The Impact of Surgical Boot Camp on Medical Student Confidence and Imposter Syndrome.

INTRODUCTION: Transitioning from medical student to surgical intern is accompanied by increased responsibility, stress, and clinical burden. This environment lends itself to imposter syndrome (IS), a psychological condition grounded in self-doubt causing fear of being discovered as fraud despite adequate abilities. We hypothesized a 2-week surgical boot camp for fourth year medical students would improve confidence in technical skills/knowledge and IS. METHODS: Thirty medical students matching into surgical specialties completed the boot-camp in February 2020. Presurveys/postsurveys assessed confidence levels using a 1-5 Likert scale regarding 32 technical skills and knowledge points. The Clance Impostor Phenomenon Scale (CIPS) assessed IS, where increasing scores correlate to greater IS. RESULTS: Median (interquartile range [IQR]) subject age was 27 y (26, 28), 20 (66.7%) were male, and 21 (70%) were Caucasian. Of the 30 students, 23 (76.7%) had a break in training with a median [IQR] of 2 [1, 3] y outside of medicine. Confidence scores were significantly improved in all five assessment categories (P < 0.05); however, there was no change in CIPS in median [IQR] presurveys versus postsurveys (65.5 [52, 75] versus 64 [52, 75], P = 0.70). Females had higher mean (standard deviation) pre-CIPS than males (68.4 [15.2] versus 61.6 [14.9], P = 0.02). There was no strong correlation between age and CIPS in the presurvey (Spearman Rank Correlation Coefficient [SRCC]: 0.29, P = 0.19) or postsurvey (SRCC: 0.31, P = 0.10). While subjects who worked outside of medicine had a stronger relationship with IS (SRCC: 0.37, P = 0.05), multivariable regression analysis did not reveal any significant differences. CONCLUSIONS: We advocate for surgical boot-camp training courses to improve trainee skill and confidence. As IS is not improved by boot camp, additional research is needed to identify opportunities to improve IS among surgical trainees.

Fever in the ICU: A Predictor of Mortality in Mechanically Ventilated COVID-19 Patients.

PURPOSE: While fever may be a presenting symptom of COVID-19, fever at hospital admission has not been identified as a predictor of mortality. However, hyperthermia during critical illness among ventilated COVID-19 patients in the ICU has not yet been studied. We sought to determine mortality predictors among ventilated COVID-19 ICU patients and we hypothesized that fever in the ICU is predictive of mortality. MATERIALS AND METHODS: We conducted a retrospective cohort study of 103 ventilated COVID-19 patients admitted to the ICU between March 14 and May 27, 2020. Final follow-up was June 5, 2020. Patients discharged from the ICU or who died were included. Patients still admitted to the ICU at final follow-up were excluded. RESULTS: 103 patients were included, 40 survived and 63(61.1%) died. Deceased patients were older {66 years[IQR18] vs 62.5[IQR10], (p = 0.0237)}, more often male {48(68%) vs 22(55%), (p = 0.0247)}, had lower initial oxygen saturation {86.0%[IQR18] vs 91.5%[IQR11.5], (p = 0.0060)}, and had lower pH nadir than survivors {7.10[IQR0.2] vs 7.30[IQR0.2] (p < 0.0001)}. Patients had higher peak temperatures during ICU stay as compared to hospital presentation {103.3°F[IQR1.7] vs 100.0°F[IQR3.5], (p < 0.0001)}. Deceased patients had higher peak ICU temperatures than survivors {103.6°F[IQR2.0] vs 102.9°F[IQR1.4], (p = 0.0008)}. Increasing peak temperatures were linearly associated with mortality. Febrile patients who underwent targeted temperature management to achieve normothermia did not have different outcomes than those not actively cooled. Multivariable analysis revealed 60% and 75% higher risk of mortality with peak temperature greater than 103°F and 104°F respectively; it also confirmed hyperthermia, age, male sex, and acidosis to be predictors of mortality. CONCLUSIONS: This is one of the first studies to identify ICU hyperthermia as predictive of mortality in ventilated COVID-19 patients. Additional predictors included male sex, age, and acidosis. With COVID-19 cases increasing, identification of ICU mortality predictors is crucial to improve risk stratification, resource management, and patient outcomes.

Understanding the course of COVID-19-induced pneumomediastinum.

