Imiquimod Is Effective in Reducing Cervical Intraepithelial Neoplasia: A Systematic Review and Meta-Analysis.

INTRODUCTION: Topical Imiquimod is an immune response modifier approved for the off-label use of vulvar intraepithelial neoplasia. We conducted this systematic review and meta-analysis to investigate the efficacy and safety of Imiquimod in treating cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV)-positive patients. METHODS: The study was prospectively registered (CRD420222870) and involved a comprehensive systematic search of five medical databases on 10 October 2022. We included articles that assessed the use of Imiquimod in cervical dysplasia and HPV-positive patients. Pooled proportions, risk ratios (RRs), and corresponding 95% confidence intervals (CIs) were calculated using a random effects model to generate summary estimates. Statistical heterogeneity was assessed using I2 tested by the Cochran Q tests. RESULTS: Eight articles reported on 398 patients who received Imiquimod out of 672 patients. Among CIN-2-3 patients, we observed a pooled regression rate of 61% (CI: 0.46-0.75; I2: 77%). When compared, Imiquimod was inferior to conization (RR: 0.62; CI: 0.42-0.92; I2: 64%). The HPV clearance rate in women who completed Imiquimod treatment was 60% (CI: 0.31-0.81; I2: 57%). The majority of side effects reported were mild to moderate in severity. CONCLUSIONS: Our findings indicate that topical Imiquimod is safe and effective in reducing cervical intraepithelial neoplasia and promoting HPV clearance. However, it was found to be inferior compared to conization. Imiquimod could be considered a potential medication for high-grade CIN patients and should be incorporated into guidelines for treating cervical dysplasia.

Trichomonas vaginalis infection is associated with increased risk of cervical carcinogenesis: A systematic review and meta-analysis of 470 000 patients.

BACKGROUND: Trichomonas vaginalis infection is the most prevalent non-viral sexually transmitted infection (STI) in women and has been suggested as a risk factor for developing cervical cancer. OBJECTIVE: We aimed to investigate the associations between T. vaginalis infection and cervical carcinogenesis. SEARCH STRATEGY: A comprehensive systematic search was conducted in five databases on 21 October 2021. SELECTION CRITERIA: Studies assessing the relationship between T. vaginalis infection, HPV co-infections, cervical dysplasia, and cervical cancer were found eligible. DATA COLLECTION AND ANALYSIS: Summary estimates for pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated with a random-effects model. Statistical heterogeneity was measured with I2 and Cochran's Q tests. MAIN RESULTS: The 29 articles included 473 740 women, of whom 8518 were T. vaginalis-positive. Our results showed that T. vaginalis-infected women had 1.79 times higher odds of being diagnosed with HPV co-infection (95% CI 1.27-2.53; I2 95%). We also found that T. vaginalis infection was associated with high-grade squamous intraepithelial lesion diagnosis (OR 2.34, 95% CI 1.10-4.95; I2 75%) and cervical cancer (OR 5.23, 95% CI 3.03-9.04; I2 3%). CONCLUSIONS: Our results showed an association between T. vaginalis and cervical carcinogenesis in sexually active women.

First-Trimester Influenza Infection Increases the Odds of Non-Chromosomal Birth Defects: A Systematic Review and Meta-Analysis.

Viral infections during pregnancy raise several clinical challenges, including birth defects in the offspring. Thus, this systematic review and meta-analysis aims to prove and highlight the risk of birth defects after first-trimester maternal influenza infection. Our systematic search was performed on 21 November 2022. Studies that reported maternal influenza infection in the first trimester and non-chromosomal congenital abnormalities were considered eligible. We used odds ratios (OR) with 95% confidence intervals (CIs) to measure the effect size. Pooled ORs were calculated with a random effects model. Heterogeneity was measured with I² and Cochran's Q tests. We found that first-trimester maternal influenza was associated with increased odds of developing any type of birth defects (OR: 1.5, CI: 1.30-1.70). Moreover, newborns were more than twice as likely to be diagnosed with neural tube defects (OR: 2.48, CI: 1.95-3.14) or cleft lip and palate (OR: 2.48, CI: 1.87-3.28). We also found increased odds of developing congenital heart defects (OR: 1.63, CI: 1.27-2.09). In conclusion, influenza increases the odds of non-chromosomal birth defects in the first trimester. The aim of the present study was to estimate the risk of CAs in the offspring of mothers affected by first-trimester influenza infection.

