Treatable Cause Research Articles

PS-BPC02-2: CLINICAL IMPACTS OF ENDOTHELIUM-DEPENDENT FLOW-MEDIATED VASODILATION ASSESSMENT ON PRIMARY ALDOSTERONISM

Objective: Primary aldosteronism (PA) is defined as autonomous aldosterone production from the adrenal glands and represents the most common and treatable cause of hypertension. Also, it is well known that the incidence of cardiovascular morbidity is higher among patients with PA than among those with essential hypertension (EH). Histologically, PA is divided into two major subtypes, aldosterone-producing adenoma (APA) and bilateral idiopathic hyperplasia (IHA). However, the nature of vascular function in PA patients remains to be determined. The aim of this study was to determine the vascular function and investigate the implications of vascular function assessments in the patients with PA. Design and Method: All patients were diagnosed with PA according to the guidelines of the Japan Endocrine Society. Flow-mediated dilation (FMD), as an index of endothelial function, and cardio-ankle vascular index (CAVI), as an index of arterial stiffness, were retrospectively compared between 42 patients with APA, 37 patients with IHA, and 42 patients with EH. These values were also compared with background factors, KCNJ5 mutation and clinical outcome in terms of blood pressure reduction after adrenalectomy in the APA group. Results: No differences were found among the three groups (APA, IHA and EH) with regard to age, sex, duration of hypertension, body mass index, blood pressure, renal function and hemoglobin A1c. FMD was significantly lower in the APA group (4.8 ± 2.1%) and IHA group (4.1 ± 1.9%) than in the EH group (5.7 ± 2.1%). CAVI did not differ significantly among APA, IHA and EH groups (7.9 ± 1.3, 7.8 ± 1.0, 7.8 ± 1.1, respectively). Although no significant correlations were seen between FMD and background factors (i.e. age, body mass index, renal function, glucose and lipid metabolic parameters, and hormonal data) in the IHA group, FMD correlated negatively with BMI and plasma aldosterone concentration in the APA group (rs = -0.313, rs = -0.342, respectively). No significant difference in FMD (4.8 ± 1.4%, 4.5 ± 2.1%, respectively) or CAVI (8.1 ± 1.8, 8.0 ± 1.1, respectively) was seen between the KCNJ5-mutant group and the wild-type group. A cut-off FMD of 4.3% was selected for complete clinical success after adrenalectomy, offering 78% sensitivity and 80% specificity. Conclusions: Patients with PA displayed impaired endothelial function. Complete clinical success after adrenalectomy was associated with preserved endothelial function. This study provides a better understanding of FMD assessment in patients with PA.

Chapter 4 - Leigh syndrome

Leigh syndrome, or subacute necrotizing encephalomyelopathy, was initially recognized as a neuropathological entity in 1951. Bilateral symmetrical lesions, typically extending from the basal ganglia and thalamus through brainstem structures to the posterior columns of the spinal cord, are characterized microscopically by capillary proliferation, gliosis, severe neuronal loss, and relative preservation of astrocytes. Leigh syndrome is a pan-ethnic disorder usually with onset in infancy or early childhood, but late-onset forms occur, including in adult life. Over the last six decades it has emerged that this complex neurodegenerative disorder encompasses more than 100 separate monogenic disorders associated with enormous clinical and biochemical heterogeneity. This chapter discusses clinical, biochemical and neuropathological aspects of the disorder, and postulated pathomechanisms. Known genetic causes, including defects of 16 mitochondrial DNA (mtDNA) genes and approaching 100 nuclear genes, are categorized into disorders of subunits and assembly factors of the five oxidative phosphorylation enzymes, disorders of pyruvate metabolism and vitamin and cofactor transport and metabolism, disorders of mtDNA maintenance, and defects of mitochondrial gene expression, protein quality control, lipid remodeling, dynamics, and toxicity. An approach to diagnosis is presented, together with known treatable causes and an overview of current supportive management options and emerging therapies on the horizon.

