Pre-treatment expectations of patients with spinal metastases: what do we know and what can we learn from other disciplines? A systematic review of qualitative studies.

BACKGROUND: Little is known about treatment expectations of patients with spinal metastases undergoing radiotherapy and/or surgery. Assuming that patients with spinal metastases share characteristics with patients who had spinal surgery for non-cancer related conditions and with advanced cancer patients, we performed a systematic review to summarize the literature on patient expectations regarding treatment outcomes of spinal surgery and advanced cancer care. METHODS: A comprehensive search was performed in MEDLINE, EMBASE and PsycINFO for studies between 2000 and sep-2019. Studies including adult patients (> 18 years), undergoing spinal surgery or receiving advanced cancer care, investigating patients' pre-treatment expectations regarding treatment outcomes were included. Two independent reviewers screened titles, abstracts and full-texts, extracted data and assessed methodological quality. RESULTS: The search identified 7343 articles, of which 92 were selected for full-text review. For this review, 31 articles were included. Patients undergoing spinal surgery had overly optimistic expectations regarding pain and symptom relief, they underestimated the probability of functional disability, and overestimated the probability of (complete) recovery and return to work. Studies highlighted that patients feel not adequately prepared for surgery in terms of post-treatment expectations. Similarly, advanced cancer patients receiving palliative treatment often had overly optimistic expectations regarding their survival probability and cure rates. CONCLUSIONS: Patients tend to have overly optimistic expectations regarding pain and symptom relief, recovery and prognosis following spinal surgery or advanced cancer care. Pretreatment consultation about the expected pain and symptom relief, recovery and prognosis may improve understanding of prognosis, and promote and manage expectations, which, in turn, may lead to better perceived outcomes. TRIAL REGISTRATION: PROSPERO registration number: CRD42020145151 .

Obliquity-paced Pliocene West Antarctic ice sheet oscillations.

Thirty years after oxygen isotope records from microfossils deposited in ocean sediments confirmed the hypothesis that variations in the Earth's orbital geometry control the ice ages, fundamental questions remain over the response of the Antarctic ice sheets to orbital cycles. Furthermore, an understanding of the behaviour of the marine-based West Antarctic ice sheet (WAIS) during the 'warmer-than-present' early-Pliocene epoch ( approximately 5-3 Myr ago) is needed to better constrain the possible range of ice-sheet behaviour in the context of future global warming. Here we present a marine glacial record from the upper 600 m of the AND-1B sediment core recovered from beneath the northwest part of the Ross ice shelf by the ANDRILL programme and demonstrate well-dated, approximately 40-kyr cyclic variations in ice-sheet extent linked to cycles in insolation influenced by changes in the Earth's axial tilt (obliquity) during the Pliocene. Our data provide direct evidence for orbitally induced oscillations in the WAIS, which periodically collapsed, resulting in a switch from grounded ice, or ice shelves, to open waters in the Ross embayment when planetary temperatures were up to approximately 3 degrees C warmer than today and atmospheric CO(2) concentration was as high as approximately 400 p.p.m.v. (refs 5, 6). The evidence is consistent with a new ice-sheet/ice-shelf model that simulates fluctuations in Antarctic ice volume of up to +7 m in equivalent sea level associated with the loss of the WAIS and up to +3 m in equivalent sea level from the East Antarctic ice sheet, in response to ocean-induced melting paced by obliquity. During interglacial times, diatomaceous sediments indicate high surface-water productivity, minimal summer sea ice and air temperatures above freezing, suggesting an additional influence of surface melt under conditions of elevated CO(2).

Novel mRNA isoforms and mutations of uridine monophosphate synthetase and 5-fluorouracil resistance in colorectal cancer.

