Tuning of Cu-Al Interactions in Complexes Derived from Tris(pyridonyl-6-methyl)aluminum Metalloligands.

A series of bioinspired polar atrane Cu-Al complexes were studied with a combined experimental and computational approach to assess the range and nature of Cu-Al interactions in these novel species. The aluminum metalloligand [Na{Me2Al(OPy-6-Me)2}] (2) was furnished in excellent yield (92%) from the nucleophilic attack of Na(OPy-6-Me) to AlMe3 and the subsequent alkane elimination reaction with 6-methyl-2-hydroxypyridine. At the same time, the metalloligand [Al(OPy-6-Me)3] (3) was isolated in an also excellent yield (95%) via alkane elimination of AlMe3 with 6-methyl-2-hydroxypyridine. The zwitterionic Cu-Al atranes [Cu{MeAl(OPy-6-Me)3}] (5Me) and [Cu{MesAl(OPy-6-Me)3}] (5Mes) were isolated (73 and 97% yields) from metalloligands 2 and 3, respectively. [(Cu{Al(OPy-6-Me)4})2(µ-Cu)]+ ([6+][B(ArCF3)4]) was isolated via a reaction that involves alkane elimination and redistribution reacting from 5Me with [H(OEt2)2][B(ArCF3)4] in benzene solution. Alkane elimination in benzene of either 5Me or 5Mes with [HNEt3][B(ArCF3)4] renders [Cu{(Et3N)Al(OPy-6-Me)3}]+ (Et3N-5+). The Lewis base-free cationic complex [Cu{Al(OPy-6-Me)3}]+ (5+) was isolated in 68% yield upon reacting 3 with [Cu(COD)2][B(ArCF3)4] in benzene. Metalloligands and complexes were fully characterized with an array of spectroscopic and analytical techniques that include multinuclear NMR, ATR-IR, ESI-spectrometry, combustion microanalysis, cyclic voltammetry (CV), and, whenever feasible, SCXRD. X-ray and DFT parameters indicate that the strength of the Cu→Al transannular interaction follows the trend 5+ > Et3N-5+ > [6+][B(ArCF3)4], 5Me, and 5Mes in a smooth transition from zwitterionic species where the Cu-Al interaction is nonexistent to moderate Cu-Al Z-type interactions. CV, in conjunction with DFT calculations of Et3N-5+ and 5+, hint at the generation in the electrochemical cell of the radical species 5rad at -1.82 V and the anionic complex 5- at -2.32 V vs Fc/Fc+, respectively. The proposed species 5rad exhibits 2-center/1-electron (2c/1e) σ bonding whereas 5- a 2-center/2-electron (2c/2e) bond.

A new cryptic species of Imparfinis (Siluriformes: Heptapteridae) from the Orinoco River basin, revealed by an iterative approach.

An iterative analysis of Imparfinis, combining phylogenetic analysis based on cytochrome oxidase gene and multivariate morphometrics, revealed a new cryptic species from the Andean tributaries of the Orinoco River basin, which is described here. The new species is sister to a clade constituted by Imparfinis hasemani and Imparfinis pijpersi, both from the river basins of the Guiana Shield, being also the most geographically proximate species. Nonetheless, the new species is most similar in general appearance to Imparfinis guttatus from the Madeira and Paraguay River drainages, being almost undistinguishable by conventional characters of external morphology, differing only by morphometric attributes overall. The new species can be distinguished from the remaining congeners by a unique combination of characters, including lower lobe of caudal fin darker than upper lobe, maxillary barbel reaching or surpassing pelvic-fin insertion, 12-15 gill rakers on first gill arch, 40-42 total vertebrae and 9-10 ribs. The new species constitutes the only representative from the Orinoco River basin belonging to Imparfinis sensu stricto.

Switch to subcutaneous infliximab during the SARS-CoV-2 pandemic: preliminary results.

A new subcutaneous formulation of the infliximab biosimilar CT-P13 has recently been developed for the treatment of inflammatory bowel disease (IBD), providing response rates similar to intravenous treatment. The use of this new formulation was requested, in an effort to limit patient attendance at intravenous infusion centers and to maintain biological treatment during the COVID-19 pandemic. The objective of this observational, retrospective and descriptive study was to assess CT-P13 efficacy and safety after switching from intravenous to a subcutaneous formulation in patients with IBD receiving maintenance therapy. This article shows preliminary results after six months of follow-up.

Association between polymorphisms in the vitamin D receptor and susceptibility to multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) is a neurodegenerative chronic inflammatory. Mutations in the vitamin D receptor (VDR) gene can substantially affect serum vitamin D levels or alter its functionality, and can consequently increase susceptibility to developing MS. The objective of this study was to evaluate the association between polymorphisms in the VDR gene and risk of MS in a (Spanish) Caucasian population. PATIENTS AND METHODS: We conducted a retrospective case-control study comprising 209 patients with relapsing-remitting multiple sclerosis (RRMS) and 836 controls of Caucasian origin from southern Spain. The ApaI (rs7975232), BsmI (rs1544410), Cdx2 (rs11568820), FokI (rs2228570), and TaqI (rs731236) gene polymorphisms were determined by allelic discrimination real-time PCR using TaqMan probes. RESULTS: The recessive logical regression model, adjusted for age and sex, revealed that the TT genotype for VDR FokI (rs2228570) polymorphism was associated with higher risk of MS (P = 0.0150; OR = 1.82; 95% CI = 1.12-2.94; TT vs. CT + CC). No association between the other polymorphisms and development of MS was found in any of the models analyzed. The haplotype analysis, adjusted for age, smoking, and sex, did not find any statistically significant association between the haplotypes analyzed and risk of MS. CONCLUSIONS: The VDR FokI (rs2228570) polymorphism was significantly associated with developing MS. We found no influence of the ApaI (rs7975232), BsmI (rs1544410), Cdx2 (rs11568820), FokI (rs2228570), and TaqI (rs731236) gene polymorphisms on the risk of developing MS in our patients.

BENEFIT: real-world effectiveness of SB4 after transition from reference etanercept in rheumatoid arthritis and axial spondyloarthritis.

OBJECTIVES: The objective of this non-interventional study was to evaluate the effectiveness and safety of the etanercept biosimilar SB4 (BenepaliTM) following transition from reference etanercept in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA). METHODS: Data were collected from clinical records of adult patients with stable RA or axSpA, in France, Germany, Italy and Spain. Key outcomes included the change from transition to 3 and 6 months in Disease Activity Score 28 (DAS28) for RA or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for axSpA. RESULTS: In total, 358 patients with RA and 199 patients with axSpA were enrolled. The mean individual change in disease score from transition was -0.02 (95% confidence interval [CI] -0.11, 0.08) at 3 months and 0.01 (95% CI -0.09, 0.11) at 6 months for DAS28, and -0.01 (95% CI -0.24, 0.21) at 3 months and -0.11 (95% CI -0.31, 0.10) at 6 months for BASDAI. In the RA cohort, 19 (5.3%) and 5 patients (1.4%) reported adverse events and serious adverse events (SAEs), respectively. In the axSpA cohort, 12 (6.0%) and 2 patients (1.0%) reported adverse events and SAEs, respectively. One SAE of pneumonia (RA cohort) was considered to be related to SB4 administration. At 6 months post-transition, the SB4 retention rate was 90.8% (95% CI 87.2%, 93.4%) in the RA cohort and 92.4% (95% CI 87.5%, 95.4%) in the axSpA cohort. CONCLUSIONS: Transition from reference etanercept to SB4 is effective and safe in patients with stable RA and axSpA.

Cyclooctadiene Rh(I) Bis- and Tris(pyrazolyl)aluminate Complexes and Their Catalytic Activity on the Polymerization of Phenylacetylene.

