Predictive value of preoperative inflammatory markers and serum CA 125 level for surgical outcome in Indonesian women with epithelial ovarian cancer

BACKGROUND: It is essential in the management of ovarian cancers to identify the patients who will benefit from primary complete cytoreductive surgery and those who will rather benefit from neoadjuvant chemotherapy. OBJECTIVE: To evaluate the predictive value of preoperative inflammatory markers, i.e. platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), red cell distribution width (RDW), and serum CA125 level for surgical outcome in epithelial ovarian cancer. METHODS: A retrospective study was carried out in Sanglah Hospital, Denpasar, Bali. A total of 54 patients with epithelial ovarian cancer who underwent primary exploratory laparotomy from January 2018 to November 2019 was recruited. Data about clinical characteristics, preoperative inflammatory markers, serum CA125 level, and surgical outcome (optimal vs. suboptimal) was collected from the medical records. Predictive value of the markers were evaluated using ROC curve to determine their accuracy (area under the curve, sensitivity, specificity, positive and negative predictive value). RESULTS: Mean age, parity, and tumor size did not differ between the study groups (p> 0.05). The group with suboptimal outcome had significantly higher PLR, NLR, MLR, and RDW value (p< 0.05). Using the ROC curve, a cut off value was determined for each predictor, i.e. PLR: 196.50, NLR: 3.34, MLR: 0.24, RDW: 13.19, CA125: 300.85. AUC for each predictor were as follows: PLR 0.718 (95% CI: 0.578–0.859), NLR 0.676 (95% CI: 0.529–0.823), MLR 0.700 (95% CI: 0.560–0.839), RDW 0.712 (95% CI: 0.572–0.852), CA125 0.593 (95% CI: 0.436–0.750). Sensitivity, specificity, and accuracy for predicting suboptimal outcome were as follows: PLR (74.2%, 69.6%, 72.2%), NLR (64.5%, 60.9%, 62.9%), MLR (74.2%, 59.1%, 66.7%), RDW (74.2%, 60.9%, 68.5%), CA125 (54.8%, 60.9%, 57.4%). We have some limitations such as small numbers of sample, we generalized whole kinds of ovarian cancer, and this study does not describe follow-up features. CONCLUSION: Preoperative serum inflammatory markers (PLR, MLR, and RDW) may serve as useful markers to predict the surgical outcome with fair accuracy in patients with epithelial ovarian cancer.

Revisiting an IgG Fc Loss-of-Function Experiment: the Role of Complement in HIV Broadly Neutralizing Antibody b12 Activity

Given the suboptimal outcome of VRC01 antibody-mediated prevention of HIV-1 infection in its first field trial, means to improve diverse antiviral activities in vivo have renewed importance. This work revisits a loss-of-function experiment that investigated the mechanism of action of b12, a similar antibody, and finds that the reason why complement-mediated antiviral activities were not observed to contribute to protection may be the inherent lack of activity of wild-type b12, raising the prospect that this mechanism may contribute in the context of other HIV-specific antibodies.

How to Evaluate the Effectiveness of Health Promotion Actions Developed Through Youth-Centered Participatory Action Research

Most actions targeting children’s health behaviors have limited involvement of children in the development, potentially contributing to disappointing effectiveness. Therefore, in the 3-year “Kids in Action” study, 9- to 12-year-old children from a lower-socioeconomic neighborhood were involved as coresearchers in the development, implementation, and evaluation of actions targeting health behaviors. The current study describes the controlled trial that evaluated the effects on children’s energy balance-related behaviors, physical fitness, and self-rated health, as well as experienced challenges and recommendations for future evaluations. Primary school children from the three highest grades of four intervention and four control schools were eligible for participation. Outcome measures assessed at baseline, and at 1- and 2-year follow-up were as follows: motor fitness by the MOPER test ( N = 656, N = 485, N = 608, respectively), physical activity and sedentary behavior by accelerometry ( N = 223, N = 149, N = 164, respectively), and consumption of sugar sweetened beverages and snacks and self-rated health by a questionnaire ( N = 322, N = 281, N = 275, respectively). Mixed-model analyses were performed adjusted for clustering within schools and relevant confounders. Significant beneficial intervention effects were found on self-reported consumption of energy/sports drinks at T2 versus T0, and on total time and ≥5-minute bouts of moderate-to-vigorous physical activity at T1 versus T0. Significant adverse effects were found on “speed and agility” and “coordination and upper-limb speed.” No other significant effects were found. The inconsistent intervention effects may be explained by the dynamic cohort and suboptimal outcome measures. We advise future studies with a similar approach to apply alternative evaluation designs, such as the delayed baseline design.

Multimodal Management of Traumatic Faecal Incontinence Focused on Sphincteroplasty: Long-term Outcomes From a Single Center Case Series

Background: The management of patients with fecal incontinence and an external anal sphincter (EAS) defect remains controversial.Methods: We present a retrospective series of overlapping anal sphincteroplasties performed between 1985-2013 by a single surgeon supplemented by selective puborectalis plication and internal anal sphincter repair. Patients were clinically followed along with anorectal manometry, continence scoring (Cleveland Clinic Incontinence Score - CCS) and patient satisfaction scales. Patients with a suboptimal outcome were managed with combinations of biofeedback therapy, (BFT) peripheral tibial nerve stimulation (PTNS), sacral nerve stimulation (SNS) or repeat sphincteroplasty.Results: There were 120 anterior sphincter repairs with 90 (75%) levatorplasties and 84 (70%) IAS repairs. Over a median follow-up of 120 months (range 60-173.7 months) there were significant improvements in the recorded CCIS values (90.8% with a preoperative CCIS > 15 vs. 2.5% postoperatively; P < 0.001). There were 42 patients who required ancillary treatment with 4 repeat sphincteroplasties, 35 patients undergoing biofeedback therapy, 10 patients treated with PTNS and 3 managed with SNS implants with an ultimate good functional outcome in 92.9% of cases. No difference was noted in ultimate functional outcome between those treated with sphincteroplasty alone compared with those who needed ancillary treatments (97.1% vs. 85.7%, respectively). Overall, 93.3% considered the outcome as either good or excellent.Conclusions: Long-term functional outcomes of an overlapping sphincteroplasty are good. If the initial outcome is suboptimal, response to ancillary treatments remains good and patients are not compromised by a first-up uncomplicated sphincter repair.

Impact of Mitral Annular Dilation on Edge-to-Edge Therapy With MitraClip-XTR

Background: Mitral annular dilation has been shown to challenge successful edge-to-edge therapy with earlier MitraClip generations. Recently, third-generation MitraClip-XTR with extended clip arm length was introduced. We assessed the impact of annular dilation on residual mitral regurgitation (MR) after MitraClip-XTR repair and sought to identify cutoffs associated with suboptimal MR reduction. Methods: We included 107 patients (78.9±6.7 years; 40.2% female) with symptomatic severe MR (46.7% primary MR; 53.3% secondary MR) undergoing MitraClip-XTR repair. Annular dimensions were retrospectively assessed by 2-dimensional and 3-dimensional-transesophageal echocardiography including a semiautomated analysis. Impact of annular diameters and area on suboptimal reduction defined as ≥2+MR on transthoracic echocardiography at discharge was assessed and predictive cutoff values identified. Previously identified predictors of suboptimal outcome after MitraClip therapy were included in multivariable analysis. Results: Technical success was achieved in 93%, 1-year mortality was 23%. Suboptimal MR reduction was observed in 26% and associated with higher 1-year mortality (odds ratio, 4.5 [1.5–14.1]). End-systolic anteroposterior and intercommissural annular diameters, annular area and further vena-contracta width, effective regurgitant orifice area and left atrial volume were associated with suboptimal outcomes. Independent predictors of suboptimal reduction were end-systolic annular area (odds ratio, 1.36 [1.08–1.71] per cm 2 ) and vena-contracta width (odds ratio, 1.47 [1.04–2.09] per mm). On receiver operating characteristic analysis, 3-dimensional-transesophageal echocardiography end-systolic anteroposterior diameter >40.5 mm, intercommisural diameter >40.5 mm, and annular-area >12.50 cm 2 were the most predictive thresholds for suboptimal reduction. If all 3 annular measurements exceeded the determined threshold values, the risk for suboptimal reduction increased by 17-fold. Conclusions: Annular dilation was found to challenge successful edge-to-edge therapy also with extended-reach MitraClip-XTR. Our proposed thresholds for preprocedural annular dimensions may serve as guidance for improved patient selection in edge-to-edge repair.

Beyond Contrail Avoidance: Efficacy of Flight Altitude Changes to Minimise Contrail Climate Forcing

Contrail cirrus introduce a short-lived but significant climate forcing that could be mitigated by small changes in aircraft cruising altitudes. This paper extends a recent study to evaluate the efficacy of several vertical flight diversion strategies to mitigate contrail climate forcing, and estimates impacts to air traffic management (ATM). We use six one-week periods of flight track data in the airspace above Japan (between May 2012 and March 2013), and simulate contrails using the contrail cirrus prediction model (CoCiP). Previous studies have predominantly optimised a diversion of every contrail-forming flight to minimise its formation or radiative forcing. However, our results show that these strategies produce a suboptimal outcome because most contrails have a short lifetime, and some have a cooling effect. Instead, a strategy that reroutes 15.3% of flights to avoid long-lived warming contrails, while allowing for cooling contrails, reduces the contrail energy forcing (EFcontrail) by 105% [91.8, 125%] with a total fuel penalty of 0.70% [0.66, 0.73%]. A minimum EFtotal strategy (contrails + CO2), diverting 20.1% of flights, reduces the EFcontrail by the same magnitude but also reduces the total fuel consumption by 0.40% [0.31, 0.47%]. For the diversion strategies explored, between 9% and 14% of diversions lead to a loss of separation standards between flights, demonstrating a modest scale of ATM impacts. These results show that small changes in flight altitudes are an opportunity for aviation to significantly and rapidly reduce its effect on the climate.

PATH-18. CSF-DERIVED CIRCULATING TUMOR DNA REFLECTS DISEASE COURSE AND CLONAL EVOLUTION IN MEDULLOBLASTOMA

Medulloblastoma (MB) is the most common malignant brain tumor in young children. A multi-modal approach comprises standard of care, and recent advances in molecular studies have identified clinically relevant subgroups. Nonetheless, 30% of MB patients relapse or progress, conferring dismal prognosis. Such suboptimal outcome is partly due to a lack of sensitive biomarkers for response-adapted personalization of treatment and relapse prediction. Circulating tumor DNA has been shown to correlate with disease status in a variety of adult cancers, but studies in pediatric brain tumors, including medulloblastoma, are scarce. Here, we aim to evaluate the utility of profiling cell-free DNA (cfDNA) derived from longitudinally-banked cerebrospinal fluid (CSF) samples collected from children with MB enrolled in two prospective, multi-center trials (SJMB03 and SJMB12, estimated sample size of 100 patients, including 50 with subsequent progression). cfDNA was extracted, quantified, and analyzed for size distribution from pre-centrifuged CSF serially banked during the course of treatment and follow-up. Low-pass whole genome sequencing (LP-WGS) enabled detection of chromosomal and focal copy number alterations (CNAs). CNAs detected in cfDNA were compared against known somatic changes in corresponding primary tumors. Detectability of tumor-specific CNAs in cfDNA was then correlated with tumor burden and patient outcome. Pilot analysis showed presence of arm level and/or focal CNAs in cfDNA from 80% of CSF samples in 20 children with metastatic MB, and longitudinal assessment revealed correlation with clinical course throughout treatment with radiotherapy and chemotherapy. Further comparison of tumor and longitudinal cfDNA derived CNAs revealed divergent genomic alterations implicating potential oncogenic mechanisms underlying treatment failure and recurrence. Our study performed on a large prospective series of MB trial patients substantiates the utility of CSF derived cfDNA as an actionable biomarker in high-risk MB patients while also facilitating understanding of tumor evolution and heterogeneity.