The drug fluorouracil (5-FU) is a widely used antimetabolite chemotherapy in the treatment of colorectal cancer. The gene uridine monophosphate synthetase (UMPS) is thought to be primarily responsible for conversion of 5-FU to active anticancer metabolites in tumor cells. Mutation or aberrant expression of UMPS may contribute to 5-FU resistance during treatment. We undertook a characterization of UMPS mRNA isoform expression and sequence variation in 5-FU-resistant cell lines and drug-naive or -exposed primary and metastatic tumors. We observed reciprocal differential expression of two UMPS isoforms in a colorectal cancer cell line with acquired 5-FU resistance relative to the 5-FU-sensitive cell line from which it was derived. A novel isoform arising as a consequence of exon skipping was increased in abundance in resistant cells. The underlying mechanism responsible for this shift in isoform expression was determined to be a heterozygous splice site mutation acquired in the resistant cell line. We developed sequencing and expression assays to specifically detect alternative UMPS isoforms and used these to determine that UMPS was recurrently disrupted by mutations and aberrant splicing in additional 5-FU-resistant colorectal cancer cell lines and colorectal tumors. The observed mutations, aberrant splicing and downregulation of UMPS represent novel mechanisms for acquired 5-FU resistance in colorectal cancer.

Accuracy of hospital-based surveillance systems for surgical site infection after adult spine surgery: a Bayesian latent class analysis.

BACKGROUND: Surgical site infections (SSIs) of the spine are morbid and costly complications. An accurate surveillance system is required to properly describe the disease burden and the impact of interventions that mitigate SSI risk. Unfortunately, uniform approaches to conducting SSI surveillance are lacking because of varying SSI case definitions, the lack of a perfect reference case definition and heterogeneous data sources. AIM: To assess the accuracy of four independent data sources that capture SSIs after spine surgery, with estimation of a measurement-error-adjusted SSI incidence. METHODS: A Bayesian latent class model assessed the sensitivity/specificity of each data source to identify SSI and to estimate a measurement-error-adjusted incidence. The four data sources used were: the discharge abstract database (DAD), the National Surgical Quality Improvement Program (NSQIP) database, the Infection Prevention and Control Canada (IPAC) database, and the Spine Adverse Events Severity database. FINDINGS: A total of 904 patients underwent spine surgery in 2017. The most sensitive data source was DAD (0.799; 95% credible interval (CrI): 0.597-0.943); the least sensitive was NSQIP (0.497; 95% CrI: 0.308-0.694). The most specific data source was IPAC (0.997; 95% CrI: 0.993-1.000) and the least specific was DAD (0.969; 95% CrI: 0.956-0.981). The measurement-error-adjusted SSI incidence was 0.030 (95% CrI: 0.019-0.045). The crude incidence using the DAD overestimated the incidence, and the three other data sources underestimated it. CONCLUSION: SSI surveillance in the spine surgery population is feasible using several data sources, provided that measurement error is considered.

[Clinical features of adults younger and older than 50 years hospitalized with influenza A H1N1 2009 in a private hospital in Santiago, Chile]. / Caracterización clínica de adultos menores y mayores de 50 años hospitalizados por influenza A H1N1 2009 en un centro hospitalario privado en Santiago, Chile.

INTRODUCTION: The new pandemic influenza A H1N1 2009 virus has shown a different clinical behavior in different age groups. OBJECTIVE: To describe the clinical features of adult patients hospitalized with influenza AH1N1 2009 and compare the clinical and demographic variables among adults < 50 years and over 50 years old. PATIENTS AND METHOD: We included hospitalized patients between May 17 and July 17, 2009 confirmed by polymerase chain reaction (PCR) and/or rapid test for influenza A. RESULTS: 124 patients were hospitalized with a median age of 33 years (range: 15-82 years). 36% had comorbidities and the main symptoms were fever, cough, myalgia and sore throat. There were 16 cases with pneumonia. From 124 patients, 77% were < 50 and 23% > or = 50, [corrected] with comorbidity of 21% and 86%, respectively. There were no fatalities. CONCLUSIONS: Hospitalized patients had mild to moderate disease, a benign course and short hospitalization stay. There were more hospitalizations in A-49 and higher comorbidity in A-50.

