Akromegália je raritné endokrinologické ochorenie charakterizované nadprodukciou rastového hormónu (RH), najčastej- šie na podklade adenómu hypofýzy s následnou zvýšenou produkciou inzulínu podobného rastového faktora 1 (IGF-1) v pečeni. Účinky RH a IGF-1 na metabolizmus glukózy sú antagonistické; RH vyvoláva inzulínovú rezistenciu, zatiaľ čo IGF-1 zvyšuje inzulínovú citlivosť. Avšak inzulín-antagonizujúci účinok RH prevyšuje inzulín-senzitizujúci účinok IGF-1 v cieľových tkanivách, čo vedie k vzniku diabetes mellitus (DM) pri akromegálii. Sekundárny DM je častou komplikáciou u pacientov s akromegáliou. DM môže byť prvým prejavom ochorenia, pretože hyperglykémia spôsobená inzulínovou rezistenciou býva často významná. Diagnostika a liečba DM u pacientov s akromegáliou je komplexná a vyžaduje multidisciplinárny prístup, ktorý zahŕňa endokrinológov, diabetológov a ďalších špecialistov. Účinná kontrola akromegálie prostredníctvom chirurgického zákroku, farmakoterapie alebo rádioterapie môže zlepšiť glukózovú homeostázu a znížiť riziko komplikácií spojených s DM. Uvedený prehľadový článok sa zaoberá patofyziologickými a klinickými zvláštnosťami DM u pacientov s akromegáliou, ako aj potenciálnymi účinkami špecifickej liečby akromegálie na glukózovú homeostázu.
Acromegaly is a rare endocrine disorder characterized by the overproduction of growth hormone (GH), most commonly due to a pituitary adenoma, leading to increased production of insulin-like growth factor 1 (IGF-1) in the liver. The effects of GH and IGF-1 on glucose metabolism are antagonistic; GH induces insulin resistance, while IGF-1 enhances insulin sensitivity. However, the insulin-antagonizing effect of GH outweighs the insulin-sensitizing effect of IGF-1 in target tissues, leading to the development of diabetes mellitus (DM) in acromegaly.Secondary DM is a frequent complication in patients with acromegaly. In fact, DM may be the first manifestation of the disease, because hyperglycemia caused by insulin resistance is often significant. The diagnosis and management of DM in patients with acromegaly are complex and require a multidisciplinary approach involving endocrinologists, diabetologists, and other specialists. Effective control of acromegaly through surgery, pharmacotherapy, or radiotherapy can improve glucose homeostasis and reduce the risk of complications associated with DM. This review article discusses the pathophysiological and clinical characteristics of DM in patients with acromegaly, as well as the potential effects of specific acromegaly treatments on glucose homeostasis.
- MeSH
- Acromegaly * diagnosis etiology drug therapy MeSH
- Diabetes Mellitus etiology MeSH
- Dopamine analogs & derivatives MeSH
- Glucose metabolism MeSH
- Insulin-Like Growth Factor I metabolism MeSH
- Insulin Resistance MeSH
- Humans MeSH
- Growth Hormone analogs & derivatives blood MeSH
- Blood Glucose Self-Monitoring MeSH
- Somatostatin analogs & derivatives MeSH
- Check Tag
- Humans MeSH
Poznatky, získané hlavne v posledných dvoch desaťročiach, umožnili lepšie porozumieť mechanizmom a dráham, prostredníctvom ktorých nervový systém, a tým aj stres, ovplyvňuje procesy súvisiace so vznikom a progresiou nádorových chorôb. Neurobiologický výskum nádorových chorôb pritom nie len rozšíril poznanie etiopatogenézy nádorového procesu, ale vytvoril podklady aj pre zavedenie nových terapeutických metód v onkológii, založených na modulácii prenosu signálov medzi nervovým systémom a nádorovým tkanivom. Bolo tiež zistené, že monitorovanie aktivity zložiek autonómneho nervového systému je možné využiť nie len na určenie miery stresu u daného pacienta, ale aj na posúdenie prognózy jeho onkologickej choroby. Jednu z efektívnych metód, umožňujúcich sledovanie flexibility a rovnováhy pôsobenia zložiek autonómneho nervového systému a nepriamo aj miery stresu u onkologických pacientov, predstavuje určovanie variability srdcovej frekvencie (HRV). Na opodstatnenosť využitia tejto metódy v onkológii poukazujú aj zistenia, že pacienti s vyššími hodnotami HRV vykazujú dlhšie prežívanie v porovnaní s pacientmi, u ktorých sú hodnoty HRV nižšie. Zámerom tohto textu je priblížiť súčasné poznatky týkajúce sa vplyvu stresu na nádory hlavy a krku a načrtnúť možnosti využitia stanovenia HRV ako prognostického markera u týchto pacientov. Diskutované sú aj možnosti využitia metód, ktoré sú zamerané na zvýšenie HRV a ich prípadné využitie v liečbe pacientov s nádormi hlavy a krku.
