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Programmed cell death protein ligand‐1 (PD‐L1) expression in non‐small cell lung cancer (NSCLC) tumors guides treatment selection. PD‐L1 expression in circulating tumor cells (CTCs) may provide further information. We have explored PD‐L1 and marker of proliferation Ki‐67 (Ki67; also known as MKI67) in CTCs in longitudinal samples of 47 advanced NSCLC patients receiving pembrolizumab. A triple immunofluorescence, against cytokeratin, PD‐L1, and Ki67, was performed on peripheral blood mononuclear cells, at baseline, post‐first cycle, post‐third, and primary resistance (PMR). Patients displaying PMR (progression at first evaluation) were classified as progressive disease (PD) and those with clinical benefit as disease control (DC). CTCs were categorized as PD‐L1high/low/medium/negative and Ki67+ or Ki67−. CTC evaluation revealed a significant increase in the PD‐L1low CTC rate at PMR compared to baseline (2.5% at baseline vs. 36.5% at PMR), whereas a reduction in the PD‐L1high CTC rate was observed (31.5% vs. 0%, respectively). Investigation of CTC status between PD and DC patients showed that PD patients more frequently increased total and PD‐L1low CTCs after first cycle compared to DC (83% of PD vs. 37% of DC and 67% of PD vs. 8% of DC, respectively). Progression‐free survival (PFS) was longer in patients with decreased total and PD‐L1low CTCs after first cycle compared to those with increased CTCs (median PFS: not reached vs. 2 months). PD‐L1+ patients presenting a high Ki67 index (% Ki67+ CTCs > 30%) before treatment had a shorter PFS compared to those with a low Ki67 (≤ 30%), and overall survival (OS) was shorter in PD‐L1+ patients harboring Ki67+ CTCs compared to those not presenting (median OS: 11.8 months vs. 33.1 months, respectively). In sequential samples of patients with a durable benefit, a low Ki67 index was observed. Our results suggest that monitoring PD‐L1 and Ki67 expression in CTCs of NSCLC patients treated with pembrolizumab may be predictive for pembrolizumab efficacy. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have contributed significantly to the treatment of various types of cancer, including skin cancer. However, not all patients respond; some patients do not respond at all (primary resistance), while others experience recurrence after the initial response (acquired resistance). Therefore, overcoming ICI resistance is an urgent priority. Numerous ICI resistance mechanisms have been reported. They are seemingly quite complex, varying from patient to patient. However, most involve T‐cell activation processes, especially in the tumor microenvironment (TME). ICIs exert their effects in the TME by reactivating suppressed T cells through inhibition of immune checkpoint molecules, such as cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) and programmed cell death protein 1 (PD‐1). Thus, this review focuses on the resistance mechanisms based on the T‐cell activation process. Here, we classify the main mechanisms of ICI resistance into three categories based on (1) antigen recognition, (2) T‐cell migration and infiltration, and (3) effector functions of T cells. By identifying and understanding these resistance mechanisms individually, including unknown mechanisms, we seek to contribute to the development of novel treatments to overcome ICI resistance. [ABSTRACT FROM AUTHOR]

Drug resistance severely limits the clinical therapeutic value of molecularly targeted drugs. Growth factors gain a tremendous amount of focus due to the ability to promote drug resistance in non-small-cell lung cancer (NSCLC). However, whether tumor cells themselves can mediate drug resistance by secreting growth factors needs further clarification. Here, we first screened growth factors to identify autocrine epidermal growth factor (EGF) and transforming growth factor alpha (TGF-α) that caused primary resistance to the ALK inhibitor TAE684 in H3122 cells and the c-MET-specific inhibitor SGX-523 in EBC-1 cells. Next, we discovered increased autocrine production of EGF and TGF-α in established acquired resistant H3122/TR and EBC-1/SR cells. Importantly, overexpression of EGF and TGF-α in two NSCLC cell lines produced resistance to TAE684 and SGX-523. Clinically, NSCLC patients with high expression of EGF and TGF-α developed primary resistance to crizotinib. Mechanistically, autocrine EGF and TGF-α activated EGFR signaling pathways to survive targeted c-Met and ALK inhibition. Furthermore, combined treatment with gefitinib circumvented EGF- and TGF-α-mediated primary and acquired resistance to TAE684/SGX-523. Taken together, these results suggested increased autocrine EGF and TGF-α conferred primary and acquired resistance to ALK/c-Met kinase inhibitors in NSCLC. [ABSTRACT FROM AUTHOR]

