Risks of Undersizing Stent Retriever Length Relative to Thrombus Length in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Results regarding the association of thrombus length, stent retriever length, and recanalization success in patients with acute ischemic stroke are inconsistent. We hypothesized that the ratio of thrombus length to stent retriever length may be of particular relevance. MATERIALS AND METHODS: Patients with acute ischemic stroke undergoing stent retriever thrombectomy at our institution between January 2010 and December 2018 were reviewed retrospectively. Thrombus length was assessed by measuring the susceptibility vessel sign on SWI using a 1.5T or 3T MR imaging scanner. Multivariable logistic regression models were used to determine the association between thrombus length, stent retriever length, and thrombus length/stent retriever length ratio with first-pass recanalization, overall recanalization, and embolization in new territories. Results are shown as adjusted ORs with 95% CIs. Additional mediation analyses were performed to test for indirect effects on first-pass recanalization and overall recanalization success. RESULTS: The main analysis included 418 patients (mean age, 74.9 years). Increasing stent retriever length was associated with first-pass recanalization. Decreasing thrombus length and lower thrombus length/stent retriever length ratios were associated with first-pass recanalization and overall recanalization. Thrombus length and stent retriever length showed no association with first-pass recanalization or overall recanalization once thrombus length/stent retriever length ratio was factored in, while thrombus length/stent retriever length ratio remained a significant factor in both models (adjusted OR, 0.316 [95% CI, 0.112-0.892]; P = .030 and adjusted OR, = 0.366 [95% CI, 0.194-0.689]; P = .002). Mediation analyses showed that decreasing thrombus length and increasing stent retriever length had a significant indirect effect on first-pass recanalization mediated through thrombus length/stent retriever length ratio. The only parameter associated with embolization in new territories was an increasing thrombus length/stent retriever length ratio (adjusted OR, 5.079 [95% CI, 1.332-19.362]; P = .017). CONCLUSIONS: Information about thrombus and stent length is more valuable when combined. High thrombus length/stent retriever length ratios, which may raise the risk of unsuccessful recanalization and embolization in new territories, should be avoided by adapting stent retriever selection to thrombus length whenever possible.

SWI Susceptibility Vessel Sign in Patients Undergoing Mechanical Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The frequency and clinical significance of the susceptibility vessel sign in patients with acute ischemic stroke remains unclear. We aimed to assess its prevalence in patients with acute ischemic stroke undergoing mechanical thrombectomy and to analyze its association with interventional and clinical outcome parameters in that group. MATERIALS AND METHODS: Six hundred seventy-six patients with acute ischemic stroke and admission MR imaging were reviewed retrospectively. Of those, 577 met the eligibility criteria for further analysis. Imaging was performed using a 1.5T or 3T MR imaging scanner. Associations between baseline variables, interventional and clinical outcome parameters, and susceptibility vessel sign were determined with multivariable logistic regression models. Results are shown as adjusted ORs with 95% CIs. RESULTS: The susceptibility vessel sign was present in 87.5% (n = 505) of patients and associated with tandem occlusion (adjusted OR, 3.3; 95% CI, 1.1-10.0; P = .032) as well as successful reperfusion, defined as an expanded TICI score of ≥2b (adjusted OR, 2.4; 95% CI, 1.28-4.6; P = .007). The susceptibility vessel sign was independently associated with functional independence (mRS ≤ 2: adjusted OR, 2.1; 95% CI, 1.1-4.0; P = .028) and lower mortality (adjusted OR, 0.4; 95% CI, 0.2-0.7; P = .003) at 90 days, even after adjusting for successful reperfusion. The susceptibility vessel sign did not influence the number of passes performed during mechanical thrombectomy, the first-pass reperfusion, or the risk of peri- or postinterventional complications. CONCLUSIONS: The susceptibility vessel sign is an MR imaging phenomenon frequently observed in patients with acute ischemic stroke and is associated with successful reperfusion after mechanical thrombectomy. However, superior clinical functional outcome and lower mortality noted in patients showing the susceptibility vessel sign could not be entirely attributed to higher reperfusion rates.

Clinical Implementation of 7T MRI for the Identification of Incidental Intracranial Aneurysms versus Anatomic Variants.

Most unruptured intracranial aneurysms can be adequately characterized using 1.5T and 3T MR imaging. Findings in a subgroup of patients can remain unclear due to difficulties in distinguishing aneurysms from vascular anatomic variants. We retrospectively analyzed clinical data from 30 patients with suspected incidental aneurysms on 3T MR imaging who underwent 7T MR imaging. In all 30 cases, the differentiation of an aneurysm versus a vascular variant could be achieved. In 20 cases (66%), the initial suspected diagnosis was revised. Our findings suggest that 7T MR imaging provides a clarification tool for the group of patients with suspected unruptured intracranial aneurysms and diagnostic ambiguity after standard 3T MR imaging.

The "vermian-crest angle": does it allow accurate categorisation of fetal upward rotation of cerebellar vermis on intrauterine MRI? A pilot study.

AIM: To test a new parameter to assess the position of the fetal cerebellar vermis in the posterior fossa (PF) using intrauterine magnetic resonance imaging (MRI). MATERIALS AND METHODS: The angle between the cerebellar vermis and the internal occipital crest (vermian-crest angle, VCA) was assessed retrospectively using MRI in fetuses with and without PF anomalies. Spearman's rank test was used to investigate correlation of the VCA with gestational age (GA). Groups were compared using Student's t-test and the one-way analysis of variance (ANOVA) with the Bonferroni adjustment. Box-and-whisker plots were also used. RESULTS: One hundred and two normal cases were identified. Mean±SD GA at MRI was 26.5±2.8 weeks (range: 22-32 weeks). The VCA was 64.49±11.5° independently of GA (r=0.19; p=0.12). In addition, 30 fetuses at 19-28 weeks were identified with Blake's pouch cyst (BPC; n=5), Dandy-Walker malformation (DWM; n=12), mega cisterna magna (MCM; n=10), and vermian hypoplasia (VH; n=3). The VCA was significantly different in the DWM (p<0.001) and BPC (p<0.001) subgroups, but was not significantly different in cases of VH (p=0.84) and MCM (p=0.95) in comparison with controls. CONCLUSIONS: A new method to assess vermian position within the PF using intrauterine MRI was assessed. In combination with the other existing parameters, it may be helpful for addressing the categorisation of upward rotation of the fetal cerebellar vermis; however, further studies are necessary to strengthen the present findings.

Cerebellar Hypoperfusion in Migraine Attack: Incidence and Significance.

BACKGROUND AND PURPOSE: Patients diagnosed with migraine with aura have an increased lifetime risk of ischemic stroke. It is not yet clear whether prolonged cortical hypoperfusion during an aura increases the immediate risk of cerebellar infarction because it may induce crossed cerebellar diaschisis and subsequent tissue damage. To address this question, we retrospectively analyzed potential relationships between cortical oligemia and cerebellar hypoperfusion in patients with migraine with aura and their potential relation to small infarct-like cerebellar lesions. MATERIALS AND METHODS: One hundred six migraineurs who underwent MR imaging, including DSC perfusion, were included in the study. In patients with apparent perfusion asymmetry, we used ROI analysis encompassing 18 infra- and supratentorial ROIs to account for differences in regional cerebral blood flow and volume. The presence of cerebellar hypoperfusion was calculated using an asymmetry index, with values of >10% being considered significant. RESULTS: We observed perfusion asymmetries in 23/106 patients, 22 in patients with migraine with aura (20.8%). Cerebellar hypoperfusion was observed in 12/23 patients (52.2%), and crossed cerebellar diaschisis, in 9/23 patients (39.1%) with abnormal perfusion. In none of the 106 patients were DWI restrictions observed during migraine with aura. CONCLUSIONS: Cerebellar hypoperfusion and crossed cerebellar diaschisis are common in patients with migraine with aura and cortical perfusion abnormalities. Crossed cerebellar diaschisis in migraine with aura may be considered a benign phenomenon because we observed no association with DWI restriction or manifest cerebellar infarctions, even in patients with prolonged symptom-related perfusion abnormalities persisting for up to 24 hours.

Communicative reprogramming non-curative hepatocellular carcinoma with low-dose metronomic chemotherapy, COX-2 inhibitor and PPAR-gamma agonist: a phase II trial.

