The introduction of primary human papillomavirus (HPV) cervical cancer screening requires the implementation of an appropriate triage strategy that will be effective in detecting high‐grade cervical disease without losing diagnostic specificity. From the 30.066 screening tests results, a total of 1086 with available high‐risk human papillomavirus (HRHPV) with limited genotyping, cytology, and p16/Ki67 dual‐stain were selected. Two triage strategies for primary HPV screening were analyzed retrospectively based on the study group. Performance characteristics for p16/Ki67 and cytology triage in the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) were calculated, detected in colposcopic biopsy. In HPV16/18‐positive cases, primary HPV with p16/Ki67 triage was significantly more specific than cytology (53.1%/16.8% for CIN2+; p < 0.0001; 45.9%/17.0% for CIN3+; p < 0.0001), with yielded sensitivity (95.7%/84.8% for CIN2+; p = 0.0955; 100.0%/87.5% for CIN3+; p = 0.0832). In other HRHPV‐positive cases (N16/N18), p16/Ki67 triage was also significantly higher specific (51.3%/15.3% for CIN2+; p < 0.0001; 44.5%/16.5% for CIN3+; p < 0.0001), with sensitivity (92.3%/74.4% for CIN2+; p = 0.0522; 90.9%/81.8% for CIN3+; p = 0.5637). Diagnostic predictive values were significantly higher for p16/Ki67 triage with the highest PPV in HPV16/18‐positive cases for CIN2+ (45.4%; 95% confidence interval [CI]: 35.2–55.8; p < 0.0001) and very high NPV in all HPV‐positive cases regardless of detected genotype (96.3%–100.0%). The risk (1‐NPV) for CIN3+ in HRHPV16/18‐positive/p16/Ki67‐negative women was 0.0%. Superior diagnostic performance compared to cytology for detecting cervical cancer precursors indicates that p16/Ki67 dual‐immunostain may be a highly effective tool of triage in primary HPV screening with limited HPV 16/18 genotyping in secondary cervical cancer prevention.
Lymphomas are one of the serious complications of the primary Sjörgen’s Syndrome (pSS). The aim of the study was to evaluate the frequency of lymphoma in pSS. The singe-center retrospective study included 198 Caucasian patients, who met diagnostic criteria for pSS. The type of lymphoproliferative disorder was classified according to the WHO 2016 classification. The mean time of observation, after pSS diagnosis, was 48 weeks. Focus score (FS) ≥ 1 was present in 85% of the patients, and anti-SSA antibodies were detected in 84%. Rheumatoid factor was detected in 130 (65%) patients. Mean disease activity index, according to EULAR Sjörgen’s Syndrome disease activity index (ESSDAI), was 8.3 points at the moment of pSS diagnosis. Complement C3 was decreased in 14% of the patients, while 10% showed reduced complement C4. Four patients (2%) were diagnosed with a lymphoma. Most of the patients were diagnosed with mucosa-associated lymphoid tissue lymphoma (MALT), in whom the tumour was located in the parotid gland, and in one patient the stomach was involved. Finally, one patient was diagnosed with a rare B-cell small lymphocytic lymphoma located in the lungs. In this article, we present detailed characteristics of each case. In analysed population the frequency of lymphoma in the course of pSS in patients with pSS is 2%. The variety of lymphoma types in pSS patients imposes individual monitoring in each patient at every check-up visit for disease activity.
The endothelin system is reported to play a significant role in glomerular and tubulointerstitial kidney disease. In the kidney, endothelins are produced in mesangial cells and the glomerular basement membrane by the endothelium and podocytes. The endothelin system regulates glomerular function by inducing proliferation, increasing permeability and in effect proteinuria, and stimulating inflammation, tubular fibrosis, and glomerular scarring. Endothelin A receptor antagonists have been proven to delay the progression of chronic kidney disease and play a protective role in immunoglobulin A nephropathy, focal segmental glomerulosclerosis, and diabetic nephropathy. There are several ongoing research studies with ETAR antagonists in nondiabetic nephropathy, Alport disease, vasculitis and scleroderma nephropathy, which results are promising. Some reports suggest that the endothelin system might contribute to ischemia–reperfusion injury, acute graft rejection and deterioration of graft function. Endothelin inhibition in renal transplantation and its influence on graft survival is the future direction needing further research. The most frequent side effects associated with ETAR antagonists is fluid retention. Additionally, it should be considered if selective ETAR antagonists therapy needs to be co-administered with sodium-glucose co-transporter 2 inhibitors, renin–angiotensin–aldosterone inhibitors or diuretics and which patients should be recruited to such treatment to minimize the risk of adverse outcomes.
PD-1/PD-L1 axis plays an important role in maintaining homeostasis and prevention from autoimmunity; however, in the tumor microenvironment, PD-1/PD-L1 interaction is responsible for the evasion of immune surveillance by tumor cells. We therefore hypothesized that single nucleotide polymorphisms (SNPs) in genes encoding PD-1 and PD-L1 molecules are associated with the development and outcome of renal cell carcinoma (RCC). Here we genotyped nine polymorphisms: five of PDCD1: rs36084323G>A, rs11568821G>A, rs2227981C>T, rs10204525G>A, rs7421861T>C and four of PD-L1: rs822335C>T, rs4143815G>C, rs4742098A>G, rs10815225G>C in 237 RCC patients (including 208 with clear cell RCC (ccRCC)) and 256 controls, with application of allelic discrimination method with use of TaqMan Assays. Interestingly, we found the SNP-SNP interaction between rs10815225 and rs7421861 polymorphisms associated with ccRCC risk. The rs7421861 TC genotype decreased the risk of ccRCC development compared to TT and CC genotypes in the group of rs10815225 GC + CC individuals (OR = 0.21, CI95% = 0.08; 0.54). While possessing of rs10815225 GC or CC genotype increased susceptibility to ccRCC when compared to rs10815225 GG genotype in individuals with rs7421861 TT or CC genotype (OR = 2.40, CI95% = 1.25; 4.61). In conclusion, genetic variants in PDCD1 and PD-L1 genes, especially taken together as SNP-SNP interactions, can be considered to be ccRCC risk factors.
The baseline data from the private-based opportunistic cervical cancer screening with HRHPV14, liquid-based cytology (LBC) and p16/Ki67 testing, and its quality assessment/quality control (QA/QC) tools are lacking. The age-stratified analysis of 30,066 screening tests results in a Polish population, including the investigation of HRHPV14 status, LBC, and p16/Ki67 dual-staining reporting rates, along with immediate histopathologic correlations, was conducted. For cytopathologic QA/QC, the College of American Pathologists (CAP) benchmarks and enhanced safety protocol were used. The NILM/ASC-US/LSIL/ASC-H/HSIL/AGC reporting rates were 93.9/3.4/2.0/0.22/0.24/0.11, respectively, with correlating HRHPV14-positive rates of 8.4/48.9/77.2/84.6/90.7/26.7. The reporting rates for HSIL (CIN2+) in HRHPV-positive women with NILM/ASC-US/LSIL/ASC-H/HSIL/AGC referred for a colposcopy with biopsy were 19.1/25.8/22.5/12.4/19.1/1.1% of the total HSIL (CIN2+). In total, of the 1130 p16/Ki67 tests, 30% were positive. In NILM HRHPV14-positive women with available histology result, HSIL(CIN2+) was detected in 28.3% of cases. In the first such large-scale Polish study presenting HRHPV14, informed LBC and HSIL (CIN2+) results, the reporting rates were highly consistent with data from American and other CAP-certified laboratories, confirming the possibility of using the 2019 ASCCP risk-based guidelines as one of the screening strategies outside of the US, in conditions of proper QA/QC. The private-based screening model can be effective in cervical cancer prevention, particularly in countries with low population coverage of public funds-based systems.
IgA nephropathy (IgAN) is the most frequent primary glomerulonephritis worldwide. Due to its heterogenicity, there is a need to establish robust biomarkers for IgAN, to support treatment decisions and evaluate the risk of progression to end-stage renal disease. Using both clinical and histopathological data, derived from renal biopsies, we aimed to find predictors of renal function deterioration and proteinuria reduction. Clinical and histopathological data of 80 patients with biopsy proven IgAN were analyzed. In a multivariate logarithmic regression model, the presence of endocapillary hypercellularity (E1) predicted a decline in estimated glomerular filtration rate (eGFR)of at least 50% with an odds ratio (OR) of 15.2, whereas serum albumin concentration had a negative influence on eGFR deterioration (OR 0.2). In the second multivariate model, the extent of interstitial fibrosis predicted the worsening of eGFR by 50% (OR 1.1) and serum albumin concentration had a protective impact (OR 0.1). In the univariate logarithmic regression, both the extent of interstitial fibrosis and the presence of endocapillary hypercellularity negatively correlated with the reduction in proteinuria below 1.0 g/24 h with an OR of 0.2 and 0.9, respectively. In our paper, we confirmed the utility of histopathological variables, especially endocapillary hypercellularity and interstitial fibrosis, and clinical parameters, particularly serum albumin concentration, in the prediction of both a decline in eGFR and a reduction in proteinuria in IgA nephropathy.