Pleistocene climates in the atlantic and pacific oceans: a reevaluated comparison based on deep-sea sediments.

Variations of the Globorotalia menardii complex in cores from the Indian Ocean can be interpreted as indicating climatic changes that are opposite to trends exhibited by the total planktonic fauna. The questionable value of correlations between different water masses based on a single species can be shown by Neogloboquadrina dutertrei subcretacea in cores obtained off the coast of California and Baja California. This information, in addition to previous correlations between Quaternary cores of the Atlantic and Pacific oceans, indicates that the Pleistocene history of the two oceans was parallel.

Relative specificities of inhibition of acid cholesteryl ester hydrolase and neutral cholesteryl ester hydrolase in cultured rabbit aortic smooth muscle cells by esterastin and cholesteryl oleyl ether.

Rabbit aortic smooth muscle cells in culture were incubated with 0.04-500 M esterastin. Acid cholesteryl ester hydrolase (ACEH) and neutral cholesteryl ester hydrolase (NCEH) activities were inhibited to a comparable degree, with 50% inhibition occurring in the range of 0.4 M esterastin. Cells incubated with cholesteryl oleyl ether showed 50% inhibition of NCEH at 5.0 M, but no inhibition of ACEH over a concentration range of 0.2-20 M. This relative specificity of cholesteryl oleyl ether for NCEH can be employed to study the relative roles of ACEH vs. NCEH in preventing cellular cholesteryl ester accumulation.

Effect of membrane cholesterol enrichment or depletion on the partition behavior of human erythrocytes in dextran-poly(ethylene glycol) aqueous phases.

It has previously been shown that by appropriate manipulation of polymer concentrations and ionic composition and concentration one can select whether charge-associated or lipid-related membrane surface properties are reflected by cell partition in dextran-poly(ethylene glycol) aqueous two-phase systems (Walter, H. (1977) in Methods of Cell Separation ((Catsimpoolas, N., ed.), Vol. 1, pp. 307-354, Plenum Press, New York). In the current experiments we have studied that partition behavior of human erythrocytes and found that not only lipid-related but also charge-associated membrane properties are altered as a consequence of cholesterol-enrichment or -depletion. Results further indicate that, just as cell partition in charged phase systems reflects membrane charge-associated properties not readily measured by means other than partition (Brooks, D.E., Seaman, G.V.F. and Walter, H. (1971) Nat. New Biol. 234, 61--62; Walter, H., Tung, R., Jackson, L.J. and Seaman, G.V.F. (1972) Biochem. Biophys. Res. Commun. 48, 565--571), cell partition in uncharged phases reflects membrane lipid-related properties also not readily measured by other means.

Accuracy of implanted port placement with the use of the electromagnetic CathTrack catheter locator system.

PURPOSE: To test whether an electromagnetic guidance system such as CathTrack would allow long-term central venous access devices to be reliably placed at a decreased cost and without radiation exposure to patients and staff. The following study was undertaken to verify accuracy of the CathTrack system for catheter placement and to develop guidelines for its use. METHODS: Twenty-nine consecutive patients were prospectively enrolled in the study and taken to the operating room for implantation of a permanent central venous access port. By protocol, the CathTrack system was used to guide initial catheter positioning using the center of the third intercostal space along the right sternal border as the desired external target. Fluoroscopy was then used to visualize tip position and relocate the catheter tip to the exact position desired by the surgeon. RESULTS: Catheter placement using the CathTrack system was successfully accomplished in 27 out of 29 patients. In two instances CathTrack was abandoned and fluoroscopy utilized because of difficulty in threading the initial guidewire into the superior vena cava. CONCLUSION: The CathTrack electromagnetic locator system can be used to reliably position catheters for the establishment of long-term central venous access. Decreased cost and elimination of radiation exposure are distinct advantages of this system over fluoroscopy.

Effects of chronic estrogen replacement therapy on beat-to-beat blood pressure dynamics in healthy postmenopausal women.

