BMC Ophthalmol. 2021 May 31;21(1):243. doi: 10.1186/s12886-021-01989-1.

ABSTRACT

BACKGROUND: To evaluate alterations in the serum concentrations of vascular endothelial growth factor (VEGF) and netrin-1 after intravitreal bevacizumab (BCZ) injection for the treatment of diabetic macular edema (DME).

METHODS: This prospective case-control study included a total of 50 participants assigned to one of three groups, including 10 individuals with DME and non-proliferative diabetic retinopathy (NPDR), 13 with DME, and proliferative diabetic retinopathy (PDR), and 27 healthy individuals as a control group. Serum VEGF and netrin-1 concentrations were measured by enzyme-linked immunosorbent assays (ELISAs) immediately before, as well as 1 week and 1 month after, intravitreal BCZ injection.

RESULTS: The mean VEGF serum concentrations in the PDR and NPDR groups were 388.4 and 196.9 pg/mL at baseline, respectively. After 1 week, these concentrations changed to 193.41 and 150.23 pg/mL, respectively (P = 0.001 and P = 0.005, respectively); after 1 month, the concentrations were 97.89 and 76.46 pg/mL, respectively (P = 0.001 and P = 0.009, respectively). The mean netrin-1 serum concentrations in the PDR patients and NPDR groups were 318.2 and 252.7 pg/mL at baseline, respectively. After 1 week, these concentrations increased to 476.6 and 416.3 pg/mL, respectively (P = 0.033 and P = 0.005, respectively), and after 1 month, they were 676.6 and 747.5 pg/mL, respectively (P = 0.001 and P = 0.005, respectively). The correlation analysis revealed a significant inverse relationship between changes in serum VEGF and netrin-1 concentrations in both the PDR and NPDR groups (r = - 0.685, P = 0.029).

CONCLUSIONS: Intravitreal BCZ injections work systemically to significantly decrease serum VEGF levels, leading to a significant upregulation in the concentration of another angiogenic mediator, netrin-1.

PMID:34058994 | DOI:10.1186/s12886-021-01989-1

ACS Biomater Sci Eng. 2021 Jun 1. doi: 10.1021/acsbiomaterials.1c00439. Online ahead of print.

ABSTRACT

Targeted delivery and extended blood circulation of anticancer drugs have been the challenges for decreasing the adverse side effects and improving the therapeutic efficiency in cancer chemotherapy. Herein, we present a drug delivery system (DDS) based on biodegradable dendritic polyglycerol sulfate-bearing poly(caprolactone) (dPGS-PCL) chains, which has been synthesized on 20 g scale using a straightforward two-step protocol. In vivo fluorescence imaging demonstrated a significant accumulation of the DDS in the tumor environment. Sunitinib, an anticancer drug, was loaded into the DDS and the drug-induced toxicity was investigated in vitro and in vivo. The drug encapsulated in dPGS-PCL and the free drug showed similar toxicities in A431 and HT-29 cells, and the cellular uptake was comparable. The straightforward and large-scale synthesis, the organic solvent-free drug-loading approach, together with the tumor targetability of the biodegradable dendritic polyglycerols, render this copolymer a promising candidate for targeted cancer nanomedicine drug delivery systems.

PMID:34061498 | DOI:10.1021/acsbiomaterials.1c00439

Ugeskr Laeger. 2021 May 24;183(21):V10200794.

ABSTRACT

This case report describes a 57-year-old male with symptoms of tardive akathisia after long-term metoclopramide treatment. As metoclopramide is a dopamine receptor antagonist, it has the potential to cause drug-induced movement disorders, including akathisia, which is characterised by an inner restlessness resulting in a need for constant movement. Tardive akathisia, in contrast to acute akathisia, evolves after prolonged exposure to the triggering medication and can be a permanent condition. Treatment duration of metoclopramide should be restricted, and awareness of neurological side effects is important.

PMID:34060465

Dermatol Ther. 2021 May 31:e15012. doi: 10.1111/dth.15012. Online ahead of print.

ABSTRACT

INTRODUCTION: Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous drug reaction. Bullous pemphigoid (BP) is an acquired autoimmune disease that might be associated with drugs. There is currently no report of tripterygium glycosides (TG)-induced AGEP-like lesions combined with BP.

