B-flow/spatiotemporal image correlation M-mode ultrasound provides novel method to quantify spiral artery remodeling during normal human pregnancy.

OBJECTIVES: During human pregnancy placental extravillous trophoblasts replace the vascular smooth muscle and elastic tissue within the walls of the uterine spiral arteries, thereby remodeling these arteries into distensible low resistance vessels to promote placental perfusion. The present study, determined whether B-flow/ spatio-temporal image correlation (STIC) M-mode ultrasonography provides an in vivo imaging method to digitally quantify spiral artery luminal distensibility, as a physiological index of spiral artery remodeling, during advancing stages of normal human pregnancy. METHODS: A prospective longitudinal observational study was conducted to quantify spiral artery distensibility, i.e. vessel luminal diameter at systole minus diameter at diastole, by B-flow/STIC M-mode ultrasonography during the first, second and third trimesters in 290 women exhibiting normal pregnancy. Maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1), growth factors that modulate events important in spiral artery remodeling, were quantified in a subset of the subjects at the first, second and third semesters. RESULTS: Median [first quartile, third quartile] spiral artery distensibility progressively increased (P < 0.0001) between the first trimester (0.17 [0.14, 0.21]), second (0.23 [0.18, 0.28]) and third (0.26 [0.21, 0.35]) trimesters of pregnancy. Spiral artery volume flow (ml/cardiac cycle) progressively increased (P < 0.001) between the first 2.49 [1.38, 4.99], second 3.86 [2.06, 6.91] and third 7.79 [3.83, 14.98] trimesters. Coinciding with the elevation in spiral artery distensibility, the median ratio of serum PlGF/sFlt-1 levels increased (P < 0.001) between the first (7.2 [4.5, 10], second (22.7 [18.6, 42.2]) and third (56.2 [41.9, 92.5] trimesters. CONCLUSIONS: The present study shows that B-flow/STIC M-mode ultrasonography provides an in vivo imaging technology to digitally quantify structural/physiological expansion of the walls of the spiral arteries during the cardiac cycle as a consequence of their transformation into compliant vessels during advancing stages of normal human pregnancy. This article is protected by copyright. All rights reserved.

The significance of initial lactate levels in emergency department presentations of abdominal wall hernia.

INTRODUCTION: Abdominal wall hernias are a frequent cause of abdominal pain-related emergency department visits. Our study aimed to establish the connection between lactate levels and patient outcomes in those with abdominal pain due to abdominal wall hernias. MATERIALS AND METHODS: Our research followed a retrospective, observational, and descriptive approach and two center. We included patients who visited the emergency department for abdominal pain and were confirmed to have abdominal wall hernias through ultrasound. RESULTS: We enrolled 493 patients meeting the criteria. Median age was 65 years, with 54% (n = 266) being male. Regarding outcomes, 40.5% (n = 200) were hospitalized, 27.7% (n = 137) underwent surgery, and 7.9% (n = 39) underwent bowel resection. Mortality rate during hernia-related hospital admission was 0.6% (n = 3). For hospitalized patients, there were significant differences in white blood cell count, neutrophil count and percentage, platelet count, lymphocyte count, and percentage (p < 0.05). Patients undergoing resection showed significant differences in neutrophil count, neutrophil percentage, lymphocyte count, and lymphocyte percentage (p < 0.05). Lactate levels were statistically significant in all patient groups requiring hospitalization, surgery, and resection (p < 0.05). Sensitivity and specificity of lactate test results indicated in patients undergoing bowel resection, lactate values ≥1.96 mmol/L had a specificity of 64%, sensitivity of 71%, and a negative predictive value of 96% (p < 0.05). CONCLUSION: Low lactate levels in patients presenting to the emergency department with abdominal pain caused by abdominal wall hernias have a high negative predictive value for excluding strangulation and the need for bowel resection. Therefore, we recommend the use of lactate as an additional diagnostic tool in emergency department presentations related to abdominal wall hernias.

Consensus protocol for management of early and late twin-twin transfusion syndrome: Delphi study.

