Clinical Laboratory Features Research Articles

Emerging functions of FMNL1 in myeloid neoplasms: insights from bioinformatics to biological and pharmacological landscapes.

Myeloid neoplasms encompass disorders characterized by abnormal myeloid cell proliferation and differentiation, including myelodysplastic syndromes (MDS), myeloproliferative neoplasms, acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Formin-like protein 1 (FMNL1) is involved in the regulation of the actin cytoskeleton and is predominantly expressed in hematopoietic cells. Given its role in leukemia cell proliferation, survival, migration, and invasion, this study investigates FMNL1 expression in normal hematopoiesis and myeloid neoplasms and explores associations with clinical-laboratory characteristics, mutational status, and survival outcomes in AML. Transcript levels of FMNL1 from several blood-forming cell populations and myeloid neoplasms were extracted from publicly available databases. Myeloid neoplasm cell lines were used for gene/protein expression and cell differentiation studies. Functional genomics analysis was performed using RNA-seq data from The Cancer Genome Atlas (TCGA) AML study, and drug sensitivity predictions were investigated using Beat AML and Genomics of Drug Sensitivity in Cancer (GDSC) datasets. Statistical analyses assessed the impact of FMNL1 expression on clinical outcomes. FMNL1 was highly expressed in metamyelocytes, neutrophils, and monocytes compared to hematopoietic stem cells, and its expression increased with granulocytic differentiation. FMNL1 expression was elevated in AML and CML patients compared to healthy donors. FMNL1 expression was not significantly associated with clinical-laboratory characteristics or survival outcomes but showed a higher frequency of WT1 transcription factor (WT1) mutations with low FMNL1 expression in AML patients. High FMNL1 expression in AML correlated with immune response and inflammatory activity pathways. FMNL1 mRNA levels influenced drug sensitivity in AML models, with correlations observed for specific antineoplastic agents. FMNL1 plays a potential role in granulocyte differentiation and function, and its differential expression is linked to critical signaling pathways in leukemogenesis and inflammation. These findings highlight FMNL1's potential therapeutic implications in myeloid neoplasia, warranting further investigation.

Pharmacological inhibition of ezrin reduces proliferative and invasive phenotype in acute lymphoblastic leukemia cells

Ezrin (EZR) is an actin-associated protein that is often upregulated in cancers. Here we investigate the role of EZR in acute lymphoblastic leukemia (ALL) and explore the therapeutic potential of a pharmacological EZR inhibitor, NSC305787. ALL patient cohorts exhibit significantly elevated EZR mRNA levels, indicating its association with the malignant phenotype. Notably, EZR expression does not impact survival outcomes or relevant clinical-laboratory characteristics, suggesting a role in disease initiation rather than therapy response. NSC305787 induces a dose-dependent reduction in ALL cell viability, and is more potent than a related EZR inhibitor, NSC668394. NSC305787 has multiple effects on ALL cells, including apoptosis induction, clonal growth reduction, and inhibition of cell cycle progression. Importantly, it diminishes adhesiveness and invasiveness in ALL cells. Proteomics analysis highlights changes in translation, RNA catabolism, and cell cycle regulation, emphasizing the broad impact of EZR inhibition on ALL cell biology. Ex vivo assays with primary cells from acute myeloid leukemia (AML) and ALL patients demonstrate NSC305787's efficacy across a molecularly heterogeneous group, independent of risk stratification or recurrent mutations. Notably, NSC305787 shows heightened potency in ALL cells, suggesting its potential as a targeted therapy. In conclusion, our results report high EZR expression in adult ALL patients and support NSC305787 as a promising targeted therapy for ALL that should be further explored.

Could Clinical-Laboratory Features Recognize Functional High Risk Multiple Myeloma Patients? a Real-World Analysis

Could Clinical-Laboratory Features Recognize Functional High Risk Multiple Myeloma Patients? a Real-World Analysis

Current Trends in HIV Infection in the Republic of Crimea.

The aim of this study was to analyse the trends in HIV infection, including diagnostic ones, in the Republic of Crimea in the period of 2014-2023. The source of data for this study was various statistical forms and reports. The findings revealed a significant downward trend in HIV incidence and a significant upward trend in HIV prevalence. The mortality rate was stable. The coverage of HIV testing and antiretroviral therapy increased over time. The number of patients with a suppressed viral load in the Republic fluctuated in different years of observation and reached 81% in 2023. In the second part of this study, we analysed the demographic and clinical laboratory characteristics of newly diagnosed patients with HIV. A predominance of men was noted. The proportion of injection drug users (IDUs) decreased, and the proportion of new HIV infection cases through heterosexual contacts increased. An increase in the median age of patients was also noted. Analysis of CD4 cell counts revealed significant differences between subgroups by gender, age, and route of infection. The longest time to disease detection was typical for IDUs. A comprehensive assessment of HIV infection trends in Crimea allows us to evaluate the effectiveness of measures and decisions taken on the issue of HIV infection.

SARS-CoV2 pneumonia patients admitted to the ICU: Analysis according to clinical and biological parameters and the extent of lung parenchymal lesions on chest CT scan, a monocentric observational study

Background CT-scan and inflammatory and coagulation biomarkers could help in prognostication of COVID-19 in patients on ICU admission. Objective The objectives of this study were to measure the prognostic value of the extent of lung parenchymal lesions on computed tomography (CT) and of several coagulation and inflammatory biomarkers, and to explore the characteristics of the patients depending on the extent of lung parenchymal lesions. Design Retrospective monocentric observational study achieved on a dataset collected prospectively. Setting Medical ICU of the university hospital of Clermont-Ferrand, France. Patients All consecutive adult patients aged ≥18 years admitted between 20 March, 2020 and 31 August, 2021 for COVID-19 pneumonia. Interventions Characteristics at baseline and during ICU stay, and outcomes at day 60 were recorded. The extent of lung parenchyma lesions observed on the chest CT performed on admission was established by artificial intelligence software. Measurements Several clinical characteristics and laboratory features were collected on admission including plasma interleukin-6, HLA-DR monocytic–expression rate (mHLA-DR), and the extent of lung parenchymal lesions. Factors associated with day-60 mortality were investigated by uni- and multivariate survival analyses. Results 270 patients were included. Inflammation biomarkers including the levels of neutrophils, CRP, ferritin and Il10 were the indices the most associated with the severity of the extent of the lung lesions. Patients with more extensive lung parenchymal lesions (≥ 75%) on admission had higher CRP serum levels. The extent of lung parenchymal lesions was associated with a decrease in the PaO2/FiO2 ratio(p<0.01), fewer ventilatory-free days (p = 0.03), and a higher death rate at day 60(p = 0.01). Extent of the lesion of more than 75% was independently associated with day-60 mortality (aHR = 1.72[1.06; 2.78], p = 0.03). The prediction of death at day 60 was improved when considering simultaneously biological and radiological markers obtained on ICU admission (AUC = 0.78). Conclusions The extent of lung parenchyma lesions on CT was associated with inflammation, and the combination of coagulation and inflammatory biomarkers and the extent of the lesions predicted the poorest outcomes.

Clinical characteristics, laboratory features and genetic profile of hemoglobin E (HBB:c.79 G > A)/β (nucleotide -28 A > G) (HBB:c.-78 A > G) -thalassemia subjects identified from community- and hospital-recruited cohorts

Despite several existing laboratory-based studies of hemoglobin (Hb) E (HBB:c.79 G > A)/ β (nucleotide (NT) -28 A > G) (HBB:c.-78 A > G) -thalassemia, no reports have ever provided clinical severity information as well as dependency of blood transfusion. Previously, a comparative study of community- and hospital-recruited Hb E/β-thalassemia subjects was conducted in the lower northern Thailand between June 2020 and December 2021. A mobile medical team visited each community hospital on-site, collecting clinical severity parameters, and conducting Hb and DNA analyses. The control included Hb E/β-thalassemia patients undergoing transfusions. Subgroup study of adult Hb E/β (NT -28 A > G) -thalassemia subjects was subsequently conducted. Additional pediatric individuals were recruited from prenatal diagnosis databases. Twenty adult and nine pediatric subjects were enrolled; all were classified as having mild disease severity. Twenty-two individuals (75.9 %) were asymptomatic. Six adults (20.7 %) required blood transfusion. The mean Hb level of subjects without transfusion (23 [79.3 %]) was 10.77 ± 1.10 g/dL. Hb analysis revealed a distinct EFA pattern with low Hb F fraction. The positive impact of genetic modifiers could not be statistically demonstrated except rs7482144-XmnI. These findings could provide essential information for parents carrying fetuses with Hb E/β (NT -28 A > G) -thalassemia.

Clinical characteristics and labial gland pathological features in children with systemic lupus erythematosus complicated by Sjögren's syndrome

To study the clinical manifestations, laboratory features, and labial gland pathological features in children with systemic lupus erythematosus (SLE) complicated by Sjögren's syndrome (SS). A retrospective analysis was conducted on 102 children with SLE who underwent labial gland biopsies at Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2022. The children were divided into two groups based on the presence of SS: the SLE with SS group (SLE-SS; 60 children) and the SLE-only group (42 children). According to the focus score (FS) of the labial glands, children in the SLE-SS group were further subdivided into FS≥4 subgroup (26 children) and FS<4 subgroup (34 children). The clinical data of the groups were compared. Compared to the SLE-only group, children in the SLE-SS group had less skin and mucosal involvement, were more likely to have positive anti-SSA and anti-SSB antibodies, and had higher levels of rheumatoid factor (P<0.05). There was no significant difference in treatment protocols between the two groups (P>0.05). Compared to the FS<4 subgroup, the FS≥4 subgroup had more frequent musculoskeletal involvement (P<0.05), but there was no significant difference in SLE disease activity or other major organ involvement between the subgroups (P>0.05). Children with SLE complicated by SS are less likely to have skin and mucous membrane involvement and exhibit specific serological characteristics. The SLE-SS children with an FS≥4 are more likely to experience musculoskeletal involvement. However, FS is not associated with disease activity or other significant organ damage.

A Review of Myositis-Associated Interstitial Lung Disease.

There is a well-established relationship between different subsets of idiopathic inflammatory myopathies (IIMs, myositis) and interstitial lung disease (ILD), with lung complications sometimes presenting prior to myopathic manifestations. The subtypes of myositis include those that are strongly associated with ILD, such as polymyositis (PM) and dermatomyositis (DM). Research has shown that in certain patients, these can then be further divided into subtypes using myositis-specific antibodies (MSAs), which are specific for myositis, and myositis-associated antibodies (MAAs), which can be found in myositis in overlap syndromes with other connective tissue diseases (CTDs). Notably, certain MSAs and MAAs are associated with ILD in patients with myositis. The clinical presentations of ILD in patients with myositis can vary widely and can be insidious in onset and difficult to diagnose. As ILD can progress rapidly in some cases, it is essential that clinicians are able to identify and diagnose ILD in patients with myositis. For this reason, the aim of this review is to highlight the clinical features, diagnostic criteria, important histopathologic, laboratory, and radiographic features, and treatment modalities for those patients with myositis-associated ILD.

Treatment response in patients with clinical and supportive laboratory features of chronic inflammatory demyelinating polyneuropathy without demyelinative findings on nerve conduction studies: A retrospective study.

