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BMC surgery 21(1), 196 (2021). doi:10.1186/s12893-021-01203-5, Published by BioMed Central, London

Surgical innovation 28(6), 714-722 (2021). doi:10.1177/1553350621991223, Published by Sage, Thousand Oaks, Calif.

BACKGROUNDLaparoscopic liver surgery is currently considered the standard of care for various liver malignancies. However, studies focusing on perioperative outcome after laparoscopic hepatectomy (LH) in overweight patients are still sparse and its benefit compared to open hepatectomy (OH) is a matter of debate.AIMTo analyze postoperative outcomes in overweight [body mass index (BMI) over 25 kg/m(2)] and obese (BMI over 30 kg/m(2)) patients undergoing LH and compare postoperative outcome with patients undergoing OH.METHODSPerioperative data of 68 overweight (BMI over 25 kg/m(2)) including a subcohort of obese (BMI over 30 kg/m(2)) patients (n = 27) who underwent LH at our institution between 2015 and 2019 were retrospectively analyzed regarding surgical outcome and compared to an equal number of patients undergoing OH.RESULTSThe mean BMI was 29.8 +/- 4.9 kg/m(2) in the LH group and 29.7 +/- 3.6 kg/m(2) in the OH group with major resections performed in 20.6% (LH) and 26.5% (OH) of cases, respectively. Operative time (194 +/- 88 min vs 275 +/- 131 min; P < 0.001) as well as intensive care (0.8 +/- 0.7 d vs 1.1 +/- 0.8 d; P = 0.031) and hospital stay (7.3 +/- 3.6 d vs 15.7 +/- 13.5 d; P < 0.001) were significant shorter in the LH group. Also, overall complications (20.6% vs 45.6%; P = 0.005) and major complications (1.5% vs 14.7%, P = 0.002) were observed less frequently after LH. An additional investigation analyzing the subgroup of obese patients who underwent LH (n = 27) and OH (n = 29) showed a shorter operative time (194 +/- 81 min vs 260 +/- 137 min; P = 0.009) and a reduced length of hospitalization (7.7 +/- 4.3 d vs 17.2 +/- 17 d; P < 0.001) but no difference in postoperative complications or overall cost.CONCLUSIONLH is safe and cost-effective in overweight and obese patients. Furthermore, LH is significantly associated with fewer postoperative complications and reduced hospital stay compared to OH in these patients.

Microbubbles (MB) are routinely used ultrasound (US) contrast agents that have recently attracted increasing attention as stimuli-responsive drug delivery systems. In order to better understand MB-based drug delivery, we studied the role of drug hydrophobicity and molecular weight on MB loading, shelf-life stability, US properties and drug release. Eight model drugs, varying in hydrophobicity and molecular weight, were loaded into the shell of poly(butyl cyanoacrylate) (PBCA) MB. In the case of drugs with progesterone as a common structural backbone (i.e. for corticosteroids), loading capacity and drug release correlated well with hydrophobicity and molecular weight. Conversely, when employing drugs with no structural similarity (i.e. four different fluorescent dyes), loading capacity and release did not correlate with hydrophobicity and molecular weight. All model drug-loaded MB formulations could be equally efficiently destroyed upon exposure to US. Together, these findings provide valuable insights on how the physicochemical properties of (model) drug molecules affect their loading and retention in and US-induced release from polymeric MB, thereby facilitating the development of drug-loaded MB formulations for US-triggered drug delivery.

Carbon monoxide (CO) is a gaseous signaling molecule that modulates inflammation, cell survival, and recovery after myocardial infarction. However, handling and dosing of CO as a compressed gas are difficult. Here, light-triggerable and magnetic resonance imaging (MRI)-detectable CO release from dimanganese decacarbonyl (CORM-1) are demonstrated, and the development of CORM-1-loaded polymeric microbubbles (COMB) is described as an ultrasound (US)- and MRI-imageable drug delivery platform for triggerable and targeted CO therapy. COMB are synthesized via a straightforward one-step loading protocol, present a narrow size distribution peaking at 2 µm, and show excellent performance as a CORM-1 carrier and US contrast agent. Light irradiation of COMB induces local production and release of CO, as well as enhanced longitudinal and transversal relaxation rates, enabling MRI monitoring of CO delivery. Proof-of-concept studies for COMB-enabled light-triggered CO release show saturation of hemoglobin with CO in human blood, anti-inflammatory differentiation of macrophages, reduction of hypoxia-induced reactive oxygen species (ROS) production, and inhibition of ischemia-induced apoptosis in endothelial cells and cardiomyocytes. These findings indicate that CO-generating MB are interesting theranostic tools for attenuating hypoxia-associated and ROS-mediated cell and tissue damage in cardiovascular disease.