OBJECTIVE: Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 and 26 weeks' gestation. High-quality evidence and guidelines regarding the optimal clinical management of very early (prior to 16 weeks), early (between 16 and 18 weeks) and late (after 26 weeks) TTTS are lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS. METHODS: A Delphi procedure was conducted among an international panel of experts. Participants were chosen based on their clinical expertise, affiliation and relevant publications. A four-round Delphi survey was conducted using an online platform and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the second and third rounds, participants were asked to grade each statement on a Likert scale (1, completely disagree; 5, completely agree) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of 5 without suggestions for change were accepted as the consensus. Statements with a median grade of 3 or less were excluded from the Delphi process. Statements with a median grade of 4 were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree with the statements, and those with more than 70% agreement without suggestions for change were considered the consensus. RESULTS: A total of 122 experts met the inclusion criteria and were invited to participate, of whom 53 (43.4%) agreed to take part in the study. Of those, 75.5% completed all four rounds. A consensus on the optimal management of early and late TTTS was obtained. FLP can be offered as early as 15 weeks' gestation for selected cases, and can be considered up to 28 weeks. Between 16 and 18 weeks, management should be tailored according to Doppler findings. CONCLUSIONS: A consensus-based treatment protocol for early and late TTTS was agreed upon by a panel of experts. This protocol should be modified at the discretion of the operator, according to their experience and the specific demands of each case. This should advance the quality of future studies, guide clinical practice and improve patient care. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Placenta accreta spectrum conservative management and coagulopathy: case series and systematic review.

OBJECTIVE: Management of placenta accreta spectrum (PAS) with the placenta kept in situ aims to preserve fertility and minimize blood loss. However, this method is itself associated with a risk of coagulopathy and subsequent bleeding. Our aim is to evaluate coagulopathy in cases of PAS managed conservatively and its pathophysiology. METHODS: We reviewed our database for cases of PAS where the placenta was kept in situ. In addition, we performed a systematic review of articles on PAS where the placenta was left in situ and was complicated by coagulopathy. PubMed was searched for publications between 1980 and 2023. Our eligibility criteria included studies where no additional interventions were performed other than keeping the placenta entirely in situ, and where coagulopathy was reported. RESULTS: After screening and full-text article selection, 10 studies were included in the review. A review of our databases yielded a case series of PAS managed conservatively with placenta in situ. When adding our case series to the results of our systematic review, a total of 87 cases were found to be managed conservatively, with 28 cases of coagulopathy. Of these, 11 cases had known time at which coagulopathy developed. The median time of coagulopathy was 58 (IQR=17) days post-delivery. CONCLUSIONS: Our findings highlight that conservative management with PAS in situ poses a risk of coagulopathy. Keeping the placenta in situ after delivery prolongs the risk factors that are integral to PAS. The pathophysiology behind coagulopathy is comparable to that of concealed placental abruption (CPA), due to the disrupted maternofetal interface and the collection of blood in the placenta. The presence of large placental lakes could thus be an indicator of developing coagulopathy. This article is protected by copyright. All rights reserved.

Index of cardiac-electrophysiological balance in relapsing-remitting multiple sclerosis patients treated with fingolimod.

BACKGROUND: Fingolimod is indicated for the treatment of relapsing-remitting multiple sclerosis (RRMS) and also targets cardiovascular system due to receptors on cardiomyocytes. Results of previous studies are controversial for the effect of fingolimod in terms of ventricular arrhythmias. Index of cardio-electrophysiological balance (iCEB) is a risk marker for predicting malignant ventricular arrhythmia. There is no evidence on the effect of fingolimod on iCEB in patients with relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to evaluate iCEB in patients with RRMS treated with fingolimod . METHODS: A total of 86 patients with RRMS treated with fingolimod were included in the study. All patients underwent a standard 12-lead surface electrocardiogram at initiation of treatment and 6 h after treatment. Heart rate, RR interval, QRS duration, QT, QTc (heart rate corrected QT), T wave peak-to-end (Tp-e) interval, Tp-e/QT, Tp-e/QTc, iCEB (QT/QRS) and iCEBc (QTc/QRS) ratios were calculated from the electrocardiogram. QT correction for heart rate was performed using both the Bazett and Fridericia formulas. Pre-treatment and post-treatment values were compared. RESULTS: Heart rate was significantly lower after fingolimod treatment (p< 0.001). While the post-treatment values of RR and QT intervals were significantly longer (p< 0.001) and post-treatment iCEB was higher (median [Q1-Q3], 4.23 [3.95-4.50] vs 4.53 [4.18-5.14]; p< 0.001), it was found that there was no statistically significant change in iCEB and other study parameters derived using QT after correcting for heart rate using both of two formulas. CONCLUSIONS: In this study, it was found that fingolimod did not statistically significantly change any of the heart rate-corrected ventricular repolarization parameters, including iCEBc, and it is safe in terms of ventricular arrhythmia.

