The role of imaging in focal neuropathies.

Electrodiagnostic testing (EDX) has been the diagnostic tool of choice in peripheral nerve disease for many years, but in recent years, peripheral nerve imaging has been used ever more frequently in daily clinical practice. Nerve ultrasound and magnetic resonance (MR) neurography are able to visualize nerve structures reliably. These techniques can aid in localizing nerve pathology and can reveal significant anatomical abnormalities underlying nerve pathology that may have been otherwise undetected by EDX. As such, nerve ultrasound and MR neurography can significantly improve diagnostic accuracy and can have a significant effect on treatment strategy. In this chapter, the basic principles and recent developments of these techniques will be discussed, as well as their potential application in several types of peripheral nerve disease, such as carpal tunnel syndrome (CTS), ulnar neuropathy at the elbow (UNE), radial neuropathy, brachial and lumbosacral plexopathy, neuralgic amyotrophy (NA), fibular, tibial, sciatic, femoral neuropathy, meralgia paresthetica, peripheral nerve trauma, tumors, and inflammatory neuropathies.

Definitions of Urinary Tract Infection in Current Research: A Systematic Review.

Defining urinary tract infection (UTI) is complex, as numerous clinical and diagnostic parameters are involved. In this systematic review, we aimed to gain insight into how UTI is defined across current studies. We included 47 studies, published between January 2019 and May 2022, investigating therapeutic or prophylactic interventions in adult patients with UTI. Signs and symptoms, pyuria, and a positive urine culture were required in 85%, 28%, and 55% of study definitions, respectively. Five studies (11%) required all 3 categories for the diagnosis of UTI. Thresholds for significant bacteriuria varied from 103 to 105 colony-forming units/mL. None of the 12 studies including acute cystitis and 2 of 12 (17%) defining acute pyelonephritis used identical definitions. Complicated UTI was defined by both host factors and systemic involvement in 9 of 14 (64%) studies. In conclusion, UTI definitions are heterogeneous across recent studies, highlighting the need for a consensus-based, research reference standard for UTI.

Intravesical aminoglycoside instillations as prophylaxis for recurrent urinary tract infection: patient satisfaction, long-term safety and efficacy.

Background: Recurrent urinary tract infections (UTIs) are common, especially in women. When oral antimicrobial prophylaxis is ineffective or not possible due to allergies or antimicrobial resistance, intravesical aminoglycoside instillations (IAIs) are a non-systemic alternative. Objectives: To assess treatment satisfaction, long-term safety and efficacy of IAIs for recurrent UTI. Methods: We conducted a cohort study using data collected between January 2013 and June 2022 at the Leiden University Medical Center. Adult patients with recurrent UTI who received prophylactic IAI were eligible for inclusion. Treatment satisfaction was assessed through a survey. Data on serum aminoglycoside concentrations, cystoscopy results and number of recurrences were obtained through chart review. Number of recurrences and UTI characteristics were compared between patients on and off IAI using Poisson and logistic mixed effects models. Results: Forty-four patients were included (median follow-up time 976 days) and 323 UTIs occurred during follow-up. Overall treatment satisfaction was high (median 79.2/100). All but one patient had undetectable serum aminoglycoside levels and no malignancies were found on follow-up cystoscopy. IAI increased the time to first recurrence (102 days versus 36 days, P = 0.02), reduced the number of recurrences (rate ratio 0.75, 95% CI 0.56-0.99, P = 0.04) and the necessity for systemic antibiotics (OR 0.33, 95% CI 0.13-0.86, P = 0.02). Conclusions: In patients with recurrent UTI, IAI was associated with high treatment satisfaction, and was found to be a safe and effective alternative to oral antimicrobial prophylaxis.

Immunogenicity of bivalent omicron (BA.1) booster vaccination after different priming regimens in health-care workers in the Netherlands (SWITCH ON): results from the direct boost group of an open-label, multicentre, randomised controlled trial.

