Mortality and failure-to-rescue after esophagectomy in the procedure-targeted National Surgical Quality Improvement Program registry.

BACKGROUND: The association between procedural volume and esophagectomy outcomes has been established, but the relationship between higher levels of care and esophagectomy outcomes has not been explored. This study aims to investigate whether hospital participation in the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) esophagectomy-targeted registry is associated with superior outcomes. METHODS: The 2016-2020 ACS NSQIP standard and esophagectomy-targeted registries were queried. Esophagectomy outcomes were analyzed overall and stratified by esophagectomy type (Ivor Lewis vs. transhiatal vs. 3-field McKeown). RESULTS: A total of 2181 and 5449 esophagectomy cases were identified in the standard and targeted databases (68% Ivor Lewis esophagectomy). The median age was 65 years and 80% were male. Preoperative characteristics were largely comparable. On univariate analysis, targeted hospitals were associated with lower mortality (2% vs. 4%, p < 0.01) and failure-to-rescue rates (11% vs. 17%, p < 0.01), higher likelihood of an optimal outcome (62% vs. 58%, p = 0.01), and shorter hospital stay (median 9 vs. 10 days, p < 0.01). On multivariable analysis, Ivor Lewis esophagectomy at targeted centers was associated with reduced odds of mortality [odds ratio (OR) 0.57 and 95% confidence intervals 0.35-0.90] and failure-to-rescue [OR 0.54 (0.33-0.90)] with no difference in serious morbidity or optimal outcome. There was no statistically significant difference in odds of mortality or failure to rescue in targeted versus standard centers when performing transhiatal or McKeown esophagectomy. CONCLUSIONS: Esophagectomy performed at hospitals participating in the targeted ACS NSQIP is associated with roughly half the risk of mortality compared to the standard registry. The factors underlying this relationship may be valuable in quality improvement.

Morbidity of colectomy during pancreatoduodenectomy: An analysis of the pancreas-targeted American College of Surgeons National Surgical Quality Improvement Program Registry.

BACKGROUND: Pancreatoduodenectomy is a complex operation with considerable morbidity and mortality. Locally advanced tumors may require concurrent colectomy. We hypothesized that a concurrent colectomy increases the risk associated with pancreatoduodenectomy. METHODS: This retrospective review of the 2014-2019 pancreas-targeted American College of Surgeons National Surgical Quality Improvement Program registry classified operations as pancreatoduodenectomy (PD) versus pancreatoduodenectomy/colectomy (PD+C). The two groups were compared with respect to demographics, comorbidities, disease characteristics, intraoperative variables, and postoperative outcomes. Main effect models were developed to examine the effect of concurrent colectomy on outcomes after adjusting for potential confounders. RESULTS: Of 24 421 pancreatoduodenectomies, 430 (1.8%) involved concurrent colectomy. PD + C patients had less comorbidities (obesity 19% vs. 27%, hypertension 43% vs. 53%, diabetes 20% vs. 26%) and were associated with malignant diagnosis (94% vs. 83%), vascular resection (28% vs. 18%), and longer operative time (median 6.9 vs. 6 h). On multivariable analysis, concurrent colectomy was independently associated with serious morbidity (adjusted odds ratio [OR] 2.62, 95% confidence interval [CI]: 1.94-3.54) but not mortality (OR 1.44 [0.63-3.31]). CONCLUSIONS: Concurrent colectomy at the time of pancreatoduodenectomy significantly increased the odds of serious morbidity but did not affect mortality. This should be considered in operative planning, preoperative counseling, and sequencing of cancer-directed treatments.

The captive husbandry and reproduction of the pink-eared turtle (Emydura victoriae) at Perth Zoo.

In 1997, Perth Zoo acquired six pink-eared turtles (Emydura victoriae) from the wild for display in the reptile facility. There is very little documented information on pink-eared turtles in captivity. This article looks at the reproductive biology, ecology, behavior, diet, and captive husbandry of the species. Eight clutches of eggs were documented over a 2-year period with an average clutch size of 10 eggs. Egg size was recorded with three clutches incubated to hatching. Ten hatchlings were maintained for a growth and development study. Measurements of weight, carapace length, width, height, and plastron length were recorded weekly for about 12 months, and then monthly for approximately 2 years. The data were analyzed and showed positive growth curves in all animals. Sexual dimorphism was observed after 20 weeks and sexual maturity in males observed after 2 years.

