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Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real‐world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first‐line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti‐drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one‐compartment model. A maximum effect (Emax) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half‐maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring “dashboard” to individualize dosing and improve treatment outcomes.

Introduction: Retraction pockets and marginal perforations of the pars tensa of the tympanic membrane (TM) are most commonly found at superior posterior quadrant (SPQ). The patulous Eustachian tube tends to manifest in the same quadrant. Variation in the structure of the TM may explain these observations., Material and Methods: A line defined by the manubrium was used to divide the pars tensa into anterior and posterior portions. A transverse line centered on the umbo divides the pars tensa into superior and inferior parts, resulting in four quadrants. Surface areas of each of the TM quadrants were measured in a sample of 23 human adult formalin-fixed temporal bones. The TMs were completely excised, faced medially, and placed against graph paper to maintain scale measurements, photoed, and measured.TM thickness was measured on a different set of 20 human temporal bones (TB) preparations with normal external and middle ears. Four random loci were chosen from each pars tensa's TM quadrant. The thickness was measured using high-magnification power microscopy., Results: The SPQ was the largest and thinnest of the four quadrants. It occupies 31% of the pars tensa area. It is 69 μm as compared to approximately 85 μm in the other quadrants. The radial lines between the umbo and the annulus are in descending order from superior posterior toward the anterior-superior radials., Conclusion: The SPQ has the largest vibratory area and is the thinnest of the four TM quadrants. Variation in the thickness of the middle, fibrous layer accounts for the variation in the thickness of the TM. These findings may explain the tendency of pathologies related to Eustachian tube dysfunction to preferentially manifest in or originate from the SPQ., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objective: The coronavirus disease 2019 (COVID-19) pandemic poses a threat to global health. Early diagnosis is an essential key to limit the outbreak of the virus., Study Design: Case series, study conducted between March 25, 2020, and April 15, 2020., Setting: Ambulatory, nonhospitalized patients who were quarantined in a designated hotel for COVID-19 patients and were recruited by an advertisement at the hotel., Subjects and Methods: In total, 140 patients participated in a web-based questionnaire assessing initial symptoms of common viral diseases, olfactory and taste functions, xerostomia, and orofacial pain., Results: A total of 58 men and 70 women participated. Initial symptoms were cough (59.4%), weakness (47.7%), myalgia (46.9%), fever (42.2%), headache (40.6%), impaired sense of smell (38.3%), impaired sense of taste (32.8%), sore throat (26.6%), runny nose (26.6%), and nasal congestion (22.7%). All symptoms were more frequent among women; however, only runny nose was statistically significant ( P = .018). The most common combination of symptoms was cough and weakness (37.5%). A total of 25.8% reported olfactory and taste dysfunctions in the absence of other symptoms. In a comparison between the sexes, cough and runny nose were the most common combination in women ( P = .018). A total of 38.3% of patients reported olfactory dysfunction as an initial symptom. Anosmia and facial pain were more common among women ( P < .001 and P = .01, respectively), and 56% of patients reported xerostomia., Conclusion: A considerable number of patients presented with olfactory and oral disorders. Interestingly, women presented with a different cluster of symptoms than men, which may suggest a new clinical approach to diagnosing COVID-19 disease.

Background: Failure to thrive is a common problem in children with congenital heart disease (CHD). Resting energy expenditure (REE) in cyanotic and noncyanotic children with CHD before and after open heart surgery has hardly been investigated., Methods: Twenty-nine children younger than 3 years of age with CHD (14 cyanotic and 15 noncyanotic CHD) who were referred for open heart surgery were enrolled. Data on dietary intake, anthropometric measurements, and indirect calorimetry parameters were measured 24 hours before the surgery, (day -1), and on day 5 after surgery. The measured REE was compared with the Schofield and World Health Organization (WHO) REE prediction equations., Results: The mean +/- SD measured REE was similar in the cyanotic and noncyanotic children before and after surgery (before surgery: 57 +/- 13 and 58 +/- 9 kcal/kg per day, respectively; 5 days after surgery: 59 +/- 10 and 62 +/- 10 kcal/kg per day, respectively). Oxygen consumption (VO2) and carbon dioxide production (VCO2) did not change significantly before and after surgery and were similar in both groups. The measured REE for all children on day -1 and day 5 was similar to the calculated REE using the Schofield equation but was significantly different from the calculated REE using the WHO equation (p < .01)., Conclusions: Significant changes in REE, VCO2, and VO2 were not observed before and 5 days after open heart surgery in children with CHD. These parameters (REE, VCO2, and VO2) were also similar in children with cyanotic versus noncyanotic CHD. The Schofield equation is more accurate than the WHO equation in predicting energy needs of children with CHD, but measurement of REE is preferred over calculation of REE.

Background: Malnutrition is common in children with congenital heart disease, while thiamine deficiency (TD) is common in malnutrition, in critically ill children, and in adults with congestive heart failure treated with loop diuretics. Our goal was to determine whether children with congenital heart disease had TD and whether treatment with loop diuretics is related to TD in these patients., Methods: Twelve children with ventricular septal defect (VSD) treated with furosemide, and 10 children with tetralogy of Fallot (TOF) referred for corrective surgery were consecutively enrolled into a prospective study. Data were collected 24 hours before surgery and 5 days after surgery for nutrition evaluation, medications used, anthropometric measurements, and laboratory markers of malnutrition. Thiamine and pyridoxine deficiencies were evaluated using activated enzyme assays., Results: Seven children (32% of patients) did not meet the recommended daily allowance (RDA) for calories and 18% of patients did not meet the RDA for thiamine intake. Anthropometric measurements were low in both groups, more so in those with VSD, although the difference did not reach statistical significance. Overall, 18% (1/12 with VSD and 3/10 with TOF) of children with congenital heart disease had thiamine deficiency before surgery. Three of the four children with TD had adequate intake of thiamine. Six children (27%) had TD 5 days postsurgery (3 children with VSD and 3 children with TOF)., Conclusions: TD is common in children with congenital heart disease (CHD) referred for corrective surgery both before and after surgery. Our results suggest that neither diuretic treatment nor malnutrition can fully explain the development of TD in these children.

A 9-month-old infant had pyoderma gangrenosum (PG) and sterile osteomyelitis. Three years later the patient developed Takayasu arteritis (TA). Sterile osteomyelitis was reported in approximately 30 patients with different skin lesions, but never together with pyoderma gangrenosum. The association of PG and TA has been reported rarely, and then mainly in adults or in children over age 9 years. This rare association should alert physicians with a case of infantile PG of unknown etiology to consider the possible diagnosis of TA.