Survival as a clinical outcome and its spiritual significance in a cohort of patients with advanced central pelvic neoplastic disease undergoing total pelvic evisceration: a poorly debated issue.

Background: Patients with either treatment-resistant or relapsing advanced central pelvic neoplastic disease present with a condition responsible for debilitating symptoms and consequently poor quality of life (QoL). For these patients, therapeutic strategies are very limited and total pelvic evisceration is the only option for relieving the symptoms and increasing survival. Of note, taking charge of these patients cannot be limited to increasing their lifespan but must also be aimed at improving the clinical, psychological, and spiritual conditions. This study aimed to prospectively evaluate the improvement in survival and QoL, focusing on spiritual wellbeing (SWB), in patients with poor life expectancy who underwent total pelvic evisceration for advanced gynecological cancers at our center. Patients and methods: The QoL and SWB were assessed using the European Organisation for Research and Treatment of Cancer QoL questionnaire (EORTC QLQ-C30), EORTC QLQ-SWB32, and SWB scale, which were repeatedly administered: 30 days before surgery, 7 days after the procedure, 1 and 3 months after surgery, and then every 3 months until death or the last follow-up assessment. Operative outcomes (blood loss, operative time, hospitalization, and incidence of complications) were evaluated as secondary endpoints. The patients and their families were included in a dedicated psycho-oncological and spiritual support protocol, which was managed by specifically trained and specialized personnel who accompanied them during all phases of the study. Results: A total of 20 consecutive patients from 2017 to 2022 were included in this study. Of these patients, 7 underwent total pelvic evisceration by laparotomy and 13 underwent laparoscopy. The median survival was 24 months (range: 1-61 months). After a median follow-up of 24 months, 16 (80%) and 10 patients (50%) were alive at 1 year and 2 years after surgery, respectively. The EORTC-QLQ-C30 scores significantly improved yet at 7 days and at 1, 3, 6, and 12 months, as compared with the preoperative values. In particular, an early improvement in pain, overall QoL, and physical and emotional functions was observed. With respect to the SWB, the global SWB item score of the EORTC QLQ-SWB32 questionnaire significantly increased after 1 month and 3 months, as compared with preoperative values (p = 0.0153 and p = 0.0018, respectively), and remained stable thereafter. The mean SWB scale score was 53.3, with a sense of low overall SWB in 10 patients, a sense of moderate SWB in eight patients, and a sense of high SWB in two patients. The SWB scale score significantly increased after 7 days, 1 month, and 3 months, as compared with the preoperative value (p = 0202, p = 0.0171, and p = 0.0255, respectively), and remained stable thereafter. Conclusion: Total pelvic evisceration is a valid approach for improving both survival and QoL in selected patients with advanced pelvic neoplasms and poor life expectancy. Our results particularly underline the importance of accompanying the patients and their families during the journey with dedicated psychological and spiritual support protocols.

Cardioprotective factors against myocardial infarction selected in vivo from an AAV secretome library.

Therapies for patients with myocardial infarction and heart failure are urgently needed, in light of the breadth of these conditions and lack of curative treatments. To systematically identify previously unidentified cardioactive biologicals in an unbiased manner in vivo, we developed cardiac FunSel, a method for the systematic, functional selection of effective factors using a library of 1198 barcoded adeno-associated virus (AAV) vectors encoding for the mouse secretome. By pooled vector injection into the heart, this library was screened to functionally select for factors that confer cardioprotection against myocardial infarction. After two rounds of iterative selection in mice, cardiac FunSel identified three proteins [chordin-like 1 (Chrdl1), family with sequence similarity 3 member C (Fam3c), and Fam3b] that preserve cardiomyocyte viability, sustain cardiac function, and prevent pathological remodeling. In particular, Chrdl1 exerted its protective activity by binding and inhibiting extracellular bone morphogenetic protein 4 (BMP4), which resulted in protection against cardiomyocyte death and induction of autophagy in cardiomyocytes after myocardial infarction. Chrdl1 also inhibited fibrosis and maladaptive cardiac remodeling by binding transforming growth factor-ß (TGF-ß) and preventing cardiac fibroblast differentiation into myofibroblasts. Production of secreted and circulating Chrdl1, Fam3c, and Fam3b from the liver also protected the heart from myocardial infarction, thus supporting the use of the three proteins as recombinant factors. Together, these findings disclose a powerful method for the in vivo, unbiased selection of tissue-protective factors and describe potential cardiac therapeutics.

Preliminary data of different methods for the indirect diagnosis of Mycobacterium bovis infection.

