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Background and purpose Nerve cross‐sectional area (CSA) is not constant over the human lifespan. The relationship between an increasing CSA and age has been described as a linear positive correlation, but few studies have found a linear decrease in nerve size with older age. The aim of the present study was to analyze the development of nerve CSA in a healthy population from early childhood to old age using high‐resolution ultrasound. Methods The median, ulnar, radial and sural nerves were examined bilaterally at 18 nerve sites in 110 healthy children, adolescents and adults aged between 2 and 98 years. The CSA of every nerve site was evaluated separately and in different age groups. The correlation of CSA with age, height and weight was analyzed in a linear, logarithmic and quadratic model and correlation coefficients were compared in a goodness‐of‐fit analysis. Models were then adjusted for weight and height. Results Linear CSA–age correlations showed the lowest correlation coefficients for all nerve sites. An inverted parabolic curve suggesting a quadratic correlation of CSA and age was the best‐fitting model. Weight and height had a higher predictive value than age in adjusted models. Conclusions There is an increase in nerve size during childhood and adolescence and a trend towards a decrease in old age, suggesting an inverted parabolic curve partly explained by age‐related changes in weight and height. Enlarged nerves in elderly individuals should not be attributed to age alone.

Background: The novel criteria for the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) have established imaging with nerve ultrasound (NUS) and magnetic resonance neurography (MRN) as complementary methods for CIDP diagnosis. Objectives: Our goal was to investigate the role of MRN and NUS for CIDP monitoring. Methods and design: We longitudinally examined 12 CIDP patients from 2016 to 2022 using NUS, MRN, nerve conduction studies (NCS), and clinical parameters (inflammatory neuropathy cause and treatment (INCAT)/overall disability sum score (ODSS)). NUS evaluated the cross-sectional area (CSA) of the median, ulnar, radial, tibial, fibular, and sural nerve as well as the intranerve CSA variability (INVcsa) of the tibial, fibular, ulnar, and median nerve, whereas MRN evaluated T2-weighted sequences of the fibular and tibial nerve at the popliteal fossa. Results: Five patients showed clinical improvement/stability with corresponding improved or stable NCS/NUS parameters (number of nerves with increased CSA and INVCSA). Seven deteriorating patients showed deteriorating NCS and either increasing or decreasing NUS markers possibly indicating inflammatory activity or degenerative CSA reduction. The difference ΔINCAT/ODSS2022–2016 correlated positively with NUS ΔINVCSA2022–2016 (p = 0.007, r = 0.731, n = 12) and with NUS ΔCSA2022–2016 of the tibial nerve (p = 0.0005, r = 0.865, n = 12). Further, NUS-CSA of the tibial nerve in the popliteal fossa in 2016 correlated inversely with the difference of the INCAT/ODSS score (ΔINCAT/ODSS2022–2016; r = −0.653; p = 0.033; n = 11). Finally, the Bland–Altman analyses for the tibial and fibular nerve showed a bias of −1.903 and 2.195 mm2 (bias = NUS-CSA − MRN-CSA) accordingly revealing a difference between MRN and NUS measurements for deeper nerves. Conclusion: CSA and INVCSA of the tibial and fibular nerve can be used for monitoring in CIDP, and increased CSA of the tibial nerve is a good prognostic marker. MRN is more reliable for evaluating inflammation in proximal leg nerve segments.

Background Nerve cross-sectional area (CSA) reference values in high-resolution ultrasound for children and adolescents are influenced by demographic and anthropometric factors such as age, height and weight. Objectives The influence of hand volume as an additional morphometric factor was evaluated and nerve echogenicity was analyzed in a prospective cross-sectional study. Methods CSA were measured in 30 healthy children and adolescents from 2 to 17 years in the median, ulnar, radial, tibial, peroneal and sural nerves. Height, weight, age, handedness and gender were recorded, the volume of the hands was measured using the water displacement method. The intra-nerve CSA variability (INV), left/right ratios and absolute differences were calculated. Age groups were compared by the Kruskal-Wallis test. The influence of demographic factors was analyzed using Spearman correlation and multiple linear regression. Echogenicity and fraction of black were determined for each nerve segment. Results Nerve CSA values were consistently lower than those reported for adults and correlated in all measured nerve sites with age, height, weight and hand volume. Weight showed the highest correlation coefficient (R = .95) with the best fitting model predicting CSA. Correlation coefficients were higher in a linear than in a logarithmic model. Ratios were stable, the absolute differences increased with age and were significantly different between age groups. Most nerves showed a mixed or hypoechogenic pattern in echogenicity analysis, hyperechogenicity is less frequently observed. Conclusions Nerve CSA in children and adolescents is lower than in adults and increases proportionally during growth with a constant INV and left/right ratio in different age groups. Weight and age are predominant anthropometric factors predicting nerve size. Hand volume is correlated with nerve size, but does not predict CSA independently. Echogenicity can provide additional information on nerve structure.

