Ivor Lewis vs Mckeown esophagectomy: analysis of operative outcomes from the ACS NSQIP database.

OBJECTIVES: Ivor Lewis and McKeown esophagectomy are common techniques to treat esophageal cancer. In this study, we aim to compare these two approaches. METHOD: We used the American College of Surgeons National Surgical Quality Improvement Project database (2005-2017) to compare both techniques using bivariate analysis after propensity matching. RESULTS: We identified 6136 patients with esophagectomy and divided them into 2 groups based on whether they received a McKeown (1676; 27.31%) or an Ivor Lewis (4460; 70.14%) esophagectomy. McKeown esophagectomy was associated with higher rates of superficial surgical site infections (8.02% vs 3.67%, p < 0.001), anastomotic leaks (9.12% vs 7.71%, p = 0.02), prolonged intubation (15.06% vs 10.10%, p < 0.001), re-intubation (15.30% vs 10.34%, p ≤ 0.001), and return to the OR (16.46% vs 11.32%, p < 0.001). The McKeown esophagectomy patients also had longer hospital length of stay (14.5 ± 11.99 vs 13.37 ± 11.8, p = 0.002), higher re-admission rate (21.56% vs 16.87%, p = 0.002), and higher discharges to nursing/rehabilitation institutions (14.06% vs 11.99%, p = 0.004).The mortality rate and positive resection margins were not significantly different. There was a trend toward more utilization of Ivor Lewis esophagectomy over years. CONCLUSION: When compared to Ivor Lewis esophagectomy, McKeown esophagectomy is associated with more unplanned intubation, increased difficulty weaning from the ventilator, incisional surgical site infections, anastomotic leak, and higher length of stay.

A novel test for determination of wild felid-domestic cat hybridization.

In October 2018, Colorado Parks and Wildlife seized an animal believed to be an illegally possessed bobcat. The owner claimed the animal was a bobcat/domestic cat hybrid, exempted from license requirements. Burden of proof lay with CPW to determine the lineage of the animal. Commercial microsatellite arrays and DNA barcoding have not been developed for identification of bobcat/domestic cat hybrids, and limited time and resources prevented development of such tests for this application. Instead, we targeted endogenous feline leukemia virus (enFeLV) to quickly and inexpensively demonstrate the absence of domestic cat DNA in the contested animal. Using this assay, we were able to confirm that the contested animal lacked enFeLV, and therefore was not a domestic cat hybrid.

Brugada Syndrome Associated With Adolescent Loperamide Abuse.

We present the case of a 14-year-old boy with obesity, hypertension, and chronic loperamide abuse who presented to our facility with symptoms of opioid withdrawal and type 1 Brugada pattern on an electrocardiogram. He was treated for anxiety and withdrawal. There were no documented dysrhythmias. His Brugada pattern resolved by hospital day 5 and remained resolved 12 days postadmission. Genetic testing revealed a heterozygous missense mutation in the SCN5A gene (c. 5038G>A, p. Ala1680Thr), which has been reported in association with Brugada syndrome. To date, there are no published reports of pediatric loperamide use associated with a Brugada pattern on an electrocardiogram. We propose that chronic loperamide use unmasked the electrocardiographic phenotype associated with his gene mutation.

Protective effect of black relative to white race against non-alcoholic fatty liver disease in patients with severe obesity, independent of type 2 diabetes.

Severe obesity (body mass index ⩾35 kg m-2) and type 2 diabetes (T2D) are potent and additive risk factors for non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH). Scant available evidence indicates that black relative to white patients with severe obesity are less susceptible to NAFLD, but it is unclear if T2D abolishes this apparent racial disparity. Therefore, we compared biopsy-proven NAFLD and its progression between black (n=71) and white (n=155) patients with severe obesity stratified by presence or absence of T2D. Although prevalence of T2D was similar between races (37%, P>0.9), whites were significantly more likely than blacks to have NAFLD, NASH and advanced fibrosis (defined as bridging fibrosis and/or cirrhosis). Importantly, T2D was associated with increased odds of NAFLD, NASH and advanced fibrosis (defined as bridging fibrosis or cirrhosis) in whites only (P<0.05). In turn, a higher proportion of blacks than whites with T2D were free of NAFLD (58 versus 22%, P<0.01). These preliminary findings question translation of the powerful interconnection between T2D and NAFLD in whites with severe obesity to blacks and point to an important role of race in the pathophysiology and treatment of these diseases.

