Fractionated brain X-irradiation profoundly reduces hippocampal immature neuron numbers without affecting spontaneous behavior in mice.

Whole brain radiotherapy (WBRT) is used to improve tumor control in patients with primary brain tumors, or brain metastasis from various primary tumors to improve tumor control. However, WBRT can lead to cognitive decline in patients. We assessed whether fractionated WBRT (fWBRT) affects spontaneous behavior of mice in automated home cages and cognition (spatial memory) using the Barnes maze. Male C57Bl/6j mice received bi-lateral fWBRT at a dosage of 4 Gy/day on 5 consecutive days. In line with previous reports, immunohistochemical analysis of doublecortin positive cells in the dentate gyrus showed a profound reduction in immature neurons 4 weeks after fWBRT. Surprisingly, spontaneous behavior as measured in automated home cages was not affected. Moreover, learning and memory measured with Barnes maze, was also not affected 4-6 weeks after fWBRT. At 10-11 weeks after fWBRT a significant difference in escape latency during the learning phase, but not in the probe test of the Barnes maze was observed. In conclusion, although we confirmed the serious adverse effect of fWBRT on neurogenesis 4 weeks after fWBRT, we did not find similar profound effects on spontaneous behavior in the automated home cage nor on learning abilities as measured by the Barnes maze. The relationship between the neurobiological effects of fWBRT and cognition seems more complex than often assumed and the choice of animal model, cognitive tasks, neurobiological parameters, and experimental set-up might be important factors in these types of experiments.

Implementación asistencial de estudios genómicos aplicados al diagnóstico molecular / Implementation of genomic studies applied to molecular diagnostics

El Hospital Garrahan ha sido pionero en el diagnóstico molecular de patologías pediátricas en Argentina. Los avances tecnológicos de las últimas décadas en el área de la biología molecular, sentaron las bases para la optimización y ampliación del diagnóstico molecular a partir de la secuenciación masiva en paralelo de múltiples genes. El presente trabajo describe el proceso de implementación de los estudios de secuenciación de nueva generación y el desarrollo de la Unidad de Genómica en un hospital público pediátrico de alta complejidad, así como su impacto en las capacidades diagnósticas de enfermedades poco frecuentes de origen genético. La creación del Grupo Interdisciplinario de Estudios Genómicos constituyó la vía institucional para la toma de decisiones que implican la implementación de nuevos estudios genómicos y el establecimiento de prioridades diagnósticas, extendiendo la disponibilidad del diagnóstico molecular a más disciplinas. La Unidad de Genómica trabaja en diseñar las estrategias que permitan la mayor optimización de los recursos con los que cuenta el hospital, teniendo en cuenta el equipamiento disponible, las prioridades establecidas y la frecuencia de las distintas patologías. Se demuestra el salto significativo operado en nuestras capacidades diagnósticas, tanto en la variedad de enfermedades como en el número de genes analizados, habiendo estudiado a la fecha alrededor de 2.000 pacientes, muchos de los cuales ven de este modo finalizada su odisea diagnóstica. Los estudios de NGS se han convertido en una herramienta de la práctica diaria para la atención de un número importante de pacientes de nuestro hospital. Continuaremos trabajando para ampliar su aplicación a la mayor cantidad de patologías, a través de los mecanismos institucionales ya existentes (AU)

The Garrahan Hospital has been a pioneer in the molecular diagnosis of pediatric diseases in Argentina. The technological advances of the last decades in the area of molecular biology have laid the foundations for the optimization and expansion of molecular diagnostics through massive parallel sequencing of multiple genes. This study describes the process of implementation of next-generation sequencing studies and the development of the Genomics Unit in a public pediatric tertiary hospital, and its impact on the capacity to diagnose rare diseases of genetic origin. The creation of the Interdisciplinary Group of Genomic Studies constituted the institutional pathway for decision-making involving the implementation of new genomic studies and the establishment of diagnostic priorities, extending the availability of molecular diagnostics to additional disciplines. The Genomics Unit is working to design strategies that allow for optimization of the resources available to the hospital, taking into account the equipment available, the priorities established, and the frequency of the different diseases. It demonstrates the significant leap in our diagnostic capabilities, both in the variety of diseases and in the number of genes analyzed. To date, around 2,000 patients have been studies, many of whom have thus completed their diagnostic odyssey. NGS studies have become a tool in daily practice for the care of a significant number of patients in our hospital. We will continue working to expand its application to as many diseases as possible, through the existing institutional mechanisms (AU)

The eye lens dose of the interventionalist: Measurement in practice.

OBJECTIVE: Early 2018, the new eye lens dose limit of 20 mSv per year for occupational exposure to ionising radiation was implemented in the European Union. Dutch guidelines state that monitoring is compulsory above an expected eye lens dose of 15 mSv/year. In this study we propose a method to investigate whether the eye lens dose of interventionalists would exceed 15 mSv/year and to determine if the eye lens dose can be derived from the regular personal dosimeter measurements. METHODS: The eye lens dose, Hp(3), of interventional radiologists (n = 2), cardiologists (n = 2) and vascular surgeons (n = 3) in the Máxima Medical Centre, The Netherlands, was measured during six months, using thermoluminescence dosimeters on the forehead. Simultaneously, the surface dose, Hp(0,07), and whole body dose, Hp(10), were measured using regular dosimeters outside the lead skirt at chest level. The dosimeters were simultaneously refreshed every four weeks. The eye lens dose was compared to both the body-worn dosimeter values. Measurements were performed in the angiography suite, Cath lab and hybrid OR. RESULTS: A clear relation was observed between the two dosimeters: Hp(3) ≈ 0,25 Hp(0,07). The extrapolated year dose for the eye lens did not exceed 15 mSv for any of the interventionalists (average 3 to 10 studies/month). CONCLUSIONS: The eye lens dose can be monitored indirectly through the regular dosimeter at chest level. Additionally, based on the measurements we conclude that all monitored interventionalists remain below the dose limit and compulsory monitoring limit for the eye lens dose.

Learning Curves in Open, Laparoscopic, and Robotic Pancreatic Surgery: A Systematic Review and Proposal of a Standardization.

Objective: To depict and analyze learning curves for open, laparoscopic, and robotic pancreatoduodenectomy (PD) and distal pancreatectomy (DP). Background: Formal training is recommended for safe introduction of pancreatic surgery but definitions of learning curves vary and have not been standardized. Methods: A systematic search on PubMed, Web of Science, and CENTRAL databases identified studies on learning curves in pancreatic surgery. Primary outcome was the number needed to reach the learning curve as defined by the included studies. Secondary outcomes included endpoints defining learning curves, methods of analysis (statistical/arbitrary), and classification of learning phases. Results: Out of 1115 articles, 66 studies with 14,206 patients were included. Thirty-five studies (53%) based the learning curve analysis on statistical calculations. Most often used parameters to define learning curves were operative time (n = 51), blood loss (n = 17), and complications (n = 10). The number of procedures to surpass a first phase of learning curve was 30 (20-50) for open PD, 39 (11-60) for laparoscopic PD, 25 (8-100) for robotic PD (P = 0.521), 16 (3-17) for laparoscopic DP, and 15 (5-37) for robotic DP (P = 0.914). In a three-phase model, intraoperative parameters improved earlier (first to second phase: operating time -15%, blood loss -29%) whereas postoperative parameters improved later (second to third phase: complications -46%, postoperative pancreatic fistula -48%). Studies with higher sample sizes showed higher numbers of procedures needed to overcome the learning curve (rho = 0.64, P < 0.001). Conclusions: This study summarizes learning curves for open-, laparoscopic-, and robotic pancreatic surgery with different definitions, analysis methods, and confounding factors. A standardized reporting of learning curves and definition of phases (competency, proficiency, mastery) is desirable and proposed.

Fifteen years' experience with methylphenidate for attention-deficit disorder during pregnancy: Effects on birth weight, Apgar score and congenital malformation rates.

BACKGROUND: Methylphenidate (MPD) is increasingly prescribed to fertile women with Attention-Deficit Disorder (AD(H)D), with or without hyperactivity, despite advice for discontinuation during pregnancy. Few studies report on results concerning safety after methylphenidate exposure during pregnancy for the offspring. AIM: Safety for the offspring of exposure to MPD during pregnancy. METHODS: This is an observational retrospective cohort study in a population of pregnant women and their offspring, treated with MPD for ADHD in the Psychiatry-Gynaecology-Pediatrics outpatient clinic between 1 January 2005 and 1 June 2020 at Isala hospital. The primary endpoints were birth weight and Apgar score in offspring exposed to MPD during pregnancy, compared to offspring unexposed to MPD. Birth weight was analysed using linear mixed model analysis. Apgar score and (secondary endpoint) neonatal malformations, at 20 week ultrasound, were analysed using basic univariate statistical analysis. RESULTS: MPD continuation, compared to discontinuation, was associated with higher neonatal birth weight (p = 0.049), but lost statistical significance after incorporating covariates (p = 0.079). There were no significant differences in Apgar scores and congenital malformations between neonates exposed and unexposed to MPD. CONCLUSIONS: MPD does not seem to affect birth weight, Apgar score and the frequency of neonatal malformations at the 20 week ultrasound.

