Endometrial Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry Number 032/034-OL, September 2022). Part 1 with Recommendations on the Epidemiology, Screening, Diagnosis and Hereditary Factors of Endometrial Cancer, Geriatric Assessment and Supply Structures.

Summary The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary. Aim The use of evidence-based risk-adapted therapies to treat women with endometrial cancer of low risk prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. This should improve the survival rates and quality of life of these patients. The S3-guideline on endometrial cancer and the quality indicators based on the guideline aim to provide the basis for the work of certified gynecological cancer centers. Methods The guideline was first compiled in 2018 in accordance with the requirements for S3-level guidelines and was updated in 2022. The update included an adaptation of the source guidelines identified using the German Instrument for Methodological Guideline Appraisal (DELBI). The update also used evidence reviews which were created based on selected literature obtained from systematic searches in selected literature databases using the PICO process. The Clinical Guidelines Service Group was tasked with carrying out a systematic search and assessment of the literature. Their results were used by interdisciplinary working groups as a basis for developing suggestions for recommendations and statements which were then modified during structured online consensus conferences and/or additionally amended online using the DELPHI process to achieve a consensus. Recommendations Part 1 of this short version of the guideline provides recommendations on epidemiology, screening, diagnosis, and hereditary factors. The epidemiology of endometrial cancer and the risk factors for developing endometrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer. The use of geriatric assessment is considered and existing structures of care are presented.

Management of Third and Fourth-Degree Perineal Tears After Vaginal Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/079, December 2020).

Purpose This guideline provides recommendations for the diagnosis, treatment and follow-up care of 3rd and 4th degree perineal tears which occur during vaginal birth. The aim is to improve the management of 3rd and 4th degree perineal tears and reduce the immediate and long-term damage. The guideline is intended for midwives, obstetricians and physicians involved in caring for high-grade perineal tears. Methods A selective search of the literature was carried out. Consensus about the recommendations and statements was achieved as part of a structured process during a consensus conference with neutral moderation. Recommendations After every vaginal birth, a careful inspection and/or palpation by the obstetrician and/or the midwife must be carried out to exclude a 3rd or 4th degree perineal tear. Vaginal and anorectal palpation is essential to assess the extent of birth trauma. The surgical team must also include a specialist physician with the appropriate expertise (preferably an obstetrician or a gynecologist or a specialist for coloproctology) who must be on call. In exceptional cases, treatment may also be delayed for up to 12 hours postpartum to ensure that a specialist is available to treat the individual layers affected by trauma. As neither the end-to-end technique nor the overlapping technique have been found to offer better results for the management of tears of the external anal sphincter, the surgeon must use the method with which he/she is most familiar. Creation of a bowel stoma during primary management of a perineal tear is not indicated. Daily cleaning of the area under running water is recommended, particularly after bowel movements. Cleaning may be carried out either by rinsing or alternate cold and warm water douches. Therapy should also include the postoperative use of laxatives over a period of at least 2 weeks. The patient must be informed about the impact of the injury on subsequent births as well as the possibility of anal incontinence.

Effects of Therapeutic Hypothermia on Macrophages in Mouse Cochlea Explants.

Globally, over the next few decades, more than 2.5 billion people will suffer from hearing impairment, including profound hearing loss, and millions could potentially benefit from a cochlea implant. To date, several studies have focused on tissue trauma caused by cochlea implantation. The direct immune reaction in the inner ear after an implantation has not been well studied. Recently, therapeutic hypothermia has been found to positively influence the inflammatory reaction caused by electrode insertion trauma. The present study aimed to evaluate the hypothermic effect on the structure, numbers, function and reactivity of macrophages and microglial cells. Therefore, the distribution and activated forms of macrophages in the cochlea were evaluated in an electrode insertion trauma cochlea culture model in normothermic and mild hypothermic conditions. In 10-day-old mouse cochleae, artificial electrode insertion trauma was inflicted, and then they were cultured for 24 h at 37 °C and 32 °C. The influence of mild hypothermia on macrophages was evaluated using immunostaining of cryosections using antibodies against IBA1, F4/80, CD45 and CD163. A clear influence of mild hypothermia on the distribution of activated and non-activated forms of macrophages and monocytes in the inner ear was observed. Furthermore, these cells were located in the mesenchymal tissue in and around the cochlea, and the activated forms were found in and around the spiral ganglion tissue at 37 °C. Our findings suggest that mild hypothermic treatment has a beneficial effect on immune system activation after electrode insertion trauma.