Aim of this study was to improve knowledge about the best conversional bariatric procedure following sleeve gastrectomy (SG).Data of conversional Roux-en-Y gastric bypass (RYGB) and of one anastomosis gastric bypass (OAGB) after SG were collected prospectively and analyzed retrospectively. Weight loss parameters, gastroesophageal reflux disease (GERD) and comorbidities outcomes were recorded.Total of 123 patients (90 female, mean age 44 ± 0.9 years, mean body mass index (BMI) 42 ± 0.8 kg/mBoth RYGB and OAGB are effective conversional procedures after SG, leading to comparable TBWL, BMI-loss and high remission rates of comorbidities including GERD. Significantly shorter operation times were in favor of OAGB. BPL, which was longer in OAGB was significantly related to higher %TBWL and %BMI-loss compared to RYGB.

Introduction With increasing life expectancy, comorbidities become overt in Duchenne muscular dystrophy (DMD). Although micturition problems are common, bladder function is poorly understood in DMD. We studied dystrophin expression and multiple isoform involvement in the bladder during maturation to gain insights into their roles in micturition. Methods Dystrophin distribution was evaluated in rat bladders by immunohistochemical colocalization with smooth muscle, interstitial, urothelial, and neuronal markers. Protein levels of Dp140, Dp71, and smooth muscle were quantitated by Western blotting of neonatal to adult rat bladders. Results Dystrophin colocalized with smooth muscle cells and afferent nerve fibers. Dp71 was expressed two‐ to threefold higher compared with Dp140, independently of age. Age‐related muscle mass changes did not influence isoform expression levels. Discussion Dystrophin is expressed in smooth muscle cells and afferent nerve fibers in the urinary bladder, which underscores that micturition problems in DMD may have not solely a myogenic but also a neurogenic origin. Muscle Nerve 60: 202–210, 2019

Background. Bariatric surgery is a widely used treatment for morbid obesity. Prediction of postoperative weight loss currently relies on prediction models, which mostly overestimate patients&rsquo, weight loss. Data about the influence of Non-alcoholic fatty liver disease (NAFLD) on early postoperative weight loss are scarce. Methods. This prospective, single-center cohort study included 143 patients receiving laparoscopic gastric bypass surgery (One Anastomosis-Mini Gastric Bypass (OAGB-MGB) or Roux-en-Y Gastric Bypass (RYGB)). Liver biopsies were acquired at surgery. NAFLD activity score (NAS) assigned patients to &ldquo, No NAFLD&rdquo, &ldquo, NAFL&rdquo, or &ldquo, NASH&rdquo, Follow up data were collected at 3, 6 and 12 months. Results. In total, 49.7% of patients had NASH, while 41.3% had NAFL. Compared with the No NAFLD group, NAFL and NASH showed higher body-mass-index (BMI) at follow-up (6 months: 31.0 kg/m2 vs. 36.8 kg/m2 and 36.1 kg/m2, 12 months: 27.0 kg/m2 vs. 34.4 and 32.8 kg/m2) and lower percentage of total body weight loss (%TBWL): (6 months: 27.1% vs. 23.3% and 24.4%, 12 months: 38.5% vs. 30.1 and 32.6%). Linear regression of NAS points significantly predicts percentage of excessive weight loss (%EWL) after 6 months (Cologne-weight-loss-prediction-score). Conclusions. Histopathological presence of NAFLD might lead to inferior postoperative weight reduction after gastric bypass surgery. The mechanisms underlying this observation should be further studied.

Organoprotective effects of noble gases are subject of current research. One important field of interest is the effect of noble gases on hepatic regenerative capacity. For the noble gas argon, promising studies demonstrated remarkable experimental effects in neuronal and renal cells. The aim of this study was to investigate the effects of argon on the regenerative capacity of the liver after ischemia/reperfusion injury (IRI). Male, Sprague-Dawley rats underwent hepatic IRI by clamping of the hepatic artery. Expression of hepatoproliferative genes (HGF, IL-1&beta, IL-6, TNF), cell cycle markers (BrdU, TUNEL, Ki-67), and liver enzymes (ALT, AST, Bilirubin, LDH) were assessed 3, 36, and 96 h after IRI. Expression of IL-1&beta, and IL-6 was significantly higher after argon inhalation after 36 h (IL-1&beta, 5.0 vs. 8.7 fold, p = 0.001, IL-6 9.6 vs. 19.1 fold, p = 0.05). Ki-67 was higher in the control group compared to the argon group after 36 h (214.0 vs. 38.7 positive cells/1000 hepatocytes, p = 0.045). Serum levels of AST and ALT did not differ significantly between groups. Our data indicate that argon inhalation has detrimental effects on liver regeneration after IRI as measured by elevated levels of the proinflammatory cytokines IL-1&beta, and IL-6 after 36 h. In line with these results, Ki-67 is decreased in the argon group, indicating a negative effect on liver regeneration in argon inhalation.

Background and Methods: Tumors infiltrating the inferior caval vein (ICV) have been considered irresectable in the past due to high perioperative risks. Consequently, the only treatment option for these patients was best supportive care, which resulted in reduced survival. Advancements in surgical techniques have since evolved, such that combined resections of the ICV and the hepatic malignancy are being performed. The aim of this study was the evaluation of the long-term outcomes (e.g., survival) and short-term risks of this procedure. In this single-center, retrospective cohort study (n = 24), we evaluated surgical and oncological outcome for patients undergoing hepatic surgery for oncological indications in combination with resections of the ICV. In addition, we investigated which factors are associated with survival. Results: First, we showed that perioperative mortality is as low as 4.1%. Second, we showed that perioperative co-morbidities are acceptable for this type of advanced hepatobiliary surgery. Third, the reconstruction of the ICV by means of a patch was superior in terms of survival compared to other types of reconstructions. This finding was independent of the type or the aggressiveness of tumor or the resections status. Discussion: In our cohort, many patients had undergone (multiple) preceding visceral surgical interventions or underwent multi-visceral surgery. Despite the medical complexity, survival was encouraging in this cohort, offering novel treatment modalities with a low risk of severe morbidities.

Magnetic resonance imaging (MRI) is considered to be well tolerated by laboratory animals. However, no systematic study has been performed yet, proving this assumption. Therefore, the aim of this study was to investigate the possible effects of longitudinal native and contrast-enhanced (CE) 1-T and 7-T MRI examinations on mouse welfare as well as 4T1 breast cancers progression and therapy response.Forty-seven healthy and 72 breast cancer-bearing mice (4T1) were investigated. One-Tesla (ICON) and 7-T (Biospec) MRI measurements were performed thrice per week under isoflurane anesthesia in healthy BALB/c mice for 4 weeks and 3 times within 2 weeks in tumor-bearing animals. Animal welfare was examined by an observational score sheet, rotarod performance, heart rate measurements, and assessment of fecal corticosterone metabolites. Furthermore, we investigated whether CE-MRI influences the study outcome. Therefore, hemograms and organ weights were obtained, and 4T1 tumor growth, perfusion, immune cell infiltration, as well as response to the multikinase inhibitor regorafenib were investigated. Statistical comparisons between groups were performed using analysis of variance and Tukey or Bonferroni post hoc tests.Mice showed no alterations in the observational score sheet rating, rotarod performance, heart rate, and fecal corticosterone metabolites (P0.05) after repeated MRI at both field strengths. However, spleen weights were reduced in all healthy mouse groups that received isoflurane anesthesia (P0.001) including the groups investigated by 1-T and 7-T MRI (P = 0.02). Neither tumor progression nor response to the regorafenib treatment was affected by isoflurane anesthesia or CE-MRI monitoring. Furthermore, immunohistological tumor analysis did not indicate an effect of isoflurane and MRI on macrophage infiltration of tumors, perfusion of tumor vessels, and apoptotic cell rate (P0.05).Repeated MRI did not influence the welfare of mice and did not affect tumor growth and therapy response of 4T1 tumors. However, systemic immunological effects of isoflurane anesthesia need to be considered to prevent potential bias.

