Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Prenatal Diagnosis and Outcome of Umbilical&ndash;Portal&ndash;Systemic Venous Shunts: Experience of a Tertiary Center and Proposal for a New Complex Type

Aims: To share our experience in the prenatal diagnosis of umbilical&ndash;portal&ndash;systemic venous shunts (UPSVS) and to study the prognostic factors for proper prenatal and perinatal management. Material and Methods: A five-year prospective study regarding the detection of UPSVS was conducted in two referral centers, Medgin Ginecho Clinic and the Prenatal Diagnostic Unit of the tertiary center, University Emergency County Hospital Craiova, Romania. We included in the analysis a series of agenesis of ductus venosus (ADV) cases previously reported by our center. We analyzed the incidence of the UPSVS types, their associations, and outcome predictors. Results: UPSVS were diagnosed in all 16 cases that were presented to our center at the time of first trimester anomaly scan, except one (94.12%). We diagnosed: 19 type I (61.2%), 4 type II (12.9%) and 5 type IIIa (16.1%) UPSVS. In three cases (9.6%) we noted multiple shunts, which we referred to as type IV (a new UPSVS type). Type IIIa-associated fetal growth restriction (FGR) was found in 60% of cases. Major anomalies worsened the outcome. Of the UPVSS cases, 57.1% were associated with PVS anomalies. Genetic anomalies were present in 40% of the tested cases. Conclusions: The incidence of UPSVS in our study was 0.2%. Early detection is feasible. The postnatal outcome mainly depends on the presence of structural, genetic and PVS anomalies. FGR may be associated. The new category presented a poor outcome secondary to poor hemodynamic and major associated anomalies

Prenatal Diagnosis and Prognosis of Abdominal Arteriovenous Fistulae: A Comprehensive Case Series and Systematic Review

This study had two main objectives. Firstly, we conducted a thorough literature review on the prenatal diagnosis of abdominal congenital arteriovenous fistulas (CAVFs) involving the abdominal aorta and hepatic arteries. Secondly, we aimed to provide detailed descriptions of eight additional cases diagnosed at our medical center and assess the outcome of this anomaly for informed counseling. We conducted a systematic search of online databases using specific keywords like “outcome”, “ultrasound”, “intrahepatic fistulae”, and “fetal venous anomalies”, focusing on studies published between 1998 and 2023. We selected 10 relevant articles and analyzed 13 cases. Additionally, we conducted a five-year prospective study in two referral centers, identifying eight CAVF cases with an incidence rate of 0.16%. Among the 21 cases evaluated, 11 resulted in live births, all of which received treatment. However, four cases (36.3%) had poor postnatal outcomes and neonatal demise due to heart failure. Prenatal signs of poor fetal hemodynamics, including cardiomegaly or hydrops, were observed in 52.3% of cases, regardless of outcome. Our findings highlight the rarity of this vascular malformation and emphasize the importance of effective treatment to avoid unfavorable outcomes. The long-term effectiveness of prenatal treatment or postnatal embolization remains uncertain, with liver transplantation being considered the most reliable treatment option

Intrauterine Transmission of Hepatitis C Virus Concomitant with Isolated Severe Fetal Ascites

Background: Perinatal Hepatitis C Virus (HCV) transmission occurs in 4&ndash;7% of the cases with detectable viremia at delivery. HCV testing in pregnancy is recommended. The fetal infection was previously described as asymptomatic although there are two cases, including this one, to report the presence of isolated fetal ascites in HCV infected fetuses. Case report: A 42-year-old patient, 3G, 3P, presented in the Emergency Room for painful uterine contraction. The third-trimester ultrasound examination noted severe fetal ascites, accompanied by hyperechoic bowels and polyhydramnios. The diagnosis required a detailed ultrasound exam, invasive testing (amniocentesis, cordocentesis, and fetal paracentesis), and a complete workup. The mother tested positive for HCV antibodies, and the fetal cord blood tested positive for HCV RNA. The ascites resolved after paracentesis, and the gastrointestinal and respiratory functions markedly improved. The fetus was delivered at term in good condition. Conclusions: The etiology of isolated fetal ascites is broad. This case may indicate that intrauterine HCV transmission is a potential cause of isolated fetal ascites in the absence of other explanation, and isolated fetal ascites can be the only sign revealed on a routine examination. We suspected, having no other detected cause for ascites, the intrauterine transmission of HCV. Invasive procedures, such as paracentesis, are required for abdominal decompression to manage isolated fetal ascites, as it may be a saving procedure. A genetic investigation is needed, and a good neonatal outcome is expected in the absence of fetal structural or genetic abnormalities, as in our case

Artificial Intelligence in Obstetric Anomaly Scan: Heart and Brain

Background: The ultrasound scan represents the first tool that obstetricians use in fetal evaluation, but sometimes, it can be limited by mobility or fetal position, excessive thickness of the maternal abdominal wall, or the presence of post-surgical scars on the maternal abdominal wall. Artificial intelligence (AI) has already been effectively used to measure biometric parameters, automatically recognize standard planes of fetal ultrasound evaluation, and for disease diagnosis, which helps conventional imaging methods. The usage of information, ultrasound scan images, and a machine learning program create an algorithm capable of assisting healthcare providers by reducing the workload, reducing the duration of the examination, and increasing the correct diagnosis capability. The recent remarkable expansion in the use of electronic medical records and diagnostic imaging coincides with the enormous success of machine learning algorithms in image identification tasks. Objectives: We aim to review the most relevant studies based on deep learning in ultrasound anomaly scan evaluation of the most complex fetal systems (heart and brain), which enclose the most frequent anomalies

The Influence of SARS-CoV-2 Pandemic in the Diagnosis and Treatment of Cervical Dysplasia

Background and objectives. The risk of developing invasive cancer increased during the COVID-19 pandemic, especially in Romania, where the incidence of this disease is high due to limited medical education and broad screening. This study’s objective is to analyze the number of patients admitted with different types of cervical dysplasia and the treatment applied for the lesions during the SARS-CoV-2 pandemic compared to the same period for the year before the pandemic. Materials and methods: This is a retrospective study that took place in the Obstetrics and Gynecology Clinics I/II (OG I/II) of the Emergency County Hospital of Craiova during the SARS-CoV-2 pandemic (SP) (15.03.2020–14.03.2021) and in the 12 months before (non-pandemic period) (NPP) (15.03.2019–14.03.2020). The study includes 396 patients with pathological PAP smear results. All the patients included in this study were clinically examined and with colposcopy. The patients with Low-Grade Dysplasia were managed in a conservatory manner and reevaluated after six months. The patients with High-Grade Dysplasia were admitted for an excisional biopsy of the lesion. The excised fragments were sent to the Pathological Anatomy Laboratory for a histopathological examination. Results: This study reveals a decrease of more than half in the number of patients admitted with cervical intraepithelial neoplasia (CIN) lesions during the pandemic compared to the same period of the year before. The number of biopsies and excisional procedures has been decreasing by more than a factor of three during the pandemic period compared to the year before. Conclusion: During the SARS-CoV-2 pandemic, we found that the patients’ admission rate, diagnosis, and treatment was almost four times lower. As hospital restrictions were not dictated for cancer/precancer management during SP, we may assume that the differences were due to the fear of becoming infected with SARS-CoV-2 due to hospitalization. In the context of poor screening performance and high cervical cancer incidence, the influence of the SP may result in a further increase of severe cases related to this condition

The Hepatic Fetal Venous System

The vascular architecture of the human liver is established at the end of the 10th week of gestation as a result of a complex process. Recent developments in ultrasonographic imaging facilitate the prenatal evaluation of this system. However, many of the involved mechanisms are poorly understood. The hepatic primordium is in contact with the vitelline veins and the umbilical veins, and by the end of the 6th week, the afferent venous system of the liver is acquired giving rise to the portal vein, the portal sinus, and the ductus venosus. The only afferent vein of the liver that remains open at birth is the portal vein. Also, the efferent venous system of the liver is formed and emerges from the vitelline veins

Specific Local Predictors That Reflect the Tropism of Endometriosis&mdash;A Multiple Immunohistochemistry Technique

Ectopic endometrial epithelium associates a wide spectrum of symptomatology. Their evolution can be influenced by inflammatory and vascular changes, that affect not only the structure and cell proliferation rate, but also symptoms. This prospective study involved tissue samples from surgically treated patients, stained using classical histotechniques and immunohistochemistry. We assessed ectopic endometrial glands (CK7+, CK20&minus;), adjacent blood vessels (CD34+), estrogen/progesterone hormone receptors (ER+, PR+), inflammatory cells (CD3+, CD20+, CD68+, Tryptase+), rate of inflammatory cells (Ki67+) and oncoproteins (BCL2+, PTEN+, p53+) involved in the development of endometriosis/adenomyosis. A CK7+/CK20&minus; expression profile was present in the ectopic epithelium and differentiated it from digestive metastases. ER+/PR+ were present in all cases analyzed. We found an increased vascularity (CD34+) in the areas with abdominal endometriosis and CD3+&minus;:T-lymphocytes, CD20+&minus;:B-lymphocytes, CD68+:macrophages, and Tryptase+: mastocytes were abundant, especially in cases with adenomyosis as a marker of proinflammatory microenvironment. In addition, we found a significantly higher division index-(Ki67+) in the areas with adenomyosis, and inactivation of tumor suppressor genes-p53+ in areas with neoplastic changes. The inflammatory/vascular/hormonal mechanisms trigger endometriosis progression and neoplastic changes increasing local pain. Furthermore, they may represent future therapeutic targets. Simultaneous-multiple immunohistochemical labelling represents a valuable technique for rapidly detecting cellular features that facilitate comparative analysis of the studied predictors

Ductus Venosus Agenesis and Portal System Anomalies&mdash;Association and Outcome

To evaluate the prenatal diagnosis of agenesis of ductus venosus (ADV) and portal venous system (PVS) anomalies and describe the outcome of these cases, either isolated or associated. We evaluated the intrahepatic vascular system regarding the presence of normal umbilical drainage and PVS characteristics in the second and third trimester of pregnancy. The associated anomalies and umbilical venous drainage were noted. Follow-up was performed at six months follow-up. Ultrasonography was performed in 3517 cases. A total of 19 cases were prenatally diagnosed: 18 ADV cases, seven abnormal PVS cases, and six associations of the two anomalies. We noted an incidence of 5.1&permil; and 1.9&permil; for ADV and PVS anomalies, respectively. Out of the 18 ADV cases, 27.7% were isolated. Five cases (26.3%) presented genetic anomalies. PVS anomalies were found in 33.3% of the ADV cases. ADV was present in 85.7% of the PVS anomalies. DV and PVS abnormalities were found with a higher than reported frequency. Normal DV is involved in the normal development of the PVS. Additional fetal anomalies are the best predictor for the outcome of ADV cases. Evaluation of PVS represents a powerful predictor for ADV cases and addresses the long-term prognosis

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin