di procreazione medicalmente assistita. I dati presenti in letteratura suggeriscono che gli anticorpi antitiroide possono alterare la fertilità femminile in diversi modi. In primo luogo, è stato ipotizzato che possano alterare la recettività endometriale attraverso una disfunzione immunitaria generalizzata che colpisce il feto allogenico e/o determinare una insufficienza tiroidea durante i trattamenti di riproduzione assistita e successiva gravidanza. Inoltre, recenti studi sperimentali negli animali hanno dimostrato che il problema potrebbe risiedere nella fertilizzazione dell'ovocita e nello sviluppo dell'embrione. In recenti modelli sperimentali animali, l'immunizzazione attiva di topi con tireoglobulina umana ha determinato la produzione di autoanticorpi antitireoglobulina e fallimento della gravidanza manifestato da un incremento del riassorbimento fetale. Studi più recenti hanno dimostrato risultati simili in seguito ad immunizzazione di topi con TPO, in assenza di ipotiroidismo. Studi animali hanno inoltre dimostrato che livelli adeguati di ormoni tiroidei sono necessari per l'angiogenesi follicolare ovarica, uno stadio importante nello sviluppo follicolare e nella maturazione dell'ovocita, in quanto determinano un'up-regulation dell'espressione di mRNA dei maggiori fattori angiogenici, come VEGF. Infine, è stato osservato che livelli adeguati di ormoni tiroidei sono necessari per l'ovulazione e la funzione del corpo luteo