Updates in Translational Science for Esophageal and Gastric Cancers.

In this article, the authors summarize the current state of translational science for esophageal and gastric cancers. The available targeted therapies, immunotherapies, and recently discovered molecular targets are reviewed. The authors introduce circulating tumor deoxyribonucleic acid and its promise as a biomarker to detect disease recurrence. The authors present patient-derived organoids as a new model for studying carcinogenesis and treatment responses. Finally, we discuss the implications of organoid models for precision oncology and describe exciting new work applying gene editing technology to organoids and studying tumor-microenvironment interactions using 3-dimensional co-culture systems.

Starting and Developing a Robotic Thoracic Surgery Program.

Robotic-assisted surgery has been widely adopted in the field of thoracic surgery as a safe, minimally invasive approach with distinct technical advantages. With increased utilization, it has become an integral part of training pathways for the next generation of thoracic surgeons. This review article highlights key steps in implementing a robotic thoracic surgery program at an academic center based on institutional experience and the available surgical literature.

Induction of Neutralizing Responses against Autologous Virus in Maternal HIV Vaccine Trials.

A maternal vaccine capable of boosting neutralizing antibody (NAb) responses directed against circulating viruses in HIV-infected pregnant women could effectively decrease mother-to-child transmission of HIV. However, it is not known if an HIV envelope (Env) vaccine administered to infected pregnant women could enhance autologous virus neutralization and thereby reduce this risk of vertical HIV transmission. Here, we assessed autologous virus NAb responses in maternal plasma samples obtained from AIDS Vaccine Evaluation Group (AVEG) protocols 104 and 102, representing historical phase I safety and immunogenicity trials of recombinant HIV Env subunit vaccines administered to HIV-infected pregnant women (ClinicalTrials registration no. NCT00001041). Maternal HIV Env-specific plasma binding and neutralizing antibody responses were characterized before and after vaccination in 15 AVEG 104 (n = 10 vaccine recipients, n = 5 placebo recipients) and 2 AVEG 102 (n = 1 vaccine recipient, n = 1 placebo recipient) participants. Single-genome amplification (SGA) was used to obtain HIV env gene sequences of autologous maternal viruses for pseudovirus production and neutralization sensitivity testing in pre- and postvaccination plasma of HIV-infected pregnant vaccine recipients (n = 6 gp120, n = 1 gp160) and placebo recipients (n = 3). We detected an increase in Env subunit MN gp120-specific IgG binding in the group of vaccine recipients between the first immunization visit and the last visit at delivery (P = 0.027, 2-sided Wilcoxon test). While no difference was observed in the levels of autologous virus neutralization potency between groups, in both groups maternal plasma collected at delivery more effectively neutralized autologous viruses from early pregnancy than late pregnancy. Immunization strategies capable of further enhancing these autologous virus NAb responses in pregnant women will be important to block vertical transmission of HIV.IMPORTANCE Maternal antiretroviral therapy (ART) has effectively reduced but not eliminated the burden of mother-to-child transmission of HIV across the globe, as an estimated 160,000 children were newly infected with HIV in 2018. Thus, additional preventive strategies beyond ART will be required to close the remaining gap and end the pediatric HIV epidemic. A maternal active immunization strategy that synergizes with maternal ART could further reduce infant HIV infections. In this study, we found that two historic HIV Env vaccines did not enhance the ability of HIV-infected pregnant women to neutralize autologous viruses. Therefore, next-generation maternal HIV vaccine candidates must employ alternate approaches to achieve potent neutralizing antibody and perhaps nonneutralizing antibody responses to effectively impede vertical virus transmission. Moreover, these approaches must reflect the broad diversity of HIV strains and widespread availability of ART worldwide.

Occurrence of Symptomatic Hypotension in Patients Undergoing Breast Free Flaps: Is Enhanced Recovery after Surgery to Blame?

BACKGROUND: Enhanced recovery after surgery (ERAS) initiatives improve postoperative function and expedite recovery, leading to a decrease in length of stay. The authors noted a high rate of postoperative symptomatic hypotension in patients undergoing abdominal free flap breast reconstruction and wished to explore this observation. METHODS: Subjects undergoing abdominal free flap breast reconstruction at the authors' institution from 2013 to 2017 were identified. The ERAS protocol was initiated in 2015 at the authors' hospital; thus, 99 patients underwent traditional management and 138 patients underwent ERAS management. Demographics and perioperative data were collected and analyzed. Postoperative symptomatic hypotension was defined as mean arterial pressure below 80 percent of baseline with symptoms requiring evaluation. RESULTS: A significantly higher rate of postoperative symptomatic hypotension was observed in the ERAS cohort compared with the traditional management cohort (4 percent versus 22 percent; p < 0.0001). Patients in the ERAS cohort received significantly less intraoperative intravenous fluid (4467 ml versus 3505 ml; p < 0.0001) and had a significantly increased amount of intraoperative time spent with low blood pressure (22 percent versus 32 percent; p =0.002). Postoperatively, the ERAS cohort had significantly lower heart rate (77 beats per minute versus 88 beats per minute; p < 0.0001) and mean arterial pressure (71 mmHg versus 78 mmHg; p < 0.0001), with no difference in urine output or adverse events. CONCLUSIONS: The authors report that ERAS implementation in abdominal free flap breast reconstruction may result in a unique physiologic state with low mean arterial pressure, low heart rate, and normal urine output, resulting in postoperative symptomatic hypotension. Awareness of this early postoperative finding can help better direct fluid resuscitation and prevent episodes of symptomatic hypotension. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Maternal Humoral Immune Responses Do Not Predict Postnatal HIV-1 Transmission Risk in Antiretroviral-Treated Mothers from the IMPAACT PROMISE Study.

To design immune interventions that can synergize with antiretroviral therapy (ART) to reduce the rate of HIV mother-to-child transmission (MTCT), it is essential to characterize maternal immune responses in the setting of ART during pregnancy and breastfeeding and define their effect on MTCT. Prior studies reported an association between breast milk envelope (Env)-specific antibodies and antibody-dependent cell cytotoxicity (ADCC) activity with reduced postnatal transmission. In this study, we investigated whether these immune correlates were similarly associated with protection in a matched case-control study of mother-infant pairs receiving maternal ART or infant nevirapine prophylaxis during breastfeeding in the International Maternal-Pediatric-Adolescent AIDS Clinical Trials Network Promoting Maternal-Infant Survival Everywhere (PROMISE) trial, assessing postnatal transmission risk in 19 transmitting and 57 nontransmitting mothers using conditional logistic regression models adjusted for maternal plasma viral load. The odds ratios of postnatal MTCT for a 1-unit increase in an immune correlate were 3.61 (95% confidence interval [CI], 0.56, 23.14) for breast milk Env-specific secretory IgA (sIgA), 2.32 (95% CI, 0.43, 12.56) for breast milk and 2.16 (95% CI, 0.51, 9.14) for plasma Env-specific IgA, and 4.57 (95% CI, 0.68, 30.48) for breast milk and 0.96 (95% CI, 0.25, 3.67) for plasma ADCC activity, with all CIs spanning 1.0. Interestingly, although mucosal IgA responses are poor in untreated HIV-infected women, there was a strong correlation between the magnitudes of breast milk and plasma Env-specific IgA in this cohort. In this analysis of the small number of postnatal virus transmissions in the landmark PROMISE study, no single antibody response was associated with breast milk transmission risk.IMPORTANCE Each year, >150,000 infants become newly infected with HIV-1 through MTCT despite ART, with up to 42% of infections occurring during breastfeeding. Several factors contribute to continued pediatric infections, including ART nonadherence, the emergence of drug-resistant HIV strains, acute infection during breastfeeding, and poor access to ART in resource-limited areas. A better understanding of the maternal humoral immune responses that provide protection against postnatal transmission in the setting of ART is critical to guide the design of maternal vaccine strategies to further eliminate postnatal HIV transmission. In this study, we found that in women treated with antiretrovirals during pregnancy, there was a positive correlation between plasma viral load and breast milk and plasma IgA responses; however, conclusions regarding odds of MTCT risk were limited by the small sample size. These findings will inform future studies to investigate maternal immune interventions that can synergize with ART to eliminate MTCT during breastfeeding.

The Effect of Enhanced Recovery after Surgery Pathway Implementation on Abdominal-Based Microvascular Breast Reconstruction.

BACKGROUND: Although Enhanced Recovery after Surgery (ERAS) pathways are becoming the standard of care in microvascular breast reconstruction, evidence supporting their use is limited or based on small sample sizes. We hypothesized that improvements in postoperative outcomes would persist when examining the largest cohort of patients undergoing abdominal-based microvascular breast reconstruction, to date. MATERIALS AND METHODS: Data were retrospectively reviewed for 276 consecutive patients who underwent abdominal-based free flap breast reconstruction before and after ERAS implementation (pre-ERAS, n = 138 patients; post-ERAS, n = 138 patients). Primary outcomes were postoperative opioid use measured in oral morphine equivalents (OMEs), median hospital length of stay (LOS) in days, and incidence of postoperative complications. RESULTS: Postoperative opioid requirements were significantly lower in the post-ERAS cohort compared with the pre-ERAS cohort (57.3 OME, [interquartile range 20.0-115.5] versus 297.3 OME [interquartile range 138.6-437.7], P < 0.0001). There was no significant difference in hospital LOS when controlling for variables that differed between the groups. In addition, there were no differences in the rate of postoperative complications, return to operating room, or readmission after ERAS pathway implementation. CONCLUSIONS: ERAS improves specific aspects of recovery for patients undergoing microvascular breast reconstruction, most notably postoperative opioid use. Patient selection and a shift toward less invasive procedures may explain a nonsignificant impact on hospital LOS.

Impact of surgical site infection and surgical debridement on lumbar arthrodesis: A single-institution analysis of incidence and risk factors.

This study identifies the rate of pseudarthrosis following surgical debridement for deep lumbar spine surgical site infection and identify associated risk factors. Patients who underwent index lumbar fusion surgery from 2013 to 2014 were included if they met the following criteria: 1) age >18years, 2) had debridement of deep lumbar SSI, and had 3) lumbar spine AP, lateral and flexion/extension X-rays and computed tomography (CT) at 12months or greater postoperatively. Criteria for fusion included 1) solid posterolateral, facet, or disk space bridging bone, 2) no translational or angular motion on flexion/extension X-rays, and 3) intact posterior hardware without evidence of screw lucency or breakage. Twenty-five patients (age 63.2±12.6years, 10 male) involving 58 spinal levels met inclusion criteria. They underwent fusion at a mean of 2.32 [range 1-4] spinal levels. Sixteen (64.0%) patients received interbody grafts at a total of 34 (58.6%) spinal levels. All underwent surgical debridement with removal of all non-incorporated posterior bone graft and devascularized tissue. At one-year postoperatively, (56%) patients and 30 (52%) spinal levels demonstrated radiographic evidence of successful fusion. Interbody cage during initial fusion was significantly associated with successful arthrodesis at follow-up (p=0.017). There is a high rate of pseudoarthrosis in 44% of patients (48% of levels) undergoing lumbar fusion surgery complicated by SSI requiring debridement. Use of interbody cage during initial fusion was significantly associated with higher rate of arthrodesis.