46 Impact of early versus late medical treatment of a hemodynamically significant patent ductus arteriosus on time to reach full feeds in preterm neonates

Primary Subject area Neonatal-Perinatal Medicine Background Prolonged exposure to a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants has been associated with an increase in neonatal morbidities. Objectives To examine the effect of timing of medical treatment (within first 7 days of life versus after 7 days of life) for a hsPDA on the duration to achieve full feeds in infants born at <30 weeks of gestation. Design/Methods This was a retrospective cohort study in a quaternary neonatal intensive care unit (NICU) with a targeted neonatal echocardiography service. Infants admitted between July 2015 – June 2019 who received medical treatment for an hsPDA were included and grouped based on those who received first medical therapy within 7 days of life (early treatment) and after 7 days of life (late treatment). An hsPDA was defined using both clinical (worsening ventilation, pulmonary hemorrhage/edema, or hypotension requiring inotrope or hydrocortisone) and echocardiographic findings (LA/Ao ratio >1.4; LVO >350 mL/kg/min, PDA >1.4 mm, IVRT < 35 ms). Duration to reach full feeds was calculated based on number of days to reach a total enteral feed ≥ 120 mL/kg/day with no parenteral source of nutrition. Results Forty-six infants met the inclusion criteria. Of the 46 infants, 24 were identified as receiving early treatment and 22 received late treatment. Infants in the early treatment group had lower median birth weight than the late treatment group (802 g vs. 1016 g, p=0.022). All other clinical characteristics were not significantly different. No significant difference was found in the use of indomethacin, ibuprofen, or acetaminophen as the initial medical treatment (Table 1). The late treatment group had elevated left ventricular output (median: 286 vs. 369 mL/kg/min, p=0.013) and tricuspid annular plane systolic excursion (median: 6 vs. 8 mm, p=0.002) (Table 2). Infants in the early treatment group reached full feeds earlier than those in the late treatment group (19 vs. 30 days, p=0.042) (Table 1). Conclusion Early medical treatment of hsPDA was associated with shorter duration to reach full feeds in our cohort of preterm infants. Further larger scale study is needed to understand the association between the timing of medical therapy and prolonged exposure of splanchnic circulation to hemodynamically significant ductus.

Angiotensin-Converting Enzyme 2 Activator Ameliorates Severe Pulmonary Hypertension in a Rat Model of Left Pneumonectomy Combined With VEGF Inhibition

Background: Pulmonary arterial hypertension (PAH) is a life-threatening and deteriorating disease with no promising therapy available currently due to its diversity and complexity. An imbalance between vasoconstriction and vasodilation has been proposed as the mechanism of PAH. Angiotensin-converting enzyme 2 (ACE2), which catalyzes the hydrolysis of the vasoconstrictor angiotensin (Ang) II into the vasodilator Ang-(1-7), has been shown to be an important regulator of blood pressure and cardiovascular diseases. Herein we hypothesized diminazene aceturate (DIZE), an ACE2 activator, could ameliorate the development of PAH and pulmonary vascular remodeling.Methods: A murine model of PAH was established using left pneumonectomy (PNx) on day 0 followed by injection of a single dose of the VEGF receptor-2 inhibitor SU5416 (25 mg/kg) subcutaneously on day 1. All hemodynamic and biochemical measurements were done at the end of the study on day 42. Animals were divided into 4 groups (n = 6–8/group): (1) sham-operated group, (2) vehicle-treatment group (SuPNx42), (3) early treatment group (SuPNx42/DIZE1−42) with DIZE at 15 mg/kg/day, subcutaneously from day 1 to day 42, and (4) late treatment group (SuPNx42/DIZE29−42) with DIZE from days 29–42.Results: In both the early and late treatment groups, DIZE significantly attenuated the mean pulmonary artery pressure, pulmonary arteriolar remodeling, and right ventricle brain natriuretic peptide (BNP), as well as reversed the overexpression of ACE while up-regulating the expression of Ang-(1-7) when compared with the vehicle-treatment group. In addition, the early treatment group also significantly decreased plasma BNP and increased the expression of eNOS.Conclusions: ACE2 activator has therapeutic potentials for preventing and attenuating the development of PAH in an animal model of left pneumonectomy combined with VEGF inhibition. Activation of ACE2 may thus be a useful therapeutic strategy for the treatment of human PAH.

Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: a retrospective cohort study.

Background The potential benefit of a combination therapy with lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) on COVID-19 has been speculated. We explored the effect of the timing of LPV/r + HCQ initiation on the outcome of patients with COVID-19. Methods A retrospective cohort study was conducted on patients with COVID-19 who started treatment with LPV/r plus HCQ between February 21 and March 20, 2020, at Luigi Sacco Hospital in Milan, Italy. Over time cumulative incidence of clinical improvement was compared between patients who started treatment less than 5 days from the onset of symptoms [early treatment group (ET)] and those who initiated it later [delayed treatment group (DT)]. The association of LPV/r plus HCQ initiation timing on 30-day mortality was also assessed by univariate and multivariate logistic models. Results The study included 172 patients, prevalently males (72%) in their sixties, with a moderate (53.4%) or severe (34.9%) disease. Fourty-three (25%) patients were included in the ET group and and 129 (75%) in the DT group. Severity of disease did not significantly differ between the two groups. Conclusion Timing of LPV/r + HCQ initiation seems to have no impact on COVID-19 clinical course in terms of improvement and 30-day mortality. These findings rise doubts on the clincial efficacy of this regimen.

Delayed Initiation of Supplemental Pain Management is Associated with Postherpetic Neuralgia: A Retrospective Study

Background: Acute pain is a risk factor for developing postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ). Supplemental analgesics are frequently used in the treatment of acute herpetic pain. However, there are insufficient data regarding when to begin supplemental analgesics, and it is unknown whether the delayed use of supplemental analgesics increases the risk of PHN in high-risk patients. Objectives: This study aimed to evaluate the association between initial time of supplemental pain management and the risk of PHN in high-risk patients. Study Design: Retrospective study. Setting: The Department of Anesthesiology and Pain Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine. Methods: We performed a retrospective study between May 13, 2017 and August 8, 2018 in our clinic. Multivariable logistic regression analysis was conducted to examine the independent factors associated with PHN. Supplemental pain management was defined as any use of opioids, tricyclic antidepressants, or nerve blocks. A subgroup analysis was conducted in patients who received supplemental pain management within the first 30 days of onset. According to the initial time of supplemental pain management, patients were divided into 2 groups: the early treatment group (≤ 14 days), and the late treatment group (> 14 days). The clinical outcomes in these 2 groups was compared for propensity score (PS) matching. Results: A total of 134 patients with HZ aged 50 years or older with moderate to severe pain were enrolled in this study. The delayed initiation of supplemental pain management (> 14 days) (odds ratio, 4.11; 95% confidence interval, 1.69-9.92; P = 0.002) and severity of rash (odds ratio, 2.93; 95% confidence interval, 1.22-7.01; P = 0.016) were independent factors associated with PHN. In the subgroup analysis, after PS matching, there were no significant differences in the baseline clinical parameters between the early and late treatment groups. The incidence of PHN was significantly lower in the early treatment group than the late treatment group (36. 4% vs. 72.7%; P = 0.015). Reduction in pain was also greater in the early treatment group. Limitations: The findings identified in the present study are specific to the patients who were relatively older and with moderate to severe pain. It is impossible to determine from our study whether younger individuals and individuals with mild acute pain will benefit from early supplemental treatments. Furthermore, because of the retrospective nature of the study, there may be some confounders that could not be controlled. Further prospective studies with larger sample sizes and longer follow-up periods are needed. Conclusions: The early use of supplemental pain management may decrease the risk of PHN. It might therefore be beneficial to consider administering supplemental pain management earlier in older patients with moderate to severe acute herpetic pain. Key words: Herpes zoster, postherpetic neuralgia, analgesia, opioid, nerve block, tricyclic antidepressant

A Multicentered Randomized Study on Early versus Rescue Calsurf Administration for the Treatment of Respiratory Distress Syndrome in Preterm Infants

Objective Surfactant and noninvasive ventilation are two major strategies for the treatment of neonates with respiratory distress syndrome (RDS). However, the optimal time for surfactant administering is yet controversial. This study compared the early and rescue Calsurf administration in preterm infants with RDS. Study Design Preterm infants born between 260/7 and 326/7 weeks of gestation and needed nasal continuous positive airway pressure (nCPAP) immediately after birth were randomly assigned to the early or rescue Calsurf treatment group. In the early treatment group, neonates were intubated, administered surfactant with bag–mask ventilation, and extubated to nCPAP (INSURE [intubation–surfactant–extubation]). In the rescue treatment group, InSurE was given until the clinical manifestation and chest X-ray displayed RDS. The primary outcome was to compare the reintubation rate within 72 hour age between the two groups. Results Among 305 neonates randomized to the early (n = 154) and rescue (n = 151) groups, the reintubation rate within 72 hours of age in these two groups did not differ significantly (p > 0.05). The incidence of oxygen dependence until 36 weeks' corrected age was similar in both groups. Conclusion No differences were observed between early and rescue Calsurf treatment groups with respect to the reintubation rate within 72 hours of age and the incidence of bronchopulmonary dysplasia.

Early corticosteroid treatment for postoperative acute lung injury after lung cancer surgery

Background: Acute lung injury (ALI) is the most serious pulmonary complication after lung resection. Although the beneficial effects of low-dose corticosteroids have been demonstrated in patients with postoperative ALI, there are limited data on optimal corticosteroid treatment. Methods: We retrospectively analyzed 58 patients who were diagnosed with ALI among 7593 patients who underwent lung cancer surgery between January 2009 and December 2016. Results: Of the 58 patients, 42 (72%) received corticosteroid treatment within 72 h (early treatment group) and 16 (28%) received corticosteroid treatment more than 72 h after ALI occurred (late treatment group). The early treatment group demonstrated a higher response to corticosteroid treatment compared with the late treatment group (95% versus 69%, respectively, p = 0.014), had an improved lung injury score (86% versus 63%, p = 0.072), and were more likely to be successfully weaned from the ventilator within 7 days (57% versus 39%, p = 0.332). During corticosteroid treatment, the early treatment group had a lower rate of delirium (24% versus 63%, p = 0.012) compared with the late treatment group. No significant differences in length of stay (30 versus 37 days, p = 0.254) or in-hospital mortality (43% versus 38%, p = 0.773) were observed; however, the early treatment group tended to have a higher rate of successful weaning than the late treatment group ( p = 0.098, log-rank test). Conclusions: Early initiation of corticosteroid treatment improved lung injury and promoted ventilator weaning in patients with ALI following lung resection for lung cancer.

Chin-throat anatomy: Normal relations and changes following orthognathic surgery and growth modification

ABSTRACT Objectives: To determine if a new facial line (T), tangent to the throat, intersects the mandibular border in anterior (ANT) and posterior (POST) parts in proportions varying with facial configuration, and to evaluate the association between chin projection and throat inclination and the potential for the T-line to reflect this association. Materials and Methods: Measurements on profile photographs and cephalograms of 135 adults (aged 18–50 years)—45 each of Class I, II, and III (CI, CII, CIII) malocclusions—included ANT and POST, chin-throat (CTA), and mento-cervical (MCA) angles. Pre- and posttreatment measurements were compared in two subgroups (n = 25 each) of CII and CIII orthognathic surgery patients and in CII, division 1 early-treatment patients (n = 63). Statistics included analysis of variance and t-test for group differences, and Pearson correlation for associations among variables. Results: ANT was nearly equal to POST in CI (50.99%) and CIII (51.86%) subjects and shorter in CII (36.01%) subjects. CTA and MCA were greater in CII profiles and smaller in CIII profiles. Significant differences (P < .0001) were observed for ANT, POST, CTA, and MCA between Classes I/II and II/III and for MCA between Classes II/III (P = .016). High correlations were noted between ANT and CTA in Classes I (r = −0.83), II (r = −0.73), and III (r = −0.68). In surgically treated patients, posttreatment measurements approached CI values. In the early-treatment group, ANT increased but remained smaller than POST; CTA decreased by nearly 13%. Conclusions: Chin-throat relations and chin extension are associated and require routine assessment in terms of diagnosis and treatment outcome. A practical tool to assess chin-throat relationship, the T-line bisects the mandibular body nearly equally in Class I faces.

Analysis of the Best Timing for Applying Tirofiban in PCI Operation for the Patients with ST Segment Elevation Myocardial Infarction

This study is a comparative analysis of the best timing for applying tirofiban in the PCI emergency treatment for STEMI patients. We selected 109 patients with ST-segment elevation myocardial infarction from October 2013 to October 2014 and divided them into two groups, the early treatment group (53 cases) received tirofiban during the operation and the later treatment group (56 cases) received tirofiban after operation. The analysis was then conducted. Results: The proportion of IRA forward flow in TIMI2-3 for the 1st group during the radiography was higher than 2nd group, 50 cases with TIMI3 blood flow and 52 cases with TIMI3 blood flow in later treatment group. Comparing the TIMI3 flow of both groups, the difference was not statistically significant; for the CK-MB 4h and 8h after operation as well as the LVEF after operation, the differences are were not statistically significant. The occurrence rate of hemorrhage complication was low for both groups. The early use of tirofiban can make the thrombus fully dissolve and coronary blood flow remains in a good state, which is not only beneficial for myocardial perfusion but also helpful for deciding the length and side branch situation of coronary artery pathological changes.

Safety of Early Pharmacological Thromboprophylaxis after Subarachnoid Hemorrhage

ObjectiveThe recent guidelines on management of aneurysmal subarachnoid hemorrhage (aSAH) advise pharmacological thromboprophylaxis (PTP) after aneurysm obliteration. However, no study has addressed the safety of PTP in the aSAH population. Therefore, the aim of this study was to assess the safety of early PTP after aSAH.MethodsRetrospective cohort of aSAH patients admitted between January 2012 and June 2013 in a single high-volume aSAH center. Traumatic SAH and perimesencephalic hemorrhage patients were excluded. Patients were grouped according to PTP timing: early PTP group (PTP within 24 hours of aneurysm treatment), and delayed PTP group (PTP started > 24 hours).ResultsA total of 174 SAH patients (mean age 56.3±12.5 years) were admitted during the study period. Thirty-nine patients (22%) did not receive PTP, whereas 135 patients (78%) received PTP after aneurysm treatment or negative angiography. Among the patients who received PTP, 65 (48%) had an external ventricular drain. Twenty-eight patients (21%) received early PTP, and 107 (79%) received delayed PTP. No patient in the early treatment group and three patients in the delayed PTP group developed an intracerebral hemorrhagic complication. Two required neurosurgical intervention and one died. These three patients were on concomitant PTP and dual antiplatelet therapy.ConclusionsThe initiation of PTP within 24 hours may be safe after the treatment of a ruptured aneurysm or in angiogram-negative SAH patients with diffuse aneurysmal hemorrhage pattern. We suggest caution with concomitant use of PTP and dual antiplatelet agents, because it possibly increases the risk for intracerebral hemorrhage.

Factors and Outcomes Associated With Early and Delayed Aneurysm Treatment in Subarachnoid Hemorrhage Patients in the United States

BACKGROUND: Recent studies from selected centers have shown that early surgical treatment of aneurysms in subarachnoid hemorrhage (SAH) patients can improve outcomes. These results have not been validated in clinical practice at large. OBJECTIVE: To identify factors and outcomes associated with timing of ruptured intracranial aneurysm obliteration treatment in patients with SAH after hospitalization in the United States. METHODS: We analyzed the data from the Nationwide Inpatient Sample (2005–2008) for all patients presenting with primary diagnosis of SAH, receiving aneurysm treatment (endovascular coil embolization or surgical clip placement). Early treatment was defined as aneurysm treatment performed within 48 hours and delayed treatment if treatment was performed after 48 hours of admission. RESULTS: Of 32 048 patients with SAH who underwent aneurysm treatment, 24 085 (75.2%) underwent early treatment and 7963 (24.8%) underwent delayed treatment. Female sex (P = .002), endovascular embolization (P < .001), and weekday admission (P < .001) were independent predictors of early treatment. In the early treatment group, patients were more likely discharged with none to minimal disability (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.14-1.47) and less likely to be discharged with moderate to severe disability (OR 0.77, 95%CI 0.67-0.87) compared with those in the delayed treatment group. The in-hospital mortality was higher in the early treatment group compared with the delayed treatment group (OR 1.36 95%CI 1.12-1.66). CONCLUSION: Patients with SAH who undergo aneurysm treatment within 48 hours of hospital admission are more likely to be discharged with none to minimal disability. Early treatment is more likely to occur in those undergoing endovascular treatment and in patients admitted on weekdays.