Intravenous versus Oral iron for Iron-Deficiency Anemia in Pregnancy (IVIDA): A Randomized Controlled Trial

Objective Iron-deficiency anemia (IDA) can have serious consequences for mothers and babies. Iron supplementation is recommended, but the administration route is controversial. We sought to conduct a randomized controlled trial (RCT) testing the effectiveness and safety of intravenous (IV) iron compared with oral iron on perinatal outcomes in pregnant women with IDA. Study Design This open-label RCT randomized patients with IDA (hemoglobin [hgb] <10 g/dL and ferritin <30 ng/mL) at 24 to 34 weeks' to oral iron or single 1,000-mg dose of IV low-molecular weight iron dextran over one hour. The primary outcome was maternal anemia at delivery (hgb < 11 g/dL). Secondary outcomes were mild/moderate or severe adverse reactions, maternal hgb and ferritin at delivery, blood transfusion, gestational age at delivery, birth weight, neonatal hgb and ferritin, and composite neonatal morbidity. Analysis was as per protocol. Results The trial was stopped early for logistical reasons, and the data analyzed as preliminary data to inform a larger, potentially externally funded, definitive trial. Of 55 patients approached, 38 consented. Of these, 15 were withdrawn: 5 received IV iron from their primary obstetrician after being randomized to oral iron and 10 declined to receive IV iron. Of the remaining 23 patients, who were included in the analytic population, 13 received oral iron and 10 received IV iron. The rate of maternal anemia at delivery (hgb < 11 g/dL) was high overall but significantly reduced with IV iron (40 vs. 85%, p = 0.039). Rates of maternal hgb < 10 g/dL were significantly lower in the IV iron group (10 vs. 54%, p = 0.029). There were no severe adverse reactions and similar rates of mild/moderate reactions between groups. Conclusion IV iron reduces rates of anemia at the time of admission for delivery, supporting a larger RCT comparing IV versus oral iron for the treatment of IDA of pregnancy powered for definitive clinical outcomes. However, issues uncovered in this RCT suggest that patient, clinician, and systems-level barriers associated with different IDA treatment modalities must be considered prior to conducting a larger RCT. This study is registered with clinicaltrials.gov with identifier no.: NCT03438227. Key Points

Nitrofurantoin-induced agranulocytosis

Idiosyncratic drug-induced agranulocytosis is a rare life-threatening adverse reaction characterised by an absolute neutrophil count <500 cells/μL of blood. Nitrofurantoin has been associated with haematological adverse events, but few agranulocytosis cases worldwide have been reported. We present a case of a 68-year-old woman who presented with fever and agranulocytosis following treatment with nitrofurantoin. Extensive workup for agranulocytosis, including a bone marrow aspirate, was unremarkable. Treatment with nitrofurantoin was discontinued, which led to a complete recovery of the complete blood count. This case stresses the importance of monitoring treatments, given that widely used drugs are not free from severe adverse reactions.

A systematic review and meta-analysis of the use of succinylcholine to facilitate tracheal intubation in neonates

Use of succinylcholine in neonates is surrounded by many controversies. The need to review this topic stems from the fact that though there is an abundance of information, but there are divergent views regarding its use in neonates. We have analyzed the incidence of intubation attempts, bradycardia, and hemodynamic changes in clinical settings.The authors conducted a meta-analysis and systematic literature search to ascertain the risks and benefits of using succinylcholine in neonatal intubation by conducting a review in the online databases of PubMed, Cochrane, Scopus, Embase, Elsevier, and Google scholar. The combination of keywords used for the search included “Succinylcholine,” “succinylcholine” AND “neonates,” “neonates” AND “difficult airway,” “neuromuscular blockers” AND “neonates,” and “non-depolarizing neuromuscular blockers” AND “neonates”. The severe adverse reactions associated with use of succinylcholine include bradycardia, asystole, hyperkalemia, and apnea. The number of attempts required for intubation was significantly lower in the patients receiving succinylcholine as compared to those who did not receive succinylcholine. Evidence suggests that conscious awake intubation leads to adverse physiological responses in neonates. The main recommended indications for using succinylcholine include emergency intubation in laryngospasm, full stomach, difficult airway, absent intravenous access, and controlled endotracheal intubation in the neonatal intensive care unit. Hence, the use of succinylcholine can be rationally accepted after considerations of the pre-operative clinical status of the neonate and risk-benefit ratio with more research further to build up strong evidence for the most appropriate agents for use in neonatal patients.

