Clinical spectrum of disease and outcomes in children with Omicron SARS-COV-2 infection in Cape Town, South Africa.

INTRODUCTION: Children with underlying comorbidities and infants are most severely affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including in low- and middle-income countries with a high prevalence of HIV and TB. We describe the clinical presentation of SARS-CoV-2 infection in children during the Omicron wave, in Cape Town, South Africa. METHODS: We analysed routine care data from a prospective cohort of children aged 0-13 years, with a positive SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) or SARS-CoV-2 antigen test, admitted to Tygerberg Hospital between 1 November 2021 until 1 March 2022. Risk factors for severity of disease were assessed. RESULTS: Ninety-five children tested positive for SARS-CoV-2, of whom 87 (91.6%) were symptomatic. Clinical data were available for 86 children. The median age was 11 months (IQR 3.0-60.0), 37 (43.0%) were females, 21 (24.7%) were HIV-exposed and 7 (8.1%) were living with HIV (CLHIV). In total, 44 (51.2%) children had at least one underlying comorbidity. TB co-infection was seen in 11 children, 6 children were newly diagnosed and 5 children were already on TB treatment at the time of admission. CONCLUSION: There was no evidence of more severe disease in children living with HIV or TB.

INTRODUCTION: Les enfants et les nourrissons présentant des comorbidités sous-jacentes sont les plus gravement touchés par l'infection par le coronavirus-2 du syndrome respiratoire aigu sévère (SARS-CoV-2), y compris dans les pays à revenu faible ou intermédiaire où la prévalence du VIH et de la TB est élevée. Nous décrivons la présentation clinique de l'infection par le SARS-CoV-2 chez les enfants pendant la vague Omicron, au Cap, en Afrique du Sud. MÉTHODES: Nous avons analysé les données de soins de routine d'une cohorte prospective d'enfants âgés de 0 à 13 ans, avec un test positif de réaction en chaîne de la polymérase de transcription inverse en temps réel (rRT-PCR) ou d'antigène du SARS-CoV-2, admis à l'hôpital Tygerberg entre le 1er novembre 2021 et le 1er mars 2022. Les facteurs de risque de gravité de la maladie ont été évalués. RÉSULTATS: Quatre-vingt-quinze enfants ont été testés positifs au SARS-CoV-2, dont 87 (91,6%) étaient symptomatiques. Des données cliniques étaient disponibles pour 86 enfants. L'âge médian était de 11 mois (IQR 3,0­60,0), 37 (43,0%) étaient des filles, 21 (24,7%) étaient exposés au VIH et 7 (8,1%) vivaient avec le VIH (CLHIV). Au total, 44 (51,2%) enfants présentaient au moins une comorbidité sous-jacente. La co-infection par la TB a été observée chez 11 enfants, 6 enfants ont été nouvellement diagnostiqués et 5 enfants étaient déjà sous traitement antituberculeux au moment de l'admission. CONCLUSION: Il n'y a pas de preuve d'une maladie plus grave chez les enfants vivant avec le VIH ou la TB.

The effect of taurolidine on the time-to-positivity of blood cultures.

Background: Taurolidine containing lock solutions (TL) are a promising method for the prevention of central line associated bloodstream infections. Per accident, the TL may not always be aspirated from the central venous catheter (CVC) before blood cultures are obtained. The TL could, unintentionally, end up in a blood culture vial, possibly altering the results. The aim of this study was to investigate the effect of the TLs on the detection of microbial growth in blood culture vials. Methods: Different lock solutions (taurolidine-citrate-heparin (TCHL), taurolidine, heparin, citrate or NaCl) were added to BD BACTECTM blood culture vials (Plus Aerobic/F, Lytic/10 Anaerobic/F or Peds Plus/F) before spiking with Staphylococcus aureus (ATCC 29213 or a clinical strain) or Escherichia coli (ATCC 25922 or a clinical strain) in the presence and absence of blood. Subsequently, blood culture vials were incubated in the BD BACTEC FX instrument with Time-to-positivity (TTP) as primary outcome. In addition, the effect of the TCHL on a variety of other micro-organisms was tested. Discussion: In the presence of taurolidine, the TTP was considerably delayed or vials even remained negative as compared to vials containing heparin, citrate or NaCl. This effect was dose-dependent. The delayed TTP was much less pronounced in the presence of blood, but still notable. Conclusion: This study stresses the clinical importance of discarding TLs from the CVC before obtaining a blood culture.