ABSTRACT: Since its discovery, COVID-19 has infected nearly 112 million people and caused about 2.5 millions deaths worldwide. Our understanding of the clinical presentation and complications of COVID-19 is still evolving. Bilateral pulmonary ground-glass opacities on imaging have become characteristic in the diagnosis of COVID-19, but pneumomediastinum has now also been reported in some patients with COVID-19. Reports on the overall prognosis for these patients are conflicting and little information exists regarding long-term complications. This article describes the clinical course of a patient who did not need mechanical ventilation but developed spontaneous pneumomediastinum.

Failure to rescue in the surgical patient: a review.

PURPOSE OF REVIEW: Evaluating patient outcomes is essential in a healthcare environment focused on quality. Mortality after surgery has been considered a useful quality metric. More important than mortality rate, failure to rescue (FTR) has emerged as a metric that is important and may be improveable. The purpose of this review is to define FTR, describe patient and hospital level factors that lead to FTR, and highlight possible solutions to this problem. RECENT FINDINGS: FTR is defined as a death following a complication. Depending on the patient population, FTR rates vary from less than 1% to over 40%. Numerous patient factors including frailty, congestive heart failure (CHF), renal failure, serum albumin <3.5, COPD, cirrhosis, and higher ASA class may predispose patients to FTR. Hospital factors including technology, teaching status, increased nurse-to-patient ratios, and closed ICUs may help reduce FTR. More difficult to measure variables, such as hospital culture and teamwork may also influence FTR rates. Early warning systems may allow earlier identification of the deteriorating patient. SUMMARY: FTR is a major clinical concern and efforts aimed at optimizing patient and hospital factors, culture and communication, as well as early identification of the deteriorating patient may improve FTR rate.

Patterns and outcomes of colorectal cancer in adolescents and young adults.

BACKGROUND: The incidence of colorectal cancer (CRC) in the adolescent and young adult (AYA) population (aged 15-39 y) is rising. MATERIALS AND METHODS: We used the Surveillance, Epidemiology, and End Results Database to study CRC in the AYA population. We studied clinical and socioeconomic factors associated with survival. RESULTS: Of the 11,071 cases of CRC, the most common site of the primary tumor was the rectum (25%), whereas 66.6% of the diseases were left sided. Most of the patients (72%) presented with regional or metastatic disease. However, the disease-specific survival (DSS) and the overall survival of the AYA population were comparable to those of the general population (DSS; 5- and 10-y: 64.8%, 57.3%; overall survival; 5- and 10-y: 61.5% and 52.4%). On multivariate analysis, disease stage at the time of the diagnosis was the strongest predictor of mortality. After controlling for disease stage, male gender, black race, and higher grade tumors were associated with worse survival. CONCLUSIONS: The AYA population presents with advanced distal CRC but have similar survival compared with the general population.

Significant Functional Improvement at 2 Years After Isolated Patellofemoral Arthroplasty With an Onlay Trochlear Implant, But Low Mental Health Scores Predispose to Dissatisfaction.

INTRODUCTION: We reviewed the clinical and radiographic outcomes of a consecutive series of patients who underwent patellofemoral arthroplasty (PFA) using a modern onlay-style trochlear design and all-polyethylene patellar component. An additional goal of the study was to elucidate, for the first time, the extent to which patients were satisfied with their implant and whether expectations were met after undergoing PFA. METHODS AND MATERIALS: We identified a consecutive series of 70 knees (53 patients) treated with primary isolated PFA between October 2007 and May 2012. For our clinical outcomes analysis, we included patients with a minimum follow-up of 2 years and available preoperative original Knee Society scores. RESULTS: At an average 4.9 years of follow-up, the mean range of motion and Knee Society Knee and Function scores improved significantly, and less than 4% of patients required revision arthroplasty. There was no radiographic evidence of component loosening or wear. Despite these improvements, new Knee Society scores indicated that fewer than two-thirds of patients were satisfied or had their expectations met. Dissatisfied patients and those whose expectations were not met had significantly lower Mental Health scores according to the Short Form-36 following PFA. CONCLUSIONS: Despite the clinical and radiographic success of this implant, patient satisfaction remained low, which may be partially explained by poor mental health.

Modular Polyethylene Inserts for Total Knee Arthroplasty: Can Surgeons Detect 1-mm Thickness Increments?

