Prognostic Value of Cerebroplacental Ratio in Appropriate-for-Gestational-Age Fetuses Before Induction of Labor in Late-Term Pregnancies.

PURPOSE: To evaluate the relationship between cerebroplacental ratio (CPR) and the need for operative delivery due to intrapartum fetal compromise (IFC) and adverse perinatal outcome (APO) in appropriate-for-gestational-age (AGA) late-term pregnancies undergoing induction of labor. The predictive performance of CPR was also assessed. MATERIALS AND METHODS: Retrospective study including singleton AGA pregnancies that underwent elective induction of labor between 41 + 0 and 41 + 6 weeks and were delivered before 42 + 0 weeks. IFC was defined as persistent pathological CTG or pathological CTG and fetal scalp pH < 7.20. Operative delivery included instrumental vaginal delivery (IVD) and cesarean section (CS). APO was defined as a composite of umbilical artery pH < 7.20, Apgar score < 7 at 5 minutes, and admission to the neonatal intensive care unit for > 24 hours. RESULTS: The study included 314 women with 32 (10 %) IVDs and 49 (16 %) CSs due to IFC and 85 (27 %) APO cases. Fetuses with CPR < 10th percentile showed a significantly higher rate of operative delivery for IFC (40 % (21/52) vs. 23 % (60/262); p = 0.008) yet not a significantly higher rate of APO (31 % (16/52) vs. 26 % (69/262); p = 0.511). The predictive values of CPR for operative delivery due to IFC and APO showed sensitivities of 26 % and 19 %, specificities of 87 % and 84 %, positive LRs of 2.0 and 1.2, and negative LRs of 0.85 and 0.96, respectively. CONCLUSION: Low CPR in AGA late-term pregnancies undergoing elective induction of labor was associated with a higher risk of operative delivery for IFC without increasing the APO rate. However, the predictive value of CPR was poor.

The COVID-19 pandemic and its impact on medical teaching in obstetrics and gynecology-A nationwide expert survey among teaching coordinators at German university hospitals.

PURPOSE: The COVID-19 pandemic has imposed severe challenges on medical education at German university hospitals. In this first German nationwide expert survey, we addressed the responsible university teaching coordinators in obstetrics and gynecology departments and investigated their experiences during the pandemic as well as their opinions on future developments, especially with regard to the broader implementation of e-learning in the standard curriculum. METHODS: The questionnaire included 42 items and was disseminated among teaching coordinators at all 41 departments of obstetrics and gynecology at German university hospitals via an email that included a weblink to the online survey provider. Responses were collected between 19 April and 7 June 2021. RESULTS: In total, 30 responses were collected from 41 departments across Germany and their respective teaching coordinators in obstetrics and gynecology. The general opinion of the medical teaching provided during the pandemic was positive, whereas the teaching quality in practical skills was considered inferior and not equivalent to the standard face-to-face curriculum. Lectures and seminars had to be substituted by remote-learning alternatives, while clinical clerkships were reduced in length and provided less patient contact. Students in their final year experienced only a few differences in the clinical and teaching routine. Teaching coordinators in obstetrics and gynecology stated that they intend to incorporate more e-learning into the curriculum in the future. CONCLUSION: The medical educators' views presented here may help to complement the already-thoroughly investigated experiences of students under the restrictions of the COVID-19 pandemic. Medical educators in obstetrics and gynecology at German university hospitals have successfully established online and hybrid teaching alternatives to their standard face-to-face courses. Building on recent experiences, digitalization could help to improve future medical education.

Value of Cerebroplacental Ratio and Uterine Artery Doppler as Predictors of Adverse Perinatal Outcome in Very Small for Gestational Age at Term Fetuses.

