Anaphylaxis associated with the mRNA COVID-19 vaccines: Approach to allergy investigation.

Reports about cases of anaphylaxis to mRNA vaccines have created anxiety in the community and could increase vaccine hesitancy in the population. There are no standardized protocols for allergy testing to mRNA vaccines. PEG is currently the only excipient in both vaccines with recognized allergenic potential. Allergy to PEG has been reported with increasing frequency over recent years, often in patients who had repeated systemic allergic reactions/anaphylaxis to several classes of drugs before diagnosis. Proposed protocols are based on current knowledge about potential mechanisms of anaphylaxis associated with the mRNA vaccines, and the assumption that polyethylene glycol (PEG) is the most likely culprit. Allergy testing to PEGs and mRNA vaccines is complex and carries the risk of anaphylaxis and should be conducted in a specialist drug allergy center. Appropriate PEG-free emergency medical treatment and supervision should be readily available.

Choline elevation in amygdala region at recovery indicates longer survival without depressive episode: a magnetic resonance spectroscopy study.

RATIONALE: Depression, with variable longitudinal patterns, recurs in one third of patients. We lack useful predictors of its course/outcome, and proton magnetic resonance spectroscopy (1H-MRS) of brain metabolites is an underused research modality in finding outcome correlates. OBJECTIVES: To determine if brain metabolite levels/changes in the amygdala region observed early in the recovery phase indicate depression recurrence risk in patients receiving maintenance therapy. METHODS: Forty-eight patients on stable-dose antidepressant (AD) maintenance therapy were analyzed from recovery onset until (i) recurrence of depression or (ii) start of AD discontinuation. Two 1H-MRS scans (6 months apart) were performed with a focus on amygdala at the beginning of recovery. N-acetylaspartate (NAA), choline-containing metabolites (Cho), and Glx (glutamine/glutamate and GABA) were evaluated with regard to time without recurrence, and risks were assessed by Cox proportional hazard modeling. RESULTS: Twenty patients had depression recurrence, and 23 patients reached AD discontinuation. General linear model repeated measures analysis displayed three-way interaction of measurement time, metabolite level, and recurrence on maintenance therapy, in a multivariate test, Wilks' lambda = 0.857, F(2,40) = 3.348, p = 0.045. Cho levels at the beginning of recovery and subsequent changes convey the highest risk for earlier recurrence. Patients experiencing higher amygdala Cho after recovery are at a significantly lower risk for depression recurrence (hazard ratio = 0.32; 95% confidence interval 0.13-0.77). CONCLUSION: Cho levels/changes in the amygdala early in the recovery phase correlate with clinical outcome. In the absence of major NAA fluctuations, changes in Cho and Glx may suggest a shift towards reduction in (previously increased) glutamatergic neurotransmission. Investigation of a larger sample with greater sampling frequency is needed to confirm the possible predictive role of metabolite changes in the amygdala region early in the recovery phase.

Choline and N-acetyl aspartate levels in the dorsolateral prefrontal cortex at the beginning of the recovery phase as markers of increased risk for depressive episode recurrence under different duration of maintenance therapy and after it: a retrospective cohort study.

AIM: To evaluate the relationship between the dynamics of proton magnetic resonance spectroscopy (1H-MRS) brain metabolite levels at the beginning of the recovery phase of the index depressive episode and the time to the recurrence of depression. METHODS: This retrospective cohort study analyzed the changes in N-acetyl aspartate (NAA), choline (Cho), and glutamate-glutamine in 48 patients with recurrent depression treated with maintenance antidepressant monotherapy at a stable dose. 1H-MRS was performed at the start of the recovery phase and 6 months later. 1H-MRS parameters, index episode descriptors, and depressive disorder course were analyzed by Cox proportional hazards model. RESULTS: NAA and Cho decrease six months after the beginning of the recovery period were time-independent risk factors for depressive episode recurrence. Hazard ratio associated with NAA decrease was 2.02 (95% confidence interval 1.06-3.84) and that associated with Cho decrease was 2.06 (95% confidence interval 1.02-4.17). These changes were not related to symptoms severity, as Montgomery-Asberg Depression Scale score remained generally unchanged (mean -0.01; standard deviation 1.6) over the first 6 months of recovery. CONCLUSION: Patients receiving maintenance antidepressant therapy after recovery who experience a decrease in NAA or Cho levels early in the recovery phase have a double risk of depressive episode recurrence. Sustained NAA and Cho levels at the beginning of the recovery phase may indicate increased brain resilience conferred by antidepressant therapy, while NAA and Cho decrease may indicate only the trait-related temporal effect of therapy in another stratum of patients.

