Minerals and the Menstrual Cycle: Impacts on Ovulation and Endometrial Health.

The role of minerals in female fertility, particularly in relation to the menstrual cycle, presents a complex area of study that underscores the interplay between nutrition and reproductive health. This narrative review aims to elucidate the impacts of minerals on key aspects of the reproductive system: hormonal regulation, ovarian function and ovulation, endometrial health, and oxidative stress. Despite the attention given to specific micronutrients in relation to reproductive disorders, there is a noticeable absence of a comprehensive review focusing on the impact of minerals throughout the menstrual cycle on female fertility. This narrative review aims to address this gap by examining the influence of minerals on reproductive health. Each mineral's contribution is explored in detail to provide a clearer picture of its importance in supporting female fertility. This comprehensive analysis not only enhances our knowledge of reproductive health but also offers clinicians valuable insights into potential therapeutic strategies and the recommended intake of minerals to promote female reproductive well-being, considering the menstrual cycle. This review stands as the first to offer such a detailed examination of minerals in the context of the menstrual cycle, aiming to elevate the understanding of their critical role in female fertility and reproductive health.

Trends in ototoxicity monitoring among cisplatin-treated patients with cancer.

PURPOSE: This study aims to characterize patterns in ototoxicity monitoring and identify potential barriers to audiologic follow-up. METHODS: We performed a single-institution retrospective cohort study on adult (≥ 18 years old) cancer patients treated with cisplatin from January 2014 to September 2021. Our primary outcomes were rates of baseline and post-treatment audiograms at the following time points: 3, 6, 12, and greater than 12 months. Time-to-event analyses were performed to describe additional insights to ototoxicity monitoring patterns. RESULTS: Nine hundred fifty-five patients with cancer were included for analysis. The most common primary cancer sites were head and neck (64%), followed by cervical (24%). Three hundred seventy-three patients (39%) underwent baseline audiometric assessment, 38 patients (4%) received audiologic evaluation during chemotherapy, and 346 patients (36%) obtained at least one post-treatment audiogram. Audiologic follow-up was greatest within 3 months of completing chemotherapy (26%), but this tapered dramatically to less than 10% at every other post-treatment time point. Patients with head and neck cancer achieved higher rates of audiologic follow-up at every time point than patients with non-head and neck cancer except for during treatment. CONCLUSIONS: Ototoxicity monitoring is an inconsistent practice, particularly during chemotherapy and for long-term surveillance of hearing loss. Patients with non-head and neck cancer may be at increased risk for loss of audiologic follow-up. IMPLICATIONS FOR CANCER SURVIVORS: Cisplatin ototoxicity is a common occurrence that can be effectively managed with auditory rehabilitation. Therefore, referrals to audiology and counseling on treatment-related ototoxicity are recommended throughout chemotherapy and cancer survivorship.

Radical vaginal trachelectomy: long-term oncologic and fertility outcomes in patients with early cervical cancer.

OBJECTIVE: Radical vaginal trachelectomy is a fertility-preserving treatment for patients with early cervical cancer. Despite encouraging oncologic and fertility outcomes, large studies on radical vaginal trachelectomy are lacking. METHOD: Demographic, histological, fertility, and follow-up data of consecutive patients who underwent radical vaginal trachelectomy between March 1995 and August 2021 were prospectively recorded and retrospectively analyzed. RESULTS: A total of 471 patients of median age 33 years (range 21-44) were included. 83% (n=390) were nulliparous women. Indications were International Federation of Gynecology and Oncology (FIGO, 2009) stages IA1 with lymphvascular space involvement (LVSI) in 43 (9%) patients, IA1 multifocal in 8 (2%), IA2 in 92 (20%), IB1 in 321 (68%), and IB2/IIA in 7 (1%) patients, respectively. LVSI was detected in 31% (n=146). Lymph node staging was performed in 151 patients (32%) by the sentinel node technique with a median of 7 (range 2-14) lymph nodes and in 320 (68%) by systematic lymphadenectomy with a median of 19 (range 10-59) lymph nodes harvested. Residual tumor was histologically confirmed in 29% (n=136). In total, 270 patients (62%) were seeking pregnancy of which 196 (73%) succeeded. There were 205 live births with a median fetal weight of 2345 g (range 680-4010 g). Pre-term delivery occurred in 94 pregnancies (46%). After a median follow-up of 159 months (range 2-312), recurrences were detected in 16 patients (3.4%) of which 43% occurred later than 5 years after radical vaginal trachelectomy. Ten patients (2.1%) died of disease (five more than 5 years after radical vaginal trachelectomy). Overall survival, disease-free survival, and cancer-specific survival were 97.5%, 96.2%, and 97.9%, respectively. CONCLUSION: Our study confirms oncologic safety of radical vaginal trachelectomy associated with a high chance for childbearing. High rate of pre-term delivery may be due to cervical volume loss. Our long-term oncologic data can serve as a benchmark for future modifications of fertility-sparing surgery.