Biallelic mutations in mitochondrial tryptophanyl-tRNA synthetase cause Levodopa-responsive infantile-onset Parkinsonism.

Mitochondrial aminoacyl-tRNA synthetases (mtARSs) are essential, ubiquitously expressed enzymes that covalently attach amino acids to their corresponding tRNA molecules during translation of mitochondrial genes. Deleterious variants in the mtARS genes cause a diverse array of phenotypes, many of which involve the nervous system. Moreover, distinct mutations in mtARSs often cause different clinical manifestations. Recently, the gene encoding mitochondrial tryptophanyl tRNA synthetase (WARS2) was reported to cause 2 different neurological phenotypes, a form of autosomal recessive intellectual disability and a syndrome of severe infantile-onset leukoencephalopathy. Here, we report the case of a 17-year-old boy with compound heterozygous mutations in WARS2 (p.Trp13Gly, p.Ser228Trp) who presented with infantile-onset, Levodopa-responsive Parkinsonism at the age of 2 years. Analysis of patient-derived dermal fibroblasts revealed decreased steady-state WARS2 protein and normal OXPHOS content. Muscle mitochondrial studies suggested mitochondrial proliferation without obvious respiratory chain deficiencies at the age of 9 years. This case expands the phenotypic spectrum of WARS2 deficiency and emphasizes the importance of mitochondrial protein synthesis in the pathogenesis of Parkinsonism.

Circadian timing and alignment in healthy adults: associations with BMI, body fat, caloric intake and physical activity.

INTRODUCTION: Disruption of circadian rhythms is one of the proposed mechanisms linking late sleep timing to obesity risk but few studies have evaluated biological markers outside of the laboratory. The goal of this study was to determine the relationship between the timing and alignment of melatonin and sleep onset (phase angle) with body mass index (BMI), body fat and obesity-related behaviors. We hypothesized that circadian alignment (relationship of melatonin to sleep timing) rather than circadian (melatonin) timing would be associated with higher BMI, body fat, dietary intake and lower physical activity. SUBJECTS/METHODS: Adults with sleep duration ⩾6.5 h completed 7 days of wrist actigraphy, food diaries and SenseWear arm band monitoring. Circadian timing, measured by dim light melatonin onset was measured in the clinical research unit. Circadian alignment was calculated as the duration between dim light melatonin onset and average sleep onset time in the prior week (phase angle). Body fat was evaluated using dual-energy X-ray absorptiometry. Data were analyzed using bivariate correlations and multivariable regression analyses controlling for age, sex, sleep duration and evening light exposure. RESULTS: Participants included 97 adults (61 F, age 26.8±7.3 years) with average sleep duration 443.7 (s.d.=50.4) minutes. Average phase angle was 2.2 h (s.d.=1.5). Circadian alignment was associated with circadian timing (P<0.001) and sleep duration (P=0.005). In multivariable analyses, later circadian timing was associated with lower BMI (P=0.04). Among males only, circadian alignment was associated with percent body fat (P=0.02) and higher android/gynoid fat ratio (P=0.04). Circadian alignment was associated with caloric intake (P=0.049) carbohydrate intake (P=0.04) and meal frequency (P=0.03) among both males and females. CONCLUSION: Circadian timing and alignment were not associated with increased BMI or body fat, among healthy adults with ⩾6.5 h of sleep, but circadian alignment was associated with dietary intake. There may be sex differences in the relationship between circadian alignment and body fat.

Transplacental passage of clindamycin from mother to neonate.

OBJECTIVE: To evaluate maternal and neonatal cord blood levels at delivery in patients receiving 900 mg of clindamycin intravenous (IV) every 8 h. STUDY DESIGN: Prospective study consented every mother that entered labor with a positive group B streptococcal culture, a high-risk penicillin allergy, and sensitivity to clindamycin and erythromycin. Maternal and cord blood clindamycin levels were obtained at delivery. Time from last dose completion to delivery, number of doses administered and body mass index (BMI) were assessed. RESULTS: Twenty-three patients were consented. All maternal clindamycin values were therapeutic and 22 (96%) of the 23 cord blood samples were therapeutic. The mean maternal level was of 4.46 µg ml-1 (range of 0.7 to 8.4 µg ml-1). The mean cord blood level was 3.35 µg ml-1 (range of <0.5 to 6.4 µg ml-1). CONCLUSION: These data show that the current dosing recommendation of 900 mg of clindamycin IV every 8 h produces therapeutic maternal and cord blood levels.

Banking placental tissue: an optimized collection procedure for genome-wide analysis of nucleic acids.

INTRODUCTION: Banking of high-quality placental tissue specimens will enable biomarker discovery and molecular studies on diseases involving placental dysfunction. Systematic studies aimed at developing feasible standardized methodology for placental collection in a typical clinical setting are lacking. METHODS: To determine the acceptable timeframe for placental collection, we collected multiple samples from first and third trimester placentas at serial timepoints in a 2-h window after delivery, simultaneously comparing the traditional snap-freeze technique to commercial solutions designed to preserve RNA (RNAlater™), and DNA (DNAgard(®)). The performance of RNAlater for preserving DNA was also tested. Nucleic acid quality was assessed by determining the RNA integrity number (RIN) and genome-wide microarray profiling for gene expression and DNA methylation. RESULTS: We found that samples collected in RNAlater had higher and more consistent RINs compared to snap-frozen tissue. Similar RINs were obtained for tissue collected in RNAlater as large (1 cm(3)) and small (∼0.1 cm(3)) pieces. RNAlater appeared to better stabilize the time zero gene expression profile compared to snap-freezing for first trimester placenta. DNA methylation profiles remained quite stable over a 2 h time period after removal of the placenta from the uterus, with DNAgard being superior to other treatments. DISCUSSION AND CONCLUSION: The collection of placental samples in RNAlater and DNAgard is simple, and eliminates the need for liquid nitrogen or a freezer on-site. Moreover, the quality of the nucleic acids and the resulting data from samples collected in these preservation solutions is higher than samples collected using the snap-freeze method and easier to implement in busy clinical environments.

Paranasal sinus masses of Rocky Mountain bighorn sheep (Ovis canadensis canadensis).

This article describes 10 cases of paranasal sinus masses in Rocky Mountain bighorn sheep (Ovis canadensis canadensis). Among 21 bighorns that were examined from 11 herds in Colorado, 10 individuals (48%) from 4 herds (36%) had masses arising from the paranasal sinuses. Affected animals included 9 of 17 females (53%) and 1 of 4 males (25%), ranging in age from approximately 2 years to greater than 10 years. Defining gross features of these masses included unilateral or bilateral diffuse thickening of the respiratory lining of the maxillary and/or frontal sinuses, with abundant seromucinous exudate in the affected sinus cavities. Defining histologic features of these masses included chronic inflammation and proliferation of mesenchymal and epithelial cells of the mucosa and submucosa. Epithelial changes included hyperplasia of mucosal epithelium, hyperplasia of submucosal glands and ducts, and neoplasia (adenocarcinoma). Mesenchymal changes included submucosal myxedema, submucosal fibroplasia/fibrosis, bone destruction, and neoplasia (myxomatous fibroma). Specific immunohistochemistry and polymerase chain reaction for Jaagsiekte sheep retrovirus and enzootic nasal tumor virus were performed with negative results.

Silene as a model system in ecology and evolution.

The genus Silene, studied by Darwin, Mendel and other early scientists, is re-emerging as a system for studying interrelated questions in ecology, evolution and developmental biology. These questions include sex chromosome evolution, epigenetic control of sex expression, genomic conflict and speciation. Its well-studied interactions with the pathogen Microbotryum has made Silene a model for the evolution and dynamics of disease in natural systems, and its interactions with herbivores have increased our understanding of multi-trophic ecological processes and the evolution of invasiveness. Molecular tools are now providing new approaches to many of these classical yet unresolved problems, and new progress is being made through combining phylogenetic, genomic and molecular evolutionary studies with ecological and phenotypic data.

Disease status and population origin effects on floral scent:: potential consequences for oviposition and fruit predation in a complex interaction between a plant, fungus, and noctuid moth.

In the Silene latifolia-Hadena bicruris nursery pollination system, the Hadena moth is both pollinator and seed predator of its host plant. Floral scent, which differs among S. latifolia individuals and populations, is important for adult Hadena to locate its host. However, the success of moth larvae is strongly reduced if hosts are infected by the anther smut fungus Microbotryum violaceum, a pathogen that is transmitted by flower visitors. There were no qualitative differences between the scent of flowers from healthy and diseased plants. In addition, electroantennographic measurements showed that Hadena responded to the same subset of 19 compounds in samples collected from healthy and diseased plants. However, there were significant quantitative differences in scent profiles. Flowers from diseased plants emitted both a lower absolute amount of floral scent and had a different scent pattern, mainly due to their lower absolute amount of lilac aldehyde, whereas their amount of (E)-beta-ocimene was similar to that in healthy flowers. Dual choice behavioral wind tunnel tests using differently scented flowers confirmed that moths respond to both qualitative and quantitative aspects of floral scent, suggesting that they could use differences in floral scent between healthy and infected plants to discriminate against diseased plants. Population mean fruit predation rates significantly increased with population mean levels of the emission rates of lilac aldehyde per flower, indicating that selection on floral scent compounds may not only be driven by effects on pollinator attraction but also by effects on fruit predation. However, variation in mean emission rates of scent compounds per flower generally could not explain the higher fruit predation in populations originating from the introduced North American range compared to populations native to Europe.

Essential fatty acid profiling for routine nutritional assessment unmasks adrenoleukodystrophy in an infant with isovaleric acidaemia.

We report a 16-month-old asymptomatic male with enzyme confirmed isovaleric acidaemia (IVA; isovaleryl-CoA dehydrogenase deficiency; OMIM 243500) who, upon routine nutritional follow-up, presented evidence of peroxisomal dysfunction. The newborn screen (2 days of life) revealed elevated C(5)-carnitine (2.95 µmol/L; cutoff <0.09 µmol/L) and IVA was subsequently confirmed by metabolic profiling and in vitro enzymology. Plasma essential fatty acid (EFA) analysis, assessed to evaluate nutritional status during protein restriction and L: -carnitine supplementation, revealed elevated C(26:0) (5.0 µmol/L; normal <1.3). Subsequently, metabolic profiling and molecular genetic analysis confirmed X-linked adrenoleukodystrophy (XALD). Identification of co-inherited XALD with IVA in this currently asymptomatic patient holds significant treatment ramifications for the proband prior to the onset of neurological sequelae, and critically important counselling implications for this family.

Cyclooxygenase-2 expression in normal and neoplastic canine mammary cell lines.

Mammary cancer is the most common cancer in female dogs. Induction of cyclooxygenase-2 (COX-2), a key enzyme in prostaglandins (PGs) biosynthesis, has been demonstrated in various cancers in humans and dogs, including mammary cancer. The objective of this study was to investigate the expression and regulation of COX-2 in canine mammary epithelial cells. Cell lines derived from normal and neoplastic canine mammary glands were cultured in the absence or presence of phorbol 12-myristate 13-acetate (PMA), and immunoblots, immunocytochemistry, radioimmunoassays, and a cell proliferation assay were used to study COX-2 expression and PGs production. Results showed that the neoplastic cell line CMT12 constitutively overexpressed COX-2 protein whereas other mammary cell lines expressed low to undetectable basal levels of COX-2 protein. Basal PGE(2) production was significantly higher (P < .05) in CMT12 compared to other cell lines. Levels of COX-2 protein in CMT12 decreased in a time-dependent manner with serum starvation, and PMA stimulation induced a strong time-dependent increase in COX-2 protein. Treatment of CMT12 cells with NS-398 (a specific COX-2 inhibitor) significantly blocked PGE(2) synthesis and reduced cell proliferation (P < .05). These results indicate that some neoplastic canine mammary cell lines constitutively overexpress COX-2, and that COX-2 inhibition decreases PGE(2) production and cell proliferation, supporting a role for COX-2 and PGs in canine mammary oncogenesis.

