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Abstract We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40–65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.

Abstract Belantamab mafodotin is the first‐in‐class antibody‐drug conjugates targeting B‐cell maturation antigen to have demonstrated effectiveness in triple‐class refractory multiple myeloma (TCR‐MM) patients. We performed a retrospective study including 78 TCR patients, with at least four prior lines of therapy (LOTs), who received belantamab mafodotin within named patient program and expanded access program in Italy between 2020 and 2022. Median age was 65 years (range 42–86 years), ECOG performance status was ≥1 in 45% of patients. Overall, a clinical benefit was obtained in 36 out of 74 evaluable patients (49%), with 43%, 28%, and 13.5% achieving at least partial response, very good partial response, and complete response, respectively. After a median follow‐up of 12 months (range 6–21 months), median duration of response, progression‐free survival (PFS), and overall survival (OS) were 14, 5.5, and 12 months, respectively. Age >70 years, good performance status and response were associated with longer PFS and OS. Keratopathy occurred in 58% of patients (G3 2.5%), corneal symptoms in 32% (G3 1.2%) and a reduction in visual acuity in 14%. Grade 3 thrombocytopenia occurred in 9% of patients. Only 3% of patients discontinued belantamab mafodotin because of side effects. This real‐life study demonstrated significant and durable responses of belantamab in TCR‐MM patients with four prior LOTs, otherwise ineligible for novel immunotherapies.

Abstract Additional copies of chromosome 1 long arm (1q) are frequently found in multiple myeloma (MM) and predict high-risk disease. Available data suggest a different outcome and biology of patients with amplification (Amp1q, ≥4 copies of 1q) vs. gain (Gain1q, 3 copies of 1q) of 1q. We evaluated the impact of Amp1q/Gain1q on the outcome of newly diagnosed MM patients enrolled in the FORTE trial (NCT02203643). Among 400 patients with available 1q data, 52 (13%) had Amp1q and 129 (32%) Gain1q. After a median follow-up of 62 months, median progression-free survival (PFS) was 21.2 months in the Amp1q group, 54.9 months in Gain1q, and not reached (NR) in Normal 1q. PFS was significantly hampered by the presence of Amp1q (HR 3.34 vs. Normal 1q, P

We report on an in situ FTIR study of the thermo-oxidative degradation of a flexible epoxy resin. Different and complementary approaches to the analysis of the spectral data were employed, providing a detailed description of the process in terms of kinetics and mechanisms. A preliminary normal coordinate analysis, based on the DFT method, allowed for a reliable interpretation of the observed spectrum, increasing the amount of available structural information. Two-dimensional correlation spectroscopy provided details on the evolution of the reacting network structure. The relative stability of the various functional groups was ranked, and the most likely sites of initiation were identified. Oxygen fixation on the network chains produced amide and ketone groups, with the latter developing at a higher rate. The kinetic profiles of various functional groups were accurately simulated by a first-order, biexponential model, which allowed a quantitative comparison among their relative stabilities. The spectroscopic analysis allowed us to propose likely mechanisms and to identify those that occur preferentially.

IntroductionPaternal nutrition before conception has a marked impact on offspring’s risk of developing metabolic disorders during adulthood. Research on human cohorts and animal models has shown that paternal obesity alters sperm epigenetics (DNA methylation, protamine-to-histone replacement, and non-coding RNA content), leading to adverse health outcomes in the offspring. So far, the mechanistic events that translate paternal nutrition into sperm epigenetic changes remain unclear. High-fat diet (HFD)-driven paternal obesity increases gonadic Reactive Oxygen Species (ROS), which modulate enzymes involved in epigenetic modifications of DNA during spermatogenesis. Thus, the gonadic pool of ROS might be responsible for transducing paternal health status to the zygote through germ cells.MethodsThe involvement of ROS in paternal intergenerational transmission was assessed by modulating the gonadic ROS content in male mice. Testicular oxidative stress induced by HFD was counterbalanced by N-acetylcysteine (NAC), an antioxidant precursor of GSH. The sires were divided into four feeding groups: i) control diet; ii) HFD; iii) control diet in the presence of NAC; and iv) HFD in the presence of NAC. After 8 weeks, males were mated with females that were fed a control diet. Antioxidant treatment was then evaluated in terms of preventing the HFD-induced transmission of dysmetabolic traits from obese fathers to their offspring. The offspring were weaned onto a regular control diet until week 16 and then underwent metabolic evaluation. The methylation status of the genomic region IGFII/H19 and cyp19a1 in the offspring gDNA was also assessed using Sanger sequencing and methylation-dependent qPCR.ResultsSupplementation with NAC protected sires from HFD-induced weight gain, hyperinsulinemia, and glucose intolerance. NAC reduced oxidative stress in the gonads of obese fathers and improved sperm viability. However, NAC did not prevent the transmission of epigenetic modifications from father to offspring. Male offspring of HFD-fed fathers, regardless of NAC treatment, exhibited hyperinsulinemia, glucose intolerance, and hypoandrogenism. Additionally, they showed altered methylation at the epigenetically controlled loci IGFII/H19 and cy19a1.ConclusionAlthough NAC supplementation improved the health status and sperm quality of HFD-fed male mice, it did not prevent the epigenetic transmission of metabolic disorders to their offspring. Different NAC dosages and antioxidants other than NAC might represent alternatives to stop the intergenerational transmission of paternal dysmetabolic traits.

Small bowel internal hernias (IHs), a rare cause of small bowel occlusion (SBO) and small bowel strangulation, while more commonly seen in young adults, can also affect elderly patients and pose a significant diagnostic challenge due to their nonspecific symptoms. In most cases, laparotomy was used to diagnose IHs. However, multidetector computed tomography (MDCT) is usually the best imaging tool to use in the emergency setting for the diagnosis of IHs. An 83-year-old man was admitted to emergency with acute abdominal pain and a coffee-ground vomitus. The abdominal MDCT showed a clustered-like appearance of proximal jejunal loops at the level of the Treitz ligament with the absence of transit of the medium water-soluble iodine oral contrast agent (Gastrografin). Mesenteric edema was also present with initial suffering of the intestinal wall. A left paraduodenal hernia (LPDH) with strangulation was suspected following the radiological report. The emergency laparotomy revealed about 20 cm of proximal jejunal loops herniated through a 3 cm wide hernia orifice (HO) along the Treitz ligament, at the level of Landzert fossa, located in the confluence of the descending mesocolon, posterior to the inferior mesenteric vein (IMV) and confirming the LPDH. The patient was discharged in good condition some days later. IHs do not have sufficient coverage in literature, especially in cases regarding elderly patients, however, they can be a cause of SBO in people older than 80 years of age. Radiologists and surgeons should be aware of the anatomical aspects of the IHs.

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يستهدف البحث الحالي إلى دراسة التغيرات الرئيسية في الإطار المفاهيمي للإبلاغ المالي الصادر عن مجلس معايير المحاسبة الدولية لعام (2018) ومردودها الإيجابي والسلبي على بيئة الممارسة المحاسبية، وذلك في في إطار فلسفي يشمل استعراض وتحليل الدراسات السابقة ذات الصلة بهذه العلاقة، اذ أستخدمت البحث المنهج الوصفي الانتقادي من خلال الإطلاع على المراجع والأبحاث والدراسات التي تخص البحث، وتحليل ما تحتويه من وجهات النظر المختلفة بخصوص التغييرات الجوهرية في الإطار المفاهيمي الجديد. وخلص الباحثان من تحليل تلك الدراسات، بأن الإطار المفاهيمي الجديد وما تتضمنه من تحديثات ساهمت بشكل جوهري في توجيه الممارسات المحاسبية بشكل الصحيح واختيار معالجات محاسبية موحدة في البيئات المختلفة، فضلاً عن إيجاد بدائل قياس ملائمة مع التغيرات والتقلبات التي تواجه تطبيقات الاعمال، الأمر الذي ترتب عليه تحسين وتعزيز محتوى جودة التقارير المالية. كما توصل الباحثان من خلال تحليل تلك الدراسات بأن الإطار المفاهيمي الجديد لم تغطي للكثير من المجالات الجديدة في بيئة الممارسة المحاسبية، فضلاً عن عدم وضوح الإرشادات في بعض المجالات الموجوده به خاصة تلك المجالات التي تتعلق بمبادىء القياس والعرض الاعتراف والسياسات المحاسبية. وذلك يمثل تحدياً لإصدار معايير تتصف بالكفاءة والفاعلية. في حين يوصي الباحثان ضورة تقييم التغييرات المقترحة في الإطار المفاهيمي للإبلاغ المالي من قبل الجهات المهنية ومعدي التقارير المالية ليواكب مع التغييرات التي تحدث في بيئة الممارسة المحاسبية.

Background: Strategies to minimize the impact of the COVID-19 pandemic led to a reduction in diagnostic testing. It is important to assess the magnitude and duration of this impact to plan ongoing care and avoid long-lasting impacts of the pandemic. Objective: We examined the association between the COVID-19 pandemic and the rate of diagnostic tests for breast, cervical, and colorectal cancer in Manitoba, Canada. Design and Participants: A population-based, cross-sectional study design with an interrupted time series analysis was used that included diagnostic tests from January 1, 2015 until August 31, 2022. Setting: Manitoba, Canada. Main Outcomes: Outcomes included mammogram, breast ultrasound, colposcopy, and colonoscopy rates per 100,000. Cumulative and percent cumulative differences between the fitted and counterfactual number of tests were estimated. Mean, median, and 90th percentile number of days from referral to colonoscopy date by referral type (elective, semiurgent, urgent) were determined. Results: In April 2020, following the declaration of the COVID-19 public health emergency, bilateral mammograms decreased by 77%, unilateral mammograms by 70%, breast ultrasounds by 53%, colposcopies by 63%, and colonoscopies by 75%. In Winnipeg (the largest urban center in the province), elective and semiurgent colonoscopies decreased by 76% and 39%, respectively. There was no decrease in urgent colonoscopies. As of August 2022, there were an estimated 7270 (10.7%) fewer bilateral mammograms, 2722 (14.8%) fewer breast ultrasounds, 836 (3.3%) fewer colposcopies, and 11 600 (13.8%) fewer colonoscopies than expected in the absence of COVID-19. As of December 2022, in Winnipeg, there were an estimated 6030 (23.9%) fewer elective colonoscopies, 313 (2.6%) fewer semiurgent colonoscopies, and 438 (27.3%) more urgent colonoscopies. Conclusions: In Manitoba, the COVID-19 pandemic was associated with sizable decreases in diagnostic tests for breast, colorectal, and cervical cancer. Two and a half years later, there remained large cumulative deficits in bilateral mammograms, breast ultrasounds, and colonoscopies.