Factors that Influence Placement of Gastrostomy Tube in Infants with Complex Congenital Heart Disease: A Single Center Study.

BACKGROUND: Factors that determine the need for Gastrostomy tube (G-tube) placement in infants with complex congenital heart defects (CHD) are variable. We aim to identify factors that improve counseling of expectant parents regarding postnatal outcomes and management. METHODS: We performed a retrospective review of medical record of infants with prenatal diagnoses of complex CHD between 2015-2019 in a single tertiary care center and assessed risk factors for G-tube placement with linear regression. RESULTS: Of the 105 eligible infants with complex CHD, 44 infants required G-tube (42%). No significant association was observed between G-tube placement and chromosomal abnormalities, cardiopulmonary bypass time or type of CHD. Median days on noninvasive ventilation (4 [IQR 2-12] vs. 3 [IQR 1-8], p = 0.035), time at which gavage-tube feeds were started postoperatively (3 [IQR 2-8] vs. 2 [IQR 0-4], p = 0.0013), time to reach full-volume gavage-tube feeds (6 [IQR 3-14] vs. 5 [IQR 0-8], p = 0.038) and intensive care unit (ICU) length of stay (LOS) (41 [IQR: 21 - 90] vs. 18 [IQR: 7 - 23], p < 0.01) were associated with G-tube placement. Infants with ICU LOS duration longer than median had almost 7 times the odds of requiring a G-tube (OR: 7.23, 95% CI: 2.71-19.32; by regression). CONCLUSIONS: Delay in initiation and in reaching full-volume gavage-tube feeds after cardiac surgery, increased number of days spent on non-invasive ventilation and in the ICU were found to be significant predictors for G-tube placement. The type of CHD and the need for cardiac surgery were not significant predictors for G-tube placement.

Prediction of dual survival following fetoscopic laser photocoagulation for twin-twin transfusion syndrome.

OBJECTIVE: To develop a model based on factors available at the time of diagnosis of twin-twin transfusion syndrome (TTTS) for predicting the probability of dual twin survival following fetoscopic laser photocoagulation (FLP) using a machine-learning algorithm. METHODS: This was a retrospective study of data collected at two university-affiliated tertiary fetal centers between 2012 and 2021. The cohort included monochorionic diamniotic twin pregnancies complicated by TTTS that underwent FLP. Data were stratified based on survival 30 days after delivery, and cases with dual survival were compared to those without dual survival. A random forest machine-learning algorithm was used to construct a prediction model, and the relative importance value was calculated for each parameter that presented a statistically significant difference between the two study groups and was included in the model. The holdout method was applied to check overfitting of the random forest algorithm. A prediction model for dual twin survival 30 days after delivery was presented based on the test set. RESULTS: The study included 537 women with monochorionic diamniotic twin pregnancy, of whom 346 (64.4%) had dual twin survival at 30 days after delivery and were compared with 191 (35.6%) cases that had one or no survivors. Univariate analysis demonstrated no differences in demographic parameters between the groups. At the time of diagnosis, the dual-survival group had lower rates of estimated fetal weight (EFW) < 10th centile for gestational age in the donor twin (56.4% vs 69.4%; P = 0.004), intertwin EFW discordance > 25% (40.8% vs 56.5%; P = 0.001) and anterior placenta (40.5% vs 50.0%; P = 0.034). Comparison of Doppler findings between the two groups demonstrated significant differences in the donor twin, with a lower rate of pulsatility index (PI) > 95th centile in the umbilical artery and ductus venosus and a lower rate of PI < 5th centile in the fetal middle cerebral artery in the dual-survival group. Relative importance values for each of these six parameters were calculated, allowing the construction of a prediction model with an area under the receiver-operating-characteristics curve of 0.916 (95% CI, 0.887-0.946). CONCLUSIONS: We developed a predictive model for dual survival in monochorionic twin pregnancies following FLP for TTTS, which incorporates six variables obtained at the time of diagnosis of TTTS, including donor EFW < 10th centile, intertwin EFW discordance > 25%, anterior placenta and abnormal PI in the umbilical artery, ductus venosus and middle cerebral artery of the donor twin. This clinically applicable tool may improve treatment planning and patient counseling. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Perinatal outcomes of fetoscopic laser surgery for twin-twin transfusion syndrome in triplet pregnancy: cohort study, systematic review and meta-analysis.

