Diagnostic potential of plasma biomarkers and exhaled volatile organic compounds in predicting the different stages of acute mesenteric ischaemia: protocol for a multicentre prospective observational study (TACTIC study).

INTRODUCTION: Acute mesenteric ischaemia (AMI) is a life-threatening condition with short-term mortality of up to 80%. The diagnosis of AMI has remained troublesome due to the non-specific clinical presentation, symptoms and laboratory findings. Early unambiguous diagnosis of AMI is critical to prevent progression from reversible to irreversible transmural intestinal damage, thereby decreasing morbidity and improving survival. The present study aims to validate a panel of plasma biomarkers and investigate volatile organic compound (VOC) profiles in exhaled air as a tool to timely and accurately diagnose AMI. METHODS AND ANALYSIS: In this international multicentre prospective observational study, 120 patients (>18 years of age) will be recruited with clinical suspicion of AMI. Clinical suspicion is based on: (1) clinical manifestation, (2) physical examination, (3) laboratory measurements and (4) the physician's consideration to perform a CT scan. The patient's characteristics, repetitive blood samples and exhaled air will be prospectively collected. Plasma levels of mucosal damage markers intestinal fatty acid-binding protein and villin-1, as well as transmural damage marker smooth muscle protein 22-alpha, will be assessed by ELISA. Analysis of VOCs in exhaled air will be performed by gas chromatography time-of-flight mass spectrometry. Diagnosis of AMI will be based on CT, endovascular and surgical reports, clinical findings, and (if applicable) verified by histopathological examination. ETHICS AND DISSEMINATION: The study protocol was approved by the Medical Research Ethics Committee (METC) of Maastricht University Medical Centre+ and Maastricht University (METC azM/UM), the Netherlands (METC19-010) and the Ethics Committee Research UZ/KU Leuven, Belgium (S63500). Executive boards and local METCs of other Dutch participating centres Gelre Ziekenhuizen (Apeldoorn), Medisch Spectrum Twente (Enschede), and University Medical Centre Groningen have granted permission to carry out this study. Study results will be disseminated via open-access peer-reviewed scientific journals and national/international conferences. TRIAL REGISTRATION NUMBER: NCT05194527.

Cost Effectiveness of Endovascular Revascularisation vs. Exercise Therapy for Intermittent Claudication Due to Iliac Artery Obstruction.

OBJECTIVE: To compare cost effectiveness of endovascular revascularisation (ER) and supervised exercise therapy (SET) as primary treatment for patients with intermittent claudication (IC) due to iliac artery obstruction. METHODS: Cost utility analysis from a restricted societal perspective and time horizon of 12 months. Patients were included in a multicentre randomised controlled trial (SUPER study, NCT01385774, NTR2648) which compared effectiveness of ER and SET. Health status and health related quality of life (HRQOL) were measured using the Euroqol 5 dimensions 3 levels (EQ5D-3L) and VascuQol-25-NL. Incremental costs were determined per allocated treatment and use of healthcare during follow up. Effectiveness of treatment was determined in quality adjusted life years (QALYs). The difference between treatment groups was calculated by an incremental cost utility ratio (ICER). RESULTS: Some 240 patients were included, and complete follow up was available for 206 patients (ER 111 , SET 95). The mean costs for patients allocated to ER were €4 031 and €2 179 for SET, a mean difference of €1 852 (95% bias corrected and accelerated [bca] bootstrap confidence interval 1 185 - 2 646). The difference in QALYs during follow up was 0.09 (95% bcaCI 0.04 - 0.13) in favour of ER. The ICER per QALY was €20 805 (95% bcaCI 11 053 - 45 561). The difference in VascuQol sumscore was 0.64 (95% bcaCI 0.39 - 0.91), again in favour of ER. CONCLUSION: ER as a primary treatment, results in slightly better health outcome and higher QALYs and HRQOL during 12 months of follow up. Although these differences are statistically significant, clinical relevance must be discussed due to the small differences and relatively high cost of ER as primary treatment.

Editor's Choice - Randomised Clinical Trial of Supervised Exercise Therapy vs. Endovascular Revascularisation for Intermittent Claudication Caused by Iliac Artery Obstruction: The SUPER study.

