Inconsistent Finding Research Articles

A systematic review of the vitamin B12, folate and homocysteine triad across body mass index.

Multiple studies have explored the association between serum or plasma vitamin B12 status and obesity, in part because of the relationship between elevated homocysteine concentrations and atherosclerosis. This review will address the inconsistent finding of these studies with the objective of determining whether vitamin B12 concentrations are lower in people with higher body mass indices. MEDLINE and EMBASE were searched to February 2017. Observational studies in general and clinical populations comparing serum/plasma B12 concentrations across groups of different body mass indices were selected. We did network and pairwise meta-analyses of serum/plasma B12, folate and homocysteine using frequentist techniques. Evidence-based items potentially indicating risk of bias were assessed. Of 844 citations, we identified 19 eligible observational studies with 7,055 participants. The overall network, while showing no significant inconsistency between indirect and direct comparisons (P=0.34), was qualitatively inconsistent. Based on the results of the meta-regression, in an exploratory sub-network meta-analysis where obesity groups were combined, we excluded disease-specific populations and studies with inadequate description of populations. The direction of the indirect and direct evidence was consistent. The pairwise results from this sub-network showed lower levels of B12 in people with higher body mass indices: obesity versus control difference in means (MD) -56pmolL-1 (95% CI -90, -23), obesity versus overweight MD -21pmolL-1 (95% CI -37, -5) and overweight versus control MD -51pmolL-1 (95% CI -51, -24). Heterogeneity remained very large for most comparisons, and all the studies carried a high risk for bias. This review did not establish an inverse association (or J-curve) between serum or plasma B12 concentrations and body mass index, but the direct pairwise evidence is consistent with an inverse association and supports further investigation.

First-line molecular therapies in the treatment of metastatic colorectal cancer - a literature-based review of phases II and III trials.

Introduction:Metastatic colorectal cancer (mCRC) is one of the most common cancers and the second leading cause of cancer worldwide. With the improvement of systemic and operative therapies, median overall survival (mOS) reached 30 months or longer. Here, we will review the use of the anti-vascular endothelial growth factor (VEGF) and anti-epidermal growth factor receptor (EGFR) antibodies in combination with doublet and triplet chemotherapy in patients with borderline and primary unresectable mCRC.Methods:Phases II and III trials were included in investigating chemotherapy in the first-line in combination with an anti-VEGF(R) or anti-EGFR in a cohort of patients with mCRC.Results:The VEGF-antibody bevacizumab has improved progression-free survival (PFS) in several phase III trials in combination with a chemotherapy doublet. More recently, a higher efficacy has been demonstrated in combination with an intensified chemotherapy including 5-fluoropyrimidine (5-FU), oxaliplatin, and irinotecan within the phase III TRIBE study. Similarly, high resectability rates have been shown in the phase II Olivia trial for patients with liver-limited disease with an intensified chemotherapeutic regime. However, this increase in efficacy was accompanied by an increase in toxicity as well. The efficacy of the EGFR-antibodies cetuximab and panitumumab has been shown in several phase III trials, but their use is restricted to patients whose tumors are RAS wildtype (WT). The phase II trials, CELIM and PLANET, demonstrated a favorable long-term survival for patients with initially non-resectable colorectal liver metastases who respond to conversion therapy with EGFR-antibodies and undergo secondary resection. The CLGB and FIRE-3 trials delivered an inconsistent finding whether anti-VEGF or -EGFR treatment is the better option in the first-line setting. However, there is increasing evidence from post hoc analyses of prospective clinical trials that patients with left-sided tumors benefit from EGFR-directed combination therapy in terms of prolongation of OS and PFS compared with limited, if any, benefit for those with right-sided tumors.Conclusion:Both anti-VEGF- and anti-EGFR-directed therapies represent efficient treatment options for patients with mCRC in the first line. For patients with RAS WT, left-sided tumor anti-EGFR-based treatment is recommended. Intensified regimens can be offered initially to unresectable patients in order to achieve resectability at a price of higher toxicity.

Malignant tumors misdiagnosed as benign vascular anomalies.

Malignant soft tissue tumors are rare and difficult to diagnose in children. These can initially be misdiagnosed as benign vascular anomalies. Management of these two conditions differs drastically and delay in diagnosis may impact overall survival. To predict qualities that may increase the index of suspicion for malignancy in patients presenting with lesions initially considered vascular anomalies. A retrospective review at a quaternary hemangioma and vascular malformation center of all patients who presented between 2008 and 2016 with an initial diagnosis of a benign vascular malformation, which on further work-up was noted to be a malignancy. Demographics, clinical presentation, and laboratory and radiologic studies were analyzed. Eleven patients were identified; the median age at presentation was 2 months (0-24years). Ten out of 11 lesions had rapid growth, which prompted biopsy. Pain was an inconsistent finding (36%). Tumor markers were positive in only one case. Median follow-up was 3 years (range 6 months to 8 years); seven patients have no evidence of disease, two patients are under treatment for progression or relapse of disease, and two patients have died. Although malignant vascular tumors are rare, a clear index of suspicion needs to be maintained particularly with rapid growth or increasing symptoms. Differentiation of malignant tumor from benign lesions relies on the comprehensive evaluation of clinical manifestations, evolution of the lesion, and abnormal clinical behavior, by an experienced multidisciplinary vascular malformation team. There should be a low threshold for biopsy of unclear vascular lesions.

Stimulated by Novelty? The Role of Psychological Needs and Perceived Creativity.

In the current research, we aimed to address the inconsistent finding in the brainstorming literature that cognitive stimulation sometimes results from novel input, yet other times from non-novel input. We expected and found, in three experiments, that the strength and valence of this relationship are moderated by people’s psychological needs for structure and autonomy. Specifically, the effect of novel input (vs. non-novel input), through perceived creativity, on cognitive stimulation was stronger for people who were either low in need for structure or high in need for autonomy. Also, when the input people received did not fit their needs, they experienced less psychological cognitive stimulation from this input (i.e., less task enjoyment and feeling more blocked) compared with when they did not receive any input. Hence, to create the ideal circumstances for people to achieve cognitive stimulation when brainstorming, input novelty should be aligned with their psychological needs.

Event-based analysis of the association between alcohol use and unsafe sex in seven sub-Saharan African countries

Aims: To examine the association between alcohol consumption at last sex and unsafe sex in seven countries in sub-Saharan Africa.Design: Multivariable logistic regression of unsafe sex was performed using cross-sectional data with a stratified sample design from seven countries.Setting: The study uses data from the Demographic and Health Surveys of Lesotho, Kenya, Mozambique, Swaziland, Uganda, Zambia, and Zimbabwe.Participants: Men and women age 15–49 years with data available on alcohol consumption and who have had sex in the last 12 months were included in the analysis.Measures: The main independent variable is alcohol consumption at last sex with a non-cohabiting partner.Findings: The analysis has shown that alcohol consumption was a strong predictor of unsafe sex for all surveys except for women in Kenya. Age and number of sexual partners were also strong predictors of unsafe sex.Conclusions: The findings indicate that there is a positive link between alcohol consumption and unsafe sex in all countries except for Kenya among women. The inconsistent finding in Kenya requires further study. One of the main limitations of the analysis is the low number of observations found for women and men who reported drinking at last sex with a non-cohabiting partner.

Location of monoclonal peak as a tool in checking specimen integrity

ObjectivesSerum protein electrophoresis is a commonly used test in the diagnosis and follow-up of patients with monoclonal gammopathies. The practice of documenting the location of the peak may serve as delta check flags in SPEP samples. MethodsWe report on the inconsistent finding on two tests performed about three months apart. The inconsistency was discovered due to recognition of the change in the location of the monoclonal immunoglobulin on protein electrophoresis. ResultsRepeat testing with a third specimen revealed that the first test was run on a wrong specimen. ConclusionRecording the location of the monoclonal spike is recommended to serve as an additional “delta” check.

The importance of early diagnosis of subdural arteriovenous fistula for clinical recovery.....

Subdural arteriovenous fistulas (SDAVF) represent a rare disease of the spinal cord with diverse neurological complains resembling polyneuropathies of myelopathies. Due to the absence of specific clinical signs the diagnosis relies upon the MRI findings, which consists of the following classical triad of 1) dilated vessels in the subdural space, 2) central spinal cord edema and 3) contrast enhancement of the affected segments. A fourth yet inconsistent finding is an enlarged conus medullaris. The triad is however often incomplete and in the absence of the engorged perimedullary vessels the diagnosis can remains elusive for an extensive period of time and until an advanced level of clinical disability is reached. Unlike most other immune of infectious causes of medullary dysfunction, SDAVF is a treatable condition, surgical treatment usually stopping the progression of neurological complains. Therefore, an early diagnosis is the most important factor associated with neurological recovery. The aim of this case report is to illustrate how essential a prompt diagnosis is by presenting two patients with very different clinical outcomes based on the time from the initial complains to the correct diagnosis.

Increased Cognitive Control During Execution of Finger Tap Movement inPeople with Parkinson's Disease.

Previous studies employed demanding and complex hand tasks to study the brain activation in people with Parkinson's Disease (PD). There is inconsistent finding about the cerebellar activity during movement execution of this patient population. This study aimed to examine the brain activation patterns of PD individuals in the on-state and healthy control subjects in a simple finger tapping task. Twenty-seven patients with PD and 22 age-matched healthy subjects were recruited for the study. Subjects were instructed to perform simple finger tapping tasks under self- and cue-initiated conditions in separate runs while their brain activations were captured using fMRI. Healthy subjects had higher brain activity in contralateral precentral gyrus during the self-initiated task, and higher brain activity in the ipsilateral middle occipital gyrus during the cue-initiated task. PD patients had higher brain activity in the cerebellum Crus I (bilateral) and lobules VI (ipsilateral) during the self-initiated task and higher brain activity in the contralateral middle frontal gyrus during the cue-initiated task. When compared with healthy controls, PD patients had lower brain activity in the contralateral inferior parietal lobule during the self-initiated task, and lower brain activity in the ipsilateral cerebellum lobule VIII, lobule VIIB and vermis VIII, and thalamus during the cue-initiated task. Conjunction analysis indicated that both groups had activation in bilateral cerebellum and SMA and ipsilateral precentral gyrus and postcentral gyrus during both self- and cue-initiated movement. Individuals with PD exhibited higher brain activity in the executive zone (cerebellum Crus I and II) during self-initiated movement, and lower brain activity in the sensorimotor zone (i.e. lobule VIIb and VIII of the cerebellum) during cue-initiated movement. The findings suggest that individuals with PD may use more executive control when performing simple movements.

The Anterolateral Ligament of the Knee: An Inconsistent Finding in Pediatric Cadaveric Specimens

The anterolateral ligament (ALL) of the knee has been identified as a structure that limits internal rotation, and thus, affects the pivot shift mechanism. It has previously been reported in a high percentage of adult subjects. The purpose of the current study was to evaluate whether the ALL could be identified on pediatric cadaveric knee specimens and compare these findings to previously published reports. Eight skeletally immature cadaver knee specimens were examined through gross dissection: ages 3 months, 4 months, 1 year, 2 years, 3 years, 3 years, 8 years, and 10 years. There were 3 male and 5 female (7 right, 1 left) specimens. The presence or absence of the ALL was documented in each specimen, through dissection, intermittent internal and external rotation of the tibia, and anterior translation of the tibia, to produce tension of the lateral collateral tissues and joint capsule. These dissections were performed by a group of fellowship-trained orthopaedic surgeons. The iliotibial band, entire lateral joint capsule, lateral collateral ligament, and popliteus were readily identified in each specimen. In 7 specimens, a distinct ALL structure was not identified during dissection. The ALL was identified in 1 of 8 specimens (1-year-old female, right knee). The ALL was further delineated under applied internal rotational stress. Previous research has suggested that this ligament is present in the majority of adult specimens. This finding was not reproduced in the current study of pediatric cadaveric specimens, where only one of 8 specimens had an identifiable ALL. This suggests that this ligament may develop later in life, after physiological loads are applied to the joint capsule. Further research in both adult and pediatric knees needs to be conducted to further elucidate the development of this ligament, and the role of this structure in knee stability. The ALL is a knee ligament that has been described in adults. However, it is unclear whether this structure is present or fully developed in younger populations. The current study sought to identify the ALL in pediatric cadaver knee specimens, identifying this structure in only one of 8 specimens. The findings of this study suggest that the ALL may be an inconsistent structure in the pediatric population.

(446) - Metabolic Profile of Broncho-Alveolar Lavage Fluid in Lung Transplant Recipients Suggests Potential Early Biomarkers of Bronchiolitis Obliterans Syndrome

Purpose: The definition of antibody-mediated rejection (AMR) after lung transplantation (LT) has undergone revision as recognition of this entity has increased. Although considered a key criterion for the diagnosis of AMR, C4d deposition has been an inconsistent finding. We compared outcomes of LT recipients who developed C4d-negative AMR to those who developed C4d-positive AMR. Methods: We performed a retrospective cohort study of patients transplanted between 1/2006 and 7/2015, and identified those who developed AMR defined as acute allograft dysfunction, DSA, and a lung injury pathology. We excluded those who did not have C4d staining at the time of diagnosis (n= 20). We grouped those who developed AMR into a C4d-positive cohort and a C4d-negative cohort and compared outcomes of the 2 groups using Kaplan-Meier method and the log rank test. Results: 37 patients developed AMR during the study period; 15 developed C4d-positive AMR and 22 developed C4d-negative AMR. All patients with AMR were treated with IVIG. Of these, 36 were treated with rituximab, 7 with bortezomib, and 9 with plasma exchange (PLEX) (Table 1). Survival and CLAD-free survival after the diagnosis of AMR were poor in both groups, and there was no significant difference in either survival or CLAD-free survival between the 2 groups (Figure 1). Conclusion: A large proportion of patients with AMR in this cohort did not have C4d deposition. However, there was no significant difference in outcome between those who had C4d-negative and those who had C4d-positive AMR. These findings suggest that C4d deposition may not be a necessary criterion for the diagnosis of AMR.

The Association Between Built Environment Attributes and Physical Activity in East Asian Adolescents: A Systematic Review.

Asian adolescents living in Australia and England were found to be less active than their Western peers. We aimed to systematically examine evidence of the associations between attributes of the built environment and physical activity in adolescents dwelling in East Asian countries. A total of 10 electronic databases for relevant observational studies without time limit were searched. Five studies met the eligibility criteria, which involved a total of 43 817 schoolchildren aged 11 to 17 years. The majority of the built environment attributes measured was significantly associated with reported physical activity. Difficult access to public facilities was associated with physical inactivity. Inconsistent finding of the association between residential density and physical activity was found. Further studies comparing participants from different Asian countries using a longitudinal design with an appropriate period of follow-up and both objective and reported measures of built environment attributes and physical activity are needed.

Cretinism muscular hypertrophy: An unorthodox reflection

The Kocher Debre Semelaigne Syndrome (KDSS) is also known as cretinism muscular hypertrophy. It is an unusual presentation in intellectually deficit children, commonly associated with congenital or iatrogenic hypothyroidism. The incidence of KDSS is less than 10%. It is more common in males, consanguineous marriage and age range from 18 months to 10 years [4]. The creatinine phosphokinase (CPK) is usually elevated [5]. It might be misdiagnosed particularly when other classical features of hypothyroidism are not dominant at first presentation. We present a case of 15-year-old intellectually deficit female. Her epilepsy had been managed on phenytoin for a decade. She had rigidity, leg cramps, malaise, oliguria, fever, myxedema, delayed deep tendon reflexes, calf muscle hypertrophy and agitation. Her agitation was controlled by haloperidol, which worsened the condition by altering her mental status. The patient was initially managed on line of Neuroleptic Malignant Syndrome due to raised CPK of 40,680 IU/L and mixed presentation. Nevertheless, no significant change was noticed until thyroid profile was done to exclude alternative resources. Thyroid stimulating hormone (TSH) was 74.5 IU, free T3 1.22 ng/dL, and free T4 0.43 ng/dL. Thyroxine was started along with change in anti-epileptic and recovery was observed within five days. This case report highlights the inconsistent finding from previously reported cases of KDSS. The female gender, non-consanguineous marriage, slightly delayed onset with primarily neuromuscular symptoms, and raised CPK is not the frequent demonstration in KDSS. On parallel, thyroid work-up is not routinely done, which can lead to misdiagnosis and mismanagement.References not available.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Microsomal epoxide hydrolase gene polymorphisms and susceptibility to prostate cancer: A systematic review.

Microsomal epoxide hydrolase (mEH) is a crucial biotransformation enzyme that has capability to metabolize a large number of structurally divergent, highly reactive epoxides, and numerous environmentally exposed carcinogens. It catalyzes the conversion of xenobiotic epoxide compounds into more polar diol metabolites and may play important part of the enzymatic defense against adverse effects of foreign compounds. Most commonly, two functional polymorphisms affecting mEH enzyme activity have been identified: One in exon 3 and other in exon 4 of the mEH gene, which results in His113Tyr and Arg139His amino acid substitutions, respectively. Recent reports have shown that polymorphisms in mEH gene loci may an important risk factor for susceptibility of prostate cancers (PCs), worldwide, but inconsistent finding were also be illustrated. To the best of our knowledge, globally, there is no any systematic review has been published related to mEH gene polymorphisms and PC risk. Thus, in the current review, we have discussed the association between mEH gene polymorphisms, gene-environmental interaction, and PC risk.

HBV Infection Status and the Risk of Cholangiocarcinoma in Asia: A Meta-Analysis.

Background. The inconsistent finding was between hepatitis B virus (HBV) infections and cholangiocarcinoma (CCA). This meta-analysis is to explore this relationship in Asia. Methods. A literature search was performed using PubMed, Web of Science, and Cochrane Library to October 30, 2015. Pooled incidence rate and OR with 95% CI were calculated using STATA 11.0. Results. Thirty-nine studies were included. The pooled incidence rate of CCA patients with HBV infection was 31% (95% CI 22%–39%). The pooled OR showed increased risk of CCA incidence with HBV infection (OR = 2.72, 95% CI 1.90–3.88), especially in ICC (OR = 3.184, 95% CI 2.356–4.302), while it showed no risk in ECC (OR = 1.407, 95% CI 0.925–2.141). Also, the pooled OR showed increased risk of ICC and ECC incidence (OR = 6.857, 95% CI 4.421–10.633 and OR = 1.740, 95% CI 1.260–2.404) in patients with HBsAg+/HBcAb+. The pooled OR showed increased risk of ICC incidence (OR = 1.410, 95% CI 1.095–1.816) in patients with HBsAg−/HBcAb+. Conclusion. It is suggested that HBV infection is associated with an increased risk of CCA in Asia. Two HBV infection models (HBsAg+/HBcAb+ and HBsAg−/HBcAb+) increase the risk of CCA, and patients with HBsAg−/HBcAb+ also had a risk of ICC. This trial is registered with PROSPERO CRD42015029264.

RARE-17NEUROENDOCRINE CARCINOMA IN THE BRAIN

OBJECT: Neuroendocrine carcinoma (NEC) is a malignant tumor that usually arises in the lung, pancreas and gastrointestinal tract. Brain metastasis of NEC is merely reported. Herein, we report two cases of NEC in the brain mimicking glioblastoma (GBM). CASES: Both patients were in their 60s, cystic lesions with peritumoral edema affected the temporal lobe. Cyst walls were thin but hyperintense in diffusion weighted images implying increased cellularity. Positron emission tomography (PET) revealed malignant nature by strong uptake of methionine (MET), fluorothymidine (FLT) and fluoromisonidazole likewise GBM. However, fluorodeoxyglucose (FDG) indicated relatively weak uptakes compared as GBM. Both tumors were resected under the preoperative diagnosis of GBM, however, pathological diagnoses were NEC by immunohistochemical finding of negative GFAP and positive markers of neuroendocrine differentiation. Systemic examination failed to reveal the origin. Both cases underwent radiotherapy. One case was lost by spinal dissemination 11 months after the operation. DISCUSSION: FDG-PET of neuroendocrine tumor in the extracranial lesion does not always demonstrate strong uptake. FDG-PET for NEC in the brain could be less accumulated than GBM, while it should be evaluated keeping in mind that the background level of FDG would be high in the brain tissue. In case of malignant tumors endorsed by other tracer such as MET and FLT, inconsistent FDG-PET finding might be useful for the diagnosis of NEC in the brain.

Gender aspects in postoperative pain.

Gender differences are well known in clinical pain and pain-related diseases. However, studies analyzing gender differences in postoperative pain yielded inconsistent finding. The aim of this review was to summarize recent findings on this matter. We found 58 recently published studies (September 2013-March 2015) assessing gender differences on patients undergoing various surgical procedures. Studies focusing on one type or one category of surgical procedures suggest that women report higher postoperative pain scores after thoracic, cardiac and neurosurgical procedures. However, gender differences after abdominal and orthopedic surgeries were inconsistent and after oral surgery inexistent. Studies including various surgical procedures indicate a more consistent gender difference, presumably because of the greater number of patients included. However, the net difference in almost every study was small. Women seem to be at higher risk to develop severe postoperative pain but gender differences seem to be small and of low clinical relevance. We argue that major confounders may explain discrepancies between studies. Large prospective studies and registry data assessing gender aspects including confounders need to be done in the future.

Intact Bone Vitality and Increased Accumulation of Nonmineralized Bone Matrix in Biopsy Specimens of Juvenile Osteochondritis Dissecans

Background: Although commonly proposed to be the starting point of juvenile osteochondritis dissecans (JOCD), avascular osteonecrosis (AVN) has been an inconsistent finding in histological studies. Analysis of early-stage lesions is required to elucidate the origins of OCD and justify proper treatment. Purpose: To analyze histological sections of JOCD lesions with special emphasis on bone vitality. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Of 64 patients with 74 JOCD lesions (20 females, mean age, 11.4 years; 44 males, mean age, 12.7 years), 34 required surgery because of lesion instability or failed nonoperative treatment. From 9 patients, 11 histological specimens were obtained. Lesions were classified according to the International Cartilage Repair Society (ICRS). Two additional histological control sections were harvested from children without JOCD manifestation. Undecalcified histological sections were histomorphometrically analyzed. To analyze the skeletal health of the patients, biochemical analyses with special emphasis on bone metabolism were performed. Results: Histologically, no osteonecrosis was visible in any of the cases. Osteocyte distribution was similar among OCD lesions and controls. ICRS OCD I lesions (n = 6) showed no intralesional separation. In ICRS OCD II and III lesions (n = 5), there was a subchondral fracture concomitant with histological characteristics of active repair mechanism (increased bone formation: osteoid volume P = .008, osteoblast number P = .046; resorption: osteoclast number P = .005; and tissue fibrosis compared with controls). Instead, in ICRS OCD I lesions, subchondral osteoid volume (P = .010) and osteoblast number (P = .046) were significantly increased compared with controls; however, no active repair mechanisms (no increased bone resorption or fibrous tissue) were detected, suggesting a focal lack of mineralization. Fifty-seven of 64 patients (89.1%) showed a vitamin D deficiency. The median vitamin D serum level of the patients with ICRS OCD I lesions was 13.6 µg/L. Conclusion: In the present study, osteonecrosis was not found in histological specimens of JOCD. As a secondary finding, focal accumulations of nonmineralized bone matrix indicating a lack of mineralization in ICRS OCD I lesions were revealed. This finding correlated with a low level of vitamin D in the affected children.

Routine Primary PCI; Whether and When Necessary for the Management of NSTEMI—An Evidence Based Evaluation

Non ST elevated myocardial infarction (NSTEMI) accounts for a significant portion of the hospitalizations due to acute coronary syndromes worldwide and is posing a huge challenge towards the health care cost globally. This signifies the need for proper triage and management stratification for the best utilization of the health care resources. Primary Percutaneous Coronary Intervention (PCI) with early revascularization is a new emerging invasive technique and application of this technique is increasing tediously among the clinicians. However, the current body of evidences is divided between the efficacy, need and critical timing of PCI compared to conservative management in the treatment protocol for NSTEMI. A review of trials done comparing the early use of PCI versus conservative management indicates inconsistent finding with strong evidence towards early use of PCI in moderate to high-risk NSTEMI patients.

Listeria Brainstem Encephalitis in Small Ruminants: Correlation of Magnetic Resonance Imaging and Histopathology.

Listeria Brainstem Encephalitis in Small Ruminants: Correlation of Magnetic Resonance Imaging and Histopathology Christina Stahl1, Anna Oevermann2, Daniela Gorgas1 1Clinical Radiology, Department of Clinical Veterinary Medicine, Vetsuisse-Faculty, University of Bern, Switzerland 2Neurocenter, Department of Clinical Research and Veterinary Public Health, Vetsuisse-Faculty, University of Bern, Switzerland Abstract Brainstem encephalitis is an intriguing form of Listeria monocytogenes central nervous system (CNS) infection in humans and ruminants and has a high fatality rate. However, intra vitam diagnosis remains difficult in both species (1, 2). We performed MRI of affected small ruminants, in which Listeria brainstem encephalitis is a common CNS disease, and correlated MRI features with histopathology in order to define MRI criteria for the diagnosis of listeria brainstem encephalitis. Fifteen small ruminants (nine sheep, six goats) with listeriosis underwent MRI examination of the brain using a 0.3 T system (five animals) and 1.0 T system (ten animals) including T2w, FLAIR and T1w sequences pre and post Gadolinium administration. Listeria brainstem encephalitis was confirmed by histopathology, and histopathological changes were correlated to MRI features. On MRI, lesions were best visualized in T2-weighted sequences. In all animals they were characterized by asymmetric increased signal intensity in the rhombencephalon in T2w and FLAIR sequences. The lesions showed a variable pattern and distribution, ranging from patchy with ill defined borders to diffusely affecting the entire cross-sectional area of the brainstem. Few animals had lesions in the diencephalon (three animals), whilst histopathologically detectable lesions commonly extended to the diencephalon and involved cranial nerve roots (twelve animals). The lesions were iso- to mildly hypointens in T1w sequence. Mild to moderate patchy or ring-like contrast uptake was observed in the rhombencephalon of five animals (one sheep, four goats), which showed vascular damage and perivascular fibrin accumulation on light microscopy. In the brainstem, the asymmetric T2-hyperintense lesions observed by MRI correlated well with the inflammatory infiltrates observed in histopathology (3). However, lesions in the diencephalon, cranial nerves and meninges of rostral brain areas were rarely detected by MRI, indicating that MRI underestimates involvement of the rostral brain and brain associated structures. Contrary to reported human cases of neurolisteriosis (4), contrast uptake was an inconsistent finding occurring in the rhombencephalon of only five animals.

Diaphragmatic neuromechanical coupling and mechanisms of hypercapnia during inspiratory loading

We hypothesized that improved diaphragmatic neuromechanical coupling during inspiratory loading is not sufficient to prevent alveolar hypoventilation and task failure, and that the latter results primarily from central-output inhibition of the diaphragm and air hunger rather than contractile fatigue. Eighteen subjects underwent progressive inspiratory loading. By task failure all developed hypercapnia. Tidal transdiaphragmatic pressure (ΔPdi) and diaphragmatic electrical activity (ΔEAdi) increased during loading – the former more than the latter; thus, neuromechanical coupling (ΔPdi/ΔEAdi) increased during loading. Progressive increase in extra-diaphragmatic muscle contribution to tidal breathing, expiratory muscle recruitment, and decreased end-expiratory lung volume contributed to improved neuromechanical coupling. At task failure, subjects experienced intolerable breathing discomfort, at which point mean ΔEAdi was 74.9±4.9% of maximum, indicating that the primary mechanism of hypercapnia was submaximal diaphragmatic recruitment. Contractile fatigue was an inconsistent finding. In conclusion, hypercapnia during acute loading primarily resulted from central-output inhibition of the diaphragm suggesting that acute loading responses are controlled by the cortex rather than bulbopontine centers.