Functional ultrasound imaging of human brain activity through an acoustically transparent cranial window.

Visualization of human brain activity is crucial for understanding normal and aberrant brain function. Currently available neural activity recording methods are highly invasive, have low sensitivity, and cannot be conducted outside of an operating room. Functional ultrasound imaging (fUSI) is an emerging technique that offers sensitive, large-scale, high-resolution neural imaging; however, fUSI cannot be performed through the adult human skull. Here, we used a polymeric skull replacement material to create an acoustic window compatible with fUSI to monitor adult human brain activity in a single individual. Using an in vitro cerebrovascular phantom to mimic brain vasculature and an in vivo rodent cranial defect model, first, we evaluated the fUSI signal intensity and signal-to-noise ratio through polymethyl methacrylate (PMMA) cranial implants of different thicknesses or a titanium mesh implant. We found that rat brain neural activity could be recorded with high sensitivity through a PMMA implant using a dedicated fUSI pulse sequence. We then designed a custom ultrasound-transparent cranial window implant for an adult patient undergoing reconstructive skull surgery after traumatic brain injury. We showed that fUSI could record brain activity in an awake human outside of the operating room. In a video game "connect the dots" task, we demonstrated mapping and decoding of task-modulated cortical activity in this individual. In a guitar-strumming task, we mapped additional task-specific cortical responses. Our proof-of-principle study shows that fUSI can be used as a high-resolution (200 µm) functional imaging modality for measuring adult human brain activity through an acoustically transparent cranial window.

Neurotropism of SARS-CoV-2: A Pathological Examination of Neurosurgical Specimens.

BACKGROUND AND OBJECTIVES: Neurological manifestations may occur in more than 80% of patients hospitalized with COVID-19 infection, including severe disruptions of the central nervous system (CNS), such as strokes, encephalitis, or seizures. Although the primary pathophysiological mechanism for the effects of COVID-19 in CNS remains unknown, evidence exists for both direct injury from neuroinvasion and indirect effects from disruptions in systemic inflammatory and coagulation pathways. In this study, we analyzed CNS tissue from living patients to better understand these processes. METHODS: With institutional review board approval and patient consent, samples that would be otherwise discarded from patients with active or recent (within 6 days of surgery) COVID-19 infection undergoing neurosurgical intervention were collected and tested for the presence of SARS-CoV-2 using immunohistochemistry, in situ hybridization, electron microscopy, and reverse transcription polymerase chain reaction. RESULTS: Five patients with perioperative mild-to-moderate COVID-19 infection met inclusion criteria (2 male, 3 female; mean age 38.8 ± 13.5 years). Neurosurgical diagnoses included a glioblastoma, a ruptured arteriovenous malformation, a ruptured posterior inferior cerebellar artery aneurysm, a middle cerebral artery occlusion, and a hemorrhagic pontine cavernous malformation. Samples analyzed included the frontal lobe cortex, olfactory nerve, arteriovenous malformation/temporal lobe parenchyma, middle cerebral artery, cerebellum, and cavernous malformation/brainstem parenchyma. Testing for the presence of SARS-CoV-2 was negative in all samples. CONCLUSION: The CNS is likely not a significant viral reservoir during mild-to-moderate COVID-19 infection, although direct neuroinvasion is not definitively excluded. Additional testing to help elucidate the relative contributions of direct and indirect pathways for CNS injury from COVID is warranted.

Civilian Ballistic Arthrotomies: Infection Rates and Operative Versus Nonoperative Management.