Knowledge, mainly gained in the last two decades, has provided a better understanding of the mechanisms and pathways through which the nervous system, and thus stress, influences processes related to cancer initiation and progression. Neurobiological research on cancer has not only increased the knowledge of the aetiopathogenesis of the tumour process, but also has laid the foundation for the introduction of new therapeutic methods in oncology based on the modulation of the transmission of signals between the nervous system andtumour tissue. It also has been found that monitoring the activity of components of the autonomic nervous system can be used not only to determine the degree of stress in a given patient, but also to assess the prognosis of his or her oncological disease. One of the effective methods to monitor the flexibility and balance of the autonomic nervous system components and indirectly the level of stress in cancer patients is the determination of heart rate variability (HRV). The validity of the use of this method in oncology is indicated by the findings that patients with higher HRV values show longer survival compared to patients with lower HRV values. The aim of this text is to review the current knowledge regarding the impact of stress on head and neck cancer and to outline the possibilities of using HRV determination as a prognostic marker in these patients. The potential use of methods aimed at increasing HRV and their potential use in the management of patients with head and neck tumours are also discussed.
INTRODUCTION: ND0612 is being investigated as a continuous, subcutaneous levodopa/carbidopa infusion, in combination with oral levodopa/carbidopa, for motor fluctuations in Parkinson's disease (PD). One-year data from the ongoing BeyoND study (NCT02726386) showed that the ND0612 regimen was safe and well tolerated and provided a sustained ≥2-h improvement in daily Good ON-time through 12 months of treatment. METHODS: We describe 3-year safety and efficacy outcomes for participants who completed 12 months of ND0612 treatment in the core study period and entered the extension phase. RESULTS: Of the 214 enrolled participants, 120 completed the core 1-year period, and 114 participants continued into the extension phase. Of these, 95/114 (83.3 %) completed 2 years and 77/114 (67.5 %) completed 3 years of study treatment. Key reasons for discontinuation were treatment-emergent adverse events (TEAEs) (n = 5 and n = 11 after 2 and 3 years, respectively) and withdrawal of consent (n = 9 and n = 5, respectively). TEAEs were reported by 105/114 (92.1 %) participants in Year 1, 77/114 (67.5 %) in Year 2, and 73/95 (76.8 %) in Year 3. While most participants experienced infusion site reactions, these led to discontinuation in only five participants during this extension. At Month 36, the mean reduction in OFF-time from baseline was 2.81 h and the increase in Good ON-time was 2.79 h. CONCLUSIONS: Three-year results from this open-label study support the long-term safety, tolerability, and efficacy of ND0612. For participants who entered the extension phase, the high rate of retention supports a favorable benefit-risk ratio of the ND0612 regimen for patients with PD experiencing motor fluctuations.
