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With increasing demand for psychotherapy services, clinicians are carrying increasingly large caseloads (Bailey et al., 2020). As the number of new intakes exceeds the number of clinical hours available each week in some settings, psychotherapy is delivered on an attenuated schedule for returning clients (rather than the traditional weekly frequency); there is, however, little support for the efficacy of this practice. The present study explored the effect of session frequency on psychotherapy outcomes using a quasi-randomized controlled design. In a working university counseling center, we assigned therapists to either a treatment-as-usual (TAU) group (attenuated session frequency) or an experimental group (weekly session frequency). Clients were randomly assigned to a therapist in either condition. Using hierarchical linear modeling and survival analyses, we examined psychotherapy outcomes (measured by session-by-session Outcome Questionnaire 45 scores) for 1,322 clients (3,919 individual sessions). We found no differences between groups when examining the full sample, but also found limited fidelity in the experimental group. When identifying individuals who were seen weekly in at least the first three sessions after intake (sensitivity analysis), we found the following: (a) weekly therapy resulted in faster trajectories of change over time, (b) weekly therapy resulted in a greater likelihood of achieving recovery, and (c) weekly therapy resulted in a greater likelihood of achieving recovery sooner. We discuss the importance of including session frequency when considering the dose of therapy, as well as the implication that prioritizing weekly therapy may increase therapy efficacy and efficiency in routine practice. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The study was aimed at exploring the clinical value of a 14-zone lung ultrasound scoring (LUS) method in treating neonatal respiratory distress syndrome (NRDS) with pulmonary surfactant (PS) and determining the timing of mechanical ventilation (MV). In this study, 88 neonates with NRDS who received PS replacement therapy were selected. We applied a new 14-zone LUS method before and 12, 24, 48 and 72 h after PS treatment to explore the clinical value of assessing PS replacement therapy efficacy in NRDS. Additionally, 67 patients with NRDS under MV received LUS during extubation. The receiver operating characteristic curve was used to analyze the diagnostic efficacy of LUS in the timing of extubation. LUS score was inversely associated with PS treatment. At 12 h after PS, only the 14-zone LUS method was significantly different (t = 4.08, p0.05) as compared with before PS, which was consistent with the change on chest x-ray (CXR); the other LUS methods did not differ (p0.05). The 14-zone LUS method exhibited better diagnostic performance for withdrawal time. A score of 41.0 points was used as the diagnostic threshold to predict the risk of withdrawal failure, with an area under the curve of 0.955, sensitivity of 92.4% and specificity of 93.8%. The new 14-zone LUS method improved scoring in the early efficacy of PS and had good diagnostic efficiency for timing the removal of MV in NRDS.

Patient-derived organoids are being considered as models that can help guide personalized therapy through in vitro anti-cancer drug response evaluation. However, attempts to quantify in vitro drug responses in organoids and compare them with responses in matched patients remain inadequate. In this study, we investigated whether drug responses of organoids correlate with clinical responses of matched patients and disease progression of patients. Organoids were established from 54 patients with colorectal cancer who (except for one patient) did not receive any form of therapy before, and tumor organoids were assessed through whole-exome sequencing. For comparisons of in vitro drug responses in matched patients, we developed an "organoid score" based on the variable anti-cancer treatment responses observed in organoids. Very interestingly, a higher organoid score was significantly correlated with a lower tumor regression rate after the standard-of-care treatment in matched patients. Additionally, we confirmed that patients with a higher organoid score (≥ 2.5) had poorer progression-free survival compared with those with a lower organoid score (< 2.5). Furthermore, to assess potential drug repurposing using an FDA-approved drug library, ten tumor organoids derived from patients with disease progression were applied to a simulation platform. Taken together, organoids and organoid scores can facilitate the prediction of anti-cancer therapy efficacy, and they can be used as a simulation model to determine the next therapeutic options through drug screening. Organoids will be an attractive platform to enable the implementation of personalized therapy for colorectal cancer patients.

Background and ObjectivesEndogenous and exogenous female sex hormones are considered important contributors to migraine pathophysiology. Previous studies have cautiously suggested that perimenstrual migraine attacks have a longer duration and are associated with higher disability compared to nonperimenstrual attacks, but they showed conflicting results on acute therapy efficacy, pain intensity, and associated symptoms. We compared perimenstrual and nonperimenstrual migraine attack characteristics and assessed premenstrual syndrome (PMS) in women with migraine.MethodsWomen with migraine were invited to complete a headache e-diary. Characteristics of perimenstrual attacks and nonperimenstrual attacks were compared. The primary outcome was attack duration. Secondary outcomes were headache intensity, accompanying symptoms, acute medication intake, and pain coping. Mixed effects models were used to account for multiple attacks within patients. PMS was assessed in patients without hormonal contraceptives. Subgroup analyses were performed for women with menstrually related migraine (MRM) and nonmenstrually related migraine (non-MRM) and women with a natural menstrual cycle and women using hormonal contraceptives.ResultsA representative group of 500 participants completed the e-diary for at least 1 month. Perimenstrual migraine attacks (n = 998) compared with nonperimenstrual attacks (n = 4097) were associated with longer duration (20.0 vs 16.1 hours, 95% confidence interval 0.2–0.4), higher recurrence risk (odds ratio [OR] 2.4 [2.0–2.9]), increased triptan intake (OR 1.2 [1.1–1.4]), higher headache intensity (OR 1.4 [1.2–1.7]), less pain coping (mean difference −0.2 [−0.3 to −0.1]), more pronounced photophobia (OR 1.3 [1.2–1.4]) and phonophobia (OR 1.2 [1.1–1.4]), and less aura (OR 0.8 [0.6–1.0]). In total, 396/500 women completed the diary for ≥3 consecutive menstrual cycles, of whom 56% (221/396) fulfilled MRM criteria. Differences in attack characteristics became more pronounced when focusing on women with MRM and women using hormonal contraceptives. Prevalence of PMS was not different for women with MRM compared to non-MRM (11% vs 15%).DiscussionThe longer duration of perimenstrual migraine attacks in women (with MRM) is associated with higher recurrence risk and increased triptan use. This may increase the risk of medication overuse and emphasizes the need to develop female-specific prophylactic treatment.

Background: Curing hemorrhagic cystitis remains a challenge. We explore a continuous and effective treatment for hemorrhagic radiation cystitis. Methods: The data of patients in 6 provincial cancer hospital urology departments between April 2015 and December 2019 was reviewed retrospectively. Patients were classified as moderate and severe groups. The 5-steps sequential method was adopted. Two groups were initiated with step 1 and step 3 respectively. Step 1 was symptomatic treatment. Thrombin solution or sodium hyaluronate was administrated for bladder irrigation in step 2. Step 3 was transurethral electrocoagulation. Step 4 was interventional embolization. Step 5 was HBO therapy. OABSS was used to assess the improvement of patients' symptoms. The outcome was evaluated after at least 6 months of follow-up. Results: A total of 650 patients (56 men and 594 women), mean age 71.2 years, were enrolled in the 5 steps sequential method. 582 patients were classified as moderate and 68 severe group. In moderate group, the cure rate of step 1 was 61.2% (356/582), 80.4% (468/582) after step 2, 93.1% (542/582) after step 3, 96.2% (560/582) after step 4, and 99.8% (581/582) after step 5. In severe group, the cure rate was 54.4% (37/68) after step 3, 76.5% (52/68) after step 4, and 94.1% (64/68) after the step 5 respectively. The mean OABSS scores of both groups significantly decreased after 5 steps sequential method treatment (P

Oncolytic virus immunotherapy is rapidly gaining interest in the field of immunotherapy against cancer. The minimal toxicity upon treatment and the dual activity of direct oncolysis and immune activation make therapy with oncolytic viruses (OVs) an interesting treatment modality. The safety and efficacy of several OVs have been assessed in clinical trials and, so far, the Food and Drug Administration (FDA) has approved one OV. Unfortunately, most treatments with OVs have shown suboptimal responses in clinical trials, while they appeared more promising in preclinical studies, with tumours reducing after immune cell influx. In several clinical trials with OVs, parameters such as virus replication, virus-specific antibodies, systemic immune responses, immune cell influx into tumours and tumour-specific antibodies have been studied as predictors or correlates of therapy efficacy. In this review, these studies are summarized to improve our understanding of the determinants of the efficacy of OV therapies in humans and to provide insights for future developments in the viro-immunotherapy treatment field.

Background Asymptom of invasive candidiasis (IC) and low positive rate of blood culture lead to delay diagnose of neonatal infection. Serum (1,3)-β-D-glucan (BDG) performs well in adult IC, but its use in neonatal IC is unclear. We evaluated the use of BDG, procalcitonin (PCT), high-sensitive C-reactive protein (hsCRP) or platelet count (PC) in neonatal IC. Methods We collected the data of neonates admitted to our institute. Eighty neonates were enrolled, and divided into IC group, bacterial infection (BI) group and control (CTRL) group. We analyzed the difference of these indicators between groups, and generated Receiver operator characteristic (ROC) curve. The value of BDG in antifungal therapy efficacy assessment was also investigated. Results The BDG level was higher in IC group compared with BI and CTRL group. C. albicans lead to significant increase of BDG compared with C. parapsilosis. IC group had highest hsCRP level and lowest PC. PCT level was similar between groups. ROC showed that BDG or hsCRP performs well in neonatal IC, the optimal cut-off for BDG was 13.69 mg/ml. Combined BDG with hsCRP, PCT and PC increased diagnostic value. Serum BDG level was decreased during antifungal treatment. Conclusion Serum BDG performs well in identification of neonatal IC and in monitoring the antifungal therapy efficacy.

The knowledge of cancer cell response to conventional therapies is crucial in order to choose the correct therapy of patients affected by cancer. The major problem is generally attributed to the lack of specific biological processes able to predict the therapy efficacy. Here, we optimized a computational method for the analysis of gene networks able to detect and quantify the effects of a drug in a pan-cancer study. Overall, our method, using several network topological measures has identified a cancer gene network with a key role in biological processes. The gene network, able to classify with a good performance cancer vs normal samples, was modulated in silico to evaluate the effects of new or approved drugs. This computational model could offer an interesting hint to decipher molecular mechanisms contributing to resistance or inefficacy of drugs.

Objectives High‐frequency spinal cord stimulation (HF‐SCS) at 10 kHz has proven to be efficacious in the treatment of chronic back and leg pain in a randomized, controlled, trial (SENZA‐RCT). However, large observational studies have yet to be published. Therefore, we performed a real‐world, multicenter, retrospective, review of therapy efficacy in 1660 patients with chronic trunk and/or limb pain. Methods Data were collected in a real‐world environment and retrospectively sourced from a global database. Included patients were trialed and/or permanently implanted with HF‐SCS at 10 kHz between April 2014 and January 2018. We evaluated responder rates at 3, 6, and 12 months post‐implantation. Response was defined as ≥50% pain relief from baseline. A last visit analysis included responder rate along with overall change in function, sleep, quality of life, and medication intake versus baseline. Results Eighty‐four percent of our HF‐SCS‐treated patients had both chronic back and leg pain. At least 70% of patients reported response to therapy throughout 12 months of follow‐up. This sustained responder rate was corroborated by the last visit value (74.1%). Most patients reported concomitant improvements in function (72.3%), sleep (68.0%), and quality of life (90.3%) at their last visit versus baseline. Thirty‐two percent of patients reported decreased medication intake at their last visit. Interpretation Sustained and effective pain relief was experienced by >70% of our HF‐SCS‐treated patients, consistent with the findings of a previously published randomized, controlled, trial. Our review provides complementary evidence to support the treatment of chronic back and leg pain with this therapy.

Objective. As one of the common symptoms of sudden sensorineural hearing loss (SSH), tinnitus seriously affects the life and work of SSH patients. The present study is aimed at exploring whether SSH can receive acoustic therapy and the factors that affect the efficacy of SSH acoustic therapy. Methods. A total of 162 patients were outpatients and inpatients, 86 were SSH, and 76 were short-term tinnitus (STT). Both groups received pure tone audiometry, tinnitus matching, and residual inhibition test (RI). The Tinnitus Handicap Inventory (THI), visual analog scale with respect to tinnitus loudness (VAS), and RI in each group were evaluated. The effects of age, degree of hearing loss, and tinnitus course on the efficacy of SSH acoustic therapy were also evaluated. Results. In the comparison of RI, THI, and VAS, there was no difference between SSH and STT ( P > 0.05 ). SSH patients with mild hearing loss showed better acoustic therapy efficacy compared with SSH patients with severe hearing loss ( P < 0.05 ), but there is no statistical difference in age and the course of tinnitus ( P > 0.05 ). Conclusion. The present study showed that SSH may improve tinnitus symptom through receiving acoustic therapy and SSH patients with mild hearing loss can get better acoustic therapy effects.

