Elevated peripheral blood monocyte count is associated with prolonged postoperative hospitalization and functional decline in patients with interstitial lung diseases undergoing surgical lung biopsy.

OBJECTIVE: Monocyte count and red cell distribution width (RDW) have shown prognostic potential in patients with fibrotic lung diseases. Their kinetics and prognostic usefulness of peripheral blood indices in patients with interstitial lung diseases (ILDs) undergoing surgical lung biopsy for diagnostic reasons have not been studied. PATIENTS AND METHODS: We retrospectively included consecutive patients with ILD who underwent surgical lung biopsy for diagnostic purposes Between 07/11/2019 and 11/10/2022. RESULTS: Fifty-five (n=55) patients were included in the study. Median age was 65.0 years (95% CI: 63.0 to 66.0). Postoperative peripheral blood monocyte count on Day 1 was significantly higher compared to preoperative, perioperative, and postoperative values on Day 90 (repeated measures ANOVA, p<0.0001). Patients in the high postoperative monocyte count group had significantly increased length of postoperative hospital stay [Mann-Whitney test, p=0.007] and significantly lower Forced Vital Capacity (FVC)% predicted 3 months after surgery [Mann-Whitney test, p=0.029] compared to patients in the low postoperative monocyte count group. Postoperative RDW on Day 90 was significantly higher compared to preoperative, perioperative and postoperative-Day 1 RDW (repeated measures ANOVA, p=0.008, p=0.006, p<0.0001, respectively). Patients in the high postoperative RDW group did not have increased hospital stay (Mann-Whitney test, p=0.49) or decreased FVC% predicted at 3 months compared to patients in the low postoperative RDW group (Mann-Whitney test, p=0.91). CONCLUSIONS: Peripheral blood monocyte count could be a prognostic biomarker for patients with ILDs undergoing diagnostic surgical lung biopsies. RDW does not seem to represent an acute phase biomarker but seems to increase over time following disease progression. Larger studies are urgently required.

Alpha1-antitrypsin deficiency in Greece: Focus on rare variants.

PURPOSE: A1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants. AIM: to investigate genotype and clinical profile of Greeks with AATD. METHODS: Symptomatic adult-patients with early-emphysema defined by fixed airway obstruction and computerized-tomography scan and lower than normal serum AAT levels were enrolled from reference centers all over Greece. Samples were analyzed in the AAT Laboratory, University of Marburg-Germany. RESULTS: Included are 45 adults, 38 homozygous or compound heterozygous for pathogenic variants and 7 heterozygous. Homozygous were 57.9% male, 65.8% ever-smokers, median (IQR) age 49.0(42.5-58.5) years, AAT-levels 0.20(0.08-0.26) g/L, FEV1(%predicted) 41.5(28.8-64.5). PI*Z, PI*Q0, and rare deficient allele's frequency was 51.3%, 32.9%,15.8%, respectively. PI*ZZ genotype was 36.8%, PI*Q0Q0 21.1%, PI*MdeficientMdeficient 7.9%, PI*ZQ0 18.4%, PI*Q0Mdeficient 5.3% and PI*Zrare-deficient 10.5%. Genotyping by Luminex detected: p.(Pro393Leu) associated with MHeerlen (M1Ala/M1Val); p.(Leu65Pro) with MProcida; p.(Lys241Ter) with Q0Bellingham; p.(Leu377Phefs*24) with Q0Mattawa (M1Val) and Q0Ourem (M3); p.(Phe76del) with MMalton (M2), MPalermo (M1Val), MNichinan (V) and Q0LaPalma (S); p.(Asp280Val) with PLowell (M1Val); PDuarte (M4), YBarcelona (p.Pro39His). Gene-sequencing (46.7%) detected Q0GraniteFalls, Q0Saint-Etienne, Q0Amersfoort(M1Ala), MWürzburg, NHartfordcity and one novel-variant (c.1A>G) named Q0Attikon.Heterozygous included PI*MQ0Amersfoort(M1Ala), PI*MMProcida, PI*Mp.(Asp280Val), PI*MOFeyzin. AAT-levels were significantly different between genotypes (p = 0.002). CONCLUSION: Genotyping AATD in Greece, a multiplicity of rare variants and a diversity of rare combinations, including unique ones were observed in two thirds of patients, expanding knowledge regarding European geographical trend in rare variants. Gene sequencing was necessary for genetic diagnosis. In the future the detection of rare genotypes may add to personalize preventive and therapeutic measures.

