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Abstract Background Ovarian cancer is one of the most common gynecological malignancies due to the lack of early symptoms, early diagnosis and limited screening. Therefore, it is necessary to understand the molecular mechanism underlying the occurrence and progression of ovarian cancer and to identify a basic biomarker for the early diagnosis and clinical treatment of ovarian cancer. Methods The association between FBXO28 and ovarian cancer prognosis was analyzed using Kaplan‒Meier survival analysis. The difference in FBXO28 mRNA expression between normal ovarian tissues and ovarian tumor tissues was obtained from The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) cohorts. The expression levels of the FBXO28 protein in ovarian cancer tissues and normal ovarian tissues were measured via immunohistochemical staining. Western blotting was used to determine the level of FBXO28 expression in ovarian cancer cells. The CCK-8, the colony formation, Transwell migration and invasion assays were performed to evaluate cell proliferation and motility. Results We found that a higher expression level of FBXO28 was associated with poor prognosis in ovarian cancer patients. Analysis of the TCGA and GTEx cohorts showed that the FBXO28 mRNA level was lower in normal ovarian tissue samples than in ovarian cancer tissue samples. Compared with that in normal ovarian tissues or cell lines, the expression of FBXO28 was greater in ovarian tumor tissues or tumor cells. The upregulation of FBXO28 promoted the viability, proliferation, migration and invasion of ovarian cancer cells. Finally, we demonstrated that FBXO28 activated the TGF-beta1/Smad2/3 signaling pathway in ovarian cancer. Conclusions In conclusion, FBXO28 enhanced oncogenic function via upregulation of the TGF-beta1/Smad2/3 signaling pathway in ovarian cancer.

Abstract Bromodomain-containing protein 4 (BRD4), the major component of bromodomain and extra-terminal domain (BET) protein family, has important functions in early embryonic development and cancer development. However, the posttranslational modification of BRD4 is not well understood. Multiple approaches were used to explore the mechanism of PRMT1-mediated BRD4 methylation and to determine the biological functions of BRD4 and PRMT1 in ovarian cancer. Here we report that BRD4 is asymmetrically methylated at R179/181/183 by PRMT1, which is antagonized by the Jumonji-family demethylase, JMJD6. PRMT1 is overexpressed in ovarian cancer tissue and is a potential marker for poor prognosis in ovarian cancer patients. Silencing of PRMT1 inhibited ovarian cancer proliferation, migration, and invasion in vivo and in vitro. PRMT1-mediated BRD4 methylation was found to promote BRD4 phosphorylation. Compared to BRD4 wild-type (WT) cells, BRD4 R179/181/183K mutant-expressing cells showed reduced ovarian cancer metastasis. BRD4 arginine methylation is also associated with TGF-β signaling. Our results indicate that arginine methylation of BRD4 by PRMT1 is involved in ovarian cancer tumorigenesis. Targeting PRMT1-mediated arginine methylation may provide a novel diagnostic target and an effective therapeutic strategy for ovarian cancer treatment.

Atrial standstill is a rare form of bradyarrhythmia and consists of a transitory or permanent loss of the electrical and mechanical activity of the atria. It has been described in a few cases of long-standing valvular disease, amyloidosis, myocarditis, and muscular dystrophy. We report on a young female with noncompaction cardiomyopathy that progressed to congestive heart failure. Electrocardiogram showed persistence atrial standstill that was confirmed clinically and by electrocardiomyopathy, Doppler two-dimensional echocardiogram, and tissue Doppler imaging. We assume that worsening of asymptomatic noncompaction and progression to the congestive form of cardiomyopathy could be presaged by the presence of persistent atrial standstill. Thus, persistence of atrail standstill in asymptomatic cardiomyopathy is a sign of poor prognosis. [ABSTRACT FROM AUTHOR]