Metal-dependent binding of a factor in vivo to the metal-responsive elements of the metallothionein 1 gene promoter.

Using the technique of genomic footprinting, we demonstrate cadmium-inducible protection from dimethyl sulfate (DMS) modification of guanine residues in vivo in five metal-responsive elements (MREs) in the promoter of the rat metallothionein 1 (MT-1) gene. We also identify a site of extreme DMS hyperreactivity which, like the MRE protection, occurs only after metal ion induction. With this hyperreactive site as an indicator, we can measure the kinetics of induction and deinduction. Changes in the intracellular metal ion concentrations are reflected in alterations in the reactivity with DMS of guanine residues in the MT-1 gene promoter. Lastly, for both control and metal-induced cells, we observe DMS protection and enhancement of a binding site (located 5' of the distal MRE) which is a consensus sequence for the Sp1 transcription factor. Transfection experiments with deletion mutations of a fusion gene construct indicate both that a sequence region which includes this GC box regulates the basal level of expression of the MT-1 gene and that increasing the number of MREs in the promoter increases the induced level of transcription. Our genomic footprinting and transfection data together suggest that (i) a transcription factor, possibly Sp1, plays an important role in regulating the basal level of expression of the MT-1 gene and (ii) metal induction involves the metal-dependent binding to a sequence-specific binding factor which responds to changes in intracellular metal ion levels.

Meiotic segregation, synapsis, and recombination checkpoint functions require physical interaction between the chromosomal proteins Red1p and Hop1p.

In yeast, HOP1 and RED1 are required during meiosis for proper chromosome segregation and the consequent formation of viable spores. Mutations in either HOP1 or RED1 create unique as well as overlapping phenotypes, indicating that the two proteins act alone as well as in concert with each other. To understand which meiotic processes specifically require Red1p-Hop1p hetero-oligomers, a novel genetic screen was used to identify a single-point mutation of RED1, red1-K348E, that separates Hop1p binding from Red1p homo-oligomerization. The Red1-K348E protein is stable, phosphorylated in a manner equivalent to Red1p, and undergoes efficient homo-oligomerization; however, its ability to interact with Hop1p both by two-hybrid and coimmunoprecipitation assays is greatly reduced. Overexpression of HOP1 specifically suppresses red1-K348E, supporting the idea that the only defect in the protein is a reduced affinity for Hop1p. red1-K348E mutants exhibit reduced levels of crossing over and spore viability and fail to undergo chromosome synapsis, thereby implicating a role for Red1p-Hop1p hetero-oligomers in these processes. Furthermore, red1-K348E suppresses the sae2/com1 defects in meiotic progression and sporulation, indicating a previously unknown role for HOP1 in the meiotic recombination checkpoint.

A role for MMS4 in the processing of recombination intermediates during meiosis in Saccharomyces cerevisiae.

The MMS4 gene of Saccharomyces cerevisiae was originally identified due to its sensitivity to MMS in vegetative cells. Subsequent studies have confirmed a role for MMS4 in DNA metabolism of vegetative cells. In addition, mms4 diploids were observed to sporulate poorly. This work demonstrates that the mms4 sporulation defect is due to triggering of the meiotic recombination checkpoint. Genetic, physical, and cytological analyses suggest that MMS4 functions after the single end invasion step of meiotic recombination. In spo13 diploids, red1, but not mek1, is epistatic to mms4 for sporulation and spore viability, suggesting that MMS4 may be required only when homologs are capable of undergoing synapsis. MMS4 and MUS81 are in the same epistasis group for spore viability, consistent with biochemical data that show that the two proteins function in a complex. In contrast, MMS4 functions independently of MSH5 in the production of viable spores. We propose that MMS4 is required for the processing of specific recombination intermediates during meiosis.

