EVALUATION OF CLINICAL AWARENESS OF DIABETIC MELLITUS AMONG RAKMHSU MEDICAL STUDENTS- A QUESTIONNAIRE SURVEY

Introduction: The number of patients with diabetes are increasing in rapid phase and the present medical students will encounter with such patients in the future very often. It was essential to understand and update their knowledge through education and awareness programs. Materials and methods: The cross-sectional questionnaire survey has been conducted in RAK Medical and Health Sciences University (RAKMHSU) with due approval from research ethics committee. After going through various indexed articles related to our topic, a pre designed pre validated questionnaire was prepared. The questionnaire assessed the knowledge about symptoms, investigations, treatment and complications. This was applied after validation to second, third, fourth and fifth year medical students. Results: The study showed the majority in both groups 93.5% and 89.2% agreed that they will be involved in taking care of diabetic patients in their future practice. The study also found that 65.2% group A agreed that excessive thirst and urination is a indicative of low blood sugar when compared with 31.7% from group B. With regard to symptoms majority in both groups agreed itchy skin is not a symptom of DM. When asked about insulin misuse, only 36.8% and 55.4% students agreed that blood glucose will go below 50mg/dl. Discussion and conclusion: Our study correlated with various studies which showed many students had problems in treatment aspects. But we also had positive results which correlated with other study showing they have good knowledge about symptoms. We also found our students had good knowledge about diabetic ketoacidosis. In conclusion, there is a need for conducting regular workshops, seminars, conferences in medical colleges to upgrade the knowledge of students and make them a competent general physician. Key words: Diabetes, Keto acidosis, Education, Knowledge, Risk factors

Advancing genomic technologies and clinical awareness accelerates discovery of disease-associated tandem repeat sequences

Expansions of gene-specific DNA tandem repeats (TRs), first described in 1991 as a disease-causing mutation in humans, are now known to cause >60 phenotypes, not just disease, and not only in humans. TRs are a common form of genetic variation with biological consequences, observed, so far, in humans, dogs, plants, oysters, and yeast. Repeat diseases show atypical clinical features, genetic anticipation, and multiple and partially penetrant phenotypes among family members. Discovery of disease-causing repeat expansion loci accelerated through technological advances in DNA sequencing and computational analyses. Between 2019 and 2021, 17 new disease-causing TR expansions were reported, totaling 63 TR loci (>69 diseases), with a likelihood of more discoveries, and in more organisms. Recent and historical lessons reveal that properly assessed clinical presentations, coupled with genetic and biological awareness, can guide discovery of disease-causing unstable TRs. We highlight critical but underrecognized aspects of TR mutations. Repeat motifs may not be present in current reference genomes but will be in forthcoming gapless long-read references. Repeat motif size can be a single nucleotide to kilobases/unit. At a given locus, repeat motif sequence purity can vary with consequence. Pathogenic repeats can be “insertions” within nonpathogenic TRs. Expansions, contractions, and somatic length variations of TRs can have clinical/biological consequences. TR instabilities occur in humans and other organisms. TRs can be epigenetically modified and/or chromosomal fragile sites. We discuss the expanding field of disease-associated TR instabilities, highlighting prospects, clinical and genetic clues, tools, and challenges for further discoveries of disease-causing TR instabilities and understanding their biological and pathological impacts—a vista that is about to expand.

SHIITAKE MUSHROOM AS A CAUSE OF BOWEL OBSTRUCTION

Shiitake mushroom, claimed to have major health benefits. It is a popular ingredient in east Asian cuisine. Given that mushrooms are rich in dietary fiber, the undigested fiber can act as a bezoar and may cause small bowel obstruction. Bezoar-induced small bowel obstructions are rare and herein we report a case of intestinal obstruction caused by shiitake mushroom. An elderly patient was admitted with features of intestinal obstruction. Preoperative imaging showed dilated small bowel with suspicious mass in ileum. Patient underwent laparotomy and undigested shiitake mushroom was retrieved at enterotomy. Clinical awareness of the mushroom induced intestinal obstruction and early use abdominal computed tomography (CT) are essential for prompt diagnosis and treatment.