In this work, we report the transfer of alkyl bis- and tris(pyrazolyl)aluminates metalloligands to an electron-rich organotransition metal center. The 16-electron heterobimetallic complexes of rhodium [Rh(COD){Al(Ph2pz)2Me2}] (3) and [Rh(COD){Al(Ph2pz)3Me}] (4) were obtained by metathesis reaction of the sodium bis- (1) and tris(pyrazolyl)aluminate (2) with [RhCl(COD)]2. For 3, 1H and 13C NMR in solution along with DFT calculations are consistent with a κ2-coordination mode of the bis(pyrazolyl)aluminate to a square-planar Rh(I) center. The X-ray structure of 4 shows a similar κ2-coordination mode of the tris(pyrazolyl)aluminate to Rh(I) with a pendant pyrazolyl moiety. The attempted synthesis of aluminate-rhodium complexes with R = CF3, tBu on the pyrazolate ring afforded [Rh(R2pz)(COD)]2 and [R2pzAlMe2]2. Complexes 3 and 4 were investigated as homogeneous catalysts in the polymerization of phenylacetylene (PA). Both complexes showed enhanced catalytic activity compared to analogous rhodium poly(pyrazolyl)borates. Optimized gas-phase DFT geometries of 3, 4, [Rh(COD){B(Ph2pz)2Me2}], and [Rh(COD){B(Ph2pz)3Me}] were used to compare bite angles, while DFT geometries of 3-CO, 4-CO, [Rh(CO)2{B(Ph2pz)2Me2}], and [Rh(CO)2{B(Ph2pz)3Me}] were employed to probe the electronic situation of the rhodium center through IR CO stretching modes. The wider bite angles and the less electron-rich rhodium center of the poly(pyrazolyl)aluminates compared with their borate analogues could be implicated in the better performance of the active catalytic species during polymerization of PA.

Analyzing the clinical benefit of newer therapies for advanced or metastatic non-small-cell lung cancer: application of the ESMO-magnitude of clinical benefit scale v1.1.

BACKGROUND: Despite newer therapies, advanced or metastatic non-small-cell lung cancer (NSCLC) continues to be the leading cause of cancer-related deaths worldwide. Deficits in the design and methods of randomized controlled trials (RCTs) may contribute to reducing the clinical benefit of therapies in oncology. To prioritize treatments based on efficacy results and toxicity data, the European Society for Medical Oncology (ESMO) has developed the Magnitude of Clinical Benefit Scale (MCBS). The objective of this study was to apply the ESMO-MCBS v1.1 to a cohort of RCTs on therapies for advanced or metastatic NSCLC. MATERIAL AND METHODS: Phase III and pivotal phase II trials, published between 2013 and 2018, investigating drug therapies for advanced NSCLC were included. PubMed was specifically searched for efficacy/toxicity updates. Treatments were graded 5 to 1 on the ESMO-MCBS v1.1, using the lower limit of the 95% confidence interval of the hazard ratio (HR), where scores 5 and 4 represent a substantial clinical benefit. Additionally, scores using the point estimate HR were generated, for comparison. Discrepancies between our grade estimations and the ones published on the ESMO website, as scorecards, were identified. RESULTS: ESMO-MCBS scores were calculated for 42 positive clinical trials. 54.8% met the ESMO-MCBS thresholds for clinically meaningful benefit (final grade of 4 or 5). That percentage decreased to 40.5% when considering the point estimate of the HR. 50.0% of the trials had no published scorecard on the ESMO website and discrepancies affected 11 (26.2%) studies. CONCLUSION: Almost half of the RCTs showing a statistically significant result favoring the experimental arm, failed to demonstrate a substantial clinical benefit according to the ESMO framework.

Relationship between gastroenterologists and hospital pharmacists: the results of a national survey. The CONDIFA study.

INTRODUCTION: project CONDIFA ("Consenso Digestivo-Farmacia Hospitalaria") aims to establish lines of agreement between both specialties in order to improve patient care and resource optimization. In this initial work our goal was to collect the views held by both fields on issues pertaining to their mutual cooperation in our country. MATERIAL AND METHODS: an online survey was administered to members of the Sociedad Española de Patología Digestiva (SEPD) and Sociedad Española de Farmacia Hospitalaria (SEFH). It comprised 31 questions, and was developed by a task force established by both Societies. RESULTS: the survey was filled out by 241 gastroenterologists and 126 pharmacists. Of these, 55 % were women. A total of 76.8 % of gastroenterologists and 88.1 % of pharmacists answered that relations between both specialties are good/very good, without reaching statistically significant differences. For both groups pharmaceutical expenditure is a priority/annual objective in their department, albeit they do not agree on prescription freedom and industry influence. Biologics committees are considered to be useful by most respondents, and both groups think it appropriate that meetings/sessions be scheduled between both specialties, and that a reference pharmacist be appointed for gastroenterology. CONCLUSIONS: this institutional research, driven by SEPD and SEFH, demonstrates that, while cooperation between the gastroenterology and hospital pharmacy departments is close and adequate, some areas remain open to improvement, which will result in better, more effective patient care.

Pharmacogenetics of platinum-based chemotherapy: impact of DNA repair and folate metabolism gene polymorphisms on prognosis of non-small cell lung cancer patients.

Chemotherapy based on platinum compounds is the standard treatment for NSCLC patients with EGFR wild type, and is also used as second line in mutated EGFR patients. Nevertheless, this therapy presents poor clinical outcomes. ERCC1, ERCC2, XRCC1, MDM2, MTHFR, MTR, and SLC19A1 gene polymorphisms may contribute to individual variation in response and survival to platinum-based chemotherapy. The aim of this study was to investigate the influence of these polymorphisms on response and survival of NSCLC patients treated with platinum-based chemotherapy. A retrospective-prospective cohorts study was conducted, including 141 NSCLC patients. Polymorphisms were analyzed by PCR real-time with Taqman® probes. Patients with ERCC1 rs3212986-GG (p = 0.0268; OR = 2.50; CI95% = 1.12-5.69) and XRCC1 rs25487-GG (p = 0.0161; OR = 2.99; CI95% = 1.26-7.62) genotype showed significantly better ORR. Cox survival analysis revealed that patients carrying the MDM2 rs1690924-GG genotype (p = 0.0345; HR = 1.99; CI95% = 1.05-3.80) presented higher risk of death. Furthermore, carriers of MTR rs1805087-A alleles (p = 0.0060; HR = 8.91; CI95% = 1.87-42.42) and SLC19A1 rs1051266-AA genotype (p = 0.0130; HR = 1.74; CI95% = 1.12-2.68) showed greater risk of progression. No influence of ERCC1 rs11615, ERCC2 rs13181, ERCC2 rs1799793, XRCC1 rs1799782, MDM2 rs1470383, MTHFR rs1801131, and MTHFR rs1801133 on platinum-based chemotherapy clinical outcomes was found. In conclusion, our results suggest that ERCC1 rs3212986, XRCC1 rs25487, MDM2 rs1690924, MTR rs1805087, and SLC19A1 rs1051266 gene polymorphisms may significantly act as predictive factors in NSCLC patients treated with platinum-based chemotherapy.

MULTI-CRITERIA DECISION ANALYSIS AS A DECISION-SUPPORT TOOL FOR DRUG EVALUATION: A PILOT STUDY IN A PHARMACY AND THERAPEUTICS COMMITTEE SETTING.

