Evaluating persistent T1-weighted lesions without concurrent abnormal enhancement on breast MRI in neoadjuvant chemotherapy patients: implications for complete pathological response.

OBJECTIVE: This study aims to determine whether persistent T1-weighted lesions signify a complete pathological response (pCR) in breast cancer patients treated with neoadjuvant chemotherapy and surgery, and to evaluate their correlation with imaging responses on MRI. MATERIALS AND METHODS: A retrospective review was conducted on data from breast cancer patients treated between January 2011 and December 2018. Patients who underwent breast MRI and pre- and post-neoadjuvant chemotherapy followed by surgery were included. Those with distant metastasis, no planned surgery, pre-surgery radiation, ineligibility for neoadjuvant chemotherapy, or unavailable surgical pathology were excluded. Groups with and without persistent T1-weighted lesions were compared using the chi-square test for categorical variables and the Student t test or Wilcox rank sum test for continuous variables. Univariate logistic regression was used to evaluate the association of the final pathological response with the presence of T1-persistent lesion and other characteristics. RESULTS: Out of 319 patients, 294 met the inclusion criteria (breast cancer patients treated with neoadjuvant chemotherapy and subsequent surgery); 157 had persistent T1 lesions on post-chemotherapy MRI and 137 did not. A persistent T1 lesion indicated reduced likelihood of complete pathological response (14% vs. 39%, p < 0.001) and imaging response (69% vs. 93%, p < 0.001). Multivariable analysis confirmed these findings: OR 0.37 (95% CI 0.18-0.76), p = 0.007. No other characteristics correlated with T1 residual lesions. CONCLUSION: Persistent T1-weighted lesions without associated abnormal enhancement on post-treatment breast MRI correlate with lower complete pathological and imaging response rates. CLINICAL RELEVANCE STATEMENT: The study underscores the importance of persistent T1-weighted lesions on breast MRI as vital clinical markers, being inversely related to a complete pathological response following neoadjuvant chemotherapy; they should be a key factor in guiding post-neoadjuvant chemotherapy treatment decisions. KEY POINTS: • Persistent T1 lesions on post-chemotherapy breast MRI indicate a reduced likelihood of achieving a complete pathological response (14% vs. 39%, p < 0.001) and imaging response (69% vs. 93%, p < 0.001). • Through multivariable analysis, it was confirmed that the presence of a persistent T1 lesion on breast MRI post-chemotherapy is linked to a decreased likelihood of complete pathological response, with an odds ratio (OR) of 0.37 (95% CI 0.18-0.76; p = 0.007). • In addition to the convention of equating the absence of residual enhancement to complete imaging response, our results suggest that the presence or absence of residual T1 lesions should also be considered.

Quality of Recovery After Unplanned and Planned Cesarean Deliveries: A Prospective Observational Study Using the Obstetric Quality of Recovery-10 Tool.

BACKGROUND: There is a paucity of literature examining the differences between patient-reported outcome measures after planned and unplanned cesarean delivery using a validated quality of recovery tool. The Obstetric Quality of Recovery-10 (ObsQoR-10) scoring tool has been validated to quantify functional recovery after cesarean delivery. We aimed to use the ObsQoR-10 to compare the postoperative recovery characteristics of patients undergoing planned and unplanned cesarean deliveries. METHODS: We conducted a prospective single-center observational study. Patients undergoing planned and unplanned cesarean deliveries under neuraxial anesthesia were asked to complete the ObsQoR-10 questionnaire 24 hours, 48 hours, and 1 week postpartum. We collected information on total in-hospital postoperative opioid consumption and patients´ perception of readiness for discharge at 24 and 48 hours postpartum. Additionally, patient characteristics were collected to assess their correlation with our findings. RESULTS: We included 112 patients (56 in each group). No statistical differences in ObsQoR-10 scores at 24 hours, 48 hours, and 1 week postpartum were observed between the planned and unplanned cesarean deliveries. Additionally, there was no difference between the groups in patients' perception of readiness for hospital discharge at 24 and 48 hours and opioid consumption in the first 2 days after surgery. Most patients in both groups did not think they would be ready for discharge at 24 hours postpartum. Analysis of the individual components of ObsQoR-10 at 24 hours showed a difference in the responses assessing the severity of shivering (higher in unplanned cesarean deliveries) and the ability to look after personal hygiene (lower in unplanned cesarean deliveries). CONCLUSIONS: As assessed by the ObsQoR-10, no significant difference in the quality of recovery was observed between patients undergoing planned and unplanned cesarean delivery.

Differential sensory block during labour epidural analgesia: a prospective observational study to investigate the relationship of lower and upper sensory block levels to cold, pinprick, and light touch.

PURPOSE: A zone of differential block to cold has been recently documented during labour epidural analgesia, with an upper sensory block level (USBL) and a lower sensory block level (LSBL). We aimed to determine the correlation between USBL and LSBL to cold and pinprick and sensory block level to light touch during labour epidural analgesia. METHODS: We conducted a prospective observational study in patients requesting labour epidural analgesia. We placed an epidural catheter at L2/L3 or L3/L4, followed by a programmed intermittent epidural bolus plus patient-controlled epidural analgesia regimen. We assessed the sensory block levels 140 min after administering the loading dose. The primary outcomes were the USBL and LSBL to cold and pinprick and the sensory block level to light touch. RESULTS: We studied 30 patients. The median [interquartile range (IQR)] USBL and LSBL to ice were T7 [T7-T6] and T9 [T10-T8], respectively. The median [IQR] USBL and LSBL to pinprick were T8 [T10-T6] and T10 [T12-T10], respectively. There was a strong correlation between USBL to ice and pinprick (Spearman correlation coefficient, 0.57) and between LSBL to ice and pinprick (Spearman correlation coefficient, 0.52). There was no significant correlation between sensory block level to light touch and either USBL or LSBL to ice or pinprick. CONCLUSION: We observed two sensory block levels to ice and pinprick. Further studies are required to understand if one modality-cold or pinprick-is superior to the other in assessing sensory block levels in this context. Light touch is unreliable as a modality of sensory block assessment during labour epidural analgesia. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05187962); registered 12 January 2022.

