Skeletal muscle wasting and long-term prognosis in patients undergoing rectal cancer surgery without neoadjuvant therapy.

BACKGROUND: Derangement of body composition has been associated with dismal long-term survival in several gastrointestinal cancers including rectal tumors treated with neoadjuvant therapies. The role of specific preoperative anthropometric indexes on the oncologic outcomes of patients undergoing upfront surgery for rectal cancer has not been investigated. The aim of the study is to evaluate the association of body composition and overall survival in this specific cohort. METHODS: Lumbar computed tomography images, obtained within the 30 days previous to surgery, between January 2009 and December 2016, were used to calculate population-specific thresholds of muscle mass (sarcopenia), subcutaneous and visceral adiposity, visceral obesity, sarcopenic obesity, and myosteatosis. These body composition variables were related with overall survival (OS), tumor-specific survival (TSS), and disease-free survival (DFS). OS, TSS, and DFS were evaluated by the Kaplan-Meier method. Cox regression analysis was used to identify independent predictors of mortality, tumor-specific mortality, and recurrence, and data were presented as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: During the study period, 411 patients underwent rectal resection for cancer, and among these, 129 were without neoadjuvant chemoradiation. The median follow-up was 96.7 months. At the end of the follow-up, 41 patients (31.8%) had died; of these, 26 (20.1%) died for tumor-related reasons, and 36 (27.1%) experienced disease recurrence. One-, three-, and five-year OS was 95.7%, 86.0%, and 76.8% for non-sarcopenic patients versus 82.4%, 58.8%, and 40.0% for sarcopenic ones respectively (p < 0.001). Kaplan-Meier survival curves comparing sarcopenic and non-sarcopenic patients showed a significant difference in terms of OS (log-rank < 0.0001). Through multivariate Cox regression, overall mortality risk was associated only with sarcopenia (HR 1.96; 95%CI 1.03-3.74; p = 0.041). Disease stage IV and III (HR 13.75; 95% CI 2.89-65.6; p < 0.001 and HR 4.72; 95% CI 1.06-21.1; p = 0.043, respectively) and sarcopenia (HR 2.62; 95% CI 1.22-5.6; p = 0.013) were independently associated with TSS. The other body composition indexes investigated showed no significant association with prognosis. CONCLUSIONS: These results support the inclusion of body composition assessment for prognostic stratification of rectal cancer patients undergoing upfront resection.

The Impact of Formula Choice for the Management of Pediatric Cow's Milk Allergy on the Occurrence of Other Allergic Manifestations: The Atopic March Cohort Study.

OBJECTIVES: To compare the impact of different formulas on the occurrence of other atopic manifestations and the time of immune tolerance acquisition. STUDY DESIGN: In a 36-month prospective cohort study, the occurrence of other atopic manifestations (eczema, urticaria, asthma, and rhinoconjunctivitis) and the time of immune tolerance acquisition were comparatively evaluated in immunoglobulin E-mediated children with cow's milk allergy (CMA) treated with extensively hydrolyzed casein formula containing the probiotic L. rhamnosus GG (EHCF + LGG), rice hydrolyzed formula, soy formula, extensively hydrolyzed whey formula (EHWF), or amino acid-based formula. RESULTS: In total, 365 subjects were enrolled into the study, 73 per formula cohort. The incidence of atopic manifestations was 0.22 (Bonferroni-corrected 95% CI 0.09-0.34) in the EHCF + LGG cohort; 0.52 (0.37-0.67) in the rice hydrolyzed formula cohort; 0.58 (0.43-0.72) in the soy formula cohort; 0.51 (0.36-0.66) in the EHWF cohort; and 0.77 (0.64-0.89) in the amino acid-based formula cohort. The incidence of atopic manifestations in the rice hydrolyzed formula, soy formula, EHWF, and amino acid-based formula cohorts vs the EHCF + LGG cohort was always greater than the prespecified absolute difference of 0.25 at an alpha-level of 0.0125, with corresponding risk ratios of 2.37 (1.46-3.86, P < .001) for rice hydrolyzed formula vs EHCF + LGG; 2.62 (1.63-4.22, P < .001) for soy formula vs EHCF + LGG; 2.31 (1.42-3.77, P < .001) for EHWF vs EHCF + LGG; and 3.50 (2.23-5.49, P < .001) for amino acid-based formula vs EHCF + LGG. The 36-month immune tolerance acquisition rate was greater in the EHCF + LGG cohort. CONCLUSIONS: The use of EHCF + LGG for CMA treatment is associated with lower incidence of atopic manifestations and greater rate of immune tolerance acquisition.

