Empirical Therapy Versus Tailored Therapy of Helicobacter pylori in Korea: Results of the K-CREATE Study.

BACKGROUND: The optimal duration of regimens for tailored therapy based on genotypic resistance for clarithromycin has yet to be established. AIM: This study was a nationwide, multicenter, randomized trial comparing empirical therapy with tailored therapy based on genotypic resistance for first-line eradication of Helicobacter pylori. We also compared the eradication rates of 7- and 14-day regimens for each group. PATIENTS AND METHODS: Patients with H. pylori infection were first randomized to receive empirical or tailored therapy. Patients in each group were further randomized into 7- or 14-day regimens. Empirical therapy consisted of a triple therapy (TT) regimen (twice-daily doses of pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg) for 7 or 14 days. Tailored therapy consisted of TT of 7 or 14 days in patients without genotypic resistance. Patients with genotypic resistance were treated with bismuth quadruple therapy (BQT) regimens (twice-daily doses of pantoprazole 40 mg, three daily doses of metronidazole 500 mg, and four times daily doses of bismuth 300 mg and tetracycline 500 mg) for 7 or 14 days. A 13C-urea breath test assessed eradication rates. The primary outcome was eradication rates of each group. RESULTS: A total of 593 patients were included in the study. The eradication rates were 65.7% (201/306) in the empirical therapy group and 81.9% (235/287) in the tailored therapy group for intention-to-treat analysis (p < 0.001). In the per-protocol analysis, the eradication rates of the empirical therapy and tailored groups were 70.3% (201/286) and 85.5% (235/274) (p < 0.001), respectively. There was no difference in compliance between the two groups. The rate of adverse events was higher in the tailored group compared to the empirical group (p < 0.001). DISCUSSION: Our study confirmed that tailored therapy based on genotypic resistance was more effective than empirical therapy for H. pylori eradication in Korea. However, no significant difference was found between 7- and 14-day regimens for each group. Future studies are needed to determine the optimal duration of therapy for empirical and tailored therapy regimens.

14-day tailored PCR-guided triple therapy versus 14-day non-Bismuth concomitant quadruple therapy for Helicobacter pylori eradication: A multicenter, open-label randomized noninferiority controlled trial.

BACKGROUND: The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established. AIM: To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication. PATIENTS AND METHODS: We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication. RESULTS: We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at -0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population. CONCLUSION: In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).

FAT4 Mutation is Related to Tumor Mutation Burden and Favorable Prognosis in Gastric Cancer.

Objective: This study aimed to investigate the frequently mutated genes in Gastric Cancer (GC), assess their association with Tumor Mutation Burden (TMB) and the patients' survival, and identify the potential biomarkers for tailored therapy. Methods: Simple somatic mutation data of GC were collected from the TCGA and ICGC databases. The high-frequency mutated genes were identified from both datasets. The samples were initially dichotomized into wild-type and mutation groups based on the status of overlapping genes. TMB difference between the two groups was evaluated by the Mann-Whitney U-test. Survival difference between the two groups was compared by the Kaplan-Meier method with a log-rank test. The prognostic value of the target gene was assessed by the Cox proportional hazards model. The signaling pathways involved in FAT4 mutation were identified by Gene Set Enrichment Analysis (GSEA). The fractions of different tumor-infiltrating immune cells were calculated by the CIBERSORT algorithm. Results: 21 overlapping genes with frequent mutation were identified in both datasets. Mutation of these genes was significantly associated with higher TMB (P<0.05) in GC. The survival of the FAT4 mutation group was superior to the wild-type group. FAT4 mutation was also identified as an independent favorable prognostic factor for the GC patients. GSEA indicated that FAT4 mutation activated the signaling pathways involved in energy metabolism. Finally, CD4 memory-activated T cells, follicular helper T cells, and gamma delta T cells were significantly more enriched, while naïve B cells and regulatory T cells (Tregs) were significantly less enriched in the FAT4 mutation group (P<0.05). Conclusion: FAT4 mutation is relevant to TMB and favorable prognosis in GC, which may become a useful biomarker for immunotherapy of GC patients.