Warfarin Dosing According to the Genotype-guided Algorithm is Most Beneficial in Patients With Atrial Fibrillation: A Randomized Parallel Group Trial.

BACKGROUND: Observational studies have indicated potential benefits of CYP2C9- and VKORC1-guided dosing of warfarin but randomized clinical trials have resulted in contradictory findings. One of the reasons for contradiction may be the negligence of possible differences between warfarin indications. This study aims to determine efficacy and safety of genotype-guided and clinically guided dosing of warfarin in atrial fibrillation (AF), deep-vein thrombosis (DVT), and pulmonary embolism (PE) within the first 5 days after the introduction of therapy. METHODS: In this single-center, single-blinded, randomized, controlled trial including patients of both sexes, ≥18 years of age, and diagnosed with AF, DVT, or PE, a total of 205 consecutive patients were allocated into the group where warfarin therapy was genotype-guided pharmacogenetics guided (PHG), and where it was adjusted according to the clinical parameters non pharmacogenetics guided (NPHG). Genotyping of CYP2C9*2, *3, and VKORC1 was performed using the real-time polymerase chain reaction method. The primary outcomes were the percentage of time in the therapeutic international normalized ratio (INR) (2.0-3.0) range and the percentage of patients who achieved a stable anticoagulation defined as the INR (2.0-3.0) range in at least 2 consecutive measurements. RESULTS: In patients with AF, the percentage of time spent in the therapeutic range of INR was higher in the PHG group [mean = 26% (SD 25.0)] than in the NPHG group [mean = 14% (SD 18.6)], [Δ = 12; 95% confidence interval, 0-23; P = 0.040]. There was no significant difference in other 2 indications for warfarin treatment. A stable dose of warfarin was achieved in a statistically higher number of patients in the PHG group 14/30 (47%) than in the NPHG group 7/32 (22%) (odds ratio = 3.13, 95% confidence interval, 0.92-10.98; P = 0.039). CONCLUSIONS: CYP2C9 and VKORC1 genotype-guided dosing of warfarin may be beneficial in patients diagnosed with AF. There is no evidence for such conclusion in patients with DVT and PE.

Hypersensitivity reactions to low molecular weight heparins: different patterns of cross-reactivity in 3 patients.

Low molecular weight heparins (LMWHs) are used for a variety of indications. The most common type of hypersensitivity reactions to LMWHs are delayed-type hypersensitivity reactions (DHR). Immediate-type hypersensitivity reactions (IHR) occur only sporadically. Cross-reactivity of different LMWHs is a common and unpredictable problem. We present 2 cases of patients who developed DHR to nadroparin and enoxaparin, respectively. The third case presents a patient who developed IHR to nadroparin. Skin tests confirmed the hypersensitivity in all cases. In the cases of DHR, a skin test negative LMWH was identified and was tolerated in a challenge test. In the IHR case, cross-reactivity to all tested LMWHs was established. We hypothesize that the degree of cross-reactivity might depend on the type of hypersensitivity reaction with immediate reactions linked to more extensive cross-reactivity than delayed reactions. This is important to consider because, at least in some cases, a safe alternative LMWH can be identified.

Lower Choline-Containing Metabolites/Creatine (Cr) Rise and Failure to Sustain NAA/Cr Levels in the Dorsolateral Prefrontal Cortex Are Associated with Depressive Episode Recurrence under Maintenance Therapy: A Proton Magnetic Resonance Spectroscopy Retrospective Cohort Study.

BACKGROUND: The aim of this study was to evaluate the relationship between changes in proton magnetic resonance spectroscopy (1H-MRS) parameters at the start of the index episode recovery phase and at recurrence in patients with recurrent depression who were treated with prolonged maintenance therapy. METHODS: 1H-MRS parameters were analyzed in 48 patients with recurrent depression who required maintenance therapy with antidepressant medication prescribed by a psychiatrist and who continued with the same antidepressant during the maintenance phase, either to recurrence of depression, completion of the 10-year observation period, or the start of the withdrawal phase (tapering-off antidepressant). N-acetylaspartate (NAA), choline-containing metabolites (Cho), creatine (Cr), and glutamine/glutamate were measured at the start of the recovery phase and 6 months later. RESULTS: Recurrent depressive episodes occurred in 20 patients. These individuals had a smaller increase in Cho/Cr after the beginning of the recovery phase compared to the non-recurrent patient group and also exhibited a decreased NAA/Cr ratio. CONCLUSION: Sustainable NAA and increased Cho levels at the onset of the recovery phase of the index episode are early markers of antidepressant effectiveness associated with a lower risk of major depressive disorder recurrence. The NAA and Cho changes in the non-recurrent group may be attributable to increased brain resilience, contrary to the transient temporal effect observed in subjects who experienced a depressive episode.