Plants have recently been recognized as meta-organisms due to a close symbiotic relationship with their microbiome. Comparable to humans and other eukaryotic hosts, plants also harbor a “second genome” that fulfills important host functions. These advances were driven by both “omics”-technologies guided by next-generation sequencing and microscopic insights. Additionally, these new results influence applied fields such as biocontrol and stress protection in agriculture, and new tools may impact (i) the detection of new bio-resources for biocontrol and plant growth promotion, (ii) the optimization of fermentation and formulation processes for biologicals, (iii) stabilization of the biocontrol effect under field conditions, and (iv) risk assessment studies for biotechnological applications. Examples are presented and discussed for the fields mentioned above, and next-generation bio-products were found as a sustainable alternative for agriculture.

Currently, there is no standardized method to evaluate operator reliability in nerve ultrasound. A short prospective protocol using Bland–Altman analysis was developed to assess the level of agreement between operators with different expertise levels. A control rater without experience in nerve ultrasound, three novices after two months of training, an experienced rater with two years of experience, and a reference rater performed blinded ultrasound examinations of the left median and ulnar nerve in 42 nerve sites in healthy volunteers. The precision of Bland–Altman agreement analysis was tested using the Preiss–Fisher procedure. Intraclass correlation coefficients (ICC), coefficients of variation, and Bland–Altman limits of agreement were calculated. The sample size calculation and Preiss–Fisher procedure showed a sufficient precision of Bland–Altman agreement analysis. Limits of agreement of all trained novices ranged from 2.0 to 2.9 mm2 and were within the test’s maximum tolerated difference. Ninety-five percent confidence intervals of limits of agreement revealed a higher precision in the experienced rater’s measurements. Operator reliability in nerve ultrasound of the median and ulnar nerve arm nerves can be evaluated with a short prospective controlled protocol using Bland–Altman statistics, allowing a clear distinction between an untrained rater, trained novices after two months of training, and an experienced rater.

Background: In an open pilot study, we studied the safety and efficacy of treatment with the nonpeptide glycoprotein IIb/IIIa antagonist tirofiban in patients with progressive ischemic stroke. The rationale for the use of tirofiban in progressive stroke is the effect on vessel patency and microcircu lation. Methods: Patients with acute ischemic stroke and progression of ≥2 points on the National Institute of Health Stroke Scale (NIHSS) in the first 96 h after stroke onset were treated with intravenous tirofiban. Serial NIHSS measurements and intra- and extracerebral bleeding complications were recorded. Results: Progressive stroke was observed in 35 patients with a mean progression of 5.4 (SD 4.1) points on the NIHSS. No severe bleeding complications occurred during tirofiban treatment. Analysis of variance revealed a significant interaction between stroke etiology (small-vessel vs. large-vessel occlusion) and NIHSS during treatment with tirofiban: patients with small-vessel occlusion showed significant improvement, while patients with large-vessel occlusion did not. The mean NIHSS improvement after tirofiban infusion was 3.4 (SD 3.4) for small-vessel occlusion versus 0.8 (SD 4.2) for large-vessel occlusion (p = 0.048). Conclusion: Treatment with tirofiban was well tolerated in patients with progressive stroke. However, only patients with small-vessel occlusion recovered significantly during infusion of tirofiban. The effect of tirofiban in progressive stroke and different subgroups of stroke deserves to be studied in a randomized controlled trial.

Introduction The value of a sural nerve biopsy for the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is controversial. Evidence-based recommendations for its implementation are lacking. We investigated factors leading to biopsy and analyzed biopsy outcomes and consequences, assessed the predictability of biopsy outcomes through clinical parameters to avoid unnecessary biopsies, and compared results with electrophysiological and clinical severity to determine their prognostic value. Methods 190 sural nerve biopsies were analyzed in two cohorts. One consisted of 163 biopsies and the second of 72 biopsies from the prospective Immune-mediated Neuropathies Biomaterial and Data registry (INHIBIT). Both have an intersection of 45 patients. 75 data sets from patients without biopsy were used. Analysis of nerve conduction studies, treatment, overall disability sum score (ODSS), biopsy outcomes, and diagnosis was performed. Results 51% of biopsied patients received the diagnosis CIDP (77% fulfilled EFNS/PNS criteria), 21% were not CIDP typical, and 27% were unspecific. Biopsied patients responded less frequently to immunotherapies at time of biopsy than non-biopsied patients ( p  = 0.003). Immunotherapy was initiated more frequently after biopsy ( p  < 0.001) and more often with intravenous immunoglobulins ( p  < 0.0001). 76% of all biopsied patients met the electrophysiological criteria for CIDP. Sensory nerve action potential amplitudes of 0 µV still provide 73% of histological diagnostic value. Histologic signs of degeneration predicted ODSS worsening after 1 year ( p  = 0.028) but disease severity did not correlate with histological damage severity. Discussion The main indication for nerve biopsy was the treatment of refractory cases of autoimmune neuropathies with the therapeutic consequence of treatment initiation or escalation. Sural biopsy also provided prognostic information. Even with extinguished sural SNAP, the biopsy can still have diagnostic value.

