Multidisciplinary lifestyle intervention to manage pancreatic cancer-related cachexia: a case report

Pancreatic cancer remains an aggressive disease, with a poor prognosis and a high risk of incurring into cachexia. Supportive care, such as exercise, nutritional and psychological support, may be effective in reducing functional loss, psychological distress and improving nutritional status. We report the effect of 12 weeks of multimodal lifestyle intervention in a 55-year-old female, diagnosed with unresectable body/tail pancreatic cancer and metastasis in the liver, bone, lymph node and lung, to counteract cachexia. The multimodal program resulted safe and feasible. Over 12 weeks, considerable improvements were found in body weight, health-related physical fitness, nutritional status, distress scores, anxiety and depression levels. These findings highlight the potential role of integrated supportive interventions to manage metastatic cancer and cancer-induced cachexia

A workflow to generate physical 3D models of cerebral aneurysms applying open source freeware for CAD modeling and 3D printing

Objectives: 3D anatomical models are becoming a new frontier in surgery for planning and simulation on an individualized patient specific basis. Since 1999, 3D cerebral aneurysms models for neurosurgery have been proposed. The possibility of reproducing in a realistic 3D fashion the malformation with the surrounding vascular structures, provides important preoperative information for the treatment strategy. The same models can be used for training and teaching.Unfortunately stereolitography is often burdened by high costs and long times of production. These factors limit the possibility to use 3D models to plan surgeries in an easy daily fashion. Patients and methods: Our study enrolled 5 patients harboring cerebral aneurysms. DICOM data of each aneurysm were elaborated by an open source freeware to obtain CAD molds. Afterwards, the 3D models were produced using a fused deposition or a stereolitography printer. Results: Models were evaluated by Neurosurgeons in terms of quality and usefulness for surgical planning. Costs and times of production were recorded. Conclusions: Models were reliable, economically affordable and quick to produce. Keywords: Stereolitography, Cerebral aneurysms, 3D printing, Surgical planning, Aneurysm model

Eagle jugular syndrome: a morphometric computed study on styloid process orientation

Cerebral venous drainage impairment is related to a wide spectrum of pathologies, both acute or chronic. Among the most intriguing and less explained there are those caused by a long-lasting compression on internal jugular vein (IJV), mono or bilaterally. Recently, a jugular variant of the Eagle syndrome has been described,1,2 in which an elongated styloid process, coming from the mastoid tip down through the neck, compresses the IJV (more frequently J3) in its passage on the C1 anterior arch. Interestingly, those patients often complaint of typical symptoms of intracranial hypertension, such as headache (not frequent in classic Eagle syndrome), tinnitus, dizziness. They also seem to have an increased risk of perimesencephalic hemorrhages. Conceptually, it is not the styloid process length in itself to determine the compression, but rather its spatial orientation. We could therefore expect to find patients suffering from Eagle jugular syndrome who present normal or short styloid process, but in close proximity to C1. To test this hypothesis, we are developing a novel software to analyze 3-D spatial orientation of styloid process in patient with a previously diagnosed Eagle jugular syndrome compared to healthy controls. Methods We collected cervical computed tomography angiography (CTA) images from 8 patients with EJS confirmed by venous angiography at our institution, and a control group of 7 random patients, homogenous for sex and age. A blind operator created with a dedicated pre-existing software3, an editable 3-D model (.stl file) of the 3 main region of interest (ROI), namely: right styloid, left styloid, C1 anterior arch. Starting from this dataset, our software, written using the open-source package management system Anaconda4 ver. 2-2.4.0, compares all the possible couples of points between each styloid process and the C1 arch, detecting the minimum and maximum distance. Then, it provides the mean spatial orientation of the process respect the CT-axis: x-axis (from left to right), y-axis (from occiput to nose) and z-axis (cranio-caudal). Results By now we included 15 patients (8 cases, 7 controls), homogeneous for sex and age. Preliminary data (Table 1), although not statistically significant yet, seems to indicate that Eagle jugular patients effectively have a more vertical styloid process, meaning an angle between styloid and y-axis greater than controls, rather than a longer one. Conclusions Our preliminary results could confirm that spatial orientation is more important in Eagle jugular patients than styloid process length. This study is currently ongoing and we planned to enroll at least 20 subjects for each arm. At the same time, we are collecting data from patients with carotic variant of Eagle syndrome, to better characterize morphometric structure of styloid in various subset of this pathology