Rosacea is a common chronic facial inflammatory skin disease. However, treatment for “difficult-to-treat rosacea” cases has not been established. This 48-week, prospective, observational study analyzed patients who underwent three non-insulated fractional microneedle radiofrequency (NFMRF) sessions at 2-month intervals. Therapy efficacy, epidermal barrier function, and side effects were evaluated. 34 subjects completed the trial. NFMRF resulted in CEA score reduction from 2.65 ± 0.59 to 1.56 ± 0.50 (P

Immune checkpoint blockade (ICB) therapies have significantly improved the prognosis and shown considerable promise for cancer therapy; however, differences in ICB treatment efficacy between the elderly and young are unknown. We analyzed the studies enrolled in the meta-analysis using the deft approach, and found no difference in efficacy except melanoma patients receiving anti–PD-1 therapy. Similarly, higher treatment response rate and more favorable prognosis were observed in elderly patients in some cancer types (e.g., melanoma) with data from published ICB treatment clinical trials. In addition, we comprehensively compared immunotherapy-related molecular profiles between elderly and young patients from public trials and The Cancer Genome Atlas (TCGA), and validated these findings in several independent datasets. We discovered a divergent age-biased immune profiling, including the properties of tumors (e.g., tumor mutation load) and immune features (e.g., immune cells), in a pancancer setting across 27 cancer types. We believe that ICB treatment efficacy might vary depending on specific cancer types and be determined by both the tumor internal features and external immune microenvironment. Considering the high mutational properties in elderly patients in many cancer types, modulating immune function could be beneficial to immunotherapy in the elderly, which requires further investigation.

Analyses for the presence of anti-neutrophil cytoplasmic antibodies (ANCA) are important in the diagnostic work-up of patients with small vessel vasculitis. Since current immuno-assays are predominantly designed for diagnosis of patients with ANCA-associated vasculitis (AAV), implementation in routine clinical practice, internal and external quality control, and harmonization are focused on this particular use. However, ANCA testing may also be relevant for monitoring therapy efficacy and for predicting a clinical relapse in AAV patients, and even for diagnostic purposes in other clinical situations. In the current review, the topics of implementation, quality control, and standardization vs. harmonization are discussed while taking into account the different applications of the ANCA assays in the context of AAV.

Human papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in various anatomical subsites, HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is the most common HPV-related malignancy of the head and neck, and its worldwide incidence is constantly rising. Patients with OPSCC are generally younger, have less co-morbidities and generally have better prognosis due to different biological mechanisms of carcinogenesis. These facts have generated hypotheses on potential treatment modifications, aiming to minimize treatment-related toxicities without compromising therapy efficacy. Numerous randomized clinical trials have been designed to verify this strategy and increasingly real-world evidence data from retrospective, observational studies is becoming available. Until now, the data do not support any modification in contemporary treatment protocols. In this narrative review, we outline recent data provided by both randomized controlled trials and real-world evidence of HPV-positive OPSCC in terms of clinical value. We critically analyze the potential value and drawbacks of the available data and highlight future research directions. This article was written by members and invitees of the International Head and Neck Scientific Group.(www.IHNSG.com). ispartof: ORAL ONCOLOGY vol:123 ispartof: location:England status: published

Recently, both doctors and patients pay particular attention to aesthetic medical services quality and efficacy of aesthetic adjustment implemented. It is essential to ensure research, analysis, and improving of botulinum toxin therapy quality and provide patients' orientation on the adjustment schedule, which includes long-term observation period, in order to accomplish the expected goals and increase degree of satisfaction. Injections of medication such as botulinum A toxin are highly demanded in many types of aesthetic treatment. However, practically, sufficient cosmetological effect may not always be achieved, and moreover, complications are possible. This article presents an attempt to evaluate botulinum toxin therapy efficacy using computer program, with calculation of integral quality factor (IQF) and plotting injection modeling visual diagram in long-term observation period. In 3 selected clinical examples, aggregate IQF figure makes: in case of static forehead wrinkles 91.67%, for dynamic forehead wrinkles 76.67%; in case of static eyebrow wrinkles 96.67%, for dynamic eyebrow wrinkles 85%; as applied to static wrinkles of the outer corned of the eye 91.67%, whereas applied to dynamic wrinkles of the outer corner of the eye 73.33%. Although the benchmark is thought to be 100% of remodeling result, the procedures outcome still meets patients' expectations. At the same time, present approach demands further discussion and collection for the purpose of development of procedural basis for aesthetic services quality assessment and interpretation of findings.

An individual’s inherited genetic makeup and acquired genomic variants may account for a significant portion of observable variability in therapy efficacy and toxicity. Pharmacogenomics (PGx) is the concept that treatments can be modified to account for these differences to increase chances of therapeutic efficacy while minimizing risk of adverse effects. This is particularly applicable to oncology in which treatment may be multimodal. Each tumor type has a unique genomic signature that lends to inclusion of targeted therapy but may be associated with cumulative toxicity, such as cardiotoxicity, and can impact quality of life. A greater understanding of therapeutic agents impacted by PGx and subsequent implementation has the potential to improve outcomes and reduce risk of drug-induced adverse effects.

To characterize the health effects of incorporated plutonium, many experiments have been conducted using different animal models. These range from (1) applied (tissue uptake/retention determination, decorporation therapy efficacy), (2) fundamental (gene expression, cancer induction), and (3) dosimetry models. In recent years, the use of animals for scientific purposes has become a public concern. The application of the 3Rs - Replace (use of alternative methods or animals not considered capable of experiencing pain, suffering, and distress), Reduce (reduction in animal numbers), and Refine (better animal welfare and minimization of suffering, pain and distress) - has increased to address ethical concerns and legislative requirements. The introduction of novel non-animal technologies is also an important factor as complementary options to animal experimentation. In radiotoxicology research, it seems there is a natural tendency to Replace given the possibility of data reuse obtained from contamination cases in man and animal studies. The creation of "registries" and "repositories" for nuclear industry workers (civil and military) is now a rich legacy for radiotoxicological measurements. Similarly, Reduction in animal numbers can be achieved by good experimental planning with prior statistical analyses of animal numbers required to obtain robust data. Multiple measurements in the same animal over time (external body counting, excreta collection) with appropriate detection instruments also allow Reduction. In terms of Refinement, this has become "de rigueur" and a necessity given the societal and legal concerns for animal welfare. For research in radiotoxicology, particularly long-term studies, better housing conditions within the constraints of radiation protection issues for research workers are an important concern. These are all pertinent considerations for the 3Rs remit and future research in radiotoxicology.

A multifunctional theranostic nanoplatform, which integrates diagnostic and therapeutic functions in a single nanosystem, holds great promise for guiding disease treatment and improving the corresponding therapy efficacy. We report the development of a novel g-C3N4 nanosheet-based theranostic nanoassembly for both enhanced imaging of cancer-relevant mRNA in living cells and imaging-guided on-demand photodynamic therapy (PDT) for tumors. The nanoassembly was constructed by using highly fluorescent and water-dispersible g-C3N4 nanosheets which act as nanocarriers, enabling efficient and self-tracking transfection of the DNA hairpin probes. The presence of intracellular mRNA will initiate the DNA hairpin probes, ultimately resulting in an amplified fluorescence signal via hybridization and displacement with mRNA. Moreover, enhanced fluorescence imaging-guided precise PDT for tumors in living cells was also demonstrated, allowing the selective ablation of tumors without any obvious side effects. Therefore, the developed theranostic approach can provide a promising platform for low-abundance biomarker discovery and early treatment of related diseases.

