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.

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.

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.

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.

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.

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.

Poractant alfa versus bovine lipid extract surfactant: prospective comparative effectiveness study.

OBJECTIVE: To compare short term respiratory outcomes in preterm infants treated with bovine lipid extract surfactant or poractant alfa. STUDY DESIGN: Prospective comparative effectiveness cohort study of infants <32 weeks' gestational age requiring surfactant in thirteen centers. Each center provided bovine lipid extract surfactant for a set period of time in the year 2019 and then changed to poractant alfa for the remainder of the year. The primary outcome was total duration of respiratory support. RESULT: 968 infants were included. 494 received bovine lipid extract surfactant and 474 received poractant alfa. No difference was observed in the total duration of respiratory support (mechanical ventilation or non-invasive) (median 38 vs 40.5 days), need to re-dose surfactant, bronchopulmonary dysplasia, survival to discharge, or length of admission. CONCLUSION: In this pragmatic study, we did not identify any difference in short term outcomes between the groups based on the type of surfactant received.

Lower Maternal Chronic Physiological Stress and Better Child Behavior at 18 Months: Follow-Up of a Cluster Randomized Trial of Neonatal Intensive Care Unit Family Integrated Care.

OBJECTIVE: To assess whether Family Integrated Care (FICare) in the neonatal intensive care unit improves maternal chronic physiological stress and child behavior at 18 months of corrected age for infants born preterm. STUDY DESIGN: Follow-up of a multicenter, prospective cluster-randomized controlled trial comparing FICare and standard care of children born at <33 weeks of gestation and parents, stratified by tertiary neonatal intensive care units, across Canada. Primary outcomes at 18 months of corrected age were maternal stress hormones (cortisol, ie, hair cumulative cortisol [HCC], dehydroepiandrosterone [DHEA]) assayed from hair samples. Secondary outcomes included maternal reports of parenting stress, child behaviors (Internalizing, Externalizing, Dysregulation), and observer-rated caregiving behaviors. Outcomes were analyzed using multilevel modeling. RESULTS: We included 126 mother-child dyads from 12 sites (6 FICare sites, n = 83; 6 standard care sites, n = 43). FICare intervention significantly lowered maternal physiological stress as indicated by HCC (B = -0.22 [-0.41, -0.04]) and cortisol/DHEA ratio (B = -0.25 [-0.48, -0.02]), but not DHEA (B = 0.01 [-0.11, 0.14]). Enrollment in FICare led to lower child Internalizing (B = -0.93 [-2.33, 0.02]) and Externalizing behavior T scores (B = -0.91 [-2.25, -0.01]) via improvements to maternal HCC (mediation). FICare buffered the negative effects of high maternal HCC on child Dysregulation T scores (B = -11.40 [-23.01, 0.21]; moderation). For mothers reporting high parenting stress at 18 months, FICare was related to lower Dysregulation T scores via maternal HCC; moderated mediation = -0.17 (-0.41, -0.01). CONCLUSIONS: FICare has long-term beneficial effects for mother and child, attenuating maternal chronic physiological stress, and improving child behavior in toddlerhood. CLINICAL TRIAL REGISTRATION: NCT01852695.

Interrater agreement for sonographic stomach position classification in fetal diaphragmatic hernia across the North American Fetal Therapy Network.

OBJECTIVE: To evaluate inter-rater agreement for sonographic classification of stomach position (as a surrogate for liver herniation) in fetal left congenital diaphragmatic hernia (LCDH) among: (i) fetal medicine specialists from the North American Fetal Therapy Network (NAFTNet) centers within and without the fetal endoscopic tracheal occlusion (FETO) consortium and in comparison to an expert external reviewer (ER1); and (iii) among two expert ERs (ER1 and ER2). METHODS: Forty-eight physicians from 26 NAFTNet centers and 2 ERs were asked to assess 13 sonographic clips of isolated LCDH and classify stomach position as "intra-abdominal," "anterior left chest," "mid to posterior left chest," or "retro-cardiac" based on the classification published by Basta et al.8 Interrater agreement was assessed by determining proportion of stomach position ratings concordant amongst NAFTNet participants and ER1. Agreement for stomach position between ERs was calculated using kappa statistics. RESULTS: Agreement for stomach position was 69% (39%-85%; n = 19) and 54% (23%-92%; n = 29) among FETO and non-FETO NAFTNet participants, respectively, when compared to ER1. Most disagreement in stomach position was related to a discrepancy of one position. ERs were in agreement for stomach position in 5 of 13 cases (38.5%) and inter-rater agreement was highest for "anterior" stomach position. CONCLUSION: Interrater agreement for stomach position assessment in CDH was poor across NAFTNet and indeed amongst expert reviewers.