High-Resolution Steady State Magnetic Resonance Angiography of the Carotid Arteries: Are Intravascular Agents Necessary? Feasibility and Preliminary Experience With Gadobenate Dimeglumine

Purpose: To prospectively evaluate the potential of gadobenate dimeglumine for high-resolution steady-state (SS) contrast-enhanced magnetic resonance angiography (CE-MRA) of the carotid arteries as an adjunct to conventional first-pass (FP) MRA, with computed tomography angiography (CTA) and digital subtraction angiography (DSA) as reference. Materials and Methods: Institutional ethics committee approval and written informed consent were obtained. Forty consecutive patients underwent conventional FP MRA with 15 mL gadobenate dimeglumine, using a conventional 3D FLASH sequence (14 see acquisition time). Immediately afterward, SS images were obtained using a high resolution coronal 3D FLASH sequence (240 see acquisition time). All patients also underwent CTA and conventional DSA within 8 +/- 3 days. Three experienced radiologists assessed FP and SS image quality and calculated sensitivity, specificity, accuracy, and predictive values for stenosis grade and length, plaque morphology, and tandem lesions using DSA as reference. Detected stenoses were quantified and compared (Spearman rank correlation coefficient, [R(s)]. McNemar test) with DSA and CTA findings. Inter-read variability was assessed using kappa (kappa) statistics. The impact of SS acquisitions on diagnostic confidence and patient management was assessed. Results: MRA FP and SS image quality was excellent in 63 (78.8%) and 46 (57.5%) vessels, adequate in 11 (13.8%) and 20 (25.0%) vessels, and poor in 6 (7.5%) and 14 (17.5%) vessels, respectively. Area under the curve analysis revealed no significant differences between MRA FP, MRA FP + SS, and CTA for the grading of stenoses (P = 0.838; accuracy values of 97.4% 97.4%, and 98.7%, respectively). Greater accuracy (P < 0.001) was noted for FP + SS images over FP images alone for the assessment of plaque morphology (96.1% for FP + SS images vs. 83.3% for FP). Increased diagnostic confidence was noted for 49 (61.3%) vessels because of additional SS images whereas an impact on final diagnosis was noted in 8 (10%) cases. Good correlation was noted between SS image quality and impact on final diagnosis (R(s) = 0.7; P < 0.0001). Conclusion: SS imaging of the carotid arteries is feasible with gadobenate dimeglumine. The increased spatial resolution attainable allows improved evaluation of stenoses and plaque irregularity, yielding comparable diagnostic performance to that of CTA and DSA

Small Extracellular Vesicles from Inflamed Adipose Derived Stromal Cells Enhance the NF-κB-Dependent Inflammatory/Catabolic Environment of Osteoarthritis

The last decade has seen exponentially growing efforts to exploit the effects of adipose derived stromal cells (ADSC) in the treatment of a wide range of chronic degenerative diseases, including osteoarthritis (OA), the most prevalent joint disorder. In the perspective of developing a cell-free advanced therapy medicinal product, a focus has been recently addressed to the ADSC secretome that lends itself to an allogeneic use and can be further dissected for the selective purification of small extracellular vesicles (sEVs). sEVs can act as "biological drug carriers" to transfer information that mirror the pathophysiology of the providing cells. This is important in the clinical perspective where many OA patients are also affected by the metabolic syndrome (MetS). ADSC from MetS OA patients are dysfunctional and "inflammatory" primed within the adipose tissue. To mimic this condition, we exposed ADSC to IL-1 beta, and then we investigated the effects of the isolated sEVs on chondrocytes and synoviocytes, either cultured separately or in co-culture, to tease out the effects of these "IL-1 beta primed sEVs" on gene and protein expression of major inflammatory and catabolic OA markers. In comparison with sEVs isolated from unstimulated ADSC, the IL-1 beta primed sEVs were able to propagate NF-kappa B activation in bystander joint cells. The effects were more prominent on synoviocytes, possibly because of a higher expression of binding molecules such as CD44. These findings call upon a careful characterization of the "inflammatory fingerprint" of ADSC to avoid the transfer of an unwanted message as well as the development of in vitro "preconditioning" strategies able to rescue the antiinflammatory/anticatabolic potential of ADSC-derived sEVs

Bleeding risk evaluation in cerebral cavernous malformation, the role of medications, and hemorrhagic factors: a case-control study