Rare abdominal bleeding from the branches of the splenic vein during pregnancy / Ritka hasuri vérzés a vena lienalis ágrendszerébol várandósság alatt.

Összefoglaló. Az "akut has", mint kórkép, a várandósság során mind diagnosztikailag, mind terápiásan nagy kihívást jelent a szülész számára a megváltozott anatómiai viszonyok és a képalkotó eljárások korlátozott használhatósága miatt. Közleményünkben bemutatjuk egy harmadik trimeszterbeli gravida hasi vérömlenyének az esetét, melynek vérzésforrása irodalmi ritkaság, a vérzés típusát a felkeresheto irodalomban még nem írták le terheseknél. Az esettanulmány megírása a páciens orvosi dokumentációi és az ellátásában résztvevo klinikusok, patológusok leletei és beszámolói alapján történt. A várandósságának 33. hetében járó gravida akut hasi tünetegyüttessel jelentkezett klinikánkon, anamnézisébol trauma kizárható volt. Az anya romló kardiorespiratorikus állapota miatt sürgosségi császármetszéssel élo, koraszülött magzatot segítettünk világra. A mutét során kb. 1500 ml vért találtunk a hasüregben, melynek okát általános sebész bevonásával kerestük. Aktív vérzésforrásként a lép ereinek területérol vénás jellegu szivárgó vérzést találtunk, ezért splenectomia mellett döntöttünk. Az eltávolított szervkomplexum teljes szövettani feldolgozása helyenként a kisebb léphilusi vénaágak izomfalának felrostozódását és fokozatos eltunését igazolta, a patológus a vérzés okát a meggyengült érfal endothelen keresztüli vérszivárgásának véleményezte, definitív érfalszakadásra utaló elváltozás nem volt azonosítható. A haemoperitoneum várandósság alatt kifejezetten ritka kórkép, azonban mortalitása mind az anyára, mind a magzatra nézve rendkívül magas. Irodalmi adatok alapján a vérzésforrás leggyakrabban a kismedencei szervek területén jelentkezik. Ritkán a lépartéria aneurysmájának rupturája is elofordul terhességben, a lépvénás eredetu vérzés viszont irodalmi ritkaságnak számít, és az összes feldolgozott és közölt esetben az ér szakadásos sérülése volt a fo ok, az esetünkben leírt, ismeretlen etiológiájú, érfalvesztéses hemorrhágiát sehol nem említik. A várandósunk ellátásánál ellátásánál kulcsfontosságú volt a gyorsan elvégzett exploratív laparotomia, mely a kórkép okát felderítette és megszüntette, lehetové téve az anya és gyermeke túlélését és felépülését. Esetünk rámutat arra, hogy a várandóssági hasuri vérömlenyek kóroktana akár irodalmi ritkaságokat is rejthet, azaz a pontos ok kiderítésével, lumenes vérzésforrás keresésével nem szabad szükségtelen idot veszteni az édesanya és gyermeke életmento ellátásának rovására. Orv Hetil. 2022; 163(8): 328-332. Summary. Acute abdomen during pregnancy is a major challenge for physicians, due to the altered anatomical conditions and the limited use of medical imaging. We present a pregnant woman with a rare form of abdominal bleeding. This case study is based on the patient's medical documentations and interviews with her physicians. A woman in the 33rd week of her pregnancy was admitted to our department with acute abdomen, trauma was ruled out. Due to the deteriorating cardiorespiratory status we performed an emergency caesarean section delivering a living premature newborn. A general surgeon was present, and 1500 ml of blood was evacuated from the abdomen. Active venous type bleeding was present from the splenic vessels, therefore we performed a splenectomy. The histopathological analysis of the whole organ complex showed that the media layer segmentally and progressively disappeared in the splenic hilar veins, giving rise to the high probability that the bleeding was caused by a diathesis-type leakage through the endothelium and to the weakened media layer in the absence of a luminal-type vessel rupture. Hemoperitoneum during pregnancy is an exceptionally rare condition, however its mortality rate is high both for the mother and the fetus. The bleeding usually originates from the pelvis. On rare occasions the bleeding occurs from the splenic vessels although most of them are arterial bleedings from an aneurysm.In our case the emergency laparotomy was essential for the correct diagnosis and the treatment, which resulted in saving and recovering both the mother and the fetus. Orv Hetil. 2022; 163(8): 328-332.

Association of PPAR Alpha Intron 7 G/C, PPAR Gamma 2 Pro12Ala, and C161T Polymorphisms with Serum Fetuin-A Concentrations.

BACKGROUND: Both peroxisome activator proteins (PPARs) and fetuin-A play a role in lipid and glucose metabolism. AIMS: We investigated whether PPARα intron 7 G2468/C and PPARγ2 Pro12Ala and PPARγ exon 6 C161T polymorphisms are associated with serum fetuin-A concentrations. PATIENTS AND METHODS: The PPARα intron 7 G/C polymorphism was studied in cohort 1 (79 reference individuals, 165 postinfarction patients). The two PPARγ polymorphisms were investigated in cohort 2 (162 reference individuals, 165 postinfarction patients). Fetuin-A levels and PPAR polymorphisms were determined by radial immunodiffusion and polymerase chain reaction-restriction fragment length polymorphism techniques. RESULTS: The C allele variant of PPARα intron 7 G2467C was associated with higher fetuin-A levels (p = 0.018). Postinfarction status (p = 0.001), PPARα intron 7 GG/GC/CC genotypes (p = 0.032), and the C allele (p = 0.021) were the strongest determinants of fetuin-A concentration in a multiple regression model. Higher fetuin-A levels were associated with the Pro variant of PPARγ2 (p = 0.047). Postinfarction status (p = 0.041) and BMI (p < 0.001) but not PPARγ2 Pro were the strongest determinants of fetuin-A concentrations. PPARγ exon 6 C161T genotypes were not associated with fetuin-A levels. CONCLUSIONS: Fetuin-A was determined mainly by the PPARα intron 7C allele and postinfarction status in cohort 1 and the BMI and postinfarction in cohort 2. The PPARα intron 7C and PPARγ2 Pro variants are associated with fetuin-A levels.

Percutaneous Ethanol Sclerotherapy of Symptomatic Nodules Is Effective and Safe in Pregnant Women: A Study of 13 Patients with an Average Follow-Up of 6.8 Years.

Background. Because of the increased risk of surgery, thyroid nodules causing compression signs and/or hyperthyroidism are concerning during pregnancy. Patients and Methods. Six patients with nontoxic cystic, four with nontoxic solid, and three with overt hyperthyroidism caused by toxic nodules were treated with percutaneous ethanol injection therapy (PEI). An average of 0.68 mL ethanol per 1 mL nodule volume was administered. Mean number of PEI treatments for patients was 2.9. Success was defined as the shrinkage of the nodule by more than 50% of the pretreatment volume (V0) and the normalization of TSH and FT4 levels. The average V0 was 15.3 mL. Short-term success was measured prior to labor, whereas long-term success was determined during the final follow-up (an average of 6.8 years). Results. The pressure symptoms decreased in all but one patient after PEI and did not worsen until delivery. The PEI was successful in 11 (85%) and 7 (54%) patients at short-term and long-term follow-up, respectively. Three patients underwent repeat PEI which was successful in 2 patients. Conclusions. PEI is a safe tool and seems to have good short-term results in treating selected symptomatic pregnant patients. Long-term success may require repeat PEI.

Elevated serum acylated (biologically active) ghrelin and resistin levels associate with pregnancy-induced weight gain and insulin resistance.

AIM: To study fasting biologically active serum ghrelin (RIA) and resistin (ELISA) levels in different trimesters of pregnancy (HP, n=45, 15 in each) and in gestational diabetes mellitus (GDM, n=30) compared to non-pregnant healthy women (NP, n=40) in correlation with TNF-alpha, soluble (s)TNF-receptor (R)-1, -2, leptin (ELISA), C-peptide (Cp, RIA) and Cp/blood glucose ratio (bg). STUDY DESIGN: Cross-sectional case control study. RESULTS: Acylated ghrelin levels were significantly increased (p<0.0001) in the 2nd (377+/-38pg/ml, X+/-S.D.) and decreased in the 3rd trimester (252+/-36) and in GDM (226+/-21) compared to NP controls (309+/-20) and HP women in the 1st trimester (314+/-41). Serum resistin levels were higher in the 1st (8.5+/-2.6ng/ml), 2nd (10.2+/-2.1) and 3rd (13.1+/-3.6) trimesters of pregnancy and in GDM (15.7+/-3.5) than in NP controls (6.5+/-2.3). Significant (p<0.01) negative linear correlations were found among fasting serum ghrelin and body mass index (BMI), the fasting C-peptide (Cp) level, C-peptide/blood glucose (Cp/bg) ratio, TNF-alpha, soluble (s)TNFR-2, leptin and resistin concentrations in both, HP and GDM groups. Significant positive correlations were observed between serum acylated ghrelin and adiponectin, and between BMI and fasting Cp, Cp/bg, TNF-alpha, sTNFR-1, -2 and leptin levels in both pregnant groups. CONCLUSION: Increased fasting serum acylated ghrelin concentrations in the 2nd trimester may associate with weight gain during pregnancy. Hyperresistinemia may also be associated with the pregnancy-induced insulin resistance. A negative regulatory feed-back mechanism between resistin, TNF-alpha and ghrelin may be hypothesized.

Influence of leptin and the TNF system on insulin resistance in pregnancy and their effect on anthropometric parameters of newborns.

BACKGROUND: We studied the contribution of the tumor necrosis factor system and leptin to insulin resistance during the course of normal pregnancy. METHODS: Forty-five healthy pregnant women (15 in the 1st, 15 in the 2nd2 and 15 in the 3rd3 trimester) and 25 age-matched healthy nonpregnant women as controls. Twenty-three newborns delivered by women followed in the 2nd and 3rd trimesters were also investigated. Fasting serum immunoreactive tumor necrosis factor-alpha, soluble tumor necrosis factor receptor-1, soluble tumor necrosis factor receptor-2, leptin (by enzyme-linked immunoassay) and C-peptide (by radioimmunoassay) concentrations in the patients and controls were measured. Body weight, length and head circumference of the newborns were analyzed in connection with the measured maternal parameters. RESULTS: Significantly elevated tumor necrosis factor-alpha, tumor necrosis factor receptor-1 and -2, leptin, and C-peptide levels were found in the 3rd3 trimester as compared with the 1st1 and 2nd2 trimesters and with the nonpregnant controls. Tumor necrosis factor-alpha, tumor necrosis factor receptor-2, C-peptide, leptin concentrations and body mass index were found to be in a significant positive linear correlation with each other. Significant negative linear correlations were calculated among maternal serum C-peptide, tumor necrosis factor-alpha and leptin concentrations and the head circumference of the newborns. CONCLUSIONS: In conclusion, increased tumor necrosis factor-alpha and leptin levels may contribute to insulin resistance in late pregnancy. Tumor necrosis factor-alpha and leptin may be regulators of intrauterine bone development of newborns.

Correlation of maternal serum fetuin/alpha2-HS-glycoprotein concentration with maternal insulin resistance and anthropometric parameters of neonates in normal pregnancy and gestational diabetes.

OBJECTIVE: Human fetuin/alpha(2)-HS-glycoprotein (AHSG) is a 49 kDa serum and tissue protein which is a natural inhibitor of insulin receptor signaling. We investigated serum AHSG levels during pregnancy and whether the protein is involved in insulin resistance observed in healthy pregnant women and patients with gestational diabetes. DESIGN: One hundred and four healthy pregnant women and 23 of their neonates, 30 patients with gestational diabetes and their neonates and 30 healthy age-matched non-pregnant females as a control group were investigated in a case-control cross-sectional study. METHODS: Serum AHSG was determined by radial immunodiffusion. RESULTS: We observed an increase of serum AHSG concentration in the second and third trimesters. Gestational diabetes patients had significantly higher AHSG levels than healthy pregnant women and non-pregnant controls. There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-alpha (TNF-alpha), leptin, C-peptide and C-peptide/blood glucose ratio. There was also a negative correlation between maternal AHSG, TNF-alpha, leptin levels and head circumference, body length and body weight of newborns. CONCLUSION: AHSG, TNF-alpha and leptin may contribute to insulin resistance during normal pregnancy and gestational diabetes. AHSG along with these cytokines may also negatively regulate neonatal skeletal development.

Tumor necrosis factor system in insulin resistance in gestational diabetes.

OBJECTIVE: The aim of the study was to investigate the pathophysiological role of the tumor necrosis factor (TNF) system in insulin resistance in patients with gestational diabetes (GDM) and during the course of normal pregnancy. PATIENTS AND METHODS: Thirty women with GDM (16-39 gestational weeks), 35 healthy pregnant women (15 first, nine second and 11 third trimester) and 25 healthy age-matched non-pregnant women were studied. Serum TNF-alpha, and its soluble receptors 1 and 2 (sTNFR-1 and -2) were measured. RESULTS: In non-diabetic pregnant women in the third trimester all measures were significantly higher (P<0.05 or less) than in the first trimester and in non-pregnant women (BMI 27.6 +/- 4.1 (+/- S.D.), 24.1 +/- 2.6, 22.4 +/- 2.4 kg/m(2)), serum TNF-alpha (4.6 +/- 0.6, 4.1 +/- 0.4, 4.1 +/- 0.4 ng/l), sTNFR-1 (2.7 +/- 0.9, 2.0 +/- 0.5, 2.0 +/- 0.1 microg/l), sTNFR-2 (5.6 +/- 2.6, 4.6 +/- 2.1, 3.3 +/- 0.2 microg/l), C-peptide (3.1 +/- 1.7, 1.1 +/- 0.7, 1.1 +/- 0.8 microg/l), and C-peptide:blood glucose ratio (0.6 +/- 0.2, 0.2 +/- 0.1, 0.2 +/- 0.1 microg/mmol). In GDM these measures were even higher than in any subgroup of healthy pregnant women (BMI) (33.4 +/- 6.4 kg/m(2), TNF-alpha) (6.3 +/- 0.6 microg/l), sTNFR-1 (3.0 +/- 0.5 microg/l), sTNFR-2 (10.0 +/- 6.9 microg/l, C-peptide 6.0 +/- 2.7 microg/l, C-peptide:blood glucose ratio: 1.2 +/- 0.5 microg/mmol, P<0.01). Significant (P<0.01) positive linear correlations were found in gestational diabetic and non-diabetic women between serum TNF-alpha, C-peptide levels, and BMI. In gestational diabetic women, in multivariate analysis studying the dependency of C-peptide only BMI remained significant (r(2)=0.67, P=0.01). CONCLUSIONS: Our observation emphasizes the obesity-related component of insulin resistance driven by adipocytokines, such as TNF-alpha and its receptors during the course of normal pregnancy and GDM.

[Changes of cell mediated immunity in malignant ovarian tumor patients after operation] / A sejtes immunitás (NK-, K-sejtek) változása rosszindulatú petefészek-daganatos betegek mûtéti kezelése során.

OBJECTIVES: The authors discuss upon the changes in the two cell types involved in cell mediated immunity (Killer and Natural Killer) as a result of operation in malignant ovarian tumor atients. METHODS: They study the preoperative and postoperative cell mediated immunity of 28 malignant cystadenocarcinoma cases (FIGO stage I/a-III/c). To determine the maximum K and NK cell activity they used the kinetic model of cytotoxicity enzyme. RESULTS AND CONCLUSIONS: They conclude that operation of malignant ovarian tumors had no significant influence on K and NK cell activity. They hypothesize that unchanged cell mediated immunity seems to be independent of malignant tumors, especially in these conditions. We need further information about this change of cell mediated immunity.