Elevated [CO2] and temperature augment gas exchange and shift the fitness landscape in a montane forb.

Climate change is simultaneously increasing carbon dioxide concentrations ([CO2]) and temperature. These factors could interact to influence plant physiology and performance. Alternatively, increased [CO2] may offset costs associated with elevated temperatures. Furthermore, the interaction between elevated temperature and [CO2] may differentially affect populations from along an elevational gradient and disrupt local adaptation. We conducted a multifactorial growth chamber experiment to examine the interactive effects of temperature and [CO2] on fitness and ecophysiology of diverse accessions of Boechera stricta (Brassicaceae) sourced from a broad elevational gradient in Colorado. We tested whether increased [CO2] would enhance photosynthesis across accessions, and whether warmer conditions would depress the fitness of high-elevation accessions owing to steep reductions in temperature with increasing elevation in this system. Elevational clines in [CO2] are not as evident, making it challenging to predict how locally adapted ecotypes will respond to elevated [CO2]. This experiment revealed that elevated [CO2] increased photosynthesis and intrinsic water use efficiency across all accessions. However, these instantaneous responses to treatments did not translate to changes in fitness. Instead, increased temperatures reduced the probability of reproduction for all accessions. Elevated [CO2] and increased temperatures interacted to shift the adaptive landscape, favoring lower elevation accessions for the probability of survival and fecundity. Our results suggest that elevated temperatures and [CO2] associated with climate change could have severe negative consequences, especially for high-elevation populations.

Risk score to predict inpatient mortality of acute pancreatitis patients admitted to the intensive care unit.

BACKGROUND/OBJECTIVES: Predicting inpatient mortality for acute pancreatitis (AP) patients in the ICU is crucial for optimal treatment planning. This study aims to develop a concise risk score model for this purpose, enhancing the predictability and management of AP in ICU settings. METHODS: We included 380 patients in our training set. Twenty-seven variables were retrospectively collected, and predictive variables were selected using LASSO penalized regression and refined through backward elimination multivariate models. Effect sizes were used to create the final model to predict 7 and 30-day mortality among AP patients admitted to the ICU. RESULTS: Of 380 patients, the mortality rate was 23.2 %. The final model included five predictors: INR, Albumin, Lactic Acid, BUN, and Bilirubin. The 5-fold cross-validated mean AUC was 0.93 (SD: 0.048) for 7-day mortality and 0.84 (SD: 0.033) for 30-day mortality, with a sensitivity of 77 % and specificity of 74 %. The risk score outperformed BISAP (AUC: 0.60) and APACHE-II (AUC: 0.76) in predicting mortality. CONCLUSION: Our model offers a convenient tool using commonly available laboratory results to predict mortality among AP patients, with potential applicability in both ICU settings.

Bartonella henselae Infection and Lymphadenopathy in a Patient With T Cell Acute Lymphoblastic Leukemia.

Patients undergoing therapy for T cell acute lymphoblastic leukemia are at risk of infections during their treatment course. Cat scratch disease caused by Bartonella hensalae can masquerade as leukemic relapse and cause systemic infection. Obtaining a thorough exposure history may aid clinicians in making the diagnosis.

Cutaneous legionellosis in an immunocompromised neonate.

Cutaneous Legionella infection is rare and primarily seen in immunosuppressed patients. Herein, we present a case of cutaneous and pulmonary legionellosis presenting with fever and erythematous subcutaneous nodules in a neonate with severe combined immunodeficiency. This case underscores the importance of considering this diagnosis and highlights the use of modern testing modalities to promptly diagnose and treat infections in immunocompromised patients.

Endoscopic sleeve gastroplasty reintervention score using supervised machine learning.

BACKGROUND AND AIMS: Reintervention after endoscopic sleeve gastroplasty (ESG) can be indicated because of postprocedural adverse events from various preinterventional or postprocedural comorbidities. We developed and internally validated an ESG reintervention score (ESG-RS) that determines the individualized risk of reintervention within the first 30 days after ESG. METHODS: We used data from a sample of 3583 patients who underwent ESG in the Metabolic and Bariatric Surgery Accreditation Quality Improvement Program database (2016-2021). The least absolute shrinkage and selection operator (LASSO)-penalized regression was used to select the most promising predictors of reintervention after ESG within 30 days. The predictive variables extracted by LASSO regression were entered into multivariate analysis to generate an ESG-RS by using the coefficients of the statistically significant variables. The model performance was assessed using receiver-operator curves by 10-fold cross-validation. RESULTS: Eleven variables were selected by LASSO regression and used in the final multivariate analysis. The ESG-RS was inferred using 5 factors (history of previous foregut surgery, preoperative anticoagulation use, female gender, American Society of Anesthesiologists class ≥II, and hypertension) weighted by their regression coefficients in the multivariable logistic regression model. The area under the curve of the ESG-RS was .74 (95% confidence interval, .70-.78). For the ESG-RS, the optimal cutpoint was 67.9 (high risk vs low risk), with a sensitivity of .76 and specificity of .71. CONCLUSIONS: The ESG-RS aids clinicians in preoperative risk stratification of patients undergoing ESG while clarifying factors contributing to a higher risk of reintervention.

CT imaging findings in lung transplant recipients with COVID-19.

OBJECTIVES: Our goal was to compare the chest computed tomography (CT) imaging findings of COVID-19 in lung transplant recipients (LTR) and a group of non-transplanted controls (NTC). METHODS: This retrospective study included 51 consecutive LTR hospitalized with COVID-19 from two centers. A total of 75 NTC were included for comparison. Images were classified regarding the standardized RSNA category, main pattern of lung attenuation, and longitudinal and axial distribution. Quantitative CT (QCT) analysis was performed to evaluate percentage of high attenuation areas (%HAA, threshold -250 to -700 HU). CT scoring was used to measure severity of parenchymal abnormalities. RESULTS: The imaging findings of COVID-19 in LTR were significantly different from controls regarding the RSNA classification and pattern of lung attenuation. LTR had a significantly higher proportion of patients with an indeterminate pattern on CT (0.31 vs. 0.11, p = 0.014). The most frequent pattern of attenuation in LTR was predominantly consolidation (0.39 vs. 0.22, p = 0.144) followed by a mixed pattern of ground-glass opacities (GGO) and consolidation (0.37 vs. 0.20, adjusted p = 0.102). On the other hand, the most common pattern in NTC was GGO predominant (0.58 vs. 0.24 of LTR, p = 0.001). LTR had significantly more severe parenchymal disease measured by CT score and %HAA by QCT (0.372 ± 0.08 vs. 0.148 ± 0.06, p < 0.001). CONCLUSION: The most frequent finding of COVID-19 in LTR is a predominant pattern of consolidation. Compared to NTC, LTR more frequently demonstrated an indeterminate pattern according to the RSNA classification and more extensive lung abnormalities on QCT and semi-quantitative scoring. KEY POINTS: • The most common CT finding of COVID-19 in LTR is a predominant pattern of consolidation followed by a mixed pattern of GGO and consolidation, while controls more often have a predominant pattern of GGO. • LTR more often presents with an indeterminate pattern of COVID-19 by RSNA classification than controls; therefore, molecular testing for COVID-19 is essential for LTR presenting with lower airway infection independently of imaging findings. • LTR had more extensive disease by semi-quantitative CT score and increased percentage areas of high attenuation on QCT.

Delaying Cardiac Catheterization in Favor of Endoscopy in Non-ST Elevation Myocardial Infarction Patients Is Associated with Worse Outcomes: A Nationwide Analysis.