Abstract Background Relapse and refractory (R/R) rates after first‐line R‐CHOP in diffuse large B cell lymphomas (DLBCL) are ~40% and ~15% respectively. Aims We conducted a retrospective real‐world analysis aimed at evaluating clinical outcomes of R/R DLBCL patients. Material and Methods Overall, 403 consecutive DLBCL patients treated in two large hematological centers in Torino, Italy were reviewed. Results At a median follow up of 50 months, 5‐year overall survival from diagnosis (OS‐1) was 66.5%, and 2‐year progression free survival (PFS‐1) was 68%. 134 (34.4%) patients relapsed (n = 46, 11.8%) or were refractory (n = 88, 22.6%) to R‐CHOP. Most employed salvage treatments included platinum salt‐based regimens in 38/134 (28.4%), lenalidomide in 14 (10.4%). Median OS and PFS after disease relapse or progression (OS‐2 and PFS‐2) were 6.7 and 5.1 months respectively. No significant difference in overall response rate, OS‐2 or PFS‐2 in patients treated with platinum‐based regimens versus other regimens was observed. By multivariate analysis, age between 60 and 80 years, germinal center B cell type cell of origin and extranodal involvement of

IntroductionRecent studies have shown gender differences in cardiovascular outcomes after left atrial appendage closure (LAAC), highlighting different complication rates and adverse events, particularly in short-term assessments. As a result, there remains a significant knowledge gap on how these differences directly impact the efficacy and safety of LAAC procedures. The aim of this retrospective study was to investigate the clinical outcomes of LAAC in women and men using the Watchman FLX device.MethodsThis retrospective, multicenter study analyzes gender-specific outcomes in 650 patients who underwent LAAC with the Watchman FLX device between March 2019 and May 2022, drawn from the ITALIAN-FLX registry.ResultsThe results show comparable rates of all-cause mortality, stroke, transient ischemic attack and major bleeding in men and women 12 months after the procedure. Notably, no significant gender differences were found for periprocedural complications.ConclusionIn conclusion, this study shows that LAAC with the Watchman FLX device has comparable clinical outcomes between genders at both short-term and long-term follow-up.

Abstract Background The wild boar (Sus scrofa) and the Apennine wolf (Canis lupus italicus) are two wild species that have both increased their presence in the Italian territory, albeit in varying numbers. They can be occasionally found in peri-urban areas as well. Both of these species can serve as intermediate hosts for Toxoplasma gondii, as they can become infected either through the consumption of oocysts found in water, soil, or on vegetables, or through the ingestion of meat containing bradyzoites. Consequently, these animals can be regarded as key indicators of Toxoplasma presence in the wild or peri-urban environment. In our study, we examined a total of 174 wild boar meat juice and 128 wolf sera from Italy for the detection of T. gondii IgG using the indirect fluorescent antibody test (IFAT). Results The results showed that 40 (22.6%) of the wild boar meat juice and 34 (26.6%) of the wolf serum samples tested positive. Interestingly, there were no significant differences in seropositivity with respect to gender, age group, or the region of origin in both species. Conclusions Overall the results indicate a moderate exposure in both the species under investigation, highlighting the spread of T. gondii in sylvatic and periurban environments. The prevalence of T. gondii in wild boar is consistent with findings from other studies conducted in Europe. Our study, with a considerably larger sample size compared to the available research in European context, provides valuable data on the seroprevalence of T. gondii in wolves.

Abstract Objective Cardio‐facio‐cutaneous syndrome (CFC) is a genetic disorder due to variants affecting genes coding key proteins of the Ras/MAPK signaling pathway. Among the different features of CFC, neurological involvement, including cerebral malformations and epilepsy, represents a common and clinically relevant aspect. Status epilepticus (SE) is a recurrent feature, especially in a specific subgroup of CFC patients with developmental and epileptic encephalopathy (DEE) and history of severe pharmacoresistant epilepsy. Here we dissect the features of SE in CFC patients with a particular focus on longitudinal magnetic resonance imaging (MRI) findings to identify clinical‐radiological patterns and discuss the underlying physiopathology. Methods We retrospectively analyzed clinical, electroencephalogram (EEG), and MRI data collected in a single center from a cohort of 23 patients with CFC carrying pathogenic BRAF variants who experienced SE during a 5‐year period. Results Seven episodes of SE were documented in 5 CFC patients who underwent EEG and MRI at baseline. MRI was performed during SE/within 72 hours from SE termination in 5/7 events. Acute/early post‐ictal MRI findings showed heterogenous abnormalities: restricted diffusion in 2/7, focal area of pcASL perfusion change in 2/7, focal cortical T2/FLAIR hyperintensity in 2/7. Follow‐up images were available for 4/7 SE. No acute changes were detected in 2/7 (MRI performed 4 days after SE termination). Significance Acute focal neuroimaging changes concomitant with ictal EEG focus were present in 5/7 episodes, though with different findings. The heterogeneous patterns suggest different contributing factors, possibly including the presence of focal cortical malformations and autoinflammation. When cytotoxic edema is revealed by MRI, it can be followed by permanent structural damage, as already observed in other genetic conditions. A better understanding of the physiopathology will provide access to targeted treatments allowing to prevent long‐term adverse neurological outcome. Plain Language Summary Cardio‐facio‐cutaneous syndrome is a genetic disorder that often causes prolonged seizures known as status epilepticus. This study has a focus on electroclinical and neuroimaging patterns in patients with cardio‐facio‐cutaneous syndrome. During these status epilepticus episodes, we found different abnormal brain imaging patterns in patients, indicating various causes like brain malformations and inflammation. Understanding these patterns could help doctors find specific treatments, protecting cardio‐facio‐cutaneous syndrome patients from long‐term brain damage.

