Patterns Of Clinical Presentation Research Articles

The Concept of α-Synuclein Strains and How Different Conformations May Explain Distinct Neurodegenerative Disorders.

In the past few years, an increasing amount of studies primarily based on experimental models have investigated the existence of distinct α-synuclein strains and their different pathological effects. This novel concept could shed light on the heterogeneous nature of α-synucleinopathies, a group of disorders that includes Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, which share as their key-molecular hallmark the abnormal aggregation of α-synuclein, a process that seems pivotal in disease pathogenesis according to experimental observations. However, the etiology of α-synucleinopathies and the initial events leading to the formation of α-synuclein aggregates remains elusive. Hence, the hypothesis that structurally distinct fibrillary assemblies of α-synuclein could have a causative role in the different disease phenotypes and explain, at least to some extent, their specific neurodegenerative, disease progression, and clinical presentation patterns is very appealing. Moreover, the presence of different α-synuclein strains might represent a potential biomarker for the diagnosis of these neurodegenerative disorders. In this regard, the recent use of super resolution techniques and protein aggregation assays has offered the possibility, on the one hand, to elucidate the conformation of α-synuclein pathogenic strains and, on the other hand, to cyclically amplify to detectable levels low amounts of α-synuclein strains in blood, cerebrospinal fluid and peripheral tissue from patients. Thus, the inclusion of these techniques could facilitate the differentiation between α-synucleinopathies, even at early stages, which is crucial for successful therapeutic intervention. This mini-review summarizes the current knowledge on α-synuclein strains and discusses its possible applications and potential benefits.

Mode of Presentation of Liver Cirrhosis: A Study in a Tertiary Level Hospital

Liver cirrhosis is an important cause of death and disability globally. This cross-sectional study was carried out in Faridpur Medical College Hospital from November 2018 to April 2019 to see the patterns of clinical presentations and associated factors among admitted liver cirrhosis patients. A total of 89 patients were included. Data were collected by detailed history from patients or their relatives followed by thorough physical examination as well as diagnostic evaluation; then those were checked, verified for consistency and edited for result. Among total respondents, the majority were male (69.7%) with a male to female ratio of 1:0.44. Age of patients ranged between 22-106 years with mean age of 52.33 year. The patients predominantly presented with ascites (49.4%), gastrointestinal bleeding (27%), peripheral edema (24.7%), and encephalopathy (21.3%). The in-hospital case fatality rate was 11.2% and the patients presented with decreased urinary output, peripheral edema and encephalopathy had statistically significant death rate. The results of the study highlighted that the patients with liver cirrhosis mostly present with features of decompensation and there is a statistically significant relation with some of these clinical presentations with in-hospital mortality. Faridpur Med. Coll. J. 2021;16(1):39-41

The neurological emergencies admitted to ICU: Frequency, etiology and outcome at Khartoum state hospitals in the period from October 2019 to April 2020

Neurological emergencies are frequent presentations and often times with devastating short and long term consequences. Neurological disorders are increasingly prevalent in Sub-Saharan Africa with paucity of data on adult neurological emergencies in our context Objective: To study etiologies, patterns of clinical presentation, and outcomes of neurological emergencies patients admitted to ICU.

Molecular and genetic characterization of a large Brazilian cohort presenting hearing loss.