The aim of this study was to evaluate the association between cerebroplacental ratio (CPR), mean uterine artery (mUtA) Doppler and adverse perinatal outcome (APO) and their predictive performance in fetuses with birth weight (BW) <3rd centile (very small for gestational age, VSGA) in comparison with fetuses with BW 3rd−10th centile (small for gestational age, SGA). This was a retrospective cohort study including singleton pregnancies delivered at term (37 + 0−41 + 6) in a single tertiary referral center over a six-year period. APO was defined as a composite of cesarean section for intrapartum fetal compromise (IFC), umbilical artery pH < 7.20, and admission to the neonatal intensive care unit for >24 h. The characteristics of the study population according to BW (VSGA and SGA) as well as the presence of composite APO were assessed. The prognostic performance of CPR and mUtA-PI was evaluated using receiver operating characteristic (ROC) analysis. In total, 203 pregnancies were included. Of these, 55 (27%) had CPR <10th centile, 25 (12%) mUtA-PI >95th centile, 65 (32%) VSGA fetuses, and 93 (46%) composite APO. VSGA showed a non-significantly higher rate of composite APO in comparison to SGA (52% vs. 43%; p = 0.202). The composite APO rate was significantly higher in SGA with CPR <10th centile (36% vs. 13%; p = 0.001), while in VSGA with CPR <10th centile was not (38% vs. 35%; p = 0.818). The composite APO rate was non-significantly higher both in VSGA (26% vs. 10%; p = 0.081) and SGA (14% vs. 6%; p = 0.742) with mUtA-PI >95th centile. The ROC analysis showed a significantly predictive value of CPR for composite APO in SGA only (AUC 0.612; p = 0.025). A low CPR was associated with composite APO in SGA fetuses. VSGA fetuses were more frequently affected by composite APO regardless of Doppler values. The predictive performance of CPR and uterine artery Doppler was poor.

Performance of sFlt-1/PIGF Ratio for the Prediction of Perinatal Outcome in Obese Pre-Eclamptic Women.

Obese women are at high risk of developing pre-eclampsia (PE). As an altered angiogenic profile is characteristic for PE, measurement of soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PIGF) ratio in the maternal serum can be helpful for PE diagnosis, as well as for adverse perinatal outcome (APO) prediction. There is growing evidence that obesity might influence the level of sFlt-1/PIGF and, therefore, the aim of the study was the evaluation of sFlt-1/PIGF as an APO predictor in obese women with PE. Pre-eclamptic women who had an sFlt-1/PIGF measurement at the time of diagnosis were retrospectively included. Women were classified according to their pre-pregnancy body mass index (BMI) as normal weight (BMI < 25 kg/m2), overweight (BMI > 25−29.9 kg/m2) or obese (BMI ≥ 30 kg/m2). APO was defined as the occurrence of one of the following outcomes: Small for gestational age, defined as a birthweight < 3rd centile, neonatal mortality, neonatal seizures, admission to neonatal unit required (NICU) or respiratory support. A total of 141 women were included. Of them, 28 (20%) patients were obese. ROC (receiver operating characteristic) analysis revealed a high predictive value for sFlt-1/PIGF and APO across the whole study cohort (AUC = 0.880, 95% CI: 0.826−0.936; p < 0.001). However, the subgroup of obese women showed a significantly lower level of sFlt-1 and, therefore, the performance of sFlt-1/PIGF as APO predictor was poorer compared to normal or overweight PE women (AUC = 0.754, 95% CI: 0.552−0.956, p = 0.025). In contrast to normal or overweight women, a ratio of sFlt-1/PIGF < 38 could not rule out APO in women with obesity.

Platelet mitochondrial membrane depolarization reflects disease severity in patients with preeclampsia.

BACKGROUND: Thrombocytopenia is a feared complication of preeclampsia (PE) that can additionally complicate the disease course and that carries a poor prognosis. The disease mechanisms of PE on a platelet level are poorly understood and only few platelet-based markers have been investigated. In sepsis, platelet mitochondrial membrane depolarization, a sensitive and early indicator of mitochondrial dysfunction and platelet cell death, correlates with disease severity and outcome as shown in previous studies. The aim of this study was to investigate platelet mitochondrial membrane potential (Mmp-Index) by flow-cytometry in patients with preeclampsia compared to controls and to assess its value in correlation with disease severity of PE and during follow-up after delivery. METHODS: In this prospective translational case-control study, platelet Mmp-Index was measured in PE (n = 16) by flow cytometry in living platelets in simultaneous comparison to healthy pregnant (n = 32) and non-pregnant controls (n = 16) and was individually reassessed after delivery to investigate recovery of platelet mitochondrial function. Subgroup analysis of patients with severe and non-severe PE was performed. Six patients with isolated gestational hypertension were also included for comparative analysis. RESULTS: Platelet Mmp-Index in patients with symptomatic preeclampsia (Mmp-Index non-severe PE 0.72 ([0.591; 0.861]; p = 0.002) was significantly reduced compared to healthy pregnant controls (Mmp-Index 0.97 [0.795; 1.117]) and even more pronounced in patients with severe PE (n = 6) (Mmp-Index severe PE 0.542 [0.361; 0.623]; p = 0.03). In the severe PE group, complementary measurements of platelet Annexin V- and CD62 (P-Selectin) surface expression showed apoptosis of platelet populations in the majority of patients. Platelet Mmp normalized after delivery within few days. Patients with isolated gestational hypertension showed normal Mmp-Index values. CONCLUSIONS: This study shows for the first time that platelet Mmp-Index is a quantifiable, easy-to-measure intracellular marker of platelet mitochondrial function in vital cells that reflects disease severity of preeclampsia. For future investigations, platelet Mmp may serve as a prognostic marker that may aid clinical risk stratification and adds novel information on potential mechanisms for thrombocytopenia in preeclampsia.