BACKGROUND: Bivalent mRNA-based COVID-19 vaccines encoding the ancestral and omicron spike (S) protein were developed as a countermeasure against antigenically distinct SARS-CoV-2 variants. We aimed to assess the (variant-specific) immunogenicity and reactogenicity of mRNA-based bivalent omicron (BA.1) vaccines in individuals who were primed with adenovirus-based or mRNA-based vaccines encoding the ancestral spike protein. METHODS: We analysed results of the direct boost group of the SWITCH ON study, an open-label, multicentre, randomised controlled trial. Health-care workers from four academic hospitals in the Netherlands aged 18-65 years who had completed a primary COVID-19 vaccination regimen and received one booster of an mRNA-based vaccine, given no later than 3 months previously, were eligible. Participants were randomly assigned (1:1) using computer software in block sizes of 16 and 24 to receive an omicron BA.1 bivalent booster straight away (direct boost group) or a bivalent omicron BA.5 booster, postponed for 90 days (postponed boost group), stratified by priming regimen. The BNT162b2 OMI BA.1 boost was given to participants younger than 45 years, and the mRNA-1273.214 boost was given to participants 45 years or older, as per Dutch guidelines. The direct boost group, whose results are presented here, were divided into four subgroups for analysis: (1) Ad26.COV2.S (Johnson & Johnson) prime and BNT162b2 OMI BA.1 (BioNTech-Pfizer) boost (Ad/P), (2) mRNA-based prime and BNT162b2 OMI BA.1 boost (mRNA/P), (3) Ad26.COV2.S prime and mRNA-1273.214 (Moderna) boost (Ad/M), and (4) mRNA-based prime and mRNA-1273.214 boost (mRNA/M). The primary outcome was fold change in S protein S1 subunit-specific IgG antibodies before and 28 days after booster vaccination. The primary outcome and safety were assessed in all participants except those who withdrew, had a SARS-CoV-2 breakthrough infection, or had a missing blood sample at day 0 or day 28. This trial is registered with ClinicalTrials.gov, NCT05471440. FINDINGS: Between Sept 2 and Oct 4, 2022, 219 (50%) of 434 eligible participants were randomly assigned to the direct boost group; 187 participants were included in the primary analyses; exclusions were mainly due to SARS-CoV-2 infection between days 0 and 28. From the 187 included participants, 138 (74%) were female and 49 (26%) were male. 42 (22%) of 187 participants received Ad/P and 44 (24%) mRNA/P (those aged <45 years), and 45 (24%) had received Ad/M and 56 (30%) mRNA/M (those aged ≥45 years). S1-specific binding antibody concentrations increased 7 days after bivalent booster vaccination and remained stable over 28 days in all four subgroups (geometric mean ratio [GMR] between day 0 and day 28 was 1·15 [95% CI 1·12-1·19] for the Ad/P group, 1·17 [1·14-1·20] for the mRNA/P group, 1·20 [1·17-1·23] for the Ad/M group, and 1·16 [1·13-1·19] for the mRNA/M group). We observed no significant difference in the GMR between the Ad/P and mRNA/P groups (p=0·51). The GMR appeared to be higher in the Ad/M group than in the mRNA/M group, but was not significant (p=0·073). Most side-effects were mild to moderate in severity and resolved within 48 h in most individuals. INTERPRETATION: Booster vaccination with mRNA-1273.214 or BNT162b2 OMI BA.1 in adult healthcare workers resulted in a rapid recall of humoral and cellular immune responses independent of the priming regimen. Monitoring of SARS-CoV-2 immunity at the population level, and simultaneously antigenic drift at the virus level, remains crucial to assess the necessity and timing of COVID-19 variant-specific booster vaccinations. FUNDING: The Netherlands Organization for Health Research and Development (ZonMw).

Analyzing the immunogenicity of bivalent booster vaccinations in healthcare workers: The SWITCH ON trial protocol.

Vaccination against coronavirus disease 2019 (COVID-19) has contributed greatly to providing protection against severe disease, thereby reducing hospital admissions and deaths. Several studies have reported reduction in vaccine effectiveness over time against the Omicron sub-lineages. However, the willingness to receive regular booster doses in the general population is declining. To determine the need for repeated booster vaccinations in healthy individuals and to aid policymakers in future public health interventions for COVID-19, we aim to gain insight into the immunogenicity of the additional bivalent booster vaccination in a representative sample of the healthy Dutch population. The SWITCH ON study was initiated to investigate three main topics: i) immunogenicity of bivalent vaccines after priming with adenovirus- or mRNA-based vaccines, ii) immunological recall responses and reactivity with relevant variants after booster vaccination, and iii) the necessity of booster vaccinations for the healthy population in the future. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05471440.

Effectiveness of Different Antimicrobial Strategies for Staphylococcal Prosthetic Joint Infection: Results From a Large Prospective Registry-Based Cohort Study.

Background: Treatment of staphylococcal prosthetic joint infection (PJI) usually consists of surgical debridement and prolonged rifampicin combination therapy. Tailored antimicrobial treatment alternatives are needed due to frequent side effects and drug-drug interactions with rifampicin combination therapy. We aimed to assess the effectiveness of several alternative antibiotic strategies in patients with staphylococcal PJI. Methods: In this prospective, multicenter registry-based study, all consecutive patients with a staphylococcal PJI, treated with debridement, antibiotics and implant retention (DAIR) or 1-stage revision surgery between January 1, 2015 and November 3, 2020, were included. Patients were treated with a long-term rifampicin combination strategy (in 2 centers) or a short-term rifampicin combination strategy (in 3 centers). Antimicrobial treatment strategies in these centers were defined before the start of the registry. Patients were stratified in different groups, depending on the used antimicrobial strategy. Cox proportional hazards models were used to compare outcome between the groups. Results: Two hundred patients were included and stratified in 1 long-term rifampicin group (traditional rifampicin combination therapy) or 1 of 3 short-term rifampicin groups (clindamycin or flucloxacillin or vancomycin monotherapy, including rifampicin for only 5 postoperative days). Adjusted hazard ratios (aHRs) for failure in patients treated with short-term rifampicin and either flucloxacillin or clindamycin were almost equal to patients treated with long-term rifampicin combination therapy (aHR = 1.21; 95% confidence interval, .34-4.40). Conclusions: A short-term rifampicin strategy with either clindamycin or flucloxacillin and only 5 days of rifampicin was found to be as effective as traditional long-term rifampicin combination therapy. A randomized controlled trial is needed to further address efficacy and safety of alternative treatment strategies for staphylococcal PJI.

A new prediction model for giant cell arteritis in patients with new onset headache and/or visual loss.

OBJECTIVE: The gold standard for diagnosis of giant cell arteritis (GCA) is a temporal artery biopsy (TAB). We sought for a clinical useful model to predict when an invasive TAB is not necessary to confirm GCA. METHODS: A prospective cohort study was conducted with patients > 50 years with possible GCA, presenting with newly onset headache and/or visual loss. Demographical, clinical, laboratory findings and histological data were collected. RESULTS: Fifty-six (70%) of the 94 patients showed 1 or more halos of the superficial temporal artery branches. Ultrasound-guided biopsy was positive in 28 patients (30%). Four independent variables predicted a positive TAB: weight loss, bilateral headache, positive halo sign and thrombocytosis. The ROC of the model had an area under the curve of 0.932 with a PPV of 83% and a NPV of 94%. CONCLUSIONS: Weight loss, bilateral headache, a positive halo sign with duplex and thrombocytosis are the most important clinical and laboratory predictors for GCA in a selected group of patients. SIGNIFICANCE: In patients > 50 years presenting with new onset headache or visual loss with 3 or more of the above mentioned risk factors, a biopsy of the temporal artery is not needed to confirm the diagnosis GCA.KEY MESSAGESIn our study biopsy of the temporal artery was positive in 30% of the patients with possible GCAWeight loss, bilateral headache, a positive halo sign on duplex and thrombocytosis are predictors for GCAThe halo sign had a high sensitivity but a low specificity for a biopsy proven GCA.

Expert consensus on the combined investigation of carpal tunnel syndrome with electrodiagnostic tests and neuromuscular ultrasound.

Expert consensus was sought to guide clinicians on the use of electrodiagnostic tests (EDX) and neuromuscular ultrasound (NMUS) in the investigation of suspected carpal tunnel syndrome (CTS). Consensus was achieved using the Delphi method via three consecutive anonymised surveys of 15 experts and was defined as rating agreement ≥ 80%. The panel agreed that combining EDX and NMUS is more informative than using each modality alone. NMUS adds value in patients with clinically suspected CTS with non-localizing or normal EDX, atypical EDX, failed CTS surgery, polyneuropathy, and CTS suspected to be secondary to structural pathology. The median nerve cross-sectional area should be measured at the site of maximal nerve enlargement, and the nerve should be scanned from mid-forearm to the palm. The group also identified those situations where the wrist-to-forearm area ratio and longitudinal scans of the median nerve should also be obtained. EDX should always be performed to quantify CTS severity and in individuals over age 70. This document is an initial step to guide clinicians on the combined investigation of CTS using EDX and NMUS, to be updated regularly with the emergence of new research.

Viral metagenomic sequencing in a cohort of international travellers returning with febrile illness.

BACKGROUND: Diagnosis of infections in returning international travellers can be challenging because of the broad spectrum of potential infectious etiologies potentially involved. Viral metagenomic next-generation sequencing (mNGS) has the potential to detect any virus present in a patient sample and is increasingly being used for difficult to diagnose cases. The aim of this study was to analyze the performance of mNGS for viral pathogen detection in the clinical setting of international travellers returning with febrile illness. METHODS: Thirty-eight serum samples from international travellers returning with febrile illness and presenting at the outpatient clinic of the Leiden University Medical Center in the Netherlands in the time period 2015-2016 were selected retrospectively. Samples were processed for viral metagenomic sequencing using a probe panel capturing all known vertebrate viruses. Bioinformatic analysis was performed using Genome Detective software for metagenomic virus detection. Metagenomic virus findings were compared with viral pathogen detection using conventional methods. RESULTS: In 8 out of the 38 patients (21%), a pathogenic virus was detected by mNGS. All viral pathogens detected by conventional assays were also detected by mNGS: dengue virus (n=4 patients), Epstein-Barr virus (n=2), hepatitis B virus (n=1). In addition, mNGS resulted in additional pathogenic findings in 2 patients (5%): dengue virus (n=1), and hepatitis C virus (n=1). Non-pathogenic viruses detected were: GB virus C (n=1) and torque teno viruses (n=3). High genome coverage and depth using capture probes enabled typing of the dengue viruses detected. CONCLUSIONS: Viral metagenomics has the potential to assist the detection of viral pathogens and co-infections in one step in international travellers with a febrile syndrome. Furthermore, viral enrichment by probes resulted in high genome coverage and depth which enabled dengue virus typing.

Nerve ultrasound for diagnosing chronic inflammatory neuropathy: A multicenter validation study.

OBJECTIVE: To validate the diagnostic accuracy of a previously described short sonographic protocol to identify chronic inflammatory neuropathy (CIN), including chronic inflammatory demyelinating polyneuropathy (CIDP), Lewis Sumner syndrome, and multifocal motor neuropathy (MMN), and to determine the added value of nerve ultrasound to detect treatment-responsive patients compared to nerve conduction studies (NCS) in a prospective multicenter study. METHODS: We included 100 consecutive patients clinically suspected of CIN in 3 centers. The study protocol consisted of neurologic examination, laboratory tests, NCS, and nerve ultrasound. We validated a short sonographic protocol (median nerve at forearm, upper arm, and C5 nerve root) and determined its diagnostic accuracy using the European Federation of Neurological Societies/Peripheral Nerve Society criteria of CIDP/MMN (reference standard). In addition, to determine the added value of nerve ultrasound in detecting treatment-responsive patients, we used previously published diagnostic criteria based on clinical, NCS, and sonographic findings and treatment response (alternative reference standard). RESULTS: Sensitivity and specificity of the sonographic protocol for CIN according to the reference standard were 87.4% and 67.3%, respectively. Sensitivity and specificity of this protocol according to the alternative reference standard were 84.6% and 72.8%, respectively, and of NCS 76.1% and 93.4%. With addition of nerve ultrasound, 44 diagnoses of CIN were established compared to 33 diagnoses with NCS alone. CONCLUSIONS: A short sonographic protocol shows high diagnostic accuracy for detecting CIN. Nerve ultrasound is able to detect up to 25% more patients who respond to treatment. CLASSIFICATION OF EVIDENCE: This multicenter study provides Class IV evidence that nerve ultrasound improves diagnosis of CIN.

Early differentiation between uncomplicated and complicated Staphylococcus aureus bacteraemia: Potential value and limitations of a clinical risk score.