Hearing loss is one of the most common sensory defects, affecting 5.5% of the worldwide population and significantly impacting health and social life. It is mainly attributed to genetic causes, but their relative contribution reflects the geographical region's socio-economic development. Extreme genetic heterogeneity with hundreds of deafness genes involved poses challenges for molecular diagnosis. Here we report the investigation of 542 hearing-impaired subjects from all Brazilian regions to search for genetic causes. Biallelic GJB2/GJB6 causative variants were identified in 12.9% (the lowest frequency was found in the Northern region, 7.7%), 0.4% carried GJB2 dominant variants, and 0.6% had the m.1555A > G variant (one aminoglycoside-related). In addition, other genetic screenings, employed in selected probands according to clinical presentation and presumptive inheritance patterns, identified causative variants in 2.4%. Ear malformations and auditory neuropathy were diagnosed in 10.8% and 3.5% of probands, respectively. In 3.8% of prelingual/perilingual cases, Waardenburg syndrome was clinically diagnosed, and in 71.4%, these diagnoses were confirmed with pathogenic variants revealed; seven out of them were novel, including one CNV. All these genetic screening strategies revealed causative variants in 16.2% of the cases. Based on causative variants in the molecular diagnosis and genealogy analyses, a probable genetic etiology was found in ~ 50% of the cases. The present study highlights the relevance of GJB2/GJB6 as a cause of hearing loss in all Brazilian regions and the importance of screening unselected samples for estimating frequencies. Moreover, when a comprehensive screening is not available, molecular diagnosis can be enhanced by selecting probands for specific screenings.

Patterns of clinical presentation of epilepsy among adult Sudanese epileptic patients seen in Singa Sudan a rural area study experience

Epilepsy is one of the commonest neurological disorders in which brain activity becomes, abnormal, causing seizure and periods of abnormal behavior, sensation, and sometimes loss of awareness.

Superficial Vein Thrombosis

A large German registry on superficial vein thrombosis (SVT) documents that risk profiles, clinical presentation and treatment patterns are highly variable in patients with SVT, including a large variation in anticoagulation treatment modalities, intensities and durations. Inspite of a high percentage of initial anticoagulation there is a substantial risk of subsequent venous thromboembolism (VTE), recurrences or extension after three months. Inspite of current guideline recommendations, one third of the patients receives heparins, oral anticoagulants or no anticoagulation at all. At initial presentation about one quarter of the patients with SVT have a concomitant, frequently asymptomatic VTE. Risk factors for this complication include prior hospitalization, immobilization, prior VTE, autoimmune disorders, higher age, cancer and SVT occurring in a non-varicose veins or SVT-extension into the perforator veins. These risk factors are also associated with thromboembolic complications during follow-up. Based on a large placebo-controlled trial with clinical endpoints (The CALISTO-Study), guidelines recommend Fondaparinux 2.5 mg once daily administered over 4 to 6 weeks. Alternatively, an intermediate dose of low molecular weight heparin can be considered. In high-risk patients, rivaroxaban 10 mg once daily was noninferior compared to Fondaparinux. A rebound of VTE recurrences was observed in both study arms after treatment had been discontinued after 45 days. Further studies are required to determine whether treatment needs to be extended beyond 45 days in high-risk patients.

A RETROSPECTIVE STUDY OF RHINO-ORBITAL MUCORMYCOSIS

BACKGROUND: Mucormycosis is a rapidly progressing, life threatening, opportunistic fungal infection caused by angioinvasive mucorales species of the phylum zygomycetes.The major risk factors of the disease are uncontrolled diabetes mellitus, COVID-19 infection,prolonged usage of high dose of systemic corticosteroids,immunocompromised status and neutropenia. These create a nidus for fungal infection through nasal mucosa which spreads up through paranasal sinuses into orbit manifesting as rhino-orbital mucormycosis. AIM 1. To study the epidemiology and various clinical patterns of presentation of rhino-orbital mucormycosis in post covid patients. 2. To analyse the risk factors associated with progression of rhino-orbital mucormycosis in post covid patients. METHODS: A retrospective study of 25 patients diagnosed as rhino-orbital mucormycosis in post covid patients at Government Kilpauk Medical College Hospital between April and July 2021 was done. RESULTS: In our study,males (64%) are more commonly affected with age preponderance of 51-60 years(28%). The mean age of presentation was 52.1+/-4.49years.The most common symptom of the disease is nasal discharge with sinus and orbital pain(52%).The most common form of presentation is orbital apex syndrome in seven patients(28%).Five patients had loss of vision, of which four were due to central retinal artery occlusion(16%) and one due to cavernous sinus thrombosis.MRI imaging of these patients showed sinus involvement(100%) in all cases ,orbital(48%) and cerebral involvement(8%).The major risk factors responsible for progression of disease in our study are uncontrolled diabetes, prolonged usage of high dose steroid therapy, medial wall involvement, optic nerve head involvement and artery thrombosis. CONCLUSION: Post covid patients presenting with nasal discharge with sinus and orbital pain symptoms need to be diagnosed and managed properly to avoid spread of infection and fatal complications. Aggressive surgical debridement of infected tissues helps in increasing the survival rate of the patients. Patients with risk factors need to be closely monitored to prevent vision loss and cosmetic disfigurement surgeries.

Clinical Presentation Patterns and Survival Outcomes of Hispanic Patients With Gastric Cancer

Hispanic patients have a higher incidence of gastric cancer when compared to non-Hispanics. Outlining clinicodemographic characteristics and assessing the impact of ethnicity on stage-specific survival may identify opportunities to improve gastric cancer care for this population. Patients with gastric cancer in the US Safety Net Collaborative (2012-2014) were retrospectively reviewed. Demographics, clinicopathologic characteristics, operative details, and outcomes were compared between Hispanic and non-Hispanic patients. Early onset gastric cancer was defined as age <50 years. Kaplan-Meier and Cox proportional-hazards models were used to identify the impact of ethnicity on disease-specific survival (DSS). Seven hundred and ninety-seven patients were included, of which 219 (28%) were Hispanic. Hispanic patients were more likely to seek care at safety-net hospitals (66 vs 39%) and be uninsured (36 vs 17%), and less likely to have a primary care provider (PCP) (46 vs 75%; all P<0.05). Hispanic patients were twice as likely to present with early onset gastric cancer (28 vs 15%) and were more frequently diagnosed in the emergency room (54 vs 37%) with both abdominal pain and weight loss (44 vs 31%; all P <0.05). Treatment paradigms, operative outcomes, and DSS were similar between Hispanic and non-Hispanic patients when accounting for cancer stage. Cancer stage, pathologically positive nodes, and negative surgical margins were independently associated with DSS. A diagnosis of gastric cancer must be considered in previously healthy Hispanic patients who present to the emergency room with both abdominal pain and weight loss. Fewer than 50% of Hispanic patients have a PCP, indicating poor outpatient support. Efforts to improve outpatient support and screening may improve gastric cancer outcomes in this vulnerable population.

Oral plasmablastic lymphoma in a HIV‐positive woman: Literature review and case report

AbstractWe provide a comprehensive review of plasmablastic lymphoma (PBL) in HIV‐positive patients and report a case of HIV‐associated oral plasmablastic lymphoma. We complied and discussed demographic, clinical, histopathological, immunohistochemical, therapeutic and prognostic features of 105 cases reported in English and Spanish literature. The inclusion criteria were documented cases of confirmed PBL of the oral cavity in HIV‐positive patients. Only cases with definitive microscopic diagnosis of PBL and description of HIV infection were included. Reports with insufficient clinical information of the patients were excluded. The literature review revealed 105 cases of HIV‐associated oral PBL in 46 published manuscripts. In addition, we reported the case of an aggressive oral PLB arising in a 30‐year‐old HIV‐positive female. This study provides a comprehensive review of clinical and microscopical landscape of PBL. Additionally, our data suggest that case reports should be more rigorous and detailed about the clinical findings, in order to facilitate the understanding of the clinical presentation pattern of oral PBL.

Clinical presentation and mortality risk factors for COVID-19 among diabetic patients in a tertiary care center in South India

