STEC colitis mimicking acute severe colitis with life-threatening consequences: a case report.

Acute colitis is a common feature of infection with Shiga-toxin producing Escherichia coli (STEC) and can mimic acute severe ulcerative colitis. Early recognition is important as there is a risk of developing Shiga toxin-induced haemolytic uremic syndrome (STEC-HUS), defined by the triad of microangiopathic haemolytic anemia, thrombocytopenia and organ damage. In severe cases STEC-HUS can cause severe neurological complications and can be fatal. We present a patient with a medical history of refractory ulcerative colitis, where making the diagnosis of STEC-HUS was challenging since the initial clinical presentation was difficult to differentiate from a flare of ulcerative colitis. This case illustrates that STEC induced colitis can mimic acute severe ulcerative colitis. This finding is of utmost clinical importance because of the potential life-threatening complications of STEC-HUS. Therefore it should be excluded promptly in patients with acute severe ulcerative colitis by using multiplex-PCR assay on a faecal sample.

Influence of Early Life Factors, including breast milk Composition, on the Microbiome of Infants Born to Mothers with and without Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Herein we analysed the influence of early life factors, including breast milk composition, on the development of the intestinal microbiota of infants born to mothers with and without IBD. METHODS: The MECONIUM [Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome] study is a prospective cohort study consisting of pregnant women with or without IBD and their infants. Longitudinal stool samples were collected from babies and analysed using 16s rRNA sequencing and faecal calprotectin. Breast milk proteomics was profiled using Olink inflammation panel. RESULTS: We analysed gut microbiota of 1034 faecal samples from 294 infants [80 born to mothers with and 214 to mothers without IBD]. Alpha diversity was driven by maternal IBD status and time point. The major influencers of the overall composition of the microbiota were mode of delivery, feeding, and maternal IBD status. Specific taxa were associated with these exposures, and maternal IBD was associated with a reduction in Bifidobacterium. In 312 breast milk samples [91 from mothers with IBD], mothers with IBD displayed lower abundance of proteins involved in immune regulation, such as thymic stromal lymphopoietin, interleukin-12 subunit beta, tumour necrosis factor-beta, and C-C motif chemokine 20, as compared with control mothers [adjusted p = 0.0016, 0.049, 0.049, and 0.049, respectively], with negative correlations with baby´s calprotectin, and microbiome at different time points. CONCLUSION: Maternal IBD diagnosis influences microbiota in their offspring during early life. The proteomic profile of breast milk of women with IBD differs from that of women without IBD, with distinct time-dependent associations with baby's gut microbiome and feacal calprotectin.

Managing metastatic Crohn's disease: a single center experience, review of the current evidence, and treatment algorithm.

BACKGROUND: Crohn's disease (CD) is an inflammatory bowel disease (IBD) that, besides gastrointestinal symptoms, may encompass extra-intestinal symptoms, such as dermatological manifestations. Of those, metastatic CD (MCD) is a rare extra-intestinal manifestation for which the management is uncertain. METHODS: We conducted a retrospective case series of patients with MCD seen at the University hospital Leuven, Belgium, combined with an overview of the recent literature. Electronic medical records were searched from January 2003 till April 2022. For the literature search, Medline, Embase, Trip Database, and The Cochrane Library were searched from inception to April 1, 2022. RESULTS: A total of 11 patients with MCD were retrieved. In all cases noncaseating granulomatous inflammation was found on skin biopsies. Two adults and one child were diagnosed with MCD prior to their diagnosis of CD. Seven patients were treated with steroids (intralesional, topical or systemic). Six patients needed a biological therapy to treat MCD. Surgical excision was performed in three patients. All patients reported a successful outcome and most cases achieved remission. The literature search yielded 53 articles, including three reviews, three systematic reviews, 30 case reports and six case series. A treatment algorithm was generated based on literature and multidisciplinary discussion. CONCLUSION: MCD remains a rare entity and diagnosis is often difficult. A multidisciplinary approach including skin biopsy is necessary to diagnose and treat MCD efficiently. Outcome is generally favorable, and lesions respond well to steroids and biologicals. We propose a treatment algorithm based on the available evidence and multidisciplinary discussion.

