Preoperative Serum Copeptin Can Predict Delayed Hyponatremia after Pituitary Surgery in the Absence of Arginine Vasopressin Deficiency.

BACKGRUOUND: Delayed postoperative hyponatremia (DPH) is the most common cause of readmission after pituitary surgery. In this study, we aimed to evaluate the cutoff values of serum copeptin and determine the optimal timing for copeptin measurement for the prediction of the occurrence of DPH in patients who undergo endoscopic transsphenoidal approach (eTSA) surgery and tumor resection. METHODS: This was a prospective observational study of 73 patients who underwent eTSA surgery for pituitary or stalk lesions. Copeptin levels were measured before surgery, 1 hour after extubation, and on postoperative days 1, 2, 7, and 90. RESULTS: Among 73 patients, 23 patients (31.5%) developed DPH. The baseline ratio of copeptin to serum sodium level showed the highest predictive performance (area under the curve [AUROC], 0.699), and its optimal cutoff to maximize Youden's index was 2.5×10-11, with a sensitivity of 91.3% and negative predictive value of 92.0%. No significant predictors were identified for patients with transient arginine vasopressin (AVP) deficiency. However, for patients without transient AVP deficiency, the copeptin-to-urine osmolarity ratio at baseline demonstrated the highest predictive performance (AUROC, 0.725). An optimal cutoff of 6.5×10-12 maximized Youden's index, with a sensitivity of 92.9% and a negative predictive value of 94.1%. CONCLUSION: The occurrence of DPH can be predicted using baseline copeptin and its ratio with serum sodium or urine osmolarity only in patients without transient AVP deficiency after pituitary surgery.

Serum copeptin levels at day two after pituitary surgery and ratio to baseline predict postoperative central diabetes insipidus.

PURPOSE: Central diabetes insipidus is a complication that may occur after pituitary surgery and has been difficult to predict. This study aimed to identify the cutoff levels of serum copeptin and its optimal timing for predicting the occurrence of central diabetes insipidus in patients who underwent transsphenoidal surgery. METHODS: This was a prospective observational study of patients who underwent transsphenoidal surgery for pituitary gland or stalk lesions. Copeptin levels were measured before surgery, 1 h after extubation, and on postoperative days 1, 2, 7, and 90. RESULTS: Among 73 patients, 14 (19.2%) and 13 (17.8%) patients developed transient and permanent central diabetes insipidus, respectively. There was no significant difference in copeptin levels before surgery and 1 h after extubation; copeptin levels on postoperative days 1, 2, 7, and 90 were significantly lower in patients with permanent central diabetes insipidus than in those without central diabetes insipidus. Copeptin measurement on postoperative day 2 exhibited the highest performance for predicting permanent central diabetes insipidus among postoperative days 1, 2, and 7 (area under the curve [95% confidence interval] = 0.754 [0.632-0.876]). Serum copeptin level at postoperative day 2(< 3.1 pmol/L) showed a sensitivity of 92.3% and a negative predictive value of 97.1%. The ratio of copeptin at postoperative day 2 to baseline (< 0.94) presented a sensitivity of 84.6% and a negative predictive value of 94.9%. The copeptin levels > 3.4 and 7.5 pmol/L at postoperative day 2 and 7 may have ruled out the occurrence of CDI with a negative predictive value of 100%. CONCLUSION: The copeptin level at postoperative day 2 and its ratio to baseline can predict the occurrence of permanent central diabetes insipidus after pituitary surgery.

Changes in copeptin levels before and 3 months after transsphenoidal surgery according to the presence of postoperative central diabetes insipidus.

Copeptin levels reflect arginine vasopressin (AVP) release from the hypothalamus. Pituitary surgery often impairs AVP release and results in central diabetes insipidus (CDI). Here, we aimed to investigate how serum copeptin level changes 3 months after pituitary surgery and whether it has a diagnostic value for postoperative permanent CDI. Consecutive patients who underwent endoscopic transsphenoidal surgery at a single tertiary hospital were recruited. Serum copeptin levels were measured preoperatively and 3 months postoperatively. Among 88 patients, transient and permanent CDI occurred in 17 (19.3%) and 23 (26.1%), respectively. Three-month postoperative copeptin levels significantly declined from preoperative levels in permanent CDI group (P < 0.001, percentage difference = - 42.2%) and also in the transient CDI group (P = 0.002, - 27.2%). Three months postoperative copeptin level < 1.9 pmol/L under normal serum sodium levels was the optimal cutoff value for diagnosing permanent CDI with an accuracy of 81.8%, while 3-month postoperative copeptin level ≥ 3.5 pmol/L excluded the CDI with a negative predictive value of 100%. Conclusively, 3 months postoperative copeptin levels significantly decreased from preoperative levels in the transient CDI group as well as the permanent CDI group. Three-month postoperative copeptin levels ≥ 3.5 pmol/L under normal serum sodium levels may be diagnostic for excluding postoperative CDI.

Novel indel mutation in the N gene of SARS-CoV-2 clinical samples that were diagnosed positive in a commercial RT-PCR assay.

Commercially available reverse transcription-polymerase chain reaction (RT-PCR) kits are being used as an important tool to diagnose SARS-CoV-2 infection in clinical laboratories worldwide. However, some kits lack sufficient clinical evaluation due to the need for emergency use caused by the current COVID-19 pandemic. Here we found that a novel insertion/deletion mutation in the nucleocapsid (N) gene of SARS-CoV-2 samples is a cause of negative results for the N gene in a widely used assay that received emergency use authorization (EUA) from US FDA and Conformite Europeenne-in vitro diagnostics (CE-IVD) from EU. Although SARS-CoV-2 is diagnosed positive by other target probes in the assay, our findings provide an evidence of the genetic variability and rapid evolution of SARS-CoV-2 as well as a reference in designing commercial RT-PCR assays.

Performance Evaluation of the QXDx BCR-ABL %IS Droplet Digital PCR Assay.

Accurate detection of BCR-ABL fusion transcripts at and below molecular response (MR) 4 (0.01% International Scale [IS]) is required for disease monitoring in patients with chronic myeloid leukemia (CML). We evaluated the analytical performance of the QXDx BCR-ABL %IS (Bio-Rad, Hercules, CA, USA) droplet digital PCR (ddPCR) assay, which is the first commercially available ddPCR-based in vitro diagnostics product. In precision analysis, the %CV was 9.3% and 3.0%, with mean values of 0.031% IS and 9.4% IS, respectively. The assay was linear in the first order, ranging from 0.032% IS to 20% IS. The manufacturer-claimed limit of blank, limit of detection, and limit of quantification were verified successfully. There was a very strong correlation between the results of the QXDx BCR-ABL %IS ddPCR assay and the ipsogen BCR-ABL1 Mbcr IS-MMR (Qiagen, Hilden, Germany) real-time quantitative PCR assay (r=0.996). In conclusion, the QXDx BCR-ABL %IS ddPCR assay can provide reliable results for CML patients.

The Asian project for collaborative derivation of reference intervals: (2) results of non-standardized analytes and transference of reference intervals to the participating laboratories on the basis of cross-comparison of test results.

BACKGROUND: The 2009 Asian multicenter study for derivation of reference intervals (RIs) featured: 1) centralized measurements to exclude reagent-dependent variations; 2) inclusion of non-standardized analytes (hormones, tumor makers, etc.) in the target; and 3) cross-check of test results between the central and local laboratories. Transferability of centrally derived RIs for non-standardized analytes based on the cross-check was examined. METHODS: Forty non-standardized analytes were centrally measured in sera from 3541 reference individuals recruited by 63 laboratories. Forty-four laboratories collaborated in the cross-check study by locally measuring aliquots of sera from 9 to 73 volunteers (average 22.2). Linear relationships were obtained by the major-axis regression. Error in converting RIs using the regression line was expressed by the coefficient of variation of slope b [CV(b)]. CV(b) <10% was set as the cut-off value allowing the conversion. The significance of factors for partitioning RIs was determined similarly as in the first report. RESULTS: Significant sex-, age-, and region-related changes in test results were observed in 17, 15, and 11 of the 40 analytes, respectively. In the cross-comparison study, test results were not harmonized in the majority of immunologically measured analytes, but their average CV(b)s were <10% except for total protein, cystatin C, CA19-9, free thyroxine, and triiodothyronine. After conversion, 74% of centrally derived RIs were transferred to each local laboratory. CONCLUSIONS: Our results point to the feasibility of: 1) harmonizing test results across different laboratories; and 2) sharing centrally derived RIs of non-standardized analytes by means of comparative measurement of a set of commutable specimens.

[Current status of external quality assessment of fecal occult blood test].

BACKGROUND: Nationwide external quality assessment (EQA) of the fecal occult blood test (FOBT) in Korea was first introduced in 2007-2009. The EQA results were analyzed to assess the current status of FOBT and to plan the continuation of the EQA program. METHODS: The surveys included 40 hospitals in the preliminary survey conducted in 2007, 249 general hospitals in 2008, and 389 hospitals in 2009. In the surveys, the participating hospitals provided the results of the distributed materials and replies to the questionnaire on the FOBT test procedures and quality controls. RESULTS: In the surveys conducted between 2007 and 2009, a total of 650 institutes submitted 653 test system results; 3 institutes used 2 kinds of methods. All of the institutes used immunologic methods; 107 institutes (16.5%) used quantitative equipments and 546 institutes (84.0%) used qualitative kits. Most quantitative tests yielded consistent positive or negative results; however, their cut-off and measured values differed according to the equipments used. A low-level material tested in 2007 was negative in the quantitative methods but positive in some qualitative methods because of lower detection limits. The discordance rates among quantitative tests were 3.2% in 2007, 4.4% in 2008, and 0% in 2009 and the rates among qualitative tests were 13.8% in 2008 and 2.6% in 2009. Semi-solid EQA materials showed the ability to evaluate the overall test procedures with acceptable stability. CONCLUSIONS: In the first Korean FOBT EQA, commercially available EQA materials were proven to be stable. Continuation of the EQA program and further education of laboratory personnel are needed to reduce inconsistency in results. Further, the test kit, procedures, and result reports must be standardized.

Neural differentiation of novel multipotent progenitor cells from cryopreserved human umbilical cord blood.

Umbilical cord blood (UCB) is a rich source of hematopoietic stem cells, with practical and ethical advantages. To date, the presence of other stem cells in UCB remains to be established. We investigated whether other stem cells are present in cryopreserved UCB. Seeded mononuclear cells formed adherent colonized cells in optimized culture conditions. Over a 4- to 6-week culture period, colonized cells gradually developed into adherent mono-layer cells, which exhibited homogeneous fibroblast-like morphology and immunophenotypes, and were highly proliferative. Isolated cells were designated 'multipotent progenitor cells (MPCs)'. Under appropriate conditions for 2 weeks, MPCs differentiated into neural tissue-specific cell types, including neuron, astrocyte, and oligodendrocyte. Differentiated cells presented their respective markers, specifically, NF-L and NSE for neurons, GFAP for astrocytes, and myelin/oligodendrocyte for oligodendrocytes. In this study, we successfully isolated MPCs from cryopreserved UCB, which differentiated into the neural tissue-specific cell types. These findings suggest that cryopreserved human UCB is a useful alternative source of neural progenitor cells, such as MPCs, for experimental and therapeutic applications.