BackgroundNon-communicable diseases (NCD) like hypertension, diabetes, cardiovascular and cerebrovascular diseases are the most common comorbidities among COVID-19 patients. The clinical presentation and mortality pattern of COVID-19 are different for patients with comorbidities and without comorbidities. ObjectiveTo determine the clinical presentation of COVID-19 and risk factors for COVID-19 mortality among diabetic patients in a tertiary care hospital in South India. MethodsA record-based cross-sectional study was conducted by reviewing the case records of COVID-19 patients admitted for treatment from June 2020 to September 2020 in a tertiary care centre in South India. Potential risk factors for COVID-19 mortality were analysed using univariate binomial logistic regression, generalized linear models (GLM) with the Poisson distribution. Survival curves were made using the Kaplan–Meier method. ResultsOut of 200 COVID-19 patients with diabetes with a mean (SD) age of 56.1 (11.8) years, 61% were men. The median survival time was slightly lesser in male COVID-19 patients (15 days) as compared to female patients (16 days). The risk of mortality among COVID-19 patients with diabetes is increased for patients who presented with breathlessness (aRR = 4.5 (95% CI: 2.3–8.8)), had positive history of smoking (aRR = 1.9 (95% CI: 1.1–3.8)), who had CKD (aRR = 1.8 (95% CI: 1.1–2.8)) and who had cardiac illness (aRR = 1.6 (95% CI: 0.9–2.7)). ConclusionDiabetes patients with COVID-19 need to be given additional care and monitoring especially if they present with breathlessness, positive history of smoking, cardiac illness and, CKD. Public health campaigns and health education activities to control smoking is needed to reduce the COVID-19 mortality in diabetes patients.

Full nucleotide sequencing of ribosomal DNA internal transcribed spacer of Leishmania species causing cutaneous leishmaniasis in Brazil and its potential for species typing

Species-specific diagnosis still represents a challenge in leishmaniasis management, particularly in regions with multiple endemic species. In Brazil, seven species have been recognized as etiological agents of cutaneous leishmaniasis. The disease comprises complex clinical presentation patterns, classified as localized, diffuse, disseminated and mucocutaneous leishmaniasis. In this study, we characterized the full nucleotide sequence of a region comprising the ribosomal DNA internal transcribed spacers 1 and 2 and 5.8 S gene of reference strains of Leishmania (Viannia) species reported as causative agents of human leishmaniasis in Brazil. The analysis of the nucleotide sequence of this region was able to discriminate species in the Leishmania (Viannia) subgenus and to determine intra- and interspecies phylogenetic relationships.

COVID-19 and Progesterone: Part 1. SARS-CoV-2, Progesterone and its potential clinical use

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection is a global medical challenge. Experience based medicines and therapies are being attempted and vaccines are being developed. SARS-CoV-2 exhibits varied patterns of infection and clinical presentations with varied disease outcomes. These attributes are strongly suggestive of some variables that differ among individuals and that affect the course of SARS-CoV-2 infection and symptoms of COVID-19 (Corona Virus Disease of 2019). Sex hormones vary with ageing, between the sexes, among individuals and populations. Sex hormones are known to play a role in immunity and infections. Progesterone is a critical host factor to promote faster recovery following Influenza A virus infection. Anti-inflammatory effects of progesterone are noted. In part 1 of the current study the regulatory role of progesterone for SARS-CoV-2 infection and COVID-19 is analyzed. The role of progesterone at different stages of the SARS CoV-2 infection is investigated with respect to two types of immunity status: immune regulation and immune dysregulation. Progesterone could have various alleviating impacts from SARS-CoV-2 entry till recovery: reversing of hypoxia, stabilizing of blood pressure, controlling thrombosis, balancing electrolytes, reducing the viral load, regulation of immune responses, damage repair, and clearance of debris among others. The present research adds to the available evidence by providing a comprehensive and thorough evaluation of the regulatory role of progesterone in SARS COV-2 infection, COVID-19 pathogenesis, and immune dysregulation. The available evidence has implications for upcoming studies about pathophysiology of COVID-19, as well as the roles of progesterone and other hormones in other infectious diseases.

Changes in Hospital Discharges with Alcohol-Related Liver Disease in a Gastroenterology and General Medical Unit Following the Introduction of Minimum Unit Pricing of Alcohol: The GRI Q4 Study.