P2X7 receptor antagonist improves gastrointestinal disorders in spontaneously hypertensive rats.

The purinergic system participates in the control of blood pressure. Hypertension promotes the occurrence of gastrointestinal disorders such as intestinal inflammation and gastric emptying delay. This study aimed i) to investigate the participation of the P2X7 receptor blocker Brilliant Blue G (BBG) on gastric emptying of solids and changes in oxidative stress in the gastric fundus, duodenum, and colon of spontaneously hypertensive rats (SHR) and ii) to study the putative relationship of this effect with the renin-angiotensin system. Rats were divided into five groups: Control, SHR, SHR+BBG, SHR+BBG+ATP, and SHR+BBG+ANG II. In the gastrointestinal tract, we assessed gastric emptying (GE) and oxidative stress markers (NOx, MPO, GSH, SOD). We observed a decrease in the GE rate (P<0.05) in SHR vs control rats (21.8±2.0% vs 42.8±3.5%). The decrease in GE was returned (P<0.05) to control levels by BBG in SHR rats (21.8±2.0% vs 41.6±3.2%). Co-administration of ATP or ANG II together with BBG bypassed the effect of the P2X7 antagonist on GE in SHR (P<0.05) (21.9±5.0% vs 25.6±3.0% vs 41.6±3.2%). The MPO activity increased (P<0.05) in the gastric fundus of SHR compared to control rats (6.12±2.26 vs 0.077±0.02 UMPO/mg tissue); this effect was prevented (P<0.05) by BBG (0.55±0.15 vs 6.12±2.26 UMPO/mg tissue). Data demonstrated that blockage of P2X7 receptors with BBG can improve the GE delay and oxidative stress biomarkers in SHR animals. This preventive effect of BBG on GE delay was abrogated by ANG II and ATP, thus prompting crosstalk between renin-angiotensin and the purinergic signaling systems underlying this phenomenon.

P2X7 receptor antagonist improves gastrointestinal disorders in spontaneously hypertensive rats

The purinergic system participates in the control of blood pressure. Hypertension promotes the occurrence of gastrointestinal disorders such as intestinal inflammation and gastric emptying delay. This study aimed i) to investigate the participation of the P2X7 receptor blocker Brilliant Blue G (BBG) on gastric emptying of solids and changes in oxidative stress in the gastric fundus, duodenum, and colon of spontaneously hypertensive rats (SHR) and ii) to study the putative relationship of this effect with the renin-angiotensin system. Rats were divided into five groups: Control, SHR, SHR+BBG, SHR+BBG+ATP, and SHR+BBG+ANG II. In the gastrointestinal tract, we assessed gastric emptying (GE) and oxidative stress markers (NOx, MPO, GSH, SOD). We observed a decrease in the GE rate (P<0.05) in SHR vs control rats (21.8±2.0% vs 42.8±3.5%). The decrease in GE was returned (P<0.05) to control levels by BBG in SHR rats (21.8±2.0% vs 41.6±3.2%). Co-administration of ATP or ANG II together with BBG bypassed the effect of the P2X7 antagonist on GE in SHR (P<0.05) (21.9±5.0% vs 25.6±3.0% vs 41.6±3.2%). The MPO activity increased (P<0.05) in the gastric fundus of SHR compared to control rats (6.12±2.26 vs 0.077±0.02 UMPO/mg tissue); this effect was prevented (P<0.05) by BBG (0.55±0.15 vs 6.12±2.26 UMPO/mg tissue). Data demonstrated that blockage of P2X7 receptors with BBG can improve the GE delay and oxidative stress biomarkers in SHR animals. This preventive effect of BBG on GE delay was abrogated by ANG II and ATP, thus prompting crosstalk between renin-angiotensin and the purinergic signaling systems underlying this phenomenon.

ECCO Position on Harmonisation of Crohn's Disease Mucosal Histopathology.

