Laparoscopic Transabdominal Needle-free Emergency Cerclage in the Early Second Trimester of Pregnancy after Failed Transvaginal Cerclage: Two Case Reports and a Review of the Literature.

Purpose: The aim of the study was to describe the preventive option and safety of laparoscopic transabdominal emergency cerclage in pregnant women with advanced cervical shortening after failed vaginal cerclage or in whom vaginal cerclage is no longer possible. Method: Laparoscopic isthmo-cervical emergency cerclage was carried out in two patients at 13+0 and 15+5 weeks of gestation (GW) respectively. Both patients had cervical shortening and it was no longer possible to expose the cervix after conization or re-conization. The attempts to carry out transvaginal cerclage were unsuccessful. The technical aspects, feasibility, safety, and pregnancy outcomes after laparoscopic transabdominal cerclage are presented here, based on two case reports. Results: The cerclages were placed after blunt dissection of the uterine vessels and careful introduction of a KELLY forceps through the avascular space between the ascending and descending branches of the uterine vessels without using a needle. The operating times were 93 and 134 minutes (min), respectively. The estimated blood loss during the procedure was less than 50 ml and neither perioperative nor postoperative complications occurred. The subsequent course of both pregnancies was uneventful and fetal development in both cases was normal. In the first case, the baby was delivered by secondary cesarean section following premature rupture of membranes in week 35+4 of gestation. The baby had a birthweight of 2786 g, APGAR scores of 8/9/10 and an umbilical cord arterial pH of 7.36. In the second case, delivery was by primary cesarean section in week 39+5 of gestation. The infant had a birth weight of 4160 g, APGAR scores of 5/9/10 and an umbilical cord arterial pH of 7.20. Conclusion: Laparoscopic transabdominal cerclage is a safe and effective treatment option, even early in the second trimester of pregnancy, for patients in whom transvaginal cerclage is no longer possible due to anatomical factors. The method is technically very feasible and is associated with positive obstetric outcomes. The overall risk of perioperative complications is within acceptable limits.

The risk of intraoperative venous air embolism from neurosurgical procedures performed in the lounging position: an in-depth analysis of detection, management, and outcomes of 1000 consecutive cases.

OBJECTIVE: The overall benefit of employing a sitting/semisitting position for neurosurgical procedures remains under criticism due to concerns for additional risk, especially the risk of intraoperative venous air embolism (VAE). The aim of this single-center cohort study was to evaluate the frequency and severity of VAEs and associated complications in patients undergoing neurosurgery in the lounging position. METHODS: From 2010 to 2020, 1000 patients, including 172 patients with a patent foramen ovale, underwent surgery in the lounging position for different neurosurgical pathologies. All patients were monitored intraoperatively using continuous transesophageal echocardiography (TEE). The anesthesia team documented any observed incidences of VAEs and scored their severity according to the Tuebingen classification system (TCS) for VAE (TCS-VAE). The patients' clinical condition, radiological findings, and hospital course were subsequently analyzed to assess complications in a retrospective analysis of prospectively collected data. RESULTS: In the cohort of 1000 patients, 5 underwent cervical spine surgery and 995 underwent suboccipital craniotomy. VAE was detected by TEE in 51.4% (95% CI 48.4%-54.5%) of patients, with synchronous changes in end-tidal CO2 (grade 2-5 TCS-VAE) noted in 10.2% (95% CI 8.3%-12.3%). None of the patients presented with hemodynamic instability (grade 5 TCS-VAE). Patients with high-grade VAEs were significantly older (p = 0.02) and had lower BMIs (p = 0.001) than the respective mean value of the cohort. VAE grade was not associated with any of the outcome measures such as Karnofsky Performance Scale score, duration of ventilation, length of intensive care unit stay, and length of hospital stay. Postoperative acute respiratory distress syndrome (ARDS) was diagnosed in 0.3% (95% CI 0.0%-0.7%, n = 3) of all cases, and ARDS was associated with perioperative VAE grade (p = 0.001). No patient suffered a new permanent neurological deficit due to a paradoxical VAE. CONCLUSIONS: In this large cohort, the risk of an intraoperative VAE during neurosurgery in the lounging position was assessed, and contrary to the general perception in the field, no permanent sequelae or fatal adverse events attributable to VAEs were observed. Furthermore, the overall incidence of ARDS was very low. This study clearly establishes that experienced interdisciplinary teams can safely use the lounging position for neurosurgical procedures.

