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Human Reproduction (Oxford, England) Apr 2021Does septum resection improve reproductive outcomes in women with a septate uterus? (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY QUESTION
Does septum resection improve reproductive outcomes in women with a septate uterus?
SUMMARY ANSWER
Hysteroscopic septum resection does not improve reproductive outcomes in women with a septate uterus.
WHAT IS KNOWN ALREADY
A septate uterus is a congenital uterine anomaly. Women with a septate uterus are at increased risk of subfertility, pregnancy loss and preterm birth. Hysteroscopic resection of a septum may improve the chance of a live birth in affected women, but this has never been evaluated in randomized clinical trials. We assessed whether septum resection improves reproductive outcomes in women with a septate uterus, wanting to become pregnant.
STUDY DESIGN, SIZE, DURATION
We performed an international, multicentre, open-label, randomized controlled trial in 10 centres in The Netherlands, UK, USA and Iran between October 2010 and September 2018.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Women with a septate uterus and a history of subfertility, pregnancy loss or preterm birth were randomly allocated to septum resection or expectant management. The primary outcome was conception leading to live birth within 12 months after randomization, defined as the birth of a living foetus beyond 24 weeks of gestational age. We analysed the data on an intention-to-treat basis and calculated relative risks with 95% CI.
MAIN RESULTS AND THE ROLE OF CHANCE
We randomly assigned 80 women with a septate uterus to septum resection (n = 40) or expectant management (n = 40). We excluded one woman who underwent septum resection from the intention-to-treat analysis, because she withdrew informed consent for the study shortly after randomization. Live birth occurred in 12 of 39 women allocated to septum resection (31%) and in 14 of 40 women allocated to expectant management (35%) (relative risk (RR) 0.88 (95% CI 0.47 to 1.65)). There was one uterine perforation which occurred during surgery (1/39 = 2.6%).
LIMITATIONS, REASONS FOR CAUTION
Although this was a major international trial, the sample size was still limited and recruitment took a long period. Since surgical techniques did not fundamentally change over time, we consider the latter of limited clinical significance.
WIDER IMPLICATIONS OF THE FINDINGS
The trial generated high-level evidence in addition to evidence from a recently published large cohort study. Both studies unequivocally do not reveal any improvements in reproductive outcomes, thereby questioning any rationale behind surgery.
STUDY FUNDING/COMPETING INTEREST(S)
There was no study funding. M.H.E. reports a patent on a surgical endoscopic cutting device and process for the removal of tissue from a body cavity licensed to Medtronic, outside the scope of the submitted work. H.A.v.V. reports personal fees from Medtronic, outside the submitted work. B.W.J.M. reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck Merck KGaA, personal fees from Guerbet, personal fees from iGenomix, outside the submitted work. M.G. reports several research and educational grants from Guerbet, Merck and Ferring (location VUMC) outside the scope of the submitted work. The remaining authors have nothing to declare.
TRIAL REGISTRATION NUMBER
Dutch trial registry: NTR 1676.
TRIAL REGISTRATION DATE
18 February 2009.
DATE OF FIRST PATIENT’S ENROLMENT
20 October 2010.
Topics: Cohort Studies; Female; Humans; Infant, Newborn; Iran; Netherlands; Pregnancy; Premature Birth; Uterus; Watchful Waiting
PubMed: 33793794
DOI: 10.1093/humrep/deab037 -
Current Opinion in Pulmonary Medicine Sep 2023Chronic thromboembolic disease (CTED) is distinct from chronic thromboembolic pulmonary hypertension (CTEPH) and is defined by dyspnea on exertion after acute pulmonary... (Review)
Review
PURPOSE OF REVIEW
Chronic thromboembolic disease (CTED) is distinct from chronic thromboembolic pulmonary hypertension (CTEPH) and is defined by dyspnea on exertion after acute pulmonary embolism with the presence of residual perfusion defects and absence of resting pulmonary hypertension. Here, we review clinical features and diagnostic criteria for CTED and summarize treatment options.