Minimum unit price (MUP) of 50 pence per unit of alcohol was introduced in Scotland on the 1 May 2018. We assessed alcohol-related liver disease (ArLD) discharges from Glasgow Royal Infirmary (GRI) before and after the introduction of MUP. Medical records of all patients discharged from Gastroenterology wards at GRI in the fourth quarter (Q4) of the years 2015-2019 were reviewed. All patients with ArLD were identified, and detailed hospitalization data were collected retrospectively. Active drinking, severity scores, presence of alcoholic hepatitis (AH) and 90-day mortality and readmission rates were assessed. There were fewer ArLD discharges per quarter after MUP than before (mean 80.3 pre-MUP; mean 68 post-MUP), and the proportion of active drinkers was lower post-MUP (64.7 vs. 70.5%). There was a significant fall in the mean number of weekly discharges of individual patients who were actively drinking (4.0 ± 2.0 pre-MUP, 2.8 ± 1.5 post-MUP, P= 0.01). There were no differences in the proportion of patients presenting with ascites, encephalopathy or AH; however, there was a reduction in presentations with acute upper gastrointestinal bleeding from 15.8% pre-MUP to 7.4% post-MUP (P= 0.02; odds ratio 0.42). Severity of liver disease remained unchanged. The 90-day mortality and readmission rates were not significantly different. Since the introduction of MUP there has been a reduction in the absolute numbers of patients discharged with ArLD and the number of individual patients involved at GRI. The pattern of clinical presentation was largely unaffected with overall ArLD severity, readmission rates and 90-day mortality similar pre- and post-MUP.

Differences between genetic dilated cardiomyopathy and myocarditis in children presenting with severe cardiac dysfunction.

Acute myocarditis is an inflammatory disease of the myocardium, and it can present as severe heart failure in children. Differential diagnosis with genetic cardiomyopathy can be difficult. The objective of this study is to identify patterns of clinical presentation and to assess invasive and non-invasive measures to differentiate patients with acute myocarditis from patients with dilated genetic cardiomyopathy. We performed a retrospective descriptive study of all paediatric patients (0–16 years old) that presented with new-onset heart failure with left ventricle ejection fraction < 35% in whom we performed an endomyocardial biopsy (EMB) during the period from April 2007 to December 2020. The patients were classified into two groups: Group 1 included 18 patients with myocarditis. Group 2 included 9 patients with genetic cardiomyopathy. Findings favouring a diagnosis of myocarditis included a fulminant or acute presentation (77.8% vs 33.3%, p = 0.01), higher degree of cardiac enzyme elevation (p = 0.011), lower left ventricular dimension z-score (2.2 vs 5.4, p = 0.03) increase of ventricular wall thickness (88.8% vs 33.3%, p = 0.03) and oedema in the EMB. Seven (77.8%) patients with genetic cardiomyopathy had inflammation in the endomyocardial biopsy fulfilling the diagnostic criteria of inflammatory cardiomyopathy.Conclusion: Differentiating patients with a myocarditis from those with genetic cardiomyopathy can be challenging, even performing an EMB. Some patients with genetic cardiomyopathy fulfil the diagnostic criteria of inflammatory cardiomyopathy. Using invasive and non-invasive measures may be useful to develop a predictive model to differentiate myocarditis from genetic cardiomyopathy. What is Known:• Acute myocarditis could present with cardiogenic shock in paediatric patients.• Parvovirus B19 is the main cause of myocarditis in this population.What is New:• Current diagnostic criteria for myocarditis have limited use in paediatric patients presenting with new-onset heart failure.• Some patients with a genetic cardiomyopathy and a new-onset heart failure fulfill the diagnostic criteria of inflammatory cardiomyopathy.Supplementary informationThe online version contains supplementary material available at 10.1007/s00431-021-04175-z.

