Endometriosis of the appendix: prevalence, associated lesions, and proposal of pathogenetic hypotheses. A retrospective cohort study with prospectively collected data.

OBJECTIVE: To assess the prevalence of endometriosis of the appendix and the association with other pelvic localizations of the disease and to provide pathogenesis hypotheses. METHODS: Monocentric, observational, retrospective, cohort study. Patients undergoing laparoscopic endometriosis surgery in our tertiary referral center were consecutively enrolled. The prevalence of the different localizations of pelvic endometriosis including appendix involvement detected during surgery was collected. Included patients were divided into two groups based on the presence of appendiceal endometriosis. Women with a history of appendectomy were excluded. MEASUREMENTS AND MAIN RESULTS: Four hundred-sixty patients were included for data analysis. The prevalence of appendiceal endometriosis was 2.8%. In patients affected by endometriosis of the appendix, concomitant ovarian and/or bladder endometriosis were more frequently encountered, with prevalence of 53.9% (vs 21.0% in non-appendiceal endometriosis group, p = 0.005) and 38.4% (vs 11.4%, p = 0.003), respectively. Isolated ovarian endometriosis was significantly associated to appendiceal disease compared to isolated uterosacral ligament (USL) endometriosis or USL and ovarian endometriosis combined (46.2% vs 15.4% vs 7.7%, p < 0.001). Poisson regression analysis revealed a 4.1-fold and 4.4-fold higher risk of ovarian and bladder endometriosis, respectively, and a 0.1-fold risk of concomitant USL endometriosis in patients with appendiceal involvement. CONCLUSION: Involvement of the appendix is not uncommon among patients undergoing endometriosis surgery. Significant association was detected between appendiceal, ovarian, and bladder endometriosis that may be explained by disease dissemination coming from endometrioma fluid shedding. Given the prevalence of appendiceal involvement, counseling regarding the potential need for appendectomy during endometriosis surgery should be considered.

Current Approaches to Worsening Heart Failure: Pathophysiological and Molecular Insights.

Worsening heart failure (WHF) is a severe and dynamic condition characterized by significant clinical and hemodynamic deterioration. It is characterized by worsening HF signs, symptoms and biomarkers, despite the achievement of an optimized medical therapy. It remains a significant challenge in cardiology, as it evolves into advanced and end-stage HF. The hyperactivation of the neurohormonal, adrenergic and renin-angiotensin-aldosterone system are well known pathophysiological pathways involved in HF. Several drugs have been developed to inhibit the latter, resulting in an improvement in life expectancy. Nevertheless, patients are exposed to a residual risk of adverse events, and the exploration of new molecular pathways and therapeutic targets is required. This review explores the current landscape of WHF, highlighting the complexities and factors contributing to this critical condition. Most recent medical advances have introduced cutting-edge pharmacological agents, such as guanylate cyclase stimulators and myosin activators. Regarding device-based therapies, invasive pulmonary pressure measurement and cardiac contractility modulation have emerged as promising tools to increase the quality of life and reduce hospitalizations due to HF exacerbations. Recent innovations in terms of WHF management emphasize the need for a multifaceted and patient-centric approach to address the complex HF syndrome.

Systematic use of intraureteral indocyanine green: a game changer in endometriosis surgery. A proof-of-concept study.

BACKGROUND: Endometriosis of the distal segment of the uterosacral ligament may lead to a displaced ureter in the surgical field and must be identified before safe disease excision can be carried out. The aim of this study is to investigate the benefit of the systematic use of preoperative intraureteral indocyanine green (ICG) fluorescence injection in patients undergoing endometriosis surgery. METHOD: In this proof-of-concept, monocentric, observational, cohort study data were prospectively collected and retrospectively analyzed. Patients underwent laparoscopic surgery for deep infiltrating endometriosis with suspected ureteral involvement between January 2022 and December 2023. Using the propensity score matching (PSM) in a 1:1 matching ratio, patients who underwent preoperative ICG injection were compared with those who did not in terms of ureterolysis length and duration, and operative time. RESULTS: The mean length of ureterolysis was shorter in the ICG group compared to the non-ICG group (p < 0.001). The ICG group also had shorter ureterolysis duration (p < 0.001) and operative time (p = 0.02). No complications were reported at mean 6.8-month follow-up visit. CONCLUSIONS: The systematic use of intraureteral ICG prior to uterosacral ligaments endometriosis surgery may be safe and could assist in reducing the length of ureterolysis and operative time. Larger prospective studies are needed to confirm our findings.

Ovarian Torsion in a Young Adolescent with Rokitansky Syndrome.