Satisfaction of Paediatric Oncology Patients, Survivors, and Nurses with the Position of Their Totally Implantable Venous Access Port (SPACE-Study).

BACKGROUND: To compare paediatric oncologic vascular access ports located on the anterior thoracic wall to ports on the lower lateral thoracic wall, in terms of perceived port-related hindrance and scar-quality. METHODS: A cross-sectional survey study including paediatric oncology patients (≥8-<19 yrs), caregivers (in patients <8 yrs), survivors (>22 yrs with only anterior ports) and nurses of the Princess Máxima Center, the Netherlands, was performed. The survey consisted of questions regarding satisfaction, hindrance during daily life, and port position preference. For survivors, scar-quality was assessed using the validated Patient and Observer Scar Assessment Scale (POSAS 2.0); a high score (i.e., a displeasing scar) was defined as a score higher than the third quartile of the median for that question. RESULTS: In total, 147 participants were included; 83 patients/caregivers, 31 survivors, and 33 nurses. Overall, 81 % was satisfied with the position of their port. Satisfaction, hindrance and complications did not differ between anterior and lower lateral ports. For the anterior position, minimal pressure on the port during daily life was a mentioned reason to prefer this position. For the lower lateral position, less visibility of the scar and easiest access were mentioned. Of all survivors with an anterior port scar, one in five had a displeasing scar and all scars observed were widened. Female patients preferred a lower lateral port, and scar-quality was better for left-sided port scars. CONCLUSION: The port position should be chosen together with patients/caregivers based on the (dis-)advantages of each position, as identified by this study. LEVEL OF EVIDENCE: II.

Tracked ultrasound registration for intraoperative navigation during pediatric bone tumor resections with soft tissue components: a porcine cadaver study.

PURPOSE: Resection of pediatric osteosarcoma in the extremities with soft tissue involvement presents surgical challenges due to difficult visualization and palpation of the tumor. Therefore, an adequate image-guided surgery (IGS) system is required for more accurate tumor resection. The use of a 3D model in combination with intraoperative tracked ultrasound (iUS) may enhance surgical decision making. This study evaluates the clinical feasibility of iUS as a surgical tool using a porcine cadaver model. METHODS: First, a 3D model of the porcine lower limb was created based on preoperative scans. Second, the bone surface of the tibia was automatically detected with an iUS by a sweep on the skin. The bone surface of the preoperative 3D model was then matched with the bone surface detected by the iUS. Ten artificial targets were used to calculate the target registration error (TRE). Intraoperative performance of iUS IGS was evaluated by six pediatric surgeons and two pediatric oncologic orthopedists. Finally, user experience was assessed with a post-procedural questionnaire. RESULTS: Eight registration procedures were performed with a mean TRE of 6.78 ± 1.33 mm. The surgeons agreed about the willingness for clinical implementation in their current clinical practice. They mentioned the additional clinical value of iUS in combination with the 3D model for the localization of the soft tissue components of the tumor. The concept of the proposed IGS system is considered feasible by the clinical panel, but the large TRE and degree of automation need to be addressed in further work. CONCLUSION: The participating pediatric surgeons and orthopedists were convinced of the clinical value of the interaction between the iUS and the 3D model. Further research is required to improve the surgical accuracy and degree of automation of iUS-based registration systems for the surgical management of pediatric osteosarcoma.

The efficacy of taurolidine containing lock solutions for the prevention of central-venous-catheter-related bloodstream infections: a systematic review and meta-analysis.

