Economic impact of immunoglobulin replacement therapy in secondary immunodeficiency to hematological cancer: a single center observational study.

This is the first report of the health economic benefits derived from preventing infections through Immunoglobulin Replacement Therapy (IgRT) in patients with secondary immunodeficiency due to hematological malignancies. We conducted a retrospective population-based cohort study using patient medical history and pharmacy data from the Hospital Clínico San Carlos for 21 patients between 2011 and 2020. The pharmacoeconomic impact of using prophylactic IgRT was assessed by comparing characteristics of the SID patients 1 year before and after initiating IgRT measured by direct medical and tangible indirect costs. Results indicate a marked reduction in hospitalization days following IgRT initiation, decreasing from an average of 13.9 to 6.1 days per patient, with the elimination of ICU admissions. While emergency department visits decreased significantly, the number of routine consultations remained unchanged. Notably, absenteeism from work dropped substantially. The financial analysis revealed significant reductions in medication use and fewer ancillary tests, resulting in considerable cost savings. Specifically, total expenditure dropped from €405,088.18 pre-IgRT to €295,804.42 post-IgRT-including the cost of IgRT itself at €156,309.60. Overall, the annual savings amounted to €109,283.84, validating the cost-effectiveness of IgRT in managing SID in patients with hematological cancers.

An Exploratory Approach of Clinically Useful Biomarkers of Cvid by Logistic Regression.

Despite advancements in genetic and functional studies, the timely diagnosis of common variable immunodeficiency (CVID) remains a significant challenge. This exploratory study was designed to assess the diagnostic performance of a novel panel of biomarkers for CVID, incorporating the sum of κ+λ light chains, soluble B-cell maturation antigen (sBCMA) levels, switched memory B cells (smB) and the VISUAL score. Comparative analyses utilizing logistic regression were performed against established gold-standard tests, specifically antibody responses. Our research encompassed 88 subjects, comprising 27 CVID, 23 selective IgA deficiency (SIgAD), 20 secondary immunodeficiency (SID) patients and 18 healthy controls. We established the diagnostic accuracy of sBCMA and the sum κ+λ, achieving sensitivity (Se) and specificity (Spe) of 89% and 89%, and 90% and 99%, respectively. Importantly, sBCMA showed strong correlations with all evaluated biomarkers (sum κ+λ, smB cell and VISUAL), whereas the sum κ+λ was uniquely independent from smB cells or VISUAL, suggesting its additional diagnostic value. Through a multivariate tree decision model, specific antibody responses and the sum κ+λ emerged as independent, signature biomarkers for CVID, with the model showcasing an area under the curve (AUC) of 0.946, Se 0.85, and Spe 0.95. This tree-decision model promises to enhance diagnostic efficiency for CVID, underscoring the sum κ+λ as a superior CVID classifier and potential diagnostic criterion within the panel.

Clinical manifestations and approach to the management of patients with common variable immunodeficiency and liver disease.

Purpose: The clinical spectrum of common variable immunodeficiency (CVID) includes predisposition to infections, autoimmune/inflammatory complications and malignancy. Liver disease is developed by a proportion of patients with CVID, but limited evidence is available about its prevalence, pathogenesis and prognostic outcome. This lack of evidence leads to the absence of guidelines in clinical practice. In this study, we aimed at defining the characteristics, course and management of this CVID complication in Spain. Methods: Spanish reference centers were invited to complete a cross-sectional survey. Thirty-eight patients with CVID-related liver disease from different hospitals were evaluated by a retrospective clinical course review. Results: In this cohort, abnormal liver function and thrombocytopenia were found in most of the patients (95% and 79% respectively), in keeping with the higher incidence of abnormal liver imaging and splenomegaly. The most common histological findings included nodular regenerative hyperplasia (NRH) and lymphocytic infiltration, which have been associated with portal hypertension (PHTN) leading to a poorer prognosis. Autoimmune/inflammatory complications occurred in 82% of the CVID patients that developed liver disease and 52% of the patients treated with immunomodulators showed a reduction in the liver function tests' abnormalities during treatment. Among the experts that conducted the survey, there was 80% or more consensus that the workup of CVID-related liver disease requires liver profile, abdominal ultrasound and transient elastography. The majority agreed that liver biopsy should be essential for diagnosis. There was 94% consensus that endoscopic studies should be performed in the presence of PHTN. However, there was 89% consensus that there is insufficient evidence on the management of these patients. Conclusion: Liver disease varies in severity and may contribute substantially to morbidity and mortality in patients with CVID. Hence the importance of close follow-up and screening of this CVID complication to prompt early targeted intervention. Further research is needed to evaluate the pathophysiology of liver disease in patients with CVID to identify personalized treatment options. This study emphasizes the urgent need to develop international guidelines for the diagnosis and management of this CVID complication.

Association of anti-SARS-COV-2 vaccine with increased incidence of myositis-related anti-RNA-synthetases auto-antibodies.

Introduction: SARS-CoV-2 is a RNA virus that associates with heterogeneous clinical manifestations and complications. Auto-antibodies are identified in approximately 50% of hospitalized COVID-19 patients. Objectives: To determine the global incidence of myositis-related auto-antibodies (non Jo1-RNA synthetases: anti-PL7, anti-PL12, anti-EJ, anti-OJ and RNA-sensor: anti-MDA5) in our laboratory during COVID-19 pandemics, and to describe the clinical and laboratory features of these patients. Study design: A retrospective study was performed from 2015 to 2021 in a cohort of 444 patients with suspected inflammatory myopathy. The incidence of positive results for the MSA was expressed as absolute value per year for the reference population. Immunoblot analysis, indirect immunofluorescence and HLA typing of 36 patients with positivity for MSAs were collected and analyzed. Results: We observed MSA positive in 28 patients in 2020 and 36 patients in 2021, representing a mean increase of 6-fold respect to previous years since 2015 (range, 0 to 19). In 2020, the most common antibody detected was anti-MDA5 (68%). In contrast, in 2021 the most common antibodies were anti-PL7 and/or anti-PL12 (69%). All patients in 2021 with positive anti-synthetases were fully vaccinated, 4 had previous documented infection, with median time from vaccine to MSA positivity of 5 months. Eight out of 36 patients (22%) reported clinical onset after SARS-CoV-2 vaccination and 6 out of 36 (17%) presented clinical and/or radiological worsening after SARS-CoV-2 vaccination. All patients presented with a known human leukocyte antigen (HLA)-DRB1* allele associated with ASS. The most prevalent alleles identified were DRB1*03:01, DRB1*04, DRB1*11:01, corresponding to 70% (16/23) of our cohort. Conclusions: Our preliminary data show an increased incidence of anti-synthetase antibodies during COVID-19 pandemic and SARS-CoV-2 vaccination associated to HLA DRB1* risk allele. Differential profiles of MSA specificities were observed: mainly against RNA-sensors in 2020 and against RNA-synthetases in 2021. Further studies are needed to support the association between SARS-CoV-2 infection and/or vaccination and the occurrence of this autoimmune syndrome.

Insights into the Complexity of a Dormant Mycobacterium tuberculosis Cluster Once Transmission Is Resumed.

Genotyping tools help identify the complexity in Mycobacterium tuberculosis transmission clusters. We carried out a thorough analysis of the epidemiological and bacteriological complexity of a cluster in Almería, Spain. The cluster, initially associated with Moroccan migrants and with no secondary cases identified in 4 years, then reappeared in Spanish-born individuals. In one case, two Mycobacterium tuberculosis clonal variants were identified. We reanalyzed the cluster, supported by the characterization of multiple cultured isolates and respiratory specimens, whole-genome sequencing, and epidemiological case interviews. Our findings showed that the cluster, which was initially thought to have restarted activity with just a single case harboring a small degree of within-host diversity, was in fact currently growing due to coincidental reactivation of past exposures, with clonal diversity transmitted throughout the cluster. In one case, within-host diversity was amplified, probably due to prolonged diagnostic delay. IMPORTANCE The precise study of the dynamics of tuberculosis transmission in socio-epidemiologically complex scenarios may require more thorough analysis than the standard molecular epidemiology strategies. Our study illustrates the epidemiological and bacteriological complexity present in a transmission cluster in a challenging epidemiological setting with a high proportion of migrant cases. The combination of whole-genome sequencing, refined and refocused epidemiological interviews, and in-depth analysis of the bacterial composition of sputa and cultured isolates was crucial in order to correctly reinterpret the true nature of this cluster. Our global approach allowed us to reinterpret correctly the unnoticed epidemiological and bacteriological complexity involved in the Mycobacterium tuberculosis transmission event under study, which had been overlooked by the usual molecular epidemiology approaches.

Flexible graphene photodetectors for wearable fitness monitoring.

Wearable health and wellness trackers based on optical detection are promising candidates for public health uses due to their noninvasive tracking of vital health signs. However, so far, the use of rigid technologies hindered the ultimate performance and form factor of the wearable. Here, we demonstrate a new class of flexible and transparent wearables based on graphene sensitized with semiconducting quantum dots (GQD). We show several prototype wearable devices that are able to monitor vital health signs noninvasively, including heart rate, arterial oxygen saturation (SpO2), and respiratory rate. Operation with ambient light is demonstrated, offering low-power consumption. Moreover, using heterogeneous integration of a flexible ultraviolet (UV)-sensitive photodetector with a near-field communication circuit board allows wireless communication and power transfer between the photodetectors and a smartphone, offering battery-free operation. This technology paves the way toward seamlessly integrated wearables, and empowers the user through wireless probing of the UV index.

Label-free electrochemical DNA sensor using "click"-functionalized PEDOT electrodes.

Here we describe a label-free electrochemical DNA sensor based on poly(3,4-ethylenedioxythiophene)-modified (PEDOT-modified) electrodes. An acetylene-terminated DNA probe, complementary to a specific "Hepatitis C" virus sequence, was immobilized onto azido-derivatized conducting PEDOT electrodes using "click" chemistry. DNA hybridization was then detected by differential pulse voltammetry, evaluating the changes in the electrochemical properties of the polymer produced by the recognition event. A limit of detection of 0.13 nM was achieved using this highly selective PEDOT-based genosensor, without the need for labeling techniques or microelectrode fabrication processes. These results are promising for the development of label-free and reagentless DNA hybridization sensors based on conducting polymeric substrates. Biosensors can be easily prepared using any DNA sequence containing an alkyne moiety. The data presented here reveal the potential of this DNA sensor for diagnostic applications in the screening of diseases, such as "Hepatitis C", and genetic mutations.

Nanoprobes for enhanced electrochemical DNA sensors.

Biosensors, small devices enabling selective bioanalysis because of properly assembled biological recognition molecules, represent the fortuitous results of years of interdisciplinary and complementary investigations in different fields of science. The ultimate role of a biosensor is to provide coupling between the recognition element and the analyte of interest, bringing a quantitative value of its concentrations into a complex sample matrix. They offer many advantages. Among them, portability, low cost with fast response times, and the possibility to operate in situ without the need for sample preparation are certainly the most important. Among biosensors, a large space is occupied by DNA biosensors. Screening genomic DNA is of fundamental importance for the development of new tools available to physicians during the clinical process. Sequencing of individual human genomes, accomplished principally by microarrays with optical detection, is complex and expensive for current clinical protocols. Efforts in research are focused on simplifying and reducing the cost of DNA biosensors. For this purpose, other transduction techniques are under study to make more portable and affordable DNA biosensors. Compared with traditional optical detection tools, electrochemical methods allow the same sensitivity and specificity but are less expensive and less labor intensive. Scalability of electrochemical devices makes it possible to use the advantages introduced by nanosized components. The involvement of nanomaterials and nanostructures with custom-tailored shapes and properties is expected to rapidly boost the field of electrochemical DNA biosensors and, in general, that of next-generation sequencing technologies.

