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Advances in Pediatrics Aug 2024Patients with differences of sex development (DSDs) have complex anatomy and surgical needs related to both Mullerian and non-Mullerian structures. Approaches to vaginal... (Review)
Review
Patients with differences of sex development (DSDs) have complex anatomy and surgical needs related to both Mullerian and non-Mullerian structures. Approaches to vaginal reconstruction for these conditions are guided by individual anatomy, with the goal of establishing unobstructed outflow for the reproductive, urinary, and gastrointestinal tracts. Patients may have anatomy requiring vaginoplasty for either outflow tract obstruction or chosen sexual function. In this article, the authors focus on management of differences in vaginal anatomy with delayed vaginoplasty for the newborn with DSD.
Topics: Humans; Female; Disorders of Sex Development; Vagina; Infant, Newborn; Plastic Surgery Procedures; Male
PubMed: 38944480
DOI: 10.1016/j.yapd.2024.04.002 -
Magnetic Resonance Imaging Clinics of... Aug 2024Fetal MR imaging has been shown to be a useful tool for the diagnosis of fetal gastro-intestinal pathologies. To recognize the various pathologies, it is, however,... (Review)
Review
Fetal MR imaging has been shown to be a useful tool for the diagnosis of fetal gastro-intestinal pathologies. To recognize the various pathologies, it is, however, essential to know the normal MR imaging appearance of the fetal bowel at various gestational ages. By providing additional information to ultrasound in case of a fetal gastrointestinal anomaly, MR imaging helps to improve planning for the delivery, postnatal management, and improves parental counseling.
Topics: Humans; Magnetic Resonance Imaging; Prenatal Diagnosis; Gastrointestinal Tract; Female; Pregnancy; Gastrointestinal Diseases; Fetal Diseases
PubMed: 38944436
DOI: 10.1016/j.mric.2024.03.005 -
American Heart Journal Jun 2024This study aims to evaluate the efficacy and cost-effectiveness of sonothrombolysis delivered pre and post primary percutaneous coronary intervention (pPCI) on infarct...
OBJECTIVES
This study aims to evaluate the efficacy and cost-effectiveness of sonothrombolysis delivered pre and post primary percutaneous coronary intervention (pPCI) on infarct size assessed by cardiac MRI, in patients presenting with STEMI, when compared against sham procedure.
BACKGROUND
More than a half of patients with successful pPCI have significant microvascular obstruction and residual infarction. Sonothrombolysis is a therapeutic use of ultrasound with contrast enhancement that may improve microcirculation and infarct size. The benefits and real time physiological effects of sonothrombolysis in a multicentre setting are unclear.
METHODS
The REDUCE (Restoring microvascular circulation with diagnostic ultrasound and contrast agent) trial is a prospective, multicentre, patient and outcome blinded, sham-controlled trial. Patients presenting with STEMI will be randomized to one of two treatment arms, to receive either sonothrombolysis treatment or sham echocardiography before and after pPCI. This tailored design is based on preliminary pilot data from our centre, showing that sonothrombolysis can be safely delivered, without prolonging door to balloon time. Our primary endpoint will be infarct size assessed on day 4±2 on Cardiac Magnetic Resonance (CMR). Patients will be followed up for six months post pPCI to assess secondary endpoints. Sample size calculations indicate we will need 150 patients recruited in total.
CONCLUSIONS
This multicentre trial will test whether sonothrombolysis delivered pre and post primary PCI can improve patient outcomes and is cost-effective, when compared with sham ultrasound delivered with primary PCI. The results from this trial may provide evidence for the utilization of sonothrombolysis as an adjunct therapy to pPCI to improve cardiovascular outcomes in STEMI. ANZ Clinical Trial Registration number: ACTRN 12620000807954.
PubMed: 38944262
DOI: 10.1016/j.ahj.2024.06.008 -
Neurocirugia (English Edition) Jun 2024Chiari malformations (CM) are often diagnosed in childhood and younger adults, with an incidence of only 0.77% in adult populations. Patients with CM may develop...
