Will I soon be out of my job? Quality and guideline conformity of ChatGPT therapy suggestions to patient inquiries with gynecologic symptoms in a palliative setting.

PURPOSE: The market and application possibilities for artificial intelligence are currently growing at high speed and are increasingly finding their way into gynecology. While the medical side is highly represented in the current literature, the patient's perspective is still lagging behind. Therefore, the aim of this study was to evaluate the recommendations of ChatGPT regarding patient inquiries about the possible therapy of gynecological leading symptoms in a palliative situation by experts. METHODS: Case vignettes were constructed for 10 common concomitant symptoms in gynecologic oncology tumors in a palliative setting, and patient queries regarding therapy of these symptoms were generated as prompts for ChatGPT. Five experts in palliative care and gynecologic oncology evaluated the responses with respect to guideline adherence and applicability and identified advantages and disadvantages. RESULTS: The overall rating of ChatGPT responses averaged 4.1 (5 = strongly agree; 1 = strongly disagree). The experts saw an average guideline conformity of the therapy recommendations with a value of 4.0. ChatGPT sometimes omits relevant therapies and does not provide an individual assessment of the suggested therapies, but does indicate that a physician consultation is additionally necessary. CONCLUSIONS: Language models, such as ChatGPT, can provide valid and largely guideline-compliant therapy recommendations in their freely available and thus in principle accessible version for our patients. For a complete therapy recommendation, an evaluation of the therapies, their individual adjustment as well as a filtering of possible wrong recommendations, a medical expert's opinion remains indispensable.

Stereospecific and redox-sensitive increase in monocyte adhesion to endothelial cells by homocysteine.

OBJECTIVE: Previous studies have shown that elevated homocysteine (Hcy) levels promote the development of atherosclerotic lesions in atherosclerosis-prone animal models. There is evidence that oxidant stress contributes to Hcy's deleterious effects on the vasculature. The accumulation and adhesion of monocytes to the vascular endothelium is a critical event in the development of atherosclerosis. We investigated the effects of Hcy on the interaction between human endothelial cells (EC) (EC line EA.hy 926 and primary human umbilical vein EC [HUVEC]) and the monocytic cell line THP-1, and the impact of vascular oxidant stress and redox-sensitive signaling pathways on these events. METHODS AND RESULTS: L-Hcy, but not D-Hcy, increases the production of reactive oxygen species inside EC, enhances nuclear factor(NF)-kappaB activation, and stimulates intercellular adhesion molecule-1 (ICAM-1) RNA transcription and cell surface expression. This leads to a time- and dose-dependent increase in monocyte adhesion to ECs. Pretreatment of ECs with superoxide scavengers (MnTBAP and Tiron) or with an inhibitor of NF-kappaB activation abolished Hcy-induced monocyte adhesion, ICAM-1 expression, and nuclear translocation of NF-kappaB. CONCLUSIONS: These findings suggest that reactive oxygen species produced under hyperhomocysteinemic conditions may induce a proinflammatory situation in the vessel wall that initiates and promotes atherosclerotic lesion development.

Acute hyperhomocysteinemia induces microvascular and macrovascular endothelial dysfunction.

BACKGROUND: Hyperhomocysteinemia (Hhcy) has been shown to induce endothelial dysfunction due to a decrease in bioavailable nitric oxide (NO) by increased vascular oxidant stress. This can be detected as an impairment of endothelium-dependent vasodilation in conductance arteries, like brachial or coronary arteries. The effect of Hhcy on endothelial function (EF) in small resistance vessels that critically determine organ perfusion, however, has not been studied systematically in humans. Therefore, we simultaneously determined macro- and microvascular EF in 11 healthy subjects before and during acute Hhcy induced by an oral methionine challenge. METHODS: Macrovascular EF was determined by measuring endothelium-dependent flow-mediated vasodilation of the brachial artery by vascular ultrasound and microvascular EF by measuring skin perfusion during iontophoresis of acetylcholine using laser Doppler fluxmetry. RESULTS: Oral methionine significantly increased homocysteine levels by about 5.1-fold. Acute Hhcy leads to a significant decrease in flow-mediated vasodilation of the brachial artery from 8.1 +/- 0.5% to 3.6 +/- 0.6% and to a significant decrease in the ratio of acetylcholine-stimulated vs. baseline laser Doppler flow in the forearm skin (from 9.2 +/- 1.0- to 7.8 +/- 1.3-fold). CONCLUSIONS: Acute Hhcy impairs macro- as well as microvascular (EF) in humans.

Apheresis in coronary heart disease with elevated Lp (a): a review of Lp (a) as a risk factor and its management.

Lipoprotein (a) (Lp (a)) increases global cardiovascular risk, especially when LDL cholesterol is concomitantly elevated. Epidemiologic data show that Lp (a) concentration in plasma can be used to predict the risk of early atherogenesis in a dose-dependent manner and late stages of atherosclerosis are accelerated by elevated Lp (a). Therapeutic means to lower Lp (a) are limited. The most effective method to reduce plasma Lp (a) concentration significantly is therapeutic apheresis. Because apheresis is laborious and expensive, patients considered for this procedure should suffer from high Lp (a) concentrations, well beyond 50 mg/dL, and have manifested and progressive coronary heart disease despite maximal drug therapy. Experimental data and therapeutic results will be discussed in the present paper.

[Public access to information about the services and quality of care in public hospitals: the need for methodologic clarity. A survey of 44 university hospital directors and administrators]. / Accès du public aux informations sur les prestations et la qualité des soins dans les établissements publics de santé. Enquête auprès de 44 décideurs de CHU.

INTRODUCTION: For the past eight years, the Ministry of Health has released information about the services and quality of care in public hospitals, in response to the increasing concern about hospital performance expressed by patient associations. The press publishes hospital ratings based on this information. This survey asked hospital administrators about their views of communication on this topic. METHODS: This survey, conducted from 7 October through 20 November 2004, sent a two-page open questionnaire to a variety of hospital executive personnel - medical directors, chief administrators, medical school deans, and public information officers - to determine their views on this subject. RESULTS: The response rate was 34%. Without contesting either the legitimacy of the expectation for information or the transparency owed to patients, health professionals expressed the need to know in advance the "rules of the game" and the methodology of the rating techniques to be used. Most reported few changes in their professional behavior due to these publications, the methodology and criteria of which they contested. They suggested changes including different criteria and indicators for the rating, the ability to contest the conclusions drawn from the PMSI data, and the need for preliminary work to define criteria by working groups composed of physicians, other professionals, and even those outside the health field. On the other hand, only half were willing to participate in such a working group. CONCLUSION: These hospital managers see a need for specialists in the analysis of hospital data, who can clarify the meaning of the statistics and improve the public's understanding of them, now shaped by the mass media's failure to provide meaningful analysis.

Screening for functional sequence variations and mutations in ABCA1.

Mutations in the ATP-binding cassette 1 transporter gene (ABCA1) are responsible for the genetic HDL-deficiency syndromes, which are characterized by severely diminished plasma HDL-C levels and a predisposition to cardiovascular disease and splenomegaly. The ABCA1 gene contains 50 exons and codes for a 2261-amino acid long membrane protein that facilitates phospholipid and cholesterol transport. Several mutations have been identified so far as responsible either for Tangier disease or for reduced HDL levels. We have selectively looked for additional polymorphisms in functionally relevant regions of the gene in cohorts constituted of individuals with altered HDL levels as well as healthy blood donors and octogenarians, and screened for mutations in the complete coding region of selected individuals with extremely aberrant HDL levels. In the promoter region, which is important for regulation of gene expression, we have identified several polymorphisms including one VNTR polymorphism, located at a putative ZNF202 binding site, which displayed different binding of ZNF202 in an electromobility shift assay. Three novel SNPs were discovered in the promoter region (G1047C, C1152T and C1440T). The prevalence of exchange G1047C (G-395C) was found significantly increased in probands with low HDL compared to probands with high HDL. Exchanges C1152T (C-290T) and C1440T (C-7T) were significantly more frequent in the cohort with low HDL compared to healthy blood donors and octogenarians. In the C-terminal part of ABCA1, known to interact with other proteins, two novel sequence variations (F2163S and V2244I) have been found in one phenotype related to cardiovascular disease, but none in the aforementioned cohorts. In one individual with extremely high HDL levels, the V771M polymorphism was found in a homozygous state. In patients with HDL deficiency, three novel mutations have been identified (W590L, W840R and R1068C). To facilitate further research in ABCA1 sequence variations and expand our understanding of their effects, we are introducing a webpage archive (http://www.abca1-mutants.all.at) containing all sequence variations reported in ABCA1 so far. This webpage provides a more recent and detailed summary of sequence variations and mutations in ABCA1 than existing databases and should also be of interest for molecular diagnosis of ABCA1-related HDL deficiency.

Indication of low-density lipoprotein apheresis in severe hypercholesterolemia and its atherosclerotic vascular complications: dextran sulfate cellulose low-density lipoprotein apheresis.

Homozygous familial hypercholesterolemia (FH) and heterozygous FH, with or without elevation of Lp(a), or isolated massive elevation of Lp(a) with clinically relevant coronary heart disease are indications for low-density lipoprotein (LDL) apheresis, as long as maximal conventional lipid lowering drug therapy does not lead to a LDL cholesterol level below 100 mg/dL. Reduction of lipoproteins and Lp(a), of oxidation of LDL, improvement of disturbed vasomotion, the procoagulatory state and disturbed hemorheology associated with atherosclerosis, as well as the stabilization of plaques and the decrease of cytokines and adhesion molecules have been induced by apheresis and are thought to favorably influence regression of artherosclerosis. Several intervention studies point in this direction.

Clinical effects of direct adsorption of lipoprotein apheresis: beyond cholesterol reduction.

Direct adsorption of lipoproteins (DALI) from whole blood is the first LDL hemoperfusion technique for extracorporeal LDL and Lp(a) elimination without initial plasma separation. Thus, this technique is characterized by high user-friendliness. In a long-term multicenter study, LDL and lipoprotein (a) (Lp(a)) reductions were 69% and 64%, respectively, per session. Adverse effects were rare, as 95% of the sessions were uneventful. Biocompatibility studies showed only minor blood-adsorber interactions for most parameters; however, there was a significant bradykinin generation. After a single session, significant reductions of plasma viscosity, erythrocyte aggregation and adhesion molecules were documented. A retrospective analysis of 18 chronic DALI patients revealed that in the majority of patients, symptoms like angina and dyspnea as well as their general status and subjective well-being improved significantly. Moreover, the objective cardiovascular event rate (MACE) decreased from a total of 26 in the 3-year period prior to DALI to 6 during a mean follow-up of 3.8 years during chronic DALI therapy. Thus, the average event rate of 0.48 per patient year at baseline could be significantly reduced to 0.09 (P < 0.004) by DALI. This impressive improvement of symptoms and coronary events can hypothetically be related to the improvement of hemorheology and the transformation of unstable into stable plaques by DALI LDL apheresis.

Role of interleukin 16 in multiple myeloma.

BACKGROUND: Multiple myeloma is a malignancy characterized by the expansion of a plasma cell clone that localizes to the human bone marrow. Myeloma cells and bone marrow stromal cells produce soluble factors that promote the survival and progression of multiple myeloma. Interleukin 16 (IL-16) is involved in regulating the migration and proliferation of normal leukocytes. However, the role of IL-16 in human cancers, including multiple myeloma, is unclear. METHODS: We investigated IL-16 expression in cell lines (n = 10) and in the bone marrow of myeloma patients (n = 62) and healthy bone marrow donors (n = 12) by quantitative reverse transcription-polymerase chain reaction, immunoblot analysis, enzyme-linked immunosorbent assay, flow cytometry, and immunohistochemistry. Transfection of two human multiple myeloma cell lines with small interfering RNAs was used to examine the effect of IL-16 gene silencing on apoptosis by flow cytometry, on proliferation by bromodeoxyuridine incorporation, and on colony formation. Protein neutralization assays were performed by treating multiple myeloma cells with a monoclonal antibody against the carboxyl-terminal fragment of IL-16. All statistical tests were two-sided. RESULTS: IL-16 was strongly overexpressed in the bone marrow of myeloma patients compared with healthy donors. Myeloma cell lines as well as primary tumor cells from myeloma patients constitutively expressed IL-16 and its receptors CD4 and/or CD9 and spontaneously secreted soluble IL-16. Silencing of IL-16 reduced the proliferative activity of myeloma cells by approximately 80% compared with untreated cells (mean relative proliferative activity IL-16 siRNA vs untransfected cells, EJM cells: 20.1%, 95% confidence interval [CI] = 14.3% to 26.0%, P = .03; KMS-12-BM cells: 22.8%, 95% CI = 5.5% to 40.0%, P = .04), and addition of a recombinant carboxyl-terminal IL-16 peptide reversed that effect. A monoclonal antibody directed against IL-16 or its receptors had a comparably strong growth-inhibiting effect on the tumor cells. CONCLUSIONS: IL-16 is an important growth-promoting factor in multiple myeloma and a candidate for novel diagnostic, prognostic, and therapeutic applications for this incurable human malignancy.

LDL-apheresis in homozygous LDL-receptor-defective familial hypercholesterolemia: the Munich experience.

23 patients, homozygotes for LDL-receptor defective familial hypercholesterolemia (FH), were diagnosed at our institute since 1960, eight of whom were heterozygous compounds. Three were lost to follow-up. Eight patients died at ages between 7 and 60 years due to cardiovascular complications, five from acute myocardial infarction, one from acute left heart failure due to severe aortic stenosis, and two from sudden death at their home. 12 patients have been treated with regular LDL-apheresis, 10 of these have continued the therapy for 8 to 27 years. The longest treatment has lasted for 31 years and is going on. The first patient started with plasma exchange in 1976.

Aged garlic extract inhibits homocysteine-induced CD36 expression and foam cell formation in human macrophages.

Elevated plasma homocysteine (Hcy) levels have been recognized as an independent risk factor for atherosclerotic vascular disease. During formation of early atherosclerotic lesions, expression of CD36, a class B scavenger receptor on macrophages, is crucially involved in the uptake of oxidized low-density lipoprotein (OxLDL) and foam-cell formation. We therefore determined the effects of Hcy on CD36 expression and foam cell formation in human monocytes/macrophages (THP-1) using flow cytometry, and the effects of aged garlic extract (AGE) on this process. Incubation of THP-1 cells with Hcy (200 micromol/L) for 72 h in the presence of phorbol 12-myristate 13-acetate (PMA) (10 nmol/L) caused a 37.8+/-5.2% increase in CD36 expression compared with PMA-stimulated cells without Hcy (P<0.01). Coincubation with AGE (5 g/L) significantly suppressed CD36 expression by 61.8+/-13.9%, compared with control conditions, and by 48.6+/-9.0% compared with Hcy-incubated cells (P<0.01). THP-1 cells in the presence of PMA (10 nmol/L) were incubated with Hcy or AGE for 72 h followed by incubation with 1,1'-dioctadecyl-3,3,3'3'-tetra-methylindocyanide percholorate (DiI)-labeled OxLDL for 3 h, and fluorescence intensity was measured by flow cytometry. AGE also inhibited DiI-labeled OxLDL uptake into PMA-stimulated THP-1 cells by 85.6+/-2.8% (P<0.01), but Hcy had no effects on it. Our data indicate that AGE inhibits CD36 expression and OxLDL uptake in macrophages and suggest that the extract could modulate the formation of early atherosclerotic lesions.

Aged garlic extract improves homocysteine-induced endothelial dysfunction in macro- and microcirculation.

Endothelial dysfunction caused by increases in vascular oxidant stress that decrease bioavailable nitric oxide (NO) plays a critical role in the vascular pathobiology of hyperhomocysteinemia. Boosting cellular glutathione levels or increasing the activity of cellular glutathione peroxidase can compensate for homocysteine's effects on endothelial function. Aged garlic extract (AGE) contains water- and oil-soluble sulfur compounds that modify the intracellular thiol and redox state, minimize intracellular oxidant stress, and stimulate NO generation in endothelial cells and animals. We performed a placebo-controlled, blinded, crossover trial to examine whether AGE reduces macro- and microvascular endothelial dysfunction during acute hyperhomocysteinemia induced by an oral methionine challenge in healthy subjects. Acute hyperhomocysteinemia leads to a significant decrease in flow-mediated vasodilation of the brachial artery as determined by vascular ultrasound, indicative of macrovascular endothelial dysfunction. In addition, acute hyperhomocysteinemia leads to a decrease in acetylcholine-stimulated skin perfusion as measured by laser-Doppler flowmetry. This indicates microvascular endothelial dysfunction, which is presumably a result of impairment of the endothelium-derived hyperpolarizing factor pathway. Pretreatment with AGE for 6 wk significantly diminished the adverse effects of acute hyperhomocysteinemia in both vascular territories. We conclude that AGE may at least partly prevent a decrease in bioavailable NO and endothelium-derived hyperpolarizing factor during acute hyperhomocysteinemia. This pilot study warrants further investigations on the effects of AGE on endothelial dysfunction in patients with other cardiovascular risk factors or established vascular disease and on the clinical outcome of patients with cardiovascular disease.

Endothelial dysfunction and atherothrombosis in mild hyperhomocysteinemia.

Mildly elevated plasma homocysteine levels are an independent risk factor for atherothrombotic vascular disease in the coronary, cerebrovascular, and peripheral arterial circulation. Endothelial dysfunction as manifested by impaired endothelium-dependent regulation of vascular tone and blood flow, by increased recruitment and adhesion of circulating inflammatory cells to the endothelium, and by a loss of endothelial cell antithrombotic function contributes to the vascular disorders linked to hyperhomocysteinemia. Increased vascular oxidant stress through imbalanced thiol redox status and inhibition of important antioxidant enzymes by homocysteine results in decreased bioavailability of the endothelium-derived signaling molecule nitric oxide via oxidative inactivation. This plays a central role in the molecular mechanisms underlying the effects of homocysteine on endothelial function. Supplementation of folic acid and vitamin B12 has been demonstrated to be efficient in lowering mildly elevated plasma homocysteine levels and in reversing homocysteine-induced impairment of endothelium-dependent vasoreactivity. Results from ongoing intervention trials will determine whether homocysteine-lowering therapies contribute to the prevention and reduction of atherothrombotic vascular disease and may thereby provide support for the causal relationship between hyperhomocysteinemia and atherothrombosis.

Influence of hyperhomocysteinemia on the cellular redox state--impact on homocysteine-induced endothelial dysfunction.

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis. An increasing body of evidence has implicated oxidative stress as being contributory to homocysteine's deleterious effects on the vasculature. Elevated levels of homocysteine may lead to increased generation of superoxide by a biochemical mechanism involving nitric oxide synthase, and, to a lesser extent, by an increase in the chemical oxidation of homocysteine and other aminothiols in the circulation. The resultant increase in superoxide levels is further amplified by homocysteine-dependent alterations in the function of cellular antioxidant enzymes such as cellular glutathione peroxidase or extracellular superoxide dismutase. One direct clinical consequence of elevated vascular superoxide levels is the inactivation of the vasorelaxant messenger nitric oxide, leading to endothelial dysfunction. Scavenging of superoxide anion by either superoxide dismutase or 4,5-dihydroxybenzene 1,3-disulfonate (Tiron) reverses endothelial dysfunction in hyperhomocysteinemic animal models and in isolated aortic rings incubated with homocysteine. Similarly, homocysteine-induced endothelial dysfunction is also reversed by increasing the concentration of the endogenous antioxidant glutathione or overexpressing cellular glutathione peroxidase in animal models of mild hyperhomocysteinemia. Taken together, these findings strongly suggest that the adverse vascular effects of homocysteine are at least partly mediated by oxidative inactivation of nitric oxide.

Highly resistant metabolically deficient dwarf mutant of Escherichia coli is the cause of a chronic urinary tract infection.

We present the case of a 68-year-old diabetic woman who has been suffering from chronic urinary tract infections, recurring over a period of at least 5 years, caused by a slowly growing metabolically deficient dwarf mutant (MDD) of Escherichia coli. This MDD strain was auxotrophic for histidine, was resistant to multiple antibiotics, and showed atypical growth behavior. Colonies were tiny on routine media but were able to revert to normal growth after extended incubation. This strain was identified as E. coli by 16S ribosomal DNA sequencing, and virulence factor profiles were determined by PCR. Seven MDD isolates collected over the 5-year period were grown from midstream urine to significant colony counts and shown to belong to the same clonal group by pulsed-field gel electrophoresis and enterobacterial repetitive intergenic consensus PCR. These MDDs were repeatedly misidentified by biochemical methods due to their slow growth and atypical colony morphology. This case highlights the importance of recognizing MDDs of Enterobacteriaceae in patients with chronic infections. To our knowledge this is the first report of an MDD of E. coli causing a chronic urinary tract infection.