Migraine and gasdermin D: a new perspective on the inflammatory basis of migraine.

Migraine is a common and disabling primary headache disorder and inflammation is a proposed factor in the complex ethiology of the disease. Gasdermin D (GSDMD) is a membrane pore-forming protein acting through the caspase system. End result is cell death caused by leakage of intracellular components to extracellular space which also results in inflammation. Stemming from this knowledge, the potential role of GSDMD in migraine was investigated in this prospective study. This prospective study was conducted between September 2022 to April 2023. 47 patients with migraine were designated as the patient group, whereas 47 healthy volunteers were designated as the control group. Serum GSDMD levels of both groups were compared, with an additional comparison between migraine patients during symptom-free and attack periods. Migraine related characteristics of the patients were also included in the study. Median GSDMD levels of the patient and control group did not reveal a significant difference. Nausea, vomiting and severity of headache were found to be correlated with GSDMD levels in migraine patients. Patients with nausea revealed a higher GSDMD level compared to patients without nausea during both symptom-free and attack periods (p = 0.021 and p = 0.01, respectively). Nausea was correlated to higher GSDMD levels in the patient population during symptom-free period (p = 0.030). The severity of pain was positively correlated with GSDMD levels during the attack period (p < 0.001). Gasdermin family and GSDMD in particular are promising prospects for therapy in a wide spectrum of disorders. Gasdermin proteins are candidates to be the focus for future studies both related to pathogenesis and drug therapy in migraine and varying inflammatory-driven clinical pictures.

Crohn's Disease and Herpes Zoster: Being Mindful of Vaccination.

Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract. Immunosuppressive therapy is the main treatment modality in Crohn's disease. Herpes zoster (HZ), caused by Varicella-zoster virus, is a relatively common albeit burdensome clinical picture mainly affecting adult population with immunosuppressive status. In this paper, we aimed to report a Crohn's disease patient with HZ to raise awareness on vaccination. There are commercially available vaccines that are shown to be safe and effective against HZ reactivation. Crohn's disease patients should be evaluated and informed about preventive options against HZ to prevent unwanted HZ-related complications.

Effect of serum vitamin D levels on the severity of acute pancreatitis: A prospective study.

Acute pancreatitis (AP) is a serious and complex disorder with varying disease course and severity. Early and prompt interventions are crucial in management of AP. Vitamin D, being a prominent actor in calcium metabolism, also takes part in immunity and thus in immune-system related disorders, ranging from infections to cancer. In this study, the role of vitamin D status of a patient on the severity of AP was investigated. This study was conducted between June 2021 to August 2022 with a total of 315 patients. Blood samples were obtained upon admission. A 25-(OH)D3 level less than 10 ng/ml was defined as vitamin D deficiency. 10-19 ng/ml was defined as vitamin D insufficiency whereas 20 ng/ml or above was considered to be sufficient. Scoring systems (Ranson score, CTSI, BISAP, Revised Atlanta Classification (RAC) were applied. Serum 25-(OH)D3 levels of patients with AP were found to be negatively correlated with severity of the disease according to RAC (p < 0.001). In concordance to this finding, both Ranson score and BISAP were found to be statistically significantly related to 25-(OH)D3 levels. Both scoring systems revealed higher scores in patients with insufficient or deficient levels of 25-(OH)D3. Serum 25-(OH)D3 levels were not found to be related to intensive care unit admission or mortality. This study revealed that serum 25-(OH)D3 level is related to the severity of AP. In the future, interventional studies with vitamin D therapy in otherwise serum 25-(OH)D3 deficient AP patients might reveal a new potential therapeutic agent in this mechanically complex, burdensome disorder.

Investigation of Serum Human Epididymitis Protein 4 Level in Rats with Experimental Acute Pancreatitis.