OBJECTIVES: The purpose of this study was to determine whether a significant difference existed in the rate of infection after ballistic traumatic arthrotomy managed operatively compared with those managed without surgery. DESIGN: Retrospective cohort study. SETTING: Academic Level I Trauma Center. PATIENT SELECTION CRITERIA: Patients with ballistic traumatic arthrotomies of the shoulder, elbow, wrist, hip, knee, or ankle who received operative or nonoperative management. OUTCOME MEASURES AND COMPARISONS: The rates of infection and septic arthritis in those who received operative or nonoperative management. RESULTS: One hundred ninety-five patients were studied. Eighty patients were treated nonoperatively (Non-Op group), 16 patients were treated with formal irrigation and debridement in the operating room (I&D group), and 99 patients were treated with formal I&D and open reduction and internal fixation (ORIF) (I&D + ORIF group). Patients in all 3 groups received local wound care and systemic antibiotics. No patients in the Non-Op or I&D group developed an infection. Six patients in the I&D + ORIF group developed extra-articular postoperative infections requiring additional interventions. CONCLUSIONS: The infection rate in the I&D + ORIF group was consistent with the infection rates reported in orthopaedic literature after fixation alone. In addition, none of the infections were cases of septic arthritis. This suggests that traumatic arthrotomy does not increase the risk for infection beyond what is expected after fixation alone. Importantly, the Non-Op group represented a series of 80 patients who were treated nonoperatively without developing an infection, indicating that I&D may not be necessary to prevent infection after ballistic arthrotomy. The results suggest that septic arthritis after civilian ballistic arthrotomy is a rare complication regardless of the choice of treatment. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Zinc deficiency impairs axonal regeneration and functional recovery after spinal cord injury by modulating macrophage polarization via NF-κB pathway.

Background: Spinal cord injury (SCI) is a devastating disease that results in permanent paralysis. Currently, there is no effective treatment for SCI, and it is important to identify factors that can provide therapeutic intervention during the course of the disease. Zinc, an essential trace element, has attracted attention as a regulator of inflammatory responses. In this study, we investigated the effect of zinc status on the SCI pathology and whether or not zinc could be a potential therapeutic target. Methods: We created experimental mouse models with three different serum zinc concentration by changing the zinc content of the diet. After inducing contusion injury to the spinal cord of three mouse models, we assessed inflammation, apoptosis, demyelination, axonal regeneration, and the number of nuclear translocations of NF-κB in macrophages by using qPCR and immunostaining. In addition, macrophages in the injured spinal cord of these mouse models were isolated by flow cytometry, and their intracellular zinc concentration level and gene expression were examined. Functional recovery was assessed using the open field motor score, a foot print analysis, and a grid walk test. Statistical analysis was performed using Wilcoxon rank-sum test and ANOVA with the Tukey-Kramer test. Results: In macrophages after SCI, zinc deficiency promoted nuclear translocation of NF-κB, polarization to pro-inflammatory like phenotype and expression of pro-inflammatory cytokines. The inflammatory response exacerbated by zinc deficiency led to worsening motor function by inducing more apoptosis of oligodendrocytes and demyelination and inhibiting axonal regeneration in the lesion site compared to the normal zinc condition. Furthermore, zinc supplementation after SCI attenuated these zinc-deficiency-induced series of responses and improved motor function. Conclusion: We demonstrated that zinc affected axonal regeneration and motor functional recovery after SCI by negatively regulating NF-κB activity and the subsequent inflammatory response in macrophages. Our findings suggest that zinc supplementation after SCI may be a novel therapeutic strategy for SCI.

Deep pathomics: A new image-based tool for predicting response to treatment in stage III non-small cell lung cancer.

Despite the advantages offered by personalized treatments, there is presently no way to predict response to chemoradiotherapy in patients with non-small cell lung cancer (NSCLC). In this exploratory study, we investigated the application of deep learning techniques to histological tissue slides (deep pathomics), with the aim of predicting the response to therapy in stage III NSCLC. We evaluated 35 digitalized tissue slides (biopsies or surgical specimens) obtained from patients with stage IIIA or IIIB NSCLC. Patients were classified as responders (12/35, 34.7%) or non-responders (23/35, 65.7%) based on the target volume reduction shown on weekly CT scans performed during chemoradiation treatment. Digital tissue slides were tested by five pre-trained convolutional neural networks (CNNs)-AlexNet, VGG, MobileNet, GoogLeNet, and ResNet-using a leave-two patient-out cross validation approach, and we evaluated the networks' performances. GoogLeNet was globally found to be the best CNN, correctly classifying 8/12 responders and 10/11 non-responders. Moreover, Deep-Pathomics was found to be highly specific (TNr: 90.1) and quite sensitive (TPr: 0.75). Our data showed that AI could surpass the capabilities of all presently available diagnostic systems, supplying additional information beyond that currently obtainable in clinical practice. The ability to predict a patient's response to treatment could guide the development of new and more effective therapeutic AI-based approaches and could therefore be considered an effective and innovative step forward in personalised medicine.

Selective prediction for extracting unstructured clinical data.

OBJECTIVE: While there are currently approaches to handle unstructured clinical data, such as manual abstraction and structured proxy variables, these methods may be time-consuming, not scalable, and imprecise. This article aims to determine whether selective prediction, which gives a model the option to abstain from generating a prediction, can improve the accuracy and efficiency of unstructured clinical data abstraction. MATERIALS AND METHODS: We trained selective classifiers (logistic regression, random forest, support vector machine) to extract 5 variables from clinical notes: depression (n = 1563), glioblastoma (GBM, n = 659), rectal adenocarcinoma (DRA, n = 601), and abdominoperineal resection (APR, n = 601) and low anterior resection (LAR, n = 601) of adenocarcinoma. We varied the cost of false positives (FP), false negatives (FN), and abstained notes and measured total misclassification cost. RESULTS: The depression selective classifiers abstained on anywhere from 0% to 97% of notes, and the change in total misclassification cost ranged from -58% to 9%. Selective classifiers abstained on 5%-43% of notes across the GBM and colorectal cancer models. The GBM selective classifier abstained on 43% of notes, which led to improvements in sensitivity (0.94 to 0.96), specificity (0.79 to 0.96), PPV (0.89 to 0.98), and NPV (0.88 to 0.91) when compared to a non-selective classifier and when compared to structured proxy variables. DISCUSSION: We showed that selective classifiers outperformed both non-selective classifiers and structured proxy variables for extracting data from unstructured clinical notes. CONCLUSION: Selective prediction should be considered when abstaining is preferable to making an incorrect prediction.

Development and Validation of a Novel Literature-Based Method to Identify Disparity-Sensitive Surgical Quality Metrics.

BACKGROUND: Disparity in surgical care impedes the delivery of uniformly high-quality care. Metrics that quantify disparity in care can help identify areas for needed intervention. A literature-based Disparity-Sensitive Score (DSS) system for surgical care was adapted by the Metrics for Equitable Access and Care in Surgery (MEASUR) group. The alignment between the MEASUR DSS and Delphi ratings of an expert advisory panel (EAP) regarding the disparity sensitivity of surgical quality metrics was assessed. STUDY DESIGN: Using DSS criteria MEASUR co-investigators scored 534 surgical metrics which were subsequently rated by the EAP. All scores were converted to a 9-point scale. Agreement between the new measurement technique (ie DSS) and an established subjective technique (ie importance and validity ratings) were assessed using the Bland-Altman method, adjusting for the linear relationship between the paired difference and the paired average. The limit of agreement (LOA) was set at 1.96 SD (95%). RESULTS: The percentage of DSS scores inside the LOA was 96.8% (LOA, 0.02 points) for the importance rating and 94.6% (LOA, 1.5 points) for the validity rating. In comparison, 94.4% of the 2 subjective EAP ratings were inside the LOA (0.7 points). CONCLUSIONS: Applying the MEASUR DSS criteria using available literature allowed for identification of disparity-sensitive surgical metrics. The results suggest that this literature-based method of selecting quality metrics may be comparable to more complex consensus-based Delphi methods. In fields with robust literature, literature-based composite scores may be used to select quality metrics rather than assembling consensus panels.

A window to the brain: ultrasound imaging of human neural activity through a permanent acoustic window.

Recording human brain activity is crucial for understanding normal and aberrant brain function. However, available recording methods are either highly invasive or have relatively low sensitivity. Functional ultrasound imaging (fUSI) is an emerging technique that offers sensitive, large-scale, high-resolution neural imaging. However, fUSI cannot be performed through adult human skull. Here, we use a polymeric skull replacement material to create an acoustic window allowing ultrasound to monitor brain activity in fully intact adult humans. We design the window through experiments in phantoms and rodents, then implement it in a participant undergoing reconstructive skull surgery. Subsequently, we demonstrate fully non-invasive mapping and decoding of cortical responses to finger movement, marking the first instance of high-resolution (200 µm) and large-scale (50 mmx38 mm) brain imaging through a permanent acoustic window.

A review of neurophysiological effects and efficiency of waveform parameters in deep brain stimulation.

Neurostimulation has diverse clinical applications and potential as a treatment for medically refractory movement disorders, epilepsy, and other neurological disorders. However, the parameters used to program electrodes-polarity, pulse width, amplitude, and frequency-and how they are adjusted have remained largely untouched since the 1970 s. This review summarizes the state-of-the-art in Deep Brain Stimulation (DBS) and highlights the need for further research to uncover the physiological mechanisms of neurostimulation. We focus on studies that reveal the potential for clinicians to use waveform parameters to selectively stimulate neural tissue for therapeutic benefit, while avoiding activating tissue associated with adverse effects. DBS uses cathodic monophasic rectangular pulses with passive recharging in clinical practice to treat neurological conditions such as Parkinson's Disease. However, research has shown that stimulation efficiency can be improved, and side effects reduced, through modulating parameters and adding novel waveform properties. These developments can prolong implantable pulse generator lifespan, reducing costs and surgery-associated risks. Waveform parameters can stimulate neurons based on axon orientation and intrinsic structural properties, providing clinicians with more precise targeting of neural pathways. These findings could expand the spectrum of diseases treatable with neuromodulation and improve patient outcomes.

Vaccination rates among international students: Insights from a university health vaccination initiative.

Objective: To examine the effects of a university's health vaccination initiative in increasing vaccination rates among international students/scholars in the United States. Methods: The vaccination initiative included: increasing vaccination opportunities by holding a pre-registration event, providing vaccine recommendations from healthcare professionals including a bilingual health interpreter, implementing campus-based marketing strategies, sending reminders using social media, and offering free and affordable vaccines. Results: Total 575 international students/scholars attended from 2016 to 2019 (N = 118, 163, 193, and 101, respectively), showing an increase compared to 2015. The most common vaccines administered were for influenza, human papillomavirus (HPV), tetanus, diphtheria, and acellular pertussis (Tdap), and Hepatitis A. Slightly less than one-quarter of participants received three or more vaccines. More women than men received HPV vaccine. Participants shared they would not have been vaccinated without this initiative and wished for more vaccination events. Conclusions: Future efforts are needed to implement this initiative across universities to further evaluate its effectiveness.

Disparity-Sensitive Measures in Surgical Care: A Delphi Panel Consensus.

BACKGROUND: In the US, disparities in surgical care impede the delivery of uniformly high-quality care to all patients. There is a lack of disparity-sensitive measures related to surgical care. The American College of Surgeons Metrics for Equitable Access and Care in Surgery group, through research and expert consensus, aimed to identify disparity-sensitive measures in surgical care. STUDY DESIGN: An environmental scan, systematic literature review, and subspecialty society surveys were conducted to identify potential disparity-sensitive surgical measures. A modified Delphi process was conducted where panelists rated measures on both importance and validity. In addition, a novel literature-based disparity-sensitive scoring process was used. RESULTS: We identified 841 potential disparity-sensitive surgical measures. From these, our Delphi and literature-based approaches yielded a consensus list of 125 candidate disparity-sensitive measures. These measures were rated as both valid and important and were supported by the existing literature. CONCLUSION: There are profound disparities in surgical care within the US healthcare system. A multidisciplinary Delphi panel identified 125 potential disparity-sensitive surgical measures that could be used to track health disparities, evaluate the impact of focused interventions, and reduce healthcare inequity.

Tissue Expanders in Staged Calvarial Reconstruction: A Systematic Review.

Cranioplasties are common procedures in plastic surgery. The use of tissue expansion (TE) in staged cranioplasties is less common. We present two cases of cranioplasties with TE and systematically review literature describing the use of TE in staged cranioplasties and postoperative outcomes. A systematic review was performed by querying multiple databases. Eligible articles include published case series, retrospective reviews, and systematic reviews that described use of TE for staged bony cranioplasty. Data regarding study size, patient demographics, preoperative characteristics, staged procedure characteristics, and postoperative outcomes were collected. Of 755 identified publications, 26 met inclusion criteria. 85 patients underwent a staged cranioplasty with TE. Average defect size was 122 cm 2 , and 30.9% of patients received a previous reconstruction. Average expansion period was 14.2 weeks. The most common soft tissue closures were performed with skin expansion only (75.3%), free/pedicled flap (20.1%), and skin graft (4.7%). The mean postoperative follow-up time was 23.9 months. Overall infection and local complication rates were 3.53 and 9.41%, respectively. The most common complications were cerebrospinal fluid leak (7.1%), hematoma (7.1%), implant exposure (3.5%), and infection (3.5%). Factors associated with higher complication rates include the following: use of alloplastic calvarial implants and defects of congenital etiology ( p = 0.023 and 0.035, respectively). This is the first comprehensive review to describe current practices and outcomes in staged cranioplasty with TE. Adequate soft tissue coverage contributes to successful cranioplasties and TE can play a safe and effective role in selected cases.

Glenoid Prosthesis Design Considerations in Anatomic Total Shoulder Arthroplasty.

Total shoulder arthroplasty is an increasingly popular option for the treatment of glenohumeral arthritis. Historically, the effectiveness of the procedure has largely been determined by the long-term stability of the glenoid component. Glenoid component loosening can lead to clinically concerning complications including pain with movement, loss of function, and accumulation of debris which may require surgery to revise. In response, there has been a push to optimize the design of the glenoid prosthesis. Traditional contemporary glenoid components use pegs for fixation and are made entirely of polyethylene. Variations on the standard implant include keeled, metal-backed, hybrid, augmented, and inlay designs. There is a wealth of biomechanical and clinical studies that report on the effectiveness of these different designs. The purpose of this review is to summarize existing literature regarding glenoid component design and identify key areas for future research. Knowledge of the rationale underlying glenoid design will help surgeons select the best component for their patients and optimize outcomes following TSA.

Impact of cerebrovascular accidents on lung transplant survival.

BACKGROUND: Cerebrovascular accidents (CVA) are a source of postoperative morbidity. Existing data on CVA after lung transplantation (LT) are limited. We aimed to evaluate the impact of CVA on LT survival. METHODS: A retrospective analysis of LT recipients at the University of Texas Southwestern Medical Center was performed. Data was obtained from the institutional thoracic transplant database between January 2012 and December 2018, which consisted of 476 patients. Patients were stratified by the presence of a postoperative CVA. Univariate comparisons of baseline characteristics, operative variables, and postoperative outcomes between the cohorts were performed. Survival was analyzed by Kaplan-Meier method. Aalen's additive regression model was utilized to assess mortality hazard over time. RESULTS: The incidence of CVA was 4.2% (20/476). Lung allocation score was higher in the CVA cohort (46.2 [41.7, 57.3] vs. 41.5 [35.8, 52.2], p = 0.04). There were no significant differences in operative variables. CVA patients had longer initial intensive care unit (ICU) stays (316 h [251, 557] vs. 124 [85, 218], p < 0.001) and longer length of stay (22 days [17, 53] vs. 15 [11, 26], p = 0.007). CVA patients required more ICU readmissions (35% vs. 15%, p = 0.02) and had a lower rates of home discharge (35% vs. 71%, p < 0.001). Thirty-day mortality was higher in the CVA cohort (20% vs. 1.3%, p < 0.001). Overall survival was lower in the CVA cohort (log rank p = 0.044). CONCLUSIONS: Postoperative CVA following LT was associated with longer ICU stays, more ICU readmissions, longer length of stay, and fewer home discharges. Thirty day and long-term mortality were significantly higher in the CVA group.

Vagus nerve stimulation paired with rehabilitation for stroke: Implantation experience from the VNS-REHAB trial.

OBJECTIVE: Vagus Nerve Stimulation (VNS) paired with rehabilitation delivered by the Vivistim® Paired VNS™ System was approved by the FDA in 2021 to improve motor deficits in chronic ischemic stroke survivors with moderate to severe arm and hand impairment. Vagus nerve stimulators have previously been implanted in over 125,000 patients for treatment-resistant epilepsy and the surgical procedure is generally well-tolerated and safe. In this report, we describe the Vivistim implantation procedure, perioperative management, and complications for chronic stroke survivors enrolled in the pivotal trial. METHODS: The pivotal, multisite, randomized, triple-blind, sham-controlled trial (VNS-REHAB) enrolled 108 participants. All participants were implanted with the VNS device in an outpatient procedure. Thrombolytic agents were temporarily discontinued during the perioperative period. Participants were discharged within 48 hrs and started rehabilitation therapy approximately 10 days after the Procedure. RESULTS: The rate of surgery-related adverse events was lower than previously reported for VNS implantation for epilepsy and depression. One participant had vocal cord paresis that eventually resolved. There were no serious adverse events related to device stimulation. Over 90% of participants were taking antiplatelet drugs (APD) or anticoagulants and no adverse events or serious adverse events were reported as a result of withholding these medications during the perioperative period. CONCLUSIONS: This study is the largest, randomized, controlled trial in which a VNS device was implanted in chronic stroke survivors. Results support the use of the Vivistim System in chronic stroke survivors, with a safety profile similar to VNS implantations for epilepsy and depression.

Ten-year safety of pluripotent stem cell transplantation in acute thoracic spinal cord injury.

OBJECTIVE: The purpose of this study was to evaluate the safety of oligodendrocyte progenitor cells (LCTOPC1) derived from human pluripotent stem cells administered between 7 and 14 days postinjury to patients with T3 to T11 neurologically complete spinal cord injury (SCI). The rationale for this first-in-human trial was based on evidence that administration of LCTOPC1 supports survival and potential repair of key cellular components and architecture at the SCI site. METHODS: This study was a multisite, open-label, single-arm interventional clinical trial. Participants (n = 5) received a single intraparenchymal injection of 2 × 106 LCTOPC1 caudal to the epicenter of injury using a syringe positioning device. Immunosuppression with tacrolimus was administered for a total of 60 days. Participants were followed with annual in-person examinations and MRI for 5 years at the time of this report and will be followed with annual telephone questionnaires for 6 to 15 years postinjection. The primary endpoint was safety, as measured by the frequency and severity of adverse events related to the LCTOPC1 injection, the injection procedure, and/or the concomitant immunosuppression administered. The secondary endpoint was neurological function as measured by sensory scores and lower-extremity motor scores as measured by the International Standards for Neurological Classification of Spinal Cord Injury examinations. RESULTS: No unanticipated serious adverse events related to LCTOPC1 have been reported with 98% follow-up of participants (49 of 50 annual visits) through the first 10 years of the clinical trial. There was no evidence of neurological decline, enlarging masses, further spinal cord damage, or syrinx formation. MRI results during the long-term follow-up period in patients administered LCTOPC1 cells showed that 80% of patients demonstrated T2 signal changes consistent with the formation of a tissue matrix at the injury site. CONCLUSIONS: This study provides crucial first-in-human safety data supporting the pursuit of future human embryonic stem cell-derived therapies. While we cannot exclude the possibility of future adverse events, the experience in this trial provides evidence that this cell type can be well tolerated by patients, with an event-free period of up to 10 years. Based on the safety profile of LCTOPC1 obtained in this study, a cervical dose escalation trial was initiated (NCT02302157).

Data resources for evaluating the economic and financial consequences of surgical care in the United States.

ABSTRACT: Evaluating the relationship between health care costs and quality is paramount in the current health care economic climate, as an understanding of value is needed to drive policy decisions. While many policy analyses are focused on the larger health care system, there is a pressing need for surgically focused economic analyses. Surgical care is costly, and innovative technology is constantly introduced into the operating room, and surgical care impacts patients' short- and long-term physical and economic well-being. Unfortunately, significant knowledge gaps exist regarding the relationship between cost, value, and economic impact of surgical interventions. Despite the plethora of health care data available in the forms of claims databases, discharge databases, and national surveys, no single source of data contains all the information needed for every policy-relevant analysis of surgical care. For this reason, it is important to understand which data are available and what can be accomplished with each of the data sets. In this article, we provide an overview of databases commonly used in surgical health services research. We focus our review on the following five categories of data: governmental claims databases, commercial claims databases, hospital-based clinical databases, state and national discharge databases, and national surveys. For each, we present a summary of the database sampling frame, clinically relevant variables, variables relevant to economic analyses, strengths, weaknesses, and examples of surgically relevant analyses. This review is intended to improve understanding of the current landscape of data available, as well as stimulate novel analyses among surgical populations. Ongoing debates over national health policy reforms may shape the delivery of surgical care for decades to come. Appropriate use of available data resources can improve our understanding of the economic impact of surgical care on our health care system and our patients. LEVEL OF EVIDENCE: Regular Review, Level V.

The Colorectal Cancer Tumor Microenvironment and Its Impact on Liver and Lung Metastasis.

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer-related mortality worldwide. A total of 20% of CRC patients present with distant metastases, most frequently to the liver and lung. In the primary tumor, as well as at each metastatic site, the cellular components of the tumor microenvironment (TME) contribute to tumor engraftment and metastasis. These include immune cells (macrophages, neutrophils, T lymphocytes, and dendritic cells) and stromal cells (cancer-associated fibroblasts and endothelial cells). In this review, we highlight how the TME influences tumor progression and invasion at the primary site and its function in fostering metastatic niches in the liver and lungs. We also discuss emerging clinical strategies to target the CRC TME.

Surgical, Obstetric, and Anesthetic Mortality Measurement at a Ugandan Secondary Referral Hospital.

BACKGROUND: The health care systems of low-income countries have severely limited capacity to treat surgical diseases and conditions. There is limited information about which hospital mortality outcomes are suitable metrics in these settings. METHODS: We did a 1-year observational cohort study of patient admissions to the Surgery and the Obstetrics and Gynecology departments and of newborns delivered at a Ugandan secondary referral hospital. We examined the proportion of deaths captured by standardized metrics of mortality. RESULTS: There were 17,015 admissions and 9612 deliveries. A total of 847 deaths were documented: 385 (45.5%) admission deaths and 462 (54.5%) perinatal deaths. Less than one-third of admission deaths occurred during or after an operation (n = 126/385, 32.7%). Trauma and maternal mortality combined with perioperative mortality produced 79.2% (n = 305/385) of admission deaths. Of 462 perinatal deaths, 412 (90.1%) were stillborn, and 50 (10.9%) were early neonatal deaths. The combined metrics of the trauma mortality rate, maternal mortality ratio, thirty-day perioperative mortality rate, and perinatal mortality rate captured 89.8% (n = 761/847) of all deaths documented at the hospital. CONCLUSIONS: The combination of perinatal, maternal, trauma, and perioperative mortality metrics captured most deaths documented at a Ugandan referral hospital.