OBJECTIVES: The aims of this study were to investigate the perinatal outcome of dichorionic triamniotic (DCTA) and monochorionic triamniotic (MCTA) triplet pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP) in two academic fetal centers, and to conduct a systematic review of previously published data to investigate perinatal survival in this targeted population. METHODS: The first part of the study was a retrospective cohort study of prospectively collected data of consecutive triplet pregnancies with TTTS that underwent FLP at two fetal treatment centers between 2012 and 2020. Demographic, preoperative and operative variables and postoperative outcome were collected. Perinatal outcomes were investigated. The second part of the study was a systematic review and meta-analysis of studies evaluating the outcome of DCTA and/or MCTA triplet pregnancies, including our cohort study. PubMed, Web of Science and Scopus were searched from inception to September 2020. Primary outcomes were fetal survival (survival to birth), neonatal survival (survival to 28 days of age) and gestational age (GA) at birth. RESULTS: A total of 31 sets of triplets with TTTS managed with FLP were included in the cohort study. Of these, 24 were DCTA and seven were MCTA. There were no significant differences in preoperative and operative variables between the two groups. There were also no significant differences between groups in GA at delivery or perinatal survival rate, including fetal and neonatal survival of at least one triplet, at least two triplets and all three triplets. Nine studies, including our cohort study, were included in the systematic review (156 DCTA and 37 MCTA triplet pregnancies treated with FLP). The overall fetal and neonatal survival was 79% (95% CI, 75-83%) and 75% (95% CI, 71-79%), respectively, in DCTA cases and 74% (95% CI, 52-92%) and 71% (95% CI, 49-89%), respectively, in MCTA cases. The rate of preterm birth before 28 weeks and before 32 weeks' gestation was 14% (95% CI, 4-29%) and 61% (95% CI, 50-72%), respectively, in DCTA triplets and 21% (95% CI, 3-45%) and 82% (95% CI, 62-96%), respectively, in MCTA triplets. CONCLUSIONS: Triplet pregnancies with TTTS are at high risk of adverse perinatal outcome and preterm birth, regardless of chorionicity. The rate of survival after FLP in MCTA triplets was higher in our study than that reported in previous studies and is currently comparable with survival in DCTA triplets, which could be due to improved surgical skills. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

B-flow/spatiotemporal image correlation M-mode: novel ultrasound method that detects decrease in spiral artery luminal diameter in first trimester in primate model of impaired spiral artery remodeling.

OBJECTIVE: To determine if B-flow/spatiotemporal image correlation (STIC) M-mode ultrasonography detects a decrease in spiral artery luminal diameter and volume flow during the first trimester in a non-human primate model of impaired spiral artery remodeling (SAR). METHODS: Pregnant baboons were treated daily with estradiol benzoate on days 25-59 of the first trimester (term, 184 days), or remained untreated. On day 60 of gestation, spiral artery luminal diameter (in seven untreated and 12 estradiol-treated baboons) and volume flow (in four untreated and eight estradiol-treated baboons) were quantified by B-flow/STIC M-mode ultrasonography. In addition, in 15 untreated and 18 estradiol-treated baboons, the percent of spiral arteries remodeled by extravillous trophoblasts was quantified ex vivo by immunohistochemical image analysis on placental basal plate tissue collected via Cesarean section on day 60. Findings were compared between treated and untreated animals. The correlation between spiral artery luminal diameter and percent of SAR was assessed in three untreated and six estradiol-treated baboons which underwent both B-flow/STIC M-mode ultrasound and quantification of SAR. RESULTS: The proportion of spiral arteries greater than 50 µm in diameter remodeled by extravillous trophoblasts was 70% lower in estradiol-treated baboons than in untreated animals (P = 0.000001). Spiral artery luminal diameter in systole and diastole, as quantified by B-flow/STIC M-mode in the first trimester of pregnancy, was 31% (P = 0.014) and 50% (P = 0.005) lower, respectively, and volume flow was 85% lower (P = 0.014), in SAR-suppressed baboons compared with untreated animals. There was a significant correlation between spiral artery luminal diameter as quantified by B-flow/STIC M-mode ultrasonography and the percent of SAR (P < 0.05). CONCLUSION: B-flow/STIC M-mode ultrasonography provides a novel real-time non-invasive method to detect a decrease in uterine spiral artery luminal diameter and volume flow during the cardiac cycle, reflecting decreased distensibility of the vessel wall, in the first trimester in a non-human primate model of defective SAR. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Iatrogenic chorioamniotic separation and septostomy following fetoscopic laser photocoagulation for twin-twin transfusion syndrome.

OBJECTIVE: To compare the perinatal outcomes of pregnancies complicated by chorioamniotic separation (CAS) vs septostomy following fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS). METHODS: This was a retrospective cohort analysis of monochorionic diamniotic twin pregnancies with TTTS that underwent FLP at one of two university-affiliated tertiary medical centers between January 2012 and December 2020. CAS and septostomy were diagnosed either during the procedure or by ultrasonography within 24-48 h after FLP. Data on procedure and postprocedure parameters, pregnancy outcomes and survival were collected from the patients' electronic medical records. Pregnancies were stratified according to the presence of CAS, septostomy or neither. Patients diagnosed with both CAS and septostomy were analyzed separately. RESULTS: Of the 522 women included in the cohort, 38 (7.3%) were diagnosed with CAS, 68 (13.0%) with septostomy and 23 (4.4%) with both CAS and septostomy. The remaining 393 (75.3%) women comprised the control group. Groups did not differ in demographic characteristics. The septostomy group had a lower rate of selective fetal growth restriction than did the CAS and control groups (24.2% vs 36.8% vs 42.7%, respectively; P = 0.017). Moreover, intertwin size discordance was lower in the septostomy group (15.1% vs 23.4% in the CAS group and 25.5% in the control group; P = 0.001). Median gestational age at FLP was significantly lower in the CAS group (19.3 weeks vs 20.4 weeks in controls and 20.9 weeks in the septostomy group; P = 0.049). The rate of delivery prior to 34 weeks was significantly higher in the CAS group (89.2%), followed by the septostomy group (80.9%), compared with the control group (69.0%) (P = 0.006). A secondary analysis demonstrated that patients with both CAS and septostomy presented the highest rates of delivery prior to 34 weeks (100%) and 32 weeks (68.2%). CONCLUSIONS: CAS and septostomy following laser surgery for TTTS are independently associated with higher rates of preterm delivery. The presence of these two findings in the same patient enhances the risk of prematurity. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Efficacy of long-term indomethacin therapy in prolonging pregnancy after fetoscopic laser surgery for twin-to-twin transfusion syndrome: a collaborative cohort study.