Influence of injection rate in determining the development of artifacts during the acquisition of dynamic arterial phase in Gd-EOB-DTPA MRI studies.

OBJECTIVE: To assess whether different Gd-EOB-DTPA injection rates could influence the development of artifacts during the arterial phase of liver MRI studies. MATERIALS AND METHODS: All Gd-EOB-DTPA liver MRI studies performed for different clinical indications at a single tertiary referral center were retrospectively evaluated. Each examination was acquired on a 1.5 T scanner with T1 In- and Out-of-Phase, T2 with and without fat-saturation, DWI, and 3D-T1 fat-sat dynamic sequences. Patients were divided into two groups according to the injection rate (1 ml/s and 1.5 ml/s). A single radiologist recorded the presence or absence of artifacts during different acquisition phases, respectively: (1) all examination; (2) only during the arterial phase; (3) only during the portal-venous phase; (4) both in arterial and portal-venous phases. From a total of 748 MRI studies performed, 229 were excluded due to the presence of artifacts during the entire examination. The remaining 519 MRI studies were divided into two groups according to the injection rate. RESULTS: The first group (flow rate = 1 ml/s) was composed by 312 (60.1%) patients and the second group (flow rate = 1.5 ml/s) by 207 (39.9%) patients. In the first group, 2 (0.6%) patients showed artifacts in all dynamic sequences; 13 (4%) only in the arterial phase, 16 (5%) only in the portal-venous phase, and 38 (12%) both in arterial and portal-venous phases; a total of 243 (78%) showed no artifacts. In the second group, 3 (1.5%) patients had artifacts in all dynamic sequences, 82 (40%) only in the arterial phase, 20 (10%) only in the portal-venous phase, and 53 (25%) both in arterial and portal-venous phases; a total of 49 (23.5%) showed no artifacts. A significant difference between the two groups regarding the absence of artifacts in all examination and the presence of artifacts only during the arterial phase was found (p < 0.001). CONCLUSION: The development of artifacts during the arterial phase of Gd-EOB-DTPA liver MRI studies could be related to the injection rate and its reduction may help to decrease the incidence of artifacts.

Computed Tomography Angiography Combined With Knowledge-Based Iterative Algorithm for Transcatheter Aortic Valve Implantation Planning: Image Quality and Radiation Dose Exposure With Low-kV and Low-Contrast-Medium Protocol.

OBJECTIVE: To evaluate image quality and radiation dose exposure of low-kV setting and low-volume contrast medium (CM) computed tomography angiography (CTA) protocol for transcatheter aortic valve implantation (TAVI) planning in comparison with standard CTA protocol. METHODS: Sixty-patients were examined with 256-row MDCT for TAVI planning: 32 patients (study group) were evaluated using 80-kV electrocardiogram-gated protocol with 60 mL of CM and IMR reconstruction; 28 patients underwent a standard electrocardiogram-gated CTA study (100 kV; 80 mL of CM; iDose4 reconstruction). Subjective and objective image quality was evaluated in each patient at different aortic levels. Finally, we collected radiation dose exposure data (CT dose index and dose-length product) of both groups. RESULTS: In study protocol, significant higher mean attenuation values were achieved in all measurements compared with the standard protocol. There were no significant differences in the subjective image quality evaluation in both groups. Mean dose-length product of study group was 56% lower than in the control one (P < 0.0001). CONCLUSION: Low-kV and low-CM volume CTA, combined with IMR, allows to correctly performing TAVI planning with high-quality images and significant radiation dose reduction compared with standard CTA protocol.

Evaluation of image quality and radiation dose saving comparing knowledge model-based iterative reconstruction on 80-kV CT pulmonary angiography (CTPA) with hybrid iterative reconstruction on 100-kV CT.

