Role of visual inspection of cervix with acetic acid and high risk human papilloma virus DNA testing in screening for cervical cancer

Background: To evaluate the role of VIA alone and in combination with high risk Human Papilloma virus DNA testing as a screening test for cervical dysplasia and cancer.Methods: 400 symptomatic patients from the gynecology outpatient department were screened using Pap smear and VIA. HPV DNA testing was done for 62 VIA positive and 100 VIA negative women. Colposcopy was done for all women. Those found positive on any or all of the screening tests were subjected to cervical biopsy. The results were analysed for PAP, VIA, HPV and a combined test using VIA and HPV both.Results: VIA had the highest sensitivity (91%) to detect any grade of dysplasia. The sensitivity of the combination test (VIA + HPV) was 80.6% which was lower than that of VIA (91%) and also lower than that of HR HPV DNA detection (86%). The specificity of the combination test (VIA + HPV) was 68.3 % which was significantly higher than that of VIA alone (39%) (p = 0.000) and also higher than that for HPV DNA detection when used alone (56%). Pap smear had the highest specificity (95.12 %) but sensitivity was much lower at 52.7 %.Conclusions: VIA is a highly sensitive screening test. The main disadvantage is its low specificity. However the combination test of VIA + HR HPV testing overcomes this and at the same time maintains a high sensitivity. Thus a test which combines VIA plus HR HPV testing is better screening method than either of the three tests (VIA, HPV, PAP) done alone

Aberrant expression and constitutive activation of STAT3 in cervical carcinogenesis: implications in high-risk human papillomavirus infection

<p>Abstract</p> <p>Background</p> <p>Recent observations indicate potential role of transcription factor STAT3 in cervical cancer development but its role specifically with respect to HPV infection is not known. Present study has been designed to investigate expression and activation of STAT3 in cervical precancer and cancer in relation to HPV infection during cervical carcinogenesis. Established cervical cancer cell lines and prospectively-collected cervical precancer and cancer tissues were analyzed for the HPV positivity and evaluated for STAT3 expression and its phosphorylation by immunoblotting and immunohistochemistry whereas STAT3-specific DNA binding activity was examined by gel-shift assays.</p> <p>Results</p> <p>Analysis of 120 tissues from cervical precancer and cancer lesions or from normal cervix revealed differentially high levels of constitutively active STAT3 in cervical precancer and cancer lesions, whereas it was absent in normal controls. Similarly, a high level of constitutively active STAT3 expression was observed in HPV-positive cervical cancer cell lines when compared to that of HPV-negative cells. Expression and activity of STAT3 were found to change as a function of severity of cervical lesions from precancer to cancer. Expression of active pSTAT3 was specifically high in cervical precancer and cancer lesions found positive for HPV16. Interestingly, site-specific accumulation of STAT3 was observed in basal and suprabasal layers of HPV16-positive early precancer lesions which is indicative of possible involvement of STAT3 in establishment of HPV infection. In HPV16-positive cases, STAT3 expression and activity were distinctively higher in poorly-differentiated lesions with advanced histopathological grades.</p> <p>Conclusion</p> <p>We demonstrate that in the presence of HPV16, STAT3 is aberrantly-expressed and constitutively-activated in cervical cancer which increases as the lesion progresses thus indicating its potential role in progression of HPV16-mediated cervical carcinogenesis.</p

Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis

From Frontiers via Jisc Publications RouterHistory: collection 2021, received 2021-08-04, accepted 2021-09-23, epub 2021-10-18Publication status: PublishedChronic histiocytic intervillositis (CHI) is a rare, but highly recurrent inflammatory placental lesion wherein maternal macrophages infiltrate the intervillous space. Pregnancies with CHI are at high risk of fetal growth restriction, miscarriage or stillbirth. Presently, the diagnosis can only be made after histopathological examination of the placenta. Given its proposed immunological etiology, current treatments include aspirin, heparin, and immunomodulatory agents. However, the rationale for these medications is largely based upon small case series and reports as there is a lack of larger studies investigating treatment efficacy. Therefore, this study sought to determine whether inclusion of immunomodulatory medications was effective at reducing the severity of lesions and improving pregnancy outcomes in subsequent pregnancies. Thirty-three women with a history of CHI in at least one pregnancy (index case) were identified retrospectively through medical records. Twenty-eight participants presented with a first subsequent pregnancy and a further 11 with a second subsequent pregnancy at a specialist clinic for pregnancy after loss. Data on maternal demographics, medical history, medication, pregnancy outcome, and placental pathology was collected and compared between pregnancies. Twenty-seven (69%) subsequent pregnancies were treated with at least one or both of prednisolone and hydroxychloroquine. Inclusion of at least one immunomodulatory agent in treatment regimen resulted in an almost 25% increase in overall livebirth rate (61.5 vs. 86.2%). In women treated with immunomodulatory medication a greater proportion of placentas had reduced severity of lesions compared to those treated without (86.7 vs. 33.3%, respectively). A reduction in CHI severity was associated with a 62.3% improvement in livebirth rate compared to those where severity remained unchanged in relation to the index case. These data provide preliminary evidence that the use of immunomodulatory medication in the management of CHI improves histopathological lesions and the chance of livebirth in subsequent pregnancies. Due to CHI's rarity and ethical and feasibility issues, randomized controlled trials in affected women are challenging to conduct. As a result, collaboration between centers is required in future to increase study sample sizes and elucidate the mechanisms of hydroxychloroquine and prednisolone in reducing pathology

Maternal Perception of Reduced Fetal Movements Is Associated with Altered Placental Structure and Function

Maternal perception of reduced fetal movement (RFM) is associated with increased risk of stillbirth and fetal growth restriction (FGR). DFM is thought to represent fetal compensation to conserve energy due to insufficient oxygen and nutrient transfer resulting from placental insufficiency. To date there have been no studies of placental structure in cases of DFM.To determine whether maternal perception of reduced fetal movements (RFM) is associated with abnormalities in placental structure and function.Placentas were collected from women with RFM after 28 weeks gestation if delivery occurred within 1 week. Women with normal movements served as a control group. Placentas were weighed and photographs taken. Microscopic structure was evaluated by immunohistochemical staining and image analysis. System A amino acid transporter activity was measured as a marker of placental function. Placentas from all pregnancies with RFM (irrespective of outcome) had greater area with signs of infarction (3.5% vs. 0.6%; p<0.01), a higher density of syncytial knots (p<0.001) and greater proliferation index (p<0.01). Villous vascularity (p<0.001), trophoblast area (p<0.01) and system A activity (p<0.01) were decreased in placentas from RFM compared to controls irrespective of outcome of pregnancy.This study provides evidence of abnormal placental morphology and function in women with RFM and supports the proposition of a causal association between placental insufficiency and RFM. This suggests that women presenting with RFM require further investigation to identify those with placental insufficiency

Data in support of the negative influence of divalent cations on (−)-epigallocatechin-3-gallate (EGCG)-mediated inhibition of matrix metalloproteinase-2 (MMP-2)

In this data article we have provided evidence for the negative influence of divalent cations on (−)‐epigallocatechin-3-gallate (EGCG)-mediated inhibition of matrix metalloproteinase-2 (MMP-2) activity in cell-free experiments. Chelating agents, such as EDTA and sodium citrate alone, did not affect MMP-2 activity. While EDTA enhanced, excess of divalent cations interfered with EGCG-mediated inhibition of MMP-2

Characterising delayed villous maturation: A narrative literature review

The normal development of the placenta is vital for fetal growth and a healthy pregnancy outcome. Delayed villous maturation (DVM) is a placental lesion that has been implicated in stillbirth. In DVM, villi do not maturate adequately for their gestational age. DVM is characterised by larger and fewer terminal placental villi, low numbers of syncytial knots, and thicker and fewer vasculosyncytial membranes. DVM is most commonly reported in conjunction with maternal diabetes; however, the occurrence of idiopathic DVM suggests that there may be multiple mechanistic pathways that contribute to DVM. DVM can only be diagnosed through histopathological examination after birth, and there is significant interobserver variability in diagnosis. Establishing objective criteria to distinguish between DVM and healthy placentas is key to increasing the understanding of DVM. Vasculosyncytial membrane count, numbers of syncytial knots and CD15, among others, have been presented as potential diagnostic criteria in the literature. This review aims to compile information on DVM, including the pathophysiology, conditions that have reported associations with DVM and potential markers that could be used as criteria to differentiate between DVM and healthy placentas

Diabetes among muslims during ramadan: A narrative review

Fasting during the month of Ramadan is one of the five fundamental principles of Islam, and it is obligatory for healthy Muslim adults and adolescents. During the fasting month, Muslims usually have two meals a day, suhur (before dawn) and iftar (after dusk). However, diabetic patients may face difficulties when fasting, so it is important for medical staff to educate them on safe fasting practices. Prolonged strict fasting can increase the risk of hypoglycemia and diabetic ketoacidosis, but with proper knowledge, careful planning, and medication adjustment, diabetic Muslim patients can fast during Ramadan. For this review, a literature search was conducted using PubMed and Google Scholar until May 2023. Articles other than the English language were excluded. Current strategies for managing blood sugar levels during Ramadan include a combination of patient education on nutrition, regular monitoring of blood glucose, medications, and insulin therapy. Insulin therapy can be continued during fasting if properly titrated to the patients\u27 needs, and finger prick blood sugar levels should be assessed regularly. If certain symptoms such as hypoglycemia, hyperglycemia, dehydration, or acute illness occur, or blood glucose levels become too high (\u3e 300 mg/dL) or too low (\u3c 70 mg/dL), the fast should be broken. New insulin formulations such as pegylated insulin and medications like tirzepatide, a dual agonist of gastric-inhibitory peptideand glucagonlike-peptide 1 receptors, have shown promise in managing blood sugar levels during Ramadan. Non-insulin-dependent medications like sodium-glucose-cotransporter-2 inhibitors, including the Food and Drug Administration-approved ertugliflozin, are also being used to provide additional cardiovascular benefits in patients with type 2 diabete

Characterizing Histopathologic Features in Pregnancies With Chronic Histiocytic Intervillositis Using Computerized Image Analysis

Context: Chronic histiocytic intervillositis (CHI) is a rare condition characterized by maternal immune cell infiltration into the human placenta. CHI is strongly associated with fetal growth restriction, miscarriage, and stillbirth, and knowledge of its etiology, and consequently effective treatment, is limited. Currently, diagnosis is largely subjective and varies between centers, making comparison between studies challenging. Objective: To objectively quantify and interrelate inflammatory cells and fibrin in placentas with CHI compared with controls and determine how pathology may be altered in subsequent pregnancies following diagnosis. Macrophage phenotype was also investigated in untreated cases of CHI. Design: Computerized analysis was applied to immunohistochemically stained untreated (index) cases of CHI, subsequent pregnancies, and controls. Index placentas were additionally stained by immunofluorescence for M1 (CD80 and CD86) and M2 macrophage markers (CD163 and CD206). Results: Quantification revealed a median 32-fold increase in macrophage infiltration in index cases versus controls, with CHI recurring in 2 of 11 (18.2%) subsequent pregnancies. A total of 4 of 14 placentas (28.6%) with a diagnosis of CHI did not exhibit infiltration above controls. Macrophages in index pregnancies strongly expressed CD163. There was no significant difference in fibrin deposition between index cases and controls, although subsequent pregnancies displayed a 2-fold decrease compared with index pregnancies. CD3+ T cells were significantly elevated in index pregnancies; however, they returned to normal levels in subsequent pregnancies. Conclusions: In CHI, intervillous macrophages expressed CD163, possibly representing an attempt to resolve inflammation. Computerized analysis of inflammation in CHI may be useful in determining how treatment affects recurrence, and alongside pathologist expertise in grading lesion severity