A Nationwide Study of GATA2 Deficiency in Norway—the Majority of Patients Have Undergone Allo-HSCT

Purpose GATA2 deficiency is a rare primary immunodeficiency that has become increasingly recognized due to improved molecular diagnostics and clinical awareness. The only cure for GATA2 deficiency is allogeneic hematopoietic stem cell transplantation (allo-HSCT). The inconsistency of genotype–phenotype correlations makes the decision regarding “who and when” to transplant challenging. Despite considerable morbidity and mortality, the reported proportion of patients with GATA2 deficiency that has undergone allo-HSCT is low (~ 35%). The purpose of this study was to explore if detailed clinical, genetic, and bone marrow characteristics could predict end-point outcome, i.e., death and allo-HSCT. Methods All medical genetics departments in Norway were contacted to identify GATA2 deficient individuals. Clinical information, genetic variants, treatment, and outcome were subsequently retrieved from the patients’ medical records. Results Between 2013 and 2020, we identified 10 index cases or probands, four additional symptomatic patients, and no asymptomatic patients with germline GATA2 variants. These patients had a diverse clinical phenotype dominated by cytopenia (13/14), myeloid neoplasia (10/14), warts (8/14), and hearing loss (7/14). No valid genotype–phenotype correlations were found in our data set, and the phenotypes varied also within families. We found that 11/14 patients (79%), with known GATA2 deficiency, had already undergone allo-HSCT. In addition, one patient is awaiting allo-HSCT. The indications to perform allo-HSCT were myeloid neoplasia, disseminated viral infection, severe obliterating bronchiolitis, and/or HPV-associated in situ carcinoma. Two patients died, 8 months and 7 years after allo-HSCT, respectively. Conclusion Our main conclusion is that the majority of patients with symptomatic GATA2 deficiency will need allo-HSCT, and a close surveillance of these patients is important to find the “optimal window” for allo-HSCT. We advocate a more offensive approach to allo-HSCT than previously described.

Clinical correlates and prognostic impact of neurologic disorders in Takotsubo syndrome

Cardiac alterations are frequently observed after acute neurological disorders. Takotsubo syndrome (TTS) represents an acute heart failure syndrome and is increasingly recognized as part of the spectrum of cardiac complications observed after neurological disorders. A systematic investigation of TTS patients with neurological disorders has not been conducted yet. The aim of the study was to expand insights regarding neurological disease entities triggering TTS and to investigate the clinical profile and outcomes of TTS patients after primary neurological disorders. The International Takotsubo Registry is an observational multicenter collaborative effort of 45 centers in 14 countries (ClinicalTrials.gov, identifier NCT01947621). All patients in the registry fulfilled International Takotsubo Diagnostic Criteria. For the present study, patients were included if complete information on acute neurological disorders were available. 2402 patients in whom complete information on acute neurological status were available were analyzed. In 161 patients (6.7%) an acute neurological disorder was identified as the preceding triggering factor. The most common neurological disorders were seizures, intracranial hemorrhage, and ischemic stroke. Time from neurological symptoms to TTS diagnosis was ≤ 2 days in 87.3% of cases. TTS patients with neurological disorders were younger, had a lower female predominance, fewer cardiac symptoms, lower left ventricular ejection fraction, and higher levels of cardiac biomarkers. TTS patients with neurological disorders had a 3.2-fold increased odds of in-hospital mortality compared to TTS patients without neurological disorders. In this large-scale study, 1 out of 15 TTS patients had an acute neurological condition as the underlying triggering factor. Our data emphasize that a wide spectrum of neurological diseases ranging from benign to life-threatening encompass TTS. The high rates of adverse events highlight the need for clinical awareness.

188 Disarming the bomb in AL amyloidosis: a case report

Aims Light-chain amyloidosis (AL) is a rapidly progressive systemic disease commonly involving also the myocardium, with poor outcome if lately diagnosed and treated. Clinical presentation can be widely varied, ranging from unapparent disease with soft symptoms to acute heart failure syndromes, requiring urgent therapies and supports. Methods and results A 52-year-old women came to our outpatient cardiomyopathy clinic because of hypertrophic cardiomyopathy (HCM) suspicion. Family history included a paternal cousin with diagnosis of unspecified cardiomyopathy and cardiac arrest. Her medical history was unremarkable until few months ago, when she started to complain with palpitations and asthenia. Given that both electrocardiogram and echocardiogram had previously showed signs of left ventricular (LV) hypertrophy, she was referred to us for HCM evaluation. Our physical examination was unremarkable, in particular there were no signs of central or peripheral venous congestion. Electrocardiogram showed a diffuse strain pattern with inferolateral ST-depression and T-wave inversion. Echocardiogram showed a thicked interventricular septum (17 mm), a pseudo-normal transmitral filling pattern with mild increase of LV filling pressure (E/E′ 11), a severely dilated left atrium (51 ml/mq). To complete the diagnostic path for HCM, we asked for a cardiac magnetic resonance (CMR), which two months later gave to us the diagnosis of myocardial amyloid infiltration. The diagnosis was quite surprising, because the patient was fine, 6 min walking test assessed a good functional capacity (500 m), no heart failure signs were recorded. So, we sent the patient to perform bone scintigraphy, which showed Perugini 0 uptake, and blood exam, showing, instead, rise of lambda free light chains, cardiac troponin (41.5 ng/l) and NTproBNP (5318 ng/l). Patient was urgently referred to haematologists, who using bone marrow and fat pad biopsy diagnosed a multiple myeloma with stage IV sec. Mayo AL amyloidosis. (Cy)BorD therapy was started, reaching a complete response in 4 months. Conclusions Diagnosis of AL amyloidosis is tricky due to heterogeneous clinical onset and multi-organ involvement. Cardiologist community should be aware of this condition, phenotypically mimicking HCM, but with very different management, in order to favour early diagnosis, prompt referral and treatment initiation. This case teaches that only 1. clinical awareness and 2. multidisciplinary approach can lead to disarm the bomb in AL amyloidosis.

Diagnostic challenges of an incidental finding: case report of definitely-congenital glioblastoma multiforme in a very preterm infant

Background Congenital brain tumors are extremely rare in the neonatal population, and often associated with a poor prognosis. The diagnostic suspicion is often aroused at antenatal scans or postnatally, if clinical signs and symptoms of increased intracranial pressure become evident. We present a case of definitely congenital glioblastoma multiforme incidentally diagnosed in a preterm infant, aiming to raise clinical awareness on this condition and to highlight the challenges of the related diagnostic work-up. Case presentation This female infant was born at 31 weeks’ gestation after an uneventful pregnancy. No abnormalities were detected at antenatal ultrasound scans and genetic tests. Head circumference at birth was on the 25th centile. A routine brain ultrasound scan performed on day 1 revealed a large, inhomogeneous lesion in the right cerebral hemisphere, with contralateral midline shift, which was confirmed by brain magnetic resonance imaging (MRI). Eye fundus and routine blood exams, including platelets count, coagulation screening and C-reactive protein, were normal. Given the high risk of complications, surgical biopsy of the lesion was temporarily hold and a daily sonographic follow-up was undertaken. Although head circumference growth was steady on the 25th centile, progressive changes of the lesion were detected by cranial ultrasound. The repeat MRI scans showed a significant enlargement of the mass, with contralateral midline shift and signs of intralesional and intraventricular bleeding. In view of this worsening, surgical resection was performed. The histological examination of the lesion biopsy documented a GFAP+ highly cellular neoplasm, with no mutation on SMARCB1 gene. At the molecular analysis, mutations on IDH and H3F3A genes were absent, whereas MGMT promoter was unmethylated. The diagnosis was grade IV glioblastoma IDH wild-type. Conclusions Congenital glioblastoma multiforme is an extremely rare but highly aggressive neoplasm. Since intralesional biopsy is not often feasible in affected neonates, knowledge of the associated clinical and neuroradiological features is particularly important, as they can also add useful information on the neoplasm behavior. Specimens from open surgical resection allow to perform a definite histological analysis and an extended molecular characterization, with relevant prognostic implications.

Factors That Influence Non-Motor Impairment Across the ALS-FTD Spectrum: Impact of Phenotype, Sex, Age, Onset and Disease Stage

Objective: This study aimed to establish (1) the pattern and severity of neuropsychiatric symptoms and other non-motor symptoms of sleep and mood, across ALS phenotypes in comparison to bvFTD and (2) the contribution of non-modifiable factors including age, sex and disease state to the severity of symptoms experienced by ALS patients.Methods: Consecutive participants were recruited to the study and underwent a detailed clinical, cognitive, behavioral and neuroimaging assessment. Neuropsychiatric and other non-motor symptoms were determined using the Cambridge Behavioral Inventory, the CBI-R. The scores were converted to define impairment in terms of mild, moderate and severe symptoms for each subscale. Rate, severity and contribution of King's staging and modifiable factors were also determined and a regression model identified predictors of symptom severity.Results: In total, 250 participants (115 ALS, 98 bvFTD, and 37 ALS-FTD patients) were recruited. A similar pattern of neuropsychiatric symptom severity was identified (apathy, disinhibition and stereotypic behavior) for all behavioral phenotypes of ALS compared to bvFTD (all p > 0.05). Neuropsychiatric symptoms were also present in cases defined as ALSpure and the cognitive phenotype of ALS (ALSci) although they occurred less frequently and were at the milder end of the spectrum. Disordered sleep and disrupted mood were common across all phenotypes (all p < 0.05). The severity of sleep dysfunction was influenced by both sex and age (all p < 0.05). Neuropsychiatric symptoms, sleep and mood disorders were common early in the disease process and deteriorated in line with progression on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R; all p < 0.05). Diagnostic phenotype, disease duration and global cognition scores were the strongest predictors of non-motor and neuropsychiatric impairments.Conclusion: The current findings reveal strikingly similar patterns of changes across the subgroups of ALS and bvFTD, supporting the concept of the ALS-FTD spectrum. The findings further highlight the impact of non-motor and neuropsychiatric symptoms in patients with ALS, that are often as severe as that seen in ALS-FTD and bvFTD. This study advances understanding across the ALS-FTD spectrum that may accelerate the early identification of patient needs, to ensure prompt recognition of symptoms and thereby to improve clinical awareness, patient care and management.

Focal Seizures and Posterior Reversible Encephalopathy Syndrome as Presenting Signs of IgA Vasculitis/Henoch-Schoenlein Purpura—An Educative Case and Systematic Review of the Literature

Background: IgA vasculitis/Henoch-Schoenlein purpura (IgAV/HSP) is a systemic small vessel vasculitis of unknown pathogenesis predominantly affecting children. While skin, GI tract, joints, and kidneys are frequently affected and considered, central nervous system (CNS) involvement of this disease is underestimated.Methods: We provide a case report and systematically review the literature on IgAV, collecting data on the spectrum of neurological manifestations.Results: We report on a 7-year-old girl with IgAV who presented with diplopia and afebrile focal seizures, which preceded the onset of purpura. Cranial magnetic resonance imaging was consistent with posterior reversible encephalopathy syndrome (PRES), showing typical focal bilateral parietal swelling and cortical and subcortical high signal intensities on T2-fluid attenuated inversion recovery (FLAIR) images predominantly without diffusion restriction. Cerebrospinal fluid analysis and blood tests excluded systemic inflammation or vasculitis. Interestingly, hypertension was not a hallmark of the developing disease in the initial phase of PRES manifestation. Renal disease and other secondary causes for PRES were also excluded. Supportive- and steroid treatment resulted in restitution ad integrum. Reviewing the literature, we identified 28 other cases of IgAV with CNS involvement. Severe CNS involvement includes seizures, cerebral edema, or hemorrhage, as well as PRES. Thirteen patients fulfilled all diagnostic criteria of PRES. The mean age was 11.2 years (median 8.0, range 5-42 years), with no reported bias toward gender or ethnic background. Treatment regimens varied from watchful waiting to oral and intravenously steroids up to plasmapheresis. Three cases showed permanent CNS impairment.Conclusion: Collectively, our data demonstrate that (I) severe CNS involvement such as PRES is an underappreciated feature of IgAV, (II) CNS symptoms may precede other features of IgAV, (III) PRES can occur in IgAV, and differentiation from CNS vasculitis is challenging, (IV) pathogenesis of PRES in the context of IgAV remains elusive, which hampers treatment decisions. We, therefore, conclude that clinical awareness and the collection of structured data are necessary to elucidate the pathophysiological connection of IgAV and PRES.

Re-emergence of enterovirus D68 in Europe after easing the COVID-19 lockdown, September 2021

We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe.