Stroke and cancer.

Association between stroke and cancer is well-established and has led to a growing literature over the past decades. Risk of ischemic and hemorrhagic stroke is increased among patients with newly diagnosed cancer and 5-10% of stroke patients bear an active cancer. All cancers are concerned, but hematological malignancy in childhood and adenocarcinoma from lung, digestive tract and pancreas in adults are most usually identified. Unique stroke mechanisms are dominated by hypercoagulation, a condition that may lead to both arterial and venous cerebral thromboembolism. Direct tumor effects, infections and therapies may also play some active role in stroke happening. Magnetic Resonance Imaging (MRI) is helpful in: i) detecting typical patterns of ischemic stroke in cancer patients (i.e. concomitant strokes in multiple arterial territories); ii) distinguishing spontaneous intracerebral hemorrhage from tumor bleeding. Recent literature suggests that acute treatment using intravenous thrombolysis is safe in non-metastatic cancer patients. First results from endovascular procedures are reassuring, although arterial reobstruction is more frequent than in cancer-free patients. Prognosis is worse in patients with compared to those without cancer and mostly depends upon several predictors such as the initial stroke severity and the presence of metastasis. In the present review, we aim to provide some practical responses to neurologists about the stroke-cancer association, including prevalence, stroke mechanisms, biomarkers indicative for an occult cancer, influence of neoplasia on acute and long-term stroke treatments, and prognosis.

A partially differentiated interior for (1) Ceres deduced from its gravity field and shape.

Remote observations of the asteroid (1) Ceres from ground- and space-based telescopes have provided its approximate density and shape, leading to a range of models for the interior of Ceres, from homogeneous to fully differentiated. A previously missing parameter that can place a strong constraint on the interior of Ceres is its moment of inertia, which requires the measurement of its gravitational variation together with either precession rate or a validated assumption of hydrostatic equilibrium. However, Earth-based remote observations cannot measure gravity variations and the magnitude of the precession rate is too small to be detected. Here we report gravity and shape measurements of Ceres obtained from the Dawn spacecraft, showing that it is in hydrostatic equilibrium with its inferred normalized mean moment of inertia of 0.37. These data show that Ceres is a partially differentiated body, with a rocky core overlaid by a volatile-rich shell, as predicted in some studies. Furthermore, we show that the gravity signal is strongly suppressed compared to that predicted by the topographic variation. This indicates that Ceres is isostatically compensated, such that topographic highs are supported by displacement of a denser interior. In contrast to the asteroid (4) Vesta, this strong compensation points to the presence of a lower-viscosity layer at depth, probably reflecting a thermal rather than compositional gradient. To further investigate the interior structure, we assume a two-layer model for the interior of Ceres with a core density of 2,460-2,900 kilograms per cubic metre (that is, composed of CI and CM chondrites), which yields an outer-shell thickness of 70-190 kilometres. The density of this outer shell is 1,680-1,950 kilograms per cubic metre, indicating a mixture of volatiles and denser materials such as silicates and salts. Although the gravity and shape data confirm that the interior of Ceres evolved thermally, its partially differentiated interior indicates an evolution more complex than has been envisioned for mid-sized (less than 1,000 kilometres across) ice-rich rocky bodies.

Diagnostic and therapeutic approach to adult central nervous system vasculitis.

The clinical manifestations of central nervous system (CNS) vasculitis are highly variable. In the absence of a positive CNS biopsy, CNS vasculitis is particularly suspected when markers of both vascular disease and inflammation are present. To facilitate the clinical and therapeutic approach to this rare condition, CNS vasculitis can be classified according to the size of the involved vessels. Vascular imaging is used to identify medium vessel disease. Small vessel disease can only be diagnosed with a CNS biopsy. Medium vessel vasculitis usually presents with focal neurological signs, while small vessel vasculitis more often leads to cognitive deficits, altered level of consciousness and seizures. Markers of CNS inflammation include cerebrospinal fluid pleocytosis or elevated protein levels, and vessel wall, parenchymal or leptomeningeal enhancement. The broad range of differential diagnoses of CNS vasculitis can be narrowed based on the disease subtype. Common mimickers of medium vessel vasculitis include intracranial atherosclerosis and reversible cerebral vasoconstriction syndrome. The diagnostic workup aims to answer two questions: is the neurological presentation secondary to a vasculitic process, and if so, is the vasculitis primary (i.e., primary angiitis of the CNS) or secondary (e.g., to a systemic vasculitis, connective tissue disorder, infection, malignancy or drug use)? In primary angiitis of the CNS, glucocorticoids and cyclophosphamide are most often used for induction therapy, but rituximab may be an alternative. Based on the available evidence, all patients should receive maintenance immunosuppression. A multidisciplinary approach is necessary to ensure an accurate and timely diagnosis and to improve outcomes for patients with this potentially devastating condition.