High bone mass phenotype in a cohort of patients with Osteogenesis Imperfecta caused due to BMP1 and C-propeptide cleavage variants in COL1A1

ObjectivesOsteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; extra-skeletal features in OI include blue sclerae, dentinogenesis imperfecta, skin laxity and joint hyper-extensibility. Most patients with OI are thought to have a low bone mass but contrary to expectations there are certain forms of OI with high bone mass which this study explores in further detail. MethodA cohort of n = 6 individuals with pathogenic variants in BMP1 and the C-propeptide cleavage variants in COL1A1 were included in this study. Detailed clinical and radiological phenotyping was done and correlated with genotype to identify patterns of clinical presentation and fracture history in this cohort of patients. This data was compared to previously reported literature in this group. Results2 patients with BMP1 and 4 patients with pathogenic variants in C-propeptide region in COL1A1 were deep-phenotyped as part of this study and 1 patient with C-propeptide variant in COL1A1, showed low bone mineral density. In those with an elevated bone mineral density, this became even more apparent on bisphosphonate therapy. Patients in this cohort had variable clinical presentation ranging from antenatal presentation to more of an insidious course resulting in later confirmation of genetic diagnosis up to 19 years of age. ConclusionsPatients with pathogenic variants in the C-propeptide region of COL1A1/A2 and BMP1 appear to have a high bone mass phenotype with increased sensitivity to bisphosphonate therapy. It is important to closely monitor patients with these genotypes to assess their response to therapy and tailor their treatment regime accordingly.

Varied Clinical Presentations of COVID-19 in Pregnant Women in Tertiary Care Hospital of Lahore-Pakistan

Background: The whole world is facing one of the biggest health related disasters of the century. As a novel disease, Covid-19 has so many parameters yet to explore. Aim: To explore varied pattern of clinical presentation of COVID-19 in obstetric population in tertiary care hospital. Study design: Cross-sectional study. Methodology: This study with enrolled pregnant females (n=36) was carried out after ethical review committee’s (ERC) approval at Department of Gynecology &amp; Obstetrics, Sir Ganga Ram Hospital, Lahore-Pakistan over a period of 3 months in 2020. Data was analyzed by SPSS software, version-20. Presenting symptoms of subjects were presented as frequency and percentage. Results: Total 36 patients were selected. Twenty four (66.66%) patients were symptomatic while the rest 12 (33.33%) patients were asymptomatic. Conclusion: We concluded that clinical presentation of COVID-19 pregnant patients is similar as in rest of the world and it is also same as in general population. Keywords: Covid-19, Pregnant Patients and Clinical Presentation.

VARIATION OF CLINICAL PATTERNS OF COVID-19 DISEASE IN CHILDREN IN THE FIRST YEAR OF PANDEMIC

Introduction. SARS-CoV-2 infection has put humanity to the test since December 2019, quickly becoming a global public health problem. There is a significant difference between the pediatric population versus the adult population in terms of infection rate, modes of transmission, clinical manifestations. The study aimed to identify some patterns of clinical presentation of SARS-CoV-2 infection in the pediatric population in “Dr. Victor Gomoiu“ Children’s Clinical Hospital in 2020, also following any possible variations between the first two waves of the pandemic. Materials and methods. The study was based on the descriptive observational analysis of two groups of SARS-CoV-2 positive patients, corresponding to the two pandemic waves. Patients were classified into some clinical patterns, using the definition of suspected / confirmed case established by the National Institute of Public Health (INSP) and transmitted through the National Center for Surveillance and Control of Communicable Diseases (CNSCBT), as well as the recommendations of the international guidelines and protocols. Results. There are found to be present some mild clinical forms of the disease secondary to SARS-CoV-2 virus infection, most children showing digestive symptoms. Starting with August (Group 2) there is a significant increase in the number of cases, as well as the appearance of a larger number of cases that associated respiratory symptoms. Conclusions. The study is showing the low impact of the SARS-CoV-2 virus infection in the pediatric population, compared to adults, especially in the first wave of the pandemic, the children having been considered “the hidden victims” of the pandemic, rather than its face. It is considered necessary the long-term monitoring of SARS-CoV-2 infected children, as the remote consciousness of the infection having been incompletely elucidated. Analyzing the epidemiological data obtained in the study, we are concluding the need for some sustained global efforts to define, more clearly, the variations in the patterns of the presentation of SARS-CoV-2 infection in children, in the context of the evolution of the pandemic.