Background Rosacea is a common inflammatory skin condition affecting approximately 5% of the world population. Therapeutic approaches to rosacea are focused on symptom suppression by means of anti-inflammatory agents. More recently, photodynamic therapy, especially light-emitting diodes, has been introduced as a valid alternative to conventional therapy. Case presentation In the present work, we reported the efficacy and safety of light-emitting diodes therapy combining blue (480 nm) and red (650 nm) light for the treatment of two patients with papulopustular rosacea: a 22-year-old Caucasian woman and a 68-year-old Caucasian man. Conclusions This kind of treatment could represent an effective, safer, and well-tolerated approach for the treatment of such conditions.

The objective of this study was to compare the safety and efficacy of 0.2% hyaluronic acid (HA) topical gel and dexamethasone topical ointment in the treatment of recurrent aphthous ulcers (RAU) in children. This retrospective observational study included 104 patients who had more than two episodes of oral aphthous ulcers per year and were treated with HA (n=52) or dexamethasone (n=52) from August 15, 2014 to September 3, 2018. Therapy efficacy was evaluated based on the ulcer size and pain score before versus 7 days after either therapy. The paired t-test, chi-squared test, and independent t-test were utilized for statistical analyses. There was no significant difference in ulcer size or pain score between the HA and dexamethasone groups, on day 1 or day 7. Both treatments were tolerated well and no side effects were reported. No significant differences in body temperature, respiration rate, pulse, or systolic/diastolic blood pressure were observed between the start (day 1) and end of treatment (day 7), for either treatment. HA and dexamethasone showed similar efficacy in reducing ulcer size and pain scores, and were tolerated equally well in children with RAU. Future high-quality studies with larger numbers of patients are needed to confirm our findings.

Large investments by pharmaceutical companies in the development of new antineoplastic drugs have not been resulting in adequate advances of new therapies. Despite the introduction of new methods, technologies, translational medicine and bioinformatics, the usage of collected knowledge is unsatisfactory. In this paper, using examples of pancreatic ductal adenocarcinoma (PaC) and castrate-resistant prostate cancer (CRPC), we proposed a concept showing that, in order to improve applicability of current knowledge in oncology, the re-clustering of clinical and scientific data is crucial. Such an approach, based on systems oncology, would include bridging of data on biomarkers and pathways between different cancer types. Proposed concept would introduce a new matrix, which enables combining of already approved therapies between cancer types. Paper provides a (a) detailed analysis of similarities in mechanisms of etiology and progression between PaC and CRPC, (b) diabetes as common hallmark of both cancer types and (c) knowledge gaps and directions of future investigations. Proposed horizontal and vertical matrix in cancer profiling has potency to improve current antineoplastic therapy efficacy. Systems biology map using Systems Biology Graphical Notation Language is used for summarizing complex interactions and similarities of mechanisms in biology of PaC and CRPC.

The physical characteristics of tumours are intricately linked to the tumour phenotype and difficulties during treatment. Many factors contribute to the increased stiffness of tumours; from increased matrix deposition, matrix remodelling by forces from cancer cells and stromal fibroblasts, matrix crosslinking, increased cellularity, and the build-up of both solid and interstitial pressure. Increased stiffness then feeds back to increase tumour invasiveness and reduce therapy efficacy. Increased understanding of this interplay is offering new therapeutic avenues.

Positron emission tomography (PET) is a powerful diagnostic nuclear medicine imaging technique. PET allows in vivo detection of a wide variety of physiologic and pathologic phenomena and it offers a noninvasive tool for the monitoring of therapy in various diseases. Invasive fungal infections (IFIs) are a global concern because of the increasing population of patients at risk of IFIs and the high morbidity and mortality. Therapy with antifungal agents is long-standing and expensive. The emerging resistant fungal strains make the management of IFIs challenging. There is an absolute need for a sensitive noninvasive biomarker capable of monitoring the disease activity of IFIs and determining the efficacy of treatment at an early time point. PET imaging with 18Ffluorodeoxyglucose (FDG) was used to detect and assess disease activity in IFI foci already over 20 years ago. At that time, it was suggested it could be a useful biomarker for monitoring antifungal therapy. However, this knowledge has still not been fully exploited for the management of IFIs. The literature reveals an increasing realization of the usefulness of PET in monitoring therapy of IFIs. In this review, we highlight the advantages of nuclear medicine techniques in the management of IFIs with emphasis of the role of PET in monitoring therapy efficacy.

Gastrointestinal cancers (GI), are a group of highly aggressive malignancies with heavy cancer-related mortalities. Even if continued development of therapy methods, therapy resistance has been a great obstruction for cancer treatment and thereby inevitably leads to depressed final mortality. Peritumoral cancer associated fibroblasts (CAFs), a versatile population assisting cancer cells to build a facilitated tumor microenvironment (TME), has been demonstrated exerting a promotion influence on cancer proliferation, migration, invasion, metastasis, and also therapy resistance. In this review, we provide an update progress in describing how CAFs mediate therapy resistance in GI by various means, meanwhile highlight the crosstalk between CAFs and cancer cells and present some vital signaling pathways activated by CAFs in this resistant process. Furthermore, we discuss the current advances in adopting novel drugs against CAFs and how the knowledge contributing to improved therapy efficacy in clinical practice. In sum, CAFs create a therapy-resistant TME in several aspects of GI progression, although some key problems about distinguishing CAFs subpopulations and controversial issues on pleiotropic CAFs in medication need to be solved for subsequent clinical application. Predictably, targeting therapy-resistant CAFs is a promising adjunctive treatment to benefit GI patients.

International audience; Diabetes mellitus is one of the most challenging threats to global public health. To improve the therapy efficacy of antidiabetic drugs, numerous drug delivery systems have been developed. Polyethylene glycol (PEG) is a polymeric family sharing the same skeleton but with different molecular weights which is considered as a promising material for drug delivery. In the delivery of antidiabetic drugs, PEG captures much attention in the designing and preparation of sustainable and controllable release systems due to its unique features including hydrophilicity, biocompatibility and biodegradability. Due to the unique architecture, PEG molecules are also able to shelter delivery systems to decrease their immunogenicity and avoid undesirable enzymolysis. PEG has been applied in plenty of delivery systems such as micelles, vesicles, nanoparticles and hydrogels. In this review, we summarized several commonly used PEG-contained antidiabetic drug delivery systems and emphasized the advantages of stimuli-responsive function in these sustainable and controllable formations.

Non-small cell lung cancer (NSCLC) therapy has entered a rapidly advancing era of precision medicine with an ever increasing number of drugs directed against a variety of specific tumor targets. Amongst these new agents, tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) are most frequently used. However, as only a sensitive subgroup of patients benefits from targeting drugs, predictive biomarkers are needed. Positron emission tomography (PET) may offer such a biomarker for predicting therapy efficacy. Some of the TKIs and mAbs that are in clinical use can be radioactively labeled and used as tracers. PET can visualize and quantify tumor specific uptake of radiolabeled targeting drugs, allowing for characterization of their pharmacokinetic behavior. In this review, the clinical potential of PET using radiolabeled TKIs (TKI-PET) and mAbs (immuno-PET) in NSCLC is discussed, and an overview is provided of the most relevant preclinical and clinical studies.

Gas therapy is an emerging and promising field, utilizing the unique therapeutic effects of several kinds of gases (NO, CO, H2S and H2) towards many major diseases, including cancer and cardiovascular diseases, and it is also facing challenges relating to enhancing gas therapy efficacy and avoiding gas poisoning risks. Here, we have proposed a new concept for precision gas therapy using a nanomedicine strategy to overcome the challenges. In this perspective, we have addressed a series of existing and potential solutions from the point of view of nanomedicine, and conveyed a collection of opinions about future expandable research into precision gas therapy.

A right choice of the internal standard is one of the most challenging tasks during bioanalytical method development. Surprisingly, among the HPLC-MS methods for the determination of a cardiovascular drug olmesartan in plasma only structural analogues or similar compounds were used as internal standards. We have tried to answer the question whether the stable isotope labelled (deuterated) internal standard, as recommended by regulatory agencies, can be used for the reliable determination of olmesartan in human plasma. An HPLC-MS method using this standard in a simplified liquid-liquid extraction procedure led to accurate and precise results in the linearity range of 5-2500ng/mL. The method is well suited for pharmacokinetic studies following a single 40mg oral dose of olmesartan medoxomil in humans. The method was fully validated according to international guidelines and successfully applied in a bioequivalence study in humans. The use of deuterated olmesartan as the internal standard afforded a reliable tool for regulatory bioanalysis that can indirectly contribute to therapy efficacy and improve the safety of patients treated with generic medicines.

This review aims to discuss the use of fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) for diagnosis and management of patients with large-vessel vasculitis (LVV). Incidence of LVV is likely underestimated, in part due to its non-specific symptoms. Nevertheless, early diagnosis of LVV is essential to initiate timely therapy in order to prevent vascular complications, such as stenoses and aneurysms. FDG PET/CT imaging has the ability to detect LVV during the acute phase, prior to edema and other vascular structural changes, with its high sensitivity for inflammatory activity. FDG PET/CT was shown to be a powerful prognostic marker by allowing identification of patients at risk of vascular complications. Additionally, preliminary data support the use of FDG PET/CT to follow therapy efficacy. FDG PET/CT allows early detection of inflammation, before morphological and irreversible vascular changes can be observed, allowing prompt diagnosis and treatment of LVV.

PURPOSE: Lung cancer heterogeneity makes response to therapy extremely hard to predict. Patient-derived xenografts (PDXs) represent a reliable preclinical model that closely recapitulates the main characteristics of the primary tumor and could represent a useful asset to test new therapies. Here, using PET imaging, we verify how lung cancer PDXs reproduce the metabolic features of the corresponding primary tumors. METHODS: We performed longitudinal [18F]FDG-PET studies on nine different PDXs, obtained by implants of primary cancer fragments harvested from patients. Max [18F]FDG uptake values of the lesion for each group were calculated and compared to corresponding patient's uptake. RESULTS: Different PDXs showed variable tumor growth rate and [18F]FDG uptake confirming the preservation of individual characteristics. A good intra-group reproducibility of PET measurements was observed. Furthermore, the subgroup of PDXs originating from primary tumors with higher metabolic rate displayed a rank order of [18F]FDG uptake similar to that of patients' original SUV. CONCLUSION: PDXs reproduced the original glucose metabolism of primary lesions and represent therefore a promising preclinical model also for the early assessment of therapy efficacy.

Contains fulltext : 167894.pdf (Publisher’s version ) (Open Access) PURPOSE: Motor imagery can improve motor function and reduce pain. This is relevant to individuals with spinal cord injury (SCI) in whom motor dysfunction and neuropathic pain are prevalent. However, therapy efficacy could be dependent on motor imagery ability, and a clear understanding of how motor imagery might be facilitated is currently lacking. Thus, the aim of the present study was to assess the immediate effects of interactive virtual feedback on motor imagery performance after SCI. METHODS: Nine individuals with a traumatic SCI participated in the experiment. Motor imagery tasks consisted of forward (i.e. simpler) and backward (i.e. more complex) walking while receiving interactive versus static virtual feedback. Motor imagery performance (vividness, effort and speed), neuropathic pain intensity and feasibility (immersion, distraction, side-effects) were assessed. RESULTS: During interactive feedback trials, motor imagery vividness and speed were significantly higher and effort was significantly lower as compared static feedback trials. No change in neuropathic pain was observed. Adverse effects were minor, and immersion was reported to be good. CONCLUSIONS: This exploratory study showed that interactive virtual walking was feasible and facilitated motor imagery performance. The response to motor imagery interventions after SCI might be improved by using interactive virtual feedback.

Hormonal dependent breast cancer is a heterogeneous disease from a molecular and clinical perspective. The relapse risk of early breast cancer patients treated with adjuvant hormonal therapy varies. Validated predictive markers concerning adjuvant cytotoxic treatment are still lacking in ER+/ HER2- breast cancer, which has a good prognosis in general. This can lead to the inefficient chemotherapy indication. Molecular classification of breast cancer reports evidence about the heterogeneity of hormonal dependent breast cancer and its stratification to different groups with different characteristics. Multigene assays work on the molecular level, and their aim is to provide patients risk stratification and therapy efficacy prediction. The position of multigene assays in clinical practice is not stabile yet. Non uniform level of evidence connected to patients prognosis interpretations and difficult comparison of tests are the key problems, which prevent their wide clinical use. The article is a summary of some of the most important multigene assays in breast cancer and their current position in oncology practice.

Non-invasive imaging has great potential to contribute to the 'Three R's' principles for more ethical use of experimental animals. It enables repetitive monitoring of disease progression and measurement of quantitative biomarkers that report on disease progression and therapy efficacy in the same animal, thereby reducing manifold the number of animals needed for in vivo studies whilst advancing our knowledge into the pathophysiology of these diseases. This article reviews applications of non-invasive imaging in the field of fibrosis and arthritis research. It provides evidence for the viability of this approach not only for ethical reasons (reducing numbers and suffering in research animals, according to the 3R principles) but also for accelerating experimental output and making it more translational. The emphasis is on promising developments which will help improving throughput by reducing experiment length and size as well as human resources for data analysis, therefore encouraging a wider spreading of novel imaging technologies.