The effects of mild hypothermia on the electrode insertion trauma in a murine whole organ cochlea culture.

Introduction: Local therapeutic hypothermia (32°C) has been linked experimentally to an otoprotective effect in the electrode insertion trauma. The pathomechanism of the electrode insertion trauma is connected to the activation of apoptosis and necrosis pathways, pro-inflammatory and fibrotic mechanisms. In a whole organ cochlea culture setting the effect of therapeutic hypothermia in an electrode insertion trauma model is evaluated. Material and Methods: The cochleae of C57Bl6/J mice (Charles River®, Freiburg, Germany) are cultured for 24 hours at 37°C and 32°C after inserting a fishing line through the round window simulating an insertion trauma. The resulting effect was evaluated for the apoptotic reaction - B-cell-Lymphoma-2-Associated-X-Protein (BAX), B-Cell-Lymphoma-2-Protein (BCL2) and Cleaved-Caspase-3 (CC3) -, the inflammatory response - Tumor-Necrosis-Factor-Alpha (TNFα), Interleukin-1-Beta (IL-1Imm) and Cyclooxygenase-2 (COX2) - and proliferation process - Transforming-Growth-Factor-Beta-1 (TGFß1) - using immunohistochemistry and real-time PCR technique. A minimum of 12 cochlea per experiment were used. Results: A pro-apoptotic situation was observed in the normothermic group (BAX, CC3 ˃ Bcl2) whereas an anti-apoptotic constellation was found at 32°C culture conditions (BAX, CC3 < Bcl2). Furthermore the effect of the IT knowing to effect the pro-inflammatory cytokine (TNFα, Il1ß) and enzyme (COX2) expression has been reproduced. This reaction was reversed with the application of therapeutic hypothermia resulting in significant lower pro-inflammatory cytokine (TNFα, Il1ß) and enzyme (COX2) expression. TGFß1 was increased by hypothermia. Discussion: Concluding a protective effect of hypothermia on the experimental electrode insertion trauma can be described by an anti-apoptotic and anti-inflammatory reaction.

Diagnosis and Therapy of Female Urinary Incontinence. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry No. 015/091, January 2022): Part 2 with Recommendations on Interventional/Surgical Therapy of Overactive Bladder, Surgical Treatment of Stress Urinary Incontinence and Diagnosis and Therapy of Iatrogenic Urogenital Fistula.

Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the surgical treatment of female patients with stress urinary incontinence and urge incontinence. Specific solutions for the diagnostic workup and treatment of uncomplicated and complicated urinary incontinence are discussed. The diagnostics and surgical treatment of iatrogenic urogenital fistula are presented.

Diagnosis and Therapy of Female Urinary Incontinence. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/091, January 2022): Part 1 with Recommendations on Diagnostics and Conservative and Medical Treatment.

Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, etiology, classification, symptoms, diagnostics, and treatment of female patients with urinary incontinence. Specific solutions for the diagnostic workup and appropriate conservative and medical therapies for uncomplicated and complication urinary incontinence are discussed.

Best Practice Guideline - DEGUM Recommendations on Breast Ultrasound. / Best Practice Guideline ­ Empfehlungen der DEGUM zur Durchführung und Beurteilung der Mammasonografie.

Alongside mammography, breast ultrasound is an important and well-established method in assessment of breast lesions. With the "Best Practice Guideline", the DEGUM Breast Ultrasound (in German, "Mammasonografie") working group, intends to describe the additional and optional application modalities for the diagnostic confirmation of breast findings and to express DEGUM recommendations in this Part II, in addition to the current dignity criteria and assessment categories published in Part I, in order to facilitate the differential diagnosis of ambiguous lesions.The present "Best Practice Guideline" has set itself the goal of meeting the requirements for quality assurance and ensuring quality-controlled performance of breast ultrasound. The most important aspects of quality assurance are explained in this Part II of the Best Practice Guideline.