Systemic therapy for advanced hepatocellular carcinoma (HCC) is still challenging. A biomodulatory therapy approach targeting the communicative infrastructure of HCC, including metronomic low-dose chemotherapy with capecitabine, pioglitazone and rofecoxib, has been evaluated in patients with non-curative HCC. Altogether 38 patients were evaluable in this one-arm, multicenter phase II trial. The primary endpoint, median progression-free survival was 2.7 months (95% CI: 1.6-3.79) for all evaluable patients and 8.4 months (95% CI: 0-18.13) for patients ≥ 6 weeks on protocol. Median overall survival (OS) was 6.7 months (95% CI: 4.08-9.31) and 9.4 months (95% CI: 4.82-13.97), respectively. Most common adverse events were edemas grade 3, which were commonly related to the advanced stage, with 66% of the patients suffering from liver cirrhosis. Exploratory data analyses showed significant impact of ECOG performance status grade 0 versus 1 and CLIP score 0/1 versus > 1 on OS, 9.8 months (95% CI: 4.24-15.35) versus 2.7 months (95% CI: 1.03-4.36; P = 0.002), and 9.8 months (95% CI: 3.23-16.37) versus 4.4 months (95% CI: 3.14-5.66; P = 0.009), respectively. Preceding tumor surgery had significant beneficial impact on survival, as well as maximal tumor diameter of < 5 cm. The correlation of C-reactive protein decrease with significantly improved OS underlines the close link between inflammation and tumor control. Biomodulatory therapy in advanced HCC may be a low toxic, efficacious treatment and principally demonstrates that such approaches should be followed further for treatment of advanced HCC.

Resting state perfusion in the language network is linked to formal thought disorder and poor functional outcome in schizophrenia.

OBJECTIVE: Formal thought disorder (FTD) is a core symptom in schizophrenia. Here, we focus on resting state cerebral blood flow (rCBF) linked to dimensions of FTD. METHODS: We included 47 schizophrenia spectrum patients and 30 age- and gender-matched healthy controls. We assessed FTD with the assessment of thought, language, and communication (TLC) and imaging on a 3T MRI scanner. Within patients, we tested the association of FTD dimensions and in a subgroup (n = 27) the association of functional outcome after 6 months with whole brain rCBF. RESULTS: Negative FTD was most prominently associated with perfusion within the superior temporal gyrus, while positive FTD was associated with perfusion within the supplementary motor area, and inferior frontal gyrus. Perfusion within the left supramarginal gyrus was associated with social functioning after 6 months. CONCLUSIONS: Distinguishable associations of rCBF with FTD dimensions point to distinct underlying pathophysiology. The location of aberrant perfusion patterns suggests that negative FTD might reflect defective access to semantic memory while positive FTD likely reflects defective suppression of irrelevant information during increased speech production. Finally, the neural correlates of thought block were also predictive of poor functional outcome. Thus, functional outcome and distinct FTD dimensions may share some pathophysiology.

Distinct resting-state perfusion patterns underlie psychomotor retardation in unipolar vs. bipolar depression.

OBJECTIVE: Psychomotor abnormalities characterize both unipolar (UP) depression and bipolar (BP) depression. We aimed to assess their neurobiological correlates in terms of motor activity (AL) and resting-state cerebral blood flow (rCBF) and investigate their association in BP, UP, and healthy controls (HC). METHOD: We enrolled 42 depressed patients (22 BP, 20 UP) and 19 HC matched for age, gender, education, income. AL and rCBF were objectively assessed with the use of wrist actigraphy and arterial spin labeling. Group differences and the association of AL and rCBF were computed. RESULTS: Activity level was significantly reduced in patients, but no difference was found between BP and UP. Increased perfusion was found in BP compared with UP and HC, in multiple brain areas. We found positive correlations of rCBF and AL in BP and UP, in different parts of the insula and frontal regions. Only BP showed a cluster in the left precentral gyrus. In HC, only inverse correlations of AL and rCBF were found. CONCLUSION: The differences in rCBF and in the localization of the clusters of positive AL/rCBF correlations between BP and UP suggest that different neural impairments may underlie motor symptoms in the two disorders, but finally converge in phenotypically similar manifestations.

EEG marker of inhibitory brain activity correlates with resting-state cerebral blood flow in the reward system in major depression.