Predicting pain after Cesarean delivery: pressure algometry, temporal summation, three-item questionnaire.

PURPOSE: Approximately one in five women will experience severe postoperative pain after Cesarean delivery (CD). Previously, a bedside three-item questionnaire (3-IQ) has shown to predict women experiencing higher evoked pain intensity after CD, with an area under the receiver operator characteristics (ROC) curve of 0.72. We hypothesized that the addition of psychophysical pain tests to the existing 3-IQ would improve the ability to predict severe pain in women undergoing elective CD under spinal anesthesia METHODS: This was a prospective cohort study on women undergoing elective CD under spinal anesthesia. Women were assessed preoperatively using the 3-IQ, pressure algometry (PA) and mechanical temporal summation (TS) response. All women received standard perioperative care, including a multimodal analgesia regimen that included intrathecal fentanyl and morphine. A 0-100 mm visual analogue scale (VAS) was used to assess the severity of pain at rest (VASr) and on movement (VASm) at 24 and 48 hr after surgery. Patient satisfaction and opioid consumption were also recorded. We performed ROC curve analyses to assess whether we could improve the ability to predict our primary outcome of severe pain on movement at 24 hr (VASm24 ≥ 70). RESULTS: We studied 195 women. Median [interquartile range] VASm24 was 53 [32-72] and 28% of patients experienced a VASm24 ≥ 70. The ability to predict a VASm24 ≥ 70 assessed by the area under the ROC curve was 0.64 using the 3-IQ and 0.67 using the 3-IQ combined with TS and PA. CONCLUSION: The addition of PA and TS to the 3-IQ model resulted in a predictive model that performed similarly to the 3-IQ model alone. Further research is warranted in this area to better predict women at risk of severe pain post CD.

RéSUMé: OBJECTIF: Environ une femme sur cinq souffrira de douleur postopératoire sévère après un accouchement par césarienne. Un questionnaire à trois critères (Q3C) administré au chevet de la patiente a déjà été utilisé pour prédire quelles femmes éprouveraient une intensité de douleur évoquée plus élevée après une césarienne, avec une aire sous la courbe ROC de 0,72. Nous avons émis l'hypothèse que l'ajout de tests psychophysiques de douleur au Q3C existant améliorerait notre capacité à prédire la douleur sévère chez les femmes bénéficiant d'une césarienne élective sous rachianesthésie. MéTHODE: Il s'agissait d'une étude de cohorte prospective auprès de femmes bénéficiant d'une césarienne élective sous rachianesthésie. Les femmes ont été évaluées en préopératoire à l'aide du Q3C, de l'algométrie par pression (AP) et de la réponse à une sommation temporale (ST) mécanique. Toutes les femmes ont bénéficié des soins périopératoires standard, ainsi que d'un régime d'analgésie multimodal incluant fentanyl et morphine intrathécaux. Une échelle visuelle analogique (EVA) de 0 à 100 mm a été utilisée pour évaluer la sévérité de la douleur au repos (EVAr) et en mouvement (EVAm) à 24 et 48 heures après la chirurgie. La satisfaction des patientes et la consommation d'opioïdes ont également été enregistrées. Nous avons effectué des analyses de la courbe ROC pour déterminer s'il nous était possible d'améliorer notre capacité à prédire notre critère d'évaluation principal, soit la douleur sévère à la mobilisation à 24 heures (EVAm24 ≥ 70). RéSULTATS: Nous avons étudié 195 femmes. L'EVAm 24 médiane [écart interquartile] était de 53 [32-72] et 28 % des patientes ont noté un score sur l'EVAm24 ≥ 70. La capacité à prédire un score sur l'EVAm24 ≥ 70 tel qu'évalué par la surface sous la courbe ROC était de 0,64 en utilisant le Q3C et de 0,67 en utilisant le Q3C combiné à la ST et l'AP. CONCLUSION: L'ajout de l'AP et de la ST au modèle de Q3C a résulté en un modèle prédictif présentant une performance similaire au modèle de Q3C seul. D'autres recherches sont nécessaires dans ce domaine pour mieux prédire les femmes à risque de douleur sévères après une césarienne.