- MeSH
- Antiparkinson Agents * administration & dosage adverse effects MeSH
- Drug Combinations * MeSH
- Carbidopa * administration & dosage MeSH
- Levodopa * administration & dosage adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Parkinson Disease * drug therapy MeSH
- Aged MeSH
- Infusions, Subcutaneous * MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
BACKGROUND: Adrenaline-producing tumors are mostly characterized by a sudden release of catecholamines with episodic symptoms. Noradrenergic ones are usually less symptomatic and characterized by a continuous overproduction of catecholamines that are released into the bloodstream. Their effects on the cardiovascular system can thus be different. The aim of this study was to determine the prevalence of cardiovascular complications by catecholamine phenotype. METHODS: We retrospectively analyzed data on the prevalence of cardiovascular events in 341 consecutive patients with pheochromocytoma and paraganglioma treated from 1995 to 2023. Biochemical catecholamine phenotype was determined based on plasma or urinary catecholamines and metanephrines. RESULTS: According to the phenotype, 153 patients had noradrenergic pheochromocytoma and paraganglioma and 188 had adrenergic pheochromocytoma and paraganglioma. In the whole sample, the incidence of serious cardiovascular complications was 28% (95 patients), with no difference between the phenotypes or sexes. The noradrenergic phenotype had significantly more atherosclerotic complications (composite end point of type 1 myocardial infarction and symptomatic peripheral artery disease; odds ratio, 3.58 [95% CI, 1.59-8.83]; P=0.003), while the adrenergic phenotype more often had type 2 myocardial infarction and takotsubo-like cardiomyopathy (OR, 0.24 [95% CI, 0.09-0.57]; P=0.002). These changes remained even after adjustment for conventional risk factors of atherosclerosis. CONCLUSIONS: We found a 28% incidence of cardiovascular complications in a consecutive group of patients with pheochromocytoma and paraganglioma. Patients presenting with a noradrenergic phenotype have a higher incidence of atherosclerotic complications, while the adrenergic phenotype is associated with a higher incidence of acute myocardial damage due to takotsubo-like cardiomyopathy.
- MeSH
- Adrenergic Agents MeSH
- Atherosclerosis * complications MeSH
- Phenotype MeSH
- Pheochromocytoma * diagnosis MeSH
- Myocardial Infarction * MeSH
- Cardiomyopathies * MeSH
- Catecholamines MeSH
- Humans MeSH
- Metanephrine MeSH
- Adrenal Gland Neoplasms * pathology MeSH
- Paraganglioma * complications MeSH
- Retrospective Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
AIM OF STUDY: To determine whether a high dose of levodopa-carbidopa intestinal gel (LCIG), expressed as levodopa equivalent daily dose (LE daily dose), is a risk factor for acute polyneuropathy in patients treated with LCIG. CLINICAL RATIONALE FOR STUDY: Treatment with LCIG is an effective device-assisted therapy in the advanced stages of Parkinson's Disease (PD). Polyneuropathy is a well-known complication of PD treatment. Patients treated with oral levodopa usually suffer from sub-clinical or mild chronic sensory polyneuropathy. However, severe acute polyneuropathy occurs in patients treated with LCIG, which is causally related to the treatment and leads to its immediate discontinuation. The etiology is not yet clear, but some patients with acute polyneuropathy have been given high doses of LCIG. MATERIAL AND METHODS: A retrospective multicentre study of patients treated with LCIG was performed. Patients with acute polyneuropathy were subjected to a detailed analysis including statistical processing. RESULTS: Of 183 patients treated with LCIG in seven centres, six patients (five females, median age 63 years) developed acute polyneuropathy with LCIG discontinuation. The median (interquartile range) initial and final LE daily dose in patients with and without acute polyneuropathy was 3,015 (2,695-3,184) and 1,898 (1,484-2,167) mg, respectively. The final LE daily dose of 2,605 mg cut-off had 83% sensitivity and 93% specificity for the prediction of acute polyneuropathy. CONCLUSIONS AND CLINICAL IMPLICATIONS: The risk of acute polyneuropathy in LCIG-treated patients was associated with a daily LE dose of greater than 2,605 mg or with more than a 62% increase in the daily LE dose during LCIG treatment.
- MeSH
- Antiparkinson Agents * adverse effects administration & dosage MeSH
- Drug Combinations * MeSH
- Gels * MeSH
- Carbidopa * administration & dosage adverse effects MeSH
- Levodopa * administration & dosage adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Parkinson Disease * drug therapy MeSH
- Polyneuropathies * chemically induced drug therapy MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
Takotsubo syndrom je definován jako syndrom akutního srdečního selhání, který se klinicky velmi často projevuje jako akutní koronární syndrom. Charakteristickým klinickým znakem je přechodná dysfunkce levé komory srdeční. Spouštějícími faktory jsou relativně často akutní neurologická onemocnění, a tak se předpokládá, že v patofyziologii hraje významnou roli právě centrální nervová soustava. Tento přehledový článek si klade za cíl představit základní informace o takotsubo syndromu se zaměřením na velmi pravděpodobné patofyziologické mechanismy v ose mozek-srdce.
Takotsubo syndrome is defined as a syndrome of acute heart failure that is very often manifested clinically as acute coronary syndrome. Transient left ventricular dysfunction is a characteristic clinical feature. Acute neurological diseases are relatively frequently the triggering factors; thus, it is assumed that it is the central nervous system that plays a significant role in the pathophysiology. The review article aims to provide basic information on Takotsubo syndrome with a focus on the very likely pathophysiological mechanisms in the brain-heart axis.
- MeSH
- Central Nervous System * physiopathology MeSH
- Mental Disorders complications physiopathology MeSH
- Catecholamines adverse effects MeSH
- Humans MeSH
- Stress, Psychological complications MeSH
- Sympathetic Nervous System physiopathology MeSH
- Takotsubo Cardiomyopathy * diagnosis physiopathology MeSH
- Check Tag
- Humans MeSH
BACKGROUND: Albumin administration is suggested in patients with sepsis and septic shock who have received large volumes of crystalloids. Given lack of firm evidence, clinical practice variation may exist. To address this, we investigated if patient characteristics or trial site were associated with albumin use in septic shock. METHODS: We conducted a post-hoc study of the CLASSIC international, randomised clinical trial of fluid volumes in septic shock. Associations between selected baseline variables and trial site with albumin use during ICU stay were assessed in Cox models considering death, ICU discharge, and loss-to-follow-up as competing events. Baseline variables were first assessed individually, adjusted for treatment allocation (restrictive vs. standard IV fluid), and then adjusted for allocation and the other baseline variables. Site was assessed in a model adjusted for allocation and baseline variables. RESULTS: We analysed 1541 of 1554 patients randomised in CLASSIC (99.2%). During ICU stay, 36.3% of patients in the restrictive-fluid group and 52.6% in the standard-fluid group received albumin. Gastrointestinal focus of infection and higher doses of norepinephrine were most strongly associated with albumin use (subgroup with highest quartile of norepinephrine doses, hazard ratio (HR) 2.58, 95% CI 1.89 to 3.53). HRs for associations between site and albumin use ranged from 0.11 (95% CI 0.05 to 0.26) to 1.70 (95% CI 1.06 to 2.74); test for overall effect of site: p < .001. CONCLUSIONS: In adults with septic shock, gastrointestinal focus of infection and higher doses of norepinephrine at baseline were associated with albumin use, which also varied substantially between sites.
- MeSH
- Albumins therapeutic use MeSH
- Adult MeSH
- Humans MeSH
- Norepinephrine therapeutic use MeSH
- Sepsis * drug therapy etiology MeSH
- Shock, Septic * drug therapy complications MeSH
- Fluid Therapy adverse effects MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
G protein-coupled estrogen receptor 1 (GPER-1) has gained recognition for its role in conferring cardioprotection. However, the extent to which GPER-1 exerts equally important effects in both sexes remains unclear. The study found similar expressions of GPER-1 in rat heart apex in both sexes. In male rats, administering epinephrine (Epi) at a dose of 31.36 microg/100 g resulted in a rapid decline in cardiac function, accompanied by a sharp increase in bax/bcl-2 levels. In contrast, female rats did not display significant changes in cardiac function under the same conditions. Additionally, compared to the injection of Epi alone (at a dose of 15.68 microg/100 g), the administration of G15 (GPER-1 antagonist) further decreased cardiac function in both male and female rats. However, it only increased mortality and lung coefficient in male rats. Conversely, G1 (GPER-1 agonist) administration improved cardiac function in both sexes. Notably, the apex of the male heart exhibited lower levels of inhibitory G protein (Galphai). Furthermore, female and male rats treated with Epi displayed elevated phosphorylated protein kinase B (p-Akt). Compared to their respective Epi groups, the administration of G15 increased p-Akt levels in female rat hearts but decreased them in male rat hearts. Conversely, the administration of G1 decreased p-Akt levels in females but rapidly increased them in male rats. Our study uncovers the vital role of GPER-1 in protecting against stress-induced heart injuries in a sex-specific manner. These findings hold immense potential for advancing targeted cardiac therapies and enhancing outcomes for both females and males.
- MeSH
- Epinephrine MeSH
- Stress, Physiological physiology MeSH
- Rats MeSH
- Sex Characteristics MeSH
- Rats, Sprague-Dawley * MeSH
- Proto-Oncogene Proteins c-akt * metabolism MeSH
- Receptors, Estrogen metabolism MeSH
- Receptors, G-Protein-Coupled * metabolism MeSH
- Sex Factors MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Hypokinetic dysarthria (HD) is a difficult-to-treat symptom affecting quality of life in patients with Parkinson's disease (PD). Levodopa may partially alleviate some symptoms of HD in PD, but the neural correlates of these effects are not fully understood. The aim of our study was to identify neural mechanisms by which levodopa affects articulation and prosody in patients with PD. Altogether 20 PD patients participated in a task fMRI study (overt sentence reading). Using a single dose of levodopa after an overnight withdrawal of dopaminergic medication, levodopa-induced BOLD signal changes within the articulatory pathway (in regions of interest; ROIs) were studied. We also correlated levodopa-induced BOLD signal changes with the changes in acoustic parameters of speech. We observed no significant changes in acoustic parameters due to acute levodopa administration. After levodopa administration as compared to the OFF dopaminergic condition, patients showed task-induced BOLD signal decreases in the left ventral thalamus (p = 0.0033). The changes in thalamic activation were associated with changes in pitch variation (R = 0.67, p = 0.006), while the changes in caudate nucleus activation were related to changes in the second formant variability which evaluates precise articulation (R = 0.70, p = 0.003). The results are in line with the notion that levodopa does not have a major impact on HD in PD, but it may induce neural changes within the basal ganglia circuitries that are related to changes in speech prosody and articulation.
- MeSH
- Antiparkinson Agents adverse effects MeSH
- Dysarthria etiology complications MeSH
- Quality of Life MeSH
- Levodopa * adverse effects MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Parkinson Disease * complications diagnostic imaging drug therapy MeSH
- Speech Disorders diagnostic imaging etiology MeSH
- Speech physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Monitoring nociception during general anaesthesia remains a substantial challenge. The Conox monitor uses two EEG indices, the qCon and the qNox. The qNox refers to the probability that a nociceptive stimulation triggers a movement of the patient and the response probability of reaction to nociceptive stimulation. We decided to test the feasibility of monitoring the qNOX index during adult cardiac surgery and to investigate whether this index correlates with hemodynamic and hormonal signs of nociceptive stimulation. METHOD: We enrolled 19 patients undergoing elective cardiac surgery. These were randomised to 2 groups receiving different doses of sufentanil via target controlled infusion: group A (n=9) 0.25 ng/mL and group B (n=10) 0.75 ng/mL. All patients were maintained at the same depth of anaesthesia. We recorded the Conox monitor indices (qNOX, qCON, electromyographic), hemodynamic variables and plasmatic levels of cortisol and noradrenaline. RESULTS: There was significantly higher blood pressure (P=0.013) and plasmatic cortisol (P=0.003) in group A and a significant increase in plasmatic noradrenaline with increasing intensity of surgical stimulation in both groups: A (P=0.001), B (P=0.008). We found no significant corresponding changes in the qNOX index. There was a positive correlation between qNOX and hemodynamic signs of stimulation (P=0.012) and between the qNOX and EMG indices (P=0.013) after endotracheal intubation, but not later after EMG index dropped. CONCLUSION: Our results do not support the assumption that signs of nociceptive stimulation during adult cardiac surgery will be reflected by the qNOX index. This may be related to compounding of qNOX processing and use of muscle relaxants. Further investigation on this field is needed.
- MeSH
- Anesthesia, General MeSH
- Adult MeSH
- Electroencephalography MeSH
- Hydrocortisone * MeSH
- Cardiac Surgical Procedures * MeSH
- Humans MeSH
- Nociception MeSH
- Norepinephrine MeSH
- Feasibility Studies MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
