Nafamostat Reduces the Incidence of post-ERCP Pancreatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). As the management of pancreatitis is limited, clinical approaches focus on the prevention of post-ERCP pancreatitis (PEP). In theory, the serine protease inhibitor nafamostat can reduce circulating inflammatory mediators in pancreatitis. We aimed to investigate the effect of nafamostat in the prevention of PEP in this systematic review and meta-analysis. The protocol for this review was registered in PROSPERO (CRD42022367988). We systematically searched 5 databases without any filters on September 26, 2022. The eligible population was adult patients undergoing ERCP. We compared the PEP preventive effect of nafamostat to placebo. The main outcome was the occurrence of PEP. We calculated the pooled odds ratios (ORs), mean differences, and corresponding 95% confidence intervals (95% CIs) and multilevel model. The risk of bias was assessed using the Rob2 tool. Seven randomized controlled trials involving 2,962 patients were eligible for inclusion. Nafamostat reduced the overall incidence rate of PEP (20 mg, OR: 0.50, 95% CI: 0.30-0.82 and 50 mg, OR: 0.48, 95% CI: 0.24-0.96). However, the occurrence of mild PEP was significantly reduced only in the subgroup receiving 20 mg nafamostat (OR, 0.49, 95% CI: 0.31-0.77). Overall, nafamostat therapy reduced moderate PEP in high-risk patients (OR: 0.18, 95% CI: 0.0.4-0.84) and mild PEP in low-risk patients (OR: 0.32, 95% CI: 0.17-0.61). Nafamostat is an effective therapy in the prevention of mild post-ERCP pancreatitis. Further research is required to determine the cost-effectiveness of this therapy.

Nabiximols is Efficient as Add-On Treatment for Patients with Multiple Sclerosis Spasticity Refractory to Standard Treatment: A Systematic Review and Meta-Analysis of Randomised Clinical Trials.

BACKGROUND: Spasticity affects 54% of multiple sclerosis (MS) patients at disease onset, but this rate gradually increases with disease progression. Spasticity does not fully respond to standard treatment in one-third of the patients. OBJECTIVE: Our systematic review and meta-analysis assessed whether add-on nabiximols, can improve MS-associated refractory spasticity. METHODS: The systematic literature search was performed in Web of Science, MEDLINE, Scopus, CENTRAL, and Embase, on 15/10/2021, without restrictions. We included in the review blinded, randomized, placebo-controlled trials evaluating the efficacy of nabiximols in adult MS patients with refractory spasticity, by comparison with placebo. The primary outcome was responder rate by spasticity numerical rating scale (NRS). Secondary outcomes were spasticity-related parameters. We used random effect models to calculate odds ratios (OR) or mean differences and the corresponding 95% CI. Bias-factors were assessed with Cochrane risk of bias tool (RoB2). (PROSPERO ID: CRD42021282177). RESULTS: We identified 9 eligible articles, of which 7 (1128 patients) were included in the meta-analysis. The spasticity numerical rating scale (NRS) was significantly higher in the nabiximols group than in the placebo group (OR 2.41 (95% CI 1.39; 4.18)). Secondary outcomes were in accordance with our primary results. At least some concerns were detected in the risk of bias analysis. CONCLUSION: Our results indicate that nabiximols is efficient in MS associated spasticity, refractory to standard treatment and it may be considered as add-on symptomatic therapy. Nevertheless, further studies are needed to establish the optimal treatment protocol - dose, duration, moment of initiation, disease type.

Type 2 Diabetes Patients' Views of Local Pharmacists and Fulfilment with Pharmaceutical Diabetes Care in Syria's Latakia Governorate: An Online Survey Research.

Assessing the attitudes of diabetic patients towards community-pharmacy services and determining the demand for new services could help monitor and evaluate the therapeutic response. This study aimed to evaluate type 2 diabetes patients' satisfaction regarding pharmacy care in community pharmacies and shed a light on the reasons for diabetic patients' non-adherence to treatments. An online survey was conducted on a random sample of patients (n = 196) at the national Diabetes Centre in Latakia, Syria, from April to November 2022. The questionnaire consisted of four primary parts: (1) demographic characteristics of responders, (2) patients' therapeutic behaviors, (3) diabetes knowledge, and (4) the general level of satisfaction with pharmacy diabetes services. The data were analyzed using descriptive analysis. Around 89% of respondents were satisfied with the information provided by community pharmacists. The patients' non-adherence showed a maximum as a function of the number of concomitantly taken medicines, which indicated that in most serious cases patients' adherence was increasing. Overall, most patients were delighted with community pharmacists' expertise and pharmacy services. This positive image allows pharmacists to expand their duties as healthcare providers in diabetes care, and increase the patient therapeutic adherence by performing a reconciliation of the patient's medicines, which involves reviewing all patients' drugs and identifying realistic solutions to their adherence issues.

