Review of Drug Storage Conditions, A Case Report.

High temperatures during the summer season are a very important factor to be considered due to their possible influence on drug stability and effectiveness. This is especially important in those patients included in clinical trials, polymedicated or with long-term pharmacological therapies.

Baricitinib or imatinib in hospitalized COVID-19 patients: Results from COVINIB, an exploratory randomized clinical trial.

Baricitinib and imatinib are considered therapies for coronavirus disease 2019 (COVID-19), but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients. Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day-by-day basis to identify differences ≥15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered, all-cause mortality, and safety. One hundred and sixty-five patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend toward better results in patients receiving baricitinib was found compared to standard care alone (hazard ratio [HR] for clinical improvement: 1.41, 95% confidence intervals [CI]: 0.96-2.06; HR for discontinuing oxygen: 1.46, 95% CI: 0.94-2.28). No differences were found regarding additional therapies administered or safety. Baricitinib plus standard care showed better results for hospitalized COVID-19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial.

Adsorption of Heavy Metals Ions from Mining Metallurgical Tailings Leachate Using a Shell-Based Adsorbent: Characterization, Kinetics and Isotherm Studies.

This study defines the optimal parameters that allow the use of waste mollusk shells (WS) to remove heavy metals from three mining and metallurgical leachates. First, the influence of parameters such as pH, contact time, initial metal concentration, adsorbent dose and the presence of co-ions in Cu2+, Cd2+, Zn2+ and Ni2+ adsorption was investigated in synthetic solutions. Metal uptake was found to be dependent on the initial pH of the solution, the removal rate increasing with the increase in pH, showing the highest affinity at pH 5-6. The removal efficiency at lower concentrations was greater than at higher values. The competitive adsorption results on bimetallic solutions showed that the adsorption capacity of the sorbent was restricted by the presence of other ions and suppressed the uptake of heavy metals compared to the single adsorption. Cu2+ was the metal that most inhibited the removal of Cd2+, Zn2+ and Ni2+. The Langmuir isotherm provided the best fit to the experimental data for Cu2+, Cd2+ and Zn2+ and the Freundlich isotherm, for Ni2+. The data showed that the maximum adsorption capacity amax for Zn2+, Cd2+ and Cu2+, was 526.32 mg g-1, 555.56 mg g-1 and 769.23 mg g-1, respectively. Sorption kinetics data best fit the pseudo-second-order kinetic model. The results obtained in the tests with three mining and metallurgical leachates showed that WS were effective in simultaneously removing several heavy metals ions such as Cu, Ni, Zn, Cd, Ni, As and Se.

Músculo esternalis: una variante anatómica a tener en cuenta / The sternalis muscle: An anatomic variant to bear in mind

El músculo esternalis es una variación anatómica poco frecuente que puede llevar a confusión a radiólogos y cirujanos. Este músculo se localiza normalmente superficial al músculo pectoral mayor paralelo al esternón. Presentamos tres casos en los que durante la realización de una mastectomía nos encontramos una estructura cuyas características son compatibles con el músculo esternalis. Este músculo tiene un tamaño variable y la gran mayoría de los casos son asintomáticos. Su inervación procede de intercostales y pectoral. La irrigación viene dada por la arteria mamaria interna.La importancia de conocer la existencia de este músculo viene dada para evitar diagnósticos erróneos en patología mamaria, ya que durante una mamografía de rutina el músculo esternalis puede ser confundido con un tumor. Es importante tener en cuenta esta entidad, pues puede llevar a errores diagnósticos y es preciso conocer su presencia antes de realizar ciertos procedimientos, como cirugías reconstructivas de mama, ya que puede variar el tipo de procedimiento y el resultado final. (AU)

The sternalis muscle is a rare anatomical variant that can cause confusion among radiologists and surgeons. It is usually located superficial to the pectoralis major and parallel to the sternum. We report three cases in which a structure compatible with the sternalis muscle was found during mastectomy. The size of this muscle varies and most cases are asymptomatic. The muscle is innervated from the intercostal and pectoral nerves. Irrigation is from the internal thoracic artery.Familiarity with this muscle is important to avoid mistaken diagnoses in breast disease since the sternalis muscle may mimic a tumour on routine mammography. This entity should be borne in mind as it can lead to diagnostic errors. It is essential to determine its presence before the performance of certain procedures such as reconstructive breast surgery as it may affect the type of procedure performed and the final result. (AU)

Prognostic factors and combined use of tocilizumab and corticosteroids in a Spanish cohort of elderly COVID-19 patients.