OBJECTIVE: A cornerstone in the management of Staphylococcus aureus bacteraemia (SAB) is the differentiation between a complicated and an uncomplicated SAB course. The ability to early and accurately identify patients with - and without - complicated bacteraemia may optimise the utility of diagnostics and prevent unnecessary prolonged antibiotic therapy. METHODS: Development and validation of a prediction score in SAB using demographic, clinical, and laboratory data from two independent Dutch cohorts; estimating the risk of complicated disease at the time of the first positive blood culture. Models were developed using logistic regression and evaluated by c-statistics, ie area under the ROC-curve, and negative predictive values (NPV). RESULTS: The development- and validation cohorts included 150 and 183 patients, respectively. The most optimal prediction model included: mean arterial pressure, signs of metastatic infection on physical examination, leucocyte count, urea level and time to positivity of blood cultures (c-statistic 0.82, 95% CI 0.74-0.89). In the validation cohort, the c-statistic of the prediction score was 0,77 (95% CI 0.69-0.84). The NPV for complicated disease for patients with a score of ≤2 was 0.83 (95% CI 0.68-0.92), with a negative likelihood ratio of 0.14 (95% CI 0.06-0.31). CONCLUSION: The early SAB risk score helps to identify patients with high probability of uncomplicated SAB. However, the risk score's lacked absolute discriminative power to guide decisions on the management of all patients with SAB on its own. The heterogenicity of the disease and inconsistency in definitions of complicated SAB are important challenges in the development of clinical rules to guide the management of SAB.

In situ decompression vs conservative treatment for mild ulnar neuropathy at the elbow.

INTRODUCTION: The best treatment strategy for mild ulnar neuropathy at the elbow (UNE) is not known, due to lack of trials comparing surgery vs conservative treatment. METHODS: We recruited patients with clinical symptoms and signs of mild UNE and an electrophysiologically or sonographically confirmed diagnosis. Patients were randomly allocated to either in situ decompression or conservative treatment. The primary outcome was the proportion of patients with subjective symptom improvement at short-term (3 months) and long-term (6-12 months) follow-up. RESULTS: One hundred seventeen patients were included: 56 and 61 patients were allocated to surgery and conservative treatment, respectively. A larger proportion of surgically treated patients showed improvement at short-term follow-up (85% vs 50%; odds ratio, 5.6; P < .001), but no differences were observed at long-term follow-up. DISCUSSION: In situ decompression for mild UNE may result in faster relief of symptoms when compared with conservative treatment, but at long-term follow-up no differences were observed.

A double-blind, placebo-controlled phase 1/2a trial of the genetically attenuated malaria vaccine PfSPZ-GA1.

Immunization with attenuated Plasmodium sporozoites can induce protection against malaria infection, as shown by Plasmodium falciparum (Pf) sporozoites attenuated by radiation in multiple clinical trials. As alternative attenuation strategy with a more homogeneous population of Pf sporozoites (PfSPZ), genetically engineered Plasmodium berghei sporozoites (SPZ) lacking the genes b9 and slarp induced sterile protection against malaria in mice. Consequently, PfSPZ-GA1 Vaccine, a Pf identical double knockout (Pf∆b9∆slarp), was generated as a genetically attenuated malaria parasite vaccine and tested for safety, immunogenicity, and preliminary efficacy in malaria-naïve Dutch volunteers. Dose-escalation immunizations up to 9.0 × 105 PfSPZ of PfSPZ-GA1 Vaccine were well tolerated without breakthrough blood-stage infection. Subsequently, groups of volunteers were immunized three times by direct venous inoculation with cryopreserved PfSPZ-GA1 Vaccine (9.0 × 105 or 4.5 × 105 PfSPZ, N = 13 each), PfSPZ Vaccine (radiation-attenuated PfSPZ, 4.5 × 105 PfSPZ, N = 13), or normal saline placebo at 8-week intervals, followed by exposure to mosquito bite controlled human malaria infection (CHMI). After CHMI, 3 of 25 volunteers from both PfSPZ-GA1 groups were sterilely protected, and the remaining 17 of 22 showed a patency ≥9 days (median patency in controls, 7 days; range, 7 to 9). All volunteers in the PfSPZ Vaccine control group developed parasitemia (median patency, 9 days; range, 7 to 12). Immunized groups exhibited a significant, dose-related increase in anti-Pf circumsporozoite protein (CSP) antibodies and Pf-specific interferon-γ (IFN-γ)-producing T cells. Although no definite conclusion can be drawn on the potential strength of protective efficacy of PfSPZ-GA1 Vaccine, the favorable safety profile and induced immune responses by PfSPZ-GA1 Vaccine warrant further clinical evaluation.