A Rare Case of Disseminated Histoplasmosis Presenting with Hemophagocytic Lymphohistiocytosis

ABSTRACT Hemophagocytic lymphohistiocytosis (HLH) encompasses a wide spectrum of causes, characterized by excessive immune system activation and release of a cascade of inflammatory markers. HLH can be familial or primary and secondary, secondary being more common. Secondary HLH holds primary concern as it involves treatable causes and hence timely diagnosis and appropriate treatment are of utmost importance in patient care. Our case report is of a 34-year-old immunocompetent male with a history of fever of 5 days duration along with breathlessness, myalgia, and cough at the onset, but the symptoms kept deteriorating over a period of 1.5 months. Due to the wide range of clinical presentations and overlap of symptoms, an array of differentials was considered, however prioritizing an infectious cause led to our final diagnosis in this case. The patient succumbed to the disease.

Spectrum of Growth Hormone Disorders in Children: A Case Series of 5 Cases

Growth Hormone Deficiency (GHD) is one of the most important treatable endocrine causes of short stature. A problem anywhere in the Growth Hormone (GH) - Insulin-Like Growth Factor-1 (IGF-1) axis can lead to short stature. Childhood GH deficiency can be congenital, acquired, or idiopathic. Hereby, the authors present a case series consisting of five cases of short stature, aimed to provide an overview of the spectrum of GH-related disorders. All five patients presented to the Paediatric Endocrinology Outpatient Department of a tertiary care Institute with complaints of not gaining height. The patients in present case series had significant short stature (Z score for height <-3 SD (Standard Deviation) in each case). These patients were suspected of having GH deficiency based on clinical presentation and investigations. After a proper diagnostic work-up and GH stimulation tests, cases 1 to 4 were found to have GH deficiency. The 5th case was suspected of having Laron Syndrome based on high GH levels and low IGF-1. There were subtle differences in the spectrum of GH deficiency. The 1st case had Multiple Pituitary Hormone Deficiency (MPHD). Cases 2 to 4 had Isolated Growth Hormone Deficiency (IGHD). Case 2 had findings of pituitary stalk interruption on brain imaging. We found a genetic association in the 3rd case, while the 4th case had almost normal brain imaging. Cases 1 to 4 received GH therapy, and all showed appreciable height gain. These subtle differences can sometimes make the diagnosis difficult, and often a different approach to treatment is required.

Clinicoetiological Profile of Cerebral Venous Sinus Thrombosis Patients at a Tertiary Care Center

Background: Cerebral venous sinus thrombosis (CVST) accounts for 10%–20% of strokes in young persons. In India, CVST accounts for around 30% of all strokes. The majority of CVSTs are caused by procoagulant circumstances, with pregnancy and early puerperium being well-established risk factors. The study aimed to look into the clinical profile, radiological characteristics, etiological variables, and outcome of CVST in venous stroke patients admitted to a tertiary care facility. Methods: We included individuals between the ages of 18 and 75 years who had a cerebral venous thrombosis (CVT) diagnosis confirmed by magnetic resonance imaging (MRI) + magnetic resonance venography computed tomography (CT) plus CT venography. The research included all individuals suspected of having CVST with or without particular neurological deficits and a confirmed imaging diagnosis. Patients were removed in situations of ambiguous neuroimaging, arterial strokes, space-occupying lesions, metabolic encephalopathy, and patient reluctance to participate. Results: This study included 82 patients, 21 (25.6%) males and 61 (74.4%) of whom were females. The most common presenting symptom was headache (79.2%), followed by vomiting (54.8%) and abnormal sensorium (35.3%). In this study, 34/82 (41.4%) patients had evident clinical triggers and were classified as induced CVT. Para infectious disease was recognized as a risk factor for CVT in 13/34 (38.2%) patients. A prothrombotic conditions could be established in 48 (58.5%) of these patients. Conclusion: CVST is a treatable and reversible cause of stroke in adolescents. The clinical presentation varies greatly, and symptoms may appear gradually over weeks or months. Although it is still an uncommon cause of headache and stroke, MRI has allowed for early detection.