Background and Objectives: Surveillance of Helicobacter pylori resistance to antibiotics was carried out in France in 2014, 2016, and 2018. We report here the results of the 2018 survey as well as the evolution over the 5‐year period. Materials and Methods: In this observational study, gastric biopsies were obtained by 62 gastroenterologists randomly selected in 5 regions of France and sent to a central laboratory where culture, antimicrobial susceptibility testing, and a real‐time PCR were performed in order to detect H pylori and its mutations associated with clarithromycin resistance. Results and Conclusion: During the year 2018, 951 patients were included: 55.3% women, mean age: 52.4 years ± 15.7, 71.6% born in France. Among them, 359 patients were H pylori positive by both culture and real‐time PCR, and 7 more by PCR only. There were 244 naive patients, 110 previously treated patients, and unknown for 5. Primary resistance to clarithromycin was 20.9% [16.3‐26.4], to levofloxacin 17.6% [13.4‐22.9], and to metronidazole 58.6% [52.3%‐64.6%]. Secondary resistance for these antibiotics was 56.4%, 22.7%, and 87.3%, respectively. There was no resistance to amoxicillin and tetracycline and very low resistance to rifampicin (1.2%) in both naive and treated patients. Primary resistance to clarithromycin decreased from 22.2% to 20.3% between 2014 and 2016, and appears to be stable since then. This can be linked to a stable consumption of macrolides over the 3‐year time period. Primary levofloxacin resistance was relatively stable while metronidazole resistance increased. Interestingly, in both naive and treated patients, amoxicillin and rifampicin resistance were rare. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) mutation‐positive non‐small cell lung cancer (NSCLC) patients benefit from EGFR tyrosine kinase inhibitors (TKIs), while some patients demonstrate a resistance to EGFR‐TKIs. In the case reported here, the NSCLC patient harboring an EGFR‐sensitive mutation and YES1 amplification was treated with afatinib as first‐line therapy, but was found to have progressive disease four weeks later. During subsequent chemotherapy, this patient's disease progressed rapidly. Mechanisms of primary resistance to EGFR‐TKIs remain unclear. This case suggested that YES1 amplification might be associated with primary resistance to EGFR‐TKIs and YES1 amplification might be a negative predictor of EGFR‐TKI treatment in NSCLC patients harboring EGFR sensitive mutations. [ABSTRACT FROM AUTHOR]

Background: Crizotinib is associated with a favorable survival benefit in patients with ALK‐positive non‐small cell lung cancer (NSCLC); however, a subset of patients harboring ALK rearrangement shows a poor response. Methods: We collected the clinical features and survival outcomes of 28 primary‐resistant responders (PRR) with progression‐free survival (PFS) of < 3 months on crizotinib and compared these with 78 long‐term responders (LTR) that achieved > 24 months PFS (control). Results: Primary resistance was observed in 6.5% of the patients. The median PFS of the PRR and LTR groups was 1.2 months (95% confidence interval [CI] 0.70–1.73) and 47.0 months (95% CI 34.39–59.64), respectively. A better Eastern Cooperative Oncology Group performance status score was significantly associated with longer PFS (odds ratio 0.06, 95% CI 0.01–0.33; P = 0.001). The median overall survival (OS) of the PRR group was 8.4 months (95% CI 3.47–13.42) and crizotinib as first‐line treatment was an independent predictive factor for survival outcome (P = 0.005). Patients administered ALK‐tyrosine kinase inhibitors after crizotinib progression had significantly longer survival than the PRR group treated with best supportive care (P = 0.007), but no significant difference was found between ALK‐tyrosine kinase inhibitor treatment and single chemotherapy (P = 0.944). Conclusion: Patients with primary resistance to crizotinib displayed unfavorable survival outcomes and the underlying mechanism cannot be identified in clinical features. Nevertheless, next‐generation ALK inhibitors and chemotherapy after crizotinib progression could confer a therapeutic and survival benefit in this population. [ABSTRACT FROM AUTHOR]

