Natural History Research Articles

The incidence of surgical intervention following a suspected scaphoid fracture.

The underlying natural history of suspected scaphoid fractures (SSFs) is unclear and assumed poor. There is an urgent requirement to develop the literature around SSFs to quantify the actual prevalence of intervention following SSF. Defining the risk of intervention following SSF may influence the need for widespread surveillance and screening of SSF injuries, and could influence medicolegal actions around missed scaphoid fractures. Data on SSF were retrospectively gathered from virtual fracture clinics (VFCs) across a large Scottish Health Board over a four-year period, from 1 January 2018 to 31 December 2021. The Bluespier Electronic Patient Record System identified any surgical procedure being undertaken in relation to a scaphoid injury over the same time period. Isolating patients who underwent surgical intervention for SSF was performed by cross-referencing the unique patient Community Health Index number for patients who underwent these scaphoid procedures with those seen at VFCs for SSF over this four-year period. In total, 1,739 patients were identified as having had a SSF. Five patients (0.28%) underwent early open reduction and internal fixation (ORIF). One patient (0.06%) developed a nonunion and underwent ORIF with bone grafting. All six patients undergoing surgery were male (p = 0.005). The overall rate of intervention following a SSF was 0.35%. The early intervention rate in those undergoing primary MRI was one (0.36%), compared with three in those without (0.27%) (p > 0.576). Surgical intervention was rare following a SSF and was not required in females. A primary MRI policy did not appear to be associated with any change in primary or secondary intervention. These data are the first and largest in recent literature to quantify the prevalence of surgical intervention following a SSF, and may be used to guide surveillance and screening pathways as well as define medicolegal risk involved in missing a true fracture in SSFs.

"How Urgent Is This Rotator Cuff Surgery, Doctor?": Commentary on an article by Bettina Hochreiter, MD, et al.: "Natural History of Quantitative Fatty Infiltration and 3D Muscle Volume After Nonoperative Treatment of Symptomatic Rotator Cuff Tears. A Prospective MRI Study of 79 Shoulders".

"How Urgent Is This Rotator Cuff Surgery, Doctor?": Commentary on an article by Bettina Hochreiter, MD, et al.: "Natural History of Quantitative Fatty Infiltration and 3D Muscle Volume After Nonoperative Treatment of Symptomatic Rotator Cuff Tears. A Prospective MRI Study of 79 Shoulders".

Pathway for Development and Validation of Multi-domain Endpoints for Amyloid Light Chain (AL) Amyloidosis.

Immunoglobin light chain (AL) amyloidosis is a rare disease in which a plasma cell dyscrasia leads to deposition of insoluble amyloid fibrils in multiple organs. To facilitate development of new therapies for this heterogenous disease, a public-private partnership was formed between the nonprofit Amyloidosis Research Consortium and the US Food and Drug Administration Center for Drug Evaluation and Research. In 2020, the Amyloidosis Forum launched an initiative to identify clinical trial endpoints and analytic strategies across affected organ systems and life impacts via specialized working groups. This review summarizes the proceedings of the Statistical Group and proposes a pathway for development and validation of multi-domain endpoints (MDEs) for potential use in AL amyloidosis clinical trials. Specifically, drawing on candidate domain-specific endpoints recommended by each organ-specific working group, different approaches to constructing MDEs were considered. Future studies were identified to assess the validity, meaningfulness and performance of MDEs through use of natural history and clinical trial data. Ultimately, for drug development, the context of use in a regulatory evaluation, the specific patient population, and the investigational therapeutic mechanism should drive selection of appropriate endpoints. MDEs for AL amyloidosis, once developed and validated, will provide important options for advancing patient-focused drug development in this multi-system disease.

The smallest worthwhile effect on pain intensity of exercise therapy for people with chronic low back pain: a discrete choice experiment study.