Assessing personality: effects of the depressive state on trait measurement.

The influence of the clinically depressed state on personality assessment was evaluated by comparing self-report personality inventories of patients while clinically depressed and at follow-up 1 year later. The authors examined two groups from the National Institute of Mental Health (NIMH)-Clinical Research Branch Collaborative Program on the Psychobiology of Depression: Clinical Studies--patients whose symptoms had completely remitted and those who had not recovered. The clinically depressed state strongly influenced assessment of emotional strength, interpersonal dependency, and extraversion. Assessment of rigidity, level of activity, and dominance did not change after symptomatic recovery.

The prevalence of dementia, depression and neurosis in later life: the Liverpool MRC-ALPHA Study.

Prevalence rates for psychiatric disorders in the elderly are presented from the initial cross-sectional stage of a longitudinal community study of the incidence of dementia in the city of Liverpool. Together with five other centres in the UK the MRC-ALPHA project forms part of the MRC multicentre incidence study of dementia and cognitive decline. An age- and sex-stratified random sample of 5222 subjects aged > or = 65 was interviewed at home using the Geriatric Mental State-AGECAT package to provide computer diagnoses. The overall age-standardized prevalence rates for organic disorder (4.7%) depressive illness (10.0%) and the neuroses (2.5%) are consistent with levels found in previous smaller studies that have used GMS-AGECAT. Each of these diagnoses is more common in females than males. A rise in organic disorder with age is confirmed as continuing into the oldest age groups for both sexes. An apparent decline with age observed for depression and neurosis diagnoses disappears when organic cases are excluded from the analysis.

Sociodemographic and prior clinical course characteristics associated with treatment response in depressed patients.

A sociodemographic and clinical picture is presented of 82 depressed subjects who had an unequivocal response or lack of response to treatment with amitriptyline or imipramine. Patients with less severe depressive illness were found more likely to respond to treatment, while those with psychotic features were more likely to be treatment resistant. Sociodemographic and other prior and current clinical course variables were not predictive of treatment response in depressed patients.

Schizophrenia and delusional disorder in older age: community prevalence, incidence, comorbidity, and outcome.

The opportunity to assess prevalence, incidence, and outcome of schizophrenia and delusional disorder was provided by an age- and sex-stratified random sample of 5,222 persons age 65 years and over. This sample was chosen from general practitioner lists, and interviewed by psychiatric nurses trained to use the Geriatric Mental State (GMS)-AGECAT computerized diagnostic system. GMS-AGECAT ensured the reliability of the selection of cases between the two waves of the study. A subsample was interviewed by a research psychiatrist. The sample was followed up 2 years later using the same method by interviewers blind to the initial findings. The protocols of all nominated cases and subcases of schizophrenia/paranoid disorder diagnosed by AGECAT were reviewed by a clinician and DSM-III-R diagnoses were made. Refusal rate was 13 percent for initial interviews (wave 1) and 15 percent for reinterview 2 years later (wave 2). The prevalence of DSM-III-R schizophrenia was 0.12 percent (95% confidence interval [CI] 0.04-0.25) and delusional disorder 0.04 percent (95% CI 0.00-0.14). The minimum incidence of schizophrenia for new cases was 3.0 (95% CI 0.00 to 110.70); for new and relapsed cases, 45.0 (95% CI 3.54-186.20); and for delusional disorder, 15.6 (95% CI 0.02-135.10) per 100,000 per year. Two of the five cases with schizophrenia were known to have been first diagnosed before age 65. After 2 years, none of the cases of schizophrenia had recovered fully, but none was deluded at followup. Two had developed dementia. The outcome was bad because they remained cases of some type of psychiatric illness but good because of the improvement in their schizophrenia/delusion disorder symptoms.

Evaluation of the prostate by magnetic resonance imaging.