OBJECTIVE: International guidelines recommend supervised exercise therapy (SET) as primary treatment for all patients with intermittent claudication (IC), yet primary endovascular revascularisation (ER) might be more effective in patients with iliac artery obstruction. METHODS: This was a multicentre RCT including patients with IC caused by iliac artery stenosis or occlusion (NCT01385774). Patients were allocated randomly to SET or ER stratified for maximum walking distance (MWD) and concomitant SFA disease. Primary endpoints were MWD on a treadmill (3.2 km/h, 10% incline) and disease specific quality of life (VascuQol) after one year. Additional interventions during a mean follow up of 5.5 years were recorded. RESULTS: Between November 2010 and May 2015, 114 patients were allocated to SET, and 126 to ER. The trial was terminated prematurely after 240 patients were included. Compliance with SET was 57/114 (50%) after six months. Ten patients allocated to ER (8%) did not receive this intervention. One year follow up was complete for 90/114 (79%) SET patients and for 104/126 (83%) ER patients. The mean MWD improved from 187 to 561 m in SET patients and from 196 to 574 m in ER patients (p = .69). VascuQol sumscore improved from 4.24 to 5.58 in SET patients, and from 4.28 to 5.88 in ER patients (p = .048). Some 33/114 (29%) SET patients had an ER within one year, and 2/114 (2%) surgical revascularisation (SR). Some 10/126 (8%) ER patients had additional ER within one year and 10/126 (8%) SR. After a mean of 5.5 years, 49% of SET patients and 27% of ER patients underwent an additional intervention for IC. CONCLUSION: Taking into account the many limitations of the SUPER study, both a strategy of primary SET and primary ER improve MWD on a treadmill and disease specific Qol of patients with IC caused by an iliac artery obstruction. It seems reasonable to start with SET in these patients and accept a 30% failure rate, which, of course, must be discussed with the patient. Patients continue to have interventions beyond one year.

Cutting the costs of coastal protection by integrating vegetation in flood defences.

Exposure to coastal flooding is increasing due to growing population and economic activity. These developments go hand-in-hand with a loss and deterioration of ecosystems. Ironically, these ecosystems can play a buffering role in reducing flood hazard. The ability of ecosystems to contribute to reducing coastal flooding has been emphasized in multiple studies. However, the role of ecosystems in hybrid coastal protection (i.e. a combination of ecosystems and levees) has been poorly quantified at a global scale. Here, we evaluate the use of coastal vegetation, mangroves, and marshes fronting levees to reduce global coastal protection costs, by accounting for wave-vegetation interaction.The research is carried out by combining earth observation data and hydrodynamic modelling. We show that incooperating vegetation in hybrid coastal protection results in more sustainable and financially attractive coastal protection strategies. If vegetated foreshore levee systems were established along populated coastlines susceptible to flooding, the required levee crest height could be considerably reduced. This would result in a reduction of 320 (range: 107-961) billion USD2005 Power Purchasing Parity (PPP) in investments, of which 67.5 (range: 22.5- 202) billion USD2005 PPP in urban areas for a 1 in 100-year flood protection level.

Spatiotemporal patterns of extreme sea levels along the western North-Atlantic coasts.

The western North-Atlantic coast experienced major coastal floods in recent years. Coastal floods are primarily composed of tides and storm surges due to tropical (TCs) and extra-tropical cyclones (ETCs). We present a reanalysis from 1988 to 2015 of extreme sea levels that explicitly include TCs for the western North-Atlantic coastline. Validation shows a good agreement between modeled and observed sea levels and demonstrates that the framework can capture large-scale variability in extreme sea levels. We apply the 28-year reanalysis to analyze spatiotemporal patterns. Along the US Atlantic coasts the contribution of tides can be significant, with the average contribution of tides during the 10 largest events up to 55% in some locations, whereas along the Mexican Southern Gulf coast, the average contribution of tides over the largest 10 events is generally below 25%. At the US Atlantic coast, ETCs are responsible for 8.5 out of the 10 largest extreme events, whereas at the Gulf Coast and Caribbean TCs dominate. During the TC season more TC-driven events exceed a 10-year return period. During winter, there is a peak in ETC-driven events. Future research directions include coupling the framework with synthetic tropical cyclone tracks and extension to the global scale.

A global reanalysis of storm surges and extreme sea levels.

Extreme sea levels, caused by storm surges and high tides, can have devastating societal impacts. To effectively protect our coasts, global information on coastal flooding is needed. Here we present the first global reanalysis of storm surges and extreme sea levels (GTSR data set) based on hydrodynamic modelling. GTSR covers the entire world's coastline and consists of time series of tides and surges, and estimates of extreme sea levels. Validation shows that there is good agreement between modelled and observed sea levels, and that the performance of GTSR is similar to that of many regional hydrodynamic models. Due to the limited resolution of the meteorological forcing, extremes are slightly underestimated. This particularly affects tropical cyclones, which requires further research. We foresee applications in assessing flood risk and impacts of climate change. As a first application of GTSR, we estimate that 1.3% of the global population is exposed to a 1 in 100-year flood.

Declining vulnerability to river floods and the global benefits of adaptation.

The global impacts of river floods are substantial and rising. Effective adaptation to the increasing risks requires an in-depth understanding of the physical and socioeconomic drivers of risk. Whereas the modeling of flood hazard and exposure has improved greatly, compelling evidence on spatiotemporal patterns in vulnerability of societies around the world is still lacking. Due to this knowledge gap, the effects of vulnerability on global flood risk are not fully understood, and future projections of fatalities and losses available today are based on simplistic assumptions or do not include vulnerability. We show for the first time (to our knowledge) that trends and fluctuations in vulnerability to river floods around the world can be estimated by dynamic high-resolution modeling of flood hazard and exposure. We find that rising per-capita income coincided with a global decline in vulnerability between 1980 and 2010, which is reflected in decreasing mortality and losses as a share of the people and gross domestic product exposed to inundation. The results also demonstrate that vulnerability levels in low- and high-income countries have been converging, due to a relatively strong trend of vulnerability reduction in developing countries. Finally, we present projections of flood losses and fatalities under 100 individual scenario and model combinations, and three possible global vulnerability scenarios. The projections emphasize that materialized flood risk largely results from human behavior and that future risk increases can be largely contained using effective disaster risk reduction strategies.

Strong influence of El Niño Southern Oscillation on flood risk around the world.

El Niño Southern Oscillation (ENSO) is the most dominant interannual signal of climate variability and has a strong influence on climate over large parts of the world. In turn, it strongly influences many natural hazards (such as hurricanes and droughts) and their resulting socioeconomic impacts, including economic damage and loss of life. However, although ENSO is known to influence hydrology in many regions of the world, little is known about its influence on the socioeconomic impacts of floods (i.e., flood risk). To address this, we developed a modeling framework to assess ENSO's influence on flood risk at the global scale, expressed in terms of affected population and gross domestic product and economic damages. We show that ENSO exerts strong and widespread influences on both flood hazard and risk. Reliable anomalies of flood risk exist during El Niño or La Niña years, or both, in basins spanning almost half (44%) of Earth's land surface. Our results show that climate variability, especially from ENSO, should be incorporated into disaster-risk analyses and policies. Because ENSO has some predictive skill with lead times of several seasons, the findings suggest the possibility to develop probabilistic flood-risk projections, which could be used for improved disaster planning. The findings are also relevant in the context of climate change. If the frequency and/or magnitude of ENSO events were to change in the future, this finding could imply changes in flood-risk variations across almost half of the world's terrestrial regions.

Has central sensitization become independent of nociceptive input in chronic pancreatitis patients who fail thoracoscopic splanchnicectomy?

