Cardiorenal syndrome (CRS) involves joint dysfunction of the heart and kidney. Acute forms share biochemical alterations like hyperuricaemia (HU) with tumour lysis syndrome (TLS). The mainstay ...treatment of acute CRS with systemic overload is diuretics, but rasburicase is used in TLS to prevent and treat hyperuricaemia. An observational, retrospective study was performed to assess the effectiveness and safety of a single dose of rasburicase in hospitalized patients with cardiorenal syndrome, worsening renal function and uric acid levels above 9 mg/dL. Rasburicase improved diuresis and systemic congestion in the 35 patients included. A total of 86% of patients did not need to undergo RRT, and early withdrawal was possible in the remaining five. Creatinine (Cr) decreased after treatment with rasburicase from a peak of 3.6 ± 1.27 to 1.79 ± 0.83 mg/dL, and the estimated glomerular filtration rate (eGFR) improved from 17 ± 8 to 41 ± 20 mL/min/1.73 m
(
= 0.0001). The levels of N-terminal type B Brain Natriuretic Peptide (Nt-ProBNP) and C-reactive protein (CRP) were also significantly reduced. No relevant adverse events were detected. Our results show that early treatment with a dose of rasburicase in patients with CRS and severe HU is effective to improve renal function and systemic congestion, avoiding the need for sustained extrarenal clearance, regardless of comorbidities and ventricular function.
What is Known and Objective
Rosai‐Dorfman disease (RDD) is an infrequent entity of unknown aetiology. Currently, there is no clear consensus on the treatment, and nothing has shown definitive safety ...and efficacy. We describe the case of a woman diagnosed with pulmonary RDD, who responded to thalidomide treatment after failure of four previous lines of systemic chemotherapy.
Case Description
We present the case of a 74‐year‐old woman diagnosed with pulmonary RDD and autoimmune complications. We decided to use thalidomide as a rescue treatment after the failure of corticosteroids and several chemotherapies. Our patient achieved remission of the disease and remained stable for years.
What is New and Conclusion
To the authors’ knowledge, this is the first reported case in which thalidomide treatment induced remission in refractory pulmonary RDD. Thalidomide showed a rapid onset of action, with lasting responses, which could make it an exciting option for treating this life‐threatening.
Purpose
Several clinical guidelines recommend genetic screening of
DPYD
, including coverage of the variants c.1905 + 1G>A(
DPYD
*2A), c.1679T>G(
DPYD
*13), c.2846A>T, and c.1129-5923C>G, before ...initiating treatment with fluoropyrimidines. However, this screening is often inadequate at predicting the occurrence of severe fluoropyrimidine-induced toxicity in patients.
Methods
Using a complementary approach combining whole
DPYD
exome sequencing and in
silico
and structural analysis, as well as phenotyping of DPD by measuring uracilemia (U), dihydrouracilemia (UH
2
), and the UH
2
/U ratio in plasma, we were able to characterize and interpret
DPYD
variants in 28 patients with severe fluoropyrimidine-induced toxicity after negative screening.
Results
Twenty-five out of 28 patients (90%) had at least 1 variant in the
DPYD
coding sequence, and 42% of the variants (6/14) were classified as potentially deleterious by at least 2 of the following algorithms: SIFT, Poly-Phen-2, and DPYD varifier. We identified two very rare deleterious mutations, namely, c.2087G>A (p.R696H) and c.2324T>G (p.L775W). We were able to demonstrate partial DPD deficiency, as measured by the UH
2
/U ratio in a patient carrying the variant p.L775W for the first time.
Conclusion
Whole exon sequencing of
DPYD
in patients with suspicion of partial DPD deficiency can help to identify rare or new variants that lead to enzyme inactivation. Combining different techniques can yield abundant information without increasing workload and cost burden, thus making it a useful approach for implementation in patient care.
Vitamin D is an environmental factor related to multiple sclerosis that plays a significant role in immune regulation. TGF-β is a superfamily of cytokines with an important dual effect on the immune ...system. TGF-β inhibits the Th1 response while facilitating the preservation of regulatory T cells (FOXP3+) in an immunoregulatory capacity. However, when IL-6 is present, it stimulates the Th17 response. Our aim was to analyze the regulatory effect of vitamin D on the in vivo TGF-β signaling pathway in patients with relapsing-remitting multiple sclerosis (RRMS). A total of 21 patients with vitamin D levels < 30 ng/mL were recruited and supplemented with oral vitamin D. All patients were receiving disease-modifying therapy, with the majority being on natalizumab. Expression of SMAD7, ERK1, ZMIZ1, BMP2, BMPRII, BMP4, and BMP5 was measured in CD4+ lymphocytes isolated from peripheral blood at baseline and one and six months after supplementation. SMAD7 was overexpressed at six months with respect to baseline and month one. ERK1 was overexpressed at six months with respect to month one of treatment. No significant differences in expression were observed for the remaining genes. No direct correlation was found with serum vitamin D levels. BMPRII expression changed differentially in non–natalizumab- versus natalizumab-treated patients. Changes were observed in the expression of ERK1, BMP2, and BMP5 based on disease activity measured using the Rio-Score, BMP2 in patients who had relapses, and BMP5 in those whose EDSS worsened. Our results suggest indirect regulation of vitamin D in TGF-β pathway genes in patients with RRMS.
Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have emerged as a therapeutic option for patients with hypercholesterolemia who do not attain low-density lipoprotein cholesterol ...(LDL-C) goals and/or are intolerant to other lipid-lowering drugs. Our aim was to analyze the effectiveness and safety of PCSK9i in routine clinical practice and factors related to poor outcomes.
We conducted an ambispective study in 115 patients who recieved alirocumab or evolocumab, in a tertiary level hospital. From February 2017 to April 2020, patients were recruited and followed up for a median of 20.4 months. The main outcomes were relative reduction in LDL-C, percentage of patients achieving the therapeutic goals established by 2016 ESC/EAS guidelines, incidence of major cardiovascular events (MACEs) and drug-related adverse events (ADRs).
The median LDL-C achieved was 57.0 mg/dL (relative reduction of 59.9% from baseline, p< 0.001). After adjusting for confounders, smaller LDL-C reductions were related to female sex, absence of concomitant lipid-lowering therapy and treatment with alirocumab. Overall, 84.6% of the patients achieved the therapeutic goals. During follow-up, 7 MACEs were detected. ADRs, generally considered mild, affected 38.1% of the participants (mainly mialgias and arthralgias) and triggered discontinuations in 8.7% of cases.
PCSK9i are effective and safe, although certain factors may influence their effectiveness. Interestingly, our results suggest that alirocumab and evolocumab may not be therapeutic equivalents, as initially suggested.
Display omitted
•PCSK9 inhibitors are effective and safe agents for the treatment of hypercholesterolemia.•Male sex and concomitant lipid-lowering therapy are favorable predictors of response to PCSK9 inhibitors.•LDL-C levels by themselves may not predict cardiovascular outcomes.•Our findings support that alirocumab and evolocumab are not therapeutic equivalents, probably due to differences in dosing.
Summary
What is known and objectives
Inadequate management of chronic medication puts patients at risk and causes unnecessary suspension of surgical procedures. The objective of the study was to ...calculate the rate of cancellation of elective surgical procedures due to inadequate management of chronic medications and to analyse the underlying causes of cancellation.
Methods
We designed an analytic, observational, retrospective study of all elective surgical procedures performed from July to October 2017 in a tertiary hospital. The main variable was the percentage of surgeries cancelled owing to inadequate management of chronic medications. Other variables recorded included demographic characteristics, time between the preanaesthesia evaluation and surgery, drug involved, and the reason for incorrect management of the medication.
Results
During the study period, 5415 surgical procedures were programmed, and 793 (14.6%) were cancelled. Cancellations due to inadequate patient preparation accounted for 5.3% (42 cases), and 19 were related to incorrect medication management (2.4% of the total number of cancellations). The 19 patients, who were mostly men (73.7%), had a median age of 76 years (IQR 68‐81). The drugs involved were acenocoumarol (6), enoxaparin (4), clopidogrel (4), direct‐acting oral anticoagulants (2), acetylsalicylic acid (1), tocilizumab (1) and leflunomide (1). The reasons for drug mishandling were poor understanding of the anaesthesiology recommendations (15) and lack of a preanaesthesia evaluation (4).
What is new and conclusion
Inadequate management of chronic medications (2.4%) is not the most frequent reason for cancellation, although it is one of the easiest to avoid. Based on our results, starting in October 2017, the Pharmacy Department began to offer a pharmaceutical service to patients with doubts about the preoperative management of chronic medications.
793 elective surgeries were canceled between July and October 2017. 2.4% of them were related to incorrect medication management. Drugs involved were mostly anticoagulants and antiplatelet drugs.
Introduction
Cerebellar mutism syndrome (CMS) is a common complication after posterior fossa tumor resection. It is characterized by a significant lack or loss of speech. Its biological origin ...remains unclear and there are no standardized treatments. However, bromocriptine seems to be a possible treatment for this condition.
Case report
In this paper, we present three cases of pediatric patients (4, 5, and 17-year old) who developed CMS after posterior fossa tumor surgery. They were treated with bromocriptine to improve neurological symptoms.
