Stereotactic body radiotherapy for pancreatic cancer - A systematic review of prospective data.

Purpose: This systematic review aims to comprehensively summarize the current prospective evidence regarding Stereotactic Body Radiotherapy (SBRT) in various clinical contexts for pancreatic cancer including its use as neoadjuvant therapy for borderline resectable pancreatic cancer (BRPC), induction therapy for locally advanced pancreatic cancer (LAPC), salvage therapy for isolated local recurrence (ILR), adjuvant therapy after radical resection, and as a palliative treatment. Special attention is given to the application of magnetic resonance-guided radiotherapy (MRgRT). Methods: Following PRISMA guidelines, a systematic review of the Medline database via PubMed was conducted focusing on prospective studies published within the past decade. Data were extracted concerning study characteristics, outcome measures, toxicity profiles, SBRT dosage and fractionation regimens, as well as additional systemic therapies. Results and conclusion: 31 studies with in total 1,571 patients were included in this review encompassing 14 studies for LAPC, 9 for neoadjuvant treatment, 2 for adjuvant treatment, 2 for ILR, with an additional 4 studies evaluating MRgRT. In LAPC, SBRT demonstrates encouraging results, characterized by favorable local control rates. Several studies even report conversion to resectable disease with substantial resection rates reaching 39%. The adoption of MRgRT may provide a solution to the challenge to deliver ablative doses while minimizing severe toxicities. In BRPC, select prospective studies combining preoperative ablative-dose SBRT with modern induction systemic therapies have achieved remarkable resection rates of up to 80%. MRgRT also holds potential in this context. Adjuvant SBRT does not appear to confer relevant advantages over chemotherapy. While prospective data for SBRT in ILR and for palliative pain relief are limited, they corroborate positive findings from retrospective studies.

Post-transplantation Cyclophosphamide-based Graft-versus-host-disease Prophylaxis Compared to Methotrexate-cyclosporine a in Matched-related Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND AND OBJECTIVES: Post-transplant cyclophosphamide (PTCy) has shown promising results with low rates of severe graft-versus-host-disease (GVHD), either alone or combined with conventional immunosuppression (CIS). However, studies comparing PTCy with CIS as a GVHD prophylaxis are scarce. The study aimed to determine the rates of GVHD and survival outcomes for patients undergoing peripheral blood stem cell transplant (PBSCT) from HLA-matched related donors (MRD) receiving PTCy-based GVHD prophylaxis and compare these outcomes with those of patients receiving methotrexate (MTX) and cyclosporine-A (CsA) as a GVHD prophylaxis. PATIENTS AND METHODS: Seventy-five patients with advanced hematologic malignancies who underwent MRD allogeneic hematopoietic cell transplantation (allo-HCT) were analyzed prospectively. These patients received PTCy and CSA as a GVHD prophylaxis (therapeutic group) and their outcomes were compared with those of 75 retrospectively collected patients who received methotrexate and CsA as a GVHD prophylaxis (historical group) from the same two transplant centers. RESULTS: The median recipient age was significantly lower in the MTX/CsA group at 28 years compared to 34 years in the PTCy/CSA group. Peripheral blood was the only graft source used. All patients had a complete MRD, with two patients having a one-antigen mismatched related donor within the PTCy/CsA group. The 1-year cumulative incidence (CI) of chronic GVHD was 13.4% with PTCy/CsA and 38.6% with MTX/CsA (P = .001). Acute GVHD CI across all grades did not differ between the groups, with 10.7% for PTCy/CsA and 14.7% for MTX/CsA (P = .46). At two years, the overall survival (OS) (54.4% vs 67.2%, P = 0.282), disease-free survival (DFS) (54.1% vs 66.1%, P = 0.358), relapse rates (27.4% vs 20.1%, P = 0.245), and non-relapse mortality (NRM) (29.3% vs 25%, P = 0.904) did not differ between PTCy/CsA and MTX/CsA, respectively. CONCLUSION: PTCy-based GVHD prophylaxis in MRD transplant is feasible and leads to lower chronic GVHD rates without causing a significantly different risk of relapse or survival than MTX/CsA. More extensive studies are needed to confirm our results.

Hematological toxicities of immune checkpoint inhibitors and the impact of blood transfusion and its microbiome on therapeutic efficacy and recipient's safety and survival outcome:A systematic narrative appraisal of where we are now!