Cardiogenic unilateral pulmonary edema (UPE) is a rare clinical condition and not readily recognized early and managed accordingly. Acute rheumatic fever, which is a common disease in developing countries, does not commonly present with UPE. We report a 13-year-old girl presenting with UPE following acute rheumatic fever mimicking pneumonia. We conclude that UPE should be considered in the differential diagnosis for the patient with clinical criteria of rheumatic fever who presents with unilateral lung opacification. With early recognition and antifailure treatment, it is possible to reduce morbidity and mortality in such patients. [ABSTRACT FROM AUTHOR]

Objective: This study quantifies change in best visual acuity (BVA) over the preoperative period and assesses factors associated with postoperative outcomes., Design: Retrospective chart review conducted at a single institution., Participants: A total of 691 patients underwent cataract surgery and had a preoperative assessment 0-30 days prior to surgery following their surgical evaluation., Methods: Baseline demographics and past medical and clinical data were collected through electronic medical record query. BVA was noted at initial surgical evaluation, preoperative assessment, and nearest postoperative assessment., Results: A total of 691 patients (911 eyes) were included with mean BVAs at the initial evaluation, preoperative assessment, and postoperative assessment of 68.3 ± 16.8, 64.6 ± 18.5, and 81.1 ± 12.0 ETDRS letters, respectively. Mean BVA was significantly higher postoperatively compared with the preoperative assessment and initial evaluation (p < 0.0001). There was a mean of 53.8 days between initial surgical evaluation and surgery date and a mean of 49.9 days between the preoperative assessment and initial surgical evaluation. The mean interval between the preoperative assessment and surgery was 11.7 days. In the preoperative period, 9.1% of eyes experienced worsening of BVA by >3 lines and 0.9% experienced improvement of BVA by >3 lines. Time to surgery was significantly associated with change in postoperative BVA (effect size, -0.03 ETDRS letters; p = 0.015) but was not significant on multiple linear regression. BVA at initial evaluation, glaucoma, and glaucoma surgery were all significantly associated with postoperative outcomes., Conclusion: Most eyes experienced stable vision in the preoperative period for cataract surgery. On average, patients with high BVAs at the time of initial surgical evaluation may be able to defer surgery without the risk of poorer surgical outcomes., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

A patient was delivered at 26 weeks (about 6 months) gestation via an emergency caesarian section. A patent ductus arteriosus (PDA) and atrial septal defect (ASD) were discovered during an echocardiogram 13 days after birth. The patient had catheter-based closure of the PDA and ASD. During a routine echocardiogram to check device placements, it was discovered that there was dilation of the superior vena cava (SVC), and it was suspected that a thrombus was present. Computed tomography angiography (CTA) was completed to better define SVC anatomy and flow acceleration. The CTA demonstrated that there was a double innominate vein., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Currently, no guidelines exist regarding the appropriate time from diagnosis to treatment among pancreatic adenocarcinoma patients. Herein, we aim to define the median time to treatment in pancreatic adenocarcinoma, factors associated with treatment delay, and prognostic significance., Methods: We conducted a retrospective study of pancreatic adenocarcinoma patients, stage I-IV, at a tertiary referral center (2017-2020). We subdivided time to treatment (days) into 4 components: (1) T i : symptom onset to initial provider evaluation, (2) T ii : initial provider evaluation to diagnosis, (3) T iii : diagnosis to specialist consultation, (4) T iv : specialist visit to treatment., Results: In total, 217 patients met the inclusion criteria. The median T i , T ii , T iii , and T iv were 20, 12, 4, and 14 days, respectively. The total time to treatment was 75 days. Patients with weight loss had longer T i (β = 108.6). More frequent hospitalizations (β = 19.5) and misdiagnosis (β = 33.4) were associated with longer T ii . Patients with a history of malignancy (β = 15) or active treatment of a second disease (β = 19.4) had longer T iii . Poor performance status (β = 6.2) or private insurance (β = 50.2) were associated with a longer T iv . Black patients had longer T i+ii+iii+iv (β = 100). Time to treatment was not associated with overall survival (P > .05)., Conclusion: It takes a median time of less than a month for a patient with pancreatic adenocarcinoma to start treatment, even after they visit a primary provider. The greatest opportunity to shorten the overall time to treatment is by having patients seek medical attention earlier (T i )., (Copyright © 2023. Published by Elsevier Inc.)