OBJECTIVES: The aim of this study was to develop and to assess a specific Multi-Criteria Decision Analysis (MCDA) framework to evaluate new drugs in an hospital pharmacy and therapeutics committee (P&TC) setting. METHODS: A pilot criteria framework was developed based on the EVIDEM (Evidence and Value: Impact on DEcisionMaking) framework, together with other relevant criteria, and assessed by a group of P&TC's members. The weighting of included criteria was done using a 5-point weighting technique. Two drugs were chosen by evaluation: an orphan-drug for Gaucher disease, and a nonorphan drug for the treatment of inflammatory bowel disease. Evidence matrices were developed, and value contribution of each drug was evaluated by P&TC's members. An agreed final framework was obtained through a discussion between the P&TC's members. RESULTS: After criteria assessment, the pilot framework included eight quantitative criteria: "disease severity," "unmet needs," "comparative efficacy/effectiveness," "comparative safety/tolerability," "comparative patient-reported outcomes," "comparative cost consequences-cost of treatment," "comparative cost consequences-other medical costs," and "quality of evidence"; and one contextual criterion: "opportunity costs and affordability." The most valued criteria were: "comparative safety/tolerability," "disease severity," and "comparative efficacy/effectiveness." When assessing the drugs most valued characteristics of the MCDA were the possibility that all team may contribute to drug assessment by means of scoring the matrices and the discussion to reach a consensus in drug positioning and value decision making. CONCLUSIONS: The reflective MCDA would integrate quantitative and qualitative criteria relevant for a P&TC setting, allowing reflective discussions based on the criteria weighting score.

Adherence of psychopharmacological prescriptions to clinical practice guidelines in patients with eating behavior disorders.

PURPOSE: The purpose of this study was to analyze the adherence of psychopharmacological prescriptions to clinical practice guidelines (CPGs) for patients with eating behavior disorders (EDs) and to compare the effectiveness, safety, and cost of treatment according to adherence. METHODS: This retrospective observational study included ED patients admitted to the eating disorders unit (EDU) of Ciudad Real Hospital (Spain) between January 2006 and December 2009 and followed until December 2014. Psychopharmaceuticals prescribed during EDU stay(s) were compared with guidelines published by American Psychiatric Association (APA), National Institute for Clinical Excellence (NICE), and Spanish Ministry of Health and Consumption (SMHC). Adherence was considered as the percentage of patients whose prescription followed all recommendations. RESULTS: The study included 113 ED patients. Adherence to APA and NICE/SMHC was 30.1% and 45.1%, respectively. Weekly weight gain during hospital stay was higher (p = 0.037) in the APA "adherence" (807.6 g) versus "non-adherence" (544.4 g) group. An association was found between CPG adherence and higher 5-year full recovery rate (p < 0.040). Adherence to NICE/SMHC was associated with lower incidence (p = 0.001) of adverse effects (33.3% in adherence vs. 66.1% in non-adherence group). CPG adherence was associated with lower medication costs (p < 0.020). The age was higher and there was a greater frequency of self-harm behavior and psychiatric comorbidities in the non-adherence than adherence group (p ≤ 0.040). CONCLUSIONS: CPG adherence was low in EDU-admitted patients. Long-term follow-up showed that clinical outcomes were better and medication costs lower in patients with versus without CPG-adherent prescriptions, likely influenced by the apparently greater severity of illness in those with non-CPG-adherent prescriptions.

Clinical utility of the ASDAS index in comparison with BASDAI in patients with ankylosing spondylitis (Axis Study).

The objective of the study was to study the clinical utility of the Ankylosing Spondylitis Disease Activity Score (ASDAS) for the assessment of disease activity in ankylosing spondylitis (AS) patients, compared to the Bath Ankylosing Spondylitis Activity Index (BASDAI). This was a prospective longitudinal observational study in patients with AS (NY-modified criteria) from 23 Spanish centers. Physical and analytical data; global, lumbar, and nocturnal pain; ASDAS, BASDAI and minimally acceptable clinical status (PASS) were collected. Psychometric characteristics of both indexes were analyzed: construct validity (convergent and divergent), discriminant capacity, criterion validity (global physician and patient assessment), and sensitivity to change. The study involved 127 patients (19.7% attrition). Both BASDAI and ASDAS showed a higher correlation with patient's global assessment (r = 0.76 and 0.70, respectively) than with physician's global assessment (r = 0.67 and 0.57). Both scores allowed discriminating patients with an acceptable clinical status, although BASDAI to a greater extent than ASDAS (Cohen δ 1.72 vs 0.88 for the medical PASS). Both scores showed sensitivity to change in patients who changed from an unacceptable symptomatic state to acceptable according to PASS criteria (physician and patient) and by BASDAI 50 response criteria (Cohen δ > 0.80). BASDAI showed better criterion validity than ASDAS, both for the patient PASS (AUC 0.85 vs 0.79) and for the physician's (AUC 0.90 vs 0.79). ASDAS shows adequate performance for disease activity in patients with AS; however, in this study, its psychometric properties do not present advantages over BASDAI in terms of criterion validity, sensitivity to change or discriminative capacity; replacement of BASDAI by ASDAS is not supported by the data.