Radiological management of postoperative lymphorrhea.

PURPOSE: Postoperative lymphorrhea can occur after different surgical procedures and may prolong the hospital stay due to the need for specific treatment. In this work, the therapeutic significance of the radiological management of postoperative lymphorrhea was assessed and illustrated. METHOD: A standardized search of the literature was performed in PubMed applying the Medical Subject Headings (MeSH) term "lymphangiography." For the review, the inclusion criterion was "studies with original data on Lipiodol-based Conventional Lymphangiography (CL) with subsequent Percutaneous Lymphatic Intervention (PLI)." Different exclusion criteria were defined (e.g., studies with <15 patients). The collected data comprised of clinical background and indications, procedural aspects and types of PLI, and outcomes. In the form of a pictorial essay, each author illustrated a clinical case with CL and/or PLI. RESULTS: Seven studies (corresponding to evidence level 4 [Oxford Centre for Evidence-Based Medicine]) accounting for 196 patients were included in the synthesis and analysis of data. Preceding surgery resulting in postoperative lymphorrhea included different surgical procedures such as extended oncologic surgery or vascular surgery. Central (e.g., chylothorax) and peripheral (e.g., lymphocele) types of postoperative lymphorrhea with a drainage volume of 100-4000 ml/day underwent CL with subsequent PLI. The intervals between "preceding surgery and CL" and between "CL and PLI" were 2-330 days and 0-5 days, respectively. CL was performed before PLI to visualize the lymphatic pathology (e.g., leakage point or inflow lymph ducts), applying fluoroscopy, radiography, and/or computed tomography (CT). In total, seven different types of PLI were identified: (1) thoracic duct (or thoracic inflow lymph duct) embolization, (2) thoracic duct (or thoracic inflow lymph duct) maceration, (3) leakage point direct embolization, (4) inflow lymph node interstitial embolization, (5) inflow lymph duct (other than thoracic) embolization, (6) inflow lymph duct (other than thoracic) maceration, and (7) transvenous retrograde lymph duct embolization. CL-associated and PLI-associated technical success rates were 97-100% and 89-100%, respectively. The clinical success rate of CL and PLI was 73-95%. CL-associated and PLI-associated major complication rates were 0-3% and 0-5%, respectively. The combined CL- and PLI-associated 30-day mortality rate was 0%, and the overall mortality rate was 3% (corresponding to six patients). In the pictorial essay, the spectrum of CL and/or PLI was illustrated. CONCLUSION: The radiological management of postoperative lymphorrhea is feasible, safe, and effective. Standardized radiological treatments embedded in an interdisciplinary concept are a step towards improving outcomes.

Radiological evaluation of pancreatic cancer: What is the significance of arterial encasement >180° after neoadjuvant treatment?

PURPOSE: This study aimed to evaluate contrast-enhanced computed tomography (CE-CT) features for prediction of arterial tumor invasion in pancreatic cancer (PDAC) patients in the event of arterial encasement >180° after neoadjuvant (radio-)chemotherapy (NAT). METHODS: Seventy PDAC patients with seventy-five arteries showing encasement >180° after completion of NAT were analyzed. All patients underwent surgical exploration with either tumor resection including arterial resection, periadventitial dissection (arterial divestment) or confirmation of locally irresectable disease. CE-CT scans were assessed regarding tumor extent and artery-specific imaging features. The results were analyzed on a per-artery basis. Based on the intraoperative and histopathological findings, encased arteries were classified as either invaded or non-invaded. RESULTS: Eighteen radiologically encased arteries were resected; of these, nine had pathologic evidence for tumor invasion. In 42 encased arteries, the tumor could be removed by arterial divestment. In 13 patients with 15 encased arteries, the tumor was deemed technically irresectable. Median tumor size, length of solid soft tissue contact, and degree of circumferential contiguity by solid soft tissue along the artery in CE-CT were significantly lower in the non-invaded than in the invaded artery group (p ≤ 0.017). Imaging features showed moderate accuracies for prediction of arterial invasion (≤72.0 %). The thresholds ≤26 mm for post-NAT solid soft tissue contact and ≤270° for circumferential contiguity by solid soft tissue had high negative predictive values (≥87.5 %). CONCLUSION: Although post-NAT prediction of arterial invasion remains difficult, arteries with ≤270° contiguity by soft tissue and arteries with ≤26 mm length of solid soft tissue contact are unlikely to be invaded, with possible implications for surgical planning.

[Perioperative fluid management in major abdominal surgery]. / Perioperatives Flüssigkeitsmanagement bei großen viszeralchirurgischen Eingriffen.

Intravascular fluid administration belongs to the cornerstones of perioperative treatment with a substantial impact on surgical outcome especially with respect to major abdominal surgery. By avoidance of hypovolemia and hypervolemia, adequate perioperative fluid management significantly contributes to the reduction of insufficient tissue perfusion as a determinant of postoperative morbidity and mortality. The effective use of intravascular fluids requires detailed knowledge of the substances as well as measures to guide fluid therapy. Fluid management already starts preoperatively and should be continued in the postoperative setting (recovery room, peripheral ward) considering a patient-adjusted and surgery-adjusted hemodynamic monitoring. Communication between all team members participating in perioperative care is essential to optimize fluid management.

Percutaneous afferent lymphatic vessel sclerotherapy for postoperative lymphatic leakage after previous ineffective therapeutic transpedal lymphangiography.

BACKGROUND: To demonstrate the efficacy of percutaneous computed tomography (CT)-guided afferent lymphatic vessel sclerotherapy (ALVS) in the treatment of postoperative lymphatic leakage (LL) after ineffective therapeutic transpedal lymphangiography (TL). METHODS: A retrospective review in this institute involving 201 patients was conducted from May 2011 to September 2018. Patients diagnosed with postoperative LL undergoing ineffective therapeutical TL before the performance of percutaneous CT-guided ALVS were involved. Technical success and clinical success of TL and ALVS were established. The technical success and efficacy of ALVS in the treatment of postoperative LL after ineffective therapeutic TL were assessed. The clinical success rate of ALVS is also assessed, and the complications are reviewed. RESULTS: In total, nine patients were involved including three patients (33.3%) presented with chylothorax, three patients (33.3%) presented with inguinal lymphatic fistula/lymphocele, and three patients (33.3%) presented with lymphatic fistula in the thigh; 27 ± 18 days (mean ± standard deviation) after surgery, therapeutic TL was successfully performed and showed definite afferent lymphatic vessel and leakage site in all the patients. Due to clinical failure after TLs, the following ALVS was performed with a mean interval of 12 ± 8 days after TL. The technical success rate was 9/9 (100.0%, 95% confidence interval [CI] 63.1-100.0%). An average of 2.7 ± 1.3 mL 95% ethanol as sclerosant agent was injected during the procedure. The clinical success was observed in 8 of the 9 patients (88.9%, 95% CI 51.8-99.7%) with a time between ALVS and the LL cure of 8 ± 6 days. No complications were reported. CONCLUSIONS: Our results showed the role of percutaneous CT-guided ALVS as a safe, feasible, and effective salvage treatment for postoperative LL after ineffective TL.

The roles of iodized oil-based lymphangiography and post-lymphangiographic computed tomography for specific lymphatic intervention planning in patients with postoperative lymphatic fistula: a literature review and case series.

In the management of patients with postoperative lymphatic fistula (LF) in different locations, iodized oil-based lymphangiography (LAG) from trans-pedal or intranodal route is an established diagnostic approach with the potential to plan further interventional treatments. However, specific lymphatic interventions are indicated depending on different locations and morphologies of the LF. After a systematic literature review, four types of interventions can be considered, including direct leakage embolization/sclerotherapy (DLE/DLS), percutaneous afferent lymphatic vessel embolization (ALVE), percutaneous afferent lymphatic vessels disruption/sclerotherapy (ALVD/ALVS), and trans-afferent nodal embolization (TNE). In the iodized oil-based LAG, three potential lymphatic targets including confined leakage, definite afferent LVs, and definite closest afferent LNs should be comprehensively assessed. For optimal prospective treatment planning for LF, iodized oil-based post-lymphangiographic computed tomography (post-LAG CT) is a useful complement to the conventional iodized oil-based LAG, which can be performed easily after LAG. This review article summarized the current evidence of the specific lymphatic interventions in patients with postoperative LF and explored the potential benefits of post-LAG CT in the intervention planning from a case series.