The incidence of central venous catheter (CVC)-related bloodstream infections is high in patients requiring a long-term CVC. Therefore, infection prevention is of the utmost importance. The aim of this study was to provide an updated overview of randomized controlled trials (RCTs) comparing the efficacy of taurolidine containing lock solutions (TL) to other lock solutions for the prevention of CVC-related bloodstream infections in all patient populations. On 15th February 2021, PubMed, Embase and The Cochrane Library were searched for RCTs comparing the efficacy of TLs for the prevention of CVC-related bloodstream infections with other lock solutions. Exclusion criteria were non-RCTs, studies describing <10 patients and studies using TLs as treatment. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. A random effects model was used to pool individual study incidence rate ratios (IRRs). Subgroup analyses were performed based on the following factors: CVC indication, comparator lock and bacterial isolates cultured. A total of 14 articles were included in the qualitative synthesis describing 1219 haemodialysis, total parenteral nutrition and oncology patients. The pooled IRR estimated for all patient groups together (nine studies; 918 patients) was 0.30 (95% confidence interval 0.19-0.46), favouring the TLs. Adverse events (10 studies; 867 patients) were mild and scarce. The quality of the evidence was limited due to a high risk of bias and indirectness of evidence. The use of TLs might be promising for the prevention of CVC-related bloodstream infections. Large-scale RCTs are needed to draw firm conclusions on the efficacy of TLs.

Systematic review and meta-analysis concerning near-infrared imaging with fluorescent agents to identify the sentinel lymph node in oncology patients.

Sentinel node procedures (SNP) are performed with the use of tracer-agents, mainly radio-colloid and/or blue dye. Fluorescent agents have emerged as a new tracer-agent to identify the SLN intra-operatively with near-infrared imaging. Our aim is to compare the detection rate of fluorescent agents to current "golden standards" (blue dye and/or radio-colloid) for the SNP by means of a systematic review and meta-analysis without any restrictions based on tumor type. A systematic search in PubMed, Embase and The Cochrane Library was performed. Articles that compared the detection rates of fluorescent agents with radio-colloid and/or blue dye were included. Meta-analyses were performed for breast, gynecological and dermatological cancer using a random effects model. In total 6195 articles were screened which resulted in a final inclusion of 55 articles. All studies used indocyanine green (ICG) as fluorescent agent. Meta-analyses comparing ICG with blue dye showed a significant and clinically relevant difference in detection rate in favor of ICG, for both breast, dermatological and gynecological cancer. Meta-analyses comparing ICG with radio-colloid did not show any significant differences, with the exception of ICG versus radio-colloid + blue dye for the bilateral SLN detection in gynecological cancer. Near-infrared fluorescence imaging using ICG provides a higher detection rate compared to blue dye for the SNP in a range of different tumor types. SLN detection rates of ICG are comparable to radio-colloid. Due to their complementary characteristics in terms of spatial resolution and transdermal sensitivity, we suggest to use a combination of both ICG and a radio-colloid.

Volar locking plate fixation of distal radius fractures: Isokinetic assessment of the influence of an ulnar styloid process fracture on pronation-supination strength.

Although distal radius fractures (DRF) are frequent, the management of associated ulnar styloid process (USP) lesions is still controversial. According to recent studies, a fracture of the USP does not appear to affect functional outcomes after treatment of a DRF with plate fixation. We sought to compare the impact of a USP fracture on pronation and supination strength in isometric and isokinetic tests. We included patients with a DRF who underwent volar locking plate fixation. We divided our population into three groups: one group consisted of patients who had a fracture of the USP base, one group composed of patients without USP fracture or with a distal ulnar fracture only, and a control group composed of subjects with normal wrists. Inclusion criteria included an age of 18 to 50 years and a minimum follow-up of 10 months post-surgery. The main exclusion criteria were complex intraarticular fractures and postoperative complications. The assessment was based on clinical examination and recording of forearm rotation strength during pronation and supination in isokinetic and isometric tests. The ratio between the operated and contralateral sides was compared for each patient. Thirty-six participants were included (mean age 31.1±4.5 years). The mean postoperative follow-up was 17.9±6.9 months. Participants with a USP fracture differed from other participants in their peak torque on the isokinetic test at 45°/s for pronation and supination, but not on isokinetic tests at 120°/s or in isometric tests. Isokinetic tests revealed a decrease in pronation-supination strength during sustained effort for patients with associated basal USP fractures. These findings may have clinical implications for management of the USP but need to be specified with further study. LEVEL OF EVIDENCE: prognostic study level III.

Ultrafast dynamics in polycyclic aromatic hydrocarbons: the key case of conical intersections at higher excited states and their role in the photophysics of phenanthrene monomer.