The periaqueductal gray matter (PAG), as one of the mostly preserved evolutionary components of the brain, is an axial structure modulating various important functions of the organism, including autonomic, behavioral, pain, and micturition control. It has a critical role in urinary bladder physiology, with respect to storage and voiding of urine. The PAG has a columnar composition and has extensive connections with its cranially and caudally located components of the central nervous system (CNS). The PAG serves as the control tower of the detrusor and sphincter contractions. It serves as a bridge between the evolutionary higher decision-making brain centers and the lower centers responsible for reflexive micturition. Glutamatergic cells are the main operational neurons in the vlPAG, responsible for the reception and relay of the signals emerging from the bladder, to related brain centers. Functional imaging studies made it possible to clarify the activity of the PAG in voiding and filling phases of micturition, and its connections with various brain centers in living humans. The PAG may be affected in a wide spectrum of disorders, including multiple sclerosis (MS), migraine, stroke, Wernicke's encephalopathy, and idiopathic normal pressure hydrocephalus, all of which may have voiding dysfunction or incontinence, in certain stages of the disease. This emphasizes the importance of this structure for the basic understanding of voiding and storage disorders and makes it a potential candidate for diagnostic and therapeutic interventions.

Animal models with constant, long-lasting motor deficits together with the right tests to assess behavioral abnormalities are needed to study the effectiveness of potential therapies to restore motor functions. In the current study, controlled cortical impact (CCI) was applied in rats to induce damage to the forelimb area of the motor cortex and the dorsal striatum. Motor behavior was assessed before and after CCI, using fine motor skill tests such as the adhesive removal test, the cylinder test, and the Montoya staircase test as well as the automated gait analysis system CatWalk XT over a 6 week period. CCI caused a variety of unilateral motor deficits, which were characterized in detail by using the selected fine motor skill tests. In striking contrast to previous studies on CCI in mice, neither forelimb impairments, nor general changes in gait, were detected with the CatWalk XT. These data suggest that the adhesive removal test, the cylinder test, and the Montoya staircase test are the methods of choice to detect long-term unilateral motor deficits in rats after CCI, whereas the use of automated gait analysis systems might not be suitable to measure these behavioral deviations. This work was supported in part by a grant from Hasselt University (BOF11603BOFMO) to S.H. and a grant from the Hersenstichting Nederland to Y.T.

Objective: Cognitive impairment is frequently observed in patients with temporal lobe epilepsy. It is hypothesized that cumulative seizure exposure causes accelerated cognitive decline in patients with epilepsy. We investigated the influence of seizure frequency on cognitive decline in a rodent model for temporal lobe epilepsy.Methods: Neurobehavioral assessment was performed before and after surgery, after the induction of self-sustaining limbic status epilepticus (SSLSE), and in the chronic phase in which rats experienced recurrent seizures. Furthermore, we assessed potential confounders of memory performance.Results: Rats showed a deficit in spatial working memory after the induction of the SSLSE, which endured in the chronic phase. A progressive decline in recognition memory developed in SSLSE rats. Confounding factors were absent. Seizure frequency and also the severity of the status epilepticus were not correlated with the severity of cognitive deficits.Significance: The effect of the seizure frequency on cognitive comorbidity in epilepsy has long been debated, possibly because of confounders such as antiepileptic medication and the heterogeneity of epileptic etiologies. In an animal model of temporal lobe epilepsy, we showed that a decrease in spatial working memory does not relate to the seizure frequency. This suggests for other mechanisms are responsible for memory decline and potentially a common pathophysiology of cognitive deterioration and the occurrence and development of epileptic seizures. Identifying this common denominator will allow development of more targeted interventions treating cognitive decline in patients with epilepsy. The treatment of interictal symptoms will increase the quality of life of many patients with epilepsy. (C) 2016 Elsevier Inc. All rights reserved.