BACKGROUND AND OBJECTIVES: Central sensitization due to visceral pancreatic nociceptive input may be important in chronic pancreatitis pain. We investigated whether bilateral thoracoscopic splanchnicectomy (BTS) to reduce nociceptive input in chronic pancreatitis patients (CPP) with poor pain control affects supraspinal and spinal sensitization. METHODS: Seventeen CPP were studied preoperatively and 6 weeks after BTS. Pressure pain thresholds (PPT) were measured in clavicle and pancreatic dermatomes reflecting supraspinal and spinal central sensitization, respectively. Patients with increased PPT after BTS (hypoalgesic) were compared to those without (hyperalgesic) and PPT vs. pain numeric rating scale (NRS) changes compared. RESULTS: After BTS, ten patients showed C5 PPT increases (hypoalgesic; median change 87 kPa), 7 patients had unaltered/lower PPT (hyperalgesic; -135 kPa). Preoperative pain NRS was similar between groups (4 vs. 5, P = 0.2). After BTS hypoalgesic group NRS was lower (1 vs. 6; P = 0.008) and NRS change greater (-2 vs. 0; P = 0.005). Whole group NRS and C5 PPT change correlated significantly and negatively (r = 0.53; P < 0.05), but not for pancreatic PPT. CONCLUSIONS: Reduced supraspinal-but not spinal-central sensitization after BTS was associated with significantly reduced pain scores in a majority of CPP. A subgroup showed no reductions in supraspinal central sensitization after BTS, coupled to no significant pain NRS reduction. Our results suggest that a subgroup of CPP has altered pain processing that may be independent of ongoing peripheral nociceptive input, resulting in persisting pain despite BTS. If confirmed, these results indicate the importance of sensory testing for indications and management of pain treatments.

S-ketamine modulates hyperalgesia in patients with chronic pancreatitis pain.

BACKGROUND AND OBJECTIVES: Upper abdominal pain is a dominant feature of chronic pancreatitis. A key phenomenon in this context is hyperalgesia, typically associated with N-methyl-d-aspartate receptor activation. This exploratory study evaluates acute effects of S-ketamine, a noncompetitive N-methyl-d-aspartate antagonist, in modulating generalized hyperalgesia in chronic pancreatitis pain. METHODS: In a blinded crossover trial, 10 chronic pancreatitis pain patients received S-ketamine for 3 hrs at 2 µg · kg · min or placebo infusion at an equivalent rate in randomized order. Clinical pain was assessed via visual analog scale (VAS) and short Dutch Language Version McGill Pain Questionnaire (sf-MPQ-DLV). Pressure pain thresholds (PPTs) were measured in dermatome C5, T4, dorsal T10, L1, and L4, and the sum of PPTs (SOPPT) calculated before, at end of, and after infusion. RESULTS: Nine patients completed the study. Median pain VAS before infusion was 29 mm at rest, 32 mm during activity; sf-MPQ-DLV score was 4. For the S-ketamine session median SOPPT change at infusion end was significantly higher than in the placebo session (218; interquartile range [IQR], 116-527, versus -123 [IQR, -330 to 24]; P = 0.005) and significant versus preinfusion values (2109 [IQR, 964-3035] vs 1914 [IQR, 842-2884]; P = 0.03). The SOPPT was unchanged versus preinfusion values and similar between groups at 1 hr after infusion end. No significant changes in VAS and sf-MPQ-DLV occurred. CONCLUSIONS: S-ketamine infusion is more effective than placebo in increasing PPTs in chronic pancreatitis pain patients immediately after infusion. This effect did not outlast the infusion. Further research is warranted into S-ketamine use for reducing generalized hyperalgesia and chronic pancreatitis pain.

Limited effect of thoracoscopic splanchnicectomy in the treatment of severe chronic pancreatitis pain: a prospective long-term analysis of 75 cases.