Aautoimmune Hemolytic Anemia: Pattern of Clinical Presentation and Management Outcome — a Nine Year Observation from a Tertiary Care Hospital in Saudi Arabia

Introduction: Autoimmune hemolytic anemia (AIHA) is characterized by production of auto-antibodies that bind to antigen on the erythrocyte surface that leads to its premature destruction and removal from the circulation by macrophages. Occurrence of AIHA in children and adolescents is rare, exact incidence unknown. Objective of this retrospective study was to assess clinical and laboratory characteristics, and management outcome of patients diagnosed with AIHA seen at Pediatric Hematology/Oncology department of King Faisal specialist Hospital and Research Center ,Riyadh from 2005 to 2014. Method: Retrospective chart review of patients (1-14 yrs.) diagnosed with AIHA was conducted. Children were excluded if they have congenital hemolytic anemia, such as hemoglobinopathies, congenital membranopathy and erythrocyte enzyme deficiencies. Result: Thirty-one patients identified, 19(61%) female and 12(39%) male with a median age at diagnosis of 6 years (0.1-12.4). The direct Coombs test was positive in 23 (74%) patients. Underlying diseases observed as cause of AIHA in 14 (45%) patients: majority secondary to viral infections followed by severe combined immunodeficiency syndrome post bone marrow transplant GVHD complication, while systemic lupus erythematosus, antiphospholipid antibody syndrome, autoimmune hepatitis, hypereosinophilic syndrome, Hyper IgE syndrome, post-liver transplant, diabetes was observed in individual cases. Remaining 17 (55%) patients diagnosed as primary AIHA .Corticosteroids and/or immunoglobulin was given as first line of treatment to 64.5% (20) patients while 35.5% (11) required Rituximab and/or splenectomy as second line of treatment, of which 73%(8) were diagnosed as primary AIHA. Five-year overall survival (Kaplan-Meir) rate of 89% was observed with twenty-seven alive patients showing partial or complete response ,while four patients died due to underlying diseases.Conclusion: Our results demonstrates patients responding to first line of treatment, however serious cases required management through second line of treatment. Further, a regional multicenter observational study will enable better understanding of differences in disease presentation and treatment outcomes. DisclosuresNo relevant conflicts of interest to declare.

Ibrutinib: A Risk Factor for Invasive Fungal Infections?