Clinical outcomes in vaccinated and unvaccinated patients with COVID-19: a population-based analysis.

OBJECTIVE: Real-life data for vaccination against COVID-19 are sorely needed. This was a population-based analysis aiming at investigating the hospitalization risk for COVID-19 of 98,982 subjects and compare features of vaccinated and unvaccinated patients. PATIENTS AND METHODS: Hospitalized patients with COVID-19 between 01/07/2021 and 11/02/2022 were included in the study. RESULTS: 582 patients were included in the analysis [males: 58.6% (n=341), vaccinated patients: 28.5% (n=166), unvaccinated patients: 71.5% (n=416)]. Median age of vaccinated patients was significantly higher compared to median age of unvaccinated [74.0 (95% CI: 72.0-77.0) vs. 59.0 (95% CI: 57.0-62.0), p=0.0001]. Mean latency time (±SD) from the second dose to hospitalization was 5.7±2.6 months. Between 01/07/2021 and 01/12/2021, unvaccinated subjects had higher risk for hospitalization compared to vaccinated [HR: 2.82, 95% CI: 2.30-3.45, p<0.0001]. Between 02/12/2021 and 11/02/2022, unvaccinated subjects presented with higher risk for hospitalization than subjects that had received booster dose [HR: 2.07, 95% CI: 1.44-2.98, p=0.005], but not than subjects that got two doses. Median value of hospitalization days was higher in unvaccinated patients compared to vaccinated [7.0 (95% CI: 7.0-8.0) vs. 6.0 (95% CI: 5.0-7.0), p=0.02]. Finally, age-adjusted analysis showed that hospitalized unvaccinated patients presented with significantly higher mortality risk compared to hospitalized vaccinated patients [HR: 2.59, 95% CI: 1.69-3.98, p<0.0001]. CONCLUSIONS: Vaccination against COVID-19 remains the best way to contain the pandemic. There is an amenable need for booster dose during the omicron era.

CTPA imaging findings, beyond pulmonary embolism, in patients with Severe Acute Respiratory Syndrome Corona Virus-2 infection and their relation to clinical outcome - a single center experience.

OBJECTIVE: The aim of our study was to investigate a potential association between the severity of COVID-19 disease and related 28-day mortality, with the presence of mediastinal lymphadenopathy, the extension of lung parenchymal infiltrates, the presence of pulmonary embolism, the density and distribution of mediastinal and subcutaneous fat, the inflammatory markers and the direct and indirect radiological signs of right heart overload and strain. PATIENTS AND METHODS: We retrospectively included patients diagnosed with SARS-CoV-2 infection, who were admitted to the Departments of Internal and Respiratory Medicine of Patras University Hospital during the second pandemic wave (February 2021 up to July 2021) and underwent CTPA for routine diagnostic workup. Demographic characteristics, routine laboratory, radiological parameters and 28-day mortality were also recorded. RESULTS: Fifty-three consecutive patients were included. The mean age was 64.47±17.1 years and 64,1% (n=34) were males. Pulmonary embolism (PE) (p=0.019), Right Ventricle-to-Left Ventricle Diameter (RV/LV)  Ratio>1 (p<0.01), Reverse Flow in Hepatic Veins (RFHV) (p=0.019), higher density in subcutaneous fat (-99 HU vs. -104HU, p=0.016), increased Lactic Dehydrogenase (LDH), Polymorphonuclear cells (PMN), ferritin, and d-dimer levels (534 vs. 367 U/L, p=0.001, 9220 vs. 5660 Κ/µL, p=001, 956 vs. 360 ng/ml, p=0.005 and 2300 vs. 1040 µg/ml, p=0.003, respectively) were statistically significant related with worse 28-day mortality. Binomial multivariate regression analysis revealed that only RV/LV diameter>1, higher subcutaneous fat density and higher LDH values were independently associated with increased 28-day mortality (OR: 82.9, 95%CI: 1.334-5158, p=0.036, OR: 1.2, 95%CI: 1.016-1.426, p=0.032 and OR:1.016, 95% CI:1.004-1.029, p=0.011, respectively). Subgroup analysis revealed that mediastinal lymph node enlargement (EML) and PE were associated to increased Pulmonary Disease Severity Index (PDSI) score (p=0.042 and p=0.007, respectively), but not to mortality. CONCLUSIONS: Our study showed that right heart strain as depicted by a RV/LV diameter>1, higher subcutaneous fat density and higher LDH values are independently associated with an increased 28-day mortality in our SARS-COV2 patient group.