In this study we reveal the detailed photocycle of a phenanthrene monomer. Phenanthrene serves as a popular building block for supramolecular systems and as an archetypal molecule to study the photochemistry of polycyclic aromatic hydrocarbons. By means of femtosecond time-resolved UV-vis transient absorption spectroscopy and molecular modeling, we found that the first bright transition involves the second excited singlet state, which relaxes toward the lowest excited singlet state with a biphasic internal conversion through a conical intersection region: a fast coherent branching followed by an exceptionally slow (∼ps) incoherent internal conversion. We succeeded to pinpoint the complete relaxation pathways and to extract the relevant parameters, e.g., the branching ratio at the conical intersection and internal conversion rates.

Architecture of a mammalian glomerular domain revealed by novel volume electroporation using nanoengineered microelectrodes.

Dense microcircuit reconstruction techniques have begun to provide ultrafine insight into the architecture of small-scale networks. However, identifying the totality of cells belonging to such neuronal modules, the "inputs" and "outputs," remains a major challenge. Here, we present the development of nanoengineered electroporation microelectrodes (NEMs) for comprehensive manipulation of a substantial volume of neuronal tissue. Combining finite element modeling and focused ion beam milling, NEMs permit substantially higher stimulation intensities compared to conventional glass capillaries, allowing for larger volumes configurable to the geometry of the target circuit. We apply NEMs to achieve near-complete labeling of the neuronal network associated with a genetically identified olfactory glomerulus. This allows us to detect sparse higher-order features of the wiring architecture that are inaccessible to statistical labeling approaches. Thus, NEM labeling provides crucial complementary information to dense circuit reconstruction techniques. Relying solely on targeting an electrode to the region of interest and passive biophysical properties largely common across cell types, this can easily be employed anywhere in the CNS.

Clinical condition and comorbidity as determinants for blood culture positivity in patients with skin and soft-tissue infections.

The utility of performing blood cultures in patients with a suspected skin infection is debated. We investigated the association between blood culture positivity rates and patients' clinical condition, including acute disease severity and comorbidity. We performed a retrospective study, including patients with cellulitis and wound infection who had been enrolled in three Dutch multicenter studies between 2011 and 2015. Patients' acute clinical condition was assessed using the Modified Early Warning Score (MEWS; severe: MEWS ≥2) and comorbidity with the Charlson Comorbidity Index (CCI; severe: CCI ≥2). A total of 334 patients with a suspected skin infection were included. Blood cultures were performed in 175 patients (52%), 28 of whom (16%) had a positive blood culture. Data on the clinical condition were collected in 275 patients. Blood cultures were performed in 76% of the patients with a severe acute condition, compared with 48% with a non-severe acute condition (OR 3.5; 95% confidence interval: 2.0-6.2; p < 0.001). Blood cultures were positive in 18% and 12% respectively (OR 1.7 (0.7-4.1); p = 0.3). Blood cultures were performed in 53% of patients with severe comorbidity, compared with 61% without severe comorbidity (OR 0.7; 0.4-1.2; p = 0.2). Blood cultures were positive in 25% and 10% respectively (OR = 3.1; 1.2-7.5; p = 0.02). The blood culture positivity rate among hospitalized patients diagnosed with skin infections was higher than the rates reported by the Infectious Diseases Society of America guidelines, particularly in patients with severe comorbidity. Therefore, the recommendations concerning blood culture performance in patients with a skin infection should be reconsidered.

Dynamic soluble changes in sVEGFR1, HGF, and VEGF promote chemotherapy and bevacizumab resistance: A prospective translational study in the BECOX (GEMCAD 09-01) trial.

