Evaluation of ear, nose, and throat-screening in liver transplantation candidates:A retrospective cohort study

Background:Patients with end-stage liver disease can be treated with a liver transplantation (LT). Before listing, candidates are subjected to a screening procedure according to the EASL Clinical Practice Guidelines for LT. In our hospital, this includes an ear, nose, and throat (ENT) examination, directed towards the identification of (asymptomatic) infections and head and neck malignancies.Methods:We retrospectively reviewed all ENT screening examinations in LT candidates from 2007 to 2022. The screening consisted of a visit to the ENT outpatient clinic combined with sinus radiography.Results:ENT screening was performed in 1099 patients. Sixty-one cases were identified, either diagnosed with an infection (n = 58, almost exclusively sinusitis) or a neoplasm (n = 3, of which two malignancies). With binary logistic regression, we could not identify significant risk factors for diagnosing sinusitis. 711 patients underwent LT. After LT, two patients developed a novel malignancy of the head and neck area, while 14 patients were diagnosed with sinusitis, two of the latter already showed opacification on sinus radiography during screening. Despite immunosuppressive drugs, no complicated sinusitis was observed.Conclusion:Sinusitis or a neoplasm was diagnosed in almost 6% in a large cohort of LT candidates. Although almost a third of sinusitis patients were not treated accordingly, we did not observe any complicated sinusitis after LT. A more conservative approach to sinusitis may therefore be justified in LT candidates, especially in asymptomatic cases. At our institution, we aim to refer only those patients with specific ENT complaintsimage.This study aimed to evaluate the outcome of routine ear, nose, and throat screening in a large cohort of liver transplantation candidates. Note that, 6% were diagnosed with either sinusitis or a neoplasm. We did not observe any complicated sinusitis after transplantation. A more conservative approach may therefore be justified, especially in asymptomatic cases.imag

Evaluation of ear, nose, and throat-screening in liver transplantation candidates:A retrospective cohort study

Background:Patients with end-stage liver disease can be treated with a liver transplantation (LT). Before listing, candidates are subjected to a screening procedure according to the EASL Clinical Practice Guidelines for LT. In our hospital, this includes an ear, nose, and throat (ENT) examination, directed towards the identification of (asymptomatic) infections and head and neck malignancies.Methods:We retrospectively reviewed all ENT screening examinations in LT candidates from 2007 to 2022. The screening consisted of a visit to the ENT outpatient clinic combined with sinus radiography.Results:ENT screening was performed in 1099 patients. Sixty-one cases were identified, either diagnosed with an infection (n = 58, almost exclusively sinusitis) or a neoplasm (n = 3, of which two malignancies). With binary logistic regression, we could not identify significant risk factors for diagnosing sinusitis. 711 patients underwent LT. After LT, two patients developed a novel malignancy of the head and neck area, while 14 patients were diagnosed with sinusitis, two of the latter already showed opacification on sinus radiography during screening. Despite immunosuppressive drugs, no complicated sinusitis was observed.Conclusion:Sinusitis or a neoplasm was diagnosed in almost 6% in a large cohort of LT candidates. Although almost a third of sinusitis patients were not treated accordingly, we did not observe any complicated sinusitis after LT. A more conservative approach to sinusitis may therefore be justified in LT candidates, especially in asymptomatic cases. At our institution, we aim to refer only those patients with specific ENT complaintsimage.This study aimed to evaluate the outcome of routine ear, nose, and throat screening in a large cohort of liver transplantation candidates. Note that, 6% were diagnosed with either sinusitis or a neoplasm. We did not observe any complicated sinusitis after transplantation. A more conservative approach may therefore be justified, especially in asymptomatic cases.imag

Assessing hearing loss in older adults with a single question and person characteristics; Comparison with pure tone audiometry in the Rotterdam Study

INTRODUCTION: Hearing loss (HL) is a frequent problem among the elderly and has been studied in many cohort studies. However, pure tone audiometry-the gold standard-is rather time-consuming and costly for large population-based studies. We have investigated if self-reported hearing loss, using a multiple choice question, can be used to assess HL in absence of pure tone audiometry. METHODS: This study was performed within 4,906 participants of the Rotterdam Study. The question (in Dutch) that was investigated was: 'Do you have any difficulty with your hearing (without hearing aids)?'. The answer options were: 'never', 'sometimes', 'often' and 'daily'. Mild hearing loss or worse was defined as PTA0.5-4(Pure Tone Average 0.5, 1, 2 & 4 kHz) ≥20dBHL and moderate HL or worse as ≥35dBHL. A univariable linear regression model was fitted with the PTA0.5-4 and the answer to the question. Subsequently, sex, age and education were added in a multivariable linear regression model. The ability of the question to classify HL, accounting for sex, age and education, was explored through logistic regression models creating prediction estimates, which were plotted in ROC curves. RESULTS: The variance explained (R2) by the univariable regression was 0.37, which increased substantially after adding age (R2 = 0.60). The addition of sex and educational level, however, did not alter the R2 (0.61). The ability of the question to classify hearing loss, reflec

Somatostatin Receptor Expression in GH-Secreting Pituitary Adenomas Treated with Long-Acting Somatostatin Analogues in Combination with Pegvisomant

Background: Growth hormone secreting pituitary adenomas (somatotroph adenoma) predominantly express somatostatin receptors (SSTRs) subtypes 2 and 5. Higher SSTR2 expression on somatotroph adenomas results in a better response to somatostatin analogues (SSAs), which preferentially bind, but also down regulate, SSTR2. The effect of the combined treatment with SSAs and the GH receptor antagonist pegvisomant (PEGV) on SSTR expression in somatotroph adenomas is currently unknown. Aim of the Study: To assess SSTR2 and SSTR5 expression in three groups of somatotroph adenomas: drug-naive, treated with long-acting (LA) SSA monotherapy, or LA-SSA/PEGV combination therapy before surgery. Additionally, we evaluated the required PEGV dose to achieve IGF-I normalization in relation to the SSTR expression. Materials and Methods: At our Pituitary Center Rotterdam, we selected acromegalic patients who underwent transsphenoidal neurosurgery. All patients were eventually treated with LA-SSA/PEGV combination therapy during their medical history. SSTR2 and SSTR5 expression in somatotroph adenomas tissues was determined using immunohistochemistry. Results: Out of 39 somatotroph adenoma tissue samples, 23 were drug-naive, 9 received pre-treatment with LA-SSA and 7 LA-SSA/PEGV combined treatment. SSTR2 expression was significantly higher in treatment-naive compared to combined treatment somatotroph adenomas (p = 0.048), while SSTR5 expression did not differ. Noteworthy, SSTR2 expression in naive somatotroph adenoma tissues was inversely correlated to the required PEGV dose to achieve IGF-I normalization during post-surgical medical treatment (ρ = -0.538, p = 0.024). Conclusion: In our specific cohort, the SSTR2 expression is lower in patients pre-treated with LA-SSA/PEGV compared to the drug-naive acromegalic patients. Additionally, the SSTR2 expression in treatment naive somatotroph adenoma tissues was inversely correlated with the required PEGV dose to achieve IGF-I normalization

MLC1 is associated with the Dystrophin-Glycoprotein Complex at astrocytic endfeet

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a progressive cerebral white matter disease with onset in childhood, caused by mutations in the MLC1 gene. MLC1 is a protein with unknown function that is mainly expressed in the brain in astrocytic endfeet at the blood–brain and cerebrospinal fluid–brain barriers. It shares its localization at astrocytic endfeet with the dystrophin-associated glycoprotein complex (DGC). The objective of the present study was to investigate the possible association of MLC1 with the DGC. To test this hypothesis, (co)-localization of DGC-proteins and MLC1 was analyzed by immunohistochemical stainings in gliotic brain tissue from a patient with multiple sclerosis, in glioblastoma tissue and in brain tissue from an MLC patient. In control tissue, a direct protein interaction was tested by immunoprecipitation. Results revealed that MLC1 is co-localized with DGC-proteins in gliotic brain tissue. We demonstrated that both MLC1 and aquaporin-4, a member of the DGC, were redistributed in glioblastoma cells. In MLC brain tissue, we showed absence of MLC1 and altered expression of several DGC-proteins. We demonstrated a direct protein interaction between MLC1 and Kir4.1. From these results we conclude that MLC1 is associated with the DGC at astrocytic endfeet

The prognostic value of systemic inflammation in patients undergoing surgery for colon cancer: comparison of composite ratios and cumulative scores

Introduction: The systemic inflammatory response has been proven to have a prognostic value. There are two methods of assessing the systemic inflammatory response composite ratios (R) and cumulative scores (S). The aim of this study was to compare the prognostic value of ratios and scores in patients undergoing surgery for colon cancer. Methods: Patients were identified prospectively in a single surgical unit. Preoperative neutrophil (N), lymphocyte (L), monocyte (M) and platelet (P) counts, CRP (C) and albumin (A) levels were recorded. The relationship between composite ratios neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), lymphocyte–monocyte ratio (LMR), C-reactive protein albumin ratio (CAR) and the cumulative scores neutrophil– lymphocyte score (NLS), platelet–lymphocyte score (PLS), lymphocyte–monocyte score (LMS), neutrophil– platelet score (NPS), modified Glasgow prognostic score (mGPS) and clinicopathological characteristics, cancer-specific survival (CSS) and overall survival (OS), were examined. Results: A total of 801 patients were examined. When adjusted for tumour node metastasis (TNM) stage, NLR >5 (p < 0.001), NLS (p < 0.01), PLS (p < 0.001), LMR <2.4 (p < 0.001), LMS (p < 0.001), NPS (p < 0.001), CAR >0.22 (p < 0.001) and mGPS (p < 0.001) were significantly associated with CSS. In patients undergoing elective surgery (n = 689), the majority of the composite ratios/scores correlated with age (p < 0.01), BMI (p < 0.01), T stage (p < 0.01), venous invasion (p < 0.01) and peritoneal involvement (p < 0.01). When NPS (myeloid) and mGPS (liver) were directly compared, their relationship with CSS and OS was similar. Conclusions: Both composite ratios and cumulative scores had prognostic value, independent of TNM stage, in patients with colon cancer. However, cumulative scores, based on normal reference ranges, are simpler and more consistent for clinical use

pT3 colorectal cancer revisited: a multicentric study on the histological depth of invasion in more than 1000 pT3 carcinomas—proposal for a new pT3a/pT3b subclassification

BACKGROUND: Pathological TNM staging (pTNM) is the strongest prognosticator in colorectal carcinoma (CRC) and the foundation of its post-operative clinical management. Tumours that invade pericolic/perirectal adipose tissue generally fall into the pT3 category without further subdivision. METHODS: The histological depth of invasion into the pericolic/perirectal fat was digitally and conventionally measured in a training cohort of 950 CRCs (Munich). We biostatistically calculated the optimal cut-off to stratify pT3 CRCs into novel pT3a (≤3 mm)/pT3b (>3 mm) subgroups, which were then validated in two independent cohorts (447 CRCs, Bayreuth/542 CRCs, Mainz). RESULTS: Compared to pT3a tumours, pT3b CRCs showed significantly worse disease-specific survival, including in pN0 vs pN+ and colonic vs. rectal cancers (DSS: P < 0.001, respectively, pooled analysis of all cohorts). Furthermore, the pT3a/pT3b subclassification remained an independent predictor of survival in multivariate analyses (e.g. DSS: P < 0.001, hazard ratio: 4.41 for pT3b, pooled analysis of all cohorts). While pT2/pT3a CRCs showed similar survival characteristics, pT3b cancers remained a distinct subgroup with dismal survival. DISCUSSION: The delineation of pT3a/pT3b subcategories of CRC based on the histological depth of adipose tissue invasion adds valuable prognostic information to the current pT3 classification and implementation into current staging practices of CRC should be considered