Background

While gastric cancer is a leading cause of cancer-related mortality in Eastern Europe and Asia, it is less common in the United States. Recommendations regarding optimal treatment of non-metastatic gastric cancer with regard to type and extent of surgery, choice and sequence of chemotherapeutic agents, and use of radiation therapy vary somewhat depending on geographic location. There is paucity in the literature for direct comparison of various practices. To determine how variability in treatment practices affects patient outcomes, we conducted a retrospective study in patients with gastric cancer who had multimodality treatment for non-metastatic gastric cancer.

Methods

We gathered clinical data (patient demographics, pathology reports, type of surgical intervention, chemotherapy, and radiation therapy) for patients diagnosed with gastric adenocarcinoma who underwent gastrectomy at five sites from 2010-2017 using Electronic Health Records and California Cancer Registry databases. Medical chart reviews were conducted to validate patient outcomes. We performed multivariate Cox regression analyses to determine predictors for cancer recurrence and survival. We also performed logistic regression analyses to determine predictors of positive resection margins and hospitalization.

Results

One hundred and sixteen patients met eligibility criteria to be included. Mean age was 65.7±11.6 years. About 65.5% were male. The most common ethnicities were Asian (44.0%) and Caucasian (37.9%). About 58.6% of the patients had localized disease (defined as pT1-3, pN0) and the remaining 41.4% had loco-regional disease (i.e., pT4 or pN+). About 41.4% of the tumors were diffuse, 27.6% intestinal, 12.0% mixed, and 19.0% unknown histology. Surgery included laparoscopic (94.8%) and open gastrectomy (5.2%). Chemotherapy and radiation therapy were given in 51.7% and 19.0% of the patients, respectively. After a median follow-up time of 19 months after gastrectomy, 16.4% of patients had recurrence and 19.8% had died. Patients who had loco-regional tumors were more likely to have recurrence and death than those who had localized tumors (hazard ratios =7.0, P=0.0228 for recurrence and hazard ratios =3.3, P=0.0160 for death). Positive resection margins were seen in 9% of the patients and were associated with diffuse histology (odds ratio =6.6, P=0.0207). Hospitalization within six months of gastrectomy was seen in 22% of the patients. Peri-operative chemotherapy was the only significant predictor for re-hospitalization (odds ratio =3.5, P=0.0415).

Conclusions

In this contemporary cohort of patients with localized gastric cancer, only the pathological stage was significantly associated with survival while positive resection margins were associated with diffuse histology. Closer monitoring of patients undergoing perioperative chemotherapy within 6 months of surgery is warranted based on our observation of higher rate of re-hospitalization.

STUDY OBJECTIVES: To determine the prevalence of occult sleep disordered breathing (SDB) and describe the relationship between classic SDB symptoms (e.g., loud snoring) and occult SDB in older veterans with insomnia. METHODS: We analyzed baseline survey and in-home sleep study data for 435 veterans (mean age = 72.0 years [SD 8.0]) who had no known history of SDB, met International Classification of Sleep Disorders 2(nd) Edition criteria for insomnia, and were enrolled in a behavioral intervention trial for insomnia. Variables of interest included apnea-hypopnea index (AHI) ≥ 15, age, race/ethnicity, marital status, body mass index (BMI), insomnia subtype (i.e., onset, maintenance, or terminal), self-reported excessive daytime sleepiness, snoring, and witnessed breathing pause items from the Berlin Questionnaire. We computed the frequency of AHI ≥ 15 and assessed whether each classic SDB symptom was associated with an AHI ≥ 15 in 4 separate multivariate logistic regression models. RESULTS: Prevalence of AHI ≥ 15 was 46.7%. Excessive daytime sleepiness (adjusted odds ratio 1.63, 95% CI 1.02, 2.60, p = 0.04), but not snoring loudness, snoring frequency, or witnessed breathing pauses was associated with occult SDB (AHI ≥ 15). Insomnia subtypes were not significantly associated with occult SDB (p > 0.38). CONCLUSIONS: In our sample of older veterans with insomnia, nearly half had occult SDB, which was characterized by reported excessive daytime sleepiness, but not loud or frequent snoring or witnessed breathing pauses. Insomnia subtype was unrelated to the presence of occult SDB.

Sudden cardiac death (SCD) is the most common cause of death in patients with Chagas disease (ChD). There are over 300,000 ChD-infected individuals living in the United States, of whom 10-15% have undiagnosed Chagas cardiomyopathy (CCM). CCM patients have a higher risk of SCD compared to non-CCM patients, although early and appropriate treatment of CCM patients can result in a 95% relative risk reduction of SCD. Emergency physicians have a unique opportunity to improve outcomes among these patients by becoming more vigilant in recognizing the signs and symptoms of CCM in patients who present in sudden cardiac arrest. We report the case of a patient presenting to the emergency department with pulseless ventricular tachycardia and an undiagnosed history of CCM.

Repair of peripheral nerve defects with current synthetic, tubular nerve conduits generally shows inferior recovery when compared with using nerve autografts, the current gold standard. We tested the ability of composite collagen and hyaluronan hydrogels, with and without the nerve growth factor (NGF), to stimulate neurite extension on a promising aligned, nanofiber poly-L-lactide-co-caprolactone (PLCL) scaffold. In vitro, the hydrogels significantly increased neurite extension from dorsal root ganglia explants. Consistent with these results, the addition of hydrogels as luminal fillers within aligned, nanofiber tubular PLCL conduits led to improved sensory function compared to autograft repair in a critical-size defect in the sciatic nerve in a rat model. Sensory recovery was assessed 3 and 12 weeks after repair using a withdrawal assay from thermal stimulation. The addition of hydrogel did not enhance recovery of motor function in the rat model. The NGF led to dose-dependent improvements in neurite out-growth in vitro, but did not have a significant effect in vivo. In summary, composite collagen/hyaluronan hydrogels enhanced sensory neurite outgrowth in vitro and sensory recovery in vivo. The use of such hydrogels as luminal fillers for tubular nerve conduits may therefore be useful in assisting restoration of protective sensation following peripheral nerve injury.

Introduction

Current tissue engineering strategies to heal critical-size bone defects through direct bone formation are limited by incomplete integration of grafts with host bone and incomplete graft vascularization. An alternative strategy for bone regeneration is the use of cartilage grafts that form bone through endochondral ossification. Endochondral cartilages stimulate angiogenesis and are remodeled into bone, but are found in very small quantities in growth plates and healing fractures. We sought to develop engineered endochondral cartilage grafts using osteoarthritic (OA) articular chondrocytes as a cell source. Such chondrocytes often undergo hypertrophy, which is a characteristic of endochondral cartilages.

Materials and methods

We compared the ability of unmodified human OA (hOA) cartilage and cartilage grafts formed in vitro from hOA chondrocytes to undergo endochondral ossification in mice. Scaffold-free engineered chondrocyte grafts were generated by pelleting chondrocytes, followed by culture with transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein 4. Samples derived from either primary or passaged chondrocytes were implanted subcutaneously into immunocompromised mice. Grafts derived from passaged chondrocytes from three patients were implanted into critical-size tibial defects in mice. Bone formation was assessed with histology after 4 weeks of implantation. The composition of tibial repair tissue was quantified with histomorphometry.

Results

Engineered cartilage grafts generated from passaged OA chondrocytes underwent endochondral ossification after implantation either subcutaneously or in bone. Cartilage grafts integrated with host bone at 15 out of 16 junctions. Grafts variably remodeled into woven bone, with the proportion of bony repair tissue in tibial defects ranging from 22% to 85% (average 48%). Bony repair tissue bridged the tibial defects in half of the animals. In contrast, unmodified OA cartilage and engineered grafts formed from primary chondrocytes did not undergo endochondral ossification in vivo.

Conclusions

hOA chondrocytes can adopt an endochondral phenotype after passaging and TGF-β superfamily treatment. Engineered endochondral cartilage grafts can integrate with host bone, undergo ossification, and heal critical-size long-bone defects in a mouse model. However, additional methods to further enhance ossification of these grafts are required before the clinical translation of this approach.

Background

Biomarkers predicting immunotherapy response in metastatic renal cell cancer (mRCC) are lacking. PD-L1 immunohistochemistry is a complementary diagnostic for immune checkpoint inhibitors (ICIs) in mRCC, but has shown minimal clinical utility and is not used in routine clinical practice.

Methods

Tumor specimens from 56 patients with mRCC who received nivolumab were evaluated for PD-L1, cell proliferation (targeted RNA-seq), and outcome.

Results

For 56 patients treated with nivolumab as a standard of care, there were 2 complete responses and 8 partial responses for a response rate of 17.9%. Dividing cell proliferation into tertiles, derived from the mean expression of 10 proliferation-associated genes in a reference set of tumors, poorly proliferative tumors (62.5%) were more common than moderately (30.4%) or highly proliferative (8.9%) counterparts. Moderately proliferative tumors were enriched for PD-L1 positive (41.2%), compared to poorly proliferative counterparts (11.4%). Objective response for moderately proliferative (29.4%) tumors was higher than that of poorly (11.4%) proliferative counterparts, but not statistically significant (p = .11). When cell proliferation and negative PD-L1 tumor proportion scores were combined statistically significant results were achieved (p = .048), showing that patients with poorly proliferative and PD-L1 negative tumors have a very low response rate (6.5%) compared to moderately proliferative PD-L1 negative tumors (30%).

Conclusions

Cell proliferation has value in predicting response to nivolumab in clear cell mRCC patients, especially when combined with PD-L1 expression. Further studies which include the addition of progression-free survival (PFS) along with sufficiently powered subgroups are required to further support these findings.