OBJECTIVES: To evaluate dose reduction and image quality of 80-kV CT pulmonary angiography (CTPA) reconstructed with knowledge model-based iterative reconstruction (IMR), and compared with 100-kV CTPA with hybrid iterative reconstruction (iDose4). MATERIALS AND METHODS: One hundred and fifty-one patients were prospectively investigated for pulmonary embolism; a study group of 76 patients underwent low-kV setting (80 kV, automated mAs) CTPA study, while a control group of 75 patients underwent standard CTPA protocol (100 kV; automated mAs); all patients were examined on 256 MDCT scanner (Philips iCTelite). Study group images were reconstructed using IMR while the control group ones with iDose4. CTDIvol, DLP, and ED were evaluated. Region of interests placed in the main pulmonary vessels evaluated vascular enhancement (HU); signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. RESULTS: Compared to iDose4-CTPA, low-kV IMR-CTPA presented lower CTDIvol (6.41 ± 0.84 vs 9.68 ± 3.5 mGy) and DLP (248.24 ± 3.2 vs 352.4 ± 3.59 mGy × cm), with ED of 3.48 ± 1.2 vs 4.93 ± 1.8 mSv. Moreover, IMR-CTPA showed higher values of attenuation (670.91 ± 9.09 HU vs 292.61 ± 15.5 HU) and a significantly higher SNR (p < 0.0001) and CNR (p < 0.0001).The subjective image quality of low-kV IMR-CTPA was also higher compared with iDose4-CTPA (p < 0.0001). CONCLUSIONS: Low-dose CTPA (80 kV and automated mAs modulation) reconstructed with IMR represents a feasible protocol for the diagnosis of pulmonary embolism in the emergency setting, achieving high image quality with low noise, and a significant dose reduction within adequate reconstruction times(≤ 120 s).

Diagnostic efficacy of model-based iterative reconstruction algorithm in an assessment of coronary artery in comparison with standard hybrid-Iterative reconstruction algorithm: dose reduction and image quality.

PURPOSE: To evaluate the image quality and radiation dose exposure of low-dose coronary CTA (cCTA) study, reconstructed with the new model-based iterative reconstruction algorithm (IMR), compared with standard hybrid-iterative reconstruction (iDose4) cCTA in patients with suspected coronary artery disease. MATERIALS AND METHODS: Ninety-eight patients with an indication for coronary CT study were prospectively enrolled. Fifty-two patients (study group) underwent 256-MDCT low-dose cCTA (80 kV; automated-mAs; 60 mL of CM, 350 mgL/mL) with prospective ECG-triggering acquisition and IMR. A control group of 46 patients underwent 256-MDCT standard prospective ECG-gated protocol (100 kV; automated-mAs; 70 mL of CM, 400 mgL/mL; iDose4). Subjective and objective image quality (attenuation value, SD, SNR and CNR) were evaluated by two radiologists subjectively. Radiation dose exposure was quantified as DLP, CTDIvol and ED. RESULTS: Mean values of mAs were significantly lower for IMR-cCTA (167 ± 62 mAs) compared to iDose-cCTA (278 ± 55 mAs), p < 0.001. With a significant reduction of 38% in radiation dose exposure (DLP: IMR-cCTA 91.7 ± 26 mGy cm vs. iDose-cCTA 148.6 ± 35 mGy cm; p value < 0.001), despite the use of different CM, we found higher mean attenuation values of the coronary arteries in IMR group compared to iDose4 (mean density in LAD: 491HU IMR-cCTA vs. 443HU iDose-cCTA; p = 0.03). We observed a significant higher value of SNR and CNR in study group due to a lower noise level. Qualitative analysis did not reveal any significant differences between the two groups (p = 0.23). CONCLUSIONS: Low-dose cCTA study combined with IMR reconstruction allows to correctly evaluate coronary arteries disease, offering high-quality images and significant radiation dose exposure reduction (38%), as compared to standard cCTA protocol.

Real-Time Elastography: Noninvasive Diagnostic Tool in the Evaluation of Liver Stiffness in Patients with Chronic Viral Hepatitis, Correlation with Histological Examination.