Classically, patients with solid and hematologic malignancies have been treated with a combination of chemotherapy with or without a holistic targeted strategy using approved conventional therapy. While the evidence-based use of Immunomodulatory drugs and Immune checkpoint inhibitors (ICIs), including those targeting the PD-1, PD-L1 and CTLA-4, have reshaped the treatment paradigm for many malignant tumors and significantly stretched the life expectancy of patients, as for any interventional therapy, the rise in ICI applications, was associated with the observation of more immune-related hematological adverse events. Many of these patients require transfusion support during their treatment in line with precision transfusion. It has been presumed that transfusion-related immunomodulation (TRIM) and the microbiome can pose immunosuppressive effects on the recipients. Looking to the past and beyond and translating available data into practice in the evolving role of pharmaceutical therapy to ICI-receiving patients, we performed a narrative review of the literature on the immune-related hematological adverse events of ICIs, immunosuppressive mechanisms linked to blood product transfusions, as well as the detrimental impact of transfusions and its related microbiome on the sustained efficacy of ICIs and the patients' survival outcomes. Recent reports are pointing to the negative impact of transfusion on ICI response. Studies have concluded that packed RBC [PRBC] transfusions lead to an inferior progression-free and overall survival in patients with advanced cancer receiving ICIs, even after adjustments for other prognostic variables. The attenuation of the effectiveness of immunotherapy likely results from the immunosuppressive effects of PRBC transfusions. It is, therefore, wise to look retrospectively and prospectively at the impact of transfusion on ICI effects and adopt, in the interim, a restrictive transfusion strategy, if applicable, for those patients.

Environmental protection and energy efficiency improvement by using natural gas fuel in maritime transportation.

Emissions from vessels are a major environmental concern because of their impacts on the deterioration of the environment, especially global warming of the atmosphere. Therefore, the International Maritime Organization (IMO) concerns significant care to environmental protection through the reduction of exhaust emission and improvement of energy efficiency through technical and operational measures. Among the suggested measures from IMO, the alternative fuel such as natural gas has the priority to be used instead of fossil fuels. The present paper calculates the effect of using natural gas in a dual-fuel engine from environmental and energy efficiency perspectives. As a case study, a container ship has been investigated. The results of the analysis show that the percent of CO2, NOx, and SOx emission reduction corresponding to using a dual-fuel engine operated by natural gas instead of a diesel engine operated by heavy fuel oil is about 30.4%, 85.3%, and 97%, respectively. Moreover, it found that NOx and SOx emission rates of the dual-fuel engine comply with the IMO 2016 and 2020 limits, respectively. Furthermore, the Energy Efficiency Design Index value in the case of using dual-fuel engine is lower than the value by using diesel engine by about 30%, and this value will be 77.18%, 86.84%, and 99.27% of the required value for the first, second, and third phases, respectively, as recommended by IMO.

Human Coronavirus NL63 Among Other Respiratory Viruses in Clinical Specimens of Egyptian Children and Raw Sewage Samples.

The objective of this study was to investigate human coronavirus NL63 (HCoV-NL63) prevalence among the other respiratory viruses such as parainfluenza, respiratory syncytial virus, and non-enteric adenoviruses in clinical specimens of Egyptian children and raw sewage samples. One hundred clinical specimens were collected from Egyptian children suffering from upper and lower respiratory viral infections in the years 2005-2006 to detect HCoV-NL63 genome using RT-PCR. All the specimens were negative for the virus. Also, a complete absence of HCoV-NL63 genome was observed in the twenty-four raw sewage samples collected from two wastewater treatment plants within Greater Cairo from February 2006 to January 2007. Using nested RT-PCR, parainfluenza virus type 1, respiratory syncytial virus type A, adenovirus type 4, and adenovirus type 7 were detected in 3%, 2%, 5%, and 2% of the clinical specimens, respectively. Of these viruses, only adenovirus type 4 was detected in 1/24 (4.17%) of the raw sewage samples, while a complete absence of the other investigated respiratory viruses was observed in the raw sewage samples. The low percentage of positivity in the clinical specimens, the concentration method of the raw sewage samples, and the indirect routes of transmission may be the reasons for the absence of respiratory viruses in raw sewage samples. On the other hand, enteric adenoviruses were detected in 21/24 (87.5%) of the raw sewage samples with a higher prevalence of adenovirus type 41 than adenovirus type 40. A direct route of transmission of enteric viruses to raw sewage may be the reason for the high positivity percentage of enteric adenoviruses in raw sewage samples.

Numerical analysis of economic and environmental benefits of marine fuel conversion from diesel oil to natural gas for container ships.