Prevalence and significance of mediastinal lymphadenopathy in patients with Severe Acute Respiratory Syndrome Corona Virus-2 infection.

Severe Acute Respiratory Syndrome Corona Virus-2 is the causative factor of Coronavirus Disease 2019. Early in the pandemic, mediastinal lymphadenopathy was not considered to be a significant radiologic finding of the SARS-COV-2 disease. Nevertheless, most recent studies associate mediastinal lymphadenopathy with more severe COVID-19 disease and poorer patient outcomes.

Prediction of adverse perinatal outcome by serum placental growth factor and soluble fms-like tyrosine kinase-1 in women undergoing induction of labor.

OBJECTIVE: To investigate the additive value of serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), measured within 24 h prior to induction of labor, to the performance of screening for adverse perinatal outcome provided by maternal risk factors and the cerebroplacental ratio (CPR). METHODS: This was a prospective observational study of 795 singleton pregnancies undergoing induction of labor at ≥ 37 weeks' gestation. Before induction of labor, Doppler ultrasound was used to measure the pulsatility index (PI) in the umbilical artery (UA) and fetal middle cerebral artery (MCA) and maternal blood was obtained for measurement of serum PlGF and sFlt-1. The measured UA-PI, MCA-PI and their ratio (CPR) were converted to multiples of the median (MoM) after adjustment for gestational age, and the measured PlGF and sFlt-1 were converted to MoM after adjustment for gestational age, maternal characteristics and the machine used for the assays. Univariable and multivariable logistic regression analysis was used to determine factors that provided a significant contribution in the prediction of adverse perinatal outcome, defined as the presence of any one of Cesarean section for non-reassuring fetal status in labor, umbilical arterial or venous cord blood pH ≤ 7 and ≤ 7.1, respectively, 5-min Apgar score < 7 or admission to the neonatal intensive care unit for ≥ 24 h. The detection rate (DR) and false-positive rate (FPR) in screening for adverse perinatal outcome were determined. RESULTS: In pregnancies with adverse perinatal outcome, compared to those without, median serum PlGF MoM was lower (0.44; interquartile range (IQR), 0.30-0.82 vs 0.60; IQR, 0.36-1.07; P = 0.003), but median sFlt-1 MoM was not significantly different (P = 0.080). Multivariable regression analysis demonstrated that, in the prediction of adverse perinatal outcome, there was significant contribution from maternal risk factors and CPR MoM but not PlGF MoM or sFlt-1 MoM. The performance of screening for adverse perinatal outcome achieved by maternal risk factors alone (DR of 28.9% at FPR of 10%) was not improved by the addition of CPR (DR of 33.8% at FPR of 10%) (area under the curve, 0.702; 95% CI, 0.654-0.750 vs 0.712; 95% CI, 0.664-0.760; P = 0.233). CONCLUSION: Serum PlGF and sFlt-1, measured within 24 h prior to induction of labor, do not provide a significant additional contribution to maternal risk factors in the prediction of adverse perinatal outcome. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of large-for-gestational-age neonate by routine third-trimester ultrasound.