Prevalence and prospective evaluation of cognitive dysfunctions after SARS due to SARS-CoV-2 virus. The COgnitiVID study.

OBJECTIVE: COVID-19 due to SARS-CoV-2 virus is a new cause of severe acute respiratory syndrome (SARS). Little is known about the short-term cognitive prognosis for these patients. We prospectively evaluated basic cognitive functions shortly after care in the intensive care unit (ICU) and three months later in post-ICU COVID-19 patients. MATERIAL AND METHODS: We performed a prospective single-center study in our institution in Paris. Patients with SARS-CoV-2 SARS were prospectively recruited via our ICU. Patients were evaluated using standardized cognitive tests at baseline and at three months' follow-up. Our primary endpoint was the evolution of the following five global tests: MMSE, FAB, oral naming test, Dubois five words test and MADRS. RESULTS: We explored 13 patients at baseline and follow-up. All patients had cognitive impairment at baseline but they all improved at three months, significantly on two of the five global tests after Bonferroni correction for multiple testing: MMSE (median 18 (IQR [15-22]) and 27 (IQR [27-29]) respectively, P=0.002) and FAB test (median 14 (IQR [14-17]) and 17 (IQR [17,18]) respectively, P=0.002). CONCLUSIONS: We report here the first longitudinal data on short-term cognitive impairment after intensive care in COVID-19 patients. We found acute and short-term cognitive impairment but significant improvement at three months. This pattern does not seem to differ from other causes of post-intensive care syndrome.

[Network model of mental disorders: Application and interest in post-stroke depression]. / Modèle en réseau et troubles mentaux : application et intérêts dans la dépression post-AVC.

In contrast to the classic models in psychopathology, the network model considers that the temporal interactions between symptoms are the causes of their occurrence. This model could also be particularly suitable for understanding the processes involved in post-stroke depression. The aim of this paper is to perform a network analysis in order to describe the temporal dynamic of the links existing between depression symptoms during the acute phase after stroke. Twenty-five patients (64% male, mean age 58.1±14.9 years old) hospitalized for a minor stroke (no neurocognitive or motor impairment) were involved in an Ecological Momentary Assessment methodology-based study. They used a smartphone application in order to complete four brief questionnaires each day during the week after hospital discharge. The questionnaire included 7-point Likert scales to measure the severity of the following depressive symptoms: sadness, anhedonia, fatigue, diminished concentration ability, negative thoughts on oneself, pessimism. We used Multilevel Vector Autoregressive analysis to describe the temporal links between those symptoms. We used the software R 3.6.0 with the mlVAR package. The p-value was set at .05. The results show two independent symptoms networks. The first one involves the anhedonia, fatigue, negative thoughts on oneself and sadness. It shows that: anhedonia predicts the activation of later fatigue (ß=0.135, P=0.037) and later negative thoughts (ß=0.152, P=0.019); negative thoughts predict later negative thoughts (ß=0.143, P=0.028) and later sadness (ß=0.171, P=0.021); fatigue predicts later fatigue (ß=0.261, P<0.000). Pessimism and diminished concentration ability compose the second network, and the results show that pessimism predicts later pessimism (ß=0.215, P=0.012) and later diminished concentration ability (ß=0.178, P=0.045). On the one hand, anhedonia thus plays an important role in the initial and progressive activation of the other symptoms of its network. On the other hand, the cognitive symptoms (negative thoughts and pessimism) cause the deterioration of the mood and the deficit of attentional abilities. Using behavioral and cognitive strategies to support patients after hospital discharge would reduce the risk of depressive complications after a stroke. This study provides convincing empirical elements for the interest of the network model for research in psychopathology and the clinical implications and perspectives allowed by network analysis.

In-flight characterization of the lunar orbiter laser altimeter instrument pointing and far-field pattern.

The Lunar Orbiter Laser Altimeter (LOLA) aboard the Lunar Reconnaissance Orbiter (LRO) has collected nearly seven billion measurements of surface height on the Moon with an absolute accuracy of ∼1 m and a precision of ∼10 cm. Converting time-of-flight laser altimeter measurements to topographic elevations requires accurate knowledge of the laser pointing with respect to the spacecraft body-fixed coordinate system. To that end, we have utilized altimetric crossovers from LOLA, as well as bidirectional observations of the LOLA laser and receiver boresight via an Earth-based laser tracking ground station. Based on a sample of ∼780,000 globally distributed crossovers from the circular-orbit phase of LRO's mission (∼27 months), we derive corrections to the LOLA laser boresight. These corrections improve the cross-track and along-track agreement of the crossovers by 24% and 33%, respectively, yielding RMS residuals of ∼10 m. Since early in the LRO mission, the bidirectional laser tracking experiments have confirmed a pointing anomaly when the LOLA instrument is facing toward deep space or the night side of the Moon and have allowed the reconstruction of the laser far-field pattern and receiver telescope pointing. By conducting such experiments shortly after launch and nearly eight years later, we have directly measured changes in the laser characteristics and obtained critical data to understand the laser behavior and refine the instrument pointing model. The methods and results presented here are also relevant to the design, fabrication, and operation of future planetary laser altimeters and their long-term behavior in the space environment.

Dual role of tumour-infiltrating T helper 17 cells in human colorectal cancer.

BACKGROUND: The immune contexture predicts prognosis in human colorectal cancer (CRC). Whereas tumour-infiltrating CD8+ T cells and myeloid CD16+ myeloperoxidase (MPO)+ cells are associated with favourable clinical outcome, interleukin (IL)-17-producing cells have been reported to correlate with severe prognosis. However, their phenotypes and functions continue to be debated. OBJECTIVE: To investigate clinical relevance, phenotypes and functional features of CRC-infiltrating, IL-17-producing cells. METHODS: IL-17 staining was performed by immunohistochemistry on a tissue microarray including 1148 CRCs. Phenotypes of IL-17-producing cells were evaluated by flow cytometry on cell suspensions obtained by enzymatic digestion of clinical specimens. Functions of CRC-isolated, IL-17-producing cells were assessed by in vitro and in vivo experiments. RESULTS: IL-17+ infiltrates were not themselves predictive of an unfavourable clinical outcome, but correlated with infiltration by CD8+ T cells and CD16+ MPO+ neutrophils. Ex vivo analysis showed that tumour-infiltrating IL-17+ cells mostly consist of CD4+ T helper 17 (Th17) cells with multifaceted properties. Indeed, owing to IL-17 secretion, CRC-derived Th17 triggered the release of protumorigenic factors by tumour and tumour-associated stroma. However, on the other hand, they favoured recruitment of beneficial neutrophils through IL-8 secretion and, most importantly, they drove highly cytotoxic CCR5+CCR6+CD8+ T cells into tumour tissue, through CCL5 and CCL20 release. Consistent with these findings, the presence of intraepithelial, but not of stromal Th17 cells, positively correlated with improved survival. CONCLUSIONS: Our study shows the dual role played by tumour-infiltrating Th17 in CRC, thus advising caution when developing new IL-17/Th17 targeted treatments.

Meta-analysis of single-port versus conventional laparoscopic cholecystectomy comparing body image and cosmesis.

BACKGROUND: The purpose of this study was to evaluate improvements in cosmetic results and postoperative morbidity for single-incision laparoscopic cholecystectomy (SILC) in comparison with multiport laparoscopic cholecystectomy (MLC). METHODS: A literature search was undertaken for RCTs comparing SILC with MLC in adult patients with benign gallbladder disease. Primary outcomes were body image and cosmesis scores at different time points. Secondary outcomes included intraoperative and postoperative complications, postoperative pain and frequency of port-site hernia. RESULTS: Thirty-seven RCTs were included, with a total of 3051 patients. The body image score favoured SILC at all time points (short term: mean difference (MD) -2·09, P < 0·001; mid term: MD -1·33, P < 0·001), as did the cosmesis score (short term: MD 3·20, P < 0·001; mid term: MD 4·03, P < 0·001; long-term: MD 4·87, P = 0·05) and the wound satisfaction score (short term: MD 1·19, P = 0·03; mid term: MD 1·38, P < 0·001; long-term: MD 1·19, P = 0·02). Duration of operation was longer for SILC (MD 13·56 min; P < 0·001) and SILC required more additional ports (odds ratio (OR) 6·78; P < 0·001). Postoperative pain assessed by a visual analogue scale (VAS) was lower for SILC at 12 h after operation (MD in VAS score -0·80; P = 0·007). The incisional hernia rate was higher after SILC (OR 2·50, P = 0·03). All other outcomes were similar for both groups. CONCLUSION: SILC is associated with better outcomes in terms of cosmesis, body image and postoperative pain. The risk of incisional hernia is four times higher after SILC than after MLC.

