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Osteoglophonic dwarfism, also known as osteoglophonic dysplasia (OD), is an uncommon skeletal dysplasia with an autosomal dominant mode of inheritance, which equally affects boys and girls. OD is saliently featured by craniosynostosis, dysmorphic facial features, impacted mandibular teeth, rhizomelic limb shortening and non-ossifying fibromas habitually at the metaphyseal regions, which usually disappear after skeletal maturity. The long bones in OD are portrayed by this distinguishable ‘hollowed-out’ appearance with metaphyseal cystic defects that have a natural history of spontaneous resolution. We report a case of a rare and unusual presentation of OD in a 23-year-old woman whom has been diagnosed with OD during her early childhood. She presented with a progressively enlarging right thigh swelling associated with pain for the past 1 year. Her right femur plain radiograph revealed diffuse lysis of the whole femur with cortical thinning. MRI revealed multiple bilateral femur benign cystic lesion synonymous with a severe spectrum of OD. She was started on a trial of oral bisphosphonates, which led to a significant improvement in pain.

Any effective screening program must satisfy 2 criteria: 1) the test must identify clinically significant disease earlier than its clinical presentation, and 2) a treatment must be available that will alter the natural history of the disease. The controversy surrounding PSA testing that has raged since 1991 centers on these 2 points. Screening and treatment trials published during the past 3 decades have provided critical insights into our understanding of the natural history of PSA identified cancers and the impact of treatment. This in turn raises questions concerning the mechanism of prostate cancer mortality reduction. This essay reflects on the mechanisms of disease progression and the implications for future screening and treatment efforts.

Over the past decades, there has been a rapid increase in the incidence and prevalence of inflammatory bowel disease (IBD) in Asia. The natural history of IBD in Asian patients could be different from that in Western patients due to variations in disease phenotypes and genotypes as well as the healthcare environment between the 2 populations. To adequately cope with this disease, it is important to fully understand the potential differences in its natural history among different populations. In this review, we evaluated the differences in the clinical course of IBD between Asian and Western patients with regards to phenotypic progression, hospitalization, major surgery, risk of colorectal cancer, and mortality, mainly based on the results of population-based studies. The findings of our narrative review suggest that the clinical course of Asian patients with IBD, especially ulcerative colitis, is better than that of Western patients, as indicated by the lower rates of major surgery and hospitalization. In addition, similar to Western patients, the clinical course of Asian patients with IBD has been improving as evidenced by the decreasing rates of disease behavior progression (in Crohn’s disease), hospitalization, and major surgery.

Introduction Splenic torsion is a rare condition but one that many surgeons will encounter once in their career. Management options are varied but due to the rarity of the condition there are no contemporary evidence-based summaries to inform a treating clinician. We aim to describe patterns of presentation and provide an evidence-based guide to the management. Methods A PRISMA structured meta-analysis was conducted of all published cases of splenic torsion and a recent case added from our institution. Results 408 cases were identified between 1888 and 2021 and a single case added from our institution, 312 cases were sourced from case reports and 96 from 40 case series. 8% of patients had a co-existing congenital anomaly and 28% an identified risk factor for splenic torsion. 82% required emergency surgery. A preoperative diagnosis is becoming more common, reaching 80% in 2020's. While spleen conserving surgery is feasible using a variety of techniques. splenectomy was the definitive management for the majority (82%). On histopatholy no occult disease was identified and a significant number of resected spleens were potentially viable; 32% were reported to be normal or congested and 14% demonstrated only partial or focal necrosis. Discussion Despite the significant publication bias implied by the methodology this is a large dataset in a rare condition. Splenic torsion frequently occurs in a premorbid population. The presence of a palpable mass in the context of abdominal pain should increase suspicion and trigger cross sectional imaging. Conservation of the spleen, using the techniques discussed, should be seriously considered.

Gallbladder (GB) Small Cell Carcinoma (SCC) is an uncommon entity with very poor prognosis. There is a paucity of literature regarding its natural history and management, with only 73 prior cases reported in the world literature. In this case report, we present three cases of SCC of the GB with varied presentations, clinical course, management, and outcomes along with a brief review of the available literature on this subject.

Cardiac allograft vasculopathy (CAV) continues to be a significant risk factor for the recipient's long-term survival following heart transplantation. Our knowledge of its etiology is constantly changing as new imaging techniques provide direct insight into the disease's natural history. CAV identification continues to be difficult since symptoms may be varied or nonexistent. Due to the irreversible nature of the disease, early diagnosis is critical to halting development. Prognostic tools and biomarkers have proliferated as a result of advancements in diagnostic techniques. Simultaneously, pharmaceutical advancements have aided in the amelioration of the disease's progressive progression.

SIGNIFICANCE: Primary lymphedema is a chronic condition without a cure. The lower extremities are more commonly affected than the arms or genitalia. The disease can be syndromic. Morbidity includes decreased self-esteem, infections, and reduced function of the area. RECENT ADVANCES: Several mutations can cause lymphedema, and new variants continue to be elucidated. A critical determinant that predicts the natural history and morbidity of lymphedema is the patient's body mass index (BMI). Individuals who maintain an active lifestyle with a normal BMI generally have less severe disease compared to subjects who are obese. Because other causes of lower extremity enlargement can be confused with lymphedema, definitive diagnosis requires lymphoscintigraphy. CRITICAL ISSUES: Most patients with primary lymphedema are satisfactorily managed with compression regimens, exercise, and maintenance of a normal body weight. Suction-assisted lipectomy is our preferred operative intervention for symptomatic patients who have failed conservative therapy. Suction-assisted lipectomy effectively removes excess subcutaneous fibro-adipose tissue and can improve underlying lymphatic function. FUTURE DIRECTIONS: Many patients with primary lymphedema do not have an identifiable mutation and thus novel variants will be identified. The mechanisms by which mutations cause lymphedema continue to be studied. In the future, drug therapy for the disease may be developed.

Objective: There is a lack of studies on the natural history of the initial stages of schizophrenia in Colombia. This study aims to assess functionality in the first five years after the diagnosis of schizophrenia. Methods: Naturalistic longitudinal study of 50 patients with early schizophrenia evaluated between 2011 and 2014. Data about demographic background, symptoms, introspection, treatment and adverse reactions were collected in all patients every 3 months for at least 3-5 years. Functionality was measured with the Global Assessment of Functioning (GAF) and Personal and Social Performance (PSP) scales. Results: Patients were followed up for a mean of 174 ± 62.5 weeks and showed moderate difficulties in overall functioning. This functioning was modified by polypharmacy, degree of introspection, changes in antipsychotic regimens, and the number of episodes, relapses and hospitalisations. Conclusions: The results suggest that functional outcomes seem to be related to the use of polypharmacy, degree of insight, changes in antipsychotic regimens, and number of episodes, relapses and hospitalisations during the first years of schizophrenia. RESUMEN Objetivo: Existe una falta de estudios en la historia natural de los estadios iniciales de la esquizofrenia en Colombia. Este estudio apunta a evaluar la funcionalidad en los primeros cinco años después del diagnóstico de esquizofrenia. Método: Estudio longitudinal naturalístico de 50 pacientes con esquizofrenia temprana evaluados entre los anos 2011 y 2014. Loa datos demográficos, síntomas, introspección, tratamiento, y reacciones adversas fueron recolectados en todos los pacientes cada 3 meses por lo menos3a5anos. La funcionalidad se midió mediante la escala global de funcionamiento (GAF), y la escala de funcionamiento personal y social (PSP). Resultados: Los pacientes fueron seguidos por una media de 174 semanas (SD: 62.5) y mostraron dificultades moderadas en su funcionamiento global. Este funcionamiento fue modificado por la presencia de polifarmacia, grado de introspección, cambios en los esquemas antipsicóticos, y el número de episodios, recaídas, y hospitalizaciones. Conclusiones: Los resultados sugieren que los desenlaces en funcionalidad parecen estar relacionados con uso de polifarmacia, grado de introspección, cambios en esquemas antipsicóticos, y numero de episodios, recaídas, y hospitalizaciones durante los primeros años de esquizofrenia.

As the number of donation after circulatory death (DCD) liver transplants (LTs) performed in the United States continues to increase annually, there has been interest by policy makers to develop a more robust exception point safety net for patients who develop ischemic cholangiopathy (IC) following DCD LT. As such, there is a need for better understanding of the clinical course and long-term outcomes in patients who develop IC, as well as determining if IC can be classified into distinct categories with distinctly different clinical outcomes.All DCD LT performed at Mayo Clinic Florida, Mayo Clinic Arizona, and Mayo Clinic Rochester from January 1999 to March 2020 were included (N = 770). Outcomes were compared between 4 distinct radiologic patterns of IC: diffuse necrosis, multifocal progressive, confluence dominant, and minor form.In total, 88 (11.4%) patients developed IC, of which 42 (5.5%) were listed for retransplantation of liver (ReLT). Patients with diffuse necrosis and multifocal progressive patterns suffered from frequent hospital admissions for cholangitis in the first year following DCD LT (median 3 and 2), were largely stent dependent (100% and 85.7%), and almost universally required ReLT. Patients with confluence dominant disease were managed with multiple stents and frequently recovered, ultimately becoming stent free without need for ReLT. Patients with the minor form IC did well with limited need for stent placement or repeat procedures and did not require ReLT. Graft survival was different between the 4 distinct IC patterns (P 0.001).The present analysis provides a detailed analysis on the natural history and clinical course of IC. Patients developing IC can be classified into 4 distinct patterns with distinct clinical courses.

To review our experience with fetal aortic valvuloplasty (FAV) in fetuses with critical aortic stenosis (CAS) and evolving hypoplastic left heart syndrome (eHLHS), including short- and medium-term postnatal outcome, and to refine selection criteria for FAV by identifying preprocedural predictors of biventricular (BV) outcome.This was a retrospective review of all fetuses with CAS and eHLHS undergoing FAV at our center between December 2001 and September 2020. Echocardiograms and patient charts were analyzed for pre-FAV ventricular and valvular dimensions and hemodynamics and for postnatal procedures and outcomes. The primary endpoints were type of circulation 28 days after birth and at 1 year of age. Classification and regression-tree analysis was performed to investigate the predictive capacity of pre-FAV parameters for BV circulation at 1 year of age.During the study period, 103 fetuses underwent 125 FAVs at our center, of which 87.4% had a technically successful procedure. Technical success per fetus was higher in the more recent period (from 2014) than in the earlier period (96.2% (51/53) vs 78.0% (39/50); P = 0.0068). Eighty fetuses were liveborn after successful intervention and received further treatment. BV outcome at 1 year of age was achieved in 55% of liveborn patients in our cohort after successful FAV, which is significantly higher than the BV-outcome rate (23.7%) in a previously published natural history cohort fulfilling the same criteria for eHLHS (P = 0.0015). Decision-tree analysis based on the ratio of right to left ventricular (RV/LV) length combined with LV pressure (mitral valve regurgitation maximum velocity (MR-Vmax)) had a sensitivity of 96.97% and a specificity of 94.44% for predicting BV outcome without signs of pulmonary arterial hypertension at 1 year of age. The highest probability for a BV outcome was reached for fetuses with a pre-FAV RV/LV length ratio of 1.094 (96.4%) and for those fetuses with a RV/LV length ratio ≥ 1.094 to 1.135 combined with a MR-Vmax of ≥ 3.14 m/s (100%).FAV could be performed with high success rates and an acceptable risk with improving results after a learning curve. Pre-FAV RV/LV length ratio combined with LV pressure estimates were able to predict a successful BV outcome at 1 year of age with high sensitivity and specificity. © 2022 The Authors. Ultrasound in ObstetricsGynecology published by John WileySons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Purpose Although intracranial dural arteriovenous fistula (DAVF) without retrograde leptomeningeal venous drainage (Borden type I) is reported to have a benign nature, no study has prospectively determined its clinical course. Here, we report a 3-year prospective observational study of Borden type I DAVF. Methods From April 2013 to March 2016, consecutive patients with DAVF were screened at 13 study institutions. We collected data on baseline characteristics, clinical symptoms, angiography, and neuroimaging. Patients with Borden type I DAVF received conservative care while palliative intervention was considered when the neurological symptoms were intolerable, and were followed at 6, 12, 24, and 36 months after inclusion. Results During the study period, 110 patients with intracranial DAVF were screened and 28 patients with Borden type I DAVF were prospectively followed. None of the patients had conversion to higher type of Borden classification or intracranial hemorrhage during follow-up. Five patients showed spontaneous improvement or disappearance of neurological symptoms (5/28, 17.9%), and 5 patients showed a spontaneous decrease or disappearance of shunt flow on imaging during follow-up (5/28, 17.9%). Stenosis or occlusion of the draining sinuses on initial angiography was significantly associated with shunt flow reduction during follow-up (80.0% vs 21.7%, p = 0.02). Conclusion In this 3-year prospective study, patients with Borden type I DAVF showed benign clinical course; none of these patients experienced conversion to higher type of Borden classification or intracranial hemorrhage. The restrictive changes of the draining sinuses at initial diagnosis might be an imaging biomarker for future shunt flow reduction.

OBJECTIVE There is a reported elevated risk of cerebral aneurysms in patients with intracranial dural arteriovenous fistulas (dAVFs). However, the natural history, rate of spontaneous regression, and ideal treatment regimen are not well characterized. In this study, the authors aimed to describe the characteristics of patients with dAVFs and intracranial aneurysms and propose a classification system. METHODS The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database from 12 centers was retrospectively reviewed. Analysis was performed to compare dAVF patients with (dAVF+ cohort) and without (dAVF-only cohort) concomitant aneurysm. Aneurysms were categorized based on location as a dAVF flow-related aneurysm (FRA) or a dAVF non–flow-related aneurysm (NFRA), with further classification as extra- or intradural. Patients with traumatic pseudoaneurysms or aneurysms with associated arteriovenous malformations were excluded from the analysis. Patient demographics, dAVF anatomical information, aneurysm information, and follow-up data were collected. RESULTS Of the 1077 patients, 1043 were eligible for inclusion, comprising 978 (93.8%) and 65 (6.2%) in the dAVF-only and dAVF+ cohorts, respectively. There were 96 aneurysms in the dAVF+ cohort; 10 patients (1%) harbored 12 FRAs, and 55 patients (5.3%) harbored 84 NFRAs. Dural AVF+ patients had higher rates of smoking (59.3% vs 35.2%, p < 0.001) and illicit drug use (5.8% vs 1.5%, p = 0.02). Sixteen dAVF+ patients (24.6%) presented with aneurysm rupture, which represented 16.7% of the total aneurysms. One patient (1.5%) had aneurysm rupture during follow-up. Patients with dAVF+ were more likely to have a dAVF located in nonconventional locations, less likely to have arterial supply to the dAVF from external carotid artery branches, and more likely to have supply from pial branches. Rates of cortical venous drainage and Borden type distributions were comparable between cohorts. A minority (12.5%) of aneurysms were FRAs. The majority of the aneurysms underwent treatment via either endovascular (36.5%) or microsurgical (15.6%) technique. A small proportion of aneurysms managed conservatively either with or without dAVF treatment spontaneously regressed (6.2%). CONCLUSIONS Patients with dAVF have a similar risk of harboring a concomitant intracranial aneurysm unrelated to the dAVF (5.3%) compared with the general population (approximately 2%–5%) and a rare risk (0.9%) of harboring an FRA. Only 50% of FRAs are intradural. Dural AVF+ patients have differences in dAVF angioarchitecture. A subset of dAVF+ patients harbor FRAs that may regress after dAVF treatment.

