Symptoms and General Pathology

All Conditions

Nervous System Diseases

Wounds and Injuries

Neoplasms

Inflammation

Brain Injuries

Brain Neoplasms

Central Nervous System Depressants

All Drugs and Chemicals

Platelet Aggregation Inhibitors

Anesthetics

Propofol

Sevoflurane

Anesthetics, Intravenous

Hypnotics and Sedatives

Anesthetics, General

Anesthetics, Inhalation

Jasmina Markovic Bozic, MD, MSC

Blaz Karpe, PHD

Iztok Potocnik, MD, MSC

Ales Jerin, PHD

Andrej Vranič, MD, PHD

Vesna Novak Jankovic, PROF, PHD

Anaesthesia and surgical stress during craniotomy can lead to brain damage and activation of inflammatory response. Consequently inflammatory cytokines (IL6, IL8, IL10) are released. Cell mediated immune balance can increase postoperative complications (infections, wound healing, multiple organ dysfunction). Many studies have shown that volatile anaesthetics reduce systemic and local inflammatory response during major surgery, but animal studies have shown that volatile anaesthetics can induce neuroinflammation (IL6, NF-κB) that leads to decline of cognitive function in rodent and possible human.

Our aim was to investigate how anaesthetic technique for craniotomy influences the release of inflammatory cytokines. Our hypothesis was that when optimal neuroprotective strategies are followed during surgery intravenous anaesthesia attenuates inflammatory response comparing to inhalational anaesthesia.

The investigators included 40 patients anaesthetised with remifentanil based anaesthesia with sevoflurane (S group) or propofol (P group).

Plasma levels of IL6, IL8, IL10 were measured during preoperative, perioperative and postoperative periods of both groups of patients. The investigators also noted emergence parameters, postoperative (pain, shivering, vomiting) and neurological complications after surgery.

Anaesthetic technique for craniotomy has to provide optimal cerebral perfusion, oxygenation and prevent brain oedema (1). It also has to lower the stress response on pain during intubation and surgical manipulation. Emergence from anaesthesia has to be rapid and smooth to permit early postoperative neurological evaluation. The most likely opioid in the last decade is short acting opioid remifentanil that can be easy titrated during the procedure and provides early recovery (2, 3, 4, 5). Currently the propofol-remifentanil and sevoflurane-remifentanil are the most frequently used combinations for craniotomy (6, 7). Recently a multicentre study was published that did not show differences in early recovery between three groups (propofol-remifentanil: TIVA, sevoflurane-remifentanil, sevoflurane-fentanyl). Either technique provided optimal surgical conditions. The group received TIVA had attenuated changes in stress biomarkers (cortizol in plasma and urine, cateholamines. (8).

Anaesthesia and surgical stress during craniotomy can lead to brain damage and activation of inflammatory response (9, 10). Consequently inflammatory cytokines (IL6, IL8, IL10) are released. Cell mediated immune balance can increase postoperative complications (infections, wound healing, multiple organ dysfunction). Many studies have shown that volatile anaesthetics reduce systemic and local inflammatory response during major surgery (11, 12, 13, 14), but animal studies have shown that volatile anaesthetics can induce neuroinflammation (IL6, NF-κB) that leads to decline of cognitive function in rodent and possible human (15,16).

Our aim was to investigate how anaesthetic technique for craniotomy influences the release of inflammatory cytokines. Our hypothesis was that when optimal neuroprotective strategies are followed during surgery intravenous anaesthesia attenuates inflammatory response comparing to inhalational anaesthesia.

Plasma levels of IL6, IL8, IL10 were measured during preoperative, perioperative and postoperative periods of both groups of patients. The investigators also noted emergence parameters, postoperative (pain, shivering, vomiting) and neurological complications after surgery.

Patients and methods

Anaesthesia regimen:

On arrival in the operating room, the patients were randomly assigned to either Group P or Group S. Randomisation was done according to computer-generated order.

All patients were on a regimen of dexamethasone 4x4mg/day with the first dose given at least one day before surgery.

After arriving to the operating room the standard monitoring was instituted. An arterial catheter was placed in the radial artery to continuously monitor blood pressure. For extended haemodynamic monitoring Vigileo system was used.

