Real-World Outcomes and Clinical Predictors of Immune Checkpoint Inhibitor Monotherapy in Advanced Lung Cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of advanced-stage non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The aim of this study was to evaluate the effectiveness and tolerance of ICIs in a real-world patient population and to investigate the predictive factors associated with survival outcomes. METHODS: Medical records of patients with advanced lung cancer who started ICI monotherapy were reviewed for data collection. Treatment outcomes included objective response rate, progression-free survival (PFS), and overall survival (OS). Immune-related adverse events (irAEs) were assessed. Multiple Cox regression models were fit to investigate the predictive factors for survival outcomes. RESULTS: We included 220 patients (median 66.5 years). Seventy-nine (35.9%) patients had Eastern Cooperative Oncology Group (ECOG) performance-status (PS) score ⩾2. Median follow-up was 11.4 months. In NSCLC, median PFS was 3.8 months (4.7 months for first line and 3.7 months for subsequent line). Median OS was 12.4 months (15.6 months for first line therapy and 11.5 months for subsequent line). In SCLC, median PFS was 1.8 months, and median OS was 4.6 months. A quarter of patients developed irAEs. There was 1 disease flare among 17 patients with pre-existing autoimmune diseases. ECOG PS of 0 to 1 and body mass index (BMI) ⩾ 25 kg/m2 (but not occurrence of irAE) were independently associated with improved OS in NSCLC, with a hazard ratio of 0.41 (95% confidence interval [CI], 0.29-0.59) and 0.62 (95% CI, 0.44-0.87), respectively. CONCLUSIONS: The clinical benefit of ICIs appears to persist in a real-world population of relatively older age, including those with poor PS and pre-existing autoimmune diseases. ECOG PS of 0 to 1 and BMI ⩾ 25 kg/m2 were independently associated with improved OS.

Risk factors for perioperative hypothermia and infectious outcomes in gastroschisis patients.

INTRODUCTION: Prior data suggest that infants with gastroschisis are at high risk for hypothermia and infectious complications (ICs). This study evaluated the associations between perioperative hypothermia (PH) and ICs in gastroschisis using a multi-institutional cohort. METHODS: Retrospective review of infants with gastroschisis who underwent abdominal closure from 2013-2017 was performed at 7 children's hospitals. Any-IC and surgical site infection (SSI) were stratified against the presence or absence of PH, and perioperative characteristics associated with PH and SSI were determined using multivariable logistic regression. RESULTS: Of 256 gastroschisis neonates, 42% developed PH, with 18% classified as mild hypothermia (35.5-35.9 °C), 10.5% as moderate (35.0-35.4 °C), and 13% severe (<35 °C). There were 82 (32%) ICs with 50 (19.5%) being SSIs. No associations between PH and any-IC (p = 0.7) or SSI (p = 0.98) were found. Pulmonary comorbidities (odds ratio (OR)=3.76, 95%CI:1.42-10, p = 0.008) and primary closure (OR=0.21, 95%CI:0.12-0.39, p<0.001) were associated with PH, while silo placement (OR=2.62, 95%CI:1.1-6.3, p = 0.03) and prosthetic patch (OR=3.42, 95%CI:1.4-8.3, p = 0.007) were associated with SSI on multivariable logistic regression. CONCLUSIONS: Primary abdominal closure and pulmonary comorbidities are associated with PH in gastroschisis, however PH was not associated with increased risk of ICs. Independent risk factors for SSI include silo placement and prosthetic patch closure.

Fetal Non-Ovarian Abdominopelvic Cystic Lesions: A Single-Center Report.

INTRODUCTION: There is a paucity of reports describing the clinical course and likely postnatal outcomes of prenatally identified simple cystic abdominopelvic lesions which are not associated with the ovary. OBJECTIVE: The aim of this study was to describe the natural history and postnatal outcomes of prenatally discovered abdominopelvic cystic lesions seen at our center. METHODS: This study is a retrospective review of all newborns with prenatally discovered non-ovarian simple cystic abdominal or pelvic lesions (September 2012-December 2018). Prenatal solid organ involvement, lesion size, and postnatal clinical outcomes are described. RESULTS: Sixty-six patients with 68 cystic lesions were identified; 22 patients with 24 lesions met the defined study criteria and were included. Eleven (46%) resolved prenatally, while 5 (21%) resolved by 18 months of age. Of the 10 lesions associated with an organ, 4 (40%) resolved prenatally. Of the remaining 14 lesions not associated with a solid organ, 7 (50%) resolved prenatally. Seven lesions (29%) required postnatal surgical intervention. Larger maximum prenatal lesions tended toward postnatal surgical intervention (one-way ANOVA: p = 0.072). CONCLUSIONS: The majority of simple non-ovarian cystic abdominopelvic lesions at our center resolved in the perinatal period. Due to the low frequency of these lesions at fetal centers, a larger multicenter study based on a consistent monitoring protocol should be undertaken to better describe the resolution patterns of simple non-ovarian cystic lesions for improved prenatal counseling.

The Rational Design of Therapeutic Peptides for Aminopeptidase N using a Substrate-Based Approach.

The M1 family of metalloproteases represents a large number of exopeptidases that cleave single amino acid residues from the N-terminus of peptide substrates. One member of this family that has been well studied is aminopeptidase N (APN), a multifunctional protease known to cleave biologically active peptides and aide in coronavirus entry. The proteolytic activity of APN promotes cancer angiogenesis and metastasis making it an important target for cancer therapy. To understand the substrate specificity of APN for the development of targeted inhibitors, we used a global substrate profiling method to determine the P1-P4' amino acid preferences. The key structural features of the APN pharmacophore required for substrate recognition were elucidated by x-ray crystallography. By combining these substrate profiling and structural data, we were able to design a selective peptide inhibitor of APN that was an effective therapeutic both in vitro and in vivo against APN-expressing prostate cancer models.