A Comparison of ChatGPT and Multidisciplinary Team Meeting Treatment Recommendations in 10 Consecutive Cervical Cancer Patients.

Background The preparation of multidisciplinary team (MDT) meetings can be time-consuming. In addition to the clinical data being available digitally in subsystems, the preparation of more complex cases requires literature research. Several expert systems have been developed to support this process. However, the interaction with these systems has to be trained. Current development enables linguistic interaction with such artificial intelligence (AI) systems. To the best of our knowledge, these have not been tested as premedical screening tools for MDT. Methods This is a retrospective consecutive case series of 10 cervical cancer cases comparing the medical recommendations of the MDT and artificial intelligence (AI) on a low level (i.e., surgery, systemic treatment, and radiotherapy). Results The clinical cases ranged from primary diagnosis via suspected recurrence to palliative settings. The AI repeatedly stated that medical professionals need to be consulted before treatment decisions. The AI answers ranged from no agreement to overachievement by mentioning treatment options for preexisting risk factors (such as obesity). In standard cases, the AI answer matched well with the expert recommendations. In some cases, the AI answers were contrary to our treatment recommendation. Conclusion The interaction with current language AIs is temptingly easy, and the replies are very understandable. Despite the AI warning regarding medical recommendations in the majority of our cases, there was a good match with the MDT recommendations. However, in some cases, the medical evidence behind the answers was missing or in the worst case fictional. In our case series, the AI did not meet the requirements to support a clinical MDT meeting by prescreening the therapeutic options. However, it did exceed the expectations regarding the risk factors of the patients.

Cystic vestibular schwannoma - a subgroup analysis from a comparative study between radiosurgery and microsurgery.

Some vestibular schwannoma (VS) show cystic morphology. It is known that these cystic VS bear different risk profiles compared to solid VS in surgical treatment. Still, there has not been a direct comparative study comparing both SRS and SURGERY effectiveness in cystic VS. This retrospective bi-center cohort study aims to analyze the management of cystic VS compared to solid VS in a dual center study with both microsurgery (SURGERY) and stereotactic radiosurgery (SRS). Cystic morphology was defined as presence of any T2-hyperintense and Gadolinium-contrast-negative cyst of any size in the pre-interventional MRI. A matched subgroup analysis was carried out by determining a subgroup of matched SURGERY-treated solid VS and SRS-treated solid VS. Functional status, and post-interventional tumor volume size was then compared. From 2005 to 2011, N = 901 patients with primary and solitary VS were treated in both study sites. Of these, 6% showed cystic morphology. The incidence of cystic VS increased with tumor size: 1.75% in Koos I, 4.07% in Koos II, 4.84% in Koos III, and the highest incidence with 15.43% in Koos IV. Shunt-Dependency was significantly more often in cystic VS compared to solid VS (p = 0.024) and patients with cystic VS presented with significantly worse Charlson Comorbidity Index (CCI) compared to solid VS (p < 0.001). The rate of GTR was 87% in cystic VS and therefore significantly lower, compared to 96% in solid VS (p = 0.037). The incidence of dynamic volume change (decrease and increase) after SRS was significantly more common in cystic VS compared to the matched solid VS (p = 0.042). The incidence of tumor progression with SRS in cystic VS was 25%. When comparing EOR in the SURGERY-treated cystic to solid VS, the rate for tumor recurrence was significantly lower in GTR with 4% compared to STR with 50% (p = 0.042). Tumor control in cystic VS is superior in SURGERY, when treated with a high extent of resection grade, compared to SRS. Therapeutic response of SRS was worse in cystic compared to solid VS. However, when cystic VS was treated surgically, the rate of GTR is lower compared to the overall, and solid VS cohort. The significantly higher number of patients with relevant post-operative facial palsy in cystic VS is accredited to the increased tumor size not its sole cystic morphology. Cystic VS should be surgically treated in specialized centers.

Three-dimensional model for improvement of endometriosis care (3D-E).