Association between Reactogenicity and Immunogenicity after Vaccination with BNT162b2

It is not clear whether there is an association between adverse reactions and immune response after vaccination. Seven hundred and thirty-five vaccinees from our University Medical Center vaccination clinic provided information about sex, age and adverse reactions after first and second vaccination with BNT162b2. Adverse reactions were categorized into three groups: no or minor on the injection side, moderate (not further classified) and severe—defined as any symptom(s) resulting in sick leave. We chose 38 vaccinees with the most severe adverse reactions and compared their humoral and T-cell-mediated immune responses after second vaccination with those of 38 sex and age matched controls without or only minor injection-side related adverse reactions. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-receptor binding domain (RBD) IgG titers were detectable in all participants (median 5528; range 958–26,285). Men with severe adverse reactions had 1.5-fold higher median SARS-CoV-2 RBD IgG titers compared to men without adverse reactions (median 7406 versus 4793; p < 0.001). Similarly; neutralization activity was significantly higher in men with severe adverse reactions (half maximal inhibitory concentrations (IC50) median 769 versus 485; p < 0.001). Reactogenicity did not influence humoral immune response in women nor T-cell-mediated immune response in any sex. To conclude; adverse reactions after vaccination with BNT162b2 do influence humoral immune response yet only in men and are not a prerequisite for a robust antibody response.

Safety and Side Effects of COVID-19 Vaccines

Introduction: COVID-19 is a respiratory disease caused by the SARS-CoV-2 virus. The types of COVID-19 vaccines have been distinguished, ie vector viral vaccines, mRNA, subunit vaccines. These include traditional approaches - inactivated, live-attenuated and protein / adjuvant-based, as well as novel, as yet unlicensed - viral vectors and nucleic acids. There are scientific publications showing the safety and possible side effects of vaccines from various companies. Purpose of the work : Analysis of the safety of COVID-19 vaccines on the basis of scientific publications published on the PubMed scientific platform. Publications have been published in the last 12 months. The safety and adverse effects of vaccines were assessed in the course of clinical trials. Results: Among the main side effects so far were mild / moderate pain at the injection site, redness, hives and rash. Allergic reactions to vaccines are - apart from pronounced local reactions (> 10 cm) at the injection site - very rare and are usually caused by the vaccine's allergy to the components of the vaccine. In addition, there may be swelling or tenderness of the lymph nodes in the armpit, headache, pain in the muscles and joints, nausea and vomiting. Conclusions: Regardless of the concern, these vaccines are characterized by similar mild, systemic side effects, which indicates the similarity in the safety of these vaccines. Severe adverse reactions occur in extreme cases. More patients only experienced side effects after the second dose. Keywords: vaccines; coronavirus; COVID-19; safety of COVID-19 vaccines; side effects

Importance of NUDT15 Polymorphisms in Thiopurine Treatments

Thiopurines, mercaptopurine, and azathioprine are used as immunosuppressants in the treatments of inflammatory bowel disease, rheumatoid arthritis, and organ transplantation and as chemotherapeutic drugs for the treatment of acute leukemia and chronic myeloid leukemia. This drug class sometimes causes severe adverse reactions, including bone marrow suppression and hair loss. Genetic polymorphisms of the metabolizing enzyme thiopurine S-methyltransferase have been used for predicting these reactions in Caucasians, but these allele frequencies are less frequently observed in Asian populations. Recently, nudix hydrolase 15 (NUDT15) polymorphisms have been shown to play an important role in thiopurine-induced adverse reactions in Asians. In this review, we summarize the NUDT15 studies, mainly in Asian countries, and their implementation in several countries.