Oncologic and Fertility Outcomes After Simple Trachelectomy in Women With Early Cervical Cancer.

STUDY OBJECTIVE: This study aimed to present our case series of patients with early-stage cervical cancer undergoing simple trachelectomy (ST). Currently, radical trachelectomy is considered the most appropriate fertility-preserving procedure for the treatment of early-stage cervical cancer. However, there is increasing debate on the appropriate radicality of the surgery to preserve oncologic safety. DESIGN: Descriptive retrospective analysis of patient records and evaluation of questionnaires. SETTING: 2 gynecologic oncologic centers, surgeries performed by one surgical team. PATIENTS: 36 women with early-stage cervical cancer undergoing ST. INTERVENTIONS: Laparoscopic assisted simple vaginal trachelectomy. MEASUREMENTS: Demographic, histologic, fertility, and follow-up data of all patients who underwent ST between April 2007 and July 2021 were prospectively recorded and retrospectively analyzed. MAIN RESULTS: A total of 36 women (mean age: 28 years) underwent ST of whom 81% were nulliparous. Indications for ST were multifocal International Federation of Gynecology and Obstetrics stage IA1 (n = 30), stage IA1 L1 (n = 1), stage IA2 (n = 2), and stage IB1 (n = 3). Mandatory staging procedure was laparoscopic pelvic lymphadenectomy, including bilateral sentinel biopsy in 92% of the cases and systematic in 8%. Residual tumor was histologically confirmed in 8 specimens (22%); 18 women (50%) were seeking parenthood, and 13 succeeded (72%). There were 16 live births, all on term, with a median fetal weight of 3110 grams (2330-4420). One patient had a medical abortion owing to fetal congenital malformation. One pregnancy is ongoing. After a median follow-up of 91.5 months (9-174), all women are alive with no evidence of disease. CONCLUSION: ST represents a de-escalation compared with radical trachelectomy and provides excellent oncologic results with an outstanding fertility rate and obstetric outcome for patients with early cervical cancer. However, clear indications for this tailored fertility-preserving surgery have to be defined in well-designed trials.

Preexisting tumor-resident T cells with cytotoxic potential associate with response to neoadjuvant anti-PD-1 in head and neck cancer.

About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration of anti-programmed cell death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the tumor microenvironment (TME). However, the mechanisms underlying the dynamics of antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, and approaches to increase pathologic responses are lacking. In a phase 2 trial (NCT02296684), we observed that 45% of patients treated with two doses of neoadjuvant pembrolizumab experienced marked pTRs (≥50%). Single-cell analysis of 17,158 CD8+ T cells from 14 tumor biopsies, including 6 matched pre-post neoadjuvant treatment, revealed that responding tumors had clonally expanded putative tumor-specific exhausted CD8+ tumor-infiltrating lymphocytes (TILs) with a tissue-resident memory program, characterized by high cytotoxic potential (CTX+) and ZNF683 expression, within the baseline TME. Pathologic responses after 5 weeks of PD-1 blockade were consistent with activation of preexisting CTX+ZNF683+CD8+ TILs, paralleling loss of viable tumor and associated tumor antigens. Response was associated with high numbers of CD103+PD-1+CD8+ T cells infiltrating pretreatment lesions, whereas revival of nonexhausted persisting clones and clonal replacement were modest. By contrast, nonresponder baseline TME exhibited a relative absence of ZNF683+CTX+ TILs and subsequent accumulation of highly exhausted clones. In HNSCC, revival of preexisting ZNF683+CTX+ TILs is a major mechanism of response in the immediate postneoadjuvant setting.

Breastfeeding in primiparous women - expectations and reality: a prospective questionnaire survey.

