Prediction of Acute COPD Exacerbation in the Swiss Multicenter COPD Cohort Study (TOPDOCS) by Clinical Parameters, Medication Use, and Immunological Biomarkers

<b><i>Background and Objective:</i></b> Whether immunological biomarkers combined with clinical characteristics measured during an exacerbation-free period are predictive of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) frequency and severity is unknown. <b><i>Method:</i></b> We measured immunological biomarkers and clinical characteristics in 271 stable chronic obstructive pulmonary disease (COPD) patients (67% male, mean age 63 years) from “The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland” cohort on a single occasion. One-year follow-up data were available for 178 patients. Variables independently associated with AECOPD frequency and severity were identified by multivariable regression analyses. Receiver operating characteristic analysis was used to obtain optimal cutoff levels and measure the area under the curve (AUC) in order to assess if baseline data can be used to predict future AECOPD. <b><i>Results:</i></b> Higher number of COPD medications (adjusted incident rate ratio [aIRR] 1.17) and platelet count (aIRR 1.03), and lower FEV₁% predicted (aIRR 0.84) and IgG2 (aIRR 0.84) were independently associated with AECOPD frequency in the year before baseline. Optimal cutoff levels for experiencing frequent (&#x3e;1) AECOPD were ≥3 COPD medications (AUC = 0.72), FEV₁ ≤40% predicted (AUC = 0.72), and IgG2 ≤2.6 g/L (AUC = 0.64). The performance of a model using clinical and biomarker parameters to predict future, frequent AECOPD events in the same patients was fair (AUC = 0.78) but not superior to a model using only clinical parameters (AUC = 0.79). The IFN-lambda rs8099917GG-genotype was more prevalent in patients who had severe AECOPD. <b><i>Conclusions:</i></b> Clinical and biomarker parameters assessed at a single point in time correlated with the frequency of AECOPD events during the year before and the year after assessment. However, only clinical parameters had fair discriminatory power in identifying patients likely to experience frequent AECOPD.

Preoperative calcitonin testing improves the diagnosis of medullary thyroid carcinoma in female and male patients

Calcitonin (Ctn) measurement in patients with thyroid disease could potentially increase the detection rates of medullary thyroid carcinoma (MTC) but remains a controversial issue. The aim of this study was to evaluate routine preoperative Ctn measurements. Methods: All patients with thyroid surgery documented in the prospective StuDoQ|Thyroid registry between 03/2017 and 09/2020 were included. Cutoff levels for Ctn were determined with ROC analyses to assess the preoperative diagnosis of MTC in subgroups for females and males. Findings: In 29.590 of 39.679 patients (75%) participating in the registry, routine preoperative Ctn testing was performed. In 357 patients (227 females, 130 males) histopathology confirmed MTC with a mean tumor size of 14.7 mm (± 12.43). Biochemical cure was achieved in 71.4% of the patients. Ctn levels between 11 and 20 pg/ml were seen in 2.6% of the patients, and only 0.7% of the patients had Ctn levels above 21 pg/ml. Cutoff levels for the diagnosis of MTC were 7.9 pg/ml for females and 15 pg/ml for males (p <0.001). The sensitivity and specificity for females were 95% and 98%, and 96% and 97% for males, respectively. Conclusion: Routine Ctn testing is a reliable predictor for MTC and provides the opportunity for earlier thyroidectomy before lymph node metastases occur, resulting in a better prognosis. Females with Ctn levels >7.9 pg/ml and males >15 pg/ml without any other extrathyroidal sources for an elevated Ctn should be monitored. Thyroid surgery should be considered if Ctn levels are increasing, or ultrasound detects suspicious thyroid lesions.

Reproducibility and refinement of urinary LH in the screening of progressive puberty in girls

Context First-voided urinary LH (FVU-LH) has been suggested as an alternative to gonadotropin-releasing hormone (GnRH) stimulation test for detection of precocious puberty. Objective To evaluate the reproducibility of FVU-LH, its correlation with basal and GnRH-stimulated gonadotropins, and its diagnostic value for differentiating progressive from non-progressive puberty. Design and participants Clinical and endocrine data were obtained from the medical records of 95 girls with suspected progressive puberty who underwent two consecutive FVU-LH tests. In 55 of these participants, GnRH stimulation test was performed close to the FVU-LH test. The reported cutoff levels of 5 IU/L and 1.16 IU/L for GnRH-stimulated LH and FVU-LH, respectively, were used as markers of progressive puberty, clinically defined as bone age advancement of &gt;1 year and/or growth velocity SDS&gt;2, in addition to thelarche. Results The two consecutive measurements of FVU-LH were highly correlated (r= 0.830; p&lt;0.001). The higher of the two results was better correlated with basal gonadotropins and GnRH-stimulated LH. Furthermore, it aligned better with the clinical outcome of girls with early thelarche, which supports the approach of double tests of FVU-LH to distinguish progressive from non-progressive puberty. By comparison to GnRH-stimulated LH, the higher FVU-LH value had better sensitivity (68%), whereas peak LH had better specificity (91%) for the diagnosis of progressive puberty. Both tests had high positive predictive value and poor negative predictive value. Conclusions The higher value of paired FVU-LH tests can be used to screen girls with suspected progressive puberty and can reduce the need for GnRH stimulation test.

Recovery Rates of Treated vs. Non-Treated Dairy Cows with Subclinical Mastitis

The term “spontaneous recovery” refers to a return to a previous condition without any external treatment. In cow mastitis, it refers to cases exhibiting visual symptoms (clinical) or an increase in somatic cell count (SCC) with no visual symptoms (subclinical), with or without identification of a pathogen, from which the animal recovers. A large retrospective analysis of data compiled from the Israeli Dairy Herd Book was performed to evaluate the occurrence of: (i) actual “spontaneous recovery” from the inflammation; (ii) recovery from the inflammation due to antibiotic treatment. In 2018, 123,958 cows from 650 herds with first elevation of SCC at monthly test-day milk yield were clustered into five SCC-cutoff levels (CL) (×103 cells/mL): CL1 (200–299), CL2 (300–399), CL3 (400–499), CL4 (500–999), CL5 (≥1000). Each cutoff level was analyzed separately, and each cow appeared only once in the same lactation and cutoff level, thus resulting in five independent analyses. Recovery was defined as decreased SCC on all three monthly test days, or on the second and third test days, set to: R1 (<100 × 103 cells/mL); R2 (<250 × 103 cells/mL). No difference was found among cutoff levels when the recovery was set to R1, with only 10–12% of the cows presenting spontaneous recovery. When the recovery was set to R2, percent spontaneous recovery was 25–27% at the three higher cutoff levels (CL3–CL5) and 35–41% at the lowest levels (CL1, CL2). Antibiotic treatment was administered to only ~10% of the cows, and in only the higher cutoff-level groups—CL4 and CL5. No difference was found between spontaneous recovery and recovery after antibiotic treatment. Moreover, percentage culled cows treated with antibiotics was significantly higher (p < 0.01) than that of non-treated culled cows (18 and 10.2, respectively), suggesting that the more severe mastitis cases were treated. We concluded that (i) actual spontaneous recovery from inflammation is low and does not depend on the number of cells in the milk at time of infection, and (ii) recovery from inflammation following antibiotic treatment is not higher.

Pulmonary Embolism Detection in COVID-19 Patients

Background: A clinically important impact of Coronavirus Disease 2019 (COVID-19) is the increased likelihood of thromboembolism, mainly pulmonary embolism (PE). To screen for these complications a biochemical marker, D-dimer, is usually done. There is a plethora of research validating the use of D-dimer cutoff levels in non-COVID-19 patients, however less so in the COVID-19 population. Aim: To determine the number of suspected COVID patients with D-dimer ≥ 0.5 and PE reported on CTPA. Methods: Non-interventional single-centre retrospective clinical correlational study. Patient cohort was patients admitted with suspected COVID-19 over a 5-week period. N=690. Results: 76.5% of suspected COVID-19 patients were PCR positive. 40% of these patients had a CTPA completed with 19% reported to have a PE. 52% of patients had a D-dimer value ≥ 0.5 10.6% patients had a PE with a D-dimer ≥ 0.5. Conclusion: Nationally, hospitals are adopting existing D-dimer cut off levels to rule out PEs, however this leads to a large proportion of admitted COVID-19 patients having possibly unnecessary computed tomography pulmonary angiogram. This study highlights that majority of patients with D-dimers above the cut off level have negative PEs and contributes to the notion that standard D-dimer cutoffs are insufficiently accurate to be used as a standalone test in diagnosis in the context of an underlying SARS-CoV-2 infection.

High-Sensitivity Cardiac Troponin T in Patients with Severe Chronic Kidney Disease and Suspected Acute Coronary Syndrome

(1) Background: Patients with severe chronic kidney disease (CKD G4–G5) often have chronically elevated high-sensitivity cardiac troponin T (hs-cTnT) values above the 99th percentile of the upper reference limit. In these patients, optimal cutoff levels for diagnosing non-ST-elevation acute coronary syndrome (NSTE-ACS) requiring revascularization remain undefined. (2) Methods: Of 11,912 patients undergoing coronary angiography from 2012 to 2017 for suspected NSTE-ACS, 325 (3%) had severe CKD. Of these, 290 with available serial hs-cTnT measurements were included, and 300 matched patients with normal renal function were selected as a control cohort. (3) Results: In the CKD cohort, 222 patients (76%) had NSTE-ACS with indication for coronary revascularization. Diagnostic performance was high at presentation and similar to that of the control population (AUC, 95% CI: 0.81, 0.75–0.87 versus 0.85, 0.80–0.89, p = 0.68), and the ROC-derived cutoff value was 4 times higher compared to the conventional 99th percentile. Combining the ROC-derived cutoff levels for hs-cTnT at presentation and absolute 3 h changes, sensitivity increased to 98%, and PPV and NPV improved up to 93% and 86%, respectively. (4) Conclusions: In patients with severe CKD and suspected ACS, the diagnostic accuracy of hs-cTnT for the diagnosis of NSTE-ACS requiring revascularization is improved by using higher assay-specific cutoff levels combined with early absolute changes.

Pulmonary Embolism Detection in COVID-19 Patients

Background: A clinically important impact of Coronavirus Disease 2019 (COVID-19) is the increased likelihood of thromboembolism, mainly pulmonary embolism (PE). To screen for these complications a biochemical marker, D-dimer, is usually done. There is a plethora of research validating the use of D-dimer cutoff levels in non-COVID-19 patients, however less so in the COVID-19 population. Aim: To determine the number of suspected COVID patients with D-dimer ≥ 0.5 and PE reported on CTPA. Methods: Non-interventional single-centre retrospective clinical correlational study. Patient cohort was patients admitted with suspected COVID-19 over a 5-week period. N=690. Results: 76.5% of suspected COVID-19 patients were PCR positive. 40% of these patients had a CTPA completed with 19% reported to have a PE. 52% of patients had a D-dimer value ≥ 0.5 10.6% patients had a PE with a D-dimer ≥ 0.5. Conclusion: Nationally, hospitals are adopting existing D-dimer cut off levels to rule out PEs, however this leads to a large proportion of admitted COVID-19 patients having possibly unnecessary computed tomography pulmonary angiogram. This study highlights that majority of patients with D-dimers above the cut off level have negative PEs and contributes to the notion that standard D-dimer cutoffs are insufficiently accurate to be used as a standalone test in diagnosis in the context of an underlying SARS-CoV-2 infection.

The Role of Interleukin in Ectopic Pregnancy: A Systematic Review

BACKGROUND: Ectopic pregnancy (EP) is the implantation of an embryo outside the eutopic cavity with the most location of EP is in the fallopian tube (FT), known as tubal EP (TEP). The FT of TEP expresses higher levels of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, and IL-8. AIM: The study aimed to look systematically into the current literature and carefully analyze the results to explore the role of IL in EP. METHODS: Three independent reviewers conducted the literature search through some electronic databases searching for articles fulfilling inclusion and exclusion criteria. The lead author independently assessed the risk of bias of each of the 313 articles identified in database searching, 12 articles met the criteria for this review. CONCLUSION: IL-6 and IL-8 have diagnostic significance in predicting EP with the cutoff levels of IL-6 and IL-8 which were 26.48 and 40 pg/mL. Further, research is needed for the role of other interleukins in EP.

High Sensitivity Cardiac Troponin T in Patients with Severe Chronic Kidney Disease and suspected Acute Coronary Syndrome

Background: Patients with severe chronic kidney disease (CKD G4-G5) often have chronically elevated high-sensitivity cardiac troponin T (hs-cTnT) values above the 99th percentile of the upper reference limit. In these patients, optimal cutoff levels for diagnosing non-ST-elevation acute cor-onary syndrome (NSTE-ACS) requiring revascularization remain undefined. Methods: Of 11,912 patients undergoing coronary angiography from 2012 to 2017 for suspected NSTE-ACS, 325 (3%) had severe CKD. Of these, 290 with available serial hs-cTnT measurements were included and 300 matched patients with normal renal function were selected as a control cohort. Results: Diagnostic performance for patients with severe CKD was high at presentation and similar to that of the control population (AUC, 95% CI: 0.81, 0.75-0.87 versus 0.85, 0.80-0.89, p=0.68) and the ROC-derived cutoff value at presentation was 4 times higher compared to the conventional 99th percentile. Combining the ROC-derived cutoff levels for hs-cTnT at presentation and absolute 3-hour changes, sensitivity increased to 98%, PPV and NPV improved up to 93% and 86%, re-spectively. (4) Conclusions: In patients with severe CKD and suspected ACS the diagnostic accu-racy of hs-cTnT for the diagnosis of NSTE-ACS requiring revascularization is improved by using higher assay specific cutoff levels combined with early absolute changes.