Context:
Vitamin D deficiency is common in renal transplant recipients (RTR). The long-term implications of vitamin D deficiency in RTR remain unclear.
Objective:
We investigated whether 25(OH) or ...1,25(OH)2 vitamin D levels are associated with mortality, renal function decline, and graft failure in stable RTR.
Design:
Observational study with longitudinal design. Followup was 7.0, interquartile range (IQR) 6.2–7.5 years.
Setting:
Single-center outpatient clinic.
Participants:
435 stable RTR (51% men, mean age 52 ± 12 years) were included at a median IQR of 6 3–12 years after kidney transplantation.
Main Outcome Measures:
All-cause mortality, annual change of estimated glomerular filtration rate (eGFR), and graft failure.
Results:
Mean 25-hydroxyvitamin D 25(OH)D and 1,25-dihydroxyvitamin D 1,25(OH)2D were 21.6 ± 9.1 ng/ml and 45.2 ± 19.0 pg/ml, respectively. During followup, 99 patients (22.8%) died and 44 patients (10.1%) developed graft failure. In univariable analysis, both 25(OH)D and 1,25(OH)2D were significantly associated with mortality (hazard ratio HR, 0.64; 95% confidence interval (CI), 0.51–0.81; P < .001 and HR 0.69 95% CI, 0.55–0.87, P = .002 per SD increase, respectively). The inverse association of 25(OH)D with mortality remained significant after adjustment for potential confounders (HR 0.68 95% CI, 0.52–0.89, P = .004 per SD increase). The associations of 1,25(OH)2D with mortality and graft failure lost significance after adjustment for renal function. Severe vitamin D deficiency (25OHD <12 ng/ml) was independently associated with stronger annual eGFR decline.
Conclusions:
Low 25(OH)D is independently associated with an increased risk of all-cause mortality and 25(OH)D <12 ng/ml with a rapid eGFR decline in stable RTR. The association of low 1,25(OH)2D with mortality or graft failure depends on renal function. These results should encourage randomised controlled trials evaluating the effect of vitamin D supplementation after kidney transplantation.
Background
The purpose of this study was to determine the additional diagnostic value of squamous cell carcinoma antigen (SCC‐Ag) in cervical lymph node fine needle aspiration (FNA) samples for the ...detection of regional metastases of head and neck squamous cell carcinoma (HNSCC).
Methods
In 149 FNA samples of 114 patients, SCC‐Ag concentration was retrospectively analyzed and associated with diagnosis to establish a cutoff concentration in relation to sensitivity and specificity of HNSCC detection.
Results
SCC‐Ag was elevated in lymph nodes from patients with HNSCC compared to lymph nodes from other patients (P < 0.01). With 0.3 μg/L as the cutoff concentration, SCC‐Ag has 96% sensitivity for detecting HNSCC.
Conclusions
SCC‐Ag in FNA is a reliable test for detecting HNSCC in cervical lymph nodes.
Objective
To determine the diagnostic value of measuring squamous cell carcinoma antigen (SCC‐Ag) and cancer antigen 15‐3 (CA15‐3) concentrations in fine‐needle aspiration (FNA) samples for the ...detection of squamous cell carcinoma (SCC) metastases in cervical lymph nodes.
Study Design
A prospective study with patients consecutively included between November 2018 and May 2021.
Setting
A tertiary head and neck oncologic center.
Methods
Out of 138 patients, SCC‐Ag concentrations were analyzed in 168 FNA cervical lymph node samples and CA15‐3 in 152 samples. Results were compared with FNA cytology (FNAC) or definitive histology to establish sensitivity and specificity rates.
Results
For the detection of cervical SCC lymph node metastases, SCC‐Ag measurement had an 89.4% sensitivity and 79.3% specificity at a cutoff concentration of 0.1 µg/L. Measurement of CA15‐3 concentration in addition to SCC‐Ag concentration did not lead to improved accuracy for the detection of SCC. In histology‐confirmed cases, FNAC had an 80.0% sensitivity and 100% specificity, as opposed to 93.3% and 57.1%, respectively, for SCC‐Ag.
Conclusion
Measurement of SCC‐Ag concentration for detection of SCC lymph node metastases has a sensitivity at least comparable to FNAC and could be used as a relatively cheap screening tool in samples with nondiagnostic or indeterminate FNAC results or when multiple lymph nodes are sampled. However, SCC‐Ag in FNA samples has a lower specificity than FNAC assessed by pathologists experienced in head and neck oncology. Addition of CA15‐3 measurement did not lead to improved accuracy.
Major Depressive Disorder (MDD) is a heterogeneous disorder with a considerable symptomatic overlap with other psychiatric and somatic disorders. This study aims at providing evidence for association ...of a set of serum and urine biomarkers with MDD. We analyzed urine and serum samples of 40 MDD patients and 47 age- and sex-matched controls using 40 potential MDD biomarkers (21 serum biomarkers and 19 urine biomarkers). All participants were of Caucasian origin. We developed an algorithm to combine the heterogeneity at biomarker level. This method enabled the identification of correlating biomarkers based on differences in variation and distribution between groups, combined the outcome of the selected biomarkers, and calculated depression probability scores (the “bio depression score”). Phenotype permutation analysis showed a significant discrimination between MDD and euthymic (control) subjects for biomarkers in urine (P < .001), in serum (P = .02) and in the combined serum plus urine result (P < .001). Based on this algorithm, a combination of 8 urine biomarkers and 9 serum biomarkers were identified to correlate with MDD, enabling an area under the curve (AUC) of 0.955 in a Receiver Operating Characteristic (ROC) analysis. Selection of either urine biomarkers or serum biomarkers resulted in AUC values of 0.907 and 0.853, respectively. Internal cross-validation (5-fold) confirmed the association of this set of biomarkers with MDD.
•This study investigates biomarker panels for Major Depressive Disorder (MDD).•The biomarker panels were assessed in serum as well as in urine.•A new method was used to combine results of multiple biomarkers into a single score.•This scoring method is based on differences in variation and distribution.•A panel of 9 serum and 8 urine biomarkers was identified to correlate with MDD.
Up to 70% of children and teenagers referred to a paediatric gastroenterology centre with suspected inflammatory bowel disease (IBD) do not have the disease.
To evaluate whether faecal calprotectin ...as an 'add-on test' improves the specificity of the clinical case definition for suspected IBD in a general paediatric practice.
A prospective diagnostic accuracy study.
Six outpatient clinics for general paediatrics and one tertiary care hospital in the Netherlands.
117 children and teenagers with a clinical suspicion of IBD.
Faecal calprotectin was measured (index test) in all patients. Patients with a high index of suspicion on the basis of the paediatrician's global assessment, physical examination and blood results were referred for endoscopy (reference standard). Children and teenagers who were not selected for endoscopy initially were followed for half a year for the appearance of possible additional symptoms (delayed type reference standard).
The proportion of referred patients with confirmed IBD.
The mean age of patients was 14 years (range 6-18). A total of 42 (36%) had confirmed IBD. The paediatricians, who were blinded to the faecal calprotectin result, referred 68 children and teenagers for endoscopy. If they had referred only those patients with a positive faecal calprotectin result (>50 μg/g), 54 patients would have undergone endoscopy.
The study relied on clinical follow-up to detect missed IBD.
A diagnostic strategy in general paediatric practice of using a simple clinical case definition for suspected IBD in combination with a positive faecal calprotectin result increases the specificity to detect IBD and reduces the need for referral to a paediatric gastroenterology centre with a very low risk of missing cases.
BackgroundMelanoma is an immune sensitive disease, as demonstrated by the activity of immune check point blockade (ICB), but many patients will either not respond or relapse. More recently, tumor ...infiltrating lymphocyte (TIL) therapy has shown promising efficacy in melanoma treatment after ICB failure, indicating the potential of cellular therapies. However, TIL treatment comes with manufacturing limitations, product heterogeneity, as well as toxicity problems, due to the transfer of a large number of phenotypically diverse T cells. To overcome said limitations, we propose a controlled adoptive cell therapy approach, where T cells are armed with synthetic agonistic receptors (SAR) that are selectively activated by bispecific antibodies (BiAb) targeting SAR and melanoma-associated antigens.MethodsHuman as well as murine SAR constructs were generated and transduced into primary T cells. The approach was validated in murine, human and patient-derived cancer models expressing the melanoma-associated target antigens tyrosinase-related protein 1 (TYRP1) and melanoma-associated chondroitin sulfate proteoglycan (MCSP) (CSPG4). SAR T cells were functionally characterized by assessing their specific stimulation and proliferation, as well as their tumor-directed cytotoxicity, in vitro and in vivo.ResultsMCSP and TYRP1 expression was conserved in samples of patients with treated as well as untreated melanoma, supporting their use as melanoma-target antigens. The presence of target cells and anti-TYRP1 × anti-SAR or anti-MCSP × anti-SAR BiAb induced conditional antigen-dependent activation, proliferation of SAR T cells and targeted tumor cell lysis in all tested models. In vivo, antitumoral activity and long-term survival was mediated by the co-administration of SAR T cells and BiAb in a syngeneic tumor model and was further validated in several xenograft models, including a patient-derived xenograft model.ConclusionThe SAR T cell-BiAb approach delivers specific and conditional T cell activation as well as targeted tumor cell lysis in melanoma models. Modularity is a key feature for targeting melanoma and is fundamental towards personalized immunotherapies encompassing cancer heterogeneity. Because antigen expression may vary in primary melanoma tissues, we propose that a dual approach targeting two tumor-associated antigens, either simultaneously or sequentially, could avoid issues of antigen heterogeneity and deliver therapeutic benefit to patients.
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