Standard Of Care For Treatment Research Articles

Efficacy and Safety of Huashi Baidu Granules in Treating Patients with SARS-CoV-2 Omicron Variant: A Single-Center Retrospective Cohort Study.

To evaluate the efficacy and safety of Huashi Baidu Granules (HSBD) in treating patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd, 2022. All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group (HSBD users) and the control group (non-HSBD users). After propensity score matching in a 1:1 ratio, 496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users. Patients in the treatment group were administrated HSBD (5 g/bag) orally for 1 bag twice a day for 7 consecutive days. Patients in the control group received standard care and routine treatment. The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7. Secondary outcomes included the hospitalized days, the time of the first nucleic acid negative conversion, and new-onset symptoms in asymptomatic patients. Adverse events (AEs) that occurred during the study were recorded. Further subgroup analysis was conducted in vaccinated (378 HSBD users and 390 non-HSBD users) and unvaccinated patients (118 HSBD users and 106 non-HSBD users). The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7 (91.73% vs. 86.90%, P=0.014). Compared with the control group, the hospitalized days in the treatment group were significantly reduced [10 days (IQR: 8-11 days) vs. 11 days (IQR: 10.25-12 days); P<0.01]. The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups [3 days (IQR: 2-4 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The incidence of new-onset symptoms including cough, pharyngalgia, expectoration and fever in the treatment group were lower than the control group (P<0.05 or P<0.01). In the vaccinated patients, the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days), P<0.01; 10 days (IQR: 8-11 days) vs. 11 days (IQR: 10-12 days), P<0.01]. In the unvaccinated patients, HSBD treatment efficiently shorten the median negative conversion time and hospitalized days [4 days (IQR: 2-6 days) vs. 5 days (IQR: 4-7 days), P<0.01; 10.5 days (IQR: 8.75-11 days) vs. 11.0 days (IQR: 10.75-13 days); P<0.01]. No serious AEs were reported during the study. HSBD treatment significantly shortened the negative conversion time of nuclear acid, the length of hospitalization, and the time of the first nucleic acid negative conversion in patients infected with SARS-COV-2 Omicron variant (Trial registry No. ChiCTR2200060472).

Enfortumab Vedotin in Metastatic Urothelial Carcinoma: Survival and Safety in a European Multicenter Real-world Patient Cohort

BackgroundTreatment options for patients with urothelial cancer (UC) refractory to platinum and immunotherapy are limited and survival is short. Enfortumab vedotin (EV) is a monoclonal anti-NECTIN4 antibody conjugated to monomethyl auristatin. It was recently approved because of superior survival in comparison to standard-of-care (SOC) chemotherapy. Real-world patients, however, often have worse characteristics than patients included in clinical trials. ObjectiveTo analyze the efficacy and safety of EV in a cohort of real-world patients. Design, setting, and participantsRetrospective data were collected from 23 hospitals and private practices for patients with metastatic and previously treated UC who received EV either when reimbursed by their insurance company before European Medicines Agency (EMA) approval, within a compassionate use program, or as SOC treatment after EMA approval. Imaging and therapy management were in accordance with local standards. Outcome measurements and statistical analysisAdverse events (AEs) were reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Objective responses were evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results and limitationsThe median age for the 125 eligible patients was 66 yr (range 31–89). The Eastern Cooperative Oncology Group performance status (ECOG PS) was 0–1 for 76.0%, 2–4 for 13.6%, and unknown for 10.4% of patients. EV was administered in the fourth or later line for 44.8% of patients. The overall response rate was 41.6% (partial response 39.2%, complete response 2.4%). Median OS was 10.0 months (mo) (95% confidence interval 7.20–12.80) and median PFS was 5.0 mo (95% confidence interval 4.34–5.67). For patients with ECOG PS of 0–1, median OS was 14 mo. Any-grade AEs were observed in 67.2% and CTCAE grade ≥3 AEs in 30.4%. The most common AEs were peripheral sensory neuropathy and skin toxicity. Three fatal events (pneumonia, pneumonitis) occurred. Limitations include the retrospective design and short follow-up. ConclusionsAdministration of EV for real-world patients was feasible with an acceptable toxicity profile. No new safety signals were reported. Antitumor activity in our cohort was comparable to data previously reported for trials. In summary, our results support the use of EV in patients with metastatic UC. Patient summaryEnfortumab vedotin is a medication that improved the survival of patients with bladder cancer in comparison to standard chemotherapy in clinical trials. However, patients included in clinical trials are highly selected and results for toxicities and improvements in survival do not always transfer to the real-world setting. We analyzed data for 125 patients who were treated with enfortumab vedotin. Our results are comparable to the outcomes from clinical trials regarding the safety and efficacy of this treatment.

Intensive chemotherapy with or without gemtuzumab ozogamicin in patients with NPM1-mutated acute myeloid leukaemia (AMLSG 09–09): a randomised, open-label, multicentre, phase 3 trial