Cuticle hydrolysis in four medically important fly species by enzymes of the entomopathogenic fungus Conidiobolus coronatus.

Entomopathogenic fungi infect insects via penetration through the cuticle, which varies remarkably in chemical composition across species and life stages. Fungal infection involves the production of enzymes that hydrolyse cuticular proteins, chitin and lipids. Host specificity is associated with fungus-cuticle interactions related to substrate utilization and resistance to host-specific inhibitors. The soil fungus Conidiobolus coronatus (Constantin) (Entomophthorales: Ancylistaceae) shows virulence against susceptible species. The larvae and pupae of Calliphora vicina (Robineau-Desvoidy) (Diptera: Calliphoridae), Calliphora vomitoria (Linnaeus), Lucilia sericata (Meigen) (Diptera: Calliphoridae) and Musca domestica (Linnaeus) (Diptera: Muscidae) are resistant, but adults exposed to C. coronatus quickly perish. Fungus was cultivated for 3 weeks in a minimal medium. Cell-free filtrate, for which activity of elastase, N-acetylglucosaminidase, chitobiosidase and lipase was determined, was used for in vitro hydrolysis of the cuticle from larvae, puparia and adults. Amounts of amino acids, N-glucosamine and fatty acids released were measured after 8 h of incubation. The effectiveness of fungal enzymes was correlated with concentrations of compounds detected in the cuticles of tested insects. Positive correlations suggest compounds used by the fungus as nutrients, whereas negative correlations may indicate compounds responsible for insect resistance. Adult deaths result from the ingestion of conidia or fungal excretions.

Coronatin-2 from the entomopathogenic fungus Conidiobolus coronatus kills Galleria mellonella larvae and incapacitates hemocytes.

Coronatin-2, a 14.5 kDa protein, was isolated from culture filtrates of the entomopathogenic fungus Conidiobolus coronatus (Costantin) Batko (Entomophthoramycota: Entomophthorales). After LC-MS/MS (liquid chromatography tandem mass spectrometry) analysis of the tryptic peptide digest of coronatin-2 and a mass spectra database search no orthologs of this protein could be found in fungi. The highest homology was observed to the partial translation elongation factor 1a from Sphaerosporium equinum (protein sequence coverage, 21%), with only one peptide sequence, suggesting that coronatin-2 is a novel fungal protein that has not yet been described. In contrast to coronatin-1, an insecticidal 36 kDa protein, which shows both elastolytic and chitinolytic activity, coronatin-2 showed no enzymatic activity. Addition of coronatin-2 into cultures of hemocytes taken from larvae of Galleria mellonella Linnaeus (Lepidoptera: Pyralidae), resulted in progressive disintegration of nets formed by granulocytes and plasmatocytes due to rapid degranulation of granulocytes, extensive vacuolization of plasmatocytes accompanied by cytoplasm expulsion, and cell disintegration. Spherulocytes remained intact, while oenocytes rapidly disintegrated. Coronatin-2 produced 80% mortality when injected into G. mellonella at 5 µg larva-1. Further study is warranted to determine the relevance of the acute toxicity of coronatin-2 and its effects on hemocytes in vitro to virulence of C. coronatus against its hosts.

Isolated tumor cells in stage I & II colon cancer patients are associated with significantly worse disease-free and overall survival.

BACKGROUND: Lymph node (LN) involvement represents the strongest prognostic factor in colon cancer patients. The objective of this prospective study was to assess the prognostic impact of isolated tumor cells (ITC, defined as cell deposits ≤ 0.2 mm) in loco-regional LN of stage I & II colon cancer patients. METHODS: Seventy-four stage I & II colon cancer patients were prospectively enrolled in the present study. LN at high risk of harboring ITC were identified via an in vivo sentinel lymph node procedure and analyzed with multilevel sectioning, conventional H&E and immunohistochemical CK-19 staining. The impact of ITC on survival was assessed using Cox regression analyses. RESULTS: Median follow-up was 4.6 years. ITC were detected in locoregional lymph nodes of 23 patients (31.1%). The presence of ITC was associated with a significantly worse disease-free survival (hazard ratio = 4.73, p = 0.005). Similarly, ITC were associated with significantly worse overall survival (hazard ratio = 3.50, p = 0.043). CONCLUSIONS: This study provides compelling evidence that ITC in stage I & II colon cancer patients are associated with significantly worse disease-free and overall survival. Based on these data, the presence of ITC should be classified as a high risk factor in stage I & II colon cancer patients who might benefit from adjuvant chemotherapy.

Dramatic improvement of severe cryptococcosis-induced immune reconstitution syndrome with adalimumab in a renal transplant recipient.

In solid organ transplant recipients, immune reconstitution inflammatory syndrome (IRIS) is a rare complication of cryptococcosis, which may require steroids in its most severe forms. Here, we report the case of a renal transplant recipient who developed severe cryptococcal meningitis-associated IRIS 1 week after immunosuppression reduction. High-dose steroids failed to improve the disease. Finally, a recombinant human monoclonal tumor necrosis factor-α (TNF-α) antagonist, adalimumab, was prescribed, and the patient rapidly experienced dramatic neurological improvement. No IRIS relapse occurred within 14 months following adalimumab discontinuation.

Susceptibility vessel sign on T2* magnetic resonance imaging and recanalization results of mechanical thrombectomy with stent retrievers: a multicentre cohort study.

BACKGROUND AND PURPOSE: The susceptibility vessel sign (SVS) on T2*-weighted magnetic resonance imaging has been reported in several studies as a negative predictor of early recanalization after intravenous thrombolysis. The meaning of SVS regarding the results of mechanical thrombectomy with stent retrievers was investigated. METHODS: Susceptibility vessel sign presence and length were studied in 153 acute ischaemic stroke patients (82 men; mean ± SD age 59 ± 17 years, baseline National Institutes of Health Stroke Scale score 17.2 ± 6.5) from three stroke centres, treated with either mechanical thrombectomy alone (n = 84) or bridging therapy (n = 69). Variables were compared between recanalizers, defined as thrombolysis in cerebral infarction (TICI) scores ≥2b, and non-recanalizers (TICI<2b). RESULTS: The SVS was present in 113 (73.8%) patients. There was no association between the presence of SVS and recanalization, obtained in 86 (56.2%) patients, in the whole population [odds ratio (OR) 1.24, 95% confidence interval (CI) 0.53-2.92, P = 0.84) and in treatment subgroups (bridging: OR = 0.91, 95% CI 0.29-2.87, P = 1.0; thrombectomy alone: OR = 1.85, 95% CI 0.48-7.16, P = 0.54). However, in SVS+ patients, recanalization decreased with SVS length (OR 0.94 for each additional mm, 95% CI 0.89-0.99; P = 0.02). CONCLUSIONS: The success of recanalization in acute stroke patients treated with stent retrievers was related to thrombus length but not to the presence of SVS.

Evaluation of polybrominated diphenyl ethers (PBDEs) in matched cat sera and house dust samples: investigation of a potential link between PBDEs and spontaneous feline hyperthyroidism.

The cause of feline hyperthyroidism (FH), a common endocrinopathy of domestic cats, is unknown. A potential association between exposure to environmental contaminants polybrominated diphenyl ethers (PBDEs) and FH was investigated. The median serum level for the sum of congeners BDE-47, BDE-99, BDE-153, BDE-154 and BDE-183 (Σ5) in hyperthyroid and euthyroid cats was 82 and 174 ng g(-1)lw respectively with no significant difference in PBDE levels or profiles between groups. Overall, the median (min to max) concentration of PBDEs in cat serum (n=65) was 118 ng g(-1)lw (5-5260 ng g(-1)lw), which is approximately 10 times higher than that observed in the Australian human population. Furthermore, congener composition in feline serum samples was dominated by congener BDE-99, followed by BDE-47 then BDE-153 which differs from results of human biomonitoring. There was no correlation between PBDE levels in feline serum samples and matched house dust samples (n=25). However the similarity of BDE-47/99 ratio in each matrix suggests dust is likely the dominant exposure. Calculation of the daily exposure dose via dust ingestion for cats equated to a mean of 33 ng kg(-1) bw d(-1) (0.2-150 ng kg(-1) bw d(-1)). Differences in exposure estimates for Australian and US cats, based on dust ingestion alone, are consistent with the observed differences in body burdens. Our results do not support a role for PBDE exposure in the aetiopathogenesis of FH.

Are the French neurology residents satisfied with their training?

BACKGROUND: There have been dramatic changes in neurology over the past decade; these advances require a constant adaptation of residents' theoretical and practical training. The French Association of Neurology Residents and the College of Neurology Teachers conducted a national survey to assess the French neurology residents' satisfaction about their training. METHODS: A 16-item questionnaire was sent via e-mail to French neurology residents completing training in 2014. Data were collected and processed anonymously. RESULTS: Of eligible respondents, 126 returned the survey, representing approximately 40% of all the French neurology residents. Most residents (78%) rated their clinical training favorably. Seventy-two percent reported good to excellent quality teaching of neurology courses from their faculty. However, many residents (40%) felt insufficient their doctoral thesis supervision. All residents intended to enter fellowship training after their residency, and most of them (68%) planned to practice in a medical center. CONCLUSION: French neurology residents seemed satisfied with the structure and quality of their training program. However, efforts are required to improve management of the doctoral thesis and make private practice more attractive and accessible during the residency. In the future, similar surveys should be scheduled to regularly assess neurology residents' satisfaction and the impact of the forthcoming national and European reforms.

[Withdrawal of artificial nutrition and hydration in severe stroke: medical, legal and ethical considerations]. / Aspects médicaux, législatifs et éthiques de l'arrêt de la nutrition et de l'hydratation artificielles dans l'accident vasculaire cérébral grave.

In the majority of cases, severe stroke is accompanied by difficulty in swallowing and an altered state of consciousness requiring artificial nutrition and hydration. Because of their artificial nature, nutrition and hydration are considered by law as treatment rather basic care. Withdrawal of these treatments is dictated by the refusal of unreasonable obstinacy enshrined in law and is justified by the risk of severe disability and very poor quality of life. It is usually the last among other withholding and withdrawal decisions which have already been made during the long course of the disease. Reaching a collegial consensus on a controversial decision such as artificial nutrition and hydration withdrawal is a difficult and complex process. The reluctance for such decisions is mainly due to the symbolic value of food and hydration, to the fear of "dying badly" while suffering from hunger and thirst, and to the difficult distinction between this medical act and euthanasia. The only way to overcome such reluctance is to ensure flawless accompaniment, associating sedation and appropriate comfort care with a clear explanation (with relatives but also caregivers) of the rationale and implications of this type of decision. All teams dealing with this type of situation must have thoroughly thought through the medical, legal and ethical considerations involved in making this difficult decision.

Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, multicentre study.

BACKGROUND: Current histopathological staging procedures in colon carcinomas depend on midline division of the lymph nodes with one section of haematoxylin & eosin (H&E) staining only. By this method, tumour deposits outside this transection line may be missed and could lead to understaging of a high-risk group of stage UICC II cases, which recurs in ∼20% of cases. A new diagnostic semiautomated system, one-step nucleic acid amplification (OSNA), detects cytokeratin (CK) 19 mRNA in lymph node metastases and enables the investigation of the whole lymph node. The objective of this study was to assess whether histopathological pN0 patients can be upstaged to stage UICC III by OSNA. METHODS: Lymph nodes from patients who were classified as lymph node negative after standard histopathology (single (H&E) slice) were subjected to OSNA. A result revealing a CK19 mRNA copy number >250, which makes sure to detect mainly macrometastases and not isolated tumour cells (ITC) or micrometastases only, was regarded as positive for lymph node metastases based on previous threshold investigations. RESULTS: In total, 1594 pN0 lymph nodes from 103 colon carcinomas (median number of lymph nodes per patient: 14, range: 1-46) were analysed with OSNA. Out of 103 pN0 patients, 26 had OSNA-positive lymph nodes, resulting in an upstaging rate of 25.2%. Among these were 6/37 (16.2%) stage UICC I and 20/66 (30.3%) stage UICC II patients. Overall, 38 lymph nodes were OSNA positive: 19 patients had one, 3 had two, 3 had three, and 1 patient had four OSNA-positive lymph nodes. CONCLUSIONS: OSNA resulted in an upstaging of over 25% of initially histopathologically lymph node-negative patients. OSNA is a standardised, observer-independent technique, allowing the analysis of the whole lymph node. Therefore, sampling bias due to missing investigation of certain lymph node tissue can be avoided, which may lead to a more accurate staging.

X-ray Bragg magnifier microscope as a linear shift invariant imaging system: image formation and phase retrieval.

We present the theoretical description of the image formation with the in-line germanium Bragg Magnifier Microscope (BMM) and the first successful phase retrieval of X-ray holograms recorded with this imaging system. The conditions under which the BMM acts as a linear shift invariant system are theoretically explained and supported by the experiment. Such an approach simplifies the mathematical treatment of the image formation and reconstruction as complicated propagation of the wavefront onto inclined planes can be avoided. Quantitative phase retrieval is demonstrated using a test sample and a proof of concept phase imaging of a spider leg is also presented.

Neurogenic appendicopathy: A rare differential diagnosis of acute appendicitis.

AIM OF THE STUDY: In histologically non-inflamed but clinically suspect appendices, changes described as neurogenic appendicopathy with fibrous or fibrolipomatous obliterations can be observed. The purpose of this study was to analyse the incidence of these entities of the appendix in a longitudinal patient cohort. PATIENTS AND METHODS: This is a retrospective single-centre study of 457 patients undergoing laparoscopic appendectomy from 2017 to 2020 due to suspected acute appendicitis. RESULTS: In 72 patients (15.8%) with clinically suspected acute appendicitis, the appendix showed no distinct signs of acute inflammation during the procedure. In 43 patients, histological analysis revealed neurogenic appendicopathy or fibrous and fibrolipomatous obliteration. Female gender (P=0.088), younger age (P<0.0001), longer pain duration (P<0.0001) and repetitive pain episodes were more frequent in these patients than in those with acute appendicitis. Inflammation markers were also decreased in the group of patients with neurogenic appendicopathy (leukocytes 9.8±3.5 vs. 13.0±4.5 G/L and C-reactive protein 38.7±60.7 vs. 59.4±70.5mg/L). CONCLUSION: Neurogenic appendicopathy with fibrous/fibrolipomatous obliteration is a differential diagnosis of acute appendicitis that can only be confirmed by pathology. Female gender, young age, prolonged duration with repetitive episodes of pain, and relatively low inflammatory markers are evocative of this diagnosis.

Effect of a colorectal bundle in an entire health care region in Switzerland: Results from a prospective cohort study (EvaCol study).

INTRODUCTION: Standardisation has the potential to serve as a measure to mitigate complication rates. The objective was to assess the impact of standardisation by implementing a colorectal bundle (CB), which comprises nine elements, on the complication rates in left-sided colorectal resections. PATIENTS AND METHODS: This prospective, multicentre, observational, cohort trial was conducted in Switzerland at nine participating hospitals. During the control period, each patient was treated in accordance with the local standard protocol at their respective hospital. In the CB period, all patients were treated in accordance with the CB. The primary endpoint was the Comprehensive Complication Index (CCI) at 30 days. RESULTS: A total of 1141 patients were included (723 in the No CB group and 418 in the CB group). Median age was 66 years and 50.6% were female. Median CCI before and after CB implementation was 0.0 (Interquartile Range [IQR]: 0.0-20.9). A hurdle model approach was used for the analysis. The CB was not associated with the presence or severity of complications. Older age (Odds Ratio [OR] 1.02, 95% Confidence Intervall [CI]: 1.00-1.03), surgery for malignancy (OR 1.34, 95% CI: 1.01-1.92), emergency surgery (OR 2.19, 95% CI: 1.31-3.41), elevated nutritional risk score (OR 1.13, 95% CI: 1.01-1.24) and Body-Mass Index (OR 1.04, 95% CI: 1.00-1.06) were associated with higher odds of postoperative complications. In a supplementary per-protocol analysis, for each additional item of the CB fulfilled, the odds of anastomotic leakage (AL) were 24% lower (OR 0.76, 95% CI: 0.64-0.93). CONCLUSIONS: Dedicated teams can establish high quality colorectal services in a network of hospitals with a joint standard. The study can serve as a model for other healthcare settings to conduct and implement quality improvement programs. The consistent implementation of the CB items can reduce the occurrence of AL.