Recent data showing gender differences in autonomic control of heart rate and acute estrogen effects on vasodilatation suggest that estrogen may influence autonomic regulation of heart rate and blood pressure. We aimed to determine the effect of postmenopausal estrogen replacement therapy on autonomic control of beat-to-beat heart rate and blood pressure dynamics. Subjects included 20 healthy postmenopausal women aged 60 to 75 years with normal exercise tolerance tests, 10 of whom were taking oral estrogen for 13 +/- 3 (+/- SEM) years. Six healthy premenopausal women were also studied. Continuous electrocardiographic and noninvasive radial artery blood pressure measurements and intermittent forearm blood flow recordings (by venous-occlusion plethysmography) were obtained before and after a 20-minute, 60 degrees head-up tilt and a 420-kcal meal during periods of spontaneous and metronomic breathing (at 0.25 Hz). Low-frequency (0.01- to 0.15-Hz) and high-frequency (0.15- to 0.50-Hz) heart rate and blood pressure spectral powers were compared with a fast Fourier transform. Cardiovascular and heart rate spectral power responses to upright tilt and meal digestion were the same in postmenopausal estrogen users and nonusers. However, during spontaneous breathing the blood pressure spectral power responses to upright tilt and meal ingestion were significantly different between the two groups of women. The low-frequency systolic pressure power response to upright tilt was smaller in estrogen users than nonusers (P = .01). After meal ingestion nonusers had an early postprandial fall (20 to 30 minutes after the meal) and late rise (50 to 60 minutes) in low-frequency systolic and diastolic pressure powers, which were significantly attenuated in estrogen users (P < .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of age and gender on autonomic control of blood pressure dynamics.

Both age and gender influence cardiovascular autonomic control, which in turn may influence the ability to withstand adverse cardiac events and respond to orthostatic stress. The purpose of this study was (1) to quantify age- and gender- related alterations in autonomic control of blood pressure (BP) and (2) to examine the impact of these autonomic alterations on BP response to orthostatic stress. We measured continuous BP and R-R intervals and vasoactive peptide levels in the supine and 60 degrees head-up tilt positions during paced respiration (0.25 Hz) in 89 carefully screened healthy subjects (41 men, 48 women, aged 20 to 83 years). Data were analyzed by gender (age adjusted) and by age group (gender adjusted). During tilt, women had greater decreases in systolic BP than men (-10.2+/-2 versus -1.2+/-3 mm Hg; P=0.02) and smaller increases in low-frequency (sympathetically mediated) BP power (P=0.02). Upright plasma norepinephrine was lower in women (P=0.02). Women had greater supine high-frequency R-R interval power than men (P=0.0001). In elderly subjects, the tilt-induced increase in low-frequency BP power was also diminished (P=0.01), despite higher supine (P=0.02) and similar upright norepinephrine levels compared with younger subjects. Thus, healthy women have less sympathetic influence on BP and greater parasympathetic influence on R-R interval than men. Elderly subjects also have reduced sympathetic influence on BP, but this appears to be more consistent with a reduction in vasomotor sympathetic responsiveness.

Hypocholesterolemic effect of yogurt and milk.

In order to determine the effect of milk products on serum cholesterol, triglycerides, and diet, 54 volunteers were studied for varying periods with dietary supplementation of nonpasteurized yogurt, pasteurized yogurt and 2% butterfat milk. Serum cholesterol was significantly reduced by 5 to 10% after 1 week of supplementation with either nonpasteurized or pasteurized yogurt; 2% butterfat milk reduced serum cholesterol to a smaller and less significant effect. Serum triglycerides were unaffected by the diet and dietary intake studies confirmed that intake of other nutrients remained relatively stable throughout the study. Supplementation of diet with yogurt may have a helpful hypocholesterolemic effect.

Comparison of acetate-1-14C metabolism in uremic and nonuremic dogs.

Acetate-1-14C was infused into six anephric uremic and six anephric nonuremic dogs during a 4-hr hemodialysis against a standard acetate containing (39.5 mM) dialysis solution. Arterial acetate (nonradioactive) levels achieved a steady state by the end of dialysis indicating that the maximum rate of acetate metabolism had not been exceeded. The mean arterial acetate level at the end of dialysis was 2.6 mM in both groups of dogs. Acetate disappearance after the cessation of dialysis followed first order kinetics with a mean half-life of 3.8 +/- 0.5 min in the uremic and 3.7 +/- 0.5 min in the nonuremic dogs. Most of the infused acetate-1-14C was metabolized to 14CO2 within 8 hr after dialysis. An average of 84 and 71% of the infused acetate-1-14C was metabolized to 14CO2 in the uremic and nonuremic dogs, respectively. Small but significant amounts of radioactivity were incorporated into lipids of plasma and other tissues. Incorporation of radioactivity into total lipids of liver, omental fat, and sciatic nerve was significantly greater in the uremic as compared to the nonuremic dogs. Incorporation of radioactivity into total lipids of heart, aorta, and plasma was the same in both groups of dogs.

Intestinal adaptation after jejunoileal bypass in man.

Gastrointestinal anatomy and function has been studied prospectively in 12 patients undergoing jejunoileal bypass surgery in order to investigate the adaptive response of the intestinal mucosa. The total thickness of the jejunal mucosa did not change after surgery, but the crypts became relatively deeper, suggesting a more rapid turnover of gastrointestinal cells. The absorption of oxalate was depressed in the immediate postoperative period but had improved toward preoperative levels by 6 months. Vitamin B12 absorption also declined postoperatively, and increased thereafter in the patients with an end-to-end jejunoileostomy, but showed a much smaller recovery in the group with an end-to-side anastomosis. The cholesterol concentration (lithogenicity) of the duodenal bile rose by 30% in the first 3 weeks after surgery, but had returned to preoperative levels by 6 months. The segmental absorption of glucose across the jejunum declined after surgery. Caloric intake also declined, whether measured as the quantity of food that patients elected to eat over a 24-hr period, or as the quantity of a liquid lunch which they consumed over a 20-min period. The level of basal gastric acid was increased postoperatively but the maximal output after histamine stimulation was not. The gastrin response to a standard liquid meal was also significantly increased after surgery. Enteroglucagon secretion showed an increase in 3 weeks and a further increase by 6 months after intestinal bypass surgery. The significance of these changes to intestinal adaptations is discussed.

Transport of cholesterol autoxidation products in rabbit lipoproteins.

Radiolabeled pure [4-14C]cholesterol was kept at 60 degrees C under air to autoxidize for 5 weeks, after which approximately 12% cholesterol oxidation products were formed. The mixture, suspended in gelatin, was given to rabbits by gastric gavage. Rabbits were killed 4, 24, and 48 h after treatment. Cholesterol and its autoxidation products were separated by thin-layer chromatography into 5 fractions and radioactivities of each fraction were measured. Percentages of each fraction of cholesterol oxidation products and cholesterol in the original mixture before administration and in the rabbit sera after administration were similar, suggesting that the rates of absorption of cholesterol oxidation products are not significantly different from that of cholesterol. Lipoproteins were fractionated by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each fraction in lipoproteins separated by thin layer chromatography showed that fractions containing cholestane-3 beta,5 alpha,6 beta-triol, 7 alpha- and 7 beta-hydroxycholesterol and 7-ketocholesterol were more selectively transported in VLDL, whereas most of the 25-hydroxycholesterol was present in LDL. HDL contained only minute amounts of cholesterol oxidation products.

Cholesterol oxidation derivatives and arterial endothelial damage.

Three groups of New Zealand male while rabbits were given either 2.5 mg/kg of 25-hydroxycholesterol, cholestane-3 beta, 5 alpha, 6 beta-triol or vehicle only, intravenously. 24 h after treatment, the luminal surfaces of aortae of rabbits receiving 25-hydroxycholesterol were examined by scanning electron microscopy (SEM) and showed numerous balloon-like protrusions and crater-like defects as well as circulating, formed elements adhering on the luminal surface. The luminal surface of aortae of rabbits given cholestane-3 beta, 5 alpha, 6 beta-triol had similar but more frequent lesions when compared with those of the 25-hydroxycholesterol group. Microthrombi were occasionally found. The aortae of the control group had significantly fewer lesions. Transmission electron-microscopic studies showed intracytoplasmic vacuoles and diffuse subendothelial edema in the aortae of the two groups receiving the oxidation derivatives of cholesterol. The balloon-like protrusions and crater-like defects observed by SEM appeared to represent the initial sterol-induced endothelial cell injury. Repeated episodes of arterial injury followed by thrombus formation could eventually lead to atherosclerosis.

A survey of radiation oncologists regarding their radiation physics instruction.

The American Association of Physicists in Medicine, Committee on Training of Radiologists conducted a survey of radiation oncologists requesting information regarding their radiation oncology physics training. General questions were asked of the oncologist regarding their radiation oncology practice such as number of oncologists, number of new patients treated, and the size and type of facility in which the practice is located. The oncologist also responded to questions regarding their educational background. The survey requested the radiation oncologists to answer questions regarding the adequacy and importance of their training in specific areas of radiation physics. The responders indicated that the importance of most physics topics in their clinical practice corresponded to the level of their understanding. The survey indicated that for most radiation oncologists their physics instruction was an important and interesting part of their residency program.

Behavioral and serotonin receptor properties of 4-substituted derivatives of the hallucinogen 1-(2,5-dimethoxyphenyl)-2-aminopropane.

The serotonin (5-HT) receptor affinities and behavioral (discriminative stimulus) properties of a series of 4-substituted derivatives of 1-(2,5-dimethoxyphenyl)-2-aminopropanes (2,5-DMA) were investigated. The substituents at the 4-position included H, OMe, OEt, Me, Et, F, Br, I, and NO2. Substituent lipophilicities (pi values) of these functionalities appear to have a minimal effect on either 5-HT receptor affinity or behavioral activity. Those derivatives previously found to be most potent in human studies possess significant affinity for 5-HT receptors. Furthermore, when rats trained to discriminate (+/-)-1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) from saline were used, generalization was found to occur upon administration of the 4-substituted 2,5-DMA derivatives. Because a direct relationship exists between the ED50 values obtained from these discrimination studies and human hallucinogenic potencies, the discriminative stimulus paradigm, with DOM as a training drug, appears to be a useful tool for comparing the quantitative and qualitative (DOM-like) effects produced by certain hallucinogenic agents.

Structure-activity relationships in potentially hallucinogenic N,N-dialkyltryptamines substituted in the benzene moiety.

A series of N,N-dialkyltryptamines with methylthio or methylenedioxy substituents in the 4, 5, and 6 positions and methyl or isopropyl on the side-chain nitrogen has been synthesized. The behavioral pharmacology of these compounds showed them to possess Bovet-Gatti profiles characteristic of hallucinogens, and the 5-methylthio congener was the most potent. Binding studies at [3H]LSD and [3H]5-HT sites demonstrated that no single structural feature correlated with binding or behavioral changes and suggest a complex mode of action for these potential hallucinogenic agents.

Structure-activity relationships for hallucinogenic N,N-dialkyltryptamines: photoelectron spectra and serotonin receptor affinities of methylthio and methylenedioxy derivatives.

Serotonin receptor affinity and photelectron spectral data were obtained on a number of substituted N,N-dimethyltryptamines. Evidence is presented that electron-donating substituents in the 5-position lead to enhanced behavioral disruption activity and serotonin receptor affinity as compared to unsubstituted N,N-dimethyltryptamine and analogues substituted in the 4- or 6-position. Some correlation was found between ionization potentials and behavioral activity, which may have implications concerning the mechanism of receptor binding.