Rates and Determinants of Mother's Own Milk Feeding in Infants Born Very Preterm.

OBJECTIVES: To examine rates and determinants of mother's own milk (MOM) feeding at hospital discharge in a cohort of infants born very preterm within the Canadian Neonatal Network (CNN). STUDY DESIGN: This was a population-based cohort study of infants born at <33 weeks of gestation and admitted to neonatal intensive care units (NICUs) participating in the CNN between January 1, 2015, and December 31, 2018. We examined the rates and determinants of MOM use at discharge home among the participating NICUs. We used multivariable logistic regression analysis to identify independent determinants of MOM feeding. RESULTS: Among the 6404 infants born very preterm and discharged home during the study period, 4457 (70%) received MOM or MOM supplemented with formula. Rates of MOM feeding at discharge varied from 49% to 87% across NICUs. Determinants associated with MOM feeding at discharge were gestational age 29-32 weeks compared with <26 weeks (aOR 1.56, 95% CI 1.25-1.93), primipara mothers (aOR 2.12, 95% CI 1.86-2.42), maternal diabetes (aOR 0.79, 95% CI 0.66-0.93), and maternal smoking (aOR 0.27, 95% CI 0.19-0.38). Receipt of MOM by day 3 of age was the major predictor of breast milk feeding at discharge (aOR 3.61, 95% CI 3.17-4.12). CONCLUSIONS: Approximately two-thirds of infants born very preterm received MOM at hospital discharge, and rates varied across NICUs. Supporting mothers to provide breast milk in the first 3 days after birth may be associated with improved MOM feeding rates at discharge.

Do all patients with HER2 positive breast cancer require one year of adjuvant trastuzumab? A systematic review and meta-analysis.

One year of adjuvant trastuzumab is considered the standard treatment for patients with HER2 positive breast cancer. However, a shorter duration of trastuzumab may be associated with reduced costs and side effects. Results from randomized trials with diverse non-inferiority margins comparing one year to a shorter duration of adjuvant trastuzumab are not consistent and have not been systematically reviewed using a non-inferiority meta-analysis approach. We conducted a systematic review and meta-analysis of randomized trials to assess whether a shorter duration of adjuvant trastuzumab was non-inferior to one year of treatment or not. The non-inferiority margin for the meta-analysis was pre-defined as the median of the margins of all the trials included. Data of 11,376 patients from 5 trials were analyzed. Non-inferiority margins in included studies varied from 1.15 to 1.53 with median of 1.29 for HR of DFS. A shorter duration of trastuzumab was non-inferior to one year of therapy for DFS (HR 1.13, 95%CI 1.03-1.24) but inconclusive for OS (HR 1.14, 95%CI 1.00-1.30). In a subgroup analysis for DFS outcome, shorter therapy was non-inferior in patients with ER positive disease (HR 1.10, 95%CI 0.95-1.28) and those with sequential therapy (HR 0.97, 95%CI 0.75-1.27) and when the duration of treatment was 6 months (HR 1.09, 95%CI 0.98-1.22). Although a shorter duration of adjuvant trastuzumab was non-inferior to one year of therapy for DFS in patients with HER2 positive breast cancer based on our HR margin of 1.29, any benefit of a shorter duration comes at a loss of efficacy with an increase in absolute risk up to 3.9% for 5 year DFS. Whether the potential increased risk is clinically acceptable for the benefits of a shorter duration remains debatable.

Comparing endometrial receptivity array to histologic dating of the endometrium in women with a history of implantation failure.

For patients with recurrent implantation failure in IVF, histologic or transcriptomic testing of the endometrium during the mid-secretory phase is often considered. Histological dating of endometrial biopsies (Noyes criteria) can determine if endometrial morphology is consistent with the period of receptivity. Alternatively, endometrial tissue can be sent for a commercial Endometrial Receptivity Array (ERA) test which characterizes the gene expression of the endometrium using a panel of 238 genes that have been implicated in endometrial receptivity. This study aimed to compare the two tests to assess their concordance and to examine the ability of the ERA to successfully predict implantation and pregnancy in a subsequent personalized embryo transfer. A retrospective review was done of 97 patients with a history of implantation failure who underwent an ERA, 35 of whom had histologic dating on the same sample. ERA and histology were classified as 'concordant' when samples were receptive by both tests or non-receptive by both tests. The ERA result was then used to personalize the embryo transfer day, and pregnancy rates from the first subsequent frozen transfer cycle were analyzed. The results indicated that there is poor concordance between ERA and histological dating with only 40.0% agreement and a kappa (95%CI) = -0.18 (-0.50, 0.14). According to the ERA, 48.5% of biopsies were receptive, 47.4% were non-receptive and 2.01% were insufficient tissue for analysis. The clinical pregnancy rate in patients shown to be receptive by ERA was 26.7% and non-receptive was 22.5% following the subsequent personalized ET (p = 0.66). This study concludes that there is a high degree of discordance between histological dating of the endometrium and molecular analysis by ERA. There was no evidence of clinical benefit when embryo transfer was personalized according to ERA in patients with a history of implantation failure.

A Systematic Review and Network Meta-analysis of Novel Androgen Receptor Inhibitors in Non-metastatic Castration-resistant Prostate Cancer.

BACKGROUND: Among men with high-risk non-metastatic castrate-resistant prostate cancer (nmCRPC), we used network meta-analysis to compare non-steroidal anti-androgens (NSAAs) and stratified class-level meta-analysis to identify subgroups with particular benefit from NSAAs with androgen deprivation therapy versus androgen deprivation therapy alone. MATERIALS AND METHODS: We performed a systematic review of phase III parallel-group randomized controlled trials in adult men with nmCRPC. Primary outcome was metastasis-free survival (MFS). Secondary outcomes included overall survival (OS), prostate-specific antigen (PSA) progression-free survival (PFS), and rates of grade 3 to 4 adverse events (AEs). We assessed class-level effects using random effects models; effect modification owing to subgroup effects using random-effects models to pool study-level differences; and comparative outcomes between agents using fixed-effect network models in a Bayesian framework. RESULTS: Three randomized controlled trials were identified. Pooled MFS, PSA-PFS, and OS were significantly greater with NSAA versus placebo (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.25-0.41; HR, 0.08; 95% CI, 0.05-0.13; and HR, 0.74; 95% CI, 0.61-0.90, respectively). Subgroup analysis demonstrated a greater benefit with NSAAs in men with Eastern Cooperative Oncology Group performance status 0 (HR, 0.30; 95% CI, 0.24-0.38) versus 1 (HR, 0.45; 95% CI, 0.36-0.56; P = .005), but no difference owing to PSA doubling time (P = .43) or use of osteoclast targeting therapy (P = .77). Bayesian analysis showed apalutamide and enzalutamide had a 56% and 44% likelihood of maximizing MFS, respectively, with subgroup analysis demonstrating these agents were preferred regardless of PSA doubling time and performance status. There was a 44%, 41%, and 15% likelihood that apalutamide, darolutamide and enzalutamide offered the greatest OS benefit, respectively. Grade 3 to 4 AEs were more common with NSAAs (odds ratio [OR], 1.47; 95% CI, 1.27-1.71) and there was a 61% chance that darolutamide was preferred. CONCLUSIONS: NSAAs improve survival in high-risk nmCRPC. Apalutamide and enzalutamide may result in improved oncologic outcomes. Darolutamide may result in fewer AEs. Phase IV data are needed to validate these findings.

A randomized controlled trial protocol comparing the feeds of fresh versus frozen mother's own milk for preterm infants in the NICU.

BACKGROUND: Necrotizing enterocolitis (NEC) is the leading cause of death among preterm infants born at < 30 weeks' gestation. The incidence of NEC is reduced when infants are fed human milk. However, in many neonatal intensive care units (NICUs), it is standard practice to freeze and/or pasteurize human milk, which deactivates bioactive components that may offer additional protective benefits. Indeed, our pilot study showed that one feed of fresh mother's own milk per day was safe, feasible, and can reduce morbidity in preterm infants. To further evaluate the benefits of fresh human milk in the NICU, a randomized controlled trial is needed. METHODS: Our prospective multicenter, double-blinded, randomized, controlled trial will include infants born at < 30 weeks' gestation and admitted to one of 29 tertiary NICUs in China. Infants in the intervention (fresh human milk) group (n = 1549) will receive at least two feeds of fresh human milk (i.e., within 4 h of expression) per day from the time of enrollment until 32 weeks' corrected age or discharge to home. Infants in the control group (n = 1549) will receive previously frozen human milk following the current standard protocols. Following informed consent, enrolled infants will be randomly allocated to the control or fresh human milk groups. The primary outcome is the composite outcome mortality or NEC ≥ stage 2 at 32 weeks' corrected age, and the secondary outcomes are mortality, NEC ≥ stage 2, NEC needing surgery, late-onset sepsis, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), weight gain, change in weight, increase in length, increase in head circumference, time to full enteral feeds, and finally, the number and type of critical incident reports, including feeding errors. DISCUSSION: Our double-blinded, randomized, controlled trial aims to examine whether fresh human milk can improve infant outcomes. The results of this study will impact both Chinese and international medical practice and feeding policy for preterm infants. In addition, data from our study will inform changes in health policy in NICUs across China, such that mothers are encouraged to enter the NICU and express fresh milk for their infants. TRIAL REGISTRATION: Chinese Clinical Trial Registry; #ChiCTR1900020577; registered January 1, 2019; http://www.chictr.org.cn/showprojen.aspx?proj=34276.

First-line Treatment of Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis.

CONTEXT: No head-to-head clinical trials compare contemporary first-line therapies for metastatic renal cell carcinoma (mRCC). A network meta-analysis provides an approach for quantitative analysis. OBJECTIVE: To indirectly compare the efficacy and safety of first-line treatments for mRCC in the intention-to-treat (ITT) population and by clinical risk group. EVIDENCE ACQUISITION: An updated systematic review from database inception to February 17, 2019 identified all parallel-group randomized controlled trials assessing first-line therapy for mRCC. "Clinically relevant" studies were selected for a network meta-analysis. Progression-free survival (PFS) was the primary outcome. Overall survival (OS), overall response rate (ORR), and grade 3 and 4 adverse events (AEs) were secondary outcomes. EVIDENCE SYNTHESIS: We identified 12 relevant trials: 12 reported outcomes for PFS, nine for OS, 10 for ORR, and nine for AEs. In the ITT population, cabozantinib (surface under the cumulative ranking curves [SUCRA] 84%), avelumab plus axitinib (SUCRA 68%), and pembrolizumab plus axitinib (SUCRA 82%) were superior to the other agents for PFS; pembrolizumab plus axitinib appeared superior for OS (SUCRA 95%); and atezolizumab demonstrated the lowest likelihood of AEs (SUCRA 100%). Findings were similar in the intermediate/poor-risk subgroup. Based on the limited data available, avelumab plus axitinib may be preferred in patients with favorable-risk disease. CONCLUSIONS: The optimal first-line treatment for mRCC appears to differ by efficacy endpoint, toxicity, and clinical risk group. Direct comparative studies remain important in guiding treatment choice. PATIENT SUMMARY: Head-to-head comparisons do not exist for the newest treatments of metastatic renal cell carcinoma (mRCC). In an indirect comparison, we found that pembrolizumab plus axitinib and cabozantinib are good options for most patients with mRCC.

Epidural electrical stimulation test versus local anesthetic test dose for thoracic epidural catheter placement: a prospective observational study.