Lithium Complexes Derived of Benzylphosphines: Synthesis, Characterization and Evaluation in the ROP of rac-Lactide and ε-Caprolactone.

A series of lithium complexes ([Ph2P(o-C6H4-CH2Li·TMEDA)] (1-Li), [PhP(o-C6H4-CH3)(o-C6H4-CH2Li·TMEDA)] (2-Li), [PhP(o-C6H4-CH2Li·TMEDA)2] (2-Li2) and [P(o-C6H4-CH2Li·TMEDA)3] (3-Li3)) was prepared from mono-, di- and tri-benzylphosphines and varying amounts of nBuLi and was characterized extensively by IR and ¹H, 7Li, 13C and 31P NMR spectroscopy. The molecular structures of complexes 1-Li and 2-Li were determined by single-crystal X-ray diffraction studies. The two complexes have monomeric structures in the solid state comprising seesaw lithium atoms. In each case, the ligand exhibits an asymmetric C-C η²-coordination mode and an intramolecular P-Li bond interaction. Theoretical calculations at Density functional theory (DFT) level M06/6111+G(2d,p) show that indeed a P-Li bond is established which can be explained as the P lone pair (sp1.26) being partially delocalized on an available sp² orbital on Li (sp2.04) and additional bonding contribution of the phosphorous atom to Li stems from further delocalization of a σ P-C orbital into the sp² orbital on Li. The observed short contact distances between an aromatic ipso carbon and Li in the crystal structures of 1-Li and 2-Li are explained as due to the interaction of a σ C-Li orbital into the π* orbital of a C-C aromatic bond. Preliminary tests show compounds 1-Li, 2-Li, 2-Li2 and 3-Li3 are active catalysts in the solvent free ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) and rac-lactide (rac-LA). High conversions to polycaprolactones were obtained in short periods of time: 1-6 min at 25 °C. Additionally, all four lithium complexes behave as moderately good initiators for the ROP of rac-LA showing high conversions to polylactides at 140 °C in one hour.

Gene polymorphisms as predictors of response to biological therapies in psoriasis patients.

Psoriasis is a chronic inflammatory autoimmune skin disease, characterized by the formation of erythematous scaly plaques on the skin and joints. The therapies for psoriasis are mainly symptomatic and sometimes with poor response. Response among patients is very variable, especially with biological drugs (adalimumab, etarnecept, infliximab and ustekimumab). This variability may be partly explained by the effect of different genetic backgrounds. This has prompted the investigation of many genes, such as FCGR3A, HLA, IL17F, IL23R, PDE3A-SLCO1C1, TNFα and other associated genes, as potential candidates to predict response to the different biological drugs used for the treatment of psoriasis. In this article, we will review the influence of gene polymorphisms investigated to date on response to biological drugs in psoriasis patients.

ABCB1 C3435T gene polymorphism as a potential biomarker of clinical outcomes in HER2-positive breast cancer patients.