EGFR‐activating mutations have been recognized as the most important predictor of response to EGFR‐tyrosine kinase inhibitors (TKIs); however, 20–30% of patients harboring EGFR‐activating mutations show poor responses. The mechanisms of such EGFR‐TKI primary resistance are still poorly understood. In our case, a non‐small cell lung cancer patient developed intrinsic EGFR‐TKI resistance and was then confirmed to simultaneously harbor an L858R mutation and ROS1 rearrangement. Salvage chemotherapy plus Endostar showed enduring therapeutic effects, achieving a disease‐free survival period of 24 months and overall survival of 30 months. This suggests that co‐activation of different oncogenic signal pathways might be a potential mechanism of EGFR‐TKI primary resistance. Chemotherapy combined with anti‐angiogenesis should be considered an important salvage strategy. Further studies are warranted to verify these findings and explore the underlying mechanisms involved. [ABSTRACT FROM AUTHOR]

Summary: Nucleoside and nucleotide analogues (NUCs) targeting hepatitis B virus are capable of selecting resistant viruses upon long‐term administration as monotherapies. The prevalence of resistance‐associated substitutions (RASs) and fitness‐associated substitutions at baseline of NUC therapy and their impact on treatment responses remain unknown. A total of 232 treatment‐naïve patients chronically infected with hepatitis B virus (HBV) consecutively referred for the first time to one of French reference centres were included. The nearly full‐length HBV reverse transcriptase was sequenced by means of deep sequencing, and the sequences were analysed. RASs were detected in 25% of treatment‐naïve patients, generally representing low proportions of the viral quasispecies. All amino acid positions known to be associated with HBV resistance to currently approved NUCs or with increased fitness of resistant variants were affected, except position 80. RASs at positions involved in lamivudine, telbivudine and adefovir resistance were the most frequently detected. All patients with RASs detectable by next‐generation sequencing at baseline who were treatment‐eligible and treated with currently recommended drugs achieved a virological response. The presence of pre‐existing HBV RASs has no impact on the outcome of therapy if potent drugs with a high barrier to resistance are used. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the malignancy derived from normal hepatocytes with increasing incidence and extremely poor prognosis worldwide. The only approved first‐line systematic treatment agent for HCC, sorafenib, is capable to effectively improve advanced HCC patients' survival. However, it is gradually recognized that the therapeutic response to sorafenib could be drastically diminished after short‐term treatment, defined as primary resistance. The present study is aimed to explore the role of stress‐inducible protein Sestrin2 (SESN2), one of the most important sestrins family members, in sorafenib primary resistance. Herein, we initially found that SESN2 expression was significantly up‐regulated in both HCC cell lines and tissues compared to normal human hepatocytes and corresponding adjacent liver tissues, respectively. In addition, SESN2 expression was highly correlated with sorafenib IC50 of HCC cell lines. Thereafter, we showed that sorafenib treatment resulted in an increase of SESN2 expression and the knockdown of SESN2 exacerbated sorafenib‐induced proliferation inhibition and cell apoptosis. Further mechanistic study uncovered that SESN2 deficiency impaired both AKT and AMPK phosphorylation and activation after sorafenib treatment. Moreover, the correlations between SESN2 expression and both phosphor‐AKT and phosphor‐AMPK expression were illustrated in HCC tissues. Taken together, our study demonstrates that SESN2 activates AKT and AMPK signaling as a novel mechanism to induce sorafenib primary resistance in HCC. Our study demonstrates that SESN2 activates AKT and AMPK signaling as a novel mechanism to induce sorafenib primary resistance in HCC. [ABSTRACT FROM AUTHOR]

Abstract: Background: Portugal presents both a high prevalence of Helicobacter pylori (Hp) infection and a high prevalence of antibiotic resistance. However, conclusive data on its magnitude are lacking. We aimed at summarizing the existing data. Materials and Methods: A systematic review was conducted after searching in two databases (PubMed and SciELO). Meta‐analysis was performed, and comparison of resistance rates between children and adults and by type of resistance (primary and secondary) was made. Results: Eight cross‐sectional studies assessing Hp resistance to antibiotics were included. Overall resistance rates were as follows: clarithromycin (CLA) 42% (95% CI: 30‐54), metronidazole (MTZ) 25% (95% CI: 15‐38), ciprofloxacin (CIP) 9% (95% CI: 3‐18), levofloxacin (LVX) 18% (95% CI: 2‐42), tetracycline (TTC) 0.2% (95% CI: 0‐1), and amoxicillin (AMX) 0.1% (95% CI: 0‐0.2). Multidrug resistance was also an important problem, with the following global resistance rates: CLA plus MTZ of 10% (adults 20% (95% CI: 15‐26) vs children 6% (95% CI: 4‐9)) and CLA plus CIP of 2% (primary resistance in children's group). High secondary resistance rates were found for all antibiotics. Resistance was higher among adults for all antibiotics, except CLA that had high resistance levels both among adults and children (42% 95% CI: 14‐71 and 40% 95% CI: 33‐47). Conclusions: Hp resistance to the most widely used antibiotics is high in Portugal. Accordingly, our results suggest that the best therapeutic strategy for Hp in Portugal may be quadruple therapy with bismuth for adults and triple therapy including AMX plus MTZ or bismuth‐based therapy for children. [ABSTRACT FROM AUTHOR]

Background Primary Helicobacter pylori ( H. pylori) infection occurs predominantly in childhood. Antimicrobial resistance is the leading cause for H. pylori eradication failure. The aims of this study were (i) to establish for the first time the antimicrobial resistance of H. pylori strains in infected Slovenian children not previously treated for H. pylori infection and (ii) to evaluate the effectiveness of tailored triple therapy, assuming that eradication rate with tailored triple therapy will be >90%. Methods Data on all treatment-naive children 1-18 years old and treated for H. pylori infection according to susceptibility testing were retrospectively analyzed. All relevant clinical information and demographical information were retrospectively collected from the hospital information systems and/or patients' medical documentation. Results The inclusion criteria were met by 107 children (64.5% girls) with a median age of 12.0 years (range 2.0-17.6 years). Primary antimicrobial resistance rates of H. pylori were 1.0% to amoxicillin ( AMO), 23.4% to clarithromycin ( CLA), 20.2% to metronidazole ( MET), 2.8% to levofloxacin ( LEV), and 0.0% to tetracycline ( TET). Dual resistances were detected to CLA and MET in 11.5% (n=12) of strains, to CLA and LEV in 2.8% (n=3), and to MET and LEV in 2.9% (n=3). Results of treatment success were available for 71 patients (66.2% girls). Eradication of H. pylori was evaluated using the 13C-urea breath test, monoclonal stool antigen test or in some cases with repeated upper GI endoscopy with histology and cultivation/molecular tests. Eradication was achieved in 61 of 71 (85.9%) patients. Conclusions The primary resistance rates of H. pylori to CLA and MET in Slovenia are high. Our data strongly support the fact that in countries with high prevalence of resistant H. pylori strains susceptibility testing and tailored therapy is essential. [ABSTRACT FROM AUTHOR]