Background and purpose The role of high‐resolution nerve ultrasound (HRUS) and corneal confocal microscopy (CCM) in the early detection of taxane‐induced polyneuropathy (TIPN) is unclear. The present prospective longitudinal controlled observational pilot study estimates the role of HRUS and CCM in the early diagnosis of TIPN in breast cancer patients. Methods Fifteen breast cancer patients receiving paclitaxel and 15 healthy age matched controls were included. Visits before and 3 weeks, 8 weeks and 6 months after treatment included clinical examination, the total neuropathy score, nerve conduction studies (NCS), monocular CCM including corneal nerve fibre length, density and branching and HRUS of bilateral median, ulnar, radial, tibial, peroneal and sural nerves. Patients were compared between different visits and to healthy controls. Results Total neuropathy score increased from 2.2 at baseline to 5.8 (p < 0.001) at week 8. NCS showed a decreased sensory amplitude in the sural, radial, ulnar and median nerve after 6 months (p < 0.001). HRUS revealed a significant increase of cross‐sectional area in the sural nerve (p = 0.004), the median nerve (p = 0.003) at the carpal tunnel and the ulnar nerve in the forearm (p = 0.006) after 6 months. CCM showed no changes at different visits. Conclusions Corneal confocal microscopy and HRUS do not detect early signs of TIPN during the paclitaxel treatment period. HRUS and NCS might detect congruent signs of an axonal, predominantly sensory polyneuropathy after 6 months. The clinical examination remains the most sensitive tool in the early detection of TIPN in breast cancer patients.

Objective Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune neuropathy characterized by progressive or relapsing–remitting weakness and sensory deficits. This study aims to evaluate the utility of corneal confocal microscopy (CCM) in diagnosing and monitoring CIDP. Methods We analysed 100 CIDP patients and 31 healthy controls using CCM to measure corneal nerve fiber density (CNFD), length (CNFL), and branch density (CNBD). Standardized clinical and electroneurographic evaluation were conducted, and statistical analyses were performed to compare CCM parameters between groups and across disease stages. Results CIDP patients and subgroups exhibited significant reduction in CNFD, CNFL, and CNBD compared to controls. This reduction was observed in late disease stages and severe overall disability sum score (ODSS), and Inflammatory Neuropathy Cause and Treatment Sensory Sum Score (ISS). CCM parameters correlated with axonal pathology in electroneurography of sensory, but not motor nerves. Despite the significant differences, the diagnostic sensitivity (41%) and specificity (77%) of CCM parameters were limited. Conclusion While CCM effectively differentiates CIDP patients from healthy controls and was associated with disease severity, its diagnostic accuracy for routine clinical use is a posteriori. However, CCM shows promise as a non-invasive tool for monitoring sensory axonal pathology in CIDP.

Summary Background The increasing spread of multidrug-resistant Plasmodium falciparum malaria emphasises the urgent need for alternative treatment regimens. The objective of the study was to establish the efficacy of a novel drug combination. We compared a combination of atovaquone and proguanil with amodiaquine in the treatment of acute uncomplicated P falciparum malaria in Lambaréné, Gabon. Methods 142 adults were randomly allocated either a combination treatment of atovaquone 1000 mg daily and proguanil 400 mg daily for 3 days or treatment with amodiaquine 600 mg on admission, 600 mg 24 h later, and 300 mg after a further 24 h. Symptoms and clinical signs were recorded and giemsa-stained thick blood smears were done every 12 h until patients had been symptom-free and aparasitaemic for 24 h. 126 patients were followed up for 28 days or until recrudescence. Findings In the atovaquone plus proguanil group 62 (87%) of 71 patients were cured and only one had recrudescent infection. By contrast, the cure rate was significantly lower (p=0·022) with amodiaquine (51 [72%] of 71; there were 12 recrudescences in the amodiaquine group). Eight patients in each group were lost to follow-up. Patients treated with atovaquone plus proguanil complained of nausea (33%) and vomiting (29%), and the most commonly reported adverse effects of amodiaquine were pruritus (43%) and insomnia (27%). Interpretation Atovaquone and proguanil was a highly effective and safe drug combination in patients with acute uncomplicated P falciparum malaria in Gabon.