Neck CT angiography in acute stroke: An open window for fast detection of COVID-19 lung involvement? Applicability in telemedicine.

BACKGROUND: Chest CT has been proposed as a screening test to rule out SARS-CoV-2 lung infection in acute stroke. Our objectives are to analyze the predictive value of neck CT angiography (CTA) source images compared with conventional chest CT, the interobserver concordance and the reliability of the diagnosis using a mobile app. METHODS: A retrospective observational study that included acute stroke patients admitted to a stroke center. Two raters blinded to the clinical data evaluated and classified the pulmonary findings in chest CT and neck CTA source images according to the COVID-19 Reporting and Data System (CO-RADS). CTA findings were evaluated using a conventional workstation and the JOIN mobile app. Scores of 3-5 were grouped as appearing typical or indeterminate for COVID-19 lung involvement and 0-2 as appearing atypical or negative for pneumonia. SARS-CoV-2 infection was confirmed by polymerase chain reaction (PCR). RESULTS: A total of 242 patients were included (42 with PCR-confirmed COVID-19). In the cohort of 43 patients with both neck CTA and chest CT, the predictive value for COVID-19 was equivalent (sensitivity, 53.8%; specificity, 92.9%). The interobserver agreement in the classification into CO-RADS 3-5 or 1-2 in CTA was good (K = 0.694; standard error, 0.107). In the cohort of 242 patients with neck CTA, the intraobserver agreement between the workstation and the JOIN app was perfect (K = 1.000; standard error 0.000). CONCLUSIONS: Neck CTA enables the accurate identification of COVID-19-associated lung abnormalities in acute stroke. CO-RADS evaluations through mobile applications have a predictive value similar to the usual platforms.

Standards for practical intravenous rapid drug desensitization & delabeling: A WAO committee statement.

Drug hypersensitivity reactions (DHRs) to intravenous drugs can be severe and might leave patients and doctors in a difficult position where an essential treatment or intervention has to be suspended. Even if virtually any intravenous medication can potentially trigger a life-threatening DHR, chemotherapeutics, biologics, and antibiotics are amongst the intravenous drugs most frequently involved in these reactions. Admittedly, suspending such treatments may negatively impact the survival outcomes or the quality of life of affected patients. Delabeling pathways and rapid drug desensitization (RDD) can help reactive patients stay on first-choice therapies instead of turning to less efficacious, less cost-effective, or more toxic alternatives. However, these are high-complexity and high-risk techniques, which usually need expert teams and allergy-specific techniques (skin testing, in vitro testing, drug provocation testing) to ensure safety, an accurate diagnosis, and personalized management. Unfortunately, there are significant inequalities within and among countries in access to allergy departments with the necessary expertise and resources to offer these techniques and tackle these DHRs optimally. The main objective of this consensus document is to create a great benefit for patients worldwide by aiding allergists to expand the scope of their practice and support them with evidence, data, and experience from leading groups from around the globe. This statement of the Drug Hypersensitivity Committee of the World Allergy Organization (WAO) aims to be a comprehensive practical guide on the technical aspects of implementing acute-onset intravenous hypersensitivity delabeling and RDD for a wide range of drugs. Thus, the manuscript does not only focus on clinical pathways. Instead, it also provides guidance on topics usually left unaddressed, namely, internal validation, continuous quality improvement, creating a healthy multidisciplinary environment, and redesigning care (including a specific supplemental section on a real-life example of how to design a dedicated space that can combine basic and complex diagnostic and therapeutic techniques in allergy).

