Patients' experiences with pre-test genetic counseling provided by breast cancer healthcare professionals: Results from a large prospective multicenter study.

BACKGROUND: Pre-test genetic counseling of patients with breast cancer is increasingly being offered by non-genetic healthcare professionals. We aimed to evaluate the experiences of patients with breast cancer receiving pre-test genetic counseling from a non-genetic healthcare professional (i.e., surgeon or nurse). METHODS: Patients who were diagnosed with breast cancer and received pre-test counseling from their surgeon or nurse (mainstream group), and patients who received pre-test counseling from a clinical geneticist (usual care group) were invited to participate in our multicenter study. Between September 2019 and December 2021, patients received a questionnaire after pre-test counseling (T0) and four weeks after receiving their test results (T1) to evaluate psychosocial outcomes, knowledge, discussed topics and satisfaction. RESULTS: We included 191 patients in our mainstream and 183 patients in our usual care group and received, respectively 159 and 145 follow-up questionnaires. Levels of distress and decisional regret were comparable in both groups. Decisional conflict was higher in our mainstream group (p = 0.01), but only 7% had clinically relevant decisional conflict (vs 2% in usual care group). The possible implications of a genetic test on (secondary) breast or ovarian cancer risks were less frequently discussed in our mainstream group (p = 0.03 and p = 0.000, respectively). In both groups knowledge about genetics was comparable, satisfaction was high and the majority of patients in both groups preferred to give both verbal and written consent for genetic testing. CONCLUSION: Mainstreamed genetic care provides sufficient information for the majority of breast cancer patients to decide about genetic testing with minimal distress.

Comparison of ultrasonography and physical examination in the diagnosis of incisional hernia in a prospective study.

PURPOSE: Incisional hernia is a frequent complication of abdominal surgery (incidence 2-20%). Diagnosis by physical examination is sometimes difficult, especially in small incisional hernias or in obese patients. The additional diagnostic value of standardized ultrasonography was evaluated in this prospective study. METHODS: A total of 456 patients participating in a randomized trial comparing two suture materials for closure of the abdominal fascia underwent physical examination and ultrasonography at 6-month intervals. Wound complaints and treatment of incisional hernia were also noted. Statistical analysis was performed using the Chi-squared and Fisher's exact tests (SPSS). Interest variability analysis was performed. RESULTS: During a median follow-up of 31 months, 103 incisional hernias were found. A total of 82 incisional hernias were found by physical examination and an additional 21 with ultrasonography. Six of these additional hernias were symptomatic and only one of the additional hernias received operative treatment. The false-negative rates for physical examination and ultrasonography were 25.3 and 24.4%, respectively. Interest variability was low, with a Kappa of 0.697 (P < 0.001). CONCLUSIONS: There are no clear diagnostic criteria for incisional hernia available in the literature. Standardized combination of ultrasonography with physical examination during follow-up yields a significant number of, mostly asymptomatic, hernias, which would not be found using physical examination alone. This is especially relevant in research settings.

Randomized clinical trial comparing polypropylene or polydioxanone for midline abdominal wall closure.

BACKGROUND: Incisional hernia is a frequent complication of abdominal surgery, often requiring surgical intervention. This prospective randomized trial compared suture materials for closure of the fascia after abdominal surgery. METHODS: In 456 patients the abdominal fascia was closed with either non-absorbable (polypropylene; Prolene(®)) or absorbable (polydioxanone; PDS(®)) suture material. Follow-up was by clinical examination and ultrasonography at 6-month intervals. Outcome measures were incisional hernia, surgical-site infection and suture sinus. RESULTS: Some 223 patients were analysed after closure with Prolene(®) and 233 after PDS(®) . Median follow-up was 32 and 31 months respectively. There was no significant difference in the incidence of incisional hernia between the groups: 20·2 per cent (45 of 223) for Prolene(®) and 24·9 per cent (58 of 233) with PDS(®) (P = 0·229). Kaplan-Meier analysis showed a cumulative rate after 4 years of 23·7 and 30·2 per cent for Prolene(®) and PDS(®) respectively (P = 0·222). Secondary outcome measures showed no significant differences. CONCLUSION: The incidence of incisional hernia in both groups was higher than expected from previous literature. There were no significant differences between the two suture methods. REGISTRATION NUMBER: ISRCTN65599814 (http://www.clinical-trials.com).

Remifentanil pharmacokinetics in obese versus lean patients.