RECENT FINDINGS
The optimal management for CTED is unclear as the long-term outcomes of conservative vs. invasive treatment for this disease have not been reported. There are a few studies evaluating outcomes of pulmonary thromboendarterectomy and balloon pulmonary angioplasty (BPA) in CTED, concluding that these procedures are safe and effective in select patients. However, these trials are small nonrandomized observational studies, reporting outcomes only up to 1 year after the intervention. Conservative management of CTED with observation, pulmonary hypertension-targeted therapy, or cardiopulmonary rehabilitation has not been studied. It is unknown whether these treatments are as effective or superior to pulmonary thromboendarterectomy or BPA in CTED.
SUMMARY
The management of CTED is individualized and based on symptoms and exercise limitations. Early referral of patients with CTED to a specialized CTEPH center is recommended to determine if watchful waiting, BPA, or pulmonary thromboendarterectomy is most beneficial.
Topics: Humans; Hypertension, Pulmonary; Pulmonary Embolism; Lung; Dyspnea; Angioplasty, Balloon; Chronic Disease; Pulmonary Artery
PubMed: 37461845
DOI: 10.1097/MCP.0000000000000987 -
World Journal of Urology Jan 2022In the past two decades, new biomarkers for prostate cancer detection and risk prediction have become available for clinical use. While tissue-based gene expression... (Review)
Review
PURPOSE
In the past two decades, new biomarkers for prostate cancer detection and risk prediction have become available for clinical use. While tissue-based gene expression assays offer molecular risk assessment after diagnoses, several serum- and urine-based 'liquid' biomarkers are available for the pre-biopsy setting which may also play a role for active surveillance (AS).
METHODS
The medical literature was queried utilizing PubMed (pubmed.ncbi.nlm.nih.gov) for all relevant original publications describing prostate cancer biomarkers that can be identified in the blood, urine, or semen. Referenced studies must have defined patient inclusion criteria and descriptions of the biomarkers. Included studies investigated the utility of liquid biomarkers for selection or monitoring of men with prostate cancer for active surveillance.
RESULTS
PSA is the most common and readily available biomarker for prostate cancer diagnosis and treatment. Contemporary AS guidelines consider diagnostic PSA level in addition to other clinical factors when selecting men for this approach, with most recommending that initial PSA should be under 10 ng/ml. Serum PSA changes are associated with outcomes on AS but are not adequately sensitive so drive men to secondary treatment in isolation. PSA derivates including the Prostate Health Index (phi) and the 4K Score can predict higher grade cancer and may help tailor repeat prostate biopsy strategies, but further data are needed prior to routine clinic use. Several urine-based biomarkers including PCA3 and TMPRSS2:ERG levels have also been studied in the AS setting.
CONCLUSIONS
Multiple serum- and urine-based liquid biomarkers are available for use in men with prostate cancer. For AS, serum PSA is utilized in part for patient selection as well as to monitor disease over time. Models that incorporate PSA kinetics with other clinical characteristics may help tailor surveillance strategies to reduce disease burden and health care costs over time. Several novel liquid biomarkers demonstrate promise and may eventually have applications for prostate cancer surveillance as well.
Topics: Biomarkers, Tumor; Humans; Male; Prostatic Neoplasms; Semen; Watchful Waiting
PubMed: 33590279
DOI: 10.1007/s00345-021-03609-5 -
Journal of Internal Medicine Jul 2020Aortic pathologies such as aneurysm, dissection and trauma are relatively common and potentially fatal diseases. Over the past two decades, we have experienced... (Review)
Review
Aortic pathologies such as aneurysm, dissection and trauma are relatively common and potentially fatal diseases. Over the past two decades, we have experienced unprecedented technical and medical developments in the field. Despite this, there is a great need, and great opportunities, to further explore the area. In this review, we have identified important areas that need to be further studied and selected priority aortic disease trials. There is a pressing need to update the AAA natural history and the role for endovascular AAA repair as well as to define biomarkers and genetic risk factors as well as influence of gender for development and progression of aortic disease. A key limitation of contemporary treatment strategies of AAA is the lack of therapy directed at small AAA, to prevent AAA expansion and need for surgical repair, as well as to reduce the risk for aortic rupture. Currently, the most promising potential drug candidate to slow AAA growth is metformin, and RCTs to verify or reject this hypothesis are warranted. In addition, the role of endovascular treatment for ascending pathologies and for uncomplicated type B aortic dissection needs to be clarified.