BACKGROUND: Non-variceal upper gastrointestinal bleeding (NVUGIB) in non-ST-elevation myocardial infarction (NSTEMI) is associated with substantial morbidity and mortality. We evaluated inpatient outcomes of esophagogastroduodenoscopy (EGD) before cardiac catheterization in patients with NSTEMI and NVUGIB. METHODS: We utilized the National Readmission Database (2016-2019) to identify all index hospitalizations with a primary diagnosis of NSTEMI and a secondary diagnosis of NVUGIB that underwent EGD before cardiac catheterization (cases). A matched comparison cohort of similar hospitalizations that undergo EGD after cardiac catheterization were identified (controls) after 1:1 propensity score matching for age, gender, cardiac comorbidities, causes, and severity of bleeding. RESULTS: A total of 796 cases were matched with 796 controls. There was a higher median length of hospital stay (8 vs. 5 days, P = 0.01) and median hospital charges ($111,218 vs. $99,115, P = 0.002) for cases compared to controls. There was a higher all-cause inpatient mortality in cases compared to controls (5.5% vs. 3.9%, P = 0.26). Furthermore, there was a higher proportion of patients with ICU admission (7% vs. 3%, P < 0.001), septic shock (7.1% vs. 5.8%, P = 0.41), atrial fibrillation (27.1% vs. 19.8%, P < 0.001) and acute kidney injury (42.8% vs. 29.1%, P < 0.001) for cases compared to controls. CONCLUSION: Delaying cardiac catheterization in favor of EGD is associated with increased hospital stay, costs, and cardiac complications. Further studies are warranted to establish our findings.

Comparable Short-Term Weight Loss and Safety of Endoscopic Sleeve Gastroplasty in Diabetic and Non-diabetic Patients.

BACKGROUND: Endoscopic sleeve gastroplasty (ESG) is a highly effective endo bariatric procedure. Data on outcomes of ESG in patients with diabetes mellitus (DM) compared to non-diabetics are limited. AIMS: We aim to assess differences in clinical outcomes of ESG in DM patients in North America. METHODS: We used the Metabolic and Bariatric Surgery Accreditation Quality Improvement Program database from 2016 to 2021 to identify all DM patients who underwent ESG as the primary procedure for weight loss. A 1:1 propensity score matched cohort of non-DM patients served as controls. Patient characteristics, clinical outcomes, and complications were compared and analyzed. Adult patients with Class I obesity and above were included. RESULTS: After matching, 310 DM and non-DM patients that underwent ESG were compared. The median % BMI decrease (3.3% vs. 3.1%, P = 0.62) and median total body weight loss (%TBWL) (4.3% vs. 4%, P = 0.75) in 30 days were similar in the DM compared to non-DM cohorts. A similar proportion of patients with major adverse events (AEs) were present after ESG in the DM (1.6% vs. 1.3%, P = 0.74) compared to the non-DM cohort. The DM cohort had more patients with 30-day readmissions (3.2% vs. 1.9%, P = 0.08) than the non-DM cohort. %TBWL was similar in patients with HbA1c < 9% compared to ≥ 9%, (4.3% each, P = 0.33) with comparable AEs. CONCLUSION: ESG is a safe procedure in DM patients, without an increase in AEs, and it shows similar short-term weight loss compared to non-DM patients.

A Study of Role of Medical Thoracoscopy in Undiagnosed Pleural Effusion.

AIM AND OBJECTIVES: b/pulli>To know the diagnostic yield of pleuroscopy (medical thoracoscopy) in cases of pleural effusions which remain undiagnosed after routine initial investigations.lili>To notice the different gross pleuroscopic findings during the procedure.lili>To observe various histopathological reports of pleural biopsy taken through medical thoracoscopy.lili>To know the various complications of pleuroscopy in patients undergoing this procedure.li/ulp! MATERIALS AND METHODS: A total of 56 patients having undiagnosed pleural effusion were taken for study after informed written consent. All patients underwent medical thoracoscopy. The clinical, demographic, and radiological profile of patients was recorded. Gross pleuroscopic findings and histopathological reports of the pleural biopsy were noted. All patients were observed for any complications that occurred during or after the procedure. RESULT: Diagnostic yield of thoracoscopy in the present study was 91.07% (malignant pleural effusion 75% and tuberculous pleuritis 12.5%). Adenocarcinoma was the commonest malignancy in 60.71% of patients amongst malignant pleural effusion in the present study. Very few complications were recorded. The most common postprocedure complication was subcutaneous emphysema (12.5%) followed by pneumothorax (10.78%). CONCLUSION: Thoracoscopy gives excellent diagnostic yield in undiagnosed pleural effusion without major complications, and should be utilized wherever feasible.