[Penoscrotal aggressive angiomyxoma]. / Angiomixoma agresivo penoescrotal.

Aggressive angiomyxoma denotes an extremely infrequent mesenchymal tumour. In virtually every case it involves genital, pelvic or perineal female structures. Cases involving male patients are extremely rare. It is a distinctive tumour with a characteristic clinical course and specific and well characterized microscopic features. The authors report an additional clinical case in a young male patient with massive scrotal and penile involvement, necessitating exeresis followed by complex reconstructive procedure implying flap and graft use. A review of the available literature concerning etiopathogenic, clinical, imagiologic, histological and differential diagnosis, therapeutic and prognostic aspects is also presented.

[Primary mucinous adenocarcinoma of the renal pelvis--adicional case report]. / Adenocarcinoma mucinoso primário de pélvis renal--caso adicional.

Mucinous adenocarcinoma of the renal pelvis may be classified as among the rarest neoplasms of the genitourinary tract. Until the present moment just a few dozen cases have been reported previously. Despite the known association with chronic inflammatory conditions of the upper urinary tract, the exact pathogenesis remains unknown. The authors report an adicional clinical case with particular aspects in what concerns differential diagnosis. A review of the available literature concerning clinical, imagiologic, therapeutic and prognostic aspects is also presented.

Angiomixoma agresivo penoescrotal / Penoscrotal agressive angiomyxoma

Angiomixoma agresivo designa una neoplasia mesenquimatosa extremadamente rara. Afecta casi exclusivamente estructuras genitales, pélvicas o perineales de pacientes de sexo femenino, siendo muy raros los casos que envuelven el sexo masculino. Se trata de neo formaciones bien caracterizadas desde el punto de vista histológico y de comportamiento benigno. Los autores presentan un caso clínico de un tumor de este tipo en un adulto joven de sexo masculino con envolvimiento penoescrotalde grandes dimensiones implicando exéresis y reconstrucción compleja, con recurso a colgajos e injertos cutáneos. Es igualmente realizada una revisión bibliográfica exhaustiva sobre el tema englobando aspectos etiopatogénicos, clínicos, de imagen, anatomo-patológicos y de diagnóstico diferencial, así como terapéuticos y de pronóstico (AU)

Aggressive angiomyxoma denotes an extremely infrequent mesenchymal tumour. In virtually every case it involves genital, pelvic or perineal female structures. Cases involving male patients are extremely rare. It is a distinctive tumour with a characteristic clinical course and specific and well characterized microscopic features. The authors report an additional clinical case in a young male patient with massive scrotal and penile involvement, necessitating exeresis followed by complex reconstructive procedure implying flap and graft use. A review of the available literature concerning etiopathogenic, clinical, imagiologic, histological and differential diagnosis, therapeutic and prognostic aspects is also presented (AU)

Adenocarcinoma mucinoso primário de pélvis renal-caso adicional / Primary mucinous adenocarcinoma of the renal pelvis–adicional case report

Los adenocarcinomas mucinosos de la pelvis renal se encuentran entre las neoplasias genitourinarias más raras, encontrándose descritas apenas algunas decenas de casos hasta el presente momento. Aunque esten asociados a alteraciones inflamatorias crónicas persistentes del aparato escretor alto, la etiopatogenia subyacente exacta permanece por esclarecer. Los autores presentan un caso adicional de este tipo de tumores, revestido de aspectos de diagnóstico diferencial particulares, así como una revisión de los aspectos clínicos, de imagen, terapeúticos y pronósticos (AU)