Glomerulonephritis (GN) is a complex disease with intricate underlying pathogenic mechanisms. The possible role of underlying complement dysregulation is not fully elucidated in some GN subsets, especially in the setting of autoimmunity or infection. In the current study, diagnosed cases of lupus nephritis (LN) and post-infectious GN (PIGN) were recruited for molecular genetic analysis and targeted next-generation DNA sequencing was performed for two main complement regulating genes: in the fluid phase; CFH , and on tissue surfaces; MCP . Three heterozygous pathogenic variants in CFH (Q172*, W701*, and W1096*) and one likely pathogenic heterozygous variant in MCP (C223R) have been identified in four of the studied LN cases. Additionally, among the several detected variants of uncertain significance, one novel variant (CFH:F614S) was identified in 74% of the studied LN cases and in 65% of the studied PIGN cases. This variant was detected for the first time in the Egyptian population. These findings suggest that subtle mutations may be present in complement regulating genes in patients with immune-complex mediated category of GN that may add to the disease pathogenesis. These findings also call for further studies to delineate the impact of these gene variants on the protein function, the disease course, and outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gouda, Talaat, Bouzid, El-Assi, Nabil, Venkatachalam, Manasa Bhamidimarri, Wohlers, Mahdami, EL-Gendi, ElKoraie, Busch, Saber-Ayad, Hamoudi and Baddour.)

Deregulation of the cell cycle regulating genes is common in urothelial bladder carcinoma (UBC). We aimed to examine the prognostic significance of ki-67, p53, p63 and cyclinD1expression in UBC and to identify optimal cut-off points to help identifying patients at high risk of tumor recurrence. We evaluated the immunohistochemical expression of ki-67, p53, p63 and cyclinD1 in 100 UBCs. The conventional and the classification and regression trees-guided (CART-guided) methods were utilized to determine the independent predictors of tumor recurrence. The p53 and Ki-67 expression didn't associate significantly with tumor recurrence.p63 and cyclinD1 exhibited significant hazard ratios. Using CART, no recurrence was observed when p63 was ≥87.5%. The recurrence incidence increased and the disease free survival (DFS) time shortened as the p63 decreased. CyclinD1 associated significantly with tumor recurrence only if p63 was <35%. Using the CART cut-off values¬, cases were categorized into three groups; (groups I: p63 ≥ 35%, II: p63 < 35% and cyclinD1 < 10% and III: p63 < 35% and cyclinD1 ≥ 10%). Group I patients revealed the least incidence of recurrence at the longest DFS. Group III had the worst prognosis followed by Group II. p63 represents a surrogant biomarker to predict UBC recurrence.CyclinD1 can be used only when p63 is <35%. CART proved helpful with data among which the number of cases with positive outcomes is too small relative to the number of studied predictors. Large cohort studies for ki-67 and p53 are recommended to be performed with standardized criteria as regards patients' characteristics, cut-off values, and follow-up time.