Management and outcome: Bromocriptine was started at a low dose and was progressively increased to reach the minimum effective dose. After four months of treatment, a normal and fluid speech was observed in the three patients. No discontinuation due to adverse events were reported.
Discussion
Bromocriptine has shown to be an effective and safe treatment for CMS in pediatric patients after posterior fossa tumor resection.
Background: The variant rs34983651 (UGT1A1*28) and its genotyping are used to prevent irinotecan-induced toxicity. Several variants are in close linkage disequilibrium. Our objective was to evaluate ...the potential correlation of genotyping UGT1A1*80 instead of UGT1A1*28 in different populations. Methods: We studied SNPs in linkage disequilibrium with UGT1A1*28 in several populations and selected rs887829 to develop an inexpensive and rapid genotyping method and compare it with the one we currently use for UGT1A1*28 genotyping. Samples from cancer patients (n = 701) already tested using PCR and electrophoresis prior to treatment with irinotecan for rs34983651 (UGT1A1*28) in a Spanish hospital were genotyped for rs887829 (UGT1A1*80) using real-time PCR with a TaqMan probe. Results: We observed a complete match for both genotypes, except in one sample. This method was 100% efficient in correctly genotyping *28/*28 patients, 99.68% efficient for *1/*28, and 100% efficient for *1/*1. Linkage disequilibrium between populations showed the Iberian population to be the most suitable for the clinical use of UGT1A1*80. This method is less expensive and the time to decision is shorter. Conclusion: Genotyping of rs887829 using the proposed method may be used to substitute genotyping of rs34983651 as a pharmacogenetics test in cancer patients prior to starting irinotecan-based treatments, mainly in the Iberian population. In addition, it is less expensive than other conventional methods and easy to implement, with a shorter time to decision than UGT1A1*28.
Objective
To design a mobile app based on the needs of the onco-hematological patient receiving oral antineoplastic agents.
Methods
A multidisciplinary working group (pharmacy–oncology–hematology) ...was created to design the app. The study was developed in three phases: first, we analyzed the features of patients receiving oral antineoplastic agents. We then analyzed available apps for cancer patients. Finally, we designed the app's functionalities.
Results
We included 51 patients with middle-advanced age (68.7 years (SD=10.7)). They were polymedicated (mean: 5.3 (SD = 2.7), with numerous drug–drug interactions and adverse effects (all patients presented adverse effects). We then analyzed 166 apps. Most apps had more than one use, the most frequent being information (39.8%) and diagnosis (38.6%). Ten apps (6%) were for registering and monitoring treatment and adverse effects. Almost half of the apps (48.8%) were developed by healthcare organizations. Finally, we designed an app (e-OncoSalud®) with the following functionalities: (a) agenda; (b) treatment and drug interactions checker; (c) continuous recording of self-controls (weight, blood pressure, general condition) and adverse effects. The management of the adverse effects are based on an algorithm which provides different recommendations according to the adverse effects severity; (d) patient–pharmacist messaging in real-time; (e) education.
Conclusions
After analysis of the main problems affecting these patients and the needs not covered by the existing apps, we designed e-OncoSalud®. It integrates relevant information about their treatment, focused on drug interactions identification and the prevention, and management of adverse effects.
Patients with pulmonary hypertension (PH) have progressive and disabling symptoms, as well as a burden of treatments and a difficult clinical evaluation that make health-related quality of life a ...particularly relevant endpoint in this disease. The objective of the study was to evaluate patient-reported outcomes of patients receiving specific treatment for PH in a tertiary hospital using a specific questionnaire (Cambridge Pulmonary Hypertension Outcome Review-CAMPHOR) in the pharmacy consultation.
A cross-sectional, observational, descriptive study was conducted. It included all patients receiving specific treatment for PH in a tertiary hospital in Madrid, Spain. The inclusion period comprised between August to December 2019. CAMPHOR questionnaires containing three domains: symptoms, activities and quality of life were completed by the patients at the pharmacy consultation. Demographic and clinical variables, including WHO Functional Class (WHO FC), PH-specific tests and hemodynamic parameters, were recorded. Non-parametric analyses to assess relations between variables and CAMPHOR domains were performed.
Thirty-six patients consented to participate in the study and completed the questionnaire. Median scores for symptoms, activities, and quality of life domains were 5.5 (2.5-10), 8.0 (4.5-10.5) and 3.5 (1-7.5), respectively. Statistically significant differences were found in the three domains when comparing by WHO FC, in the activities domain for 6-m walking test and in the quality of life domain for patients who had emergency visits or hospitalizations in the last year.
The CAMPHOR questionnaire could be useful as a complementary test to achieve an integrated evaluation of PH patients, who could complete it easily during their routine pharmacy visits.
PDF
