ChatGPT's Gastrointestinal Tumor Board Tango: A limping dance partner?

Objectives: This study aimed to assess the consistency and replicability of treatment recommendations provided by ChatGPT 3.5 compared to gastrointestinal tumor cases presented at multidisciplinary tumor boards (MTBs). It also aimed to distinguish between general and case-specific responses and investigated the precision of ChatGPT’s recommendations in replicating exact treatment plans, particularly regarding chemotherapy regimens and follow-up protocols. Material and methods: A retrospective study was carried out on 115 cases of gastrointestinal malignancies, selected from 448 patients reviewed in MTB meetings. A senior resident fed patient data into ChatGPT 3.5 to produce treatment recommendations, which were then evaluated against the tumor board’s decisions by senior oncology fellows. Results: Among the examined cases, ChatGPT 3.5 provided general information about the malignancy without considering individual patient characteristics in 19% of cases. However, only in 81% of cases, ChatGPT generated responses that were specific to the individual clinical scenarios. In the subset of case-specific responses, 83% of recommendations exhibited overall treatment strategy concordance between ChatGPT and MTB. However, the exact treatment concordance dropped to 65%, notably lower in recommending specific chemotherapy regimens. Cases recommended for surgery showed the highest concordance rates, while those involving chemotherapy recommendations faced challenges in precision. Conclusions: ChatGPT 3.5 demonstrates potential in aligning conceptual approaches to treatment strategies with MTB guidelines. However, it falls short in accurately duplicating specific treatment plans, especially concerning chemotherapy regimens and ollow-up procedures. Ethical concerns and challenges in achieving exact replication necessitate prudence when considering ChatGPT 3.5 for direct clinical decision-making in MTBs

Monocytes and γδ T cells control the acute phase response to intravenous zoledronate: insights from a phase IV safety trial

Aminobisphosphonates (NBPs) are used widely against excessive bone resorption in osteoporosis and Paget’s disease as well as in metastatic bone disease and multiple myeloma. Intravenous NBP administration often causes mild to severe acute phase responses (APRs) that may require intervention with analgesics and antipyretics and lead to treatment noncompliance and non-adherence. We here undertook a phase IV safety trial in patients with osteoporosis to investigate the APR of otherwise healthy individuals to first-time intravenous treatment with the NBP zoledronate. This study provides unique insight into sterile acute inflammatory responses in vivo, in the absence of confounding factors such as infection or cancer. Our data show that both periphera

第913回千葉医学会例会・第28回麻酔科例会・第56回千葉麻酔懇話会

Introduction Pulmonary Surfactant reduces surface tension in the terminal airways thus facilitating breathing and contributes to host’s innate immunity. Surfactant Proteins (SP) A, B, C and D were recently identified as inherent proteins of the CNS. Aim of the study was to investigate cerebrospinal fluid (CSF) SP levels in hydrocephalus patients compared to normal subjects. Patients and Methods CSF SP A-D levels were quantified using commercially available ELISA kits in 126 patients (0–84 years, mean 39 years). 60 patients without CNS pathologies served as a control group. Hydrocephalus patients were separated in aqueductal stenosis (AQS, n = 24), acute hydrocephalus without aqueductal stenosis (acute HC w/o AQS, n = 16) and idiopathic normal pressure hydrocephalus (NPH, n = 20). Furthermore, six patients with pseudotumor cerebri were investigated. Results SP A—D are present under physiological conditions in human CSF. SP-A is elevated in diseases accompanied by ventricular enlargement (AQS, acute HC w/o AQS) in a significant manner (0.67, 1.21 vs 0.38 ng/ml in control, p<0.001). SP-C is also elevated in hydrocephalic conditions (AQS, acute HC w/o AQS; 0.87, 1.71 vs. 0.48 ng/ml in controls, p<0.001) and in Pseudotumor cerebri (1.26 vs. 0.48 ng/ml in controls, p<0.01). SP-B and SP-D did not show significant alterations. Conclusion The present study confirms the presence of SPs in human CSF. There are significant changes of SP-A and SP-C levels in diseases affecting brain water circulation and elevation of intracranial pressure. Cause of the alterations, underlying regulatory mechanisms, as well as diagnostic and therapeutic consequences of cerebral SP’s requires further thorough investigations

Anti-CD3 antibody treatment reduces scar formation in a rat model of myocardial infarction

Introduction: Antibody treatment with anti-thymocyte globulin (ATG) has been shown to be cardioprotective. We aimed to evaluate which single anti-T-cell epitope antibody alters chemokine expression at a level similar to ATG and identified CD3, which is a T-cell co-receptor mediating T-cell activation. Based on these results, the effects of anti-CD3 antibody treatment on angiogenesis and cardioprotection were tested in vitro and in vivo. Methods: Concentrations of IL-8 and MCP-1 in supernatants of human peripheral blood mononuclear cell (PBMC) cultures following distinct antibody treatments were evaluated by Enzyme-linked Immunosorbent Assay (ELISA). In vivo, anti-CD3 antibodies or vehicle were injected intravenously in rats subjected to acute myocardial infarction (AMI). Chemotaxis and angiogenesis were evaluated using tube and migration assays. Intracellular pathways were assessed using Western blot. Extracellular vesicles (EVs) were quantitatively evaluated using fluorescence-activated cell scanning, exoELISA, and nanoparticle tracking analysis. Also, microRNA profiles were determined by next-generation sequencing. Results: Only PBMC stimulation with anti-CD3 antibody led to IL-8 and MCP-1 changes in secretion, similar to ATG. In a rat model of AMI, systemic treatment with an anti-CD3 antibody markedly reduced infarct scar size (27.8% (Inter-quartile range; IQR 16.2–34.9) vs. 12.6% (IQR 8.3–27.2); p < 0.01). The secretomes of anti-CD3 treated PBMC neither induced cardioprotective pathways in cardiomyocytes nor pro-angiogenic mechanisms in human umbilical vein endothelial cell (HUVECs) in vitro. While EVs quantities remained unchanged, PBMC incubation with an anti-CD3 antibody led to alterations in EVs miRNA expression. Conclusion: Treatment with an anti-CD3 antibody led to decreased scar size in a rat model of AMI. Whereas cardioprotective and pro-angiogenetic pathways were unaltered by anti-CD3 treatment, qualitative changes in the EVs miRNA expression could be observed, which might be causal for the observed cardioprotective phenotype. We provide evidence that EVs are a potential cardioprotective treatment target. Our findings will also provide the basis for a more detailed analysis of putatively relevant miRNA candidates

Scientific Opportunities with an X-ray Free-Electron Laser Oscillator

An X-ray free-electron laser oscillator (XFELO) is a new type of hard X-ray source that would produce fully coherent pulses with meV bandwidth and stable intensity. The XFELO complements existing sources based on self-amplified spontaneous emission (SASE) from high-gain X-ray free-electron lasers (XFEL) that produce ultra-short pulses with broad-band chaotic spectra. This report is based on discussions of scientific opportunities enabled by an XFELO during a workshop held at SLAC on June 29 - July 1, 2016Comment: 21 pages, 12 figure

Hypoadiponectinemia in Extremely Low Gestational Age Newborns with Severe Hyperglycemia – A Matched-Paired Analysis