Immunogenicity and efficacy of heterologous ChadOx1/BNT162b2 vaccination

Following severe adverse reactions in patients vaccinated with the AstraZeneca ChadOx1 (Chad) vaccine, European health authorities have recommended that patients under the age of 55 who received one dose of Chad vaccine receive a second dose of Pfizer BNT162b2 (BNT) vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here, we show that the heterologous Chad/BNT combination confers better protection against SARS-CoV-2 infection than the homologous BNT/BNT combination in a population of health care workers. To understand the underlying mechanism, we monitored in a longitudinal way the anti-spike immunity conferred by each vaccinal combination. Both combinations induced strong anti-spike antibody responses after boost in all vaccinated individuals. However, sera from heterologous vaccinated individuals displayed a stronger neutralizing activity, regardless of the SARS-CoV-2 variant analyzed, and this was associated with more switched memory RBD-specific B cells with an activated phenotype and less IgA. The Chad vaccine induced a stronger T cell response than the BNT vaccine after the priming dose, and the reciprocal was true for the IgG response, which could explain the complementarity of both vaccines when used in an heterologous setting. This strongly protective vaccination regimen could be therefore particularly suitable for immunocompromised individuals.

SARS-CoV-2 Vaccination and Anaphylaxis: Recommendations of the French Allergy Community and the Montpellier World Health Organization Collaborating Center

Vaccines against COVID-19 (and its emerging variants) are an essential global intervention to control the current pandemic situation. Anaphylactic reactions have been reported after SARS-CoV2 RNA vaccines. Anaphylaxis is defined as a severe life-threatening generalized or systemic hypersensitivity reaction. This risk is estimated at 1/1,000,000 in the context of vaccine safety surveillance programs. The COVID-19 vaccination is rolling-out vastly in different courtiers and surveillance programs are key to monitor severe adverse reactions, such as anaphylaxis. Anaphylaxis due to vaccine is extremely rare and specific cases should receive individualized investigation and care. The here presented recommendations and follow-up from the French allergy community and the Montpellier WHO Collaborating Center in order to support the vaccination program and intends to support to healthcare professionals in their daily basis.

New Clinical Applications-sintilimab Combined with Albumin-bound Paclitaxel/cisplatin in Treatment of Relapsed or Refractory ES-SCLC

Introduction: This study is aimed to evaluate the efficacy and safety of sintilimab combined with albumin-bound paclitaxel/ cisplatin as a second-line treatment in these patients with relapsed or refractory extensive-stage small cell lung cancer (ES-SCLC). Methods and Materials: ES-SCLC patients received a second-line regimen of sintilimab combined with albumin-bound paclitaxel/cisplatin. Albumin-bound paclitaxel/cisplatin can be used for up to 6 cycles. Sintilimab use was not stopped until the disease progressed or untolerable side effects occurred. After 2 cycles of chemotherapy or when the patient's condition progressed significantly, computed tomography was rechecked to observe the clinical curative effect and adverse reactions. Results: Totally 38 patients with recurrent SCLC were included for efficacy evaluation. The objective response rate and disease control rate were 26.3% and 84.2% respectively. The median PFS and OS were 6.5 months (95% CI: 3.8-7.8) and 10.8 months (95% CI: 8.5-16.2), respectively. The main adverse reactions are bone marrow suppression, alopecia, peripheral neurotoxicity, muscle and joint pain, gastrointestinal reactions, and fatigue. The severe adverse reactions (grade 3-4) are mainly leukopenia (21.1%), neutropenia (21.1%) and decreased hemoglobin (7.9%). No significant correlation was found between PD-L1 expression and efficacy.Conclusion: Sintilimab combined with albumin-bound paclitaxel/cisplatin has a positive effect on the treatment of ES-SCLC, and the adverse reactions are tolerable.