Nano-Based Drug Approaches to Proliferative Vitreoretinopathy Instead of Standard Vitreoretinal Surgery.

Proliferative vitreoretinopathy (PVR) has traditionally been managed with vitreoretinal surgery. Although there have been several recent innovations in this surgery to make the retinal approach as uninvasive as possible, the outcomes remain unsatisfactory. Significant complications remain and the complexity of the surgical approach is challenging. The focus of this review was to investigate and discuss the effectiveness of nanomedicine, featuring a wide range of drugs and molecules, as a novel potential treatment for PVR. To date, ocular drug delivery remains a significant issue due to the physiological and anatomical barriers, dynamic or static, which prevent the entry of exogenous molecules. We tried to summarize the nanotechnology-based ophthalmic drugs and new nanoparticles currently under research, with the intention of tackling the onset and development of PVR. The purpose of this review was to thoroughly and analytically examine and assess the potential of nano-based techniques as innovative strategies to treat proliferative vitreoretinopathy (PVR). This study aimed to emphasize the breakthroughs in nanomedicine that provide promising therapeutic options to enhance the results of vitreoretinal surgery and halt disease progression, considering the complexity and difficulty of PVR treatment. The future directions of the nanoparticles and nanotherapies applied to PVR highlight the importance of investing in the development of better designs and novel ophthalmic formulations in order to accomplish a mini-invasive ocular approach, replacing the standard-of-care vitreoretinal surgery.

Efficacy of genotypic susceptibility-guided tailored therapy for Helicobacter pylori infection: A systematic review and single arm meta-analysis.

BACKGROUND AND AIM: The prevalence of antibiotic resistance for Helicobacter pylori (H. pylori) has been increasing over the year, making it more difficult for traditional empirical therapy to successfully eradicate H. pylori. Thus, tailored therapy (TT) guided by molecular-based antibiotic susceptibility testing (AST) has been frequently recommended. We conducted a single-arm meta-analysis to determine the efficacy of tailored therapy guided by molecular-based AST. METHODS: A systematic literature review was performed on multiple databases, and studies on molecular-based TT were included. The eradication rates of TT by intention-to-treat (ITT) and per-protocol (PP) analyses were pooled respectively. RESULTS: A total of 35 studies from 31 literature (4626 patients) were included in the single-arm meta-analysis. Overall, the pooled eradication rate of TT was 86.9% (95% CI:84.7%-89.1%) by the ITT analysis, and 91.5% (95% CI:89.8%-93.2%) by PP analysis. The pooled eradication rates of first-line TT and rescue TT were 86.6% and 85.1% by ITT analysis and 92.0% and 87.9% by PP analysis, respectively. When tailored rescue therapy was based on the genotypic resistance to at least four antibiotics, the pooled eradication rates reached 89.4% by ITT analysis and 92.1% by PP analysis. For genotype-susceptive strains, the pooled eradication rate of TT with targeted antibiotics was 93.1% (95% CI:91.3%-94.9%), among which the pooled eradication rate of tailored bismuth quadruple therapy was the highest (94.3%). Besides, the eradication rate of 7-day TT or tailored triple therapy without bismuth for genotype-susceptive strains could both reach more than 93.0%. CONCLUSION: Tailored therapy guided by molecular-based AST can achieve somewhat ideal therapeutic outcomes. TT with a 7-day duration or without bismuth for genotype-susceptible strains can achieve good eradication efficacy. The effectiveness of TT can be improved to some extent by expanding the coverage of AST or by adding bismuth.

A novel cardiac arrest severity score for the early prediction of hypoxic-ischemic brain injury and in-hospital death.

INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) outcomes are unsatisfactory despite postcardiac arrest care. Early prediction of prognoses might help stratify patients and provide tailored therapy. In this study, we derived and validated a novel scoring system to predict hypoxic-ischemic brain injury (HIBI) and in-hospital death (IHD). METHODS: We retrospectively analyzed Korean Hypothermia Network prospective registry data collected from in Korea between 2015 and 2018. Patients without neuroprognostication data were excluded, and the remaining patients were randomly divided into derivation and validation cohorts. HIBI was defined when at least one prognostication predicted a poor outcome. IHD meant all deaths regardless of cause. In the derivation cohort, stepwise multivariate logistic regression was conducted for the HIBI and IHD scores, and model performance was assessed. We then classified the patients into four categories and analyzed the associations between the categories and cerebral performance categories (CPCs) at hospital discharge. Finally, we validated our models in an internal validation cohort. RESULTS: Among 1373 patients, 240 were excluded, and 1133 were randomized into the derivation (n = 754) and validation cohorts (n = 379). In the derivation cohort, 7 and 8 predictors were selected for HIBI (0-8) and IHD scores (0-11), respectively, and the area under the curves (AUC) were 0.85 (95% CI 0.82-0.87) and 0.80 (95% CI 0.77-0.82), respectively. Applying optimum cutoff values of ≥6 points for HIBI and ≥7 points for IHD, the patients were classified as follows: HIBI (-)/IHD (-), Category 1 (n = 424); HIBI (-)/IHD (+), Category 2 (n = 100); HIBI (+)/IHD (-), Category 3 (n = 21); and HIBI (+)/IHD (+), Category 4 (n = 209). The CPCs at discharge were significantly different in each category (p < 0.001). In the validation cohort, the model showed moderate discrimination (AUC 0.83, 95% CI 0.79-0.87 for HIBI and AUC 0.77, 95% CI 0.72-0.81 for IHD) with good calibration. Each category of the validation cohort showed a significant difference in discharge outcomes (p < 0.001) and a similar trend to the derivation cohort. CONCLUSIONS: We presented a novel approach for assessing illness severity after OHCA. Although external prospective studies are warranted, risk stratification for HIBI and IHD could help provide OHCA patients with appropriate treatment.

Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines.

There is an ongoing need for patient-specific chemotherapy for pancreatic cancer. Tumour cells isolated from human tissues can be used to predict patients' response to chemotherapy. However, the isolation and maintenance of pancreatic cancer cells is challenging because these cells become highly vulnerable after losing the tumour microenvironment. Therefore, we investigated whether the cells retained their original characteristics after lentiviral transfection and expansion. Three human primary pancreatic cancer cell lines were lentivirally transduced to create expandable (Ex) cells which were then compared with primary (Pri) cells. No obvious differences in the morphology or epithelial-mesenchymal transition (EMT) were observed between the primary and expandable cell lines. The two expandable cell lines showed higher proliferation rates in the 2D and 3D models. All three expandable cell lines showed attenuated migratory ability. Differences in gene expression between primary and expandable cell lines were then compared using RNA-Seq data. Potential target drugs were predicted by differentially expressed genes (DEGs), and differentially expressed pathways (DEPs) related to tumour-specific characteristics such as proliferation, migration, EMT, drug resistance, and reactive oxygen species (ROS) were investigated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We found that the two expandable cell lines expressed similar chemosensitivity and redox-regulatory capability to gemcitabine and oxaliplatin in the 2D model as compared to their counterparts. In conclusion, we successfully generated expandable primary pancreatic cancer cell lines using lentiviral transduction. These expandable cells not only retain some tumour-specific biological traits of primary cells but also show an ongoing proliferative capacity, thereby yielding sufficient material for drug response assays, which may provide a patient-specific platform for chemotherapy drug screening.

Updates on targeted therapies for acute myeloid leukaemia.