BACKGROUND: Hyperglycemia is commonly observed in extremely low gestational age newborns (ELGANs) and is associated with both increased morbidity and mortality. The objective of this study was to examine the relationship between neonatal hyperglycemia and adiponectin levels in ELGANs. METHODOLOGY/PRINCIPAL FINDINGS: Ten preterm infants between 22+6/7 and 27+3/7 weeks' gestation with neonatal hyperglycemia (defined as pre-feeding blood glucose levels above 200mg/dl on two consecutive measurements with a maximum parenteral glucose infusion of 4 mg/kg*min(-1)) formed the case cohort of this study. To every single patient of this case cohort a patient with normal fasting ( = pre-feeding) blood glucose levels was matched in terms of gestational age and gender. Adiponectin ELISAs were performed both at onset of hyperglycemia and at term-equivalent age. In the case cohort 9/10 patients had to be treated with insulin for 1-26 days (range 0.01-0.4 IU/kg*h(-1)). Compared to matched-paired controls, significant hypoadiponectinemia was observed at onset of hyperglycemia in these affected patients (6.9 µg/ml versus 15.1 µg/ml, p = 0.009). At term equivalent age, normoglycemia without any insulin treatment was found in both groups. Moreover, adiponectin levels at that time were no longer significantly different (12.3 µg/ml versus 20.0 µg/ml; p = 0.051) possibly indicating a mechanistic relevance of this adipokine in regulating insulin sensitivity in ELGANs. CONCLUSIONS/SIGNIFICANCE: Decreased circulating adiponectin levels are correlated with hyperglycemia in ELGANs and may contribute to the pathogenesis of impaired glucose homeostasis in these infants. These findings suggest that adiponectin might be a potential future drug target for the potentially save treatment of hyperglycemia in pre-term infants

HIV-Nef Protein Persists in the Lungs of Aviremic Patients with HIV and Induces Endothelial Cell Death

It remains a mystery why HIV-associated end-organ pathologies persist in the era of combined antiretroviral therapy (ART). One possible mechanism is the continued production of HIV-encoded proteins in latently HIV-infected T cells and macrophages. The proapoptotic protein HIV-Nef persists in the blood of ART-treated patients within extracellular vesicles (EVs) and peripheral blood mononuclear cells. Here we demonstrate that HIV-Nef is present in cells and EVs isolated from BAL of patients on ART. We hypothesize that HIV-Nef persistence in the lung induces endothelial apoptosis leading to endothelial dysfunction and further pulmonary vascular pathologies. The presence of HIV-Nef in patients with HIV correlates with the surface expression of the proapoptotic endothelial-monocyte–activating polypeptide II (EMAPII), which was implicated in progression of pulmonary emphysema via mechanisms involving endothelial cell death. HIV-Nef protein induces EMAPII surface expression in human embryonic kidney 293T cells, T cells, and human and mouse lung endothelial cells. HIV-Nef packages itself into EVs and increases the amount of EVs secreted from Nef-expressing T cells and Nef-transfected human embryonic kidney 293T cells. EVs from BAL of HIV+ patients and Nef-transfected cells induce apoptosis in lung microvascular endothelial cells by upregulating EMAPII surface expression in a PAK2-dependent fashion. Transgenic expression of HIV-Nef in vascular endothelial–cadherin+ endothelial cells leads to lung rarefaction, characterized by reduced alveoli and overall increase in lung inspiratory capacity. These changes occur concomitantly with lung endothelial cell apoptosis. Together, these data suggest that HIV-Nef induces endothelial cell apoptosis via an EMAPII-dependent mechanism that is sufficient to cause pulmonary vascular pathologies even in the absence of inflammation

Validierung eines Fragebogens zu Problemen der Krankheitsakzeptanz bei Diabetes mellitus: Diabetes Acceptance Scale (DAS)

Fragestellung: Probleme der Diabetesakzeptanz sind assoziiert mit non-adhärentem Selbstbehandlungsverhalten und hyperglykämischer Blutzuckereinstellung. Zur Erfassung von Diabetesakzeptanzproblemen existierte bisher allerdings nur ein recht limitiertes Messinstrument, der Acceptance and Action Diabetes Questionnaire (AADQ). Um differenziertere Messungen zu ermöglichen, wurde die Diabetes Acceptance Scale (DAS) entwickelt, deren Validierung hier berichtet wird. Methodik: Die DAS ist eine 28-Item-Selbstberichtsskala mit Subskalen zur diabetesbezogenen „Akzeptanz/Integration“, „Behandlungsmotivation“, „Abwehr/Vermeidung“ und „emotionalen Belastung“ sowie einer Summenskala zur Gesamt-Diabetesakzeptanz; Entwicklung beschrieben in Diabetologie und Stoffwechsel 2015; 10 – P137. 460 Diabetespatienten (50% Typ-1, 48% Typ-2, 2% Typ-3; 50% weiblich; Alter 52 ± 15 Jahre; BMI 30 ± 7 kg/m2; Diabetesdauer 15 ± 12 Jahre; HbA1c 7,8 ± 1,4%) bearbeiteten die DAS sowie Fragebögen zu Diabetesakzeptanzproblemen (AADQ), diabetesbezogener Belastung (PAID-5), depressiver Stimmung (PHQ-9) und Diabetes-Selbstbehandlungsverhalten (DSMQ). Gleichzeitig wurde der HbA1c-Wert bestimmt. Anhand dieser Daten wurden Kennwerte der Reliabilität (Cronbachs α) und Validität (kriterienbezogene Korrelationen) der DAS untersucht. Ergebnisse: Alle DAS-Skalen zeigten durchweg hohe Reliabilität (Subskalen: α= 0,89 – 0,93; Summenskala: α= 0,96). Höhere DAS-Summenwerte (bessere Diabetesakzeptanz) waren hoch korreliert mit weniger Diabetesakzeptanzproblemen nach AADQ (r=-0,65), geringerer diabetesbezogener Belastung (r=-0,69) und weniger Depressivität (r=-0,56); alle P< 0,001. Weiter korrelierten höhere DAS-Summenwerte mit günstigeren Selbstbehandlungsverhaltensweisen nach DSMQ (diabetesgerechte Ernährung: r= 0,56; Medikamentenadhärenz: r= 0,54; Blutzuckerselbstkontrolle: r= 0,42; körperliche Betätigung: r= 0,26; Arztkontakt: r= 0,51) sowie einer besseren Blutzuckereinstellung (HbA1c-Wert: r=-0,42); alle P< 0,001. Schlussfolgerungen: Die Ergebnisse sprechen für eine hohe Reliabilität und Validität der Diabetes Acceptance Scale. Die Skala erscheint als sehr gutes Messinstrument zur Erkennung von Problemen der Diabetesakzeptanz sowie zur besseren Erforschung dieser gravierenden psychologischen Problematik

47 patients with FLNA associated periventricular nodular heterotopia

Background: Heterozygous loss of function mutations within the Filamin A gene in Xq28 are the most frequent cause of bilateral neuronal periventricular nodular heterotopia (PVNH). Most affected females are reported to initially present with difficult to treat seizures at variable age of onset. Psychomotor development and cognition may be normal or mildly to moderately impaired. Distinct associated extracerebral findings have been observed and may help to establish the diagnosis including patent ductus arteriosus Botalli, progressive dystrophic cardiac valve disease and aortic dissection, chronic obstructive lung disease or chronic constipation. Genotype-phenotype correlations could not yet be established. Methods: Sanger sequencing and MLPA was performed for a large cohort of 47 patients with Filamin A associated PVNH (age range 1 to 65 years). For 34 patients more detailed clinical information was available from a structured questionnaire and medical charts on family history, development, epileptologic findings, neurological examination, cognition and associated clinical findings. Available detailed cerebral MR imaging was assessed for 20 patients. Results: Thirty-nine different FLNA mutations were observed, they are mainly truncating (37/39) and distributed throughout the entire coding region. No obvious correlation between the number and extend of PVNH and the severity of the individual clinical manifestation was observed. 10 of the mutation carriers so far are without seizures at a median age of 19.7 years. 22 of 24 patients with available educational data were able to attend regular school and obtain professional education according to age. Conclusions: We report the clinical and mutation spectrum as well as MR imaging for a large cohort of 47 patients with Filamin A associated PVNH including two adult males. Our data are reassuring in regard to psychomotor and cognitive development, which is within normal range for the majority of patients. However, a concerning median diagnostic latency of 17 to 20 years was noted between seizure onset and the genetic diagnosis, intensely delaying appropriate medical surveillance for potentially life threatening cardiovascular complications as well as genetic risk assessment and counseling prior to family planning for this X-linked dominant inherited disorder with high perinatal lethality in hemizygous males