Infectious events in pediatric patients with acute lymphoblastic leukemia/lymphoma undergoing evaluation for fever without severe neutropenia.

BACKGROUND: Infections cause significant treatment-related morbidity during pediatric acute lymphoblastic leukemia/lymphoma (ALL/LLy) therapy. Fevers during periods without severe neutropenia are common, but etiologies are not well-described. This study sought to describe the bloodstream infection (BSI) and non-BSI risk in children undergoing therapy for ALL/LLy. METHODS: Demographic and clinical data were abstracted for febrile episodes without severe neutropenia at two children's hospitals. Treatment courses were stratified by intensity. Multivariate logistic regression evaluated characteristics associated with infection. RESULTS: There were 1591 febrile episodes experienced by 524 patients. Of these, 536 (34%) episodes had ≥1 infection; BSI occurred in 30 (1.9%) episodes. No BSIs occurred in episodes with a recent procedural sedation or cytarabine exposure. Presence of hypotension, chills/rigors, higher temperature, and infant phenotype were independently associated with BSI (p < .05). Of the 572 non-BSIs, the most common was upper respiratory infection (URI) (n = 381, 67%). Compared to episodes without infection, URI symptoms, higher temperature, absolute neutrophil count 500-999/µl, and evaluation during a low-intensity treatment course were more likely to be associated with a non-BSI (p < .05) and inpatient status was less likely to be associated with a non-BSI (p < .05). CONCLUSIONS: The BSI rate in pediatric patients with ALL/LLy and fever without severe neutropenia is low, but one-third of the time, patients have a non-BSI. Future research should test if the need for empiric antibiotics can be tailored based on the associations identified in this study.

Chest MRI with CT in the assessment of interstitial lung disease progression in patients with systemic sclerosis.

OBJECTIVE: To describe the performance of CT and MRI in the assessment of the progression of interstitial lung disease (ILD) associated with SSc and demonstrate the correlations of MRI with pulmonary function test (PFT) and CT scores. METHODS: This prospective single-centre observational study included patients with SSc diagnoses, and magnetic resonance (MR) images were assessed visually using the Scleroderma Lung Study (SLS) I system. Differences in the median scores were assessed with Student's t-test and the Wilcoxon rank-sum test. Pearson's and Spearman's rank correlation coefficients were calculated to correlate imaging scores and PFT results. Using disease progression as the gold standard, we calculated the area under the curve (AUC) of the CT and MRI scores with Harrel's c-index. The best thresholds for the prediction of disease progression were determined by receiver operating characteristic curve analysis with maximum Youden's Index (P < 0.05). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the scores were calculated. RESULTS: The AUCs for MRI and CT scores were 0.86 (0.72-0.98; P = 0.04) and 0.83 (0.70-0.99; P = 0.05), respectively. CT and MRI scores correlated with Forced vital capacity (%FVC) (MRI: r = -0.54, P = 0.0045; CT: r = -0.44; P = 0.137) and diffusing capacity of the lung for carbon monoxide (MRI: r = -0.39, P = 0.007; CT r = -0.36, P = 0.006). The sensitivity, specificity, PPV and NPV were 85%, 87.5%, 88.34% and 86.11% (MRI score) and 84.21%, 82.35%, 84.14% and 82.4% (CT score), respectively. CONCLUSIONS: MRI scores from patients with SSc may be an alternative modality for the assessment of ILD progression in patients with SSc.

