Genetic Characterization of Extensively Drug-Resistant Shigella sonnei Infections, Spain, 2021-2022.

In 2022, the United Kingdom reported an increase in drug resistance in Shigella sonnei isolates. We report 33 cases in Spain genetically related to the UK cases and 4 cases with similar antimicrobial resistance profiles infected with genetically distant strains. Our results suggest circulation of multiple genetic clusters of multidrug-resistant S. sonnei in Spain.

Prospective comparative multi-centre study on imported Plasmodium ovale wallikeri and Plasmodium ovale curtisi infections.

BACKGROUND: Few previous retrospective studies suggest that Plasmodium ovale wallikeri seems to have a longer latency period and produces deeper thrombocytopaenia than Plasmodium ovale curtisi. Prospective studies were warranted to better assess interspecies differences. METHODS: Patients with imported P. ovale spp. infection diagnosed by thick or thin film, rapid diagnostic test (RDT) or polymerase chain reaction (PCR) were recruited between March 2014 and May 2017. All were confirmed by DNA isolation and classified as P. o. curtisi or P. o. wallikeri using partial sequencing of the ssrRNA gene. Epidemiological, analytical and clinical differences were analysed by statistical methods. RESULTS: A total of 79 samples (35 P. o. curtisi and 44 P. o. wallikeri) were correctly genotyped. Males predominate in wallikeri group (72.7%), whereas were 48.6% in curtisi group. Conversely, 74.3% of curtisi group were from patients of African ethnicity, whilst 52.3% of Caucasians were infected by P. o. wallikeri. After performing a multivariate analysis, more thrombocytopaenic patients (p = 0.022), a lower number of platelets (p = 0.015), a higher INR value (p = 0.041), and shorter latency in Caucasians (p = 0.034) were significantly seen in P. o. wallikeri. RDT sensitivity was 26.1% in P. o. curtisi and 42.4% in P. o. wallikeri. Nearly 20% of both species were diagnosed only by PCR. Total bilirubin over 3 mg/dL was found in three wallikeri cases. Two patients with curtisi infection had haemoglobin under 7 g/dL, one of them also with icterus. A wallikeri patient suffered from haemophagocytosis. Chemoprophylaxis failed in 14.8% and 35% of curtisi and wallikeri patients, respectively. All treated patients with various anti-malarials which included artesunate recovered. Diabetes mellitus was described in 5 patients (6.32%), 4 patients of wallikeri group and 1 curtisi. CONCLUSIONS: Imported P. o. wallikeri infection may be more frequent in males and Caucasians. Malaria caused by P. o. wallikeri produces more thrombocytopaenia, a higher INR and shorter latency in Caucasians and suggests a more pathogenic species. Severe cases can be seen in both species. Chemoprophylaxis seems less effective in P. ovale spp. infection than in P. falciparum, but any anti-malarial drug is effective as initial treatment. Diabetes mellitus could be a risk factor for P. ovale spp. infection.

Epidemiology of Pediatric Uveitis in Argentina.

PURPOSE: To explore the geographic variability of the epidemiology of pediatric uveitis, which, although rare in children, carries a significant risk of morbidity. METHODS: This was a retrospective review conducted at two tertiary referral centers in Buenos Aires, Argentina. Demographic and clinical data of patients younger than 16 years diagnosed as having uveitis between January 1, 2006 and October 1, 2014 were collected. RESULTS: A total of 257 patients (380 eyes) were included in the study. Cases tended to be unilateral (134, 52.1%), granulomatous (146, 56.8%), and localized to the posterior segment (121, 47.1%). Toxoplasmosis was the most common etiology (98, 38.1%). DISCUSSION: The spectrum of pediatric uveitis in Buenos Aires most closely resembles that of Colombia. Understanding these geographic variations is important to aid providers who are caring for children in an increasingly globalized world. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].

Alginate Microsponges as a Scaffold for Delivery of a Therapeutic Peptide against Rheumatoid Arthritis.

The quest for biocompatible drug-delivery devices that could be able to open new administration routes is at the frontier of biomedical research. In this contribution, porous polysaccharide-based microsponges based on crosslinked alginate polymers were developed and characterized by optical spectroscopy and nanoscopic microscopy techniques. We show that macropores with a size distribution ranging from 50 to 120 nm enabled efficient loading and delivery of a therapeutic peptide (CIGB814), presently under a phase 3 clinical trial for the treatment of rheumatoid arthritis. Alginate microsponges showed 80% loading capacity and sustained peptide release over a few hours through a diffusional mechanism favored by partial erosion of the polymer scaffold. The edible and biocompatible nature of alginate polymers open promising perspectives for developing a new generation of polysaccharide-based carriers for the controlled delivery of peptide drugs, exploiting alternative routes with respect to intravenous administration.

Feasibility of an Activity Control System in Patients with Diabetes: A Study Protocol of a Randomised Controlled Trial.

Purpose: Patients with diabetes mellitus have an increased risk of developing various serious health problems that could be life-threatening. These problems are associated with the difficulty of these patients in managing their lifestyle, which may even lead to the abandonment of treatment. The present study was designed to evaluate the feasibility of a multipurpose activity control solution for home activity (home activity control system), which will provide information on the activities of daily living carried out outside in real time, to improve adherence to each of the therapeutic objectives agreed on with the diabetic patient. Patients and Methods: A pilot randomised controlled feasibility study will be carried out to evaluate a home activity control system (Beprevent) in managing patients with type 2 diabetes mellitus. Twenty patients with type 2 diabetes mellitus will be included (10 in the intervention group and 10 in the control group). Data on satisfaction with the tool will be collected from professionals and patients, as well as other clinical/epidemiological data from their digital health records and several questionnaires, at baseline and six months. In addition, data will also be recorded regarding the degree of adherence to the behaviors agreed on with the patients before starting the study to assess changes throughout the study and their relationship with clinical results (glycosylated haemoglobin (HbA1c), cholesterol, etc), and to compare these outcomes between two study groups. Discussion: This project involves the incorporation of telemedicine in the management of patients with diabetes. Thus, according to the currently published bibliography, the use of smart devices in this population could help improve the quality of life of these people, reduce medical visits and improve adherence to home care patterns for diabetes mellitus. There are currently no published clinical trials or protocols that monitor activities of daily living in patients with diabetes individually using artificial intelligence (AI) devices.

CIGB-300, a synthetic peptide-based drug that targets the CK2 phosphoaceptor domain. Translational and clinical research.

CK2 represents an oncology target scientifically validated. However, clinical research with inhibitors of the CK2-mediated phosphorylation event is still insufficient to recognize it as a clinically validated target. CIGB-300, an investigational peptide-based drug that targets the phosphoaceptor site, binds to a CK2 substrate array in vitro but mainly to B23/nucleophosmin in vivo. The CIGB-300 proapoptotic effect is preceded by its nucleolar localization, inhibition of the CK2-mediated phosphorylation on B23/nucleophosmin and nucleolar disassembly. Importantly, CIGB-300 shifted a protein array linked to apoptosis, ribosome biogenesis, cell proliferation, glycolisis, and cell motility in proteomic studies which helped to understand its mechanism of action. In the clinical ground, CIGB-300 has proved to be safe and well tolerated in a First-in-Human trial in women with cervical malignancies who also experienced signs of clinical benefit. In a second Phase 1 clinical trial in women with cervical cancer stage IB2/II, the MTD and DLT have been also identified in the clinical setting. Interestingly, in cervical tumors the B23/nucleophosmin protein levels were significantly reduced after CIGB-300 treatment at the nucleus compartment. In addition, expanded use of CIGB-300 in case studies has evidenced antitumor activity when administered as compassional option. Collectively, our data outline important clues on translational and clinical research from this novel peptide-based drug reinforcing its perspectives to treat cancer and paving the way to validate CK2 as a promising target in oncology.

Effectiveness of Thrombectomy in Stroke According to Baseline Prognostic Factors: Inverse Probability of Treatment Weighting Analysis of a Population-Based Registry.

BACKGROUND AND PURPOSE:  In real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors. METHODS:  Retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score ≤2) and survival at 3 months was studied using inverse probability of treatment weighting (IPTW) analysis in three pre-defined baseline prognostic groups: poor (if pre-stroke disability, age >85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score <6, proximal vertebrobasilar occlusion, supratherapeutic international normalized ratio >3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups' criteria). RESULTS:  Patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3). CONCLUSIONS:  Despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors.

Safety and Therapeutic Profile of a GnRH-Based Vaccine Candidate Directed to Prostate Cancer. A 10-Year Follow-Up of Patients Vaccinated With Heberprovac.

Heberprovac is a GnRH based vaccine candidate containing 2.4 mg of the GnRHm1-TT peptide as the main active principle; 245 µg of the very small size proteoliposomes adjuvant (VSSP); and 350 µL of Montanide ISA 51 VG oil adjuvant. The aim of this study was to assess the safety and tolerance of the Heberprovac in advanced prostate cancer patients as well as its capacity to induce anti-GnRH antibodies, the subsequent effects on serum levels of testosterone and PSA and the patient overall survival. The study included eight patients with histologically-proven advanced prostate cancer with indication for hormonal therapy, who received seven intramuscular immunizations with Heberprovac within 18 weeks. Anti-GnRH antibody titers, testosterone and PSA levels, as well as clinical parameters were recorded and evaluated. The vaccine was well tolerated. Significant reductions in serum levels of testosterone and PSA were seen after four immunizations. Castrate levels of testosterone were observed in all patients at the end of the immunization schedule, which remained at the lowest level for at least 20 months. In a 10-year follow-up three out of six patients who completed the entire trial survived. In contrast only one out eight patients survived in the same period in a matched randomly selected group receiving standard anti-hormonal treatment. Heberprovac vaccination showed a good security profile, as well as immunological, biochemical and, most importantly, clinical benefit. The vaccinated group displayed survival advantage compared with the reference group that received standard treatment. These results warrant further clinical trials with Heberprovac involving a larger cohort.

Adalimumab Treatment in Patients with Vogt-Koyanagi-Harada Disease.

PURPOSE: To evaluate the clinical outcome and safety of adalimumab in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: VKH patients treated with adalimumab seen at the University of Buenos Aires were reviewed. Main outcome measures were visual acuity, anterior segment inflammation, optic nerve inflammation (ONI), steroid sparing effect, number of immunosuppressives, and relapses. RESULTS: In total, 14 VKH patients, mean age 23.07 ± 8 years; median of adalimumab treatment 10 months, were analyzed. At start of adalimumab treatment (baseline), median of corticosteroid dose was 20 mg and at 6 months, 4 mg. At baseline, 11 patients were on immunosuppressive treatment and at 6 months only four continued with immunosuppressive therapy. In the 28 eyes, the median of active inflammation was 2 at baseline and 0 after 6 months on adalimumab. CONCLUSIONS: Treatment with adalimumab is an effective and safe option, reducing the need for oral corticosteroid and conventional immunosuppressive therapy.

Chronic Anterior Uveitis in Children.

PURPOSE: To describe the visual prognosis and remission rate of chronic anterior uveitis in pediatric patients. METHODS: A retrospective case series of children with chronic anterior uveitis treated in the University of Buenos Aires. Juvenile idiopathic arthritis was defined according to the International League of Associations for Rheumatology criteria. Uveitis remission was defined according to SUN criteria. RESULTS: There were 35 pediatric patients (61 eyes), mean age of uveitis onset was 7.69 ± 3 years, 60% were females and 74% had bilateral disease, median follow-up was 60 months (range: 12-192 months). JIA was more frequent in females (80.95 vs 21.43; p<0.0001) and oligoarthritis was the most common form. Remission rate was higher in males (HR = 4.99; 95% CI = 1.16-21.51; p = 0.031). More than 40 eyes remained with the same BCVA at 1 year of follow-up. CONCLUSIONS: Although remission was not common and only occurred after long-term follow-up, visual prognosis was good Received 30 August 2015; revised 6 March 2016; accepted 14 March 2016; published online 18 May 2016.

Síndrome de Moebius. A propósito de un caso / Moebius syndrome. A case report

Desde 1880 Von Graefe y Saemish agruparon algunos pacientes con trastornos congénitos infrecuentes de la región facial y no progresivos, lo cual fue descrito posteriormente por Paul Julius Moebius, en 1888, como síndrome de Moebius, definido como "parálisis congénita de los núcleos de los pares craneales VI, motor ocular externo VII, facial y otros pares craneales como XII, hipogloso, III, motor ocular común, cuyo espectro clínico es variable; afecta a otros pares craneales y se asocia con múltiples malformaciones. Se presentan las características oftalmológicas y clínicas de una paciente a quien se le diagnosticó este síndrome genético. Por ser esta una entidad clínica poco conocida, factor que ha condenado a muchos pacientes a ser tratados como incapacitados mentales, el apoyo social es determinante, tanto para los afectados como para sus familiares.

In 1880 Von Graefe and Saemish grouped some patients with infrequent non progressive congenital disorders in facial region which was later described by Julius Moebius in 1888, as a Moebius syndrome, defined as “congenital paralysis” of the nucleus of the 6th cranial nerves, 7th external motor ocular nerve, facial and other cranial nerves as: 12th, 3rd hypoglossal, common motor ocular which clinical spectrum is variable; other cranial nerves are affected and it is associated with multiple malformations. Clinical and Ophthalmologic characteristics of a female patient who was diagnosed with this genetic syndrome were presented. As this is a very rare condition, many patients were condemned to be treated as mentally handicapped, where social support is indispensable for both patients and families.

Síndrome de los cabellos impeinables, asociación con Pili torti, seudomoniletrix, Pili atroficans y Heterocromía de los cabellos / The uncombable hair syndrome, association with Pili torti, Pseudomonoletrix, Pili atrophicans and hair heterochromy

El síndrome de los cabellos impeinables es un cuadro de rara observación, caracterizado clínicamente por cabellos difíciles de acomodar por el peinado y estructuralmente porque esos cabellos tienen un canal longitudinal (pili canaliculi) bien demostrable en los estudios con microscopía electrónica de barrido. En el presente trabajo se comunican dos observaciones, un caso aislado y otro familiar. El primero asociaba seudomoniletrix y pili torti. El caso familiar, también con pili torti y además heterocromía del cabello e hipotriquia generalizada. Consideramos de interés estas comunicaciones en lo que hace a la casuística nacional, planteando el diagnóstico diferencial con otras alteraciones pilosas, especialmente con el síndrome del cabello lanoso familiar.

Estudio de biodisponibidad de tres formulaciones de difenilhidantoinato sódico / Bioavailability study of 3 formulations of sodium diphenylhydantoinate

Se estudió la biodisponibilidad de tres formulaciones de difenilhidantoinato de sodio en 26 varones voluntarios sanos que recibieron una dosis única de 100 mg por la vía bucal a las 7 a.m. Las formulaciones A y B provenían de proveedores del Instituto Mexicano del Seguro Social, y se obtuvieron de sus Almacenes Centrales. La formulación C o producto innovador se adquirió en una farmacia de venta al público. Como testigo se preparó la formulación D de un estándar conocido, a la misma concentración que las precedentes (100 mg/100 ml de agua). Las formulaciones A y B mostraron un buen porcentaje de disolución (94.89 + ou - 4.07 y 109.20 + ou - 2.98 por ciento respectivamente) y una buena absorción según los resultados de la concentración plasmática máxima (Cmax), el tiempo necesario para alcanzarla (tmax) y el área, bajo la curva de las concentraciones estudiadas, del tiempo 0 a 12 horas (ABC0-12). La formulación C presentó un porcentaje de disolución bajo (24.12 + ou - 3.15 por ciento) y valores inferiores de los otros aspectos estudiados