Visualization of macrophage subsets in the development of the fetal human inner ear.

Background: Human inner ear contains macrophages whose functional role in early development is yet unclear. Recent studies describe inner ear macrophages act as effector cells of the innate immune system and are often activated following acoustic trauma or exposure to ototoxic drugs. Few or limited literature describing the role of macrophages during inner ear development and organogenesis. Material and Methods: We performed a study combining immunohistochemistry and immunofluorescence using antibodies against IBA1, CX3CL1, CD168, CD68, CD45 and CollagenIV. Immune staining and quantification was performed on human embryonic inner ear sections from gestational week 09 to 17. Results: The study showed IBA1 and CD45 positive cells in the mesenchymal tissue at GW 09 to GW17. No IBA1 positive macrophages were detected in the sensory epithelium of the cochlea and vestibulum. Fractalkine (CX3CL1) signalling was initiated GW10 and parallel chemotactic attraction and migration of macrophages into the inner ear. Macrophages also migrated into the spiral ganglion, cochlear nerve, and peripheral nerve fibers and tissue-expressing CX3CL1. The mesenchymal tissue at all gestational weeks expressed CD163 and CD68. Conclusion: Expressions of markers for resident and non-resident macrophages (IBA1, CD45, CD68, and CD163) were identified in the human fetal inner ear. We speculate that these cells play a role for the development of human inner ear tissue including shaping of the gracile structures.

Clinical Differences between Invasive Lobular Breast Cancer and Invasive Carcinoma of No Special Type in the German Mammography-Screening-Program.

Invasive lobular carcinoma (ILC) of the breast is known to have typical molecular, clinical, and pathological characteristics that differ from invasive cancer of no special type (NST). In the German mammography screening program (MSP), we evaluated clinical differences between these tumor types at the time of their detection. Clinical features of NSTs (n = 785) and ILCs (n = 141) diagnosed in the MSP between 2009 and 2016 were compared. Compared to NST, ILC was significantly correlated with advanced age (59.1 years versus 60.6 years) and larger tumor size (1.5 cm versus 2.3 cm). ILC was significantly more frequently associated with moderate tumor differentiation (G2), whereas NST was associated with a higher rate of poorly differentiated tumors (p < .001). Furthermore, ILC presented more often as multifocal tumors (36% versus 11%, p < .001), and mastectomies were performed more often in the ILC group (27% versus 12%, p < .001). ILCs and NSTs had different clinical features at the time of detection. The pathological profile of ILC may explain some of these features. Specialists should be aware of the fact that ILC may escape detection by conventional imaging modalities for a long time, and may present later in life as more advanced multifocal disease.

Best Practice Guideline - DEGUM Recommendations on Breast Ultrasound. / Best Practice Guideline ­ Empfehlungen der DEGUM zur Durchführung und Beurteilung der Mammasonografie ­ TEIL I ­ Untersuchungstechnik, Ultraschall-DEGUM-Kriterien und deren Dokumentation.

For many years, breast ultrasound has been used in addition to mammography as an important method for clarifying breast findings. However, differences in the interpretation of findings continue to be problematic 1 2. These differences decrease the diagnostic accuracy of ultrasound after detection of a finding and complicate interdisciplinary communication and the comparison of scientific studies 3. In 1999, the American College of Radiology (ACR) created a working group (International Expert Working Group) that developed a classification system for ultrasound examinations based on the established BI-RADS classification of mammographic findings under consideration of literature data 4. Due to differences in content, the German Society for Ultrasound in Medicine (DEGUM) published its own BI-RADS-analogue criteria catalog in 2006 3. In addition to the persistence of differences in content, there is also an issue with formal licensing with the current 5th edition of the ACR BI-RADS catalog, even though the content is recognized by the DEGUM as another system for describing and documenting findings. The goal of the Best Practice Guideline of the Breast Ultrasound Working Group of the DEGUM is to provide colleagues specialized in senology with a current catalog of ultrasound criteria and assessment categories as well as best practice recommendations for the various ultrasound modalities.

The Prevention of Positioning Injuries During Gynecologic Surgery. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/077, October 2020).

Purpose Positioning injuries are relatively common, forensically highly relevant complications of gynecologic surgery. The aim of this official AWMF S2k-guideline is to provide statements and recommendations on how to prevent positioning injuries using the currently available literature. The literature was evaluated by an interdisciplinary group of experts from professional medical societies. The consensus on recommendations and statements was achieved in a structured consensus process. Method The current guideline is based on the expired S1-guideline, which was updated by a systematic search of the literature and a review of relevant publications issued between February 2014 and March 2019. Statements were compiled and voted on by a panel of experts. Recommendations The guideline provides general and specific recommendations on the prevention, diagnosis and treatment of positioning injuries.

Measurement of the Intracochlear Hypothermia Distribution Utilizing Tympanic Cavity Hypothermic Rinsing Technique in a Cochlea Hypothermia Model.

Introduction: Cochlea implants can cause severe trauma leading to intracochlear apoptosis, fibrosis, and eventually to loss of residual hearing. Mild hypothermia has been shown to reduce toxic or mechanical noxious effects, which can result in inflammation and subsequent hearing loss. This paper evaluates the usability of standard surgical otologic rinsing as cooling medium during cochlea implantation as a potential hearing preservation technique. Material and Methods: Three human temporal bones were prepared following standard mastoidectomy and posterior tympanotomy. Applying a retrocochlear approach leaving the mastoidectomy side intact, temperature probes were placed into the basal turn (n = 4), the middle turn (n = 2), the helicotrema, and the modiolus. Temperature probe positions were visualized by microcomputed tomography (µCT) imaging and manually segmented using Amira® 7.6. Through the posterior tympanotomy, the tympanic cavity was rinsed at 37°C in the control group, at room temperature (in the range between 22 and 24°C), and at iced water conditions. Temperature changes were measured in the preheated temporal bone. In each temperature model, rinsing was done for 20 min at the pre-specified temperatures measured in 0.5-s intervals. At least five repetitions were performed. Data were statistically analyzed using pairwise t-tests with Bonferroni correction. Results: Steady-state conditions achieved in all three different temperature ranges were compared in periods between 150 and 300 s. Temperature in the inner ear started dropping within the initial 150 s. Temperature probes placed at basal turn, the helicotrema, and middle turn detected statistically significant fall in temperature levels following body temperature rinses. Irrigation at iced conditions lead to the most significant temperature drops. The curves during all measurements remained stable with 37°C rinses. Conclusion: Therapeutic hypothermia is achieved with standard surgical irrigation fluid, and temperature gradients are seen along the cochlea. Rinsing of 120 s duration results in a therapeutic local hypothermia throughout the cochlea. This otoprotective procedure can be easily realized in clinical practice.

Consensus Meeting of Breast Imaging: BI-RADS® and Beyond.

Organizers of medical educational courses are often confronted with questions that are clinically relevant yet trespassing the frontiers of scientifically proven, evidence-based medicine at the point of care. Therefore, since 2007 organizers of breast teaching courses in German language met biannually to find a consensus in clinically relevant questions that have not been definitely answered by science. The questions were prepared during the 3 months before the meeting according to a structured process and finally agreed upon the day before the consensus meeting. At the consensus meeting, the open questions concerning 2D/3D mammography, breast ultrasound, MR mammography, interventions as well as risk-based imaging of the breast were presented first for electronic anonymized voting, and then the results of the audience were separately displayed from the expert votes. Thereafter, an introductory statement of the moderator was followed by pros/cons of two experts, and subsequently the final voting was performed. With ≥75% of votes of the expert panel, an answer qualified as a consensus statement. Seventeen consensus statements were gained, addressing for instance the use of 2D/3D mammography, breast ultrasound in screening, MR mammography in women with intermediate breast cancer risk, markers for localization of pathologic axillary lymph nodes, and standards in risk-based imaging of the breast. After the evaluation, comments from the experts on each field were gathered supplementarily. Methodology, transparency, and soundness of statements achieve a unique yield for all course organizers and provide solid pathways for decision making in breast imaging.

Standards of hygiene for ultrasound-guided core cut biopsies of the breast. / Hygienestandards bei der ultraschallgesteuerten Stanzbiopsie an der Mamma.

PURPOSE: The aim was to obtain an overview of the hygiene measures undertaken during ultrasound guided core cut biopsies of the breast by experts certified by the German Society for Ultrasound in Medicine in order to derive recommendations for clinical routine, taking into account the available literature and the lack of evidence based guidelines. MATERIALS AND METHODS: A survey was conducted with all members of the levels I to III of the breast ultrasound working group of the German Society for Ultrasound in Medicine. The estimation of the risk of infection after a core cut biopsy of the breast was asked for as well as the hygiene measures undertaken in practice to avoid infection. RESULTS: The risk of infection after a core cut biopsy of the breast was estimated to be one per thousand (median value). The most commonly performed hygiene measures were a spray, wipe, spray desinfection (98.1 %) and the use of sterile gloves (54.7 %). CONCLUSION: Due to the very low risk of infection we recommend the routine use of gloves and an adequate skin disinfection. Contact of the transducer or of an unsterile contact medium with the biopsy needle is considered highly unlikely und should be avoided.

Gynecologic oncologists' attitudes and practices relating to integrative medicine: results of a nationwide AGO survey.

PURPOSE: The growing popularity and acceptance of integrative medicine is evident both among patients and among the oncologists treating them. As little data are available regarding health-care professionals' knowledge, attitudes, and practices relating to the topic, a nationwide online survey was designed. METHODS: Over a period of 11 weeks (from July 15 to September 30, 2014) a self-administered, 17-item online survey was sent to all 676 members of the Research Group on Gynecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie) in the German Cancer Society. The questionnaire items addressed the use of integrative therapy methods, fields of indications for them, advice services provided, level of specific qualifications, and other topics. RESULTS: Of the 104 respondents (15.4%) using integrative medicine, 93% reported that integrative therapy was offered to breast cancer patients. The second most frequent type of tumor in connection with which integrative therapy methods were recommended was ovarian cancer, at 80% of the participants using integrative medicine. Exercise, nutritional therapy, dietary supplements, herbal medicines, and acupuncture were the methods the patients were most commonly advised to use. CONCLUSION: There is considerable interest in integrative medicine among gynecological oncologists, but integrative therapy approaches are at present poorly implemented in routine clinical work. Furthermore there is a lack of specific training. Whether future efforts should focus on extending counseling services on integrative medicine approaches in gynecologic oncology or not, have to be discussed. Evidence-based training on integrative medicine should be implemented in order to safely guide patients in their wish to do something by themselves.

Registry of implants for the reconstruction of pelvic floor in males and females: A feasibility case series.

INTRODUCTION: Most aspects of implant-assisted reconstruction of pelvic floor in males and females are under debate and the research is not standardized. Registries are supposed to shed light to the indications, surgical techniques and material properties and to establish a standardized evaluation. METHODS: A working group was formed to create an online platform for registration and outcome measurement of implant-assisted operations for pelvic organ prolapse (POP) and female and male stress urinary incontinence (SUI). 20 patients with modified mesh materials were evaluated over 23 months follow up in the registry to prove the feasibility of the registry. For validation a previously published modified "satisfaction, anatomy, continence, safety - S.(A.)C.S score" was used. RESULTS: A consensus was met on definitions and classifications of patient variables, surgical procedures and implants, as well as outcome parameters (efficacy, continence, satisfaction, complications). Different subgroup modules were formed in accordance with treated condition. The maximum score of cure was reached by 25-100% of patients depending on the indication. CONCLUSION: A prospective registry in accordance with IDEAL-D framework is justified for the evaluation and regulation of implants for pelvic floor reconstruction.

A Novel Operative Procedure for Pelvic Organ Prolapse Utilizing a MRI-Visible Mesh Implant: Safety and Outcome of Modified Laparoscopic Bilateral Sacropexy.

INTRODUCTION: Sacropexy is a generally applied treatment of prolapse, yet there are known possible complications of it. An essential need exists for better alloplastic materials. METHODS: Between April 2013 and June 2014, we performed a modified laparoscopic bilateral sacropexy (MLBS) in 10 patients using a MRI-visible PVDF mesh implant. Selected patients had prolapse POP-Q stages II-III and concomitant OAB. We studied surgery-related morbidity, anatomical and functional outcome, and mesh-visibility in MRI. Mean follow-up was 7.4 months. RESULTS: Concomitant colporrhaphy was conducted in 1/10 patients. Anatomical success was defined as POP-Q stage 0-I. Apical success rate was 100% and remained stable. A recurrent cystocele was seen in 1/10 patients during follow-up without need for intervention. Out of 6 (6/10) patients with preoperative SUI, 5/6 were healed and 1/6 persisted. De-novo SUI was seen in 1/10 patients. Complications requiring a relaparoscopy were seen in 2/10 patients. 8/10 patients with OAB were relieved postoperatively. The first in-human magnetic resonance visualization of a prolapse mesh implant was performed and showed good quality of visualization. CONCLUSION: MLBS is a feasible and safe procedure with favorable anatomical and functional outcome and good concomitant healing rates of SUI and OAB. Prospective data and larger samples are required.

Inactivation of hepatitis C virus infectivity by human breast milk.

BACKGROUND: Hepatitis C virus (HCV) is spread through direct contact with blood, although alternative routes of transmission may contribute to the global burden. Perinatal infection occurs in up to 5% of HCV-infected mothers, and presence of HCV RNA in breast milk has been reported. We investigated the influence of breast milk on HCV infectiousness. METHODS/RESULTS: Human breast milk reduced HCV infectivity in a dose-dependent manner. This effect was species-specific because milk from various animals did not inhibit HCV infection. Treatment of HCV with human breast milk did not compromise integrity of viral RNA or capsids but destroyed the lipid envelope. Fractionation of breast milk revealed that the antiviral activity is present in the cream fraction containing the fat. Proteolytic digestion of milk proteins had no influence on its antiviral activity, whereas prolonged storage at 4°C increased antiviral activity. Notably, pretreatment with a lipase inhibitor ablated the antiviral activity and specific free fatty acids of breast milk were antiviral. CONCLUSIONS: The antiviral activity of breast milk is linked to endogenous lipase-dependent generation of free fatty acids, which destroy the viral lipid envelope. Therefore, nursing by HCV-positive mothers is unlikely to play a major role in vertical transmission.

Funneling before and after anti-incontinence surgery--a prognostic indicator? Part 2: tension-free vaginal tape.

Does the presence of pre- and postoperative funneling of the proximal urethra affect the outcome of tension-free vaginal tape (TVT)? This prospective study of 191 women with proven primary genuine stress urinary incontinence treated by TVT insertion and assessed by pre- and postoperative introital ultrasound aims to answer that question. At 36-month follow-up, the cure rate was 89.5% (Kaplan-Meier estimator). At 6-month follow-up, 6.3% of the women had urge symptoms and 0.5% de novo urge incontinence. The cure rate in preoperative funneling was 77.5% as opposed to 96.6% in the group without funneling (P<0.0001). The funneling rate significantly decreased from 37.2% preoperatively to 17.3% immediately postoperatively (P<0.0001). The continence rate was 57.5% in persistent postoperative funneling vs 96.2% in the group without postoperative funneling (P<0.0001). The complication rate was not higher in the group with persistent postoperative funneling. The TVT procedure significantly reduces bladder neck funneling. Both preoperative and persistent postoperative funneling are associated with an increased probability of therapeutic failure or recurrence.