Evidence-Based Severity Assessment of Animal Models for Pancreatic Cancer.

Animal models are crucial to preclinical oncological research and drug development. Animal experiments must be performed in accordance with the 3R principles of replacement and reduction, if possible, and refinement where these procedures remain crucial. In addition, European Union legislations demand a continuous refinement approach, as well as pro- and retrospective severity assessment. In this study, an objective databased severity assessment was performed in murine models for pancreatic cancer induced by orthotopic, subcutaneous, or intravenous injection of Panc02 cells. Parameters such as body weight change, distress score, perianal temperature, mouse grimace scale, burrowing, nesting behavior, and the concentration of corticosterone in plasma and its metabolites in feces were monitored during tumor progression. The most important parameters were combined into a score and mapped against a reference data set by the Relative Severity Assessment procedure (RELSA) to obtain the maximum achieved severity for each animal (RELSAmax). This scoring revealed a significantly higher RELSAmax for the orthotopic model than for the subcutaneous and intravenous models. However, compared to animal models such as pancreatitis and bile duct ligation, the pancreatic cancer models are shown to be less severe. Data-based animal welfare assessment proved to be a valuable tool for comparing the severity of differently induced cancer models.

Arsenic removal with zero-valent iron filters in Burkina Faso: Field and laboratory insights.

Groundwater contaminated with geogenic arsenic (As) is frequently used as drinking water in Burkina Faso, despite adverse health effects. This study focused on testing low-cost filter systems based on zero-valent iron (ZVI), which have not yet been explored in West Africa for As removal. The active ZVI bed was constructed using small-sized iron nails, embedded between sand layers. Household filters were tested for nine months in a remote village relying on tube well water with As concentrations of 400-1350 µg/L. Daily filtered volumes were 40-60 L, with flow rates of ~10 L/h. In parallel, downscaled laboratory filter columns were run to find the best set-up for optimal As removal, with special attention given to the influence of input pH, flow rate and water/nail contact time. Arsenic removal efficiencies in the field were 60-80% in the first six months of operation. The laboratory experiments revealed that trapped air in the nail layer greatly lowered As removal due to preferential flow and decreased water/nail contact time. Measures taken to avoid trapped air led to a partial improvement in the field filters, but effluent As remained >50 µg/L. Similar structural modifications were however very successful in the laboratory columns, where As removal efficiencies were consistently >95% and effluent concentrations frequently <10 µg/L, despite inflow As >1000 µg/L. A constantly saturated nail bed and careful flow control is necessary for optimal As removal. Slow flow and longer pauses between filtrations are important for sufficient contact times and for transformation of brown amorphous Fe-hydroxides to dense magnetite with incorporated As(V). This preliminary study has shown that nail-based filters have the potential to achieve As removal >90% in a field context if conditions (filter bed saturation, flow rate, pauses between filtrations) are well controlled.

Cerebral oxygenation during pediatric congenital cardiac surgery and its association with outcome: a retrospective observational study.

PURPOSE: Non-invasive cerebral oxygen saturation (ScO2) monitoring is an established tool in the intraoperative phase of pediatric congenital cardiac surgery (CCS). This study investigated the association between ScO2 and postoperative outcome by investigating both baseline ScO2 values and intraoperative desaturations from baseline. METHODS: All CCS procedures performed in the period 2010-2017 in our institution in which ScO2 was monitored were included in this historical cohort study. Baseline ScO2 was determined after tracheal intubation, before surgical incision. Subgroups were based on cardiac pathology and degree of intracardiac shunting. Poor outcome was defined based on length of stay (LOS) in the intensive care unit (ICU)/hospital, duration of mechanical ventilation (MV), and 30-day mortality. Intraoperatively, ScO2 total time below baseline (TBBL) and ScO2 time-weighted average (TWA) were calculated. RESULTS: Data from 565 patients were analyzed. Baseline ScO2 was significantly associated with LOS in ICU (odds ratio [OR] per percentage decrease in baseline ScO2, 0.95; 95% confidence interval [CI], 0.93 to 0.97; P < 0.001), with LOS in hospital (OR, 0.93; 95% CI, 0.91 to 0.96; P < 0.001), with MV duration (OR, 0.92; 95% CI, 0.90 to 0.95; P < 0.001) and with 30-day mortality (OR, 0.94; 95% CI, 0.91 to 0.98; P = 0.007). Cerebral oxygen saturation TWA had no associations, while ScO2 TBBL had only a small association with LOS in ICU (OR, 1.02; 95% CI, 1.01 to 1.03; P < 0.001), MV duration (OR,1.02; 95% CI, 1.01 to 1.03; P = 0.002), and LOS in hospital (OR, 1.02; 95% CI, 1.01 to 1.04; P < 0.001). CONCLUSION: In pediatric patients undergoing cardiac surgery, low baseline ScO2 values measured after tracheal intubation were associated with several adverse postoperative outcomes. In contrast, the severity of actual intraoperative cerebral desaturation was not associated with postoperative outcomes. Baseline ScO2 measured after tracheal intubation may help identify patients at increased perioperative risk.