In the last two decades there has been significant progress in research on and diagnosis of hepatocellular adenoma (HCA), resulting in the establishment of a molecular and immunohistological HCA classification. This review aims to fine-tune the current expertise in order to enhance the histopathological diagnostic possibilities, by refining issues that are already known, addressing diagnostic difficulties, and identifying still unknown aspects of HCA. We discuss novel methods to identify HCA subtypes, in particular the sonic hedgehog HCAs and the interpretation of glutamine synthetase patterns for the recognition of β-catenin-mutated HCAs. The major complications of HCAs, i.e. bleeding and malignant transformation, are considered, including the dilemmas of atypical and borderline lesions. HCAs in different clinical and geographical settings, e.g. pregnancy, cirrhosis and non-western countries, are also discussed. The natural history of the different HCA subtypes in relation to age, sex and risk factors is a feature that is still insufficiently investigated. This is also true for the risks of clinical bleeding and malignant transformation in association with HCA subtypes. As HCA is a relatively rare tumour, a multicentre and multidisciplinary approach across geographical boundaries will be the appropriate method to establish prospective programmes with which to identify, classify and manage HCAs, focusing on several aspects, e.g. aetiology, underlying liver disease, complications, regression, and growth. Updating what we know and identifying and addressing what we do not know matters for optimal patient management.

With the increasing practice of gender-affirming mastectomy as a therapeutic procedure in the setting of gender dysphoria, there has come a profusion of literature on the pathologic findings within these specimens. Findings reported in over 1500 patients have not included either prostatic metaplasia or pilar metaplasia of breast epithelium. We encountered both of these findings in the course of routine surgical pathology practice and therefore aimed to analyze these index cases together with a retrospective cohort to determine the prevalence, anatomic distribution, pathologic features, and associated clinical findings of prostatic metaplasia and pilar metaplasia in the setting of gender-affirming mastectomy. In addition to the 2 index cases, 20 additional archival gender-affirming mastectomy specimens were studied. Before mastectomies, all but 1 patient received testosterone cypionate, 6/22 patients received norethindrone, and 21/22 practiced breast binding. Prostatic metaplasia, characterized by glandular proliferation along the basal layer of epithelium in breast ducts, and in one case, within lobules, was seen in 18/22 specimens; 4/22 showed pilar metaplasia, consisting of hair shafts located within breast ducts, associated with squamoid metaplasia resembling hair matriceal differentiation. By immunohistochemistry, prostatic metaplasia was positive for PSA in 16/20 cases and positive for NKX3.1 in 15/20 cases. Forty-three reduction mammoplasty control cases showed no pilar metaplasia and no definite prostatic metaplasia, with no PSA and NKX3.1 staining observed. We demonstrate that prostatic metaplasia and pilar metaplasia are strikingly common findings in specimens from female-assigned-at-birth transgender patients undergoing gender-affirming mastectomy. Awareness of these novel entities in the breast is important, to distinguish them from other breast epithelial proliferations and to facilitate accrual of follow-up data for better understanding their natural history.

Iron deficiency anaemia is highly prevalent worldwide. In the surgical patient, anaemia of any cause implies higher morbidity and mortality in the post-operative period. This is especially important in patients with peripheral artery disease, as they have very high rates of anaemia due to iron deficiency or other causes. In intermittent claudication, anaemia is a predictor of death in the medium term. Patients with critical ischaemia have higher prevalence of anaemia and it is an indicator of amputation and death in the medium term. Specific protocols need to be developed for these patients since the natural history of their disease does not allow for the correction of anaemia before surgery.

Urinary tract infection (UTI) is the most common type of urogenital disease. UTI affects the urethra, bladder, ureter, and kidney. A total of 13.3% of women, 2.3% of men, and 3.4% of children in the United States will require treatment for UTI. Traditionally, bladder (cystitis) and kidney (pyelonephritis) infections are considered independently. However, both infections induce host defenses that are either shared or coordinated across the urinary tract. Here, we review the chemical and biophysical mechanisms of bacteriostasis, which limit the duration and severity of the illness. Urinary bacteria attempt to overcome each of these defenses, complicating description of the natural history of UTI. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

As trials and treatments for Spinal Muscular Atrophy (SMA) rapidly evolve, understanding the natural history and potential utility of the 10-meter walk/run test (10MWRT) in ambulant individuals is critical. Study aims were to: 1) establish change over time and across age for 10MWRT time in an untreated natural history cohort of young, ambulatory participants with SMA and 2) identify relations between 10MWRT time and age, SMA type, SMN2 copy number and anthropometrics. Untreated individuals (n=56) age 2 to 21 years who were enrolled in a long-term natural history study between 2005 and 2014 and met inclusion criteria were included. Linear mixed effects models were used to assess changes in 10MWRT time with age and associations with SMA type, SMN2 copy number, and body mass. SMA type 3b (versus 3a), SMN2 copy number 4 (versus 3) and lower body mass were associated with faster 10MWRT. 10MWRT performance improved between 3 and 8 years of age, was stable between 9 and 10, and gradually declined from 11 to 18. Findings provide the first longitudinal natural history report of 10MWRT time in young individuals with SMA and offer a critical foundation for interpreting childhood change in short distance walking speed with pharmacologic treatment.

The prevalence of sesame allergy is increasing; strict avoidance is the mainstay of therapy. Lately, sesame oral immunotherapy was presented as an alternative treatment, with a high rate of success. Therefore, data on the natural history and the clinical characteristics of patients with persistent sesame allergy are important for the management of patients with sesame allergy.To describe the natural history of patients with sesame allergy and the clinical characteristics of patients with spontaneous resolution of sesame allergy compared with patients with persistent sesame allergy.In our retrospective study, electronic health records of patients with sesame allergy diagnosis were reviewed for demographic and clinical data. Statistical analysis of clinical characteristics of patients with spontaneous resolution compared with persistent sesame allergy was performed.A total of 190 patients with sesame allergy were followed for 3.86 ±4.43 years. Of these patients, 61 (32.1%) had spontaneous resolution of sesame allergy. Patients with mild, early (before the age of 10 months) first sesame allergic reaction, with smaller than 7-mm skin prick test and without concomitant tree nut allergy had better resolution rate (56.1%).Sesame allergy spontaneously resolved in approximately one-third of our patients and in more than half of the patients with mild first reaction (grade 1) at a young age (10 months), with small skin prick test (7 mm) and no concomitant tree nut allergy. Larger prospective studies with longer follow-up period are needed to better characterize the sesame allergic patients with persistent allergy who may need oral immunotherapy.