Coronavirus disease 2019 (COVID-19) infection in elderly patients is more aggressive and treatments have shown limited efficacy. Our objective is to describe the clinical course and to analyze the prognostic factors associated with a higher risk of mortality of a cohort of patients older than 80 years. In addition, we assess the efficacy of immunosuppressive treatments in this population. We analyzed the data from 163 patients older than 80 years admitted to our institution for COVID-19, during March and April 2020. A Lasso regression model and subsequent multivariate Cox regression were performed to select variables predictive of death. We evaluated the efficacy of immunomodulatory therapy in three cohorts using adjusted survival analysis. The mortality rate was 43%. The mean age was 85.2 years. The disease was considered severe in 76.1% of the cases. Lasso regression and multivariate Cox regression indicated that factors correlated with hospital mortality were: age (hazard ratio [HR] 1.12, 95% confidence interval [CI]: 1.03-1.22), alcohol consumption (HR 3.15, 95% CI: 1.27-7.84), CRP > 10 mg/dL (HR 2.67, 95% CI: 1.36-5.24), and oxygen support with Venturi Mask (HR 6.37, 95% CI: 2.18-18.62) or reservoir (HR 7.87, 95% CI: 3.37-18.38). Previous treatment with antiplatelets was the only protective factor (HR 0.47, 95% CI: 0.23-0.96). In the adjusted treatment efficacy analysis, we found benefit in the combined use of tocilizumab (TCZ) and corticosteroids (CS) (HR 0.09, 95% CI: 0.01-0.74) compared to standard treatment, with no benefit of CS alone (HR 0.95, 95% CI: 0.53-1.71). Hospitalized elderly patients suffer from a severe and often fatal form of COVID-19 disease. In this regard, several parameters might identify high-risk patients upon admission. Combined use of TCZ and CS could improve survival.

Selection of AmpC ß-Lactamase Variants and Metallo-ß-Lactamases Leading to Ceftolozane/Tazobactam and Ceftazidime/Avibactam Resistance during Treatment of MDR/XDR Pseudomonas aeruginosa Infections.

Infections caused by ceftolozane-tazobactam and ceftazidime-avibactam-resistant P. aeruginosa infections are an emerging concern. We aimed to analyze the underlying ceftolozane-tazobactam and ceftazidime-avibactam resistance mechanisms in all multidrug-resistant or extensively drug-resistant (MDR/XDR) P. aeruginosa isolates recovered during 1 year (2020) from patients with a documented P. aeruginosa infection. Fifteen isolates showing ceftolozane-tazobactam and ceftazidime-avibactam resistance were evaluated. Clinical conditions, previous positive cultures, and ß-lactams received in the previous month were reviewed for each patient. MICs were determined by broth microdilution. Multilocus sequence types (MLSTs) and resistance mechanisms were determined using short- and long-read whole-genome sequencing (WGS). The impact of Pseudomonas-derived cephalosporinases (PDCs) on ß-lactam resistance was demonstrated by cloning into an ampC-deficient PAO1 derivative (PAOΔC) and construction of 3D models. Genetic support of acquired ß-lactamases was determined in silico from high-quality hybrid assemblies. In most cases, the isolates were recovered after treatment with ceftolozane-tazobactam or ceftazidime-avibactam. Seven isolates from different sequence types (STs) owed their ß-lactam resistance to chromosomal mutations and all displayed specific substitutions in PDC: Phe121Leu and Gly222Ser, Pro154Leu, Ala201Thr, Gly214Arg, ΔGly203-Glu219, and Glu219Lys. In the other eight isolates, the ST175 clone was overrepresented (6 isolates) and associated with IMP-28 and IMP-13, whereas two ST1284 isolates produced VIM-2. The cloned PDCs conferred enhanced cephalosporin resistance. The 3D PDC models revealed rearrangements affecting residues involved in cephalosporin hydrolysis. Carbapenemases were chromosomal (VIM-2) or plasmid-borne (IMP-28, IMP-13) and associated with class-1 integrons located in Tn402-like transposition modules. Our findings highlighted that cephalosporin/ß-lactamase inhibitors are potential selectors of MDR/XDR P. aeruginosa strains producing PDC variants or metallo-ß-lactamases. Judicious use of these agents is encouraged.

Autoimmune glial fibrillary acidic protein astrocytopathy presented as ataxia, myoclonus and bulbar syndrome: a case report and review of the literature.