An automated home-cage-based 5-choice serial reaction time task for rapid assessment of attention and impulsivity in rats.

RATIONALE: The 5-choice serial reaction time task (5-CSRTT) is a widely used operant task for measuring attention and motor impulsivity in rodents. Training animals in this task requires an extensive period of daily operant sessions. Recently, a self-paced, automated version of this task has been developed for mice, which substantially reduces training time. Whether a similar approach is effective for rats is currently unknown. OBJECTIVE: Here, we tested whether attention and impulsivity can be assessed in rats with a self-paced version of the 5-CSRTT. METHODS: Operant boxes were connected to home-cages with tunnels. Two groups of rats self-paced their training by means of an automated script. The first group of animals was allowed unlimited access (UA) to start trials in the task; for the second group, trial availability was restricted to the first 2.5 h of the dark cycle (TR). Task parameter manipulations, such as variable inter-trial intervals and stimulus durations as well as pharmacological challenges with scopolamine, were tested to validate the task. RESULTS: Self-paced training took less than 1 week. Animals in the UA group showed higher levels of omissions compared with the TR group. In both protocols, variable inter-trial intervals increased impulsivity, and variable stimulus durations decreased attentional performance. Scopolamine affected cognitive performance in the TR group only. CONCLUSIONS: Home-cage-based training of the 5-CSRTT in rats, especially the TR protocol, presents a valid and fast alternative for measuring attention and impulsivity.

Comparison of different types of landfill leachate treatments by employment of nontarget screening to identify residual refractory organics and principal component analysis.

Three different chemical oxidation processes were investigated in terms of their capability to degrade organic chemical components of real mature landfill-leachate in combination with biological treatment run in a Sequencing Batch Biofilter Granular Reactor (SBBGR). H2O2, H2O2 + UV and O3 were integrated with SBBGR and respective effluents were analyzed and compared with the effluent obtained from biological SBBGR treatment alone. In agreement with their respective oxidative power, conventional bulk parameters (residual COD, TOC, Ntot, TSS) determined from the resulting effluents evidenced the following efficacy ranking for degradation: SBBGR/O3 > SBBGR/UV + H2O2 > SBBGR/H2O2 > SBBGR. A more detailed characterization of the organic compounds was subsequently carried out for the four treated streams. For this, effluents were first subjected to a sample preparation step, allowing for a classification in terms of acidic, basic, strongly acidic and strongly basic compounds, and finally to analysis by liquid chromatography/high resolution mass spectrometry (LC/HR-MS). This classification, combined with further data post-processing (non-target screening, Venn Diagram, tri-dimensional plot and Principal Component Analysis), evidenced that the SBBGR/H2O2 process is comparable to the pure biological oxidation. In contrast, SBBGR/O3 and SBBGR/UV + H2O2 not only resulted in a very different residual composition as compared to SBBGR and SBBGR/H2O2, but also differ significantly from each other. In fact, and despite of the SBBGR/O3 being the most efficient process, this treatment remained chemically more similar to SBBGR/H2O2 than to SBBGR/UV + H2O2. This finding may be attributable to different mechanism of degradation involved with the use of UV radiation. Apart from these treatment differences, a series of recalcitrant compounds was determined in all of the four treatments and partly identified as hetero-poly-aromatic species (humic acids-like species).

Constitutive loss and acute pharmacological manipulation of ErbB4 signaling do not affect attention and inhibitory control in mice.

The receptor tyrosine kinase ErbB4 and its ligand trophic factors of the neuregulin (NRG) family have been associated with schizophrenia and other mental disorders in human genetic studies. In vivo studies in mice have shown how abnormal Nrg-ErbB4 signaling leads to deviant behaviors relevant to distinct aspects of schizophrenia, including hyperactivity, sensory gating deficits, working and spatial memory deficits and impaired social behavior. However, so far little is known on the role of ErbB4 in attention and inhibitory control, two aspects of executive functions that are impaired in schizophrenia. Here we investigated the effects of constitutive loss of ErbB4 in the central nervous system of mice on performance in a 5-choice serial reaction time task (5CSRTT) assessing attention and inhibitory control. In this task, ErbB4-/- mice did not show deficits in various parameters of attention, and premature responses as measure of inhibitory control. Nonetheless, ErbB4-/- mice recapitulated a specific set of behavioral phenotypes associated with schizophrenia, including a deficit in spatial learning and memory in the Barnes Maze and in contextual fear learning, and a trend for a deficit in sensorimotor gating. Furthermore, we investigated the effect of acute pharmacological inhibition of ErbB tyrosine kinase receptor using the pan-ErbB kinase inhibitor JNJ-28871063 (JNJ), in an automated version of the 5CSRTT. JNJ did not affect attention and inhibitory control. In conclusion, our data suggest no direct involvement of a classical Nrg-ErbB4 pathway in attention and inhibitory control in mice, while it confirms the involvement of this pathway in other domains relevant to schizophrenia.

Cognitive flexibility deficits in a mouse model for the absence of full-length dystrophin.

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder, caused by mutations in the DMD gene and the resulting lack of dystrophin. The DMD gene has seven promoters, giving rise to multiple full-length and shorter isoforms. Besides the expression of dystrophin in muscles, the majority of dystrophin isoforms is expressed in brain and dystrophinopathy can lead to cognitive deficits, including intellectual impairments and deficits in executive function. In contrast to the muscle pathology, the impact of the lack of dystrophin on the brain is not very well studied. Here, we study the behavioral consequences of a lack of full-length dystrophin isoforms in mdx mice, particularly with regard to domains of executive functions and anxiety. We observed a deficit in cognitive flexibility in mdx mice in the absence of motor dysfunction or general learning impairments using two independent behavioral tests. In addition, increased anxiety was observed, but its expression depended on the context. Overall, these results suggest that the absence of full-length dystrophin in mice has specific behavioral effects that compare well to deficits observed in DMD patients.

Randomized clinical trial comparing self-gripping mesh with a standard polypropylene mesh for open inguinal hernia repair.

BACKGROUND: The introduction of mesh for open inguinal hernia repair has reduced the rate of recurrence, allowing research to focus on prevention of postoperative pain. In an effort to reduce chronic pain, a semiresorbable, lighter and self-gripping mesh was developed. METHODS: A double-blind randomized clinical trial was conducted comparing the self-gripping mesh with a standard polypropylene mesh repair. Patients over 18 years of age undergoing open primary hernia repair were included. Pain was measured on a six-point verbal rating scale (VRS) and a 150-mm visual analogue scale (VAS). Postoperative pain reduction from baseline pain (ΔVAS), complications and return to work/hobbies were studied. Data were collected at baseline, 3 weeks, 3 months and 1 year after surgery (primary outcome). RESULTS: A total of 363 patients were analysed. Median age was 59 (range 19-88) years. Baseline VRS and VAS scores were similar for the two groups. There was no difference in VRS scores at 1-year follow-up. Duration of surgery was significantly shorter with the self-gripping mesh (mean 40 min versus 49 min for standard mesh repair; P < 0·001). At 3 weeks, ΔVAS in patients receiving the self-gripping mesh was significantly larger (-10·6 versus -5·0 respectively; P = 0·049) and less subjective discomfort was reported (P = 0·016). Complication rates, return to work and recurrence rates were similar, although there were more recurrences in the self-gripping mesh group (5·5 versus 2·2 per cent; P = 0·103). CONCLUSION: A self-gripping mesh for hernia repair may result in less pain in the early postoperative phase but chronic postherniorraphy pain is not affected. Recurrence rates may be a potential disadvantage. REGISTRATION NUMBER: NTR1212 (http://www.trialregister.nl).

Neurobiological changes by cytotoxic agents in mice.

Cognitive deficit is a frequently reported side-effect of adjuvant chemotherapy. A large number of animal studies has been performed to examine the neurobiological mechanisms underlying this phenomenon, however, definite conclusions from these studies are restricted due to differences in experimental set-up. We systematically investigated the effects of 6 cytotoxic agents on various neurobiological parameters. C57Bl/6J mice were treated with cyclophosphamide, docetaxel, doxorubicin, 5-fluorouracil, methotrexate, or topotecan. The animals were sacrificed 3 or 15 weeks after treatment and the effect on neurogenesis, blood vessel density, and neuroinflammation was analyzed using immunohistochemistry. None of the cytostatic agents tested affected neurogenesis (cell survival or cell proliferation). Blood vessel density was increased in the hippocampus and prefrontal cortex 3 weeks after treatment with docetaxel and doxorubicin compared with control animals. A decrease in the number of microglial cells was observed in the prefrontal cortex after treatment with cyclophosphamide, docetaxel, 5-FU, and topotecan compared with control mice. The observed decrease in microglia cells is indicative of inflammation that occurred after treatment. Overall, the magnitude of the effects was relatively modest. Therefore, we conducted a similar study with topotecan in Abcg2;Abcb1a/b knock out and wildtype FVB mice. Animals were sacrificed 3 weeks after treatment and no notable effect was seen in hippocampal cell differentiation (DCX), microglia activation, or blood vessel density. Perhaps the FVB strain is more resistant to the neurotoxic effects of topotecan which makes this not the correct model to study the mechanism of chemotherapy-induced cognitive impairment.

Surgery for chronic inguinodynia following routine herniorrhaphy: beneficial effects on dysejaculation.

PURPOSE: Pain during sexual activities and ejaculation is reported by 3-4% of men after routine inguinal herniorrhaphy. The potential beneficial effects of surgery for chronic groin pain on dysejaculation are unknown. The objective of this study was to determine dysejaculation rates in a series of patients reporting chronic postherniorrhaphy pain and evaluate the effects of tailored neurectomy on dysejaculation. METHODS: We evaluated male patients (>18 years) operated for chronic groin pain after inguinal herniorrhaphy during a 6-year time period (2004-2010). Dysejaculation was defined as a burning or searing sensation associated with ejaculation. Men reporting symptoms possibly associated with dysejaculation were sent a questionnaire investigating pain characteristics (VAS, 0-100), influence on sex life and effects of the tailored neurectomy. A Post-Herniorrhaphy Dysejaculation Score (PHDS, 0-12 points) was introduced to quantify the severity of the dysejaculation syndrome. RESULTS: A series of 100 males operated for chronic inguinal pain after standard herniorrhaphy were studied. Thirty-four men reported symptoms of dysejaculation prior to the tailored neurectomy. Sex life was negatively influenced in 20 of these, and 5 completely abstained from any sexual activity. Following surgery including tailored neurectomy, funicular release and/or mesh removal, VAS for dysejaculation pain was significantly reduced [n = 20, 55 (95% CI 47-63) versus 21 (95% CI 13-29), p < 0.001]. PHDS scores were also significantly attenuated [n = 20, 10 (3-12) versus 2 (0-10), p < 0.001]. Sex life normalized in two-thirds of these men (13/20). CONCLUSION: Dysejaculation in men suffering from chronic pain after routine inguinal herniorrhaphy is not uncommon. A tailored neurectomy, funicular release and/or mesh removal offer relief in the majority of these patients.

Risk factors associated with postnecrotizing enterocolitis strictures in infants.

INTRODUCTION: Survivors of necrotizing enterocolitis (NEC) often develop a post-NEC intestinal stricture, causing severe and prolonged morbidity. OBJECTIVES: We first aimed to determine the incidence of post-NEC strictures. Second, we aimed to determine risk factors associated with intestinal post-NEC strictures. MATERIALS AND METHODS: A total of 441 patients diagnosed with NEC Bell's stage ≥2 were retrospectively included in three academic pediatric surgical centers between January 2005 and January 2013. Clinical data were related to the occurrence of intestinal post-NEC strictures. Post-NEC strictures were defined as clinically relevant strictures with a radiological and/or surgical confirmation of this post-NEC stricture. RESULTS: The median gestational age of the 337 survivors of the acute phase of NEC was 29weeks (range 24-41) and median birth weight was 1130g (range 410-4130). Of the survivors, 37 (17%) medically treated NEC patients developed a post-NEC strictures versus 27 surgically treated NEC patients (24%; p=0.001). Highest C-reactive protein (CRP) level measured during the NEC episode was associated with the development of post-NEC strictures (OR 1.20, 95% confidence interval 1.11-1.32; p=0.03). No post-NEC strictures were detected in patients with CRP levels <46mg/L. CONCLUSION: This multicenter retrospective cohort study demonstrates an overall incidence of clinical relevant post-NEC strictures of 19%, with a higher rate (24%) in NEC cases treated surgically. Increased CRP levels during the NEC episode were associated with the development of post-NEC strictures.