BACKGROUND: Some manufacturers have introduced polyethylene (PE) inserts in 1-mm increment thickness options to allow for finer adjustments in total knee arthroplasty kinematics. METHODS: Two surgeons with extensive experience performed 88 total knee arthroplasties using implants with 1-mm PE inserts. After trial components were inserted and the optimal PE thickness was selected, the insert was removed and a trial insert size was randomly chosen from opaque envelopes (1-mm smaller, same size, and 1-mm larger). The knee was re-examined and the surgeon determined which size PE had been placed. RESULTS: Surgeons reliably determined insert thicknesses in 62.5% (55 of 88; P = .050) of trials. Surgeons were not able to accurately detect 1-mm incremental changes of trial PE implants on a consistent basis. CONCLUSION: The potential clinical usefulness of this concept should be further evaluated.

Performance characteristics of broth-only cultures after revision total joint arthroplasty.

BACKGROUND: Surgeons frequently obtain intraoperative cultures at the time of revision total joint arthroplasty. The use of broth or liquid medium before applying the sample to the agar medium may be associated with contamination and false-positive cultures; however, the degree to which this is the case is not known. QUESTIONS/PURPOSES: We (1) calculated the performance characteristics of broth-only cultures (sensitivity, specificity, positive predictive value, and negative predictive value) and (2) characterized the organisms identified in broth to determine whether a specific organism showed increased proclivity for true-positive periprosthetic joint infection (PJI). METHODS: A single-institution retrospective chart review was performed on 257 revision total joint arthroplasties from 2009 through 2010. One hundred ninety (74%) had cultures for review. All culture results, as well as treatment, if any, were documented and patients were followed for a minimum of 1 year for evidence of PJI. Cultures were measured as either positive from the broth only or broth negative. The true diagnosis of infection was determined by the Musculoskeletal Infection Society criteria during the preoperative workup or postoperatively at 1 year for purposes of calculating the performance characteristics of the broth-only culture. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value were 19%, 88%, 13%, and 92%, respectively. The most common organism identified was coagulase-negative Staphylococcus (16 of 24 cases, 67%). Coagulase-negative Staphylococcus was present in all three true-positive cases; however, it was also found in 13 of the false-positive cases. CONCLUSIONS: The broth-only positive cultures showed poor sensitivity and positive predictive value but good specificity and negative predictive value. The good specificity indicates that it can help to rule in the presence of PJI; however, the poor sensitivity makes broth-only culture an unreliable screening test. We recommend that broth-only culture results be carefully scrutinized and decisions on the diagnosis and treatment of infection should be based specifically on the Musculoskeletal Infection Society criteria. LEVEL OF EVIDENCE: Level IV, diagnostic study. See Instructions for Authors for a complete description of levels of evidence.

Aquacel surgical dressing reduces the rate of acute PJI following total joint arthroplasty: a case-control study.

An effort to prevent PJI has led to the development of antimicrobial dressings that support wound healing. We sought to determine whether Aquacel Surgical dressing independently reduces the rate of acute PJI following TJA. A single institution retrospective chart review of 903 consecutive cases who received the Aquacel Surgical dressing and 875 consecutive cases who received standard gauze dressing was conducted to determine the incidence of acute PJI (within 3 months). The incidence of acute PJI is 0.44% in the Aquacel dressing group compared to 1.7% in the standard gauze dressing group (P = 0.005). Multivariate analysis revealed that use of Aquacel dressing was an independent risk factor for reduction of PJI (odds ratio of 0.165, 95% confidence interval: 0.051-0.533). Aquacel Surgical dressing significantly reduces the incidence of acute PJI.

Warfarin, not direct oral anticoagulants nor antiplatelet therapy, is associated with increased bleeding risk in emergency general surgery patients: implications in this new era of novel anticoagulants: An EAST Multicenter study.

