HPV Test as Test of Cure After Conization for CIN2+: A Nationwide Register-Based Cohort Study.

OBJECTIVE: The purpose of this study was to assess if cytology can be omitted in the follow-up after treatment for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and if human papillomavirus (HPV) test can be used alone as test of cure (TOC) after stratifying for resection margins. MATERIAL AND METHODS: In this retrospective register-based study, women who had a conization performed in Denmark between January 1 and December 31, 2013, were included. Histology, cytology, and HPV test results were obtained from The Danish Pathology Data Bank for a 3-year follow-up. RESULTS: A total of 5,174 women were included, of whom 6.1% (318/5,174) had histological residual/recurrent disease in the follow-up period. In the group with free margins, 2.6% (73/2,780) had residual/recurrent disease in contrast to 10.2% (245/2,394) in the group with involved margins. In the group with free resection margins and negative HPV test results, residual/recurrent disease was found in 0.5% (13/2,780) compared with 0.3% (9/2,780) in the group with negative HPV test results and normal cytology at 6 months' follow-up. Based on margin status and HPV test result as follow-up, the sensitivity, specificity, and positive and negative predictive values were 95.9%, 43.2%, 10.0%, and 99.4% respectively, and for combined testing (margin status, HPV, and cytology), 97.2%, 41.2%, 9.8%, and 99.6%, respectively. CONCLUSIONS: Using the HPV test at the first post-treatment control as TOC for cervical intraepithelial neoplasia grade 2 or worse after stratifying for resection margins in cone resections yields an equally high sensitivity and negative predictive value as cotesting with cytology. We suggest that women with free resection margins return to the routine screening program after negative HPV test result as TOC at 6 months.

Role of immunohistochemistry for interobserver agreement of Peritoneal Regression Grading Score in peritoneal metastasis.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC)-directed therapy is a new treatment option for peritoneal metastasis (PM). The 4-tiered Peritoneal Regression Grading Score (PRGS) has been proposed for assessment of histological treatment response. We aimed to evaluate the effect of immunohistochemistry (IHC) on interobserver agreement of the PRGS. Hematoxylin and eosin (H&E)-stained and IHC-stained slides (n = 662) from 331 peritoneal quadrant biopsies (QBs) taken prior to 99 PIPAC procedures performed on 33 patients were digitalized and uploaded to a web library. Eight raters (five consultants and three residents) assessed the PRGS, and Krippendorff's alpha coefficients (α) were calculated. Results (IHC-PRGS) were compared with data published in 2019, using H&E-stained slides only (H&E-PRGS). Overall, agreement for IHC-PRGS was substantial to almost perfect. Agreement (all raters) regarding single QBs after treatment was substantial for IHC-PRGS (α = 0.69, 95% confidence interval [CI] = 0.66-0.72) and moderate for H&E-PRGS (α = 0.60, 95% CI = 0.56-0.64). Agreement (all raters) regarding the mean PRGS per QB set after treatment was higher for IHC-PRGS (α = 0.78, 95% CI = 0.73-0.83) than for H&E-PRGS (α = 0.71, 95% CI = 0.64-0.78). Among residents, agreement was almost perfect for IHC-PRGS and substantial for H&E-PRGS. Agreement (all raters) regarding maximum PRGS per QB set after treatment was substantial for IHC-PRGS (α = 0.61, 95% CI = 0.54-0.68) and moderate for H&E-PRGS (α = 0.60, 95% CI = 0.53-0.66). Among residents, agreement was substantial for IHC-PRGS (α = 0.66, 95% CI = 0.57-0.75) and moderate for H&E-PRGS (α = 0.55, 95% CI = 0.45-0.64). Additional IHC seems to improve the interobserver agreement of PRGS, particularly between less experienced raters.

NT-proBNP to exclude heart failure in primary care - a pragmatic, cluster-randomized study.