PURPOSE: This study examined the concordance between epidural electrical stimulation test (EEST) and local anesthetic (LA) test dose to indicate correct thoracic epidural catheter position. The relationship between the test results and epidural postoperative analgesia was also assessed. METHODS: This prospective observational cohort study was done in patients receiving thoracic epidural analgesia for abdominal surgery. After insertion, the epidural catheter was tested using a nerve stimulator to elicit a motor response. The LA test dose was then administered, and sensory block to ice and pinprick was assessed. The primary outcome was the presence/absence of motor response to EEST and sensory block to test dose. Concordance of responses was assessed using kappa statistics, and their predictive power of postoperative epidural analgesia was evaluated. RESULTS: Sixty-eight thoracic epidural catheters were inserted, of which 62 were used perioperatively. The kappa agreement between EEST and LA test dose responses was moderate at 0.42 (95% confidence interval [CI], 0.18 to 0.67). Positive responses to EEST and LA test dose were observed in 62 (100%) and 50 (81%) patients, respectively, while 52 patients (84%) showed adequate analgesia postoperatively. The sensitivity (95% CI) of EEST and LA test dose to predict adequate postoperative epidural analgesia was 1 (0.93 to 1) and 0.79 (0.65 to 0.89), respectively, and the positive predictive values (95% CI) of EEST and LA test dose were 0.84 (0.75 to 0.93) and 0.82 (0.71 to 0.92), respectively. CONCLUSION: Following thoracic epidural catheter insertion, the responses to the EEST and LA test dose showed "moderate" agreement. The EEST has a higher sensitivity than the LA test dose to predict adequate epidural analgesia following abdominal surgery, however, both tests have a comparable positive predictive value.

RéSUMé: OBJECTIF: Cette étude a porté sur la concordance entre le test de stimulation électrique péridurale (EEST) et le test par une dose d'anesthésique local (AL) pour indiquer la position adéquate d'un cathéter thoracique. La relation entre les résultats des tests et l'analgésie péridurale postopératoire a également été évaluée. MéTHODES: Cette étude de cohorte observationnelle prospective a été menée chez des patients recevant une analgésie péridurale thoracique pour chirurgie abdominale. Après insertion, le cathéter épidural a été testé au moyen d'un stimulateur nerveux pour déclencher une réponse motrice. La dose test d'AL a alors été administrée et le blocage sensitif à la glace et aux piqûres a été évalué. Le critère d'évaluation principal était la présence ou l'absence de réponse motrice à l'EEST et au blocage sensitif à la dose test. La concordance des réponses a été évaluée au moyen de statistiques kappa et leur prédiction de l'efficacité de l'analgésie péridurale postopératoire a été évaluée. RéSULTATS: Soixante-huit cathéters périduraux thoraciques ont été insérés parmi lesquels 62 ont été utilisés en périopératoire. La concordance kappa entre les réponses à l'EEST et à la dose test d'AL a été modérée : 0,42 (intervalle de confiance [IC] à 95 %, 0,18 à 0,67). Les réponses positives à l'EEST et à la dose test d'AL ont été observées chez respectivement 62 (100 %) et 50 (81 %) patients, tandis que 52 patients (84 %) ont présenté une analgésie postopératoire adéquate. La sensibilité (IC à 95 %) de l'EEST et de la dose test d'AL pour la prédiction de l'analgésie péridurale postopératoire a été, respectivement, de 1 (0,93 à 1) et 0,79 (0,65 à 0,89) et les valeurs prédictives positives (IC à 95 %) de l'EEST et de la dose test d'AL ont été, respectivement, de 0,84 (0,75 à 0,93) et 0,82 (0,71 à 0,92). CONCLUSION: Après insertion d'un cathéter péridural thoracique, la concordance entre l'EEST et la dose test d'AL s'est avérée « modérée ¼. La sensibilité de l'EEST pour la prédiction d'une analgésie péridurale adéquate après chirurgie abdominale est supérieure à celle de la dose test d'AL; toutefois les deux tests ont des valeurs prédictives positives comparables.