Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.

BACKGROUND: The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1manifestations (e.g., neurocognitive function, growth reduction, and café-au-lait spots) are unknown. METHODS: This open-label, phase 2 trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥ 3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hrs for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated. RESULTS: Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22±5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥ 20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P <0.05). Prepubertal patients showed increases in height score and growth velocity (P <0.05). Café-au-lait spot intensity decreased significantly (P <0.05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation. CONCLUSION: Selumetinib decrease PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in non-malignant diverse NF1 manifestations.

Comparative Biological Half-Life of Penthiopyrad and Tebufenpyrad in Angelica Leaves and Establishment of Pre-Harvest Residue Limits (PHRLs).

To prevent pesticides from exceeding maximum residue limits (MRLs) in crops during export and shipment, it is necessary to manage residue levels during the pre-harvest stages. Therefore, the Republic of Korea establishes pre-harvest residue limits (PHRLs) per crop and pesticide. This study was conducted to set PHRLs for penthiopyrad and tebufenpyrad in angelica leaves, where the exceedance rates of MRLs are expected to be high. The LOQ of the analytical method used was 0.01 mg/kg and it demonstrated good linearity, with a correlation coefficient of 0.999 or higher within the quantitation range of 0.005 to 0.5 mg/kg. The recovery and storage stability accuracy values were in the range of 94.5-111.1%, within the acceptable range (70-120%, RSD ≤ 20%). The matrix effect for both pesticides was in the medium-to-strong range, and it did not significantly impact the quantitative results as a matrix-matched calibration method was employed. Using the validated method, residue concentrations of penthiopyrad 20 (%) EC and tebufenpyrad 10 (%) EC were analyzed. Both pesticides exhibited a decreasing residue trend over time. In Fields 1-3 and their integrated results, the biological half-life was within 2.6-4.0 days for penthiopyrad and 3.0-4.2 days for tebufenpyrad. The minimum value of the regression coefficient in the dissipation curve regression equation was selected as the dissipation constant. The selected dissipation constants for penthiopyrad in Fields 1-3 and their integration were 0.1221, 0.2081, 0.2162, and 0.1960. For tebufenpyrad, the dissipation constants were 0.1451, 0.0960, 0.1725, and 0.1600, respectively. The dissipation constant was used to calculate PHRL per field. Following the principles of the PHRL proposal process, residue levels (%) on PHI dates relative to MRLs were calculated, and fields for proposing PHRLs were selected. For penthiopyrad, since the residue level (%) was less than 20%, the PHRL for Field 3 with the largest dissipation constant was proposed. For tebufenpyrad, as the residue level (%) exceeded 80%, the PHRL proposal could not established. It is deemed necessary to reassess the MRL and 'guidelines for safe use' for tebufenpyrad in angelica leaves.

Direct Electroplating Ruthenium Precursor on the Surface Oxidized Nickel Foam for Efficient and Stable Bifunctional Alkaline Water Electrolysis.

Water electrolysis to produce hydrogen (H2) using renewable energy is one of the most promising candidates for realizing carbon neutrality, but its reaction kinetics is hindered by sluggish anodic oxygen evolution reaction (OER). Ruthenium (Ru) in its high-valence state (oxide) provides one of the most active OER sites and is less costly, but thermodynamically unstable. The strong interaction between Ru nanoparticles (NPs) and nickel hydroxide (Ni(OH)2) is leveraged to directly form Ru-Ni(OH)2 on the surface of a porous nickel foam (NF) electrode via spontaneous galvanic replacement reaction. The formation of Ru─O─Ni bonds at the interface of the Ru NPs and Ni(OH)2 (Ru-Ni(OH)2) on the surface oxidized NF significantly enhance stability of the Ru-Ni(OH)2/NF electrode. In addition to OER, the catalyst is active enough for the hydrogen evolution reaction (HER). As a result, it is able to deliver overpotentials of 228 and 15 mV to reach 10 mA cm-2 for OER and HER, respectively. An industry-scale evaluation using Ru-Ni(OH)2/NF as both OER and HER electrodes demonstrates a high current density of 1500 mA cm-2 (OER: 410 mV; HER: 240 mV), surpassing commercial RuO2 (OER: 600 mV) and Pt/C based performance (HER: 265 mV).

The long-term effects of the fenestration in patients with extracardiac Fontan circulation-a multicenter Korean cohort study based on national Fontan registry.

Introduction: The long-term effects of fenestration in patients with Fontan circulation remain unclear. We aim to evaluate the fenestration impact on early and late outcomes in patients with extracardiac Fontan (ECF) using a propensity score matching analysis. Methods: We performed an extensive retrospective multicenter clinical data review of the Korean Fontan registry and included 1,233 patients with surgical ECF (779 fenestrated, 454 non-fenestrated). Demographics, baseline, and follow-up data were collected and comprehensively analyzed. Patients were divided into two groups according to the baseline presence or absence of surgical fenestration. Subsequently, patients were sub-divided according to the fenestration status at the last follow-up. Propensity-score matching was performed to account for collected data between the 2 groups using a multistep approach. The primary outcomes were survival and freedom from Fontan failure (FFF). We also looked at postoperative hemodynamics, cardiopulmonary exercise test results, oxygen saturations, and functional status. Results: After propensity-score matching (454 matched pairs), there was no difference in survival or FFF between the 2 groups. However, ECF patients with baseline fenestration had significantly lower oxygen saturation (p = 0.001) and lower functional status (p < 0.001). Patients with fenestration had significantly longer bypass times, higher postoperative central venous pressure, higher postoperative left atrial pressure, and less prolonged pleural effusion in the early postoperative period. The propensity score matching according to the fenestration status at the last follow-up (148 matched pairs) showed that patients with a persistent fenestration had significantly lower oxygen saturation levels (p < 0.001). However there were no intergroup differences in the functional status, survival and FFF. Conclusions: Our results showed no long-term benefits of the Fenestration in terms of survival and FFF. Patients with persistent fenestration showed oxygen desaturation but no difference in exercise intolerance was shown between the 2 groups.

Higher body mass index increases the risk of shoulder adhesive capsulitis in young adults: A nationwide cohort study.

BACKGROUND: The impact of overweight on the incidence of shoulder adhesive capsulitis (AC) has not been clearly proven. This study aimed to investigate the association between overweight and AC by age using a large-scale nationwide population-based cohort in Korea. METHODS: We analyzed clinical data from 3,517,066 individuals older than 20 years who had undergone a National Health Insurance Service health checkup in 2009. Patients who visited a hospital or private clinic to treat shoulder pain at least three times in one year and were assigned a diagnostic code for AC (ICD-10 code M75.00) were identified using claims data during a median follow-up duration of 8.3 years. Hazard ratios (HRs) and 95% confidence intervals for AC were calculated using the Cox proportional hazards model. RESULTS: The adjusted HR for AC in the < 40 year group started to increase in overweight status and was associated with the severity of obesity (body mass index (BMI) < 18.5; 0.654 (0.613-0.697), < 23; 1, < 25; 1.272 (1.231-1.315), < 30; 1.322 (1.281-1.364), ≥ 30; 1.332 (1.253-1.416)). But in the 40-64 year group and the ≥65 year group, there was no significant increasing trend of HR for AC according to BMI level. We conducted a subgroup analysis based on the BMI 23 for defining overweight and presence of comorbidities including diabetes and hyperlipidemia. The adjusted HR for AC was highest with overweight and comorbidities of diabetes and hyperlipidemia (diabetes; 1.528 (1.508-1.549), hyperlipidemia; 1.212 (1.199-1.226)). CONCLUSIONS: In the young age group (20-40 years), a higher BMI level increased the HR for AC. Overweight along with diabetes or hyperlipidemia significantly increased the risk of AC.

