Association of HLA-DR11 with the anaphylactoid reaction caused by nonsteroidal anti-inflammatory drugs

BACKGROUND: Several HLA alleles have been associated with asthma induced by nonsteroidal anti-inflammatory drugs (NSAIDs). The existence of HLA markers linked to other NSAID-induced reactions, such as cutaneous and anaphylactoid reactions, has not been established. OBJECTIVE: The purpose of our work was to study the HLA-DRB1 and HLA-DQB1 alleles in patients with cutaneous and anaphylactoid reactions caused by NSAIDs. METHODS: We have analyzed 114 HLA DRB1 and 26 HLA-DQB1 alleles in 21 patients with anaphylactoid reactions caused by NSAIDs, 47 patients who had exclusively cutaneous reactions during single-blind, placebo-controlled oral challenges with NSAIDs, and 167 tolerant control subjects (29 of whom had also had an IgE-mediated anaphylaxis to different agents). HLA-DRB1 and HLA-DQB1 alleles were typed by the polymerase chain reaction sequence-specific primers method with genomic DNA. RESULTS: The frequency of HLA-DR11 alleles was 58.8% in the anaphylactoid reaction group, compared with 15.9% in the NSAID-tolerant healthy control subjects (OR, 7:3; 95% confidence interval, 2.8-19.0; P <.02) and 6.3% in the group of the patients with a tolerance for NSAIDs and with IgE-mediated anaphylaxis (OR, 18.75; 95% confidence interval, 4.3-81.1; P <.004). No differences were observed among HLA-DR11 alleles analyzed. There were no significant HLA-DQB1 associations with NSAID-induced anaphylactoid reactions. Patients with cutaneous reactions had HLA frequencies that did not differ significantly from the tolerant control subjects. CONCLUSION: The HLA-DRB1*11 alleles showed a positive association with NSAID-induced anaphylactoid reactions.     

COVID-19 Treatment: Drug Safety Prior to Conception and During Pregnancy and Breastfeeding

In December 2019, a new viral respiratory infection known as coronavirus disease 2019 (COVID-19) was first diagnosed in the city of Wuhan, China. COVID-19 quickly spread across the world, leading the World Health Organization to declare it a pandemic on March 11, 2020. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a similar virus to those involved in other epidemics such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Epidemiological studies have shown that COVID-19 frequently affects young adults of reproductive age and that the elderly and patients with chronic disease have high mortality rates. Little is known about the impact of COVID-19 on pregnancy and breastfeeding. Most COVID-19 cases present with mild flu-like symptoms and only require treatment with symptomatic relief medications, whereas other cases with COVID-19 require treatment in an intensive care unit. There is currently no specific effective treatment for COVID-19. A large number of drugs are being used to fight infection by SARS-CoV-2. Experience with this therapeutic arsenal has been gained over the years in the treatment of other viral, autoimmune, parasitic, and bacterial diseases. Importantly, the search for an effective treatment for COVID-19 cannot expose pregnant women infected with SARS-CoV-2 to the potential teratogenic risks of these drugs. Therefore, it is necessary to determine and understand the safety of anti-COVID-19 therapies prior to conception and during pregnancy and breastfeeding.Key words: COVID-19, SARS-CoV-2, antiviral, pregnancy, breastfeeding     

Personality and clinical predictors of recurrence of depression

OBJECTIVE: To help clinicians more accurately predict outcomes of treatment for depression, variables associated with recurrence of depression in the year after treatment were examined in a group of patients who completed treatment for an index episode of depression. METHODS: Forty-two depressed patients who participated in a double-blind pharmacological treatment study were followed for one year after treatment was discontinued. Length of treatment for the index episode was determined by clinicians and ranged from eight to 76 consecutive weeks. Eighteen patients who had a recurrent episode (43 percent) and 24 patients who did not (57 percent) were compared on sociodemographic and clinical variables, including scores on the Eysenck Personality Questionnaire (EPQ). RESULTS: A combination of three variables predicted recurrence of depression in 90 percent of cases. They were an elevated EPQ score on the neuroticism subscale, a short duration of treatment of the index episode, and a slow onset of response to treatment of the index episode. CONCLUSIONS: The findings suggest that personality traits, treatment duration, and variations in response to treatment might have an impact on long-term treatment outcome. Clinicians should consider these factors when making treatment decisions for depressed patients.     

Ascaris–Trichuris association and malnutrition in Brazilian children

This work was designed to evaluate the role of intestinal parasites on nutritional status in three rural areas of Brazil. A total of 520 children aged 1–12 years were studied through a questionnaire concerning housing, socio-economic conditions and a 24-h food intake recall. Measurements of weight and height were also performed, and three stool samples were collected on consecutive days for parasitological analysis. Scores of the standard deviation (z-scores) for the weight-for-height and height-for-age were used to characterise the growth profile. A high prevalence of intestinal parasites was detected, with Giardia lamblia (44%), Endolimax nana (43%), Ascaris lumbricoides (41%) and Trichuris trichiura (40%) being the most prevalent. Eleven per cent of the children were classified as showing stunting. Inadequate daily caloric intake was observed in 78% of the population and the proportion of those with inadequate protein intake was 34%. Logistic regression analysis was employed for the multivariate study. Stunting was significantly associated with estimators of low economic income, inadequate protein intake and polyparasitism, especially the association between Ascaris lumbricoides and Trichuris trichiura .     

Quantifying excess length of postoperative stay attributable to infections: a comparison of methods

To quantify the net effect of deep surgical site infection (DSSI) on postoperative stay (POS) among patients who had undergone open heart surgery, and to assess the comparability of two methods, two observational studies were conducted: one on a retrospective cohort of 701 operated patients, and the other on a cohort of 31 infected patients versus a cohort of uninfected patients, with 1:1 matching. In addition to DSSI, a further three factors were identified by multivariate analysis as independent POS-related predictor variables. After internal validation of the multivariate model, excess POS attributable to DSSI amounted to 20.7 days (95% confidence interval [CI] 16.7–24.9). In contrast, excess length of stay attributable to DSSI among the matched pairs who survived infection (22) totaled 14.3 days (95% CI 3.2–25.4) and 26.5 days (mean and median differences). Multivariate techniques may prove a more appropriate and reliable analysis than matched-pair comparisons for the purpose of evaluating the extra stay and cost attributable to the nosocomial infections.     

Proportion of mortality caused by severe hospital-acquired infection in open-heart surgery

OBJECTIVE: To investigate severe hospital-acquired infection as an independent risk factor for in-hospital mortality and the proportion of mortality caused by severe hospital-acquired infections in patients under going open-heart surgery. SETTING: A 1,300-bed teaching hospital in Spain. METHODS: A retrospective cohort study of 702 patients who underwent open-heart surgery procedures between January 1989 and December 1991. The mean age was 57 years, and 68% of the subjects were men. Of the 702 patients, 42% underwent a valve operation, 41% had coronary artery bypass grafting, 4% had both a valve operation and coronary artery bypass grafting, 5% underwent repair of congenital heart disease, and 8% had other surgical procedures. RESULTS: The cumulative incidence of severe hospital infection was 16.8%. The overall mortality rate was 5.4%. The mortality risk was 5.15 times higher in nosocomially infected patients than in uninfected patients. In addition, univariate analysis revealed up to 18 perioperative variables associated with in-hospital mortality. By multiple logistic regression, we identified four factors that independently predicted increased risk of mortality: preoperative New York Heart Association functional class level IV; long duration of cardiopulmonary bypass; low cardiac output syndrome; and severe hospital-acquired infection. The proportion of mortality caused by severe hospital-acquired infection in the cohort was 31.1%. CONCLUSIONS: Severe hospital-acquired infection is a principal factor in in-hospital mortality. One third of all deaths are caused by infection. Major efforts should be devoted to the prevention and control of severe nosocomial infections in open-heart surgery patients to prevent mortality.     

Polyclonal 111In-IgG, 125I-LDL and 125I-endothelin-1 accumulation in experimental arterial wall injury

To test iodine-125 labelled low-density lipoprotein (¹²⁵I-LDL), polyclonal indium-111 labelled immunoglobulin G (¹¹¹In-IgG) and iodine-125 labelled endothelin-1 uptake in metabolically active atheromatous plaques after arterial wall injury, we performed balloon de-endothelialization of carotid arteries or abdominal aortas in 24 New Zealand male rabbits which were fed with a normal diet (n=14) or a hypercholesterolaemic diet (n=10) after surgery. Six weeks later the animals were injected with 200 Ci of (¹²⁵I-LDL), and/or with 100 Ci of ¹¹¹In-IgG or with 9 Ci of ¹²⁵I-endothelin-1. Forty-eight hours later the animals were sacrificed. Carotid arteries and aortas were removed, counted and fixed for autoradiography and light microscopy examination. Contralateral carotid arteries and thoracic aortas served as controls.Significant ¹¹¹In-IgG uptake was observed in the injured arteries at autoradiography, with localization mainly in the healing edges, and at well counting. The percentage of the injected dose per gram (%D.inj/g) was 0.0188±0.06 versus 0.0059±0.003 in controls (P< 0.05). There was no difference in ¹¹¹In-IgG uptake between arteries with injury alone and those with active atheroma formation at the site of the injury. Significant (¹²⁵I-LDL), uptake was observed only when lipid deposition was present at light microscopy (%D.inj/g of 0.0024±0.0005 vs 0.0010±0.0003 in controls, P < 0.05). ¹²⁵I-endothelin-1 accumulation was observed in four of five injured aortas both at autoradiography, with diffuse localization, and at well counting (%D.inj/g of 0.0012±0.0004 in the abdominal aortas vs 0.0008±0.0003 in the thoracic aortas).Polyclonal IgG may accumulate in injured arteries without active atheroma formation. Inflammatory reaction at the site of the injury may cause ¹¹¹In-IgG uptake independently of atheromatous plaque formation. LDL accumulation takes place only with active atheroma formation at the site of the injury. Use of labelled peptides such as endothelin-1 may provide further insight into the mechanisms of atheromatous plaque formation.