Abstract Background The only natural hosts of Pseudorabies virus (PRV) are members of the family Suidae (Sus scrofa scrofa). In mammals, the infection is usually fatal and typically causes serious neurologic disease. This study describes four Aujeszky’s disease cases in free-ranging Italian wolves (Canis lupus italicus). In Italy, the wolf is a strictly protected species and is in demographic expansion. Case presentation Three wolves (Wolf A, B, and C) were found in a regional park in Northern Italy, and one (Wolf D) was found in Central Italy. Wolf A and D were alive at the time of the finding and exhibited a fatal infection with epileptic seizures and dyspnoea, dying after a few hours. Wolf B presented scratching lesions under the chin and a detachment of the right earlobe, whilst Wolf C was partially eaten. The wolves showed hepatic congestion, diffuse enteritis, moderate pericardial effusion, severe bilateral pneumonia, and diffuse hyperaemia in the brain. The diagnostic examinations included virological analyses and detection of toxic molecules able to cause serious neurological signs. All four wolves tested positive for pseudorabies virus (PrV). The analysed sequences were placed in Italian clade 1, which is divided into two subclades, “a” and “b”. The sequences of Wolf A, B, and C were closely related to other Italian sequences in the subclade b, originally obtained from wild boars and hunting dogs. The sequence from Wolf D was located within the same clade and was closely related to the French hunting dog sequences belonging to group 4. Conclusion Results showed the presence of PrV strains currently circulating in wild boars and free-ranging Italian wolves. The genetic characterisation of the PrV UL44 sequences from the four wolves confirmed the close relationship with the sequences from wild boars and hunting dogs. This fact supports a possible epidemiological link with the high PrV presence in wild boars and the possibility of infection in wolves through consumption of infected wild boar carcasses or indirect transmission. To the best of our knowledge, this study is the first detection of Pseudorabies virus in free-ranging Italian wolves in northern and central Italy.

Abstract Introduction Health care in Manitoba, Canada is divided into five regions, each with unique geographies, demographics, health care access, and health status. COVID‐19‐related restrictions and subsequent responses also differed by region. To understand the impact of the pandemic on cancer incidence in the context of these differences, we examined age‐standardized cancer incidence rates by region over time before and after the COVID‐19 pandemic. Methods We used a population‐based quasi‐experimental study design, population‐based data, and an interrupted time series analysis to examine the rate of new cancer diagnoses before (January 2015 until December 2019) and after the start of COVID‐19 and the interventions implemented to mitigate its impact (April 2020 until December 2021) by region. Results Overall cancer incidence differed by region and remained lower than expected in Winnipeg (4.6% deficit, 447 cases), Prairie Mountain (6.9% deficit, 125 cases), and Southern (13.0% deficit, 238 cases). Southern was the only region that had a significantly higher deficit in cases compared to Manitoba (ratio 0.92, 95% CI 0.86, 0.99). Breast and colorectal cancer incidence decreased at the start of the pandemic in all regions except Northern. Lung cancer incidence decreased in the Interlake‐Eastern region and increased in the Northern region. Prostate cancer incidence increased in Interlake‐Eastern. Conclusions The impact of the COVID‐19 pandemic on cancer incidence differed by region. The deficit in the number of cases was largest in the southern region and was highest for breast and prostate cancers. Cancer incidence did not significantly decrease in the most northern, remote region.

Background: In this study, we examined and compared ex vivo mechanical properties of aortic walls in patients with bicuspid (BAV) and tricuspid (TAV) aortic valve aortopathy to investigate if the anatomical peculiarities in the BAV group are related to an increased frailty of the aortic wall and, therefore, if a different surgical cutoff point for ascending aortic replacement could be reasonable in such patients. Methods: Ultimate stress tests were performed on fresh aortic wall specimens harvested during elective aortic surgery in BAV (n. 33) and TAV (n. 77) patients. Three mechanical parameters were evaluated at the failure point, under both longitudinal and circumferential forces: the peak strain (Pstr), peak stress (PS), and maximum elastic modulus (EM). The relationships between the three mechanical parameters and preoperative characteristics were evaluated, with a special focus on evaluating potential risk factors for severely impaired mechanical properties, cumulatively and comparatively (BAV vs. TAV groups). Results: The patient populations were inhomogeneous, as BAV patients reached surgical indication, according to the maximum aortic dilatation, at a younger age (58 ± 15 vs. 64 ± 13; p = 0.0294). The extent of the maximum aortic dilatation was, conversely, similar in the two groups (52 ± 4 vs. 54 ± 7; p = 0.2331), as well as the incidences of different phenotypes of aortic dilatation (with the ascending aorta phenotype being the most frequent in 81% and 66% of the BAV and TAV patients, respectively (p = 0.1134). Cumulatively, the mechanical properties of the aortic wall were influenced mainly by the orientation of the force applied, as both PS and EM were impaired under longitudinal stress. An age of >66 and a maximum dilatation of >52 mm were shown to predict severe Pstr reduction in the overall population. Comparative analysis revealed a trend of increased mechanical properties in the BAV group, regardless of the position, the force orientation, and the phenotype of the aortic dilatation. Conclusions: BAV aortopathy is not correlated with impaired mechanical properties of the aortic wall as such. Different surgical cutoff points for BAV aortopathy, therefore, seem to be unjustified. An age of >66 and a maximum aortic dilatation of >52 mm, however, seem to significantly influence the mechanical properties of the aortic wall in both groups. These findings, therefore, could suggest the need for more accurate monitoring and evaluation in such conditions.

Background: Hematopoietic cell transplantation (HCT) is an established therapy for hematologic malignancies and serious non-malignant blood disorders. Despite its curative potential, HCT is associated with substantial toxicity and health resource utilization. Effective delivery of HCT requires complex hospital-based care, which limits the number of HCT centres in Canada. In Canada, the quantity, indications, temporal trends, and outcomes of patients receiving HCT are not known. Methods: A retrospective cohort study of first transplants reported to the Cell Therapy Transplant Canada (CTTC) registry between 2000 and 2019. We determined overall survival (OS) and non-relapse mortality (NRM), categorizing the cohort into early (2000–2009) and later (2010–2019) eras to investigate temporal changes. Results: Of 18,046 transplants, 7571 were allogeneic and 10,475 were autologous. Comparing the two eras, allogeneic transplants increased in number by 22.3%, with greater use of matched unrelated donors in the later era. Autologous transplants increased by 10.9%. Temporal improvements in NRM were observed in children and adults. OS improved in pediatric patients and in adults receiving autologous HCT. In adults receiving allogeneic HCT, OS was stable despite the substantially older age of patients in the later era. Interpretation: HCT is an increasingly frequent procedure in Canada which has expanded to serve older adults. Noted improvements in NRM and OS reflect progress in patient and donor selection, preparation for transplant, and post-transplant supportive care. In allogeneic HCT, unrelated donors have become the most frequent donor source, highlighting the importance of the continued growth of volunteer donor registries. These results serve as a baseline measure for quality improvement and health services planning in Canada.

Graft-versus-host disease (GVHD) is an expected and relatively common complication after allogeneic hematopoietic stem cell transplantation. It may affect different organs and typically involves the skin, liver, and gastrointestinal tract (GI-GVHD). GI-GVHD may show heterogeneous presentations with peculiar diagnostic implications. Although an endoscopic biopsy is considered the “gold standard” for the diagnosis of GI-GVHD, its broad application is limited due to the poor clinical conditions usually present in these patients, including thrombocytopenia. In the emergency department, enhanced computed tomography (CECT) has emerged as the best imaging modality for the evaluation of GI damage in frail patients. However, the role of CT in the context of either acute or chronic GI-GVHD has not been systematically investigated. Herein, we focus on the radiological features found on CECT in five patients with GI-GVHD confirmed on histology. CECT was performed for the persistence of GI symptoms in three cases (case 1, case 3, and case 4), for small bowel occlusion in one case (case 5), and for acute GI symptoms in one case (case 2). Serpiginous intestinal wall appearance with multisegmental parietal thickness and homogeneous, mucosal, or stratified small bowel enhancement were common features. Colic involvement with segmental or diffuse parietal thickness was also present. One patient (case 5) presented with inflammatory jejunal multisegmental stenosis with sub-occlusion as a chronic presentation of GI-GVHD. Regarding mesenterial findings, all five patients presented comb signs in the absence of lymphadenopathy. Extraintestinal findings included biliary tract dilatation in two cases (case 2 and case 4). These data support the utility of appropriate radiological investigation in GI-GVHD, paving the way for further serial and systematic investigations to track the appearance and evolution of GI damage in GVHD patients.

Superior mesenteric artery syndrome also known as Wilkie's syndrome (WS) and Nutcracker syndrome (NCS) are 2 rare vascular syndromes characterized by the reduction of the aortomesenteric space. In the WS the reduction of the aortomesenteric angle leads to compression of the third portion of the duodenum. In the NCS the reduced aortomesenteric space usually causes a left renal vein (LVR) entrapment and the clinical presentation is a left flank pain, micro/macrohematuria and proteinuria. Arterial hypertension can be an unusual manifestation of the NCS. Herein, we describe the case of a 37-year-old woman with a history of breast cancer and abdominal subocclusion, with a recent onset of arterial hypertension whose enhanced computed tomography (CT) showed a reduced angle between the abdominal aorta and superior mesenteric artery with the CT findings of both the WS and NCS.

CancerCare Manitoba (CCMB) introduced virtual visits at the beginning of the COVID-19 pandemic to replace many in-person visits. This study examines the impact of virtual visits for cancer care on travel distance, travel time, and carbon dioxide (CO2) emissions. We included all visits to CCMB for invasive and in situ cancers from 1 April 2020 to 31 December 2022. Data were extracted from CCMB’s electronic health record. The percentage of visits done virtually by month was reported by age, gender, cancer diagnosis, and regional health authority of residence. Postal codes for patients’ residences and clinic locations were converted into latitude and longitude values. Travel distance, travel time, and CO2 emissions associated with travel were estimated. The percentage of virtual visits was highest during the months when COVID-19 restrictions were present in Manitoba and represent more than 50% of such monthly visits. Virtual visits increased with age, were highest among men with urogenital cancer, and were lowest among northern Manitoba residents. The median travel time per visit ranged from 30 min in Winnipeg to 15 h in the Northern Region. The estimated travel distance saved varied from 420,000 to 750,000 km per month. Estimated travel time saved varied from 5500 to 9600 h per month. Estimated CO2 emissions prevented varied from 87 to 155 metric tons per month. Virtual care is an important tool for better supporting those living with cancer by substantially decreasing travel distance and time. Virtual care also contributes to reducing greenhouse gas emissions.

Cynthia De la Garza-Ramos,1 S Ali Montazeri,1 Kaitlyn R Musto,1 Melissa D Kapp,1 Andrew R Lewis,1 Gregory Frey,1 Ricardo Paz-Fumagalli,1 Sumera Ilyas,2 Denise M Harnois,3 Umair Majeed,4 Tushar Patel,3 Beau Toskich1 1Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA; 2Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, USA; 3Department of Transplant, Mayo Clinic, Florida, FL, USA; 4Division of Hematology and Medical Oncology, Mayo Clinic Florida, Jacksonville, FL, USACorrespondence: Beau Toskich, Division of Interventional Radiology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA, Tel +1 904-953-1496, Email Toskich.Beau@mayo.eduPurpose: To compare the outcomes of radiation segmentectomy for early-stage hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) versus hepatitis C virus (HCV).Materials and Methods: A retrospective analysis of consecutive patients with NAFLD- or HCV-related HCC treated with radiation segmentectomy from 01/2017-06/2022 was performed. Eligibility criteria included solitary tumor ≤ 8 cm or up to 3 HCC ≤ 3 cm, ECOG 0– 1, and absence of vascular invasion or extrahepatic spread. Imaging best response was assessed per modified Response Evaluation Criteria in Solid Tumors. Target tumor and overall progression, time-to-progression (TTP), and overall survival (OS) were calculated. All outcomes were censored for liver transplantation (LT). Complete pathologic response (CPN) was assessed in patients who underwent LT.Results: Of 142 patients included (NAFLD: 61; HCV: 81), most had cirrhosis (NAFLD: 87%; HCV: 86%) and small tumors (median size NAFLD: 2.3 cm; HCV: 2.5 cm). Patients with NAFLD had higher BMI (p< 0.001) and worse ALBI scores (p=0.003). Patients with HCV were younger (p< 0.001) and had higher AFP levels (p=0.034). Median radiation dose (NAFLD: 508 Gy; HCV: 452 Gy) and specific activity (NAFLD: 700 Bq; HCV: 698 Bq) were similar between cohorts. Objective response was 100% and 97% in the NAFLD and HCV cohorts, respectively. Target tumor progression occurred in 1 (2%) NAFLD and 8 (10%) HCV patients. Target tumor TTP was not met for either cohort. Overall progression occurred in 23 (38%) NAFLD and 39 (48%) HCV patients. Overall TTP was 17.4 months (95% CI 13.5– 22.2) in NAFLD and 13.5 months (95% CI 0.4– 26.6) in HCV patients (p=0.86). LT was performed in 27 (44%) NAFLD and 33 (41%) HCV patients, with a CPN rate of 63% and 54%, respectively. OS was not met in the NAFLD cohort and was 53.9 months (95% CI 32.1– 75.7) in the HCV cohort (p=0.15).Conclusion: Although NAFLD and HCV are associated with different mechanisms of liver injury, patients with early-stage HCC treated with radiation segmentectomy achieve comparable outcomes.Keywords: hepatocellular carcinoma, radiation segmentectomy, NAFLD, viral hepatitis

El factor internacional ha sido un aspecto importante en la elaboración de políticas de drogas a nivel nacional. El análisis de los mecanismos de transferencia internacional de políticas refiere a las acciones intencionales de actores significativos para involucrase en el intercambio de políticas, acuerdos administrativos, instituciones e ideas de un sistema político a otro. Este tipo de proceso ha sido identificado como clave en la literatura para entender la difusión de herramientas de guerra contra las drogas, centrada en la venta, así como de la reducción de riesgos y daños, enfocada en los usuarios. En un contexto de creciente experimentación de modelos de control del cannabis en países de Occidente, este estudio explora el rol de la transferencia internacional de herramientas para la regulación del cannabis en Uruguay. El análisis se basa en la observación participante del proceso (2007-2014) y entrevistas formales e informales con una red de aproximadamente cincuenta informantes compuesta por miembros del poder legislativo (n=once), del poder ejecutivo (n=cuatro), del poder judicial (n=uno), representantes de la sociedad civil nacional (n=dieciséis), de la sociedad civil internacional (n=trece) y profesionales (n=cinco). En el caso del diseño de la ley, se identifican un conjunto de herramientas internacionalmente transferidas como el límite de seis plantas, el modelo de clubes sociales de cannabis o importante conocimiento técnico y tecnológico para el cultivo de cannabis y su control. A nivel de tecnología de campaña las cinco estrategias transferidas refirieron al etiquetado, el encuadre, el triángulo de la comunicación, la definición de emisarios y la definición de la estética. Se identifican los principales actores involucrados, las condiciones necesarias para la transferencia, como la disponibilidad de parejas compatibles, y los motivos que lo facilitaron o bloquearon, como los diferentes niveles de desarrollo del mercado o las culturas jurídicas y políticas. Se concluye que el factor internacional, y en particular los actores norteamericanos y europeos, tienen una importancia duradera en las reformas sudamericanas de políticas de drogas.