A controlled human Schistosoma mansoni infection model to advance novel drugs, vaccines and diagnostics.

Schistosomiasis treatment relies on the use of a single drug, praziquantel, which is insufficient to control transmission in highly endemic areas1. Novel medicines and vaccines are urgently needed2,3. An experimental human model for schistosomiasis could accelerate the development of these products. We performed a dose-escalating clinical safety trial in 17 volunteers with male Schistosoma mansoni cercariae, which do not produce eggs (clinicaltrials.gov NCT02755324), at the Leiden University Medical Center, the Netherlands. The primary endpoints were adverse events and infectivity. We found a dose-related increase in adverse events related to acute schistosomiasis syndrome, which occurred in 9 of 17 volunteers. Overall, 5 volunteers (all 3 of the high dose group and 2 of 11 of the medium dose group) reported severe adverse events. Worm-derived circulating anodic antigen, the biomarker of the primary infection endpoint, peaked in 82% of volunteers at 3-10 weeks following exposure. All volunteers showed IgM and IgG1 seroconversion and worm-specific cytokine production by CD4+ T cells. All volunteers were cured with praziquantel provided at 12 weeks after exposure. Infection with 20 Schistosoma mansoni cercariae led to severe adverse events in 18% of volunteers and high infection rates. This infection model paves the way for fast-track product development for treatment and prevention of schistosomiasis.

Whole-blood transcriptomic signatures induced during immunization by chloroquine prophylaxis and Plasmodium falciparum sporozoites.

A highly effective vaccine that confers sterile protection to malaria is urgently needed. Immunization under chemoprophylaxis with sporozoites (CPS) consistently confers high levels of protection in the Controlled Human Malaria infection (CHMI) model. To provide a broad, unbiased assessment of the composition and kinetics of direct ex vivo human immune responses to CPS, we profiled whole-blood transcriptomes by RNA-seq before and during CPS immunization and following CHMI challenge. Differential expression of genes enriched in modules related to T cells, NK cells, protein synthesis, and mitochondrial processes were detected in fully protected individuals four weeks after the first immunization. Non-protected individuals demonstrated transcriptomic changes after the third immunization and the day of treatment, with upregulation of interferon and innate inflammatory genes and downregulation of B-cell signatures. Protected individuals demonstrated more significant interactions between blood transcription modules compared to non-protected individuals several weeks after the second and third immunizations. These data provide insight into the molecular and cellular basis of CPS-induced immune protection from P. falciparum infection.

Using local clinical and microbiological data to develop an institution specific carbapenem-sparing strategy in sepsis: a nested case-control study.

Background: From a stewardship perspective it is recommended that antibiotic guidelines are adjusted to the local setting, accounting for the local epidemiology of pathogens. In many settings the prevalence of Gram-negative pathogens with resistance to empiric sepsis therapy is increasing. How and when to escalate standard sepsis therapy to a reserve antimicrobial agent, is a recurrent dilemma. The study objective was to develop decision strategies for empiric sepsis therapy based on local microbiological and clinical data, and estimate the number needed to treat with a carbapenem to avoid mismatch of empiric therapy in one patient (NNTC). Methods: We performed a nested case control study in patients (> 18 years) with Gram-negative bacteremia in 2013-2016. Cases were defined as patients with Gram-negative bacteremia with in vitro resistance to the combination 2nd generation cephalosporin AND aminoglycoside (C-2GC + AG). Control patients had Gram-negative bacteremia with in vitro susceptibility to cefuroxime AND/OR gentamicin, 1:2 ratio. Univariate and multivariable analysis was performed for demographic and clinical predictors of resistance. The adequacy rates of empiric therapy and the NNTC were estimated for different strategies. Results: The cohort consisted of 486 episodes of Gram-negative bacteremia in 450 patients. Median age was 66 years (IQR 56-74). In vitro resistance to C-2GC + AG was present in 44 patients (8.8%). Independent predictors for resistance to empiric sepsis therapy were hematologic malignancy (adjusted OR 4.09, 95%CI 1.43-11.62, p < 0.01), previously cultured drug resistant pathogen (adjusted OR 3.72. 95%CI 1.72-8.03, p < 0.01) and antibiotic therapy during the preceding 2 months (adjusted OR 12.5 4.08-38.48, p < 0.01). With risk-based strategies, an adequacy rate of empiric therapy of 95.2-99.3% could be achieved. Compared to treating all patients with a carbapenem, the NNTC could be reduced by 82.8% (95%CI 78.5-87.5%) using the targeted approaches. Conclusions: A risk-based approach in empiric sepsis therapy has the potential to better target the use of reserve antimicrobial agents aimed at multi-resistant Gram-negative pathogens. A structured evaluation of the expected antimicrobial consumption and antibiotic adequacy rates is essential to be able to weigh the costs and benefits of potential antibiotic strategies and select the most appropriate approach.