In the past few years research in the underlying pathogenic mechanisms of acute myeloid leukaemia (AML) has led to remarkable advances in our understanding of the disease. Cytogenetic and molecular aberrations are the most important factors in determining response to chemotherapy as well as long-term outcome, but beyond prognostication are potential therapeutic targets. Our increased understanding of the pathogenesis of AML facilitated by next-generation sequencing has spurred the development of new compounds in the treatment of AML, particularly the creation of small molecules that target the disease on a molecular level. Many of the hopeful predictions outlined in our AML review of 2018 are now therapeutic realities: gemtuzumab ozogamicin, venetoclax, FLT3 inhibitors (midostaurin, gilteritinib), IDH inhibitors (ivosidenib, enasidenib), CPX-351, glasdegib, oral decitabine, and oral azacitidine. Others may soon be (quizartinib, APR246 magrolimab, menin inhibitors). The wealth of positive data allows reconsideration of what might soon be new standards of care in younger and older patients with AML. In this review we give an overview of recently approved therapies in AML and address present and future research directions.

Personalized-Inherent Variability in a Time-Dependent Immune Response: A Look into the Fifth Dimension in Biology.

INTRODUCTION: Individualized response to the immune triggers influences the course of immune-mediated diseases and the response to immunotherapies. Both inter- and intra-subject variations occur in time-dependent dynamics of biological systems. The present study aimed to establish a model for inherent personalized-time-dependent variability in response to immune triggers. METHODS: Male C57BL/6 mice were administered concanavalin A (ConA) and followed every 2 h for 10 h and at 24 h for serum alanine aminotransferase (ALT) levels. RESULTS: A marked intragroup variability was noted for both the timing of the effect of ConA, the magnitude of the increase in ALT levels, and the time to peak. While in some mice, a peak level was achieved, whereas a continuous increase in liver damage was noted in others. Four mice died at different time points during the study irrespective of their liver damage, further supporting the individualized-based response to the trigger. CONCLUSIONS: This feasibility study established a model for determining the personalized-inherent variability in a time-dependent response to the immune triggers. These results highlight the importance of considering both the time and the wide range of individualized variability in immune responses while designing personalized-based immunotherapies.

Age-Adjusted Charlson Comorbidity Index Predicts Survival in Endometrial Cancer Patients.

OBJECTIVE: Comorbidity scores are increasingly used to reduce potential confounding in oncologic research. This is of paramount importance in endometrial cancer (EC) since it is characterized by quite indolent behavior. Here, we aim to evaluate the impact of various comorbidities and concurrent medications used on survival outcomes, adopting the age-adjusted Charlson comorbidity index (A-CCI). DESIGN: This is an observational study. Charts of 257 EC patients were retrieved. METHODS: We retrospectively evaluated data of patients who underwent surgical treatment for EC. A-CCI was calculated by summing the weighted comorbidities and age of each patient. A binomial value was assigned to different comorbidities and different drugs. Oncologic outcomes were evaluated using Cox proportional hazard models adjusted for age. RESULTS: A-CCI ≥3 correlated with more aggressive tumor features (47.6% vs. 26.8%, p = 0.001), higher risk of recurrence (29.7% vs. 11.6%, p = 0.001), death (20.7% vs. 7.1%, p = 0.002), and death due to disease (16.6% vs. 6.3%, p = 0.012). Considering comorbidities and drugs at parsimonious multivariable analysis model: cardiac disease, liver disease, and proton pump inhibitors (PPIs) use were independent predictors of disease-free survival. Cardiac disease, autoimmune disease, and PPIs use were independent predictors of overall survival. Diabetes was the only independent predictor for cause-specific survival. LIMITATIONS: The major limitation of the present study is its retrospective nature and the relatively small sample size that limit the possibility to have firm conclusions. CONCLUSION: Patients with EC are characterized by a high burden of comorbidities. Comorbidities are associated directly with survival outcomes. Further attention is needed to improve the active management of comorbidities soon after EC treatments. Interventional studies are needed to improve patients' outcomes.

Preoperative chemoradiotherapy affects postoperative outcomes and functional results in patients treated with transanal endoscopic microsurgery for rectal neoplasms.