INTRODUCTION: To assess perioperative bleeding complications & in-hospital mortality in patients requiring emergency general surgery (EGS) presenting with a history of antiplatelet (AP) vs. direct oral anticoagulant (DOAC) vs warfarin use. METHODS: Prospective observational study across 21 centers between 2019-2022. Inclusion criteria were age ≥ 18 years, & DOAC, warfarin or AP use within 24 hours of an EGSP. Outcomes included perioperative bleeding and in-hospital mortality. The study was conducted using ANOVA, Chi-square, and multivariable regression models. RESULTS: Of the 413 patients, 221 (53.5%) reported AP use, 152 (36.8%) DOAC use, & 40 (9.7%) warfarin use. Most common indications for surgery were obstruction (23% (AP), 45% (DOAC), 28% (warfarin)), intestinal ischemia (13%, 17%, 23%), & diverticulitis/peptic ulcers (7%, 7%, 15%). Compared to DOAC use, warfarin use was associated with significantly higher perioperative bleeding complication (OR 4.4 [2.0, 9.9]). There was no significant difference in perioperative bleeding complication between DOAC & AP use (OR 0.7 [0.4, 1.1]). Compared to DOAC use, there was no significant difference in mortality between warfarin use (0.7 [0.2, 2.5]) or AP use (OR 0.5 [0.2, 1.2]). After adjusting for confounders, warfarin use (OR 6.3 [2.8, 13.9]), medical history and operative indication were associated with an increase in perioperative bleeding complications. However, warfarin was not independently associated with risk of mortality (OR 1.3 [0.39, 4.7]), whereas intraoperative vasopressor use (OR 4.7 [1.7, 12.8)), medical history & postoperative bleeding (OR 5.5 [2.4, 12.8]) were. CONCLUSIONS: Despite ongoing concerns about the increase in DOAC use & lack of readily available reversal agents, this study suggests that warfarin, rather than DOACs, is associated with higher perioperative bleeding complications. However, that risk does not result in an increase in mortality, suggesting that perioperative decisions should be dictated by patient disease & comorbidities rather than type of antiplatelet or anticoagulant use.

Anticoagulation in emergency general surgery: Who bleeds more? The EAST multicenter trials ACES study.

BACKGROUND: While direct oral anticoagulant (DOAC) use is increasing in the Emergency General Surgery (EGS) patient population, our understanding of their bleeding risk in the acute setting remains limited. Therefore, the objective of this study was to determine the prevalence of perioperative bleeding complications in patients using DOACs versus warfarin and AP therapy requiring urgent/emergent EGS procedures (EGSPs). METHODS: This was a prospective observational trial, conducted between 2019 and 2022, across 21 centers. Inclusion criteria were 18 years or older, DOAC, warfarin/AP use within 24 hours of requiring an urgent/emergent EGSP. Demographics, preoperative, intraoperative, and postoperative data were collected. ANOVA, χ 2 , and multivariable regression models were used to conduct the analysis. RESULTS: Of the 413 patients enrolled in the study, 261 (63%) reported warfarin/AP use and 152 (37%) reported DOAC use. Appendicitis and cholecystitis were the most frequent indication for operative intervention in the warfarin/AP group (43.4% vs. 25%, p = 0.001). Small bowel obstruction/abdominal wall hernias were the main indication for operative intervention in the DOAC group (44.7% vs. 23.8%, p = 0.001). Intraoperative, postoperative, and perioperative bleeding complications and in-hospital mortality were similar between the two groups. After adjusting for confounders, a history of chemotherapy (odds ratio [OR], 4.3; p = 0.015) and indication for operative intervention including occlusive mesenteric ischemia (OR, 4.27; p = 0.016), nonocclusive mesenteric ischemia (OR, 3.13; p = 0.001), and diverticulitis (OR, 3.72; p = 0.019) were associated with increased perioperative bleeding complications. The need for an intraoperative transfusion (OR, 4.87; p < 0.001), and intraoperative vasopressors (OR, 4.35; p = 0.003) were associated with increased in-hospital mortality. CONCLUSION: Perioperative bleeding complications and mortality are impacted by the indication for EGSPs and patient's severity of illness rather than a history of DOAC or warfarin/AP use. Therefore, perioperative management should be guided by patient physiology and indication for surgery rather than the concern for recent antiplatelet or anticoagulant use. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

Randomized controlled trial of oatmeal consumption versus noodle consumption on blood lipids of urban Chinese adults with hypercholesterolemia.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in China and worldwide. Whole grain oats can reduce risk of CVD by reducing total and LDL-cholesterol, major risk factors for CVD. While this association has been established in many populations, data from Asian populations is limited. Thus, this study investigated the impact of oat consumption on cholesterol levels in Chinese adults. Male and female data from this work were previously published separately in mandarin in two Chinese journals. The combined male and female data were reanalyzed and are presented here. METHODS: A randomized, controlled, parallel-arm study was conducted at Beijing Hospital, Beijing china. Subjects were adults (men and women) with mild to moderate hypercholesterolemia. The oat group (n=85) consumed 100 grams of instant oat cereal versus the control group (n=81) who consumed 100 grams of wheat flour-based noodles daily for 6 weeks. Laboratory and anthropometric measurements were conducted at baseline and at the end of the 6-week intervention. RESULTS: Dietary fiber intake increased significantly in the oat group compared to the control group at the end of the 6-week intervention. Total-, LDL-cholesterol and waist circumference decreased significantly in the oat group compared to the control. HDL-cholesterol decreased significantly in the control group versus the oat group. There were no significant changes in blood pressure, other anthropometric or laboratory measures between the two groups at the end of the intervention. CONCLUSIONS: Instant oatmeal consumed daily for 6 weeks significantly increased fiber intake and decreased major risk factors for CVD in Chinese adults with hypercholesterolemia. Increased consumption of whole grains, including oats, should continue to be encouraged.

Designing Studies to Inform Tobacco Harm Reduction: Learnings From an Oral Nicotine Pouch Actual Use Pilot Study.

BACKGROUND: Introduction of new tobacco products in the United States, including those that may be lower on the risk continuum than traditional combustible cigarettes, requires premarket authorization by the US Food and Drug Administration and information on the potential impact of the products on consumer behaviors. Efficient recruitment and data capture processes are needed to collect relevant information in a near-to-real-world environment. OBJECTIVE: The aim of this pilot study was to develop and test a protocol for an actual use study of a new tobacco product. The product included in this study was a commercially available oral nicotine pouch. Through the process of study design and execution, learnings were garnered to inform the design, execution, analysis, and report writing of future full-scale actual use studies with tobacco products. METHODS: A small sample (n=100) of healthy adult daily smokers of 7 or more cigarettes per day were recruited to participate in an 8-week prospective observational study conducted at 4 geographically dispersed sites in the United States. A smartphone-based customized electronic diary (eDiary) was employed to capture daily tobacco product use, including 1 week of baseline smoking and 6 weeks during which participants were provided with oral nicotine pouches for use as desired. RESULTS: Online screening procedures with follow-up telephone interviews and on-site enrollment were successfully implemented. Of 100 participants, 97 completed the study, with more than half (59/99, 60%) identifying as dual- or poly-users of cigarettes and other types of tobacco products at baseline. There was more than 90% (91-93/99, 92%-94%) compliance with daily eDiary reporting, and the majority (92/99, 93%) of participants expressed satisfaction with the study processes. Product use data from the eDiary indicated that after an initial period of trial use, pouches per day increased among those continuing to use the products, while per day average cigarette consumption decreased for 82% (79/97) of all study participants. At the end of the week 6, 16% (15/97) of participants had reduced their cigarette consumption by more than half. CONCLUSIONS: The design of this study, including recruiting, enrollment, eDiary use, and oversight, was successfully implemented through the application of a detailed protocol, a user-friendly eDiary, electronically administered questionnaires, and remote monitoring procedures. High-resolution information was obtained on prospective changes in tobacco product use patterns in the context of availability of a new tobacco product. Future, larger actual use studies will provide important evidence supporting the role that alternatives to combustible cigarettes may play in smoking reduction and/or cessation and lowering the population health burden of tobacco and nicotine-containing products.

Numb regulates Tau levels and prevents neurodegeneration in tauopathy mouse models.

Accumulation of the microtubule-associated protein Tau is linked to neuronal cell death in tauopathies, but how intraneuronal Tau levels are regulated in health and disease remains unclear. Here, we show that conditional inactivation of the trafficking adaptor protein Numb in retinal ganglion cells (RGCs) increases Tau levels and leads to axonal blebbing, which is followed by neuronal cell loss in aged mice. In the TauP301S mouse model of tauopathy, conditional inactivation of Numb in RGCs and spinal motoneurons accelerates neurodegeneration, and loss of Numb in motoneurons also leads to precocious hindlimb paralysis. Conversely, overexpression of the long isoform of Numb (Numb-72) decreases intracellular Tau levels and reduces axonal blebbing in TauP301S RGCs, leading to improved electrical activity in cultured neurons and improves performance in a visually guided behavior test in vivo. These results uncover Numb as a key regulator of intracellular Tau levels and identify Numb-72 as a potential therapeutic factor for tauopathies.

