Severe autoimmune hemolytic anemia; epidemiology, clinical management, outcomes and knowledge gaps.

Autoimmune hemolytic anemia (AIHA) is an acquired hemolytic disorder, mediated by auto-antibodies, and has a variable clinical course ranging from fully compensated low grade hemolysis to severe life-threatening cases. The rarity, heterogeneity and incomplete understanding of severe AIHA complicate the recognition and management of severe cases. In this review, we describe how severe AIHA can be defined and what is currently known of the severity and outcome of AIHA. There are no validated predictors for severe clinical course, but certain risk factors for poor outcomes (hospitalisation, transfusion need and mortality) can aid in recognizing severe cases. Some serological subtypes of AIHA (warm AIHA with complement positive DAT, mixed, atypical) are associated with lower hemoglobin levels, higher transfusion need and mortality. Currently, there is no evidence-based therapeutic approach for severe AIHA. We provide a general approach for the management of severe AIHA patients, incorporating monitoring, supportive measures and therapeutic options based on expert opinion. In cases where steroids fail, there is a lack of rapidly effective therapeutic options. In this era, numerous novel therapies are emerging for AIHA, including novel complement inhibitors, such as sutimlimab. Their potential in severe AIHA is discussed. Future research efforts are needed to gain a clearer picture of severe AIHA and develop prediction models for severe disease course. It is crucial to incorporate not only clinical characteristics but also biomarkers that are associated with pathophysiological differences and severity, to enhance the accuracy of prediction models and facilitate the selection of the optimal therapeutic approach. Future clinical trials should prioritize the inclusion of severe AIHA patients, particularly in the quest for rapidly acting novel agents.

[A pregnant woman with de novo atrial fibrillation]. / Atriumfibrilleren bij een zwangere vrouw.

BACKGROUND: De novo atrial fibrillation (AF) is rare in pregnancy. The exact pathophysiology of AF is unclear; it might be caused by several cardiovascular and hemodynamic changes that occur in pregnancy, leading to an increased stretch in myocardial cells of the atrial wall. CASE DESCRIPTION: A 26-year-old primigravida with a thus far uncomplicated pregnancy presents with symptoms of heart palpitations, shortness of breath and chest pain. The CTG was normal but an ECG showed de novo atrial fibrillation. The patient was given two doses of digoxin 0.25mg after which sinus rhythm was achieved. No anatomical substrate was found; hence it was seen as most likely caused by increased hemodynamic demands in pregnancy. The delivery and postpartum period were uncomplicated. CONCLUSION: AF is rarely seen in pregnancy. Treatment favours rate and/or rhythm control with metoprolol and digoxin, respectively. Anticoagulation is not indicated in lone AF during pregnancy. Vaginal birth is preferred.

The long-term effect of mTOR inhibition on lipid and glucose metabolism in tuberous sclerosis complex: data from the Dutch TSC registry.

BACKGROUND: MTOR inhibition is an effective treatment for many manifestations of tuberous sclerosis complex. Because mTOR inhibition is a disease modifying therapy, lifelong use will most likely be necessary. This study addresses the long-term effects of mTOR inhibitors on lipid and glucose metabolism and aims to provide better insight in the incidence and time course of these metabolic adverse effects in treated TSC patients. METHODS: All patients who gave informed consent for the nationwide TSC Registry and were ever treated with mTOR inhibitors (sirolimus and/or everolimus) were included. Lipid profiles, HbA1c and medication were analysed in all patients before and during mTOR inhibitor treatment. RESULTS: We included 141 patients, the median age was 36 years, median use of mTOR inhibitors 5.1 years (aimed serum levels 3.0-5.0 µg/l). Total cholesterol, LDL- and HDL-cholesterol levels at baseline were similar to healthy reference data. After start of mTOR inhibition therapy, total cholesterol, LDL-cholesterol and triglycerides increased significantly and were higher compared to healthy reference population. Mean total cholesterol levels increased by 1.0 mmol/L after 3-6 months of mTOR inhibition therapy but did not increase further during follow-up. In this study, 2.5% (3/118) of patients developed diabetes (defined as an HbA1c ≥ 48 mmol/mol) during a median follow-up of 5 years. CONCLUSIONS: Hypercholesterolemia is a frequent side effect of mTOR inhibition in TSC patients, and predominantly occurs within the first year of treatment. Although hyperglycemia is a frequent side effect in other indications for mTOR inhibition, incidence of diabetes mellitus in TSC patients was only 2.5%. This may reflect the difference of mTOR inhibition in patients with normal mTOR complex pathway function versus patients with overactive mTOR complex signaling due to a genetic defect (TSC patients).