Background : Invasive fungal infections (IFI) are life threatening infections reported mainly in acute leukemia patients with prolonged deep neutropenia and patients post bone marrow or organ transplants.IFI are an uncommon consequence of CLL and NHL, cranial (brain, sinuses) involvement is distinctly rare. Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. The Italian SEIFEM group reported the frequency of IFI in a retrospective multicenter study of CLL patients as 4 per 1104 patients over 5 years and among patients with NHL 27 per 3457 over 5 years. In a report combining 8 European countries, only 10 cases of CNS aspergillosis were identified in non-neutropenic ICU patients, between the years 2006-2011.Ibrutinib is a kinase inhibitor effective in the treatment of CLL and other NHLs has also been shown to have inhibitory activity against macrophages essential for defense against molds and Cryptococcus species.In 2016 we described 3 non-neutropenic CLL patients who developed invasive cranial aspergillosis while on treatment with ibrutinib (NEJM, 2016). In all three patients this developed shortly after beginning therapy with ibrutinib. All were on steroids before starting therapy and the course was fulminant. In two of the three patients the infection was fatal.Recently Lionakis et al (Cancer Cell, 2017) reported invasive aspergillosis in seven of 18 (39%) PCNSL patients treated with ibrutinib. Sites of involvement were cranial, pulmonary or both. None had prolonged neutropenia. The authors suggest that ibrutinib impairs fungal immune surveillance which may be exacerbated by the combined use of steroids and/or chemotherapy.In order to better understand if these cases were isolated events or connected to therapy with ibrutinib, in this retrospective, investigator initiated international study we summarize the clinical and laboratory parameters of patients who developed invasive fungal infections while being treated with ibrutinib.Methods : Patients with IFI were identified by treating physicians. Clinical and laboratory data were collected and managed using REDCap electronic data capture tools hosted at Shaare-Zedek Medical Center1(doi:10.1016/j.jbi.2008.08.010). The study received an IRB approval.Results : Twenty-eight patients with IFI were enrolled from 15 centers in 6 countries by 18 physicians (Table 1). The median age at the start of ibrutinib treatment was 71, and 71% had CLL. The median number of prior therapies was 3. Six out of 11 (54%) of patients with FISH results had 17pdel/ TP53 mutations. Twenty patients (71%) had at least 1 predisposing factor, 36% were treated with steroids when starting ibrutinib and three patients were post bone marrow transplants. The median lowest neutrophil count in the month before starting ibrutinib was 1.5 x 103/µl. Aspergillus was the main pathogen (64% of the cases), the main site being the lungs (75%) and cranial (brain, sinuses) in 57%. Six patients had multiple sites of involvement. The diagnosis of the pathogen was definite in 25 (89%) and probable in 11%. IFI resolved in only 25% of patients and mortality was 61% from all causes.Discussion : This cohort of 28 patients developed IFI on therapy with ibrutinib in the absence of common risk factors. Other unique features of our cohort are the high prevalence of CNS involvement (almost half of the patients); and the presentation of Aspergillus and Mucor ycosis spp infections at multiple sites, which is not a typical presentation for these pathogens. As the differential diagnosis was wide, most patients went through an invasive diagnostic procedure and therefore a high rate of a definite diagnosis was achieved rapidly in comparison to acute leukemia patients. Our preliminary results suggest that ibrutinib might be a risk factor for IFI resulting in unique patterns of clinical presentations. Subsequent comparative studies are urgently needed to better identify which patients on ibrutinib treatment are at greater risk for IFI. [Display omitted] DisclosuresBrown:Astellas Pharma: Consultancy; Sun BioPharma: Consultancy, Research Funding; Redx: Consultancy; Infinity Pharmaceuticals: Consultancy; Roche/Genentech: Consultancy; Janssen: Consultancy; Celgene: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy, Honoraria; Pfizer: Consultancy; Janssen Oncology: Honoraria; Pharmacyclics: Consultancy; Gilead: Consultancy, Research Funding. Nijland:Novartis Pharmaeuticals Corporation: Honoraria; Kite Pharma: Honoraria; Roche: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; MIllennium/Takeda: Honoraria, Research Funding; Mundipharma: Honoraria; Gilead Sciences: Honoraria; BMS: Honoraria; MSD: Honoraria; Amgen: Honoraria.

A Case Report on Budd Chiari Syndrome – Which Mimics Multiple Disorders

Background: Budd Chiari Syndrome (BCS) is the king of disorders which will mimic other disorders like chronic biliary disease, constrictive pericarditis, sinusoidal obstruction syndrome and so on, as it be like that, it is less diagnosed and treated in many countries. The prevalence of BCS is one in one million population, so it is a very rare case therefore it should be treated properly because many disorders like hematologic or malignant disease are the complications of BCS [1], [2].&#x0D; Objective: To access the clinical variants of BCS along with the similarities and differences in clinical presentation, diagnostic approaches, and general treatment pattern which mimic, BCS thus gives the physician a clear outline about those disorders.&#x0D; Method: A man of 42 years old having BCS was taken for the study to carry out the differences in clinical features of BCS which distinguish the mimicking disorders. Clinical presentations were noted. Laboratory tests and diagnostic tests showed that the patient is having comorbidities including fatty liver with cholelithiasis, mild splenomegaly, liver parenchyma diseases, large esophageal varies with signs of recent hemorrhage, port hypertensive gastropathy and minimal ascites [3]. Patient get discharged after feeling better.&#x0D; Result: This patient is having chronic BCS with DIPS dysfunction. The patient had no history of liver disease before diagnosing BCS. BCS is almost curable when it is diagnosed correctly as early as possible. If not diagnosed early and treated well, comorbidities will occur, and it will affect the patient quality of life.&#x0D; Discussion: Early detection and proper treatment will help to control the disease up to an extent. This is depending on the physician’s knowledge. Hence, this case study clearly explains the disorders which mimic BCS for better understanding.