OBJECTIVE: To evaluate the efficacy of long-term indomethacin therapy (LIT) in prolonging pregnancy and reducing spontaneous preterm birth (PTB) in patients undergoing fetoscopic laser surgery (FLS) for the management of twin-to-twin transfusion syndrome (TTTS). DESIGN: Retrospective cohort study of prospectively collected data. SETTING: Collaborative multicentre study. POPULATION: Five hundred and fifty-seven consecutive TTTS cases that underwent FLS. METHODS: Long-term indomethacin therapy was defined as indomethacin use for at least 48 hours. Log-binomial regression was used to estimate the relative risk of PTB in the LIT group compared with a non-LIT group. Cox regression was used to evaluate the association between LIT use and FLS-to-delivery survival. MAIN OUTCOME MEASURES: Gestational age (GA) at delivery. RESULTS: Among the 411 pregnancies included, a total of 180 patients (43.8%) received LIT after FLS and 231 patients (56.2%) did not. Median GA at fetal intervention did not differ between groups (20.4 weeks). Median GA at delivery was significantly higher in the LIT group (33.6 weeks) compared with the non-LIT group (31.1 weeks; P < 0.001). FLS-to-delivery interval was significantly longer in the LIT group (P < 0.001). The risks of PTB before 34, 32, 28 and 26 weeks of gestation were all significantly lower in the LIT group compared with the non-LIT group (relative risks 0.69, 0.51, 0.37 and 0.18, respectively). The number needed to treat with LIT to prevent one PTB before 32 weeks of gestation was four, and to prevent one PTB before 34 weeks was five. CONCLUSION: Long-term indomethacin after FLS for TTTS was found to be associated with prolongation of pregnancy and reduced risk for PTB. TWEETABLE ABSTRACT: Long-term indomethacin used after fetoscopic laser surgery for twin-to-twin transfusion syndrome is effective in prolonging pregnancy and reducing the risk for preterm birth; especially extreme preterm birth.

The outcome of a national MS-Covid-19 study: What the Turkish MS cohort reveals?

BACKGROUND: The pandemic of the new type of corona virus infection 2019 [Covid-19] also affect people with Multiple Sclerosis (pwMS). Currently, the accumulating information on the effects of the infection regarding the demographic and clinical characteristics of the disease, as well as outcomes within different DMTs¸ enable us to have better practices on the management of the Covid-19 infection in pwMS. OBJECTIVE: To investigate the incidence of coronavirus disease 2019 (Covid-19) and to reveal the relationship between the demographic-clinical and therapeutic features and the outcome of Covid-19 infection in a multi-center national cohort of pwMS. METHODS: The Turkish Neurological Society-MS Study Group in association with the Italian MuSC-19 Study Group initiated this study. A web-based electronic Case Report Form (eCRF) of Study-MuSC-19 were used to collect the data. The demographic data and MS histories of the patients were obtained from the file tracking forms of the relevant clinics. RESULTS: 309 MS patients with confirmed Covid-19 infection were included in this study. Two hundred nineteen (219) were females (70.9%). The mean age was 36.9, ranging from 18 to 66, 194 of them (62.8%) were under 40. The clinical phenotype was relapsing-remitting in 277 (89.6%) and progressive in 32 (10.4%). Disease duration ranged from 0.2 years to 31.4 years. The median EDSS was 1.5, ranging from 0 to 8.5. The EDSS score was<= 1 in 134 (43%) of the patients. 91.6% of the patients were on a DMT, Fingolimod was the most frequently used drug (22.0%), followed by Interferon (20.1%). The comorbidity rate is 11.7%. We were not able to detect any significant association of DMTs with Covid-19 severity. CONCLUSION: The Turkish MS-Covid-19 cohort had confirmed that pwMS are not at risk of having a more severe COVID-19 outcome irrespective of the DMT that they are treated. In addition, due to being a younger population with less comorbidities most had a mild disease further highlight that the only associated risk factors for having a moderate to severe COVID-19 course are similar with the general population such as having comorbid conditions and being older.

Transitions between COPD groups: A cross-sectional study in Turkey.