OBJECTIVE: To identify the smallest worthwhile effect (SWE) of exercise therapy for people with non-specific chronic low back pain (CLBP). DESIGN: Discrete choice experiment. METHODS: The SWE was estimated as the lowest reduction in pain that participants would consider exercising worthwhile, compared to not exercising i.e., effects due to natural history and other components (e.g., regression to the mean). We recruited English-speaking adults in Australia with non-specific CLBP to our online survey via email obtained from a registry of previous participants and advertisements on social media. We used discrete choice experiment to estimate the SWE of exercise compared to no exercise for pain intensity. We analysed the discrete choice experiment using a mixed logit model, and mitigated hypothetical bias through certainty calibration, with sensitivity analyses performed with different certainty calibration thresholds. RESULTS: Two-hundred and thirteen participants completed the survey. The mean age (±SD) was 50.7±16.5, median (IQR) pain duration 10 years (5-20), and mean pain intensity (±SD) was 5.8±2.3 on a 0-10 numerical rating scale. For people with CLBP the SWE of exercise was a between-group reduction in pain of 20%, compared to no exercise. In the sensitivity analyses, the SWE varied with different levels of certainty calibration; from 0% without certainty calibration to 60% with more extreme certainty calibration. CONCLUSION: This patient-informed threshold of clinical importance could guide the interpretation of findings from randomised trials and meta-analyses of exercise therapy compared to no exercise.

Vascular Ehlers-Danlos Syndrome: A Comprehensive Natural History Study in a Dutch National Cohort of 142 Patients.

Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder with a high risk for arterial, bowel, and uterine rupture, caused by heterozygous pathogenic variants in COL3A1. The aim of this cohort study is to provide further insights into the natural history of vEDS and describe genotype-phenotype correlations in a Dutch multicenter cohort to optimize patient care and increase awareness of the disease. Individuals with vEDS throughout the Netherlands were included. The phenotype was charted by retrospective analysis of molecular and clinical data, combined with a one-time physical examination. A total of 142 individuals (50% female) participated the study, including 46 index patients (32%). The overall median age at genetic diagnosis was 41.0 years. More than half of the index patients (54.3%) and relatives (53.1%) had a physical appearance highly suggestive of vEDS. In these individuals, major events were not more frequent (P=0.90), but occurred at a younger age (P=0.01). A major event occurred more often and at a younger age in men compared with women (P<0.001 and P=0.004, respectively). Aortic aneurysms (P=0.003) and pneumothoraces (P=0.029) were more frequent in men. Aortic dissection was more frequent in individuals with a COL3A1 variant in the first quarter of the collagen helical domain (P=0.03). Male sex, type and location of the COL3A1 variant, and physical appearance highly suggestive of vEDS are risk factors for the occurrence and/or early age of onset of major events. This national multicenter cohort study of Dutch individuals with vEDS provides a valuable basis for improving guidelines for the diagnosing, follow-up, and treatment of individuals with vEDS.

Reviewing the impact of obesity on inflammatory bowel disease and considerations for optimizing management.

This review examines the complex relationship between obesity and inflammatory bowel disease (IBD), encompassing their potentially shared pathogenesis, the impact of obesity on the natural history and treatment outcomes of IBD, and the management of obesity in the patient with IBD. Obesity represents a state of chronic inflammation that may not only contribute to IBD pathogenesis, but also influence disease progression, complications, and response to treatment. Increased visceral adiposity may carry negative prognostic implications for disease and treatment-specific outcomes. Antiobesity medications, endoscopic bariatric therapies, and even bariatric surgery may be effective and well tolerated in selected patients with IBD. The intersection of obesity and IBD presents a significant clinical challenge, with obesity influencing the natural history of IBD and potentially affecting treatment efficacy. As obesity prevalence among IBD patients rises, a tailored approach to management is crucial, taking into account the individualized risks and benefits of various treatment strategies, including lifestyle interventions, pharmacotherapy, endoscopic procedures, and bariatric surgery.

Clonal expansion in normal tissues.