No evidence for the benefit of PPIs in the treatment of acute pancreatitis: a systematic review and meta-analysis.

Although current guidelines do not recommend the use of proton pump inhibitors (PPIs) in the standard of care of acute pancreatitis (AP), they are often prescribed in clinical practice, mainly for ulcer stress prophylaxis. In this systematic review and meta-analysis we evaluated the association between the use of PPIs in the management of AP and various clinical outcomes. We conducted the systematic research in six databases without restrictions on January 24th, 2022. We investigated adult patient with AP, who were treated with PPI compared to conventional therapy. The pooled odds ratios, mean differences, and corresponding 95% confidence intervals were calculated with random effect model. We included six RCTs and three cohort studies, consisting of 28,834 patients. We found a significant decrease in the rate of pancreatic pseudocyst formation in patients who received PPI treatment. PPI use was associated with a higher risk of GI bleeding, however this finding could be due to the patients' comorbid conditions. We found no significant difference in the rates of 7-day mortality, length of hospital stay, and acute respiratory distress syndrome between the groups. The available data on this topic are limited; therefore, further well designed RCTs are needed to evaluate the potential benefits and adverse effects of PPIs in AP.

The combination of ulinastatin and somatostatin reduces complication rates in acute pancreatitis: a systematic review and meta-analysis of randomized controlled trials.

Currently, there is no specific pharmaceutical agent for treating acute pancreatitis (AP). Somatostatin and its analogues have been used to prevent the autolysis of the pancreas in AP, however, their effectiveness has not been confirmed. This investigation aimed to examine the efficacy of ulinastatin, a protease inhibitor, combined with somatostatin analogues in the treatment of AP. We conducted a systematic database search in 4 databases to identify randomized controlled trials in which the efficacy of ulinastatin in combination with somatostatin analogue was compared to somatostatin analogue alone in patients with AP. Since the patient populations of analysed papers were slightly different, we used random effect models to pool odds ratios (OR) and mean differences (MD) and the corresponding 95% confidence intervals (CI). A total of 9 articles comprising 1037 patients were included in the meta-analysis. The combination therapy significantly reduced the complication rates for acute respiratory distress syndrome, acute kidney injury, and multiple organ dysfunction. Symptoms were relieved threefold with the combination therapy compared to somatostatin alone, and combination therapy significantly shortened the length of hospital stay. The decrease in mortality was not statistically significant..

Implementation of a personal health planning program and health promotion in the community pharmacies.

It is well known that one of the most accessible health providers are community pharmacists; hence, their role in sanitarian programs should not be neglected. Although they were not present in the first pilot trial of the Hungarian Health Planning Application (HHPA) made by the National Healthcare Services Center, they were involved in the latter phases of the personal health planning program. The aim was the detailed assessment of the HHPA, with regard to the newly introduced online form. The HHPA is a software designed to identify health risks and help in the health planning and management of the risks. The present study was started in the 2016/2017 academic year, and the enrollment of citizens was carried out by resident pharmacists, who had received additional training on the software and primary (and tertiary) prevention. The resident pharmacists also filled two opinion survey questionnaires, one at the beginning of the study and one after the study period. Seventy-five pharmacists enrolled 594 citizens. At the 190 participants who enrolled by online application, the drop-out rate was similar to the personal way. The main four risks that were identified in the study were the risk of an inactive lifestyle (47.8%), weight problems (38.7%), risk of diabetes mellitus (26.9%), and cardiovascular risks (25.3%). About the project, the majority of the pharmacists thought that it was a useful project. Highlighted supporting factors were colleges in the pharmacies that were very encouraging; however, factors such as long risk-assessment or the non-cooperation of the other healthcare providers were discouraging. The personal health planning program is a favorable initiative for identifying health risks and determining health plans. Furthermore, the used software seems to be same effective as personal way, but more suitable in the present pandemic situation.

Fat rich diet-induced steatosis and changes in the gut­liver axis / A zsírdús étrend indukálta steatosis és a bél-máj tengely változásai.

INTRODUCTION: Fatty liver can develop as a result of diseases, surgical procedures, medicaments, malnutrition or excessive alcohol consumption, however, fat and poor fiber feeding can be attributed as the primary cause. Non-alcoholic fatty liver can be found in 20-30% of the population. Generally, alimentary-induced fatty liver in early state is described as uncomplicated liver injury. AIM: The aim of our research was to study the effect of fat rich nutrition on the gut-liver axis by routine laboratory, analytical and histological methods in rats. METHODS: We also examined the redox parameters of the liver and of the bowel. Fatty acid composition and element content of liver were measured. RESULTS: Significant changes were found in parameters of redox homeostasis as well as alterations in liver enzymes and metabolites. The changes could be detected in the liver, blood and bowel parts. The development of fatty liver is associated with the decrease of transmethylation capacity. Fatty acid composition and metal ion homeostasis were also altered in liver. Histological examinations showed that hepatocytes were swollen in the central part of the liver lobules, showed droplets and pycnotic nuclei, which were characterized by fatty degeneration. Small and large bowel enterocytes were damaged, sometimes pushed from the surface, and sometimes inflammatory reactions in the mucous membrane were observed. CONCLUSION: Our results suggest that alimentary fatty liver in early state is not considered simply as a reversible alteration because it alters the entire body's redox homeostasis and establishes heart and serious metabolic diseases as well as hasten the development of gastrointestinal tumors. Orv Hetil. 2020; 161(35): 1456-1465.

Metal- and redox homeostasis in prostate cancer with vitamin D3 supplementation.

Vitamin D3 supplementation has a beneficial effect on cancerous patients, although it can influence the redox- and metal homeostasis. The aim of our investigation was to demonstrate the effect of vitamin D3 consumption on the redox- and metal homeostasis in prostate cancer, because of the recommended daily dose increased from 200 IU to 2000 IU in recent years in Hungary. Forty-three volunteers were involved in the study. The grouping was applied according to the clinical routine laboratory parameters (vitamin D3) and the tumor markers (PSA, fPFA). Patients were divided into 5 groups: (A) patient control (N = 8), (B) patient control with vitamin D3 treatment (N = 9), (C) high-risk prostate cancer group (N = 6), (D) high-risk prostate cancer group with vitamin D3 treatment (N = 8) and (E) vitamin D3 treated cancerous group with androgen deprivation therapy (N = 11). The element concentrations were determined with ICP-OES. Among the redox parameters, free radical scavenging capacity and H-donating ability were determined with luminometry and spectrometry. Vitamin D3 treatment caused differences in the metal- and redox homeostasis in either patient control and cancerous groups. The concentration of Fe, Cr, and Pb significantly increased in the erythrocytes of prostate cancer patients. According to the higher scavenging capacity by vitamin D3 treatment, it seems that vitamin D3 helps to equilibrate the redox homeostasis that could affect the outcome of cancer positively. However, the tendency in the metal element status does not give a clear explanation of cancer's outcome, but the accumulation of Pb by vitamin D3 supplementation needs to be taken into more serious consideration in set terms of occupational diseases.

[Evaluation of free radical quantity in the anterior chamber following femtosecond laser-assisted capsulotomy]. / Szabadgyök-felszabadulás vizsgálata femtoszekundum lézerrel asszisztált capsulotomiát követoen.

INTRODUCTION: Femtosecond laser is a revolutionary, innovative treatment method used in cataract surgery. AIM: To evaluate free radical quantity in the anterior chamber of the eye, during femtosecond laser assisted capsulotomy, in a porcine eye model. METHOD: Seventy fresh porcine eyes were collected within 2 hours post mortem, were transported at 4 ºC and treated within 7 hours. Thirty-five eyes were used as control and 35 as femtosecond laser assisted capsulotomy group. A simple luminol-dependent chemiluminescence method was used to measure the total scavenger capacity in the aqueous humour, as an indicator of free radical production. The emitted photons were expressed in relative light unit %. RESULTS: The relative light unit % was lower in the control group (median 1%, interquartile range [0.4-3%]) than in the femtosecond laser assisted capsulotomy group (median 4.4%, interquartile range [1.5%-21%]) (p = 0.01). CONCLUSIONS: Femtosecond laser assisted capsulotomy decreases the antioxidant defense of the anterior chamber, which refers to a significant free radical production during femtosecond laser assisted capsulotomy. Orv. Hetil., 2016, 157(47), 1880-1883.

Changes of erythrocyte element status of colectomysed cancerous patients: Retrospective study.

Nowadays it has been established that metals and metal-induced oxidative stress act on signal transduction pathways, and are in association with cancer growth and spreading as well as in neurodegenerative disorders. In cases of several neurodegenerative diseases metals, especially Al, can be considered as a risk factor. Frequency of chemotherapy-related cognitive impairment or "chemobrain" is mentioned to be significant in literature, although very little is known about the chemotherapy-caused chemobrain and its connection with metal homeostasis alteration. Dysregulation of metal homeostasis can be assumed as one of the key factors in the progression of neurodegeneration. Therefore we were interested in studying metal element status of 27 adult patients in 3 years after their colectomy, 22 outpatients and 10 healthy volunteers in both genders. Tumour markers, laboratory parameters and metal element concentrations were determined. We found significant difference among the Al concentrations in operated patients compared with controls. Redox active Fe and Cu levels were also elevated slightly in this patient group. P and S concentrations changed in different ways, and Ca levels were slightly lower, than in healthy controls. Because of all above mentioned, examination of metal homeostasis in cancerous patients is necessary to moderate the risk of chemobrain and other redox-related disorders.

Neural elements behind the hepatoprotection of remote perconditioning.

BACKGROUND: The ability of remote ischemic perconditioning (RIPER) to protect the liver from ischemic-reperfusion (IR) injury has been reported before; however, the mechanism behind the positive effects of RIPER remains unrevealed. Therefore, we aimed to investigate the potential role of neural elements to transfer protective signals evoked by perconditioning. MATERIALS AND METHODS: Male Wistar rats were randomly allocated into six groups (sham, IR, RIPER ± denervation; n = 7 per group). Half of the animals underwent left femoral and sciatic nerve resection. In IR and RIPER groups, normothermic, partial (70%) liver ischemia lasting for 60 min was induced; parallel animals in the RIPER groups received perconditioning treatment (4 × 5 - 5 min IR, left femoral artery clamping). Hepatic microcirculation and systemic blood pressure were monitored during the first postischemic hour. After 24 h of reperfusion, liver samples were taken for histology and redox-state analysis. Automated image analysis software was used for necrosis quantification. Serum alanine aminotransferase, aspartate aminotransferase, and bilirubin levels were measured. RESULTS: Microcirculation and blood pressure showed significant improvement during reperfusion after perconditioning. This phenomenon was completely abolished by nerve resection (P < 0.05; RIPER versus IR, IR + denervation, and RIPER + denervation). Results of necrosis quantification showed similar pattern. Besides noncharacteristic changes in aspartate aminotransferase levels, alanine aminotransferase values were significantly lower (P < 0.05) in the RIPER group compared with the other IR groups. Mild but significant alterations were observed in liver function assessed by total bilirubin levels. Further supporting results were obtained from analysis of redox homeostasis. CONCLUSIONS: Perconditioning was able to reduce liver IR injury in our model via a mechanism most probably involving interorgan neural pathways.

[Transmethylation and the redox homeostasis]. / Transzmetilezési folyamatok és a redox-homeosztázis.

INTRODUCTION: Transmethylation modifies configuration and proceeds via formaldehyde. It has a significant role for example in epigenetic regulation. The whole methyl-pool can be evaluated by the measurement of bound formaldehyde. AIM: The bound formaldehyde was measured in wheat, bean, beetroot, cabbage, broiler- and rabbit liver. The relationship between transmethylation and redox homeosthasis was studied in the liver of domestic animals, and in the rat model of fatty liver. METHOD: The diet of rats was enriched with cholesterol, sunflower oil and cholic acid. The bound formaldehyde was determined by overpressured layer chromatography. The hydrogen-donating ability was measured with 1.1-diphenyl-2-picrylhydrazylt free radical using spectrophotometric measurement. RESULTS: Beans had the most bound formaldehyde. The liver of broilers possessed significantly elevated hydrogen-donating ability and transmethylation ability. Rats with severe fatty liver had significantly less bound formaldehyde and the hydrogen-donating ability tendentiously decreased. CONCLUSIONS: These results draw attention to the diet, especially in obesity and obesity-related diseases.

[The potential use of cannabidiol in the therapy of metabolic syndrome]. / A kannabidiol gyógyászati alkalmazhatósága metabolikus szindrómában.

Cannabidiol, a cannabinoid and serotonin receptor antagonist, may alleviate hyperphagia without the side effects of rimonabant (for example depression and reduced insulin sensitivity). Similar to the peroxisome proliferator-activated receptor-gamma agonists, it may also help the differentation of adipocytes. Cannabidiol has an immunomodulating effect, as well, that helps lessen the progression of atherosclerosis induced by high glucose level. It may also be effective in fighting ischaemic diseases, the most harmful complications of metabolic syndrome. However, it can only be administered as an adjuvant therapy because of its low binding potency, and its inhibiting effect of cytochrome P450 enzymes should also be considered. Nevertheless, it may be beneficially used in adjuvant therapy because of its few side effects.