BACKGROUND: Breastfeeding provides the optimal nutrition for infants and offers numerous benefits for both mother and child. The World Health Organisation recommends exclusive breastfeeding during the first 6 months of life and the introduction of complementary feeding between the fifth and seventh months of life. There is a discrepancy between breastfeeding recommendations and the actual duration of breastfeeding. The aim of this study was to analyse breastfeeding behaviour in primiparous women in order to be able to provide support for mothers. METHODS: In this prospective, questionnaire-based study conducted between 2020 and 2022, primiparous women were asked to complete three questionnaires at three defined survey time points (routine prepartum presentation, postpartum hospitalization, completed sixth month of life). RESULTS: A total of 140 women were included and returned all three questionnaires. Fifty-eight percent performed breastfeeding exclusively at least until their baby had reached the age of 6 months, whereas 20% already stopped within the first 6 months. The main reasons given for early cessation were insufficient milk supply and inadequate infant weight gain. A comprehensive level of prepartum knowledge had a significant positive effect on participants' sense of confidence with breastfeeding. Sociodemographic factors such as age and educational level were also associated with breastfeeding behaviour, but significant corresponding differences in the duration of breastfeeding were not observed. Women with postpartum midwifery care breastfed significantly longer (p < 0.05). CONCLUSIONS: Breastfeeding behaviour and duration are influenced by multiple factors. Although certain sociodemographic factors are unalterable, comprehensive prepartum knowledge transfer and postpartum midwifery care have a positive impact on breastfeeding behaviour. TRIAL REGISTRATION: The study was retrospectively registered at the German Clinical Trials Register (Deutsches Register Klinischer Studien, DRKS) on 6 December 2022 (DRKS00030763).

Fertility sparing therapy in women with lymph node negative cervical cancer >2cm - oncologic and fertility outcomes of neoadjuvant chemotherapy followed by radical vaginal trachelectomy.

OBJECTIVE: Simple or radical trachelectomy are accepted fertility sparing therapies for patients diagnosed with cervical cancer ≤2 cm. In patients with larger tumors a fertility sparing concept is considered experimental. The aim of our study is to present oncological and fertility outcomes of laparoscopic pelvic lymphadenectomy followed by neoadjuvant chemotherapy and subsequent radical vaginal trachelectomy. These procedures were performed in two centers in patients diagnosed with cervical cancer of diameter >2 cm. METHOD: We retrospectively analyzed the demographic, histological, fertility and follow-up data of all patients with cervical cancer assessed as stage IB2, IB3 or IIA1 under the International Federation of Gynecology and Obstetrics (FIGO) 2018 system. These patients had undergone pelvic lymphadenectomy, followed by neoadjuvant chemotherapy and radical vaginal trachelectomy between February 2006 and June 2020 at Charité University Berlin and Asklepios Hospital, Hamburg. RESULTS: A total of 31 patients (mean age 29.5 years, range; 26-40) underwent neoadjuvant chemotherapy followed by radical vaginal trachelectomy in case of proven tumor-free lymph nodes. Twenty-six (84%) of these patients were nulliparous. Across all 31 patients, the initial tumor stages were FIGO 2018 stage IB2 (n=27), IB3 (n=3) and IIA1 (n=1).Lymphadenectomy was completed in all but one patient (sentinel) with a median of 33 (range; 11-47) pelvic lymph nodes. The neoadjuvant chemotherapy regimen was two cycles of paclitaxel, ifosfamide and cisplatin in 17 patients; three cycles of paclitaxel, ifosfamide and cisplatin in eight patients; two cycles of paclitaxel and cisplatin in four patients; two cylces cisplatin monoagent in one patient; and two cycles of paclitaxel and cisplatin followed by two cycles of paclitaxel, ifosfamide and cisplatin in one patient. Residual tumor was histologically confirmed in 17 specimens (55%). The median residual tumor size following neoadjuvant chemotherapy was 12 mm (range; 1-60). Fertility could be preserved in 27 patients (87%); two patients underwent adjuvant chemoradiation after radical vaginal trachelectomy due to high-risk histological features; two other patients underwent radical hysterectomy with adjuvant chemoradiation therapy following neoadjuvant chemotherapy. Of 18 (67%) patients seeking motherhood, 13 became pregnant (72%). There were 12 live births in 10 women, with a median fetal weight of 2490 grams (range; 1640-3560) and five miscarriages. After a median follow-up of 94.5 months (range; 6-183) three recurrences (11.1%) were detected, one patient (3.7%) died of the disease. CONCLUSION: Neoadjuvant chemotherapy followed by radical vaginal trachelectomy may be offered to patients seeking motherhood with cervical cancer >2 cm and histopathologically tumor-free lymph nodes, the rate of healthy baby pregnancy on discharge was 10/18 women (55%). This fertility-preserving strategy is associated with higher recurrence and death compared with what was published in the literature for women undergoing radical vaginal trachelectomy for tumors up to 2 cm.