RéSUMé: OBJECTIF: Une zone de bloc différentiel de réaction au froid a récemment été documentée pendant l'analgésie péridurale obstétricale, avec un niveau de bloc sensoriel supérieur (USBL, pour upper sensory block level) et un niveau de bloc sensoriel inférieur (LSBL, pour lower sensory block level). Notre objectif était de déterminer la corrélation entre l'USBL et le LSBL au contact du froid et de la piqûre et le niveau de bloc sensoriel au toucher léger pendant l'analgésie péridurale obstétricale. MéTHODE: Nous avons mené une étude observationnelle prospective chez des patient·es demandant une analgésie péridurale obstétricale. Nous avons placé un cathéter péridural au niveau L2/L3 ou L3/L4, suivi d'une administration programmée de bolus périduraux plus un régime d'analgésie péridurale contrôlée par le/la patient·e. Nous avons évalué les niveaux de bloc sensoriel 140 min après l'administration de la dose de charge. Les critères d'évaluation principaux étaient l'USBL et le LSBL en réaction au froid et à la piqûre d'épingle et le niveau de bloc sensoriel en réaction au toucher léger. RéSULTATS: Nous avons étudié 30 patient·es. Les USBL et LSBL médians [écart interquartile (ÉIQ)] à la glace étaient situés au niveau T7 [T7-T6] et T9 [T10-T8], respectivement. Les USBL et LSBL médians [écart interquartile (ÉIQ)] à la piqûre étaient localisés au niveau T8 [T10­T6] et T10 [T12­T10], respectivement. Il y avait une forte corrélation entre l'USBL à la glace et à la piqûre (coefficient de corrélation de Spearman, 0,57) et entre le LSBL à la glace et à la piqûre (coefficient de corrélation de Spearman, 0,52). Il n'y avait pas de corrélation significative entre le niveau de bloc sensoriel en réaction au toucher léger et l'USBL ou le LSBL en réaction à la glace ou à la piqûre. CONCLUSION: Nous avons observé deux niveaux de bloc sensoriel à la glace et à la piqûre. D'autres études sont nécessaires pour comprendre si une modalité ­ le froid ou la piqûre ­ est supérieure à l'autre pour évaluer les niveaux de bloc sensoriel dans ce contexte. Le toucher léger n'est pas fiable en tant que modalité d'évaluation du bloc sensoriel pendant l'analgésie péridurale obstétricale. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT05187962); enregistré le 12 janvier 2022.

Long-Term Neurodevelopmental Impairment among Very Preterm Infants with Sepsis, Meningitis, and Intraventricular Hemorrhage.

INTRODUCTION: Sepsis and intraventricular hemorrhage (IVH) are associated with poorer long-term neurodevelopmental outcomes in very preterm infants (VPIs), but less is known about the long-term effect of meningitis and the combined impact of both meningitis and IVH. Our objective was to examine the long-term neurodevelopmental outcomes of VPIs with late onset sepsis and meningitis, with and without IVH, in Canada. METHODS: We conducted a retrospective cohort study of all infants <29 weeks GA who were admitted to 26 tertiary-level neonatal intensive care units in the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-Up Network (CNFUN) databases, from January 1, 2010, to December 31, 2016. RESULTS: Of the 6,322 infants in the cohort, 4,575 had no infection, 1,590 had late onset culture-positive bloodstream infection (CPBSI) only, and 157 had late onset meningitis. There was a significant (p < 0.05) trend of increasing rates of significant neurodevelopmental delay (sNDI) when comparing infants with no infection (sNDI rate 15.0%), late onset CPBSI (sNDI rate 22.9%), and late onset meningitis (sNDI rate 32.0%), even after adjustment for infant characteristics. Similar trends were observed for neurodevelopmental impairment, cerebral palsy, and individual Bayley-III scores <85 for cognitive, language, and motor development. There was an additive effect of IVH in all infant categories, but there was no multiplicative effect between IVH and late onset meningitis. CONCLUSION: There was an increasing trend of adverse neurodevelopmental outcomes when infants with no infection, late onset CPBSI and late onset meningitis are compared. IVH had an additive effect.

The impact of multidisciplinary cancer conferences on overall survival: a meta-analysis.