Rapidly Progressing to ESRD in an Individual with Coexisting ADPKD and Masked Klinefelter and Gitelman Syndromes.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic hereditary renal disease, promoting end-stage renal disease (ESRD). Klinefelter syndrome (KS) is a consequence of an extra copy of the X chromosome in males. Main symptoms in KS include hypogonadism, tall stature, azoospermia, and a risk of cardiovascular diseases, among others. Gitelman syndrome (GS) is an autosomal recessive disorder caused by SLC12A3 variants, and is associated with hypokalemia, hypomagnesemia, hypocalciuria, normal or low blood pressure, and salt loss. The three disorders have distinct and well-delineated clinical, biochemical, and genetic findings. We here report a male patient with ADPKD who developed early chronic renal failure leading to ESRD, presenting with an intracranial aneurysm and infertility. NGS identified two de novo PKD1 variants, one known (likely pathogenic), and a previously unreported variant of uncertain significance, together with two SLC12A3 pathogenic variants. In addition, cytogenetic analysis showed a 47, XXY karyotype. We investigated the putative impact of this rare association by analyzing possible clinical, biochemical, and/or genetic interactions and by comparing the evolution of renal size and function in the proband with three age-matched ADPKD (by variants in PKD1) cohorts. We hypothesize that the coexistence of these three genetic disorders may act as modifiers with possible synergistic actions that could lead, in our patient, to a rapid ADPKD progression.

Drug allergy desensitization is not a unique recipe.

PURPOSE OF REVIEW: Drug desensitization is the only therapeutic option for patients with drug allergies who need to receive the drugs they are allergic to, and it is especially critical in patients with an urgent need for chemotherapy, biologics, or antibiotics, where equally effective alternatives might not be available. However, drug desensitization is not a cookbook where anyone with no experience or specific training can find a general recipe. This review article will approach the singularities that make personalized and highly specialized care essential in this field. RECENT FINDINGS: Drug desensitization needs to be personalized for each individual patient bearing in mind countless factors. Recent articles have tried to define the optimal resources and the most important factors to account for in personalization. However, drug desensitization is only a tool within the wider management pathway, and we will discuss recent findings in allergy delabelling in chemotherapy, biologics, and antibiotics. SUMMARY: Risk-assessment, delabelling, and desensitization protocols, as a part of wider management pathways, can be adapted locally along with comprehensive and multifactorial risk-management strategies. These high-complexity and high-risk procedures, such as drug desensitization, need to be managed by expert allergists who can provide personalization, innovation, continuous improvement, research, and teaching in expert centres.

Hypersensitivity reactions to chemotherapy: an EAACI Position Paper.

Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section.

Hypersensitivity reactions to biologicals: An EAACI position paper.

Biologicals are crucial targeted therapeutic agents in oncological, immunological, and inflammatory diseases, and their use in clinical practice is broadening. In recent years, the spread of Personalized Precision Medicine has facilitated a proliferation of new treatment options, especially biologicals. Consequently, biologicals are now among the drugs that most frequently cause hypersensitivity reactions (HSRs). Patients can develop HSRs to these agents during the first-lifetime exposure or after repeated exposure, and these HSRs can be potentially life-threatening or limit therapeutic options. Despite the relatively high prevalence, the underlying mechanisms of these HSRs remain obscure, and the optimal management pathways are still a matter of discussion. In this Position Paper, the authors will provide evidence-based recommendations for diagnosing and managing HSRs to biologicals. Additionally, the document defines unmet needs as an opportunity to shape future research.

Co-occurrence of neurofibromatosis type 1 and optic nerve gliomas with autosomal dominant polycystic kidney disease type 2.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) and neurofibromatosis type 1 (NF1) are both autosomal dominant disorders with a high rate of novel mutations. However, the two disorders have distinct and well-delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and NF1 in a single individual have been reported, but the possible implications of this association are unknown. METHODS: We report an ADPKD male belonging to a family of several affected members in three generations associated with NF1 and optic pathway gliomas. The clinical diagnosis of ADPKD and NF1 was performed by several image techniques. RESULTS: Linkage analysis of ADPKD family was consistent to the PKD2 locus by a nonsense mutation, yielding a truncated polycystin-2 by means of next-generation sequencing. The diagnosis of NF1 was confirmed by mutational analysis of this gene showing a 4-bp deletion, resulting in a truncated neurofibromin, as well. The impact of this association was investigated by analyzing putative genetic interactions and by comparing the evolution of renal size and function in the proband with his older brother with ADPKD without NF1 and with ADPKD cohorts. CONCLUSION: Despite the presence of both conditions there was not additive effect of NF1 and PKD2 in terms of the severity of tumor development and/or ADPKD progression.

Coexistence of autosomal dominant polycystic kidney disease type 1 and hereditary renal hypouricemia type 2: A model of early-onset and fast cyst progression.

Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous inherited disease characterized by renal and extrarenal manifestations with progressive fluid-filled cyst development leading to end-stage renal disease. The rate of disease progression in ADPKD exhibits high inter- and intrafamilial variability suggesting involvement of modifier genes and/or environmental factors. Renal hypouricemia (RHUC) is an inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury and chronic kidney disease (CKD). However, the two disorders have distinct and well-delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and RHUC (type 1) in a single individual have been reported. We report a family with two members: an ADPKD 24-year-old female which presented bilateral renal cysts in utero and hypouricemia since age 5, and her mother with isolated hypouricemia. Next-generation sequencing identified two mutations in two genes PKD1 and SLC2A9 in this patient and one isolated SLC2A9 mutation in her mother, showing RHUC type 2, associated to CKD. The coexistence of these two disorders provides evidence of SLC2A9 variant could act as a modifier change, with synergistic actions, that could promote cystogenesis and rapid ADPKD progression. This is the first case of coexistence of PKD1 and SLC2A9 mutations treated with tolvaptan.

A Large Single-Hospital Experience Using Drug Provocation Testing and Rapid Drug Desensitization in Hypersensitivity to Antineoplastic and Biological Agents.

BACKGROUND: Large-scale studies of drug provocation testing (DPT) or rapid drug desensitization (RDD) for hypersensitivity to antineoplastics and biologicals are scarce and limited to a few institutions. OBJECTIVE: Our aim was to review our experience with DPT and RDD in a large number of patients with a history of hypersensitivity to antineoplastics and biologicals and summarize the practical implications of that experience. METHODS: This was a 7-year prospective, observational, longitudinal study with reactive patients referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were selected after following our systematic and validated diagnostic approach (clinical history, skin test, risk assessment, specific IgE, DPT) before RDD. Candidate patients underwent RDD using the RCUH protocol. Cetuximab reactors underwent 1-bag RDDs. RESULTS: A total of 1027 intravenous RDDs were performed using the RCUH protocol (399 platins, 395 taxanes, 178 biologicals, 55 other drugs), and 1026 were successfully accomplished in the 186 patients (of 515 referred patients) who met inclusion criteria for RDD. No breakthrough reactions occurred in 88% of RDDs. Most breakthrough reactions were mild. A total of 341 DPTs were performed, and 229 results were negative (67%). DPTs helped exclude hypersensitivity in 44% (229 of 515) of referred patients. In addition, 77 one-bag RDDs were performed in 6 cetuximab-reactive patients. CONCLUSIONS: This experience allows us to describe general management plans, as well as specific patient phenotypic patterns, predictors for reactions, and risk considerations that need a tailored approach (taking into account the 3 prominent drug categories: platins, taxanes, and biologicals).

[Successful oral desensitization to levothyroxine. Report of one case]. / Desensibilización a levotiroxina. Caso clínico.

We report a 39-year-old female who underwent a total thyroidectomy as treatment for a thyroid papillary cancer. She suffered several episodes of mild angioedema in lips and tongue, after using different commercial Levothyroxine formulations, with and without excipients. Given the need to use this drug, the patient was admitted in our hospital and we proceeded to desensitize her with oral Levothyroxine. The patient fasted throughout the whole procedure, was properly monitored and had an adequate peripheral venous access. On the first day of the procedure, a 15-step protocol was performed, first administering placebo and then, compounded formulations of Levothyroxine starting from 0.01 ug, followed by doubling doses every 15 minutes until the cumulative dose of 111.95 ug was completed, corresponding to the daily dose of Levothyroxine her endocrinologist prescribed (112 ug). The patient was monitored at baseline, between each dose and up to 3 hours after the procedure was completed. There were no incidents such as urticaria, angioedema, or others. On the second day, the patient received a single-full dose of 112 ug on an empty stomach. The medication was successfully tolerated and she was discharged. Thereafter, she tolerates daily Levothyroxine.

Desensibilización a levotiroxina: caso clínico / Successful oral desensitization to levothyroxine: report of one case

We report a 39-year-old female who underwent a total thyroidectomy as treatment for a thyroid papillary cancer. She suffered several episodes of mild angioedema in lips and tongue, after using different commercial Levothyroxine formulations, with and without excipients. Given the need to use this drug, the patient was admitted in our hospital and we proceeded to desensitize her with oral Levothyroxine. The patient fasted throughout the whole procedure, was properly monitored and had an adequate peripheral venous access. On the first day of the procedure, a 15-step protocol was performed, first administering placebo and then, compounded formulations of Levothyroxine starting from 0.01 ug, followed by doubling doses every 15 minutes until the cumulative dose of 111.95 ug was completed, corresponding to the daily dose of Levothyroxine her endocrinologist prescribed (112 ug). The patient was monitored at baseline, between each dose and up to 3 hours after the procedure was completed. There were no incidents such as urticaria, angioedema, or others. On the second day, the patient received a single-full dose of 112 ug on an empty stomach. The medication was successfully tolerated and she was discharged. Thereafter, she tolerates daily Levothyroxine.

Assessment of Antihistamines and Corticosteroids as Premedication in Rapid Drug Desensitization to Paclitaxel: Outcomes in 155 Procedures.

BACKGROUND: In early clinical trials, infusion reactions during the administration of taxanes were managed using systematic premedication with antihistamines and corticosteroids before standard infusions. Consequently, these premedications are also administered before rapid drug desensitization (RDD) with taxanes. However, their role in RDD has not been studied. OBJECTIVE: To assess the need for premedication with antihistamines and corticosteroids to prevent hypersensitivity reactions in RDD to paclitaxel. METHODS: Over a 4-year period, we selected patients with confirmed hypersensitivity to paclitaxel (positive skin testing and/or drug provocation testing results) who had received paclitaxel through RDD. These patients were assigned to 2 prospective noninception cohorts: one cohort premedicated with antihistamine and corticosteroids and another cohort that was not. RESULTS: We assessed 66 paclitaxel-reactive patients, of whom 22 met the inclusion criteria. A total of 155 RDDs to paclitaxel were performed. There were no significant differences in tolerance to RDD between the cohorts. CONCLUSIONS: Administering systematic premedication with corticosteroids and antihistamines had no significant effect on the effectiveness or safety of RDD in patients with confirmed hypersensitivity to paclitaxel in the study population. Moreover, these premedications can mask early signs of hypersensitivity and delay treatment. We believe that systematic premedication with these drugs for patients undergoing RDD should be carefully and individually assessed if their only purpose is to prevent breakthrough reactions during RDD.

A Phase I clinical trial with subcutaneous immunotherapy vaccine of Timothy grass pollen extract according to EMA guidelines.

AIM: A double-blind placebo-controlled study was conducted according to EMA guidelines, to evaluate safety, tolerability and short-term treatment effects of three up-dosing regimens of Phleum pratense subcutaneous immunotherapy. MATERIALS & METHODS: Forty-two patients were randomized to groups: A (6 weekly doses), B (8 weekly doses) or C (eight doses, two clustered increasing doses over 3 weeks). RESULTS: The most frequent adverse events were local reactions. No serious adverse events were found. Higher number and more severe systemic reactions were reported in group C. A decrease in cutaneous responses and an increase of specific antibodies was shown in all active groups even at very short-term. CONCLUSION: Phleum pratense subcutaneous immunotherapy in depot presentation exhibited good safety and tolerability. Group A seemed to show the best profile.