Although many studies highlighted the potential of COVID-19 to reshape existing models of wildlife management, empirical research on this topic has been scarce, particularly in Europe. We investigated the potential of COVID-19 pandemic to accelerate the ongoing decline in an aging population of recreational hunters in Italy. Namely, we modelled spatiotemporal trends between 2011 and 2021 in the number of recreational hunters in 50 Italian provinces with a varying incidence of COVID-19, and temporally delayed waves of infection. Compared to projections from 2011-2019 data, we detected a lower number of hunters who enrolled for the hunting season, both in 2020 (14 provinces) and in 2021 (15 provinces). The provinces with the highest incidence of COVID-19 in the Lombardy and Emilia-Romagna regions were also those experiencing the most marked decrease in hunting participation. Our findings revealed that a wildlife management system based on recreational hunting can be rapidly destabilized by epidemics and their associated public health measures, particularly when the average age of hunters is high, like in Italy. Considered the high incidence attained by COVID-19 in many European countries, where hunters are pivotal for the management of large ungulates and where they were already declining before the pandemic, our findings call for further large-scale research about the impact of COVID-19 on hunting participation.

The identification of patients at high risk of herpes zoster (HZ) requiring a prevention strategy with antiviral prophylaxis and anti-HZ vaccine is a clinically relevant issue in patients with immunological impairment. Absence of trials comparing vaccination to pharmacological prophylaxis or defining their sequential use makes the optimal prevention strategy uncertain. This article presents the results of group discussion among an ad hoc constituted panel of experts aimed to review the literature regarding antiviral prophylaxis and vaccine efficacy and safety in populations with malignant and non-malignant hematological diseases, and submitted to hematopoietic stem cell transplantation. The panel used the consensus methodology and proposed solutions for prevention strategy producing advice for the management of the most relevant unmet clinical needs. Such a comprehensive overview aims to support at the practice of HZ pharmacological and vaccine prevention and informing the design and the need of implementation of new studies in the field.

Background: For children with inflammatory bowel disease (IBD), understanding their condition may lead to better outcomes. Knowledge assessment is imperative to identify where education may be required. An IBD knowledge assessment tool (IBD-KID2) is available in English; the aim of this study was to translate IBD-KID2 in to Italian and assess its validity/reliability among children with IBD. Methods: IBD-KID2 has fifteen items, scoring one point per correct answer. IBD-KID2 items were assessed for cultural comprehension/relevance by Italian gastroenterologists using a content validity index; those items with a maximum score proportion t-test). Results: Twenty-five children participated: 16 (64%) male, mean age 14.9 years (SD2.4), Crohn’s disease 13 (52%). The mean IBD-KID2 score was 8.8 (SD2.8), with no association with independent variables. Test–retest showed strong correlation between scores (r = 0.78, p < 0.001), with no mean difference (p = 0.39). Comparison with other pediatric IBD populations (NZ/Australia/Canada) showed no score difference (p = 0.62, CI −0.9 to 1.5). Conclusions: The translation of IBD-KID2 to Italian used a rigorous methodology. Scores showed the translated tool has equivalence and generalizability to Italian children with IBD.

This work deals with the performance evaluation of novel flat photovoltaic–thermal (PV–T) modules under vacuum. Through a 1D (dimensional) steady-state-energy-balance numerical model developed in MATLAB, two different layouts are studied: the first consisting of a photovoltaic (PV) cell installed just below the glass encapsulating the flat panel, and the second where the PV cell is placed on the selective solar absorber (SSA). In both cases the thermal and electrical efficiencies have been evaluated at different SSA operating temperatures, in the range of 323 K to 423 K. The analysis has been conducted at different energy bandgap (Ebg) of the PV cell and assuming a variable transmittance or emittance of the PV cell, depending on the design. The two systems efficiency comparison has been carried out at the same operating temperature. Overall, this work highlights the importance of high vacuum insulation, which guarantees the reduction of convective thermal losses, and shows that the maximum energy is produced for PV cells with Ebg≈1.5-1.7 eV, depending on layout and operating temperature, by including the thermal output in the PV–T​ optimization. The energy and exergy efficiencies obtainable using the proposed PV–T​ systems are considerably improved compared to the results previously reported in the literature.

Gallstone ileus (GI) is a rare cause of acute abdomen in an emergency setting and a rare complication of cholelithiasis in the elderly, with a female prevalence. Radiologists play a key role in the diagnosis and management of this condition and, with a multimodal approach, diagnostic accuracy usually increases. Spontaneous resolution of GI has previously been reported for stones smaller than 2 cm. Gallstones usually require surgical management; however, in patients with comorbidities and at high risk of surgical complications, a conservative approach may be considered. Herein, we report the case of an 84-year-old woman who came to the emergency department with an acute abdomen pain caused by a GI, with a 2.6 cm gallstone that was revealed on computed tomography and which was followed by diagnostic imaging with spontaneous resolution.