BACKGROUND: The aim of this study was to quantify the incidence of short-term postoperative complications and functional disorders at 1 year from transanal endoscopic microsurgery (TEM) for rectal neoplasms, to compare patients treated with TEM alone and with TEM after preoperative chemoradiotherapy (CRT) and to analyse factors influencing postoperative morbidity and functional outcomes. METHODS: A retrospective study was conducted on all patients treated with TEM for rectal neoplasms at our institution in January 2000-December 2017. Data from a prospectively maintained database were retrospectively analysed. Patients were divided into two groups: adenoma or early rectal cancer (no CRT group) and locally advanced extraperitoneal rectal cancer with major or complete clinical response after preoperative CRT (CRT group). Short-term postoperative mortality and morbidity and the functional results at 1 year were recorded. The two groups were compared, and a statistical analysis of factors influencing postoperative morbidity and functional outcomes was performed. Functional outcome was also evaluated with the low anterior resection syndrome (LARS) score (0-20 no LARS, 21-29 minor LARS and 30-42 major LARS). RESULTS: One hundred and thirteen patients (71 males, 42 females, median age 64 years [range 41-80 years]) were included in the study (46 in the CRT group). The overall postoperative complication rate was 23.0%, lower in the noCRT group (p < 0.001), but only 2.7% were grade ≥ 3. The most frequent complication was suture dehiscence (17.6%), which occurred less frequently in the noCRT group (p < 0.001). At 1 year from TEM, the most frequent symptoms was urgency (11.9%, without significant differences between the CRT group and the noCRT group); the noCRT group experienced a lower rate of soiling than the CRT group (0% vs. 7.7%; p: 0.027). The incidence of LARS was evaluated in 47 patients from May 2012 on and was 21.3% occurring less frequently in the noCRT group (10% vs. 41.2%; p: 0.012). Only 6.4% of the patients evaluated experienced major LARS. In multivariate analysis, preoperative CRT significantly worsened postoperative morbidity and functional outcomes. CONCLUSIONS: TEM is a safe procedure associated with only low risk of severe postoperative complications and major LARS. Preoperative CRT seems to increase the rate of postoperative morbidity after TEM and led to worse functional outcomes at 1 year after surgery.

Proteogenomic biomarkers in colorectal cancers: clinical applications.

INTRODUCTION: Colorectal cancer (CRC) is one of the leading cancers in terms of incidence and mortality, rate requiring a multidisciplinary approach. The discovery of specific CRC biomarkers has caused a paradigm shift in its clinical management. AREAS COVERED: The aim is to illustrate the possible clinical applications of CRC biomarkers through an updated literature review (from 2015 to 2020) based on the PubMed database. A relationship between cancer localization and genetic profile has been identified. Nowadays, the tumor markers are largely used to select patients that could really benefit from a specific type of adjuvant therapy, in order to optimize treatment programs, especially in metastatic patients. This review highlights both CRC biomarkers' advantages and critical issues. EXPERT OPINION: New biomarker discoveries allow to set noninvasive tests that could increase patient's compliance with therapy. They also permit a cost-effective early diagnosis, as well as patient-tailored treatments, improving the overall survival. The CRC biomarkers could also have a prognostic value, and usually, they are included in follow-up programs. However, despite the continuous progression of new technologies, their clinical validation is still debated. In this context, additional clinical studies are still necessary to identify, among potential markers, the most effective ones.

An update on emerging drugs in osteosarcoma: towards tailored therapies?

Introduction: Current treatment of conventional and non-conventional high-grade osteosarcoma (HGOS) is based on the surgical removal of primary tumor and, when possible, of metastases and local reccurrence, together with systemic pre- and post-operative chemotherapy with drugs that have been used since decades. Areas covered: This review is intended to summarize the new agents and therapeutic strategies that are under clinical evaluation in HGOS, with the aim to increase the cure probability of this highly malignant bone tumor, which has not significantly improved during the last 30-40 years. The list of drugs, compounds and treatment modalities presented and discussed here has been generated by considering only those that are included in presently ongoing and recruiting clinical trials, or which have been completed in the last 2 years with reported results, on the basis of the information obtained from different and continuously updated databases. Expert opinion: Despite HGOS is a rare tumor, several clinical trials are presently evaluating different treatment strategies, which may hopefully positively impact on the outcome of patients who experience unfavorable prognosis when treated with conventional therapies.