Basal cell carcinomas (BCCs) and a subset of medulloblastomas are characterized by loss-of-function mutations in the tumor suppressor gene, PTCH1. PTCH1 normally functions by repressing the activity of the Smoothened (SMO) receptor. Inactivating PTCH1 mutations result in constitutive Hedgehog pathway activity through uncontrolled SMO signaling. Targeting this pathway with vismodegib, a novel SMO inhibitor, results in impressive tumor regression in patients harboring genetic defects in this pathway. However, a secondary mutation in SMO has been reported in medulloblastoma patients following relapse on vismodegib to date. This mutation preserves pathway activity, but appears to confer resistance by interfering with drug binding. Here we report for the first time on the molecular mechanisms of resistance to vismodegib in two BCC cases. The first case, showing progression after 2 months of continuous vismodegib (primary resistance), exhibited the new SMO G497W mutation. The second case, showing a complete clinical response after 5 months of treatment and a subsequent progression after 11 months on vismodegib (secondary resistance), exhibited a PTCH1 nonsense mutation in both the pre- and the post-treatment specimens, and the SMO D473Y mutation in the post-treatment specimens only. In silico analysis demonstrated that SMO G497W undergoes a conformational rearrangement resulting in a partial obstruction of the protein drug entry site, whereas the SMO D473Y mutation induces a direct effect on the binding site geometry leading to a total disruption of a stabilizing hydrogen bond network. Thus, the G497W and D473Y SMO mutations may represent two different mechanisms leading to primary and secondary resistance to vismodegib, respectively. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy (ART) has increased in resource-limited settings. This study determined the prevalence of HIV-1 drug resistance-associated mutations (DRAMs) among patients with chronic HIV-1 infections and compare DRAMs between CRF01_AE and B subtypes. ART-naive Thai patients who had ART initiation between 2010 and 2011 were enrolled prospectively. Genotypic assays were performed on viral reverse transcriptase and protease genes within 4 weeks before starting ART. DRAMs were assessed using the International AIDS Society-USA 2011 list. A total of 330 patients were included. HIV-1 subtypes included CRF01_AE (73%), B (23.9%), and others (3.1%). Median (IQR) CD4+ was 66 (23-172) cells/mm3 and median (IQR) HIV-1 RNA was 5.2 (4.6-5.8) log copies/ml. The prevalence of patients with ≥1 DRAMs for any antiretroviral agents was 17.6%. DRAM prevalence was 17% for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 0.6% for NRTIs, and 0.6% for protease inhibitors (PIs). DRAMs to NNRTIs were V106I (7%), V179D (4.2%), V179T (1.8%), E138A (1.5%), V90I (1.2%), K103N (0.9%), Y181C (0.9%), and P225H (0.3%). DRAMs to NRTIs were M184V (0.3%) and T215S (0.3%). The only major DRAM for PIs was M46L (0.6%). Minor DRAMs to PIs including I13V, M36I, H69K, and L89M were observed more frequently in CRF_01 AE. By multivariate analysis, the factors 'HIV-1 subtype B' and 'low pretreated CD4+ cell count' were associated with a higher rate of DRAMs. HIV-1 DRAMs, especially to NNRTIs, are emerging in a middle-income country after widespread use of NNRTI-based ART. HIV genotypic assays before ART initiation in patients with chronic HIV-1 infection should be considered. J. Med. Virol. 85:194-199, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Yimer SA, Agonafir M, Derese Y, Sani Y, Bjune GA, Holm-Hansen C. Primary drug resistance to anti-tuberculosis drugs in major towns of Amhara Region, Ethiopia. APMIS 2012; 120: 503-9. Drug resistance is a major obstacle to effective TB control program performance. In this study, we assessed the prevalence of primary drug resistance in Mycobacterium tuberculosis (Mtb) isolates in Amhara Region, Ethiopia. A total of 112 Mtb isolates from cases with newly diagnosed pulmonary TB were subjected to drug susceptibility testing (DST) in a cross-sectional study. Isolates were tested for sensitivity to isoniazid, rifampicin, ethambutol, and streptomycin using the MGIT 960 protocol. A total of 93 Mtb isolates yielded valid DST results and 28 (30.1%) were resistant to one or more of first line anti-TB drugs. One isolate (1.0%) was multi-drug resistant (MDR), five (5.4%) were classified as poly-resistant and 22 showed single drug resistance to either streptomycin (n = 19) or isoniazid (n = 3). Isolates from HIV-positive patients were more likely to be resistant to at least one of the four anti-TB drugs compared with HIV-negative individuals (odds ratio 2.76, 95% confidence interval 1.06-7.22; p = 0.03). The study showed a high prevalence of primary drug resistance. Even though the prevalence of MDR was low, conditions that can contribute to the development of MDR are increasing. Therefore, regular monitoring of drug resistance and enhanced implementation of TB/HIV collaborative activities in the study region are imperative. [ABSTRACT FROM AUTHOR]