Potential Application of Non-Invasive Optical Imaging Methods in Orthodontic Diagnosis.

During orthodontic treatment, the early diagnosis of microscopic changes in soft and hard tissues, including periodontal tissue, is very important to prevent iatrogenic side effects like root resorption and periodontal diseases. Cervical periodontal tissue is the most critical area that reacts first to mal-habits or orthodontic forces, and it is also the place where bacteria deposits in the early stage of periodontal diseases. The early diagnosis of hard tissue changes, such as demineralization, is also very important in maintaining a patient's health during orthodontic treatment. Many diagnostic devices, including radiographic equipment and intra-oral scanners, are helpful in diagnosing these problems, but have certain limitations in invasiveness and precision. The purpose of this study is to verify the possible utilities of non-invasive diagnostic devices in the orthodontic field that can compensate for these limitations. For this, non-invasive optical diagnostic devices, including optical coherence tomography and optical Doppler tomography, were used in vivo with animal and human examination for hard and soft tissues. These devices can provide real-time three-dimensional images at the histological scale. The results of this study verified these devices can be used in clinical practice during orthodontic treatment and introduced a new diagnostic paradigm differentiating microstructural changes in tissues in orthodontic diagnosis.

Pacemaker-Related Factors and Outcomes of Fontan Patients　- Impact of Paced QRS Duration.

BACKGROUND: Permanent pacemaker (PPM) implantation has been identified as a risk factor for morbidity and mortality after Fontan operation. This study investigated the factors associated with outcomes in patients with Fontan physiology who underwent PPM implantation.Methods and Results: We retrospectively reviewed 508 patients who underwent Fontan surgery at Asan Medical Center between September 1992 and August 2022. Of these patients, 37 (7.3%) received PPM implantation. Five patients were excluded, leaving 32 patients, of whom 11 were categorized into the poor outcome group. Poor outcomes comprised death, heart transplantation, and "Fontan failure". Clinical, Fontan procedure-related, and PPM-related factors were compared between the poor and good outcome groups. Ventricular morphology, Fontan procedure-associated factors, pacing mode, high ventricular pacing rate, and time from first arrhythmia to PPM implantation did not differ significantly between the 2 groups. However, the poor outcome group exhibited a significantly longer mean paced QRS duration (P=0.044). Receiver operating characteristic curve analysis revealed a paced QRS duration cut-off value of 153 ms with an area under the curve of 0.73 (P=0.035). CONCLUSIONS: A longer paced QRS duration was associated with poor outcomes, indicating its potential to predict adverse outcomes among Fontan patients.

Genetic heterogeneity of cardiomyopathy and its correlation with patient care.

BACKGROUND: Cardiomyopathy, which is a genetically and phenotypically heterogeneous pathological condition, is associated with increased morbidity and mortality. Genetic diagnosis of cardiomyopathy enables accurate phenotypic classification and optimum patient management and counseling. This study investigated the genetic spectrum of cardiomyopathy and its correlation with the clinical course of the disease. METHODS: The samples of 72 Korean patients with cardiomyopathy (43 males and 29 females) were subjected to whole-exome sequencing (WES). The familial information and clinical characteristics of the patients were reviewed and analyzed according to their genotypes. RESULTS: Dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular non-compaction cardiomyopathy, and restrictive cardiomyopathy was detected in 41 (56.9%), 25 (34.7%), 4 (5.6%), and 2 (2.8%) patients, respectively. WES analysis revealed positive results in 37 (51.4%) patients. Subsequent familial testing identified ten additional familial cases. Among DCM cases, 19 (46.3%) patients exhibited positive results, with TTN variants being the most common alteration, followed by LMNA and MYH7 variants. Meanwhile, among HCM cases, 15 (60%) patients exhibited positive results with MYH7 variants being the most common alteration. In six patients with positive results, extracardiac surveillance was warranted based on disease information. The incidence of worse outcomes, such as mortality and life-threatening arrhythmic events, in patients with DCM harboring LMNA variants, was higher than that in patients with DCM harboring TTN or MYH7 variants. CONCLUSIONS: Diverse genotypes were identified in a substantial proportion of patients with cardiomyopathy. Genetic diagnosis enables personalized disease surveillance and management.

Assessment of the feasibility of same-day discharge following minimally invasive hysterectomy in the elderly population.

Objective: To determine the safety and feasibility of same-day discharge (SDD) following minimally invasive hysterectomy (MIH) for elderly patients and to evaluate associations between age, frailty, and postoperative outcomes. Methods: Retrospective review was conducted of patients aged ≥ 70 who underwent MIH within a single gynecologic oncology institution from 2018 to 2020. Demographics, peri-operative factors, postoperative complications, and 30-day readmission rates were collected. Frailty was determined by an 11-point modified frailty index ≥ 2. Outcomes were compared between SDD and observation groups using Fisher's exact and Wilcoxon rank-sum tests. Results: Of 169 patients included in the analysis, 8.9% (n = 15) underwent SDD, and 91.1% (n = 154) were admitted for OBS following MIH. Demographics, peri-operative factors, and frailty rates (33% SDD vs 43.5% observation; p = 0.59) were similar between groups. 86.7% (n = 13) of SDD cases were completed before 12PM, and none were completed after 6PM. No SDD patients had early post-operative complications or hospital readmissions. Early postoperative complications were diagnosed in 9 (5.8%) patients admitted for OBS, and the 30-day hospital readmission rate for patients who underwent OBS was 8.4% (n = 13). While elderly patients who met objective frailty criteria (n = 72) did not have a higher likelihood of early post-operative complications (44.4% vs 55.6%; p = 0.909), they did have a higher likelihood of ED visit within 30 days of discharge (15.3 vs 3.1%; p = 0.009), and a trend was noted toward a higher rate of 30-day hospital readmission (12.5% vs 4.1%; p = 0.080). Conclusions: Elderly patients undergoing SDD following MIH did not have increased morbidity or mortality. Elderly patients who meet objective criteria for frailty, however, represent a more vulnerable population.

Hybrid Right Ventricular Outflow Stent Insertion in a Small Neonate with Muscular Pulmonary Atresia with Intact Ventricular Septum: A Case Report.

Pulmonary atresia with intact ventricular septum (PAIVS) is a rare congenital heart disease that often needs a critical decision on whether to open the right ventricular outflow tract (RVOT). Significant morbidity and considerable mortality might preclude the safe use of percutaneous or surgical right ventricular decompression in patients with muscular PAIVS. We report the case of a 21-day-old neonate weighing less than 3 kg who underwent hybrid RVOT stent insertion as initial palliation for muscular PAIVS and subsequent anatomical correction at 5 months of age, with 6 years of follow-up.

Development of a Soil Moisture Prediction Model Based on Recurrent Neural Network Long Short-Term Memory (RNN-LSTM) in Soybean Cultivation.

Due to climate change, soil moisture may increase, and outflows could become more frequent, which will have a considerable impact on crop growth. Crops are affected by soil moisture; thus, soil moisture prediction is necessary for irrigating at an appropriate time according to weather changes. Therefore, the aim of this study is to develop a future soil moisture (SM) prediction model to determine whether to conduct irrigation according to changes in soil moisture due to weather conditions. Sensors were used to measure soil moisture and soil temperature at a depth of 10 cm, 20 cm, and 30 cm from the topsoil. The combination of optimal variables was investigated using soil moisture and soil temperature at depths between 10 cm and 30 cm and weather data as input variables. The recurrent neural network long short-term memory (RNN-LSTM) models for predicting SM was developed using time series data. The loss and the coefficient of determination (R2) values were used as indicators for evaluating the model performance and two verification datasets were used to test various conditions. The best model performance for 10 cm depth was an R2 of 0.999, a loss of 0.022, and a validation loss of 0.105, and the best results for 20 cm and 30 cm depths were an R2 of 0.999, a loss of 0.016, and a validation loss of 0.098 and an R2 of 0.956, a loss of 0.057, and a validation loss of 2.883, respectively. The RNN-LSTM model was used to confirm the SM predictability in soybean arable land and could be applied to supply the appropriate moisture needed for crop growth. The results of this study show that a soil moisture prediction model based on time-series weather data can help determine the appropriate amount of irrigation required for crop cultivation.

Outcomes of Arterial Switch Operation With Aortic Arch Reconstruction.

BACKGROUND: This study investigated the outcomes and factors associated with reintervention or development of significant pulmonary stenosis (PS) after repair of transposition of the great arteries (TGA) or Taussig-Bing anomaly (TBA) with aortic arch obstruction. METHODS: A total of 51 patients with TGA or TBA who underwent an arterial switch operation and aortic arch reconstruction between 2004 and 2020 were included. The outcomes of interest were all-cause death, including heart transplantation, all-cause reintervention, right-sided reintervention, and development of significant PS. RESULTS: The median age and body weight at repair were 9 days and 3.2 kg, respectively. Forty-nine patients (96.1%) underwent 1-stage repair. A total of 28 patients (54.9%) had TBA, and 8 patients (15.7%) had interrupted aortic arch. There were 5 early deaths (9.8%) and 2 late deaths during a median follow-up duration of 59 months. The transplant-free survival rate 10 years after repair was 82.6%. A total of 21 reinterventions were required in 10 patients. The significant PS-free survival rate 10 years after repair was 68.8%. In univariable analysis, a higher ratio of the diameter of the main pulmonary artery to the ascending aorta was associated with all-cause reintervention (P = .007) and right-sided reintervention (P = .002). A smaller aortic annulus z-score at the pulmonary position was associated with the development of significant PS (P = .049). CONCLUSIONS: The rates of overall mortality and reintervention after repair were not negligible. A higher degree of size discrepancy between the 2 great arteries was associated with all-cause or right-sided reintervention. A smaller aortic annulus z-score at the pulmonary position was associated with the development of significant PS.

Safety and feasibility of same-day discharge following minimally invasive hysterectomy in the morbidly obese patient population.

OBJECTIVES: To determine whether morbid obesity should serve as an independent factor in the decision for same day discharge following minimally invasive hysterectomy. METHODS: Retrospective review was performed of patients with BMI ≥ 40 who underwent minimally invasive hysterectomy within a single comprehensive cancer center between January 2018 - August 2020. Demographics, perioperative factors, post-operative monitoring, complications, and readmissions were compared between patients who underwent same day discharge and overnight observation using Fisher's exact tests and Wilcoxon rank-sum tests. RESULTS: 374 patients with BMI ≥ 40 were included. Eighty-three (22.2%) patients underwent same day discharge, and 291 (77.8%) patients underwent overnight observation. Factors associated with increased likelihood of same day discharge included younger age (median age 53 vs 58; p = 0.001), lower BMI (median BMI 45 vs 47; p = 0.005), and fewer medical co-morbidities (Charlson Co-Morbidity Index 2 vs 3; p < 0.001). On multivariate regression analysis, frailty (OR 2.16 [1.14-4.11], p = 0.019) and surgical completion time after 12 PM (OR 3.67 [2.16-6.24], p < 0.001) were associated with increased risk of overnight observation. Few patients admitted for routine overnight observation required medical intervention (n = 14, 4.8%); most of these patients were frail (64.3%). The overall hospital readmission rate within 30 days of discharge was 3.2% (n = 12), with no patients discharged on the day of surgery being readmitted. CONCLUSIONS: Morbid obesity alone should not serve as a contraindication to same day discharge following minimally invasive hysterectomy. Admission for observation was associated with low rates of clinically meaningful intervention, and patients who underwent same day discharge were not at increased risk of adverse outcome.

Outcomes of pulmonary artery sling repair without tracheoplasty.

OBJECTIVE: This study aimed to investigate surgical outcomes of pulmonary artery (PA) sling without tracheoplasty. METHODS: From 2001 through 2020, among 22 patients who underwent PA sling repair, all but 1 patient who underwent concomitant tracheal surgery were analyzed. The outcomes of interest were all-cause death, PA reintervention, tracheal intervention, and readmission for respiratory symptoms. Computed tomography was used to measure the narrowest tracheal diameter. RESULTS: The median age and weight at repair were 7.6 months and 7.7 kg, respectively. Most patients (20 out of 21, 95.2%) had preoperative respiratory symptoms. Associated airway anomalies included tracheal ring in 12 (57.1%), bridging bronchus in 8 (38.1%), and tracheal bronchus in 2 patients (9.5%). There was 1 in-hospital death (4.8%). The median ventilator time and intensive care unit stay were 23 hours and 3 days, respectively. There was neither late death nor tracheal intervention during follow-up. Five patients (25.0%) underwent reintervention for left PA stenosis. Hospital readmission for respiratory symptom was required in 7 patients and was associated with the narrowest preoperative tracheal diameter (P = .025) and cardiopulmonary bypass time (P = .040) in univariable analysis. The narrowest tracheal diameter of 3.4 mm was identified as a cutoff value for readmission for respiratory symptom. Freedom from readmission for respiratory symptom was 63.3% at 10 years. CONCLUSIONS: PA sling repair without tracheal surgery might be a reasonable surgical option with rare need for tracheal intervention. Hospital readmissions for respiratory symptoms are more frequently required in patients with smaller tracheal diameter and all readmissions were limited to within 2 years after repair.

Spontaneous defervescence and its prediction in the acute phase of Kawasaki disease.

Background: In Kawasaki disease (KD), fever occasionally resolves spontaneously before 10 days from the onset, right after diagnosing. However, there is not enough evidence of intravenous immunoglobulin (IVIG) treatment in this case. The aim of this study was to investigate the relationship between spontaneous defervescence and coronary artery aneurysm and to develop a scoring model for its prediction in acute KD. Methods: All patients admitted for acute KD in Asan Medical Center were considered for inclusion. Acute management involved the administration of 2 g/kg of IVIG and 5 mg/kg/day of aspirin. The patient whose temperature was <37.5°C for more than 48 h from the diagnosis was discharged under the judgment of spontaneous defervescence, without IVIG administration. Results: The incidence of coronary artery aneurysm was 5.7% in 94 defervesced patients and 4.6% in the 1,277 patients treated with IVIG in the subacute phase (P = 0.593), and 2.5 and 2.2% in respective patient groups in the convalescent phase (P = 0.924). A scoring model which predicted spontaneous defervescence under the combination of C-reactive protein ≤10mg/dL and ≥2 conditions of no rash, neutrophil ≤65%, and/or alanine aminotransferase ≤80 IU/L, was developed and showed 80.7% sensitivity, 68.8% specificity, 15.8% positive predictive value, and a 97.8% negative predictive value. Conclusion: The incidence of coronary artery aneurysm in patients with the defervesced KD was not different from the IVIG treated patients. In the cases suitable for the predictive model, patients can wait for the spontaneous defervescence under intensive observation by medical professionals.

High pre-treatment neutrophil-to-lymphocyte ratio as a prognostic marker for worse survival in patients with recurrent/metastatic cervical cancer treated with immune checkpoint inhibitors.

Objective: To evaluate the association between pre-treatment neutrophil-to-lymphocyte ratio (NLR) and survival outcomes among patients with recurrent/metastatic cervical cancer treated with PD-1/PD-L1 inhibitors. Methods: A retrospective analysis of patients with recurrent/metastatic cervical cancer treated with PD-1/PD-L1 inhibitors from 2016 to 2021 was conducted. Progression free survival (PFS) and overall survival (OS) outcomes were assessed for patients stratified by NLR (<8 vs ≥ 8) utilizing Kaplan-Meier method. Univariable analysis was performed to compare baseline characteristics between the two groups. Results: A total of 49 patients were included in analysis. A majority of patients had squamous cell histology (57%), were PD-L1 positive (55%), received ≤ 1 prior lines of systemic therapy (57%), and had distant metastatic disease at the time of treatment (69%). The groups were well-balanced with respect to age, race, histology, smoking status, PD-L1 positivity, prior lines of treatment (≤1 vs > 1), prior radiation therapy, ECOG performance status, and disease distribution for patients with a NLR < 8 (n = 35) compared to those with a NLR ≥ 8 (n = 14). A pre-treatment NLR of < 8 was associated with improved survival (p < 0.01), with 57% (95% CI: 41%, 78%) probability of survival at one year compared to 26% (95% CI: 10%, 66%) for those with NLR ≥ 8. No statistically significant differences in probability of PFS at 1 year were seen between NLR < 8 compared to those with NLR ≥ 8 (p = 0.70). Conclusions: Pre-treatment NLR may hold prognostic value for patients with metastatic/recurrent cervical cancer treated with PD-1/PD-L1 inhibitors, with NLR < 8 associated with improved survival.

Beyond mismatch repair deficiency? Pre-treatment neutrophil-to-lymphocyte ratio is associated with improved overall survival in patients with recurrent endometrial cancer treated with immunotherapy.

OBJECTIVE: To determine the association of pre-treatment neutrophil-to-lymphocyte ratio (NLR) with progression-free survival (PFS) and overall survival (OS) for patients with recurrent endometrial cancer (EC) treated with immunotherapy. METHODS: Recurrent EC patients treated with immunotherapy alone or in combination from 2016 to 2021 were included. Demographics, pre-treatment laboratory results, pathologic data, response at first radiographic assessment, and cancer outcomes were obtained from the medical record. Kaplan-Meier curves were generated to compare PFS and OS stratified by NLR. RESULTS: The 106 patients included in the study were stratified by NLR <6 (n = 77, 72.6%) or NLR ≥6 (n = 29, 27.3%). Most had endometrioid pathology (59%), widely metastatic disease, and 36.8% had received ≥2 treatment lines before initiating immunotherapy. Mismatch repair deficiency (dMMR) was noted in 52 (49.1%) tumors. Most dMMR patients (94.3%) were treated with single-agent pembrolizumab, and most MMR proficient patients (78.7%) were treated with lenvatinb plus pembrolizumab. In the overall cohort, 40.2% (partial response (PR) 29.9%, complete response (CR) 10.4%) of patients with a NLR <6 responded at first radiographic assessment, compared to 31% (PR 27.5%, CR 3.4%) of patients with NLR ≥6 (p 0.691). Kaplan-Meier curves stratified by NLR <6 vs. ≥6 showed no difference in PFS. However, NLR <6 was associated with improved OS (p < 0.05). In the NLR < 6 group, the probability of survival at one year was 69% (95% CI: 58%, 82%), compared to 41% (95% CI: 26%, 67%) for the NLR > 6 group. CONCLUSIONS: Pre-treatment NLR <6 was associated with improved OS for recurrent EC patients treated with immunotherapy. NLR holds promise as a predictive biomarker for survival after immunotherapy treatment for patients with recurrent EC.

An investigation into human papillomavirus (HPV) vaccination for patients undergoing surgery for high-grade cervical or vulvar dysplasia.

Introduction: Eligibility for the human papillomavirus (HPV) vaccine now includes adults 27 through 45 years. It has not been reported how providers are addressing HPV vaccination in patients with existing preinvasive disease. Our objectives were to determine the rates at which vaccination is offered to and received by patients undergoing surgery for high-grade cervical or vulvar dysplasia. Materials and Methods: This was a single-institution retrospective cohort study including patients ages 18 through 45 years undergoing surgery for high-grade cervical or vulvar dysplasia from 10/2018 to 2/2020. Our primary outcome was the rate at which HPV vaccination was discussed at the pre- and/or post-operative visits. The secondary outcome was the rate of vaccine uptake in these individuals. Characteristics of those offered HPV vaccination were compared to those not offered vaccination. Results: Of the 115 patients included, 36 (31.3%) had HPV vaccination addressed in the perioperative setting. Thirty-two of these patients had never been vaccinated, and 21 of these (65.6%) went on to receive partial or complete HPV vaccination. Those in whom HPV vaccination was addressed were more likely to be under 27 years (RR 3.2; 95% CI 2.1-4.8) and less likely to be smokers (RR 0.5; 95% CI 0.2-0.9) or have prior excisional procedures (RR 0.3; 95% CI 0.1-0.9). The absolute rate of discussing HPV vaccination with patients improved from 26.0% within six months of vaccine age eligibility expansion, to 35.4% after six months (P = 0.32). Conclusions: Providers did not consistently address HPV vaccination among patients being treated for high-grade cervical or vulvar dysplasia despite the potential benefits. However, a high proportion of these patients are amenable to vaccination. Quality improvement initiatives are warranted to increase the rate of HPV vaccine counseling in this context.

Human papillomavirus genotype distribution of genital keratotic lesions.

Genital keratotic lesions include bowenoid papulosis (BP), which histologically resembles squamous cell carcinoma in situ containing high-risk HPV, condyloma acuminatum (CA) that is a genital wart containing mostly low-risk HPV, and genital seborrheic keratosis (GSK), which is a benign epidermal tumour lacking a clear etiologic relationship with HPV. This study compared HPV genotype distributions among BP, CA and GSK and revealed that BP and GSK were related to high-risk HPV whereas CA was related to low-risk HPV. It is plausible that GSK is a distinct epidermal tumour often related to high-risk HPV rather than merely a senescent form of CA considering the overall discrepancy in the frequency distribution of HPV genotypes along with histopathological differences, and the detection of high-risk HPV in GSK alerts physicians to consider more active treatment and continued follow-ups.

Contemporary Outcomes After Pulmonary Artery Banding in Complete Atrioventricular Septal Defect.

BACKGROUND: This study investigated the clinical outcomes and the effect of band tightness on outcome after pulmonary artery banding (PAB) in patients with complete atrioventricular septal defect (AVSD). METHODS: From 2000 through 2019, among 133 patients with isolated complete AVSD pursuing biventricular repair, 34 patients (25.6%) who underwent PAB were included in this study. Factors associated with adverse outcome, which was defined as prolonged stay in the intensive care unit (>10 days), were analyzed using a multiple logistic regression model. Receiver operating characteristic analysis was performed to identify a threshold band tightness for adverse outcome. RESULTS: The median age and weight were 43 days and 3.6 kg, respectively. There were 4 early deaths. The median intensive care unit stay was 8 days. Twenty-eight patients (28/34; 82.4%) underwent definitive repair 10 months (interquartile range, 7-12 months) after PAB. In multivariable analysis, indexed band diameter was identified as a factor associated with adverse outcome (odds ratio, 1.60; 95% CI, 1.03-2.48; P = .035). Receiver operating characteristic analysis indicated 22.2 mm/m2 of indexed PAB diameter measured at discharge as a threshold band tightness for adverse outcome (area under curve, 0.871; P < .001). The level of B-type natriuretic peptide similarly decreased after PAB regardless of band tightness, although the probability of worsening in atrioventricular valve regurgitation was significantly decreased in patients with a tighter band (P = .027). CONCLUSIONS: PAB is a viable option for early-presenting patients with complete AVSD. Tighter PAB might be beneficial for early postoperative outcomes and preventing progression of atrioventricular valve regurgitation in complete AVSD.