Frontal alpha band asymmetry (FAA) is a marker of altered reward processing in major depressive disorder (MDD), associated with reduced approach behavior and withdrawal. However, its association with brain metabolism remains unclear. The aim of this study was to investigate FAA and its correlation with resting-state cerebral blood flow (rCBF). We hypothesized an association of FAA with regional rCBF in brain regions relevant to reward processing and motivated behavior, such as the striatum. We enrolled 20 patients and 19 healthy subjects. FAA scores and rCBF were quantified with the use of EEG and arterial spin labeling. Correlations of the two were evaluated, as well as the association with FAA and psychometric assessments of motivated behavior and anhedonia. Patients showed a left-lateralized pattern of frontal alpha activity and a correlation of FAA lateralization with subscores of Hamilton Depression Rating Scale linked to motivated behavior. An association of rCBF and FAA scores was found in clusters in the dorsolateral prefrontal cortex bilaterally (patients), in the left medial frontal gyrus, in the right caudate head and in the right inferior parietal lobule (whole group). No correlations were found in healthy controls. Higher inhibitory right-lateralized alpha power was associated with lower rCBF values in prefrontal and striatal regions, predominantly in the right hemisphere, which are involved in the processing of motivated behavior and reward. Inhibitory brain activity in the reward system may contribute to some of the motivational problems observed in MDD.

Grey matter volumetric changes related to recovery from hand paresis after cortical sensorimotor stroke.

Preclinical studies using animal models have shown that grey matter plasticity in both perilesional and distant neural networks contributes to behavioural recovery of sensorimotor functions after ischaemic cortical stroke. Whether such morphological changes can be detected after human cortical stroke is not yet known, but this would be essential to better understand post-stroke brain architecture and its impact on recovery. Using serial behavioural and high-resolution magnetic resonance imaging (MRI) measurements, we tracked recovery of dexterous hand function in 28 patients with ischaemic stroke involving the primary sensorimotor cortices. We were able to classify three recovery subgroups (fast, slow, and poor) using response feature analysis of individual recovery curves. To detect areas with significant longitudinal grey matter volume (GMV) change, we performed tensor-based morphometry of MRI data acquired in the subacute phase, i.e. after the stage compromised by acute oedema and inflammation. We found significant GMV expansion in the perilesional premotor cortex, ipsilesional mediodorsal thalamus, and caudate nucleus, and GMV contraction in the contralesional cerebellum. According to an interaction model, patients with fast recovery had more perilesional than subcortical expansion, whereas the contrary was true for patients with impaired recovery. Also, there were significant voxel-wise correlations between motor performance and ipsilesional GMV contraction in the posterior parietal lobes and expansion in dorsolateral prefrontal cortex. In sum, perilesional GMV expansion is associated with successful recovery after cortical stroke, possibly reflecting the restructuring of local cortical networks. Distant changes within the prefrontal-striato-thalamic network are related to impaired recovery, probably indicating higher demands on cognitive control of motor behaviour.

Neuroimaging of epilepsy: lesions, networks, oscillations.

While analysis and interpretation of structural epileptogenic lesion is an essential task for the neuroradiologist in clinical practice, a substantial body of epilepsy research has shown that focal lesions influence brain areas beyond the epileptogenic lesion, across ensembles of functionally and anatomically connected brain areas. In this review article, we aim to provide an overview about altered network compositions in epilepsy, as measured with current advanced neuroimaging techniques to characterize the initiation and spread of epileptic activity in the brain with multimodal noninvasive imaging techniques. We focus on resting-state functional magnetic resonance imaging (MRI) and simultaneous electroencephalography/fMRI, and oppose the findings in idiopathic generalized versus focal epilepsies. These data indicate that circumscribed epileptogenic lesions can have extended effects on many brain systems. Although epileptic seizures may involve various brain areas, seizure activity does not spread diffusely throughout the brain but propagates along specific anatomic pathways that characterize the underlying epilepsy syndrome. Such a functionally oriented approach may help to better understand a range of clinical phenomena such as the type of cognitive impairment, the development of pharmacoresistance, the propagation pathways of seizures, or the success of epilepsy surgery.

Adjuvant therapy after resection of brain metastases. Frameless image-guided LINAC-based radiosurgery and stereotactic hypofractionated radiotherapy.