Acute myeloid leukaemia with mutated NPM1 is associated with high CD33 expression and intermediate-risk cytogenetics. The aim of this study was to evaluate intensive chemotherapy with or without the anti-CD33 antibody-drug conjugate gemtuzumab ozogamicin in participants with newly diagnosed, NPM1-mutated acute myeloid leukaemia. This open-label, phase 3 trial was conducted at 56 hospitals in Germany and Austria. Eligible participants were 18 years or older and had newly diagnosed NPM1-mutated acute myeloid leukaemia and an Eastern Cooperative Oncology Group performance status of 0-2. Participants were randomly assigned, using age as a stratification factor (18-60 years vs >60 years), 1:1 to the two treatment groups using allocation concealment; there was no masking of participants and investigators to treatment groups. Participants received two cycles of induction therapy (idarubicin, cytarabine, and etoposide) plus all-trans retinoic acid (ATRA) followed by three consolidation cycles of high-dose cytarabine (or an intermediate dose for those older than 60 years) and ATRA, without or with gemtuzumab ozogamicin (3 mg/m2 administered intravenously on day 1 of induction cycles 1 and 2, and consolidation cycle 1). The primary endpoints were short-term event-free survival and overall survival in the intention-to-treat population (overall survival was added as a co-primary endpoint after amendment four of the protocol on Oct 13, 2013). The secondary endpoints were event-free survival with long-term follow-up, rates of complete remission, complete remission with partial haematological recovery (CRh), and complete remission with incomplete haematological recovery (CRi), cumulative incidences of relapse and death, and number of days in hospital. This trial is registered with ClinicalTrials.gov (NCT00893399) and has been completed. Between May 12, 2010, and Sept 1, 2017, 600 participants were enrolled, of which 588 (315 women and 273 men) were randomly assigned (296 to the standard group and 292 to the gemtuzumab ozogamicin group). No difference was found in short-term event-free survival (short-term event-free survival at 6-month follow-up, 53% [95% CI 47-59] in the standard group and 58% [53-64] in the gemtuzumab ozogamicin group; hazard ratio [HR] 0·83; 95% CI 0·65-1·04; p=0·10) and overall survival between treatment groups (2-year overall survival, 69% [63-74] in the standard group and 73% [68-78] in the gemtuzumab ozogamicin group; 0·90; 0·70-1·16; p=0·43). There was no difference in complete remission or CRi rates (n=267 [90%] in the standard group vs n=251 [86%] in the gemtuzumab ozogamicin group; odds ratio [OR] 0·67; 95% CI 0·40-1·11; p=0·15) and complete remission or CRh rates (n=214 [72%] vs n=195 [67%]; OR 0·77; 0·54-1·10; p=0·18), whereas the complete remission rate was lower with gemtuzumab ozogamicin (n=172 [58%] vs n=136 [47%]; OR 0·63; 0·45-0·80; p=0·0068). Cumulative incidence of relapse was significantly reduced by gemtuzumab ozogamicin (2-year cumulative incidence of relapse, 37% [95% CI 31-43] in the standard group and 25% [20-30] in the gemtuzumab ozogamicin group; cause-specific HR 0·65; 0·49-0·86; p=0·0028), and there was no difference in the cumulative incidence of death (2-year cumulative incidence of death 6% [4-10] in the standard group and 7% [5-11] in the gemtuzumab ozogamicin group; HR 1·03; 0·59-1·81; p=0·91). There were no differences in the number of days in hospital across all cycles between treatment groups. The most common treatment-related grade 3-4 adverse events were febrile neutropenia (n=135 [47%] in the gemtuzumab ozogamicin group vs n=122 [41%] in the standard group), thrombocytopenia (n=261 [90%] vs n=265 [90%]), pneumonia (n=71 [25%] vs n=64 [22%]), sepsis (n=85 [29%] vs n=73 [25%]). Treatment-related deaths were documented in 25 participants (4%; n=8 [3%] in the standard group and n=17 [6%] in the gemtuzumab ozogamicin group), mostly due to sepsis and infections. The primary endpoints of the trial of event-free survival and overall survival were not met. However, an anti-leukaemic efficacy of gemtuzumab ozogamicin in participants with NPM1-mutated acute myeloid leukaemia is shown by a significantly lower cumulative incidence of relapse rate, suggesting that the addition of gemtuzumab ozogamicin might reduce the need for salvage therapy in these participants. The results from this study provide further evidence that gemtuzumab ozogamicin should be added in the standard of care treatment in adults with NPM1-mutated acute myeloid leukaemia. Pfizer and Amgen.

Sustained Biweekly Aflibercept For Refractory Neovascular Age-Related Macular Degeneration: The Prospective TRISTAR Study.

To assess the safety and efficacy of biweekly (every 2 week) intravitreal aflibercept injections (IAI) 2 mg in eyes with refractory neovascular age-related macular degeneration (NVAMD). A prospective, single-arm, interventional study was conducted. Eyes with refractory NVAMD received six biweekly IAIs through week 12, followed by a 4-week treatment pause until week 16. Eyes with residual SRF at week 16 were randomized 1:1 to either four additional biweekly IAIs or to 4-week (q4W) IAI dosing through week 24. All eyes were subsequently treated q4W through week 52. Enrolled eyes (n=22) had persistent SRF despite a mean of 11.8 injections over the prior 12 months. One patient developed endophthalmitis at week 12. There were no additional drug/procedure-related adverse events. BCVA improved significantly from baseline to week 14 (2.52 letters, p<0.001). Mean CST was also significantly improved at week 14 (-31.9µm, p<0.001) with 8 of 22 eyes achieving complete SRF resolution. Only 2 of 8 eyes remained free of SRF at week 16, with a corresponding increase in mean CST of 26.7µm compared with week 14. By week 52, improvements in BCVA and CST were lost. In patients with refractory NVAMD-related SRF, sustained biweekly IAIs resulted in significant functional and anatomic improvements during biweekly dosing. These gains, however, were lost upon return to monthly dosing. These findings suggest that efforts to reduce refractory SRF in NVAMD with biweekly dosing may provide added benefit compared with standard of care treatment if biweekly dosing is sustained.

Abstract 242: A Novel Strategy To Combat The Procoagulant Phenotype In Immune Thrombotic Thrombocytopenia Using 12-LOX Inhibition

The risk of stroke or other thrombotic complications following vaccination of SARS-CoV-2 has been extensively reported since widespread vaccination efforts began in early 2021. This disorder, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), has remarkable overlap in clinical manifestations to that of heparin-induced thrombocytopenia (HIT). HIT and VITT are pathologies caused by IgG immune complexes that activate platelets via Fc Receptor for IgG IIA (FcγRIIA), which are collectively categorized as immune thrombotic thrombocytopenia (ITT) disorders. Thrombotic events remain high following the standard of care treatment with concurrent risk of bleeding complications. This study sought to investigate a novel approach to treatment of ITT. Recent reports demonstrate increased procoagulant activity in ITT. However, these reports required ex vivo analysis, and in vivo relevance remains unclear. Using human and mouse model systems, we investigated the cooperativity of protease activated receptors (PARs) and FcγRIIA in ITT. We challenged humanized FcγRIIA transgenic mice with or without endogenous mouse Par4 (denoted as IIA-Par4 +/+ or IIA-Par4 -/- , respectively) with a well-established model IgG immune complex (αCD9). IIA-Par4 +/+ mice given αCD9 were severely thrombocytopenic, with extensive platelet-fibrin deposition in the lung. In contrast, IIA-Par4 -/- mice had negligible thrombocytopenia or pulmonary platelet-fibrin thrombi. These data demonstrate for the first time the need for dual platelet receptor (PAR and FcγRIIA) stimulation for fibrin formation in ITT in vivo . In human platelets, we observed that PAR1, PAR4, and FcγRIIA each contributed to the procoagulant phenotype, via receptor-specific increases in cytosolic Ca 2+ . As inhibition of 12(S)-lipoxygenase has been reported to decrease platelet activation downstream of FcγRIIA and PAR4, we used inhibitor VLX-1005 and observed significant reduction in both platelet procoagulant phenotype ex vivo , and thrombocytopenia and thrombosis in our humanized mouse model of HIT in vivo . These results extend our understanding of ITT pathophysiology and provide a scientific rationale for targeting the procoagulant phenotype as a possible therapeutic strategy in ITT.

Medical therapy for refractory pituitary adenomas.

Refractory pituitary adenomas are those that have progressed following standard of care treatments. Medical therapy options for these challenging tumors are limited. To review the landscape of tumor directed medical therapies and off-label investigational approaches for refractory pituitary adenomas. Literature on medical therapies for refractory adenomas was reviewed. The established first-line medical therapy for refractory adenomas is temozolomide, which importantly may increase survival, but clinical trial data are still needed to clearly establish its efficacy, identify biomarkers of response, and clarify eligibility and outcome criteria. Other therapies for refractory tumors have only been described in case reports and small case series. There are currently no approved non-endocrine medical therapies for refractory pituitary tumors. There is an urgent need for identifying effective medical therapies and studying them in multi-center clinical trials.

Direct oral anticoagulant (DOACs) prescribing practices of members of the Society of Gynecologic Oncology and American Society of Clinical Oncology

BackgroundCancer associated venous thromboembolism (VTE) is associated with significant morbidity and mortality. Direct oral anticoagulants (DOACs) have emerged as alternatives to injectable medications for both thromboprophylaxis and treatment of VTE. Several recent clinical trials have demonstrated safety and efficacy of DOACs in high risk patients receiving systemic chemotherapy as well as postoperative prophylaxis after surgery for gynecologic cancer. Major consensus guidelines from multiple organizations support the use of DOACs for these indications but prescription practices are not well characterized. MethodsA survey study was sent concurrently to members of the Society of Gynecologic Oncology (SGO) and American Society of Clinical Oncology (ASCO) Research Survey Pool between May and June of 2021. The study was designed to assess DOAC prescription practices amongst members of these societies who routinely prescribe chemotherapy. Bivariate analyses comparing responses from ASCO participants and SGO participants were compared using chi-squared and Fisher exact tests. ResultsA total of 103 physicians were included in the ASCO group and 139 in the SGO group. A majority of participants in both groups reported familiarity with prescribing DOACs (99% of ASCO and 96% of SGO respondents). ASCO respondents were more likely to consider DOACs as first line therapy for treatment of cancer-associated VTE than SGO members (82% vs 63%, p < 0.01) and SGO members were more likely to consider low molecular weight heparin (LMWH) the standard of care treatment (66% vs 25% p < 0.01). Most respondents in both groups (75%) felt DOACs were equally safe and effective compared to LMWH but more ASCO members felt DOACs were cost effective (70% vs 49%, p < 0.01). More SGO respondents reported having prescribed prophylactic anticoagulation during chemotherapy than ASCO members (53% vs 35%, p < 0.01). ConclusionASCO respondents were more likely to prescribe DOACs for both treatment and prophylaxis of cancer-associated VTE than SGO members. However, SGO members were more likely to prescribe prophylactic anticoagulation to high risk patients initiating chemotherapy compared to ASCO members.

Prognostic Markers in Glioblastoma Patients Treated with Temozolomide (P13-13.002)

<h3>Objective:</h3> To identify biomarkers that are able to predict favorable outcomes for patients with glioblastoma treated with temozolomide (TMZ) <h3>Background:</h3> Glioblastoma is the most aggressive primary brain tumor. The standard of care treatment is maximum safe resection, radiation plus oral temozolomide (TMZ) chemotherapy, followed by six months of cyclic oral TMZ. Treatment-related side effects are common while the 5-year overall survival is less than 10%. Previous studies have reported that TMZ-induced myelosuppression is associated with improved overall survival. <h3>Design/Methods:</h3> Adults with histology-confirmed glioblastoma treated at Beth Israel Deaconess Medical Center from (2017–2018) who had completed both radiation therapy and temozolomide for at least 6 months were identified. Lab values (WBC, ANC, ALC, RBC, PLT), molecular markers (IDH1 R132H, MGMT promoter methylation ), progression free survival (PFS), overall survival (OS) will be collected retrospectively. This data will be combined with published data of 86 cases [Vaios et al.]. <h3>Results:</h3> 60 new patients with glioblastoma were identified and data collected. 32 were included in this study and their data combined with previous data collected from 2012–2017 for a total of 173 patients. Preliminary results according to Kaplan-Meier analysis with a log-rank test confirms that leukopenia is associated with increased survival (p=0.008) and progression free status (p=0.02). <h3>Conclusions:</h3> Decreased white blood cell counts may serve as a peripheral blood biomarker for OS and PFS in glioblastoma patients treated with radiation therapy and TMZ. It is possible that leukopenia reflects adequate temozolomide dosing and anti-tumor activity or reflects changes in the tumor micro-environment. Standardized approaches to peripheral blood monitoring in glioblastoma patients undergoing chemotherapy is likely to improve prognostic stratification and overall survival. <b>Disclosure:</b> Dr. McMillan has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. McGuinness has nothing to disclose. Dr. Trudeau has nothing to disclose. Dr. Uhlmann has nothing to disclose.

Safety, tolerability, and clinical and neural effects of single-dose psilocybin in obsessive-compulsive disorder: protocol for a randomized, double-blind, placebo-controlled, non-crossover trial.

Psilocybin may help treat obsessive-compulsive disorder (OCD). To date, only one open-label study of psilocybin for OCD exists, necessitating further investigation with a randomized controlled design. The neural correlates of psilocybin's effects on OCD have also not been studied. This first-of-its-kind trial aims to evaluate the feasibility, safety, and tolerability of psilocybin in the treatment of OCD, provide preliminary evidence on the effects of psilocybin on OCD symptoms, and elucidate neural mechanisms that may mediate psilocybin's effects on OCD. We use a randomized (1:1), double-blind, placebo-controlled, non-crossover design to examine the clinical and neural effects of either a single dose of oral psilocybin (0.25 mg/kg) or active placebo-control agent (250 mg of niacin) on OCD symptoms. We are enrolling 30 adult participants at a single site in Connecticut, USA who have failed at least one trial of standard care treatment (medication/psychotherapy) for OCD. All participants will also receive unstructured, non-directive psychological support during visits. Aside from safety, primary outcomes include OCD symptoms over the past 24 h, assessed by the Acute Yale-Brown Obsessive-Compulsive Scale and Visual Analog Scale ratings. These are collected by blinded, independent raters at baseline and the primary endpoint of 48 h post-dosing. Total follow-up is 12 weeks post-dosing. Resting state neuroimaging data will be collected at baseline and primary endpoint. Participants randomized to placebo will be offered the chance to return for an open-label dose of 0.25 mg/kg. All participants will be required to provide written informed consent. The trial (protocol v. 5.2) was approved by the institutional review board (HIC #2000020355) and registered with ClinicalTrials.gov (NCT03356483). This study may represent an advance in our ability to treat refractory OCD, and pave the way for future studies of neurobiological mechanisms of OCD that may respond to psilocybin.

Intravenous magnesium as an adjunct to standard of care for treatment of atrial fibrillation with rapid ventricular response.

Academic Emergency MedicineAccepted Articles THE BRASS TACKS: CONCISE REVIEWS OF PUBLISHED EVIDENCE “Intravenous Magnesium As An Adjunct To Standard Of Care For Treatment Of Atrial Fibrillation With Rapid Ventricular Response” Pierre-Carole Tchouapi MD, Pierre-Carole Tchouapi MD New YorkSearch for more papers by this authorKevin E. Anderson, Kevin E. Anderson New YorkSearch for more papers by this authorPaul Narayan Hein MD, Corresponding Author Paul Narayan Hein MD [email protected] orcid.org/0000-0001-5016-5338 New York Correspondence Paul Narayan Hein, MD, Department of Emergency Medicine, SUNY Downstate Medical Center, 450 Clarkson Ave, Brooklyn, New York 11203. Email: [email protected], Tel: (858) 337-1747Search for more papers by this author Pierre-Carole Tchouapi MD, Pierre-Carole Tchouapi MD New YorkSearch for more papers by this authorKevin E. Anderson, Kevin E. Anderson New YorkSearch for more papers by this authorPaul Narayan Hein MD, Corresponding Author Paul Narayan Hein MD [email protected] orcid.org/0000-0001-5016-5338 New York Correspondence Paul Narayan Hein, MD, Department of Emergency Medicine, SUNY Downstate Medical Center, 450 Clarkson Ave, Brooklyn, New York 11203. Email: [email protected], Tel: (858) 337-1747Search for more papers by this author First published: 06 April 2023 https://doi.org/10.1111/acem.14734 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/acem.14734. AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future. RelatedInformation

Use of anti-viral therapies in hospitalised COVID-19 patients in the United Arab Emirates: a cost-effectiveness and health-care resource use analysis

BackgroundThis study attempts to estimate the cost-effectiveness of the antiviral remdesivir, as recommended in the 2021 COVID treatment guidelines for the United Arab Emirates, compared to standard of care (SOC), but also favipiravir (FAVI), which was also recommended for the treatment of hospitalized COVID patients.MethodsA cost-effectiveness model was built using published efficacy data for RDV, FAVI and SOC as well as local epidemiology data. The outcomes measured included hospital bed days averted, mortality, costs and cost per outcome over one year. One-way, probabilistic and scenario analyses were undertaken to reflect uncertainty in the estimates.ResultsWhen modelled over one year, the results indicated that treatment of adults in need of supplemental oxygen with RDV + SOC could result in 11,338 fewer general ward bed days, 7,003 fewer ICU days and 5,451 fewer ICU + MIV bed days compared to SOC alone and similar results when compared with FAVI + SOC. The model results also showed that there were 374 fewer deaths associated with the use of RDV + SOC compared to SOC alone. The model also estimates substantial potential cost-savings associated with RDV + SOC treatment compared with SOC alone (USD 3,454 per patient). The results of the one-way sensitivity analysis showed that the model was sensitive to estimates of length of stay and the cost of hospitalization. Despite this, the model predicted cost-savings in all scenarios versus all comparators.ConclusionsThe model estimated that using RDV + SOC could result in substantial reductions in HCRU and cost savings regardless of the comparator. However, it should be noted that reliable clinical information on FAVI was limited therefore it is challenging to interpret these results. All the potential benefits modelled here for RDV + SOC can have implications not only for the health of the UAE population but for improving hospital capacity to deal with other conditions.

Critical Approach to Hypothyroid Patients With Persistent Symptoms.