Helicobacter pylori eradication rates with concomitant and tailored therapy based on 23S rRNA point mutation: A multicenter randomized controlled trial.

BACKGROUND: We evaluated the efficacy of tailored therapy based on point mutation presence identified with the dual-priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) method compared with concomitant therapy. MATERIALS AND METHODS: Subjects were randomly assigned concomitant therapy (amoxicillin 1 g, clarithromycin 500 mg, metronidazole 500 mg, and lansoprazole 30 mg twice/day for 14 days) or tailored therapy (amoxicillin 1 g, clarithromycin 500 mg, and lansoprazole 30 mg twice/day for 14 days in point mutation-negative subjects; and amoxicillin 1 g, metronidazole 500 mg, and lansoprazole 30 mg twice/day for 14 days in point mutation-positive subjects). RESULTS: A total of 397 and 352 subjects were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. Point mutations were identified in 25.9% of the subjects. The overall eradication rate was not significantly different between the groups by ITT (86.2% vs 81.6%, P = .132) and PP analyses (90.2% vs 86.5%, P = .179). There was no significant difference in the eradication rates between the groups in both the point mutation-negative subjects (91.7% vs 87.3%, P = .154) and the point mutation-positive subjects (71.2% vs 64.7%, P = .312). The eradication rates were significantly lower in the point mutation-positive subjects than in the point mutation-negative subjects in both the concomitant and tailored therapy groups. CONCLUSIONS: Tailored therapy based on point mutation presence identified with the DPO-based multiplex PCR method was as effective as concomitant therapy. The eradication rates of both therapy regimens were suboptimal in point mutation-positive subjects.

Favorable outcomes of culture-based Helicobacter pylori eradication therapy in a region with high antimicrobial resistance.

BACKGROUND: The eradication rate of Helicobacter pylori has declined, mainly due to antimicrobial resistance. To overcome resistance-associated treatment failure, the efficacy of culture-based, susceptibility-guided therapy was demonstrated as the first-line eradication therapy for H pylori infection. AIMS: To evaluate the efficacy of culture-based therapy as the first-line eradication therapy in regions with high levels of antimicrobial resistance. METHODS: Helicobacter pylori-positive patients without previous eradication treatment history were recommended to undergo culture to determine the minimal inhibitory concentration (MIC). If they consented, 7-day clarithromycin-containing PPI triple; 7-day esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; or 7- or 14-day esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy were administered based on the agar dilution-determined MIC. Eradication, treatment compliance, and adverse events were examined. RESULTS: In total, 74 patients were enrolled, and 69 patients completed the protocols. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 6.7%, 31.0%, 41.8%, and 39.2%, respectively. The patients were allocated to the PPI triple (n = 50), MEA (n = 8) or quadruple (n = 16) therapy. The eradication rate in the intention-to-treat analysis was 93.1% (69 of 74 patients). The eradication rates in the per-protocol analysis were 100.0% (69 of 69 patients). Epigastric pain, nausea, and vomiting were less common than those of other empirical therapies. CONCLUSIONS: Culture-based, susceptibility-guided therapy is effective first-line eradication therapy, especially in regions with high levels of antimicrobial resistance.

[Remote assessment of idiopathic Parkinson's disease : Developments in diagnostics, monitoring and treatment]. / Remote-Messung bei idiopathischem Parkinson-Syndrom : Entwicklungen in Diagnose, Monitoring und Therapie.

The idiopathic Parkinson's disease (iPD) is a progressive neurodegenerative disorder primarily resulting in impaired movement execution. In the course of the disease symptom fluctuation is common and makes adequate treatment difficult. In this overview the current approaches using modern and especially mobile technologies for diagnosis, monitoring and treatment of iPD are presented. Currently, there are no medical aids ready for point of care application; however, the development of these technologies has great potential for improving care for patients suffering from iPD.

