Time trajectories and within-subject correlations of matrix metalloproteinases 3, 8, 9, 10, 12, and 13 serum levels and their ability to predict mortality in polytraumatized patients: a pilot study.

BACKGROUND: Managing polytrauma victims poses a significant challenge to clinicians since applying the same therapy to patients with similar injury patterns may result in different outcomes. Using serum biomarkers hopefully allows for treating each multiple injured in the best possible individual way. Since matrix metalloproteinases (MMPs) play pivotal roles in various physiological processes, they might be a reliable tool in polytrauma care. METHODS: We evaluated 24 blunt polytrauma survivors and 12 fatalities (mean age, 44.2 years, mean ISS, 45) who were directly admitted to our Level I trauma center and stayed at the intensive care unit for at least one night. We determined their MMP3, MMP8, MMP9, MMP10, MMP12, and MMP13 serum levels at admission (day 0) and on days 1, 3, 5, 7, and 10. RESULTS: Median MMP8, MMP9, and MMP12 levels immediately rose after the polytrauma occurred; however, they significantly decreased from admission to day 1 and significantly increased from day 1 to day 10, showing similar time trajectories and (very) strong correlations between each two of the three enzyme levels assessed at the same measurement point. For a two-day lag, autocorrelations were significant for MMP8 (- 0.512) and MMP9 (- 0.302) and for cross-correlations between MMP8 and MMP9 (- 0.439), MMP8 and MMP12 (- 0.416), and MMP9 and MMP12 (- 0.307). Moreover, median MMP3, MMP10, and MMP13 levels significantly increased from admission to day 3 and significantly decreased from day 3 to day 10, showing similar time trajectories and an (almost) strong association between every 2 levels until day 7. Significant cross-correlations were detected between MMP3 and MMP10 (0.414) and MMP13 and MMP10 (0.362). Finally, the MMP10 day 0 level was identified as a predictor for in-hospital mortality. Any increase of the MMP10 level by 200 pg/mL decreased the odds of dying by 28.5%. CONCLUSIONS: The time trajectories of the highly varying individual MMP levels elucidate the involvement of these enzymes in the endogenous defense response following polytrauma. Similar time courses of MMP levels might indicate similar injury causes, whereas lead-lag effects reveal causative relations between several enzyme pairs. Finally, MMP10 abundantly released into circulation after polytrauma might have a protective effect against dying.

Serum levels of matrix metalloproteinases 1, 2, and 7, and their tissue inhibitors 1, 2, 3, and 4 in polytraumatized patients: Time trajectories, correlations, and their ability to predict mortality.

There has been limited research on assessing metalloproteinases (MMPs) 1, 2, and 7, as well as their tissue inhibitors (TIMPs) 1, 2, 3, and 4 in the context of polytrauma. These proteins play crucial roles in various physiological and pathological processes and could be a reliable tool in polytrauma care. We aimed to determine their clinical relevance. We assessed 24 blunt polytrauma survivors and 12 fatalities (mean age, 44.2 years, mean ISS, 45) who were directly admitted to our Level I trauma center and spent at least one night in the intensive care unit. We measured serum levels of the selected proteins on admission (day 0) and days 1, 3, 5, 7, and 10. The serum levels of the seven proteins varied considerably among individuals, resulting in similar median trend curves for TIMP1 and TIMP4 and for MMP1, MMP2, TIMP2, and TIMP3. We also found a significant interrelationship between the MMP2, TIMP2, and TIMP3 levels at the same measurement points. Furthermore, we calculated significant cross-correlations between MMP7 and MMP1, TIMP1 and MMP7, TIMP3 and MMP1, TIMP3 and MMP2, and TIMP4 and TIMP3 and an almost significant correlation between MMP7 and TIMP1 for a two-day-lag. The autocorrelation coefficient reached statistical significance for MMP1 and TIMP3. Finally, lower TIMP1 serum levels were associated with in-hospital mortality upon admission. The causal effects and interrelationships between selected proteins might provide new insights into the interactions of MMPs and TIMPs. Identifying the underlying causes might help develop personalized therapies for patients with multiple injuries. Administering recombinant TIMP1 or increasing endogenous production could improve outcomes for those with multiple injuries. However, before justifying further investigations into basic research and clinical relevance, our findings must be validated in a multicenter study using independent cohorts to account for clinical and biological variability.