Indications for neuromuscular ultrasound: Expert opinion and review of the literature.

Over the last two decades, dozens of applications have emerged for ultrasonography in neuromuscular disorders. We wanted to measure its impact on practice in laboratories where the technique is in frequent use. After identifying experts in neuromuscular ultrasound and electrodiagnosis, we assessed their use of ultrasonography for different indications and their expectations for its future evolution. We then identified the earliest papers to provide convincing evidence of the utility of ultrasound for particular indications and analyzed the relationship of their date of publication with expert usage. We found that experts use ultrasonography often for inflammatory, hereditary, traumatic, compressive and neoplastic neuropathies, and somewhat less often for neuronopathies and myopathies. Usage significantly correlated with the timing of key publications in the field. We review these findings and the extensive evidence supporting the value of neuromuscular ultrasound. Advancement of the field of clinical neurophysiology depends on widespread translation of these findings.

The diagnostic value of 18F-FDG-PET/CT and MRI in suspected vertebral osteomyelitis - a prospective study.

PURPOSE: The aim of this study was to determine the diagnostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) and magnetic resonance imaging (MRI) in diagnosing vertebral osteomyelitis. METHODS: From November 2015 until December 2016, 32 patients with suspected vertebral osteomyelitis were prospectively included. All patients underwent both 18F-FDG-PET/CT and MRI within 48 h. All images were independently reevaluated by two radiologists and two nuclear medicine physicians who were blinded to each others' image interpretation. 18F-FDG-PET/CT and MRI were compared to the clinical diagnosis according to international guidelines. RESULTS: For 18F-FDG-PET/CT, sensitivity, specificity, PPV, and NPV in diagnosing vertebral osteomyelitis were 100%, 83.3%, 90.9%, and 100%, respectively. For MRI, sensitivity, specificity, PPV, and NPV were 100%, 91.7%, 95.2%, and 100%, respectively. MRI detected more epidural/spinal abscesses. An important advantage of 18F-FDG-PET/CT is the detection of metastatic infection (16 patients, 50.0%). CONCLUSION: 18F-FDG-PET/CT and MRI are both necessary techniques in diagnosing vertebral osteomyelitis. An important advantage of 18F-FDG-PET/CT is the visualization of metastatic infection, especially in patients with bacteremia. MRI is more sensitive in detection of small epidural abscesses.

Nerve ultrasound in neurofibromatosis type 1: A follow-up study.

OBJECTIVE: To investigate development of sonographic abnormalities and applications of high-resolution ultrasonography (HRUS) in neurofibromatosis type 1 (NF1). METHODS: Sixteen asymptomatic or minimally symptomatic NF1 patients underwent HRUS at inclusion and 1 year follow-up. Upper and lower extremity nerves were investigated. Peripheral nerve involvement was graded. RESULTS: Plexiform neurofibromas (PNFs) were found in 7 patients (43.8%) at inclusion and 10 (62.5%) at follow-up. All initially identified PNFs were also found at follow-up; additional PNFs were found by extended longitudinal assessment at follow-up. All 3 patients with minor and 7 patients with severe peripheral nerve involvement had similar involvement at follow-up. Mean nerve size change was -0.2 mm2 (±1.6) and 0.3 mm2 (±6.2) in patients with minor and severe involvement. Mean PNF size change was -0.1 mm2 (±9.9). CONCLUSIONS: HRUS allows qualitative assessment of peripheral nerves, which makes it advantageous as initial imaging technique in suspected neuropathy. Patients with minimal nerve involvement remained so, and might therefore require less follow-up for malignant peripheral nerve sheath tumor (MPNSTs) development. Measured change in PNF size was highly variable. Repeating an extensive standardized HRUS protocol during follow-up thus seems less useful to screen for MPNSTs. SIGNIFICANCE: HRUS has potential applications as diagnostic and screening tool in NF1.