BACKGROUND: Tumor bed stereotactic radiosurgery (SRS) after resection of brain metastases is a new strategy to delay or avoid whole-brain irradiation (WBRT) and its associated toxicities. This retrospective study analyzes results of frameless image-guided linear accelerator (LINAC)-based SRS and stereotactic hypofractionated radiotherapy (SHRT) as adjuvant treatment without WBRT. MATERIALS AND METHODS: Between March 2009 and February 2012, 44 resection cavities in 42 patients were treated with SRS (23 cavities) or SHRT (21 cavities). All treatments were delivered using a stereotactic LINAC. All cavities were expanded by ≥ 2 mm in all directions to create the clinical target volume (CTV). RESULTS: The median planning target volume (PTV) for SRS was 11.1 cm(3). The median dose prescribed to the PTV margin for SRS was 17 Gy. Median PTV for SHRT was 22.3 cm(3). The fractionation schemes applied were: 4 fractions of 6 Gy (5 patients), 6 fractions of 4 Gy (6 patients) and 10 fractions of 4 Gy (10 patients). Median follow-up was 9.6 months. Local control (LC) rates after 6 and 12 months were 91 and 77 %, respectively. No statistically significant differences in LC rates between SRS and SHRT treatments were observed. Distant brain control (DBC) rates at 6 and 12 months were 61 and 33 %, respectively. Overall survival (OS) at 6 and 12 months was 87 and 63.5 %, respectively, with a median OS of 15.9 months. One patient treated by SRS showed symptoms of radionecrosis, which was confirmed histologically. CONCLUSION: Frameless image-guided LINAC-based adjuvant SRS and SHRT are effective and well tolerated local treatment strategies after resection of brain metastases in patients with oligometastatic disease.

Classification of mild cognitive impairment and Alzheimer disease using model-based MR and magnetization transfer imaging.

BACKGROUND AND PURPOSE: Early stratification of degenerative processes is a prerequisite to warrant therapeutic options in prodromal Alzheimer disease. Our aim was to investigate differences in cerebral macromolecular tissue composition between patients with AD, mild cognitive impairment, and age- and sex-matched healthy controls by using model-based magnetization transfer with a binary spin-bath magnetization transfer model and magnetization transfer ratio at 1.5 T. MATERIALS AND METHODS: We investigated patients with de novo AD (n=18), MCI (n=18), and CTRLs (n=18). A region-of-interest analysis of the entorhinal cortex, hippocampal head and body, insula, and temporal neocortex was performed with fuzzy clustering to associate every subregion to a cluster representative for each group. RESULTS: Cluster analysis achieved a concordance of 0.92 (50 of 54 subjects) between a combination of the calculated mMT parameters (kf,kr,T2r,F,T2f) in the entorhinal cortex and the neuropsychological diagnosis. The sensitivity and specificity for the discrimination of AD from MCI reached 1 and 0.94, with a positive predictive value of 0.95 and a negative predictive value of 1. Compared with mMT, the concordance for MTR was 0.83 (45 of 54 subjects) with a lower specificity of 0.5 and positive predictive value of 0.67 to discriminate patients with AD and MCI. CONCLUSIONS: mMT imaging detects macromolecule-related alterations and allows an improved classification of patients with early AD and MCI compared with MTR.

Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: impact of exogenous neuropeptide Y.

BACKGROUND & AIMS: Splanchnic vasodilation is an essential disturbance in portal hypertension. Increased systemic sympathetic nerve activity is well known, but potential corresponding vascular desensitization is incompletely characterized. Release of splanchnic sympathetic neurotransmitters noradrenaline (NA) and co-transmitter neuropeptide Y (NPY) remains to be elucidated. Finally, the effects of exogenous NPY on these mechanisms are unexplored. METHODS: Portal vein ligated cirrhotic, and control rats were used for in vitro perfusion of mesenteric arteries. Depletion of vascular pressure response was induced by repetitive electric sympathetic perivascular nerve stimulation (PNS) and performed in the absence and presence of exogenous NPY. Additionally, PNS-induced release of NA and NPY was measured. RESULTS: Mesenteric PNS-induced pressure response was lower in portal hypertension. Depletion of the pressure response to PNS, representing the degree of desensitization, was enhanced in portal hypertension. NA release was elevated, whereas NPY release was attenuated in cirrhosis. Administration of exogenous NPY led to marked recovery from desensitization and vasoconstrictive improvement in cirrhotic rats, being associated with more pronounced decrease of NA release. CONCLUSIONS: Pronounced depletion of splanchnic arterial pressure-response to repetitive sympathetic nerve stimulation in cirrhosis is partly attributable to altered NA release as well as to deficient NPY release. External NPY restores vascular contractility and attenuates pathologically elevated NA release in the portal hypertensive mesenteric vasculature, revealing post-, and prejunctional effects at the vascular smooth muscle motor endplate; therefore outlining encouraging therapeutic strategies.