A Health System's Response to the Ongoing Global Shortage of Iodinated Contrast Media.

A production facility shutdown related to containment measures during the COVID-19 pandemic has resulted in a global shortage of iodinated contrast media. This article describes the strategies implemented at one large U.S. health system to maintain care continuity during the ongoing shortage. The strategies have included attempts to procure additional stock, repackage existing stock for use in larger numbers of patients, use noncontrast CT or alternative imaging modalities in place of contrast-enhanced CT, and collaborate with specialties outside of radiology to participate in conservation efforts. In addition, individual CT protocols underwent tailored modifications to use dual-energy technique and/or lower tube voltages, to allow lower contrast media doses with maintained visualization of tissue enhancement. The experiences during this period provide insights to facilitate long-term reductions in contrast media doses and ongoing CT protocol optimization after supplies return to normal levels. Critical throughout the efforts to mitigate the impact of the shortage have been system-level action, operational flexibility, and close communication by the health system's radiologists, technologists, physicists, pharmacists, and ordering providers.

Comparative analysis and trends in liver transplant hospitalizations with Clostridium difficile infections: A 10-year national cross-sectional study.

GOALS AND BACKGROUND: Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea in the United States. We aimed to determine comparative trends in inpatient outcomes of liver transplant (LT) patients based on CDI during hospitalizations. METHODS: The national inpatient sample database was used to conduct the present retrospective study regarding CDI among the LT hospitalizations from 2009 to 2019. Primary outcomes included 10-year comparative trends of the length of stay (LOS) and mean inpatient charges (MIC). Secondary outcomes included comparative mortality and LT rejection trends. RESULTS: There was a 14.05% decrease in CDI in LT hospitalizations over the study period (p = .05). The trend in LOS did not significantly vary (p = .9). MIC increased significantly over the last decade in LT hospitalizations with CDI (p < .001). LT hospitalizations of autoimmune etiology compared against non-autoimmune did not increase association with CDI, adjusted odds ratio (aOR) 0.97 (95% confidence interval [CI] 0.75-1.26, p = .87). CDI was associated with increased mortality in LT hospitalizations, aOR 1.84 (95% CI 1.52-2.24, p < .001). In-hospital mortality for LT hospitalizations with CDI decreased by 7.75% over the study period (p = .3). CDI increased transplant rejections, aOR 1.3 (95% CI 1.08-1.65, p < .001). There was a declining trend in transplant rejection for LT hospitalization with CDI from 5% to 3% over the study period (p = .0048). CONCLUSION: CDI prevalence does not increase based on autoimmune LT etiology. It increases mortality in LT hospitalizations; however, trend for mortality and transplant rejections has been declining over the last decade.

Quantitative Computed Tomography: What Clinical Questions Can it Answer in Chronic Lung Disease?

Quantitative computed tomography (QCT) has recently gained an important role in the functional assessment of chronic lung disease. Its capacity in diagnostic, staging, and prognostic evaluation in this setting is similar to that of traditional pulmonary function testing. Furthermore, it can demonstrate lung injury before the alteration of pulmonary function test parameters, and it enables the classification of disease phenotypes, contributing to the customization of therapy and performance of comparative studies without the intra- and inter-observer variation that occurs with qualitative analysis. In this review, we address technical issues with QCT analysis and demonstrate the ability of this modality to answer clinical questions encountered in daily practice in the management of patients with chronic lung disease.

Narrowing the Differential Diagnosis of Cystic Lesions in Smokers with Expiratory CT Acquisition Using the Cyst-Airway Communication Hypothesis.

