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Lower pretreatment CD4 counts were associated with acute hematologic toxicity, and lower posttreatment CD4 count levels were associated with an increased risk of tumor recurrence. These results suggest that immune surveillance may play an important role in long-term disease control in anal cancer.

Cognitive-behavioral therapy (CBT) is effective for pediatric obsessive-compulsive disorder (OCD), but non-response is common. Brain glutamate (Glu) signaling may contribute to OCD pathophysiology and moderate CBT outcomes. We assessed whether Glu measured with magnetic resonance spectroscopy (MRS) was associated with OCD and/or CBT response. Youths aged 7-17 years with DSM-IV OCD and typically developing controls underwent 3 T proton echo-planar spectroscopic imaging (PEPSI) MRS scans of pregenual anterior cingulate cortex (pACC) and ventral posterior cingulate cortex (vPCC)-regions possibly affected by OCD-at baseline. Controls returned for re-scan after 8 weeks. OCD youth-in a randomized rater-blinded trial-were re-scanned after 12-14 weeks of CBT or after 8 weeks of minimal-contact waitlist; waitlist participants underwent a third scan after crossover to 12-14 weeks of CBT. Forty-nine children with OCD (mean age 12.2±2.9 years) and 29 controls (13.2±2.2 years) provided at least one MRS scan. At baseline, Glu did not differ significantly between OCD and controls in pACC or vPCC. Within controls, Glu was stable from scan-to-scan. Within OCD subjects, a treatment-by-scan interaction (p=0.034) was observed, driven by pACC Glu dropping 19.5% from scan-to-scan for patients randomized to CBT, with minor increases (3.8%) for waitlist participants. The combined OCD participants (CBT-only plus waitlist-CBT) also showed a 16.2% (p=0.004) post-CBT decrease in pACC Glu. In the combined OCD group, within vPCC, lower pre-CBT Glu predicted greater post-CBT improvement in symptoms (CY-BOCS; r=0.81, p=0.00025). Glu may be involved in the pathophysiology of OCD and may moderate response to CBT.

patients had tumoral PD-L1 expression !5%. Patients with tumoral PD-L1 !5% had better OS vs those with lower expression, HRZ0.29 (CI 0.10-0.78), pZ0.009; 10 years OS: 84% for PD-L1 !5% vs. 46% for PD-L1 <5%. On univariate analysis, OS was associated with PD-L1 status, as well as T stage, N stage, ECOG status and gender. On multivariate analysis, PD-L1 !5% remained statistically significant for better OS, HRZ0.35 (CI 0.12-0.99), pZ0.047. 33 of 65 (51%) of tumors had high CD8 levels (3 or 4). There was no association between CD8 status and OS; further stratifying PD-L1 high patients by CD8 did not improve the prognostic impact vs PD-L1 status alone. Conclusion: This is the first study reporting significant association of PD-L1 expression with OS in patients with anal cancer treated with CRT. PD-L1 status warrants consideration in the prognostication of patients with anal cancer. Future studies are required to determine the benefit of alternative treatment strategies based on PD-L1 status.

Cigarette smoke is an aerosol containing microparticles that carry nicotine into the lung alveolar region where nicotine is rapidly absorbed into circulation. Nicotine exposure in smokers is a chronic intermittent process, with episodic intake during wakefulness and abstinence during sleep resulting in circadian fluctuation of blood nicotine levels. We developed an integrated platform where freely moving rodents can be exposed to episodic nicotine aerosol on an investigator-designed schedule. Plasma nicotine and its metabolite cotinine levels were determined with a LC-MS/MS method. We characterized the aerosol in the breathing zone of the rodent exposure chamber. The droplet-size distribution was within the respirable diameter range. The system can generate a wide range of nicotine concentrations in air that meet a variety of experimental needs. Rats were exposed to nicotine aerosol once every half hour in the dark phase of 12:12-h light-dark cycles for 10 days. We optimized the parameters of aerosol generation and exposure: plasma nicotine and cotinine concentrations reached 30–35 and 190–240 ng/ml, respectively. The nicotine levels and circadian patterns resembled the pharmacokinetic pattern of human smokers. In summary, we developed an aerosol system that can produce clinically relevant chronic intermittent nicotine exposure in unanesthetized, unrestrained rodents with route of administration and circadian blood pharmacokinetics resembling human smokers. This methodology is a novel tool for understanding the health effects of chronic intermittent nicotine exposure such as with tobacco cigarettes and electronic cigarettes for studies of behavior, pharmacology and toxicology, nicotine addiction, tobacco-related diseases, and teratogenicity, and for the discovery of therapeutics. NEW & NOTEWORTHY We developed a lung alveolar region-targeted aerosol method and a system that provides chronic intermittent nicotine exposure in freely moving rodents. The method produces in rodents clinically relevant nicotine exposure with the route and circadian pharmacokinetics resembling human smokers. This method is a novel tool for understanding the health impacts of chronic nicotine exposures such as with tobacco cigarettes and electronic cigarettes, for studying nicotine pharmacology, toxicology, addiction, and tobacco-related diseases, and for the discovery of therapeutics.

To improve the quality of cancer operations, the American College of Surgeons published Operative Standards for Cancer Surgery, which has been incorporated into Commission on Cancer (CoC) accreditation requirements. We sought to determine if compliance with operative standards was associated with technical surgical outcomes. Oncologic operative reports from 2017 at a CoC and non-CoC institution were examined for documentation of Operative Standards essential steps. Lymph node (LN) yield for lung and colon cases and re-excision rates for breast cases were recorded. Correct documentation was poor for colon, breast, and lung cases with numerous elements documented in <10% of operative reports at both centers. For lung cases, there was no significant difference in meeting ≥10 LN benchmark or average LN yield between the 2 institutions. For colon cases, average lymph node yield was lower in the non-CoC facility, but there was no significant difference in meeting ≥12 LN benchmark. For breast cases, re-excision rates were similar in both programs. Many essential steps in Operative Standards were poorly documented in operative reports, regardless of CoC status. Achieving benchmark technical surgical outcomes was not associated with documented compliance with these standards. Whether improved documentation leads to better surgical outcomes requires further investigation.

Background: Ventral hernia repair (VHR) is one of the most common general surgery procedures; however, few studies with long-term follow-up of VHR outcomes exist. Methods: We performed a retrospective review of VHRs performed from 2000 to 2009 at a single institution. Our primary outcome was recurrence, and secondary outcomes were reoperations and complications including seroma, hematomas, abdominal wall abscess, wound infections, and mesh infections. Results: Our sample population (n=420; mean age 46.3±11.7 years) included 230 females (54.8%), and cases included laparoscopic (n=31; 7.5%), laparoscopic converted to open (n=7; 1.7%), and open (n=373, 90%). As compared to suture repairs, mesh repair was associated with lower rates of complications (25.7% vs 29.5%, p=0.10) and recurrence (12.8% vs 15.2%, p=0.67). Laparoscopic repairs had lower rates of complications than open repairs (25% vs 26.8%; p=0.70) but similar rates of recurrence (13.8% and 13.6%; p=0.53). After logistic regression, obesity, chronic obstructive pulmonary disease, component separation technique, and prolonged operating time (>75th percentile) were associated with increased complications. Conclusion: Obesity is a modifiable risk factor and must be addressed in patients undergoing VHRs. Mesh repair does not increase the risk of adverse long-term outcomes and may be performed safely in patients undergoing VHR.

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