[Is there a possibility that you are pregnant? No doctor, I am using an IUD]. / 'Kunt u zwanger zijn?' 'Nee dokter, ik heb een spiraal'.

BACKGROUND: The perforation of the device through the myometrium of the uterus is a well-known complication after the placement of an intra-uterine device (IUD). A laparoscopy is often performed to remove the IUD. The omentum or the recto-uterine pouch, also known as the pouch of Douglas, are the most likely locations of the IUD when this is dislocated. CASE DESCRIPTION: This case reports describes the case of a 36-year-old woman, where three months after giving birth an IUD was placed and the uterine wall was perforated. The patient came to the outpatient clinic because of an unwanted pregnancy. The IUD was eventually laparoscopic found in the retropubic space, the cavum Retzii CONCLUSION: After placement of an IUD, especially placed after the first months of giving birth, additional examination is recommended to check the placement. Besides the pouch of Douglas and the omentum, the IUD can be dislocated in the cavum Retzii.

Two-Year Outcome after Laparoscopic Fundoplication in Pediatric Patients with Gastroesophageal Reflux Disease.

Introduction: Many studies on short-term efficacy of laparoscopic antireflux surgery (LARS) have shown good to excellent results on reflux symptom control and health-related quality of life (HRQoL). Prospective studies on the long-term efficacy, however, are scarce and indicate that the efficacy of symptom control may decline over time. The aim of this study is to assess the 2-year outcome on reflux symptoms and HRQoL after LARS. Materials and Methods: Between 2011 and 2013, 25 children (12 males, median age 6 [2-18] years) with proton pump inhibitor-resistant gastroesophageal reflux disease were included in a prospective longitudinal cohort study. To assess reflux symptoms and HRQoL, patients and/or their caregivers were asked to fill out the validated age-appropriate gastroesophageal reflux symptom questionnaire and Pediatric Quality of Life Inventory™ before, 3 months, 1 year, and 2 years after LARS. Results: Two years after LARS, 29% of patients had moderate to severe reflux symptoms compared with 92% (P < .001) before operation and 12% 3-4 months after operation (P = .219). The significant increase in HRQoL shortly after fundoplication (80.0 compared with 69.5 (P = .004)) is not observed after 2 years (72.0 compared with 69.5, P = .312). Correlation between the impaired HRQoL scores and the recurrence of symptoms could not be verified. Conclusions: Although the efficacy of LARS tends to deteriorate after 2 years, LARS is still effective in controlling reflux symptoms in the majority of patients. The short-term improvement in HRQoL after LARS appears to be transient.

Accuracy of postvoid residual volumes after vaginal delivery: a prospective equivalence study to compare an automatic scanning device with transurethral catheterization.

INTRODUCTION AND HYPOTHESIS: Abnormal postvoid residual volumes (PVRV) after delivery are common in daily clinical practice. By using an automatic scanning device, unnecessary catheterizations can be prevented. The aim of this study was to determine the accuracy of PVRV after vaginal delivery measured by an automatic scanning device through a comparison with transurethral catheterization. MATERIALS AND METHODS: This prospective observational equivalence study was performed in patients who delivered vaginally between June 2012 and May 2017 in three teaching hospitals in The Netherlands. After the first spontaneous void after delivery, postvoid residual volume (PVRV) was measured with a portable automatic scanning device (BladderScan® BVI 9400). Directly afterward, it was measured by catheterization. Correlation between measurements was calculated using Spearman's correlation coefficient and agreement plot. The primary outcome was to validate the correlation between the BladderScan® compared with the gold standard of transurethral catheterization. RESULTS: Data of 407 patients was used for final analysis. Median PVRV as measured by BladderScan® was 380 ml (± 261-0-999 ml) and by catheterization was 375 ml (± 315-1800 ml). Mean difference between measurements was -12.9 ml (± 178 ml). There was a very good correlation between methods (Spearman's rho = 0.82, p < 0.001). Using a cut-ff value of >500 ml, specificity and sensitivity were 85.4 and 85.6%, respectively. CONCLUSIONS: The BladderScan® (BVI 9400) measures PVRV precisely and reliably after vaginal delivery and should be preferred over catheterization.