[Tailored therapy in treatment of Helicobacter pylori infectionbasedon clarithromycinsensitivity].

Objective: To compare eradication rates and compliance of patients with Helicobacter pylori(H. pylori)infection based on clarithromycin sensitivity. Methods: From July 2015 to January 2018,patients with H. pylori infection in Peking university people's hospital were randomly assignedto a 14-day treatment with clarithromycin quadruple therapy versus tailored quadruple therapy for a prospective study. In the group of tailored therapy, medications were adjusted based on clarithromycin sensitivity. In the control group, all patients were given proton pump inhibitors (PPI), amoxicillin, clarithomycin and bismuth. Eradication status was assessed 4 weeks after treatment withurea breath test. Results: The H.pylori eradication rate were higher in the tailor therapy group than that in the control group in intention-to-treat[77.8% vs 65.3%,(P=0.001)] and per,protocol analyses [86.4% vs 70.2%,(P<0.001)], the differences between the two groups were statistically significant.The incidence of compliance between the two groups were also comparable. Conclusions: The tailored therapy basedon clarithromycinsensitivity has a better eradication efficacy and a higher eradication ratesin the patients with H. pylori infection.

Overview of Current Targeted Anti-Cancer Drugs for Therapy in Onco-Hematology.

The upgraded knowledge of tumor biology and microenviroment provides information on differences in neoplastic and normal cells. Thus, the need to target these differences led to the development of novel molecules (targeted therapy) active against the neoplastic cells' inner workings. There are several types of targeted agents, including Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA (iRNA) molecules and microRNA. In the clinical practice, these new medicines generate a multilayered step in pharmacokinetics (PK), which encompasses a broad individual PK variability, and unpredictable outcomes according to the pharmacogenetics (PG) profile of the patient (e.g., cytochrome P450 enzyme), and to patient characteristics such as adherence to treatment and environmental factors. This review focuses on the use of targeted agents in-human phase I/II/III clinical trials in cancer-hematology. Thus, it outlines the up-to-date anticancer drugs suitable for targeted therapies and the most recent finding in pharmacogenomics related to drug response. Besides, a summary assessment of the genotyping costs has been discussed. Targeted therapy seems to be an effective and less toxic therapeutic approach in onco-hematology. The identification of individual PG profile should be a new resource for oncologists to make treatment decisions for the patients to minimize the toxicity and or inefficacy of therapy. This could allow the clinicians to evaluate benefits and restrictions, regarding costs and applicability, of the most suitable pharmacological approach for performing a tailor-made therapy.

Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study.

BACKGROUND: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). OBJECTIVES: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. METHOD: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell's C statistics, and Royston's explained variation in univariable and multivariable analyses. RESULTS: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. CONCLUSIONS: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.

Treatment of Helicobacter pylori infection in 2018.

Treatment options for the eradication of Helicobacter pylori continue to evolve. There have been many guidelines for H. pylori treatment published, which may lead to some confusion. However, most are in agreement with the most recent iteration of the Maastricht treatment guidelines. Triple therapy is still the most frequently used treatment, especially in areas of low clarithromycin resistance. Its best results are achieved when taken for a minimum of 10 days and with high-dose acid suppression. Quadruple therapy is gaining in popularity particularly in areas with increasing resistance to standard triple therapy. Whether three antibiotics, or bismuth and two antibiotics are used, excellent eradication rates are achieved, albeit with increased side effects. Levofloxacin second-line therapy is widely used; however bismuth, when available, is an increasingly successful option. Sequential therapy is challenging in terms of compliance and is no longer recommended. This past year witnessed a notable increase in the number of studies based on antimicrobial susceptibility testing and tailored eradication therapy, reflecting the role of culture-guided treatment, which may well represent the future of H. pylori treatment and prevent the inappropriate use of antibiotics.