Responsiveness of the aging circadian clock to light.

The present study assessed whether advances in sleep times and circadian phase in older adults might be due to decreased responsiveness of the aging circadian clock to light. Sixteen young (29.3+/-5.6 years) and 14 older adults (67.1+/-7.4 years) were exposed to 4h of control dim (10lux) or bright light (3500lux) during the night. Phase shifts of the melatonin rhythm were assessed from the nights before and after the light exposure. Bright light delayed the melatonin midpoint in both young and older adults (p<0.001). Phase delays for the older subjects were not significantly different from those of the young subjects for either the bright or dim light conditions. The magnitude of phase delays was correlated with both sleep offset and phase angle in the older, but not the younger subjects. The present results indicate that at light intensities commonly used in research as well as clinical practice older adults are able to phase delay to the same extent as younger subjects.

Orphan seven transmembrane receptor screening.

Drug discovery has successfully exploited the superfamily of seven transmembrane receptors (7TMR), with over 35% of clinically marketed drugs targeting them. However, it is clear that there remains an undefined potential within this protein family for successful drugs of the future. The human genome sequencing project identified approximately 720 genes that belong to the 7TMR superfamily. Around half of these genes encode sensory receptors, while the other half are potential drug targets. Natural ligands have been identified for approximately 215 of these, leaving 155 receptors classified as orphan 7TMRs having no known ligand. Deorphanisation of these receptors by identification of natural ligands has been the traditional method enabling target validation by use of these ligands as tools to define biological relevance and disease association. Such ligands have been paired with their cognate receptor experimentally by screening of small molecule and peptide ligands, reverse pharmacology and the use of bioinformatics to predict candidate ligands. In this manuscript, we review the methodologies developed for the identification of ligands at orphan 7TMRs and exemplify these with case studies.

Postoperative complications are not increased in super-super obese patients who undergo laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: It has been suggested that super-super obesity (body mass index [BMI] > or =60 kg/m2) increases the risk of complications after laparoscopic Roux-en-Y gastric bypass (LapRYGB). We hypothesized that a higher BMI does not increase risk the morbidity or mortality rate. METHODS: Complication rates for patients with a BMI > or =60 kg/m2 were compared to those for patients with a BMI <60 kg/m2 who underwent LapRYGB during the same time period. Differences between the groups were analyzed by Fisher's exact test, t-tests, and analysis of variance. RESULTS: Forty-five patients with a BMI > or =60 kg/m2 and 640 patients with a BMI <60 kg/m2 underwent LapRYGB. There were no statistically significant differences between the two groups in the complication or mortality rates. Excess weight loss was less, but actual weight lost was greater in the BMI > or =60 kg/m2 group. CONCLUSIONS: The complication and mortality rates are not increased in super-super obese patients who undergo LapRYGB. Acceptable weight loss can be achieved safely in these patients.

Stability of melatonin and temperature as circadian phase markers and their relation to sleep times in humans.