OBJECTIVE: To describe an atypical case of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. RESULTS: A patient in his 60s presented with 6 months of progressive ataxia, proximal myoclonus and bulbar symptomatology. Cerebrospinal fluid (CSF) analysis showed monocytic pleocytosis, elevated protein level and elevated adenosine deaminase (ADA) level. CSF microbiological studies were negative and brain and cervical MRI showed no significant findings. We tested for nuclear, cytoplasmatic and synaptic neural autoantibodies as well as anti-GFAP antibodies. While awaiting these results, the patient was commenced on methylprednisolone boluses (1 g/day for 5 days), noting rapid neurological improvement. Eventually, CSF tests were positive for anti-GFAP antibodies. CONCLUSION: We report atypical manifestations of GFAP astrocytopathy. Further research is needed to fully understand the spectrum of neurological manifestations of this autoimmune disease and facilitate timely diagnosis.

Estudio de sensibilidad de Escherichia coli productores de infecciones del tracto urinario comunitarias en Galicia. Período: 2016-2017 / Antimicrobial susceptibility of Escherichia coli producers of community urinary tract infections in Galicia (Spain). Period: 2016-2017

OBJETIVO: Escherichia coli (E. coli) es el responsable de la mayoría de las infecciones del tracto urinario comunitarias. El objetivo del estudio es conocer el espectro de sensibilidad de E. coli en infecciones del tracto urinario para recomendar el tratamiento antibiótico empírico adecuado. DISEÑO: Estudio transversal, multicéntrico, retrospectivo. EMPLAZAMIENTO: Ocho hospitales públicos gallegos, prácticamente toda la población de Galicia (España). PARTICIPANTES: Cuarenta y tres mil ciento treinta y siete pacientes ambulatorios con infección del tracto urinario por E. coli aislados en orina en 2016/2017. MEDICIONES PRINCIPALES: Variables analizadas: demográficas, concentración mínima inhibitoria e interpretación de la sensibilidad según criterios de CLSI y mecanismos de resistencia. Los antibióticos estudiados fueron: ampicilina, amoxicilina-ácido clavulánico, ciprofloxacino, cefotaxima, cefepime, gentamicina, nitrofurantoína, fosfomicina, cotrimoxazol, imipenem y ertapenem. La identificación y sensibilidad se hicieron principalmente por sistemas automatizados. RESULTADOS: Los porcentajes de no sensibilidad de los aislamientos de E. coli fueron: ampicilina 49,2%, amoxicilina-ácido clavulánico 17,8%, cefotaxima 6,7%, cefepime 5,7%, ertapenem 0,04%, imipenem 0,05%, gentamicina 9,1%, ciprofloxacino 26,2%, fosfomicina 3,3%, nitrofurantoína 2,4% y cotrimoxazol 23,9%. Las no sensibilidades fueron superiores en hombres y a medida que aumenta la edad. El 6% fueron productores de betalactamasas de espectro extendido. CONCLUSIONES: El tratamiento empírico en Galicia para cistitis no complicadas producidas por E. coli en mujeres continúa siendo nitrofurantoína y fosfomicina. En hombres menores de 15 años se indica fosfomicina y en hombres mayores de 15 años el tratamiento en nuestro medio debe incluir la realización de cultivo y administrar una cefalosporina de 3.a generación oral empíricamente. No se recomienda cotrimoxazol ni ciprofloxacino como tratamiento empírico por sus altos porcentajes de resistencia

OBJECTIVE: Escherichia coli (E. coli) is responsible for the majority of community urinary tract infections. The objective of the study is to know the sensitivity spectrum of E. coli in urinary tract infections to be able to recommend the appropriate empirical antibiotic treatment. DESIGN: Cross-sectional, multicentric, retrospective study. LOCATION: Galician 8 public hospitals, practically the entire population of Galicia (Spain). PARTICIPANTS: 43,137 outpatients with urinary tract infection due to E. coli isolated in urine in 2016/2017. MAIN MEASUREMENTS: Analyzed variables: demographic, minimum inhibitory concentration and interpretation of sensitivity according to CLSI criteria and resistance mechanisms. The antibiotics studied were: ampicillin, amoxicillin-clavulanic acid, ciprofloxacin, cefotaxime, cefepime, gentamicin, nitrofurantoin, fosfomycin, cotrimoxazole, imipenem and ertapenem. The identification and sensitivity were made mainly by automated methods. RESULTS: The percentages of non-sensitivity of E. coli isolates were: ampicillin 49.2%, amoxicillin-clavulanic acid 17.8%, cefotaxime 6.7%, cefepime 5.7%, ertapenem 0.04%, imipenem 0.05%, gentamicin 9,1%, ciprofloxacin 26.2%, fosfomycin 3.3%, nitrofurantoin 2.4% and cotrimoxazole 23.9%. The non-sensitivities were higher in men and as age increases. Six percent of E. coli were producers of extended-spectrum beta-lactamases. CONCLUSIONS: The empirical treatment in Galicia for uncomplicated cystitis produced by E. coli in women continues to be nitrofurantoin and fosfomycin. In men under 15 years of age, fosfomycin is indicated and in men older than 15 years, treatment in our environment should include culture and administer a 3rd generation oral cephalosporin empirically. Cotrimoxazole and ciprofloxacin are not recommended as empirical treatment because of their high resistance rates