Despite initial responsiveness, acquired resistance to both bevacizumab and chemotherapy in metastatic colorectal cancer is universal. We have recently published that in vitro, chronically oxaliplatin resistance upregulates soluble vascular endothelial growth factor receptor 1, downregulates vascular endothelial growth factor, and also promotes c-MET, b-catenin/transcription factor 4, and AKT activation. We tested whether variation in three serum biomarkers such as the natural c-MET ligand (hepatocyte growth factor), soluble vascular endothelial growth factor receptor 1, and vascular endothelial growth factor-A was associated with efficacy in metastatic colorectal cancer patients treated in the prospective BECOX study. Serum levels of vascular endothelial growth factor-A165, soluble vascular endothelial growth factor receptor 1, and hepatocyte growth factor were assessed by enzyme-linked immunosorbent assay method basally and every 3 cycles (at the time of computed tomography evaluation) in a preplanned translational study in the first-line BECOX trial in metastatic colorectal cancer patients treated with CAPOX plus bevacizumab. Response was evaluated by routine contrast-enhanced computed tomography by RECIST 1.1 by investigator assessment and by three blinded independent radiologists. Ratios between soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A and hepatocyte growth factor/vascular endothelial growth factor-A were established and variations through time were related to RECIST 1.1 by investigator assessment and independent radiologist. The BECOX trial included 68 patients, and 27 patients were analyzed in the translational trial. A total of 80 RECIST 1.1 evaluations were done by investigator assessment and 56 by independent radiologist. We found that a 3.22-fold increase in soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A by investigator assessment and a 3.06-fold increase in soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A by independent radiologist from previous determination were associated with responses compared with 1.38-fold increase by investigator assessment and 1.59 by independent radiologist in non-responders (p = 0.0009 and p = 0.03, respectively). Responders had a 3.36-fold increase in hepatocyte growth factor/vascular endothelial growth factor-A from previous determination by investigator assessment and 3.66-fold increase in hepatocyte growth factor/vascular endothelial growth factor-A by independent radiologist compared with 1.43-fold increase by investigator assessment and 1.53 by independent radiologist for non-responders (p = 0.002 and 0.003, respectively). In conclusion, a decrease in vascular endothelial growth factor-A and an increase in soluble vascular endothelial growth factor receptor 1 during chemotherapy and bevacizumab exposure can contribute to both chemotherapy (due to c-MET/b-catenin activation) and bevacizumab (due to low vascular endothelial growth factor requirements) resistance. Because hepatocyte growth factor levels decrease also during acquired resistance, alternative strategies to hepatocyte growth factor-ligand inhibition should be investigated.

[Surgical exposures for distal radius fractures]. / Les voies d'abord des fractures du radius distal : une mise au point.

This is a review of the various approaches that can be used for open reduction and internal fixation (ORIF) of distal radius fractures. The main dissection steps are exposed and the specific indications for each approach are described. The anterior approach is discussed extensively as it is now the gold standard for ORIF of distal radius fractures. The lateral and posterior approaches are also described as they are sometimes needed for complex fractures.

Applicability of generic quality indicators for appropriate antibiotic use in daily hospital practice: a cross-sectional point-prevalence multicenter study.

The ability to monitor the appropriateness of hospital antibiotic use is a key element of an effective antibiotic stewardship program. A set of 11 generic quality indicators (QIs) was previously developed to assess the quality of antibiotic use in hospitalized adults treated for a bacterial infection. The primary aim of the current study was to assess the clinimetric properties of these QIs (nine process and two structure indicators) in daily clinical practice. In a cross-sectional point-prevalence survey, performed in 2011 and 2012, 1890 inpatients from 22 hospitals in the Netherlands treated with antibiotics for a suspected bacterial infection were included, and data were extracted from medical records. In this cohort we tested the measurability, applicability, reliability, room for improvement and case mix stability of the previously developed QIs. Low applicability (≤10% of reviewed patients) was found for the QIs 'therapeutic drug monitoring', 'adapting antibiotics to renal function' and 'discontinue empirical therapy in case of lack of clinical and/or microbiological evidence of infection'. For the latter, we also found a low inter-observer agreement (kappa <0.4). One QI showed low improvement potential. The remaining seven QIs had sound clinimetric properties. Case-mix correction was necessary for most process QIs. For all QIs, we found ample room for improvement and large variation between hospitals. Establishing the clinimetric properties was essential, as four of the 11 previously selected QIs showed unsatisfactory properties in this practice test. Since the quality of antibiotic use and the process of documenting data is changing over time and may vary per country, QIs should always be tested in practice first.

Temporal trends in classical and alternative flame retardants in bird eggs from Doñana Natural Space and surrounding areas (south-western Spain) between 1999 and 2013.