Patients were premedicated with midazolam (2-3 mg i.v.) and ondansetron (4-8 mg i.v.). Antibiotic prophylaxis with intravenous cefazolin 2g/100 ml 0.9% NaCl was invariably used in all patients.

Anaesthesia induction in Group P was performed with propofol (Propoven, Fresenius Kabi) and in Group S with sevoflurane (Sevorane, Abbott Laboratories). Before intubation all patients received remifentanil (Ultiva, GlaxoSmithKline) and rocuronium (Esmeron, MSD).

After intubation, patient's lungs were ventilated mechanically, with 1:2 oxygen-air mixtures in P and S group. Ventilation was adjusted to maintain normocapnia. Anaesthesia was maintained by continuous infusion of propofol 4-6 mg/kg/h in the P group and with sevoflurane 0,8-1 MAC in the S group. Remifentanil was adjusted regarding to anaesthesia response (0.1 - 2 μg/kg/min). The depth of anaesthesia was measured by a bispectral index (BIS) monitor; BIS values were maintained at 40-60.

For haemodynamic management the following algorithm was used: continuous infusion of 0.9% NaCl 6 mL kg-¹ for the first hour, followed by 2.5 ml kg-¹h-¹ . If CI \< 2 L/min/m2and SVV \> 10%, 6% hydroxyethyl starch (Voluven, Fresenius Kabi) until SVV-10% ; if there is no improvement after 250 ml 6% HES-a, ephedrine (0.5% Efedrin, UMC Ljubljana Pharmacy) 5-10 mg iv or fenilefrin 50-100 μg (0.01%, UMC Ljubljana Pharmacy). If CI \< 2 L/min/m2, SVV \< 10% and heart beat \< 40/min, atropine 0,5 mg. If the mean arterial pressure increases by more than 30% and the heart rate by more than 30% from baseline, the infusion of remifentanil is increased. Any adverse hemodynamic events that did not respond to changes in anaesthetic regimen could be managed with urapidil or metoprolol, as appropriate. Hypotension following blood losses was maintained with colloids (6% HAES) and blood replacement. Hemodynamic parameters were monitored continuously at 5-min intervals from the beginning of induction until the patients were discharged from the PACU.

30 minutes before the end of the surgery (at the time of dura closer) piritramid 5-10 mg was administered. Continuous intravenous infusion of piritramid was started postoperatively as patient control analgesia (PCA). The time of the operation was determined as the time from pin head-holder placement to its removal. The time from the end of the operation to the tracheal extubation was also noted. All patients were extubated in the operating theatre and then transferred to the recovery room.

Postoperative management:

After surgery, the patients stayed in the recovery room for one hour and were then transferred to the intensive care unit of the Department of Neurosurgery.

Standard postoperative monitoring generally used in these procedures was implemented. Oxygen titrated to the lowest level needed to achieve the target arterial oxygen saturation of 96%, was administered via a Venturi mask. Post anaesthetic adverse events and medication in ICU were recorded for a period of 24 h after anaesthesia. Adverse events were defined as any unintended changes in body function or well being, such as hypertension, postoperative nausea and vomiting, pain, neurological complications, in particular if clinical intervention or drug therapy was required.

Hospital stay was also recorded.

Study design:

This prospective randomised single centre study was conducted at the Department of Anaesthesiology and Surgical Intensive Care and at the Department of Neurosurgery, in close cooperation with the Department of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana. The investigators included 40 patients anaesthetised with remifentanil based anaesthesia with sevoflurane (S group) or propofol (P group). The study was approved by the National Medical Ethics Committee of the Republic of Slovenia. All the procedures were performed in accordance with Helsinki declaration. The written informed concern was obtained from all included patients. The patients included in the study were given anaesthesia by the same anaesthesiologist.

The data recorded included demographic characteristics, time of surgery, time to extubation, hemodynamic parameters.

Arterial blood samples for the determinations of cytokines (IL 6, IL 8, IL 10) were drawn at the following time points: 1. before induction, 2. During tumor resection 3. at the end of the surgery, and 4. 24 hours after surgery 5. 48 hours after surgery.