PURPOSE: To determine the value of real-time elastography (RTE) in the assessment of liver stiffness in patients with chronic viral hepatitis, correlating RTE data with the extent of fibrosis based on biopsy findings (Ishak score). METHODS: We evaluated 98 patients (45-75 years) with chronic viral hepatitis (51 HCV, 47 HBV) by using ultrasonography (US) study combined with RTE analysis. In the RTE images, relative tissue stiffness is expressed, according to color scale, with soft areas represented in green/red colors and hard areas in blue. We divided the patients into 2 groups based on the fibrosis degree: soft degree (D1, corresponding to F1-F3 Ishak score) and hard degree (D2, corresponding to F4-F6). Before RTE, all patients underwent a US-guided percutaneous liver biopsy (right lobe). RESULTS: Quantitative RTE data were compared with liver biopsy by using the Spearman correlation coefficient in order to assess the correlation between the RTE (D) and fibrosis, according to Ishak score (F) at histology. At RTE, out of 98 patients 55 had degree D1 and 43 had degree D2; at histological analysis, we observed the following: 15 patients with F1, 28 with F2, 17 with F3, 16 with F4, 12 with F5, and 10 with F6. The Spearman's coefficient showed significant correlation between D and F degree, obtaining rho = 0.573, p = 0.003. CONCLUSIONS: RTE analysis showed high diagnostic accuracy in the assessment of fibrosis, and it appears to be a useful diagnostic tool for noninvasive quantification of fibrosis in patients with chronic viral hepatitis.

"Hyperdense artery sign" in early ischemic stroke: diagnostic value of model-based reconstruction approach in comparison with standard hybrid iterative reconstruction algorithm.

PURPOSE: Hyperdense artery sign is the earliest sign of ischemic stroke on non-enhanced computed tomography and it can be visible long before parenchymal changes. The aim of our study was to compare diagnostic value of model-based iterative reconstruction algorithm (IMR) with that of iterative reconstruction algorithm (iDose4) in identifying hyperdense artery sign. METHODS: We selected 56 consecutive patients suspected for ischemic stroke, who underwent a NCCT and that demonstrated a vessel occlusion at angio-CT or developed ischemic lesion at follow-up CT. Two readers randomly analyzed images of NCCT reconstructed both with iDose4 (4 mm) and IMR (2 mm), reporting presence of hyperdense artery sign (0: no; 1: yes; 2: not sure). They rated image quality on a 4-point scale (1: unacceptable; 4: more than average) and recorded HU values of clot and of normal vessel and measured noise index, CNR and SNR. RESULTS: Mean values of CTDI, DLP, and ED were respectively of 43 mGy, 819.7 mGy cm, and 1.72 mSv. By analyzing the IMR reconstruction, both readers were able to recognize hyperdense vessel sign in 55/56 patients, while only in 12/56 patients were identified with iDose. IMR obtained better rating of image quality (mean score for IMR 3.32 vs 2.53 for iDose), higher clot density (57.2 vs 46.7 HU), lower noise index (5 vs 2), higher CNR and SNR (respectively 4.2 vs 2 and 16.8 vs 8.5). CONCLUSIONS: Model-based approach significantly increases sensitivity in detecting hyperdense artery sign, offering higher SNR and CNR in brain CT images in comparison with standard hybrid reconstruction algorithm.

Diagnostic accuracy of 256-row multidetector CT coronary angiography with prospective ECG-gating combined with fourth-generation iterative reconstruction algorithm in the assessment of coronary artery bypass: evaluation of dose reduction and image quality.

BACKGROUND: Effective radiation dose in coronary CT angiography (CTCA) for coronary artery bypass graft (CABG) evaluation is remarkably high because of long scan lengths. Prospective electrocardiographic gating with iterative reconstruction can reduce effective radiation dose. OBJECTIVES: To evaluate the diagnostic performance of low-kV CT angiography protocol with prospective ecg-gating technique and iterative reconstruction (IR) algorithm in follow-up of CABG patients compared with standard retrospective protocol. METHODS: Seventy-four non-obese patients with known coronary disease treated with artery bypass grafting were prospectively enrolled. All the patients underwent 256 MDCT (Brilliance iCT, Philips) CTCA using low-dose protocol (100 kV; 800 mAs; rotation time: 0.275 s) combined with prospective ECG-triggering acquisition and fourth-generation IR technique (iDose4; Philips); all the lengths of the bypass graft were included in the evaluation. A control group of 42 similar patients was evaluated with a standard retrospective ECG-gated CTCA (100 kV; 800 mAs).On both CT examinations, ROIs were placed to calculate standard deviation of pixel values and intra-vessel density. Diagnostic quality was also evaluated using a 4-point quality scale. RESULTS: Despite the statistically significant reduction of radiation dose evaluated with DLP (study group mean DLP: 274 mGy cm; control group mean DLP: 1224 mGy cm; P value < 0.001). No statistical differences were found between PGA group and RGH group regarding intra-vessel density absolute values and SNR. Qualitative analysis, evaluated by two radiologists in "double blind", did not reveal any significant difference in diagnostic quality of the two groups. CONCLUSIONS: The development of high-speed MDCT scans combined with modern IR allows an accurate evaluation of CABG with prospective ECG-gating protocols in a single breath hold, obtaining a significant reduction in radiation dose.