Chiari malformations (CM) are often diagnosed in childhood and younger adults, with an incidence of only 0.77% in adult populations. Patients with CM may develop syringomyelia and increased intracranial pressure (ICP) due to cerebrospinal fluid (CSF) obstruction and altered fluid dynamics at the cervicomedullary junction. We describe the case of a 65-year-old female presenting with an angionegative subarachnoid hemorrhage (SAH) with concomitant new diagnosis of CM type I with syringomyelia. After ruling out any aneurysm or vascular malformations, she underwent a suboccipital craniectomy for a Chiari decompression with a C1 laminectomy. There were no complications with the surgery and her symptoms improved. This case report highlights the unusual presentation of a CM. A menudo, las malformaciones de Chiari (CM) son diagnosticadas en los niños y los adultos jóvenes, y la incidencia en la populación adulto es solamente 0.77%. A veces, los pacientes con CM desarrollan una siringomielia y la hipertensión intracraneal debido a la obstrucción del líquido cefalorraquídeo y los cambios a los dinámicos del fluido a la unión craneocervical. Nosotros describimos el caso de una mujer de 65-años que presentó con una hemorragia subaracnoideo, que no apareció en el angiograma, y con un nuevo diagnóstico de CM 1 con una siringomielia. Después de nosotros excluimos cualquier aneurisma o malformación vascular, hicimos una craneotomía suboccipital para una descompresión de Chiari con una laminectomía de C1. No fue otras complicaciones con la cirugía y sus síntomas mejoraron. Este caso clínico recalca una presentación anormal de una CM.
PubMed: 38944205
DOI: 10.1016/j.neucie.2024.06.002 -
Transplantation and Cellular Therapy Jun 2024Transplant associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic cell transplant (HCT) associated with endothelial injury resulting in severe...
BACKGROUND
Transplant associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic cell transplant (HCT) associated with endothelial injury resulting in severe end organ damage, acute and long-term morbidity, and mortality. Myeloablative conditioning is a known risk factor, though specific causative agents have not been identified. We hypothesized that the combination of cyclophosphamide and thiotepa (CY+TT) is particularly toxic to the endothelium, placing patients at elevated risk for TA-TMA.
METHODS
We conducted a retrospective review of pediatric and young adult patients who received conditioned autologous and allogeneic HCT between 2012 and August 2023 at UCSF Benioff Children's Hospital, San Francisco. We excluded patients undergoing gene therapy or triple tandem transplants for brain tumors. Neuroblastoma tandem transplants were classified a single transplant occurrence. High dose N-acetylcysteine (NAC) prophylaxis was incorporated into the institutional standard of care from December 2016-May 2019 and May 2022-August 2023. Defibrotide was given prophylactically to patients deemed high-risk for sinusoidal obstruction syndrome (SOS) per institutional guidelines or on clinical trial NCT#02851407 for SOS prophylaxis or NCT#03384693 for TA-TMA prophylaxis. Kaplan-Meier analysis was used to estimate the 1-year cumulative incidence of TA-TMA. Univariate analysis was performed for each of the potential risk factors of interest using log-rank tests and bivariate analysis with Cox regression models using backward selection and hazard ratios were built using all covariates with a univariate p-value <0.2 for allogeneic HCT. SPSS (v29) was used to estimate all summary statistics, cumulative incidences, and uni- and bi-variate analyses.
RESULTS
A total of 558 transplants were performed with 43 patients developing TA-TMA, for a 1-year cumulative incidence of 8.6% (95% CI, 5.9-11.3%) and 7.2% (95% CI, 2.9-11.5%) in allogeneic and autologous HCTs, respectively (p=0.62). In allogeneic recipients (n=417), the 1-year cumulative incidence of TA-TMA with CY+TT as part of conditioning was 35.7% (95% CI, 15.7-55.7%) compared to 11.7% (95% CI, 7.2-16.2%) with either CY or TT alone, and 1.2% (95% CI, 0-2.8%) if neither agent was included in the conditioning regimen (p<0.001). Use of either CY or TT (HR=10.14; p=0.002) or CY+TT (HR=35.93; p<0.001), viral infections (HR=4.3; p=0.017) and fungal infections (HR=2.98; p=0.027) were significant factors resulting in increased risk for developing TA-TMA. In subjects undergoing autologous HCT (n=141), the 1-year cumulative incidence of TA-TMA with CY+TT was 19.6% (95% CI, 8.8-30.6%) while TA-TMA did not occur in patients receiving either CY or TT alone or when neither were included (p<0.001). TA-TMA occurred only in patients with neuroblastoma receiving CY+TT as part of their conditioning. For autologous patients who received CY+TT, those who were CMV seronegative at the time of HCT had an incidence of TA-TMA of 6.7% (95% CI, 0.1-15.7%) compared to 38.1% (95% CI, 35-41.2%) for those CMV seropositive (p=0.007).
CONCLUSIONS
These data show that CY or TT alone or in combination as part of pre-transplant conditioning prior to HCT increase the incidence of TA-TMA. Alternative conditioning excluding the combination of CY+TT should be considered whenever possible to limit the development of TA-TMA.
PubMed: 38944154
DOI: 10.1016/j.jtct.2024.06.020 -
The Lancet. Oncology Jun 2024There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for...
BACKGROUND
There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for all types of cancers combined. The aim of this study was to quantify deficits in birth rates and risks of obstetric complications for female survivors of 17 specific types of adolescent and young adult cancer.
METHODS
The Teenage and Young Adult Cancer Survivor Study (TYACSS)-a retrospective, population-based cohort of 200 945 5-year survivors of cancer diagnosed at age 15-39 years from England and Wales-was linked to the English Hospital Episode Statistics (HES) database from April 1, 1997, to March 31, 2022. The cohort included 17 different types of adolescent and young adult cancers. We ascertained 27 specific obstetric complications through HES among 96 947 women in the TYACSS cohort. Observed and expected numbers for births and obstetric complications were compared between the study cohort and the general population of England to identify survivors of adolescent and young adult cancer at a heighted risk of birth deficits and obstetric complications relative to the general population.
FINDINGS
Between April 1, 1997, and March 31, 2022, 21 437 births were observed among 13 886 female survivors of adolescent and young adult cancer from England, which was lower than expected (observed-to-expected ratio: 0·68, 95% CI 0·67-0·69). Other survivors of genitourinary, cervical, and breast cancer had under 50% of expected births. Focusing on more common (observed ≥100) obstetric complications that were at least moderately in excess (observed-to-expected ratio ≥1·25), survivors of cervical cancer were at risk of malpresentation of fetus, obstructed labour, amniotic fluid and membranes disorders, premature rupture of membranes, preterm birth, placental disorders including placenta praevia, and antepartum haemorrhage. Survivors of leukaemia were at risk of preterm delivery, obstructed labour, postpartum haemorrhage, and retained placenta. Survivors of all other specific cancers had no more than two obstetric complications that exceeded an observed-to-expected ratio of 1·25 or greater.
INTERPRETATION
Survivors of cervical cancer and leukaemia are at risk of several serious obstetric complications; therefore, any pregnancy should be considered high-risk and would benefit from obstetrician-led antenatal care. Despite observing deficits in birth rates across all 17 different types of adolescent and young adult cancer, we provide reassurance for almost all survivors of adolescent and young adult cancer concerning their risk of almost all obstetric complications. Our results provide evidence for the development of clinical guidelines relating to counselling and surveillance of obstetrical risk for female survivors of adolescent and young adult cancer.
FUNDING
Children with Cancer UK, The Brain Tumour Charity, and Academy of Medical Sciences.
PubMed: 38944050
DOI: 10.1016/S1470-2045(24)00269-9 -
Cell Genomics Jun 2024The phenotypic impact of compound heterozygous (CH) variation has not been investigated at the population scale. We phased rare variants (MAF ∼0.001%) in the UK...
The phenotypic impact of compound heterozygous (CH) variation has not been investigated at the population scale. We phased rare variants (MAF ∼0.001%) in the UK Biobank (UKBB) exome-sequencing data to characterize recessive effects in 175,587 individuals across 311 common diseases. A total of 6.5% of individuals carry putatively damaging CH variants, 90% of which are only identifiable upon phasing rare variants (MAF < 0.38%). We identify six recessive gene-trait associations (p < 1.68 × 10) after accounting for relatedness, polygenicity, nearby common variants, and rare variant burden. Of these, just one is discovered when considering homozygosity alone. Using longitudinal health records, we additionally identify and replicate a novel association between bi-allelic variation in ATP2C2 and an earlier age at onset of chronic obstructive pulmonary disease (COPD) (p < 3.58 × 10). Genetic phase contributes to disease risk for gene-trait pairs: ATP2C2-COPD (p = 0.000238), FLG-asthma (p = 0.00205), and USH2A-visual impairment (p = 0.0084). We demonstrate the power of phasing large-scale genetic cohorts to discover phenome-wide consequences of compound heterozygosity.
PubMed: 38944039
DOI: 10.1016/j.xgen.2024.100602 -
International Journal of Surgery Case... Jun 2024Enteric duplication cysts (EDC) are rare anomalies of the gastrointestinal tract, with only 0.4 % occurring in the cecum. Meckel's diverticulum (MD) is a common...
INTRODUCTION
Enteric duplication cysts (EDC) are rare anomalies of the gastrointestinal tract, with only 0.4 % occurring in the cecum. Meckel's diverticulum (MD) is a common congenital anomaly affecting up to 2 % of the population. The simultaneous occurrence of these two conditions is rare with no existing guideline on treatment.
CASE PRESENTATION
An 11-month-old boy presented with fever, vomiting, and abdominal distension. A contrast-enhanced computed tomography scan confirmed the diagnosis of an enteric duplication cyst causing intestinal obstruction. The patient underwent exploratory laparotomy, during which a cecal duplication cyst measuring 30 × 20 mm was found along with MD in the distal ileum. Right limited hemicolectomy was performed. Histopathological examination revealed features consistent with an enteric duplication cyst and the presence of gastric mucosal heterotopia.
CLINICAL DISCUSSION
Differentiating EDC from MD is a significant challenge, as both can present with similar symptoms and be positive on a Tc-99 m radionuclide scan. The final diagnosis of EDC and MD can only be made by correlating the imaging findings with the surgical findings and pathological features.
CONCLUSION
Cecal duplication cysts should be considered a differential diagnosis in infants who present with intestinal obstruction. Although their presentation may resemble that of Meckel's diverticulum, both conditions can coexist. Excision of duplication cysts in children is considered a safe and efficient treatment approach.
PubMed: 38943938
DOI: 10.1016/j.ijscr.2024.109943 -
Diagnostic Microbiology and Infectious... Jun 2024Retropharyngeal abscess (RPA) is considered one of the life threatening conditions which can present either as dysphagia or dyspnoea. Timely management for the airway...
Retropharyngeal abscess (RPA) is considered one of the life threatening conditions which can present either as dysphagia or dyspnoea. Timely management for the airway obstruction along with etiology identification plays a pivotal role in saving a patient's life. Here we present a case of RPA due to a rare pathogen.
PubMed: 38943820
DOI: 10.1016/j.diagmicrobio.2024.116416 -
Brazilian Journal of Physical Therapy Jun 2024Functional capacity impairment is a crucial consequence of chronic obstructive pulmonary disease (COPD). Although it can be identified with simple tests, such as the...
Functional capacity using sit-to-stand tests in people with chronic obstructive pulmonary disease and its relationship with disease severity-a cross-sectional study with matched controls.
BACKGROUND
Functional capacity impairment is a crucial consequence of chronic obstructive pulmonary disease (COPD). Although it can be identified with simple tests, such as the sit-to-stand tests, its prevalence, relation with disease severity, and the characteristics of people presenting this impairment remain unknown.
OBJECTIVE
To explore the functional capacity of people with COPD.
METHODS
A cross-sectional study with people with COPD and age-/sex-matched healthy controls was conducted. Functional capacity was assessed with the 5-repetitions (5-STS) and the 1-minute (1-minSTS) sit-to-stand tests. People with COPD were grouped according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications. Comparisons between people with COPD and healthy controls, and among GOLD groups were established. Associations between symptoms, muscle strength, quality of life, and measures of functional capacity were explored.
RESULTS
302 people with COPD [79% male; mean (SD) 68 (10) years old] and 304 healthy controls [75% male; 66 (9) years old] were included. 23% of people with COPD presented impairment in the 5-STS and 33% in the 1-minSTS. People with COPD from all GOLD classifications presented significantly lower functional capacity than healthy controls (5-STS: COPD median [1st quartile; 3rd quartile] 8.4 [6.7; 10.6] versus healthy 7.4 [6.2; 9.3] s; 1-minSTS: COPD 27 [21; 35] vs healthy 35 [29; 43] reps). Correlations with symptoms, muscle strength, and quality of life were mostly weak (5-STS: r [-0.34; 0.33]; 1-minSTS: r [-0.47; 0.40]).
CONCLUSION
People with COPD have decreased functional capacity independently of their GOLD classifications. The prevalence of functional impairment is 23-33%. Because impaired functional capacity is a treatable trait not accurately reflected by other outcomes, comprehensive assessment and management is needed.
PubMed: 38943740
DOI: 10.1016/j.bjpt.2024.101090