In inflammatory bowel disease [IBD], mucosal healing is a major therapeutic target and a reliable predictor of clinical course. However, endoscopic mucosal healing is not synonymous with histological healing, and the additional benefits of including histological remission as a target are unclear. In Crohn´s disease [CD], there are few studies highlighting the value of histological remission as a therapeutic target. Histological activity can persist in CD patients who are in endoscopic remission, and the absence of histological activity may be associated with lower relapse rates. Therefore, standardisation of procedures to evaluate CD histological activity is desirable. Topics that would benefit from standardisation and harmonisation include biopsy procedures, biopsy processing techniques, the content of histological scores, and the definitions of histological remission, histological response, and histological activity. In line with these needs, the European Crohn's and Colitis Organisation [ECCO] assembled a consensus group with the objective of developing position statements on CD histology based on published evidence and expert consensus. There was agreement that definitions of histological remission should include absence of erosion, ulceration, and mucosal neutrophils; that the absence of neutrophilic inflammation is an appropriate histological target in CD; that CD histological scores, such as the Global Histological Disease Activity Score, lack formal validation; and that histological scoring systems for ulcerative colitis, including the Geboes Score, Robarts Histopathology Index, and Nancy Histological Index, can be used for scoring intestinal biopsies in CD patients.

Non-conventional Versus Conventional Strictureplasties for Crohn's Disease. A Systematic Review and Meta-analysis of Treatment Outcomes.

BACKGROUND: Strictureplasties [SXP] represent an alternative to bowel resection in Crohn's disease [CD]. Over the years, there has been growing interest in the role of non-conventional SXP for the treatment of extensive CD. A systematic review was performed on complications and recurrence following conventional and non-conventional SXP. METHODS: The available literature was screened according to the PRISMA statement, until June 2020. Results were categorised into three groups: studies reporting on conventional SXPs; studies with a mixed cohort of conventional and non-conventional SXPs [% non-conventional SXPs ≤15%]; and studies reporting on non-conventional SXPs. Considered endpoints were postoperative complications and overall and SXP site-specific surgical recurrence. Random-effect meta-analysis and meta-regression were used to obtain and compare combined estimates between groups. RESULTS: A total of 26 studies for a total of 1839 patients with CD were included. The pooled postoperative complication rates were was 15.5% (95% confidence interval [CI] 11.2%-20.3%), 7.4% [95% CI 0.2%-22.9%], and 19.2% [95% CI 5-39.6%] for the three groups, respectively. The rates of septic complications were 4% [95% CI 2.2%-6.2%], 1.9% [95% CI 0.4%-4.3%], and 4.2% [95% CI 0.9%-9.8%], respectively. Cumulative overall surgical recurrence rates were 27.5% [95% CI 18.5%-37.6%], 13.2% [95% CI 8.6%-18.7%], and 18.1% [95% CI 6.8%-33.3%]; and SXP site-specific surgical recurrence rates were 13.2% [95% CI 6.9%-21.2%], 8.3% [95% CI 1.6-19.3%], and 8.8% [95% CI 2.2%-19%], respectively. Formal comparison between the groups revealed no differences. CONCLUSIONS: Non-conventional SXP did not differ from conventional SXP with respect to safety and long-term recurrence. Consistent heterogeneity was observed and partially limits the conclusions of this study.

Long-term clinical outcome after thiopurine discontinuation in elderly IBD patients.

INTRODUCTION AND AIM: Thiopurines - although used frequently in inflammatory bowel diseases (IBD) - carry a significant safety risk, particularly with prolonged use and/or in elderly patients. Stopping therapy, however, may trigger relapses. We assessed the long-term outcome of elderly IBD patients after discontinuation of thiopurine while in clinical remission. METHODS: Electronic medical records from IBD patients >60 years whoever received thiopurine treatment were reviewed. Patients who stopped thiopurine after 60 years of age while in clinical and/or endoscopic remission were included. Long-term outcomes included duration of clinical remission, time to clinical relapse, and development of malignancy. RESULTS: In total, 142 patients receiving thiopurines while they were >60 years were identified. Ninety-one patients stopped thiopurines at >60years while in clinical and/or endoscopic remission. After a median follow-up of 66 months, 28 (30.8%) developed a clinical relapse. The median duration of TP therapy in relapses was significantly shorter than in patients who remained in remission (median 45 vs. 103 months, respectively; p = .005). After relapse, 10 patients started a biological (36%) and seven received steroids (25%). Surgery was needed in 36% of patients (10/28). Overall, 26 malignancies developed. CONCLUSION: Discontinuation of TP in elderly IBD patients in clinical and/or endoscopic remission results in sustained clinical remission in two-thirds of patients. Patients who flare can mostly be rescued with biologicals although one-third necessitate surgery. A significant proportion of patients developed malignancies under but also after thiopurines discontinuation, indicating that these patients necessitate a continued close follow-up. Decision-making in this vulnerable subgroup of patients remains difficult.