Predicting 60-Day Mortality in a Home-Care Service: Development of a New Inter-RAI 49-Frailty Index in Patients with Chronic Disease and without a Cancer Diagnosis.

OBJECTIVE: Frailty Index (FI) is used to define the level of frailty in various clinical settings. Fifteen- and 26-item FIs have been demonstrated to predict 1-year mortality and intensity of care in home care (HC) and palliative home care (PHC). The objective of this study was to develop a new FI to predict the 60-day risk of death or transition to a PHC service after the initiation of an HC service in patients with chronic disease and without a cancer diagnosis. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Patients 18 years and older followed in an HC service of a "Frailty Department-Local Palliative Care Network" from January 1, 2017, to October 31, 2021. METHODS: A 49-item FI (FI-49) was developed selecting variables within the standardized international Residential Assessment Instrument assessments (interRAI-HC) and compared to existing FIs with 15 and 26 variables. RESULTS: A total of 2099 patients were included in the study with a median age of 80.0 years (IQR: 72.0-86.0) and a predominantly female population (62.4%). Among these patients, 8% died or were transferred to PHC within the 60-day follow-up. The FI-49 demonstrated a higher ability to predict 60-day mortality (C index 0.8165, 95% CI 0.7848-0.8481) compared to the 26- and 15-item FI. An FI-49 cutoff of 0.33 was also selected to provide clinicians with a more practical approach (C-index of 0.7044, 95% CI 0.6796-0.7292). CONCLUSION AND IMPLICATION: The FI-49 is a good predictor of short-term mortality or transition to palliative care among older patients referred to an HC service. The automatic calculation of this tool could facilitate more appropriate care planning and the correct allocation of healthcare resources, especially considering the rapid ageing of the population.

Translating knowledge into policy: Organizational model and minimum requirements for the implementation of a regional pancreas unit network.

Pancreatic and periampullary cancers pose significant challenges in oncological care due to their complexity and diagnostic difficulties. Global experiences underscore the crucial role of multidisciplinary collaboration and centralized care in improving patient outcomes in this context. Recognizing these challenges, Lombardy, Italy's most populous region, embarked on establishing pancreas units across its territory to enhance clinical outcomes and organizational efficiency. This initiative, driven by a multistakeholder approach involving the Lombardy Welfare Directorate, clinicians, and a patient association, emphasizes the centralization of complex care in high-volume hospitals, adopting a hub-and-spoke model and a multidisciplinary approach. This article outlines the process and criteria set forth for pancreas unit implementation, aiming to provide a structured framework for enhancing pancreatic cancer care. Central to this initiative is the establishment of structured criteria and minimal requirements, not only for surgery but also for other essential components of care, ensuring a comprehensive approach to pancreatic cancer management. The Lombardy model offers a structured framework for enhancing pancreatic cancer care, with potential applicability to other regions and countries seeking to improve their cancer care infrastructure.

Feasibility of Low-Dose and Low-Contrast Media Volume Approach in Computed Tomography Cardiovascular Imaging Reconstructed with Model-Based Algorithm.

Aim: To evaluate the dose reduction and image quality of low-dose, low-contrast media volume in computed tomography (CT) examinations reconstructed with the model-based iterative reconstruction (MBIR) algorithm in comparison with the hybrid iterative (HIR) one. Methods: We prospectively enrolled a total of 401 patients referred for cardiovascular CT, evaluated with a 256-MDCT scan with a low kVp (80 kVp) reconstructed with an MBIR (study group) or a standard HIR protocol (100 kVp-control group) after injection of a fixed dose of contrast medium volume. Vessel contrast enhancement and image noise were measured by placing the region of interest (ROI) in the left ventricle, ascending aorta; left, right and circumflex coronary arteries; main, right and left pulmonary arteries; aortic arch; and abdominal aorta. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were computed. Subjective image quality obtained by consensus was assessed by using a 4-point Likert scale. Radiation dose exposure was recorded. Results: HU values of the proximal tract of all coronary arteries; main, right and left pulmonary arteries; and of the aorta were significantly higher in the study group than in the control group (p < 0.05), while the noise was significantly lower (p < 0.05). SNR and CNR values in all anatomic districts were significantly higher in the study group (p < 0.05). MBIR subjective image quality was significantly higher than HIR in CCTA and CTPA protocols (p < 0.05). Radiation dose was significantly lower in the study group (p < 0.05). Conclusions: The MBIR algorithm combined with low-kVp can help reduce radiation dose exposure, reduce noise, and increase objective and subjective image quality.

Inter-observer agreement and image quality of model-based algorithm applied to the Coronary Artery Disease-Reporting and Data System score.

PURPOSE: To evaluate the inter-observer agreement of the CAD-RADS reporting system and compare image quality between model-based iterative reconstruction algorithm (MBIR) and standard iterative reconstruction algorithm (IR) of low-dose cardiac computed tomography angiography (CCTA). METHODS: One-hundred-sixty patients undergone a 256-slice MDCT scanner using low-dose CCTA combined with prospective ECG-gated techniques were enrolled. CCTA protocols were reconstructed with both MBIR and IR. Each study was evaluated by two readers using the CAD-RADS lexicon. Vessels enhancement, image noise, signal-to-noise (SNR), and contrast-to-noise (CNR) were computed in the axial native images, and inter-observer agreement was assessed. Radiation dose exposure as dose-length product (DLP) and effective dose were finally reported. RESULTS: The reliability analysis between the two readers was almost perfect for all CAD-RADS standard categories. Moreover, a significantly higher value of subjective qualitative analysis, SNR, and CNR in MBIR images compared to IR were found, due to a lower noise level (all p < 0.05). The mean DLP measured was 63.9 mGy*cm, and the mean effective dose was 0.9 mSv. CONCLUSION: Inter-observer agreement of CAD-RADS was excellent confirming the importance, the feasibility, and the reproducibility of the CAD-RADS scoring system for CCTA. Moreover, lower noise and higher image quality with MBIR compared to IR were found. IMPLICATIONS FOR PRACTICE: MBIR, by reducing noise and improving image quality, can help a better assessment of CAD-RADS, in comparison with standard IR algorithm.

Low skeletal muscle index and myosteatosis as predictors of mortality in critically ill surgical patients.

OBJECTIVES: After elective surgeries, low muscle mass and other specific body composition indexes, assessed by computed tomography (CT), are associated with adverse outcomes such as an increased risk for postoperative complications and higher mortality. However, limited information is available about the role of these indexes on short- and long-term outcomes in surgical patients admitted to the intensive care unit (ICU). The aim of this study was to assess the association of body composition indexes with 90-d mortality in this specific patient cohort. METHODS: This was a retrospective study including adult surgical patients admitted to the ICU between 2014 and 2018 who underwent a CT scan at the time of admission. Total muscle area (TMA), total fat area (TFA), visceral fat area (VFA), and intramuscular fat area (IMFA) were measured. We then calculated skeletal muscle index (SMI; TMA/m2), myosteatosis (IMFA/TMA), and visceral fat-to-muscle ratio (VFA/TMA). We analyzed the effects of these indexes on mortality. RESULTS: The study included 204 patients. Overall, 90-d mortality was 28%. Log-rank test and Cox multivariate analysis on 90-d mortality showed a significant association of low SMI and myosteatosis with 90-d mortality. Myosteatosis was also significantly associated with prolonged mechanical ventilation and increased ICU length of stay. CONCLUSIONS: Specific body composition indexes may predict mortality in surgical patients admitted to the ICU. Low SMI and myosteatosis were independently associated with increased 90-d mortality.