Dynamics of mortality of the population of the Krasnoyarsk Territory from preventable and treatable causes

INTRODUCTION: In the context of the development of measures aimed at reducing the mortality of the population, it is BACKGROUND: In developing measures to reduce mortality in the population, it is important not to directly analyze the mortality of the population but to study its manageable components attributed to preventable and treatable deaths.
 AIM: To analyze trends in mortality due to preventable and treatable causes in the population of the Krasnoyarsk Territory.
 MATERIALS AND METHODS: A retrospective observational study was done using data from primary mortality databases of urban districts and municipal districts of the Krasnoyarsk Territory for the period 19992020, as well as data from the Office of the Federal State Statistics Service for the Krasnoyarsk Territory, the Republic of Khakassia and the Republic of Tyva on the population. The study examines how f preventable and curable causes contribute to the mortality structure of the population of the Krasnoyarsk Territory for the period 19992020.
 RESULTS: Over the period 19992019, the mortality rate of the population decreased by 13.4% (from 1413.2 to 1224.2 cases per 100,000 people), but in 2020 mortality rate increased by 16.7%, becoming slightly higher than its 1999 level. Analysis of the structure of mortality from leading causes of mortality showed a systematic increase in the proportion of unavoidable and incurable causes from 1999 to 2020.
 CONCLUSION: The results of this study can serve as a guideline for determining the reserves for reducing the mortality of the population and for determining promising directions for reducing it at the regional level. However, to achieve this, a more detailed analysis of the mortality structure of the population is required in order to identify groups of headings, headings or individual causes of death, for which there is a high proportion of preventable and curable mortality.

Rare case of hereditary spherocytosis with rheumatic mitral stenosis

A rare case of hereditary spherocytosis (HS) and rheumatic mitral stenosis coexisting in a patient having severe stenosis, atrial fibrillation, and symptoms of the left ventricular dysfunction, along with hemolytic anemia attributed to HS. We present the case of a 58-year-old lady who presented to the emergency department with complaints of increasing shortness of breath for the past week. She was examined to have atrial fibrillation with a fast ventricular rate. On investigations, she was found to have severe rheumatic mitral stenosis with evidence of hemolytic anemia. Further, evaluation of the cause of her anemia revealed HS. This case highlights the importance of the evaluation of anemia in patients with valvular heart diseases. If a treatable cause is found, anemia can be treated to reduce the cardiac burden. Abstract: Background- A rare case of Hereditary Spherocytosis and Rheumatic Mitral Stenosis coexisting in a patient having severe stenosis, atrial fibrillation and symptoms of left ventricular function, along with hemolytic anemia attributed to HS. . Case presentation- We present a case of a 58-year-old lady presented to the Emergency Department with complaints of increasing shortness of breath in the last one week. She was examined to have Atrial Fibrillation with a Fast Ventricular Rate. Upon Investigations, she was found to have severe Rheumatic Mitral Stenosis with evidence of Hemolytic anemia. Further evaluation of the cause of her anemia revealed Hereditary Spherocytosis. Conclusion- This case highlights the importance of evaluation of anemia inpatients with valvular heart diseases. If a treatable cause is found, anemia can be treated to reduce the cardiac burden.

Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians.

The most recent International League Against Epilepsy (ILAE) classification has included "immune etiology" along with other well-known causes of epilepsy. This was possible thanks to the progress in detection of pathogenic neural antibodies (Abs) in a subset of patients, and resulted in an increased interest in identifying potentially treatable causes of otherwise refractory seizures. Most autoimmune encephalitides (AE) present with seizures, but only a minority of cases evolve to long-term epilepsy. The risk of epilepsy is higher for patients harboring Abs targeting intracellular antigens (T cell-mediated and mostly paraneoplastic, such as Hu, CV2/CRMP5, Ma2, GAD65 Abs), compared with patients with neuronal surface Abs (antibody-mediated and less frequently paraneoplastic, such as NMDAR, GABAbR, LGI1, CASPR2 Abs). To consider these aspects, conceptual definitions for two entities were provided: acute symptomatic seizures secondary to AE, and autoimmune-associated epilepsy, which reflect the different pathophysiology and prognoses. Through this manuscript, we provide an up-to-date review on the current state of knowledge concerning diagnosis and management of patients with Ab-mediated encephalitis and associated epilepsy. Special emphasis is placed on clinical aspects, such as brain magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) specificities, electroencephalographic (EEG) findings, cancer screening and suggestions for a rational therapeutic approach.

Congestive myelopathy due to craniocervical junction arteriovenous fistulas mimicking transverse myelitis: a multicenter study on 27 cases.

The purpose was to clarify diagnostic clues and pitfalls in cranio-cervical junction arteriovenous fistulas (CCJ AVFs) with congestive myelopathy. In a multicenter observational study by the Neurospinal Society of Japan, we described the demographics, clinical courses, imaging findings, and outcomes of consecutive patients with CCJ AVFs presenting with congestive myelopathy between 2009 and 2019. Twenty-seven patients were included (mean age, 70years; male, 96%). Progressive symptoms within one day to one month were more common (63%) than chronic symptoms. Myelopathic symptoms were characterized by ascending paralysis beginning from the legs, involving the trunk and arms, and sometimes ending in the brainstem. Fifteen patients (56%) received a misdiagnosis, including acute transverse myelitis. The most common MRI findings were venous congestive edema of the cervical cord (96%) and the brainstem (63%) and surrounding vascular flow voids (100%). The mean extension of congestive edema was 5.5 ± 2.9 vertebral segments. The most common angiographic findings were a dural AVF (78%) at the C1 level (81%) with descending venous drainage (85%). Seven patients (26%) were administered steroids, which resulted in neurological decline in 3. Neurosurgical obliteration of the AVF led to improvements in MRI findings in 75% and a functional status in 67%; however, 44% remained dependent. The myelopathy of CCJ AVFs was characterized by acute ascending paralysis in elderly men. A misdiagnosis was common because of the acute presentation due to a longitudinally extensive spinal cord lesion. Dilated vessels on MRI were a key finding for the correct diagnosis. What is already known on this topic? Slowly progressive myelopathy is a well-known symptom that results from impaired spinal venous drainage due to thoracolumbar AVFs. Although cranio-cervical junction arteriovenous fistulas (CCJ AVFs) constitute a treatable cause of congestive myelopathy, detailed information is not currently available due to their rarity. What does this study add? CCJ AVFs often presented with acute ascending myelopathy in elderly men due to a longitudinally extending cervical cord lesion with surrounding flow voids. Steroid pulse therapy was not effective or even harmful to congestive myelopathy, while neurosurgical treatment effectively obliterated AVFs. How might this study affect research, practice or policy? The results obtained revealed diagnostic clues and pitfalls from the largest dataset of patients with CCJ AVFs in a multicenter cohort.

Characterization of Cardiac Bradyarrhythmia Associated With LGI1-IgG Autoimmune Encephalitis

Objective To evaluate and characterize cardiac arrhythmias associated with LGI1-IgG (Leucine-rich glioma inactivated 1–IgG) autoimmune encephalitis (AE). Background AE is increasingly identified as a potentially treatable cause of encephalitis. LGI1-IgG is one of the most common pathogenic neural specific autoantibodies associated with AE in adults. Prior cases of bradyarrhythmias and sudden death have been reported in LGI1-IgG AE, however, larger cohort studies are lacking. Design/Methods In this retrospective descriptive study, we identified Mayo Clinic patients (May 1, 2008–December 31, 2020) with LGI1-IgG AE who had electrocardiogram proven bradyarrhythmias during the initial presentation. Inclusion criteria were 1) LGI1-IgG positivity with a consistent clinical syndrome; 2) electrocardiographic evidence of bradyarrhythmia; and 3) sufficient clinical details. We excluded patients with alternate reason for bradyarrhythmias. We collected demographic/clinical data including details of bradyarrhythmia (severity, duration, treatments), and neurologic and cardiac outcomes. Results We found that patients with LGI1-IgG AE had bradyarrhythmia at a frequency of 8% during the initial presentation. The bradyarrhythmia was often asymptomatic (6/11, 55%); however, the episode was severe with one patient requiring a pacemaker. Outcome was also generally favorable with the majority (8/11, 73%) having full resolution without further cardiac intervention. Lastly, we found that mouse and human cardiac tissues express LGI1 (mRNA and protein), suggesting that LGI1-IgG may influence cardiac tissue itself. Conclusions LGI1-IgG AE can be rarely associated with bradyarrhythmias. Although the disease course is mostly favorable, some cases may require pacemaker placement to avoid devastating outcomes.

Giant Cell Arteritis of the Superior Mesenteric Artery Presenting With Wernicke Encephalopathy From Thiamine Deficiency

Objective N/A. Background Giant cell arteritis (GCA) is one of the most common systemic vasculitides in adults over the age of 50 with incidence ranging from 15 to 35 per 100,000 individuals. The disorder is often included in the differential diagnosis of maladies producing atypical facial pain, headache, visual loss, amaurosis fugax, jaw pain, elevated inflammatory markers, and anemia. GCA is typically known to affect cranial arteries with physical exam findings of tenderness to palpation of the temporal arteries and cranial neuropathies. Clinical diagnosis is further supported by new headache, temporal artery abnormality, elevated ESR (= 50 mm/h), and abnormal artery biopsy. Design/Methods N/A. Results A 68-year-old female with history of primary generalized seizures presented to clinic with a 6-week history of paroxysms of acute confusional episodes, the inability to arise from a seated position due to lower extremity weakness bilaterally, alterations of consciousness without loss of consciousness, severe anorexia, and weight loss. MRI with contrast including Axial FLAIR/T2/Diffusion revealed bilateral pan-lobar cortical and subcortical atrophy with ex-vacuo ventriculomegaly and mild leukoaraiosis in the subcortical white matter tracts. PET-CT body revealed linear uptake involving the aortic root, extending into subclavian arteries bilaterally with segmental involvement of proximal common carotids, and extending inferiorly to the level of the common iliac arteries and the mesenteric arteries. Temporal artery biopsy revealed presence of granulomas with multinucleated giant cells. Serology panel revealed pan hypovitaminoses in Vitamins A, B1, B6, B12, and D. Conclusions Traditional GCA workup initially resulted inconclusive for the patient, whose condition deteriorated as the patient's altered mental status and dizziness spells continued unremittingly. This case highlights the link between large vessel vasculitis and malabsorption syndromes, with the involvement of the superior mesenteric artery, a medium sized vessel, in GCA previously unrecognized. Furthermore, this case is a superb example of multiple etiologies of treatable causes of reversible dementia.

Determining Etiologic Diagnoses in Patients with Rapidly Progressive Dementia

AbstractBackgroundOverlap in the presenting clinical features and test results in patients with rapidly progressive dementia (RPD) confounds the etiologic diagnoses of RPD, contributing to diagnostic delays, missed treatment opportunities, and poorer outcomes. There is a need to improve diagnostic accuracy in patients with RPD, with particular emphasis on identifying patients with potentially treatment‐responsive causes of RPD early in the symptomatic course.MethodPatients with RPD were prospectively enrolled and evaluated in inpatient settings and outpatient subspecialty (memory) clinics at Washington University (Saint Louis, MO; 2016–2019) and Mayo Clinic (Jacksonville, FL; 2020–2021). Etiologic diagnoses were independently assigned by two dementia specialists integrating clinical features and the results of widely accessible diagnostic testing and referencing established diagnostic criteria. Diagnostic disagreements were resolved via blinded review by a third specialist. Clinicopathologic correlation was evaluated using neuropathological and genetic data when available.Result160 patients with RPD were assessed, with average age‐at‐symptom onset 60.0±15.9 years; 50% were female. Diagnostic inter‐rater reliability (91% agreement; Cohen’s κ = 0.88, p<0.001) and clinicopathologic correlation were excellent (100% agreement in 24 patients with neuropathologic or genetic data). Autoimmune encephalitis was the leading cause of RPD (39%), followed by Alzheimer disease and related dementias (29%—i.e., frontotemporal dementia, Lewy body dementia, vascular cognitive impairment), Creutzfeldt‐Jakob disease (15%), and other causes (15%—e.g., neurosarcoid, metabolic disruptions, neoplastic disease). The average age of patients with potentially treatable causes (AE and selected “other” causes; 54.4±18.2) was younger than those with neurodegenerative dementing illnesses (67.3±9.5) or CJD (67.4±7.9; p<0.001). Patients with potentially treatable causes were more likely to present with altered level of consciousness and seizures (p<0.05). CSF pleocytosis (>5 WBC/hpf) was more common in AE patients (p<0.05).ConclusionEtiologic diagnoses can be reliably established in RPD patients using available clinical data. Treatment‐responsive causes of RPD are common warranting consideration, particularly in younger patients with altered consciousness, seizures, and CSF pleocytosis.

PP143 International Assessment of the Health Care System in Kazakhstan. A performance analysis.

IntroductionMeasuring the performance of the health systems is an important challenge at international level. The main objective of this work is to analyze the outcomes of the Kazakhstan Health Care System in order to establish the main causes of avoidable mortality in the country. Also, to identify benchmarking possibilities that may support public policy decisions to improve the results.MethodsTo calculate the avoidable mortality indicators due to preventable and treatable causes, the methodology agreed by the OECD and Eurostat based on the International Classification of Diseases, ICD-10 was applied. Starting from the mortality database of the World Health Organization, the standardized indicators of avoidable mortality was calculated for those countries that had available data based on this classification. Based on the outcomes obtained, a “Two-Step” Cluster Analysis was used to identify and characterize the different clusters of countries that present similar results to identify possible affinities and detect benchmarking possibilities.ResultsThe main causes of mortality from treatable diseases in Kazakhstan are those related to the circulatory system, followed by different types of cancer and respiratory diseases.Applying the cluster analysis in the international context, we find important differences between the different clusters, both in the standardized ratios of avoidable mortality and in its causes. Notable differences have also been identified between Kazakhstan and the countries that make up its cluster. Overall, Kazakhstan presents better avoidable mortality results, both from preventable and treatable causes, than the average of the cluster to which it belongs. However, in some causes of death, it presents worse results and high mortality rates, as in the case of those related to the circulatory and respiratory systems or different types of injuries.ConclusionsThe cluster analysis based on the avoidable mortality indicators reveals different conglomerates of countries that show important similarities between them and also some significant differences. Groups of avoidable diseases that characterize each cluster and subcluster, provide key information for the benchmarking and the design of future actions.

Causes of Mortality Among Veterans Previously Hospitalized After Traumatic Brain Injury

<h3>Research Objectives</h3> To examine mortality rates and causes among Veterans with traumatic brain injury (TBI) following discharge from inpatient rehabilitation. <h3>Design</h3> Secondary analysis; Cohort study. <h3>Setting</h3> Five Veterans Affairs (VA) Polytrauma Rehabilitation Centers. <h3>Participants</h3> Persons enrolled in the VA Traumatic Brain Injury Model Systems (TBIMS) who were admitted to rehabilitation within one year of TBI and discharged (alive) from rehabilitation between 01/01/2009 and 03/31/2020, and who died after rehabilitation discharge (N=82). <h3>Interventions</h3> N/A. <h3>Main Outcome Measures</h3> Mortality. <h3>Results</h3> The mortality rate was 8.3% for participants within this study's time frame. Most deaths (46.9%) occurred between 2 and 5 years from discharge. Reasons for death (among the known causes: 67.1%) were as follows: external causes of injury (29%), circulatory (22%), respiratory (18%), digestive (13%), neoplasm (9%), nervous system (7%), and infectious disease (2%). <h3>Conclusions</h3> Overall mortality rate was comparable to research in the civilian TBIMS (9-10%). Prior research implicated circulatory conditions as the most common cause of death, but in this study, the primary reasons were external causes (e.g., late effects of intracranial trauma; suicide). Digestive conditions (e.g., alcoholic liver disease) were the fourth most common cause of death yet a negligible cause in the general TBI population. Implications of the current findings include targeted clinical interventions for prevention or treatment of causes of mortality among veterans following discharge. <h3>Author(s) Disclosures</h3> Supported in part by NIDILRR [grant #90DPTB0002] (Hammond). Conducted with resources and use of facilities at the following: Hunter Holmes McGuire VA, Richmond, VA; James A. Haley VA, Tampa, FL; Minneapolis VA, Palo Alto VA, and South Texas VA. The authors declare no conflicts of interest. The views expressed here are the authors' and do not necessarily represent official policy/position of any federal government agency. This work was prepared under Contract HT0014-21-C-0012 [DHA Contracting Office (CO-NCR) HT0014] and defined as U.S. Government work under Title 17 U.S.C.§101. Per Title 17 U.S.C.§105, copyright protection is not available. For more information, contact TBICOEinfo@mail.mil. UNCLASSIFIED

Screening for Memory Concerns at the Well-Woman Visit.

Routine healthcare visits offer the opportunity to screen older adults for cognitive changes that accompany the earliest clinical stages of Alzheimer's disease (AD) including Mild Cognitive Impairment (MCI) and Subjective Cognitive Decline (SCD). It is well-established that women are at increased risk for AD and that many women see their gynecologist as their primary care doctor. Given this unique relationship, the Women's Preventive Services Initiative and the American College of Obstetrics and Gynecology now advocate for integrated care of women at all ages. Memory screening of older women should be paramount in this effort. Research is needed to determine which screening tools are most effective and practical. Here we assess the feasibility and utility of a subjective memory screener at the well-woman visit. Women aged 60 and above completed a 5-item screener at their well-woman visit at the Columbia University Integrated Women's Health Center (Table 1). Women who endorsed any item were considered to have a positive screen and were given the option to pursue clinical evaluation for memory concerns through the Division of Aging and Dementia. Only 8 of 354 women declined to complete the screener. Of the completed screeners, 16% (n = 56) were positive. The most frequently endorsed item was difficulty with memory or thinking compared to others the same age (8%, n = 28) (See Table 1). 44% (n = 24) of women with positive screens pursued referral, and six have been seen to date. One woman was diagnosed with MCI. Clinical impressions of the remainder were unremarkable. All six cases had family history of dementia or memory problems. The well-woman visit provides a key opportunity to routinely screen older women for early indicators of AD and treatable causes of cognitive impairment. Preliminary results support the feasibility and value of such screening as part of a comprehensive well-woman program. Early identification of women experiencing SCD will enable investigation into the cause of their memory concerns, and longitudinal monitoring of cognitive change. Future work should evaluate the added value of an objective cognitive screen to complement SCD screening and identify women who may benefit from further evaluation.

Adipositas aus viszeralonkologischer Perspektive

Up to 40% of all adults worldwide are overweight or obese. Besides the established obesity-related comorbidities, such as type 2 diabetes mellitus, hypertension or NAFLD (non-alcoholic fatty liver disease), the focus of interest is shifting towards the influence of increased body weight as a risk factor for the development of malignant diseases. For more than 20 different types of malignancies, interactions between increased body weight and cancer risk have been established. Pathophysiological influences of obesity on carcinogenesis are diverse, including factors such as chronic inflammation, hyperinsulinaemia and insulin resistance, various changes in growth factor and changes in sex hormones. In cohorts of visceral oncology patients, malignancies such as colorectal carcinomas, hepatocellular carcinomas, adenocarcinomas of the pancreas, oesophageal and gastric carcinomas are also linked to an increased disease risk with increasing body weight. Since obesity must be considered a preventable or at least treatable cause of cancer, this review examines the influence of obesity in the field of visceral oncology, examining the effects of obesity on tumour prevalence, prevention and diagnostic testing, as well as its influence on treatment and prognosis. Furthermore, this review explores the current evidence on the influence of bariatric surgery on the prevalence of these obesity associated tumours. For example, in the case of colorectal carcinomas, the evidence base following bariatric surgery is mixed, painting an inhomogeneous picture. On the other hand, significantly lower prevalence of pancreatic adenocarcinoma and hepatocellular carcinomas is to be noted. The latter effect can be explained by the decrease in non-alcoholic fatty liver disease (NAFLD) associated with weight loss. Despite the justified concern that bariatric procedures (especially gastric sleeve resection) lead to increased prevalence of malignancies of the oesophageal junction, the currently available epidemiological data does not seem to identify a relevant increase in the incidence of these malignancies.

Arginase 1 Deficiency in Patients Initially Diagnosed with Hereditary Spastic Paraplegia.

Arginase 1 Deficiency (ARG1-D) is a rare autosomal recessive urea cycle disorder (UCD) characterized by pathologic elevation of plasma arginine and debilitating manifestations. Based on clinical commonalities and low disease awareness, ARG1-D can be diagnosed as hereditary spastic paraplegia (HSP), leading to treatment delays. A Hispanic woman with unremarkable medical history experienced progressive lower-limb spasticity in her 20s and received a diagnosis of HSP. She developed significant gait abnormalities and is unable to walk without assistance. More recently, two Hispanic brothers with childhood-onset manifestations including lower-limb spasticity, developmental delays, and seizures presented with suspected HSP. All three patients were ultimately diagnosed with ARG1-D based on plasma arginine several-fold above normal levels and loss-of-function ARG1 variants. Disease progression occurred before ARG1-D was correctly diagnosed. Retrospective analyses demonstrate that diagnostic delays in ARG1-D are common and can be lengthy. Because of clinical similarities between ARG1-D and HSP, such as insidious onset and progressive spasticity, accurate diagnosis of ARG1-D is challenging. Timely ARG1-D diagnosis is critical because this UCD is a treatable genetic cause of progressive lower-limb spasticity. Arginase 1 Deficiency should be considered in HSP differential diagnosis until biochemically/genetically excluded, and should be routinely included in HSP gene panels.

Autoimmune hepatitis unmasked by dengue infection - An unexplored and rare association.

Dengue hepatitis is mostly asymptomatic but can lead to liver failure. Autoimmune hepatitis is mainly the disease of females and a potentially treatable cause of chronic liver disease. We report a rare case in which autoimmune hepatitis was unmasked by Dengue infection. The patient was managed for AIH with steroids and azathioprine and became asymptomatic in 30 days. Dengue is a proven risk factor for many autoimmune conditions but its association with AIH is not studied.

Clinical and paraclinical features of small fiber neuropathy in Sjögren’s syndrome

Sjögren’s syndrome is a potentially treatable cause of Small Fiber Neuropathy (SFN)—a condition that severely affects patients’ quality of life. We therefore aimed to characterize patients with SFN and Sjögren’s syndrome to raise awareness of this disease and facilitate its early recognition as an essential step for appropriate treatment. In 97 SFN patients (median age 48 years, 77% female), we studied the clinical features associated with Sjögren’s syndrome compared to the idiopathic SFN subtype. According to the current ACR/EULAR classification criteria (Shiboski et al., Ann Rheum Dis 76:9–16, 2017), 24/97 individuals (25%, median age 48.5 years, 75% female) were diagnosed with Sjögren’s syndrome. We did not observe any differences in SFN-defining sensory plus symptoms. Furthermore, intraepidermal nerve fiber densities (IENFD) were significantly lower in patients with SFN and Sjögren’s syndrome (mean 2.6 ± 1.2/mm) compared to patients with idiopathic SFN (mean 3.2 ± 1.5/mm; p = 0.048). There were no significant group differences when analyzing cerebrospinal fluid (CSF) parameters. We conclude that Sjögren’s syndrome-associated SFN is difficult to distinguish from idiopathic forms based on initial clinical symptoms and CSF results. However, lower IENFD values in patients with Sjögren's syndrome-associated SFN might indicate a distinct different pathomechanism in this entity compared to idiopathic SFN.

The future of Artificial Intelligence in Ophthalmology

Health systems across the world are facing a growing challenge of providing eye care for their populations. The prevalence of eye conditions which can lead to visual impairments in projected to increase, from 596 million people with distance vision impairment in 2020, to 895 million people in 2050 [1]. However over 90% of those affected have a treatable or preventable cause, and are primarily found in low and middle-income countries.