Trastuzumab is the first Food and Drug Administration (FDA)-approved therapeutic targeting a HER-family receptor tyrosine kinase (HER2/ErbB2/neu). Although trastuzumab is effective in the treatment of HER2-positive breast cancer, a substantial proportion of patients will not respond to trastuzumab-based regimens (primary resistance), and those who do respond will often lose clinical benefits (i.e., secondary resistance). Although multiple mechanisms underlying the development of secondary trastuzumab resistance have been identified, few studies have specifically examined the basis of primary trastuzumab resistance. Here, we review these studies, which together demonstrate that trastuzumab induces phenotypic changes in tumor cells, even when they are not growth inhibited by trastuzumab, including changes in gene expression. These changes have important clinical implications, including the sensitization of malignant cells to other therapeutic drugs. In light of these observations, we propose that the conventional definition of resistance as it pertains to trastuzumab and, perhaps, to other targeted therapeutics, may require revision. The results of these studies will be useful in informing the direction of future basic and clinical research focused on overcoming primary trastuzumab resistance. [ABSTRACT FROM AUTHOR]

Background As access to antiretroviral drugs increases in developing countries, it will become increasingly important to monitor the emergence of resistance and to define the molecular pathways involved to identify optimal therapeutic regimens. Methods We performed genotypic resistance testing on plasma obtained from 101 HIV-infected treatment-naïve individuals from Mali. Genotyping was carried out using the Virco protocols and HXB2 was used as the reference strain. Results CRF02_AG was the most common subtype, present in 71.3% of our patient population. Other subtypes included B, C, G, CRF06_CPX, CRF09_CPX, CRF01_AE, A2/CRF16_A2D, A1 and CRF13_CPX. A total of 9.9% [95% confidence interval (CI) 6.9–12.9%] of patients had at least one resistance mutation. The prevalences of mutations conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 5% (95% CI 0.7–9.2%), 6% (95% CI 1.3–10.6%) and 0%, respectively. The most frequent mutations were T215A/Y for NRTIs and K103N/T for NNRTIs. One patient harboured three NRTI resistance mutations and one NNRTI mutation. This is the first reported case of multi-drug-resistant viral transmission in Mali. Polymorphisms at protease codons 10I/V and 33F potentially associated with resistance were observed in 18.8% and 1% of patients, respectively. Several polymorphisms in the C-terminal domain of reverse transcriptase were observed: A371V (in 63.4% of patients), G335D (76.2%), E399D (10.9%) and G333E (1%). Conclusion Primary resistance was seen in 9.9% of subjects, which is higher than previously reported in Mali. Taking into consideration other polymorphisms in protease such as L10I/V and 33F, primary resistance could reach 28.7% (95% CI 19.9–37.5%). Our study reflects the need to monitor the evolution of resistance on a regular basis and trends of transmitted resistance. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to elucidate primary drug resistance and transmission of HIV-1 in acute and recent drug-naïve seroconverters in Singapore. Methods Acute and recent HIV-1 seroconverters were enrolled in the study. The HIV-1 polymerase ( pol) gene was sequenced and used for genotypic drug resistance analysis and phylogenetic analysis. HIV-1 transmission clusters were inferred from phylogenetic clustering analysis. Results Of the 60 subjects analysed, 95% were men, and 73.3% were men who have sex with men (MSM). Six HIV-1 subtypes were identified, including CRF01_AE (46.7%), subtypes B (30%), B′ (15%) and G (1.7%), CRF33_01B (1.7%) and CRF34_01B (5%). Primary genotypic resistance was detected in only one (1.7%) subtype B variant. Thirty-one patients (51.7%) were phylogenetically clustered, of whom 90% reported having local risk exposure, compared with 59% of the patients who were not phylogenetically clustered [odds ratio (OR) 6.35, 95% confidence interval (CI) 1.65–23.95]. MSM (OR 5.63, 95% CI 1.17–27.15), high viral load (OR 4.28, 95% CI 1.37–13.36) and young age (OR 0.92, 95% CI 0.85–0.99) were independently associated with clustered individuals. Conclusions In Singapore, HIV-1 primary resistance is insignificant; individuals with seroconversion account for about half of onward transmission among recently infected seroconverters. MSM, high viral load and young age are factors that facilitate transmission. Early detection of these individuals is of paramount importance for the prevention of HIV-1 transmission. [ABSTRACT FROM AUTHOR]

Background: Levofloxacin has been proposed as an alternative to classic therapy in secondary resistance to Helicobacter pylori. Aim: To evaluate primary and secondary resistance of H. pylori to levofloxacin, and to test the role of susceptibility test on the efficacy of levofloxacin-based triple therapy. Methods: Eighty consecutive dyspeptic patients with positive 13C-urea breath test never treated were randomly allocated into group A1 (40 patients) and group B1 (39 patients). Eighty-three patients already treated unsuccessfully with positive 13C-urea breath test were divided into group A2 (51 patients) and group B2 (32 patients). Patients in group A1 and group A2 underwent upper gastrointestinal endoscopy for H. pylori susceptibility test to amoxicillin, clarithromycin, tinidazole, rifabutin, and levofloxacin. These patients were treated with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.) and esomeprazole (20 mg b.i.d.) for 10 days if sensitive to these two antibiotics. If H. pylori was found resistant to amoxicillin and/or levofloxacin the treatment was based on the indications of the susceptibility test. Patients in group B1 and group B2 were treated empirically with levofloxacin, amoxicillin, and esomeprazole at the same dose and duration as group A. All patients underwent 13C-urea breath test 2 months after the end of therapy. Results: The antibiotic resistance of H. pylori strains in group A1 and group A2 was (%): amoxicillin: 2.4, 10; clarithromycin: 21.9, 43.1; tinidazole: 31.7, 70; rifabutin: 2.4, 4; and levofloxacin: 9.7, 12.2, respectively. In group A1 with susceptibility test-driven therapy, eradication was 97.2%, and in group B1 with empirical treatment, 94.1% (n.s.). In group A2 with susceptibility test, eradication was 97.5%, whereas in group B2 with empirical treatment 81.2% ( p < .01). Conclusion: Primary and secondary resistance of H. pylori to levofloxacin is approximately 10% of the tested strains. The susceptibility test does not influence therapeutic outcome of triple therapy with amoxicillin and levofloxacin in patients never treated, while it is determinant for patients who were previously treated without success. [ABSTRACT FROM AUTHOR]

This paper proposes a novel quick-response torque control strategy of an induction motor, which is robust against variations of primary and secondary resistances. Conventional field-oriented control originally is robust against the variation of the primary resistance, but has very high parameter sensitivity of the secondary resistance. To compensate for its effect, considerable research has been conducted by using a stator voltage model, a low-sensitivity flux observer, an adaptive system, and so on. It is assumed that successful results have not been made in practice because each method requires not only complicated configurations but also motor parameters. Therefore its compensation has to be carried out with no relation to the motor parameter, especially the primary resistance. In this paper, a robust parameter-identification technique is applied to a field-oriented control system with a flux simulator as a means to solve the problem. The technique is based on instantaneous reactive power which is never affected by the primary resistance. The authors describe the aforementioned control theory and practical implementation. As a result, excellence performance was confirmed by some computer simulations and experimental tests. © 1997 Scripta Technica, Inc. Electr Eng Jpn, 118 (2): 30–40, 1997 [ABSTRACT FROM AUTHOR]