BACKGROUND: Multidisciplinary cancer conferences consist of regular meetings between diverse specialists working together to share clinical decision making in cancer care. The aim of this study was to systematically review and meta-analyze the effect of multidisciplinary cancer conference intervention on the overall survival of patients with cancer. METHODS: A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and the Cochrane Controlled Register of Trials for studies published up to July 2023. Studies reporting on the impact of multidisciplinary cancer conferences on patient overall survival were included. A standard random-effects model with the inverse variance-weighted approach was used to estimate the pooled hazard ratio of mortality (multidisciplinary cancer conference vs non-multidisciplinary cancer conference) across studies, and the heterogeneity was assessed by I2. Publication bias was examined using funnel plots and the Egger test. RESULTS: A total of 134 287 patients with cancer from 59 studies were included in our analysis, with 48 467 managed by multidisciplinary cancer conferences and 85 820 in the control arm. Across all cancer types, patients managed by multidisciplinary cancer conferences had an increased overall survival compared with control patients (hazard ratio = 0.67, 95% confidence interval = 0.62 to 0.71, I2 = 84%). Median survival time was 30.2 months in the multidisciplinary cancer conference group and 19.0 months in the control group. In subgroup analysis, a positive effect of the multidisciplinary cancer conference intervention on overall survival was found in breast, colorectal, esophageal, hematologic, hepatocellular, lung, pancreatic, and head and neck cancer. CONCLUSIONS: Overall, our meta-analysis found a significant positive effect of multidisciplinary cancer conferences compared with controls. Further studies are needed to establish nuanced guidelines when optimizing multidisciplinary cancer conference integration for treating diverse patient populations.

The Role of Adjuvant Radiotherapy for the Treatment of Resected High-Risk Stage III Cutaneous Melanoma in the Era of Modern Systemic Therapies.

Modern adjuvant systemic therapies (STs) have revolutionized the management of stage III melanoma. Currently, the role of adjuvant radiotherapy (RT) remains unclear. In this single-center retrospective study, patients with clinically detectable stage III melanoma with high-risk features for lymph node basin (LNB) recurrence and whose tumors were fully resected with complete lymphadenectomy (CLD) between 2010 and 2019 were assessed. We determined the cumulative incidence (CIF) of LNB recurrence and any disease recurrence or progression using competing risk analysis. A total of 108 patients were identified; the median age was 59 years (24-92), and 74 (69%) were men. A total of 51 (42%) received adjuvant RT, 22 (20%) received adjuvant ST, and 35 (32%) received no adjuvant therapy. The advent of ST changed clinical practice, with a significant increase in the use of adjuvant ST and a decrease in the use of RT when comparing practice patterns before and after 2015 (p < 0.001). The 3-year CIF of LNB recurrence was similar in patients treated with adjuvant RT (6.3%) and adjuvant ST (9.8%). The 3-year CIF of any disease recurrence or progression was lower in patients receiving adjuvant ST (24%) compared to those receiving adjuvant RT (52%) or no adjuvant therapy (55%, p = 0.06). Three-year overall survival (OS) was not significantly different in patients treated with ST compared to those not treated with any ST (p = 0.118). Despite ST replacing RT as the dominant adjuvant treatment modality, this change in practice has not resulted in increased LNB recurrence for patients at high risk of LNB recurrence following CLD.

Toxicity and outcomes of melanoma brain metastases treated with stereotactic radiosurgery: the risk of subsequent symptomatic intralesional hemorrhage exceeds that of radiation necrosis.

PURPOSE: We aimed to assess the outcomes and patterns of toxicity in patients with melanoma brain metastases (MBM) treated with stereotactic radiosurgery (SRS) with or without immunotherapy (IO). METHODS: From a prospective registry, we reviewed MBM patients treated with single fraction Gamma Knife SRS between 2008 and 2021 at our center. We recorded all systemic therapies (chemotherapy, targeted therapy, or immunotherapy) administered before, during, or after SRS. Patients with prior brain surgery were excluded. We captured adverse events following SRS, including intralesional hemorrhage (IH), radiation necrosis (RN) and local failure (LF), as well as extracranial disease status. Distant brain failure (DBF), extracranial progression-free survival (PFS) and overall survival (OS) were determined using a cumulative Incidence function and the Kaplan-Meier method. RESULTS: Our analysis included 165 patients with 570 SRS-treated MBM. Median OS for patients who received IO was 1.41 years versus 0.79 years in patients who did not (p = 0.04). Ipilimumab monotherapy was the most frequent IO regimen (30%). In the absence of IO, the cumulative incidence of symptomatic (grade 2 +) RN was 3% at 24 months and remained unchanged with respect to the type or timing of IO. The incidence of post-SRS g2 + IH in patients who did not receive systemic therapy was 19% at 1- and 2 years compared to 7% at 1- and 2 years among patients who did (HR: 0.33, 95% CI 0.11-0.98; p = 0.046). Overall, neither timing nor type of IO correlated to rates of DBF, OS, or LF. Among patients treated with IO, the median time to extracranial PFS was 5.4 months (95% IC 3.2 - 9.1). CONCLUSION: The risk of g2 + IH exceeds that of g2 + RN in MBM patients undergoing SRS, with or without IO. IH should be considered a critical adverse event following MBM treatments.

Fungal infection and neurodevelopmental outcomes at 18-30 months in preterm infants.