Introduction: Many of the currently available therapies for urinary incontinence target the peripheral autonomic system, despite many etiologies residing in the central nervous system. Following previous experiments that determined the ventrolateral column of the periaqueductal gray matter (vlPAG), to be the main afferent station of bladder sensory signals, we aimed for electrophysiological characterization of vlPAG neurons using single unit recording.Methods: 15 rats were anesthetized and underwent implantation with electrodes at the dome and the neck of the bladder, to electrically stimulate the detrusor. After craniotomy, a glass micropipette was inserted in vlPAG to record neuronal action potentials. The detrusor was stimulated by a series of 20 Hz pulses, for a total duration of 50 s at an intensity of 2 mA, for each vlPAG neuron selected. Single unit recordings were performed on a total of 26 neurons. Confirmation of electrode position was made by iontophoretic ejection of Pontamine sky blue.Results: The firing rate of vlPAG neurons decreased significantly during the stimulation period. Peristimulus time histogram (PSTH) analysis showed 24 out of 26 neurons to be unresponsive to stimulation. All recorded vlPAG neurons showed irregular firing patterns.Conclusions: The change in firing rate may point to an overall inhibitory influence of bladder stimulation on vlPAG neurons. These data suggest an inhibitory relay station at the vlPAG, before sensory bladder signals would affect pontine micturition center. The lack of the inhibitory effect on PSTH may be due to a longer interval between neuronal response and the stimulation.

Duchenne muscular dystrophy (DMD) is a recessive hereditary form of muscular dystrophy caused by a mutation in the dystrophin gene on the X chromosome. Clinical observations show that in addition to progressive muscular degeneration, DMD is more often accompanied by neurocognitive symptoms and learning disabilities, especially in automatisation of reading, attention processes, and expressive language skills. Additionally, three studies reported a higher prevalence of epilepsy in DMD, suggesting that the absence of dystrophin might be related to increased CNS excitability. In this article, we aim to review current clinical and experimental evidence for a potential role of brain dystrophin in seizure generation.

Deep brain stimulation (DBS) is an established symptomatic treatment modality for movement disorders and constitutes an emerging therapeutic approach for the treatment of memory impairment. In line with this, fornix DBS has shown to ameliorate cognitive decline associated with dementia. Nonetheless, mechanisms mediating clinical effects in demented patients or patients with other neurological disorders are largely unknown. There is evidence that DBS is able to modulate neurophysiological activity in targeted brain regions. We therefore hypothesized that DBS might be able to influence cognitive function via activity-dependent regulation of hippocampal neurogenesis. Using stimulation parameters, which were validated to restore memory loss in a previous behavioral study, we here assessed long-term effects of fornix DBS. To do so, we injected the thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), after DBS and perfused the animals 6.5 weeks later. A week prior to perfusion, memory performance was assessed in the water maze. We found that acute stimulation of the fornix improved spatial memory performance in the water maze when the probe trial was performed 1 h after the last training session. However, no evidence for stimulation-induced neurogenesis was found in fornix DBS rats when compared to sham. Our results suggest that fornix DBS improves memory functions independent of hippocampal neurogenesis, possibly through other mechanisms such as synaptic plasticity and acute neurotransmitter release.

Background: Motor impairments are among the major complications that develop after cortical damage caused by either stroke or traumatic brain injury. Motor cortex stimulation (MCS) can improve motor functions in animal models of stroke by inducing neuroplasticity. Objective: In the current study, the therapeutic effect of chronic MCS was assessed in a rat model of severe cortical damage. Methods: A controlled cortical impact (CCI) was applied to the forelimb area of the motor cortex followed by implantation of a flat electrode covering the lesioned area. Forelimb function was assessed using the Montoya staircase test and the cylinder test before and after a period of chronic MCS. Furthermore, the effect of MCS on tissue metabolism and lesion size was measured using [F-18]-fluorodesoxyglucose (FDG) mu PET scanning. Results: CCI caused a considerable lesion at the level of the motor cortex and dorsal striatum together with a long-lasting behavioral phenotype of forelimb impairment. However, MCS applied to the CCI lesion did not lead to any improvement in limb functioning when compared to non-stimulated control rats. Also, MCS neither changed lesion size nor distribution of FDG. Conclusion: The use of MCS as a standalone treatment did not improve motor impairments in a rat model of severe cortical damage using our specific treatment modalities. This work was supported in part by a grant from Hasselt University (BOF11603BOFMO) to SH and a grant from the Hersenstichting Nederland and Medtronic Europe (A1196117) to YT and AJ.