[Antimicrobial susceptibility of Escherichia coli producers of community urinary tract infections in Galicia (Spain). Period: 2016-2017]. / Estudio de sensibilidad de Escherichia coli productores de infecciones del tracto urinario comunitarias en Galicia. Período: 2016-2017.

OBJECTIVE: Escherichia coli (E. coli) is responsible for the majority of community urinary tract infections. The objective of the study is to know the sensitivity spectrum of E. coli in urinary tract infections to be able to recommend the appropriate empirical antibiotic treatment. DESIGN: Cross-sectional, multicentric, retrospective study. LOCATION: Galician 8 public hospitals, practically the entire population of Galicia (Spain). PARTICIPANTS: 43,137 outpatients with urinary tract infection due to E. coli isolated in urine in 2016/2017. MAIN MEASUREMENTS: Analyzed variables: demographic, minimum inhibitory concentration and interpretation of sensitivity according to CLSI criteria and resistance mechanisms. The antibiotics studied were: ampicillin, amoxicillin-clavulanic acid, ciprofloxacin, cefotaxime, cefepime, gentamicin, nitrofurantoin, fosfomycin, cotrimoxazole, imipenem and ertapenem. The identification and sensitivity were made mainly by automated methods. RESULTS: The percentages of non-sensitivity of E. coli isolates were: ampicillin 49.2%, amoxicillin-clavulanic acid 17.8%, cefotaxime 6.7%, cefepime 5.7%, ertapenem 0.04%, imipenem 0.05%, gentamicin 9,1%, ciprofloxacin 26.2%, fosfomycin 3.3%, nitrofurantoin 2.4% and cotrimoxazole 23.9%. The non-sensitivities were higher in men and as age increases. Six percent of E. coli were producers of extended-spectrum beta-lactamases. CONCLUSIONS: The empirical treatment in Galicia for uncomplicated cystitis produced by E. coli in women continues to be nitrofurantoin and fosfomycin. In men under 15 years of age, fosfomycin is indicated and in men older than 15 years, treatment in our environment should include culture and administer a 3rd generation oral cephalosporin empirically. Cotrimoxazole and ciprofloxacin are not recommended as empirical treatment because of their high resistance rates.

Transcutaneous Supraorbital Stimulation as a Preventive Treatment for Chronic Migraine: A Prospective, Open-Label Study.

BACKGROUND AND OBJECTIVE: Successful preventive treatment in chronic migraine (CM) remains an unmet need in some cases, and new therapeutic strategies are emerging. We aimed to test the effect of noninvasive, transcutaneous supraorbital nerve stimulation (tSNS) in a group of patients with CM. PATIENTS AND METHODS: This was an open label, quasi-experimental design. Twenty-five CM patients were recruited from two hospital headache clinics. After a one-month baseline period, monthly visits were scheduled during three months. Headache occurrence, its intensity, and symptomatic medication intake were recorded through a diary kept by each patient. Both a per-protocol analysis and an intention-to-treat analysis were performed for the main outcome measures. RESULTS: Twenty-one and 24 patients were included in the per-protocol and the intention-to-treat analyses, respectively. In the per-protocol analysis, a significant four-day decrease in the mean monthly days with moderate or severe headache was observed from baseline to the end of the study (t test, P = 0.0163), and there was a nonsignificant reduction of 2.95 in the mean monthly total headache days. In the intention-to-treat analysis, a nonsignificant 3.37 reduction in the mean monthly days with moderate or severe headache was observed for the same period, and there was a significant 2.75 reduction in the mean monthly days with any headache (t test, P = 0.016). CONCLUSIONS: tSNS could hold preventive properties in the treatment of CM, but the effect may be either mild or controversial. Double blind, sham-controlled studies are essential to confirm these findings and to outline their clinical relevance in the CM therapeutic scenario.