Experiences with alternative online lectures in medical education in obstetrics and gynecology during the COVID-19 pandemic-possible efficient and student-orientated models for the future?

PURPOSE: The onset of the COVID-19 pandemic posed an eminent challenge for medical teachers worldwide. Face-to-face lectures and seminars were no longer possible, and alternatives had to be found. E-learning concepts quickly emerged as the only practicable solutions and also offered the opportunity to evaluate whether traditional face-to-face lectures could be translated into an online format, independent of the COVID-19 pandemic. METHODS: We offered an e-learning program consisting of lecture notes, screencasts with audio narration, and online webinars that covered topics normally taught in traditional lectures and seminars. To evaluate the learning behavior and quality of our e-learning program, we drafted a questionnaire that students completed at the end of the 2020 summer semester that had been designed to enable a comparative analysis of the different e-learning modules. RESULTS: Voluntary participation in the online courses was high. Survey analysis revealed high satisfaction with and a distinctive preference for the format, even under regular, COVID-19-independent conditions. In general, a positive appraisal of e-learning-especially as a substitute for regular lectures-was found. Students also reported higher studying efficiency. Exam results were equal to those of previous semesters. CONCLUSION: Both acceptance of and satisfaction with our e-learning modules were high, and students displayed increased demand for this kind of e-learning format. We, therefore, conclude that e-learning offerings could serve as reasonable, efficient, student-orientated substitutes for certain medical courses, especially lectures. These curricular adaptations would correlate with the high digitalization seen in students' everyday lives. This correlation may also hold true independent of the ongoing COVID-19 pandemic.

The role of gender-specific factors in the choice of specialty training in obstetrics and gynecology: results from a survey among medical students in Germany.

PURPOSE: The field of obstetrics and gynecology (OB/GYN) is facing growing competition for young professionals in Germany, with high interest rates among female graduates and a declining proportion of male students who choose residency training in the field. The aim of this study is to analyze general and gender-dependent factors that influence the decision for or against specialty training in OB/GYN among medical students in Germany. METHODS: Between February and November 2019, n = 346 medical students in their 5th and 6th year of undergraduate training at Heidelberg University received a questionnaire with 44 items. RESULTS: n = 286 students (61.3 female; 38.7% male) participated in the study. 28% of the female students and 9% of the male students had considered OB/GYN for their specialty training. The students reported different general and gender-specific influencing factors in their choice of a specialty. Both genders desired a good work-life-balance, however, in comparison with their female colleagues, male students had heavily weighted factors related to their later careers and professional success, including competition among colleagues. Male students had gained little practical experience during compulsory internships (26.9% for females vs. 8.8% for males) or had chosen their final-year elective in OB/GYN (15.9% for females vs. 5.5% for males). Female students had worried about the negative effects of their sex on their career (35.4% for females vs. 5.9% for males). CONCLUSION: OB/GYN must become more appealing and attractive to young female and male professionals alike. A better compatibility of career and family should go hand in hand with the implementation of differentiated, (extra) curricular teaching approaches that take the different preferences of female and male students into account.

Does gestational age at term play a role in the association between cerebroplacental ratio and operative delivery for intrapartum fetal compromise?