Comparison of clean intermittent and transurethral indwelling catheterization for the treatment of overt urinary retention after vaginal delivery: a multicentre randomized controlled clinical trial.

INTRODUCTION AND HYPOTHESIS: Overt postpartum urinary retention (PUR) is the inability to void after delivery and affects up to 7% of patients. Clean intermittent catheterization (CIC) and transurethral indwelling catheterization (TIC) are both standard treatments, but have not previously been compared. Clinical guidelines on postpartum bladder management are lacking. METHODS: A total of 85 patients were randomised for TIC (n=45) and CIC (n=40). In total 68 patients (34 patients with TIC and 34 patients with CIC) completed the UDI-6 questionnaire 3 months after delivery.. Patients allocated to TIC received an indwelling catheter for 24 h and if necessary, another catheter for 48 h. Patients with CIC were intermittently catheterized or taught to self-catheterize until adequate voiding with a postvoid residual volume (PVRV) of <150 mL was achieved. The primary outcome was the presence of bothersome micturition symptoms as measured using the Dutch-validated Urogenital Distress Inventory (UDI-6). RESULTS: Only seven patients (10%) reported bothersome micturition problems 3 months after delivery. No significant differences in the occurrence of micturition symptoms were found. Median PVRV was 800 mL in the CIC group and 650 mL in the TIC group. PVRV was ≥1,000 mL in 24% of the patients. The median duration of catheterization was significantly shorter in the CIC group than in the TIC group (12 h vs. 24 h, p < 0,01). In patients with CIC, 35% required only one catheterization before complete bladder emptying occurred. The duration of treatment was not related to the initial PVRV. Both treatments were equally well accepted by the patients. CONCLUSIONS: In patients with overt PUR, CIC is the preferred treatment as a considerable percentage of patients appear to be over-treated when the standard duration of TIC is 24 h. The occurrence of micturition symptoms is not associated with the catheterization method used. CIC is well tolerated in patients with overt PUR.

Long-term micturition problems of asymptomatic postpartum urinary retention: a prospective case-control study.

INTRODUCTION AND HYPOTHESIS: Covert (asymptomatic) postpartum urinary retention (PUR) is defined as post-void residual volume (PVRV) ≥150 mL. Although often supposed to be a common and harmless phenomenon, no data are available on the potential long-term micturition problems of increased PVRV after vaginal delivery. METHODS: After the first spontaneous void post-vaginal delivery, PVRV was measured using a portable scanning device. Micturition symptoms were compared using validated questionnaires between women with PVRV < 150 mL and those with PVRV ≥150 mL until 1 year after delivery. Women with PVRV ≥ 150 mL were followed until complete bladder emptying was achieved. RESULTS: Data of 105 patients with PVRV < 150 mL and 119 with PVRV ≥ 150 mL were available for analysis. 75% of all patients included had PVRV ≥ 250 mL. More primiparous patients had PVRV ≥ 150 mL (p < 0.02). 92% of women with PVRV ≥ 150 mL after delivery were able to adequately empty their bladder within 4 days. One year after delivery, no statistically significant differences were found. CONCLUSIONS: Covert PUR according to the definition of PVRV ≥ 150 mL, is a common and transient phenomenon that does not result in more lower urinary tract symptoms 1 year after delivery. Although the current definition is not useful in identifying postpartum women with a pathological condition, we suggest that the definition of covert PUR should be change to: "PVRV≥500 mL after the first spontaneous void after (vaginal) delivery." This cut-off value is the value at which some women do need more time to normalise emptying of the bladder. The exact clinical implications of covert PUR need to be further studied in this subcategory of women.

The Development of a New Medical Device for Standardized Episiotomy: A Pre-Clinical Validation Study.

BACKGROUND: The aim of this study was to present the validation and optimization process for a new innovative medical device to create a standardized episiotomy. DESIGN: We performed a preclinical validation study. SETTING: This study was performed at the University hospital. SAMPLE: Animal, cadaver. METHODS: Together with technical engineers, we designed a new medical device that involves a knife and cuts back from buttock toward introitus, in contrast to the conventional episiotomy. We optimized the design and its performance in consecutive animal and cadaver studies. MAIN OUTCOME MEASURES: Ability to perform a standardized incision, ease of use. RESULTS: After multiple adjustments, based on the results of multiple animal and cadaver studies, a medical device was developed to perform a standardized clean-cut episiotomy of 4-6 cm length. CONCLUSION: We have shown that optimizing the technical performance and safety of an innovative device in animals, prior to opposing patients to its potential hazards, is feasible. Our design optimizing study can be used as a model for the pre-clinical validation of future innovative medical devices.

Delivery-related risk factors for covert postpartum urinary retention after vaginal delivery.

INTRODUCTION AND HYPOTHESIS: Postpartum urinary retention (PUR) is a common consequence of bladder dysfunction after vaginal delivery. Patients with covert PUR are able to void spontaneously but have a postvoid residual bladder volume (PVRV) of ≥150 mL. Incomplete bladder emptying may predispose to bladder dysfunction at a later stage of life. The aim of this cross-sectional study was to identify independent delivery-related risk factors for covert PUR after vaginal delivery in order to identify women with an increased risk of covert PUR. METHODS: The PVRV of women who delivered vaginally was measured after the first spontaneous micturition with a portable bladder-scanning device. A PVRV of 150 mL or more was defined as covert PUR. Independent risk factors for covert PUR were identified in multivariate regression analysis. RESULTS: Of 745 included women, 347 (47%) were diagnosed with covert PUR (PVRV ≥150 mL), of whom 197 (26%) had a PVRV ≥250 mL (75th percentile) and 50 (7%) a PVRV ≥500 mL (95th percentile). In multivariate regression analysis, episiotomy (OR 1.7, 95% CI 1.02 - 2.71), epidural analgesia (OR 2.08, 95% CI 1.36 - 3.19) and birth weight (OR 1.03, 95% CI 1.01 - 1.06) were independent risk factors for covert PUR. Opioid analgesia during labour (OR 3.19, 95% CI 1.46 - 6.98), epidural analgesia (OR 3.54, 95% CI 1.64 - 7.64) and episiotomy (OR 3.72, 95% CI 1.71 - 8.08) were risk factors for PVRV ≥500 mL. CONCLUSIONS: Episiotomy, epidural analgesia and birth weight are risk factors for covert PUR. We suggest that the current cut-off values for covert PUR should be reevaluated when data on the clinical consequences of abnormal PVRV become available.

Translabial three-dimensional ultrasonography compared with magnetic resonance imaging in detecting levator ani defects.

OBJECTIVE: To assess the diagnostic performance of translabial three-dimensional ultrasonography in detecting major levator ani defects in women with pelvic organ prolapse compared with magnetic resonance imaging (MRI) and to assess the interobserver agreement in detecting levator ani defects with translabial three-dimensional ultrasonography. METHODS: In a multicenter cohort study, 140 women indicated for primary surgery of pelvic organ prolapse quantification stage II or more cystocele were included. Patients undergoing mesh surgery or concomitant stress incontinence surgery were excluded. All consenting patients underwent translabial three-dimensional ultrasonography and MRI of the pelvic floor before surgery. Two observers (out of a pool of four observers) assessed translabial three-dimensional ultrasound images; two other observers (out a pool of five observers) assessed MRIs for levator ani muscle damage. In case of disagreement, the images were discussed in a consensus meeting. RESULTS: Of the 135 scans, 45 major levator ani defects were detected on ultrasonogram (33.3%) and 32 were confirmed at MRI (23.7%). Of the 41 major levator ani defects detected on MRI, nine were missed at translabial three-dimensional ultrasonogram. Sensitivity was 0.78 (32 of 41) (95% confidence interval [CI] 0.65-0.91) and specificity was 0.86 (81 of 94) (95% CI 0.79-0.93) in detecting major levator ani defects with translabial three-dimensional ultrasonography compared with MRI. There was good agreement scoring levator ani defects on translabial three-dimensional ultrasonography, with a κ of 0.67 (95% CI 0.58-0.76); agreement in recognizing major levator ani defects was moderate, with a κ of 0.53 (95% CI 0.37-0.69). CONCLUSION: Translabial three-dimensional ultrasonography shows reasonable agreement with MRI in detecting major levator defects. Because of the moderate interobserver agreement, it will be difficult to implement ultrasonography in daily practice. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register, www.trialregister.nl, NTR2220.

What's a proper push? The Valsalva manoeuvre revisited.

In daily practice, the Valsalva manoeuvre is used to assess pelvic organ prolapse, virtually always without standardisation of pressure. We undertook a study to determine maximum pressures reached and pressures required to obtain 80% of maximal pelvic organ descent, to investigate the need for such standardisation. Clinical data and ultrasound data sets of 75 women seen for urodynamic testing were reviewed retrospectively, with three Valsalva manoeuvres registered per patient. Maximum rectal pressures generated during Valsalva were 107 cm H (2) O on average (range, 45-190 cm H (2) O). Ninety-seven percent of all women managed to reach pressures ≥60 cm H (2) O. On average, 80% of maximal bladder neck descent was reached at 56 cm H (2) O, 80% of maximal pelvic organ descent at 38 cm H (2) O. Our results imply that virtually all patients were able to generate pressures resulting in ≥80% of maximal pelvic organ descent. This implies that standardisation of Valsalva pressures for prolapse assessment may be unnecessary.

Protocol for translabial 3D-ultrasonography for diagnosing levator defects (TRUDIL): a multicentre cohort study for estimating the diagnostic accuracy of translabial 3D-ultrasonography of the pelvic floor as compared to MR imaging.

BACKGROUND: Pelvic organ prolapse (POP) is a condition affecting more than half of the women above age 40. The estimated lifetime risk of needing surgical management for POP is 11%. In patients undergoing POP surgery of the anterior vaginal wall, the re-operation rate is 30%. The recurrence risk is especially high in women with a levator ani defect. Such defect is present if there is a partially or completely detachment of the levator ani from the inferior ramus of the symphysis. Detecting levator ani defects is relevant for counseling, and probably also for treatment. Levator ani defects can be imaged with MRI and also with Translabial 3D ultrasonography of the pelvic floor. The primary aim of this study is to assess the diagnostic accuracy of translabial 3D ultrasonography for diagnosing levator defects in women with POP with Magnetic Resonance Imaging as the reference standard. Secondary goals of this study include quantification of the inter-observer agreement about levator ani defects and determining the association between levator defects and recurrent POP after anterior repair. In addition, the cost-effectiveness of adding translabial ultrasonography to the diagnostic work-up in patients with POP will be estimated in a decision analytic model. METHODS/DESIGN: A multicentre cohort study will be performed in nine Dutch hospitals. 140 consecutive women with a POPQ stage 2 or more anterior vaginal wall prolapse, who are indicated for anterior colporapphy will be included. Patients undergoing additional prolapse procedures will also be included. Prior to surgery, patients will undergo MR imaging and translabial 3D ultrasound examination of the pelvic floor. Patients will be asked to complete validated disease specific quality of life questionnaires before surgery and at six and twelve months after surgery. Pelvic examination will be performed at the same time points. Assuming a sensitivity and specificity of 90% of 3D ultrasound for diagnosing levator defects in a population of 120 women with POP, with a prior probability of levator ani defects of 40%, we will be able to estimate predictive values with good accuracy (i.e. confidence limits of at most 10% below or above the point estimates of positive and negative predictive values).Anticipating 3% unclassifiable diagnostic images because of technical reasons, and a further safety margin of 10% we plan to recruit 140 patients. TRIAL REGISTRATION: Nederlands trial register NTR2220.