Short- and Long-term Outcomes Following Side-to-side Strictureplasty and its Modification Over the Ileocaecal Valve for Extensive Crohn's Ileitis.

BACKGROUND AND AIMS: Postoperative recurrence remains a challenging problem in patients with Crohn's disease [CD]. To avoid development of short bowel syndrome, strictureplasty techniques have therefore been proposed. We evaluated short- and long-term outcomes of atypical strictureplasties in CD patients with extensive bowel involvement. METHODS: Side-to-side isoperistaltic strictureplasty [SSIS] was performed according to the Michelassi technique or modification of this over the ileocaecal valve [mSSIS]. Ninety-day postoperative morbidity was assessed using the comprehensive complication index [CCI]. Clinical recurrence was defined as symptomatic, endoscopically or radiologically confirmed, stricture/inflammatory lesion requiring medical treatment or surgery. Surgical recurrence was defined as the need for any surgical intervention. Endoscopic remission was defined as ≤i1, according to the modified Rutgeerts score. Deep remission was defined as the combination of endoscopic remission and absence of clinical symptoms. Perioperative factors related to clinical recurrence were evaluated. RESULTS: A total of 52 CD patients [SSIS n = 12; mSSIS n = 40] were included. No mortality occurred. Mean CCI was 10.3 [range 0-33.7]. Median follow-up was 5.9 years [range 0.8-9.9]. Clinical recurrence [19 patients] was 29.7% and 39.6% after 3 and 5 years, respectively. Surgical recurrence [seven patients] was 2% and 14.1% after 3 and 5 years, respectively. At the end of the follow-up, 92% of patients kept the original strictureplasty and deep remission was observed in 25.7% of the mSSIS patients. None of the perioperative variables considered showed a significant association with clinical recurrence. CONCLUSIONS: SSIS is safe, effective, and provides durable disease control in patients with extensive CD ileitis.

Motion Tolerant Unfocused Imaging of Physiological Waveforms for Blood Pressure Waveform Estimation Using Ultrasound.

This paper details unfocused imaging using single-element ultrasound transducers for motion tolerant arterial blood pressure (ABP) waveform estimation. The ABP waveform is estimated based on pulse wave velocity and arterial pulsation through Doppler and M-mode ultrasound. This paper discusses approaches to mitigate the effect of increased clutter due to unfocused imaging on blood flow and diameter waveform estimation. An intensity reduction model (IRM) estimator is described to track the change of diameter, which outperforms a complex cross-correlation model (C3M) estimator in low contrast environments. An adaptive clutter filtering approach is also presented, which reduces the increased Doppler angle estimation error due to unfocused imaging. Experimental results in a flow phantom demonstrate that flow velocity and diameter waveforms can be reliably measured with wide lateral offsets of the transducer position. The distension waveform estimated from human carotid M-mode imaging using the IRM estimator shows physiological baseline fluctuations and 0.6-mm pulsatile diameter change on average, which is within the expected physiological range. These results show the feasibility of this low cost and portable ABP waveform estimation device.

A Wearable Transcranial Doppler Ultrasound Phased Array System.