High blood levels of low-density lipoprotein (LDL)-cholesterol (LDL-C) are associated with atherosclerosis, mainly by promoting foam cell accumulation in vessels. As cholesterol is an essential component of cell plasma membranes and a regulator of several signaling pathways, LDL-C excess may have wider cardiovascular toxicity. We examined, in untreated hypercholesterolemia (HC) patients, selected regardless of the cause of LDL-C accumulation, and in healthy participants (HP), the expression of the adenosine A2A receptor (A2AR), an anti-inflammatory and vasodilatory protein with cholesterol-dependent modulation, and Flotillin-1, protein marker of cholesterol-enriched plasma membrane domains. Blood cardiovascular risk and inflammatory biomarkers were measured. A2AR and Flotillin-1 expression in peripheral blood mononuclear cells (PBMC) was lower in patients compared to HP and negatively correlated to LDL-C blood levels. No other differences were observed between the two groups apart from transferrin and ferritin concentrations. A2AR and Flotillin-1 proteins levels were positively correlated in the whole study population. Incubation of HP PBMCs with LDL-C caused a similar reduction in A2AR and Flotillin-1 expression. We suggest that LDL-C affects A2AR expression by impacting cholesterol-enriched membrane microdomains. Our results provide new insights into the molecular mechanisms underlying cholesterol toxicity, and may have important clinical implication for assessment and treatment of cardiovascular risk in HC.

تهدف الدراسة الحالية بيان الأبعاد التطبيقية لمعايير المحاسبة الدولية للقطاع العام (IPSAS) وبيان انعكاساته على موازنة البرامج والأداء في احدى الوحدات الحكومية الخدمية في إقليم كوردستان العراق والتي تمثلت في كلية الإدارة والاقتصاد بجامعة دهوك، وبغرض تحقيق هدف الدراسة فقد تم تبني المنهج التطبيقي لبيان آليات ومنافع التطبيق المقارن لمتغيرات الدراسة بالاعتماد على التقارير والقوائم المالية للوحدة الحكومية المختارة عينة الدراسة للسنة المالية 2021، فضلا عن تقرير الموازنة المصادقة للوحدة الحكومية للسنة المالية (2013)، بالإضافة الى التعليمات المالية الحكومية في إقليم كوردستان العراق، وذلك لاختبار فرضية الدراسة، والتي تمثلت في فرضية رئيسية واحدة، توصلت الدراسة الى مجموعة من الاستنتاجات كان من أبرزها، أهمية ومنفعة التطبيق المتكامل للمعايير المحاسبة الدولية للقطاع العام (IPSAS) في تبني موازنة البرامج والأداء من خلال تحسين التخطيط والرقابة على الأنفاق العام وفاعلية الوحدة الحكومية في ترجمة أهدافها الاستراتيجية كمخرجات. وفي ضوء ذلك فقد أوصت الدراسة ضرورة وضع البرامج المدروسة للإصلاح النظام المحاسبي الحكومي من خلال الانتقال لمرحلة أكثر تطوراً من الموازنة العامة في إقليم كوردستان العراق بشكل خاص والعراق بشكل عام من خلال تطبيق (IPSAS) والتي تستهدف استخدام مجموعة من المعايير التي تدعم اتخاذ القرارات بشأن أسلوب الموازنة التي تكون موجهه نحو البرامج والأداء، ووضع الخطط (الاقتصادية، الاجتماعية، السياسية) متكاملة، وذلك من أجل المساعدة في الإدارة الفاعلة للمال العام.

Core competencies for public health (CCPH) define the knowledge, skills, and attitudes required of a public health workforce. Although numerous sets of CCPH have been established, few studies have systematically examined the governance of competency development, review, and monitoring, which is critical to their implementation and impact. This rapid review included 42 articles. The findings identified examples of collaboration and community engagement in governing activities (e.g., using the Delphi method to develop CCPH) and different ways of approaching CCPH review and revision (e.g., every 3 years). Insights on monitoring and resource management were scarce. Preliminary lessons emerging from the findings point towards the need for systems, structures, and processes that support ongoing reviews, revisions, and monitoring of CCPH.

Objectives BCR-ABL1 and JAK2 V617F coexistence in myeloproliferative neoplasms has been described as concomitant or sequential events. Despite this, we present a unique case of chronic myeloid leukemia (CML) not referable to either of the known scenarios.Methods BCR-ABL1 molecular monitoring was performed by real-time quantitative PCR (RQ-PCR). At the time of molecular relapse, a targeted next-generation sequencing analysis with a customized panel of 26 genes commonly mutated in myeloid diseases was performed. To investigate the kinetics of the JAK2 variant and its association with the BCR-ABL1 rearrangement, RQ-PCR was performed at different time points during the patient’s follow-up.Results While negative at CML diagnosis, the JAK2 mutation was first detected 9 years later (VAF: 7.2%). The mutational burden of JAK2 remained stable in multiple determinations, with minor fluctuations independent of BCR-ABL1 kinetics. At the last available time point, the patient was in deep molecular response (MR4), the JAK2 mutational burden was 7%, and no clinical-laboratory findings of Ph-MPN were detectable.Discussion In the presented case, the JAK2variantoccurring during the course of the disease seems to stay in the shadows of CML, just as a bystander. The impact of this event (that may be considered suggestive of clonal hematopoiesis of indeterminate potential) on the disease outcome, even if seemingly irrelevant, has still to be explored.