A multi-center study: intra-scan and inter-scan variability of diffusion spectrum imaging.

The objective of this study was to investigate whether it is possible to pool together diffusion spectrum imaging data from four different scanners, located at three different sites. Two of the scanners had identical configuration whereas two did not. To measure the variability, we extracted three scalar maps (ADC, FA and GFA) from the DSI and utilized a region and a tract-based analysis. Additionally, a phantom study was performed to rule out some potential factors arising from the scanner performance in case some systematic bias occurred in the subject study. This work was split into three experiments: intra-scanner reproducibility, reproducibility with twin-scanner settings and reproducibility with other configurations. Overall for the intra-scanner and twin-scanner experiments, the region-based analysis coefficient of variation (CV) was in a range of 1%-4.2% and below 3% for almost every bundle for the tract-based analysis. The uncinate fasciculus showed the worst reproducibility, especially for FA and GFA values (CV 3.7-6%). For the GFA and FA maps, an ICC value of 0.7 and above is observed in almost all the regions/tracts. Looking at the last experiment, it was found that there is a very high similarity of the outcomes from the two scanners with identical setting. However, this was not the case for the two other imagers. Given the fact that the overall variation in our study is low for the imagers with identical settings, our findings support the feasibility of cross-site pooling of DSI data from identical scanners.

Localizing seizure-onset zones in presurgical evaluation of drug-resistant epilepsy by electroencephalography/fMRI: effectiveness of alternative thresholding strategies.

BACKGROUND AND PURPOSE: Simultaneous EEG/fMRI is an effective noninvasive tool for identifying and localizing the SOZ in patients with focal epilepsy. In this study, we evaluated different thresholding strategies in EEG/fMRI for the assessment of hemodynamic responses to IEDs in the SOZ of drug-resistant epilepsy. MATERIALS AND METHODS: Sixteen patients with focal epilepsy were examined by using simultaneous 92-channel EEG and BOLD fMRI. The temporal fluctuation of epileptiform signals on the EEG was extracted by independent component analysis to predict the hemodynamic responses to the IEDs. We applied 3 different threshold criteria to detect hemodynamic responses within the SOZ: 1) PA, 2) a fixed threshold at P < .05 corrected for multiple comparison (FWE), and 3) FAV (4000 ± 200 activated voxels within the brain). RESULTS: PA identified the SOZ in 9 of 16 patients; FWE resulted in concordant BOLD signal correlates in 11 of 16, and FAV in 13 of 16 patients. Hemodynamic responses were detected within the resected areas in 5 (PA), 6 (FWE), and 8 (FAV) of 10 patients who remained seizure-free after surgery. CONCLUSIONS: EEG/fMRI is a noninvasive tool for the presurgical work-up of patients with epilepsy, which can be performed during seizure-free periods and is complementary to the ictal electroclinical assessment. Our findings suggest that the effectiveness of EEG/fMRI in delineating the SOZ may be further improved by the additional use of alternative analysis strategies such as FAV.

[Spontaneous bacterial peritonitis]. / Spontan bakterielle Peritonitis.

Spontaneous bacterial peritonitis (SBP) is the most frequent infection in patients with cirrhosis during hospitalization and is associated with high acute and long-term mortality. Diagnosis is made by paracentesis with determination of neutrophil count in ascitic fluid. Empirical antibiotic therapy must be initiated immediately. The choice of drug is dependent on prior therapies. Liver transplantation has to be considered in the absence of contra-indications. Prophylaxis of SBP is indicated in patients with ascites and gastrointestinal hemorrhage, and in patients after SBP. Primary prophylaxis should be considered in high-risk patients with cirrhosis and ascites. The development of resistance to antibiotic drugs is a relevant side-effect.