Different Dosages of Progesterone in Luteal Phase Support Reflect Varying Endometrial microRNA Expression in Frozen Embryo Transfer Cycles.

Despite serum progesterone being a widely accepted method for luteal phase support during embryo transfer cycles, debates persist regarding the optimal strategy for guiding clinical decisions on progesterone dosages to maximize reproductive outcomes. This retrospective study explored the utility of microRNA (miRNA) biomarkers in guiding personalized progesterone dosage adjustments for frozen embryo transfer (FET) cycles in 22 in vitro fertilization (IVF) patients undergoing hormone replacement therapy. Utilizing MIRA, an miRNA-based endometrial receptivity test, we analyzed patients' miRNA expression profiles before and after progesterone dosage adjustments to determine suitable dosages and assess endometrial status. Despite patients receiving identical progesterone dosages, variations in miRNA profiles were observed in the initial cycle, and all patients presented a displaced window of implantation. Following dosage adjustments based on their miRNA profiles, 91% of patients successfully transitioned their endometrium towards the receptive stages. However, two patients continued to exhibit persistent displaced receptivity despite the adjustments. Given the evident variation in endometrial status and serum progesterone levels among individuals, analyzing miRNA expression profiles may address the challenge of inter-personal variation in serum progesterone levels, to deliver more personalized dosage adjustments and facilitate personalized luteal phase support in IVF.

Exposure and health risk assessment of volatile organic compounds among drivers and passengers in long-distance buses.

Exposure to volatile organic compounds (VOCs) such as benzene, toluene, ethylbenzene, xylene, and formaldehyde from long-distance buses has been reported to adversely affect human health. This study investigates the concentrations of these five VOCs and evaluates their health risks to drivers and passengers on board. Ten trips from Taipei to Taichung were performed during the warm and cold seasons of 2021-2022. Two locations inside the bus were established to collect air samples by a 6-liter canister for drivers and passengers. Exposure concentrations of benzene, toluene, ethylbenzene, and xylene were analyzed via gas chromatography with a flame ionization detector and the formaldehyde concentration was monitored using a formaldehyde meter. Subsequently, a Monte Carlo simulation was conducted to evaluate the carcinogenic and non-carcinogenic risks of the five VOCs. Formaldehyde emerged as the highest detected compound (9.06 ± 3.77 µg/m3), followed by toluene (median: 6.11 µg/m3; range: 3.86-14.69 µg/m3). In particular, formaldehyde was identified to have the significantly higher concentration during non-rush hours (10.67 ± 3.21 µg/m3) than that during rush hours (7.45 ± 3.41 µg/m3) and during the warm season (10.71 ± 2.97 µg/m3) compared with that during the cold season (7.41 ± 4.26 µg/m3). Regarding non-carcinogenic risks to drivers and passengers, the chronic hazard indices for these five VOCs were under 1 to indicate an acceptable risk. In terms of carcinogenic risk, the median risks of benzene and formaldehyde for drivers were 2.88 × 10-6 (95% confidence interval [CI]: 2.11 × 10-6 - 5.13 × 10-6) and 1.91 × 10-6 (95% CI: 4.54 × 10-7 - 3.44 × 10-6), respectively. In contrast, the median carcinogenic risks of benzene and formaldehyde for passengers were less than 1 × 10-6 to present an acceptable risk. This study suggests that benzene and formaldehyde may present carcinogenic risks for drivers. Moreover, the non-carcinogenic risk for drivers and passengers is deemed acceptable. We recommended that the ventilation frequency be increased to mitigate exposure to VOCs in long-distance buses.

Pulse granuloma presenting as a lateral neck mass: An unusual presentation of a fourth branchial cleft fistula.

BACKGROUND: The pulse granuloma (PG) is believed to represent a distinctive foreign body reaction to ingested particles of legumes. Its presentation in the neck is entirely unexpected. METHODS: A woman presented with a mass of the lower neck that recurred following incision and drainage. The recurrent mass was found to be associated with an open sinus tract at the apex of the left pyriform sinus. The opening of the sinus tract was closed and the cyst was removed. RESULTS: Histologic examination of the neck mass showed vegetable material with an associated granulomatous reaction known as PG. CONCLUSIONS: The documentation of a PG arising in the neck would seemingly discredit the legume theory, but it only further supports it. Its association with a fourth branchial cleft cyst provides evidence for the existence of the complete fourth branchial cleft fistula with seeding of ingested material through sinus tract opening.

Reproducibility of laryngeal force sensor measurements.

OBJECTIVE: The laryngeal force sensor (LFS) measures force during suspension microlaryngoscopy (SML) procedures, and has been previously shown to predict postoperative complications. Reproducibility of its measurements has not been described. STUDY DESIGN: Prospective cohort study. SETTING: Academic medical center. METHODS: 291 adult patients had force data collected from 2017 to 2021 during various SML procedures. 94 patients had passive LFS monitoring (surgeon blinded to intraoperative recordings) and 197 had active LFS monitoring (surgeon able to see LFS recordings). 27 of these patients had repeat procedures, with unique LFS metrics for each procedure. The 27 patients were divided into three groups. Group 1 had passive use for both procedures, group 2 had passive use for the first procedure and active use for the second, and group 3 had active use for both procedures. Force metrics from the two procedures were compared with a paired samples t-test. RESULTS: For airway dilation procedures and cancer resection procedures, average force variances were significantly lower with active versus passive use of the LFS. Group 1-no significant changes in maximum force (procedure 1 = 163.8 N, procedure 2 = 133.8 N, p = 0.324) or average force (procedure 1 = 93.6 N, procedure 2 = 78.3 N, p = 0.617). Group 2-maximum force dropped by 35 % between procedures 1 (219.2 N) and 2 (142.5 N), p = 0.013. Average force dropped by 42.5 % between procedures 1 (147.2 N) and 2 (84.6 N), p = 0.007. Group 3-no significant changes in maximum force (procedure 1 = 158.6 N, procedure 2 = 158.2 N, p = 0.986) or average force (procedure 1 = 94.2, procedure 2 = 81.8, p = 0.419). CONCLUSIONS: LFS measurements were reproducible for similar procedures in the same patient when the type of LFS monitoring was not a confounder.

Carbohydrate-Small Molecule Hybrids as Lead Compounds Targeting IL-6 Signaling.

In the past 25 years, a number of efforts have been made toward the development of small molecule interleukin-6 (IL-6) signaling inhibitors, but none have been approved to date. Monosaccharides are a diverse class of bioactive compounds, but thus far have been unexplored as a scaffold for small molecule IL-6-signaling inhibitor design. Therefore, in this present communication, we combined a structure-based drug design approach with carbohydrate building blocks to design and synthesize novel IL-6-signaling inhibitors targeting glycoprotein 130 (gp130). Of this series of compounds, LS-TG-2P and LS-TF-3P were the top lead compounds, displaying IC50 values of 6.9 and 16 µM against SUM159 cell lines, respectively, while still retaining preferential activity against the IL-6-signaling pathway. The carbohydrate moiety was found to improve activity, as N-unsubstituted triazole analogues of these compounds were found to be less active in vitro compared to the leads themselves. Thus, LS-TG-2P and LS-TF-3P are promising scaffolds for further development and study as IL-6-signaling inhibitors.

Predictive Outcomes of Deep Learning Measurement of the Anterior Glottic Angle in Bilateral Vocal Fold Immobility.

OBJECTIVE: (1) To compare maximum glottic opening angle (anterior glottic angle, AGA) in patients with bilateral vocal fold immobility (BVFI), unilateral vocal fold immobility (UVFI) and normal larynges (NL), and (2) to correlate maximum AGA with patient-reported outcome measures. METHODS: Patients wisth BVFI, UVFI, and NL were retrospectively studied. An open-source deep learning-based computer vision tool for vocal fold tracking was used to analyze videolaryngoscopy. Minimum and maximum AGA were calculated and correlated with three patient-reported outcomes measures. RESULTS: Two hundred and fourteen patients were included. Mean maximum AGA was 29.91° (14.40° SD), 42.59° (12.37° SD), and 57.08° (11.14° SD) in BVFI (N = 70), UVFI (N = 70), and NL (N = 72) groups, respectively (p < 0.001). Patients requiring operative airway intervention for BVFI had an average maximum AGA of 24.94° (10.66° SD), statistically different from those not requiring intervention (p = 0.0001). There was moderate negative correlation between Dyspnea Index scores and AGA (Spearman r = -0.345, p = 0.0003). Maximum AGA demonstrated high discriminatory ability for BVFI diagnosis (AUC 0.92, 95% CI 0.81-0.97, p < 0.001) and moderate ability to predict need for operative airway intervention (AUC 0.77, 95% CI 0.64-0.89, p < 0.001). CONCLUSIONS: A computer vision tool for quantitative assessment of the AGA from videolaryngoscopy demonstrated ability to discriminate between patients with BVFI, UVFI, and normal controls and predict need for operative airway intervention. This tool may be useful for assessment of other neurological laryngeal conditions and may help guide decision-making in laryngeal surgery. LEVEL OF EVIDENCE: III Laryngoscope, 133:2285-2291, 2023.

Development of a Predictive Model for Optimization of Embryo Transfer Timing Using Blood-Based microRNA Expression Profile.

MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (n = 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria: p-value < 0.05 and fold change greater than 1.5 or less than -1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses.

The global landscape of approved antibody therapies.

Antibody therapies have become an important class of therapeutics in recent years as they have exhibited outstanding efficacy and safety in the treatment of several major diseases including cancers, immune-related diseases, infectious disease and hematological disease. There has been significant progress in the global research and development landscape of antibody therapies in the past decade. In this review, we have collected available data from the Umabs Antibody Therapies Database (Umabs-DB, https://umabs.com) as of 30 June 2022. The Umabs-DB shows that 162 antibody therapies have been approved by at least one regulatory agency in the world, including 122 approvals in the US, followed by 114 in Europe, 82 in Japan and 73 in China, whereas biosimilar, diagnostic and veterinary antibodies are not included in our statistics. Although the US and Europe have been at the leading position for decades, rapid advancement has been witnessed in Japan and China in the past decade. The approved antibody therapies include 115 canonical antibodies, 14 antibody-drug conjugates, 7 bispecific antibodies, 8 antibody fragments, 3 radiolabeled antibodies, 1 antibody-conjugate immunotoxin, 2 immunoconjugates and 12 Fc-Fusion proteins. They have been developed against 91 drug targets, of which PD-1 is the most popular, with 14 approved antibody-based blockades for cancer treatment in the world. This review outlined the global landscape of the approved antibody therapies with respect to the regulation agencies, therapeutic targets and indications, aiming to provide an insight into the trends of the global development of antibody therapies.

Updates, Controversies, and Emerging Approaches in Colorectal Screening.

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths. Despite the threatening statistics, the US burden for CRC has been decreasing, which is likely multifactorial and has partial contribution from widespread timely screening, more advanced CRC treatment, and daily aspirin use in some patients. While overall death rate from CRC decreased by approximately a half between 1975 and 2012, epidemiologic studies demonstrate that CRC incidence is increasing in the younger population. This pattern has prompted the American Cancer Society (ACS) to revise their guidelines. In this review, we plan to discuss the most recent changes in guidelines, data to support them, controversies concerning CRC screening methods, age to start and to stop screening, and post-colonoscopy/polypectomy surveillance guidelines.

Perioperative pain management and opioid-reduction in head and neck endocrine surgery: An American Head and Neck Society Endocrine Surgery Section consensus statement.

BACKGROUND: This American Head and Neck Society (AHNS) consensus statement focuses on evidence-based comprehensive pain management practices for thyroid and parathyroid surgery. Overutilization of opioids for postoperative pain management is a major contributing factor to the opioid addiction epidemic however evidence-based guidelines for pain management after routine head and neck endocrine procedures are lacking. METHODS: An expert panel was convened from the membership of the AHNS, its Endocrine Surgical Section, and ThyCa. An extensive literature review was performed, and recommendations addressing several pain management subtopics were constructed based on best available evidence. A modified Delphi survey was then utilized to evaluate group consensus of these statements. CONCLUSIONS: This expert consensus provides evidence-based recommendations for effective postoperative pain management following head and neck endocrine procedures with a focus on limiting unnecessary use of opioid analgesics.

Synergistic Effect of Bazedoxifene and PARP Inhibitor in the Treatment of Ovarian Cancer Regardless of BRCA Mutation.

BACKGROUND/AIM: Poly (ADP-ribose) polymerase inhibitors (PARPis) are one of the targeted therapies proven to treat breast cancer gene (BRCA)-mutant ovarian cancer. Because most ovarian cancers are BRCA wild-type, it is necessary to extend the usage of PARPis. In the present study, we combined the PARPi, talazoparib, and the IL-6 inhibitor, bazedoxifene, for the treatment of human ovarian cancer cells. MATERIALS AND METHODS: The human ovarian cancer cell lines, SKOV3, UWB1.289 (BRCA1-null) and OV75, were treated with talazoparib and bazedoxifene, as monotherapy or combination treatment. The effects of treatment on cell viability, migration, growth and colony formation were examined. Western blot was used to investigate pathways that may be involved in the antitumor effects of the two agents. RESULTS: The combination of talazoparib and bazedoxifene showed synergistic inhibition of cell viability, cell migration, cell growth, and cell colony formation on all the studied cell lines. The expression of p-AKT, c-myc, p-ERK, ERα was inhibited, and γ-H2AX expression was induced. CONCLUSION: Combined inhibition of PARP and IL-6 may be an efficacious treatment for ovarian cancer, independently of BRCA mutation status.

First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: A phase I/II study.

BACKGROUND: This open-label, phase I/II study evaluated safety and efficacy for first-line liposomal irinotecan + oxaliplatin + 5-fluorouracil + leucovorin (NALIRIFOX). METHODS: Patients (aged ≥18 years) had locally advanced/metastatic pancreatic ductal adenocarcinoma (mPDAC), with an Eastern Cooperative Oncology Group performance status score of 0/1 and adequate organ function. Primary objectives were to determine the maximum tolerated dose (MTD) and to evaluate safety and tolerability. Treatment-emergent adverse events (TEAEs) were graded using National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. Efficacy end-points included progression-free survival (PFS) and overall survival (OS); disease assessments used Response Evaluation Criteria in Solid Tumors 1.1. RESULTS: The MTD (liposomal irinotecan 50 mg/m2 [free-base equivalent], oxaliplatin 60 mg/m2, 5-fluorouracil 2400 mg/m2, leucovorin 400 mg/m2 every 2 weeks) was based on dose-limiting toxicities and cumulative safety data in four dose-exploration cohorts. The MTD was received by 32 of 56 patients, seven during dose exploration and 25 during dose expansion (median age 58.0 years [range, 39-76], 28 [87.5%] with metastatic disease at diagnosis [29 at study entry], and one receiving study treatment at data cutoff [26 February 2020]). Of these patients, 22 of 32 had grade ≥3 treatment-related TEAEs, most commonly neutropenia (31.3%), febrile neutropenia (12.5%) and hypokalaemia (12.5%); ten had serious treatment-related TEAEs; and three died from TEAEs considered unrelated to treatment. Median PFS and OS were 9.2 (95% CI: 7.69-11.96) and 12.6 (8.74-18.69) months, respectively. CONCLUSION: First-line NALIRIFOX for patients with locally advanced/mPDAC was generally manageable and tolerable. A randomised, controlled phase III study is underway.

Colorectal cancer screening in the COVID-19 era.

Colorectal cancer (CRC) is the third most diagnosed form of cancer and second most deadly cancer worldwide. Introduction of better screening has improved both incidence and mortality. However, as the coronavirus disease 2019 (COVID-19) pandemic began, healthcare resources were shunted away from cancer screening services resulting in a sharp decrease in CRC screening and a backlog of patients awaiting screening tests. This may have significant effects on CRC cancer mortality, as delayed screening may lead to advanced cancer at diagnosis. Strategies to overcome COVID-19 related disruption include utilizing stool-based cancer tests, developing screening protocols based on individual risk factors, expanding telehealth, and increasing open access colonoscopies. In this review, we will summarize the effects of COVID-19 on CRC screening, the potential long-outcomes, and ways to adapt CRC screening during this global pandemic.

One institution's experience with self-audit of opioid prescribing practices for common cervical procedures.

BACKGROUND: We aim to audit our institution's opioid prescribing practices after common cervical procedures. METHODS: Retrospective cohort study from one medical center. Reviewed records from 2016-2019 for 472 patients who underwent one of several common cervical procedures. Data collected on demographics, perioperative details, in-hospital pain medication use, and opioids prescribed at discharge. Multivariable logistic regression was run. RESULTS: In hospital, median daily milligram morphine equivalents (MME) was 4 (IQR 0-15). Median MME prescribed at discharge was 112.5 MME (IQR 75-150). 3/472 patients received NSAIDs. Predictors of decreased discharge MME were age 70 and older (OR 0.33, p = 0.037) and more recent year (compared to 2016, OR 0.23 [p = 0.031] for 2017, OR 0.13 [p = 0.001] for 2018, and OR 0.070 [p < 0.001] for 2019). CONCLUSIONS: MME prescribed at discharge was 28 times the daily in-hospital MME. Only 3/472 patients received postoperative NSAIDs. Self-auditing of opioid prescribing practices identifies actionable items for change.

A novel platform for discovery of differentially expressed microRNAs in patients with repeated implantation failure.

OBJECTIVE: To identify predictor microRNAs (miRNAs) from patients with repeated implantation failure (RIF). DESIGN: Systemic analysis of miRNA profiles from the endometrium of patients undergoing in vitro fertilization (IVF). SETTING: University research institute, private IVF center, and molecular testing laboratory. PATIENT(S): Twenty five infertile patients in the discovery cohort and 11 patients in the validation cohort. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): A signature set of miRNA associated with the risk of RIF. RESULT(S): We designed a reproductive disease-related PanelChip to access endometrium miRNA profiles in patients undergoing IVF. Three major miRNA signatures, including hsa-miR-20b-5p, hsa-miR-155-5p, and hsa-miR-718, were identified using infinite combination signature search algorithm analysis from 25 patients in the discovery cohort undergoing IVF. These miRNAs were used as biomarkers in the validation cohort of 11 patients. Finally, the 3-miRNA signature was capable of predicting patients with RIF with an accuracy >90%. CONCLUSION(S): Our findings indicated that specific endometrial miRNAs can be applied as diagnostic biomarkers to predict RIF. Such information will definitely help to increase the success rate of implantation practice.

Application of a Computer Vision Tool for Automated Glottic Tracking to Vocal Fold Paralysis Patients.

OBJECTIVES: (1) Demonstrate true vocal fold (TVF) tracking software (AGATI [Automated Glottic Action Tracking by artificial Intelligence]) as a quantitative assessment of unilateral vocal fold paralysis (UVFP) in a large patient cohort. (2) Correlate patient-reported metrics with AGATI measurements of TVF anterior glottic angles, before and after procedural intervention. STUDY DESIGN: Retrospective cohort study. SETTING: Academic medical center. METHODS: AGATI was used to analyze videolaryngoscopy from healthy adults (n = 72) and patients with UVFP (n = 70). Minimum, 3rd percentile, 97th percentile, and maximum anterior glottic angles (AGAs) were computed for each patient. In patients with UVFP, patient-reported outcomes (Voice Handicap Index 10, Dyspnea Index, and Eating Assessment Tool 10) were assessed, before and after procedural intervention (injection or medialization laryngoplasty). A receiver operating characteristic curve for the logistic fit of paralysis vs control group was used to determine AGA cutoff values for defining UVFP. RESULTS: Mean (SD) 3rd percentile AGA (in degrees) was 2.67 (3.21) in control and 5.64 (5.42) in patients with UVFP (P < .001); mean (SD) 97th percentile AGA was 57.08 (11.14) in control and 42.59 (12.37) in patients with UVFP (P < .001). For patients with UVFP who underwent procedural intervention, the mean 97th percentile AGA decreased by 5 degrees from pre- to postprocedure (P = .026). The difference between the 97th and 3rd percentile AGA predicted UVFP with 77% sensitivity and 92% specificity (P < .0001). There was no correlation between AGA measurements and patient-reported outcome scores. CONCLUSIONS: AGATI demonstrated a difference in AGA measurements between paralysis and control patients. AGATI can predict UVFP with 77% sensitivity and 92% specificity.

Laryngeal Force Sensor for Suspension Microlaryngoscopy: A Prospective Controlled Trial.

OBJECTIVES: The laryngeal force sensor (LFS) provides real-time force data for suspension microlaryngoscopy. This study investigates whether active use of the LFS can prevent the development of complications. STUDY DESIGN: Prospective controlled trial. SETTING: Academic tertiary center. METHODS: The LFS and custom software were developed to track intraoperative force metrics. A consecutive series of 100 patients had force data collected with operating surgeons blinded to intraoperative readings. The subsequent 100 patients had surgeons actively use the LFS monitoring system. Patients were prospectively enrolled, completing pre- and postoperative surveys to assess the development of tongue pain, paresthesia, paresis, dysgeusia, or dysphagia. RESULTS: On univariate analysis, the active monitoring group had lower total impulse (P < .001) and fewer extralaryngeal complications (P < .01). On multiple logistic regression, maximum force (odds ratio [OR], 1.08; 95% CI, 1.01-1.16; P = .02) was a significant predictive variable for the development of postoperative complications. Similarly, active LFS monitoring showed a 29.1% (95% CI, 15.7%-42.4%; P < .001) decrease in the likelihood of developing postoperative complications. These effects persisted at the first postoperative visit for maximum force (P = .04) and active LFS monitoring (P = .01). Maximum force (OR, 1.11; 95% CI, 1.04-1.18; P < .01) and active LFS monitoring (16.6%; 95% CI, 2.7%-30.5%; P = .02) were also predictive for the development of an abnormal 10-item Eating Assessment Tool score. These effects also persisted at the first postoperative visit for maximum force (P = .01) and active LFS monitoring (P = .01). CONCLUSION: Maximum force is predictive of the development postoperative complications. Active monitoring with the LFS is able to mitigate these forces and prevent postoperative complications. LEVEL OF EVIDENCE: 2.

Coverage for Gender-Affirming Voice Surgery and Therapy for Transgender Individuals.

OBJECTIVES/HYPOTHESIS: To determine insurance coverage for gender-affirming surgery and voice therapy for individuals who seek to align their voice with their gender identity, and to analyze differences based on state-by-state transgender equality. STUDY DESIGN: Cross-sectional study. METHODS: Policies from the top three commercial insurers per state in 2019 were reviewed. Coverage status was determined by web-based search, telephone interviews, and email inquiries. A state-by-state equality score was calculated based on the number of laws and policies relating to the transgender community. Correlation between number of preauthorized procedures and state equality scores was assessed. RESULTS: Of the 150 insurance companies reviewed, only four (2.7%) held favorable policies, whereas 113 (75.8%) provided no coverage. Endoscopic surgery, open surgery, individual voice therapy, and group voice therapy interventions were equally excluded (n = 93, 62.4%). Coverage was not correlated with laws driving transgender equality (P = .782). CONCLUSIONS: Gender-affirming voice interventions are seldom covered by commercial insurance companies. Despite established medical necessity and years of experience in practice, gender-affirming interventions for voice have not yet been fully considered by third-party payors. Further investigation regarding cost-effectiveness and treatment efficacy is warranted to improve insurance coverage of voice-related gender-affirming care. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E896-E902, 2021.

Phase I study of liposomal irinotecan in patients with metastatic breast cancer: findings from the expansion phase.

PURPOSE: Metastatic breast cancer (mBC) remains incurable and is associated with low survival rates. This study assessed the efficacy and safety of liposomal irinotecan in heavily pretreated patients with mBC, with or without active brain metastases (BM). METHODS: Following the dose escalation phase and determination of recommended phase 2 dose, the expansion phase of this phase I, open-label, non-randomized study, assigned adult women to cohorts based on mBC subtype: cohort 1, hormone receptor +/human epidermal growth factor receptor 2-; cohort 2, triple-negative breast cancer; or cohort 3, any mBC subtype with active BM. Patients received liposomal irinotecan 50 or 70 mg/m2 free base every 2 weeks. Here, we report secondary outcomes including best overall response (BOR), objective response rate (ORR), and treatment-emergent adverse events (TEAEs). RESULTS: For non-central nervous system (non-CNS) disease across all cohorts (intent-to-treat population, N = 29), the ORR was 34.5% (95% confidence interval: 17.94-54.33), with a BOR of partial response in 10 patients (34.5%), stable disease in five (17.2%), progressive disease in 10 (34.5%); four patients were unevaluable (13.8%). The ORR for the CNS cohort was 30.0% (95% confidence interval: 6.67-65.25) using modified Response Evaluation Criteria in Solid Tumors. Common grade 3 or higher TEAEs were diarrhea (27.6%), nausea (17.2%), fatigue (13.8%), asthenia (10.3%), and hypokalemia (10.3%). Serious treatment-related TEAEs were reported in six patients (20.7%). No treatment-related TEAEs resulted in death. CONCLUSIONS: Liposomal irinotecan monotherapy demonstrated antitumor activity in heavily pretreated patients with mBC, with or without BM. The observed safety profile was consistent with that in previous studies. CLINICAL TRIAL REGISTRATION: Trial registration ID NCT01770353.

Pretreatment clamping of pulmonary artery during uniportal thoracoscopic lobectomy.

BACKGROUND: Intraoperative pulmonary artery (PA) hemorrhage is one of the leading reasons for conversion from uniportal VATS to open thoracotomy, especially for the small incision (≤3 cm) uniportal VATS performed by our department. So, We designed a technology called pretreatment clamping of the pulmonary artery, which may be helpful to solve the problem. METHODS: A retrospective analysis of 19 patients who had pulmonary artery bleeding during uniportal thoracoscopic lobectomy in which one group had undergone preventive pulmonary artery clamping, the clamping group (n = 11), and one group which did not receive preventive clamping, the non-clamping group (n = 8). We compared the rates of conversion from the uniportal VATS approach to open thoracotomy or multi-incision operation, duration of pulmonary artery repair, blood loss, length of postoperative hospital stay and postoperative complications of the two groups. RESULTS: Compared to the non-clamping group, the clamping group had lower rates of conversion to open thoracotomy (0% vs 62.5%, p < 0.05) and lower rates of conversion to multi-incision operations (18.2% of non-clamping converted to 2-port approach vs 12.5% of clamping converted to 2-port approach and 12.5% converted to 3-port approach, p < 0.05). Duration of pulmonary artery repair was reduced in the clamping group (10.1 ± 3.2 min vs 18.3 ± 5.5 min, p < 0.05). The clamping group also had decreased blood loss (23.6 ± 11.2 ml vs 47.5 ± 14.9 ml, p<0.05). There were no significant differences in postoperative hospital stay and postoperative complications between the two groups. CONCLUSION: Pretreatment clamping of the pulmonary artery in VATS lobectomy can decrease conversion rates, decrease blood loss, shorten repairing time of the pulmonary artery, and feasibly can be applied in uniportal thoracoscopic lobectomy.