Several halogenated flame retardants were detected in black kite, white stork and greater flamingo unborn eggs from Doñana Natural Space (Spain) collected in 1999, 2003, 2011 and 2013. The main components of Penta-BDE commercial mixture (BDE-47, -99 and -100) showed a decrease in the studied time interval, concurring with the ban of this mixture in the European Union (EU) in 2006. On the other hand, BDE-209, the main component of Deca-BDE mixture showed a clear trend in black kites but further monitoring is needed since its production ceased at the end of 2013. Besides, even if Dechlorane Plus (DP) was proposed by the EU as an alternative to BDE-209 no time trends were observed. Furthermore, total concentrations of PBDEs (classical FRs) are still higher than concentrations of hexabromocyclododecane (HBCD) and alternative FRs halogenated norbornenes (HNs), which are theoretically substitutes of the already banned PBDEs.

Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trial†.

BACKGROUND: The primary results of our phase II randomized trial suggested that compared with conventional preoperative chemoradiation (CRT), the addition of chemotherapy (CT) before CRT and surgery allows most patients receive their planned treatment with a better toxicity profile without compromising the pathological complete response and complete resection rates. We now report the 5-year outcomes. PATIENTS AND METHODS: Patients with distal or middle third, T3-T4 and/or N+ rectal adenocarcinoma selected by magnetic resonance imaging, were randomly assigned to arm A-preoperative CRT followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-four cycles of CAPOX followed by CRT and surgery. The following 5-year actuarial outcomes were assessed: the cumulative incidence of local relapse (LR) and distant metastases (DM), disease-free (DFS) and overall survival (OS). RESULTS: A total of 108 eligible patients were randomly assigned to arm A (n = 52) or arm B (n = 56). With a median follow-up of 69.5 months, 5-year DFS was 64% in arm A and 62% in arm B (P = 0.85) and 5-year OS was 78% in arm A and 75% in arm B (P = 0.64). The 5-year cumulative incidence of LR was 2% and 5% (P = 0.61) and 5-year cumulative incidence of DM was 21% and 23%; (P = 0.79) in arms A and B, respectively. CONCLUSION: Both treatment approaches yield similar outcomes. Given the lower acute toxicity and improved compliance with induction CT compared with adjuvant CT, integrating effective systemic therapy before CRT and surgery is a promising strategy and should be examined in phase III trials.

Diagnosis and surgical treatment of dysplasia epiphysealis hemimelica. A report of nine cases.

BACKGROUND: Dysplasia epiphysealis hemimelica (DEH) is a rare developmental bone disorder with hemimelic involvement of one or more epiphysis. We report on nine new cases and discuss the clinical manifestations, the value of MRI, and the results of complete and early surgical resection of these lesions. MATERIALS AND METHODS: In this retrospective study, nine patients with a diagnosis of DEH were evaluated. Age at presentation ranged from 1 year to 12 years. The main complaint at diagnosis was a swelling bony mass. Angular deformities were recorded in two patients. All patients were surgically treated and followed up clinically and by imaging. Eight patients underwent excision only. RESULTS: The average follow-up was 5.6 years (range, 2-10.5 years). All patients had a good outcome without related symptoms. No epiphysiodesis, angular deformity or recurrence was observed. One patient with femoral lesion involving the distal medial part of the epiphysis developed, four months after surgical excision, a calcification outside the area of total excision. This calcification did not increase in size at two years follow-up. Another patient with lateral involvement of the proximal tibial epiphysis presented a postoperative nervous complication. Spontaneous nervous recovery occurred three months after surgery. DISCUSSION: MRI was useful to find a potential plane of cleavage between the epiphysis and the pathological tissue. We recommend early removing ossifications when a cleavage plane is identified. Waiting a possible complication or increasing of size does not seem logical. Of course, the treatment will be not the same if no cleavage plane is found on MRI. LEVEL OF EVIDENCE: IV.

First-line bevacizumab and capecitabine-oxaliplatin in elderly patients with mCRC: GEMCAD phase II BECOX study.

