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Background  Foot ulcer is a common complication of poorly controlled diabetes and peripheral vascular disease (PVD). The current standard of treatment for diabetic foot ulcers includes the management of underlying risk factors, wound debridement, use of antibiotics for infection, off-loading with cast, and revascularisation surgery. The glyceryl trinitrate (GTN) patch is currently off-licence in treating PVD or diabetic foot ulcers. This study aims to evaluate the effectiveness of the GTN patch in preventing amputation, improving pain control, and reducing the size of tissue loss (ulcer/gangrene) or localised ischaemic area. Method This is a pilot study of 30 patients who were started on the GTN patch from February 2020 to October 2021. Inclusion criteria were patients who have critical limb-threatening ischaemia (CLTI) and with no viable options or are at high risk for revascularisation, both endovascular and open surgery. Patients who were on a GTN patch for less than six weeks at the time of data collection or had unclear outcomes were excluded. The outcomes were retrospectively collected on prevention of amputation, improvement in pain control, and reduction in tissue loss (the size of ulcer/gangrene) or localised ischaemic area with the use of a GTN patch. The binomial test was used to compare the observed outcome of the GTN patch and the expected outcome, which was assumed to be 50% in this study. Results  Ninety-three per cent (93%) of the patients who had GTN patches successfully avoided amputation (p<0.0001). Eighty-four per cent (84%) of patients reported better pain control (p=0.0022) and improvement in the size of ulcer/gangrene/localised ischaemic areas (p=0.0005). Conclusion The GTN patch is effective in preventing amputation, improving pain control, and reducing the size of ulcer/gangrene/localised ischaemic areas in patients who have end-stage CLTI and no viable options or who are at high risk for revascularisation surgery.

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INTRODUCTION: Choricocarcinoma is a highly malignant tumor. It metastasize commonly to the lungs. Metastasis to the kidney is uncommon, and bilateral metastasis is described rarely. Initial presentation with spontaneous bleeding of the renal metastatic tumor is scarce in the literatures. Here we present a case report of a choriocarcinoma patient with bilateral renal metastasis, presenting with spontaneous renal hemorrhage. CASE PRESENTATION: A 22 years old female presented to our emergency department with sudden onset of left flank pain. She has history of spontaneous abortion 02 years back with biopsy from the manual vacuum aspiration (MVA) showing molar pregnancy. Up on evaluation, patient was anemic. CT scan showed left renal bleeding tumor. Exploratory laparotomy and radical nephrectomy was done with the impression of bleeding renal cell carcinoma. The biopsy revealed choriocarcinoma. On her follow up, CT scan showed right renal and brain metastasis. She was given multi agent chemotherapy and her serum beta-hCG became undetectable after 01 year. DISCUSSION: Choriocarcinoma can be gestational or nongestational. The commonest route of metastasis is hematogenous. Presenting symptoms of renal metastasis can be hematuria, pain or more commonly incidental finding during work up. Choriocarcinoma is highly chemo sensitive. CONCLUSION: Bilateral renal metastatic choriocarcinoma is uncommon. Spontaneous renal hemorrhage as an initial presentation is even rare, and it can mimic a bleeding renal cell carcinoma. High index of suspicion is needed in a young women with recent history of spontaneous abortion.

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In order to study the multi-mode damage and fracture mechanisms of thin-walled tubular parts with cross inner ribs (longitudinal and transverse inner ribs, LTIRs), the Gurson-Tvergaard-Needleman (GTN) model was modified with a newly proposed stress state function. Thus, tension damage and shear damage were unified by the new stress state function, which was asymmetric with respect to stress triaxiality. Tension damage dominated the modification, which coupled with the shear damage variable, ensured the optimal prediction of fractures of thin-walled tubular parts with LTIRs by the modified GTN model. This included fractures occurring at the non-rib zone (NRZ), the longitudinal rib (LIR) and the interface between the transverse rib (TIR) and the NRZ. Among them, the stripping of material from the outer surface of the tubular part was mainly caused by the shearing of built-up material in front of the rollers under a large wall thickness reduction (ΔT). Shear and tension deformation were the causes of fractures occurring at the NRZ, while axial tension under a large TIR interval (l) mainly resulted in fractures on LIRs. Fractures at the interface between the TIR and NRZ were due to the shearing applied by rib grooves and radial tension during the formation of ribs. This study can provide guidance for the manufacturing of high-performance aluminum alloy thin-walled tubular components with complex inner ribs.

