Citations

Importance Physical abuse is a common but preventable cause of long-term childhood morbidity and mortality. Despite the strong association between abuse in an index child and abuse in contact children, there is no guidance outlining how to screen the latter, significantly more vulnerable group, for abusive injuries. Consequently, the radiological assessment of contact children is often omitted, or variably performed, allowing occult injuries to go undetected and increasing the risk of further abuse. Objective To report an evidence-based and consensus-derived set of best practices for the radiological screening of contact children in the context of suspected child physical abuse. Evidence Review This consensus statement is supported by a systematic review of the literature and the clinical opinion of an internationally recognized group of 26 experts. The modified Delphi consensus process comprised 3 meetings of the International Consensus Group on Contact Screening in Suspected Child Physical Abuse held between February and June 2021. Findings Contacts are defined as the asymptomatic siblings, cohabiting children, or children under the same care as an index child with suspected child physical abuse. All contact children should undergo a thorough physical examination and a history elicited prior to imaging. Contact children younger than 12 months should have neuroimaging, the preferred modality for which is magnetic resonance imaging, and skeletal survey. Contact children aged 12 to 24 months should undergo skeletal survey. No routine imaging is indicated in asymptomatic children older than 24 months. Follow-up skeletal survey with limited views should be performed if abnormal or equivocal at presentation. Contacts with positive findings should be investigated as an index child. Conclusions and Relevance This Special Communication reports consensus recommendations for the radiological screening of contact children in the context of suspected child physical abuse, establishing a recognized baseline for the stringent evaluation of these at-risk children and providing clinicians with a more resilient platform from which to advocate for them.

Background: Multiple studies have compared outcomes among patients undergoing revision anterior cruciate ligament reconstruction (ACLR) with autograft versus allograft, but these data are inconsistently reported and long-term outcomes depending on graft type are yet to be determined. Purpose: To perform a systematic review of clinical outcomes after revision ACLR (rACLR) with autograft versus allograft. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of the literature was performed by searching PubMed, the Cochrane Library, and Embase to identify studies that compared the outcomes of patients undergoing rACLR with autograft versus allograft. The search phrase used was autograft allograft revision anterior cruciate ligament reconstruction. Graft rerupture rates, return-to-sports rates, anteroposterior laxity, and patient-reported outcome scores (subjective International Knee Documentation Committee, Tegner, Lysholm, and Knee injury and Osteoarthritis Outcome Score) were evaluated. Results: Eleven studies met inclusion criteria, including 3011 patients undergoing rACLR with autograft (mean age, 28.9 years) and 1238 patients undergoing rACLR with allograft (mean age, 28.0 years). Mean follow-up was 57.3 months. The most common autograft and allograft types were bone–patellar tendon–bone grafts. Overall, 6.2% of patients undergoing rACLR experienced graft retear, including 4.7% in the autograft group and 10.2% in the allograft group ( P < .0001). Among studies that reported return-to-sports rates, 66.2% of patients with an autograft returned to sports as opposed to 45.3% of patients with an allograft ( P = .01). Two studies found significantly greater postoperative knee laxity in the allograft group as compared with the autograft group ( P < .05). Among all patient-reported outcomes, 1 study found 1 significant difference between groups: patients with an autograft had a significantly higher postoperative Lysholm score when compared with patients with an allograft. Conclusion: Patients undergoing revision ACLR with an autograft can be expected to experience lower rates of graft retear, higher rates of return to sports, and less postoperative anteroposterior knee laxity when compared with patients undergoing revision ACLR with an allograft.