AC BioScience is a Swiss biotech company based at the EPFL Innovation Park and Biopôle, dedicated to developing groundbreaking therapies to fight a range of cancers and infectious diseases. We are about to start clinical trials with two of four leading-edge cancer drugs mainly focusing on immune-oncology and tumor vascular normalization with multi-billion $ sales potential. Here, we present our strategy and one of our pioneering drug candidates that has already shown exceptional results with tumor cell conditioning to improve the efficacy of immune checkpoint inhibitors.

Background Over the last decade, therapy of relapsing remitting multiple sclerosis (RRMS) has evolved with the approval of several new treatment concepts. Thus, treatment goals have become more ambitious aiming at “no evidence of disease activity” (NEDA). As NEDA-3, this concept comprises freedom of clinical disease progression and relapses as well as inflammatory MRI activity. So far, data on NEDA status mainly stem from post-hoc analyses of drug approval studies. Yet, less is known about the significance of NEDA in “real-world” clinical settings. Hence, our study aims at investigation of NEDA in a heterogeneous cohort of relapsing MS patients. Methods This is a retrospective single-center study at the Department of Neurology of the University Hospital Erlangen, Germany, including data of 306 patients with relapsing forms of MS (RMS) or clinical isolated syndrome (CIS) from 2009 to 2016. Inclusion required sufficient clinical information and in house cranial MRI follow-up data sets at baseline and at follow-up after one year with a potential extension to two and three year follow-up, if possible. NEDA-3 status, its correlation to clinical features, associated medication and NEDA failure (EDA) were analyzed. Results In a cohort of RMS patients at the early stages of the disease (median EDSS 1.5, mean disease duration 30 months) at baseline, 45% retained NEDA-3 status after one year. This percentage decreased in year two (29%) and three (21%) of follow-up. MRI criteria were responsible for loss of NEDA status in 64% of cases and CIS patients were more likely to sustain NEDA status. Therapy with monoclonal antibodies appeared superior in sustaining NEDA status as compared to injectables or oral treatment options. Discussion In our real-world analysis, we confirm the potential of NEDA for the evaluation and surveillance of MS disease activity, progression and therapy efficacy. Despite highly efficient immunomodulatory treatment, NEDA-3 was only preserved in a minority of patients. Monoclonal antibodies may yield best NEDA rates. Further studies are warranted to evaluate the value of the NEDA concept in real-world settings beyond standardized clinical studies.

An understanding of the thermal performance of biological tissue under moxibustion with ash cleaning and distance adjustment (ACDA) is helpful for the optimization and standardization of moxibustion clinical treatment. This study compared surface temperature distribution of burning moxa stick with and without ash cleaning. The experimental of moxibustion treatment on in-vitro tissue and human abdomen were conducted and corresponding numerical models were developed. The effect of ACDA on thermal performance of biological tissue under moxibustion therapy were analyzed. The results show that the surface temperature of burning moxa stick with ash cleaning maintained at a higher range compared to that without ash cleaning. During moxibustion with ACDA process in in-vitro tissue experiment, the temperature increase (ΔT) at skin surface almost fluctuated in the same temperature range, and the ΔT in subcutaneous tissue (>11 mm) kept increasing. Relatively, these ΔT under moxibustion treatment without ACDA showed different trends and these values were all much smaller than those with ACDA. In addition, the position of maximum temperature of tissue under moxibustion with and without ACDA was fixed on treatment acupoint and moved away from treatment acupoint, respectively. Besides, the surface temperature of human abdomen tissue under moxibustion treatment with ACDA can be maintained at 46 °C–50 °C for a longer time compared to that under moxbustion without ACDA. In conclusion, moxibustion with ACDA can create a larger and more durable thermal effect on biological tissue. The results also suggest that ACDA may be helpful to improve moxibustion therapy efficacy in clinic treatments.

Purpose We investigated whether outcomes of therapy for persistent developmental stuttering differ in individuals who carry a mutation in one of the known genes associated with stuttering compared to individuals without such mutations. Method We studied outcomes of an intensive fluency shaping-based therapy program in individuals with persistent developmental stuttering. We evaluated a cohort of 51 stuttering individuals with who carried a mutation in either the GNPTAB, GNPTG, NAGPA, or AP4E1 gene. We compared therapy outcomes in these individuals with outcomes in 51 individuals matched for age, gender, and ethnicity, who stutter and underwent the same therapy program, and did not carry a mutation in any of these genes. Fluency pre- and post-therapy was evaluated using blinded observer-based quantitative stuttering dysfluency measures (Dysfluent Words Score, DWS), and by subjects’ self-reported measures of struggle, avoidance and expectancy behavior associated with speaking (Perceptions of Stuttering Inventory, PSI). The difference between pre- and post-therapy fluency scores was taken as the measure of near-term therapy efficacy. Results Comparison of fluency measures showed a strong effect of therapy overall. Mutation carriers achieved significantly less resolution in PSI following therapy, with PSI scores showing significantly less improvement in individuals who carry a mutation (p = 0.0157, RR = 1.75, OR = 2.92) while the group difference in DWS between carriers and non-carriers was statistically not significant in the present study, the trend observed in the results warrants further research focused on this important issue. Conclusions These results suggest stuttering is more resistant to therapy in individuals who carry a mutation in one of the genes known to be associated with stuttering.

European Radiology, 17 (10), ISSN:0938-7994, ISSN:1432-1084

Objective Serum adenosine deaminase (ADA) activity is a marker of immune reaction to several diseases. We evaluated changes in serum ADA in patients with lung cancer undergoing chemotherapy or anti-programmed cell death-1 (PD-1) therapy to examine the correlation between serum ADA and the therapy efficacy. Materials and methods We assessed 50 patients with advanced lung cancer receiving chemotherapy or anti-PD-1 therapy. Serum ADA was measured before and on day 7 of the first treatment cycle and day 0 of subsequent cycles. Correlations between ADA change and efficacy of treatment were evaluated. Results Of the 50 patients, 20 were treated with chemotherapy and 30 were treated with anti-PD-1 therapy. Serum ADA decreased significantly between baseline and day 7 of the first cycle in patients undergoing chemotherapy, regardless of response (partial response [PR] or stable disease [SD]: −23% [−38 to +32; p = 0.002]; progressive disease [PD]: −12% [−42 to +6; p = 0.500]). Conversely, in patients undergoing anti-PD-1 therapy, serum ADA increased significantly between baseline and 7 days after the first dose and before subsequent doses in patients who had PR or SD. (day 7 of first cycle: +6% [−10 to +34; p = 0.034], day 0 of second cycle: 8% [−5 to +37; p = 0.002], day 0 of third cycle: 9% [−3 to +55; p = 0.002]). However, serum ADA did not significant change in PD patients undergoing anti-PD-1 therapy. Furthermore, early increases in serum ADA were associated with longer progression-free survival in patients receiving anti-PD-1 therapy (p = 0.006). Conclusion Changes in serum ADA could be used to predict clinical benefit from anti-PD-1 therapy in patients with lung cancer. The association between changes in serum ADA and the efficacy of ant-PD-1 therapy thus remains inconclusive and requires further study.

MicroRNAs (miRNAs), a recently discovered class of small non-coding RNAs, constitute a promising approach to anti-cancer treatments when they are used in combination with other agents. MiRNAs are evolutionarily conserved non-coding RNAs that negatively regulate gene expression by binding to the complementary sequence in the 3'-untranslated region (UTR) of target genes. MiRNAs typically suppress gene expression by direct association with target transcripts, thus decreasing the expression levels of target proteins. The delivery to cells of synthetic miRNAs that mimic endogenous miRNA targeting genes involved in the DNA-Damage Response (DDR) can perturb the process, making cells more sensitive to chemotherapy or radiotherapy. This review examines how cells respond to combined therapy and it provides insights into the role of miRNAs in targeting the DDR repair pathway when they are used in combination with chemical compounds or ionizing radiation to enhance cellular sensitivity to treatments.

As an ideal nanovector candidate, microvesicles (MVs) have been gradually utilized for packaging kinds of functional molecules for effective tumor diagnosis and therapy; however, the deficiency of their tumor targeting influenced their therapy efficacy. Through a facile phospholipid substitution strategy, MVs-based drug delivery system (DDS) was apparently endowed with high tumor targeting toward breast cancer thanks to the modified folate onto the membrane of MVs, simultaneously possessing a synergistic antitumor effect, and in vivo tumor imaging attributed to the SA-QDs labeling. Tumor killing effect could be improved up to 15 percentages with the help of the improved tumor targeting ability.

Purpose: To compare therapy-induced reading and distance visual acuity (dVA) increases in neovascular age-related macular degeneration (nAMD) and uveitis-associated cystoid macular edema. Methods: This longitudinal study included 68 treatment-naive eyes: 39 subfoveal nAMD eyes with disrupted photoreceptor layers treated with monthly ranibizumab and 29 uveitis-associated cystoid macular edema eyes with intact photoreceptor layer treated with 1 triamcinolone injection. Patients were examined with high-definition optical coherence tomography, Early Treatment Diabetic Retinopathy Study dVA (logarithm of the minimum angle of resolution), reading acuity (logRADscore), and maximum reading speed (words per minute) over 3 months of therapy. Results: In uveitis-associated cystoid macular edema, logarithm of the minimum angle of resolution and logRADscore improved 1 day post treatment, from 0.49 ± 0.28 to 0.39 ± 0.3 (P = 0.018) and 0.71 ± 0.53 to 0.56 ± 0.49 (P = 0.012), respectively. In nAMD, logarithm of the minimum angle of resolution improved 1 week after anti–vascular endothelial growth factor therapy from 0.59 ± 0.29 to 0.49 ± 0.24 (P = 0.002), with no change in logRADscore. One month after treatment, logRADscore improved from 1.09 ± 0.65 to 0.90 ± 0.60 (P = 0.002). In uveitis-associated cystoid macular edema, the recovery course of reading and dVA was comparable, and in nAMD, reading acuity recovery was delayed. Irrespective of disease, a small reduction in dVA resulted in a larger reading acuity decrease. Conclusion: Cystoid macular edema resolution was associated with rapid synchronous reading and dVA improvement, whereas nAMD was followed by faster recovery of distance than reading acuity. In both conditions, reading acuity expressed by critical angular resolution was more suppressed by active disease and recovered relatively more than distance acuity. These discrepancies indicate that reading acuity might be a more sensitive measure for vision decrease in macular diseases than dVA. Reading acuity seems to be an important adjunct assessing intravitreal therapy efficacy.

Objective This study aimed to explore the relationship between urinary metabolites and clinical chemotherapy response in breast cancer by CE-MS coupled with on-line concentration. Design and methods Urine samples were obtained from patients with advanced or locally advanced breast cancer (n = 21) before and after chemotherapy and healthy volunteers (n = 21). A rapid and sensitive hexadimethrine bromide-coating CE-MS method coupled with normal stacking is developed for the determination of organic acids in human urine. Another CE-MS method coupled with pH-mediated sample stacking is used for the analysis of amino acids and organic acids. Results After receiving chemotherapy, chemotherapy-sensitive patients showed 30% change in metabolite levels compared to healthy people, while chemotherapy-insensitive patients showed only 9% change in metabolite levels compared to healthy people showing recurrence. The extent of energy insufficiency for chemotherapy-insensitive patients was greater than that for chemotherapy-sensitive patients. Conclusions Urinary metabolic products may be new potential predictive markers for therapy efficacy. However, more studies with a larger sample size are required to confirm these conclusions.

Programmed death-ligand 1 (PD-L1) expression in pulmonary adenocarcinomas (pADCs) was implicated in predicting anti-PD-1/PD-L1 therapy efficacy. However, the differential expression of PD-L1 between primary and metastatic pADC remains unclear. Thus, we addressed this issue. In total, 161 paired primary and metastatic tumour tissues from 146 patients with pADC were collected. Most of the cases had regional nodal metastasis (134/161, 83.2%). PD-L1 expression was categorised based on the proportion of immunostained tumour cells using cutoff values of 1%, 5%, 10% and 50%. In primary tumours, PD-L1 positivity was observed in 28.1% (41/146), 27.4% (40/146), 22.6% (33/146) and 13.0% (19/146) of cases using cutoff values of 1%, 5%, 10% and 50%, respectively. The overall concordance rate for PD-L1 expression between primary and metastatic tumours was 75.2% (121/161). The concordance rate in primary tumours expressing PD-L1 in1% or ≥50% of tumour cells was 87.2% (102/117) or 70% (14/20), respectively. In contrast, the concordance rate in tumours expressing PD-L1 in ≥1% to50% of cells was only 20.8% (5/24). After dichotomising the cases using cutoff values of 1% and 50%, the concordance rate increased to 80.1% (129/161) and 90.7% (146/161) in all paired cases and to 70.4% (19/27) and 85.2% (23/27) in cases with distant metastases, respectively. This study demonstrates that the concordance of PD-L1 expression between primary and metastatic pADC is high when using cutoff values of 1% and 50%. Thus, evaluation of PD-L1 in either primary or metastatic tumours would be helpful for guiding anti-PD-1/PD-L1 immunotherapy in patients with advanced pADC.