Forty-seven male patients with suspected prostatic disease underwent magnetic resonance imaging (MRI) of the pelvis on a Picker resistive magnet operating at 0.15 T; 33 had histologically proved adenocarcinoma, 12 benign prostatic hypertrophy, 1 a transitional cell carcinoma, and 1 a seminoma. Eleven normal subjects also were included in the study. The study attempted to (1) define the MRI characteristics of the normal prostate, benign prostatic hypertrophy, and prostatic adenocarcinoma, (2) evaluate various pulse sequences in imaging the prostate, and (3) compare MRI findings with clinical, pathologic, and computed tomography results. Various pulse sequences, including inversion recovery and spin-echo with short and long TE and TR, were used. MRI was sensitive in detecting intracapsular and extracapsular prostatic disease. The finding of inhomogeneous signal texture throughout the gland was a sensitive but nonspecific finding for adenocarcinoma. A focal nodule with prolonged T1 and T2 relaxation times was the most specific MRI finding for adenocarcinoma. Extracapsular spread of neoplasm was often demonstrated, and because of its superior soft-tissue contrast ability, MRI was more accurate than computed tomography in delineating extracapsular extension.

Understanding bone banking.

Allograft bone tissue is frequently used in orthopaedic reconstructive surgery. At many major medical centers, this procedure is as routine as the implantation of manmade metallic prosthetics. The harvesting, preparation, and delivery of bone used for transplantation is a complex and intricate process coupled with varying practices among different bone banks. This article provides the reader with information on current standards and practices in bone banking and transplantation. This will help the perioperative orthopaedic nurse deliver safe patient care during procedures using cadaveric bone and tissue.

NF-κB subunits are differentially distributed in cells of lumbar dorsal root ganglia in naïve and diabetic rats.

Previous studies demonstrated that nuclear factor κB (NF-κB) activation is decreased in dorsal root ganglia (DRG) of rats having streptozotocin (STZ)-induced diabetes. DRG contain cell bodies of neurons that convey sensory signals from the periphery. To determine the relationship between diabetes-induced neuropathy and NF-κB expression in DRG, behavioral, immunohistochemical, and biochemical studies were performed on naïve and 3-month diabetic rats. Behavioral studies confirmed that many diabetic rats develop tactile allodynia, or increased sensitivity to light touch, in the hind paws. Immunohistochemical studies on lumbar DRG that receive input from the affected regions revealed that p50 and p65, frequent NF-κB subunit partners, are differentially localized. Intense p65 immunostaining was detected in the cytoplasm of small- and medium-sized neurons as well as in satellite cells. In contrast, p50 was localized in the cytoplasm of virtually all neurons. In many cases, prominent staining was also present in nuclei, a location consistent with transcription factor activation. Immunohistochemical and biochemical studies found that the nuclear to cytoplasmic ratio of p50 expression was significantly reduced in diabetic rats compared to that in naïve animals. Our findings raise the possibility that changes in NF-κB activation in a subset of DRG neurons participates in mediating diabetes-induced sensory neuropathy.

Functional analysis of two Kir6.2 (KCNJ11) mutations, K170T and E322K, causing neonatal diabetes.

Heterozygous activating mutations in Kir6.2 (KCNJ11), the pore-forming subunit of the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel, are a common cause of neonatal diabetes (ND). We assessed the functional effects of two Kir6.2 mutations associated with ND: K170T and E322K. K(ATP) channels were expressed in Xenopus oocytes, and the heterozygous state was simulated by coexpression of wild-type and mutant Kir6.2 with SUR1 (the beta cell type of sulphonylurea receptor (SUR)). Both mutations reduced the sensitivity of the K(ATP) channel to inhibition by MgATP and enhanced whole-cell K(ATP) currents. In pancreatic beta cells, such an increase in the K(ATP) current is expected to reduce insulin secretion and thereby cause diabetes. The E322K mutation was without effect when Kir6.2 was expressed in the absence of SUR1, suggesting that this residue impairs coupling to SUR1. This is consistent with its predicted location on the outer surface of the tetrameric Kir6.2 pore. The kinetics of K170T channel opening and closing were altered by the mutation, which may contribute to the lower ATP sensitivity. Neither mutation affected the sensitivity of the channel to inhibition by the sulphonylurea tolbutamide, suggesting that patients carrying these mutations may respond to these drugs.

Alpha: the Liverpool MRC Study of the incidence of dementia and cognitive decline.