Shipping is a significant contributor to global greenhouse gas (GHG) and air pollutant emissions. These emissions mainly come from using diesel fuel for power generation. In this paper, the natural gas is proposed as an alternative marine fuel to be used instead of conventional marine diesel oil. Numerical analysis of environmental and economic benefits of the natural gas-diesel dual-fuel engine is carried out. As a case study, a container ship of class A7 owned by Hapag-Lloyd has been investigated. The results show that the proposed dual-fuel engine achieves environmental benefits for reducing carbon dioxide (CO2), nitrogen oxides (NOx), sulfur oxides (SOx), particulate matter (PM), and carbon monoxide (CO) emissions by 20.1%, 85.5%, 98%, 99%, and 55.7% with cost effectiveness of 109, 840, 9864, 27761, and 4307 US$/ton, respectively. The results show that the conversion process to the dual-fuel engine will comply with the current and future IMO regulations regarding air pollutant emissions. On the other hand, using the proposed dual-fuel engine on the container ship will improve the ship energy efficiency index by 29.6 % with annual fuel cost saving of 4.77 million US dollars.

A CT-based radiomics model to detect prostate cancer lymph node metastases in PSMA radioguided surgery patients.

PURPOSE: In recurrent prostate carcinoma, determination of the site of recurrence is crucial to guide personalized therapy. In contrast to prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) imaging, computed tomography (CT) has only limited capacity to detect lymph node metastases (LNM). We sought to develop a CT-based radiomic model to predict LNM status using a PSMA radioguided surgery (RGS) cohort with histological confirmation of all suspected lymph nodes (LNs). METHODS: Eighty patients that received RGS for resection of PSMA PET/CT-positive LNMs were analyzed. Forty-seven patients (87 LNs) that received inhouse imaging were used as training cohort. Thirty-three patients (62 LNs) that received external imaging were used as testing cohort. As gold standard, histological confirmation was available for all LNs. After preprocessing, 156 radiomic features analyzing texture, shape, intensity, and local binary patterns (LBP) were extracted. The least absolute shrinkage and selection operator (radiomic models) and logistic regression (conventional parameters) were used for modeling. RESULTS: Texture and shape features were largely correlated to LN volume. A combined radiomic model achieved the best predictive performance with a testing-AUC of 0.95. LBP features showed the highest contribution to model performance. This model significantly outperformed all conventional CT parameters including LN short diameter (AUC 0.84), LN volume (AUC 0.80), and an expert rating (AUC 0.67). In lymph node-specific decision curve analysis, there was a clinical net benefit above LN short diameter. CONCLUSION: The best radiomic model outperformed conventional measures for detection of LNM demonstrating an incremental value of radiomic features.

Tumor grading of soft tissue sarcomas using MRI-based radiomics.

BACKGROUND: Treatment decisions for multimodal therapy in soft tissue sarcoma (STS) patients greatly depend on the differentiation between low-grade and high-grade tumors. We developed MRI-based radiomics grading models for the differentiation between low-grade (G1) and high-grade (G2/G3) STS. METHODS: The study was registered at ClinicalTrials.gov (number NCT03798795). Contrast-enhanced T1-weighted fat saturated (T1FSGd), fat-saturated T2-weighted (T2FS) MRI sequences, and tumor grading following the French Federation of Cancer Centers Sarcoma Group obtained from pre-therapeutic biopsies were gathered from two independent retrospective patient cohorts. Volumes of interest were manually segmented. After preprocessing, 1394 radiomics features were extracted from each sequence. Features unstable in 21 independent multiple-segmentations were excluded. Least absolute shrinkage and selection operator models were developed using nested cross-validation on a training patient cohort (122 patients). The influence of ComBatHarmonization was assessed for correction of batch effects. FINDINGS: Three radiomic models based on T2FS, T1FSGd and a combined model achieved predictive performances with an area under the receiver operator characteristic curve (AUC) of 0.78, 0.69, and 0.76 on the independent validation set (103 patients), respectively. The T2FS-based model showed the best reproducibility. The radiomics model involving T1FSGd-based features achieved significant patient stratification. Combining the T2FS radiomic model into a nomogram with clinical staging improved prognostic performance and the clinical net benefit above clinical staging alone. INTERPRETATION: MRI-based radiomics tumor grading models effectively classify low-grade and high-grade soft tissue sarcomas. FUND: The authors received support by the medical faculty of the Technical University of Munich and the German Cancer Consortium.

Prevalence and Anti-Microbial Susceptibility of Hospital Acquired Infections in Two Pediatric Intensive Care Units in Egypt.