For analyses of serum interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10), blood samples were collected in tubes without additive. After centrifugation serum samples were stored at -20 ºC until analysis. Analyses of samples were performed in one batch. Chemiluminescent immunometric assay (Immulite analyzer; Siemens Healthcare, Erlangen, Germany) was used to measure the concentrations of IL-6, IL-8, and IL-10.

Comparison of Two Anaesthetics on Brain During Brain Tumour Surgery

Phase 1 Study of the Impact of Propofol vs. Sevoflurane on Brain Damage and Inflammatory Response During Brain Tumour Surgery

Drugs consumption, volume loading, blood loss and post anaesthetic adverse events and medication were recorded:

Drugs consumption, volume loading, blood loss and post anaesthetic adverse events and medication were recorded.

Efedrin was used for correction of low blood pressure

Post anaesthetic adverse events and medication:

Fenilefrin was used for low blood pressure correction

The interleukin 10 plasma concentrations during craniotomy (preoperative, perioperative and postoperative periods)

Post anaesthetic adverse events and medication in ICU were recorded for a period of 24 h after anaesthesia. Adverse events were defined as any unintended changes in body function or well being.

Post anaesthetic adverse events and medication in ICU were recorded for a period of 24 h after anaesthesia. Adverse events were defined as any unintended changes in body function or well being, in particular if clinical intervention or drug therapy was required.

University Medical Centre Ljubljana

MD, MSC

Blood and Lymph Conditions

Nutritional and Metabolic Diseases

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Vitamin D Deficiency

Neoplasms by Histologic Type

Hematologic Diseases

Avitaminosis

Deficiency Diseases

Malnutrition

Nutrition Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Pharmaceutical Solutions

Bone Density Conservation Agents

Micronutrients

Vitamins

Vitamin D

Cholecalciferol

Hormones

Calcium

Calcium, Dietary

Trace Elements

Vitamin D3

Calciferol

Group with deficient Vitamin D \< 20 ng/mL No treatment for the Vitamin D deficiency

Group with deficient Vitamin D + Daily oral dose of Cholecalciferol for 28 days for correcting the deficiency

Group with normal Vitamin D level \> 20 ng/mL

(Cholecalciferol 2800 I.U. ml) Oral Drops 15 ml. supplied with a dropper.

* Composition:

Each 1 ml (= 28 drops) of oral solution contains: Vitamin D3 (Cholecalciferol) 2800 I.U., (each drop contains 100 IU of vitamin D3).

Cholecalciferol 2800 I.U. ml oral drops

A Disintegrin-like And Metalloprotease with Thrombospondin type 1 motif 13 (ADAMTS13) deficiency was incriminated in poor prognosis, high probability of serious complications and mortality in acute myeloid leukemia (AML) patients. Interleukin 6 (IL-6) produced from AML blasts decreases Cluster of differentiation 34 positive(CD34+) cells differentiation, and inhibits the ADAMTS13 actions. Vitamin D "as an Immune-modulator" inhibits the pro-inflammatory cytokines including IL-6. So, supplementation of vitamin D might help down regulation of interleukin-6 production.

Aim of the study To evaluate the potential relation between Vitamin D status, ADAMTS13 and IL-6 in AML patients.

Objectives

1. Assess Vitamin D level in AML patients
2. Assess ADAMTS13 and IL-6 in AML patients
3. Correlate between Vitamin D level and both of ADAMTS13 and IL-6

I. Setting The study will be carried out in wards of ZAGAZIG University Hospitals II. Subjects The study will be conducted on patients with de novo diagnosis with acute myeloid leukemia III. Inclusion criteria

1. Patient's consent to share in the study
2. Patients' age \>18 years
3. Patients with de novo acute myeloid leukemia IV. Exclusion criteria

1. Patients refusing to share in the study 2. Non-Egyptian patients 3. Patients' age \< 18 years 4. Pregnant women 5. Patient's with other malignancies 6. Patients with known congenital thrombotic/ hemorrhagic diseases 7. Patients with Thrombotic Thrombocytopenic Purpura 8. Patients with auto-immune diseases

V. Study Design This is a Non-randomized control trial I. Sample size up Finding that ADAMTS13 level in AML patients before treatment is 455+_120 ng/ml versus 570+_100 ng/ml after treatment, the sample was calculated to be 30 patients, 15 patients in each group by using (open EPI) at confidence level 95 and power 80 I. Activities Patients attending to ZAGAZIG University Hospitals. Upon agreement, every patient will be asked to provide written informed consent according to the Declaration of Helsinki of 1979.

All patients will be subjected to the following:

1. Full History taking through an interview
2. Clinical examination
3. Laboratory investigations including:

   1. Complete blood picture ( CBC) using ( Sysmex XS 500)
   2. Peripheral blood film examination
   3. Erythrocyte sedimentation rate ( Westergren tubes )
   4. Prothrombin time, Partial thromboplastin time (Sysmex CS)
   5. C-reactive protein , Liver function tests \& Kidney function tests (Roche Diagnostics, Cobas 8000 c702, Switzerland)
   6. Hepatitis C virus antibody, Hepatitis B virus surface antigen and Human deficiency virus antibody
   7. Diagnosis of Acute myeloid leukemia according to clinical findings, CBC, peripheral blood film examination, Bone marrow aspiration, Immunophenotyping (a FACSCAN, Becton Dickinson, San Jose, California, USA)and Cytogenetic analysis.
4. Measuring IL-6 and ADAMTS13 using (Luminex Corporation, Luminex® 200 trademark , Austin, USA) before and after induction therapy
5. Measuring Vitamin D serum level using (Roche Diagnostics, Cobas 6000 e 601, Switzerland) before and after induction therapy and vitamin D supplementation based on its deficiency.
6. Radiology:

   * Echocardiogram
   * Abdominal ultrasound ( If needed)
   * Chest X-Ray II. Data collection Demographic data of the patients will be recorded including name, age, sex and residence. In addition, careful history taking and clinical examination will be done, and data will be registered in special form III. Statistical analysis Our study will be carried on 30 patients with de novo AML. Subjects will be divided into (2) groups as regard treatment of Vitamin D deficiency at the onset of AML diagnosis. Vitamin D therapy will be given to 15 deficient subjects for one month with the recommended doses. All the analytes will be assayed before and after the induction chemotherapy course. Both of these groups will be compared statistically using Statistics program smart solution 22 (SPSS22).

Administrative design:

Approval will be asked from ZAGAZIG University Institutional Review Board (IRB).

C. Ethical considerations

1. The study group will be informed about the nature and the purpose of the study and informed consent will be taken.
2. The study group will not be exposed to any harm or risk.
3. Patient's data will be confidential.

Vitamin D Effect on A Disintegrin-like And Metalloprotease Thrombospondin1 Motif 13& Interleukin 6 in Leukemia

Effect of Vitamin D Status on A Disintegrin-like And Metalloprotease With Thrombospondin Type 1 Motif 13 (ADAMTS13) and Interleukin 6 (IL-6) in Patients With Acute Myeloid Leukemia

Serum Vitamin D (ng/ml) measured using (Roche Diagnostics, Cobas 6000 e 601, Switzerland) on day 1 and day 28 . ADAMTS13 (ng/ml) is measured using (Luminex Corporation, Luminex® 200TM , Austin, USA) on day 1 and day 28 The inter-relation ship will be statistically assessed

Serum Vitamin D (ng/ml) measured using (Roche Diagnostics, Cobas 6000 e 601, Switzerland) on day 1 and day 28 . IL-6 (PG/ml) is measured using (Luminex Corporation, Luminex® 200TM , Austin, USA) on day 1 and day 28 The inter-relation ship will be statistically assessed

Using 1ml of Cholecalciferol as daily Oral drops for 28 days to correct the Vitamin D deficiency in acute myeloid leukemia patients.

On day 1;The patient is considered deficient with serum Vitamin D level measuring \< 20ng/ml using serum samples operated on (Roche Diagnostics, Cobas 6000 e 601, Switzerland) On using the drug for 28 days and measuring the Vitamin D level on the day 28, Vitamin D is considered to be "corrected" with levels \> 20 ng/ml

Zagazig University

Principal Investigator

Gland and Hormone Related Diseases

Diabetes Mellitus, Type 2

Diabetes Mellitus

Metabolic Diseases

Glucose Metabolism Disorders

Endocrine System Diseases

Hypoglycemic Agents

Empagliflozin

Dapagliflozin

Sodium-Glucose Transporter 2 Inhibitors

Canagliflozin

follow up of type 2 diabetes with SGLT2 inhibitors like empagliflozin, canagliflozin, and dapagliflozin for measurement of inflammatory factors like interleukin-6, CRP

interleukin 6

Since the discovery of SGLT2 inhibitors, there is a great shift in diabetic treatment, so this drug is magic, this drug can reduce the blood sugar level by blocking the reabsorption of glucose in the kidney and increasing glucose excretion the first discovery by Josef von Mering who discovered the glucosuric effect of phlorizin. Phlorizin is the progenitor of contemporary SGLT2 inhibitors, the FDA did not consider the work of Baron Josef von Mering, since he had already discovered acidosis following the administration of phlorizin in 1888.

Now SGLT2 inhibitors are used widely and even for heart failure without diabetes as this drug is useful and with lower risk of death from observational studies The 2008 FDA guidance had a major impact on the cardiovascular (CV) risk assessment of recently approved antidiabetic drugs, many trials were done on SGLT2 inhibitors like the EMPA-REG OUTCOME trial, the CANVAS trial program, MACE these groups have CVS benefits and also renal benefits as regards, we suspect long-term benefits and immunity aspect these groups play an important role in cancer incidence from meta-analysis and systematic review, suggests that SGLT2 inhibition results in a reduction of inflammatory markers like interleukin-6 in animal models, further validating the suggested anti-inflammatory mechanism of action.

The map of treatment of diabetes and obesity was changed dramatically and newer drugs were discovered in the last 10 years for improving the quality of patients and prevent complications and cardiovascular and renal benefits from SGLT2 inhibitors In our study, we will discuss the risk of cancer among diabetics on SGLT2 inhibitors and measurement of inflammatory factors like CRP and interleukin -6 alongside the other investigations the study included 200 adults patients with type 2 diabetes on SGLT2 inhibitors and follow up these patients for one year for the inflammatory factors and risk of cancer among them and this study include patients from 18 years to 70 years having diabetes type 2 male or female, smoker or not smokers, non-diabetic ketoacidosis

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Comparison of Two Anaesthetics on Brain During Brain Tumour Surgery	NCT02229201	Inflammation	Propofol Sevoflurane	18 Years - 80 Years	University Medical Centre Ljubljana
Vitamin D Effect on A Disintegrin-like And Metalloprotease Thrombospondin1 Motif 13& Interleukin 6 in Leukemia	NCT05149339	Acute Myeloid L... Vitamin D Defic... ADAMTS13 Interleukin 6	Cholecalciferol...	18 Years - 70 Years	Zagazig University
SGLT2 Inhibitors and Reducing the Risk of Cancers Among Diabetics , an Observational Study	NCT05612269	Cancer Diabetes Mellit... Interleukin 6 SGLT2 Inhibitor...	interleukin 6	18 Years - 70 Years	Ministry of Health, Saudi Arabia
Comparison of Two Anaesthetics on Brain During Brain Tumour Surgery	NCT02229201	Inflammation	Propofol Sevoflurane	18 Years - 80 Years	University Medical Centre Ljubljana
Vitamin D Effect on A Disintegrin-like And Metalloprotease Thrombospondin1 Motif 13& Interleukin 6 in Leukemia	NCT05149339	Acute Myeloid L... Vitamin D Defic... ADAMTS13 Interleukin 6	Cholecalciferol...	18 Years - 70 Years	Zagazig University
Vitamin D Effect on A Disintegrin-like And Metalloprotease Thrombospondin1 Motif 13& Interleukin 6 in Leukemia	NCT05149339	Acute Myeloid L... Vitamin D Defic... ADAMTS13 Interleukin 6	Cholecalciferol...	18 Years - 70 Years	Zagazig University

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