BACKGROUND: Remifentanil is a short-acting opioid whose pharmacokinetics have been characterized in detail. However, the impact of obesity on remifentanil pharmacokinetics has not been specifically examined. The goal of this study was to investigate the influence of body weight on remifentanil pharmacokinetics. METHODS: Twelve obese and 12 matched lean subjects undergoing elective surgery received a 1-min remifentanil infusion after induction of anesthesia. Arterial blood samples were collected for determination of remifentanil blood concentrations. Each subject's pharmacokinetic parameters were estimated by fitting a two-compartment model to the concentration versus time curves. Nonlinear mixed-effects population models examining the influence of lean body mass (LBM) and total body weight (TBW) were also constructed. Clinical simulations using the final population model were performed. RESULTS: The obese patient cohort reached substantially higher remifentanil concentrations. The individual pharmacokinetic parameters of a two-compartment model were not significantly different between the obese versus lean cohorts (unless normalized to TBW). The final population model scaled central clearance and the central and peripheral distribution volumes to LBM. The simulations illustrated that remifentanil pharmacokinetics are not grossly different in obese versus lean subjects and that TBW based dosing in obese patients can result in excessively high remifentanil concentrations. CONCLUSIONS: The essential findings of the study are that remifentanil's pharmacokinetics are not appreciably different in obese versus lean subjects and that remifentanil pharmacokinetic parameters are therefore more closely related to LBM than to TBW. Clinically this means that remifentanil dosing regimens should be based on ideal body weight (or LBM) and not TBW.

The molecular fossil record of oleanane and its relation to angiosperms.

Oleanane has been reported in Upper Cretaceous and Tertiary source rocks and their related oils and has been suggested as a marker for flowering plants. Correspondence of oleanane concentrations relative to the ubiquitous microbial marker 17alpha-hopane with angiosperm diversification (Neocomian to Miocene) suggests that oleanane concentrations in migrated petroleum can be used to identify the maximum age of unknown or unavailable source rock. Rare occurrences of pre-Cretaceous oleanane suggest either that a separate lineage leads to the angiosperms well before the Early Cretaceous or that other plant groups have the rarely expressed ability to synthesize oleanane precursors.

The role of minerals in the thermal alteration of organic matter--IV. Generation of n-alkanes, acyclic isoprenoids, and alkenes in laboratory experiments.

A series of pyrolysis experiments, utilizing two different immature oil-prone kerogens ("type I": Green River Formation kerogen; "Type II": Monterey Formation kerogen) mixed with common sedimentary minerals (calcite, illite, or Na-montmorillonite), was conducted to study the effects of minerals on the generation of n-alkanes, acyclic isoprenoids, and alkenes during laboratory-simulated catagenesis of kerogen. The influence of clay minerals on the aliphatic hydrocarbons is critically dependent on the water concentration during laboratory thermal maturation. Under extremely low contents of water (i.e., dry pyrolysis, where only pyrolysate water is present), C12(+) -range n-alkanes and acyclic isoprenoids are mostly destroyed by montmorillonite but undergo only minor alteration with illite. Both clay minerals significantly reduce alkene formation during dry pyrolysis. Under hydrous conditions (mineral/water = 2:1), the effects of the clay minerals are substantially reduced. In addition, the dry pyrolysis experiments show that illite and montmorillonite preferentially retain large amounts of the polar constituents of bitumen, but not n-alkanes or acyclic isoprenoids. Therefore, bitumen fractionation according to polarity differences occurs in the presence of these clay minerals. By this process, n-alkanes and acyclic isoprenoids are concentrated in the bitumen fraction that is not strongly adsorbed on the clay matrices. The extent of these concentrations effects is greatly diminished during hydrous pyrolysis. In contrast, calcite has no significant influence on the thermal evolution of the hydrocarbons. In addition, calcite is incapable of retaining bitumen. Therefore, the fractionation of n-alkanes or acyclic isoprenoids relative to the polar constituents of bitumen is insignificant in the presence of calcite.

The role of minerals in the thermal alteration of organic matter--III. Generation of bitumen in laboratory experiments.

A series of pyrolysis experiments, utilizing two different immature kerogens (from the Monterey and Green River Formations) mixed with common sedimentary minerals (calcite, illite, or Na-montmorillonite), was conducted to study the impact of the mineral matrix on the bitumen that was generated. Calcite has no significant influence on the thermal evolution of bitumen and also shows virtually no adsorption capacity for any of the pyrolysate. In contrast, montmorillonite and illite, to a lesser extent, alter bitumen during dry pyrolysis. Montmorillonite and illite also display strong adsorption capacities for the polar constituents of bitumen. By this process, hydrocarbons are substantially concentrated within the pyrolysate that is not strongly adsorbed on the clay matrices. The effects of the clay minerals are significantly reduced during hydrous pyrolysis. The strong adsorption capacities of montmorillonite and illite, as well as their thermocatalytic properties, may in part explain why light oils and gases are generated from certain argillaceous source-rock assemblages, whereas heavy immature oils are often derived from carbonate source rocks.

Role of minerals in thermal alteration of organic matter--II: a material balance.

Pyrolysis experiments were performed on Green River and Monterey Formation kerogens (Types I and II, respectively) with and without calcite, illite, or montmorillonite at 300 degrees C for 2 to 1,000 hours under dry and hydrous conditions. Pyrolysis products were identified and quantified, and a material balance of product and reactants resulted. Significant differences were found in the products generated by pyrolysis of kerogens with and without minerals. Both illite and montmorillonite adsorb a considerable portion (up to 80%) of the generated bitumen. The adsorbed bitumen is almost exclusively composed of polar compounds and asphaltenes that crack to yield low molecular weight compounds and insoluble pyrobitumen during prolonged heating. Montmorillonite shows the most pronounced adsorptive and catalytic effects. With calcite however, the pyrolysis products are similar to those from kerogen heated alone, and bitumen adsorption is negligible. Applying these results to maturation of organic matter in natural environments, we suggest that a given type of organic matter associated with different minerals in source rocks will yield different products. Furthermore, the different adsorption capacities of minerals exert a significant influence on the migration of polar and high molecular weight compounds generated from the breakdown of kerogen. Therefore, the overall accumulated products from carbonate source rocks are mainly heavy oils with some gas, whereas light oils and gases are the main products from source rocks that contain expandable clays with catalytic and adsorptive properties.

Biological marker distribution in coexisting kerogen, bitumen and asphaltenes in Monterey Formation diatomite, California.

Organic-rich (18.2%) Monterey Formation diatomite from California was studied. The organic matter consist of 94% bitumen and 6% kerogen. Biological markers from the bitumen and from pyrolysates of the coexisting asphaltenes and kerogen were analyzed in order to elucidate the relationship between the various fractions of the organic matter. While 17 alpha(H), 18 alpha(H), 21 alpha(H)-28,30-bisnorhopane was present in the bitumen and in the pryolysate of the asphaltenes, it was not detected in the pyrolysates of the kerogen. A C40-isoprenoid with "head to head" linkage, however, was present in pyrolysates of both kerogen and asphaltenes, but not in the bitumen from the diatomite. The maturation level of the bitumen, based on the extent of isomerization of steranes and hopanes, was that of a mature oil, whereas the pyrolysate from the kerogen showed a considerably lower maturation level. These relationships indicate that the bitumen may not be indigenous to the diatomite and that it is a mature oil that migrated into the rock. We consider the possibility, however, that some of the 28,30-bisnorhopane-rich Monterey Formation oils have not been generated through thermal degradation of kerogen, but have been expelled from the source rock at an early stage of diagenesis.

Long-chain carboxylic acids in pyrolysates of Green River kerogen.

Long-chain fatty acids (C10-C32), as well as C14-C21 isoprenoid acids (except for C18), have been identified in anhydrous and hydrous pyrolyses products of Green River kerogen (200-400 degrees C, 2-1000 hr). These kerogen-released fatty acids are characterized by a strong even/odd predominance (CPI: 4.8-10.2) with a maximum at C16 followed by lesser amounts of C18 and C22 acids. This distribution is different from that of unbound and bound geolipids extracted from Green River shale. The unbound fatty acids show a weak even/odd predominance (CPI: 1.64) with a maximum at C14, and bound fatty acids display an even/odd predominance (CPI: 2.8) with maxima at C18 and C30. These results suggest that fatty acids were incorporated into kerogen during sedimentation and early diagenesis and were protected from microbial and chemical changes over geological periods of time. Total quantities of fatty acids produced during heating of the kerogen ranged from 0.71 to 3.2 mg/g kerogen. Highest concentrations were obtained when kerogen was heated with water for 100 hr at 300 degrees C. Generally, their amounts did not decrease under hydrous conditions with increase in temperature or heating time, suggesting that significant decarboxylation did not occur under the pyrolysis conditions used, although hydrocarbons were extensively generated.

Volatile organic acids generated from kerogen during laboratory heating.

Low molecular weight organic acids were studied in the course of pyrolysis experiments (200-400 degrees C, 2-1,000 h) of kerogen (Green River Formation and Monterey Formation) with and without the presence of water and minerals (montmorillonite, illite and calcite). C1-C10 aliphatic acids and benzoic acid were identified in the pyrolysis products of kerogen. Their distribution is characterized by a dominance of acetic acid followed by formic and propionic acids with an even/odd preference in the range of C4-C10. Total concentrations of these acids amounted to 0.3% of initial kerogen, indicating that kerogen has a good potential for producing organic acids. Geochemical implications of these organic acids are; (1) they are possible intermediates from kerogen to natural gas (CO2, H2, CH4, C2H6, etc.) by decarboxylation, and (2) they may be important and potential contributors to the generation of secondary porosity by dissolving minerals.