The aim of this study was to assess percentage respiratory changes (δ) in the size of pulmonary cysts of different smoking-related etiologies. Retrospectively, we measured the cystic lesions due to histopathological-confirmed honeycombing from interstitial pulmonary fibrosis, pulmonary Langerhans cell histiocytosis (PLCH), and paraseptal emphysema, using paired inspiratory and expiratory CT scans. In a sample of 72 patients and 216 lesions, the mean diameter of PLCH and honeycombing decreased during expiration (PLCH, δ = 60.9%; p = 0.001; honeycombing, δ = 47.5%; p = 0.014). Conversely, paraseptal emphysema did not show any changes (δ = 5.2%; p = 0.34). In summary, our results demonstrated that cysts in smokers with PLCH and honeycombing fibrosis get smaller during expiratory CT scans, whereas the size of cystic-like lesions due to paraseptal emphysema and bullae tend to remain constant during respiratory cycles. These results support the hypothesis of cyst-airway communication in some cystic diseases, which could assist in the differential diagnosis in smoking-related lung diseases.

Between Scylla and Charybdis: risks of early therapeutic anticoagulation for venous thromboembolism after acute intracranial hemorrhage.

OBJECTIVE: To assess the risk of hematoma expansion in patients with acute intracranial hemorrhage (ICH) requiring therapeutic anticoagulation for the treatment of venous thromboembolism. METHODS: We retrospectively reviewed all patients at our institution between 2014 and 2019 who were therapeutically anticoagulated for venous thromboembolism within 4 weeks after ICH. We included subtypes of traumatic ICH and spontaneous intraparenchymal hemorrhage. Our main outcome was the incidence of hematoma expansion within 14 days from initiating therapeutic anticoagulation. Hematoma expansion was defined as (1) radiographically proven expansion leading to cessation of therapeutic anticoagulation or (2) death due to hematoma expansion. Secondary outcomes included mortality due to hematoma expansion and characteristics associated with hematoma expansion. RESULTS: Fifty patients met inclusion criteria (mean age: 54 years, 80% male, 76% Caucasian); 24% had undergone a neurosurgical procedure prior to therapeutic anticoagulation. Median time from ICH to therapeutic anticoagulation initiation was 9.5 days (IQR 4-17), 40% received therapeutic anticoagulation in <7 days after ICH. Six patients (12%) developed hematoma expansion, of whom two (4%) died. While not statistically significant, patients with hematoma expansion tended to be older (57.8 vs. 53.5 years), were anticoagulated sooner (4 vs. 10 days), presented with lower GCS (50% vs. 39% with GCS <8), higher hematoma volume (50% vs. 42% >30 cc), and higher SDH diameter (16 mm vs. 8.35 mm). There was a trend towards greater risk of hematoma expansion for patients undergoing endoscopic ICH evacuation (16% vs. 2%, p = 0.09); patients with hematoma expansion were more likely to present with hydrocephalus (67% vs. 16%, p = 0.02). CONCLUSIONS: Our study is among the first to explore characteristics associated with hematoma expansion in patients undergoing therapeutic anticoagulation after acute ICH. Larger studies in different ICH subtypes are needed to identify determinants of hematoma expansion in this high-acuity population.

Health-care Professionals' Perceptions of Critical Care Resource Availability and Factors Associated With Mental Well-being During Coronavirus Disease 2019 (COVID-19): Results from a US Survey.

BACKGROUND: Assessing the impact of coronavirus disease 2019 (COVID-19) on intensive care unit (ICU) providers' perceptions of resource availability and evaluating the factors associated with emotional distress/burnout can inform interventions to promote provider well-being. METHODS: Between 23 April and 7 May 2020, we electronically administered a survey to physicians, nurses, respiratory therapists (RTs), and advanced practice providers (APPs) caring for COVID-19 patients in the United States. We conducted a multivariate regression to assess associations between concerns, a reported lack of resources, and 3 outcomes: a primary outcome of emotional distress/burnout and 2 secondary outcomes of (1) fear that the hospital is unable to keep providers safe; and (2) concern about transmitting COVID-19 to their families/communities. RESULTS: We included 1651 respondents from all 50 states: 47% were nurses, 25% physicians, 17% RTs, and 11% APPs. Shortages of intensivists and ICU nurses were reported by 12% and 28% of providers, respectively. The largest supply restrictions reported were for powered air purifying respirators (56% reporting restricted availability). Provider concerns included worries about transmitting COVID-19 to their families/communities (66%), emotional distress/burnout (58%), and insufficient personal protective equipment (PPE; 40%). After adjustment, emotional distress/burnout was significantly associated with insufficient PPE access (adjusted relative risk [aRR], 1.43; 95% confidence interval [CI], 1.32-1.55), stigma from community (aRR, 1.32; 95% CI, 1.24-1.41), and poor communication with supervisors (aRR, 1.13; 95% CI, 1.06-1.21). Insufficient PPE access was the strongest predictor of feeling that the hospital is unable to keep providers safe and worries about transmitting infection to their families/communities. CONCLUSIONS: Addressing insufficient PPE access, poor communication from supervisors, and community stigma may improve provider mental well-being during the COVID-19 pandemic.

Fungemia in COVID-19 ICU patients, a single medical center experience.

A known proportion of patients who are admitted for the novel coronavirus disease 2019 (COVID-19) requires intensive care unit (ICU) level of care. Prolonged ICU stay is a risk factor for the development of nosocomial candidemia. The current study aimed to investigate the incidence and risk factors associated with the development of nosocomial candidemia among patients admitted to the ICU for COVID-19. Patients who developed nosocomial candidemia were identified, and their clinical course was reported. A 1:3 case control matching was used to identify non-candidemia patients who served as controls. 89 patients were admitted to the ICU for COVID-19 during the study period. The incidence of nosocomial candidemia was 8.9% (n = 8). Case-control matching identified 24 patients with similar disease severity at the time of ICU admission. Median time to first isolation of yeast was 26 days. Candidemia patients reported longer median ICU stay than controls. (40 vs. 10 days, p = .004). In hospital death rates were comparable in both groups (38% vs. 54%, p = .548). Prolonged mechanical ventilation support was associated with the development of nosocomial candidemia.

Splenic macrophage phagocytosis of intravenously infused mesenchymal stromal cells attenuates tumor localization.

Mesenchymal stromal cells (MSCs) possess remarkable tumor tropism, making them ideal vehicles to deliver tumor-targeted therapeutic agents; however, their value in clinical medicine has yet to be realized. A barrier to clinical utilization is that only a small fraction of infused MSCs ultimately localize to the tumor. In an effort to overcome this obstacle, we sought to enhance MSC trafficking by focusing on the factors that govern MSC arrival within the tumor microenvironment. Our findings show that MSC chemoattraction is only present in select tumors, including osteosarcoma, and that the chemotactic potency among similar tumors varies substantially. Using an osteosarcoma xenograft model, we show that human MSCs traffic to the tumor within several hours of infusion. After arrival, MSCs are observed to localize in clusters near blood vessels and MSC-associated bioluminescence signal intensity is increased, suggesting that the seeded cells expand after engraftment. However, our studies reveal that a significant portion of MSCs are eliminated en route by splenic macrophage phagocytosis, effectively limiting the number of cells available for tumor engraftment. To increase MSC survival, we transiently depleted macrophages with liposomal clodronate, which resulted in increased tumor localization without substantial reduction in tumor-associated macrophages. Our data suggest that transient macrophage depletion will significantly increase the number of MSCs in the spleen and thus improve MSC localization within a tumor, theoretically increasing the effective dose of an anti-cancer agent. This strategy may subsequently improve the clinical efficacy of MSCs as vehicles for the tumor-directed delivery of therapeutic agents.

Colocolic intussusception secondary to submucosal lipoma.

Adult intussusception is an uncommon cause of abdominal pain and poses diagnostic challenges for emergency physicians due to its varied presenting symptoms and time course. We report a case of chronic colocolic intussusception secondary to a lead point submucosal lipoma. Dedifferentiating intussusception with or without a lead point is important in determining appropriate management.