[Pelvic floor reconstruction-update 2024: prolapse-associated symptoms and their treatment]. / Rekonstruktive Beckenbodenchirurgie ­ Update 2024: prolapsassoziierte Symptome und deren Heilung.

Pelvic organ prolapse (POP) and associated symptoms of urinary incontinence, fecal incontinence, obstructive micturition, defecation, and pain are frequent and a widespread disease with relevant reduction of quality of life and high costs. New insights into functional anatomy and pathophysiology of these pelvic floor dysfunctions let us recognize how ligamentous laxities/defects lead to these dysfunctions. Results of the PROpel study (ClinicalTrials.gov-Identifier: NCT00638235) are shown in which a detailed observation of symptoms (patient-related outcome measures) pre- and postoperatively was performed. Ligamentous vaginal repair of POP enables symptom cure in high percentages for urinary urge incontinence (up to 82%), nocturia (up to 92%), obstructive micturition (up to 87%), fecal incontinence (58-72%), obstructive defecation (71-84%), and pain (53-90%), if caused by POP. Women with POP­Q stage 2 have similar symptom frequencies as women with POP­Q stage 3-4, and also similar cure rates of their symptoms. If good anatomical prolapse repair (in responders) was achieved, the cure rates for obstructive micturition, urinary urgency incontinence, and nocturia were significantly higher than in those women with less effective surgical repair. In the future, pelvic floor surgery should have symptom cure as the primary objective and should lead to improved quality of life. The different, currently performed techniques for POP repair have to be investigated concerning this matter.

[S3 guidelines on "full-term vaginal birth" from an anesthesiological perspective : Worthwhile knowledge for anesthesiologists]. / S3-Leitlinie "Vaginale Geburt am Termin" aus anästhesiologischer Sicht : Wissenswertes für den Anästhesisten.

The publication of the new S3 guidelines on "full-term vaginal birth" and the guidelines on cesarean section, also published in 2020, provide further steps towards the promotion of evidence-based medicine in obstetrics, even if the exact configuration of neonatal monitoring during birth, in particular, is still the subject of current discussions. The multiprofessionality in the medical supervision of a birth is also fundamentally well-represented in the compilation of the S3 guidelines by the participating actors and specialist societies. Important from an anesthesiological perspective is the fact that neuraxial procedures still represent the gold standard in obstetric analgesia. With remifentanil PCA an alternative option is available that enables a reliable analgesia to be accomplished, e.g. when there are contraindications to performing neuraxial methods, if this is appropriate under the prevailing circumstances (1:1 support and appropriate monitoring). During an uncomplicated birth the strict fasting rules are relaxed. Overall, the guidelines underline the importance of self-determination and self-control for the expectant mother and give the highest priority to the safety and well-being of mother and child; however, this presupposes that the expectant mother is sufficiently informed about the value of neuraxial analgesia. For this it appears to be of importance to initiate information proposals, which go beyond the usual information sessions for parents that are often organized exclusively by midwives.

[Non-cardiac surgery in adults with congenital heart defects : Most important parameters in anesthesia management]. / Nichtkardiale Eingriffe bei Erwachsenen mit angeborenen Herzfehlern : Wichtigste Parameter des anästhesiologischen Managements.

BACKGROUND: Adults with congenital heart disease (CHD) represent an increasing proportion of patients undergoing non-cardiac surgery. OBJECTIVE: To identify the most important parameters for management of anesthesia. MATERIAL AND METHODS: Evaluation and discussion of the current original research and guideline recommendations. RESULTS: There are approximately 300,000 patients with CHD living in Germany. The preoperative evaluation is an important influencing factor affecting perioperative morbidity and mortality. Echocardiography is the key instrument for identifying cardiac conditions predisposing to adverse events. The subdivision of CHD into lesions with left-to-right shunt, obstructive lesions and complex congenital heart diseases facilitates the classification of the pathophysiology. CONCLUSION: Decisive for the perioperative outcome of patients with CHD are the identification of high-risk patients, understanding of the individual situation with respect to the underlying pathophysiology and the intraoperative maintenance of cardiac output.

Emergence of tick-borne encephalitis in new endemic areas in Austria: 42 years of surveillance.

Human infections with tick-borne encephalitis (TBE)virus are a public health concern in certain regions of Europe, central and eastern Asia. Expansions of endemic areas and increased incidences have been associated with different factors including ecological changes supporting tick reproduction, socioeconomic changes increasing human outdoor activities and climatic changes favouring virus circulation in natural foci. Austria is among the most strongly affected countries in Central Europe, but the annual number of cases has strongly declined due to vaccination. Here,we have analysed changes of the incidence of TBE in the unvaccinated population of all federal states of Austria over a period of 42 years. The overall incidence in Austria has remained constant, but new strongly affected endemic regions have emerged in alpine valleys in the west of Austria. In parallel, the incidence in low-land regions in the north-east of the country is decreasing. There is no evidence for a shift to higher altitudes of infection sites in the traditional TBE zones,but the average altitudes of some newly established endemic areas in the west are significantly higher. Our analyses underscore the focal nature of TBE endemic areas and the potential of TBE virus to emerge in previously unaffected regions.

Lipidomic analysis of human placental syncytiotrophoblast microvesicles in adverse pregnancy outcomes.

PROBLEM: Syncytiotrophoblast microvesicles (STBM) are shed from placenta into the maternal circulation. STBM circulate in increased amounts in adverse pregnancies, e.g., preeclampsia and recurrent miscarriages (RM). Recently dysregulation of lipid metabolites has been proposed to be associated with their pathogenesis. Lipid composition of STBM in healthy and adverse pregnancies remains unknown. OBJECTIVE: To determine lipid composition of STBM and whether STBM lipid composition differs in pathologic and normal pregnancies. STUDY DESIGN: Patients with Preeclampsia (n = 6) or history of RM (n = 9) (>2 consecutive losses <20 weeks) and gestational age-matched normal pregnant controls (same number as cases) were recruited. STBM were prepared from placental explant culture supernatant. Lipid profiling of STBM was performed by mass spectrometry in combination with liquid chromatography. We quantified ∼200 lipids in STBM including (i) glycerophospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylinositol, PI; phosphatidylglycerol, PG; phosphatidylserine, PS; phosphatidic acid, PA); (ii) sphingolipids (sphingomyelin, SM; ceramide, Cer; Glucosylceramide, GluCer; ganglioside mannoside 3, GM3); (iii) free cholesterol and cholesteryl esters, CE. RESULTS: The major lipid classes in STBM were SM, Chol, PS, PC and PI, along with PA and GM3 enrichments. SM/PC ratio showed a unique reversal (3:1) compared to that normally found in human cells or plasma. Level of total PS was significantly upregulated (p < 0.005) in preeclampsia patients, while PI (p < 0.0005), PA (p < 0.005), and GM3 (p < 0.05) were significantly downregulated. Similar trends were obtained in RM. CONCLUSIONS: Differential lipid expression of STBM in preeclampsia or RM includes those that are implicated in immune response, coagulation, oxidative stress, and apoptosis.

Long-term quality of sleep after remifentanil-based anaesthesia: a randomized controlled trial.

BACKGROUND: Clinical and pre-clinical data agree that opioids disrupt sleep architecture. Recently, remifentanil has been suggested to cause possible long-term disturbances of sleep quality. This randomized controlled clinical trial was designed to substantiate or refute a possible long-term effect of remifentanil on the quality of sleep. METHODS: One hundred patients undergoing elective surgery were randomized to receive either fentanyl or remifentanil-based anaesthesia. Before operation (T0) and 3 (T3) and 6 (T6) months after operation, the quality of sleep was assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Overall, the quality of sleep for patients in the remifentanil or fentanyl group was not significantly different at any time point. Patients in the fentanyl group screened as good sleepers before operation showed no differences across time course of the study in PSQI scores. In contrast, good sleepers in the remifentanil group had significantly impaired sleep quality for at least 3 months after operation. Patients who were before operation screened as poor sleepers showed no significant changes in PSQI scores at T3 and T6 in both groups. CONCLUSIONS: The intraoperative use of remifentanil in a general patient population does not significantly alter the quality of sleep in the postoperative period. However, it may result in a significant reduction in the quality of sleep in patients before operation considered good sleepers. These changes were not observed in the group of patients receiving fentanyl. The relevance of these findings in terms of patient recovery and quality-of-life warrants further investigation. Trial Registration. ACTRN12610000362099.

Procedural complications of central venous catheter insertion.