RéSUMé: OBJECTIF: Le monitorage non invasif de la saturation cérébrale en oxygène (ScO2) est un outil bien établi en phase peropératoire de chirurgie cardiaque congénitale pédiatrique. Cette étude a examiné l'association entre la ScO2 et le pronostic postopératoire en étudiant les valeurs de ScO2 initiales et les désaturations peropératoires par rapport à ces valeurs. MéTHODE: Toutes les interventions en chirurgie cardiaque congénitale réalisées entre 2010 et 2017 dans notre établissement et au cours desquelles la ScO2 a été monitorée ont été incluses dans cette étude de cohorte historique. La ScO2 de base était déterminée après l'intubation trachéale, avant l'incision chirurgicale. Les sous-groupes ont été catégorisés en fonction de la pathologie cardiaque et des shunts intracardiaques. Un mauvais pronostic était défini en fonction de la durée de séjour à l'unité de soins intensifs (USI)/ l'hôpital, de la durée de ventilation mécanique et de la mortalité à 30 jours. Pendant l'intervention, le temps total pendant lequel la ScO2 était au-dessous des valeurs de base et la moyenne pondérée dans le temps ont été calculés. RéSULTATS: Les données de 565 patients ont été analysées. Une association significative a été observée entre la ScO2 de base et la durée de séjour à l'USI (diminution du rapport de cotes [RC] par pourcentage de la ScO2 de base, 0,95; intervalle de confiance [IC] 95 %, 0,93 à 0,97; P < 0,001), la durée de séjour à l'hôpital (RC, 0,93; IC 95 %, 0,91 à 0,96; P < 0,001), la durée de ventilation mécanique (RC, 0,92; IC 95 %, 0,90 à 0,95; P < 0,001) et la mortalité à 30 jours (RC, 0,94; IC 95 %, 0,91 à 0,98; P = 0,007). La moyenne pondérée dans le temps de la saturation cérébrale en oxygène n'a pas révélé d'association, alors que le temps total au-dessous des valeurs de base de ScO2 n'a révélé qu'une petite association avec la durée de séjour à l'USI (RC, 1,02; IC 95 %, 1,01 à 1,03; P < 0,001), la durée de ventilation mécanique (RC, 1,02; IC 95 %, 1,01 à 1,03; P = 0,002), et la durée de séjour à l'hôpital (RC, 1,02; IC 95 %, 1,01 à 1,04; P < 0,001). CONCLUSION: Chez les patients pédiatriques subissant une chirurgie cardiaque, des valeurs de ScO2 basses lorsque mesurées après l'intubation trachéale étaient associées à plusieurs complications postopératoires. En revanche, la gravité de la désaturation cérébrale peropératoire n'était pas associée aux devenirs postopératoires. La ScO2 de base mesurée après l'intubation trachéale pourrait nous aider à identifier les patients courant un risque périopératoire accru.

Eligibility of Endovascular Repair for Popliteal Artery Aneurysms According the Instructions for Use.

BACKGROUND: Popliteal artery aneurysms (PAAs) are the most common peripheral aneurysms. Although rare and often asymptomatic, there is a significant risk of thrombosis, embolism, and limb loss. The aim of this study was to evaluate the eligibility for endovascular repair of patients treated for symptomatic and asymptomatic PAAs in accordance with the instructions for use (IFU). METHODS: All patients treated for PAA with open surgical repair between the years 2010 and 2017 were analyzed if suitable for endovascular treatment. Preoperative imaging was reviewed for applicability with an interventional radiologist and 2 vascular surgeons. Evaluation was performed in accordance with the following criteria adopted from the IFU of the Gore ® Viabahn stent graft: at least a single-vessel tibial runoff, proximal and distal landing zone more than 2 cm, no large difference in vessel diameter proximal and distal to the aneurysm, no overstenting of significant collaterals necessary, and no inadequate kinking of the artery. The patients were classified in 3 categories: the patient was eligible, endovascular treatment was feasible, and endovascular treatment was not appropriate. RESULTS: 51 patients with 61 symptomatic and asymptomatic PAAs were identified. Forty-five cases were asymptomatic, 11 cases showed clinical symptoms such as claudication, and in 5 cases, the patients presented with acute ischemia. Twenty-four patients were eligible for endovascular intervention, 14 cases were feasible, and in 23 cases, it was not appropriate in accordance with the IFU. CONCLUSIONS: In this study, more than one-third of the patients with PAA were not eligible for endovascular treatment in accordance with the IFU and another 23 % showed substantial reasons against endovascular treatment. These data suggest that endovascular repair remains a treatment option for selected patients only. Cross-sectional imaging is mandatory for procedure selection.