HER2-positive breast cancer patients treated with trastuzumab schemes have good initial clinical outcomes. Despite this beneficial effect, many patients experiment resistance to these drugs. Several gene polymorphisms in ABCB1, HER2, and CCND1 have been proposed as potential predictors of clinical outcomes of trastuzumab schemes. The aim of this study was to evaluate the association between 4 gene polymorphisms potentially responsible for bad prognosis (HER2-Ile655Val, CCND1-A870G and ABCB1C1236T, C3435T) and clinical outcomes in HER2-positive BC patients. A retrospective cohorts study was performed. Eighty-four HER2-positive BC patients treated with trastuzumab schemes were included. The four gene polymorphisms were analyzed by PCR Real-Time with Taqman® probes. Genotypes were investigated for their association with tumor response, survival and resistance. Patients with CC genotype of ABCB1-C3435T presented higher risk of resistance to chemotherapy/trastuzumab schemes, compared to those carrying the T-allele (RR: 2.71; CI95%:1.29-5.68; p=0.013888), progression (RR: 1.89; p=0.017964); and exitus (RR: 2.09; p=0.03276). Multivariate logistic regression analysis considering clinical variables and ABCB1-C3435T revealed that the only independent factor associated to resistance to therapy was ABCB1-C3435T gene polymorphism (ORCT/CC: 0.25; p=0.0123; ORTT/CC: 0.09; p=0.0348. The protective effect of ABCB1-C3435T T-allele was confirmed in the multivariate Cox regression analysis for PFS (HRCT/CC: 0.41; p=0.00806; HRTT/CC: 0.22; p=0.01982) and OS (HRCT/CC: 0.49; p=0.0555; HRTT/CC: 0.12; p=0.0398). ABCB1-C1236T, CCND1-A870G and HER2-Ile655Val polymorphisms were not associated to resistance, PFS or OS (p>0.05). The A-allele for CCND1-rs9344 was associated with higher response rates (RR: 3.44; uncorrected p-value: 0.03816) in the bivariate analysis, but no statically association was found after Bonferroni correction (p=0.15264). ABCB1-C3435T, ABCB1-C1236T and HER2-Ile655Val gene polymorphisms were not associated with response. Although this study demonstrates a prognostic value of ABCB1-C3435T gene polymorphism to predict clinical outcomes, further studies with a larger sample will be necessary to validate this result.

[Frontal fibrosing alopecia (FFA): Report on four cases and review of the literature]. / Alopecia frontal fibrosante (AFF): reporte de cuatro casos y revisión de la literatura.

Frontal fibrosing alopecia was recently described by Kossard, et al. as a progressive symmetrical recession of the frontal-temporal-parietal hairline affecting particularly postmenopausal women. Besides affecting the scalp, there are some cases in the literature with partial or total loss of the eyebrows, also involving the trunk, and superior extremities. Because the clinical, histological, and immunochemical findings are indistinguishable from those seen in lichen planopilaris, frontal fibrosing alopecia is now considered a localized variant of lichen planopilaris. We report four cases of Mexican postmenopausal women with this kind of dermatosis evaluated at the Dermatological Center Dr. Ladislao de la Pascua.

Non-HER2 signaling pathways activated in resistance to anti-HER2 therapy in breast cancer.

HER2 receptor is overexpressed approximately in 20 % of human breast cancer (BC) and is a poor prognostic factor. Although therapies targeting this receptor have improved the prognosis of this cancer, up to 62 % patients treated with these drugs experiment progression during the first year of treatment. Some molecular mechanisms have been proposed to be responsible for this resistance, such as activation of alternative signaling pathways (through ERBB receptors and non-ERBB receptors or increased expression of ligands and alterations in HER2 signaling components). In this article, we will review the influence of genetic markers in non-HER2 signaling pathways investigated to date as cause of resistance to HER2-targeted drugs in HER2-positive BC patients. GRB7, included in the 17q12 amplicon, has been associated to poor prognosis in BC patients. Biomarkers like EPHAR and SRC, have demonstrated clinical relevance and prognostic value in HER2-positive BC patients. Non-invasive biomarkers, such as elevated IGF1 serum levels have been revealed as interesting biomarkers to be considered as predictors of trastuzumab clinical outcomes in BC patients. However, the prognostic value of most of the biomarkers investigated to date, such as HER3, IGF1R, PIK3CA, or AKT1 cannot be fully established yet, since results have not been conclusive.