Subjective Long-Term Outcomes After Vaginal Native Tissue Hysteropexy: Cohort Study.

IMPORTANCE: There are still doubts about long-term satisfaction rates of native tissue uterine preserving surgical techniques for pelvic organ prolapse. OBJECTIVE: The objective of this study was to compare long-term subjective success rates and satisfaction rates between vaginal sacrospinous hysteropexy (SSHP) and vaginal hysterectomy with uterosacral ligament suspension (VH-USLS). STUDY DESIGN: This was a retrospective single-center, observational matched cohort study in women receiving either SSHP or VH-USLS between 2004 and 2021. Primary outcome was overall subjective success (combined outcome of absence of bulge nor retreatment, and satisfaction with operation) at least 12 months after surgery. Satisfaction with the operation was defined as a combined Patient Global Impression of Improvement rating ≤ 2 and a patient satisfaction score ≥7. RESULTS: Of 583 patients, 192 patients could be matched (SSHP, 96; VH-USLS, 96), with 55% (SSHP, 60; VH-USLS, 45) participating at the telephone interview. Mean follow-up time was 77 months for VH-USLS, and 36 months for SSHP, respectively. No difference in overall subjective success rates was found between the groups (45% VH-USLS and 51% SSHP; P = 0.54). Overall satisfaction was similar between both groups (70% vs 71%, P = 0.90). Logistic regression found no influence of duration of follow-up and the overall subjective success rate. Both procedures would be recommended to a relative or friend by a large majority of patients (88% vs 85%, P = 0.761). Operative time and hospitalization time were significantly shorter in the SSHP group. No serious complications were reported. CONCLUSIONS: Overall success rates did not differ between both procedures after at least 1 year of follow-up with relatively high satisfaction rates. Sacrospinous hysteropexy had shorter operative time and shorter duration of hospitalization.

Long-term adherence to pessary use in women with pelvic organ prolapse: A retrospective cohort study.

PURPOSE OF THE RESEARCH: Vaginal pessary use is an established, non-surgical treatment option for pelvic organ prolapse. While satisfaction rates are initially high, they seem to decline over time. We aimed to determine the median duration of pessary use among our patients and to evaluate reasons for discontinuation. METHODS: All patients who were treated with a vaginal pessary for pelvic organ prolapse between 2007 and 2022 at our institution (a maximum observation period of 15 years) were included in this retrospective cohort study. Data were collected from the in-house electronic databases and the date of pelvic floor surgery was defined as the primary endpoint. In case of no documented surgery, the date of the last follow-up visit (for patients lost to follow-up or who discontinued pessary use without subsequent surgery) or the date of final data collection (for those with presumed continued pessary use) was used as the primary endpoint. Duration of pessary use is represented by Kaplan-Meier curves. Effects of possible confounders were investigated by Cox regression models. A Cox regression model was evaluated for patients with the three most common types of pessary: ring, cube and shell. A chi-square test was performed to compare therapy adherence according to pessary type. PRINCIPAL RESULTS: Data of 779 patients could be included in the statistical analysis. The estimated median duration of pessary use was 173 weeks (95 % CI 104-473) - approximately 3.3 years. Overall, 30 % of patients opted for surgical therapy and the majority of them did so within 4 months of initiation of pessary use (median time: 19 weeks, 95 % CI 16-26). In 5 % of cases a discontinuation of pessary use without subsequent surgery was documented and 18 % were lost to follow-up before a planned visit, thus leaving 47 % of our patients with presumed continued pessary use. Possible confounding factors for discontinuation of pessary use were tested but were found to be non-significant (body mass index, Pelvic Organ Prolapse - Quantification score, pelvic floor training, age, parity, menopausal status, nicotine consumption, incontinence or size of pessary). Reasons for discontinuation of pessary use were documented in 51 % of patients: unspecified patient wish (23 %), pessary use tiredness (10 %), general dissatisfaction with pessary therapy (7 %), unspecified reasons (5 %), pessary self-change not possible (1 %), erosion, bleeding, pain (2 %); none of the pessary types fitted (2 %). CONCLUSIONS: According to our data, almost half of our patients with pelvic organ prolapse and pessary therapy continued pessary use until a maximum follow-up time of 15 years, whereas about one-third of patients finally opted for surgical repair (a majority of these within 4 months after pessary therapy initiation). The remaining patients were either lost to follow-up or discontinued pessary use without subsequent surgery. The stated reasons for discontinuation of pessary use were mostly non-specific, but only 1 % reported that pessary self-change was not possible. Erosion bleeding or pain was documented in only 2 % of cases as reason for discontinuation. This information helps clinicians to inform their patients with pelvic organ prolapse about expected pessary therapy success and strengthens individual counselling. Furthermore, our data indicates vaginal pessary use for pelvic organ prolapse is feasible and safe for all women and that therapy adherence can extend beyond 5 years.

Krukenberg Progression of Gastric Carcinoma in Pregnancy: Is Early Diagnosis Possible? Case Report and Review of the Literature.

Krukenberg tumors are metastatic tumors of the ovaries, associated with poor outcomes. Most commonly, these tumors are of gastric origin. The diagnosis of Krukenberg tumors in pregnant patients is extremely rare and poses specific difficulties for clinicians. We report a case of a pregnant woman presenting with an unknown abdominal tumor. Through the use of magnetic resonance imaging, multiple differential diagnoses were proposed, including a malignant ovarian tumor. A cesarean section and explorative laparotomy were conducted, revealing Krukenberg metastases of a gastric tumor, discovered during intraoperative gastroscopy. Tumor resection with concomitant chemotherapy was conducted. The main aim of this paper was to evaluate whether earlier diagnosis seems possible in such cases. A thorough literature review was conducted, unfortunately revealing no reliable method for early detection. Furthermore, no consensus regarding diagnostics or therapy exists to date. Thus, more research should be conducted regarding this rare condition to offer recommendations regarding early detection, diagnostics, and therapeutic approaches.

Sacrospinous Hysteropexy Versus Prolapse Hysterectomy with Apical Fixation: A Retrospective Comparison over an 18 Year Period.

BACKGROUND: Pelvic organ prolapse (POP) is a common health problem, with a high lifetime risk for prolapse surgery. Uterine-preserving procedures such as vaginal sacrospinous hysteropexy (SSH) have become an increasingly utilized surgical option for the primary treatment of POP. We wanted to evaluate peri- and postoperative outcome parameters of SSH as an alternative to vaginal hysterectomy with apical fixation. METHODS: A retrospective cohort study was conducted (2003-2021). All patients who underwent primary SSH (study group) for symptomatic POP were matched 1:1 by age and BMI with patients who underwent primary prolapse hysterectomy with apical fixation (control group). RESULTS: A total of 192 patients were included with 96 patients in the each of the SSH and hysterectomy groups. There were no statistically significant differences in baseline characteristics. The SSH group show a significantly shorter mean surgery time (p < 0.001), significantly fewer hospitalization days (p < 0.001), and significantly less intraoperative blood loss (p = 0.033) in comparison to the control group. Neither group had any intraoperative complication, or an intraoperative conversion to other surgical management options. No statistically significant difference was found in postoperative complications as categorized by the Clavien-Dindo classification or in postoperative urogynecological issues (UTI, de-novo, incontinence, residual urine, voiding disorders). Through log regression, none of the confounding factors such as age, BMI, or preoperative POP-Q stage could be identified as independent risk factors for the occurrence of postoperative complications. CONCLUSIONS: Our results confirm that a uterus-preserving technique has many benefits and, thus, should be considered as an additional intermediate step in a long-term treatment plan of pelvic organ prolapse.

Choosing the Most Efficacious and Safe Oral Treatment for Idiopathic Overactive Bladder: A Systematic Review and Network Meta-analysis.

CONTEXT: The choice of the most efficacious drug for patients with idiopathic overactive bladder (IOAB) remains challenging. OBJECTIVE: The aim of this network meta-analysis was to determine the most efficacious oral antimuscarinic or ß-adrenoceptor agonist accounting for adverse events for the management of IOAB. EVIDENCE ACQUISITION: A comprehensive electronic search was done in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Ovid for studies in any language in February 2021 considering the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. We included all randomized controlled trials assessing oral antimuscarinics or ß-adrenoceptor agonists for the treatment of IOAB. We determined the effect of specific bothersome symptoms separately. EVIDENCE SYNTHESIS: Fifty-four articles were included in our analysis. The most efficacious agents considering the evaluated outcomes were oxybutynin 15 mg/d in reducing incontinence episodes, imidafenacin 0.5 mg/d together with solifenacin 10 and 5 mg/d in reducing micturition episodes, fesoterodine 4 and 8 mg/d as well as solifenacin 10 mg/d in reducing urgency episodes, imidafenacin 0.5 mg/d and solifenacin 10 mg/d in reducing urgency urinary incontinence episodes, and solifenacin 10 mg/d, vibegron 50 mg/d, and fesoterodine 8 mg/d in improving the voided volume. Gastrointestinal problems, especially due to antimuscarinic agents, were the most prevalent adverse events. CONCLUSIONS: Taken together, there is only minimal difference between the efficacy of oral antimuscarinics and that of ß-adrenoceptor agonists. Although finding the best medication for all is impossible, finding the best treatment for every individual patient can be done by considering the efficacy of a medicine for the most bothersome symptom(s) in balance with drug-specific adverse events. PATIENT SUMMARY: This study aimed to find the most efficient oral medication to treat overactive bladder, taking into consideration the adverse events. Based on our study, there is a minimal difference in the efficacy between the two major drug classes used to treat overactive bladder. Gastrointestinal problems were the most common adverse events in medical treatment of overactive bladder. Selection of the best treatment is possible through shared decision-making between the doctor and the patient based on the patient's most bothersome symptom. We provide a framework for physicians to facilitate shared decision-making with each individual patient.

Clinical risk factors for recurrence of pelvic organ prolapse after primary native tissue prolapse repair.

OBJECTIVE: To define potential risk factors for recurrence of prolapse. METHODS: This short report included all women who presented with recurrence of prolapse as well as without any recurrence signs after a vaginal approach of native tissue prolapse repair at an urogynecological center in Austria. RESULTS: A total of 124 recurrence cases and 64 women with no signs of recurrence after their index prolapse surgery were included. Multivariate analysis identified advanced preoperative POP­Q stage (pelvic organ prolapse-quantification) as an independent risk factor for postoperative recurrence of prolapse (p = 0.045). CONCLUSION: Initial proper preoperative counseling is of particular importance to modulate patients' expectations after prolapse surgery.

The placebo and nocebo effects in functional urology.

A placebo is an inert substance normally used in clinical trials for comparison with an active substance. However, a placebo has been shown to have an effect on its own; commonly known as the placebo effect. A placebo is an essential component in the design of conclusive clinical trials but has itself become the focus of intense research. The placebo effect is partly the result of positive expectations of the recipient on the state of health. Conversely, a nocebo effect is when negative expectations from a substance lead to poor treatment outcomes and/or adverse events. Randomized controlled trials in functional urology have demonstrated the importance of the placebo and nocebo effects across different diseases such as overactive bladder, urinary incontinence, lower urinary tract symptoms and interstitial cystitis/painful bladder syndrome, as well as male and female sexual dysfunction. Understanding the true nature of the placebo-nocebo complex and the scope of its effect in functional urology could help urologists to maximize the positive effects of this phenomenon while minimizing its potentially negative effects.

Female Pelvic Floor Dysfunction Continues to Negatively Impact Quality-of-Life during the COVID-19 Lockdown.

The COVID-19 pandemic led to dramatical changes in elective medical care. We analysed its impact on patients with female pelvic floor dysfunction during the 6 weeks of lockdown in Austria. A cross-sectional study was conducted: All 99 women who presented at the urogynaecologic outpatient clinic of the Medical University of Vienna with pelvic organ prolapse (POP) or urinary incontinence (UI) from December 2019 up to the lockdown in March 2020 were included and contacted. 97% of these women (96 participants) agreed to participate in the survey conducted to asses pelvic floor related quality of life (QoL) through telephone- interrogation. The mean age was 59 ± 14.8 years, the POP group consisted of 42 women while the UI group included 54 women. Most participants (83% of POP and 81% of UI cases) stated that their female pelvic floor dysfunction had remained equally relevant or had become even more significant during the lockdown. Associated symptoms and psychological strain also maintained their relevance during the lockdown (UI: p = 0.229; POP: p = 0.234). Furthermore, 97% of all interviewed women indicated to be strongly willing to continue their treatment. A generalised linear model regression revealed no clinical or demographic risk factors for psychological strain during the lockdown (p > 0.05). Our results demonstrate that women's QoL remains significantly impaired by their pelvic-floor disorders even during a worldwide crisis such as COVID-19. Therefore, elective disciplines such as urogynaecology urgently require novel and innovative strategies for continued patient care even in times of a lockdown.

Does the choice of pelvic organ prolapse treatment influence subjective pelvic-floor related quality of life?

OBJECTIVES: The relationship between pelvic organ prolapse (POP) treatment and subjective pelvic-floor related quality of life (QoL) was examined. STUDY DESIGN: 130 postmenopausal women with symptomatic POP were included: 45 % (59/130) were treated conservatively with pessary and 55 % (71/130) underwent pelvic floor surgery. All participants answered the validated German pelvic floor questionnaire at the time of baseline examination, as well as three months later. RESULTS: Our results demonstrated a significant improvement regarding mean score in the domains "prolapse" (p = 0.001) and "sexual function" (p = 0.001) three months after prolapse surgery, whereas in the pessary group only the score in the "prolapse" domain improved (p < 0.001). When comparing the two treatment arms after three months, patients reported a significant advancement regarding their "sexual function" domain in the surgery group (p < 0.0001). Furthermore, univariate analysis revealed a significant positive correlation between "prolapse" domain score (correlation coefficient = 0.0001) as well as "bladder" domain score (correlation coefficient <0.001) and POP-Q stage. Additionally, a significant negative correlation between "sexual function" domain score and POP-Q stage was found (correlation coefficient = 0.0001). CONCLUSION: Our results revealed that three months after prolapse surgery, pelvic-floor related QoL showed significant improvement in the domain "sexual function" compared to three months pessary treatment. Besides, advanced prolapse stage correlated with higher symptom burden and worse sexual function.

Impact of COVID-19 lockdown on suicide attempts : A retrospective analysis of the springtime admissions to the trauma resuscitation room at the Medical University of Vienna from 2015-2020.

BACKGROUND: In response to the current coronavirus disease 2019 (COVID-19) pandemic the Austrian government issued a lockdown from 16 March to 15 May 2020. As periods of economic and emotional burden have proven to detrimentally affect people's psychological health, healthcare officials warned that the strict measures could have a serious impact on psychological health, leading to an increase in suicide attempts. Thus, the objective was to provide evidence for this assumption. METHODS: All adult patients admitted to the trauma resuscitation room of the Medical University of Vienna during the lockdown period following a suicide attempt were included in this analysis, forming the study group. Suicidal patients treated during the same period in 2015, 2016, 2018, and 2019 were pooled to create the control group. The year 2017 was excluded because another major hospital in Vienna was partially closed due to a change in infrastructure, resulting in an increased number of severely injured patients treated at our department. As the lockdown caused a markedly decreased number of patients admitted due to other reasons than suicide the actual number was replaced with the average number of patients admitted in the relevant previous 4 years. RESULTS: By comparing the study and the control group based on this realistic estimate we revealed an increase in attempted suicides during the lockdown period (p = 0.001). Demographic, mental health-related, and injury specific patient data did not differ between the groups. CONCLUSION: The results strongly urge for an improvement in crisis intervention and suicide prevention measures in the event of a future lockdown.

The effectiveness of surgical procedures to prevent post-hysterectomy pelvic organ prolapse: a systematic review of the literature.

INTRODUCTION AND HYPOTHESIS: Hysterectomy is one of the most commonly performed gynecological surgical procedures. One of the long-term risks associated with hysterectomy is the occurrence of pelvic organ prolapse (POP). To prevent post-hysterectomy POP, several suspension procedures are routinely performed at the time of hysterectomy. We performed a systematic review of published data in order to define the most effective surgical procedures for the prevention of post-hysterectomy POP. METHODS: We performed a systematic review of the literature by searching PubMed, the Cochrane Library, EMBASE, Ovid MEDLINE, and clinicaltrials.gov up to 24 May 2020. The search strategy included the keywords hysterectomy, post-hysterectomy, prolapse, colposuspension, culdoplasty, McCall, and combinations thereof. The inclusion criterion was a surgical procedure at the time of hysterectomy to prevent de novo POP. The outcome was incidence of post-hysterectomy POP. RESULTS: Six out of 553 retrieved studies met the methodological criteria for complete analysis. In this review, 719 women aged over 18 years were included. Only 2 studies were designed as prospective trials; however, only 1 compared women undergoing a procedure at the time of hysterectomy with controls. The prevalence of post-hysterectomy prolapse varied from 0% to 39%. CONCLUSION: A systematic review of published literature suggests that performing variations of McCall culdoplasty at the time of hysterectomy might be the most effective prophylactic surgical procedure for preventing post-hysterectomy pelvic organ prolapse.

The role of transforming growth factor-ß (TGF-ß1) in postmenopausal women with pelvic organ prolapse: An immunohistochemical study.

OBJECTIVE: Aim of the study was to investigate the expression of transforming growth factor-ß1 (TGF-ß1), a key regulator of the extracellular matrix composition, in the uterosacral ligaments (USLs) of women with pelvic organ prolapse (POP) compared with controls. We hypothesized that the expression pattern of TGF-ß1 differs between postmenopausal women with or without POP. METHODS: Under ethical approval, USL samples were obtained from postmenopausal women undergoing vaginal hysterectomy for stage two or greater pelvic organ prolapse (cases, n = 70) and from postmenopausal women without pelvic organ prolapse undergoing vaginal hysterectomy for benign indications (controls, n = 30). Immunohistochemical staining was performed from paraffin embedded tissue using anti-TGF-ß1 antibodies. The expression of TGF-ß1 was evaluated by the pathologist, who was blinded to all clinical data. RESULTS: The expression of TGF-ß1 was similar in patients with symptomatic POP (89 % positive) and in controls (90 % positive) without any signs of prolapse (p = 0.091). Age-adjusted analysis did not significantly alter these results. Regarding POP-Q stages, TGF-ß1 was significantly more frequently expressed in severe prolapse cases compared to moderate/mild cases (POP-Q stage IV versus POP-Q stage II and III; p = 0.001). No significant association could be detected between TGF-ß1 expression and age, BMI and parity in cases with POP (p > 0.05). As published previously, advanced patients' age as well as early menopausal age remained independent risk factors associated with POP in multiple logistic regression analysis (p = 0.001; p = 0.02). CONCLUSION: Although our study detected POP-Q stage related alterations in USL composition and TGF-ß1 expression, there was no significant difference in the expression of TGF-ß1 in cases with or without prolapse.