Proteomic detection of a large amount of SCGFα in the stroma of GISTs after imatinib therapy.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors to develop in the digestive tract. These tumors are highly resistant to conventional chemotherapy and only the introduction of imatinib mesylate has improved the prognosis of patients. However, Response Evaluation Criteria in Solid Tumors are inappropriate for assessing tumor response, and the histological/pathological response to imatinib is variable, heterogeneous, and does not associate with clinical response. The effects of imatinib on responding GISTs are still being explored, and few studies correlate the clinical response with the histological response after pharmacological treatment. Recently, apoptosis and autophagy were suggested as possible alternative mechanisms of pharmacological response. METHODS: Here, we used a proteomic approach, combined with other analyses, to identify some molecular stromal components related to the response/behavior of resected, high-risk GISTs after neoadiuvant imatinib therapy. RESULTS: Our proteomic results indicate an elevated concentration of Stem Cell Growth Factor (SCGF), a hematopoietic growth factor having a role in the development of erythroid and myeloid progenitors, in imatinib-responsive tumor areas. SCGFα expression was detected by mass spectrometry, immunohistochemistry and/or western blot and attributed to acellular matrix of areas scored negative for KIT (CD117). RT-PCR results indicated that GIST samples did not express SCGF transcripts. The recently reported demonstration by Gundacker et al. 1 of the secretion of SCGF in mature pro-inflammatory dendritic cells would indicate a potential importance of SCGF in tissue inflammatory response. Accordingly, inflammatory infiltrates were detected in imatinib-affected areas and the CD68-positivity of the SCGF-positive and KIT-negative areas suggested previous infiltration of monocytes/macrophages into these regions. Thus, chronic inflammation subsequent to imatinib treatment may determine monocyte/macrophage recruitment in imatinib-damaged areas; these areas also feature prominent tumor-cell loss that is replaced by dense hyalinization and fibrosis. CONCLUSIONS: Our studies highlight a possible role of SCGFα in imatinib-induced changes of GIST structure, consistent with a therapeutic response.

Application of low-dose CT combined with model-based iterative reconstruction algorithm in oncologic patients during follow-up: dose reduction and image quality.

OBJECTIVES: To compare image quality and radiation dose of CT images reconstructed with model-based iterative reconstruction (MBIR) and hybrid-iterative (HIR) algorithm in oncologic patients. METHODS: 125 oncologic patients underwent both contrast-enhanced low- (100 kV), and standard (120 kV) dose CT, were enrolled. Image quality was assessed by using a 4-point Likert scale. CT attenuation values, expressed in Hounsfield unit (HU), were recorded within a regions of interest (ROI) of liver, spleen, paraspinal muscle, aortic lumen, and subcutaneous fat tissue. Image noise, expressed as standard deviation (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were calculated. Radiation dose were analyzed. Paired Student's t-test was used to compare all continuous variables. RESULTS: The overall median score assessed as image quality for CT images with the MBIR algorithm was significantly higher in comparison with HIR [4 (range 3-4) vs 3 (3-4), p = 0.017].CT attenuation values and SD were significantly higher and lower, respectively, in all anatomic districts in images reconstructed with MBIR in comparison with HIR ones (all p < 0.001). SNR and CNR values were higher in CT images reconstructed with MBIR, reaching a significant difference in all districts (all p < 0.001). Radiation dose were significantly lower in the MBIR group compared with the HIR group (p < 0.001). CONCLUSIONS: MBIR combined with low-kV setting allows an important dose reduction in whole-body CT imaging, reaching a better image quality both qualitatively and quantitatively. ADVANCES IN KNOWLEDGE: MBIR with low-dose approach allows a reduction of dose exposure, maintaining high image quality, especially in patients which deserve a longlasting follow-up.

Proteome profile in Myotonic Dystrophy type 2 myotubes reveals dysfunction in protein processing and mitochondrial pathways.

Myotonic Dystrophy type 2 (DM2) is caused by a DNA microsatellite expansion within the Zinc Finger Protein 9 gene leading to an abnormal splicing pattern largely responsible for the pathological condition. To better define the functional changes occurring in human DM2 myotubes we performed a quantitative proteome comparison between myotubes of DM2 and control patients using two-dimensional gel electrophoresis followed by mass spectrometry. Our results indicate that the proteins, altered in DM2 cultures, belong to two major functional categories: i) mitochondrial components, with a reduction of EFTu, HSP60, GRP75 and Dienoyl-CoA-Isomerase, an enzyme involved in fatty acids degradation; ii) the ubiquitin proteasome system with increase of the 26S proteasome regulatory subunit 13 and a reduction of Proteasome subunit Alfa6 and of Rad23B homolog. Altered ubiquitin-proteasomal activity is supported by a global reduction of cytosolic ubiquitinated proteins. Although future work is required to clarify how these changes affect the degradation machinery and mitochondrial function and to evaluate if these changes also occur in the biopsies of DM2 patients, these results identify the mitochondrial proteins and the ubiquitin-proteasomal system as candidates potentially relevant to DM2 pathogenesis.