The design and methods of this longitudinal study of dementia which is underway are described. An age- and sex-stratified random sample of 6,000 elderly community subjects are being re-assessed after a 2-year interval using the GMS-AGECAT package. Alpha forms part of the MRC funded UK multicentre incidence study and an international network of collaborative studies using comparable measures.

Community-based case-control study of depression in older people. Cases and sub-cases from the MRC-ALPHA Study.

BACKGROUND: Risk factors of depression in later life, particularly for sub-cases and for psychotic and neurotic types of depression, are unclear. AIMS: To identify such risk factors. METHOD: Over 5200 older people (> or = 65 years), randomly selected from Liverpool, were interviewed using the Geriatric Mental State (GMS) and the Minimum Data Set (MDS). The computer-assisted diagnosis AGECAT identified 483 cases and 575 sub-cases of depression and 2451 with no mental problems. Logistic regression was employed to examine factors relevant to caseness. RESULTS: In multiple logistical regression, odds ratios (ORs) were significantly high for being female (2.04, 95% CI 1.56-2.69), widowed (2.00, 1.18-3.39), having alcohol problems (4.37, 1.40-2.94), physical disablement (2.03, 1.40-2.94), physical illness (1.98, 1.25-3.15), taking medications to calm down (10.04, 6.41-15.71), and dissatisfaction with life (moderate 4.54, 3.50-5.90; more severe 29.00, 16.00-52.59). Good social networks reduced the ORs. If sub-cases were included as controls, the statistical significance was reduced. CONCLUSIONS: Age was not associated with depression in later life whereas gender, physical disablement and dissatisfaction with life were. The sub-cases shared many risk factors with cases, suggesting that prevention may need to be attempted at an early stage.

Alzheimer's disease, other dementias, depression and pseudodementia: prevalence, incidence and three-year outcome in Liverpool.

A group of 1070 community-living persons aged 65 and over was assessed using the GMS-AGECAT package and other interviews at years 0 and 3. Year 3 interviewers were 'blind' to the findings at year 0, and the prevalence of organic disorders and depression was very similar in both years. According to the results at year 3, minimum and maximum prevalence figures for dementia at year 0 were 2.4% and 3.8% for moderate to severe and 0.4% and 2.4% for mild or early cases, with a best estimate of 3.5% and 0.8%, or 4.3% overall, divided into: senile, Alzheimer's type 3.3%; vascular 0.7%; and alcohol-related 0.3%. The overall incidence of dementia, clinically confirmed by six-year follow-up, was 9.2/1000 per year (Alzheimer type 6.3, vascular 1.9, alcohol related 1.0). Three years later, 72.0% of those with depressive psychosis and 62.3% of those with depressive neurosis were either dead or had some kind of psychiatric illness. Nearly 60% of milder depressive cases (7.2% of the total sample) had either died or developed a chronic mental illness. The outcome of depressive pseudodementias is equivocal so far. Findings at year 3 provide validation of AGECAT computer diagnosis against outcome; organic and depression diagnoses are seen to have important implications for prognosis.

The natural history of neurotic disorder in an elderly urban population. Findings from the Liverpool longitudinal study of continuing health in the community.

A random community sample of 1070 subjects aged 65 years and over was interviewed at home using the GMS-AGECAT package and followed up three years later. Neurotic symptoms were common, but symptoms sufficient to reach 'case' level were much less frequent. The overall prevalence of neurotic 'cases' was 2.4% in year 0 and 1.4% in year 3. The incidence was estimated as a minimum of 4.4 per 1000 per year over the age of 65. Women were more likely to be 'cases' than men but not 'subcases', and there was a general decline in prevalence with increasing age, particularly for 'subcases'. Anxiety was the commonest neurotic subtype. After three years, 'cases' were shown not to persist, but this did not reflect wellness. There was a tendency still to have some symptoms, but the predominant symptom appeared to change, suggesting a possible chronic neurotic disorder with changing presentation over time. Depressive symptoms were closely associated with this presentation, suggesting that depression may be an important and integral part of a general, changing neurotic disorder.