Topics: Aortic Dissection; Aorta; Aortic Aneurysm, Abdominal; Balloon Occlusion; Biomarkers; Clinical Trials as Topic; Disease Progression; Endovascular Procedures; Humans; Hypoglycemic Agents; Metformin; Sex Factors; Stents; Vascular Surgical Procedures; Watchful Waiting
PubMed: 32187752
DOI: 10.1111/joim.13042 -
Current Urology Reports Oct 2023Many prostate cancer active surveillance protocols mandate serial monitoring at defined intervals, including but certainly not limited to serum PSA (often every... (Review)
Review
PURPOSE OF REVIEW
Many prostate cancer active surveillance protocols mandate serial monitoring at defined intervals, including but certainly not limited to serum PSA (often every 6 months), clinic visits, prostate multiparametric MRI, and repeat prostate biopsies. The purpose of this article is to evaluate whether current protocols result in excessive testing of patients on active surveillance.
RECENT FINDINGS
Multiple studies have been published in the past several years evaluating the utility of multiparametric MRI, serum biomarkers, and serial prostate biopsy for men on active surveillance. While MRI and serum biomarkers have promise with risk stratification, no studies have demonstrated that periodic prostate biopsy can be safely omitted in active surveillance. Active surveillance for prostate cancer is too active for some men with seemingly low-risk cancer. The use of multiple prostate MRIs or additional biomarkers do not always add to the prediction of higher-grade disease on surveillance biopsy.
Topics: Male; Humans; Prostate-Specific Antigen; Watchful Waiting; Prostatic Neoplasms; Biopsy; Prostate; Magnetic Resonance Imaging
PubMed: 37436691
DOI: 10.1007/s11934-023-01177-2 -
Translational Andrology and Urology Jun 2021Many men diagnosed with localized prostate cancer can postpone definitive treatment without raising their risk of metastasis or death from disease. Active surveillance... (Review)
Review
Many men diagnosed with localized prostate cancer can postpone definitive treatment without raising their risk of metastasis or death from disease. Active surveillance (AS) is a method of monitoring select men, with the option of switching to active treatment upon signs of progression, thereby avoiding the well-known side-effects of surgery and radiotherapy. This review analyzes the data from long-running AS cohorts to determine the safety and efficacy of AS. We conducted a narrative review of recently published data, including 14 articles from 13 AS cohorts. The cohorts used varying inclusion criteria, with reported differences in clinical T stage and Gleason Score (Grade Group), among other features. Some studies (n=5) limited their cohorts to low-risk patients, while others (n=8) also included intermediate-risk patients. The heterogeneity of the cohorts produced mixed results, with the risk of prostate cancer metastasis ranging from 0.1-1.0% at 10 years and the risk of prostate cancer mortality ranging from 0-1.9% at 10 years. However, the majority of studies reported risks of less than 0.5% at 10 years for both metastasis and death. For most cohorts, half of men remained untreated for 5-10 years, with estimates ranging from 37% receiving active treatment in the Toronto cohort to 73% in the Prostate Cancer Research International AS (PRIAS) study. Current data do not support the use of negative magnetic resonance imaging (MRI) to avoid scheduled biopsy. Taken together, the data collected from these AS cohorts suggests that AS is a safe approach for men with low-grade prostate cancer and some men with intermediate risk disease. AS should be more broadly implemented for eligible patients to avoid the decreases in quality of life from undergoing active treatment. Studies expanding the inclusion criteria and further defining a subset of men with favorable intermediate-risk prostate cancer who might safely benefit from AS are needed to assess the long-term outcomes of using AS in intermediate-risk groups.
PubMed: 34295763
DOI: 10.21037/tau-20-1370 -
Thyroid : Official Journal of the... Oct 2023During active surveillance (AS), serum thyrotropin (TSH) levels may affect papillary thyroid microcarcinoma (PTMC) progression. We investigated AS outcomes according to...
During active surveillance (AS), serum thyrotropin (TSH) levels may affect papillary thyroid microcarcinoma (PTMC) progression. We investigated AS outcomes according to whether levothyroxine (LT4) treatment was administered. From 2005 to 2019, 2896 patients with low-risk PTMC underwent AS. Of these, 2509 patients were included: 2187 patients did not receive LT4 at diagnosis (group I), 1935 patients did not receive LT4 during AS (group IA), and 252 patients started LT4 during AS (group IB). The remaining 322 patients were administered LT4 before or at diagnosis (group II). The tumor volume doubling rate (TVDR) and tumor size based on ultrasound examination results and time-weighted detailed TSH scores were calculated. Disease progression was defined as tumor enlargement ≥3 mm and/or the appearance of novel lymph node metastasis. At diagnosis, group II had more high-risk features, such as younger age and larger tumors, than group I. However, group II had a lower disease progression rate (2.9% at 10 years) than group I (6.1%) ( = 0.091). The disease progression rate of group IB (13.8% at 10 years) was significantly higher than that of groups IA (5.0%) and II (2.9%) ( < 0.01). The TVDR of group IB before LT4 administration was significantly higher than that of groups IA and II (0.095 per year, -0.0085 per year, and -0.057 per year, respectively; < 0.01), suggesting that patients with progression signs during AS were selectively prescribed LT4. The time-weighted detailed TSH score of group IB significantly decreased after LT4 administration compared with those before administration (3.35 and 3.05, respectively; < 0.01). The TVDR also decreased from 0.13 per year to 0.036 per year ( = 0.08). The proportions of patients with rapid or moderate growth decreased significantly after LT4 (from 26.8% to 12.5%, < 0.01). A multivariable analysis revealed group IB status was independently associated with disease progression (odds ratio [OR] = 3.42 [CI 2.15-5.44], < 0.01), whereas age ≥40 years and <60 years and age ≥60 years were independently negatively associated with this outcome (OR = 0.23 [CI 0.14-0.38, < 0.01 and OR = 0.16 [CI 0.10-0.27], < 0.01). LT4 treatment may be associated with decreased tumor growth during AS of PTMC, but further confirmatory research is needed.
Topics: Humans; Adult; Middle Aged; Thyroxine; Watchful Waiting; Thyroid Neoplasms; Risk Factors; Thyrotropin; Disease Progression
PubMed: 37310904
DOI: 10.1089/thy.2023.0046 -
Current Treatment Options in Oncology Apr 2020Despite its rarity, hairy cell leukemia (HCL) remains a fascinating disease and the physiopathology is becoming more and more understood. The accurate diagnosis of HCL... (Review)
Review
Despite its rarity, hairy cell leukemia (HCL) remains a fascinating disease and the physiopathology is becoming more and more understood. The accurate diagnosis of HCL relies on the recognition of hairy cells by morphology and flow cytometry (FCM) in the blood and/or bone marrow (BM). The BRAF V600E mutation, an HCL-defining mutation, represents a novel diagnostic parameter and a potential therapeutic target. The precise cellular origin of HCL is a late-activated postgerminal center memory B cell. BRAF mutations were detected in hematopoietic stem cells (HSCs) of patients with HCL, suggesting that this is an early HCL-defining event. Watch-and-wait strategy is necessary in approximately 10% of asymptomatic HCL patients, sometimes for several years. Purine analogs (PNAs) are the established first-line options for symptomatic HCL patients. In second-line treatment, chemoimmunotherapy combining PNA plus rituximab should be considered in high-risk HCL patients. The three options for relapsed/refractory HCL patients include recombinant immunoconjugates targeting CD22, BRAF inhibitors, and BCR inhibitors. The clinical interest to investigate blood minimal residual disease (MRD) was recently demonstrated, with a high risk of relapse in patients with positive testing for MRD and a low risk in patients with negative testing. However, efforts must be made to standardize MRD analyses in the near future. Patients with HCL are at risk of second malignancies. The increased risk could be related to the disease and/or the treatment, and the respective role of PNAs in the development of secondary malignancies remains a topic of debate.
Topics: Animals; Biomarkers, Tumor; Biopsy; Bone Marrow; Clinical Decision-Making; Combined Modality Therapy; Disease Management; Disease Progression; Disease Susceptibility; Genetic Predisposition to Disease; Histocytochemistry; Humans; Immunophenotyping; Leukemia, Hairy Cell; Mutation; Retreatment; Signal Transduction; Treatment Outcome; Watchful Waiting
PubMed: 32350628
DOI: 10.1007/s11864-020-00732-0 -
Current Topics in Behavioral... 2023Virtual reality (VR) allows us to create visual stimuli that are both immersive and reactive. VR provides many new opportunities in vision science. In particular, it...
Virtual reality (VR) allows us to create visual stimuli that are both immersive and reactive. VR provides many new opportunities in vision science. In particular, it allows us to present wide field-of-view, immersive visual stimuli; for observers to actively explore the environments that we create; and for us to understand how visual information is used in the control of behaviour. In contrast with traditional psychophysical experiments, VR provides much greater flexibility in creating environments and tasks that are more closely aligned with our everyday experience. These benefits of VR are of particular value in developing our theories of the behavioural goals of the visual system and explaining how visual information is processed to achieve these goals. The use of VR in vision science presents a number of technical challenges, relating to how the available software and hardware limit our ability to accurately specify the visual information that defines our virtual environments and the interpretation of data gathered in experiments with a freely moving observer in a responsive environment.
Topics: Virtual Reality; Vision, Ocular; Optometry; Humans; Ophthalmology
PubMed: 36723780
DOI: 10.1007/7854_2023_416 -
Pediatrics Jul 2022Updated guidelines continue to support watchful waiting as an option for uncomplicated acute otitis media (AOM) and provide explicit diagnostic criteria. To determine...
BACKGROUND AND OBJECTIVES
Updated guidelines continue to support watchful waiting as an option for uncomplicated acute otitis media (AOM) and provide explicit diagnostic criteria. To determine treatment prevalence and associated determinants of watchful waiting for AOM in commercially insured pediatric patients.
METHODS
This was a retrospective cohort study using IBM Marketscan Commercial Claims Databases (2005 to 2019) of patients 1 to 12 years old with AOM, without otitis-related complications within 6 months prior, with no tympanostomy tubes, and no other infections around index diagnosis of AOM. We examined monthly antibiotic treatment prevalence (defined as pharmacy dispensing within 3 days of AOM diagnosis) and used multivariable logistic regression models to examine determinants of watchful waiting.
RESULTS
Among 2 176 617 AOM episodes, 77.8% were treated within 3 days. Whereas some clinical characteristics were moderate determinants for watchful waiting, clinician antibiotic prescribing volume and specialty were strong determinants. Low-volume antibiotic prescribers (≥80% of AOM episodes managed with watchful waiting) had 11.61 (95% confidence interval 10.66-12.64) higher odds of using watchful waiting for the index AOM episode than high-volume antibiotic prescribers (≥80% treated). Otolaryngologists were more likely to adopt watchful waiting (odds ratio 5.45, 95% CI 5.21-5.70) than pediatricians, whereas other specialties deferred more commonly to antibiotics.
CONCLUSIONS
Adoption of watchful waiting for management of uncomplicated, nonrecurrent AOM was limited and stagnant across the study period and driven by clinician rather than patient factors. Future work should assess motivators for prescribing and evaluate patient outcomes among clinicians who generally prefer versus reject watchful waiting approaches to guide clinical decision-making.
Topics: Acute Disease; Anti-Bacterial Agents; Child; Child, Preschool; Humans; Infant; Otitis Media; Pediatricians; Retrospective Studies; Watchful Waiting
PubMed: 35726560
DOI: 10.1542/peds.2021-055613