A case report of a premenarcheal patient with ovarian torsion and mullerian agenesis is presented. A 12-year-old prepubertal girl is presented with severe right lower quadrant abdominal pain and mild rebound. Laparoscopy showed mullerian agenesis and twisted right adnexa. Detorsion and cystectomy of the right ovary were done, and the ovary was fixed to the pelvic sidewall. The postoperative course was uneventful. An association between the lax attachment of the adnexa and torsion may be a contributing factor in this condition.

The Changing Role of Loop Diuretics in Heart Failure Management across the Last Century.

Congestion is the main therapeutic target of acute heart failure (HF) treatment, and loop diuretics (LDs) are widely used drugs for this purpose. Despite their extensive use, these agents remain largely understudied in terms of modality administration, treatment duration, and escalation dose for subjects responding poorly to therapy. LDs were initially investigated in several edematous statuses such as cirrhosis, nephrotic syndrome, and congestive HF and initially approved for the treatment of cardiogenic congestion in 1966. Despite the long history and the undoubted role in congestion management, the use of LDs in the acute phase is mostly based on the physician's experience, the oral amount chronically administered, and clinical decongestion response. Recent literature suggests monitoring diuretic activity by the evaluation of daily diuresis, weight loss, and sample urinary sodium assessment after early intravenous LD administration. More recently, the measurement of urinary sodium integrated with urinary and blood creatinine values and fluid status has been suggested as optimal marker to predict whole diuretic efficiency and to target the optimal dose. However, this method is not easily available in the chronic setting or in patients with recurrent hospitalization taking a high loop diuretic amount. Since high loop diuretic dose is related to diuretic resistance (DR) and poorer outcome, additional diuretics acting in different nephron sites are often required. Current sequential nephron blockade can stimulate diuresis by synergic mechanisms. This strategy is attempted in patients with poor response, revealing good results in the early period, but the effects of neuro-endocrine stimulation and electrolyte balance across long-term follow-up are still questioned. This paper reviews the historical course of loop diuretics and highlights the need for a universal approach based on clinical conditions, cardio-renal interactions, and HF phenotypes.

Histological Features of Neovaginal Epithelium after Vaginoplasty in Mayer-Rokitansky-Küster-Hauser Syndrome.

OBJECTIVE: To analyze the features of the epithelia coating neovaginas after vaginoplasty in women affected by Mayer-Rokitansky-Küster-Hauser syndrome STUDY DESIGN: We conducted a retrospective analysis of prospectively collected data. Women affected by Rokitansky syndrome who underwent neovaginal biopsy after vaginoplasty (McIndoe surgery, intestinal vaginoplasty, Vecchietti surgery, and Davydov surgery) were included. Macroscopic mucosal features were assessed through clinical examination and the Schilling test. Each biopsy specimen was prepared for examination by light microscopy and in some cases by scanning electron microscopy (SEM). RESULTS: Thirty-six patients (4 McIndoe, 2 intestinal vaginoplasty, 14 Vecchietti, and 16 Davydov) were included. All biopsies were performed without complications. In McIndoe's neovaginas, the mucosal microscopic features were similar to normal skin, with large areas of preserved epithelium, heterogeneous presence of dermal papillae, and superficial keratinization. The characteristics of the intestinal neovagina's surface were similar to those of a sigmoid colon, with well-shaped glands, cylindrical cells, and a secreting mucosa. In Vecchietti neovaginas, the surface the epithelium was flat and multilayered, highly similar to that of a normal vagina, with the presence of glycogen and superficial desquamation. On medium SEM magnification evaluation, the epithelium presented flattened polygonal cells. Finally, in Davydov neovaginas, none of the specimens had persistent mesothelial elements. The squamous neo-epithelium had regular aspects of differentiation with the presence of glycogen. At greater SEM magnification, microridges were evident, with a regular distribution. CONCLUSION: Each different technique of vaginoplasty leads to unique histological and structural features of the neovagina's mucosa. Knowledge of these elements must be the basis for the choice of the most appropriate intervention.

Endometriosis-Related Ovarian Cancer: Where Are We Now? A Narrative Review towards a Pragmatic Approach.

BACKGROUND: Endometriosis affects more than 10% of reproductive-aged women, causing pelvic pain and infertility. Despite the benign nature of endometriosis, ovarian endometriomas carry a higher risk of developing endometrioid carcinomas (EnOCs) and clear cell ovarian carcinomas (CCCs). Atypical endometriosis, defined as cytological atypia resembling intraepithelial cancer, is considered the precursor of endometriosis-associated ovarian cancer (EAOC). This narrative review aims to provide an overview of EAOC, proposing a practical approach to clinical and therapeutic decision making. METHODS: An electronic literature search was conducted from inception up to January 2023, using the MEDLINE database via PubMed to evaluate the existing literature on EAOC, including its pathogenesis, the diagnostic process, and the therapeutic possibilities, with articles not relevant to the topic or lacking scientific merit being excluded. RESULTS: Eighty-one articles were included in the review to present the current state of the art regarding EAOC. A pragmatic clinical flowchart is proposed to guide therapeutic decisions and improve patient outcomes. CONCLUSIONS: Endometriosis patients may have an increased risk of developing EAOC (either EnOC or CCC). Despite not being fully accepted, the concept of AE may reshape the endometriosis-ovarian cancer relationship. Further research is needed to understand the unaddressed issues.

Deep Infiltrating Endometriosis in Adolescence: Early Diagnosis and Possible Prevention of Disease Progression.

Endometriosis has a prevalence of 10% worldwide in premenopausal women. Probably, endometriosis begins early in the life of young girls, and it is commonly diagnosed later in life. The prevalence of deep infiltrating endometriosis (DIE) in adolescence is currently unknown due to diagnostic limits and underestimation of clinical symptoms. Dysmenorrhea is a common symptom in adolescents affected by DIE, often accompanied by dyspareunia and chronic acyclic pelvic pain. Ultrasonography-either performed transabdominal, transvaginal or transrectal-should be considered the first-line imaging technique despite the potential for missed diagnosis due to early-stage disease. Magnetic resonance imaging should be preferred in the case of virgo patients or when ultrasonographic exam is not accepted. Diagnostic laparoscopy is deemed acceptable in the case of suspected DIE not responding to conventional hormonal therapy. An early medical and/or surgical treatment may reduce disease progression with an immediate improvement in quality of life and fertility, but at the same time, painful symptoms may persist or even recur due to the surgery itself. The aim of this narrative review is to report the prevalence of DIE in adolescents, describe the pathogenetic theories and discuss the management in adolescent women, including the challenging road to diagnosis and the treatment alternatives.

Strategy for an early simultaneous introduction of four-pillars of heart failure therapy: results from a single center experience.

INTRODUCTION: The 2021 European Society of Cardiology (ESC) Guidelines recommend the use of four different classes of drugs for heart failure with reduced ejection fraction (HFrEF): beta blockers (BB), sodium-glucose cotransporter-2 inhibitors (SGLT2i), angiotensin receptor/neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonists (MRAs). Moreover, the 2023 ESC updated Guidelines suggest an intensive strategy of initiation and rapid up-titration of evidence-based treatment before discharge, based on trials not using the four-pillars. We hypothesized that an early concomitantly administration and up-titration of four-pillars, compared with a conventional stepwise approach, may impact the vulnerable phase after hospitalization owing to HF. METHODS: This prospective, single center, observational study included consecutive in-hospital patients with HFrEF. After performing propensity score matching, they were divided according to treatment strategy into group 1 (G1), with predischarge start of all four-pillars, with their up-titration within 1 month, and group 2 (G2) with the pre Guidelines update stepwise four-pillars introduction. HF hospitalization, cardiovascular (CV) death, and the composite of both were evaluated between the two groups at 6-month follow-up. RESULTS: The study included a total of 278 patients who completed 6-month follow-up (139 for both groups). There were no differences in terms of baseline features between the two groups. At survival analysis, HF hospitalization risk was significantly lower in G1 compared with G2 (p < 0.001), while no significant differences were observed regarding CV death (p = 0.642) or the composite of CV death and HF hospitalization (p = 0.135). CONCLUSIONS: In our real-world population, patients with HF treated with a predischarge and simultaneous use of four-pillars showed a reduced risk of HF hospitalization during the vulnerable phase after discharge, compared with  a conventional stepwise approach.

Adenomyosis among patients undergoing postpartum hysterectomy for uncontrollable uterine bleeding: A multicenter, observational, retrospective, cohort study on histologically-based prevalence and clinical characteristics.

OBJECTIVE: To assess the prevalence of adenomyosis at pathologic examination, and its association with obstetric complications, peripartum maternal clinical characteristics and neonatal birth weight in patients undergoing postpartum hysterectomy due to postpartum hemorrhage (PPH). METHODS: A multicenter, observational, retrospective, cohort study was carried out including all women who underwent postpartum hysterectomy due to PPH at gestational week 23+0 or later, between January 2010 and May 2023. Patients were categorized into two groups based on the presence of adenomyosis at pathologic examination, and were compared for obstetric complications, peripartum maternal clinical characteristics, and neonatal birth weight. RESULTS: The histologically-based prevalence of adenomyosis in patients undergoing postpartum hysterectomy due to PPH was 39.4%. Adenomyosis was associated with a longer hospitalization time (regression coefficient: 4.43 days, 95% CI: 0.34-8.52, P = 0.034) and a higher risk of hypertensive disorders (OR: 5.82, 95% CI: 1.38-24.46, P = 0.016), threatened preterm labor (OR: 3.34, 95% CI: 1.08-10.31, P = 0.036), urgent/emergency C-section (OR: 24.15, 95% CI: 2.60-223.96, P = 0.005), postpartum maternal complications (OR: 4.96, 95% CI: 1.48-16.67, P = 0.012), maternal intensive care unit admission (OR: 3.56, 95% CI: 1.05-12.05, P = 0.041), and low birth weight neonates (OR: 3.8, 95% CI: 1.32-11.02, P = 0.013). CONCLUSION: In patients undergoing postpartum hysterectomy due to PPH, adenomyosis is a highly prevalent condition among, and is associated with adverse obstetric, maternal, and neonatal outcomes.

The Role of High-Sensitivity Troponin T Regarding Prognosis and Cardiovascular Outcome across Heart Failure Spectrum.

Background: Cardiac troponin release is related to the cardiomyocyte loss occurring in heart failure (HF). The prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) in several settings of HF is under investigation. The aim of the study is to assess the prognostic role of intrahospital hs-cTnT in patients admitted due to HF. Methods: In this observational, single center, prospective study, patients hospitalized due to HF have been enrolled. Admission, in-hospital peak, and discharge hs-cTnT have been assessed. Patients were followed up for 6 months. Cardiovascular (CV) death, HF hospitalization (HFH), and worsening HF (WHF) (i.e., urgent ambulatory visit/loop diuretics escalation) events have been assessed at 6-month follow up. Results: 253 consecutive patients have been enrolled in the study. The hs-cTnT median values at admission and discharge were 0.031 ng/mL (IQR 0.02-0.078) and 0.031 ng/mL (IQR 0.02-0.077), respectively. The risk of CV death/HFH was higher in patients with admission hs-cTnT values above the median (p = 0.02) and in patients who had an increase in hs-cTnT during hospitalization (p = 0.03). Multivariate Cox regression analysis confirmed that hs-cTnT above the median (OR: 2.06; 95% CI: 1.02-4.1; p = 0.04) and increase in hs-cTnT during hospitalization (OR:1.95; 95%CI: 1.006-3.769; p = 0.04) were predictors of CV death/HFH. In a subgroup analysis of patients with chronic HF, hs-cTnT above the median was associated with increased risk of CV death/HFH (p = 0.03), while in the subgroup of patients with HFmrEF/HFpEF, hs-cTnT above the median was associated with outpatient WHF events (p = 0.03). Conclusions: Inpatient hs-cTnT levels predict CV death/HFH in patients with HF. In particular, in the subgroup of chronic HF patients, hs-cTnT is predictive of CV death/HFH; while in patients with HFmrEF/HFpEF, hs-cTnT predicts WHF events.

Prognostic Assessment of HLM Score in Heart Failure Due to Ischemic Heart Disease: A Pilot Study.

Background: Ischemic heart disease (IHD) represents the main cause of heart failure (HF). A prognostic stratification of HF patients with ischemic etiology, particularly those with acute coronary syndrome (ACS), may be challenging due the variability in clinical and hemodynamic status. The aim of this study is to assess the prognostic power of the HLM score in a population of patients with ischemic HF and in a subgroup who developed HF following ACS. Methods: This is an observational, prospective, single-center study, enrolling consecutive patients with a diagnosis of ischemic HF. Patients were stratified according to the four different HLM stages of severity, and the occurrence of CV death, HFH, and worsening HF events were evaluated at 6-month follow-up. A sub-analysis was performed on patients who developed HF following ACS at admission. Results: The study included 146 patients. HLM stage predicts the occurrence of CV death (p = 0.01) and CV death/HFH (p = 0.003). Cox regression analysis confirmed HLM stage as an independent predictor of CV death (OR: 3.07; 95% IC: 1.54-6.12; p = 0.001) and CV death/HFH (OR: 2.45; 95% IC: 1.43-4.21; p = 0.001) in the total population of patients with HF due to IHD. HLM stage potentially predicts the occurrence of CV death (p < 0.001) and CV death/HFH (p < 0.001) in patients with HF following ACS at admission. Conclusions: Pathophysiological-based prognostic assessment through HLM score is a potentially promising tool for the prediction of the occurrence of CV death and CV death/HFH in ischemic HF patients and in subgroups of patients with HF following ACS at admission.