BACKGROUND/PURPOSE Patients with pancreatic ductal adenocarcinoma (PDAC) with peritoneal dissemination have a dismal prognosis because discontinuation of systemic chemotherapy is required for massive ascites or poor performance status. The natural history, diagnosis and treatment of PDAC with peritoneal dissemination have not been fully investigated. METHODS We systematically reviewed published information on the clinical diagnosis and treatment of PDAC with peritoneal dissemination using the PubMed database (2000-2020) and provided recommendations in response to clinical questions. This guideline was created according to the "Minds Clinical Practice Guideline Development Guide 2017". The literature quality and body of evidence were evaluated with the GRADE System and classified into four levels ("strong", "medium", "weak", "very weak"). The strength of each final recommendation was decided by a vote of committee members based on the GRADE Grid method. RESULTS These guidelines address 3 subjects: diagnostic, chemotherapeutic, and surgical approaches. They include 9 clinical questions and statements with recommendation strengths, evidence levels, and agreement rates, in addition to one "column". CONCLUSIONS This is the English synopsis of the 2021 Japanese clinical practice guideline for PDAC with peritoneal dissemination. It summarizes the clinical evidence for the diagnosis and treatment of PDAC with peritoneal dissemination and provides future perspectives.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The majority of FMD patients are women. Although a variety of genetic, mechanical, and hormonal factors play a role in the pathogenesis of FMD, overall, its cause remains poorly understood. It is probable that the pathogenesis of FMD is linked to a combination of genetic and environmental factors. Extensive studies have correlated the arterial lesions of FMD to histopathological findings of arterial fibrosis, cellular hyperplasia, and distortion of the abnormal architecture of the arterial wall. More recently, the vascular phenotype of lesions associated with FMD has been expanded to include arterial aneurysms, dissections, and tortuosity. However, in the absence of a string-of-beads or focal stenosis, these lesions do not suffice to establish the diagnosis. While FMD most commonly involves renal and cerebrovascular arteries, involvement of most arteries throughout the body has been reported. Increasing evidence highlights that FMD is a systemic arterial disease and that subclinical alterations can be found in non-affected arterial segments. Recent significant progress in FMD-related research has led to improve our understanding of the disease’s clinical manifestations, natural history, epidemiology, and genetics. Ongoing work continues to focus on FMD genetics and proteomics, physiological effects of FMD on cardiovascular structure and function, and novel imaging modalities and blood-based biomarkers that can be used to identify subclinical FMD. It is also hoped that the next decade will bring the development of multi-centred and potentially international clinical trials to provide comparative effectiveness data to inform the optimal management of patients with FMD.

The authors sought to determine whether global longitudinal strain (GLS) is independently associated with the natural history of patients with heart failure (HF) with improved ejection fraction (HFimpEF).Left ventricular (LV) ejection fraction (EF) often improves in patients with reduced EF. The clinical course of patients with HFimpEF, however, is quite variable. GLS, a sensitive indicator of LV systolic function, could help predict risk of future events in this population.Retrospective analysis of HF patients with LVEF40% on index echocardiogram who had LVEF 40% on initial study and improvement of ≥10%. GLS was assessed by 2-dimensional speckle-tracking software on index echocardiography. Primary outcome was time to first occurrence of cardiovascular mortality or HF hospitalization/emergency treatment.Of the 289 patients with HFimpEF, median absolute values of GLS (aGLS) and LVEF from index echocardiography were 12.7% (IQR: 10.8%-14.7%) and 52% (IQR: 46%-58%), respectively. Over 53 months following index echocardiography, the primary endpoint occurred less frequently in patients with aGLS above the median than below it (21% vs 34%; P = 0.014); HR of 0.51; 95% CI: 0.33-0.81; P = 0.004. When assessed as a continuous variable, each 1% increase in aGLS on index echocardiogram was associated with a lower likelihood of the composite endpoint; HR of 0.86; 95% CI: 0.79-0.93; P 0.001, an association that persisted after multivariable adjustment; HR 0.90; 95% CI: 0.82-0.97; P = 0.01. Lower aGLS was associated with increased likelihood of deterioration in LVEF.In patients with HFimpEF, GLS is a strong predictor for future HF events and deterioration in cardiac function.

Background Hemorrhage rates of conservatively managed brainstem cavernous malformations (BSCMs) vary widely in the literature. We aimed to elucidate the reason for the variation and to add the results of our experience of BSCMs management over the past decade. Methods We performed a review of consecutive patients with BSCMs referred to our department in the period 2006–2018. A hemorrhagic event was defined as a radiographically verified intralesional and extralesional hemorrhage. Both retrospective and prospective hemorrhage rates were calculated based on the patient age in years, counted either from birth or from the time of initial presentation until the last contact (or until surgical resection). In addition, we retrieved and reviewed publications with a clear definition of hemorrhagic event and a detailed description of BSCM hemorrhage rate. Results In total, 118 patients with BSCMs were reviewed, and 78 patients (mean age on admission 45.9 years) were included in the final analysis. The retrospective and prospective hemorrhage rates were 1.9% (95% confidence interval 1.6%–2.3%) per year and 11.9% (95% confidence interval 7.5%–17.8%), respectively. The retrospective hemorrhage rate in the literature review ranged from 1.9% to 6.8% per year with a median value of 3.8%, whereas the prospective hemorrhage rate ranged between 4.1% and 21.5%, with a median value of 10.2%. Conclusions The reported hemorrhage rates are calculated in 2 different ways. In our patient cohort, both the retrospective and prospective hemorrhage rates were in accordance with those in the literature. The long-term hemorrhage rate lies between the prospective and retrospective rate.

Medicine is characterized by the application of the scientific method through clinical judgment, by correct interpretation and use of the clinical course and/or natural history of the disease; its best description is observed in the architecture of clinical research. Through a temporal sequence, this model explains the phenomenon of causality with three sections: baseline status, maneuver, and outcome. The baseline status assesses who the patient is, where does he come from, his general conditions, the diagnosis, stage and aggressiveness of the pathology, complications, previous therapies, socioeconomic-cultural level, habits, therapeutic indications or contraindications, and the expected evolution is anticipated. In the maneuver, risk or prognostic factors, specific or symptomatic treatment, and general measures can be evaluated. In the outcome, early and late evolution are monitored. The model also allows the causes of follow-up loss to be determined. Anticipating patient evolution by recognizing his condition, disease, and expected effect of medical decisions allows acting in advance, since waiting for the manifestations of the evolutionary process of disease results in detriment to the patient.La medicina se caracteriza por la aplicación del método científico a través del juicio clínico, por la correcta interpretación y el uso del curso clínico o historia natural de la enfermedad; su descripción más lograda la observamos en la arquitectura de la investigación clínica. A través de una secuencia temporal, este modelo explica el fenómeno de causalidad con tres apartados: estado basal, maniobra y desenlace. En el estado basal se evalúa quién es el paciente, de donde proviene, sus condiciones generales, el diagnóstico, el estadio y la agresividad de la patología, las complicaciones, terapias previas, nivel socioeconómi­co-cultural, hábitos, indicaciones o contraindicaciones terapéuticas y se prevé la evolución esperada. De la maniobra se pueden evaluar los factores de riesgo o pronóstico, tratamiento específico, sintomático y medidas generales. En el desenlace se vigila la evolución temprana y tardía. El modelo también permite determinar las causas de pérdida de seguimiento. Anticipar la evo­lución del paciente al reconocer su condición, enfermedad y efecto esperado de la decisiones médicas permite actuar antici­padamente, ya que esperar las manifestaciones del proceso evolutivo de la enfermedad resulta en detrimento del paciente.

BACKGROUND & AIMS: Globally, 25% of people have nonalcoholic fatty liver disease (NAFLD), and, currently, there are no approved pharmacologic treatments for NAFLD. With a slow disease progression, long-term impact of pharmacologic treatments can be assessed only by complementing emerging clinical trial evidence with data from other sources in disease progression modeling. Although this modeling is crucial for economic evaluation studies assessing the clinical and economic con-sequences of new treatments, the approach to modeling the natural history of NAFLD differs in contemporary research. This systematic literature review investigated modeling of the natural history of NAFLD.METHODS: A systematic literature review was conducted searching PubMed, Scopus, Cochrane, and the National Health Service Economic Evaluation Database to identify articles focusing on modeling of the natural history of NAFLD. Model structure and transition probabilities were extracted from included studies.RESULTS: Of the 28 articles identified, differences were seen in model structure and data input. Clear definitions of nonalcoholic steatohepatitis and NAFLD often were lacking; differences in the granularity of modeling fibrosis progression, the approach to disease regression, and modeling of advanced liver disease varied across studies. Observed transition probabilities for F0 to F1, F1 to F2, F2 to F3, and F3 to compensated cirrhosis varied between 0.059 to 0.095, 0.023 to 0.140, 0.018 to 0.070, and 0.040 to 0.118, respectively.CONCLUSIONS: The difference in disease progression modeling for seemingly similar models warrants further inquiry regarding how to model the natural course of NAFLD. Such differences may have a large impact when assessing the value of emerging pharmacologic treatments. Funding Agencies|Vinnova [2019-01189]

OBJECTIVE To investigate the incidence, risk factors, and natural history of parastomal hernia. MATERIALS AND METHODS We reviewed the records of patients who underwent radical cystectomy and ileal conduit from 2007 to 2020. Patients who had available follow-up CT imaging were included in this study. All CT scans were re-reviewed for detection of parastomal hernia per Moreno-Matias classification. Patients who developed hernia were followed up and classified into stable or progressive (defined as radiologic upgrading and/or need for surgical intervention). Multivariable cox regression was performed to identify independent predictors of hernia development and progression. RESULTS A total of 361 patients were included in this study. The incidence of radiologic parastomal hernia was 30%, graded as I (56.5%), II (12%), and III (31.5%). Median (IQR) time to radiologic hernia was 8 (5-15) months. During the median (IQR) follow-up of 27 (13-47) months in 108 patients with a hernia, 26% progressed. Median (IQR) time to progression was 12 (6-21) months. On multivariable analysis, female gender (HR 1.86), diabetes (HR 1.81), chronic obstructive pulmonary disease (HR 1.78), and higher body mass index (HR 1.07 for each unit) were independent predictors for radiologic parastomal hernia development. No significant factor was found to be associated with hernia progression. CONCLUSION The incidence of radiologic parastomal hernia following radical cystectomy and ileal conduit is 30%; a quarter of whom progress in a median time of 12 months. Female gender, diabetes, chronic obstructive pulmonary disease, and high body mass index are independent predictors for radiologic hernia development.

Objective Penetrating atherosclerotic ulcers (PAUs) in aortic branch vessels are rare. There is a paucity of data regarding their long-term natural history and associated management. This study aimed to determine the prevalence and natural history of aortic branch PAUs. Methods Institutional data on all patients with an aortic branch PAU from 2005 to 2020 were retrospectively reviewed. Branch PAUs were defined as any PAU in the iliac, mesenteric, or arch vessels. End points included symptoms, end-organ events, and interventions. All computed tomography angiographies (CTAs) for each patient were reviewed, and total diameter, ulcer width, and ulcer depth were recorded on each computed tomography scan for the branch PAUs. Rate of change was compared between groups (iliac vs arch and visceral vessels) using a linear mixed-effects model. Results Among 58,800 patients who underwent a CTA, 367 patients had an aortic PAU (prevalence: 0.6%) and 58 patients had a branch PAU (prevalence: 0.1%). Among those 58 patients, there were 66 ulcerated branches. There were 50 iliac (42 common iliac, 7 internal, and 1 external), 11 arch (8 left subclavian, 3 innominate), and 5 visceral ulcers (3 superior mesenteric artery, 1 celiac, and 1 renal). Mean age was 74.0 ± 8.8 years, and 86% of patients were male; 74% had hypertension, 79% had hyperlipidemia, and 59% had a concomitant aortic aneurysm. There were 45 PAU vessels with >1 CTA (total of 167 CTAs) with a median follow-up of 4.0 years (interquartile range: 2.0-6.2 years). Total vessel diameter increased in size by 0.27 mm/y but did not differ between groups (iliac vs visceral/arch vessels). PAU width and depth also did not significantly change over time, nor did it differ between groups. No branch PAUs caused symptoms, end-organ events, or rupture, nor required intervention due to symptoms and/or progression. Four PAUs spontaneously resolved (2 iliac, 2 other), and 1 iliac PAU progressed to a saccular aneurysm. Conclusions This is one of the largest studies evaluating the natural history of branched PAUs objectively via CTA. Branch PAUs are rare—the prevalence was one-sixth that of aortic PAUs. There was minimal growth noted in a median follow-up of 4 years, and no PAUs required intervention for symptoms or progression. Asymptomatic branch PAUs may be safely observed.

Early-onset scoliosis (EOS) is a heterogeneous group of spinal deformities affecting children under the age of 10 years of which the aetiology, natural history and treatment options vary considerably. In progressive EOS, treatment is based on exhausting conservative measures (casting or bracing) to halt curve progression while allowing for continuous growth of the spine and chest development. Early spinal fusion leads to loss of longitudinal spinal growth and restriction of cardiopulmonary function. In rapidly progressive curves that have failed conservative treatment a range of ‘growth-friendly’ surgical techniques have been developed to control curve deterioration. The indications and characteristics of distraction-based or compression-based methods, growth guidance and promising new techniques are discussed according to aetiology of EOS. Definitive spinal fusion remains reserved for patients ideally towards the end of their spinal growth and for short-segment treatment in congenital scoliosis.

Background and Purpose: Paravertebral arteriovenous shunts (PVAVSs) are rare. Whether the intradural venous system is involved in drainage may lead to differences in clinical characteristics through specific pathophysiological mechanisms. This study aims to comprehensively evaluate the natural history and clinical outcomes of PVAVSs with or without intradural drainage. Methods: Sixty-four consecutive patients with PVAVSs from 2 institutes were retrospectively reviewed. Lesions were classified as type A (n=28) if the intradural veins were involved in drainage; otherwise, they were classified as type B (n=36). The clinical course from initial presentation to the last follow-up was analyzed. Results: The patients with type A shunts were older at presentation (52.5 versus 35.5 years, P P =0.00006). After presentation, the deterioration rates related to gait and sphincter dysfunction were significantly higher in patients with type A than type B shunts (gait dysfunction: 71.8%/y versus 17.0%/y, P =0.0006; sphincter dysfunction: 63.7%/y versus 11.3%/y, P =0.0002). According to the angiogram at the end of the latest treatment, 79% of type A and 75% of type B PVAVSs were completely obliterated. If the lesions were partially obliterated, a significantly higher clinical deterioration rate was observed in patients with type A shunts than those with type B shunts (69.9%/y versus 3.2%/y, P =0.0253). Conclusions: Type A PVAVSs feature rapid progressive neurological deficits; therefore, early clinical intervention is necessary. For complex lesions that cannot be completely obliterated, surgical disconnection of all refluxed radicular veins is suggested.

The most common congenital intraspinal abnormalities presenting to medical attention is either a Chiari malformation with or without associated syringomyelia or caudal anomalies, such as tethered cord and fatty filum terminale. These intraspinal defects are usually diagnosed at birth or in early childhood, but they may also be identified in adult life due to newly presented neurological symptoms. Availability and use of appropriate imaging modalities, such as MRI and regular fetal screening has reduced the incidence of delayed diagnosis of spinal dysraphism and other accompanying congenital systemic anomalies. In view of the risk for neurological complications, prophylactic surgery is often recommended in spinal dysraphism; hence knowledge of various intraspinal abnormalities, their clinical presentation and natural history will allow early diagnosis and treatment in order to prevent neurological deterioration and irreversible morbidity. This review summarizes the embryological aspects and clinical manifestations of intraspinal abnormalities and provides a rational approach for evaluation and management in this group of patients.

Acute traumatic central cord syndrome (ATCCS) is the most common form of spinal cord injury in the United States. Treatment remains controversial, which is a consequence of ATCCS having an inherently different natural history from conventional spinal cord injury, thus requiring a separate classification system. We devised a novel Central Cord Score (CCscore), which both guides treatment and tracks improvement over time with symptoms specific to ATCCS.Medical records of patients with a diagnosis of ATCCS were retrospectively reviewed at a single institution. The CCscore was devised based on signs, symptoms, and imaging findings we believed to be critical in assessing severity of ATCCS. Numeric values were assigned for distal upper extremity motor strength, upper extremity sensation, ambulatory status, magnetic resonance imaging cord signal, and urinary retention.We identified 51 patients with follow-up data; there were 17 cases of mild injury (CCscore 1-5), 23 moderate cases (CCscore 6-10), and 11 severe cases (CCscore 11-15). Patients treated surgically had significantly greater improvement in upper extremity motor scores and total CCscore only up to 3 months. In terms of timing of surgery, patients treated24 hours after injury had significantly improved upper extremity motor scores and overall CCscores at last follow-up of ≥3 months.Based on these data and their alignment with past literature, the CCscore is able to objectively and specifically categorize the severity and outcome of ATCCS, which represents a step forward in the quest to determine the ultimate efficacy and timing of surgery for ATCCS.

Neurosyphilis is a rare but life-threatening complication of syphilis that can develop even decades after the primary infection and can be unrecognized. Seizures and status epilepticus (SE) may represent the first manifestation in a previously undiagnosed syphilitic patient. We present an exemplification case of a new onset refractory status epilepticus caused by neurosyphilis and we reviewed the existing literature. We selected all studies reporting cases of SE in the context both of patients with a known diagnosis of syphilis and as the first manifestation of neurosyphilis. We identified 50 patients, mostly composed of immunocompetent, middle-aged males. Thirty-nine patients (83%) presented a new onset SE. A history of subtle and rapidly progressive mood and/or cognitive impairment suggesting a limbic encephalitis-like presentation was frequently observed. Focal frontal or temporal SE was reported in 26. Brain MRI frequently showed T2/FLAIR hyperintensities widely involving the medial temporal structures and the frontal lobes. This review should increase the clinician’s awareness of neurosyphilis as a possible etiology of a new onset SE of unknown etiology, especially in the context of a “limbic encephalitis”-like clinical presentation. Prompt recognition and treatment for neurosyphilis partially or completely reverse neurologic sequelae, changing the natural history of the disease.

Surgical repair of Truncus arteriosus aims to improve long term survival. A clear understanding of the natural history and achievable surgical outcomes informs surgical decision making with respect to the timing of surgery. We sought to determine if it is ever too late to repair T. arteriosus. Pubmed and Google scholar were searched between January 1st 1966 and July 31st 2021. The proximal similarly model was used to determine the most externally valid natural history and surgical outcome data. The most externally valid data were used to develop a composite survival graph to help clinicians optimize surgical decision making. Four hundred and twenty eight results were retrieved. Five studies representing 938 patients who had repair of T. arteriosus were included for external validity assessment. The resultant composite graph suggests that repair after 5 month of age, may not improve 15 year survival when compared to non-operative care. T. arteriosus repair after 5 months of age may not improve survival. Key words: Pediatric, truncus artriosus, operative, outcomes.

Clear cell meningioma (CCM) is an uncommon histologic subtype of meningioma classified as a WHO grade II tumor and accounting for less than 1% of all meningiomas. Demographically, younger patients are commonly affected without any remarkable gender preference. Moreover, CCM shows a unique anatomical site of involvement. It tends to occur in the cranium than the spine, whereas the basilar skull, posterior fossa, and lumbar spine have been the most frequently affected area. Although most cases present as typical the mass effect by the tumor, CCM exhibits characteristic imaging and histologic patterns. Even though surgical resection is the treatment of choice, recurrence-free survival is the biggest challenge and has been attempting to improve by adjuvant therapy. There is still debate about its management, outcome, and factors defining it. Herein, we aimed to summarize natural history, radiographic characteristics, histological features, treatment strategies to guide the best possible individualized care for the most favorable outcome.

WDR45-related neurodevelopmental disorder (NDD) is a clinically-heterogenous congenital disorder of macroautophagy/autophagy. The natural history of this ultra-orphan disease remains incompletely understood, leading to delays in diagnosis and lack of quantifiable outcome measures. In this cross-sectional study, we model quantitative natural history data for WDR45-related NDD using a standardized analysis of 160 published cases, representing the largest cohort to date. The primary outcome of this study was survival. Age at disease onset, diagnostic delay and geographic distribution were quantified as secondary endpoints. Our tertiary aim was to explore and quantify the spectrum of WDR45-related phenotypes. Survival estimations showed low mortality until 39 years of age. Median age at onset was 10 months, with a median diagnostic delay of 6.2 years. Geographic distribution appeared worldwide with clusters in North America, East Asia, Western Europe and the Middle East. The clinical spectrum was highly variable with a bi-phasic evolution characterized by early-onset developmental and epileptic encephalopathy during childhood followed by a progressive dystonia-parkinsonism syndrome along with cognitive decline during early adulthood. Female individuals showed milder disease severity. The majority of pathogenic WDR45 variants were predicted to result in a loss of WDR45 expression, without clear genotype-phenotype associations. Our results provide clinical and epidemiological data that may facilitate an earlier diagnosis, enable anticipatory guidance and counseling of affected families and provide the foundation for endpoints for future interventional trials. Abbreviations: BPAN: beta-propeller protein-associated neurodegeneration; CNS: central nervous system; DEE: developmental and epileptic encephalopathy; MRI: magnetic resonance imaging; NBIA: neurodegeneration with brain iron accumulation; NDD: neurodevelopmental disorder; NGS: next-generation sequencing; WDR45/WIPI4: WD repeat domain 45

INTRODUCTION Respiratory syncytial virus (RSV) is associated with significant morbidity worldwide, especially among infants. We evaluated the potential impact of prophylactic nirsevimab, a monoclonal antibody, in infants experiencing their first RSV season, and the number of medically-attended lower respiratory tract infection episodes caused by RSV (RSV-MALRTI) in the USA. METHODS We developed an age-structured, dynamic, deterministic compartmental model reflecting RSV natural history, incorporating USA demographic data and an age-specific contact matrix. We assumed either no effect of nirsevimab on transmission (scenario 1) or a 50% reduction of viral shedding (scenario 2). Model outcomes were RSV-MALRTIs, ICD-9 coded in the Marketscan® database by month. We focused on age groups corresponding to the first 2 years of life, during seven RSV seasons (2008-2015). RESULTS Scenario 1 illustrated the direct individual benefit when a universal immunization strategy is applied to all infants. In scenario 2, herd protection was observed across age groups, with 15.5% of all avoided cases due to reduced transmission; the greatest impact was in the youngest age group and a benefit was observed in those aged 65+ years. CONCLUSION These preliminary data suggest that single-dose nirsevimab will benefit infants experiencing their first RSV season, with a potential increase in effectiveness dependent on nirsevimab's mechanism of action.

The evolution of our management armamentarium for inflammatory bowel disease (IBD) has changed the therapeutic goal beyond symptom control and towards altering the disease course. This review article aims to update the natural history of IBD. In the biologic era, the disease phenotype at the time of IBD diagnosis is generally similar to that of historical reports. More than half of patients with IBD achieved disease remission within 5 years after diagnosis. The rates of hospitalization and surgery and the risk of colorectal cancer have been decreasing over time. IBD did not increase the risk of mortality. Factors associated with disease-related complications include young age at diagnosis, extensive anatomical involvement, intestinal complicating behavior, and concurrent primary sclerosing cholangitis, while the introduction of immunomodulators and biologics was associated with better disease outcomes. New evidence supports the favorable impact of modern-day IBD care on the natural history of IBD.

Ewing sarcoma (ES) is the second most common bone malignancy in young patients, with 80% occurring in the first two decades of life. In contrast, extraskeletal ES accounts for approximately 12% of cases and is more common in older patients.[1] The clinical behaviour is aggressive, with a 5-year survival of 70-80% for localized disease, less than 30% for metastatic or early-relapsing disease, and possibly a worse prognosis in adults compared to children.[1,2] ES is defined by FET-ETS family gene fusions. The majority of cases harbour t(11;22)(q24;q12) translocations, corresponding to EWSR1-FLI1 fusion (85%), or t(21;22)(q22;q12) resulting in EWSR1-ERG (10%).[1] Herein we report the case of an FUS-ERG fusion-positive extraskeletal ES, which exhibited an indolent natural history over 25 years without any intervention, diagnosed via endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA) biopsy following progression.

OBJECTIVE: To evaluate the effect of sauna bathing on lower urinary tract symptoms (LUTS) in a Finnish population-based cohort. METHODS: A mail survey was sent to a population-based cohort of 50-, 60-, and 70-year-old men in 1994 followed by repeat questionnaires in 1999 and 2004. The evaluation of ten different types of LUTS was based on Danish Prostatic Symptom Score (DAN-PSS-1). The weekly frequency of sauna bathing was assessed in the first questionnaire and divided into three subgroups (0-1, 2, and ≥3). The prevalence, incidence, and remission rate of each LUTS was assessed based on the initial and follow-up assessments. In addition, the mean DAN-PSS-1 symptoms score, medication for LUTS, and operative treatment were determined at each time-point. Chi-square test, a linear-by-linear test, and binary logistic regression analysis were used to assess statistical significance. RESULTS: The population-based cohort included initially 3,163, men of whom 1,306 (41.3%) responded to all three questionnaire rounds and were included in the analysis. There was no clear association between sauna bathing frequency and prevalence of the nine LUTS, nor with incidence and remission rates. The only exception was feelings of incomplete emptying, with lower prevalence associated with frequent sauna bathing. There were no clear differences in the medications or operations for LUTS by sauna bathing habits. CONCLUSION: Based on our results, sauna bathing does not affect LUTS development or natural history in the long-term. acceptedVersion

BACKGROUND: One of the harshest side effects following anticancer agent treatments is chemotherapy-induced neuropathic pain. After surgical staging, chemotherapy combination of paclitaxel carboplatin could be a choice of therapy for Stage II or more advanced stage of ovarian cancer. Different side effects may appear after the application of paclitaxel. CASE REPORT: Here, we show an uncommon case of paclitaxel-acute pain syndrome (P-APS), and how we deal with such cases according to our experiences. One uncommon side effect is P-APS, which can be treated effectively with the administration of non-steroidal anti-inflammatory drugs, corticosteroid, and supportive therapy. CONCLUSION: One uncommon side effect of Paclitaxel induced neuropathic can be treated effectively with the administration of non-steroidal anti inflammatory drugs, corticosteroid, and supportive therapy.

BackgroundThe natural history of unruptured intracranial aneurysms (UIAs) in Western populations is still debated, especially for those MethodsFrom January 2011 to June 2019, 662 UIAs were followed up by yearly MR angiography. Morphologically stable UIAs were managed conservatively while unstable UIAs were offered treatment. The patients’ clinical and radiological data were analyzed retrospectively.ResultsUIAs were ≤4 mm in 60%, 4.1–7.0 mm in 33%, and >7 mm in 7%. They were located on the anterior circulation in 90% of cases. The mean follow-up duration was 51.32 months for a total of 2831 aneurysm-years. During follow-up, 37 UIAs (5.5%) were treated because of an increase in size, and 8 UIAs were treated because of patient decision. Three aneurysms ruptured during follow-up for an annual risk of rupture of 0.1% (95% CI 0% to 0.24%). No risk factors for rupture were identified. The three ruptured cases made an excellent recovery. During follow-up, annual mortality from unrelated causes was 0.8% (95% CI 0.51% to 1.18%).ConclusionsThis single-center cohort evaluated our watchful waiting policy applied in two-thirds of all incidental UIAs. Morphological change of UIAs during follow-up led to treatment in 5.5% of cases. With such a management paradigm, we found a low rupture rate in these selected UIAs and the mortality was unrelated to aneurysms.

Background Mississippi (MS) has among the highest rates of cervical cancer incidence and mortality in the United States, with disproportionately higher rates among Blacks compared to Whites. Here, we evaluate the prevalence of high‐risk human papillomavirus (HPV) and abnormal cytology in a representative baseline sample from a diverse statewide cohort of individuals attending cervical screening in MS from the STRIDES Study (STudying Risk to Improve DisparitiES in cervical cancer). Methods We included individuals aged 21–65 years undergoing screening at the University of Mississippi Medical Center (UMMC) and the Mississippi State Department of Health (MSDH) from May to November 2018. We calculated age‐specific HPV prevalence, overall and by partial HPV16/18 genotyping, and abnormal cytology by race. Results A total of 6871 individuals (mean age 35.7 years) were included. HPV prevalence was 25.6% and higher in Blacks (28.0%) compared to Whites (22.4%). HPV prevalence was significantly higher in Blacks aged 21–24 years (50.2%) and 30–34 years (30.2%) compared to Whites in the same age groups (32.1% and 20.7%; p < 0.0001, respectively). The prevalence of high‐grade cytologic abnormalities, a cytologic sign of cervical precancer, peaked earlier in Blacks (ages 25–29) compared to Whites (35–39). For comparison, we also analyzed HPV prevalence data from the National Health and Nutrition Examination Survey (NHANES, 2013–2016) and observed similar racial differences in HPV prevalence among women aged 21–24 years. Conclusions Our findings suggest that Blacks undergoing cervical cancer screening in MS have higher prevalence of other high‐risk 12 HPV types at younger ages and experience an earlier peak of high‐grade cytologic abnormalities compared to Whites., We evaluated the age‐specific prevalence of human papillomavirus (HPV) and abnormal cytology in a baseline sample from a large, diverse statewide screening cohort in Mississippi. Overall, HPV prevalence was high (25.6%), and varied by race, with Blacks having significantly higher prevalence of other high‐risk 12 HPV types at younger ages compared to Whites, corresponding to an earlier peak of high‐grade cytologic abnormalities.

Thoracic aortic aneurysms are common. Most thoracic aortic aneurysms are degenerative. However, some are associated with connective tissue disorders, bicuspid aortic valves, or familial/genetic predisposition. Most are asymptomatic, discovered incidentally on imaging. Aortic diameter is the best predictor of the natural history and risk of complications. Treating hypertension and smoking cessation can slow their growth. Surveillance imaging and referral for prophylactic aortic repair based on absolute aneurysm diameter is the primary means to decrease mortality from thoracic aortic aneurysm. We provide a practical evidence-based summary of the pathophysiology, risk factors, associated genetic syndromes, and clinical management of thoracic aortic aneurysms.

Background Understanding the natural history of rare bone and mineral conditions is essential for improving clinical practice and the development of new diagnostics and therapeutics. Recruitment and long-term participation in registries are key challenges for researchers. Methods To understand the user needs, the European Reference Network on Rare Bone Diseases (ERN BOND) and European Patient Advocacy Groups developed and implemented a multinational survey about the patient’s preferred database content and functionality through an iterative consensus process. The survey was disseminated by national and international patient groups and healthcare professionals. The findings were analysed using descriptive statistics and multivariate regression. Results There were 493 eligible responses from 378 adults, 15 children and 100 parents, guardians or carers (PGC) across 22 rare bone and mineral conditions. Osteogenesis imperfecta constituted 53.4% of responses. Contents related to improving treatment and medical services scored the highest and contents about anxiety and socializing scored less highly. Additional content was recommended by 205 respondents. Respondents preferred data entry by their Healthcare Provider (HCP). However, less than 50% of adults received followup from their specialist HCP at least annually and 29% were followed up as needed. Conclusions This survey of individuals, their family, guardians and carers has prioritised the key components for an EU-based rare bone and mineral condition research database. The survey highlights issues around collecting psychosocial impacts as well as measures of HCP trust. The survey demonstrated that using only specialist centre visits for data collection, while preferred by patients, will miss a substantial number of individuals, limiting generalisability. Combined HCP and patient platforms will be required to collect representative and complete natural history data for this patient group.

Nonalcoholic steatohepatitis (NASH) can progress to cirrhosis and its complications, including hepatocellular carcinoma. Given that the majority of patients with NASH are asymptomatic, developing screening strategies to identify those individuals at risk for progressive NASH remains a highly unmet need. Furthermore, noninvasive tests that accurately predict disease progression as part of the natural history of NASH or regression in response to treatment are urgently needed to decrease the reliance on repeat liver biopsies. To date, there are no US Food and Drug Administration (FDA)‐approved medications for NASH that can resolve steatohepatitis and lead to fibrosis regression. The lack of FDA‐approved therapy has led to apathy in diagnosis and referral for specialty care. However, several therapeutic agents are rapidly progressing through the different phases of clinical trials with several already in phase 3 programs. In this review, we provide a summary of recent developments in NASH diagnostics and therapeutics that are likely to shape the future management of this underdiagnosed and undertreated disease., We summarize data on noninvasive tests for nonalcoholic steatohepatitis (NASH) that accurately predict disease severity, progression as part of the natural history, or regression in response to treatment. We provide an update on several NASH therapeutic agents that are rapidly progressing through the different phases of clinical trials.

Sjögren disease increasingly is recognized in pediatric patients. Clinical features, primarily parotitis and sicca symptoms, and results of diagnostic tests may be different from those in adult disease. Adult criteria fail to capture most pediatric patients. Pediatric-specific criteria are urgently needed to define the natural history of the disease, identify risk and prognostic factors, and evaluate the impact of therapeutics and other interventions on disease course in young patients.

Purpose Phenylalanine hydroxylase deficiency, or phenylketonuria (PKU), is a rare autosomal recessive metabolic disorder. Early diagnosis via newborn screening (NBS) and initiation of treatment prevent the development of cognitive impairment and other co-morbidities. The purpose of this study is to describe the natural history of PKU in the United States, including prevalence of co-morbidities and predictors of outcomes. Methods We analyzed data from a self-report survey in the NBS-PKU Connect online registry. We describe the participants' nutrition management strategies, barriers to management, outcomes of bone disorders, skin, and psychological co-morbidities, and the use of special education or other special services. Predictors of outcomes were identified and assessed, including the impact of sex, age, age at diagnosis, blood phenylalanine concentration, use of sapropterin, use of medical food, adherence to prescribed diet, use of low protein modified foods, whether they had ever been off-diet, and use of tyrosine supplementation. Results The 219 respondents included individuals with PKU or hyperphenylalanemia (n = 78), or their caregivers (n = 141). Most (84.3%) started treatment before the age of two weeks. About one-third indicated that they had been off-diet at some point in their lives, and 81.4% reported that they currently adhered to their prescribed diet, with adherence to prescribed diet decreasing with age. Blood phenylalanine concentration was under the recommended threshold of 360 μmol/L for 68.5% of participants. One-quarter of respondents reported psychological co-morbidities, with anxiety and ADD/ADHD being the most common. The incidence of psychological co-morbidities increased with age and with ever having been off diet. Special education or other special services were more likely to be reported by individuals who were diagnosed after one week of age. Skin disorders such as acne and eczema were more common in females than males, and a minority of participants reported bone disorders. Conclusions Despite recommendations to maintain blood phenylalanine concentrations in the therapeutic range throughout life, it is not uncommon for adults with PKU to discontinue dietary management of their disorder. Early diagnosis was associated with reduced need for special education or other special services, and continuous treatment was associated with decreased psychological co-morbidities.

OBJECTIVE Carotid webs (CWs) have increasingly been recognized as a cause of recurrent ischemic stroke. However, the natural history and clinical course of CWs remain unclear. The authors aimed to clarify the prevalence, imaging features, and optimal treatment of CWs in a Japanese cohort study. METHODS A series of 444 consecutive Japanese patients who had undergone CTA of the head and neck between April 2011 and October 2016 was retrospectively reviewed. CW was diagnosed on CT angiograms as a membrane-like intraluminal filling defect along the posterior wall of the carotid bulb or the origin of the internal carotid artery (ICA) on oblique sagittal images and a corresponding thin septum on axial images. RESULTS Two patients with CWs were identified among 132 patients with suspected stroke. The prevalence of CWs among symptomatic patients with suspected stroke was 1.5%. The prevalence of asymptomatic CWs was 2.2% (7 of 312 cases). The CWs were located in the posterior wall of the carotid bulb in 7 patients and just distal to the ICA origin in 2 patients. There were no apparent differences in the location or lesion length between symptomatic and asymptomatic CWs. Four of the 7 asymptomatic CWs remained asymptomatic for at least 2 years of follow-up. Two patients with symptomatic CWs developed recurrent cerebral infarction and transient ischemic attack despite being on a regimen of oral antiplatelet agents, and carotid endarterectomy was performed as radical treatment. Patients with CWs were younger than controls (median age 55 vs 69 years, p = 0.003) and were less frequently male than controls (33% vs 72%, p = 0.025). CW cases showed significantly fewer common atherosclerosis risk factors than the control group (p < 0.05). CONCLUSIONS Although limited to CTA patients, this study reported on the prevalence and common site of CWs, focusing on symptomatic and asymptomatic Japanese patients. Extensive cross-sectional and prospective observational studies are warranted to elucidate the overall prevalence and natural history of CWs.

Purpose Mucolipidosis (ML) II, MLIII alpha/beta, and MLIII gamma are rare autosomal recessive lysosomal storage disorders. Data on the natural course of the diseases are scarce. These data are important for counseling, therapies development, and improvement of outcome. The aim of this study is to gain knowledge on the natural history of ML by obtaining data on survival, symptom onset, presenting symptoms, diagnosis, and pathogenic variants associated with the MLII or MLIII phenotype. Methods A systematic review on all published MLII and MLIII cases between 1968 and August 2019 was performed. Results Three hundred one articles provided data on 843 patients. Median age at diagnosis: 0.7 for MLII and 9.0 years for MLIII. Median survival: 5.0 for MLII and 62.0 years for MLIIIII. Median age of death: 1.8 for MLII and 33.0 years for MLIII. Most frequent causes of death in all ML were pulmonary and/or cardiac complications. Pathogenic variants were described in 388 patients (GNPTAB: 571, GNPTG 179). Conclusion This review provides unique insights into the natural history of MLII and MLIII, with a clear genotype–phenotype correlation with the most frequent pathogenic variant c.3503_3504del in MLII and in MLIII alpha/beta c.22A>G for GNPTAB. All pathogenic GNPTG variants resulted in MLIII gamma.

Since the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide, there is still limited knowledge about this condition and its natural history. Children have been relatively spared during COVID-19 pandemic but a novel syndrome known as multisystem inflammatory syndrome (MIS-C) has emerged, following a SARS-CoV-2 infection in children and adolescents. This syndrome can lead to shock and multiple organ failure requiring intensive care. Although COVID-19 clinical research focuses on respiratory symptoms, extrapulmonary involvement such as gastrointestinal (GI) and hepatic manifestations should also be considered. In fact, GI and hepatic involvement play an important role among the most common presenting symptoms of both pediatric and adult COVID-19 and MIS-C. This involvement can not only be one of the most common presenting clinical features but also one of the sequelae of these syndromes. Abdominal ultrasonography monitoring could be very useful to identify a potential involvement of the GI tract and liver. Moreover, long-term follow-up is needed and would be essential to define the long-term outcomes of these patients.

Purpose: To compare the tumor growth kinetics between sporadic clear cell renal cell carcinoma (ccRCC) and Von Hippel-Lindau disease-associated renal cell carcinoma (VHL-associated RCC). To analyze predictive markers for the growth rate of these two types of RCC.Methods: The clinical data of patients with renal tumors who received active surveillance were collected retrospectively. Immunohistochemical staining was utilized to analyze the expression levels of VHL, PBRM1, H3K36me3, and BAP1 in the postoperative specimens.Results: The age of the VHL group was significantly younger than that of the sporadic group (PConclusion: Sporadic ccRCC grew faster than VHL-associated RCC. High histologic grade, low VHL expression and negative PBRM1 expression were predictors of faster growth in sporadic ccRCC. A large initial MTD was a predictor of faster growth for VHL-associated RCC.