Background: Invasive fungal infection (IFI) is associated with significant mortality and morbidity among preterm infants but there has been no population-based study of long-term neurodevelopmental outcomes. The objective of this study was to examine population-based incidence trends as well as mortality, short term in-hospital morbidity and long-term neurodevelopmental outcomes among preterm infants with IFI, non-fungal infections (NFI) and no infections in Canada. Methods: We conducted a retrospective cohort study of 8,408 infants born at <29 weeks gestational age (GA), admitted to Canadian Neonatal Network neonatal intensive care units (NICU) from April 2009 to December 2017, and followed up at 18-30 months corrected age (CA) in Canadian Neonatal Follow-Up Network clinics. We compared mortality, long term neurodevelopmental outcomes and short term in-hospital morbidity among 3 groups of infants (IFI, NFI, and no infections). Results: The incidence of IFI was 1.3%, non-IFI 26.9% and no infections 71.7%. IFI incidence varied between 0.93% and 1.94% across the study period with no significant trend over time. Infants of higher gestational age were significantly (p < 0.01) less likely to have IFI. Among infants with IFI, NFI and no infections, the incidence of the significant neurodevelopmental impairment (sNDI) was 44.26%, 21.63% and 14.84% respectively, while mortality was 50%, 25.35% and 22.25% respectively. Even after risk adjustment for confounders (GA, Score for Neonatal Acute Physiology Version II, ruptured membranes >24 h, maternal antibiotic treatment, antenatal steroid use, cesarean section), infants with IFI had significantly higher odds of sNDI than NFI (aOR: 2.19; 95% CI: 1.23, 3.91) or no infections (aOR: 2.97; 95% CI: 1.55, 5.71), and higher odds of mortality than NFI (aOR: 1.55; 95% CI: 1.07, 2.26) or no infections (aOR: 1.45; 95% CI: 0.97, 2.17). Conclusions: Preterm infants with invasive fungal infections have significantly higher incidence of mortality and adverse neurodevelopmental outcomes than those with non-invasive fungal infections and no infections.

Anatomical and surgical characteristics correlate with pachymeningeal failure in patients with brain metastases after neurosurgical resection and adjuvant stereotactic radiosurgery.

PURPOSE: Neurosurgery (NS) is an essential modality for large brain metastases (BM). Postoperative stereotactic radiosurgery (SRS) is the standard of care adjuvant treatment. Pachymeningeal failure (PMF) is a newly described entity, distinct from classical leptomeningeal failure (LMF), that is uniquely observed in postoperative patients treated with adjuvant SRS. We sought to identify risk factors for PMF in patients treated with NS + SRS. METHODS: From a prospective registry (2009 to 2021), we identified all patients treated with NS + SRS. Clinical, imaging, pathological, and treatment factors were analyzed. PMF incidence was evaluated using a competing risks model. RESULTS: 144 Patients were identified. The median age was 62 (23-90). PMF occurred in 21.5% (31/144). Female gender [Hazard Ratio (HR) 2.65, p = 0.013], higher Graded Prognostic Assessment (GPA) index (HR 2.4, p < 0.001), absence of prior radiation therapy (HR N/A, p = 0.018), controlled extracranial disease (CED) (HR 3.46, p = 0.0038), and pia/dura contact (PDC) (HR 3.30, p = 0.0053) were associated with increased risk for PMF on univariate analysis. In patients with PDC, wider target volumes correlated with reduced risk of PMF. Multivariate analysis indicated PDC (HR 3.51, p = 0.0053), piecemeal resection (HR 2.38, p = 0.027), and CED (HR 3.97, p = 0.0016) independently correlated with PMF risk. PMF correlated with reduced OS (HR 2.90, p < 0.001) at a lower rate compared to LMF (HR 10.15, p < 0.001). CONCLUSION: PMF correlates with tumor PDC and piecemeal resection in patients treated with NS + SRS. For unclear reasons, it is also associated with CED. In tumors with PDC, wider dural radiotherapy coverage was associated with a lower risk of PMF.

Organ dysfunction and mortality in preterm neonates with late-onset bloodstream infection.

BACKGROUND: Organ dysfunction (ODF) in late-onset bloodstream infection (LBSI) is associated with increased risk of adverse outcomes. However, no established definition of ODF exists among preterm neonates. Our objective was to describe an outcome-based ODF definition for preterm infants, and assess factors associated with mortality. METHODS: This is a six-year retrospective study of neonates <35 weeks gestational age, >72 h of age, with non-CONS bacterial/fungal LBSI. Discriminatory ability of each parameter for mortality was evaluated: base deficit ≤-8 mmol/L (BD8), renal dysfunction (urine output <1 cc/kg/h or creatinine ≥100 µmol/L), hypoxic respiratory failure (HRF, ventilated, FiO2 = 1.0), or vasopressor/inotrope use (V/I). Multivariable logistic regression analysis was performed to derive a mortality score. RESULTS: One hundred and forty-eight infants had LBSI. BD8 had the highest individual predictive ability for mortality (AUROC = 0.78). The combination BD8 + HRF + V/I was used to define ODF (AUROC = 0.84). Fifty-seven (39%) infants developed ODF, among which 28 (49%) died. Mortality increased inversely relative to GA at LBSI-onset (aOR 0.81 [0.67, 0.98]) and directly relative to ODF occurrence (12.15 [4.48, 33.92]). Compared to no-ODF, ODF infants had lower GA and age at illness, and higher frequency of Gram-negative pathogen. CONCLUSIONS: Among preterm neonates with LBSI, significant metabolic acidosis, HRF, and vasopressor/inotrope use may identify infants high risk for mortality. These criteria could help identify patients for future studies of adjunctive therapies. IMPACT: Sepsis-related organ dysfunction is associated with increased risk of adverse outcomes. Among preterm neonates, significant metabolic acidosis, use of vasopressors/inotropes, and hypoxic respiratory failure may identify high-risk infants. This can be used to target research and quality improvement efforts toward the most vulnerable infants.

Dopamine or norepinephrine for sepsis-related hypotension in preterm infants: a retrospective cohort study.