BACKGROUND: Subgroup analyses of clinical studies suggest that bevacizumab plus XELOX is effective and tolerable in elderly patients with metastatic colorectal cancer (mCRC). The prospective BECOX study examined the efficacy and safety of bevacizumab plus XELOX, followed by bevacizumab plus capecitabine in elderly patients with mCRC. METHODS: Patients aged ⩾70 years with Eastern Cooperative Oncology Group performance status 0 out of 1 and confirmed mCRC were included. Patients received bevacizumab 7.5 mg kg(-1) and oxaliplatin 130 mg m(-2) on day 1, plus capecitabine 1000 mg m(-2) bid orally on days 1-14 every 21 days; oxaliplatin was discontinued after 6 cycles. The primary end point was time to progression (TTP). RESULTS: The intent-to-treat population comprised 68 patients (65% male, median age 76 years). Median TTP was 11.1 months; median overall survival was 20.4 months; overall response rate was 46%. Grade 3 or 4 adverse events included diarrhoea (18%) and asthenia (16%). Grade 3 or 4 adverse events of special interest for bevacizumab included deep-vein thrombosis (6%) and pulmonary embolism (4%). CONCLUSIONS: Bevacizumab plus XELOX was effective and well tolerated in elderly patients in the BECOX study. The adverse-event profile was similar to previous reports; no new safety concerns were identified. Fit elderly patients with mCRC should be considered for treatment with bevacizumab plus XELOX.

Functional analysis of endo-1,4-ß-glucanases in response to Botrytis cinerea and Pseudomonas syringae reveals their involvement in plant-pathogen interactions.

Plant cell wall modification is a critical component in stress responses. Endo-1,4-ß-glucanases (EGs) take part in cell wall editing processes, e.g. elongation, ripening and abscission. Here we studied the infection response of Solanum lycopersicum and Arabidopsis thaliana with impaired EGs. Transgenic TomCel1 and TomCel2 tomato antisense plants challenged with Pseudomonas syringae showed higher susceptibility, callose priming and increased jasmonic acid pathway marker gene expression. These two EGs could be resistance factors and may act as negative regulators of callose deposition, probably by interfering with the defence-signalling network. A study of a set of Arabidopsis EG T-DNA insertion mutants challenged with P. syringae and Botrytis cinerea revealed that the lack of other EGs interferes with infection phenotype, callose deposition, expression of signalling pathway marker genes and hormonal balance. We conclude that a lack of EGs could alter plant response to pathogens by modifying the properties of the cell wall and/or interfering with signalling pathways, contributing to generate the appropriate signalling outcomes. Analysis of microarray data demonstrates that EGs are differentially expressed upon many different plant-pathogen challenges, hormone treatments and many abiotic stresses. We found some Arabidopsis EG mutants with increased tolerance to osmotic and salt stress. Our results show that impairing EGs can alter plant-pathogen interactions and may contribute to appropriate signalling outcomes in many different biotic and abiotic plant stress responses.

[Nerve transfer in isolated deltoid palsy: branch of the long head of the triceps to the axillary nerve]. / Neurotisation du nerf du chef long du muscle triceps sur le nerf axillaire, dans les paralysies isolées du deltoïde.

AIM: Nerve transfer of the nerve branch to long head of triceps onto the axillary nerve has joined the therapeutic armamentarium for isolated deltoid paralysis cases. We report our experience in the case of a non-excisable neuroma of the axillary nerve at its origin from the posterior cord. METHODS: Eight patients of average age 28 (15-38) were included in a retrospective study with one operating surgeon. Clinical assessment included analytical testing of the deltoid muscle, pain score (VAS) and a functional assessment. Minimum follow-up was 24 months. RESULTS: Preoperative delay was 10.8 months. In seven cases, recovery was M4 for the posterior deltoid, M3 for the middle deltoid and M2 for the anterior deltoid. The elbow was stable, strong and painless (VAS=2). Cocontraction was found. No morbidity was found at the donor site. The last case was a failure. DISCUSSION: In absence of spontaneous recovery, the surgical treatment of deltoid palsy restores a stable strong shoulder and prevents overloading of the rotator cuff. This nerve transfer initially used in brachial plexus surgery gives results comparable to those using grafts, which is the standard treatment of reference avoiding approach of the plexus. The inconvenience is the persistence of cocontractions and a fatigue phenomenon. CONCLUSION: The nerve transfer of the nerve to the long head of triceps to the axillary nerve is the technique of choice for re-innervation of the deltoid.