OBJECTIVE: Practical deficiencies related to conventional transcranial Doppler (TCD) sonography have restricted its use and applicability. This work seeks to mitigate several such constraints through the development of a wearable, electronically steered TCD velocimetry system, which enables noninvasive measurement of cerebral blood flow velocity (CBFV) for monitoring applications with limited operator interaction. MATERIALS AND METHODS: A highly-compact, discrete prototype system was designed and experimentally validated through flow phantom and preliminary human subject testing. The prototype system incorporates a custom two-dimensional transducer array and multi-channel transceiver electronics, thereby facilitating acoustic beamformation via phased array operation. Electronic steering of acoustic energy enables algorithmic system controls to map Doppler power throughout the tissue volume of interest and localize regions of maximal flow. Multi-focal reception permits dynamic vessel position tracking and simultaneous flow velocimetry over the time-course of monitoring. RESULTS: Experimental flow phantom testing yielded high correlation with concurrent flowmeter recordings across the expected range of physiological flow velocities. Doppler power mapping has been validated in both flow phantom and preliminary human subject testing, resulting in average vessel location mapping times <14 s. Dynamic vessel tracking has been realized in both flow phantom and preliminary human subject testing. CONCLUSIONS: A wearable prototype CBFV measurement system capable of autonomous vessel search and tracking has been presented. Although flow phantom and preliminary human validation show promise, further human subject testing is necessary to compare velocimetry data against existing commercial TCD systems. Additional human subject testing must also verify acceptable vessel search and tracking performance under a variety of subject populations and motion dynamics-such as head movement and ambulation.

Polarization effects on the electric properties of urea and thiourea molecules in solid phase.

We present theoretical results for the dipole moment, linear polarizability, and first hyperpolarizability of the urea and thiourea molecules in solid phase. The in-crystal electric properties were determined by applying a supermolecule approach in combination with an iterative electrostatic scheme, in which the surrounding molecules are represented by point charges. It is found for both urea and thiourea molecules that the influence of the polarization effects is mild for the linear polarizability, but it is marked for the dipole moment and first hyperpolarizability. The replacement of oxygen atoms by sulfur atoms increases, in general, the electric responses. Our second-order Møller-Plesset perturbation theory based iterative scheme predicts for the in-crystal dipole moment of urea and thiourea the values of 7.54 and 9.19 D which are, respectively, increased by 61% and 58%, in comparison with the corresponding isolated values. The result for urea is in agreement with the available experimental result of 6.56 D. In addition, we present an estimate of macroscopic quantities considering explicit unit cells of urea and thiourea crystals including environment polarization effects. These supermolecule calculations take into account partially the exchange and dispersion effects. The results illustrate the role played by the electrostatic interactions on the static second-order nonlinear susceptibility of the urea crystal.

Noninvasive arterial blood pressure waveform monitoring using two- element ultrasound system.

This work details noninvasive arterial blood pressure (ABP) waveform estimation based on an arterial vessel cross-sectional area measurement combined with an elasticity measurement of the vessel, represented by pulse wave velocity (PWV), using a two-element ultrasound system. The overall ABP waveform estimation is validated in a custom-designed experimental setup mimicking the heart and an arterial vessel segment with two single element transducers, assuming a constant hemodynamic system. The estimation of local PWV using the flow-area method produces unbiased elasticity estimation of the tube in a pressure waveform comparison. The measured PWV using 16 cardiac cycles of data is 8.47 + 0.63 m/s with an associated scaling error of -1.56 + 14.0% in a direct pressure waveform comparison, showing negligible bias error on average. The distension waveform obtained from a complex cross-correlation model estimator (C3M) reliably traces small pressure changes reflected by the diameter change. The excellent agreement of an estimated pressure waveform to the reference pressure waveform suggests the promising potential of a readily available, inexpensive, and portable ABP waveform monitoring device.

Carotid arterial blood pressure waveform monitoring using a portable ultrasound system.

This work presents a non-invasive arterial blood pressure (ABP) waveform monitoring technique using ultrasound. A portable ultrasound system to excite ultrasound transducers and acquire data is designed with off-the-shelf components. The insonation angles are identified using a vector Doppler technique based on the cosine dependency of the Doppler signals. The pulse pressure of an estimated waveform at the left common carotid artery is compared to the standard sphygmomanometer measurement in a clinical test. The estimated carotid ABP waveform shows excellent agreement to the finger ABP waveform with expected discrepancy of the systolic peak shape due to different measurement sites. The proposed method also tracks slow blood pressure fluctuations. This validation on human subjects shows potential for a noninvasive blood pressure waveform monitoring device at central arterial sites.

