A New Endoscopically Implantable Device (SatiSphere) for Treatment of Obesity—Efficacy, Safety, and Metabolic Effects on Glucose, Insulin, and GLP-1 Levels

Background

The endoluminal mechanical device SatiSphere is a new endoscopically implantable device designed to delay transit time of nutrients through the duodenum. It consists of a 1-mm nitinol wire with pigtail ends and several mesh spheres mounted along its course, released in the duodenum and gastric antrum to conform to the duodenal C loop configuration and thereby self-anchor.

Methods

The objective is to test the safety, efficacy, and effect on body weight in a 2:1 randomized study, as well as incretin secretion in a subgroup.

Results

Of 31 included cases (11 men, mean age 42.9 years, mean BMI 41.3 kg/m²), 21 patients treated with endoscopic device insertion with scheduled device removal after 3 months were compared with 10 controls. In 10 of 21 patients, device migration occurred, in two cases necessitating emergency surgery, which led to termination of the trial. Weight loss after 3 months was 6.7, 4.6, and 2.2 kg in the groups completing therapy, all treatment cases using intention to treat (ITT) analysis and controls. Excess weight loss was significantly increased by endoluminal mechanical device insertion (18.4, 12.2, and 4.4 % in completers, ITT analysis group and controls; p?=?0.02 for completers vs. controls). Measuring glucose, insulin, and glucagon-like peptide 1 (GLP-1) following a mixed-meal test with the device in place and after removal (n?=?7), the device delayed glucose absorption and insulin secretion and altered kinetics in GLP-1 levels.

Conclusions

The device might be short-term effective in reducing body weight, which might be mediated through alterations in incretin metabolism. However, frequent device migration necessitates device modifications.     

Monitoring c-reactive protein after laparoscopic colorectal surgery excludes infectious complications and allows for safe and early discharge

Background

Early detection of infectious complications is urgently needed in the era of DRG-based compensation. This work assessed the diagnostic accuracy of c-reactive protein (CRP) level in the detection of infectious complications after laparoscopic colorectal resection.

Methods

Laparoscopic colorectal resections were identified from a prospective database. Complications were graded according to the Dindo–Clavien classification. Surgical site infections were defined according to the Centers of Disease Control. CRP level was routinely measured until postoperative day (POD) 7. Uni- and multivariate analysis were performed. Diagnostic accuracy was evaluated using receiver operating curves.

Results

355 patients were operated for diverticulosis (88.7 %), neoplasia (6.8 %), and other causes (4.5 %). Mean age and body mass index were 59.8 ± 13.7 years and 26.5 ± 15 kg/m². Left, right, and total laparoscopic colectomies were performed in 316, 33, and 6 patients. Complications occurred in 85 patients and 16 patients (4.5 %) were reoperated. Fifty-one patients (14.4 %) suffered from infectious complications at a median of 6 POD, while 9 anastomoses leaked (2.7 %). In multivariate analysis, presence of an abscess at surgery was predictive of an infectious complication (OR 2.5, 95 % CI 1.1–5.3), as were a body mass index >30 kg/m² and operative time >160 min in a bootstrap analysis. Overall, CRP peaked on POD 2 and declined thereafter. Most infectious complications were apparent starting on POD 6. A CRP <56 mg/l on POD 4 had a negative predictive value of 100 % (95 % CI 94.9–100 %) to rule out infectious complications. Above 56 mg/l, sensitivity was 100 % (95 % CI 0.8–1) and specificity 49 % (95 % CI 0.4–0.6) for the development of infectious complications in the absence of clinical signs. This translated into a remarkable diagnostic accuracy of 78 % (95 % CI 0.7–0.9).

Conclusion

Monitoring CRP level in laparoscopic colorectal surgery demonstrated a high diagnostic accuracy for infectious complications, thus allowing for safe and early discharge.     

Single-cell resolution mapping of neuronal damage in acute focal cerebral ischemia using thallium autometallography

Neuronal damage shortly after onset or after brief episodes of cerebral ischemia has remained difficult to assess with clinical and preclinical imaging techniques as well as with microscopical methods. We here show, in rodent models of middle cerebral artery occlusion (MCAO), that neuronal damage in acute focal cerebral ischemia can be mapped with single-cell resolution using thallium autometallography (TlAMG), a histochemical technique for the detection of the K⁺-probe thallium (Tl⁺) in the brain. We intravenously injected rats and mice with thallium diethyldithiocarbamate (TlDDC), a lipophilic chelate complex that releases Tl⁺ after crossing the blood–brain barrier. We found, within the territories of the affected arteries, areas of markedly reduced neuronal Tl⁺ uptake in all animals at all time points studied ranging from 15 minutes to 24 hours after MCAO. In large lesions at early time points, areas with neuronal and astrocytic Tl⁺ uptake below thresholds of detection were surrounded by putative penumbral zones with preserved but diminished Tl⁺ uptake. At 24 hours, the areas of reduced Tl⁺uptake matched with areas delineated by established markers of neuronal damage. The results suggest the use of ²⁰¹TlDDC for preclinical and clinical single-photon emission computed tomography (SPECT) imaging of hyperacute alterations in brain K⁺ metabolism and prediction of tissue viability in cerebral ischemia.     