Impact of Palliative Care in Evaluating and Relieving Symptoms in Patients with Advanced Cancer. Results from the DEMETRA Study.

Background: Cancer patients experience multiple symptoms throughout the course of the disease. We aimed to provide a comprehensive analysis of the symptom burden in patients with advanced cancer at admission to specialist palliative care (PC) services and seven days later to estimate the immediate impact of PC intervention. Patient and methods: The analysis was based on an observational, prospective, multicenter study (named DEMETRA) conducted in Italy on new patients accessing network specialist PC centers during the period May 2017-November 2017. The prevalence and intensity of symptoms were assessed at baseline and after seven days using three tools including the Edmonton Symptom Assessment System (ESAS). Results: Five PC centers recruited 865 cancer patients. Thirty-three different symptoms were observed at the baseline, the most frequent being asthenia (84.9%) and poor well-being (71%). The intensity of the most frequent symptoms according to ESAS ranged from 5.5 for asthenia to 3.9 for nausea. The presence and intensity of physical symptoms increased with increasing levels of anxiety and depression. After seven days, prevalence of nausea and breathlessness as well as intensity of almost all symptoms significantly decreased. Conclusions: The study confirmed the considerable symptom burden of patients with advanced cancer. PC intervention has significantly reduced the severity of symptoms, despite the patients' advanced disease and short survival.

Clinical Care Conditions and Needs of Palliative Care Patients from Five Italian Regions: Preliminary Data of the DEMETRA Project.

In order to plan the right palliative care for patients and their families, it is essential to have detailed information about patients' needs. To gain insight into these needs, we analyzed five Italian local palliative care networks and assessed the clinical care conditions of patients facing the complexities of advanced and chronic disease. A longitudinal, observational, noninterventional study was carried out in five Italian regions from May 2017 to November 2018. Patients who accessed the palliative care networks were monitored for 12 months. Sociodemographic, clinical, and symptom information was collected with several tools, including the Necesidades Paliativas CCOMS-ICO (NECPAL) tool, the Edmonton Symptom Assessment System (ESAS), and interRAI Palliative Care (interRAI-PC). There were 1013 patients in the study. The majority (51.7%) were recruited at home palliative care units. Cancer was the most frequent diagnosis (85.4%), and most patients had at least one comorbidity (58.8%). Cancer patients reported emotional stress with severe symptoms (38.7% vs. 24.3% in noncancer patients; p = 0.001) and were less likely to have clinical frailty (13.3% vs. 43.9%; p < 0.001). Our study confirms that many patients face the last few months of life with comorbidities or extreme frailty. This study contributes to increasing the general knowledge on palliative care needs in a high-income country.

COVID-19 emergency and palliative medicine: an intervention model'.

OBJECTIVES: The aim of this work is to describe the multidisciplinary model of intervention applied and the characteristics of some COVID-19 patients assisted by the hospital palliative care unit (UCP-H) of an Italian hospital in Lombardy, the Italian region most affected by the COVID-19 pandemic. METHODS: A retrospective study was conducted on patients admitted to the A. Manzoni Hospital (Lecco, Lombardy Region, Italy) and referred to the UCP-H between 11 March 2020 and 18 April 2020, the period of maximum spread of COVID-19 in this area. Data were collected on the type of hospitalisation, triage process, modality of palliative care and psychological support provided. RESULTS: 146 COVID-10 patients were referred to the UCP-H. Of these, 120 died during the observation time (82%) while 15 (10.2%) improved and were discharged from the UCP-H care. 93 had less favourable characteristics (rapid deterioration of respiratory function, old age, multiple comorbidities) and an intensive clinical approach was considered contraindicated, while 48 patients had more favourable presentations. Mean follow-up was 4.8 days. A mean of 4.3 assessments per patient were performed. As to respiratory support, 94 patients were treated with oxygen only (at different volumes) and 45 with Continuous Positive Airway Pressure (CPAP). CONCLUSION: The ongoing pandemic highlighted the need for dedicated palliative care teams and units for dying patients. This work highlights how palliative medicine specialist can make a fundamental contribution thanks to their ability and work experience in an organised multiprofessional context.