Hypothyroidism is a common condition, and numerous studies have been published over the last decade to assess the potential risks associated with this disorder when inappropriately treated. The standard of care for treatment of hypothyroidism remains levothyroxine (LT4) at doses to achieve biochemical and clinical euthyroidism. However, about 15% of hypothyroid patients experience residual hypothyroid symptoms. Some population-based studies and international population-based surveys have confirmed dissatisfaction with LT4 treatment in some hypothyroid patients. It is well established that hypothyroid patients treated with LT4 exhibit higher serum thyroxine:triiodothyronine ratios and can have a persistent increase in cardiovascular risk factors. Moreover, variants in deiodinases and thyroid hormone transporter genes have been associated with subnormal T3 concentrations, persistent symptoms in LT4-treated patients, and improvement in response to the addition of liothyronine to LT4 therapy. The American (ATA) and European Thyroid Association (ETA) guidelines have recently evolved in their recognition of the potential limitations of LT4. This shift is reflected in prescribing patterns: Physicians' use of combination therapy is prevalent and possibly increasing. Randomized clinical trials have recently been published and, while they have found no improvement in treating hypothyroid patients, a number of important limitations did not allow generalizability. Meta-analyses have reported a preference rate for combination therapy in 46.2% hypothyroid patients treated with LT4. To promote discussions about an optimal study design, the ATA, ETA, and British Thyroid Association have recently published a consensus document. Our study provides a useful counterpoint on the controversial benefits of treating hypothyroid patients with combination therapy.

Abstract CT234: A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors

Abstract Background: Despite recent therapeutic developments for patients with advanced, metastatic, unresectable HER2+ solid tumors, significant unmet medical needs still exist, especially in tumors other than breast and gastric. The T cell antigen coupler (TAC) technology is a novel approach to modifying T cells, allowing them to recognize and treat HER2+ solid tumors. The TAC receptor redirects T cells to tumor cells, and upon tumor cell recognition, co-opts the natural T cell receptor (TCR) to yield safer anti-tumor responses versus chimeric antigen receptor (CAR) T cells. In preclinical studies, TAC T cells led to complete tumor clearance in mouse models of human cancer, without any TAC-related toxicities. In the ongoing clinical trial (NCT04727151), TAC01-HER2 treatment of HER2+ solid tumors is hypothesized to result in safe and effective anti-tumor responses. Subjects undergo leukapheresis, bridging therapy (if needed) while their TAC01-HER2 are engineered, lymphodepletion chemotherapy (LDC), and finally TAC01-HER2 infusion. Trial Design and Early Results: In phase I dose escalation, the primary objective is to evaluate the safety of TAC01-HER2 at increasing doses of 0.3, 0.8, 3, and 8 × 106 cells/kg in HER2+ solid tumors (1+, 2+ or 3+ as identified by immunohistochemistry) in adult subjects who have progressed after ≥2 lines of systemic therapy. Dose limiting toxicities (DLTs) are assessed up to 28 days from cell infusion. In Phase II, dose expansion groups will further evaluate the safety, efficacy, and pharmacokinetics of the optimal TAC01-HER2 dose in HER2+ breast and other solid tumor types. As of 12 Dec 2022, 12 patients have been treated in Cohorts 1-4 with breast, colorectal, gall bladder, gastro-esophageal junction, gastric and ovarian tumors. No DLTs or neurotoxicity events have been reported. All patients treated so far at Cohorts 3 and 4 (3 × 106 and 8 × 106 cells/kg, respectively) experienced Grade ≤2 CRS which were resolved with standard of care treatments. Eight subjects have reported a total of 15 serious adverse events, all unrelated to TAC01-HER2 except for a Grade 1 and a Grade 2 CRS, both resolved with standard of care. Most adverse events were related to LDC or the underlying neoplasm. At Cohort 2, a partial response was observed in a subject with refractory metastatic gastric adenocarcinoma (3+ HER2) at 1st scan, with a 36.5% reduction in measurable disease and clinical benefit was maintained for 6 months. A 71% disease control rate was observed at Cohorts 2 and 3 at 1st scan (0.8 × 106 and 3 × 106 cells/kg, respectively)). Dose escalation of TAC01-HER2 is ongoing, with the first subject treated at Cohort 4. These results in a heavily pre-treated cancer population show manageable safety and promising clinical activity with a novel T cell therapy that may have broad clinical applicability in HER+ cancers. Citation Format: Ecaterina Elena Dumbrava, Daniel Olson, Samuel Saibil, Brooke Pieke, Mridula A. George, Riemke Bouvier, Miriam Gavriliuc, Kelly Gruber, Kara Moss, Nathan Ternus, Maria Apostolopoulou, Deyaa Adib, Benjamin L. Schlechter. A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT234.

Transarticular Versus Retroarticular Drilling of Stable Osteochondritis Dissecans of the Knee: A Prospective Multicenter Randomized Controlled Trial by the ROCK Group

Background: When stable osteochondritis dissecans (OCD) lesions of the femoral condyle in a skeletally immature patient fail to heal with nonoperative methods, the standard of care treatment is condylar OCD drilling. Two primary OCD drilling techniques have been described, but no prospective studies have compared their relative effectiveness. Purpose/Hypothesis: The purpose of this study was to compare the healing and function after transarticular drilling (TAD) with that after retroarticular drilling (RAD). It was hypothesized that there would be no difference in rate or time to healing, rate or time to return to sports, patient-reported outcomes (PROs), or secondary OCD-related surgery. Study Design: Randomized controlled clinical trial; Level of evidence, 1. Methods: Skeletally immature patients with magnetic resonance imaging–confirmed stable OCD lesions of the medial femoral condyle who did not demonstrate substantial healing after a minimum of 3 months of nonoperative treatment were prospectively enrolled by 1 of 17 surgeon-investigators at 1 of 14 centers. Patients were randomized to the TAD or RAD group. Tourniquet time, fluoroscopy time, and complications were compared between the treatment groups. Postoperatively, serial radiographs were obtained every 6 weeks to assess healing, and PROs were obtained at 6 months, 12 months, and 24 months. Results: A total of 91 patients were included, consisting of 51 patients in the TAD and 40 patients in the RAD group, who were similar in age, sex distribution, and 2-year PRO response rate. Tourniquet time and fluoroscopy time were significantly shorter with TAD (mean, 38.1 minutes and 0.85 minutes, respectively) than RAD (mean, 48.2 minutes and 1.34 minutes respectively) (P = .02; P = .004). In the RAD group, chondral injury from K-wire passage into the intra-articular space was reported in 9 of 40 (22%) patients, but no associated postoperative clinical sequelae were identified in these patients. No significant differences between groups were detected in follow-up Pediatric–International Knee Documentation Committee, Lysholm, Marx Activity Scale, or Knee injury and Osteoarthritis Outcome Score Quality of Life scores. Healing parameters were superior at 6 months and 12 months in the TAD group, compared with the RAD group, and secondary OCD surgery occurred in 4% of patients who underwent TAD and 10% of patients who underwent RAD (P = .40). Patients in the TAD group returned to sports earlier than those in the RAD group (P = .049). Conclusion: TAD showed shorter operative time and fluoroscopy time and superior healing parameters at 6 and 12 months, but no differences were seen in 24-month healing parameters or PROs at all follow-up time points, when compared with RAD. Registration: NCT01754298 (ClinicalTrials.gov identifier).

Abstract 4499: The peptide-drug conjugate sudocetaxel zendusortide (TH1902) potentiates anti-tumoral activity of the anti-PD-L1 checkpoint inhibitor and induces immune cell infiltration in a B16-F10 syngeneic melanoma model

Abstract Tumor-infiltrating immune cells are involved in the control of cancer and are closely related to clinical outcomes. Sudocetaxel Zendusortide (TH1902), a peptide-drug conjugate (PDC) of the sortilin (SORT1)-binding peptide TH19P01 ester-linked to two docetaxel moieties, has been shown to exert superior anti-cancer activities in multiple cancer models including melanoma syngeneic and xenograft murine models. Melanomas express elevated levels of SORT1 and are considered as one of the most immunogenic tumors where immune checkpoint inhibitors are among the standard of care treatment used. Here, we first questioned whether TH1902 anti-cancer effects involved infiltration of immune cells in a murine SORT1-positive syngeneic, non-immunogenic and highly aggressive B16-F10 melanoma model in C57BL/6 mice. Weekly administration of docetaxel reduced by half the growth of B16-F10 tumor allografts, while administration of TH1902 as a single agent and at equivalent docetaxel doses, was well tolerated and resulted in tumor regression after only 2 treatments. Surprisingly, in this immunologically cold tumor, immunohistochemistry analysis of tumors for immune cell infiltration showed a net increase in total leukocytes (CD45+) infiltration within TH1902-treated tumors compared with docetaxel-treated tumors, especially with for tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). Furthermore, the increased staining intensities for Perforin and Granzyme B were indicative of the elevated cytotoxic T and natural killer (NK) cells activity in TH1902-treated tumors. This corroborated with increased caspase-3 apoptotic activity. TH1902 and docetaxel doses were next halved and combined with the checkpoint inhibitor anti-PD-L1. In a first study, the TH1902/anti-PD-L1 combination resulted in increased tumor growth inhibition when compared with both agents alone. Interestingly, TH1902 as a single agent showed better tumor growth inhibition than docetaxel or docetaxel/anti-PD-L1 combination. In a second study, the TH1902/anti-PD-L1 combination significantly increased animal survival over either anti-PD-L1 or TH1902 as single agents (21 days increased median survival compared to 2.5 and 12.5 days respectively). We conclude that the superiority of TH1902 anticancer activity over docetaxel involves, in part, the modulation of infiltrating immune cells within the tumor microenvironment. This is the first demonstration that immune cell infiltration patterns play a pivotal role in the TH1902-associated anti-tumoral response. Combination of TH1902 with checkpoint inhibitors (anti-PD-L1) further reveals that this may lead to improved clinical outcomes in future immunotherapy translational approaches. Citation Format: Michel Demeule, Jean-Christophe Currie, Cyndia Charfi, Alain Zgheib, Isabelle Cousineau, Richard Béliveau, Christian Marsolais, Borhane Annabi. The peptide-drug conjugate sudocetaxel zendusortide (TH1902) potentiates anti-tumoral activity of the anti-PD-L1 checkpoint inhibitor and induces immune cell infiltration in a B16-F10 syngeneic melanoma model. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4499.

Abstract 3221: Patients with glioblastoma (GBM) treated with tumor treating fields (TTFields) therapy: post-marketing safety data over the last decade

Abstract Patients with glioblastoma (GBM) face poor outcomes; the 5-year survival rate is 7% with standard of care treatments, which are frequently associated with systemic toxicity. Tumor Treating Fields (TTFields) are electric fields that disrupt critical cancer cell processes. The TTFields therapy device consists of a portable electric field generator and arrays placed on the patient’s scalp, thus delivery is locoregional and noninvasive. Currently, TTFields therapy is approved for recurrent and newly diagnosed GBM, based on the phase 3 EF-11 (TTFields 200 kHz) and EF-14 studies (TTFields therapy 200 kHz + temozolomide), respectively. These studies confirmed that TTFields therapy had a tolerable safety profile with mild-to-moderate localized skin adverse events (AEs) being the most common related AEs. Here, we present an updated analysis of the largest global real-world evidence dataset of patients with brain tumors receiving TTFields therapy over an 11-year time period. Unsolicited safety data were obtained from routine post-marketing activities, including published literature and interactions with patients, caregivers, and healthcare professionals. Safety data were grouped according to age, diagnosis, and sex. AEs were categorized using MedDRA version 25. Data from 25,898 patients were included in this analysis; median age was 59 years (range: 3-103) for patients with known age. Diagnoses were ndGBM (67.7%), rGBM (26.1%), anaplastic astrocytoma/oligodendroglioma (4.2%) and other (2.1%). Most (n=17,817, 68.8%) patients were 18-65 years of age; n=93 (0.4%) were pediatric/adolescent patients (&amp;lt;18 years), and n=7,808 (30.2%) were elderly patients (&amp;gt;65 years). For 130 patients (0.5%) age was not known. Two-thirds of patients were male, which reflects the preponderance of CNS tumors in males. Most patients were based in North America (72.1%), followed by Europe, the Middle East and Africa (23.3%), and Japan (4.6%). Overall, 72.4% of patients experienced at least one AE, with 55.9% being related to TTFields therapy. The most common AEs (overall and related to TTFields therapy) were skin reactions (42.0%), electric (tingling) sensations (13.5%), and heat (warmth) sensations (11.8%). The percentage of patients experiencing ≥1 AE in the pediatric/adolescent, 18-65, and elderly groups was 63.4%, 74.6%, and 68.4%, respectively. The percentage of females and males experiencing ≥1 AE was 75.2% and 70.9%, respectively. These long-term, real-world data from the largest global dataset of patients with brain tumors using TTFields therapy to date demonstrate a tolerable safety profile consistent with pivotal clinical studies. There were no new safety signals, and most AEs were manageable localized mild-moderate skin events that can be resolved. The distribution of AEs between age and sex was similar, with broad applicability among different patient groups. Citation Format: Maciej M. Mrugala, Wenyin Shi, Fabio Iwamoto, Rimas V. Lukas, Joshua D. Palmer, John H. Suh, Martin Glas. Patients with glioblastoma (GBM) treated with tumor treating fields (TTFields) therapy: post-marketing safety data over the last decade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3221.

Abstract 6254: The discovery and preclinical characterization of the SAM-competitive PRMT5 inhibitor UCT-000445

Abstract Protein arginine methyltransferase 5 (PRMT5) is a methyltransferase enzyme that symmetrically dimethylates arginine residues of histones, transcription elongation factors, translation regulators, and transcription factors like p53. It also regulates the activity of MAPK and PI3K signaling through methylation and activation of various receptor tyrosine kinases. As such, it has epigenetic effects that may be therapeutic in oncology. Successful clinical development of PRMT5 inhibitors will depend on upon utilizing this unique inhibitor modality and identifying those cancers with sensitivity to PRMT5 inhibition. By evaluating the potency and efficacy of several SAM-competitive, substrate-competitive, and MTA-cooperative PRMT5 inhibitors using a large (n&amp;gt;500), diverse panel of human cancer cell lines, we determined that the SAM-competitive inhibitor modality offers the best therapeutic potential thanks to its larger therapeutic window in vitro. This screening approach also identified several solid tumor histologies that were extremely sensitive to PRMT5 inhibition. Using our proprietary chemistry and by screening through the panel of human cancer cell lines, we identified UCT-000445, a SAM-competitive PRMT5 inhibitor with high selectivity over PRMT9 and good pharmacokinetic properties. Moreover, efficacy UCT-000445 is achieved regardless of MTAP gene status in histologies outside of hematological malignancies and including colon. UCT-000445 potently inhibits tumor growth in multiple human xenograft models of cancers, including but not limited to colon and lung cancers. The responses observed are durable upon cessation of treatment. Marked combined efficacy was also observed with standard of care treatment in these cancer types. UCT-000445 was well tolerated in vivo and using a CD-1 nude mouse model we found that while reticulocyte proliferation (a surrogate marker for bone marrow cytopenias) is abrogated by continuous treatment with UCT-000445, the use of intermittent dosing schedules overcomes this effect, while yielding equivalent efficacy. Our data with UCT-000445 indicate that SAM-competitive PRMT5 inhibitors may represent a novel and compelling therapeutic strategy for the treatment of multiple solid tumors. Citation Format: Martina S. McDermott, Neil A. O'Brien, Brendan O'Boyle, Michael Bartberger, Oliver C. Losón, Kevin Chau, Ella Schwab, Jenny Hong, Jiaying Zhou, Chuhong Hu, Tong Luo, Raul Ayala, John Glasby, Brian M. Stoltz, Dennis J. Slamon. The discovery and preclinical characterization of the SAM-competitive PRMT5 inhibitor UCT-000445 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6254.

Abstract 579: Mini-tumors: Pre-clinical HCI assays to screen anti-cancer drugs in the context of organoids, cancer-associated fibroblasts and immune cells

Abstract Introduction Effective drug development relies on representative pre-clinical models to discover and characterize novel cancer therapies. Recapitulating the human specific tumor micro-environment (TME) is essential for IO studies or TME-targeting agents and detection of human-specific (off-)target effects to better predict therapeutic response and clinical outcomes. The recently developed patient-derived organoid (PDO) technology, provides access to representative organotypic cultures, established from patient cancer stem cells. These cultures can be further improved by including additional cell types with strong clinical implications, especially cancer-associated fibroblasts (CAFs) and immune cells. Both CAFs and immune cells from various lineages modulate tumor growth and metastasis, drug resistance and immune-mediated cancer cell killing in the TME and have become popular targets for therapy in the recent decades. Here, we present our improved pre-clinical platform for drug testing, consisting of organotypic mini-tumors combined with high-content imaging screening (HCI) to discriminate different cell types and assess morphological, cytostatic and cytotoxic effects of drugs simultaneously. Methods 3D mini-tumor co-cultures were established of allogenic CAFs and PDOs from pancreatic, colon and breast cancer patients. The mini-tumors were expanded in a TME stimulating medium cocktail that drives myofibroblast expansion and differentiation through PDGFRβ and TGFβ signaling. Subsequently, drug responses to various standard of care (SoC) treatments were determined. Additionally, allogenic PBMCs were included in mini-tumor cultures to assess mini-tumor infiltration and killing. Results Mini-tumor co-cultures were successfully established and characterized in different stimulating cocktails. We found mini-tumor sensitivity to SoC treatment to be altered compared to PDO mono-cultures or co-cultures without TME stimulating factors. Moreover, we observed changes in PBMC infiltration and cancer cell killing in mini-tumors grown in TME stimulating conditions. Conclusion and discussion Taken together, our newly developed pre-clinical mini-tumor HCI platform provides the unique opportunity to screen and test drugs targeting human cancer cells, CAFs or immune cells in vitro in a pathology and TME-resembling context. This will ultimately result in effective target validation and mode of action analysis, timeline and cost reductions, and most importantly, a more efficient entry into the clinic. Citation Format: Marten Hornsveld, Guusje Odenkirchen, Cyrelle van Dort, Jara Garcia Mateos, Saskia de Man, Gera Goverse, Bram Herpers, Mariusz Madej, Leo Price, Marrit Putker. Mini-tumors: Pre-clinical HCI assays to screen anti-cancer drugs in the context of organoids, cancer-associated fibroblasts and immune cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 579.

Abstract 67: Blockade of VEGF-A signaling by Bevacizumab did not affect significantly in vivo metastatic dissemination of three colorectal cancer cells with different metastatic potential

Abstract Colorectal cancer (CRC) is one of the deadliest cancers worldwide due to the high occurrence of metastasis in patients. Previous studies demonstrated that soluble factors modulates cancer-associated biological processes, including cell proliferation, angiogenesis and survival. Therefore, the dysregulation of secretory pathways is a crucial driver of CRC progression. This study aims to explore the influence of the microenvironment on the and the impact of the secretome on tumor biology. Initially, we implanted in immune-compromised NSG mice one representative CRC cell line (highly metastatic HCT-116, low metastatic HT-29 and non-metastatic 269) of a cluster analysis performed on cytokines profiles data of 20 CRC cells cultured in different in vitro conditions. Orthotopic and subcutaneous implantations of the cells were performed in two different set of experiments. Here, we found that the secretome pattern of the selected CRC lines was predictive of their tumor growth and metastatic dissemination in vivo. To determine if CRC standard care treatment might affect specific secretory pathways and in vivo metastasis, we orthotopically implanted again the three CRC cells (n=10 NSG mice for each cell line) and treated the mice with Bevacizumab (n=5) or with a control vehicle (n=5). Bevacizumab, was chosen due to the high expression of VEGF-A in the in vitro cytokine analysis and an upregulation in the serum of orthotopically implanted mice compared to the subcutaneous group. Serum was harvested before each treatment and at the termination time point. Tumor growth was followed by optical imaging and metastases were confirmed by terminal ex vivo imaging of the organs. As observed in the previous experiments, mice implanted with HCT-116 cells had the shortest latency and the highest intensity of tumor signal, compared to HT-29 and 269 lines, which belonged to the clusters of weakly and non-metastatic cells. The treatment with Bevacizumab did not influence the metastatic dissemination in the mice bearing HCT-116 and 269, whereas Bevacizumab-treated group implanted with HT-29 showed lower tumor signals compared to the control group, suggesting a sensitivity of these cells to Bevacizumab. Nevertheless, no statistically significant differences were observed in the ex vivo imaging analysis between Bevacizumab-treated and control groups in the different organs. A marked influence of Bevacizumab on tumor invasion in vivo was not determined. Future investigations could evaluate the co-injection of human monocytes and/or the administration of cross-reactive antibodies such as 2G11-2A05 to enhance the in vivo antitumoral activity of Bevacizumab. Furthermore, the human and mouse cytokine analysis of the organs and serum will help us to identify key players of the secretome to investigate their functional role in metastasis. Citation Format: Jacqueline Bersano, Dorothee Lenhard, Julia Schueler. Blockade of VEGF-A signaling by Bevacizumab did not affect significantly in vivo metastatic dissemination of three colorectal cancer cells with different metastatic potential [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 67.

Association between hepatitis C infection during pregnancy with maternal and neonatal outcomes: a systematic review and meta-analysis.

Studies of possible implications of the maternal hepatitis C virus (HCV) infection in terms of intrauterine fetal growth restriction (IUGR), preterm birth (PTB), low birth weight (LBW) infants, premature rupture of membranes (PROM), maternal and neonatal mortality are limited and inconclusive. Our study aims to assess the impact of HCV on maternal and neonatal outcomes. Systematic literature search was done in PubMed, Scopus, and Google Scholar, Cochrane Library, and TRIP databases for all observational studies published from 1st January 1950 to 15th October 2022. The pooled odds ratio (OR) or risk ratio (RR) with a 95% confidence interval (CI) was estimated. STATA version 12.0 software was used for analysis. Heterogeneity among the included articles was evaluated by sensitivity, meta-regression, and publication bias analyses. A total of 14 studies involving 12,451 HCV (+) and 56,42,910 HCV (-) pregnant women were included in our meta-analysis. Maternal HCV during pregnancy was significantly associated with the increased risk of PTB (OR=1.66, 95% CI: 1.59-1.74), IUGR (OR=2.09, 95% CI: 2.04-2.14) and LBW (OR=1.96, 95% CI: 1.63-2.36) as compared to healthy pregnant women. Subgroup analysis based on ethnicity also suggested a strong association between maternal HCV infection and a higher risk of PTB in Asian and Caucasian populations. Maternal (RR=3.44, 95% CI: 1.85-6.41), as well as neonatal (RR=1.54, 95% CI: 1.18-2.02) mortality was significantly higher in HCV (+) cases. Mothers with HCV infection had a markedly increased probability of PTB and/or IUGR and/or LBW. In clinical practice, standard care of treatment and proper monitoring are needed for the pregnant population with HCV infection. Our findings may provide useful information for selecting appropriate therapy methods for HCV-positive pregnant women.