BACKGORUND: We aimed to show whether the serum level of Human Epididymitis Protein 4 increases in rats with an experimental acute pancreatitis model created by cerulein. METHODS: This study included 24 male Sprague-Dawley rats which were randomly divided into 4 groups each containing 6 rats. CONTROL: the group treated with saline, Group 1: pancreatitis group created with cerulein at a total dose of 80 µg/kg, Group 2: pancreatitis group created with cerulein at a total dose of 120 µg/kg, Group 3: pancreatitis group created with cerulein at a total dose of 160 µg/kg. RESULTS: There were statistically significant differences between edema, acinar necrosis, fat necrosis, and perivascular inflammation scores among the study groups. While the degree of all histopathological findings is lowest in the control group, pancreatic parenchyma damage increases as the amount of injected cerulein increases. There was no statistically significant difference between alanine aminotransferase, aspartate aminotransferase, and Human Epididymis Protein 4 values between study groups. On the other hand, there was a statistically significant difference between amylase and lipase values. The lipase value of the control group was significantly lower than the lipase value of the second and third groups. The amylase value of the control group was significantly lower than all other groups. The highest Human Epididymis Protein 4 value was measured as 104 pmol/L in the first pancreatitis group, where the severity of pancreatitis was mild. CONCLUSIONS: In the present study, it was concluded that the Human Epididymis Protein 4 value increased in the case of mild pancreatitis, but there is no correlation between the severity of pancreatitis and the Human Epididymis Protein 4 value.

Relationship between Helicobacter pylori infection and white matter lesions in patients with migraine.

BACKGROUND/AIM: White matter lesions (WML) are more frequently observed in migraine patients than in the average population. Associations between Helicobacter pylori (H. pylori) infection and different extraintestinal pathologies have been identified. Here, we aimed to investigate the association between H. pylori infection and WML in patients diagnosed with episodic migraine. MATERIALS AND METHODS: A retrospective study was conducted with 526 subjects with a diagnosis of episodic migraine. Hyperintensity of WML had been previously evaluated in these patients with brain magnetic resonance imaging (MRI) examinations. Previous endoscopic gastric biopsy histopathological examination of the same patients and reports on H. pylori findings were recorded. The demographic characteristics of the patients, such as age, gender and chronic systemic diseases such as hypertension and diabetes mellitus (DM) were recorded. Statistical evaluation was made. RESULTS: Evaluation was made among 526 migraine patients who met the inclusion criteria, comprising 397 (75.5%) females and 129 (24.5%) males with a mean age of 45.57 ± 13.46 years (range, 18-69 years). WML was detected on brain MRI in 178 (33.8%) patients who were also positive for H. pylori (p <  0.05). Subjects who are H. pylori-positive with migraine, WML were observed at a 2.5-fold higher incidence on brain MRI (odds ratio: 2.562, 95% CI 1.784-3.680). WML was found to be more significant in patients with hypertension and migraine than those without (p <  0.001). Older age was also found to be associated with WML (OR = 1.07, 95% CI: 0.01-0.04, p <  0.001). The age (p <  0.001), H. pylori (p <  0.001), hypertension (p <  0.001), and hypertension + DM (p <  0.05), had significant associations in predicting WML according to the multivariate logistic regression analysis. The presence of hypertension had a higher odds ratio value than the other variables. CONCLUSION: It was concluded that H. pylori infection, as a chronic infection, can be considered a risk factor in developing WML in subjects with migraine.

Effect of Liver Transplant on Neurologic Manifestations and Brain Magnetic Resonance Imaging Findings in Wilson Disease.

OBJECTIVES: Wilson disease is an autosomal recessive disorder of copper metabolism. It leads to copper accumulation in various organs (liver, eye, brain) and deteriorates their functions. Symptoms usually appear in the second and third decades of life. Neurologic symptoms and manifestations may appear 2 to 5 years after liver involvement, and neurologic symptoms are usually movement disorders. The main treatment objective is to decrease accumulation of copper by increasing urinary copper excretion. With early diagnosis and treatment, the quality of life of patients with Wilson disease evolves. In this study, we aimed to evaluate the effects of liver transplant on neurologic manifestations and radiologic findings in patients with Wilson disease. MATERIALS AND METHODS: Since 1988, our center has performed 642 liver transplant procedures. Fifty-three patients with Wilson disease received a liver transplant during this period, with 15 adults patients included in our study. All study patients were evaluated by the same neurologist and radiologist. Tremor was scored by the glass scale test. Radiologic evaluations were made by cranial magnetic resonance imaging. RESULTS: Before liver transplant, 4/15 study patients had tremor. In 1 patient, tremor was accompanied by dystonia; the patient's imaging findings and neurologic manifestations had regressed posttransplant. In the other 3 study patients with tremor, tremor decreased without any change in imaging findings. New-onset tremor was seen in 1 patient after liver transplant, but this patient had no observed imaging changes. This situation was correlated with immunosuppressive therapy. CONCLUSIONS: Neurologic recovery can be achieved in patients with Wilson disease with early diagnosis and treatment. Radiologic findings can be improved after therapy.

Effect of Propranolol Treatment on the Incidence of Hepatocellular Carcinoma in Patients Waiting for Liver Transplant With Cirrhosis: A Retrospective, Surveillance Study in a Tertiary Center.

OBJECTIVES: Hepatocellular carcinoma is the most frequent primary malignant tumor of the liver and the third most common cause of all cancer-related mortalities. There is a need to develop new strategies to prevent hepatocellular carcinoma, as the incidence of this cancer continues to increase despite all advancements. In this study, our aim was to determine the effects of propranolol treatment on the incidence of hepatocellular carcinoma in cirrhotic patients waiting for liver transplant. MATERIALS AND METHODS: We retrospectively reviewed the data of patients waiting for liver transplant with cirrhosis due to various causes registered at the Hepatocellular Carcinoma Surveillance Program between June 2011 and December 2017 in our center. These data were compared between patients using propranolol and those not using propranolol. RESULTS: Of the 231 patients, 135 (58.4%) were male and 96 (41.6%) were female. The mean age was 58.1 ± 14 years. We noted that 153 of total patients (66.2%) were using propranolol. Three patients (2%) were using 20 mg propranolol, 125 (81.7%) were using 40 mg propranolol, 10 (6.5%) were using 60 mg propranolol, and 15 (9.8%) were using 80 mg propranolol. Of total patients, 36 (15.6%) developed hepatocellular carcinoma, including in 12 patients (7.8%) using propranolol and 24 patients (30.8%) who did not use this agent (P < .001). Thus, the hepatocellular carcinoma frequency was 5.22 times lower in patients receiving propranolol than in those not receiving propranolol. CONCLUSIONS: Although causes of cirrhosis and initial stages were similar in both groups using and not using propranolol, incidence of hepatocellular carcinoma was significantly lower in the propranolol group than in the group without propranolol. This result showed that propranolol treatment has a protective effect for hepatocellular carcinoma in patients waiting for liver transplant with cirrhosis.

Successful Treatment With Direct-Acting Antiviral Agents of Hepatitis C in Patients With End-Stage Renal Disease and Kidney Transplant Recipients.

OBJECTIVES: The introduction of direct-acting antiviral agents has allowed significant chances for treatment for difficult-to-treat populations. This study aimed to investigate the efficacy, tolerability, and safety of these therapies in both patients with end-stage renal disease and kidney transplant recipients with chronic hepatitis C virus infection. MATERIALS AND METHODS: This study was a retrospective analysis with prospective follow-up of patients. The antiviral combination of ombitasvir 25 mg, paritaprevir 75 mg, ritonavir 50 mg, and dasabuvir 50 mg was prescribed to patients with end-stage renal disease or kidney transplant recipients with noncirrhotic or compensated cirrhotic liver disease. The other antiviral combination consisted of sofosbuvir 400 mg and ledipasvir 90 mg, which was recommended to patients with decompensated cirrhosis or those who could not tolerate the first combination regimen. Ribavirin was given to all patients with genotype 1a hepatitis C virus infection. All clinical and laboratory data were recorded at week 4, at end of the treatment, and at 12 weeks after completion of treatment. RESULTS: In terms of efficacy, sustained virologic response at 12 weeks was achieved in 94% of patients in the end-stage renal disease group and 92% of patients in the kidney transplant group. In terms of tolerability, antiviral treatment was well tolerated in both groups. Cardiac arrest and cerebrovascular accident were seen in the end-stage renal disease group; severe mucositis and glossitis were seen in the kidney transplant group. Hospitalization was needed in 2 patients for treatment of drug interactions with tacrolimus and sirolimus. Renal allograft function worsened in 2 patients, with 1 patient having biopsyproven antibody-mediated rejection. CONCLUSIONS: We observed great efficacy and safety in both kidney transplant recipients and patients with end-stage renal disease with these agents in treatment of chronic hepatitis C. However, clinicians should remain aware of drug interactions and adverse events in this fragile patient population.

Anxiety, depression, and anger in functional gastrointestinal disorders: A Cross-sectional observational study.

Previous studies have identified a link between anger and somatization. However, little is known about the associations between anger and the development and progression of Functional Gastrointestinal Disorders (FGID). The study aim was to determine the associations between FGID and anger, anxiety, and depression. Participants in this cross-sectional observational study were 109 consecutive patients aged 18-64 years with FGID at Gastroenterology Clinic of Baskent University Hospital. A control group comprised of 96 individuals with no chronic gastrointestinal disorders recruited via snowball sampling. Sociodemographic and clinical information were obtained and participants completed the Hospital Anxiety and Depression Scale and the State-Trait Anger Expression Inventory-2. FGID participants scored higher than controls on depression, anxiety, state anger, and anger expression-in. When the FGID group was divided into upper and lower gastrointestinal symptom groups, the lower symptom group showed higher anger expression-out scores than the upper symptom group. Anger may contribute to the etiology and development of FGID. This is the first study to demonstrate a significant psychological difference between individuals with lower and upper FGID. Interdisciplinary collaboration with gastroenterologists and psychiatrists could strengthen FGID evaluation and may improve treatment compliance.

Complications of Liver Transplant in Adult Patients With the Hepatic Form of Wilson Disease.

OBJECTIVES: Wilson disease is an autosomal, recessive, inherited disorder of copper metabolism that results in the accumulation of copper in many organs and tissues. This disease is mainly characterized by dysfunction due to copper accumulation in the liver, kidney, brain, cornea, bone, heart, and blood cells. The clinical spectrum is broad in Wilson disease. Asymptomatic Wilson disease may be present, but findings related to the involvement of an individual organ or multiple organ failure can be seen. These findings can include neurologic and neuropsychiatric complications. Our aim here was to examine the neurologic complications and our clinical experience in patients who underwent liver transplant for Wilson disease in our clinic. MATERIALS AND METHODS: We retrospectively reviewed the medical records of transplant patients with Wilson disease who were seen at Baskent University Faculty of Medicine Transplantation Science between 2005 and 2017. Patient demographics, neurologic complaints, findings from neurologic examinations, and imaging findings were recorded. We also recorded the presence of the Kayser-Fleischer ring, serum ceruloplasmin, 24-hour copper urine levels, and levels of dry copper in liver in each patient. RESULTS: Our study included 19 patients who ranged in age range from 18 to 44 years (mean age of 26 years). Seven of 19 patients (36.8%) had neurologic symptoms, including epileptic seizures in 2 patients (10.5%), encephalopathy in 1 patient (5.2%), tremor in 3 patients (15.7%), and headache in 1 patient (5.2%). The cause of these long-term neurologic complications was the immunosuppressive drugs. Patients with epileptic seizures were provided with seizure control medication (levetiracetam). Tremor did not need treatment. CONCLUSIONS: In Wilson disease, neurologic complications can be severe. The most common complication seen in our patients was tremor. Early diagnosis and treatment may slow down neurologic disability.