Abstract Objective: Aberrantly methylated DNA may be used to detect minimal residual disease or early recurrence in breast cancer. As a 1st step, we aimed to develop an MDM panel to delineate between healthy women, stage I-III breast cancer in remission with no evidence of disease (NED), and metastatic breast cancer (MBC). Methods: We prospectively enrolled patients into 3 groups: healthy controls (adult females with a normal mammogram in past 12 months with no history of breast cancer), NED [stage I-III breast cancer with no clinical evidence of recurrence 6 months - 3 years post-treatment (adjuvant endocrine therapy allowed)], and MBC (collected either at initial diagnosis of untreated metastatic disease or radiographic progression). DNA was extracted from 6 mL of plasma derived from blood collected in LBgard tubes (Exact Sciences Corp., San Diego CA), and was bisulfite-treated and assayed by target enrichment long-probe quantitative amplified signal (TELQASTM) method for a panel of 15 previously identified MDMs [Table], normalized by the control gene, B3GALT6. Areas under the receiver operating characteristic curve (AUC) were calculated for each MDM to assess discrimination of MBC from other groups. With 60 patients per group, we had greater than 80% power to detect a difference of 0.20 from the null AUC of 0.7. Results: We tested samples from 60 MBC (10 untreated, 50 recurrent), 60 NED, and 60 healthy women. The median age was 63 (IQR, 55-72) and was not different between groups. The NED group was all hormone-receptor (HR) positive, with 47 (78%) being human epidermal growth factor receptor 2 negative (HER2-) and 13 (22%) HER2+; 48 (80%) were stage I and 9 (15%) were N+. The MBC group had 35 (58%) patients with HR+/HER2- tumors, 11 (18%) HR+/HER2+, and 6 (10%) HR-/HER2-, 4 (7%) HR-/HER2+, with 4 (7%) unknown. Of the 41 MBC whose original stage and nodal status were known 9 (22%) were stage I and 22 (54%) were N+. The markers were able to discriminate between MBC and NED patient samples with AUCs from 0.97 to 0.72. AUCs for 10/15 MDMs (ITPRIPL1, EMX1, C17orf64, OSR2, TRIM67, CHST2, IFFO1, TRH, FAM59B, and MPZ) were &gt;0.90. No difference in MDMs was observed between the healthy and NED groups. Conclusions: MDMs, assayed from plasma, appear highly discriminant for metastatic breast cancer cases in comparison to control patients with NED or healthy controls. Further clinical validation of this MDM panel in a larger cohort is warranted. Table 1. Plasma MDM discrimination of metastatic breast cancer (MBC) from healthy controls and previously treated breast cancer patients with no evidence of disease (NED) Citation Format: Karthik V. Giridhar, Fergus J. Couch, Jason P. Sinnwell, Seth W. Slettedahl, William R. Taylor, Douglas W. Mahoney, Patrick H. Foote, Maria C. O’Connell, Mariah J. Robran, Mary E. Devens, Anna M. Gonser, Nicole Larson, Karen A. Doering, Kelli N. Burger, Michael Kaiser, Hatim Allawi, Kathryn Ruddy, Janet Olson, John B. Kisiel. Plasma assay of methylated DNA markers (MDM) detects patients with metastatic breast cancer (MBC) compared to healthy controls and treated breast cancer patients with no evidence of disease [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-06.

Abstract Background Adjuvant abemaciclib (a CDK4 and 6 inhibitor) combined with ET resulted in significant and clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in patients (pts) with HR+, HER2-, node-positive, high risk EBC in the monarchE trial, and is an approved adjuvant therapy for these patients. Here we present efficacy results from a pre-specified overall survival interim analysis (OS IA2) which was planned to occur 2 years (yrs) after the primary outcome analysis. Methods Pts were randomized (1:1) to receive ET for up to 10 yrs +/- abemaciclib for 2 yrs (study treatment period). High-risk EBC was defined as either ≥4 positive axillary lymph nodes (ALN), or 1-3 ALN with either Grade 3 disease and/or tumor ≥5 cm (Cohort 1). While the proliferation biomarker Ki-67 was centrally assessed in all pts with available tissue sample, an additional smaller group of pts with 1-3+ ALN and central Ki-67 ≥20% as the only high-risk feature were included (Cohort 2). The intent-to-treat (ITT) population consisted of both Cohort 1 (5120 pts) and Cohort 2 (517 pts). Hazard ratios (HR) were estimated using Cox proportional hazard model. Results At a median follow-up of 42 months, all pts were off abemaciclib. IDFS and DRFS data illustrate a sustained benefit beyond the treatment period. In the ITT population, the HR for IDFS was 0.664 (95% CI: 0.578, 0.762) and DRFS was 0.659 (95% CI: 0.567, 0.767). At 4 yrs, this reflected an improvement in IDFS rates from 79.4% to 85.8% (absolute difference 6.4%), and in DRFS rates from 82.5% to 88.4% (absolute difference 5.9%). The continued separation of the curves was associated with an increase in absolute benefit in IDFS 4-year rates compared to 2-and 3-year IDFS rates (absolute difference 2.8% and 4.8% respectively). While OS remained immature, there was a lower number of deaths observed in the abemaciclib plus ET arm compared to the ET alone arm (157 [5.6%] vs 173 [6.1%], HR 0.929 [95% CI: 0.748, 1.153], p = 0.503), suggesting that the robust benefit in IDFS and DRFS began to translate into a numerically favorable OS HR. As previously described, within Cohort 1, a Ki-67 index of ≥20% was associated with a worse prognosis, but similar abemaciclib treatment effects were observed regardless of Ki-67 index. No new safety signals were observed. Conclusion The clinically meaningful benefit of adjuvant abemaciclib added to ET in HR+, HER2-, node-positive, high-risk EBC persists beyond completion of abemaciclib therapy, yielding an increase in absolute IDFS and DRFS benefit at 4 yrs. While OS remains immature at this time, the lower number of deaths in the abemaciclib arm compared to the ET arm suggest that a survival signal favoring abemaciclib is emerging. Citation Format: Stephen Johnston, Masakazu Toi, Joyce O’Shaughnessy, Priya Rastogi, Mario Campone, Patrick Neven, Chiun Sheng Huang, Jens Huober, Georgina Garnica Jaliffe, Irfan Cicin, Sara Tolaney, Matthew P. Goetz, Hope Rugo, Elżbieta Senkus, Laura Testa, Lucia Del Mastro, Chikako Shimizu, Ran Wei, Ashwin Shahir, Maria Munoz, Belen San Antonio, Valerie Andre, Nadia Harbeck, Miguel Martín. Abemaciclib plus endocrine therapy for HR+, HER2-, node-positive, high-risk early breast cancer: results from a pre-planned monarchE overall survival interim analysis, including 4-year efficacy outcomes [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS1-09.