Early Intermodal Integration in Offspring of Parents With Psychosis

Identifying early developmental indicators of risk for schizophrenia is important for prediction and possibly illness prevention. Disturbed intermodality has been proposed as one important neurodevelopmental risk for schizophrenia. Early intermodal integration (EII) is the infant’s ability to link motility and perception and to relate perception across modalities. We hypothesized that infants of parents with schizophrenia would have more EII abnormalities than infants of healthy parents and that infants of parents with affective psychosis would be intermediate in severity. The New England Family Study high-risk sample, ascertained from community populations, was utilized. Eight-month-old infants of parents with schizophrenia (n = 58), affective psychoses (n = 128), and healthy controls (n = 174) were prospectively assessed. Diagnoses of parents were determined 30 years later blind to offspring data. EII measures were grouped into 3 domains characterizing different aspects of infant development: (1) one’s own body, (2) objects, and (3) social interactions. Results demonstrated that body- and object-related EII abnormalities were significantly increased for infants of parents with schizophrenia compared with control infants and not significantly increased for infants of parents with affective psychoses. EII abnormalities in relation to social interactions were significantly increased in infants of parents with schizophrenia and affective psychoses. Thus, body- and object-related EII abnormalities were most severe in infants of parents with schizophrenia, supporting the importance of intermodality dysfunction as an early indicator of the vulnerability to schizophrenia. Future research should evaluate how this dysfunction evolves with development and its associations with other psychopathological and neurodevelopmental deficits in youth at risk for psychosis.Key words: schizophrenia, high-risk study, developmental psychology     

Multimodel assessment of water scarcity under climate change

Water scarcity severely impairs food security and economic prosperity in many countries today. Expected future population changes will, in many countries as well as globally, increase the pressure on available water resources. On the supply side, renewable water resources will be affected by projected changes in precipitation patterns, temperature, and other climate variables. Here we use a large ensemble of global hydrological models (GHMs) forced by five global climate models and the latest greenhouse-gas concentration scenarios (Representative Concentration Pathways) to synthesize the current knowledge about climate change impacts on water resources. We show that climate change is likely to exacerbate regional and global water scarcity considerably. In particular, the ensemble average projects that a global warming of 2 °C above present (approximately 2.7 °C above preindustrial) will confront an additional approximate 15% of the global population with a severe decrease in water resources and will increase the number of people living under absolute water scarcity (<500 m³ per capita per year) by another 40% (according to some models, more than 100%) compared with the effect of population growth alone. For some indicators of moderate impacts, the steepest increase is seen between the present day and 2 °C, whereas indicators of very severe impacts increase unabated beyond 2 °C. At the same time, the study highlights large uncertainties associated with these estimates, with both global climate models and GHMs contributing to the spread. GHM uncertainty is particularly dominant in many regions affected by declining water resources, suggesting a high potential for improved water resource projections through hydrological model development.     

Corneal confocal microscopy detects small fiber damage in chronic inflammatory demyelinating polyneuropathy (CIDP)

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune‐mediated peripheral neuropathy with multifocal involvement. Reliable biomarkers for diagnosis, disease progression, and treatment response remain to be developed. We assessed the utility of corneal confocal microscopy (CCM) as a diagnostic marker for CIDP in 16 patients. CCM parameters including corneal nerve fiber density (NFD), nerve fiber length, number of main nerve trunks, number of nerve branches, nerve tortuosity, and dendritic cell density (DCD) were compared to those from 15 healthy controls and correlated with clinical and electrophysiological findings. CIDP patients had a significantly lower corneal NFD compared to healthy controls. The total nerve fiber length and the number of nerve branches were significantly decreased, whereas nerve tortuosity was increased in patients with CIDP. There was no positive correlation between corneal NFD and clinical or electrophysiological assessments. The average DCD was not significantly different in CIDP patients and controls. CCM measures suggest damage to small sensory afferents in the cornea in CIDP patients. Further studies are needed to compare different neuropathic conditions and to explore longitudinal changes of CCM parameters.     

Investigation of the involvement of MIR185 and its target genes in the development of schizophrenia

Background

Schizophrenia is a complex neuropsychiatric disorder of unclear etiology. The strongest known genetic risk factor is the 22q11.2 microdeletion. Research has yet to confirm which genes within the deletion region are implicated in schizophrenia. The minimal 1.5 megabase deletion contains MIR185, which encodes microRNA 185.

Methods

We determined miR-185 expression in embryonic and adult mouse brains. Common and rare variants at this locus were then investigated using a human genetics approach. First, we performed gene-based analyses for MIR185 common variants and target genes using Psychiatric Genomics Consortium genome-wide association data. Second, MIR185 was resequenced in German patients (n = 1000) and controls (n = 500). We followed up promising variants by genotyping an additional European sample (patients, n = 3598; controls, n = 4082).

Results

In situ hybridization in mice revealed miR-185 expression in brain regions implicated in schizophrenia. Gene-based tests revealed association between common variants in 3 MIR185 target genes (ATAT1, SH3PXD2A, NTRK3) and schizophrenia. Further analyses in mice revealed overlapping expression patterns for these target genes and miR-185. Resequencing identified 2 rare patient-specific novel variants flanking MIR185. However, follow-up genotyping provided no further evidence of their involvement in schizophrenia.

Limitations

Power to detect rare variant associations was limited.

Conclusion

Human genetic analyses generated no evidence of the involvement of MIR185 in schizophrenia. However, the expression patterns of miR-185 and its target genes in mice, and the genetic association results for the 3 target genes, suggest that further research into the involvement of miR-185 and its downstream pathways in schizophrenia is warranted.