INTRODUCTION: To assess the impact of gestational age at term on the association between cerebroplacental ratio (CPR) and operative delivery for intrapartum fetal compromise (IFC) and prognostic performance of CPR to predict operative delivery for IFC. MATERIAL AND METHODS: This was a retrospective cohort study including 2052 singleton pregnancies delivered between 37+0 and 41+6  weeks of gestation in a single tertiary referral center over an 8-year period. CPR was measured within 1 week of delivery. IFC was defined as the presence of persistent pathological cardiotocography pattern or the combination of pathological cardiotocography pattern and fetal scalp pH < 7.20. Operative delivery included instrumental vaginal delivery and cesarean section. Pregnancies were grouped according to birthweight (small for gestational age [SGA, birthweight <10th centile] and appropriate for gestational age [AGA, birthweight 10th-90th centile]) and gestational age by week at delivery. Rates of operative delivery were compared between the subgroups. Prognostic value of CPR was assessed using receiver operating characteristic curve. RESULTS: Of the study cohort, 308 (15%) had a CPR <10th centile, 374 (18%) operative delivery for IFC, and 298 (15%) were SGA at birth. Overall, the rates of operative delivery for IFC were higher in the low CPR group both in SGA (35% vs. 22%; p = 0.023) and in AGA (23% vs. 16%; p = 0.007). According to gestational age by week at delivery, fetuses with low CPR showed higher rates of operative delivery for IFC with advancing gestational age, mainly in pregnancies delivered at 40 weeks (54% vs. 23%; p = 0.004) and at 41 weeks (60% vs. 19%; p = 0.010) for SGA and at 41 weeks (39% vs. 20%; p = 0.001) for AGA. The predictive value of CPR remained stable throughout term and was poor both in SGA and in AGA. CONCLUSIONS: Both SGA and AGA fetuses with low CPR showed higher rates of operative delivery for IFC at term with advancing gestational age. Prognostic value of CPR throughout term was poor.

Prediction of adverse perinatal outcome and the mean time until delivery in twin pregnancies with suspected pre-eclampsia using sFlt-1/PIGF ratio.

PURPOSE: An elevated soluble fms-like tyrosine kinase-1 (sFlt-1) / placental growth factor (PlGF) ratio is associated with adverse perinatal outcome (APO) and the mean time until delivery (MTUD) in singleton pregnancies complicated by pre-eclampsia (PE). Data on APO and MTUD prediction in twin pregnancies using sFlt-1/PlGF ratio are scarce. We evaluated the predictive value of the sFlt-1/PIGF ratio regarding APO and MTUD in twin pregnancies with suspected PE and/or HELLP syndrome. METHODS: This is a single center retrospective cohort study. All twin pregnancies with suspected PE/HELLP and determined sFlt-1/PIGF were included. Composite APO (CAPO) was defined as the presence of at least one of the following outcomes: respiratory distress syndrome (RDS), intubation, admission to neonatal intensive care unit (NICU) and arterial umbilical cord pH value < 7.10. Selective fetal growth restriction (s-FGR) was analyzed separately. RESULTS: For final analysis, 49 twin pregnancies were included. Median sFlt-1/PIGF ratio was not significantly different in patients with CAPO compared to those without (89.45 vs. 62.00, p = 0.669). MTUD was significantly negative correlated with sFlt-1/PIGF ratio (r = -0.409, p < 0.001). For the whole study cohort, ROC analysis revealed no predictive value for sFlt-1/PIGF and CAPO (AUC = 0.618, 95% CI: 0.387-0.849, p = 0.254). However, sFlt-1/PIGF ratio showed a predictive value for s-FGR (AUC = 0.755, 95% CI: 0.545-0.965, p = 0.032). CONCLUSION: In twin pregnancies with PE and/or HELLP, sFlt-1/PIGF ratio may be helpful for s-FGR prediction and decision-making regarding close monitoring of high-risk patients. However, further prospective studies are warranted to define the role of sFlt-1/PlGF ratio as outcome predictor in twin pregnancies.

Role of sFlt-1/PIGF ratio and uterine Doppler in pregnancies with chronic kidney disease suspected with Pre-eclampsia or HELLP syndrome.

PURPOSE: Pregnancies of women with chronic kidney disease (CKD) are at higher risk of experiencing adverse perinatal (APO) and maternal outcome (AMO). Mean uterine artery pulsatility index (mUtA-PI) as well as the ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are helpful tools in diagnosing pre-eclampsia (PE) in women with CKD. The aim of the study was to evaluate the role of sFlt-1/PIGF ratio and mUtA-PI as predictors for APO, AMO, preterm delivery and decline of kidney function in CKD pregnancies. METHODS: A total of 28 CKD pregnancies with suspected PE/HELLP syndrome were retrospectively included, in whom both sFlt-1/PIGF and mUtA-PI were determined during the third trimester. APO was defined as fetal growth restriction, respiratory distress syndrome, intubation, admission to NICU, 5 min Apgar <7 and intracerebral hemorrhage. AMO was defined as the development of PE, HELLP syndrome or resistant hypertension. Decline of kidney function was defined as a 25% increase of creatinine level after delivery. RESULTS: Of all included women, eight (28.6%) developed a PE/HELLP syndrome. AMO (28.6%) and APO (32.1%) were frequently observed. ROC analyses revealed a predictive value for AMO and sFlt-1/PIGF or mUtA-PI. Neither sFlt-1/PIGF nor mUtA-PI could predict APO or decline of postnatal kidney function. mUtA-PI was a predictor for preterm delivery. CONCLUSION: Uterine Doppler and sFlt-1/PIGF are predictors of AMO in CKD pregnancies. Therefore, both markers might be helpful for an improved risk assessment. However, neither sFlt-1/PIGF nor mUtA-PI were able to predict a decline of postnatal kidney function or APO.

Role of sFlt-1/PlGF ratio and feto-maternal Doppler for the prediction of adverse perinatal outcome in late-onset pre-eclampsia.

PURPOSE: The sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio and uterine artery Doppler have shown to be helpful in the diagnosis of pre-eclampsia (PE). The predictive value of the cerebroplacental ratio (CPR) regarding adverse perinatal outcome (APO) in low-risk pregnancies is intensively discussed. We evaluated the extent to which sFlt-1/PlGF ratio and feto-maternal Doppler may be useful in predicting APO in singleton pregnancies complicated by late-onset PE and/or HELLP syndrome. METHODS: This is a retrospective study from 2010 to 2018 consisting of singleton pregnancies with confirmed diagnosis of late-onset (lo ≥ 34 weeks) PE/HELLP syndrome in which sFlt-1/PlGF ratio and feto-maternal Doppler (mUtA-PI: mean uterine artery pulsatility index and CPR) were determined. The ability of sFlt-1/PlGF ratio, mUtA-PI, CPR and their combination to predict APO or SGA was evaluated using receiver operating characteristic (ROC) curves. RESULTS: 67 patients were included in the final analysis. Of these, sFlt-1/PlGF was > 110 (defining angiogenic lo PE) in 40.3% (27/67), mUtA-PI was above the 95th centile in 34.3% (23/67) patients and CPR was lower than the 5th centile in 10.4% (7/67). Abnormal sFlt-1/PlGF and mUtA-PI as well as CPR were associated with a lower birth weight (BW). Late-preterm birth (< 37 weeks) as well as postnatal diagnosis of small for gestational age (SGA: BW < 3rd centile) was significantly more often in angiogenic lo PE cases. Neither sFlt-1/PIGF nor CPR or mUtA-PI were APO predictors. Only for sFlt-1/PlGF, ROC analysis revealed a significant predictive value for postnatal SGA (AUC = 0.856, p = 0.001, 95% CI 0.75-0.97). There was no statistical added value of combined SGA predictors as compared to sFlt-1/PlGF alone. CONCLUSIONS: In patients with lo PE, adding sFlt-1/PlGF ratio to routine antepartum fetal surveillance may be useful to identify cases of postnatal SGA. However, further prospective studies are warranted to define the role of feto-maternal Doppler and sFlt-1/PlGF ratio as outcome predictors.

[Maternal Tumor Disease as a Reason for Repeated Test Failure in Cell-Free DNA Screening]. / Mütterliches Malignom in der Schwangerschaft als Ursache eines wiederholten Testversagens im nicht-invasiven Pränataltest.

Noninvasive prenatal testing (NIPT) is a screening test for fetal chromosome disorders. Recent studies show an incidental detection of maternal malignancies in NIPT diagnostics, where the simultaneous presence of multiple aneuploidies is described as an NIPT "anomaly". In this case, the diagnosis of a maternal tumor disease was made due to a repeat NIPT failure (no call).

Application of the INTERGROWTH-21st chart compared to customized growth charts in fetuses with left heart obstruction: late trimester biometry, cerebroplacental hemodynamics and perinatal outcome.

PURPOSE: Birth weight (BW) is crucial for surgical outcome in children with left heart obstruction (LHO). Head circumference (HC) is believed to correlate with the neurocognitive outcome in LHO. Our aim was to investigate the application of international standardized growth charts from the INTERGROWTH-21st project in comparison to customized growth charts in fetal LHO. METHODS: This is a retrospective cohort study consisting of 60 singleton pregnancies complicated by fetal LHO. For the z score calculation of estimated fetal weight (EFW) and biometric parameters, the INTERGROWTH-21st calculator was used as well as algorithms of customized growth charts. Antenatal measurements were compared to newborn biometry and the association with fetal Doppler results (MCA PI: middle cerebral artery pulsatility index and CPR: cerebroplacental ratio) was examined. Furthermore, the ability of each antenatal chart to predict adverse perinatal outcome was evaluated. RESULTS: At a mean gestational age of 37 weeks, all assessment charts showed significantly smaller mean values for antenatal head circumference (HC) z scores. Highest detection rate for restricted HC growth antenatally was achieved with Hadlock charts. MCA PI and CPR were not associated with neonatal HC. A significant association was observed between EFW and 1-year survival, independent of the considered growth chart. CONCLUSIONS: Growth chart independently, antenatal HC did tend to be smaller in LHO fetuses. A significant association was observed between EFW and 1-year survival rate. Prospective investigations in CHD fetuses should be carried out with internationally standardized growth charts to better examine their prognostic value in this high-risk population.

sFlt-1/PlGF ratio for the prediction of the time of delivery.

PURPOSE: The soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio has been shown to be a useful parameter for the diagnosis and prediction of preeclampsia (PE). An increased sFlt-1/PlGF ratio can be closely linked to the need to deliver. The aim of the study was to examine the mean time until delivery (MTUD) in pregnant women with a strongly increased sFlt-1/PlGF ratio. METHODS: From 2010 to 2018, the sFlt-1/PlGF ratio was determined in 995 singleton pregnancies with diagnosis or suspicion of PE/HELLP syndrome and/or intrauterine growth restriction (IUGR). MTUD of patients with a value above 655 in < 34 weeks of gestation (group 1: n = 13) and above 201 in ≥ 34 weeks of gestation (group 2: n = 15) was calculated. Patients with a value > 85 but < 655 in < 34 weeks of gestation (group 3: n = 70) and a value > 110 but < 201 (group 4: n = 44) in ≥ 34 weeks of gestation acted as controls. RESULTS: 28 pregnant women with severely elevated sFlt-1/PlGF ratio and 114 controls were included. In group 1, MTUD was longer compared to group 2 without reaching statistical significance (96.7 h ± 132.2 vs. 47.7 h ± 44, p = 0.222). In pregnancies < 34 weeks of gestation (early onset), MTUD was significantly longer in group 3 compared to group 1 (361 h ± 317.3 vs. 96.7 h ± 132.2, p < 0.001). In pregnancies ≥ 34 weeks of gestation (late onset), MTUD was significantly longer in group 4 compared to group 2 (123.6 h ± 139.2 vs. 47.7 h ± 44, p = 0.002). CONCLUSIONS: The sFlt-1/PlGF ratio is suitable for decision-making regarding close monitoring of high-risk patients and need for lung maturation. However, for planning of delivery itself further prospective interventional studies are required to define its role as outcome predictor.

Induction of cathepsin B by the CXCR3 chemokines CXCL9 and CXCL10 in human breast cancer cells.

Cathepsin B (CTSB) is a lysosomal cysteine protease that has been linked to the progression of breast cancer, for example by activation of other proteases and tumor-promoting cytokines, thereby supporting tumor invasion and metastasis. Previously, it was shown that CTSB cleaves and inactivates C-X-C motif chemokine receptor 3 (CXCR3) chemokines. As CXCR3 ligands have been demonstrated to induce proteases in cancer cells, the present study hypothesized that they may also affect CTSB in breast cancer cells. The results demonstrated that the human breast cancer tumor cell lines MCF-7 and MDA-MB-231 express the CXCR3 splice variants A and B and CTSB. Upon binding to CXCR3, the two chemokine ligands C-X-C motif chemokine ligand (CXCL) 9 and CXCL10 trigger upregulation of CTSB in these breast cancer cells, whereas the CXCR3-B-specific ligand CXCL4 has no such effect, suggesting the involvement of CXCR3-A in the regulation of CTSB. In early-stage human breast cancer specimens (n=81), overexpression of CXCR3 is associated with statistically significant poorer overall survival, independent of lymph node status, tumor size and nuclear grading (hazard ratio=1.99; 95% confidence interval=1.00-3.97; P=0.050). In conclusion, the data from the current study propose a so far unknown mechanism by which breast cancer cells may exploit tumor-suppressive chemokines to enhance their invasiveness and reduce immune cell infiltration by the degradation of these chemokines. This mechanism may support the established unfavorable prognostic feature of CXCR3 expression in breast cancer.