We compared the response induced by QuantiFERON-TB Gold antigens to that obtained with the Intradermal Comparative Tuberculin Test and BOVIGAM assay. Our results showed that the QuantiFERON-TB Gold technique used in humans could also be applied for the diagnosis of TB infection in cattle.

Heparin binding haemagglutin as potential diagnostic marker of Mycobacterium bovis.

In this study, we characterized the humoral responses in cattle of Sardinia. The animals were divided into three groups: 1) 28 cattle infected with Mycobacterium bovis; 2) 48 cattle from herds in which foci of infection was notified; 3) 50 cattle from herds that were TB-free. Levels of IgG antibody were measured against the following antigens of M. tuberculosis: Heparin-Binding-Haemagglutin (HBHA), Ag85B, PPE44, and PE_PGRS33 to investigate their potential to diagnose TB in animals. Our results indicated that HBHA is a potential candidate for the development of a serological assay for rapid diagnosis of cattle infected with M. bovis.

Identification of mycobacterial infections in wild boars in Northern Sardinia, Italy.

During a six-month period a region of Northern Sardinia was monitored to check the presence of mycobacterial infections in wild boars. Forty-eight serum and 229 biopsy samples were collected from different animals and examined by both traditional diagnostic techniques (culture, bacterioscopic and molecular tests) and enzyme-linked immunosorbent assay (ELISA). The latter was used to determine the antibody response against both methylated and nonmethylated Heparin-Binding Haemagglutinin (HBHA) protein. Nine mycobacterial strains were isolated: three M. avium ssp. paratuberculosis (Map), three M. avium, one M. interjectum and two M. scrofulaceum strains. By PCR, only one animal was positive for M. bovis, whereas 10 animals were positive for Map. Out of the 48 sera tested, 19 showed a good humoral response to methylated HBHA and 17 to nonmethylated HBHA. Our data provide new information on the prevalence of mycobacterial infection among wild boars in Northern Sardinia and suggest that a more effective program should be developed to monitor mycobacterial infections in the wild animal population.

Tratamiento endovascular de aneurismas de arterias viscerales. Experiencia de 10 años en un solo centro / Endovascular treatment of visceral artery aneurysms. A single center 10-year experience

RESUMEN Antecedentes : los aneurismas de arterias viscerales (AAV) tienen una frecuencia baja (0,1 a 2%). Hasta un 25% puede presentarse como rotura, con una alta mortalidad (hasta 70%). La terapia endovascular ha ganado terreno y se recomienda como primera opción según las últimas guías. Hoy en día, es posible adaptarse a casi cualquier anatomía utilizando tecnología cerebral. Objetivo : describir la experiencia y enfoque en el manejo endovascular de AAV, con resultados a corto, mediano y largo plazo. Material y métodos : llevamos a cabo una evaluación retrospectiva de pacientes tratados por AAV verdaderos por vía endovascular en un solo centro entre 2010 y 2020, con un seguimiento mínimo de 6 meses. Resultados : analizamos 19 procedimientos en 18 pacientes (9 hombres y 9 mujeres). La edad promedio fue 61,9 años; el promedio de tiempo de internación fue 1,94 días y el promedio de seguimiento de 40 meses. La arteria más involucrada fue la esplénica (n = 9, 50%). El tamaño aneurismático promedio fue 30,1 mm. La estrategia terapéutica más utilizada fue colocación de diversor de flujo (n = 8, 42,1%). Dos pacientes fueron reintervenidos (11,1%). Las tasas de exclusión completa fueron del 47,4%, 68,4% y 94,7% a los 3, 6 y 12 meses, respectivamente. No hubo casos de mortalidad a 30 días ni mortalidad relacionada con el aneurisma durante el seguimiento. Conclusión : el tratamiento endovascular de los AAV es seguro y eficaz. Sin embargo, se debe contar con la tecnología adecuada, para la planificación preoperatoria y el tratamiento.

ABSTRACT Background : the prevalence of visceral artery aneurysms (VAAs) is low (0.1 to 2%). Up to 25% may present as rupture which is associated with high mortality (up to 70%). Endovascular treatment has gained ground and is even considered the first option according to the most recent recommendations. Nowadays, almost any anatomy can be approached with endovascular techniques used to treat intracranial aneurysms. Objective : the aim of our study was to describe the experience and approach for the endovascular management of VAAs with short-, mid-, and long-term results. Material and methods : we conducted a retrospective evaluation of patients with true VAAs undergoing endovascular treatment in a single center between 2010 and 2020 who were followed up for a minimum of 6 months. Results : we analyzed 19 procedures in 18 patients (9 men and 9 women). Mean age was 61.9 years; mean length of hospital stay was 1.94 days and mean follow-up was 40 months. The splenic artery was the vessel most affected (n = 9, 50%). Mean aneurysm size was 30.1 mm. Flow diversion was the strategy most used (n = 8, 42.1%). Two patients required reintervention (11%). Complete exclusion rate was 38.4%, 47.4%, 68.4% and 94.7% at 3, 6 and 12 months, respectively. There were no cases of mortality within the first 30 days and no aneurysm-related mortality during the follow-up period. Conclusion : endovascular treatment of VAAs is a safe and efficient strategy but requires adequate technology for preoperative planning and treatment.