The purpose of this study is to compare the clinical effectiveness of dopamine (DA) versus norepinephrine (NE) as first-line therapy for sepsis-related hypotension in preterm infants. This is a retrospective cohort study over 10 years at two tertiary neonatal units. Preterm infants born < 35 weeks post-menstrual age (PMA), who received DA or NE as primary therapy for hypotension during sepsis, defined as culture-positive or culture-negative infections or necrotizing enterocolitis (NEC), were included. Episode-related mortality (< 7 days from treatment), pre-discharge mortality, and major morbidities among survivors were compared between two groups. Analyses were adjusted using the inverse probability of treatment weighting estimated by propensity score (PS). A total of 156 infants were included, 113 received DA and 43 NE. The mean ± SD PMA at birth and at treatment for the DA and NE groups were 25.8 ± 2.3 vs. 25.2 ± 2.0 weeks and 27.7 ± 3.0 vs. 27.1 ± 2.6 weeks, respectively (p > 0.05). Pre-treatment, the NE group had higher mean airway pressure (14 ± 4 vs. 12 ± 4 cmH2O), heart rate (185 ± 17 vs. 175 ± 17 beats per minute), and median (IQR) fraction of inspired oxygen [0.67 (0.42, 1.0) vs. 0.52 (0.32, 0.82)] (p < 0.05 for all). After PS adjustment, NE was associated with lower episode-related mortality [adjusted odds ratio (95% CI) 0.55 (0.33, 0.92)], pre-discharge mortality [0.60 (0.37, 0.97)], post-illness new diagnosis of significant neurologic injury [0.32 (0.13, 0.82)], and subsequent occurrence of NEC/sepsis among the survivors [0.34, (0.18, 0.65)]. CONCLUSION: NE may be more effective than DA for management of sepsis-related hypotension among preterm infants. These data provide a rationale for prospective evaluation of these commonly used agents. WHAT IS KNOWN: •Dopamine is the commonest vasoactive agent used to support blood pressure among preterm infants. •For adult patients, norepinephrine is recommended as the preferred therapy over dopamine for septic shock. WHAT IS NEW: •This is the first study examining the relative clinical effectiveness of dopamine and norepinephrine as first-line pharmacotherapy for sepsis-related hypotension among preterm infants. •Norepinephrine use may be associated with lower mortality and morbidity than dopamine in preterm infants with sepsis.

Clinical impact of less invasive surfactant administration using video laryngoscopy in extremely preterm infants.

BACKGROUND: Examine the real-world clinical impact of adopting less invasive surfactant administration (LISA) as the primary surfactant administration method in extremely preterm infants. METHODS: Single-center pre-post cohort study conducted over a 4-year period comparing outcomes of spontaneously breathing inborn infants 24+0-28+6 weeks gestational age (GA) receiving surfactant via endotracheal tube (pre-cohort, n = 154) or LISA via thin catheter (post-cohort, n = 70). Primary outcome was need for invasive mechanical ventilation (IMV, ≥2 h) ≤72 h of age. Secondary outcomes were a composite of mortality, bronchopulmonary dysplasia, intraventricular hemorrhage ≥grade 3 or necrotizing enterocolitis, and its individual components. Groups were compared using propensity score methods, including covariates: GA, birth weight, sex, small for GA, SNAP II ≥20, premature rupture of membranes, maternal hypertension/diabetes, and C-section. RESULTS: GA and birth weight were 27.1 (26, 28.1) weeks and 914 (230) g, and 27.1 (26.1, 28.1) weeks and 920 (236) g for pre- and post-cohorts, respectively. Pre-cohort had higher C-section rates, (67% vs. 51%, p = 0.03). After adjustment for covariates, LISA was associated with reduced IMV exposure [AOR (95% CI) 0.07 (0.04, 0.11)], lower odds of the composite clinical outcome [0.49 (0.33, 0.73)], and most of its individual components. CONCLUSION: Real-world experience favors LISA as the primary method in extremely preterm infants with established spontaneous respiration. IMPACT: Less invasive surfactant administration (LISA) is associated with a reduction in respiratory morbidity, but real-world data of routine use among extremely preterm infants are limited. LISA is associated with reduced frequency of exposure to and duration of IMV in both ≤72 h after birth and during hospital stay. LISA is associated with a reduction in mortality, and most other major morbidities including bronchopulmonary dysplasia, and interventricular hemorrhage. Data from a large North American center providing real-world clinical outcomes following LISA as the primary method of surfactant administration.

Oxytocin at Elective Cesarean Delivery: A Dose-Finding Study in Pregnant People With Twin Pregnancy.

BACKGROUND: Multiple pregnancy is associated with higher risk of uterine atony, postpartum hemorrhage (PPH), blood transfusion, hysterectomy, and death. The optimal dose of oxytocin at cesarean delivery in people with twin pregnancy is unknown. We sought to determine the effective bolus dose of oxytocin required to initiate adequate uterine tone in 90% of people (ED90) with twin pregnancy undergoing elective cesarean delivery. Our hypothesis was that the dose of oxytocin would be higher than 0.5 international units (IU) but lower than 5 IU. METHODS: A double-blind dose-finding study using the biased coin up-down method was undertaken in people with twin pregnancy ≥36 weeks gestational age undergoing elective cesarean delivery under neuraxial anesthesia. Those with additional risk factors for PPH, apart from twin pregnancy, were excluded. Oxytocin was administered as an intravenous bolus over 1 minute on delivery of the second fetus. The first patient received 0.5 IU, and subsequent oxytocin doses were administered according to a sequential allocation scheme. The actual doses administered were 0.5, 1, 2, 3, 4, and 5 IU of oxytocin. The primary outcome was the response defined as the satisfactory uterine tone at 2 minutes after completion of administration of the oxytocin bolus, as assessed by the operating obstetrician. Secondary outcomes included need for rescue uterotonic drugs, adverse effects, and estimated blood loss. The ED90 was estimated using the Dixon-Mood and the isotonic regression methods. RESULTS: Thirty patients were included in study. The estimated ED90 of oxytocin was 4.38 IU (95% confidence interval [CI], 3.68-4.86 IU) and 3.41 IU (95% CI, 2.83-3.98 IU) by the isotonic regression and Dixon-Mood methods, respectively. Seven patients had inadequate tone at the 2-minute evaluation point and required rescue uterotonic drugs. The median (interquartile range [IQR]) estimated blood loss was 1031 mL (732-1462 mL) calculated by the change in 24-hour hematocrit. Incidence of hypotension after oxytocin administration was 27%, nausea 30%, and vomiting 17%. CONCLUSIONS: Our results demonstrated that people with twin pregnancy require a much higher dose of oxytocin than those with singleton pregnancies. We recommended people with twin pregnancies should receive an initial 5 IU bolus over at least 1 minute when undergoing elective cesarean delivery under neuraxial anesthesia.

Timing of Systemic Steroids and Neurodevelopmental Outcomes in Infants < 29 Weeks Gestation

Objective: To determine the association between postnatal age (PNA) at first administration of systemic postnatal steroids (sPNS) for bronchopulmonary dysplasia (BPD) and mortality or significant neurodevelopmental impairment (sNDI) at 18−24 months corrected age (CA) in infants < 29 weeks' gestation. Methods: Data from the Canadian Neonatal Network and Canadian Neonatal Follow-up Network databases were used to conduct this retrospective cohort study. Infants exposed to sPNS for BPD after the 1st week of age were included and categorized into 8 groups based on the postnatal week of the exposure. The primary outcome was a composite of mortality or sNDI. A multivariable logistic regression model adjusting for potential confounders was used to determine the association between the sPNS and ND outcomes. Results: Of the 10,448 eligible infants, follow-up data were available for 6200 (59.3%) infants. The proportion of infants at first sPNS administration was: 8%, 17.5%, 23.1%, 18.7%, 12.6%, 8.3%, 5.8%, and 6% in the 2nd, 3rd, 4th, 5th, 6th, 7th, 8−9th, and ≥10th week of PNA respectively. No significant association between the timing of sPNS administration and the composite outcome of mortality or sNDI was observed. The odds of sNDI and Bayley-III motor composite < 70 increased by 1.5% (95% CI 0.4, 2.9%) and 2.6% (95% CI 0.9, 4.4%), respectively, with each one-week delay in the age of initiation of sPNS. Conclusions: No significant association was observed between the composite outcome of mortality or sNDI and PNA of sPNS. Among survivors, each week's delay in initiation of sPNS may increase the odds of sNDI and motor delay.

Role of ultrasonography in an impalpable tissue larynx model during a simulated front-of-neck access scenario: a randomized simulation study.

PURPOSE: A large vertical incision is recommended when performing front-of-neck access in patients with impalpable neck landmarks during a cannot intubate-cannot oxygenate (CICO) scenario. We investigated the impact of ultrasonography on vertical incision size of a front-of-neck access on an ultrasound-compatible impalpable porcine larynx model. METHODS: Emergency medicine and anesthesia trainees were randomized to the Ultrasound (US, n = 21) and Non-Ultrasound (NUS, n = 21) groups. Within 1 week after a teaching session on airway ultrasound and Scalpel-Bougie-Tube (SBT) technique, participants were instructed to perform cricothyroidotomy on the model during a simulated cannot intubate-cannot oxygenate scenario. The primary outcome was a vertical size incision. Secondary outcomes were procedural completion time, horizontal size incision, tissue injury severity, and correct tube placement. RESULTS: The ultrasound group performed a significantly smaller vertical incision [median (IQR), 35.0 (15, 40) vs 65.0 (52, 100) mm (95% CI) - 30.0 (- 55.1, - 4.9), p = 0.02] and took longer total time to complete the procedure [median (IQR), 200.5 (126, 267) vs 93.5 (71.0, 167.5) secs (95% CI) 91.0 (3.73, 178.3), p = 0.04]. Tissue injury severity and correct tube placement were similar between groups. CONCLUSIONS: Ultrasound-guided identification of the cricothyroid membrane significantly reduced the recommended vertical incision size with similar success rates. However, there was an increased time when performing a Scalpel-Bougie-Tube cricothyroidotomy on an impalpable porcine larynx model by physicians in training. Ultrasonography should not be used in an emergency scenario of airway rescue. Its potential use to pre-mark the cricothyroid membrane should be considered in difficult airway management of impalpable neck.