Mesenteric venous thrombosis: A lethal complication of hyperglycemic crises.

PURPOSE: Although hyperglycemic crises can lead to a hypercoagulable state, few instances of associated mesenteric venous thrombosis (MVT) have been reported. Worsening abdominal pain in the context of shock requiring vasopressor support should prompt urgent further investigation. SUMMARY: A 44-year-old Hispanic male arrived at an emergency department with chief complaints of lethargy, polydipsia, and polyuria. His past medical history included type 2 diabetes, epilepsy, obesity, tobacco smoking, and noncompliance with his medications. On arrival the patient had a serum glucose concentration of >1,600 mg/dL, and hyperosmolar hyperglycemic syndrome (HHS) was diagnosed. The patient was admitted to the intensive care unit with respiratory failure and subsequently developed shock refractory to fluid resuscitation, necessitating vasopressor support. On hospital day 4, a computerized tomogram obtained for investigation of increasing abdominal tenderness revealed superior MVT and pneumatosis intestinalis. Despite an emergency laparotomy and enterectomy, the patient ultimately succumbed on hospital day 41 due to recurrent pneumonia complicated by acute respiratory distress syndrome and septic shock. CONCLUSION: Shock that is refractory to aggressive fluid resuscitation, necessitating pressor support, in the setting of HHS or diabetic ketoacidosis should prompt investigation for the underlying source of shock. Other etiologies, including hypovolemic, cardiogenic, and obstructive shock, should be considered; however, infection is the leading trigger of hyperglycemic crises. Although rarely reported, MVT should be considered in the diagnostic algorithm in the absence of an identified infectious source. Prompt investigation should include use of diagnostic modalities such as computed tomography to assess for MVT.

Astrocyte activation imaging with 11C-acetate and amyloid PET in mild cognitive impairment due to Alzheimer pathology.

BACKGROUND: Neuroinflammation is a well-known feature of early Alzheimer disease (AD) yet astrocyte activation has not been extensively evaluated with in vivo imaging in mild cognitive impairment (MCI) due to amyloid plaque pathology. Unlike neurons, astrocytes metabolize acetate, which has potential as a glial biomarker in neurodegeneration in response to AD pathologic features. Since the medial temporal lobe (MTL) is a hotspot for AD neurodegeneration and inflammation, we assessed astrocyte activity in the MTL and compared it to amyloid and cognition. METHODS: We evaluate spatial patterns of in vivo astrocyte activation and their relationships to amyloid deposition and cognition in a cross-sectional pilot study of six participants with MCI and five cognitively normal participants. We measure 11C-acetate and 18F-florbetaben amyloid standardized uptake values ratios (SUVRs) and kinetic flux compared to the cerebellum on PET, with MRI and neurocognitive testing. RESULTS: MTL 11C-acetate SUVR was significantly elevated in MCI compared to cognitively normal participants (P = 0.03; Cohen d = 1.76). Moreover, MTL 11C-acetate SUVR displayed significant associations with global and regional amyloid burden in MCI. Greater MTL 11C-acetate retention was significantly related with worse neurocognitive measures including the Montreal Cognitive Assessment (P = 0.001), word list recall memory (P = 0.03), Boston naming test (P = 0.04) and trails B test (P = 0.04). CONCLUSIONS: While further validation is required, this exploratory pilot study suggests a potential role for 11C-acetate PET as a neuroinflammatory biomarker in MCI and early AD to provide clinical and translational insights into astrocyte activation as a pathological response to amyloid.

Cloning and apoptosis-inducing activities of canine and feline TRAIL.

