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Introduction: Clinical trials that involve medicines are performed in order to determine their effectiveness and safety. In Argentina, these studies are presented either to National Administration of Drugs, Food and Medical Technology (ANMAT) to obtain drug registration, or to the National Ministry of Health (MSAL) (to obtain the official recognition). This work was carried out to increase the knowledge about the clinical trials performed in Argentina., Materials and Methods: The MSAL/ANMAT databases were explored. The variables were: dates of request, institution, phase of the study, enrollment modality, product investigated, therapeutic group, comparator, pathology involved, and location of laboratory performance., Results: A total of 201 protocols were detected in the period of study, all of them performed with registration purposes. Twenty pharmaceutical companies carried out 60% of the studies (17 with foreign capital). Seventy percent were phase III (90% multicenter protocols). Three out of 4 trials corresponded to the oncology / immunosuppressant therapeutical group. In 65% the comparator used was placebo. A 71% of the studies were carried out in health institutions of Buenos Aires City. Ninety-eight per cent of laboratory controls were carried out abroad., Discussion: Foreign pharmaceutical companies are the only ones that carry out clinical trials on medicines in Argentina, all of them for registration purposes. The use of placebo as a comparator is inappropriate, since each drug is expected to be validated against another of recognized efficacy already available in the market. Oncological/immunological pathologies are the ones that arouse greater interest among local researchers due to their prevalence and their greater profitability in the pharmaceutical market.

Introduction: Knowing the characteristics of the pharmaceutical market allows obtaining sensitive information to understand the supply, demand and access of the population to medicines. In order to provide primary data regarding the marketing of drugs in Argentina, the following research was performed., Method: This is a cross-sectional quantitative-qualitative descriptive study of the Argentine pharmaceutical market, taking into account 30 years of official information provided by the National Regulatory Agency (ANMAT)., Results: Two hundred and sixteen laboratories (182 national) drug producers / importers, 53 distributors and 479 drugstores (wholesale drug distribution establishments) were identified. A high concentration of marketing was detected, grouping 90% in only 5 intermediaries. There are currently 6670 products/certificates in the country, an amount that fluctuated over the last 30 years. Six laboratories are owners of between 116 and 208 certificates; 84% of these products come from national laboratories, 5002 are mono-drugs, while 83% are marketed under a fancy name. The three main indications for which the registration of drugs in Argentina is intended are diseases of digestive system, nervous system and infectious diseases; 58% of the marketed products consist of oral formulations., Discussion: Based on data provided by this study, it is possible to assert that the Argentinian pharmaceutical market has a majority share of national capital, with a great concentration in a few pharmaceutical companies and distributors. The products are mostly available as non-combined drugs, in their oral form, and available by their brand names.

Background: Irrational use of antimicrobials (ATMs) triggers microbial resistance (AMR) which has severe consequences for human health. ATM consumption varies among countries and within each territory. These data should be known, in order to perform local policies towards AMR reduction. This work aimed to expose the association of the level of consumption of carbapenems and fluoroquinolones with their resistance rates in Pseudomonas aeruginosa in Argentina., Method: Consumption of antimicrobials was expressed by defined daily dose (DDD)/1000 inhabitants for each ATM during one year period, discriminating by each country region. Resistance of P. aeruginosa to carbapenems/fluoroquinolones groups was recorded. Consumption/resistance ratio "R" was calculated for each region of the country, comparing results with other countries., Results: P . aeruginosa resistance rate to fluoroquinolone (F) was 26.4% in blood samples and 29.7% in urine samples, whereas resistance rates to carbapenems (C) were 19.9 and 17.7% in blood and urine, respectively. Correlation between consumption and resistance was demonstrated for both antimicrobials (C :  R  = 0.58; p =0.003 and F :  R  = 0.77; p =0.0001). Great fluctuations of resistance levels were seen among regions within the country, always correlating resistance with areas in which a higher level of ATM consumption was detected., Conclusion: P. aeruginosa resistance to fluoroquinolone/carbapenems in Argentina directly correlated with antimicrobial consumption levels. A great heterogeneity in resistance profile was observed among areas where ATMs were widely used. Global data at the national level might mask local realities that require specific health policies in order to control the irrational use of ATMs., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Silvia Boni et al.)

Objective: To describe bacterial resistance and antimicrobial consumption ratio at the subnational level in Argentina during 2018, considering beta-lactams group as a case-study., Methods: Antimicrobial consumption was expressed as defined daily doses (DDD)/1000 inhabitants. Resistance of Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus to beta-lactams was recorded. Resistance/consumption ratio was estimated calculating "R" for each region of Argentina, and this data was compared with other countries., Results: The most widely consumed beta-lactams in Argentina were amoxicillin (3.64) for the penicillin sub-group, cephalexin (0.786) for first generation cephalosporins, cefuroxime (0.022) for second generation; cefixime (0.043) for third generation and cefepime (0.0001) for the fourth generation group. Comparison between beta-lactams consumption and bacterial resistance demonstrated great disparities between the six regions of the country., Conclusions: The case-study of Argentina shows that antimicrobial consumption and resistance of the most common pathogens differed among regions, reflecting different realities within the same country. Because this situation might also be occurring in other countries, this data should be taken into account to target local efforts towards better antimicrobial use, to improve antimicrobial stewardship programs and to propose more suitable sales strategies in order to prevent and control antimicrobial resistance.

Background: The malignant mechanisms that control the development of cutaneous T-cell lymphoma (CTCL) are beginning to be identified. Recent evidence suggests that disturbances in specific intracellular signalling pathways, such as RAS-mitogen-activated protein kinase, T-cell receptor (TCR)-phospholipase C gamma 1 (PLCG1)-nuclear factor of activated T cells (NFAT) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT), may play an essential role in the pathogenesis of CTCL., Objectives: To investigate the mechanisms controlling disease development and progression in mycosis fungoides (MF), the most common form of CTCL., Methods: We collected 100 samples that were submitted for diagnosis of, or a second opinion regarding, MF between 2001 and 2018, 80% of which were in the early clinical stages of the disease. Formalin-fixed paraffin-embedded tissues were used for histological review and to measure the expression by immunohistochemistry of surrogate markers of activation of the TCR-PLCG1-NFAT, JAK-STAT and NF-κB pathways. Folliculotropism and large-cell transformation were also examined., Results: NFAT and nuclear factor kappa B (NF-κB) markers showed a comparable activation status in early and advanced stages, while STAT3 activation was more frequent in advanced stages and was associated with large-cell transformation. Consistently with this observation, STAT3 activation occurred in parallel with MF progression in two initially MF-negative cases. A significant association of NFAT with NF-κB markers was also found, reflecting a common mechanism of activation in the two pathways. Genomic studies identified nine mutations in seven genes known to play a potential role in tumorigenesis in T-cell leukaemia/lymphoma, including PLCG1, JAK3 and STAT3, which underlies the activation of these key cell-survival pathways. A higher mutational allele frequency was detected in advanced stages., Conclusions: Our results show that STAT3 is activated in advanced cases and is associated with large-cell transformation, while the activation of NFAT and NF-κB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. What's already known about this topic? Mycosis fungoides is characterized by a clonal expansion of T cells in the skin. The mechanisms controlling disease development and progression are not fully understood. What does this study add? An association of the nuclear factor of activated T cells and nuclear factor kappa B pathways was found, which could reflect a common mechanism of activation. These pathways were activated in early and advanced stages at the same level. Signal transducer and activator of transcription 3 activation was associated with large-cell transformation and was more frequent in advanced stages. A genomic analysis of cutaneous T-cell lymphoma-associated genes was performed. Nine mutations were detected. What is the translational message? These results could have important implications for the treatment of MF in the near future., (© 2019 British Association of Dermatologists.)

Objective: To assess the value of fine needle aspiration cytology (FNAC) in the diagnosis of pleomorphic adenoma and to determine the cytologic variations responsible for diagnostic errors., Study Design: We retrospectively studied 212 cases cytologically diagnosed as pleomorphic adenoma. In 184 a histologic diagnosis was available. Fourteen cases of histologically proven pleomorphic adenomas with a previously erroneous cytologic diagnosis were also reviewed. This study was based on those cases with a histologic diagnosis., Results: The sensitivity and specificity of the cytologic diagnosis of pleomorphic adenoma in our series were 92.6% and 98.4%, respectively. In relation to malignancy, the series showed six false negative and three false positive diagnoses. In those cases correctly diagnosed on aspiration (175), a typical cytologic appearance, with no diagnostic difficulties, was observed in 118 cases (67.4%); the remainder showed cytologic variations. Cellular atypia (20.6%), cystic transformation (7%) and the presence of a cylindromatous pattern (5%) resembling adenoid cystic carcinoma were the most common cytologic variations observed and responsible for the majority of the errors., Conclusion: The cytologic variations in FNAC of pleomorphic adenoma must be considered in order to avoid important errors in the preoperative management of and surgical approach to salivary gland lesions.

The immunohistochemical expression of E-cadherin (E-CD) was correlated to differentiation grade, tumor size, axillary lymph node metastasis, hormone receptor status and disease outcome in 230 infiltrating ductal breast carcinomas. E-CD expression was reduced in 116 tumors (50.4%). Reduced E-CD expression was more frequently found in high histological grade and progesterone receptor negative tumors. In contrast, preserved E-CD expression was more frequently observed in tumors with axillary lymph node metastasis, particularly in the group of patients with 1 to 3 positive lymph nodes. A weak association between reduced E-CD expression and shortened overall survival was found in univariate survival analysis, that was lost when the patients were adjusted for other pathological factors in multivariate analysis. These data indicate that E-CD may be considered a differentiation marker in ductal carcinomas of non special type. However, the relationship between E-CD expression and lymph node metastasis and disease outcome remains to be established.

We report a solitary fibrous tumor of the abdominal cavityt that presented as a encapsulated mass attached to the mesentery in a 33-yr-old man. Histologically, the lesion showed a disorganized arrangement of spindle cells in a collagenous background and prominent vascular channels of varying size. Tumor cells showed immunohistochemical reactivity for vimentin only. Cytokeratins and CD34 were negative. This report further extends the anatomic range of solitary fibrous tumor, a neoplasm that must be included in the differential diagnosis of well-defined abdominal masses. The behavior of this mesenteric solitary fibrous tumor has been benign.

Meconium ileus is the earliest clinical manifestation of cystic fibrosis. We report 22 neonates with meconium ileus who had clinical evidence of cystic fibrosis. Patients were categorized as simple with inspissated meconium in the ileum with dilated loops proximally or complicated with volvulus or atresia and/or a perforation resulting in meconium peritonitis. Histopathology of the surgically resected specimens of small bowel revealed lesions typical of cystic fibrosis. Genetic studies were performed on all subjects, this study analyzes the usefulness in the detection of delta F508 mutation in formalin-fixed paraffin-embedded tissues obtained from patients with meconium ileus, ten of whom had the delta F508/delta F508 mutation.

A recent in vitro study has suggested that overexpression of ERBB2 may mediate breast tumour progression and metastasis by inhibiting the transcription of the E-cadherin (E-CD) gene. To test this hypothesis in human breast cancer in vivo, we studied the relationship between the expression of both molecules in 247 breast carcinomas immunohistochemically. Five ductal carcinomas in situ overexpressed ERBB2 and showed preserved E-CD expression. Forty-four of 226 infiltrating ductal carcinomas (19.47%) showed ERBB2 overexpression, and a statistically significant relationship was found between ERBB2 overexpression and high histological grade. E-CD expression was preserved in 111 cases (49.1%) and correlated with the histological grade. However, no significant relationship was found between ERBB2 and E-CD expression. None of the 16 infiltrating lobular carcinomas expressed ERBB2 or E-CD. These observations in different histological types of breast carcinoma strongly argue against a role for ERBB2 as a transcriptional regulator of E-CD expression in most human breast carcinomas in vivo.

This study analyzes the usefulness of the polymerase chain reaction technique in the detection of delta F508 mutation in 11- to 25-yr-old formalin-fixed paraffin-embedded tissues obtained from the autopsy of 38 cystic fibrosis patients (nine with meconium ileus). Two different pairs of oligonucleotide primers were used: C16 B/C16 D that amplify 98 and/or 95 bp and FQ1/FQ2 that amplify 50 and/or 47 bp. After two independent rounds of polymerase chain reactions with the two sets of primers, amplification products were obtained in 67.5% of the cases when using C16 B/C16 D primers and in all cases when using FQ1/FQ2 primers. Fifty percent of the chromosomes analyzed in the 29 patients without meconium ileus had the delta F508 mutation, which was present in 13 heterozygous and 8 homozygous patients. The remaining eight cystic fibrosis patients did not carry that mutation. These results are similar to those reported in cystic fibrosis patients from Spain. In the meconium ileus group, we found a higher than expected proportion of delta F508 mutation; all patients showed the delta F508 mutation in at least one chromosome, seven patients (77.8%) being homozygous and two (22.2%) heterozygous. Present results indicate that delta F508 mutation can be detected by polymerase chain reaction in old paraffin-embedded tissues when appropriate primers are used.(ABSTRACT TRUNCATED AT 250 WORDS)