Circadian rhythms of core body temperature and melatonin are commonly used as phase markers of the circadian clock. Melatonin is a more stable marker of circadian phase when measured under constant routine conditions. However, little is known about the variability of these phase markers under less controlled conditions. Moreover, there is little consensus about the preferred method of analysis. The objective of this study was to assess various methods of calculating melatonin and temperature phase in subjects with regular sleep schedules living in their natural environment. Baseline data were analyzed from 42 healthy young subjects who were studied on at least two occasions. Each hospital admission was separated by at least 3 weeks. Subjects were instructed to maintain a regular sleep schedule, which was monitored for 1 week before admission by sleep logs and actigraphy. Subjects spent one habituation night under controlled conditions prior to collecting baseline temperature and melatonin measurements. The phase of the melatonin rhythm was assessed by 9 different methods. The temperature nadir (Tmin) was estimated using both Cleveland and Cosine curve fitting procedures, with and without demasking. Variability between admissions was assessed by correlation analysis and by the mean absolute difference in timing of the phase estimates. The relationship to sleep times was assessed by correlation of sleep onset or sleep offset with the various phase markers. Melatonin phase markers were more stable and more highly correlated with the timing of sleep than estimates of Tmin. Of the methods for estimating Tmin, simple cosine analysis was the least variable. In addition, sleep offset was more strongly correlated with the various phase markers than sleep onset. The relative measures of melatonin offset had the highest correlation coefficients, the lowest study-to-study variability, and were more strongly associated with sleep timing than melatonin onsets. Concordance of the methods of analysis suggests a tendency for the declining phase of the melatonin profile to be more stable and reliable than either markers of melatonin onset or measures of the termination of melatonin synthesis.

Non-resective ablation therapy for hepatocellular carcinoma: effectiveness measured by intention-to-treat and dropout from liver transplant waiting list.

BACKGROUND: Orthotopic liver transplantation (OLT) for patients with small hepatocellular carcinoma (HCC) is widely accepted, and the usefulness of local ablation techniques as a bridge for liver transplantation is still under investigation. METHODS: From December 1997 to February 2003, patients with cirrhosis and T0-T1-T2-T3 stage HCC received multi-modality ablative therapy (MMT) for the treatment of their HCC and were evaluated for OLT; listed, and transplanted when an allograft became available. MMT included radiofrequency ablation (RFA), and/or Trans-Arterial Chemo-Embolization (TACE), and alcohol (EtOH) ablation, followed by Trans-Arterial Chemo-Infusion (TACI), with repeated treatments based on follow up hepatic magnetic resonance imaging (MRI) during the waiting period for OLT. RESULTS: A total of 135 HCC patients were seen at our center within this time frame. The intention-to-treat group included 33 (24.4%) patients with T0, T1, T2, T3 HCC and cirrhosis. There were 31 men and two women. The mean age was 53.6 +/- 7.2 yr. All patients received MMT with a mean of 2.90 +/- 1.5 procedures per patient. Tumor-node-metastasis (TNM) stages at time of listing were: T0 in one patient, T1 in nine patients, T2 in 17 patients, and T3 in six patients. Twenty-eight (85%) patients have received OLT. Five (12.19%) patients were listed and removed (dropout) from the transplant waiting list after waiting 5, 5, 5, 8, and 14 months respectively. The waiting time of the HCC listed group was 9.1 +/- 14.8 months with a mean follow up of 32 months. OLT patient survival and cancer-free survival are 92.9% and 95.24%, respectively; the overall survival of intention-to-treat group was 79% at 32 months follow up. Predictors of dropout included an alpha-fetoprotein (AFP, >400 ng/mL) and T3 HCC stage. CONCLUSION: Aggressive ablation therapy with a short transplant waiting time optimizes the use of OLT for curative intent in selective cirrhotic HCC patients.

Experience with over 3,000 open and laparoscopic bariatric procedures: multivariate analysis of factors related to leak and resultant mortality.

BACKGROUND: Intestinal leak is a potentially lethal complication of Roux en-Y gastric bypass (GBP). Identification of patients at high risk for leak may reduce complication rates of surgeons early in the procedure learning curve. METHODS: A total of 3073 patients who underwent GBP were analyzed using univariate and multivariate logistic regression analyses of the following preoperative factors: hypertension (HTN), diabetes mellitus (DM), sleep apnea (SA), age, gender, weight, body mass index (BMI), and surgery type. Multivariate logistic regression analysis was performed for each procedure type. RESULTS: There were 48 (1.5%) deaths. Independent risk factors for death included leak, weight, procedure type, and HTN. A total of 102 (3.2%) leaks were found. Independent factors for leak included age, male gender, SA, and procedure type. CONCLUSION: The data suggests that older, heavier male patients with multiple comorbid conditions are at increased risk for leak and mortality. Surgeons early in their learning curve should avoid these high-risk patients to reduce complications.