Objective: Cerebral cavernous malformations (CCMs) are vascular lesions with an overall risk of rupture from 2% to 6% per year, which is associated with significant morbidity and mortality. The diagnostic incidence is increasing, so it is of paramount importance to stratify patients based on their risk of rupture. Data in the literature seem to suggest that specific medications, particularly antithrombotic and cardiovascular agents, are associated with a reduced risk of bleeding. However, the effect of the patient coagulative status on the cumulative bleeding risk remains unclear. The aim of this study was to assess the impact of different radiological, clinical, and pharmacological factors on the bleeding risk of CCMs and to assess the predictive power of an already validated scale for general bleeding risk, the HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly). Method: This was a multicenter retrospective observational study. The authors collected imaging, clinical status, and therapy data on patients with bleeding and nonbleeding CCMs. Univariate analysis and subsequent multivariate logistic regression were performed between the considered variables and bleeding or nonbleeding status to identify potential independent predictors of bleeding. Results: The authors collected data on 257 patients (46.7% male, 25.3% with bleeding CCMs). Compared with patients with nonbleeding lesions, those with bleeding CCMs were younger, less frequently had hypertension, and less frequently required antiplatelet drugs and beta-blockers (all p &lt; 0.05). Bleeding lesions, however, had significantly higher median volumes (1050 mm3 vs 523 mm3 , p &lt; 0.001). On multivariate analyses, after adjusting for age, history of hypertension and diabetes, and use of antiplatelet drugs or beta-blockers, lesion volume ≥ 300 mm3 was the only significant predictor of bleeding (adjusted OR 3.11, 95% CI 1.09-8.86). When the diagnostic accuracy of different volume thresholds was explored, volume ≥ 300 mm3 showed a limited sensitivity (36.7%, 95% CI 24.6%-50.0%), but a high specificity 78.2% (95% CI 71.3%-84.2%), with an area under the curve of 0.57 (95% CI 0.51-0.64). Conclusions: This study supports previous findings that the CCM volume is the only factor influencing the bleeding risk. Antithrombotic agents and propranolol seem to have a protective role against the bleeding events. A high HAS-BLED score was not associated with an increased bleeding risk. Further studies are needed to confirm these results

TP53 drives abscopal effect by secretion of senescence-associated molecular signals in non small cell lung cancer

Background Recent developments in abscopal effect strongly support the use of radiotherapy for the treatment of metastatic disease. However, deeper understanding of the molecular mechanisms underlying the abscopal effect are required to best benefit a larger proportion of patients with metastasis. Several groups including ours, reported the involvement of wild-type (wt) p53 in radiation-induced abscopal effects, however very little is known on the role of wtp53 dependent molecular mechanisms. Methods We investigated through in vivo and in vitro approaches how wtp53 orchestrates radiation-induced abscopal effects. Wtp53 bearing (A549) and p53-null (H1299) NSCLC lines were xenotransplanted in nude mice, and cultured in 2D monolayers and 3D tumor spheroids. Extracellular vesicles (EVs) were isolated from medium cell culture by ultracentrifugation protocol followed by Nanoparticle Tracking Analysis. Gene expression was evaluated by RT-Real Time, digital qRT-PCR, and dot blot technique. Protein levels were determined by immunohistochemistry, confocal anlysis, western blot techniques, and immunoassay. Results We demonstrated that single high-dose irradiation (20 Gy) induces significant tumor growth inhibition in contralateral non-irradiated (NIR) A549 xenograft tumors but not in NIR p53-null H1299 or p53-silenced A549 (A549sh/p53) xenografts. We further demonstrates that irradiation of A549 cells in vitro induces a senescence-associated secretory phenotype (SASP) producing extracellular vesicles (EVs) expressing CD63 and carrying DNA:RNA hybrids and LINE-1 retrotransposon. IR-A549 EVs also hamper the colony-forming capability of recipient NIR A549 cells, induce senescent phenotype, nuclear expression of DNA:RNA hybrids, and M1 macrophage polarization. Conclusions In our models, we demonstrate that high radiation dose in wtp53 tumors induce the onset of SASP and secretion of CD63+ EVs loaded with DNA:RNA hybrids and LINE-1 retrotransposons that convey senescence messages out of the irradiation field triggering abscopal effect in NIR tumors

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p &lt; 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p &lt; 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p &lt; 0.0001) or urgent (20.4% vs. 38.5%; p &lt; 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p &lt; 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice