Acute infectious supraglottitis in adult population: epidemiology, management, outcomes and predictors of airway intervention.

PURPOSE: The purpose is to analyze the incidence of acute infectious supraglottitis in our center between 2010 and 2020, define the characteristics and trends of those patients and identify factors associated with the need of airway intervention. METHODS: A retrospective single-center observational study of a cohort of patients diagnosed with acute infectious supraglottitis between January 2010 and December 2020. Patients were stratified according to airway management. RESULTS: Eighty eight patients were included: 59 men (67%) and 29 women (33%). A significant upward trend of 9% in the annual incidence rate of supraglottitis was seen during 2010-2020, with an important increase in cases during 2019. Muffled voice (41%) and respiratory distress (38%) were the most common presenting symptoms; and the median duration of symptoms before hospital admission was 2 days [IQR 1; 3]. Airway intervention was performed in fifteen patients (17%). Nine patients (10%) were intubated and six required tracheotomy (7%). Comparing the patients who required airway intervention with those who received a conservative treatment, younger patients (p < 0.01) were more likely to need airway intervention. In logistic regression analysis, we found that epiglottic abscess (p = 0.015), hypersalivation (p = 0.027) and smoking (p = 0.036) were independent factors with a significant association with airway intervention. CONCLUSION: There was an important increase in cases and its severity in 2019, but due to COVID-19 pandemic, it was not possible to define if it was an isolate event or an upward trend. Epiglottic abscess, hypersalivation and smoking could be possible risk factors for airway intervention.

Outcomes and survival of tracheostomised patients during the COVID-19 pandemic in a third level hospital.

PURPOSE: Analyse the evolution and outcomes of COVID-19 tracheostomised patients. Clarify if this cohort presents an increased risk of haemorrhagic complications and verify the correlation between some risk factors with increased mortality. METHODS: A retrospective single-centre observational study of a prospective cohort of all COVID-19 patients admitted to our centre between March and April 2020. A control group was obtained from a historical cohort of patients who required tracheostomy due to prolonged invasive mechanical ventilation (IMV) before 2020. RESULTS: A total of 1768 patients were included: 67 tracheostomised non-COVID-19 patients (historic cohort), 1371 COVID-19 patients that did not require ICU admission, 266 non-tracheostomised COVID-19 patients and 64 tracheostomised COVID-19 patients. Comparing the obesity prevalence, 54.69% of the tracheostomised COVID-19 patients were obese and 10.53% of the non-tracheostomised COVID-19 patients (p < 0.001). The median of ICU admission days was lower (p < 0.001) in the non-tracheostomised cohort (12.5 days) compared with the COVID-19 tracheostomised cohort (34 days). The incidence of haemorrhagic complications was significantly higher in tracheostomised COVID-19 patients (20.31%) compared with tracheostomised non-COVID-19 patients (5.97%) and presented a higher percentage of obesity, hypertension, diabetes and smoking, significantly different from the historic cohort (p < 0.001). A Cox model showed that tracheostomy had no statistically significant effect on mortality in COVID-19 patients. CONCLUSION: Obesity and smoking may be risk factors for tracheostomy in COVID-19 patients, tracheostomised COVID-19 patients present a higher risk of bleeding complications than those admitted for other reasons and an elevated LDH and INR on ICU admission may be associated with increased mortality.

Effect of CYP3A4, CYP3A5, MDR1 and POR Genetic Polymorphisms in Immunosuppressive Treatment in Chilean Kidney Transplanted Patients.

Cyclosporine (CsA) and tacrolimus (TAC) are immunosuppressant drugs characterized by a narrow therapeutic range and high pharmacokinetic variability. The effect of polymorphisms in genes related to the metabolism and transport of these drugs, namely CYP3A4, CYP3A5, MDR1 and POR genes, has been evaluated in diverse populations. However, the impact of these polymorphisms on drug disposition is not well established in Latin American populations. Using TaqMan® probes, we determined the allelic frequency of seven variants in CYP3A4, CYP3A5, MDR1 and POR in 139 Chilean renal transplant recipients, of which 89 were treated with CsA and 50 with TAC. We tested associations between variants and trough and/or 2-hour concentrations, normalized by dose (C0/D and C2/D) at specific time points post-transplant. We found that CYP3A5*3/*3 carriers required lower doses of TAC. In TAC treated patients, most CYP3A5*3/*3 carriers presented higher C0/D and a high proportion of patients with C0 levels outside the therapeutic range relative to other genotypes. These results reinforce the value of considering CYP3A5 genotypes alongside therapeutic drug monitoring for TAC treated Chilean kidney recipients.

Pharmacogenetic Associations Between Atazanavir/UGT1A1*28 and Efavirenz/rs3745274 (CYP2B6) Account for Specific Adverse Reactions in Chilean Patients Undergoing Antiretroviral Therapy.

Background: Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, and atazanavir (ATV), a protease inhibitor, are drugs widely used in antiretroviral therapy (ART) for people living with HIV. These drugs have shown high interindividual variability in adverse drug reactions (ADRs). UGT1A1*28 and CYP2B6 c.516G>T have been proposed to be related with higher toxicity by ATV and EFV, respectively. Objective: To study the association between genetic polymorphisms and ADRs related to EFV or ATV in patients living with HIV treated at a public hospital in Chile. Methods: Epidemiologic, case-control, retrospective, observational study in 67 adult patients under EFV or ATV treatment was conducted, in the San Juan de Dios Hospital. Data were obtained from patients' medical records. Genotype analyses were performed using rtPCR for rs887829 (indirect identification of UGT1A1*28 allele) and rs3745274 (CYP2B6 c.516G>T), with TaqMan® probes. The association analyses were performed with univariate logistic regression between genetic variants using three inheritance models (codominant, recessive, and dominant). Results: In ATV-treated patients, hyperbilirubinemia (total bilirubin >1.2 mg/dl) had the main incidence (61.11%), and moderate and severe hyperbilirubinemia (total bilirubin >1.9 mg/dl) were statistically associated with UGT1A1*28 in recessive and codominant inheritance models (OR = 16.33, p = 0.028 and OR = 10.82, p = 0.036, respectively). On the other hand, in EFV-treated patients adverse reactions associated with CNS toxicity reached 34.21%. In this respect, nightmares showed significant association with CYP2B6 c.516G>T, in codominant and recessive inheritance models (OR = 12.00, p = 0.031 and OR = 7.14, p = 0.042, respectively). Grouped CNS ADRs (nightmares, insomnia, anxiety, and suicide attempt) also showed a statistically significant association with CYP2B6 c.516G > T in the codominant and recessive models (OR = 30.00, p = 0.011 and OR = 14.99, p = 0.021, respectively). Conclusion: Our findings suggest that after treatment with ATV or EFV, UGT1A1*28 and CYP2B6 c.516G>T influence the appearance of moderate-to-severe hyperbilirubinemia and CNS toxicity, respectively. However, larger prospective studies will be necessary to validate these associations in our population. Without a doubt, improving adherence in patients living with HIV is a critical issue to the success of therapy. Hence, validating and applying international pharmacogenetic recommendations in Latin American countries would improve the precision of ART: a fundamental aspect to achieve the 95-95-95 treatment target proposed by UNAIDS.

Dehiscencia de la lámina papirácea del etmoides / Dehiscence of the lamina papyracea of the ethmoid bone

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