CASE PRESENTATION: A 66-year-old male with a 20-year history of psoriasis was prescribed oral TG at 1 mg/kg, three times a day, due to aggravated psoriasis. Seven days later, erythemas and blisters appeared. After another 3 days, there were two types of blisters: (1) numerous small tension blisters with a lot of neutrophils on the top similar to AGEP combined with BP; (2) a BP. After intravenous injection of methylprednisolone and gamma globulin, the lesions were controlled.

CONCLUSION: This patient developed two types of lesions，including one similar to AGEP combined BP (AGEP-like) and a BP. It's a rare drug reaciton induced by TG.

PMID:34060189 | DOI:10.1111/dth.15012

Crit Care Clin. 2021 Jul;37(3):625-641. doi: 10.1016/j.ccc.2021.03.008.

ABSTRACT

Drug-induced iatrogenic toxicities are common in critically ill patients and have been associated with increased morbidity and mortality. Early recognition and management of iatrogenic toxicities is essential; however, the diagnosis is usually complicated by the underlying critical illness, comorbidities, and administration of multiple medications. This article reviews several types of iatrogenic toxicities associated with medications that are commonly used in critically ill patients. The mechanism of the iatrogenic toxicities, clinical presentation, and diagnosis, as well as management are discussed.

PMID:34053710 | DOI:10.1016/j.ccc.2021.03.008

Crit Care Clin. 2021 Jul;37(3):475-486. doi: 10.1016/j.ccc.2021.03.001.

ABSTRACT

Pharmacokinetic and pharmacodynamic interactions between drugs and the body play a vital role in the therapeutic effects of drugs as well as their toxicity. Toxic effects may evolve from high doses of drugs or from alterations in the absorption, distribution, metabolism, and excretion of those drugs. The effective dose of a drug is influenced by the initial dose, route of administration, drug formulation, and bioavailability. This effective dose, in conjunction with the frequency of dosing, duration of exposure, and pharmacodynamic variability, directly affects the toxicity experienced in the body.

PMID:34053701 | DOI:10.1016/j.ccc.2021.03.001

J Oncol Pharm Pract. 2021 May 30:10781552211020805. doi: 10.1177/10781552211020805. Online ahead of print.

ABSTRACT

PURPOSE: Medication non-adherence to treatment regimens can severely impact the mortality of patients afflicted with breast cancer.The purpose of this study was to identify factors that contribute to non-adherence to endocrine therapy in breast cancer treatment plans.

METHODS: Thirty-two women with a breast cancer diagnosis were surveyed by pharmacists and pharmacy students to identify the patient- related factors (e.g. patient personal beliefs, education level), drug-related factors (e.g. patient drug allergies), socio-economic factors (e.g. patient ability to pay for the medication) and healthcare system factors (e.g. poor patient-healthcare provider relationship) that may impact non-adherence to endocrine therapy in breast cancer treatment plans. Medication adherence rates were measured using the Medication Adherence Rating Scale (MARS-8) system. Associations between adherence rate scores and clinical variables (e.g. age, tobacco use, alcohol consumption, cost of treatment, education level, personal beliefs, drug allergies, patient/provider relationship, adverse events) were carried out using Spearman Correlation, T-Test, Mann-Whitney U Test, and X2 tests. A p value of ≤ 0.05 was considered statistically significant.

RESULTS: Our study found that 59% of survey respondents were non-adherent to their endocrine therapy in breast cancer treatment plans. Drug allergies (p = 0.000069), patient ability to pay (p = 0.005), poor personal beliefs about the prescribed therapy (p = 0.009), low education level (p = 0.025), adverse drug events (p = 0.026), and poor patient-provider relationship (p = 0.05) were found to play a role in patient non-adherence to treatment.

CONCLUSIONS: Our study found that drug- (e.g. allergies), socio-economic (e.g. patient ability to pay), and patient-related factors (e.g. personal beliefs) are the strongest predictors of adherence among breast cancer patients undergoing endocrine therapy. These findings support the need for a better relationship between breast cancer patients and their healthcare providers, including drug experts such as pharmacists.

PMID:34053357 | DOI:10.1177/10781552211020805

Adv Anat Pathol. 2021 May 27. doi: 10.1097/PAP.0000000000000307. Online ahead of print.

ABSTRACT

Eighteen histologic patterns of drug-induced liver injury (DILI) are described, most of which are also seen in other commonly occurring acute and chronic liver diseases. However, certain patterns such as sinusoidal obstruction syndrome/veno-occlusive disease, "bland" cholestasis and cholestatic hepatitis are more often caused by drugs than other competing etiologies. Amiodarone, acetaminophen, anabolic androgenic steroids and estrogens, result in histologic patterns that are virtually diagnostic of the respective drug. Recognition of a DILI or drug specific injury pattern enables the clinician to focus on eliciting an appropriate history to identify the offending agent, which may otherwise be rare and not immediately apparent. Although drugs can mimic any and every liver disease, the mimicry is often imperfect. Unusual features that do not completely fit the clinicopathologic paradigm of the mimicked liver disease are clues to diagnosis of DILI. When mimicking a liver disease, drugs tend to hasten or accelerate the natural progression of the disease. Novel immunomodulatory drugs for inflammatory disorders and cancer may cause unintended effects on the immune system, resulting in immune-related side effects. The role of the pathologist in diagnosis of DILI is to recognize known patterns of DILI, and either confirm a diagnosis when clinically suspected, or alert the clinician to the possibility of DILI when it is not suspected. The latter is particularly vital in contemporary practice, which is witnessing an accelerated pace of drug development, and a surge in consumption of nutritional supplements and herbal compounds by an increasingly health conscious society.

PMID:34050060 | DOI:10.1097/PAP.0000000000000307

Lancet Haematol. 2021 Jun;8(6):e433-e445. doi: 10.1016/S2352-3026(21)00103-4.

ABSTRACT

BACKGROUND: Novel approaches are required to improve outcomes in relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma. We aimed to evaluate camidanlumab tesirine, an anti-CD25 antibody-drug conjugate, in this patient population.

METHODS: This was a phase 1, dose-escalation (part 1), dose-expansion (part 2), multicentre trial done in 12 hospital sites (seven in the USA and five in the UK). Adults (≥18 years old) with pathologically confirmed relapsed or refractory classical Hodgkin lymphoma or non-Hodgkin lymphoma, an Eastern Cooperative Oncology Group performance status 0-2, who had no therapies available to them with established clinical benefit for their disease stage were enrolled. Camidanlumab tesirine was administered intravenously (3-150 μg/kg) once every 3 weeks. Primary objectives were to assess dose-limiting toxicity, determine maximum tolerated dose and recommended expansion dose(s), and assess safety of camidanlumab tesirine. Safety was assessed in all treated patients; antitumour activity was assessed in patients with one or more valid baseline and post-baseline disease assessment and in those who had disease progression or died after first study-drug dose. This trial was registered with ClinicalTrials.gov, NCT02432235.

FINDINGS: Between Oct 5, 2015, and Jun 30, 2019, 133 patients were enrolled (77 [58%] had classical Hodgkin lymphoma and 56 (42%) had non-Hodgkin lymphoma). Median follow-up was 9·2 months (IQR 4·2-14·3). Eight dose-limiting toxicities were reported in five (6%) of 86 patients who were evaluable; the maximum tolerated dose was not reached. The recommended doses for expansion were 30 μg/kg and 45 μg/kg for patients with classical Hodgkin lymphoma and 80 μg/kg for patients with T-cell non-Hodgkin lymphomas. No recommended doses for expansion were defined for B-cell non-Hodgkin lymphomas. Grade 3 or worse treatment-emergent adverse events (reported by ≥10% of the 133 patients) included increased γ-glutamyltransferase (20 [15%] patients), maculopapular rash (16 [12%]), and anaemia (15 [11%]); 74 (56%) patients had serious treatment-emergent adverse events, most commonly pyrexia (16 [12%]). One (1%) fatal treatment-emergent adverse event and two (2%) deaths outside the reporting period were considered at least possibly study-drug related. Antitumoural activity was seen in classical Hodgkin and non-Hodgkin lymphomas; notably in all patients with classical Hodgkin lymphoma, the overall response was 71% (95% CI 60-81).

INTERPRETATION: These results warrant evaluation of camidanlumab tesirine as a potential treatment option for relapsed or refractory lymphoma, particularly in patients with classical Hodgkin lymphoma.

FUNDING: ADC Therapeutics.

PMID:34048682 | DOI:10.1016/S2352-3026(21)00103-4

Pediatr Pulmonol. 2021 May 28. doi: 10.1002/ppul.25513. Online ahead of print.

ABSTRACT

INTRODUCTION: Hypersensitivity pneumonitis (HP) in children is a severe interstitial lung disease and potentially, a chronic condition, if not treated appropriately. No evidence-based guidelines are available; in particular, the role of systemic glucocorticoid therapy is unclear.

METHODS: The aim of this randomized, double-blind, placebo-controlled, parallel-group, multi-center, phase II trial in pediatric HP was to assess the outcome of HP in children after 6 months of treatment and to compare 3 months of treatment with oral prednisolone or placebo.

RESULTS: After 1.5 years and the inclusion of only four children, we terminated the study prematurely. Two of the children randomized to prednisolone did not achieve the predefined response of FVC to normal. One child treated with placebo recovered to normal, similar to another child treated with prednisolone. All children treated with steroids developed drug-related side effects.

DISCUSSION: This uncompleted study illustrates the urgent medical need for evidence-based treatment protocols for this condition. We discuss the hurdles which were specific for completion of this trial in a rare condition. Among other options, we suggest the inclusion of children into an all-age study of HP, as in adults the same questions are unanswered.

PMID:34048641 | DOI:10.1002/ppul.25513

Invest New Drugs. 2021 May 28. doi: 10.1007/s10637-021-01136-z. Online ahead of print.

ABSTRACT

Background Immune-related hepatotoxicity is often regarded as immune-related hepatitis (irHepatitis) despite including immune-related sclerosing cholangitis (irSC). This study examined the clinical differences between irSC and irHepatitis. Methods A single-center retrospective study of 530 consecutive patients who received immunotherapy between August 2014 and April 2020 was performed. IrSC and irHepatitis were respectively defined as the radiological presence and absence of bile duct dilation and wall thickness. Results Forty-one patients (7.7%) developed immune-related hepatotoxicity. A CT scan was performed on 12 patients, including 11 of 12 with ≥ grade 3 aminotransferase elevations. IrSC and irHepatitis were diagnosed in 4 (0.8%) and 8 (1.5%) patients, respectively. All the irSC patients had been treated with anti-PD-1. IrHepatitis was more common among patients receiving anti-CTLA-4 than among those receiving anti-PD-1/PD-L1 inhibitors (14%, 7/50 vs. 0.2%, 1/480, P < 0.001). A ≥ grade 2 alkaline phosphatase (ALP) elevation resulting in a cholestatic pattern was seen in all 4 irSC patients. Among the irSC patients, 3 (3/4, 75%) developed ≥ grade 3 aminotransferases elevation. The median duration from the start of immunotherapy until ≥ grade 2 liver enzymes elevation was 257 and 55.5 days in irSC and irHepatitis patients. The median times for progression from grade 2 to 3 liver enzyme elevation were 17.5 and 0 days, respectively. Conclusions IrSC and irHepatitis have different characteristics in the class of immune checkpoint inhibitor and onset pattern. Radiological examination for the diagnosis of irSC should be considered for patients with ≥ grade 2 ALP elevation resulting in a cholestatic pattern. (Registration number J2020-36, Date of registration June 3, 2020).

PMID:34046801 | DOI:10.1007/s10637-021-01136-z

Front Neurol. 2021 May 11;12:669493. doi: 10.3389/fneur.2021.669493. eCollection 2021.

ABSTRACT

Introduction: Anti-PD1 agents are widely used in the treatment of solid tumors. This has prompted the recognition of a class of immune-related adverse events (irAEs), due to the activation of autoimmune T-cells. Pembrolizumab is an anti-PD1 agent, which has been related to an increased risk of various neurological irAE (n-irAEs). Here, we present a rare case of pembrolizumab-induced neuropathy of cranial nerves. Case Report: A 72-year-old patient was diagnosed with a lung adenocarcinoma in February 2018 (EGFR-, ALK-, and PDL1 90%). According to the molecular profile, pembrolizumab was started. After three administrations, the patient developed facial paresis, ptosis, ophthalmoplegia, and dysphonia. As brain metastases and paraneoplastic markers were excluded, a drug-related disorder was suspected and pembrolizumab was discontinued. A nerve conduction study and electromyography excluded signs of neuropathy and myopathy at four limbs, and repetitive nerve stimulation was negative. However, altered blink reflex and nerve facial conduction were consistent with an acute neuropathy of the cranial district. Thus, the patient was treated with two cycles of intravenous immunoglobulins (IVIg), which rapidly allowed improvement of both symptoms and neurophysiological parameters. However, the patient died in October 2018 for a progression of lung tumor. Discussion: Only 16 cases of pembrolizumab-related neuropathies have been described so far. Our case is of particular interest for the isolated involvement of cranial nerves and the prompt response to IVIg. Conclusion: N-irAEs are insidious conditions that require solid knowledge of onco-immunotherapy complications: it is mandatory not to delay any treatment that would potentially modify the course of a neurological complication.

PMID:34046006 | PMC:PMC8144636 | DOI:10.3389/fneur.2021.669493

Mol Cancer Ther. 2021 May 27:molcanther.0014.2020. doi: 10.1158/1535-7163.MCT-20-0014. Online ahead of print.

ABSTRACT

MEDI4276 is a biparatopic tetravalent antibody targeting 2 nonoverlapping epitopes in subdomains 2 and 4 of the HER2 ecto-domain, with site-specific conjugation to a tubulysin-based microtubule inhibitor payload. MEDI4276 demonstrates enhanced cellular internalization and cytolysis of HER2+ tumor cells in vitro. This was a first-in-human, dose-escalation clinical trial in patients with HER2+ advanced or metastatic breast cancer (BC) or gastric cancer. MEDI4276 doses escalated from 0.05-0.9 mg/kg (60-90-minute IV infusion Q3W). Primary endpoints were safety and tolerability; secondary endpoints included antitumor activity (objective response, progression-free survival, and overall survival), pharmacokinetics, and immunogenicity. Forty-seven patients (median age 59 years; median of 7 prior treatment regimens) were treated. The maximum tolerated dose was exceeded at 0.9 mg/kg with 2 patients experiencing dose-limiting toxicities (DLT) of grade 3 liver function test (LFT) increases, 1 of which also had grade 3 diarrhea, which resolved. Two additional patients reported DLTs of grade 3 LFT increases at lower doses (0.4 and 0.6 mg/kg). The most common (all grade) drug-related adverse events (AEs) were nausea (59.6%), fatigue (44.7%), aspartate aminotransferase (AST) increased (42.6%), and vomiting (38.3%). The most common grade 3/4 drug-related AE was AST increased (21.3%). Five patients had drug-related AEs leading to treatment discontinuation. In the as-treated population, there was 1 complete response (0.5 mg/kg; BC), and 2 partial responses (0.6 and 0.75 mg/kg; BC)-all had prior trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1). MEDI4276 has demonstrable clinical activity but displays intolerable toxicity at doses >0.3 mg/kg.

PMID:34045233 | DOI:10.1158/1535-7163.MCT-20-0014

BMC Med Inform Decis Mak. 2021 May 26;21(1):171. doi: 10.1186/s12911-021-01518-6.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADRs) are statistically characterized within randomized clinical trials and postmarketing pharmacovigilance, but their molecular mechanism remains unknown in most cases. This is true even for hepatic or skin toxicities, which are classically monitored during drug design. Aside from clinical trials, many elements of knowledge about drug ingredients are available in open-access knowledge graphs, such as their properties, interactions, or involvements in pathways. In addition, drug classifications that label drugs as either causative or not for several ADRs, have been established.

METHODS: We propose in this paper to mine knowledge graphs for identifying biomolecular features that may enable automatically reproducing expert classifications that distinguish drugs causative or not for a given type of ADR. In an Explainable AI perspective, we explore simple classification techniques such as Decision Trees and Classification Rules because they provide human-readable models, which explain the classification itself, but may also provide elements of explanation for molecular mechanisms behind ADRs. In summary, (1) we mine a knowledge graph for features; (2) we train classifiers at distinguishing, on the basis of extracted features, drugs associated or not with two commonly monitored ADRs: drug-induced liver injuries (DILI) and severe cutaneous adverse reactions (SCAR); (3) we isolate features that are both efficient in reproducing expert classifications and interpretable by experts (i.e., Gene Ontology terms, drug targets, or pathway names); and (4) we manually evaluate in a mini-study how they may be explanatory.

RESULTS: Extracted features reproduce with a good fidelity classifications of drugs causative or not for DILI and SCAR (Accuracy = 0.74 and 0.81, respectively). Experts fully agreed that 73% and 38% of the most discriminative features are possibly explanatory for DILI and SCAR, respectively; and partially agreed (2/3) for 90% and 77% of them.

CONCLUSION: Knowledge graphs provide sufficiently diverse features to enable simple and explainable models to distinguish between drugs that are causative or not for ADRs. In addition to explaining classifications, most discriminative features appear to be good candidates for investigating ADR mechanisms further.

PMID:34039343 | PMC:PMC8157660 | DOI:10.1186/s12911-021-01518-6

Sci Rep. 2021 May 26;11(1):11022. doi: 10.1038/s41598-021-90551-6.

ABSTRACT

The novel coronavirus outbreak began in late December 2019 and rapidly spread worldwide, critically impacting public health systems. A number of already approved and marketed drugs are being tested for repurposing, including Favipiravir. We aim to investigate the efficacy and safety of Favipiravir in treatment of COVID-19 patients through a systematic review and meta-analysis. This systematic review and meta-analysis were reported in accordance with the PRISMA statement. We registered the protocol in the PROSPERO (CRD42020180032). All clinical trials which addressed the safety and efficacy of Favipiravir in comparison to other control groups for treatment of patients with confirmed infection with SARS-CoV2 were included. We searched electronic databases including LitCovid/PubMed, Scopus, Web of Sciences, Cochrane, and Scientific Information Database up to 31 December 2020. We assessed the risk of bias of the included studies using Cochrane Collaboration criteria. All analyses were performed using the Comprehensive Meta-Analysis software version 2, and the risk ratio index was calculated. Egger and Begg test was used for assessing publication bias. Nine studies were included in our meta-analysis. The results of the meta-analysis revealed a significant clinical improvement in the Favipiravir group versus the control group during seven days after hospitalization (RR = 1.24, 95% CI: 1.09-1.41; P = 0.001). Viral clearance was more in 14 days after hospitalization in Favipiravir group than control group, but this finding marginally not significant (RR = 1.11, 95% CI: 0.98-1.25; P = 0.094). Requiring supplemental oxygen therapy in the Favipiravir group was 7% less than the control group, (RR = 0.93, 95% CI: 0.67-1.28; P = 0.664). Transferred to ICU and adverse events were not statistically different between two groups. The mortality rate in the Favipiravir group was approximately 30% less than the control group, but this finding not statistically significant. Favipiravir possibly exerted no significant beneficial effect in the term of mortality in the general group of patients with mild to moderate COVID-19. We should consider that perhaps the use of antiviral once the patient has symptoms is too late and this would explain their low efficacy in the clinical setting.

PMID:34040117 | PMC:PMC8155021 | DOI:10.1038/s41598-021-90551-6

Stud Health Technol Inform. 2021 May 27;281:1110-1111. doi: 10.3233/SHTI210368.

ABSTRACT

As social media are an interesting source of information for pharmacovigilance, we implemented a novel visualisation method for pharmacovigilance specialists applied to French discussion forums. A word embedding model was trained on posts to facilitate the identification of patterns associated with adverse drug reactions.

PMID:34042861 | DOI:10.3233/SHTI210368

Stud Health Technol Inform. 2021 May 27;281:1089-1090. doi: 10.3233/SHTI210358.

ABSTRACT

Clinical Decision Support Systems (CDSS) could play a prominent role in preventing Adverse Drug Reactions (ADRs) especially when integrated in larger healthcare systems (e.g. Electronic Health Record - EHR systems, Hospital Management Systems - HMS, e-Prescription systems etc.). This poster presents an approach to model Therapeutic Prescription Protocols (TPPs) via the Business Process Management Notation (BPMN), as part of the e-Prescription CDSS developed in the context of the PrescIT project.

PMID:34042851 | DOI:10.3233/SHTI210358

Korean J Intern Med. 2021 May 28. doi: 10.3904/kjim.2021.210. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: This study aimed to assess the association between local and systemic reactogenicity and humoral immunogenicity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination.

METHODS: Adverse events were prospectively evaluated using an electronic diary in 135 healthy adults who received a SARS-CoV-2 vaccine (AZD1222, AstraZeneca/Oxford, n = 42; or BNT162b2, Pfizer/BioNTech, n = 93). We semi-quantitatively measured anti-S1 immunoglobulin G (IgG) using an enzyme-linked immunosorbent assay at baseline, 3 weeks after the first dose of AZD1222 or BNT162b2, and 2 weeks after the second dose of BNT162b2. We evaluated the association between the maximum grade of local or systemic adverse events and the anti-S1 IgG optical density using multivariate linear regression with adjustment for age, sex, and use of antipyretics.

RESULTS: The median age of the 135 vaccinees was 30 years (36 years in the AZD1222 group and 29 years in the BNT162b2 group) and 25.9% were male (9.5% in the AZD1222 group and 33.3% in the BNT162b2 group). Local and systemic adverse events were generally comparable after the first dose of AZD1222 and the second dose of BNT162b2. The grades of local and systemic adverse events were not significantly associated with anti-S1 IgG levels in the AZD1222 or BNT162b2 group.

CONCLUSIONS: Local and systemic reactogenicity may not be associated with humoral immunogenicity after SARS-CoV-2 vaccination.

PMID:34038996 | DOI:10.3904/kjim.2021.210

J Emerg Med. 2021 May 22:S0736-4679(21)00187-6. doi: 10.1016/j.jemermed.2021.03.002. Online ahead of print.

ABSTRACT

BACKGROUND: Sulfhemoglobinemia is a rare dyshemoglobinemia that presents similarly to methemoglobinemia.

CASE REPORT: An 83-year-old woman with stage IV ovarian cancer presented to the Emergency Department after a near syncopal spell and was found to be cyanotic with a pulse oximetry reading of 71%. Pulse oximetry improved to only the mid-80s range with administration of high-flow oxygen. Her arterial blood gas on supplemental high-flow oxygen demonstrated a PaO2 of 413 mm Hg and methemoglobin of 1.2%, but also noted the interference of the co-oximetry with sulfhemoglobinemia. Further history revealed that the patient had recently been started on phenazopyridine. The phenazopyridine was stopped, an exchange transfusion was offered but declined, and the patient was discharged to home hospice. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The diagnosis of sulfhemoglobinemia can be challenging given that routine co-oximetry does not identify it. The clue to the diagnosis is that the cyanotic-appearing patient has a normal or elevated PaO2 and seems to be less ill than expected, given the degree of cyanosis. Sulfhemoglobinemia does not reverse with the administration of methylene blue.

PMID:34034895 | DOI:10.1016/j.jemermed.2021.03.002

Zhonghua Yu Fang Yi Xue Za Zhi. 2021 May 6;55(5):574-582. doi: 10.3760/cma.j.cn112150-20210317-00265.

ABSTRACT

Adverse drug reactions are often encountered in the process of medication and are quite troublesome for clinicians. Skin is one of the most frequently affected organs by adverse drug reactions. Adverse drug reactions involving skin are called "drug-induced dermatitis" or "drug eruption". In some rare instances, drug eruption can be severe and life-threatening which is known as severe cutaneous adverse drug reaction. However, due to the mixed use of drugs, it is difficult to identify the culprit drug, which makes multiple drugs needed to be avoided. Recently, many studies have found that HLA alleles are closely related to the certain culprit drug. HLA genotyping before administration can significantly reduce the incidence of severe cutaneous adverse drug reaction related to certain drugs. Since limited HLA alleles are found, HLA genotyping can only prevent adverse drug reaction to a limited extent. At present, drug provocation tests are regarded as the "gold standard" to identify the culprit drug. However, this diagnostic program has not been widely developed because of the high risk. In addition, a variety of in vivo and in vitro diagnostic methods (including drug patch test, drug skin test, drug specific IgE test, basophil activation test, lymphocyte transformation test, et al) also provide evidences to identify the culprit drug.

PMID:34034396 | DOI:10.3760/cma.j.cn112150-20210317-00265