G-CSF Is a Novel Mediator of T-Cell Suppression and an Immunotherapeutic Target for Women with Colon Cancer.

PURPOSE: G-CSF enhances colon cancer development. This study defines the prevalence and effects of increased G-CSF signaling in human colon cancers and investigates G-CSF inhibition as an immunotherapeutic strategy against metastatic colon cancer. EXPERIMENTAL DESIGN: Patient samples were used to evaluate G-CSF and G-CSF receptor (G-CSFR) levels by IHC with sera used to measure G-CSF levels. Peripheral blood mononuclear cells were used to assess the rate of G-CSFR+ T cells and IFNγ responses to chronic ex vivo G-CSF. An immunocompetent mouse model of peritoneal metastasis (MC38 cells in C57Bl/6J) was used to determine the effects of G-CSF inhibition (αG-CSF) on survival and the tumor microenvironment (TME) with flow and mass cytometry. RESULTS: In human colon cancer samples, the levels of G-CSF and G-CSFR are higher compared to normal colon tissues from the same patient. High patient serum G-CSF is associated with increases in markers of poor prognosis, (e.g., VEGF, IL6). Circulating T cells from patients express G-CSFR at double the rate of T cells from controls. Prolonged G-CSF exposure decreases T cell IFNγ production. Treatment with αG-CSF shifts both the adaptive and innate compartments of the TME and increases survival (HR, 0.46; P = 0.0237) and tumor T-cell infiltration, activity, and IFNγ response with greater effects in female mice. There is a negative correlation between serum G-CSF levels and tumor-infiltrating T cells in patient samples from women. CONCLUSIONS: These findings support G-CSF as an immunotherapeutic target against colon cancer with greater potential benefit in women.

The Mental Status Exam at the Movies: The Use of Film in a Behavioral Medicine Course for Physician Assistants.

OBJECTIVE: This study evaluated student satisfaction with an educational exercise using feature films to learn about performing a psychiatric mental status examination. METHODS: Following the completion of an educational exercise designed by the first author, students in a behavioral medicine course completed surveys regarding their satisfaction with the exercise as a tool for learning how to perform a mental status examination. The educational exercise involved an initial didactic lecture followed by group exercises and individual presentations, utilizing feature films as tools for understanding the mental status examination. Each student selected a movie depicting a character with a psychiatric or substance-use disorder and performed a hypothetical mental status examination for the character, which they presented to their classmates. RESULTS: One hundred nine (109) students (97.3%) in the course completed evaluations of the educational exercise, and the majority found the exercise valuable; 93.6% of respondents felt that their ability to conceptualize a case had improved because of the exercise. In general evaluations of the course, this particular educational exercise was frequently mentioned in response to a free-form question about "the best part of the course." CONCLUSION: Movies depicting psychiatric illness and substance use disorders can be a fun and highly effective tool for helping students to learn and develop competency in the performance of mental status examinations.

Lower Extremity Salvage in the Setting of Bullous Pemphigoid Exacerbation: A Case Report.

Bullous pemphigoid is an autoimmune blistering disease where patients suffer from painful bullae, often covering large portions of the skin and requiring management with immune-suppression. Our case report of recurring bullous pemphigoid illustrates the importance of considering immunosuppressive perioperative management in patients with a history of autoimmune blistering even when the disease has been quiescent for some time. With multidisciplinary care and immune suppressive therapies in the perioperative period, a free flap complicated by recurrent bullous pemphigoid can be salvaged.

Women survive longer than men undergoing cytoreductive surgery and HIPEC for appendiceal cancer.

BACKGROUND: We hypothesize that women undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis from appendiceal cancer will have a survival advantage compared to men. METHODS: The National Cancer Database (NCDB) public user file (2004-2014) was used to select patients with PC undergoing CRS and HIPEC from appendiceal cancer. Univariate and multivariable analyses were performed. RESULTS: 1,190 patients with PC from appendiceal cancer underwent HIPEC and CRS. OS was significantly longer for women than for men, with mean and median OS being 73.8 months and 98.2 months for women vs 58.7 months and 82.5 months for men, respectively (p = 0.0032). On multivariable analysis, male sex (HR: 1.444, 95% CI: 1.141-1.827, p = 0.0022) and increasing age (HR: 1.017, 95% CI: 1.006-1.027, p = 0.0017) were both found to be independent risk factors for worse OS. CONCLUSION: Women undergoing CRS and HIPEC for PC from appendiceal origin live longer than men undergoing the same treatment. Increasing age was also found to be independent risk factors for worse survival.

