Thrombophilia in hemodialysis patients: Transfer to peritoneal dialysis is life saving

The majority of vascular access thrombosis episodes in hemodialysis patients are due to anatomic abnormalities. Thrombophilias are inherited, acquired or mixed disorders which also predispose to venous thromboembolism. They include protein C, protein S and antithrombin deficiencies, as well as gene mutations for prothrombin and factor V Leiden. The most important of the mixed cases is hyperhomocysteinemia, which includes both a genetic and an acquired substrate. We report two patients undergoing hemodialysis who suffered from multiple thrombotic events, the first due to factor V Leiden heterozygosity and the second because of hyperhomocysteinemia due to homozygosity for MTHFR C677T mutation. As no site for vascular access was left, transfer to peritoneal dialysis for both patients improved solute clearance and quality of life with no additional thrombotic events noted.     

Use of XenX™, the latest ureteric occlusion device with guide wire utility: results from a prospective multicentric comparative study

Purpose

This is a prospective multicentric comparative study evaluating the performance of XenX—a new dual-purpose device for the prevention of stone fragments migration during ureteroscopic lithotripsy (URS).

Methods

Between March 2014 and January 2015, 41 patients undertaking URS + XenX were matched with 41 patients undergoing standard URS. Patients included had unilateral ureteric stone(s) of 0.5–1.5 cm in maximum size. Demographics, complication rates and surgical outcomes were recorded for comparison. A Likert-like 5-grade scoring system was used for surgeons’ evaluation of XenX properties. Cost analysis was performed by comparing weighted mean costs of the relevant procedures.

Results

Patients’ characteristics between the two groups were comparable. Lasering time was longer for XenX group (13.59 vs. 5.17 min; p = 0.0001) whilst use of basket and need of JJ stent insertion was more frequent in control group (19.5 vs. 97.6 %; p = 0.0001 and 22 vs. 35 %; p = 0.001, respectively). Intra-operative SFR was significantly higher for XenX group (100 vs. 85.4 %; p = 0.0001), but not at 4-week follow-up, after ancillary procedures were needed in 17.1 % of the control group. Surgeons’ evaluations for XenX were suboptimal for “Ease of Basketing” (2/5) and “Advancement of double J stent” (3/5). The use of XenX increased costs of procedures, but spared the costs associated to ancillary procedures and stent removals.

Conclusions

XenX confirmed to be a safe and effective device especially for the treatment of upper ureteric tract stones; moreover, XenX may reduce the risk for the need of auxiliary procedures and for the insertion of a JJ stent.

     

Circulating sclerostin and Dickkopf-1 levels in patients with nonalcoholic fatty liver disease

There is increasing evidence for bone-liver interplay. The main aim of this study was to determine serum sclerostin and Dickkopf (DKK)-1 levels in patients with nonalcoholic fatty liver disease (NAFLD) and their association with the disease severity. Patients with biopsy-proven NAFLD, 13 with nonalcoholic simple steatosis (SS) and 14 with steatohepatitis (NASH), and 20 gender-, age-, body mass index- and waist circumference-matched controls were enrolled. Serum sclerostin, DKK-1, bone turnover markers, vitamin D, insulin and standard biochemical and hematologic parameters were measured; lumbar spinal dual-energy X-ray absorptiometry was performed. We observed that there was a progressive decline in serum sclerostin levels from the controls (76.1 ± 6.8) to SS (53.5 ± 6.4) and NASH (46.0 ± 8.1 pmol/l) patients (p = 0.009); in adjusted pairwise comparisons, sclerostin was significantly higher in the controls than in NASH patients (p = 0.012). Although serum DKK-1 did not differ between groups (p = 0.135), there was a trend toward U-shaped distribution (controls 35.8 ± 2.8; SS 27.3 ± 2.9; NASH 36.8 ± 4.4 pmol/l). Higher DKK-1 levels were independently associated with NASH. Regarding specific histological lesions, DKK-1 levels were marginally lower in NAFLD patients with lower (≤33 %) than higher (>33 %) steatosis grade (27.7 ± 3.1 and 38.8 ± 4.7 pmol/l, respectively; p = 0.049). No other significant difference was observed within histological lesions. In conclusion, serum sclerostin levels were lower in NASH patients than in controls. DKK-1 levels were independently associated with NASH in NAFLD patients. The potential importance of these findings indicates a possible bone-liver interaction and warrants further investigation.     

Whole-spine magnetic resonance imaging in patients with neurofibromatosis type 1 and spinal deformity

OBJECTIVE: Whole-spine magnetic resonance imaging (MRI) has been recommended in the preoperative evaluation of patients with neurofibromatosis type 1 (NF-1). However, no large study has identified the role of MRI in the classification and management of this condition. A retrospective study of 27 patients with NF-1, presenting with spinal deformity, who were investigated with plain radiographs and whole-spine MRI, was conducted to determine the role of whole-spine MRI in the classification and management of patients with NF-1 and spinal deformity. METHODS: The medical records, radiographs, and MRI studies of 27 neurologically intact patients with NF-1 and spinal deformity, who had been followed for a minimum of 2 years, were reviewed. RESULTS: The study group comprised 27 patients, 11 of whom were categorized as having nondystrophic and 16 as having dystrophic curves based on radiographic features. All patients had normal neurologic function. In the nondystrophic group, MRI identified dystrophic changes in four patients (associated with a high rate of curve progression in one). A high incidence of intraspinal and paraspinal neurofibromas was documented (overall 37%) in both nondystrophic and dystrophic groups. Significantly more tumors were identified adjacent to the convexity of the curve in the dystrophic group. CONCLUSION: In a mixed population of pediatric and adult patients with NF-1, normal neurologic function, and spinal deformity, MRI of the whole spine proved useful in the identification of occult vertebral dysplasia and in demonstration of intraspinal and paraspinal neoplasms.     

Histone Mark Profiling in Pediatric Astrocytomas Reveals Prognostic Significance of H3K9 Trimethylation and Histone Methyltransferase SUV39H1

Alterations in global histone methylation regulate gene expression and participate in cancer onset and progression. The profile of histone methylation marks in pediatric astrocytomas is currently understudied with limited data on their distribution among grades. The global expression patterns of repressive histone marks H3K9me3, H3K27me3, and H4K20me3 and active H3K4me3 and H3K36me3 along with their writers SUV39H1, SETDB1, EZH2, MLL2, and SETD2 were investigated in 46 pediatric astrocytomas and normal brain tissues. Associations between histone marks and modifying enzymes with clinicopathological characteristics and disease-specific survival were studied along with their functional impact in proliferation and migration of pediatric astrocytoma cell lines using selective inhibitors in vitro. Upregulation of histone methyltransferase gene expression and deregulation of histone code were detected in astrocytomas compared to normal brain tissues, with higher levels of SUV39H1, SETDB1, and SETD2 as well as H4K20me3 and H3K4me3 histone marks. Pilocytic astrocytomas exhibited lower MLL2 levels compared to diffusely infiltrating tumors indicating a differential pattern of epigenetic regulator expression between the two types of astrocytic neoplasms. Moreover, higher H3K9me3, H3K36me3, and SETDB1 expression was detected in grade IIΙ/IV compared to grade II astrocytomas. In univariate analysis, elevated H3K9me3 and MLL2 and diminished SUV39H1 expression adversely affected survival. Upon multivariate survival analysis, only SUV39H1 expression was revealed as an independent prognostic factor of adverse significance. Treatment of pediatric astrocytoma cell lines with SUV39H1 inhibitor reduced proliferation and cell migration. Our data implicate H3K9me3 and SUV39H1 in the pathobiology of pediatric astrocytomas, with SUV39H1 yielding prognostic information independent of other clinicopathologic variables.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01090-x.     

Brain-derived neurotrophic factor levels influence the balance of migration and differentiation of subventricular zone cells, but not guidance to the olfactory bulb

New progenitor cells in the subventricular zone (SVZ) migrate rostrally and differentiate into interneurons in the olfactory bulb (OB) throughout life. Brain-derived neurotrophic factor (BDNF) may influence the normal progression of this migration. In the present study, mouse SVZ explant cultures were used to investigate how BDNF modulates the behavior of these migrating progenitors. Concentrations of BDNF in the physiological range (e.g. 1 ng/mL) stimulated migration, whereas doses of 10 ng/mL or higher induced SVZ cell differentiation and reduced migration. Pharmacological inhibition of the mitogen-activated protein kinase (MAPK) pathway blocked the BDNF-induced differentiation of SVZ progenitors, indicating that differentiation of SVZ progenitors in response to high-dose BDNF is initiated through MAPK. Physiological concentrations of BDNF, like the presence of polysialic acid in the tissue, stimulated migration of cells from the explant without affecting the speed at which this occurs. Interestingly, in vivo immunohistochemical and molecular analysis showed similar levels of BDNF in both the SVZ and OB; that is, there was no positive gradient attracting SVZ cells towards the OB. Our data show that SVZ cells respond differently to different concentrations of BDNF.     

Current concepts on gingival fibromatosis‐related syndromes

Gingival fibromatosis is a rare, benign, slowly‐growing fibrous overgrowth of the gingiva, with great genetic and clinical heterogeneity. Gingival fibromatosis/overgrowth can be inherited as an isolated trait (hereditary gingival fibromatosis) and/or as a component of a syndrome, or it can be drug induced. As a clinical manifestation of a syndrome, gingival fibromatosis is usually associated with generalized hypertrichosis, mental retardation, or epilepsy. Gingival fibromatosis and its related syndromes are mainly inherited in an autosomal‐dominant manner, but autosomal‐recessive inheritance has also been reported. Clinical syndromic presentation includes Zimmermann–Laband syndrome, Ramon syndrome, Rutherford syndrome, Cowden syndrome, Cross syndrome, Göhlich–Ratmann syndrome, Avani syndrome, and I‐cell disease. However, a phenotypic overlap has been suggested, as many combinations of their systemic manifestations have been reported. Treatment of choice is usually gingivectomy with gingivoplasty. Before any therapy, clinical practitioners must take into consideration the clinical course of a particular syndrome and every possible functional and esthetic disorder.     

Outcome factors in surgically treated patients for cervical spondylotic myelopathy

Context/Objective: To investigate prospectively preoperative parameters that might be related to the outcome of surgically treated patients for cervical spondylotic myelopathy (CSM).

Design: Prospective study.

Setting: Single Center in Ioannina, Greece.

Participants: Thirty-six patients were included in the study. There were 21 males and 15 females, mean age 50.8 years, range 39–70 years. The mean BMI was 27.3.

Outcome measures: From each patient, we recorded age, sex, BMI, symptoms, duration of symptoms, comorbidities, lifestyle, myelopathy grade based on MRI and levels of compression. All patients completed the modified JOA (mJOA) and NPE questionnaires preoperatively and at 1, 3, 12 months and 5-years postoperatively.

Results: The mean mJOA score significant improved from 10.8?±?1.9 points preoperatively to 16.6?±?2.2 points at 12 months postoperatively. The mean mJOA score at 5-years postoperatively was 15.5?±?3 points. The difference was still highly significant. The mean NPE score significant improved from 59.8?±?12.2 points preoperatively to 28.2?±?8.5 points at 1 month, to 35.8?±?8.1 points at 3 month and to 28.2?±?8.8 points at 12 months postoperatively. Younger patients had significant higher baseline mJOA scores and significant higher mJOA scores 5-year postoperatively. No correlation was found between sex, BMI, symptom duration, baseline mJOA or myelopathy grade and outcome at 12 months or 5-year postoperatively.

Conclusion: Age was highly predictive factor of outcome for patients undergoing surgical treatment of CSM.     

Gastric Hepatoid Adenocarcinoma

Gastric Hepatoid AdenoCarcinoma (GHAC) is a special type of gastric cancer characterized by morphological features similar to hepatocellular carcinoma (HAC). GHAC has been found in different organs such as the stomach, lung, pancreas, oesophagus, papilla of Vater, colon, kidney, uterus and peritoneum. The diagnosis of GHAC is not dependent on production of AFP, but mainly based on recognition of characteristic histologic features. We report the case of a 72-year-old male patient who underwent a total gastrectomy for a large poorly differentiated gastric tumour. The microscopic examination of the tumour showed an adenocarcinoma with two distinct patterns: that of an adenocarcinoma with glandular differentiation and another with a morphological pattern consisting of polygonal neoplastic cells with abundant eosinophilic cytoplasm, prominent nuclei and high mitotic activity. Immunohistochemical staining revealed positive Hep Par1 and AFP, while CK7 and CK20 were negative, the percentage of hepatoid differentiation being about 60%. On the basis of histological and immunohistochemical findings, the diagnosis of hepatoid gastric adenocarcinoma was established. In general, GHACs have an unfavourable prognosis. The majority have already metastasized by the time of diagnosis, usually to the liver and lymph nodes.