Estrobolome and Hepatocellular Adenomas-Connecting the Dots of the Gut Microbial ß-Glucuronidase Pathway as a Metabolic Link.

Hepatocellular adenomas are benign endothelial tumors of the liver, mostly associated with female individual users of estrogen-containing medications. However, the precise factors underlying the selective development of hepatic adenomas in certain females remain elusive. Additionally, the conventional profile of individuals prone to hepatic adenoma is changing. Notably, male patients exhibit a higher risk of malignant progression of hepatocellular adenomas, and there are instances where hepatic adenomas have no identifiable cause. In this paper, we theorize the role of the human gastrointestinal microbiota, specifically, of bacterial species producing ß-glucuronidase enzymes, in the development of hepatic adenomas through the estrogen recycling pathway. Furthermore, we aim to address some of the existing gaps in our knowledge of pathophysiological pathways which are not yet subject to research or need to be studied further. As microbial ß-glucuronidases proteins recycle estrogen and facilitate the conversion of inactive estrogen into its active form, this process results in elevated levels of unbound plasmatic estrogen, leading to extended exposure to estrogen. We suggest that an imbalance in the estrobolome could contribute to sex hormone disease evolution and, consequently, to the advancement of hepatocellular adenomas, which are estrogen related.

Neurological and Dermatological Manifestations of Tuberous Sclerosis Complex: Report from a Romanian Tertiary Hospital Cohort.

Tuberous sclerosis complex is a rare multisystem genetic disorder characterized by multiorgan involvement, frequently associated with intellectual impairment and epilepsy. The aim of our study was to describe the neurological and dermatological manifestations of TSC in 32 adult patients (of whom 19 were females) who attended the Neurology and Nephrology Clinics of Fundeni Clinical Institute in Romania from 2015 to 2020. Seventeen patients were diagnosed with epilepsy, nine patients had intellectual impairment, and complete neuroimaging was available for twenty-two patients. As expected, the most frequent dermatological lesions were cutaneous angiofibromas in 20 patients, but with a lower frequency than described in the current literature. Statistical analysis was performed considering the small number of patients. Cortical tubers in neuroimaging seemed to be associated with the diagnosis of epilepsy, while subependymal nodules represented a risk factor for intellectual impairment. Males showed a larger number of dermatological types of lesions, especially café -au-lait patches. Interestingly, we found a statistically significant positive association between epilepsy and the presence of cutaneous angiofibromas, as well as total dermatological involvement. Females had significantly higher Charlson comorbidity index scores, indicating a higher burden of disease. Everolimus seemed to be a well-tolerated treatment and showed promising results in controlling epileptic seizures alone in two patients. More studies, with the inclusion of a larger number of patients, are needed to confirm these results.

Thunderclap headache revealing dural tears with symptomatic intracranial hypotension: Report of two cases.

Cerebrospinal fluid (CSF) leakage is considered the cause of spontaneous intracranial hypotension (SIH), an important etiology for new daily persistent headaches and a potentially life-threatening condition. Minor traumatic events rarely lead to CSF leakage, contrasting with iatrogenic interventions such as a lumbar puncture or spinal surgery, which are commonly complicated by dural tears. Most meningeal lesions are found in the cervicothoracic region, followed by the thoracic region, and rarely in the lumbar region, and extremely rarely in the sacral region. We describe two patients admitted to our hospital for severe headaches aggravated in the orthostatic position, with a recent history of minor trauma and sustained physical effort, respectively. In the first case, a bone fragment pierced an incidental congenital meningocele creating a dural fistula. An extensive extradural CSF collection, spanning the cervicothoracic region (C4-T10), was described in the second case. In both patients, the clinical evolution was favorable under conservative treatment.

Chorea and Cognitive Impairment in JAK2V617F-Positive Myeloproliferative Disorders: A Case Report and Literature Review.

Chorea is a hyperkinetic movement disorder, accompanied by dystonia, myoclonus, tics, stereotypies, and tremors. It is characterized by excessive, purposeless movements that are distressing, irregularly timed, and randomly distributed. Chorea can be present in many diseases, such as hereditary, metabolic disturbance, drug-induced, and functional disorders, and, rarely, genetic, autoimmune, and infectious diseases. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm that leads to ineffective clonal hematopoiesis, fibrous tissue deposits in the bone marrow, extramedullary hematopoiesis, and splenomegaly. In rare cases, following uncertain pathological mechanisms, it can present with chorea, particularly affecting the limbs, head, and orofaciolingual muscles. We present a case of a male patient with evolving PMF over several years who was admitted for progressive cognitive impairment and generalized involuntary movement disorder. We also present a review of all cases of myeloproliferative disorders presenting with chorea published in the last 40 years.

Magnetic Resonance Imaging of Multiple Cerebral and Spinal Cavernous Malformations of a Patient with Dementia and Tetraparesis.

Cavernomas are rare cerebrovascular malformations that usually occur in sporadic forms with solitary lesions located most often in the hemispheric white matter, but also in the infratentorial or spinal region. Multiple lesions at different CNS levels are considered a hallmark for the familial form of the disease. The diagnostic modality of choice for cerebral cavernous malformations (CCMs) is magnetic resonance imaging (MRI). We present an intriguing case of a 65-year-old male admitted to our hospital with tetraparesis and cognitive impairment where highly sensitive MRI sequences identified many cerebral cavernous lesions at the supra-, infratentorial and cervical-thoracic spine levels, some of them with recent signs of bleeding in a patient with oral anticoagulant therapy due to atrial fibrillation. The mechanism of cognitive impairment in this patient is most probably the interruption of strategic white matter tracts, as it is known to happen in other subcortical vascular pathologies. MRI can be helpful not only in mapping the anatomical distribution of lesions, but also in weighing the risks and making decisions regarding whether or not to continue oral anticoagulant therapy.

Influence of anti-TNF therapy and homocysteine level on carotid intima-media thickness in rheumatoid arthritis patients.

It is a well-known fact that disruptions in the immune system and systemic inflammation are associated with accelerated atherosclerosis in rheumatoid arthritis (RA) patients. Elevated levels of tumor necrosis factor α (TNF-α), a major pro-inflammatory cytokine, are involved in endothelial cell activation of medium and large arteries, leading to increased endothelial permeability, generation of superoxide anion radical and hydrogen peroxide, and decreased availability of nitric oxide (NO). The present study aims to determine the influence of anti-TNF therapy and homocysteine (Hcy) levels on the carotid intima-media thickness (IMT) in patients with RA. Assessments were performed on 115 patients diagnosed with RA on biological treatment to determine the evolution of IMT and Hcy levels. Carotid ultrasonography was used to assess the IMT, as a fast and easy tool for the prediction of cardiovascular events in patients with RA. The first measurement of IMT was noted as IMT1, followed by a second measurement after 1 year, noted as IMT2. The group of patients was divided into approximately three equal groups, each being treated with a different biological product, respectively, etanercept, adalimumab, and infliximab. In the 3 groups, after 1 year of anti-TNF-α therapy, IMT2 progression was significantly reduced compared to baseline. No significant differences were found among the three groups of treatment. A strong association was observed between IMT1-IMT2 in the etanercept group (P<0.001, r=0.758), in the adalimumab group (P<0.001, r=0.761) and in the infliximab group (P<0.001, r=0.829). The low level of Hcy2 after 12 months of anti-TNF-α therapy was significantly correlated with a decrease in IMT2 (P<0.001) in patients who had a high level of Hcy and IMT >0.9 mm at baseline. The results from the present study showed that biological treatment and the low level of homocysteinemia reduced the cardiovascular risk in RA, regardless of the treatment chosen (infliximab, adalimumab, or etanercept).

Variation of clinical and laboratory features in chronic dialysis patients treated with high-flux hemodialysis after switching to online hemodiafiltration.

PURPOSE: The study of online hemodiafiltration (HDF) benefits over high-flux hemodialysis (HD) raises great interest. The purpose was to compare clinical and laboratory parameters in patients treated with HD who were switched to HDF. METHODS: Forty-eight HD patients (study group) were switched to HDF, while other 521 patients remained on HD as a control group. During last 6 HD months and during first year of HDF, we determined in both groups the following parameters: monthly-weekly dialysis time, systolic and diastolic blood pressure, body mass index (BMI), interdialytic body weight gain (IBWG), blood flow rate (Qb), weekly erythropoietin-stimulating agents dose (EPO), single-pool Kt/V, calcium, phosphorus (P), hemoglobin and normalized protein catabolic ration (nPCR), plus every 3 months--albumin, parathormone (PTH), ferritin and transferrin saturation (TSAT). In both groups, parameters in the last 6 HD months were compared to those in the first 6 months and, respectively, to those in the first year of HDF. RESULTS: In the study group, albumin and nPCR were significantly higher in the HD period not only compared to the first 6 months of HDF, but also compared to the first year of HDF. IBWG and P were higher with HD compared to the first year of HDF, but not with the first 6 months. PTH, Kt/V, Qb and EPO were higher in both HDF periods. In the control group, albumin was significantly higher in the first 6 months after the switch, but it was significantly lower in the first year. BMI, ferritin, PTH, Kt/V, Qb, TSAT and weekly dialysis time were higher in both HDF periods, while nPCR, EPO, SBP and DBP were lower. IBWG and Hb rose only during the first year after the switch, while P was lower in the first year, but not in the first 6 months. CONCLUSIONS: Nutrition, assessed by albumin, nPCR and BMI, was not improved by HDF compared to HD. With HDF, Kt/V and phosphorus control were better, similar results were observed in the control group. A larger EPO dose was needed with HDF for maintaining a similar hemoglobin level.

The His1069Gln mutation in the ATP7B gene in Romanian patients with Wilson's disease referred to a tertiary gastroenterology center.

BACKGROUND AND AIM: Wilson's disease (WD) is a rare autosomal recessive disease. More than 500 mutations have been described so far, out of which 29 in exon 14. H1069Q mutation in the exon 14 of ATP7B gene is the most frequently encountered in Europe. The aim of the present study was to evaluate the incidence of mutations occurring in exon 14 of ATP7B gene in Romanian patients referred to a tertiary gastroenterology center, with known or suspected WD and in asymptomatic first degree relatives of index cases. METHODS: 93 patients were included in the study. Exon 14 of ATP7B gene has been amplified by PCR from genomic DNA and mutations identified by sequencing. RESULTS: Only H1069Q missense mutation was detected in our study group. In patients with an established diagnosis of WD (38 cases), 34.2% were heterozygous for H1069Q and 21.1% were homozygous, with an allelic frequency of 38.1%. In paediatric WD patients (12 cases) 25% were heterozygous and 16.7% were homozygous (not significant versus adult population). Among asymptomatic first degree relatives of patients with WD (12 siblings, 25 parents) there were 40.5% cases heterozygous for H1069Q. In patients with suspected WD (17 cases), only 5.9% were heterozygous and no homozygous patient was identified. In our study group, H1069Q screening alone could not raise the Leipzig score to confirm diagnosis in patients with suspected WD or in asymptomatic first degree relatives. CONCLUSION: H1069Q mutation is highly prevalent in Romanian WD patients and first degree relatives, similar to other central and continental western European populations.