INTRODUCTION: Since GOLD 2017 separates spirometry results from 'ABCD' groups, there have been some changes to the stages of COPD patients. Our aim was to investigate the shifts in COPD groups after GOLD 2017. METHODS: COPD patients from outpatient clinics of 3 hospitals in Turkey were stratified into old and new ABCD groups according to exacerbation history, mMRC evaluation and spirometry results for both GOLD 2011 and 2017 assessments. Treatment protocols were also evaluated if they were suitable for both classifications. RESULTS: There were 578 patients (334 men, 244 women) with a mean age of 65.21±10.42. The distribution of patients from group A to D was 28%, 15%, 15%, 42% (GOLD 2011) and 36%, 22%, 7% and 35% (GOLD 2017) respectively. There were shifts from group C to A (53.4%) and D to B (18.4%). The treatment suitability was 66.3% in GOLD 2011 and 60.9% in GOLD 2017. The most common inappropriate treatment protocol was triple therapy. Presence of exacerbations in last year, mMRC score, FEV1 level (p < 0.01 for three parameters) and proportion of males (p = 0.029) were statistically significantly higher in groups C and D of GOLD 2017 compared with new patients in group A and B of GOLD 2017 (shifted from GOLD 2011's C-D groups). CONCLUSION: There were shifts from group C to A and D to B with GOLD 2017, which means some high-risk COPD patients were reclassified into low-risk groups. Despite guideline updates, there are still many COPD patients with overtreatment. To our knowledge, this is the first study examining transitions between COPD groups after GOLD 2017 in Turkey.

Early laser surgery is not associated with very preterm delivery or reduced neonatal survival in TTTS.

OBJECTIVE: To evaluate the association of laser photocoagulation of placental anastomoses (LPA) prior to 18 weeks' gestation (early LPA) with very preterm delivery and neonatal survival in pregnancies with twin-twin transfusion syndrome (TTTS). METHODS: This was a retrospective cohort study of monochorionic diamniotic twin pregnancies with TTTS undergoing LPA between 2002 and 2018 at two institutions. The rates of delivery < 28, < 30 and < 32 weeks' gestation, preterm prelabor rupture of membranes (PPROM) and 30-day survival of one or both infants were compared between pregnancies undergoing early LPA and those undergoing LPA ≥ 18 weeks' gestation. Regression analysis was performed to determine the association of early LPA with very preterm delivery and 30-day survival, adjusted for Quintero stage, study phase, selective fetal growth restriction, gestational age at delivery, maternal age ≥ 35 years, body mass index > 35 kg/m2 , placental location, use of Seldinger method to place the operative trocar, size of the trocar, participating center, use of Solomon technique, cerclage and PPROM. Survival analysis using the Cox proportional hazard model was applied to examine the LPA-to-delivery interval according to the timing of surgery, adjusted for confounding variables. RESULTS: A total of 414 TTTS pregnancies were included in the study, of which 68 (16.4%) underwent early LPA. In the total cohort, the incidence of delivery at < 28, < 30 and < 32 weeks' gestation was 22.7%, 39.6% and 53.4%, respectively. Survival of both twins and survival of at least one twin at 30 days were 67.5% and 90.8%, respectively. No significant difference was noted between pregnancies that underwent early LPA and those that had LPA ≥ 18 weeks in the rate of delivery < 28 weeks (19.1% vs 23.4%; P = 0.4), < 30 weeks (38.2% vs 39.9%; P = 0.8) and < 32 weeks (44.1% vs 55.2%; P = 0.1) and PPROM (29.0% vs 24.1%; P = 0.4), or in the incidence of double-twin survival (63.9% vs 68.1%; P = 0.5) and survival of at least one infant (91.8% vs 90.6%; P = 0.7) at 30 days. Early LPA was not associated with very preterm delivery or neonatal survival in the regression analyses. Early LPA was associated with a longer LPA-to-delivery interval compared with LPA performed ≥ 18 weeks (median, 106.9 days (range, 2-164 days) vs median, 69.3 days (range, 0-146 days); P < 0.001) when adjusted for confounding variables (hazard ratio, 2.56 (95% CI, 1.76-3.73); P < 0.001). CONCLUSION: Laser surgery before 18 weeks is not associated with an increased rate of very preterm delivery and PPROM or with reduced neonatal survival when compared with LPA after 18 weeks. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

The effect of bilirubin on long-term mortality in patients with chronic total coronary occlusion.

AIM: We intended to investigate the association of bilirubin with total mortality in patients with chronic total coronary occlusion (CTO). METHODS: We included 172 patients who underwent coronary angiography due to stable angina pectoris and had CTO. We checked the viability of patients after 9 years of follow-up. RESULTS: Direct bilirubin levels were significantly lower in the non-viable group. We revealed age (OR = 1.045, 95% C.I: 1.009‒1.083; p = 0.015) and direct bilirubin concentrations (OR = 0.029, 95% C.I: 0.002‒0.435; p = 0.029) as independent predictors of mortality. Direct bilirubin value of > 0.2 mg/dL was associated with decreased mortality with a sensitivity of 85 %, and a specificity of 46 %. CONCLUSION: Serum direct bilirubin concentrations independently predict total mortality in patients with chronic total occlusion over 9 years of follow-up (Tab. 1, Fig. 2, Ref. 23).

Delivery of drugs into brain tumors using multicomponent silica nanoparticles.

Glioblastomas are highly lethal cancers defined by resistance to conventional therapies and rapid recurrence. While new brain tumor cell-specific drugs are continuously becoming available, efficient drug delivery to brain tumors remains a limiting factor. We developed a multicomponent nanoparticle, consisting of an iron oxide core and a mesoporous silica shell that can effectively deliver drugs across the blood-brain barrier into glioma cells. When exposed to alternating low-power radiofrequency (RF) fields, the nanoparticle's mechanical tumbling releases the entrapped drug molecules from the pores of the silica shell. After directing the nanoparticle to target the near-perivascular regions and altered endothelium of the brain tumor via fibronectin-targeting ligands, rapid drug release from the nanoparticles is triggered by RF facilitating wide distribution of drug delivery across the blood-brain tumor interface.

Treatment of glioblastoma using multicomponent silica nanoparticles.

Glioblastomas (GBMs) remain highly lethal. This partially stems from the presence of brain tumor initiating cells (BTICs), a highly plastic cellular subpopulation that is resistant to current therapies. In addition to resistance, the blood-brain barrier limits the penetration of most drugs into GBMs. To effectively deliver a BTIC-specific inhibitor to brain tumors, we developed a multicomponent nanoparticle, termed Fe@MSN, which contains a mesoporous silica shell and an iron oxide core. Fibronectin-targeting ligands directed the nanoparticle to the near-perivascular areas of GBM. After Fe@MSN particles deposited in the tumor, an external low-power radiofrequency (RF) field triggered rapid drug release due to mechanical tumbling of the particle resulting in penetration of high amounts of drug across the blood-brain tumor interface and widespread drug delivery into the GBM. We loaded the nanoparticle with the drug 1400W, which is a potent inhibitor of the inducible nitric oxide synthase (iNOS). It has been shown that iNOS is preferentially expressed in BTICs and is required for their maintenance. Using the 1400W-loaded Fe@MSN and RF-triggered release, in vivo studies indicated that the treatment disrupted the BTIC population in hypoxic niches, suppressed tumor growth and significantly increased survival in BTIC-derived GBM xenografts.

Primary Pulmonary Diffuse Large B-Cell Lymphoma Presenting as an Endobronchial Lesion: The Youngest Adult Patient in the Literature.

A 20-year-old female patient was admitted to hospital with complaints of chest and back pain in September 2018. There was a cavitary lesion in the upper zone of the left lung in the chest X-ray. Thorax CT revealed an irregular contoured and shaped mass with 87x67x79 mm sizes, in the upper lobe of the left lung lying to paramediastinal area. Since there was a doubt about malignancy, positron emission tomography (PET) was performed; there was a cavitary lesion in the left upper lobe with high FDG uptake (SUVmax: 23.2). Bronchoscopic examination revealed an endobronchial lesion with nearly complete occlusion in the apicoposterior segment of the left upper lobe. Bronchoalveolar lavage (BAL) performed in this session for acid-fast bacilli (AFB) was negative. The patient was diagnosed as primary pulmonary diffuse large B-cell lymphoma (DLBCL) by histopathological and immunohistochemical evaluation of endobronchial biopsy specimens. Following the final diagnosis of Bronchus-Associated Lymphoid Tissue Lymphoma (BALTOMA), the patient was referred to the department of haematology, and chemotherapy was planned for therapy. Since DLBCL is extremely rare, and uncommonly presenting with an endobronchial lesion, we want to present this patient as the youngest adult case of primary endobronchial BALT lymphoma in the literature.