BACKGROUND: Hospital-acquired (nosocomial) infection is a common serious health problem worldwide, especially in pediatric intensive care units and is associated with high mortality and morbidity, prolonged hospital stays and high cost. AIM: To determine the types of organisms involved in hospital-acquired an infection in two pediatric intensive care units during the one-year study and its anti-microbial susceptibility. MATERIAL AND METHODS: This study was carried out in the pediatric intensive care units (PICU) of Ain Shams & Cairo Universities, where 86 pediatric patients were recruited. Their age ranged from 1 month to 156 months with mean 20.7 ± 25.8 months. Male to female ratio was 37:29. Four samples were collected from each child for culture and sensitivity: blood, endotracheal aspirate, urine and skin swab. RESULTS: The most common microorganism was staphylococcus while Gram-negative bacteria were the commonest group. Amikacin and imipenem are the most sensitive antibiotics. Risk estimate for different risk factors among studied patients revealed no significance. CONCLUSION: Staphylococcus was the commonest micro-organism while Gram-negative infections were the commonest group among PICU with a predominance of Acinetobacter and Klebsiella. Respiratory infections were the most common, followed by blood-borne infection. Risk factors for mortality were not significant.

Oxidative Stress in Hemodialysis Pediatric Patients.

BACKGROUND: Oxidative stress may play a role in complications of hemodialysis patients as atherosclerosis, thrombosis, and inflammation. AIM: The aim of the study was to evaluate the oxidative stress in hemodialysis pediatric patients through measurement of oxidative stress enzymes as paraoxanase activity (PON), arylesterase activity (ASA), superoxide dismutase (SOD) and also non-enzymatic antioxidant vitamins as vitamins A, C and E levels. METHODS: The study included 50 hemodialysis pediatric patients with mean age 11.4 ± 5.4 years and 30 normal children of matched sex and age as a control group. Assessment of oxidative stresses was done using ELIZA technique. RESULTS: SOD, ASA, and vitamin C were significantly lower among hemodialysis patients in comparison to control group (p = 0.004, 0.004, > 0.001 respectively). CONCLUSION: The study concluded that oxidative stress was common finding in hemodialysis pediatric patients which may play a role in complications encountered among these patients.

Visfatin versus Flow-Mediated Dilatation as a Marker of Endothelial Dysfunction in Pediatric Renal Transplant Recipients.

BACKGROUND: Renal transplantation (RTx) is the treatment of choice for paediatric end-stage renal disease (ESRD). A major cause of morbidity and mortality after RTx is cardiovascular disease. Independent predictors of cardiovascular events were shown to constitute an endothelial dysfunction (ED). This study aims to evaluate Visfatin serum level in comparison to brachial artery flow-mediated dilatation (FMD) as a marker of endothelial dysfunction in paediatric RTx recipients. METHODS: Visfatin serum level has been evaluated in 30 patients on regular hemodialysis (HD), 36 patients post-RTx and 30 controls as a measure for ED, and has been compared to brachial artery FMD. RESULTS: Visfatin level in transplant recipients was significantly lower than the hemodialysis group as well as FMD was better in transplant recipients. In spite of marked improvement of FMD and marked reduction of visfatin in post-RTx no direct statistical correlation was found between serum Visfatin level and flow-mediated dilatation. CONCLUSION: Pediatric RTx recipients show lower serum Visfatin level and better FMD than those on regular hemodialysis, reflecting less endothelial dysfunction (ED) and less cardiovascular risk. FMD in kidney transplant recipients tends to be less than normal subjects while visfatin level of the same group is similar to controls. Pediatric RTx appears to have a positive impact on the growth development of children with ESRD.

Fetuin-A and Ghrelin Levels in Children with End Stage Renal Disease and the Effect of a Single Hemodialysis Session on Them.

BACKGROUND: Fetuin-A and ghrelin have been implicated in cardiovascular diseases and mortality among end stage renal disease patients. The exact mechanisms have not been fully elucidated. There is robust data supporting an association between ghrelin and various cardiovascular conditions, and some common processes such as inflammation, oxidative stress, and endoplasmic reticulum stress have been implicated. AIM: This study was conducted to assay serum fetuin-A and ghrelin in chronic renal failure pediatric patients and to study changes in their level that may occur after a single hemodialysis. MATERIAL AND METHODS: Forty nine pediatric patients suffering from ESRD on maintenance hemodialysis (HD), 20 patients with chronic renal failure (CRF) not on dialysis and 35 healthy subjects as control group were included. The mean age of the study population was 10.58 ± 3.94, 10.62 ± 3.24 and 10.61 ± 3.97 years respectively. Serum fetuin-A and plasma acyl ghrelin levels were measured by using ELISA method. RESULTS: The present study revealed that predialysis serum fetuin-A level was significantly increased in pediatric HD patients compared with the normal population, while ghrelin levels were significantly reduced. Furthermore, serum levels of fetuin-A decreased significantly after a single HD session. CONCLUSION: Our study concluded that fetuin-A and acyl ghrelin may play a role in inflammatory process among HD pediatric patients which may account for cardiovascular insults and mortality but their use as biochemical markers among ESRD pediatric patients have limitations due to wide fluctuations.