New frontiers in applied veterinary point‐of‐capture diagnostics: Toward early detection and control of zoonotic influenza

Among the chief limitations in achieving early detection and control of animal‐origin influenza of pandemic potential in high‐risk livestock populations is the existing lag time between sample collection and diagnostic result. Advances in molecular diagnostics are permitting deployment of affordable, rapid, highly sensitive, and specific point‐of‐capture assays, providing opportunities for targeted surveillance driving containment strategies with potentially compelling returns on investment. Interrupting disease transmission at source holds promise of disrupting cycles of animal‐origin influenza incursion to endemicity and limiting impact on animal production, food security, and public health. Adoption of new point‐of‐capture diagnostics should be undertaken in the context of promoting robust veterinary services systems and parallel support for operationalizing pre‐authorized plans and communication strategies that will ensure that the full potential of these new platforms is realized.     

Recurrent respiratory papillomatosis in northern Sweden: Clinical characteristics and practical guidance

Conclusion: Recurrent respiratory papillomatosis (RRP) patients with high surgical treatment frequency (≥ 1/year, HF) were significantly younger and had a more widespread laryngeal disease compared to a low frequency treated group (< 1 treatment/year, LF). This study confirms the existence of a clinical RRP group, not primarily related to HPV sub-type, but more care-intensive and in need of more vigilant follow-up. Objectives: RRP is associated with high morbidity due to its influence on breathing and voice. The purpose of this study was to characterize RRP patients in northern Sweden and investigate possible predictor factors affecting therapeutic needs. Method: Patients from the regional referral area (northern Sweden) were categorized for age, disease duration, juvenile or adult onset, profile of disease development, number of surgical sessions in relation to disease duration, laryngeal deposition of papilloma, gender, and HPV sub-types, in order to identify patients with increased need for frequent surgical treatment. Results: The median age of the RRP patients (n = 48) was 44.5 years; 34 (71%) were males and 14 (29%) females, most were infected with HPV 6. Patients with high surgical treatment frequency/year were significantly younger and showed more widespread papillomatous vegetation in the larynx, compared to the low frequency treated group.     

Motion‐compensated b‐tensor encoding for in vivo cardiac diffusion‐weighted imaging

Motion is a major confound in diffusion‐weighted imaging (DWI) in the body, and it is a common cause of image artefacts. The effects are particularly severe in cardiac applications, due to the nonrigid cyclical deformation of the myocardium. Spin echo‐based DWI commonly employs gradient moment‐nulling techniques to desensitise the acquisition to velocity and acceleration, ie, nulling gradient moments up to the 2nd order (M2‐nulled). However, current M2‐nulled DWI scans are limited to encode diffusion along a single direction at a time. We propose a method for designing b‐tensors of arbitrary shapes, including planar, spherical, prolate and oblate tensors, while nulling gradient moments up to the 2nd order and beyond. The design strategy comprises initialising the diffusion encoding gradients in two encoding blocks about the refocusing pulse, followed by appropriate scaling and rotation, which further enables nulling undesired effects of concomitant gradients. Proof‐of‐concept assessment of in vivo mean diffusivity (MD) was performed using linear and spherical tensor encoding (LTE and STE, respectively) in the hearts of five healthy volunteers. The results of the M2‐nulled STE showed that (a) the sequence was robust to cardiac motion, and (b) MD was higher than that acquired using standard M2‐nulled LTE, where diffusion‐weighting was applied in three orthogonal directions, which may be attributed to the presence of restricted diffusion and microscopic diffusion anisotropy. Provided adequate signal‐to‐noise ratio, STE could significantly shorten estimation of MD compared with the conventional LTE approach. Importantly, our theoretical analysis and the proposed gradient waveform design may be useful in microstructure imaging beyond diffusion tensor imaging where the effects of motion must be suppressed.     

CTLA4 antagonists in phase I and phase II clinical trials,current status and future perspectives for cancer therapy

Introduction: In cancer, the immune response to tumor antigens is often suppressed by inhibitors and ligands. Checkpoint blockade, considered one of the most promising frontiers for anti-cancer therapy, aims to stimulate the immune anti-cancer response. Agents such as cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) inhibitors offer prolonged survival with manageable side effects.

Areas covered: We summarize the recent clinical successes of CTLA-4 inhibitors and place a strong emphasis on those in early phase clinical trials, often in combination with other immune check-point inhibitors, i.e., programmed cell death protein 1 (PD-1) and BRAF/mitogen-activated protein kinase inhibitors.

Expert opinion: Recent phase I and phase II clinical trials confirm the efficacy of anti-CTLA-4 therapy for treatment of cancers such as renal cell carcinoma. These studies also indicated increased efficacy with combined immune checkpoint blockade with PD-1 or Ras/Raf/mitogen-activated protein kinase/ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) inhibitors. Researchers must search for new immune targets that may enable more effective and safe immune checkpoint blockade and cancer therapy. This goal may be achieved by next-generation combination therapies to overcome immune checkpoint therapy resistance.     

Loa loa macrofilariasis in the eyelid: case report of the first periocular subcutaneous manifestation in Germany

Purpose We report a case of periocular subcutaneous macrofilariasis as an initial sign of a systemic Loa loa infection.Methods Thorough history, eye examination and surgical intervention. Parasitological and serological analysis.Results A periocular adult Loa loa worm was extracted from the left upper eyelid in an African student living in Germany after presenting to our department with intermittent attacks of painful lid swelling. Four weeks later he presented with Calabar swellings in his arms without serological evidence of microfilaria and was treated with diethylcarbamazine.Conclusion Due to increasing migration of populations to Europe rare manifestations of ocular loiasis are becoming more common. Intermittent painful eyelid swelling in patients who visited or have lived in Africa should always raise the suspicion of systemic loiasis.     

Inverse Planning – a Comparative Intersystem and Interpatient Constraint Study

PURPOSE: To compare commercial treatment-planning systems (TPS) for inverse planning (IP) and to assess constraint variations for specific IMRT indications. MATERIAL AND METHODS: For IP, OTP, XiO and BrainSCAN were used and step-and-shoot intensity-modulated radiotherapy (IMRT) delivery was assumed. Based on identical constraints, IP was performed for a prostate, head and neck, brain, and gynecologic case. IMRT plans were compared in terms of conformity/homogeneity, dose-volume histograms (DVHs), and delivery efficiency. For ten patients each of a class of indications, constraint variations were evaluated. RESULTS: IMRT plans were comparable concerning minimum target dose, homogeneity, conformity, and maximum doses to organs at risk. Larger differences were seen in dose gradients outside the target, monitor units, and segment number. Using help structures proved efficient to shape isodoses and to reduce segmentation workload. For IMRT class solutions, IP constraint variations depended on anatomic site. CONCLUSION: IP systems requiring doses as input and having objective functions based on physical parameters had a very similar performance. Constraint templates can be established for a class of IMRT indications.