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INTRODUCTION: COVID-19 causes severe inflammatory respiratory distress syndrome. The global pandemic caused millions of cases of morbidity and mortality worldwide. Patients may present with variable symptoms including dyspnea, fever, and GIT manifestations. The HMOX-1 gene is located on the long (q) arm of chromosome 22 at position 12.3. HMOX-1 is expressed in all mammalian tissues at basal levels and is considered as a stress response enzyme. HMOX-1 has a specific polymorphic site with variable GT(n) repeats at the promotor region. Several authors evaluated the HMOX-1 GT(n) promoter polymorphism in different inflammatory conditions. We evaluated HMOX-1 promoter polymorphism in relation to serum Hemoxygenase level and inflammatory makers (CRP, Ferritin, PCT, IL-6 and D-dimer) in patients affected by SARS-COV-2 disease. SUBJECTS AND METHODS: Ninety patients confirmed to be infected with COVID-19 were followed up till the study end point (recovery and discharge or death). HMOX-1 promotor GT(n) polymorphism was evaluated using Sanger sequencing. HMOX-1 enzyme serum level was measured by ELISA and the level of different inflammatory markers was assessed by available commercial kits. RESULTS: A novel Single nucleotide polymorphism (SNP) (A > G) - rs13057211 in the GT(n) region of HMOX-1 promoter gene was found in 40 (61.5%) COVID-19 patients out of the studied 65 patients. This (A > G) SNP was associated with higher mortality rate in COVID-19 as it was detected in 27 patients (75% of the patients who succumbed to the disease) (p = 0.021, Odds ratio = 3.7; 95% CI:1.29-10.56). Serum IL-6 (Interleuken-6) was positively correlated the length of Hospital Stay (LOHS) and procalcitonin (PCT); (p = 0.014, r: 0.651 and p < 0.001, r:0.997) respectively while negatively correlated with levels of HMOX-1 enzyme serum level (p = 0.013, r: -0.61). CRP correlated positively with LOHS (p = 0.021, r = 0.4), PCT (p = 0.044, r = 0.425) and age (p < 0.001, r = 0.685). Higher levels of D-Dimer and PCT were observed in patients with the long repeat. There was no significant difference between patients who recovered and those who died from COVID-19 as regards HMOX-1 level and GT(n) polymorphism. CONCLUSION: We report a novel SNP (A > G, rs13057211) in the GT(n) region of HMOX-1 promoter gene that was associated with mortality in COVID-19 patients, however no significant difference was found in HMOX-1 serum level or HMOX-1 (GT)n repeats within the studied groups.

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Gestational trophoblastic neoplasia (GTN) is a group of pregnancy-related disorders that arise from the cells of conception. They include gestational choriocarcinoma (CC), placental site trophoblastic tumor, and epithelioid trophoblastic tumor with these forms arising from a molar pregnancy, abortion, or a normal genetic pregnancy. Most cases of GTN are diagnosed when the serum hCG levels plateau or rise in patients being followed up after the diagnosis of hydatidiform mole but can also be suspected due to persistent vaginal bleeding after a normal pregnancy and delivery. Early diagnosis and treatment are pivotal for ensuring optimal outcomes and given the rarity of the disease, clinical management and treatment should be provided in specialized centers. Here, we present a rare case of a 31-year-old woman diagnosed with choriocarcinoma with pulmonary metastasis following an uncomplicated full-term pregnancy. After the suction evacuation and curettage, she underwent six cycles of chemotherapy with an excellent response, a fact that resulted in a subsequent pregnancy and birth without complications, occurring 18 months thereafter.

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Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic tumor, first described by Shih and Kurman in 1998. ETT often present as abnormal vaginal bleeding in women of reproductive age, but unlike more common forms of GTN tend to produce much less human chorionic gonadotropin (hCG) for the volume of disease present. ETT can occur after any gestational event and can occur in both intrauterine and extrauterine sites. We present a case of a 46-year-old female patient incidentally diagnosed with ETT and hepatic metastasis. Therapy was multimodal and involved chemotherapy, operation, thermoablation of liver metastases and immunocheckpoint inhibitor. The patient remains disease free for almost four years now. ETT presents a diagnostic challenge due to their rarity and histologic resemblance to other pathologies. ETT can be relatively chemo resistant and are therefore often treated surgically. Misdiagnosis might delay effective treatment and affects survival.

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Gestational trophoblastic neoplasia (GTN) arising in the placenta and presenting as a metastatic disease concurrently in the mother and the baby is extremely rare. GTN poses a diagnostic dilemma to the treating clinicians. In the current review, an electronic search of Scopus, PubMed, Embase and other databases was conducted for case reports and case series of GTN co-existing or metastatic to both the mother and the baby, published to date. Globally, a total of twenty-two cases of GTN with metastasis to both the mother and baby was found. The previous history of histopathology confirmed molar pregnancy was present in 4/22 cases. The median time to diagnose GTN in the mother was six weeks post-partum. In the majority of cases, diagnosis of maternal disease was made after the infant presented with clinical manifestation. Overall survival was reported in 17/22 mothers up to varying latest follow-up and in 6/22 infants. A knowledge of the varied clinical presentation, eliciting a history of previous pregnancy loss/term pregnancy and serum beta human chorionic gonadotrophin (ß-hCG) estimations were helpful for early diagnosis. The concurrent presence of GTN in the mother and baby is a rare entity and poses a diagnostic dilemma. Diagnosis in the mother often follows diagnosis in the baby after an infant presents with clinical manifestations. GTN is a highly chemo-sensitive tumour, but the main prognostic factors determining survival are the time to diagnosis following previous pregnancy and serum ß-hCG levels.

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We report a case of pulmonary embolism caused by gestational trophoblastic neoplasia (GTN) accompanied by pulmonary metastasis to improve the recognition ability of the disease in young female patients with pulmonary embolism and hemoptysis.

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BACKGROUND: Migraine is a severely debilitating disorder that affects millions of people worldwide. Studies have indicated that activation of protease-activated receptor-2 (PAR2) in the dura mater causes headache responses in preclinical models. It is also well known that vasodilators such as nitric oxide (NO) donors can trigger migraine attacks in migraine patients but not controls. In the current study we examined whether activation of PAR2 in the dura causes priming to the NO donor glyceryl trinitrate (GTN). METHODS: A preclinical behavioral model of migraine was used where stimuli (PAR2 agonists: 2at-LIGRL-NH2 (2AT) or neutrophil elastase (NE); and IL-6) were applied to the mouse dura through an injection made at the intersection of the lamdoidal and sagittal sutures on the skull. Following dural injection, periorbital von Frey thresholds and facial grimace responses were measured until their return to baseline. GTN was then given by intraperitoneal injection and periorbital hypersensitivity and facial grimace responses observed until they returned to baseline. RESULTS: We found that application of the selective PAR2 agonist 2at-LIGRL-NH2 (2AT) onto the dura causes headache-related behavioral responses in WT but not PAR2-/- mice with no differences between sexes. Additionally, dural PAR2 activation with 2AT caused priming to GTN (1 mg/kg) at 14 days after primary dural stimulation. PAR2-/- mice showed no priming to GTN. We also tested behavioral responses to the endogenous protease neutrophil elastase, which can cleave and activate PAR2. Dural neutrophil elastase caused both acute responses and priming to GTN in WT but not PAR2-/- mice. Finally, we show that dural IL-6 causes acute responses and priming to GTN that is identical in WT and PAR2-/- mice, indicating that IL-6 does not act through PAR2 in this model. CONCLUSIONS: These results indicate that PAR2 activation in the meninges can cause acute headache behavioral responses and priming to an NO donor, and support further exploration of PAR2 as a novel therapeutic target for migraine.

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This paper presents the characterisation of selective-laser-sintered (SLS) samples of polyamide 12 (PA12) under shear loading. PA12 is a semi-crystalline thermoplastic and is used in various industries. Its behaviour under shear stress, which is particularly important for product reliability, has not yet been sufficiently investigated. This research focuses on understanding the material and damage behaviour of PA12 under shear-induced stress conditions. The study included quasi-static experiments and numerical simulations. Samples were prepared via SLS and tested according to ASTM standards. Digital image correlation (DIC) was used for precise deformation measurements. The Chaboche material model was used for the viscoplastic behaviour in the numerical simulations. Due to existing material discontinuities in the form of voids, the material model was coupled with the Gurson-Tvergaard-Needleman (GTN) damage model. A modified approach of the GTN model was used to account for low stress triaxiality under shear loading. These models were implemented in MATLAB and integrated into Abaqus via a User Material (UMAT) subroutine. The results of the experiments and simulations showed a high degree of accuracy. An important finding was the significant influence of the shear factor kw on the damage behaviour, especially during failure. This factor proved to be essential for the accurate prediction of material behaviour under shear-induced stress conditions. The integration of the modified GTN model with the Chaboche material model in UMAT enables an accurate prediction of the material and damage behaviour and thus makes an important contribution to the understanding of the mechanical material behaviour of SLS PA12 specimens.

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Objective: The efficacy of the first-line monodrug chemotherapy has been generally established for low-risk GTN. Most patients can achieve a complete response after the first-line monodrug chemotherapy. However, which monodrug chemotherapy regimen is better for individual patients with GTN is not yet certain. This study aimed to assess the efficacy of first-line monodrug chemotherapy in low-risk gestational trophoblastic neoplasia (GTN). Method: Databases, including PubMed, Embase, Web of Science, and Cochrane Library, were searched from inception to November 1, 2022, for case-control studies on first-line monodrug chemotherapy in GTN. Network meta-analysis was performed to compare the efficacy outcome of six monodrug chemotherapy regimens in GTN, with a complete response rate as the endpoint. Result: Twenty-four studies were considered eligible, including 9 randomized controlled trials (RCTs) and 15 non-RCTs. A total of 3344 patients with low-risk GTN were involved. Six monodrug chemotherapy regimens were included and analyzed. In descending order of efficacy, these six regimens were VP-16 (5 days), ACT-D (5 days), MTX (5 days), ACT-D (1.25 mg/m2), MTX (8 days), and MTX (30-50 mg/m2) in all study, and five regimens were ACT-D (5 days), MTX (5 days), ACT-D (1.25 mg/m2), MTX (8 days), and MTX (30-50 mg/m2) in RCT. Conclusion: Among the six first-line monodrug chemotherapy regimens for low-risk GTN in all study, VP-16 (5 days) was the best in terms of efficacy. And five regimens in RCT, ACT-D was the best. However, the finding needs to be validated through more high-quality clinical studies.

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BACKGROUND: Calcitonin gene-related peptide (CGRP) antagonizing drugs represents the most important advance in migraine therapy for decades. However, these new drugs are only effective in 50-60% of patients. Recent studies have shown that the pituitary adenylate cyclase-activating peptide (PACAP38) pathway is independent from the CGRP signaling pathway. Here, we investigate PACAP38 signaling pathways in relation to glyceryl trinitrate (GTN), levcromakalim and sumatriptan. METHODS: In vivo mouse models of PACAP38-, GTN-, and levcromakalim-induced migraine were applied using tactile sensitivity to von Frey filaments as measuring readout. Signaling pathways involved in the three models were dissected using PACAP-inhibiting antibodies (mAbs) and sumatriptan. RESULTS: We showed that PACAP mAbs block PACAP38 induced hypersensitivity, but not via signaling pathways involved in GTN and levcromakalim. Also, sumatriptan has no effect on PACAP38-induced hypersensitivity relevant to migraine. This is the first study testing the effect of a PACAP-inhibiting drug on GTN- and levcromakalim-induced hypersensitivity. CONCLUSIONS: Based on the findings in our mouse model of migraine using migraine-inducing compounds and anti-migraine drugs, we suggest that PACAP acts via a distinct pathway. Using PACAP38 antagonism may be a novel therapeutic target of interest in a subgroup of migraine patients who do not respond to existing therapies.

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Objective: To investigate the monotherapy for gestational trophoblastic neoplasia (GTN) patients with FIGO/WHO prognostic score of 5-6. Methods: The low-risk GTN patients from 2012 to 2019 were enrolled. The study is a retrospective report to analyze the efficacy and safety of single-agent chemotherapy and combination chemotherapy in patients with a high FIGO/WHO prognostic score of 5-6. Results: 75 cases (33.5%) were included. Complete remission was in all patients. Among the 29 cases taking single-agent chemotherapy, 22 cases (75.9%) developed drug resistance. Among the 46 cases taking combination chemotherapy, 7 patients (15.2%) developed drug resistance. There was a statistically significant difference in the drug resistance rate between these two subgroups (P < 0.05), but there was not statistically significant difference in the total number of chemotherapy courses (<2mIU/ml) (P < 0.05). Conclusion: Monotherapy showed remarkable advantages in GTN patients with FIGO/WHO prognostic score of 5-6.

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Background: The therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. Hemoglobin tightly binds to NO forming methemoglobin altering the erythrocytic antioxidant defense system. Aim: The principal objective of our research is to show the ameliorating effect of l-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs used in cardiovascular diseases such as oxidative stresses and tolerance. Method: We studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered different concentrations of Isosorbide-5-mononitrate (ISMN) 0.3 mg/kg, 0.6 mg/kg and 1.2 mg/kg. Afterwards, we evaluated the role of l-ascorbic acid against these biochemical changes in cardiac tissues. Results: Chronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of the pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in the myocardium muscles in a dose-dependent manner. Meanwhile, such exposure caused a decline in the enzymatic effect of SOD, GSH and CAT accompanied by a decrease in the level of mitochondrial oxidative stress marker (nrf2) in the myocardium muscles and a decrease in the serum iron and total iron-binding capacity (TIBC) in a dose-dependent manner. Concomitant treatment with l-ascorbic acid significantly diminished these changes for all examined parameters. Conclusion: Chronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to the generation of reactive oxygen species. Using l-ascorbic acid can effectively ameliorate such intoxication to overcome nitrate tolerance.

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Objective: Molar pregnancy coexistent with a live fetus can be a diagnostic and therapeutic challenge. With increasing incidence of multiple pregnancies, there has also been an increase in twin pregnancy with one mole in the recent years. The authors discuss the epidemiology, clinical presentation, and prenatal diagnosis and attempt to design a possible management strategy, to help guide the treating physician, in the management of partial mole with live pregnancy, thereby improving maternal and fetal prognosis. Material and Methods: Numerous case reports have been published in various journals regarding management of individual cases of partial molar pregnancy coexistent with live fetus (PMCF). Therefore, we conducted a systematic review of all the case reports and short case series in English concerning partial mole with live pregnancy from 1999 to 2019, that is in the last 20 years. Results: In total, 44 case reports of PMCF were analyzed. The mean gestational age at diagnosis was 20+6 (range: 10-40) weeks. Less than half (19/44; 43.2%) were asymptomatic at the time of detection and PMCF was detected on routine scan done for fetal well-being or 11-13-week scan. The majority (56.8%) resulted in the birth of a healthy live fetus. Gestational trophoblastic neoplasia developed in 3/44 (6.8%). Conclusion: PMCF involves a high risk of bleeding, preterm labour, intrauterine growth restriction and stillbirth. Successful management of such cases needs prenatal diagnosis, antepartum surveillance and post-natal follow-up. An obstetrician, maternal fetal medicine specialist, gynecology oncologist and neonatal intensivist should be involved in the care of such pregnancies.

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To determine the Gurson-Tvergaard-Needleman (GTN)damage model parameters of 6061 aluminum alloy after secondary heat treatment, the uniaxial tensile test was carried out on the aluminum alloy circular arc specimen, and the mechanical properties parameters and the load-displacement curve of aluminum alloy tube were obtained. With the help of the finite element reverse method, scanning electron microscope and a orthogonal test method, the GTN damage model parameters (f0, fN, fC, and fF) were calibrated, and their values were 0.004535, 0.04, 0.1, and 0.2135, respectively. Then the shear specimen and notch specimen were designed to verify the damage model, the results show that the obtained GTN damage model parameters can effectively predict the fracture failure of 6061 aluminum alloy after secondary heat treatment during the tensile process.

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Intratumoral injection of various effector cells combined with oncolytic adenovirus expressing antitumor cytokines exert an effective antitumor immune effect by oncolysis and altering the tumor microenvironment. However, this combination therapy had certain limitations. When used in high concentrations, effector cells and oncolytic viruses can spread rapidly to surrounding non-target tissues. And because both therapies used in combination are immunogenic and exhibit shorter biological activity, multiple injections were required to attain an adequate therapeutic index. To overcome these drawbacks, we encapsulated gelatin-based hydrogel capable of co-deliver oncolytic adenovirus armed with IL12 and IL15 (CRAd-IL12-IL15) and CIK cells for enhancing and prolonging the antitumor effects of both therapies after a single intratumoral injection. The injectable and biodegradable hydrogel reduced the dispersion of high-dose oncolytic adenovirus and CIK cells from the injection site to the liver and other non-target tissues. In this study, a novel oncolytic adenoviral vector CRAd-IL12-IL15 was constructed to verify the cytokine expression and oncolytic ability, which can upregulate the expression levels of Bcl-2, Cish and Gzmb in tumor cells. The CRAd-IL12-IL15 + CIKs/gelatin treatment maintained sustained release of CRAd-IL12-IL15 and active CIK cells over a longer period of time, attenuating the antiviral immune response against adenovirus. In conclusion, the results suggested that hydrogel-mediated co-delivery of CRAd-IL12-IL15 and CIK cells might be a an approach to overcome limitations. Both treatments could be effectively retained in tumor tissue and sustained to induce potent anti-tumor immune responses with a single administration.

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Neuron loss and disruption of neural circuits are associated with many neurological conditions. A key question is how to rebuild neural circuits for functional improvements. In vivo glia-to-neuron (GtN) conversion emerges as a potential solution for regeneration-based therapeutics. This approach takes advantage of the regenerative ability of resident glial cells to produce new neurons through cell fate reprogramming. Significant progress has been made over the years in this emerging field. However, inappropriate analysis often leads to misleading conclusions that create confusion and hype. In this perspective, we point out the most salient pitfalls associated with some recent studies and provide solutions to prevent them in the future. The goal is to foster healthy development of this promising field and lay a solid cellular foundation for future regeneration-based medicine.

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Background: Pulmonary hypertension (PH) is an established risk factor in patients with heart failure (HF). However, right heart catheterisation (RHC) and vasoreactivity testing (VRT) are not routinely recommended in these patients. Methods: The primary objective of the present study was to explore the impact of VRT using sublingual glyceryl trinitrate (GTN) on transplant/ventricular assist device-free survival in HF patients with post-capillary PH. RHC parameters were correlated retrospectively with the primary outcome. Results: The cohort comprised 154 HF patients with post-capillary PH undergoing RHC with GTN-VRT at a tertiary heart failure centre. Multiple parameters were associated with survival. After adjustment for established prognosis-relevant clinical variables from the MAGGIC Score, variables with the most relevant odds ratios (OR) obtained after GTN-VRT were: calculated effective pulmonary arterial (PA) elastance (adjusted OR 2.26, 95%CI 1.30-3.92; p = 0.004), PA compliance (PAC-GTN; adjusted OR 0.45, 95%CI 0.25-0.80; p = 0.006), and total pulmonary resistance (adjusted OR 2.29, 95%CI 1.34-3.93; p = 0.003). Forest plot analysis including these three variables as well as PAC at baseline, delta PAC, and the presence of combined post- and pre-capillary PH revealed prognostic superiority of PAC-GTN, which was confirmed by Kaplan-Meier analysis. Conclusions: In our cohort of symptomatic HF patients with post-capillary PH, improved PAC after administration of GTN was associated with survival independent of established hemodynamic and clinical risk factors. VRT using GTN may be better described as unloading test due to GTN's complex effects on the circulation. This could be used for advanced prognostication and should be investigated in further studies.

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OBJECTIVES: The International Federation of Gynecology and Obstetrics (FIGO) 2000 scoring system classifies gestational trophoblastic neoplasia (GTN) patients into low- and high-risk groups, so that single- or multi-agent chemotherapy can be administered accordingly. However, a number of FIGO-defined low-risk patients still exhibit resistance to single-agent regimens, and the risk factors currently adopted in the FIGO scoring system possess inequable values for predicting single-agent chemoresistance. The purpose of this study is therefore to evaluate the efficacy of risk factors in predicting single-agent chemoresistance and explore the feasibility of simplifying the FIGO 2000 scoring system for GTN. METHODS: The clinical data of 578 GTN patients who received chemotherapy between January 2000 and December 2018 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were carried out to identify risk factors associated with single-agent chemoresistance in low-risk GTN patients. Then, simplified models were built and compared with the original FIGO 2000 scoring system. RESULTS: Among the eight FIGO risk factors, the univariate and multivariate analyses identified that pretreatment serum human chorionic gonadotropin (hCG) level and interval from antecedent pregnancy were consistently independent predictors for both first-line and subsequent single-agent chemoresistance. The simplified model with two independent factors showed a better performance in predicting single-agent chemoresistance than the model with the other four non-independent factors. However, the addition of other co-factors did improve the efficiency. Overall, simplified models can achieve favorable performance, but the original FIGO 2000 prognostic system still features the highest discrimination. CONCLUSIONS: Pretreatment serum hCG level and interval from antecedent pregnancy were independent predictors for both first-line and subsequent single-agent chemoresistance, and they had greater weight than other non-independent factors in predicting single-agent chemoresistance. The simplified model composed of certain selected factors is a promising alternative to the original FIGO 2000 prognostic system, and it shows comparable performance.

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