Differential presentation of hypersensitivity reactions to carboplatin and oxaliplatin: Phenotypes, endotypes, and management with desensitization.

BACKGROUND: Drug hypersensitivity reactions (DHRs) to platinum-based drugs are heterogenous and restrict their access, and drug desensitization (DD) has provided a ground-breaking procedure for their re-introduction, although the response is heterogeneous. We aimed to identify the phenotypes, endotypes, and biomarkers of reactions to carboplatin and oxaliplatin and their response to DD. METHODS: Seventy-nine patients presenting with DHRs to oxaliplatin (N = 46) and carboplatin (N = 33) were evaluated at the Allergy Departments of two tertiary care hospitals in Spain. Patient symptoms, skin testing, biomarkers, and outcomes of 267 DDs were retrospectively analyzed. RESULTS: Oxaliplatin-reactive patients presented with type I (74%), cytokine release reaction (CRR) (11%), and mixed (Mx) (15%) phenotypes. In contrast, carboplatin reactive patients presented with predominantly type I (85%) and Mx (15%) but no CRRs. Out of 267 DDs, breakthrough reactions (BTRs) to oxaliplatin occurred twice as frequently as carboplatin (32% vs. 15%; p < .05). Phenotype switching from type I to another phenotype was observed in 46% of oxaliplatin DDs compared to 21% of carboplatin DDs. Tryptase was elevated in type I and Mx reactions, and IL-6 in CRR and Mx, indicating different mechanisms and endotypes. CONCLUSION: Carboplatin and oxaliplatin induced three different types of reactions with defined phenotypes and endotypes amendable to DD. Although most of the initial reactions for both were type I, oxaliplatin presented with unique CRR reactions. During DD, carboplatin reactive patients presented mostly type I BTR, while oxaliplatin-reactive patients frequently switched from type I to CRR, providing a critical difference and the need for personalized DD protocols.

Urogenital sinus cyst in a 21-year-old man.

We report a case of a rare congenital malformation, a urogenital sinus cyst in a young patient with non-specific symptoms for several months. A 21-year-old male presented with vague and intermittent abdominal pain. Ultrasound scan showed a retrovesical hypoechoic collection (approximately 6 cm) and left renal agenesis, compatible with a possible congenital malformation. These findings were confirmed by MRI. A laparoscopic excision of the cyst was performed with no complications. Pathology report confirmed a urogenital sinus cyst. The postoperative recovery was uneventful and the patient was discharged within 48 h. Urogenital sinus cysts are rare entities with few cases described in the literature. Imaging techniques such as ultrasound, CT or MRI may help with diagnosis. Therapeutic modalities range from observation to needle aspiration or surgical removal. In our case, we chose a laparoscopic approach to minimize morbidity and achieve an early recovery.

Allergological study in patients vaccinated against COVID-19 with suspected allergic reactions.

BACKGROUND: One of the main barriers to vaccination against SARS-CoV-2 is the fear of developing hypersensitivity reactions to any of its components. Although these reactions are very rare, it is necessary to establish an effective protocol to detect patients at risk of developing them. The aim of this study was to evaluate hypersensitivity reactions in vaccinated patients in order to allow or not to complete the vaccination protocol. METHODS: Descriptive and cross-sectional study in which patients with suspected hypersensitivity to SARS-CoV-2 vaccines were evaluated. All patients underwent skin prick test (SPT) and/or intradermal test (IDT) with the vaccines and their excipients. In patients with positive IDT with the vaccine, a histopathological and immunohistochemical study was performed by skin biopsy. A basophil activation test (BAT) and a lymphoblastic transformation test (LTT) were also performed. RESULTS: Sixteen patients with suspected hypersensitivity to SARS-CoV-2 vaccine (12 received Comirnaty®, 3 received Vaxzevria®, and 1 received Spikevax®) were evaluated. Half had immediate hypersensitivity reactions and half had delayed reactions. All SPTs to excipients and vaccines were negative. IDTs with all excipients were negative. IDTs with vaccines were positive in 11 patients and negative in 5. The histological and immunohistochemical study of the two selected patients with positive IDT with vaccine showed T-lymphocyte involvement. BAT and LTT were negative in both cases. The vaccination protocol could be completed in 7 of 16 patients (44%) studied. The remaining 9 patients did not receive the second dose: 5 because vaccination was not required and 4 because they refused to be vaccinated. CONCLUSIONS: Thanks to the allergological and immunohistochemical study, the vaccination protocol could be completed in about half of the patients who presented suspected hypersensitivity reactions to SARS-CoV-2 vaccines. IDTs with vaccines could be a valuable method for assessing the immunogenicity of the vaccines.

Detection of Neutralizing Antibodies against SARS-CoV-2 Post-Vaccination in Health Care Workers of a Large Tertiary Hospital in Spain by Using a Rapid Test LFIC and sVNT-ELISA.

The presence of neutralizing antibodies (NAbs) against SARS-CoV-2 represent a surrogate marker of immunologic protection in populations at high risk of infection such as healthcare workers caring for hospitalized patients with COVID-19. As recommended by CDC and the European CDC, the use of rapid diagnostic tests during population-based evaluations offers an opportunity to identify individuals with serologic evidence of natural infection or who have undergone vaccination. We carried out a cross-sectional study to assess the presence of neutralizing antibodies against SARS-CoV-2 among medical providers at an intensive care unit of a large referral hospital in Alicante, Spain. In addition, we tested for the presence of neutralizing antibodies compared to serum of uninfected individuals from a Biobank. We were also interested in evaluating the use of a rapid lateral flow immunochromatography (LFIC) test against a surrogate ELISA viral neutralization test (sVNT). This rapid test demonstrated a specificity of 1.000 95% CI (0.91-1.00) and the sensitivity of 0.987 95% CI (0.93-1.00). The negative predictive value was 95%. After six months, this rapid test demonstrated that those immunized with two doses of BioNTech/Pfizer vaccine, maintained optimal levels of neutralizing antibodies. We concluded that all Health Care Workers develop NAbs and the use of this rapid immunochromatographic test represents a potential tool to be used in population-based studies to detect serological antibody responses to vaccination. Vaccination policies could benefit from this tool to assess additional doses of vaccine or boosters among high-risk populations.

Flow cytometry detection of sustained humoral immune response (IgG + IgA) against native spike glycoprotein in asymptomatic/mild SARS-CoV-2 infection.

SARS-CoV-2 is the virus that causes the disease called COVID-19, which has caused the worst pandemic of the century. Both, to know the immunological status of general population and to evaluate the efficacy of the vaccination process that is taking place around the world, serological tests represent a key tool. Classic serological tests, based on colorimetric techniques, such as ELISA or CLIA, continue to be the most widely used option. However, a real improvement in results is still needed. We developed a highly sensitive and specific FCM assay that allows the detection of IgG and IgA antibodies, directed against the native and functional S-protein of SARS-CoV-2 exposed on the membrane of a transfected cell line, up to 8 months after infection.

[Granulomatous lymphocytic interstitial lung disease: description of a series of 9 cases]. / Enfermedad pulmonar intersticial linfocítica granulomatosa: descripción de una serie de 9 casos.

INTRODUCTION: Granulomatous-lymphocytic interstitial lung disease (GLILD) is one of the most serious non-infectious complications in patients with common variable immunodeficiency (CVID). Its diagnosis and treatment are challenging. OBJECTIVE: To analyse the characteristics of Hospital General Universitario de Alicante patients with CVID and GLILD. MATERIAL AND METHODS: Descriptive study of patients with CVID and GLILD diagnosed from 2000 to 2020. RESULTS: Of the 42 patients with CVID, 9 had GLILD (21%). Mean age at diagnosis of 39 years. Sixty-six percent of the CVID was type MB0. Fifty-five percent had decreased BLs. There was a decrease in DLCO by 89%. Surgical lung biopsy (SLB) was performed in 78%. The most frequent extrapulmonary manifestation was adenopathy (78%). One patient had a heterozygous pathological mutation in the CTLA4 gene. Of the patients, 67% received combined corticosteroid treatment with Rituximab. CONCLUSIONS: GLILD is a rare complication of CVID whose diagnosis and treatment are a challenge. Its diagnosis requires a high index of suspicion, therefore a multidisciplinary diagnostic approach and combined treatment could provide a good result in the adult population.

Converter Phenotype: A New Profile That Is Not Exclusive to Taxanes.

Introduction: Phenotype I hypersensitivity reactions are the most commonly reported drug reactions; however, precision medicine has made it possible to characterize new phenotypes. A recent communication proposed the existence of a "converter phenotype," which would affect patients who present non-immediate hypersensitivity reactions and in subsequent exposures develop immediate hypersensitivity reactions. This study aimed to describe the clinical characteristics of converter phenotype reactions and their evolution during desensitization to chemotherapeutic drugs and monoclonal antibodies. Methods: We retrospectively reviewed our database of patients undergoing desensitization to chemotherapy or biological agents and selected those with a converter phenotype. Demographic and clinical characteristics of the patients, the results of skin tests, tryptase and IL-6 levels, and desensitization outcomes were assessed. Results: Of 116 patients evaluated, 12 (10.3%) were identified as having a converter phenotype. The median interval between drug exposure and reaction was 90.6 h (range 8-288 h). After the conversion, phenotype I was the most frequent (58.3%), followed by cytokine release reactions (33.3%). Fifty-one desensitizations were undertaken and all treatments completed, with 10 (19.6%) breakthrough reactions. No new changes in the phenotype were detected. Conclusions: The symptoms of non-immediate drug hypersensitivity reactions may indicate the need for an early allergological evaluation to assess the risk of future immediate drug reactions. Clinical characteristics, skin test results, and biomarkers can help predict responses to rapid drug desensitization, guiding clinicians on how to optimize therapy delivery while maintaining patient safety.

Immediate hypersensitivity to polyethylene glycols in unrelated products: when standardization in the nomenclature of the components of drugs, cosmetics, and food becomes necessary.

BACKGROUND: Polyethylene glycols (PEGs) and their derivatives are non-ionic polymers of ethylene oxide commercially available with numerous synonyms, such as macrogol, oxyethylene polymer, and laureth-9. Although these polymers are usually safe, mild to life-threatening immediate-type hypersensitivity reactions have been reported. Nevertheless, awareness about their allergic potential is minimal due to the non-standardization of their nomenclature. CASE PRESENTATION: We present the case of a 29-years-old woman who developed several local and systemic type I hypersensitivity reactions including a severe anaphylactic reaction to different pharmacologic and cosmetic products whose excipients included PEG. Prick tests and basophil activation tests were performed to several pharmacological and cosmetic products, but only those containing PEGs and their derivatives were positive. The patient was diagnosed with immediate hypersensitivity IgE-mediated to PEGs and its derivatives. CONCLUSIONS: Standardization of the terminology used to describe the presence of PEGs in products would help patients to identify them clearly and unequivocally and thus avoid the development of hypersensitivity reactions. It is also recommended studying PEG allergy in reactions to products containing PEGs, once allergy to the active ingredients has been excluded and in reactions to multiple unrelated drugs.Clinical study protocol number PI2018/29 (registered on 24 September 2018).

Hallazgos por imagen de lipoma pericárdico. Revisión de la literatura / Imaging findings of pericardial lipoma. Review of the literature

Introducción: El lipoma pericárdico es un tumor benigno infrecuente cuya presentación clínica es variada. Se revisaron los hallazgos por imagen descritos en la literatura en las modalidades de radiografía, ecocardiografía, tomografía axial computarizada (TAC) y resonancia magnética (RM). Metodología:Se identificaron reportes de caso, presentaciones en congreso y estudios observacionales de lipomas pericárdicos en PubMed, Scopus, Web of Science, Embase y Cochrane hasta el 01 de junio de 2022. Resultados: El lipoma pericárdico se ha descrito proporcionalmente en hombres y mujeres, en promedio a los 51 años de edad. Por lo general, los pacientes no presentan comorbilidades y de presentarlas, corresponden a factores de riesgo cardiovascular. Los síntomas más comunes son el dolor torácico y las palpitaciones. Hasta el 15 % de los casos son hallazgos incidentales en pacientes asintomáticos. Los métodos de imagen más frecuentemente descritos son la ecografía y la TAC, seguidos de la radiografía y la RM. Las descripciones incluyen masas ecogénicas, cardiomegalia, masas con densidad grasa menor a las 0 UH y por RM hiperintensas en T1 y T2 con saturación grasa y sin realce del medio de contraste. Un hallazgo frecuente es el derrame pericárdico. Conclusión: El rendimiento de las imágenes para el diagnóstico de lipomas pericárdicos no se ha calculado. Sin embargo, los hallazgos multimodales son altamente confiables para el diagnóstico no invasivo.

Introduction: Pericardial lipomas are benign and infrequent cardiac tumors with variable clinical presentation. We reviewed the imaging findings reported in the literature in radiography, echocardiography, computed tomography, and magnetic resonance. Methodology: We identified case reports, congress presentations and observational studies published in PubMed, Scopus, Web of Science, Embase and Cochrane until June 1st, 2022. Results: Pericardial lipoma occurs proportionally in women and men, at a mean age of 51 years. Past medical history is unremarkable and if present, cardiovascular risk factors are the most common comorbidity. The most common symptoms are chest pain and palpitations. Up to 15% of cases are incidental findings in asymptomatic patients. The most frequent imaging methods are echocardiography and computed tomography followed by radiography and magnetic resonance. Descriptions include echogenic masses, cardiomegaly, densities below 0 UH, T1 and T2 hyperintensity, fat saturation and lack of contrast enhancement. A frequent finding was pericardial effusion. Conclusions: The accuracy of the different imaging methods for lipomas has not been estimated. However, multimodal imaging is highly reliable for non-invasive diagnosis.

En busca de un biomarcador fidedigno en el asma grave: ¿el basófilo? / Might Basophils Be a Reliable Biomarker in Severe Asthma?

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Enfermedad pulmonar intersticial linfocítica granulomatosa: descripción de una serie de 9 casos / Granulomatous lymphocytic interstitial lung disease: description of a series of 9 cases

Introducción: La enfermedad pulmonar intersticial linfocítica granulomatosa (GLILD) es una de las complicaciones no infecciosas más graves de los pacientes con inmunodeficiencia común variable (IDCV). Su diagnóstico y tratamiento suponen un reto.ObjetivoAnalizar las características de los pacientes con IDCV y GLILD del Hospital General Universitario de Alicante.Material y métodosEstudio descriptivo de los pacientes con IDCV y GLILD diagnosticados desde 2000 a 2020.ResultadosDe los 42 pacientes con IDCV 9 presentaban GLILD (21%). La edad media al diagnóstico fue de 39 años. El 66% de IDCV fue de tipo MB0. El 55% tenía los linfocitos LB disminuidos. Se observó una disminución de la capacidad de transferencia del monóxido de carbono en un 89%. La biopsia pulmonar quirúrgica (BPQ) se realizó en el 78%. La manifestación extrapulmonar más frecuente fue adenopatías (78%). Una paciente presentó mutación patológica en heterocigosis en el gen CTLA4. El 67% de los pacientes recibió tratamiento combinado de corticoides con rituximab.ConclusionesLa GLILD es una complicación infrecuente de las IDCV cuyo diagnóstico y tratamiento es un reto. Su diagnóstico requiere un alto índice de sospecha, por lo que el enfoque diagnóstico multidisciplinar y el tratamiento combinado podrían proporcionar un buen resultado en la población adulta. (AU)

Introduction: Granulomatous-lymphocytic interstitial lung disease (GLILD) is one of the most serious non-infectious complications in patients with common variable immunodeficiency (CVID). Its diagnosis and treatment are challenging.ObjectiveTo analyse the characteristics of Hospital General Universitario de Alicante patients with CVID and GLILD.Material and methodsDescriptive study of patients with CVID and GLILD diagnosed from 2000 to 2020.ResultsOf the 42 patients with CVID, 9 had GLILD (21%). Mean age at diagnosis of 39 years. Sixty-six percent of the CVID was type MB0. Fifty-five percent had decreased BLs. There was a decrease in DLCO by 89%. Surgical lung biopsy (SLB) was performed in 78%. The most frequent extrapulmonary manifestation was adenopathy (78%). One patient had a heterozygous pathological mutation in the CTLA4 gene. Of the patients, 67% received combined corticosteroid treatment with Rituximab.ConclusionsGLILD is a rare complication of CVID whose diagnosis and treatment are a challenge. Its diagnosis requires a high index of suspicion, therefore a multidisciplinary diagnostic approach and combined treatment could provide a good result in the adult population. (AU)

Displasia arritmogénica del ventrículo derecho / Arrhythmogenic right ventricular dysplasia

La displasia arritmogénica del ventrículo derecho (DAVD) es una cardiomiopatía caracterizada por el reemplazo de miocitos por tejido fibroadiposo con herencia autosómica dominante. Ocupa el segundo lugar como muerte súbita en adultos jóvenes y es causante de un gran porcentaje en atletas. Su clínica es variable, debido a que puede presentarse en reposo o luego de actividad física con síntomas inespecíficos como palpitaciones, síncope y dolor torácico. Se presentan tres casos autópsicos de diferentes instituciones cuya manifestación clínica fue muerte súbita.

Arrhythmogenic right ventricular dysplasia (ARVD) is a cardiomyopathy inherited in an autosomal dominant pattern characterized by replacement of myocytes with fibrofatty tissue. ARVD is the second cause of sudden death in young adults and accounts for a great proportion of deaths in athletes. Clinical presentation is variable, it may occur during rest or after physical activity involving unspecific symptoms such as palpitations, syncope and chest pain. We here report three autopsy cases, referred from various healthcare institutions, in which sudden death was the first manifestation

Adenocarcinoma de uraco con metástasis cerebrales tardías / Urachal adenocarcinoma with late brain metastases

OBJETIVO: Describir un caso de adenocarcinoma uracal con metástasis cerebrales tardías en un paciente de 61 años que consultó por molestias abdominales y hematuria de 6 meses de evolución.MÉTODO: Con la sospecha clínica de tumoración vesical se realizaron pruebas diagnósticas (citología seriada de orina, cistoscopia, ecografía abdominal y TAC abdominopélvico). Se indicó tratamiento quirúrgico.RESULTADOS: La citología de orina fué negativa. En la cistoscopia se observó una lesión infiltrante en la cúpula vesical. En la ecografía y la TAC se apreció una lesión redondeada de 5 cm, con densidad intermedia, ecos internos ycalcificaciones en la línea media supravesical anterior, que infiltraba la vejiga. El estudio de extensión no mostró hallazgos. Se realizó cistectomía parcial y linfadenectomía. El diagnóstico histopatológico fué adenocarcinoma uracal mucosecretor. Tras 5 años libre de enfermedad el paciente desarrolló metástasis pulmonar y cerebrales.CONCLUSIONES: El adenocarcinoma de uraco es un tumor que debe distinguirse del adenocarcinoma primario vesical. El tipo mucosecretor puede asociar calcificaciones detectables en las pruebas de imagen que deben hacer sospechar el diagnóstico. La presencia de metástasis tardías (tras 5 años libre de enfermedad) y sin signos de recidiva local es un hecho clinicopatológico infrecuente(AU)

OBJECTIVE: To describe a case of urachal adenocarcinoma with late brain metastases in a sixtyone year old man who presented abdominal discomfort and hematuria during six months.METHODS: The clinical suspicion was bladder tumor and diagnostic studies were performed (urinary cytology, cys-toscopy, abdominal ultrasound and abdominopelvic CT scan). Surgical treatment was performed.RESULTS: Negative urinary cytology. Cystoscopy showed a lesion with infiltration of the bladder dome. Ultrasound and CT scan showed a five centimeter rounded lesion, with intermediate density, internal echoes and calcificatio-ns on the anterior supravesical middle line, that infiltrated the bladder. The extension study had not findings. Partial cystectomy and lymphadenectomy were performed. The histopathologic diagnosis was mucin-secreting urachal adenocarcinoma.After five years without disease the patient suffered lung and brain metastases.CONCLUSIONS: Urachal adenocarcinoma is a tumor which must be distinguished of primary bladder adeno-carcinoma. The mucing-secreting adenocarcinoma can be associated with calcifications that can be demostrated on imaging studies. Late metastases without signs of local recurrence (after five years without disease) are an infrequent clinical-pathologic finding(AU)