Tris[2-(1,3-thiazol-2-yl-κN)-1H-benzimidazole-κN3]zinc(II) dinitrate ethanol hemisolvate monohydrate at 100 K.

The Zn(II) center in the dicationic complex of the title compound, [Zn(C(10)H(7)N(3)S)(3)](NO(3))(2)·0.5C(2)H(5)OH·H(2)O, is in a distorted octahedral environment with imperfect noncrystallographic C(3) symmetry. Each 2-(1,3-thiazol-2-yl)-1H-benzimidazole ligand coordinates in a bidentate manner, with the Zn-N(imidazole) bond lengths approximately 0.14 Å shorter than the Zn-N(thiazole) bond lengths. Charge-assisted hydrogen bonds connect cations, anions and water molecules. A lattice void is occupied by an ethanol solvent molecule disordered about a crystallographic inversion center and π-stacking is observed between one type of symmetry-related benzene rings.

A conservation agenda for the Pantanal's biodiversity.

The Pantanal's biodiversity constitutes a valuable natural resource, in economic, cultural, recreational, aesthetic, scientific and educational terms. The vegetation plus the seasonal productivity support a diverse and abundant fauna. Many endangered species occur in the region, and waterfowl are exceptionally abundant during the dry season. Losses of biodiversity and its associated natural habitats within the Pantanal occur as a result of unsustainable land use. Implementation of protected areas is only a part of the conservation strategy needed. We analyse biodiversity threats to the biome under seven major categories: 1) conversion of natural vegetation into pasture and agricultural crops, 2) destruction or degradation of habitat mainly due to wild fire, 3) overexploitation of species mainly by unsustainable fishing, 4) water pollution, 5) river flow modification with implantation of small hydroelectric plants, 6) unsustainable tourism, and 7) introduction of invasive exotic species.

A conservation agenda for the Pantanal's biodiversity

The Pantanal's biodiversity constitutes a valuable natural resource, in economic, cultural, recreational, aesthetic, scientific and educational terms. The vegetation plus the seasonal productivity support a diverse and abundant fauna. Many endangered species occur in the region, and waterfowl are exceptionally abundant during the dry season. Losses of biodiversity and its associated natural habitats within the Pantanal occur as a result of unsustainable land use. Implementation of protected areas is only a part of the conservation strategy needed. We analyse biodiversity threats to the biome under seven major categories: 1) conversion of natural vegetation into pasture and agricultural crops, 2) destruction or degradation of habitat mainly due to wild fire, 3) overexploitation of species mainly by unsustainable fishing, 4) water pollution, 5) river flow modification with implantation of small hydroelectric plants, 6) unsustainable tourism, and 7) introduction of invasive exotic species.

A biodiversidade do Pantanal constitui recurso natural com reconhecido valor na economia, na cultura, na recreação, na estética, na ciência e na educação. A vegetação, mais a produtividade sazonal, suporta uma fauna abundante. Muitas espécies ameaçadas de extinção ocorrem na região e aves aquáticas são excepcionalmente abundantes durante a estação seca. Perdas da biodiversidade do Pantanal e de seus hábitats naturais associados ocorrem como resultado do uso não sustentável da terra. A implementação de áreas protegidas é somente uma parte da estratégia necessária. Analisamos as ameaças ambientais do bioma sob sete tópicos principais: 1) conversão da vegetação natural em pasto e campos agrícolas; 2) destruição e degradação de hábitats, principalmente pelo emprego de fogo; 3) sobre uso de espécies, principalmente pela pesca; 4) poluição de água; 5) modificação de fluxo de rios, principalmente pela implantação de pequenas usinas hidrelétricas; 6) turismo não sustentável; e 7) introdução de espécies invasoras exóticas.