BACKGROUND: Central venous catheters (CVC) have complication rates as high as 20% and are associated with significant morbidity and mortality. In this study we wished to determine the incidence of procedural related complications at different venous access sites as well as the impact of ultrasound (US) use, operator experience and level of supervision of trainees in a prospective observational study. METHODS: Five hundred consecutive patients undergoing elective CVC insertion were prospectively followed. Data with regards to US use, operator experience, level of supervision, site of insertion and procedural complications were collected. RESULTS: The overall rate of procedural complications was 19.5%. Operators with <25 insertions caused significantly more complications (25.2% vs. 13.6%). Arterial punctures occurred significantly more frequently when US was not used (7.2 vs. 2.1%) and at the subclavian site (8% vs. 1.6%). Higher levels of supervision were significantly associated with a decreased number of complications (10.7% vs. 23.8%). Subclavian vein as access point for the CVC resulted in significantly more overall complications (29.2% vs. 17.7%). Inexperienced operators combined with SCV approach were significant predictors for increased procedural-related complications. CONCLUSION: Immediate procedural-related complications during CVC insertion are common. To reduce the incidence of procedural-related complications we advocate multiple strategies to assure central venous cannulation safety: 1) the internal jugular vein should be the primary target vessel; 2) trainees with <25 previous catheter insertions should be supervised at all times; 3) ultrasound may reduce the incidence of procedural-related complications.

Lanosterol induces mitochondrial uncoupling and protects dopaminergic neurons from cell death in a model for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder marked by the selective degeneration of dopaminergic neurons in the nigrostriatal pathway. Several lines of evidence indicate that mitochondrial dysfunction contributes to its etiology. Other studies have suggested that alterations in sterol homeostasis correlate with increased risk for PD. Whether these observations are functionally related is, however, unknown. In this study, we used a toxin-induced mouse model of PD and measured levels of nine sterol intermediates. We found that lanosterol is significantly (∼50%) and specifically reduced in the nigrostriatal regions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, indicative of altered lanosterol metabolism during PD pathogenesis. Remarkably, exogenous addition of lanosterol rescued dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in culture. Furthermore, we observed a marked redistribution of lanosterol synthase from the endoplasmic reticulum to mitochondria in dopaminergic neurons exposed to MPP+, suggesting that lanosterol might exert its survival effect by regulating mitochondrial function. Consistent with this model, we find that lanosterol induces mild depolarization of mitochondria and promotes autophagy. Collectively, our results highlight a novel sterol-based neuroprotective mechanism with direct relevance to PD.

Systems wide analyses of lipids in the brainstem during inflammatory orofacial pain - evidence of increased phospholipase A(2) activity.

Recent studies suggest that CNS phospholipase A(2) (PLA(2) ) isoforms play a role in nociception, but until now, direct evidence of increased brain PLA(2) activity during allodynia or hyperalgesia is lacking. The present study was carried out, using lipidomics or systems wide analyses of lipids using tandem mass spectrometry, to elucidate possible changes in rat brain lipids after inflammatory pain induced by facial carrageenan injection. The caudal medulla oblongata showed decreases in phospholipids including phosphatidylethanolamine and phosphatidylinositol species, but increases in lysophospholipids, including lysophosphatidylethanolamine, lysophosphatidylinositol and lysophosphatidylserine, indicating increased PLA(2) activity and release of arachidonic acid after facial carrageenan injection. These changes likely occur in the spinal trigeminal nucleus which relays nociceptive input from the orofacial region. High levels of sPLA(2) -III, sPLA(2) -XIIA, cPLA(2) and iPLA(2) mRNA expression were detected in the medulla oblongata. Increase in sPLA(2) -III mRNA expression was found in the caudal medulla of carrageenan-injected rats, although no difference in sPLA(2) -III protein expression was detected. The changes in lipids as determined by lipidomics were therefore consistent with an increase in PLA(2) enzyme activity, but no change in enzyme protein expression. Together, these findings indicate enhanced PLA(2) activity in the caudal medulla oblongata after inflammatory orofacial pain.

Intraoperative thrombolysis in a patient with cardiopulmonary arrest undergoing caesarean delivery.

Thromboembolic events during pregnancy remain a major cause of morbidity and mortality with possible catastrophic sequelae for the patient. The decision whether to use high-risk therapeutic thrombolytics during pregnancy or perinatally is complicated and many considerations pertain. We report on the thrombolytic management of a 34-year-old woman who had an asystolic cardiac arrest secondary to massive pulmonary embolism while undergoing emergency caesarean delivery. The patient was thrombolysed during successful cardiopulmonary resuscitation. Return of spontaneous circulation was accompanied by massive uterine bleeding. Instead of performing a postpartum hysterectomy, the uterus was preserved through continuous manual pressure and packing for four hours by the obstetric team until haemostasis was achieved. The patient survived and was later discharged without any major neurological deficit.

Hormonal male contraception in men with normal and subnormal semen parameters.

Hormonal male contraception based on testosterone alone or on a combination of testosterone with a gestagen has been shown to suppress spermatogenesis effectively and to be fully reversible. However, clinical studies to date have only included volunteers with so-called 'normal' semen values by WHO standards. As a male contraceptive should be available to all interested men regardless of their semen parameters, we investigated how volunteers with subnormal semen parameters would respond to hormonal male contraception. During a 34-week treatment phase, the volunteers received injections of 1000 mg testosterone undecanoate in weeks 0, 6, 14 and 24. This was followed by a 24-week recovery and follow-up period. As it was not known whether men with subnormal semen parameters would recover to starting levels, cryopreservation of semen was offered to all subnormal volunteers. Twenty-three men with normal semen parameters and 18 with sperm counts below 20 million completed the trial. The normal volunteers showed the expected response with 17 suppressing sperm counts below 1 million/ejaculate (13 showing azoospermia) and six not-suppressing below 1 million sperm/ejaculate. By the end of the recovery period, all sperm counts had returned to the range of starting values. The subnormal group showed a similar pattern with 13 of 18 (= 72%) men suppressing below 1 million/ejaculate (8/18 = 44% showing azoospermia) and the remaining 5 of 18 (= 28%) not-suppressing sperm counts below 1 million/ejaculate. All sperm counts returned to the starting range. The study shows that in Caucasian men with normal sperm counts as well as in men with subnormal sperm counts, testosterone alone can produce azoospermia in about half and suppression below one million in about two-thirds of the volunteers. The same proportion of men in both groups appears to require an additional gestagen for full contraceptive protection. Most importantly, regarding suppressibility and reversibility, volunteers with normal and subnormal sperm counts display the same pattern.

Continuous spinal anesthesia versus continuous femoral nerve block for elective total knee replacement.

BACKGROUND: Continuous spinal analgesia (CSA) and continuous femoral nerve blockade (CFNB) are well-established procedures for postoperative pain relief. This study compares the efficacy, adverse effects and complications associated with these two analgesic methods in patients undergoing total knee arthroplasty (TKA). METHODS: Data were analyzed from consecutive patients undergoing TKA under either CSA or spinal anesthesia plus CFNB. Quality of analgesia was assessed based on opioid consumption and pain intensity (visual analogue scale [VAS] where 0=no pain and 10=utmost imaginable pain) until postoperative day 4. In addition, joint mobility was assessed, and any adverse reactions or side effects were noted. RESULTS: Sixty-two patients had satisfactory postoperative pain relief, and maximum pain scores were reported between 12 and 24 hrs. Median pain scores in the CSA group were significantly lower than those in the CFNB group (1.0 [0.9-1.9] vs. 2.0 [1.5-3.6] for resting pain and 2.0 [1.7-3.1] vs. 5.0 [3.0-5.5] for dynamic pain, respectively; P<0.001 for days 0 and 1; P<0.05 for all other days). Piritramide consumption was significantly higher in the CFNB group (P<0.01). There were no significant differences between the groups for postoperative mobility of the joint or patient satisfaction. CONCLUSION: Both methods demonstrated analgesic efficacy after total knee arthroplasty, although there was less pain severity and opioid consumption use reported with continuous spinal analgesia. However, the use of continuous spinal analgesia is limited by concerns about the risk profile and absence of approved devices for continuous intrathecal infusion.

The effect of APOE genotype on brain levels of oxysterols in young and old human APOE epsilon2, epsilon3 and epsilon4 knock-in mice.

Despite apolipoprotein E's important role in cholesterol transport and metabolism in the brain as well as its influence on Alzheimer's disease, the impact of the human APOE genotype on cholesterol metabolism in brain has not been fully examined. This study was carried out to investigate APOE genotype effects on oxysterols measured. In this study the measurement of cholesterol and several oxysterols in the brains of human APOE epsilon2, epsilon3 and epsilon4 knock-in mice at 8 weeks and 1 year of age using gas chromatography mass spectrometry (GC-MS) demonstrated no APOE genotype or age effect on total brain cholesterol and the oxysterol 24-hydroxycholesterol. The level of 27-hydroxycholesterol was elevated in 1 year old animals for all APOE genotypes. Interestingly, lathosterol an indicator of cholesterol synthesis was significantly reduced in the 1 year old animals for all APOE genotypes. APOE epsilon4 expressing mice exhibited statistically lower levels of lathosterol compared to APOE epsilon2 in both the young and old mice. Oxidized cholesterol metabolites were significantly lower in APOE epsilon2 mice compared to other genotypes at 8 weeks old. Although minimal differences were observed between APOE E3 and E4 knock-in (KI) mice, these findings indicate that there are some clear APOE genotype specific effects on brain cholesterol synthesis and associated metabolic pathways, particularly in APOE epsilon2 KI mice.

Feasibility of infusion pumps for continuous spinal administration of local anesthetics in post-operative pain therapy.

BACKGROUND AND OBJECTIVES: For completion of perioperative care and for general ethical considerations, any intraoperatively used catheter technique should be utilizable for post-operative pain therapy. Continuous spinal anesthesia (CSA) is an established form of local anesthetic application. However, for its use in post-operative therapy, infusion pumps are required that are technically able to deliver low rates and are distinctive in design to avoid possible pump or medication swaps. Because of a lack of devices specifically designed for CSA, we investigated the potential deployability of infusion pumps for post-operative pain therapy via CSA microcatheters, which were originally designed and approved for different applications. METHODS: The accuracy of infusion rates of three different pumps was measured in a liquor model environment. Furthermore, we investigated safety and user-friendliness by interviewing 30 anesthesiologists and 15 pain nurses. RESULTS: Except for the first hour of infusion, all pumps provided comparable and adequate flow profiles. However, interviews revealed significant risk factors for all pumps in terms of swapping devices, lines or medications and misprogramming the units. DISCUSSION: All pumps tested were technically able to deliver accurate flow rates; however, because the non-CSA-specific design involves the risk of medication overdosage and syringe swaps, none of the systems tested can be recommended for routine use in post-operative CSA, irrespective of the fact that it was an off-label application anyway. Therefore, to ensure patient safety, continuous spinal administration of local anesthetics via microcatheters is a questionable method of post-operative pain therapy as long as non-specific pumps are used.

[Scoliosis surgery in children from the viewpoint of anaesthesiology]. / Skoliosechirurgie bei Kindern aus anästhesiologischer Sicht.

Anaesthesia for scoliosis surgery in children is a challenge for the paediatric anaesthesiologist. The large range of underlying pathologies causing deranged physiology in an inhomogeneous patient group ranging from neonates to adolescents necessitates diligent and individual preparation for each case. Due to the invasiveness of the operation demanding anaesthetic care is necessary. This review highlights current approaches to monitoring, anaesthetic regimen, positioning of the patient, blood conservation and transfusion, age-related pathophysiology, ventilation and postoperative pain therapy. The introduction of neurophysiologic spinal cord monitoring requires certain adaptations of the anaesthetic regimen to suit technological advances.

Network "Rodent-borne pathogens" in Germany: longitudinal studies on the geographical distribution and prevalence of hantavirus infections.

Hantavirus infections are known in Germany since the 1980s. While the overall antibody prevalence against hantaviruses in the general human population was estimated to be about 1-2%, an average of 100-200 clinical cases are recorded annually. In the years 2005 and 2007 in particular, a large increase of the number of human hantavirus infections in Germany was observed. The most affected regions were located in the federal states of Baden-Wuerttemberg, Bavaria, North Rhine Westphalia, and Lower Saxony. In contrast to the well-documented situation in humans, the knowledge of the geographical distribution and frequency of hantavirus infections in their rodent reservoirs as well as any changes thereof was very limited. Hence, the network "Rodent-borne pathogens" was established in Germany allowing synergistic investigations of the rodent population dynamics, the prevalence and evolution of hantaviruses and other rodent-associated pathogens as well as their underlying mechanisms in order to understand their impact on the frequency of human infections. A monitoring of hantaviruses in rodents from endemic regions (Baden-Wuerttemberg, Bavaria, North Rhine Westphalia, Lower Saxony) and regions with a low number of human cases (Mecklenburg Western-Pomerania, Brandenburg, Saxony, Saxony-Anhalt) was initiated. Within outbreak regions, a high prevalence of Puumala virus (PUUV) was detected in bank voles. Initial longitudinal studies in North Rhine Westphalia (city of Cologne), Bavaria (Lower Bavaria), and Lower Saxony (rural region close to Osnabrück) demonstrated a continuing presence of PUUV in the bank vole populations. These longitudinal studies will allow conclusions about the evolution of hantaviruses and other rodent-borne pathogens and changes in their distribution, which can be used for a risk assessment of human infections. This may become very important in order to evaluate changes in the epidemiology of rodent-borne pathogens in the light of expected global climate changes in the future.