Mucinous adenocarcinoma of the renal pelvis may be classified as among the rarest neoplasms of the genitourinary tract. Until the present moment just a few dozen cases have been reported previously. Despite the known association with chronic inflamatory conditions of the upper urinary tract, the exact pathogenesis remains unknown. The authors report an adicional clinical case with particular aspects in what concerns diferencial diagnosis. A review of the available literature concerning clinical, imagiologic, therapeutic and prognostic aspects is also presented (AU)

Carcinoma de bajo grado de conductos colectores / Low grade collecting duct carcinoma

El carcinoma de los conductos colectores (CCC) es una entidad poco frecuente que representa menos del 1 por ciento del total de las neoplasias renales. La mayoría de los casos publicados han sido descritos como tumores de gran agresividad y de mal pronóstico. Presentamos un caso de un CCC de bajo grado y de pronóstico favorable al que se le realizó una nefrectomía radical sin evidencia de recidiva tumoral tras dos años de seguimiento (AU)

Consulta de indicación farmacéutica en una farmacia comunitaria / Responding to symptoms in community pharmacy

Objetivos: Estudiar las características de las consultas de indicación farmacéutica desde una farmacia comunitaria. Diseño: Estudio observacional transversal. Emplazamiento: Farmacia comunitaria de Madrid. Muestra: Durante dos años, se registraron todas las consultas de indicación que tuvo el farmacéutico. El total de consultas fue de 556. Esto representó 718 problemas de salud consultados. Mediciones y resultados: En el 71,4% de las consultas fue el propio paciente el que consultó directamente. El 62% de los pacientes pertenecían al sexo femenino, estando comprendidos entre os 13 y los 50 años el 62,6% de los pacientes. Los problemas de salud más consultados fueron: tracto respiratorio (42,5%), dolores (10,6%), tracto gastrointestinal (9,2%), problemas oculares (7,2%). El resultado de las consultas fue que en un 85,4% (con respecto al total de consultas) se recomienda un tratamiento farmacológico. Otro resultado de las consultas fue derivar el paciente al médico. Así, en un 9,71% se derivó al paciente al médico directamente sin recomendarle ningún tratamiento; en un 10,25%, se derivó al médico, pero recomendándole un tratamiento y en un 15,28% se realizaron derivaciones condicionadas. En total en el 15% aproximadamente no se recomendó ningún medicamento, con un 4,85% de las consultas que además no se derivan al médico ni se recomienda ningún tratamiento. Conclusiones: La mayoría de las consultas al farmacéutico se engloban dentro del resfriado. El 10% de las consultas son derivadas al médico y en un 15% no se recomienda ningún medicamento, lo que indica que la retribución del farmacéutico basada exclusivamente en un margen comercial del medicamento podría no ser la más adecuada (AU)

Objectives: To study the features of the responding to symptoms consultations in a Community Pharmacy. Design: Cross sectional study. Setting: Community pharmacy. Data sources: All consultations were recorded during two years. The number of consultations were 556 and 718 the health problem consulted. Measurements and main results: The patient consult for himself on 71,4% occasions. 62% of the patients were female and 62,6% were between 13 and 50 years old. The majority of health problems consulted to pharmacist were respiratory problems (42,5 %), pain (10,6%), gastrointestinal problems (9,2%) and eyes problems (22%). In 9,71% of the total of the consultations, the patients were referred to the physician without recommending any medicine; 10,25% were derived to the doctor but were recommended a medicine and 15,28% were conditional derived. In 15% of the pharmacist consultations did not recommend any medicine with 4,85% of the consultations neither deriving nor selling a medicine. Conclusions: The health problem most consulted was influenza. 10% of the consultations were derived to the doctor and in nearly 15% no drug was recommended. This could mean that the retribution of the pharmacists based only on the drug price may be no longer the most appropriate system (AU)