Heart failure (HF) is difficult to recognize in primary care. N-terminal pro B-type natriuretic peptide (NT-proBNP) can be used as a rule-out test in HF due to its high negative predictive value. We aim to determine whether the number per 1000 patients of HF diagnoses increase among patients referred from primary care to an outpatient HF clinic, if general practitioners (GPs) were offered NT-proBNP in a real-life setting. All GP practices covered by Randers Regional Hospital were randomized to an intervention group (34 GP practices) and a control group (35 GP practices) in this pragmatic, cluster-randomized controlled trial. The main outcome was the number of patients referred to echocardiography and diagnosed with HF in each group. The number of patients per 1000 diagnosed with HF in the two groups was the same (0.09 (0.02-0.16) vs. 0.14 (0.07-0.21), p = .3541). A total of 700 NT-proBNP analyses, of which 611 were unique, were requested from 31 GP practices in 17.5 months. A total of 184 patients were referred to echocardiography on suspicion of HF. The number of patients per 1000 referred in the intervention group was significantly higher (p < .010). NT-proBNP was measured in 36.6% of referred patients in the intervention group. Significantly more women were diagnosed with HF in the intervention group (56.3% vs. 0%, p = .019). Hence, increased diagnostic effectiveness could not be shown in this real-life setting.

HPV-testing versus HPV-cytology co-testing to predict the outcome after conization.

INTRODUCTION: The purpose of this study was to determine the feasibility of human Papillomavirus (HPV) testing alone as a prognostic tool to predict recurrent disease within a three-year follow-up period after treatment for cervical intraepithelial neoplasia (CIN)2+ . MATERIAL AND METHODS: Retrospectively, 128 women with histologically verified CIN2+ who had a conization performed at Southern Jutland Hospital in Denmark between 1 January 2013 and 31 December 2013 were included. Histology, cytology and HPV test results were obtained for a three-year follow-up period. RESULTS: 4.7% (6/128) of the cases developed recurrent disease during follow-up. Of the cases without free margins, recurrent dysplasia was detected normal in 10.4% (5/48), whereas in the group with free margins it was 1.3% (1/80). The post-conization HPV test was negative in 67.2% (86/128) and Pap smear normal in 93.7% (120/128). Combining resection margins, cytology and HPV had sensitivity for prediction of recurrent dysplasia of 100%. Specificity was 45.8%, positive predictive value (PPV) 8.5% and negative predictive value (NPV) 100%. Using HPV test alone as a predictor of recurrent dysplasia gave a sensitivity of 83.3%, specificity 69.7%, PPV 11.9% and NPV 98.8%. Combining resection margin and HPV test had a sensitivity of 100%, specificity 45.9%, PPV 8.3% and NPV 100%. CONCLUSION: HPV test at six months control post-conization gave an NPV of 98.8% and can be used as a solitary test to identify women at risk for recurrent disease three years after treatment for precursor lesions. Using both resection margin and HPV test had a sensitivity of 100% and NPV 100%. Adding cytology did not increase the predictive value.

Calprotectin in patients with chronic rheumatoid arthritis correlates with disease activity and responsiveness to methotrexate.

OBJECTIVE: Calprotectin (myeloid-related protein 8/14) is elevated in inflammatory diseases and a correlation of serum calprotectin and disease activity in rheumatoid arthritis (RA) has been shown. In this study, we investigated plasma calprotectin as a disease marker in patients with chronic RA treated with methotrexate (MTX) monotherapy and compared plasma calprotectin with C-reactive protein (CRP) in this matter. METHODS: Seventy-six patients with chronic RA were included in this open prospective study and of these 40 were included prior to initiation of MTX therapy. The patients were followed with laboratory and clinical parameters for 52-56 weeks. Plasma calprotectin was analyzed at the start of study and at various intervals. Radiographic evaluation was performed at baseline and after 17.2 months and progression in joint destruction was measured with Larsen score. The response to MTX was evaluated according to the American College of Rheumatology criteria. RESULTS: Patients starting MTX treatment had significantly higher levels of plasma calprotectin compared to patients well established on MTX therapy (p = .008). Among the 40 patients naive to MTX, 25 responded to MTX therapy and serum calprotectin decreased significantly in these patients (p = .0007). The radiographic damage showed no relation to calprotectin. CONCLUSIONS: Plasma calprotectin is associated with disease activity in patients with chronic RA and is more strongly correlated to MTX response compared to CRP. The role of calprotectin as a disease marker is promising and the advantages compared to CRP needs to be further investigated.