OBJECTIVE: Endometriosis affects approximately 10% of women of reproductive age and leads to significant morbidity and financial burden. Consequently, countries such as France and Germany are formulating strategies to combat endometriosis. In this study, we propose the implementation of our three-dimensional model (3D-E) to raise awareness about endometriosis and enhance timely diagnosis, treatment, and long-term care for affected patients. METHODS: Based on the adapted Six Sigma Principle and the modified recommendation of Sales et al. for implementing evidence-based findings into a clinical routine, we first conducted a comprehensive investigation to identify risk factors leading to diagnostic delay of endometriosis. After identifying improvable factors, the applicable options were selected due to defined criteria such as integrability in the clinical routine, cost-effectiveness, and evidence-based-principle. Finally, solutions feasible for health care providers were integrated and the 3D-E model was established. RESULTS: Some of the main risk factors contributing to diagnostic delays are symptoms acceptance and misinterpreted symptoms, especially if presenting to nongynecologists in cases of extragenital endometriosis with atypical presentation. Therefore, we tried to sensitize colleagues (first dimension) with a review paper in Germany's largest medical journal and started an elective for medical students (second dimension) at our university. In order to involve additional health care professionals in endometriosis care (third dimension), we are preparing the concept of the EndoNurse. CONCLUSION: The 3D-E model is a relatively low-cost, comprehensive, and worldwide adaptable approach for facilitating knowledge transfer, sensitizing health care providers, and improving endometriosis diagnostics and therapy for patients with endometriosis who are in the center of the model.

Effect of histological breast cancer subtypes invasive lobular versus non-special type on survival in early intermediate-to-high-risk breast carcinoma: results from the SUCCESS trials.

BACKGROUND: Invasive lobular breast carcinomas (ILC) have different histological features compared to non-special type carcinomas (NST), but the effect of histological subtypes on survival is controversial. In this study, we compared clinicopathological characteristics and outcomes between ILC and NST based on a large pooled data set from three adjuvant breast cancer trials (SUCCESS A, B, and C) and investigated a potential differential effect of recurrence risk related to nodal stage on survival. METHODS: From 2005 to 2017, the large randomized controlled SUCCESS A, B, and C trials enrolled 8190 patients with primary, intermediate-to-high-risk breast carcinoma. All patients received adjuvant chemotherapy, and endocrine and/or HER2-targeted treatment was given where appropriate. Survival outcomes in terms of disease-free survival (DFS), overall survival (OS), breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) were estimated using the Kaplan-Meier method and analyzed using log-rank tests as well as univariable and adjusted multivariable Cox regression models. RESULTS: In the SUCCESS trials, 6284 patients had NST and 952 had ILC. The median follow-up time was 64 months. ILC patients were older, more likely to receive mastectomy, and more likely to have larger tumor sizes, lymph node infiltration, hormone receptor-positive, HER2neu-negative, and luminal A-like tumors than NST patients. In the overall cohort, no significant differences between ILC and NST were detectable regarding the four survival endpoints, with hazard ratios obtained in adjusted multivariable cox regressions of 0.96 (95% CI 0.77-1.21, p = 0.743) for DFS, 1.13 (95% CI 0.85-1.50, p = 0.414) for OS, 1.21 (95% CI 0.89-1.66, p = 0.229) for BCSS, and 0.95 (95% CI 0.73-1.24, p = 0.689) for DDFS. However, a differential effect of nodal stage on survival was observed, with better survival for ILC patients with pN0/pN1 tumors and worse survival for ILC patients with pN2/pN3 tumors compared to NST patients. CONCLUSIONS: Our results revealed that ILC was associated with worse survival compared to NST for patients at high risk of recurrence due to advanced lymph node infiltration. These findings should be taken into account for treatment decisions and monitoring.

Quantitative Anatomical Comparison of Surgical Approaches to Meckel's Cave.

