Lack of Lymphocyte Recovery After Esophagectomy Predicts Overall and Recurrence-Free Survival.

BACKGROUND: Lymphocytes have become the target of cancer interventions through engineering or immune checkpoint antibodies. We previously found decreased lymphocyte counts to be a predictor of mortality and complications in trauma and cardiac surgery patients. We hypothesized lack of lymphocyte count recovery postoperatively would predict outcomes in esophagectomy patients. METHODS: A retrospective review of all patients undergoing esophagectomy for adenocarcinoma performed over 13 y at our center by a single surgeon after institutional review board approval was performed. Patients were grouped by postoperative lymphocytes counts: never low, low with recovery, and low without recovery. Resolution of lymphopenia was assessed by day 4. Primary end points were overall and recurrence-free survival. RESULTS: In total, 198 patients were included with a minimum 6-mo follow-up. Collectively the 5-y recurrence and overall survival rates were 36% and 50%, respectively. Recurrence was significantly higher at 5 y in patients with persistent lymphopenia (43%) compared with those who recovered (14% P = 0.0017) and those who never dropped (0% P = 0.0009). The persistent lymphopenia group had significantly lower survival (45%) compared with the two other groups (67% P = 0.0232). CONCLUSIONS: There is a significant decrease in the overall and recurrence-free survival in those patients whose lymphocyte count drops without recovery after their esophagectomy. These data imply differences in immune responses to the stress of surgery that can be measured with routine postoperative laboratory values and are indicative of overall outcomes.

Prehospital shock index outperforms hypotension alone in predicting significant injury in trauma patients.

BACKGROUND: The American College of Surgeons Resources for Optimal Care of the Injured Patient recommends using hypotension, defined as systolic blood pressure ≤90 mm Hg, as an indicator of a full team trauma activation. We hypothesized that an elevated shock index (SI) predicts significant traumatic injuries better than hypotension alone. METHODS: This is a retrospective cohort study analyzing full team trauma activations between February 2018 and January 2020, excluding transfers and those who had missing values for prehospital blood pressure or heart rate. We reviewed patients' demographics, prehospital and emergency department vitals, injury pattern, need for operation, and clinical outcomes. The primary outcome was rate of significant injury defined as identified injured liver, spleen, or kidney, pelvis fracture, long bone fracture, significant extremity soft tissue damage, hemothorax, or pneumothorax. RESULTS: Among 544 patients, 82 (15.1%) had prehospital hypotension and 492 had normal blood pressure. Of the patients with prehospital hypotension, 34 (41.5%) had a significant injury. There was no difference in age, gender, medical history, or injury pattern between the two groups. There was no difference between the two groups in rate of serious injury (41.5% vs. 46.1%, NS), need for emergent operation (31.7% vs. 28.1%, NS) or death (20.7% vs. 18.8%, NS). On the other hand, SI ≥1 was associated with increased rate of serious injury (54.6% vs. 43.4%, p=0.04). On a logistic regression analysis, prehospital hypotension was not associated with significant injury or need for emergent operation (OR 0.83, 95% CI 0.51 to 1.33 and OR 1.32, 95% CI 0.79 to 2.25, respectively). SI ≥1 was associated with both increased odds of significant injury and need for emergent operation (OR 1.57, 95% CI 1.01 to 2.44 and OR 1.64, 95% CI 1.01 to 2.66). DISCUSSION: SI was a better indicator and could replace hypotension to better categorize and triage patients in need of higher level of care. LEVEL OF EVIDENCE: Prognostic and epidemiologic, level III.

Characterization of retinal biomechanical properties using Brillouin microscopy.

SIGNIFICANCE: The retina is critical for vision, and several diseases may alter its biomechanical properties. However, assessing the biomechanical properties of the retina nondestructively is a challenge due to its fragile nature and location within the eye globe. Advancements in Brillouin spectroscopy have provided the means for nondestructive investigations of retina biomechanical properties. AIM: We assessed the biomechanical properties of mouse retinas using Brillouin microscopy noninvasively and showed the potential of Brillouin microscopy to differentiate the type and layers of retinas based on stiffness. APPROACH: We used Brillouin microscopy to quantify stiffness of fresh and paraformaldehyde (PFA)-fixed retinas. As further proof-of-concept, we demonstrated a change in the stiffness of a retina with N-methyl-D-aspartate (NMDA)-induced damage, compared to an undamaged sample. RESULTS: We found that the retina layers with higher cell body density had higher Brillouin modulus compared to less cell-dense layers. We have also demonstrated that PFA-fixed retina samples were stiffer compared with fresh samples. Further, NMDA-induced neurotoxicity leads to retinal ganglion cell (RGC) death and reactive gliosis, increasing the stiffness of the RGC layer. CONCLUSION: Brillouin microscopy can be used to characterize the stiffness distribution of the layers of the retina and can be used to differentiate tissue at different conditions based on biomechanical properties.

The Hippo Pathway Blocks Mammalian Retinal Müller Glial Cell Reprogramming.

In response to retinal damage, the Müller glial cells (MGs) of the zebrafish retina have the ability to undergo a cellular reprogramming event in which they enter the cell cycle and divide asymmetrically, thereby producing multipotent retinal progenitors capable of regenerating lost retinal neurons. However, mammalian MGs do not exhibit such a proliferative and regenerative ability. Here, we identify Hippo pathway-mediated repression of the transcription cofactor YAP as a core regulatory mechanism that normally blocks mammalian MG proliferation and cellular reprogramming. MG-specific deletion of Hippo pathway components Lats1 and Lats2, as well as transgenic expression of a Hippo non-responsive form of YAP (YAP5SA), resulted in dramatic Cyclin D1 upregulation, loss of adult MG identity, and attainment of a highly proliferative, progenitor-like cellular state. Our results reveal that mammalian MGs may have latent regenerative capacity that can be stimulated by repressing Hippo signaling.

Neuroimaging in Alzheimer's disease: preclinical challenges toward clinical efficacy.

The scope of this review focuses on recent applications in preclinical and clinical magnetic resonance imaging (MRI) toward accomplishing the goals of early detection and responses to therapy in animal models of Alzheimer's disease (AD). Driven by the outstanding efforts of the Alzheimer's Disease Neuroimaging Initiative (ADNI), a truly invaluable resource, the initial use of MRI in AD imaging has been to assess changes in brain anatomy, specifically assessing brain shrinkage and regional changes in white matter tractography using diffusion tensor imaging. However, advances in MRI have led to multiple efforts toward imaging amyloid beta plaques first without and then with the use of MRI contrast agents. These technological advancements have met with limited success and are not yet appropriate for the clinic. Recent developments in molecular imaging inclusive of high-power liposomal-based MRI contrast agents as well as fluorine 19 ((19)F) MRI and manganese enhanced MRI have begun to propel promising advances toward not only plaque imaging but also using MRI to detect perturbations in subcellular processes occurring within the neuron. This review concludes with a discussion about the necessity for the development of novel preclinical models of AD that better recapitulate human AD for the imaging to truly be meaningful and for substantive progress to be made toward understanding and effectively treating AD. Furthermore, the continued support of outstanding programs such as ADNI as well as the development of novel molecular imaging agents and MRI fast scanning sequences will also be requisite to effectively translate preclinical findings to the clinic.