Objective To evaluate the efficacy of laser photothermal therapy in a group of Chilean women with SUI. Material and methods Longitudinal prospective study based on 42 women with mild-to-severe SUI, intervened with non ablative Er:YAG laser, between July 2014 and October 2015, in Santiago, Chile. The therapy efficacy was evaluated through the difference between every patient's scores obtained, before and after treatment, with the International Consultation on Incontinence Questionnaire – Urinary Incontinence Short Form (ICIQ-SF), at a confidence level of 95%. Also, the patient satisfaction with treatment was reported through an ordinal scale. Results ICIQ-SF median score was 11 before treatment and 3 after 6 months, with a significant difference per patient ( p n =33) reported improvement and 38.1% ( n =16), a complete healing of SUI at follow up. 66.7% ( n =28) reported high satisfaction and 81.8% ( n =27) of sexually active women, also reported improvement of sexual gratification. Only mild pain during the procedure was reported as adverse effect. Conclusions Based on this short-term pilot study, non-ablative Er:YAG laser procedure seems to be a safe and efficacious alternative for patients with SUI. Further controlled studies will help to validate the use of non-ablative Er:YAG for treatment of SUI.

Background Radiofrequency therapy (RFT) generates molecular motion and produces heat and electromagnetic effects on tissues, which attenuate pain sensation and thereby relieve pain. This study was to observe the altering trend of physiological parameters after RFT for chronic cervical or lumbar pain. Methods This study recruited 66 patients with chronic cervical or lumbar pain and recorded their physiological parameters before and after RFT using heart rate variability (HRV) and photoplethysmography (PPG) to explore the feasibility of RFT efficacy assessment. Results The patients' visual analog scale scores significantly decreased after RFT and the HRV parameters that represented parasympathetic activity significantly changed (HR decreased, and R-R interval and low- and high-frequency power increased significantly). Meanwhile, the PPG parameters that represented sympathetic activity also increased (PPG amplitude and autonomic nervous system state significantly decreased). Conclusions This study showed significant efficacy of RFT in patients with chronic cervical or lumbar pain. The changes of HRV and PPG parameters may explain part of the mechanisms of RFT.

Background/Aims: Although recombinant human growth hormone (rhGH) is not approved to treat short stature of achondroplasia (ACH), some studies suggested growth improvement during short-term rhGH treatment. Methods: A meta-analysis of rhGH therapy efficacy in ACH children was performed. Results: From 12 English-language studies, 558 (54.0% males) rhGH-treated ACH children were enrolled. Administration of rhGH (median dosage 0.21 mg/kg/ week; range 0.16-0.42 mg/kg/week) improved height (Ht) from baseline [-5.069 standard deviation score (SDS; 95% CI -5.109 to -5.029); p < 0.0001] to 12 [-4.325 SDS (95% CI -4.363 to -4.287); p < 0.0001] and 24 months [-4.073 SDS (95% CI -4.128 to -4.019); p < 0.0001]. Then, Ht remained approximately constant up to 5 years [-3.941 SDS (95% CI -4.671 to -3.212); p < 0.0001]. Conclusions: In ACH children, rhGH treatment increased Ht from -5.0 to -4.0 SDS during 5 years, but insufficient data are available on both the adult Ht and the changes of body proportions.

Background: Therapeutic drug monitoring (TDM) of infliximab (IFX, Remicade®) can aid to optimize therapy efficacy. Many assays are available for this purpose. However, a reference standard is lacking. Therefore, we evaluated the analytical performance, agreement and clinically relevant differences of three commercially available IFX ELISA kits on an automated processing system. Methods: The kits of Theradiag (Lisa Tracker Infliximab), Progenika (Promonitor IFX) and apDia (Infliximab ELISA) were implemented on an automated processing system. Imprecision was determined by triplicate measurements of patient samples on five days. Agreement was evaluated by analysis of 30 patient samples and four spiked samples by the selected ELISA kits and the in-house IFX ELISA of Sanquin Diagnostics (Amsterdam, The Netherlands). Therapeutic consequences were evaluated by dividing patients into four treatment groups using cut-off levels of 1, 3 and 7 μg/mL and determining assay concordance. Results: Within-run and between-run imprecision were acceptable (≤12% and ≤17%, respectively) within the quantification range of the selected ELISA kits. The apDia assay had the best precision and agreement to target values. Statistically significant differences were found between all assays except between Sanquin Diagnostics and the Lisa Tracker assay. The Promonitor assay measured the lowest IFX concentrations, the apDia assay the highest. When patients were classified in four treatment categories, 70% concordance was achieved. Conclusions: Although all assays are suitable for TDM, significant differences were observed in both imprecision and agreement. Therapeutic consequences were acceptable when patients were divided in treatment categories, but this could be improved by assay standardization.

Genetically engineered mouse models (GEMMs) have contributed greatly to the field of cancer research. In contrast to tumor cell transplantation models, GEMMs have the potential to capture both the cell-intrinsic and cell-extrinsic factors that drive de novo formation of autochthonous tumors and their progression toward metastatic disease. In addition, GEMMs provide experimentally tractable in vivo platforms for validating candidate cancer genes, determining therapy efficacy, and defining mechanisms of drug resistance. Studies in GEMMs of human cancer provide new insight in the molecular biology of cancer and contribute to development of novel therapeutic strategies that may ultimately lead to more cures rather than temporal remissions.

To evaluate efficacy of, satisfaction with, and confidence in SDP (SUMAVEL DosePro *) among triptan users requiring a change in therapy. SDP is a needle-free, subcutaneous sumatriptan product that confers relief as early as 10 minutes postdose.In an open-label study, SDP was administered for ≤4 migraine attacks over ≤60 days by migraineurs currently treated with triptans (any form/dosage). In the 90 patients with baseline Migraine-ACT scores ≤2 (indicating the need for a change in therapy), efficacy data were collected from patient diaries, and satisfaction was measured with the revised Patient Perception of Migraine Questionnaire (PPMQ-R).NCT01016834 on clinicaltrials.gov.Across all attacks, the rates of pain relief were 30.7%, 66.4%, 80.1%, 81.6%, and 77.6% at 0.25, 0.5, 1, 2, and 24 hours postdose, respectively. Corresponding results for pain-free response were 0.7%, 14.8%, 35.0%, 48.0, and 65.7%. Sustained 24-hour pain relief was observed in 61.0% of attacks. PPMQ-R scores (transformed to 0-100 scales, mean ± SD) improved from baseline to end of treatment for Efficacy (52.5 ± 17.8 versus 74.8 ± 23.4, p 0.0001) and Functionality (46.2 ± 22.3 versus 71.3 ± 25.2, p 0.0001) with no deterioration in Tolerability (80.6 ± 14.7 versus 83.5 ± 17.7, p = 0.12). PPMQ-R Overall Satisfaction score increased from baseline to end of treatment (55.1 ± 23.2 versus 74.6 ± 27.7, p 0.0001). The percentage of patients (90% confidence interval) confident or very confident in treating migraine attacks increased from 22.2% (15.2, 30.6) at baseline to 57.8% (48.6, 66.6) at end of treatment. Results should be interpreted in the context of the open-label design of the original study.With SDP, triptan users requiring a change in therapy experienced increased efficacy, satisfaction with therapy, and confidence in treatment without deterioration in tolerability.