Cerebrovascular effects of cilostazol in patients with atherosclerotic disease.

BACKGROUND: Cilostazol is a potent selective inhibitor of phosphodiesterase-3 of proven efficacy in intermittent claudication. It has antiplatelet effect and produces vasodilatation in several vascular territories. This drug has been approved in some countries for the prevention of recurrence of cerebral infarction. Limited data in patients with cerebral infarcts suggest improvement in cerebral blood flow. Dilatation of cerebral vessels with carbon-dioxide challenge can be assessed by transcranial Doppler technique. The percentage increase in blood flow velocity is called cerebral vasomotor reactivity (CVR). OBJECTIVE: In this investigation we sought to measure CVR before and after oral administration of cilostazol. METHODS: We studied patients with risk factors for atherosclerosis before they received cilostazol (100 mg twice daily) for intermittent claudication. CVR was assessed by measuring bilateral middle cerebral artery blood flow velocity during normoventilation and after 3 minutes of breathing 8% carbon dioxide. One average value was obtained from each patient. CVR was measured the day before cilostazol first dose, at 1 month, and 3 to 6 months later. RESULTS: We examined 9 patients (8 men and 1 woman) aged 67.6 +/- 8.4 years. All patients had hypertension, 5 had diabetes, 4 were smokers, 5 had high cholesterol levels, and 4 had coronary artery disease. CVR was 54.4 +/- 14.4% at baseline, and increased to 64.2 +/- 18.6% after 1 month (P < .05) and to 67.1 +/- 13.3% at 3 to 6 months later (P < .01). CONCLUSION: Our findings suggest that cilostazol increases CVR in patients with atherosclerotic disease.

Complicaciones venosas centrales asociadas al aneurisma de aorta abdominal roto / Central Venous Complications Associated with Ruptured Abdominal Aortic Aneurysm

RESUMEN La ruptura del aneurisma de aorta abdominal (AAA) representa una verdadera emergencia quirúrgica. Asociada con dolor abdominal, hipotensión e incluso shock, exige una transferencia inmediata a una sala de operaciones adecuadamente equipada para tratar el aneurisma en forma efectiva y sin demora. Ocasionalmente puede manifestarse como resultado de su relación con estructuras adyacentes. Dos complicaciones venosas asociadas con el AAA roto son la fístula aortocava y la compresión de la vena cava inferior (VCI). Los autores informan casos particulares de fístula aortocava y compresión de VCI con trombosis venosa profunda (TVP) por AAA roto. Los cuatro pacientes fueron tratados mediante reparación endovascular. Además de discutir las circunstancias asociadas con las complicaciones venosas por AAA, los autores también discuten la estrategia de tratamiento adoptada y las posibles alternativas.

ABSTRACT Ruptured abdominal aortic aneurysms (rAAAs) represent a real surgical emergency. In the presence of abdominal pain, hypotension or even shock, patients require emergency transfer to an operating room adequately equipped to treat the aneurysm effectively and without delay. Occasionally, symptoms are the consequence of involvement of the adjacent structures, Aortocaval fistula and compression of the inferior vena cava (IVC) are venous complications associated with rAAAs. We report cases of aortocaval fistula and IVC compression with deep venous thrombosis (DVT) due to rAAA. The four patients underwent endovascular repair. The circumstances associated with the venous complications of rAAA, the treatment strategy used and the therapeutic options are described.

Two-particle anomalous diffusion: probability density functions and self-similar stochastic processes.

Two-particle dispersion is investigated in the context of anomalous diffusion. Two different modelling approaches related to time subordination are considered and unified in the framework of self-similar stochastic processes. By assuming a single-particle fractional Brownian motion and that the two-particle correlation function decreases in time with a power law, the particle relative separation density is computed for the cases with time sub-ordination directed by a unilateral M-Wright density and by an extremal Lévy stable density. Looking for advisable mathematical properties (for instance, the stationarity of the increments), the corresponding self-similar stochastic processes are represented in terms of fractional Brownian motions with stochastic variance, whose profile is modelled by using the M-Wright density or the Lévy stable density.