Cancer originates from a single ancestral cell that acquires a driver mutation, which confers a growth or survival advantage, followed by the acquisition of additional driver mutations by descendant cells. Recently, it has become evident that somatic cell mutations accumulate in normal tissues with aging and exposure to environmental factors, such as alcohol, smoking, and UV rays, increases the mutation rate. Clones harboring driver mutations expand with age, leading to tissue remodeling. Lineage analysis of myeloproliferative neoplasms and der(1;16)-positive breast cancer revealed that driver mutations were acquired early in our lives and that the development of cancer takes decades, unveiling the previously unknown early process of cancer development. Evidence that clonal hematopoiesis affects various diseases, including nonneoplastic diseases, highlights the potential role of the identification and functional analysis of mutated clones in unraveling unknown pathologies. In this review, we summarize the recent updates on clonal expansion in normal tissues and the natural history of cancer revealed through lineage analysis of noncancerous and cancerous tissues.

The natural history of celiac artery aneurysms.

The goal of this study was to document the natural history of celiac artery aneurysms (CAAs). Celiac artery aneurysms are rare. Existing literature is skewed towards outcomes after intervention of large, symptomatic aneurysms but the behavior of untreated CAAs is poorly understood. This is a single institution, retrospective analysis of patients with CAA diagnosed by CT imaging (2015-2019) identified through an institutional radiology database. Radiologic, demographic, and follow-up data were analyzed. The primary endpoint was the mean growth rate of CAAs. Of the 76 patients included, 86.8% were men with a mean age at presentation of 69.8years. The mean CAA diameter on index imaging was 15.4 +/- 3.8mm (range, 7-30mm). All were classified as true aneurysms and 76.3% were saccular. All patients had clinical follow-up with mean follow-up 31.2months +/- 21.6months. No patient developed symptoms or rupture. The mean radiological follow-up among 45 patients was 25.2 +/- 16.8months. Over this period, 16 CAAs (35.6%) enlarged, while 29 (64.4%) remained stable. One patient (1.3%) underwent intervention for increasing size in the setting of a chronic dissection. On multivariate analysis, age <70 was significantly associated with increased risk of aneurysm growth. In this institutional review of patients with CAAs, the majority of aneurysms remained stable in size, with no patients developing symptoms or rupture over clinical follow-up. Given the observed benign behavior of these aneurysms, guidelines that suggest conservative management of CAAs less than 2cm seems appropriate.

SWOT analysis of Ecotourism development in Sembilang National Park, Banyuasin Regency, South Sumatra, Indonesia

Tourism is one of the dynamic industrial activities for a country's income. Tourism can take the form of ecotourism with potential factors for nature conservation and development. Ecotourism is a form of tourism that is primarily inspired by the natural history of an area, including the area's indigenous culture. Effective sustainable ecotourism management must use strategic planning. Strategic planning can use the SWOT matrix. In general, the strengths of Sembilang National Park are the uniqueness of migratory birds from Siberia that do not exist anywhere else and the presence of exotic animal habitats. The weakness of Sembilang National Park is that transportation is still dominated by waterways and there is a lack of clean water sources. The opportunities for Sembilang TN include financial assistance and international recognition. Meanwhile, the threat to Sembilang National Park is weather conditions which greatly affect waterways. From the weighting results, it is found that the position of Sembilang TN is on the X axis with a value of 9. So it can be concluded that Sembilang TN is at a positive point on the The position of the Sembilang National Park development strategy is in Quadrant I, namely the strategy of utilizing all strengths to seize and exploit maximum opportunities.

Precirrhotic Primary Biliary Cholangitis with Portal Hypertension: Bile Duct Injury Correlate.

: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. : This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. : Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. : Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Protocol on establishing a national disease registry-Swiss Pediatric Inflammatory Brain Disease Registry.

Pediatric-onset inflammatory brain diseases are a group of potentially life-threatening central nervous system disorders. Overall, pediatric-onset inflammatory brain diseases are rare and therefore difficult to study. Patient registries are well suited to study the natural history of (rare) diseases and have markedly advanced the knowledge on pediatric-onset inflammatory brain diseases in other countries. Following their example, we established a national pediatric-onset inflammatory brain disease registry in Switzerland (Swiss-Ped-IBrainD). The Registry aims to describe epidemiology, demographics, diagnostics, management, and treatment, since these areas remain understudied in Switzerland. Additionally, we want to promote research by fostering the knowledge exchange between study centers and setting up studies such as national quality of life surveys. We further aim to facilitate the access to national and international studies for patients with a pediatric-onset inflammatory brain disease living and/or treated in Switzerland. The Swiss-Ped-IBrainD is a multicentric, population-based, observational cohort study (IRB number: 2019-00377) collaborating with 11 neuropediatric centers in Switzerland. Patient screening, information and recruitment is mainly conducted by the local principal investigators. The data collection is organized centrally by the Executive Office of the registry. The collected data is purely observational. Medical records are the primary data source. All patients who have been diagnosed with a pediatric-onset inflammatory brain disease since 2005 are eligible. We aim to include all pediatric-onset inflammatory brain disease patients living and/or treated in Switzerland who meet the inclusion criteria. Considering existing literature and our single-center experience we anticipate 300-400 eligible patients. Currently, all 11 neuropediatric centers have been initiated and are recruiting. As of the first of May 2023, we have identified 275 eligible participants and obtained informed consent from 101 patients and/or families. None of the informed patients and/or families have refused participation.

Corneal neuropathic pain: a review to inform clinical practice

AbstractCorneal neuropathic pain (CNP) is a poorly defined disease entity characterised by an aberrant pain response to normally non-painful stimuli and categorised into having peripheral and central mechanisms, with the former responding to instillation of topical anaesthetic. CNP is a challenging condition to diagnose due to numerous aetiologies, an absence of clinical signs and ancillary tests (in vivo confocal microscopy and esthesiometry), lacking the ability to confirm the diagnosis and having limited availability. Symptomatology maybe mirrored by severe and chronic forms of dry eye disease (DED), often leading to misdiagnosis and inadequate treatment. In practice, patients with suspected CNP can be assessed with questionnaires to elicit symptoms. A thorough ocular assessment is also performed to exclude any co-existent ocular conditions. A medical and mental health history should be sought due to associations with autoimmune disease, chronic pain syndromes, anxiety and depression. Management begins with communicating to the patient the nature of their condition. Ophthalmologists can prescribe topical therapies such as autologous serum eyedrops to optimise the ocular surface and promote neural regeneration. However, a multi-disciplinary treatment approach is often required, including mental health support, particularly when there are central mechanisms. General practitioners, pain specialists, neurologists and psychologists may be needed to assist with oral and behavioural therapies. Less data is available to support the safety and efficacy of adjuvant and surgical therapies and the long-term natural history remains to be determined. Hence clinical trials and registry studies are urgently needed to fill these data gaps with the aim to improve patient care.

Infected pancreatic necrosis-Current trends in management.

Acute necrotizing pancreatitis is a common gastrointestinal disease requiring hospitalization and multiple interventions resulting in higher morbidity and mortality. Development of infection in such necrotic tissue is one of the sentinel events in natural history of necrotizing pancreatitis. Infected necrosis develops in around 1/3rd of patients with necrotizing pancreatitis resulting in higher mortality. So, timely diagnosis of infected necrosis using clinical, laboratory and radiological parameters is of utmost importance. Though initial conservative management with antibiotics and organ support system is effective in some patients, amajority of patients still requires drainage of the collection by various modalities. Mode of drainage of infected pancreatic necrosis depends on various factors such as the clinical status of the patient, location and characteristics of collection and availability of the expertise and includes endoscopic, percutaneous and minimally invasive or open surgical approaches. Endoscopic drainage has proved to be a game changer in the management of infected pancreatic necrosis in the last decade with rapid evolution in procedure techniques, development of novel metal stent and dedicated necrosectomy devices for better clinical outcome. Despite widespread adoption of endoscopic transluminal drainage of pancreatic necrosis with excellent clinical outcomes, peripheral collections are still not amenable for endoscopic drainage and in such scenario, the role of percutaneous catheter drainage or minimally invasive surgical necrosectomy cannot be understated. In a nutshell, the management of patients with infected pancreatic necrosis involves a multi-disciplinary team including a gastroenterologist, an intensivist, an interventional radiologist and a surgeon for optimum clinical outcomes.

New records of earthworms (Clitellata: Oligochaeta) from Georgia, USA, including eight new state records

We present here new county records for 13 counties within Georgia, USA from the collections of the Georgia Museum of Natural History and the authors. These include four families, eight genera, and 23 species. Of these, eight species are new state records: Amynthas carnosus (Goto &amp; Hatai, 1899); Aporrectodea longa (Ude, 1885); Bimastos parvus (Eisen, 1874); Diplocardia deborahae Damoff &amp; Reynolds, 2017; Diplocardia gatesi Murchie, 1965; Diplocardia michaelseni Eisen, 1899; Metaphire hilgendorfi (Michaelsen, 1892); and Murchieona minuscula (Rosa, 1906). These findings are presented alongside an updated checklist for Middle Georgia building on data compiled by Reynolds (2015) to create a practical record for the region.

Exploring a Scientific Research Station from a Bygone Era: Historical Archaeology at Orr’s Camp, Santa Rosa Island (Wimaɬ), Alta California

ABSTRACT The northwest coast of Wimaɬ (Santa Rosa Island) has long been a focus of archaeological research, including former Santa Barbara Museum of Natural History archaeologist, geologist, and paleontologist Phil Orr's work from the 1940s–1960s. Orr pioneered the use of radiocarbon dating on the California Channel Islands, built extensive archaeological collections, and constructed a detailed cultural sequence. Here, we discuss the history and status of Orr's island research camp, archaeological site CA-SRI-766H, describing monitoring and erosion of the site during the past several decades. Two radiocarbon dates obtained from adjacent CA-SRI-7 (Orr's Camp shell midden) document Island Chumash occupation of the site between ∼2820–1160 cal BP, helping place the area into broader regional context. Revisiting the historical documents and physical remains of past research can help understand the evolution of archaeological practice, evaluate outdated procedures of conducting research without tribal consultation and consent, and promote a more inclusive future of the discipline.

Hidden treasures—historical specimens from the late blight pandemic discovered in the Herbarium of the State Museum of Natural History Karlsruhe

Hidden treasures—historical specimens from the late blight pandemic discovered in the Herbarium of the State Museum of Natural History Karlsruhe

Late Adverse Effects after Treatment for Childhood Acute Leukemia

The aim of this review is to raise awareness and knowledge among healthcare professionals and policymakers about late adverse effects in survivors of childhood leukemia. With contemporary treatment, over 90% of children with acute lymphoblastic leukemia (ALL) and over 60% with acute myeloid leukemia (AML) are cured. Large cohort studies demonstrate that 20% of ALL and most AML survivors have at least one chronic health condition by 20-25 years after diagnosis. These are life-changing or threatening in some survivors and contribute to increased premature mortality. We describe the frequency, causes, clinical features, and natural history of the most frequent and severe late adverse effects in childhood leukemia survivors, including subsequent malignant neoplasms, metabolic toxicity, gonadotoxicity and impaired fertility, endocrinopathy and growth disturbances, bone toxicity, central and peripheral neurotoxicity, cardiotoxicity, psychosocial late effects, accelerated ageing and late mortality. The wide range of late effects in survivors of haemopoietic stem cell transplant is highlighted. Recent developments informing the approach to long-term survivorship care are discussed, including electronic personalized patient-specific treatment summaries and care plans such as the Survivor Passport (SurPass), surveillance guidelines and models of care. The importance of ongoing vigilance is stressed given the increasing use of novel targeted drugs with limited experience of long-term outcomes. Conclusion. It is vital to raise awareness of the existence and severity of late effects of childhood leukemia therapy among parents, patients, health professionals, and policymakers. Structured long-term surveillance recommendations are necessary to standardize follow-up care.

The formation of tourists’ pro-environmental behavior in natural history museum scene: A configuration analysis based on motivation–opportunity–ability theory

Tourists’ pro-environmental behavior is crucial for the sustainable growth of the tourism sector. While existing studies mainly examine the direct effects of individual factors on such behavior, there is a gap in understanding the comprehensive antecedent system that drives it. In this study, grounded in MOA theory and focused on a natural history museum scene, we developed a comprehensive framework to analyze the antecedent system of tourists’ pro-environmental behavior. We argue that the formation of this behavior in museum tourists is not a single element but a combination of three critical factors: motivation, opportunity, and ability (MOA). Using the fsQCA method to analyze data from 276 tourists, we identified four distinct pathways that promote pro-environmental behavior in museum tourists: MOA equilibrium type, motivation–ability-oriented type, motivation–opportunity-oriented type, and ability-oriented type. This study enhances our understanding of the complex interactions among various factors influencing tourists’ pro-environmental behavior and provides insightful implications for the practice of museum tourism.

Issues, Challenges and Opportunities for Economic Evaluations of Orphan Drugs in Rare Diseases: An Umbrella Review.

There are significant challenges when obtaining clinical and economic evidence for health technology assessments of rare diseases. Many of them have been highlighted in previous systematic reviews but they have not been summarised in a comprehensive manner. For all stakeholders working with rare diseases, it is important to be aware and understand these issues. The objective of this review is to identify the main challenges for the economic evaluation of orphan drugs in rare diseases. An umbrella review of systematic reviews of economic studies concerned with orphan and ultra-orphan drugs was conducted. Studies that were not systematic reviews, or on advanced therapeutic medicinal products, personalised medicines or other interventions that were not considered orphan drugs were excluded. The database searches included publications from 2010 to 2023, and were conducted in MEDLINE, EMBASE and the Cochrane library using filters for systematic reviews, and economic evaluations and models. These filters were combined with search terms for rare diseases and orphan drugs. A hand search supplemented the literature searches. The findings were reported by a compliant Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. Two hundred and eighty-two records were identified from the literature searches, of which 64 were duplicates, whereas five reviews were identified from the hand search. A total of 36 reviews were included after screening against inclusion/exclusion criteria, 35 from literature searches and one from hand searching. Of those studies 1, 27 and 8 were low, moderate and high quality, respectively. The reviews highlight the scarcity of evidence for health economic parameters, for example, clinical effectiveness, costs, quality of life and the natural history of disease. Health economic evaluations such as cost-effectiveness and budget-impact analyses were scarce, and generally low-to-moderate quality. The causes were limited health economic parameters, together with publications bias, especially for cost-effectiveness analyses. The results highlighted issues around a considerable paucity of evidence for economic evaluations and few cost-effectiveness analyses, supporting the notion that a paucity of evidence makes economic evaluations of rare diseases more challenging compared with more prevalent diseases. Furthermore, we provide recommendations for more sustainable approaches in economic evaluations of rare diseases.

How to Curate and Digitize Bryozoa: Experiences at the Santa Barbara Museum of Natural History

We report on curation and digitization experiences of a large collection of Bryozoa (&gt;19,759 of estimated 38,000 lots digitized, &gt;1,000 type lots). Storage of one to two histology slides in capped glass vials and larger series in twenty-five-slot histology boxes is optimal. Bulk dry material is stored in acid-free containers (cardboard, plastic). Fluid specimens are stored in 70 percent ethanol, with small specimens housed in 20 ml scintillation vials with conical polypropylene lined screw caps. Digitizing is most effective by georeferencing immediately. Unidentified material should at least be roughly identified (family, genus) to encourage loans and ensuing expert identification. Taxonomy and nomenclature are challenging and require an experienced taxonomist. Approaches to specimen counts are discussed.