RéSUMé: OBJECTIF: Il est recommandé de pratiquer une grande incision verticale lors de l'accès à l'avant du cou chez les patients dont les repères du cou sont impalpables, dans le cadre d'un scénario d'intubation impossible à oxygéner (CICO). Nous avons étudié l'impact de l'échographie sur la taille de l'incision verticale d'un accès à la face avant du cou sur un modèle de larynx porcin impalpable compatible avec l'échographie. MéTHODES: Des stagiaires en médecine d'urgence et en anesthésie ont été répartis de manière aléatoire entre les groupes "échographie" (US, n = 21) et "non-échographie" (NUS, n = 21). Une semaine après une session d'enseignement sur l'échographie des voies aériennes et la technique Scalpel-Bougie-Tube (SBT), les participants ont reçu l'instruction de réaliser une cricothyroïdotomie sur le modèle lors d'un scénario simulé d'impossibilité d'intubation et d'oxygénation. Le résultat primaire était une incision de taille verticale. Les résultats secondaires étaient le temps de réalisation de la procédure, la taille horizontale de l'incision, la gravité de la lésion tissulaire et le placement correct du tube. RéSULTATS: Le groupe échographie a réalisé une incision verticale significativement plus petite [médiane (IQR), 35,0 (15,40) vs 65,0 (52,100) mm (IC à 95 %) -30,0 (-55,1, -4,9), p = 0,02] et a pris un temps total plus long pour terminer la procédure [médiane (IQR), 200,5 (126, 267) vs 93,5 (71,0, 167,5) secondes (IC à 95 %) 91,0 (3,73, 178,3), p = 0,04]. La gravité des lésions tissulaires et le placement correct du tube étaient similaires entre les groupes. CONCLUSIONS: L'identification échoguidée de la membrane cricothyroïdienne a réduit de manière significative la taille de l'incision verticale recommandée avec des taux de réussite similaires. Cependant, il y avait une augmentation du temps lors de la réalisation d'une cricothyroïdotomie Scalpel-Bougie-Tube sur un modèle de larynx porcin impalpable par des médecins en formation. L'échographie ne doit pas être utilisée dans un scénario d'urgence de sauvetage des voies respiratoires. Son utilisation potentielle pour pré-marquer la membrane cricothyroïdienne devrait être envisagée dans la gestion des voies aériennes difficiles du cou impalpable.

Association of NEDA-4 With No Long-term Disability Progression in Multiple Sclerosis and Comparison With NEDA-3: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: No evidence of disease activity (NEDA)-4 has been suggested as a treatment target for disease-modifying therapy (DMT) in relapsing-remitting multiple sclerosis (RRMS). However, the ability of NEDA-4 to discriminate long-term outcomes in MS and how its performance compares with NEDA-3 remain uncertain. We conducted a systematic review and meta-analysis to evaluate (1) the association between NEDA-4 and no long-term disability progression in MS and (2) the comparative performance of NEDA-3 and NEDA-4 in predicting no long-term disability progression. METHODS: English-language abstracts and manuscripts were systematically searched in MEDLINE, Embase, and the Cochrane databases from January 2006 to November 2021 and reviewed independently by 2 investigators. We selected studies that assessed NEDA-4 at 1 or 2 years after DMT start and had at least 4 years of follow-up for determination of no confirmed disability progression. We conducted a meta-analysis using random-effects model to determine the pooled odds ratio (OR) for no disability progression with NEDA-4 vs EDA-4. For the comparative analysis, we selected studies that evaluated both NEDA-3 and NEDA-4 with at least 4 years of follow-up and examined the difference in the association of NEDA-3 and NEDA-4 with no disability progression. RESULTS: Five studies of 1,000 patients (3 interferon beta and 2 fingolimod) met inclusion criteria for both objectives. The median duration of follow-up was 6 years (interquartile range: 4-6 years). The prevalence of NEDA-4 ranged from 4.2% to 13.9% on interferon beta therapy and 24.9% to 25.1% on fingolimod therapy. The pooled OR for no long-term confirmed disability progression with NEDA-4 vs EDA-4 was 2.14 (95% confidence interval: 1.36-3.37; I2 = 0). We did not observe any significant difference between NEDA-4 and NEDA-3 in the comparative analyses. DISCUSSION: In patients with RRMS, NEDA-4 at 1-2 years was associated with 2 times higher odds of no long-term disability progression, at 6 years compared with EDA-4, but offered no advantage over NEDA-3.

Changes in sensory block level during a programmed intermittent epidural bolus regimen for labour analgesia: a prospective observational cohort study.

PURPOSE: In the context of a programmed intermittent epidural bolus (PIEB) regimen for labour analgesia, one can identify an upper sensory block level (USBL), defined as the highest dermatome with any altered sensation to cold, and a lower sensory block level (LSBL), defined as the highest dermatome with complete sensory block to cold. This study investigated whether and how these sensory block levels vary within PIEB cycles. METHODS: We enrolled patients requesting epidural analgesia. An epidural catheter was placed at L2/L3 or L3/L4. A test dose of 3 mL of bupivacaine 0.125% with fentanyl 3.3 µg·mL-1 was administered, followed by 12 mL of the same solution as the loading dose. A PIEB plus patient-controlled epidural analgesia (PCEA) regimen was initiated 40 min after the loading dose, with bupivacaine 0.0625% with fentanyl 2 µg·mL-1: PIEB 10 mL, PIEB interval 40 min, PCEA 5 mL, lockout interval 10 min, maximum hourly 30 mL. As per institutional protocol, sensory block levels to ice were assessed 20 min after the loading dose and then hourly. Patients included in the study underwent eight extra assessments: immediately before the second and fourth PIEB and 10, 20, and 30 min after the second and third PIEB. RESULTS: We studied 30 patients. The USBL and LSBL achieved their peak value 100 min after the loading dose. The median [interquartile range] USBL was T8 [T9-T7] and T6 [T7-T4] 20 and 100 min after the loading dose, respectively; LSBL was T10 [T11-T6] and T8 [T9-T6], respectively. There was no significant variation in USBL or LSBL within the PIEB cycle between the second and the third or the third and the fourth PIEB. CONCLUSION: Once peak sensory block levels are established, there is no significant variation in the USBL and LSBL within the PIEB cycles. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT04716660); registered 21 January 2021.

RéSUMé: OBJECTIF: Dans le contexte du schéma de bolus périduraux intermittents programmés (PIEB) pour l'analgésie du travail, on peut identifier un niveau de bloc sensoriel haut (USBL) défini comme étant le dermatome le plus haut ayant une quelconque modification de la sensation au froid et un niveau de bloc sensoriel bas (LSBL) défini comme étant le dermatome le plus haut ayant un bloc sensoriel complet au froid. Cette étude a cherché à savoir si et comment ces niveaux de blocs sensoriels varient au cours des cycles de PIEB. MéTHODES: Nous avons recruté des patientes demandant une analgésie péridurale. Un cathéter péridural a été placé au niveau L2/L3 ou au niveau L3/L4. Une dose test de 3 mL de bupivacaïne 0,125% avec fentanyl 3,3 µg·ml−1 était administrée, suivie de 12 mL de la même solution représentant la dose de base. Un protocole de PIEB plus analgésie péridurale contrôlée par la patiente (PCEA) a débuté 40 min après l'administration de la dose de base, comportant de la bupivacaïne 0,0625% et du fentanyl 2 µg·ml−1: PIEB 10 mL; intervalle de PIEB 40 min.; PCEA 5 ml; intervalle de verrouillage 10 min.; maximum par heure 30 mL. Conformément au protocole de l'établissement, les niveaux de bloc sensoriel à la glace ont été évalués 20 min après l'administration de la dose de base, puis toutes les heures. Les patientes incluses dans l'étude ont eu huit évaluations supplémentaires: immédiatement avant le deuxième et le quatrième PIEB et 10, 20 et 30 min après les deuxième et troisième PIEB. RéSULTATS: Nous avons étudié 30 patientes. L'USBL et le LSBL ont atteint leur valeur pic 100 min après l'administration de la dose de base. L'USBL médian [plage interquartile] était T8 [T9­T7] et T6 [T7­T4], respectivement 20 et 100 min après la dose de base; Le LSBL était, respectivement, T10 [T11­T6] et T8 [T9­T6]. Il n'y avait pas de variation significative de l'USBL ou du LSBL dans le cycle de PIEB entre le deuxième et le troisième ou le troisième et le quatrième PIEB. CONCLUSION: Une fois les niveaux maximums de blocs sensoriels établis, il n'y a pas de variation significative dans l'USBL et le LSBL dans les cycles de PIEB. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT04716660); enregistrée le 21 janvier 2021.

Validity of the vasoactive-inotropic score in preterm neonates receiving cardioactive therapies.

BACKGROUND: Vasoactive-Inotropic Score (VIS) is a weighted sum of various vasopressors and inotropes; its utility among preterm neonates is understudied. OBJECTIVE: To investigate the association between maximum VIS (VISmax) during the first 12, 24 and 48 h of treatment among preterm neonates who received vasopressors/inotropes, and the composite outcome of death/severe neuroinjury (sNI). METHODS: Retrospective cohort study, over 6-years, including neonates <35 weeks gestational age (GA). Infants who met the primary composite outcome of death or sNI (defined as new intraventricular hemorrhage ≥grade 3 or periventricular leukomalacia) were compared to those who survived without sNI. Maximum VIS was categorized as <10, 10-19 or ≥ 20 for comparison. RESULTS: 192 infants (mean GA and birth weight 26.8 ± 3.3 weeks and 952 ± 528 g, respectively) were included. The most common primary diagnosis was sepsis/necrotizing enterocolitis (69 %). Median VIS for the entire cohort was 10. Death/sNI was associated with lower GA at birth and treatment, as well as higher frequency of VISmax of 10-19 or ≥20, compared to <10, during each time period (all p < 0.01). Multivariable regression revealed GA at treatment and VISmax ≥ 20 [not 10-19, referenced to <10] were associated death/sNI; adjusted odds ratio (95 % CI) for VISmax ≥ 20 within 12, 24, and 48 h were 4.2 (1.6-11.0), 4.9 (1.9-12.3), and 6.7 (2.7-16.7), respectively. CONCLUSIONS: Vasoactive-Inotropic Score may be a valid measure to quantify cardiovascular support in preterm infants needing hemodynamic support. Maximum VIS ≥20 within 48 h of treatment initiation may identify patients at high risk of adverse outcomes.

Epidemiology of post-hemorrhagic ventricular dilatation in very preterm infants.

OBJECTIVE: To describe the incidence, trends, management's variability and short-term outcomes of preterm infants with severe post-hemorrhagic ventricular dilatation (sPHVD). METHODS: We reviewed infants <33 weeks' gestation who had PHVD and were admitted to the Canadian Neonatal Network between 2010 and 2018. We compared perinatal characteristics and short-term outcomes between those with sPHVD and those with mild/moderate PHVD and those with and without ventriculo-peritoneal (VP) shunt. RESULTS: Of 29,417 infants, 2439 (8%) had PHVD; rate increased from 7.3% in 2010 to 9.6% in 2018 (P = 0.005). Among infants with PHVD, sPHVD (19%) and VP shunt (29%) rates varied significantly across Canadian centers and between geographic regions (P < 0.01 and P = 0.0002). On multivariable analysis, sPHVD was associated with greater mortality, seizures and meningitis compared to mild/moderate PHVD. CONCLUSIONS: Significant variability in sPHVD and VP shunt rates exists between centers and regions in Canada. sPHVD was associated with increased mortality and morbidities.