In-hospital Mortality and the Predictive Ability of the Modified Early Warning Score in Ghana: Single-Center, Retrospective Study.

BACKGROUND: The modified early warning score (MEWS) is an objective measure of illness severity that promotes early recognition of clinical deterioration in critically ill patients. Its primary use is to facilitate faster intervention or increase the level of care. Despite its adoption in some African countries, MEWS is not standard of care in Ghana. In order to facilitate the use of such a tool, we assessed whether MEWS, or a combination of the more limited data that are routinely collected in current clinical practice, can be used predict to mortality among critically ill inpatients at the Korle-Bu Teaching Hospital in Accra, Ghana. OBJECTIVE: The aim of this study was to identify the predictive ability of MEWS for medical inpatients at risk of mortality and its comparability to a measure combining routinely measured physiologic parameters (limited MEWS [LMEWS]). METHODS: We conducted a retrospective study of medical inpatients, aged ≥13 years and admitted to the Korle-Bu Teaching Hospital from January 2017 to March 2019. Routine vital signs at 48 hours post admission were coded to obtain LMEWS values. The level of consciousness was imputed from medical records and combined with LMEWS to obtain the full MEWS value. A predictive model comparing mortality among patients with a significant MEWS value or LMEWS ≥4 versus a nonsignificant MEWS value or LMEWS <4 was designed using multiple logistic regression and internally validated for predictive accuracy, using the receiver operating characteristic (ROC) curve. RESULTS: A total of 112 patients were included in the study. The adjusted odds of death comparing patients with a significant MEWS to patients with a nonsignificant MEWS was 6.33 (95% CI 1.96-20.48). Similarly, the adjusted odds of death comparing patients with a significant versus nonsignificant LMEWS value was 8.22 (95% CI 2.45-27.56). The ROC curve for each analysis had a C-statistic of 0.83 and 0.84, respectively. CONCLUSIONS: LMEWS is a good predictor of mortality and comparable to MEWS. Adoption of LMEWS can be implemented now using currently available data to identify medical inpatients at risk of death in order to improve care.

The show must go on: Dermatologic procedural education in the era of COVID-19.

COVID-19 procedural restrictions and concerns from both practitioners and patients have led to a decrease in cosmetic procedures performed. Reduced clinic space, the necessity of distancing between people, and patient preference for a smaller care team may restrict trainees from observing, assisting with, or performing procedures. Thus, trainees may be limited in their ability to learn, practice, and meet the required number of cases to achieve competence, subsequently necessitating a sustained demand for alternative methods of learning. In this review, we examine the efforts made thus far by both dermatologists and dermatology organizations to meet the educational procedural needs of trainees and compensate for limitations during the pandemic and highlight areas in which innovation may still be needed.

Time to Initiation of Antihypertensive Therapy After Onset of Elevated Blood Pressure in Patients With Primary Proteinuric Kidney Disease.

RATIONALE & OBJECTIVE: The objective of the study was to estimate the prevalence of hypertension in patients with proteinuric kidney disease and evaluate blood pressure (BP) control. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Data from adults and children with proteinuric kidney disease enrolled in the multicenter Kidney Research Network Registry were used for this study. EXPOSURE: Proteinuric kidney disease. OUTCOMES: Hypertension and BP control. ANALYTICAL APPROACH: Patients with white-coat hypertension were excluded. Patients were censored at end-stage kidney disease onset. Patients were defined as hypertensive either by hypertension diagnosis code, having 2 or more encounters with elevated BPs, or treatment with antihypertensive therapy excluding renin-angiotensin-aldosterone system blockade. Elevated BP was defined as greater than 95th percentile for children and >140/90 mm Hg in adults. Sustained BP control was defined as 2 or more consecutive encounters with BPs lower than 95th percentile for children and <140/90 mm Hg for adults. Kaplan-Meier and Cox proportional hazards analyses were used to evaluate the time to initiation of antihypertensive therapy. RESULTS: 842 patients, 69% adults and 31% children, with a total observation period of 6,722 patient-years were included in the analysis. 644 (76%) had hypertension during observation. There was no difference in the prevalence of hypertension between children and adults (74% vs 78%; P = 0.3). Hypertension was most common among those of African American race compared with other races (90% vs 72%-75%; P = 0.003). 504 (78%) patients with hypertension achieved BP control but only 51% achieved control within 1 year. 140 (22%) patients with hypertension never achieved BP control during a median of 41 (IQR, 24-73) months of observation. LIMITATIONS: Differing BP control goals that may lead to overestimation of the controlled patient population. CONCLUSIONS: Hypertension affects most patients with proteinuric kidney disease regardless of age. Time to BP control exceeded 1 year in 50% of patients with hypertension and 22% did not demonstrate control. This study highlights the need to address hypertension early and completely in disease management of patients with proteinuric kidney disease.

COVID-19 Blind Spots: A Consensus Statement on the Importance of Competent Political Leadership and the Need for Public Health Cognizance.

As the COVID-19 pandemic continues, important discoveries and considerations emerge regarding the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pathogen; its biological and epidemiological characteristics; and the corresponding psychological, societal, and public health (PH) impacts. During the past year, the global community underwent a massive transformation, including the implementation of numerous nonpharmacological interventions; critical diversions or modifications across various spheres of our economic and public domains; and a transition from consumption-driven to conservation-based behaviors. Providing essential necessities such as food, water, health care, financial, and other services has become a formidable challenge, with significant threats to the existing supply chains and the shortage or reduction of workforce across many sectors of the global economy. Food and pharmaceutical supply chains constitute uniquely vulnerable and critically important areas that require high levels of safety and compliance. Many regional health-care systems faced at least one wave of overwhelming COVID-19 case surges, and still face the possibility of a new wave of infections on the horizon, potentially in combination with other endemic diseases such as influenza, dengue, tuberculosis, and malaria. In this context, the need for an effective and scientifically informed leadership to sustain and improve global capacity to ensure international health security is starkly apparent. Public health "blind spotting," promulgation of pseudoscience, and academic dishonesty emerged as significant threats to population health and stability during the pandemic. The goal of this consensus statement is to provide a focused summary of such "blind spots" identified during an expert group intense analysis of "missed opportunities" during the initial wave of the pandemic.

Dose management software implementation in mammography.

PURPOSE: This work aimed to evaluate the use of a dose management software (DMS) in mammography and analyse the clinical practice in terms of radiation exposure in screening and diagnostic mammography. METHODS: Mean glandular dose (MGD) from approximately 10,000 images were collected and analysed taking into account anode/filter combination, projection, compressed breast thickness (CBT) and compression force. Causes of increased MGD were investigated and actions were taken when malpractice was detected. RESULTS: MGD values for craniocaudal (CC) and mediolateral oblique (MLO) exposures for different CBT were defined. The average MGD for CBT of 60-69 mm was 1.84 mGy for CC images and 1.85 mGy for MLO images for screening examinations, while for diagnostic examinations the MGD was 1.95 mGy for CC and 2.01 mGy for MLO images. As no national diagnostic reference levels (DRLs) for mammography exist in Switzerland, typical mean glandular dose (MGD) values were defined as a first step towards their establishment for both screening and diagnostic examinations. CONCLUSIONS: The use of DMS facilitated immensely the analysis of all clinical and technical parameters, the evaluation of radiation dose received by the patients, as well as the overall evaluation of radiographers' performance. The DMS disclosed the role of the medical physicist in dose management and optimization.

Data of plant diversity, spectral reflectance at specie level and satellite spectral variables from the largest dry forest nucleus in South America.

The use of satellite remote sensing makes it possible to acquire useful information about the environment, since it presents tools capable of assisting the practical search of information related to species richness. Here we present data on richness and Shannon index from phytosociological researches, vegetation indices and individual bands spectral reflectance from satellite images and leaf-level spectral reflectance from eight Caatinga species. For further interpretation of the data presented in this article, please see the research article "Predicting plant species richness with satellite images in the largest dry forest nucleus in South America" [1].

Cutaneous basal cell carcinoma mimicking small cell carcinoma.

Neuroendocrine differentiation seen in basal cell carcinomas (BCC) is not generally appreciated by oncologists and can introduce a component of confusion when diagnosing a tumor and developing a management plan. Understanding that BCC commonly have this feature can assist the treating oncologist.

Sentinel node mapping and ductal carcinoma in situ.

BACKGROUND: Pure ductal carcinoma in situ (DCIS) is typically unassociated with a risk of regional lymph node involvement. Retrospective series maintain that larger tumors or high-grade histopathology may harbor a risk of lymph node involvement. PURPOSE: Our community hospital retrospectively reviewed a series wherein women with DCIS were subjected to sentinel lymph node biopsy based on large tumor size and/or high-grade histopathology. MATERIALS AND METHODS: 232 consecutive women with a diagnosis of pure DCIS were evaluated independently by two breast surgeons, one who typically offers sentinel node mapping to patients with tumors larger than 10 mm and the other who offers sentinel node mapping to women with grade 3 tumors. 60 women (26%) underwent sentinel node mapping along with appropriate surgery directed to the breast. Women were offered risk-adjusted adjuvant radiotherapy and anti-endocrine therapy. RESULTS: At a median follow-up of 18 months (range 6-132 months), 9 women (15%) were identified with regional axillary nodal disease. A statistical analysis was conducted between women who did or did not undergo sentinel node mapping because there was overlap in large tumor size and high grade between the two groups. A univariate logistic regression statistic showed a trend toward a significant relationship between grade 3 tumors and a risk of occult nodal involvement. This was not confirmed by multivariate analysis. CONCLUSIONS: In our moderate-sized surgical experience evaluating women with pure DCIS who underwent a sentinel node mapping due to large tumor size or high grade histology, we were unable to confirm that either is predictive of occult node involvement.

Short-term heat shock proteins 70 and 90 mRNA expression profile and its relation to thermo-physiological parameters in goats exposed to heat stress.

To follow the inheritance potential for heat tolerance after a crossing program in goats, 24 kids from four groups of goat kids (6 kids in each) from Aradi (A) and Damascus (D), their crossbred first-generation F1 (½D½A) and second-generation F2 (¾D»A), were exposed to acute elevated environmental temperature in controlled climatic chambers. Rectal temperature (RT), respiratory rate (RR), heat tolerance coefficient (HTC), adaptability coefficient (AC), and mRNA expression of heat shock proteins 70 and 90 ((HSP70 and HASP90, respectively), using real-time PCR were estimated. Results showed that Aradi breed goats had the highest level of expression for heat shock proteins 70 and 90, followed by F1, F2, and Damascus (P ≤ 0.01). Crossbreeds and Damascus showed the highest RT, while Aradi breed showed the lowest value (P ≤ 0.01). Aradi and crossbreeds showed the highest RR, while Damascus showed the lowest RR (P ≤ 0.05). Aradi and F1 showed the highest HTC (P ≤ 0.05), while there was no significant difference between pure breeds and crossbreeds in AC. A significant positive phenotypic correlation (0.81) was observed between HSP70 and HSP90. In addition, RR showed moderate positive correlation with both HSP70 and HSP90. It could be concluded that Aradi breed had putative heat tolerance in comparison to its crossbred progeny from the Damascus breed. The crossbreeding may result in some loss of heat tolerance potential, but the crossbreeds still better adapted to high environmental temperature than the Damascus breed.

Current applications of ultrasound-guided wire localization in head and neck surgery.

Ultrasound-guided wire localization (USGWL) was originally developed for the removal of impalpable breast lesions. More recently, USGWL has been described in head and neck surgical practice and it has a number of applications in this field, with the potential to guide surgical exploration and the benefits of reducing operative time and morbidity. This technical note describes the use of preoperative USGWL to facilitate the removal of an impalpable neck node. A review of the current literature relating to the present applications of this technique in head and neck surgery is reported, highlighting its advantages and disadvantages.

Central venous catheter placement after ultrasound guided peripheral IV placement for difficult vascular access patients.

OBJECTIVES: Ultrasound guided peripheral intravenous catheters (USPIV) are frequently utilized in the Emergency Department (ED) and lead to reduced central venous catheter (CVC) placements. USPIVs, however, are reported to have high failure rates. Our primary objective was to determine the proportion of patients that required CVC after USPIV. Our secondary objective was to determine if classic risk factors for difficult vascular access were predictive of future CVC placement. METHODS: We performed a retrospective review for patients treated at a large academic hospital. Patients were identified by electronic health record and were restricted to age older than 21 years, had received USPIV, and admittance. Exclusion criteria included an existing CVC. Descriptive statistics, t-tests, chi-square proportions, and logistic regression were performed to test associations. RESULTS: Of 363 eligible patients, 20 were excluded allowing for 343 for analysis. Of 343, 45 (13.1% 95% CI 9.9-17.1%) required CVC after USPIV. For secondary outcomes, no expected characteristics (diabetes, end-stage renal disease, IV drug abuse, peripheral vascular disease, or sickle cell disease) were predictive of CVC placement. The only predictive variables were admission to ICU/stepdown and length of stay. Each additional day of hospitalization had an OR 1.11 (95% CI 1.06-1.16%) of having a CVC placed. CONCLUSION: Of those admitted after USPIV placement, approximately 7 out of every 8 patients did not require a subsequent CVC. Of the nearly 1 in 8 patients that required a CVC, factors associated with CVC placement were admission to a higher level of care and length of stay.

Comparative Molecular Transporter Efficiency of Cyclic Peptides Containing Tryptophan and Arginine Residues.

Cyclic peptides containing tryptophan (W) and arginine (R) residues, [WR]5, [WR]6, [WR]7, [WR]8, and [WR]9, were synthesized through Fmoc solid-phase chemistry to compare their molecular transporter efficiency. The in vitro cytotoxicity of the peptides was evaluated using human leukemia carcinoma cell line (CCRF-CEM) and normal kidney cell line (LLC-PK1). [WR]6, [WR]7, [WR]8, and [WR]9 were not significantly cytotoxic to LLC-PK1cells at a concentration of 10 µM after 3 h incubation. Among all the peptides, [WR]9 was found to be a more efficient transporter than [WR]5, [WR]6, [WR]7, and [WR]8 in CCRF-CEM cells for delivery of a cell-impermeable fluorescence-labeled negatively charged phosphopeptide (F'-GpYEEI). [WR]9 (10 µM) improved the cellular uptake of F'-GpYEEI (2 µM) by 20-fold. The cellular uptake of a fluorescent conjugate of [WR]9, F'-[W9R8K], was increased in a concentration- and time-dependent pattern in CCRF-CEM cells. The uptake of F'-[W9R8K] was slightly reduced in CCRF-CEM cells in the presence of different endocytic inhibitors, such as nystatin, 5-(N-ethyl-N-isopropyl)amiloride, chlorpromazine, chloroquine, and methyl ß-cyclodextrin. Furthermore, the uptake of F'-[W9R8K] was shown to be temperature-dependent and slightly adenosine 5'-triphosphate-dependent. The intracellular/cellular localization (in the nucleus and cytoplasm) of F'-[W9R8K] was confirmed by fluorescent microscopy in CCRF-CEM cells. These studies suggest that large cyclic peptides containing arginine and tryptophan can be used as a molecular transporter of specific compounds.

Influence of dietary chromium yeast supplementation on apparent trace elements metabolism in growing camel (Camelus dromedarius) reared under hot summer conditions.

This study aimed to evaluate the effect of dietary chromium (Cr) supplementation on the apparent metabolism of some trace elements in camel calves reared under hot summer conditions. The study was conducted on a total of 15 male camel calves (5-6 months old) reared under hot summer conditions for 12 weeks. The animals were housed individually under shelter and divided into three dietary treatment groups (diets supplemented with 0.0, 0.5, or 1.0 mg Cr/kg DM), five animals each. At the end of the study, a metabolic trial was conducted on all camels for the evaluation of trace elements metabolism. Cr excretion, absorption, and retention showed an increasing trend with the increasing level of dietary Cr supplementation. Dietary Cr supplementation at 0.5 mg Cr/kg DM to camel calves resulted in a significant (P < 0.05) increase in Cu and an increasing trend in Zn and Mn excretion via urine and feces. However, Fe retention increased significantly (P < 0.05) in camel calves fed on diet supplemented with Cr. Dietary Cr supplementation to camel calves resulted in an increasing trend of plasma Cr concentration, while plasma concentration of Cu and Zn tended to decrease and without any effect on plasma Fe concentration. The results of the present study suggests that care should be taken for the negative interaction of Cr with the utilization of other trace elements, in cases where Cr is supplemented to the diet as a feed additive to promote growth and immunity under hot climatic conditions.

A large animal model for a failed two-stage revision of intramedullary nail-related infection by methicillin-resistant Staphylococcus aureus.

The treatment of chronic orthopaedic device-associated infection (ODRI) often requires multiple surgeries and prolonged antibiotic therapy. Despite this extensive treatment protocol, the procedure is associated with significant failure rates. Currently, no large animal model is available that recapitulates a failed revision. Therefore, our aim was to establish a large animal model for failed treatment of an ODRI in order to serve as a testbed for future interventional strategies. Adult Swiss Alpine sheep received an intramedullary nail in the tibia and a localised inoculum of either a methicillin-sensitive or methicillin-resistant Staphylococcus aureus (MSSA, MRSA respectively). After 8 weeks, when chronic infection had been established, the animals underwent a staged revision with debridement and temporary placement of an antibiotic-loaded cement spacer. Antibiotics were delivered systemically in a standard or pathogen-adapted manner. Debridement and implant exchange alone failed to treat the MSSA infection. Neither local therapy alone nor systemic therapy alone were effective in resolving infection with MSSA, but a combination of local and systemic therapy was effective against it. MRSA infection was not resolved by the combination of local and systemic antibiotics (standard or pathogen-adapted). A model for failed revision of MRSA infection is described despite the use of local and systemic antibiotics. Novel interventions may be assessed using this model, including antibiotic and non-antibiotic interventions.