BACKGROUND: Bilateral thoracoscopic splanchnicectomy is a minimally invasive method of treating pain in patients with chronic pancreatitis. It offers good, short-term pain relief, but long-term success is difficult to predict. We analyze long-term results and identify factors predicting success of splanchnicectomy. METHODS: A total of 75 consecutive chronic pancreatitis patients underwent bilateral thoracoscopic splanchnicectomy with long term follow-up (>or=1 year). Treatment success was analyzed using the Kaplan-Meier method, and possible predictive factors (etiology, gender, onset of pancreatitis, previous pancreatitis-related surgery, opioid use, pathology at imaging, technical success, and post-splanchnicectomy complications) via the Cox proportional hazards regression model. We compared patients with long-term pain relief, patients who failed the procedure within 1 year, and those who had pain recurrence after > 1 year. Further treatments after failed splanchnicectomy were evaluated. RESULTS: A total of 66 patients (88%) were on continuous opioids; 47 (63%) had prior pancreatitis-related interventions. Treatment was successful in 52% of patients at 12 months, 38% at 24 months, and 28% at 48 months. At the end of follow-up, 21 patients (28%) reported pain relief, of whom 13 were completely pain free without any additional treatment. Pancreatic surgery after failed splanchnicectomy relieved pain in only 13% of patients. Technical success was the only independent factor significantly associated with successful splanchnicectomy outcome (P = .03). Preoperative opioid use showed a strong tendency to be associated with unsuccessful outcome (P = .07). CONCLUSION: Splanchnicectomy offers prolonged (>4 years) benefit in 1 of 4 patients with severe chronic pancreatitis pain. Prior opioid use may adversely impact pain relief after splanchnicectomy.

Guidelines and legislation for dye house effluents.

Increasing attention has been paid over the years to the environmental problems related to industrial activities. Environmental standards have been established and control organisms have been created with a view to applying restrictive legislation. In the dyeing industry, ennoblers discharge in the environment large volumes of strongly coloured effluents that are heavily loaded with pollutants and highly concentrated in salts. This chemical load is generated during the different steps of textile preparation. After reviewing the characteristics of these effluents, this paper gives a comparative review of the current legislations on the dyeing industry emissions. It examines more closely the discharge legislation, first in France and then in other countries around the world. A comparison of the six most representative parameters shows how different the applied constraints are in different countries.

Chronic pancreatitis patients show hyperalgesia of central origin: a pilot study.

BACKGROUND: The pain of chronic pancreatitis remains challenging to manage, with treatment all too often being unsuccessful. A main reason for this is lacking understanding of underlying mechanisms of chronic pain in these patients. AIM: To document, using somatic quantitative sensory testing, changes in central nervous system processing (neuroplasticity) associated with chronic pancreatitis pain and thus gain insight into underlying pain mechanisms. PATIENTS AND METHODS: We studied 10 chronic pancreatitis patients on stable opioid analgesic medication. Ten matched surgical patients without pain served as controls. Pain verbal numeric rating scores (NRS) and thresholds to electric skin stimulation and pressure pain were measured in dermatomes T10 (pancreatic area), C5, T4, L1 and L4. RESULTS: The pancreatitis patients had a median NRS pain score of 5 (range 3-8). Electric sensation and pain thresholds were significantly increased in the pancreatic region, tending to be more so in female pancreatitis patients. Pressure pain thresholds were significantly lower in pancreatitis patients than in controls, with men tending towards greater generalised relative hyperalgesia than women. CONCLUSIONS: Chronic pancreatitis patients show pronounced generalised deep hyperalgesia that is present despite opioid therapy. These signs, consistent with central sensitisation, appear relatively more prominent in men than women. There is also evidence suggesting that women may have a better segmental inhibitory response than men, possibly explaining their relatively less prominent generalised deep tissue hyperalgesia compared to men.

Occupational therapy for independent-living older adults. A randomized controlled trial.

CONTEXT: Preventive health programs may mitigate against the health risks of older adulthood. OBJECTIVE: To evaluate the effectiveness of preventive occupational therapy (OT) services specifically tailored for multiethnic, independent-living older adults. Design.-A randomized controlled trial. SETTING: Two government subsidized apartment complexes for independent-living older adults. SUBJECTS: A total of 361 culturally diverse volunteers aged 60 years or older. INTERVENTION: An OT group, a social activity control group, and a nontreatment control group. The period of treatment was 9 months. MAIN OUTCOME MEASURES: A battery of self-administered questionnaires designed to measure physical and social function, self-rated health, life satisfaction, and depressive symptoms. RESULTS: Benefit attributable to OT treatment was found for the quality of interaction scale on the Functional Status Questionnaire (P=.03), Life Satisfaction Index-Z (P=.03), Medical Outcomes Study Health Perception Survey (P=.05), and for 7 of 8 scales on the RAND 36-Item Health Status Survey, Short Form: bodily pain (P=.03), physical functioning (P=.008), role limitations attributable to health problems (P=.02), vitality (P=.004), social functioning (P=.05), role limitations attributable to emotional problems (P=.05), and general mental health (P=.02). CONCLUSIONS: Significant benefits for the OT preventive treatment group were found across various health, function, and quality-of-life domains. Because the control groups tended to decline over the study interval, our results suggest that preventive health programs based on OT may mitigate against the health risks of older adulthood.

[Loss of innervation of the anterior cruciate ligament in idiopathic gonarthrosis]. / Innervationsstörungen des vorderen Kreuzbandes bei der idiopathischen Gonarthrose.

This study quantifies the neurological structures of the ACL from proximal to distal in the zones A, B and C. 37 knee cadavers of healthy patients were analyzed to determinate the innervation for each age decade. This investigation was undertaken with high specific immuno-histologic sections (APAAP method). Neurofilaments and Schwann cells were isolated identified. In a second group consisting of 15 patients with idiopathic arthritis the ACLs were analyzed. This showed a significant loss of innervation, often, there was a complete deficit. In conclusion, this study revealed that idiopathic arthritis of the knee is associated with a significant deficit of the innervation of the ACL. If this is the reason for the arthritis or a secondary phenomenon is still unknown.

Software for logging of surgical cases.

A compiled database program is described to log surgical cases for otolaryngologists. It provides a time-efficient mechanism to manage a large database and also generates reports in two formats. In the first format, patient demographics, surgeons, and procedures are printed. In the second format, numerical tallies of performed procedures are listed.

Mucosal leishmaniasis in Brazil.

The clinical diagnosis and laboratory identification of Leishmania braziliensis braziliensis, a parasitic disease affecting the upper aerodigestive tract, is difficult. A retrospective computer-assisted analysis of patient records was done after examination of 58 patients with mucosal leishmaniasis in an endemic area of L. braziliensis braziliensis in Bahia, Brazil during January 1987. Biopsies of clinically active and clinically inactive mucosal patients were examined for parasites using routine hematoxylin and eosin histopathology and a new technique for rapid detection of Leishmania amastigotes using a genus-specific indirect immunofluorescent assay. No amastigotes were found in specimens from seven patients with clinically inactive mucosal disease using immunofluorescent monoclonal assay techniques, whereas specimens from seven out of 14 patients with clinically active mucosal disease were positive. These results suggest that the immunofluorescent antibody technique is markedly superior in identifying the intracellular amastigote in tissue sections of mucosal biopsies when compared to histopathology techniques or with other standard tests done in rural areas of Brazil. Various clinical and laboratory test data of the entire group of patients were examined and the efficacy of treatment evaluated. The median interval of time noted between cutaneous and mucosal disease was 4.5 years. Relapse was noted in 31% of patients treated with a low dose of meglumine antimoniate (10 mg per kg of body weight). Patients treated with a high dose of meglumine antimoniate (20 mg per kg of body weight) had a relapse rate of 27.3%. A chi-square statistical analysis revealed no significant difference (chi 2 = 0.049) between the two groups. Patients were considered cured if mucosal granulations were clinically absent after 4.6 years.

Patterns of bilirubin staining in nonhemolytic kernicterus.

Patterns of bilirubin staining were studied in nine infants with kernicterus related to nonhemolytic hyperbilirubinemia, all weighing less than 1200 g, and nine matched controls. Three staining patterns were disclosed: a localized pattern in the central nervous system of kernicteric infants, with only the thalamus staining significantly often; staining, in extraneural tissues (adrenal, myocardial, renal, and colonic mucosa) only in kernicteric infants, despite similar bilirubin levels in both groups; and yellow staining of the alveolar hyaline membranes as a function of survival duration in both groups. Bilirubin staining of tissue is apparently a generalized phenomenon, most recognized in the central nervous system as kernicterus. Failure to maintain the impermeability of the cell membrane coupled with regional differences in blood flow would best explain bilirubin distribution. In contrast, the degree of bilirubin staining of alveolar hyaline membranes is time related in kernicteric and control infants.