Tonic GABAA receptors are a subpopulation of receptors that generate long-lasting inhibition and thereby control network excitability. In recent years, these receptors have been implicated in various neurological and psychiatric disorders, including Parkinson’s disease, schizophrenia, and epilepsy. Their distinct subunit composition and function, compared to phasic GABAA receptors, opens the possibility to specifically modulate network properties. In this review, the role of tonic GABAA receptors in epilepsy and as potential antiepileptic target will be discussed.

Tonic GABA(A) receptors are a subpopulation of receptors that generate long-lasting inhibition and thereby control network excitability. In recent years, these receptors have been implicated in various neurological and psychiatric disorders, including Parkinson's disease, schizophrenia, and epilepsy. Their distinct subunit composition and function, compared to phasic GABA(A) receptors, opens the possibility to specifically modulate network properties. In this review, the role of tonic GABA(A) receptors in epilepsy and as potential antiepileptic target will be discussed.

Objective: Dystrophin is part of a protein complex that connects the cytoskeleton to the extracellular matrix. In addition to its role in muscle tissue, it functions as an anchoring protein within the central nervous system such as in hippocampus and cerebellum. Its presence in the latter regions is illustrated by the cognitive problems seen in Duchenne Muscular Dystrophy (DMD). Since epilepsy is also supposed to constitute a comorbidity of DMD, it is hypothesized that dystrophin plays a role in neuronal excitability. Here, we aimed to study brain dystrophin distribution and expression in both, human and experimental temporal lobe epilepsy (TLE).Method: Regional and cellular dystrophin distribution was evaluated in both human and rat hippocampi and in rat cerebellar tissue by immunofluorescent colocalization with neuronal (NeuN and calbindin) and glial (GFAP) markers. In addition, hippocampal dystrophin levels were estimated by Western blot analysis in biopsies from TLE patients, post-mortem controls, amygdala kindled (AK)-, and control rats.Results: Dystrophin was expressed in all hippocampal pyramidal subfields and in the molecular-, Purkinje-, and granular cell layer of the cerebellum. In these regions it colocalized with GFAP, suggesting expression in astrocytes such as Bergmann glia (BG) and velate protoplasmic astrocytes. In rat hippocampus and cerebellum there were neither differences in dystrophin positive cell types, nor in the regional dystrophin distribution between AK and control animals. Quantitatively, hippocampal full-length dystrophin (Dp427) levels were about 60% higher in human TLE patients than in post-mortem controls (p Conclusion: Dystrophin is ubiquitously expressed by astrocytes in the human and rat hippocampus and in the rat cerebellum. Hippocampal full-length dystrophin (Dp427) levels are upregulated in human TLE, but not in AK rats, possibly indicating a compensatory mechanism in the chronic epileptic human brain.

It is unclear to what extent neuropathological changes contribute to brain inflammation observed in temporal lobe epilepsy (TLE). Here, we compared cytokine levels between histopathologically-confirmed sclerotic hippocampi and histopathologically-confirmed normal hippocampi from TLE patients. We analyzed a similar cytokine panel in the hippocampi of amygdala-kindled rats and we evaluated neuropathological changes by immunohistochemistry. In TLE patients, cytokine levels were not significantly different between sclerotic and non-sclerotic hippocampi. Though kindling resulted in increased astrocyte activation, cytokine levels and microglia activation were unchanged. These results suggest that the chronic epileptic state in TLE can also occur in the absence of intracerebral inflammation. Highlights • HS in TLE patients is not associated with a sustained brain inflammatory response. • Amygdala kindled seizures are not associated with a sustained inflammatory response. • Brain inflammation is not necessarily present in temporal lobe epilepsy.