An exploratory study on the quality of patient screening and counseling for hypertension management in Tanzania.

BACKGROUND: The global burden of hypertension, currently estimated at 1 billion, is a leading Non-Communicable Disease (NCD) in Sub Saharan Africa. In Tanzania, the reported prevalence of hypertension is 25%. Inherent limitations of the healthcare system to control hypertension include inadequate provider knowledge, system capacity, medication access, and patient awareness, all of which hinder effective screening and disease management. To assess the quality of hypertension screening and patient counseling, we conducted a study in an ambulatory setting in Tanzania. METHODS: Observations of patient screening were conducted on 69 adult patients during routine outpatient care and screening camps. In addition, 33 healthcare providers participated in a pre-post knowledge assessment after observing instructional training videos. RESULTS: Patient observations indicated that blood pressure (BP) measurement was explained to 65% of patients, and 77% of the measurements were made with mercury sphygmomanometers. For several aspects of BP measurement, nurses performed better than doctors: patient's arm supported on a flat surface (doctors, 58% vs nurses 67%, p<0.05), and patient's back was supported (doctors, 50% vs nurses 88%, p<0.01). Among those diagnosed with hypertension, 7% were prescribed medications, 14% were advised on reduced salt during cooking, 29% on reduced salt consumption, 21% on reduced consumption of sodium rich foods, 21% on reducing caloric intake, 21% on increasing physical activity, and 43% were informed about follow up appointments. Provider knowledge assessments showed critical gaps in consequences of hypertension, 1st line medicines, and awareness of guidelines at baseline. Following the instructional videos there were improvements in some aspects: diagnostic criteria for hypertension (pre 45% vs post 91%, p<0.001) and counseling for controlling hypertension (pre 30% vs post 58%, p<0.01). CONCLUSION: Enhancing knowledge and performance competencies of health providers at the primary care level is a critical prerequisite for effective hypertension management in low resource settings.

Late-onset tumor necrosis factor receptor-associated periodic syndrome in multiple sclerosis patients carrying the TNFRSF1A R92Q mutation.

OBJECTIVE: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal-dominantly inherited autoinflammatory disorder caused by mutations in the TNFRSF1A gene. It is characterized by episodes of autoinflammation usually associated with fever, abdominal pain, myalgia, exanthema, arthralgia/arthritis, and ocular involvement. We undertook this study to investigate the prevalence of TRAPS in patients with multiple sclerosis (MS) who reported, in addition to their neurologic symptoms, at least 2 other symptoms compatible with TRAPS. METHODS: Twenty-five unrelated MS patients were prospectively screened for TNFRSF1A mutations. In addition, blood samples from 365 unrelated MS patients and 407 unrelated Caucasian controls were analyzed to determine the R92Q carrier frequency. RESULTS: Six of 25 adult MS patients (24%) with symptoms suggestive of TRAPS were found to carry the identical arginine-to-glutamine substitution at amino acid position 92 (R92Q or p.Arg121Gln) encoded by exon 4 of the TNFRSF1A gene. All R92Q heterozygotes had similar symptoms, including arthralgias/arthritis, myalgias, urticarial rash, and severe fatigue, which began before the onset of MS. In 5 of the 6 patients, we could identify family members who had TRAPS symptoms and had inherited the identical mutation. The R92Q exchange was also detected in 17 of 365 unselected MS patients (4.66%) and in 12 of 407 controls (2.95%) (P = 0.112). Three patients were heterozygous carriers of MEFV variants, in 1 patient in combination with the R92Q mutation. CONCLUSION: Autoinflammatory syndromes and especially late-onset TRAPS should be considered in MS patients who report symptoms such as arthralgias/arthritis, myalgias, urticarial rash, and severe fatigue.