OBJECTIVES: First, to evaluate and compare the performance of routine ultrasonographic estimated fetal weight (EFW) and fetal abdominal circumference (AC) at 31 + 0 to 33 + 6 and 35 + 0 to 36 + 6 weeks' gestation in the prediction of a large-for-gestational-age (LGA) neonate born at ≥ 37 weeks' gestation. Second, to assess the additive value of fetal growth velocity between 32 and 36 weeks' gestation to the performance of EFW at 35 + 0 to 36 + 6 weeks' gestation for prediction of a LGA neonate. Third, to define the predictive performance for a LGA neonate of different EFW cut-offs on routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. Fourth, to propose a two-stage strategy for identifying pregnancies with a LGA fetus that may benefit from iatrogenic delivery during the 38th gestational week. METHODS: This was a retrospective study. First, data from 21 989 singleton pregnancies that had undergone routine ultrasound examination at 31 + 0 to 33 + 6 weeks' gestation and 45 847 that had undergone routine ultrasound examination at 35 + 0 to 36 + 6 weeks were used to compare the predictive performance of EFW and AC for a LGA neonate with birth weight > 90th and > 97th percentiles born at ≥ 37 weeks' gestation. Second, data from 14 497 singleton pregnancies that had undergone routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation and had a previous scan at 30 + 0 to 34 + 6 weeks were used to determine, through multivariable logistic regression analysis, whether addition of growth velocity, defined as the difference in EFW Z-score or AC Z-score between the early and late third-trimester scans divided by the time interval between the scans, improved the performance of EFW at 35 + 0 to 36 + 6 weeks in the prediction of delivery of a LGA neonate at ≥ 37 weeks' gestation. Third, in the database of the 45 847 pregnancies that had undergone routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation, the screen-positive and detection rates for a LGA neonate born at ≥ 37 weeks' gestation and ≤ 10 days after the initial scan were calculated for different EFW percentile cut-offs between the 50th and 90th percentiles. RESULTS: First, the areas under the receiver-operating characteristics curves (AUC) of screening for a LGA neonate were significantly higher using EFW Z-score than AC Z-score and at 35 + 0 to 36 + 6 than at 31 + 0 to 33 + 6 weeks' gestation (P < 0.001 for all). Second, the performance of screening for a LGA neonate achieved by EFW Z-score at 35 + 0 to 36 + 6 weeks was not significantly improved by addition of EFW growth velocity or AC growth velocity. Third, in screening by EFW > 90th percentile at 35 + 0 to 36 + 6 weeks' gestation, the predictive performance for a LGA neonate born at ≥ 37 weeks' gestation was modest (65% and 46% for neonates with birth weight > 97th and > 90th percentiles, respectively, at a screen-positive rate of 10%), but the performance was better for prediction of a LGA neonate born ≤ 10 days after the scan (84% and 71% for neonates with birth weight > 97th and > 90th percentiles, respectively, at a screen-positive rate of 11%). Fourth, screening by EFW > 70th percentile at 35 + 0 to 36 + 6 weeks' gestation predicted 91% and 82% of LGA neonates with birth weight > 97th and > 90th percentiles, respectively, born at ≥ 37 weeks' gestation, at a screen-positive rate of 32%, and the respective values of screening by EFW > 85th percentile for prediction of a LGA neonate born ≤ 10 days after the scan were 88%, 81% and 15%. On the basis of these results, it was proposed that routine fetal biometry at 36 weeks' gestation is a screening rather than diagnostic test for fetal macrosomia and that EFW > 70th percentile should be used to identify pregnancies in need of another scan at 38 weeks, at which those with EFW > 85th percentile should be considered for iatrogenic delivery during the 38th week. CONCLUSIONS: First, the predictive performance for a LGA neonate by routine ultrasonographic examination during the third trimester is higher if the scan is carried out at 36 than at 32 weeks, the method of screening is EFW than fetal AC, the outcome measure is birth weight > 97th than > 90th percentile and if delivery occurs within 10 days than at any stage after assessment. Second, prediction of a LGA neonate by EFW > 90th percentile is modest and this study presents a two-stage strategy for maximizing the prenatal prediction of a LGA neonate. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.