Background: Current literature is lacking level 1 evidence for surgical and oncologic outcomes of hepatocellular carcinoma (HCC) undergoing laparoscopic versus open hepatectomy. Aim was to compare feasibility, safety, and surgical and oncologic efficiency of laparoscopic versus open liver resection (OLR) in management of solitary small (<5 cm) peripheral HCC in Child A cirrhotic patients., Methods: Patients were randomly assigned to either OLR group (25 patients) or laparoscopic liver resection (LRR) group (LRR: 25 patients). All were treated with curative intent aiming at achieving R0 resection using radiofrequency-assisted technique., Results: LLR had significantly less operative time (120.32 ± 21.58 versus 146.80 ± 16.59 minutes, P < .001) and shorter duration of hospital stay (2.40 ± 0.58 versus 4.28 ± 0.79 days, P < .001), with comparable overall complications (25 versus 28%, P = .02). LLR had comparative resection time (66.56 ± 23.80 versus 59.56 ± 14.74 minutes, P = .218), amount of blood loss (250 versus 230 mL, P = .915), transfusion rate (P = 1.00), and R0 resection rate when compared with OLR. After median follow-up of 34.43 (31.67-38.60) months, LLR achieved similar adequate oncological outcome of OLR, no local recurrence, with no significant difference in early recurrence or number of de novo lesions (P = .49). One-year and 3-year disease free survival (DFS) rates, 88% and 59%, in the LLR were comparable to corresponding rates of 84% and 54% in OLR (P = .9)., Conclusion: LLR is superior to the OLR with significantly shorter duration of hospital stay and does not compromise the oncological outcomes.

Fibroblast growth factor 18 (FGF18) has been suggested to play important roles in promoting progression of ovarian high-grade serous carcinoma. Our aim was to investigate FGF18 expression in the whole spectrum of serous and mucinous ovarian tumors, highlighting differences in expression within the adenoma-carcinoma sequence and differences between type I and type II tumors. We also aimed to test the prognostic significance of this expression and its relation to microvessel density (MVD). We evaluated the immunohistochemical expression of FGF18 and CD31 in 103 ovarian tumors and statistically analyzed their association with clinicopathological variables and patients' outcome. FGF18 score increased significantly within the adenoma-carcinoma sequence for serous and mucinous tumors. MVD increased significantly only among serous tumors. FGF18 and MVD correlated significantly (overall and among serous tumors only) and were significantly higher in type II than type I tumors. Cox regression models were built. Independent predictors could not be determined due to multicollinearity between the predictors. However, the combination of International Federation of Gynecology and Obstetrics (FIGO) stage, ovarian carcinoma type, and/or FGF18 score achieved the highest predictability of poor prognosis. FGF18 could play a role within the adenoma-carcinoma sequence in type I tumors and might modulate angiogenesis among serous tumors. Our findings further augment the differences between type I and type II tumors. The combination of FIGO stage, ovarian carcinoma type, and/or FGF18 score could predict poor prognosis among ovarian carcinoma patients. Our work identifies FGF18 in ovarian neoplasia as a promising field of research, although evaluation of the performance of the developed models is still needed.

The use of medications plays a pivotal role in the management of children with heart diseases. Most children with increased pulmonary blood flow require chronic use of anticongestive heart failure medications until more definitive interventional or surgical procedures are performed. The use of such medications, particularly inotropic agents and diuretics, is even more amplified during the postoperative period. Currently, children are undergoing surgical intervention at an ever younger age with excellent results aided by advanced anesthetic and postoperative care. The most significant of these advanced measures includes invasive and noninvasive monitoring as well as a wide array of pharmacologic agents. This review update provides a medication guide for medical practitioners involved in care of children with heart diseases.

Myocardial performance index (MPI), or Tei index, has become a commonly used parameter for the noninvasive, Doppler-derived assessment of global systolic and diastolic performance of the heart in both adults and children. Normal values have been established in adults and children; however, limited data exist in fetal hearts. The aim of this study was to further elucidate normal values of fetal left (LV) and right ventricle (RV) MPI values in second- and third-trimester fetuses and compare these values with other previously published data. This was a retrospective study to measure MPI in healthy fetuses. After Institutional Review Board approval, 2000 fetal echocardiography studies (FES) were acquired during a period of 4 years. Demographic parameters examined included gestational age (GA), maternal age (MA), and indication for fetal echocardiography. Fetuses with congenital heart disease, arrhythmias, or significant noncardiac fetal anomalies were excluded. The following echocardiography parameters were collected: LV ejection time (LVET), mitral valve close-to-open time (MVCO), RVET, tricuspid valve CO (TVCO), and fetal heart rate. For simplicity, LV and RV MPI values were calculated as follows: LV MPI = MVCO - LVET/LVET and RV MPI = TVCO - RVET/RVET. Four hundred twenty FES met the study criteria. LV MPI was evaluated in 230 and 190 FES in the second and third trimester, respectively. Of the 420 FES, 250 (150 in the second trimester and 100 in the third trimester) had all of the measurements required for RV MPI calculation. MA ranged between 16 and 49 years. Indications for FES included diabetes mellitus (N = 140; 33 %), suspected fetal anomalies on routine obstetrical ultrasound (N = 80; 20 %), autoimmune disorder (N = 60; 14 %), family history of CHD (N = 76; 18 %), medication exposure (N = 22; 5 %), increase nuchal thickness (N = 13; 3 %), and other indications (N = 29; 6 %). Averaged LV and RV MPI values were 0.464 ± 0.08 and 0.466 ± 0.09, respectively. Further analysis based on gestational period showed slightly greater LV and RV MPI values during the third compared with the second trimester, i.e., 0.48 and 0.49, respectively, with no statistically significant difference. There was no significant association of LV and RV MPI with heart rate. To our knowledge, this is the first study to establish normal values of fetal MPI based on a large fetal population from a single tertiary center. LV and RV MPI values were independent of GA and fetal heart rate. MPI is a useful parameter for the assessment of global cardiac function in the fetus and demonstrates good reproducibility with narrow interobserver and intraobserver variability. Its usefulness should be studied in fetal hearts with complex congenital anomalies.

Introduction: Duodenal gastrointestinal stromal tumors (GISTs) are rare but still represent approximately 30 % of primary duodenal tumors. This study aimed to audit the feasibility and oncological outcomes of limited duodenal resection in patients with primary nonmetastatic duodenal GIST., Methods: Twelve patients who underwent surgery at our institution since 2002 were prospectively followed up. The duodenal GISTs were located in the first (n = 3), second (n = 1), third (n = 3), and fourth of duodenum (n = 1). Involving both D1/D2 (n = 2), D2/D3 (n = 1), and D3/D4 (n = 1). The primary endpoint for this analysis was disease-free survival., Results: The commonest presentation was melena and anemia (83 %). All the patients underwent limited resection; six wedge resections with primary closures and six segmental resections with end-to-end anastomosis. The median tumor size was 8 cm (range, 5-16 cm). According to Fletcher scale, two GISTs were low risk, while 10 patients were intermediate and high risk. The latter received adjuvant therapy. All the patients had a complete resection with no postoperative mortality. One patient had three liver metastases 4 months after limited resection and had partial hepatectomy. After median follow-up of 45 (15-78) months, all patients are alive and disease free., Conclusion(s): When technically feasible, limited resection should be considered a reliable and curative option for duodenal GIST achieving satisfactory disease-free survival. The technical feasibility is guided by the tumor size, possible adjacent organ involvement, and its exact anatomical location.

Angiogenesis and lymphangiogenesis are essential for breast cancer growth and progression. This study aimed at investigating lymphatic microvessel density (LVD) and microvessel density (MVD) as prognostic markers in breast carcinoma. Forty breast carcinomas were immunostained for D2-40, CD31 and VEGF. Median lymphatic and blood microvessel densities, as well as VEGF expression, were related to each other and to clinicopathologic parameters including lymph node (LN) status. The efficacy of haematoxylin and eosin (H&E) in detecting lymphatic vessel invasion (LVI) compared to D2-40 immunostaining was also investigated. D2-40 stained normal lymphatic endothelium and myoepithelial cells, but with different staining patterns. D2-40 LVD related significantly to CD31 counts (r=0.470; p=0.002), and LN metastasis (Mann-Whitney U=101.500; p=0.043); however, it did not relate to age, tumor grade, tumor size or LVI. D2-40 identified LVI in 3 more cases (7.5%) than those detected by H&E. VEGF was expressed in 85%of cases, and was significantly related to CD31 and D2-40 counts (p=0.033 and 0.007, respectively). In conclusion, D2-40 LVD showed a significant association with LN metastasis, and can be considered to segregate patients with positive from those with negative LNs. D2-40 enhances the detection of LVI relative to H&E staining reflecting a potential for lymphatic metastatic spread and possible poor prognosis.

Fenestrated atrial septal defects (F-ASDs) may pose a challenge to device closure; recently, a cribriform device with a minimal connecting intrawaist diameter and large, equal left- and right-sided discs has been designed to cover more than one adjacent defect. This study demonstrates the feasibility and technical aspects of closing F-ASDs using this new device. Sixteen patients between August 2003 and January 2006 were included in this study. The inclusion criterion was the presence of a F-ASD diagnosed by transesophageal echocardiography. One of the three available cribriform ASD device sizes (18, 25, or 35 mm) was implanted. Patients were followed for at least 1 year after the procedure. Thirteen patients had successful cribriform ASD device implantation (median age and weight, 12.5 years and 36 kg, respectively). Ten patients (62%) had an associated atrial septal aneurysm. The mean procedure time was 75.6 +/- 28.5 min and the mean fluoroscopy time 14.8 +/- 6.3 min. The RVEDD was significantly reduced, from a mean of 24.2 mm to 21.0 (p < 0.05). One patient developed atrial tachycardia requiring cardioversion during the procedure. There were no embolic events, heart block, or mortality. Complete closure was 10 of 13 (77 %) the next day and 12 of 13 (92%) at 6 and 12 months. We conclude that the cribriform Amplatzer device can be successfully and safely used in patients with F-ASDs. Complete closure may take up to 6 months.

Background: A variety of transcatheter atrial septal defect (ASD) occluders are currently in use, the most commonly used device is the Amplatzer Septal Occluder (ASO) yet there is no perfect device. The Helex Septal Occluder is a new device (by W.L. Gore & Associates, Inc.) designed to improve the results of transcatheter ASD closure. We report our first experience in closing secundum ASDs with this new device after its recent modifications., Methods: Thirteen patients were selected for Helex device closure with median age of 8 years (2.5-44 years) and median weight 30 Kg (12-96 Kg). Inclusion criteria were: small to moderate Secundum ASDs with sufficient rims by transthoracic echo (TTE) and confirmed by transoesophageal echo (TEE). Two cardiologists carried out the decision of device size. One of the five available Helex ASD device sizes was used (15-35 mm). Follow up TTE was performed the next day, one month, six months and one year later., Results: Twelve patients had successful Helex septal occluder implantation. One patient was switched to Cribriform ASD device during the procedure because of failure of the locking mechanism. Two patients had trivial residual left to right shunt which disappeared at one month follow up in one patient. No embolic event, AV block or mortality was observed., Conclusion: This feasibility study of the novel Helex septal occluder after its recent modification showed that it can successfully and safely close well selected secundum ASDs. There are several advantages over the currently available devices.

Atrial standstill is a rare form of bradyarrhythmia and consists of a transitory or permanent loss of the electrical and mechanical activity of the atria. It has been described in a few cases of long-standing valvular disease, amyloidosis, myocarditis, and muscular dystrophy. We report on a young female with noncompaction cardiomyopathy that progressed to congestive heart failure. Electrocardiogram showed persistence atrial standstill that was confirmed clinically and by electrocardiomyopathy, Doppler two-dimensional echocardiogram, and tissue Doppler imaging. We assume that worsening of asymptomatic noncompaction and progression to the congestive form of cardiomyopathy could be presaged by the presence of persistent atrial standstill. Thus, persistence of atrial standstill in asymptomatic cardiomyopathy is a sign of poor prognosis.