BACKGROUND: Meckel's cave is a challenging surgical target due to its deep location and proximity to vital neurovascular structures. Surgeons have developed various microsurgical transcranial approaches (MTAs) to access it, but there is no consensus on the best method. Newer endoscopic approaches have also emerged. This study seeks to quantitatively compare these surgical approaches to Meckel's cave, offering insights into surgical volumes and exposure areas. METHODS: Fifteen surgical approaches were performed bilaterally in six specimens, including the pterional approach (PTA), fronto-temporal-orbito-zygomatic approach (FTOZA), subtemporal approach (STA), Kawase approach (KWA), retrosigmoid approach (RSA), retrosigmoid approach with suprameatal extension (RSAS), endoscopic endonasal transpterygoid approach (EETPA), inferolateral transorbital approach (ILTEA) and superior eyelid approach (SEYA). All the MTAs were performed both with 10 mm and 15 mm of brain retraction, to consider different percentages of surface exposure. A dedicated navigation system was used to quantify the surgical working volumes and exposure of different areas of Meckel's cave (ApproachViewer, part of GTx-Eyes II, University Health Network, Toronto, Canada). Microsurgical transcranial approaches were quantified with two different degrees of brain retraction (10 mm and 15 mm). Statistical analysis was performed using a mixed linear model with bootstrap resampling. RESULTS: The RSAS with 15 mm of retraction offered the maximum exposure of the trigeminal stem (TS). If compared to the KWA, the RSA exposed more of the TS (69% vs. 46%; p = 0.01). The EETPA and ILTEA exposed the Gasserian ganglion (GG) mainly in the anteromedial portion, but with a significant 20% gain in exposure provided by the EETPA compared to ILTEA (42% vs. 22%; p = 0.06). The STA with 15 mm of retraction offered the maximum exposure of the GG, with a significant gain in exposure compared to the STA with 10 mm of retraction (50% vs. 35%; p = 0.03). The medial part of the three trigeminal branches was mainly exposed by the EETPA, particularly for the ophthalmic (66%) and maxillary (83%) nerves. The EETPA offered the maximum exposure of the medial part of the mandibular nerve, with a significant gain in exposure compared to the ILTEA (42% vs. 11%; p = 0.01) and the SEY (42% vs. 2%; p = 0.01). The FTOZA offered the maximum exposure of the lateral part of the ophthalmic nerve, with a significant gain of 67% (p = 0.03) and 48% (p = 0.04) in exposure compared to the PTA and STA, respectively. The STA with 15 mm of retraction offered the maximum exposure of the lateral part of the maxillary nerve, with a significant gain in exposure compared to the STA with 10 mm of retraction (58% vs. 45%; p = 0.04). The STA with 15 mm of retraction provided a significant exposure gain of 23% for the lateral part of the mandibular nerve compared to FTOZA with 15 mm of retraction (p = 0.03). CONCLUSIONS: The endoscopic approaches, through the endonasal and transorbital routes, can provide adequate exposure of Meckel's cave, especially for its more medial portions, bypassing the impediment of major neurovascular structures and significant brain retraction. As far as the most lateral portion of Meckel's cave, MTA approaches still seem to be the gold standard in obtaining optimal exposure and adequate surgical volumes.

A comparative study of microsurgery and gamma knife radiosurgery in vestibular schwannoma evaluating tumor control and functional outcome.

Background: Both stereotactic radiosurgery (SRS) and microsurgical resection (SURGERY) are available as treatment options for sporadic vestibular schwannoma (VS). There are very few direct comparative studies comparing both treatment modalities in large cohorts allowing detailed subgroup analysis. This present study aimed to compare the nuances in the treatment of VS by SURGERY and SRS in 2 highly specialized neurosurgical centers. Methods: This is a retrospective bicentric cohort study. Data from patients treated between 2005 and 2011 were collected retrospectively. Recurrence-free survival (RFS) was assessed radiographically by contrast-enhanced magnetic resonance imaging. Results: The study population included N = 901 patients with a mean follow-up of 7 years. Overall, the incidence of recurrence was 7% after SURGERY, and 11% after SRS with superior tumor control in SURGERY in the Kaplan-Meier-analysis (P = 0.031). In small tumors (Koos I and II), tumor control was equivalent in both treatment arms. In large VS (Koos III and IV), however, RFS was superior in SURGERY. The extent of resection correlated with RFS (P < .001). Facial and hearing deterioration was similar in both treatment arms in small VS, but more pronounced in SURGERY of large VS. Tinnitus, vertigo, imbalance, and trigeminal symptoms were more often improved by SURGERY than SRS. Conclusions: SRS can achieve similar tumor control compared to SURGERY in smaller VS (Koos I and II)-with similar postinterventional morbidities. In large VS (Koos III and IV), long-term tumor control of SRS is inferior to SURGERY. Based on these results, we suggest that if combination therapy is chosen, the residual tumor should not exceed the size of Koos II.

Evaluating ChatGPT as an adjunct for the multidisciplinary tumor board decision-making in primary breast cancer cases.

BACKGROUND: As the available information about breast cancer is growing every day, the decision-making process for the therapy is getting more complex. ChatGPT as a transformer-based language model possesses the ability to write scientific articles and pass medical exams. But is it able to support the multidisciplinary tumor board (MDT) in the planning of the therapy of patients with breast cancer? MATERIAL AND METHODS: We performed a pilot study on 10 consecutive cases of breast cancer patients discussed in MDT at our department in January 2023. Included were patients with a primary diagnosis of early breast cancer. The recommendation of MDT was compared with the recommendation of the ChatGPT for particular patients and the clinical score of the agreement was calculated. RESULTS: Results showed that ChatGPT provided mostly general answers regarding chemotherapy, breast surgery, radiation therapy, chemotherapy, and antibody therapy. It was able to identify risk factors for hereditary breast cancer and point out the elderly patient indicated for chemotherapy to evaluate the cost/benefit effect. ChatGPT wrongly identified the patient with Her2 1 + and 2 + (FISH negative) as in need of therapy with an antibody and called endocrine therapy "hormonal treatment". CONCLUSIONS: Support of artificial intelligence by finding individualized and personalized therapy for our patients in the time of rapidly expanding amount of information is looking for the ways in the clinical routine. ChatGPT has the potential to find its spot in clinical medicine, but the current version is not able to provide specific recommendations for the therapy of patients with primary breast cancer.

Musculoskeletal demands in microsurgery-an explorative study comparing the ergonomics of microscope and 3D exoscope.

To assess neurosurgeons' physical demands and investigate ergonomic aspects when using microsurgical visualization devices. Six neurosurgeons performed micro-surgical procedures on cadaveric specimens using the prototype of a digital 3D exoscope system (Aeos®, Aesculap, Tuttlingen, Germany) and a standard operating microscope (Pentero 900, Zeiss, Oberkochen, Germany) at two different patient positions (semisitting (SS), supine (SP)). The activities of the bilateral upper trapezius (UTM), anterior deltoid (ADM), and lumbar erector spinae (LEM) muscles were recorded using bipolar surface electromyography and neck flexion, arm abduction, and arm anteversion angles by gravimetrical posture sensors. Perceived discomfort frequency was assessed and subjects compared the two systems in terms of usability, posture, physical and mental demands, and working precision. Using the exoscope led to reduced ADM activity and increased UTM and LEM activity during SS position. The neck was extended when using the exoscope system with lower arm anteversion and abduction angles during the SS position. Subjects reported discomfort at the shoulder-neck area less frequently and lower physical demands when using the Aeos®. However, mental demands were slightly higher and two subjects reported lower working precision. The exoscope system has the potential to reduce the activity of the ADM by changing surgeons arm posture which may be accompanied by less discomfort in the shoulder-neck area. However, dependent on the applied patient position higher muscle activities could occur in the UTM and LEM.

Association of extent of resection on recurrence-free survival and functional outcome in vestibular schwannoma of the elderly.

Background: Despite the ongoing debate on the risk-benefit ratio of vestibular schwannoma (VS) treatment options, watchful observation and radiation are usually favored in the elderly (>65 years). If surgery is inevitable, a multimodal approach after deliberate subtotal resection has been described as a valid option. The relationship between the extent of resection (EOR) of surgical and functional outcomes and recurrence-free survival (RFS) remains unclear. This present study aims to evaluate the functional outcome and RFS of the elderly in relation to the EOR. Methods: This matched cohort study analyzed all consecutive elderly VS patients treated at a tertiary referral center since 2005. A separate cohort (<65 years) served as a matched control group (young). Clinical status was assessed by the Charlson Comorbidity Index (CCI), the Karnofsky Performance (KPS), and the Gardner and Robertson (GR) and House & Brackmann (H&B) scales. RFS was evaluated by Kaplan-Meier analysis using contrast-enhanced magnetic resonance imaging to identify tumor recurrence. Results: Among 2,191 patients, 296 (14%) patients were classified as elderly, of whom 133 (41%) were treated surgically. The elderly were characterized by a higher preoperative morbidity and worse gait uncertainty. Postoperative mortality (0.8% and 1%), morbidity (13% and 14%), and the functional outcome (G&R, H&B, and KPS) did not differ between the elderly and the young. There was a significant benefit in regard to the preoperative imbalance. Gross total resection (GTR) was accomplished in 74% of all cases. Lower grades of the EOR (subtotal and decompressive surgery) raised the incidence of recurrence significantly. Mean time to recurrence in the surgELDERLY was 67.33 ± 42.02 months and 63.2 ± 70.98 months in the surgCONTROL. Conclusions: Surgical VS treatment aiming for complete tumor resection is feasible and safe, even in advanced age. A higher EOR is not associated with cranial nerve deterioration in the elderly compared to the young. In contrast, the EOR determines RFS and the incidence of recurrence/progression in both study cohorts. If surgery is indicated in the elderly, GTR can be intended safely, and if only subtotal resection is achieved, further adjuvant therapy, e.g., radiotherapy, should be discussed in the elderly, as the incidence of recurrence is not significantly lower compared to the young.

Implications for surveillance for breast cancer patients based on the internally and externally validated BRENDA-metastatic recurrence score.

PURPOSE: Although the incidence of distant relapse is decreasing, 20-30% of patients with early breast cancer die of metastasis. The aim of this study is to characterize patients with metastasis-free survival(MFS) less than 5 years, to analyze the most probable site of metastases according to the internally and externally validated BRENDA-score. The BRENDA-score is a combination of the biological subtype and clinical staging. METHOD: 3832 patients with primary diagnosis of breast cancer and either distant metastatic recurrence within 5 years or MFS ≥ 5 years were assigned to this study. Patients were classified for metastatic recurrence according to the BRENDA-score. 1765 patients were in a validation set. Statistical methods were Kaplan-Meier curves, Cox regression analysis, Exhausted CHAID, likelihood-ratio tests and the Nearest Neighbor Estimation method. RESULTS: There was a significant(p < 0.001) difference between the Kaplan-Meier MFS-functions of M0-patients stratified by BRENDA-score. The BRENDA score outperforms intrinsic subtypes and the Nottingham prognostic score. It fits the original data and the validation set equally well (p = 0.179).There was a significant(p < 0.001) difference between mean BRENDA-Index for patients with MFS < 5y(21.0 ± 9.0) and patients with MFS ≥ 5y(mean BRENDA-Index 11.7 ± 8.2). 55.6% of the very high risk patients(BRENDA-Index ≥ 27) had metastases within 5 years. The most likely primary metastatic site was bone(30%) followed by liver(19%) and lung(18%). The discriminatory ability(areas under the time dependent ROC curve) of the BRENDA score is good to acceptable for the first 5 years. In the very low/low risk (intermediate, high/very high) risk group 50% of all metastases were diagnosed within 26 months. Guideline adherence had a highly significant influence on outcome independent of the risk group. CONCLUSION: The evaluation showed that the BRENDA-Score is a robust predictive tool for breast cancer recurrence and site of metastases in the first five years after diagnosis. It outperforms intrinsic subtypes and the Nottingham prognostic score. The BRENDA-score could be a tool for a risk orientated and targeted follow up.

Pharmacodynamic and Antitumor Activity of BI 836880, a Dual Vascular Endothelial Growth Factor and Angiopoietin 2 Inhibitor, Alone and Combined with Programmed Cell Death Protein-1 Inhibition.

Vascular endothelial growth factor (VEGF) and angiopoietin (ANG)-2 have complementary roles in angiogenesis and promote an immunosuppressive tumor microenvironment. It is anticipated that the combination of VEGF and ANG2 blockade could provide superior activity to the blockade of either pathway alone and that the addition of VEGF/ANG2 inhibition to an anti-programmed cell death protein-1 (PD-1) antibody could change the tumor microenvironment to support T-cell-mediated tumor cytotoxicity. Here, we describe the pharmacologic and antitumor activity of BI 836880, a humanized bispecific nanobody comprising two single-variable domains blocking VEGF and ANG2, and an additional module for half-life extension in vivo. BI 836880 demonstrated high affinity and selectivity for human VEGF-A and ANG2, resulting in inhibition of the downstream signaling of VEGF/ANG2 and a decrease in endothelial cell proliferation and survival. In vivo, BI 836880 exhibited significant antitumor activity in all patient-derived xenograft models tested, showing significantly greater tumor growth inhibition (TGI) than bevacizumab (VEGF inhibition) and AMG386 (ANG1/2 inhibition) in a range of models. In a Lewis lung carcinoma syngeneic tumor model, the combination of PD-1 inhibition with VEGF inhibition showed superior efficacy versus the blockade of either pathway alone. TGI was further increased with the addition of ANG2 inhibition to VEGF/PD-1 blockade. VEGF/ANG2 inhibition had a strong antiangiogenic effect. Our data suggest that the blockade of VEGF and ANG2 with BI 836880 may offer improved antitumor activity versus the blockade of either pathway alone and that combining VEGF/ANG2 inhibition with PD-1 blockade can further enhance antitumor effects. SIGNIFICANCE STATEMENT: Vascular endothelial growth factor (VEGF) and angiopoietin (ANG)-2 play key roles in angiogenesis and have an immunosuppressive effect in the tumor microenvironment. This study shows that BI 836880, a bispecific nanobody targeting VEGF and ANG2, demonstrates substantial antitumor activity in preclinical models. Combining VEGF/ANG2 inhibition with the blockade of the PD-1 pathway can further improve antitumor activity.

Resemblance of the Recurrence Patterns in Primary Systemic, Primary Surgery and Secondary Oncoplastic Surgery.

PURPOSE: Surgical interventions tend to have an effect on the generation of recurrences in tumor patients due to the anesthesia involved as well as tissue damage and subsequent inflammation. This can also be found in patients with breast cancer. METHODS: In this multicenter study, we investigated data of 632 patients with breast cancer and the subsequent diagnosis of a recurrence. The patient data were acquired from 1 January 2006 to 31 December 2019 in eight different centers in Germany. The data sets were separated into those with primary surgery, primary systemic therapy with subsequent surgery, and reconstructive surgery. Three different starting points for observation were defined: the date of diagnosis, the date of first surgery, and the date of reconstructive surgery, if applicable. The observational period was divided into steps of six months and maxima of recurrences were compared. Furthermore, the variance was calculated using the difference of the distribution in percent. RESULTS: The descriptive analysis showed no resemblance between the groups. The variance of the difference of the recurrence rates analysis using the surgical date as the starting point showed similarities in the age subgroup. CONCLUSION: Our clinical analysis shows different metastatic behavior in different analysis and treatment regimes. These findings justify further investigations on a larger database. These results may possibly identify an improved follow-up setting depending on tumor stage, biology, treatment, and patient factors (i.e., age, …).

Oxygen targets and 6-month outcome after out of hospital cardiac arrest: a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial.

BACKGROUND: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients' outcome. METHODS: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. RESULTS: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93-1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95-1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). CONCLUSIONS: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. TRIAL REGISTRATION: clinicaltrials.gov NCT02908308 , Registered September 20, 2016.

Mobile Applications Available in Germany Supporting Breast Cancer Patients During Treatment and Aftercare: a Systematic Review.

Purpose Systematic evaluation of health apps designed to support and aid remote monitoring of patients during breast cancer treatment and aftercare. Method A systematic search and assessment of apps was conducted using search terms: breast cancer; breast cancer therapy; and breast cancer aftercare. Evaluation criteria were user assessments, scientifically published benefits, user-friendliness, data protection, app individualization, motivation, and financial aspects. Up to two points (P) could be awarded per criterion. The lowest possible score was 0P and the maximum was 28P. Three examiners from different institutions independently assessed the apps according to the specified criteria. Reference value was defined as the average value given by the examiners. Apps with > 18P were classified as "recommended"; ≥ 11-≤ 18P as "partially recommended" and ≤ 10P as "not recommended". Results A total of 776 apps (n = 24 from the Apple App Store, n = 752 from the Google Play Store) were identified via search query. After applying exclusion criteria, 36 apps (n = 1 from the Apple App Store; n = 35 from the Google Play Store) were evaluated. Using the mean point values of the examiners, 20 apps were classified as not recommended and 12 as partially recommended (≥ 11-≤ 18P). Four apps were rated partially recommended by two examiners and recommended by one examiner. Three apps were rated as recommended by all examiners. Conclusion Only a small minority of available apps meet recommendation criteria. Use of these apps may benefit breast cancer patients.

FSFI score and timing of tubal ligation in patients: preliminary results of an online survey.

INTRODUCTION: Tubal ligation is the most common contraceptive method worldwide. Apart from a very low pearl index and anxiety relief, other benefits are not commonly recognised. In young patients, there is the post-operative risk of regretting the decision with the need for In-Vitro-Fertilisation or refertilising surgery. Positive side effects have not been widely published. In our study we investigated the change in the female sexual function index score after tubal ligation. MATERIAL AND METHOD: In this survey the FSFI score of participants around the time of the tubal ligation was compared with the FSFI score of intermediate and long-term time distance to the ligation. RESULTS: The data indicate an increase in younger women seeking information on permanent contraception and whilst the FSFI score of the early group indicates a risk of female sexual dysfunction, the intermediate and long-term FSFI scores are comparable to published control groups. DISCUSSION: Besides the obvious benefit of a low pearl index, tubal ligation may contribute to reduce the risk of female sexual dysfunction in the mid and long term. Informed consent is essential for the surgeon and patient to weigh up the risks and benefits individually including possible future perspectives on family planning.

Effects of Transcutaneous Electrical Nerve Stimulation on Pain and Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Systematic Review.

Transcutaneous electrical nerve stimulation (TENS) is the usage of a mild electrical current through electrodes that stimulate nerves. Patients with malignancies experience pain and chemotherapy-induced peripheral neuropathy. A systematic review was performed to find research evaluating the effect of TENS on these two common symptoms decreasing the quality of life in cancer patients. PubMed, the Cochrane Central Register of Controlled Trials and EMBASE were searched. Original studies, namely randomized controlled trials, quasi-randomized controlled trials and controlled clinical trials, published between April 2007 and May 2020, were considered. The quality of the selected studies was assessed. Seven papers were incorporated in a qualitative synthesis, with 260 patients in total. The studies varied in terms of design, populations, endpoints, quality, treatment duration, procedures and follow-up period. Based on the results, no strict recommendations concerning TENS usage in the cancer patient population could be issued. However, the existing evidence allows us to state that TENS is a safe procedure that may be self-administered by the patients with malignancy in an attempt to relieve different types of pain. There is a need for multi-center, randomized clinical trials with a good methodological design and adequate sample size.

Scalp Cooling for Prevention of Chemotherapy-Induced Alopecia for Women and Men with Various Cancer Entities: A Two-Year Survey of an Outpatient Cancer Center in Germany.

INTRODUCTION: The aim of this survey was to assess the efficacy and the feasibility of scalp cooling (SC) in an outpatient hematological and oncological center in a real-world setting. METHODS: We prospectively monitored cancer patients from August 2017 to October 2019 receiving oncological treatments with SC, using the sensor-controlled system "DigniCap." Effectiveness was defined by a self-estimated hair loss < Grad 2 (<50%) according to the Common terminology Criteria for adverse events V4.0 or not requiring a wig. Withdrawal from SC on patient's demand was considered as failure. Tolerability and safety were also evaluated. RESULTS: Ninety-four patients with chemotherapy for their primary (52%) or metastatic (48%) disease had a total of 634 SC sessions. SC was well accepted with increasing experience of the nurses (withdrawal for any reason 29/94). Among the female population (N = 85) 54% received a (neo-)adjuvant chemotherapy. Forty-eight percentages received a taxane-based therapy, 35% anthracycline-based, 17% platin compounds, and others. The overall success rate in the female sample was 72%. In the male group (N = 9), the majority had a metastatic disease (6/9) and received a taxane-based therapy (5/9). The rate of withdrawal by discomfort and pain was high, and the success rate was 44%. CONCLUSION: Our study confirms the satisfaction of patients with SC to prevent chemotherapy-induced alopecia. SC increases acceptance of the recommendation and administration of chemotherapy and decreases the degree of distress of patients and their treating physicians. Reimbursement remains a major issue in the out patient setting.