Background: Left bundle area branch pacing (LBBP) is a novel conduction system pacing method to achieve effective physiological pacing and an alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) for patients with heart failure and reduced ejection fraction (HFrEF). Objective: To review current data comparing BVP and LBBP in patients with HFrEF and indication CRT. Methods: We searched PubMed/Medline, Web of Science, and Cochrane Library from the inception of the database to November 2022. All studies that compared LBBP with BVP in patients with HFrEF and indications of CRT were included. Two reviewers performed the study selection, data abstraction, and risk of bias assessment. We calculated risk ratios with the Mantel-Haenszel method and mean difference with inverse variance using random effect models. We assessed heterogeneity using the I 2 index, with I 2 > 50% indicating significant heterogeneity. Results: Ten studies (9 observational studies and 1 randomized controlled trial; 616 patients; 15 centers) published between 2020 and 2022 were included. We observed a shorter fluoroscopy time [mean difference (MD) 9.68, 95% CI 4.49-14.87, I 2 =95%, P<0.01, minutes] as well as a shorter procedure time (MD 33.68, 95% CI 17.80-49.55, I 2 =73%, P<0.01, minutes) during implantation of LBBP CRT compared to conventional BVP CRT. LBBP was shown to have a greater reduction in QRSd (MD 25.13, 95%CI 20.06-30.20, I 2 = 51%, P<0.01, milliseconds) a greater left ventricular ejection fraction (LVEF) improvement (MD 5.80, 95% CI 4.81-6.78, I 2 =0%, P<0.01, percentage) and a greater ventricular end-diastolic diameter (LVEDD) reduction (MD 2.11, 95% CI 0.12-4.10, I 2 =18%, P=0.04, millimeter). There was a greater improvement in New York Heart Association function (NYHA) class with LBBP (MD 0.37, 95% CI 0.05-0.68, I 2 =61%, P=0.02).LBBP was also associated with a lower risk of a composite of heart failure hospitalizations and all-cause mortality [Risk ratio (RR) 0.48, 95% CI 0.25-0.90, I 2 =0%, p=0.02] driven by reduced heart failure hospitalizations (RR 0.39, 95% CI 0.19-0.82, I 2 =0%, p=0.01). However, all-cause mortality rates were low in both groups (1.52% vs. 1.13%) and similar (RR 0.98, 95%CI 0.21-4.68, I 2 =0%, p=0.87). Conclusion: Compared to BVP, LBBP is associated with, a greater improvement in LV systolic function, and a lower rate of heart failure-related hospitalization. Dedicated randomized controlled trials and larger patient populations are needed to further elucidate the long-term safety and efficacy of LBBP CRT.