Intestinal Dysbiosis in the Infant and the Future of Lacto-Engineering to Shape the Developing Intestinal Microbiome

PurposeThe goal of this study was to review the role of human milk in shaping the infant intestinal microbiota and the potential of human milk bioactive molecules to reverse trends of increasing intestinal dysbiosis and dysbiosis-associated diseases.MethodsThis narrative review was based on recent and historic literature.FindingsHuman milk immunoglobulins, oligosaccharides, lactoferrin, lysozyme, milk fat globule membranes, and bile salt–stimulating lipase are complex multifunctional bioactive molecules that, among other important functions, shape the composition of the infant intestinal microbiota.ImplicationsThe co-evolution of human milk components and human milk–consuming commensal anaerobes many thousands of years ago resulted in a stable low-diversity infant microbiota. Over the past century, the introduction of antibiotics and modern hygiene practices plus changes in the care of newborns have led to significant alterations in the intestinal microbiota, with associated increases in risk of dysbiosis-associated disease. A better understanding of mechanisms by which human milk shapes the intestinal microbiota of the infant during a vulnerable period of development of the immune system is needed to alter the current trajectory and decrease intestinal dysbiosis and associated diseases.     

Quantitative Blood Volume Analysis and Hemodynamic Measures of Vascular Compliance in Patients With Worsening Heart Failure

BackgroundThe role of blood volume (BV) expansion vs a change in vascular compliance in worsening heart failure (HF) remains under debate. We aimed to assess the relationship between BV and resting and stress hemodynamics in worsening HF and to further elucidate the significance of BV in cardiac decompensation.Methods and ResultsPatients with worsening HF underwent radiolabeled indicator-dilution BV analysis and cardiac catheterization. Intravascular volumes and resting/stress hemodynamics were recorded. Provocative stress maneuvers included change in systolic blood pressure (ΔSBP) from lying to standing and Valsalva and intracardiac pressure changes with leg raise. Correlation between BV and invasive hemodynamics were assessed by linear regression. Of 27 patients with worsening HF, patients’ characteristics included mean age 61 ± 12 years, 70% male, 19% Black, and mean ejection fraction 29% ± 15%. Of the patients, 13 (48%) had hypervolemia as measured by total BV, which weakly correlated with ΔSBP by position (R² = 0.009) and Valsalva (R² = 0.003) and with right atrial (R² = 0.049) and pulmonary capillary wedge (R² = 0.047) pressure changes during leg raise.ConclusionsIn patients with worsening HF, BV mildly correlated with intracardiac pressures at rest. Provocative maneuvers intended to test vascular compliance did not correlate with BV, indicating that compliance may serve as a stand-alone metric in HF.     

Percutaneous liver venous deprivation: outcomes in heavily pretreated metastatic colorectal cancer patients

BackgroundTo evaluate liver venous deprivation (LVD) outcomes in patients with colorectal liver metastasis (CRLM) heavily pretreated with systemic and hepatic arterial infusion pump (HAIP) chemotherapies that had an anticipated insufficient future liver remnant (FLR) hypertrophy after portal vein embolization (PVE).MethodsPVE was performed with liquid embolics using a transsplenic or ipsilateral transhepatic approach. Simultaneously and via a trans-jugular approach, the right hepatic vein was embolized with vascular plugs. Liver volumetry was assessed on computed tomography before and 3–6 weeks after LVD.ResultsTwelve consecutive CRLM patients that underwent LVD before right hepatectomy or trisectionectomy were included, all previously treated with systemic chemotherapy for a mean of 11.9 months. Six patients had additional HAIP. After embolization, FLR ratio increased from 28.7% ± 5.9 to 42.2% ± 9.0 (P < 0.01). Mean kinetic growth rate (KGR) was 3.56%/week ± 2.3, with a degree of hypertrophy (DH) of 13.8% ± 7.1. In the HAIP subgroup, mean KGR and DH were respectively 3.58%/week ± 2.8 and 14.3% ± 8.7. No severe complications occurred. Ten patients reached surgery after 39 days ± 7.5.ConclusionIn heavily pretreated patients, LVD safely stimulated a rapid and effective FLR hypertrophy, with a resultant high rate of resection.     

Review of Variables Associated With Positive Surgical Margins Using Scout Reflector Localizations for Breast Conservation Therapy

ObjectiveTo evaluate factors contributing to positive surgical margins associated with reflector guidance for patients undergoing breast conserving therapy for malignancy.Materials and MethodsA retrospective IRB-approved review of our institutional database was performed for malignant breast lesions preoperatively localized from January 1, 2018 to December 31, 2020. The following data was recorded using electronic medical records: lesion type and grade, lesion location, reflector and wire placement modality, use of intraoperative ultrasound, margin status, patient age, family history, BMI, and final pathology. Statistical analysis was performed with univariate summary statistics and logistic regression. P < .05 was significant.ResultsA total of 606 image-guided pre-surgical localizations were performed for lumpectomies of breast malignancies. A total of 352 of 606 (58%) wire localizations and 254 of 606 (42%) SCOUT reflector localizations were performed. Sixty out of 352 (17%) of wire-localized patients had positive surgical margins, whereas forty-eight out of 254 (19%) of reflector-localized patients had positive surgical margins. (OR = 1.12, P value: .59). For reflector guided cases, the use of intraoperative ultrasound (IOUS) was associated with decreased positive margin status (OR = 0 .28, 95% CI = [0.14, 0.58]) while in situ disease was associated with increased positive margin status (OR = 1.99, 95% CI = [1.05, 3.75]). No association between modality used for localization (mammography vs. ultrasound) and positive margin status was observed (OR = 0.63, 95% CI = [0.33, 1.19]). No association between positive margins and age, family history, tumor location and BMI was observed.ConclusionFor reflector guided surgeries, the use of IOUS was associated with decreased positive margins, by contrast the presence of ductal carcinoma in situ was associated with increased positive margins. There was no statistically significant difference in surgical outcomes for reflector-guided localization compared to wire localizations of the breast.