The apoptosis process is crucial to various biological processes including embryo development and organism homeostasis. Inducing apoptosis of cancer cells has become a very attractive field for cancer therapy in the recent years. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL; also called Apo2L, TNFSF10, CD253, or TL2) is a member of tumor necrosis factor family. Preclinical studies showed that human TRAIL induced apoptosis of various tumor cell lines, whereas nontransformed normal cell lines were not affected. We have cloned both canine and feline TRAIL full-length genes by using Rapid Amplification of cDNA Ends-PCR technology. Truncated soluble versions of the canine and feline TRAIL genes were also constructed. The degree of identity between canine TRAIL protein and the human, mouse, chicken, porcine, and rat homologues is 81.3%, 61.7%, 54.3%, 82.9%, and 63.2%, respectively. The degree of identity between the feline TRAIL protein and the human, mouse, chicken, porcine, and rat homologues is 84.2%, 64.2%, 54.4%, 86.8% and 65.7%, respectively. The identity between the canine and feline TRAIL proteins is 93.2%. The canine and feline soluble TRAIL proteins were expressed in both mammalian and bacterial expression systems. Western immunoblot assays with TRAIL-specific antibody confirmed the identity of expressed protein. Both canine and feline TRAIL proteins were shown to specifically induce apoptosis and inhibit cell growth of cancer cells at a level comparable with their human counterpart.

Pharmacological effects of nicotine on norepinephrine metabolism in rat brown adipose tissue: relevance to nicotinic therapies for smoking cessation.

In a two-year carcinogenicity study with administration of high doses of the partial nicotinic agonist varenicline (recently approved for smoking cessation), mediastinal hibernomas occurred in three male rats. To investigate potential mechanisms for partial and full nicotinic agonists to contribute to development of hibernomas, the effects of nicotine on rat brown adipose tissue (BAT) were studied. Male and female rats were administered nicotine at doses of 0, 0.3, and 1 mg/kg subcutaneously for fourteen days. Intrathoracic (mediastinal periaortic and mediastinal perithymic) BAT and interscapular BAT were examined microscopically, and determinations of uncoupling protein-1 (UCP-1) expression and norepinephrine (NE) content were made. Additionally, NE turnover was measured in mediastinal periaortic and perithymic BAT. Nicotine (1 mg/kg) administration resulted in decreased vacuolation only in mediastinal periaortic and mediastinal perithymic BAT of males and elevated UCP-1 in mediastinal periaortic BAT of males and females. Increased NE content occurred only in mediastinal periaortic BAT of males given 0.3 and 1 mg/kg doses, whereas NE turnover was decreased in both males and females given 1 mg/kg. Together, these data demonstrate that nicotine primarily affects mediastinal BAT in male rats, consistent with the gender and location of the hibernomas observed in the two-year carcinogenicity study.

Aggressive Soft Tissue Infections.

Necrotizing soft tissue infections (NSTI) are characterized by rapidly progressive infection that causes tissue necrosis with associated sepsis and multisystem organ failure. A rapid diagnosis is essential to decreasing the morbidity and mortality of NSTIs. There must be a high index of suspicion based on history and physical examination. There are no adjunct laboratory values or imaging that have high sensitivity and specificity in the diagnosis of NSTI. The treatment involves emergent, radical surgical debridement of involved tissues and broad spectrum antibiotics. Follow-up should include close monitoring of the wound and repeat debridements in the operating room.

Validation of gallbladder absorbed radiation dose reduction simulation: human dosimetry of [18F]fluortriopride.

BACKGROUND: [18F]Fluortriopride (FTP) was developed as a dopamine D3-selective radiotracer, thought to be important to neurobiological reward pathways and implicated in drug addiction, Parkinson's disease, and schizophrenia. Preclinical radiation dosimetry studies found the gallbladder wall received the highest dose. A gallbladder dose reduction intervention was simulated using a novel reduction model for healthy adults following fatty-meal consumption. The goals of this study were to assess whole body FTP human dosimetry and determine the feasibility of reducing absorbed dose to the gallbladder wall. RESULTS: Effective dose without a fatty meal was 0.022 ± 0.002 mSv/MBq (± standard deviation) with highest organ dose of 0.436 ± 0.178 mSv/MBq to the gallbladder wall (n = 10). Predicted gallbladder dose reduction with fatty meal consumed was 67.4% (n = 10). Meal consumption by four repeat volunteers decreased average gallbladder dose by 71.3% (n = 4) compared to the original ten volunteers. CONCLUSIONS: Observed effective doses were adequately low to continue studying FTP uptake in humans. Validated dosimetry simulations indicate up to a 71% reduction in gallbladder dose can be achieved by employing intrinsic physiology to contract the gallbladder via fatty meal ingestion. This methodology for predicting gallbladder absorbed dose reduction from fatty meal consumption can be applied to other radiopharmaceuticals and radiotherapies.