Can Classifications Adequately Represent Genital Malformations?: EVA Study ( E SHRE/ESGE | V CUAM | A FS) - A Prospective Multicenter Study to Evaluate the Current Female Genital Malformation Classifications.

Introduction Genital malformations are a common clinical occurrence that can be represented using different classifications. Reproducibility is an essential quality characteristic for a classification, and it plays an important role, especially in consultations and the treatment of infertile patients and in obstetric management. The aim of this study is to demonstrate the reproducibility and clinical practicality of three commonly used classifications: the ESHRE/ESGE (European Society of Human Reproduction and Embryology/ European Society for Gynecological Endoscopy), VCUAM (Vagina Cervix Uterus Adnex-associated Malformation), and AFS (American Fertility Society) classifications. Materials and Methods Sixty-five patients with female genital malformations were included in this prospective, multicenter, exploratory, observational study. All participants underwent a clinical examination and a medical interview. The investigators were instructed to classify the presenting malformations according to the ESHRE/ESGE, VCUAM, and AFS classifications using a structured questionnaire. Investigators were asked whether the malformation could be reproducibly classified (yes/no) and about the grade (grade 1-5 from "very good" to "deficient") they would assign to each classification. Classification assessment was queried for vagina, cervix, uterus, adnexa, and associated malformations and was scored from 1 to 5. Results Reproducibility was rated as 80% (n = 52/65), 92.3% (n = 60/65), and 56.9% (n = 37/65) for the ESHRE/ESGE, VCUAM, and AFS classification, respectively. ESHRE/ESGE, VCUAM and AFS were rated as "very good" or "good" for 83.3%, 89.2%, and 10.8% of vaginal malformations; for 75.8%, 87.5%, and 24.2% of cervical malformations; and for 89.7%, 89.5%, and 86.2% of uterine malformations, respectively. VCUAM was rated as "very good" or "good" for 77.8% and 69.6% of adnexal malformations and associated malformations, respectively. ESHRE/ESGE and AFS were rated as "sufficient" or "deficient" for 100% and 75% of adnexal malformations and for 77.3% and 69.6% of associated malformations, respectively. Conclusion The prospective multicenter EVA ( E SHRE/ESGE | V CUAM | A FS) study revealed that the organ-based ESHRE/ESGE and VCUAM classifications of female genital malformations perform better in terms of reproducibility as well as in the assessment of individual compartments than the non-organ-based AFS classification.

Predicting adverse outcomes in pregnant patients positive for SARS-CoV-2: a machine learning approach- a retrospective cohort study.

BACKGROUND: Pregnant people are particularly vulnerable to SARS-CoV-2 infection and to ensuing severe illness. Predicting adverse maternal and perinatal outcomes could aid clinicians in deciding on hospital admission and early initiation of treatment in affected individuals, streamlining the triaging processes. METHODS: An international repository of 1501 SARS-CoV-2-positive cases in pregnancy was created, consisting of demographic variables, patient comorbidities, laboratory markers, respiratory parameters, and COVID-19-related symptoms. Data were filtered, preprocessed, and feature selection methods were used to obtain the optimal feature subset for training a variety of machine learning models to predict maternal or fetal/neonatal death or critical illness. RESULTS: The Random Forest model demonstrated the best performance among the trained models, correctly identifying 83.3% of the high-risk patients and 92.5% of the low-risk patients, with an overall accuracy of 89.0%, an AUC of 0.90 (95% Confidence Interval 0.83 to 0.95), and a recall, precision, and F1 score of 0.85, 0.94, and 0.89, respectively. This was achieved using a feature subset of 25 features containing patient characteristics, symptoms, clinical signs, and laboratory markers. These included maternal BMI, gravidity, parity, existence of pre-existing conditions, nicotine exposure, anti-hypertensive medication administration, fetal malformations, antenatal corticosteroid administration, presence of dyspnea, sore throat, fever, fatigue, duration of symptom phase, existence of COVID-19-related pneumonia, need for maternal oxygen administration, disease-related inpatient treatment, and lab markers including sFLT-1/PlGF ratio, platelet count, and LDH. CONCLUSIONS: We present the first COVID-19 prognostication pipeline specifically for pregnant patients while utilizing a large SARS-CoV-2 in pregnancy data repository. Our model accurately identifies those at risk of severe illness or clinical deterioration, presenting a promising tool for advancing personalized medicine in pregnant patients with COVID-19.

A Phase I, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Patients with Advanced Gastrointestinal Stromal Tumor.

PURPOSE: To evaluate DS-6157a, an antibody-drug conjugate targeting G protein-coupled receptor 20 (GPR20), in gastrointestinal stromal tumors (GIST). PATIENTS AND METHODS: In this phase I multicenter, open-label, multiple-dose study, patients with previously treated advanced GIST received intravenous DS-6157a on Day 1 of 21-day cycles, with a starting dose of 1.6 mg/kg. The primary objective evaluated the safety and tolerability of DS-6157a, while determining dose-limiting toxicity (DLT) and the MTD. Secondary objectives included plasma pharmacokinetics parameters, plasma antidrug antibodies (ADA), and efficacy. RESULTS: A total of 34 patients enrolled. DS-6157a was well tolerated, with DLTs in 4 patients (11.8%) at doses of 6.4 mg/kg, 9.6 mg/kg, and 12.8 mg/kg; the MTD was determined to be 6.4 mg/kg. Treatment-emergent adverse events (TEAE) grade ≥3 occurred in 17 patients (50.0%), including decreased platelet count (23.5%), anemia (20.6%), decreased neutrophil count (14.7%), and decreased white blood cell count (11.8%). Four patients (11.8%) experienced serious adverse events related to DS-6157a. Six patients died with 5 due to disease progression and 1 due to DS-6157a-related TEAE. Tumor shrinkage was observed in 7 patients (20.6%), and 1 patient (2.9%) achieved a partial response. Plasma concentrations and exposure of intact DS-6157a, DXd, and total anti-GPR20 antibody all demonstrated a dose-dependent profile. No treatment-emergent ADAs were observed. CONCLUSIONS: Targeting GPR20 with DS-6157a was tolerated in patients with advanced GIST with tumor shrinkage demonstrated in KIT/PDGFRA wild-type GIST. However, the study did not proceed further due to lower efficacy outcomes than anticipated.

Effects of age on the diagnostic value of the soluble fms-like tyrosine kinase-1/ placental growth factor ratio in preeclampsia: a retrospective cohort study.

OBJECTIVE: Measurement of the ratio between soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) supports the diagnosis of preeclampsia. sFlt-1/PlGF ratios of at least 85 and at least 110 have previously been suggested for diagnosis of early-onset and late-onset preeclampsia, respectively. However, angiogenic and antiangiogenic factors change throughout the process of aging, potentially influencing preeclampsia diagnosis. In this study, we therefore evaluated in detail the effect of maternal age on sFlt-1/PlGF ratios. METHODS: A total of 2775 pregnant female patients were included in this retrospective cohort study, spread across three maternal age groups: 18-25 years, 26-35 years, and more than 35 years at delivery. Receiver-operating characteristic (ROC) curve analysis was employed to evaluate sFlt-1/PlGF ratio cutoffs for use in preeclampsia diagnosis. RESULTS: Controls (2462 pregnant women) showed a significant difference in sFlt-1/PlGF ratios between the youngest and oldest age groups, which resulted in differences in the best-performing sFlt-1/PlGF ratio cutoffs: optimized cutoffs were 143.4 (52.9%, 98.2%), 8.6 (84.4%, 75.3%), and 22.9 (78.6%, 82.3%) in early-onset preeclampsia, and 46.4 (67.5%, 81.5%), 40.8 (77.3%, 73%), and 44.1 (65.1%, 74.5%) in late-onset preeclampsia in age groups, 1, 2, and 3, respectively. CONCLUSION: sFlt-1/PlGF ratios change with maternal age, which has important clinical implications for their use in the diagnosis of preeclampsia: Better differentiated sFlt-1/PlGF cutoffs should be used that take maternal and gestational age into account.

Enhanced recovery after cesarean section (ERAC): Where are we in Austria?

OBJECTIVE: Enhanced recovery after surgery (ERAS) recommendations for cesarean section (ERAC), likely the most common reason for laparotomy in women, were issued in 2018-19. We examined how current perioperative management at cesarean section in Austrian hospitals aligns with ERAS recommendations. STUDY DESIGN: We surveyed the 21 largest public obstetric units in Austria for alignment with 20 of the 31 strong ERAS recommendations regarding perioperative maternal care at cesarean section. We also looked at how the German-language clinical guideline for cesarean section (AWMF Guideline Sectio caesarea) aligns with ERAS recommendations. RESULTS: The 21 obstetric units cared for about 51% of all births in Austria in 2019. Cesarean section rates ranged from 17.7% to 50.4%. All 21 units implemented the five strong recommendations regarding patient information and counselling, regional anesthesia, euvolemia and multimodal analgesia. The least implemented strong recommendation was the one for the use of pneumatic compression stockings to prevent thromboembolic disease (0/21 units). Overall, all 21 units implemented ≥11 and 13 (62%) implemented ≥15 (≥75%) of the 20 strong recommendations; no unit implemented all 20 strong recommendations. There were no differences in the implementation of strong recommendations according to hospital volume. CONCLUSIONS: Even in the absence of formal adoption of ERAS program for cesarean section many perioperative ERAS recommendations are already implemented in Austria. The least implemented recommendations were the use of pneumatic compression stockings (0 of 21 units) and immediate catheter removal (4 of 21 units). Only 10 of the 20 ERAS recommendations we looked at are included in the current German-language clinical guideline for cesarean section.

Audiologic Follow-up in Patients With Head and Neck Cancer Treated With Cisplatin and Radiation.

OBJECTIVES: Evaluate factors associated with adherence to ototoxicity monitoring among patients with head and neck cancer treated with cisplatin and radiation therapy at a tertiary care center. METHODS: We performed a single-institution retrospective cohort study on adults with head and neck cancer treated with cisplatin and radiation therapy who participated in an ototoxicity monitoring program. The primary outcomes were rates of post-treatment audiograms at the following time points: one, three, six, 12, and greater than 12 months. Multivariable logistic regression was performed to identify risk factors associated with complete loss of follow-up after pre-treatment evaluation. RESULTS: Two hundred ninety-four head and neck cancer patients were analyzed. Overall, 220 (74.8%) patients had at least one post-treatment audiogram; 58 (20.0%) patients had more than one audiogram. The time point with the highest follow-up rate was at 3 months (n = 170, 57.8%); rates at the remaining times ranged from 7.1% to 14.3%. When controlling for covariates, patients without insurance and those with stage IV cancers were associated with complete loss of audiologic follow-up (aOR = 7.18, 95% CI = 2.75-19.90; aOR = 1.96, 95% CI = 1.02-3.77, respectively). Among 156 patients recommended for a hearing aid, only 39 (24.8%) patients received one. CONCLUSIONS: Head and neck cancer patients enrolled in an ototoxicity monitoring program demonstrate moderately high follow-up rates for at least one post-treatment audiogram. However, follow-up tapers dramatically after 6 months, and overall hearing aid utilization is low. Further research is needed to understand barriers to long-term audiologic follow-up and hearing aid utilization to decrease untreated hearing loss in cancer survivorship. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 133:3161-3168, 2023.

Reproductive and Obstetric Outcomes after UAE, HIFU, and TFA of Uterine Fibroids: Systematic Review and Meta-Analysis.

Novel treatment options for uterine fibroids, such as uterine artery embolization (UAE), ultrasound-guided and magnetic resonance-guided high-intensity focused ultrasound (USgHIFU and MRgHIFU), and transcervical radiofrequency ablation (TFA) methods, are widely used in clinical practice. This systematic review and meta-analysis (CRD42022297312) aims to assess and compare reproductive and obstetric outcomes in women who underwent these minimally invasive approaches for uterine fibroids. The search was performed in PubMed, Google Scholar, ScienceDirect, Cochrane Library, Scopus, Web of Science and Embase. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) and Cochrane guidelines. The articles were selected to meet the following eligibility criteria: (1) research article, (2) human subject research, and (3) the study of pregnancy outcomes after the treatment of uterine fibroids by either one of three methods-UAE, HIFU, and TFA. The analysis of 25 eligible original articles shows a similar rate of live births for UAE, USgHIFU, MRgHIFU, and TFA (70.8%, 73.5%, 70%, and 75%, respectively). The number of pregnancies varied considerably among these studies, as well as the mean age of pregnant women. However, the results of pregnancy outcomes for TFA are insufficient to draw firm conclusions, since only 24 women became pregnant in these studies, resulting in three live births. The miscarriage rate was highest in the UAE group (19.2%). USgHIFU was associated with a higher rate of placental abnormalities compared to UAE (2.8% vs. 1.6%). The pooled estimate of pregnancies was 17.31% to 44.52% after UAE, 18.69% to 78.53% after HIFU, and 2.09% to 7.63% after TFA. The available evidence confirmed that these minimally invasive uterine-sparing treatment options for uterine fibroids are a good approach for patients wishing to preserve their fertility, with comparable reproductive and obstetric outcomes among the different techniques.

Maintenance tocolysis, tocolysis in preterm premature rupture of membranes and in cervical cerclage - a Germany-wide survey on the current practice after dissemination of the German guideline.

OBJECTIVES: To investigate the adherence of German perinatal specialist units and those of basic obstetric care to the national guideline we compared data from a nation-wide survey on the practice of maintenance tocolysis, tocolysis in preterm premature rupture of membranes and in the perioperative setting of cervical cerclage, and bedrest during and after tocolysis with recommendations from the current German Guideline 015/025 "Prevention and Treatment of Preterm Birth". METHODS: A total of 632 obstetric clinics in Germany were approached and received a link to an online questionnaire. Data were descriptively analyzed by performing measures of frequency. To compare two or more groups Fisher's exact test was used. RESULTS: The response rate was 19%; 23 (19.2%) of respondents did not perform maintenance tocolysis, while 97 (80.8%) conducted maintenance tocolysis; 30 (25.0%) of obstetric units performed cervical cerclage without tocolysis and 90 (75.0%) combined cervical cerclage with tocolysis; 11 (9.2%) of respondents did not use tocolytics in patients with preterm premature rupture of membranes, while 109 (90.8%) conducted tocolysis in these patients; 69 (57.5%) of obstetric units did not recommend bed rest during tocolysis, whereas 51 (42.5%) favored bedrest. Perinatal care centers of basic obstetric care recommend bed arrest during tocolysis statistically significant more often to their patients than those of higher perinatal care levels (53.6 vs. 32.8%, p=0.0269). CONCLUSIONS: The results of our survey are in accordance to others from different countries and reveal considerable discrepancies between evidence-based guideline recommendations and daily clinical practice.

Hearing Outcomes in a Deintensification Trial of Adjuvant Therapy for HPV-Related Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: To explore whether deintensification of adjuvant therapy reduces ototoxicity among patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Retrospective cohort study. SETTING: Single academic center. METHODS: The ototoxicity rate among adult patients with HPV-related OPSCC enrolled in the Minimalist Trial (MINT), a prospective phase 2 trial of surgery followed by risk-adjusted deintensified adjuvant therapy (42 Gy radiation given alone or with a single 100 mg/m2 dose of cisplatin), was compared to that among a historical cohort treated with standard adjuvant therapy (60-66 Gy radiation with up to three 100 mg/m2 doses of cisplatin). Ototoxicity was defined as Common Terminology Criteria for Adverse Events v5.0 ≥ Grade 2. Mixed model analysis was performed to investigate the association between deintensified adjuvant therapy and treatment-related hearing loss. RESULTS: A total of 29 patients (58 ears) were analyzed in the MINT cohort, and 27 patients (54 ears) in the historical cohort. The ototoxicity rate was 5% (n = 3/58 ears) in the MINT cohort and 46% (n = 25/54 ears) in the historical cohort (difference, 41%; 95% confidence interval [CI] = 27%-56%). Patients in the MINT cohort demonstrated a 95% decrease in risk of ototoxicity compared to those in the historical cohort (adjusted odds ratio: 0.05, 95% CI = 0.01-0.31). Differences in estimated marginal mean threshold shifts were statistically and clinically significant at frequencies ≥ 3 kHz. CONCLUSION: The deintensified adjuvant therapy given in MINT led to less ototoxicity than standard adjuvant therapy among patients with HPV-related OPSCC.

Teenage Pregnancies in Austria - an Epidemiological Study on Prevalence and Perinatal Outcome.

Introduction Even though teenage pregnancy rates have been declining in the last decades, their global prevalence is still high and shows country-specific discrepancies. Insufficient sexual education, poor availability of contraceptives and early marriage are some of the multifactorial causes for adolescent pregnancies. Very often teenage pregnancies are classified as high-risk pregnancies. Studies have found higher rates of peripartal complications, such as preterm birth, low birth weight or low fetal Apgar-Scores. The aim of this retrospective cohort study is to evaluate the prevalence of teenage pregnancies in Austria and to identify principal differences in maternal and neonatal outcome. Material and methods Data were collected from the Austrian Birth Registry between 01/2012 and 12/2020. A total of 751661 deliveries in Austria were documented. Obstetric, maternal and neonatal parameters were descriptively analyzed. Mothers were subclassified into two age groups: teenage mothers of 19 years and younger and adult mothers of 20 to 39 years of age. Results Newborns of teenage mothers were significantly smaller (49.98 ± 3.11 vs. 50.31 ± 3.16 cm, p < 0.001) and had a lower birth weight (3216 ± 564 vs. 3247 ± 576 g, p < 0.001) than newborns of adult mothers. The percentage of caesarean deliveries in the teenage group was significantly lower than in adult mothers (21.1 vs. 31.8%, p < 0.001). Newborns of teenage mothers had significantly higher rates of very low (< 4) and low (< 7) 5-minute Apgar scores (5-minute Apgar < 4: 0.75 vs. 0.54%, p = 0.004) (5-minute Apgar < 7: 1.77 vs. 1.37%, p = 0.001) and significantly lower arterial umbilical-cord pH (7.25 ± 0.08 vs. 7.26 ± 0.08, p < 0.001). Perinatal mortality was higher in the age group below 20 years (0.7 vs. 0.6%, p = 0.043). Conclusion The data of this study show significantly poorer outcomes in pregnancies of teenagers compared to adult women, even though the healthcare system in Austria is considered excellent. Future guideline recommendations should focus on important aspects of obstetric care in teenage mothers.

A Single-Arm Phase II Trial of Sitravatinib in Advanced Well-Differentiated/Dedifferentiated Liposarcoma.

PURPOSE: To evaluate sitravatinib, an inhibitor of multiple receptor tyrosine kinases (RTK), for the treatment of well-differentiated/dedifferentiated liposarcoma (WD/DD LPS). PATIENTS AND METHODS: This multicenter, open-label, Phase II trial enrolled patients with advanced WD/DD LPS who had received at least one prior systemic regimen and had progression within 12 weeks of enrollment. Patients received sitravatinib 150 mg (later amended to 120 mg) orally daily. A Simon two-stage design was used to evaluate for an improvement in the primary endpoint, progression-free rate at 12 weeks (PFR12), from 20% to 40%. Secondary endpoints included antitumor activity and safety. A subset of patients underwent paired biopsies analyzed using reverse-phase protein array. RESULTS: Twenty-nine patients enrolled. Median age was 62 years and 31% had received 3 or more prior lines. Most patients (93%) had DDLPS or mixed WD/DD LPS. Overall, 12 of 29 patients (41%) were alive and progression-free at 12 weeks and the study met the primary endpoint. There were no confirmed responses. Median progression-free survival was 11.7 weeks [95% confidence interval (CI): 5.9-35.9] and median overall survival was 31.7 weeks (95% CI: 18.1-90.1). The most common treatment-related adverse events were diarrhea (59%), hypertension (52%), hoarseness (41%), mucositis (31%), and nausea (31%). Baseline expression of phospho-RTKs was not significantly different between patients with and without clinical benefit from sitravatinib, but the number of samples was small. CONCLUSIONS: Sitravatinib provided a PFR12 of 41% and meaningful disease control in a subset of patients with advanced, progressive WD/DD LPS.

Risk Factors for Functional Outcomes in Advanced Laryngeal Squamous Cell Carcinoma.

OBJECTIVE: Chemoradiation for patients with laryngeal squamous cell carcinoma (SCC) may achieve organ preservation, but appropriate patient selection remains unknown. This study investigates pre-treatment risk factors associated with functional and survival outcomes after radiation-based therapy in patients with advanced laryngeal SCC. METHODS: A retrospective cohort study was performed on 75 adult patients with stage III or IV laryngeal SCC receiving definitive radiation-based therapy from 1997 to 2016 at a tertiary care center. Tracheostomy and gastrostomy dependence were the primary functional outcomes. Multivariable logistic regressions were performed to evaluate relationships between pre-treatment factors and tracheostomy and gastrostomy dependence. Time-to-event analyses were performed to determine risk factors associated with overall survival. RESULTS: Among 75 patients included in the analysis, 30 (40%) patients were tracheostomy dependent and 31 (41%) were gastrostomy tube dependent. The median length of follow-up was 31 months (range = 1 to 142 months). Pre-treatment tracheostomy was a significant predictor of post-treatment tracheostomy (aOR = 13.9, 95% CI = 3.35 to 57.5) and moderate-severe comorbidity was a significant predictor of post-treatment gastrostomy dependence (aOR = 2.96, 95% CI = 1.04 to 8.43). The five-year overall survival was 51% (95% CI = 38 to 64%). Pre-treatment gastrostomy tube dependence was associated with an increased risk of death (aHR = 2.45, 95% CI = 1.09 to 5.53). CONCLUSIONS: Baseline laryngeal functional status and overall health in advanced laryngeal SCC are associated with poor functional outcomes after radiation-based therapy, highlighting the importance of patient selection when deciding between surgical and non-surgical treatment plans. Laryngoscope, 133:594-600, 2023.