Not all patients with chronic inflammatory demyelinating polyneuropathy (CIDP) have evidence of demyelination on nerve conduction studies (NCS). Patients with "supportive" evidence of CIDP on cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), ultrasound (US), or nerve biopsy but not on NCS, often receive immunomodulating therapy. We evaluated the treatment response of patients with clinical and supportive features of CIDP lacking NCS evidence of demyelination. Retrospective chart review was conducted on 232 patients who met CIDP clinical criteria and were treated with disease-modifying therapy. Patients included did not have NCS criteria of demyelination, but did have supportive CSF, MRI, or US findings consistent with CIDP. A positive treatment response was defined as at least a one-point improvement in the modified Rankin scale (mRS), or a four-point increase in the Medical Research Council sum score (MRCSS). Twenty patients met criteria: 17 of the 18 (94%) patients with CSF protein >45 mg/dL, 6 of the 14 (43%) with MRI lumbosacral root or plexus enhancement, and 4 of the 6 (67%) with enlarged proximal nerves on US. Eighteen patients received intravenous immunoglobulin, 10 corticosteroids, one plasma exchange, and six other immunomodulatory therapies. Twelve patients had a positive treatment response on the MRCSS or mRS. The presence of MRI lumbosacral root or plexus enhancement was associated with a positive treatment response. A trial of immunomodulating treatment should be considered for patients with clinical features of CIDP in the absence of NCS evidence of demyelination, particularly when there is MRI lumbosacral root or plexus enhancement.

Tibial cortex transverse transport surgery improves wound healing in patients with severe type 2 DFUs by activating a systemic immune response: a cross-sectional study.

Tibial cortex transverse transport (TTT) surgery has become an ideal treatment for patients with type 2 severe diabetic foot ulcerations (DFUs) while conventional treatments are ineffective. Based on our clinical practice experience, the protective immune response from TTT surgery may play a role against infections to promote wound healing in patients with DFUs. Therefore, this research aimed to systematically study the specific clinical efficacy and the mechanism of TTT surgery. Between June 2022 and September 2023, 68 patients with type 2 severe DFUs were enrolled and therapized by TTT surgery in this cross-sectional and experimental study. Major clinical outcomes including limb salvage rate and antibiotics usage rate were investigated. Ten clinical characteristics and laboratory features of glucose metabolism and kidney function were statistically analyzed. Blood samples from 6 key time points of TTT surgery were collected for label-free proteomics and clinical immune biomarker analysis. Besides, tissue samples from 3 key time points were for spatially resolved metabolomics and transcriptomics analysis, as well as applied to validate the key TTT-regulated molecules by RT-qPCR. Notably, 64.7% of patients did not use antibiotics during the entire TTT surgery. TTT surgery can achieve a high limb salvage rate of 92.6% in patients with unilateral or bilateral DFUs. Pathway analysis of a total of 252 differentially expressed proteins (DEPs) from the proteomic revealed that the immune response induced by TTT surgery at different stages was first comprehensively verified through multi-omics combined with immune biomarker analysis. The function of upward transport was activating the systemic immune response, and wound healing occurs with downward transport. The spatial metabolic characteristics of skin tissue from patients with DFUs indicated downregulated levels of stearoylcarnitine and the glycerophospholipid metabolism pathway in skin tissue from patients with severe DFUs. Finally, the expressions of PRNP (prion protein) to activate the immune response, PLCB3 (PLCB3, phospholipase C beta 3) and VE-cadherin to play roles in neovascularization, and PPDPF (pancreatic progenitor cell differentiation and proliferation factor), LAMC2 (laminin subunit gamma 2) and SPRR2G (small proline rich protein 2G) to facilitate the developmental process mainly keratinocyte differentiation were statistically significant in skin tissues through transcriptomic and RT-qPCR analysis. Tibial cortex transverse transport (TTT) surgery demonstrates favorable outcomes for patients with severe type 2 DFUs by activating a systemic immune response, contributing to anti-infection, ulcer recurrence, and the limb salvage rate for unilateral or bilateral DFUs. The specific clinical immune responses, candidate proteins, genes, and metabolic characteristics provide directions for in-depth mechanistic research on TTT surgery. Further research and public awareness are needed to optimize TTT surgery in patients with severe type 2 DFUs.

Thrombotic Microangiopathy and acute kidney injury with malaria: One-year experience at SIUT

Acute Kidney Injury (AKI) may occur with malarial infection, falciparum and vivax species. AKI, anemia, jaundice and thrombocytopenia are documented associated findings. Thrombotic Microangiopathy (TMA) in relation with malarial AKI is less reported subject. Patients and Methods: Between January 2023 to December 2023, patients with diagnosis of malaria and developing AKI (according to KDOQI guidelines definition), who were brought to our institute, showing some clinical and basic laboratory features of TMA or shown delayed recovery were subjected to renal biopsy. Only those where histological diagnosis of TMA was confirmed were included in present study. Results: During last calendar year 17 adult patients fulfilled criteria of malaria, AKI and TMA, of these 15 (88%) were female. Malaria was caused by vivax species in 15 (88%), falciparum in one and one patient who arrived late here had report of malarial parasite seen in private laboratory, species was not mentioned. All had febrile illness, associated symptoms were oligo-anuria in 15(88%), vomiting 13 (76%), body aches 12(70%), and jaundice in 6 (35%). The mean age was 26.58±8.9 years, hemoglobin 7.84±1.78, urea 162.70±67.94, creatinine 8.06±4.69 and LDH 1434.05±925.36. Hemodialysis was required in 16 (94%) patients. After getting biopsy results plasma exchanges done in 15 (88%) patients. Complete recovery of renal function seen in 6 (35%), CKD in 7 (41%). Conclusion: TMA in association with malarial AKI is less reported in literature. Vivax malaria has shown devastating complications with this previously labelled “benign” species of plasmodium.

Timing and Modality of Kidney Replacement Therapy in Children and Adolescents

IntroductionThe choice and timing of kidney replacement therapy (KRT) is influenced by clinical factors, laboratory features, feasibility issues, family preferences and clinicians´ attitudes. We analyzed the factors associated with KRT modality and timing in a multicenter, multinational prospective pediatric cohort study. Methods695 pediatric chronic kidney disease patients enrolled into the 4C study at age 6 to 17 years with estimated glomerular filtration rate (eGFR) 10 to 60 ml/min/1.73 m2 were investigated. Competing risk regression was performed to identify factors associated with initiation of dialysis or pre-emptive transplantation (Tx), including primary renal diagnosis, demographics, anthropometrics and laboratory parameters. ResultsDuring the 8-year observation period, 342 patients (49%) started KRT. Of these, 200 patients started dialysis whereas 142 patients underwent pre-emptive Tx. A lower eGFR at enrolment (HR (hazard ratio) 0.76 [95% confidence interval 0.74-0.78], a steeper eGFR slope (HR 0.90 [0.85-0.95] and a higher systolic blood pressure standard deviation score (SDS) (HR 2.07 [1.49-2.87]) increased the likelihood of KRT initiation. Patients with glomerulopathies were more likely to start dialysis than children with CAKUT (HR 3.81 [2.52-5.76]). Lower BMI SDS (HR 0.73 [0.6-0.89]) and lower hemoglobin (HR 0.8 [0.72-0.9]) were associated with higher likelihood of dialysis. A significant center effect was observed, accounting for 6.8% (dialysis) to 8.7% (pre-emptive Tx) of explained variation. ConclusionThe timing and choice of KRT in pediatric patients is influenced by the rate of kidney function loss, the underlying kidney disease, nutritional status, blood pressure, anemia and center-specific factors.

Evaluation of clinical and laboratory characteristics of dengue viral infection and risk factors of dengue hemorrhagic fever: a multi-center retrospective analysis

BackgroundDengue Viral Infection (DVI) has become endemic in Pakistan since the first major outbreak in Karachi in 1996. Despite aggressive measures taken by relevant authorities, Pakistan has been dealing with a worsening dengue crisis for the past two decades. DHF is severe form of dengue infection which is linked with significant morbidity and mortality. Early identification of severe dengue infections can reduce the morbidity and mortality. In this context we planned current study in which we find out the different factors related with DHF as well as clinical laboratory features of DHF and compare them to DF so that patients can be best evaluated for DHF and managed accordingly at admission.MethodsRetrospective study conducted over a period of 6 years (2013–2018) in two tertiary care hospitals in Pakistan. Data were collected by using a pre-structured data collection form. Data were statistically analyzed to determine the clinical and laboratory characteristics of DVI and risk factors of dengue hemorrhagic fever (DHF).ResultsA total 512 dengue cases (34.05 ± 15.08 years; Male 69.53%) were reviewed. Most common clinical manifestations of DVI were fever (99.60%), headache (89.1%), chills (86.5%), rigors (86.5%), myalgia (72.3%). Less common clinical manifestations were vomiting (52.5%), arthralgia (50.2%) and skin rashes (47.5%). Furthermore, nasal bleeding (44.1%), gum bleeding (32.6%), pleural effusion (13.9%) and hematuria (13.1%) were more profound clinical presentations among DHF patients. Mortality rate was 1.5% in this study. Logistic regression analysis indicated that delayed hospitalization (OR: 2.30) and diabetes mellitus (OR:2.71), shortness of breath (OR:2.21), association with risk groups i.e., living near stagnant water, travelling to endemic areas, living in endemic regions (OR:1.95), and presence of warning signs (OR:2.18) were identified as risk factors of DHF. Statistically we found that there is strong association of diabetes mellitus (DM) with DHF while the patient suffering from DM individually had higher odds (2.71) of developing DHF than patients without disease.ConclusionsThe current study demonstrated that the clinical and laboratory profiles of DF and DHF are significantly distinct. Significant predictors of DHF were advanced age, diabetes mellitus, ascites, pleural effusion, thick gallbladder and delayed hospitalization. The identification of these factors at early stage provides opportunities for the clinicians to identify high risk patients and to reduce dengue-related morbidity and mortality.

The importance of histomorphological features and ERG expression in the diagnosis of malignancy in cases with atypical small acinar proliferation.

Atypical small acinar proliferation (ASAP) cases typically require rebiopsy, which are invasive and associated with increased risk of complications. Our aim in this study was to determine the importance of laboratory and histological findings and E-26 transformation-specific-related gene (ERG) expression in the diagnosis of malignancy. Between March 2016 and March 2022, 84 patients who were diagnosed with ASAP on biopsy or rebiopsy were included in the study. Clinical-laboratory features of age, serum prostate-specific antigen level, and histopathological features were compared and included multifocality, number of suspicious acini, nuclear enlargement, nucleolar prominence, hyperchromasia, cytoplasmic amphophilia, luminal amorphous acellular secretion, crystalloid presence, infiltrative appearance, inflammation, atrophy, α-methyl acyl-CoA racemase, p63, and/or high molecular weight cytokeratin were analyzed. In addition, ERG expression was evaluated immunohistochemically. Statistically significant correlation was found between nucleolar prominence, nuclear hyperchromasia, crystalloid presence, infiltrative pattern, and prostate cancer (p < .001). In 19 of 84 cases (22.6%) ERG was positive in the nucleus. Prostate cancer was diagnosed at rebiopsy in 15 of the 19 ERG-positive cases (78.9%). A statistically significant correlation was found between ERG positivity and prostate cancer (p= .002). Our findings suggest that evaluation of these markers during initial transrectal ultrasound biopsies may decrease and prevent unnecessary prostate rebiopsy.

Clinical phenotype and laboratory characteristics of 93 patients with congenital fibrinogen disorders from unrelated 36 families

BackgroundCongenital fibrinogen disorders (CFDs) are rare bleeding disorders (RBDs) caused by mutations in 1 of the 3 fibrinogen genes (FGA, FGB, and FGG). ObjectivesTo investigate the clinical phenotype, laboratory features, diagnosis, treatment, and prognosis of CFDs. MethodsClinical data of 93 subjects with CFDs identified from June 2018 to December 2023 were retrospectively analyzed. ResultsAmong the 93 patients, there were 46 males (49.5%) and 47 females (50.5%), with a median age of 23 years. Fifty-three of 93 (57%) subjects experienced bleeding, 3/93 (3.2%) experienced thrombosis, and 37/93 (39.8%) were asymptomatic. Females were more prone to experience bleeding (P < .0001). The 93 patients exhibited prolonged thrombin time, significantly decreased fibrinogen activity (Fg:C), and normal or decreased fibrinogen antigen. The 93 patients included 3 with hypofibrinogenemia, 16 with hypodysfibrinogenemia, and 74 with dysfibrinogenemia. Among the 53 patients with bleeding, bleeding episodes were identified in 3.8% (2/53), 20.8% (11/53), and 75.5% (40/53) patients with hypofibrinogenemia, hypodysfibrinogenemia, and dysfibrinogenemia, respectively. Genetic analysis was performed on 22 cases from 8 pedigrees, revealing 10 mutations, including 1 novel splice mutation. Twenty-eight (30.1%) subjects received replacement therapy to treat or prevent bleeding, consisting of 8 fresh frozen plasma transfusions, 3 packing and suture treatment, and 61 fibrinogen infusions. ConclusionMost patients with CFDs have mild or no bleeding symptoms. Fg:C combined with fibrinogen antigen and pedigree investigation can improve the feasibility and accuracy of diagnosis of CFDs. The severity of bleeding symptoms was negatively correlated with Fg:C.

Clinical laboratory characteristics and gene mutation spectrum of Ph-negative MPN patients with atypical variants of JAK2, MPL, or CALR.

To evaluate the incidence, clinical laboratory characteristics, and gene mutation spectrum of Ph-negative MPN patients with atypical variants of JAK2, MPL, or CALR. We collected a total of 359 Ph-negative MPN patients with classical mutations in driver genes JAK2, MPL, or CALR, and divided them into two groups based on whether they had additional atypical variants of driver genes JAK2, MPL, or CALR: 304 patients without atypical variants of driver genes and 55 patients with atypical variants of driver genes. We analyzed the relevant characteristics of these patients. This study included 359 patients with Ph-negative MPNs with JAK2, MPL, or CALR classical mutations and found that 55 (15%) patients had atypical variants of JAK2, MPL, or CALR. Among them, 28 cases (51%) were male, and 27 (49%) were female, with a median age of 64 years (range, 21-83). The age of ET patients with atypical variants was higher than that of ET patients without atypical variants [70 (28-80) vs. 61 (19-82), p = 0.03]. The incidence of classical MPL mutations in ET patients with atypical variants was higher than in ET patients without atypical variants [13.3% (2/15) vs. 0% (0/95), p = 0.02]. The number of gene mutations in patients with atypical variants of driver genes PV, ET, and Overt-PMF is more than in patients without atypical variants of PV, ET, and Overt-PMF [PV: 3 (2-6) vs. 2 (1-7), p < 0.001; ET: 4 (2-8) vs. 2 (1-7), p < 0.05; Overt-PMF: 5 (2-9) vs. 3 (1-8), p < 0.001]. The incidence of SH2B3 and ASXL1 mutations were higher in MPN patients with atypical variants than in those without atypical variants (SH2B3: 16% vs. 6%, p < 0.01; ASXL1: 24% vs. 13%, p < 0.05). These data indicate that classical mutations of JAK2, MPL, and CALR may not be completely mutually exclusive with atypical variants of JAK2, MPL, and CALR. In this study, 30 different atypical variants of JAK2, MPL, and CALR were identified, JAK2 G127D being the most common (42%, 23/55). Interestingly, JAK2 G127D only co-occurred with JAK2V617F mutation. The incidence of atypical variants of JAK2 in Ph-negative MPNs was much higher than that of the atypical variants of MPL and CALR. The significance of these atypical variants will be further studied in the future.

IJCM_309A: Epidemiological Trends, Clinical Features, and Outcomes in Scrub typhus patients admitted to a tertiary care hospital in Odisha

Background: Scrub typhus is an emerging public health threat in South-Asian countries; with the growing number of cases in India, an understanding of local patterns of disease and factors that place individuals at risk is pivotal to future preventive measures. Objective: To analyze the epidemiological features- annual number of cases, age distribution, sex distribution, and seasonal distribution over the four years. To find out the clinical profile, laboratory features and outcomes of cases of scrub typhus, and to identify the predictors of disease severity. Methodology: A comprehensive retrospective review of scrub typhus cases reported over a 4-year period (2019-2023) was done, with a monthly trend of patients admitted. Data was collected from the case records of patients for demographic characteristics, clinical features, treatment, and outcomes, length of stay (LOS), complications, and mortality. Data was presented in frequencies and proportions, odds ratio (OR) was calculated and a p-value of Results: A total of 886 cases were reported over the four-years. There was a declining epidemiological trend in 2020-21 and then an increasing one. Scrub typhus cases exhibited seasonality, with a peak incidence during winter season. Males were more commonly affected (58.01%), and the age group most susceptible was 19-64 years (52.22%), followed by one-month to 18years (32.22%). Clinical presentations typically included fever (96%), eschar formation (8%) and rash (8%). Complications like pneumonia (13.88%) and AKI (11.73%), were observed in a significant proportion of cases. Mortality was reported in 4.40% of cases. Altered sensorium, deranged LFT, hypotension requiring ionotropic support, requirement of ventilatory support predicted poor outcome. Conclusion: Scrub typhus was seen to cause a multi-system infection among the studied population, causing significant morbidity and mortality. The conditions found associated with poor outcome and mortality can be used as risk factor predictors and help patient management.

Epidemiology and factors associated with amoebic liver abscess at a tertiary care hospital in Northern India

Liver abscess is a collection of purulent material in the liver most commonly seen in the tropical countries. It can sometimes lead to significant morbidity and mortality if not treated timely and adequately. Through this study we wish to put light upon the current status of clinical aspects, laboratory features, and outcomes of liver abscess. The study was conducted at a tertiary care hospital in Northern India in the period of August 2020 to July 2021. All patients diagnosed with liver abscess of size &amp;#62;5 cm or left lobe liver abscess of any size were included in the study. All relevant laboratory investigations were conducted. The outcomes were noted and data was entered in MS Excel sheet. Analysis was done using SPSS version 26. Sixty-three patients were included in the study. A male predominance was noted. Mean age at presentation was 37.8 years. Most patients were part of the lower socioeconomic class. Pain abdomen and fever were the most common presenting symptoms. Amoebic liver abscess was much more frequently seen than pyogenic liver abscess. Deranged coagulation profile was seen in 88.9% patients. 85.7% patients were amenable to treatment with minimal intervention. Mortality as an outcome was seen in 9.5% patients Significant correlation was found between various laboratory parameters and outcomes such as length of hospital stay and mortality. Early diagnosis and treatment is crucial in management of patients with liver abscess even today.

The Relationship Between Living with Family and Clinical, Demographic, and Laboratory Characteristics in Patients with Heart Failure

Heart failure (HF) is a progressive clinical syndrome associated with significant morbidity and mortality. It is known that during the course of this syndrome, social factors can impact clinical outcomes alongside medical interventions. Studies have demonstrated that social support provides favorable developments in mortality rates, event-free survival, and readmission rates in HF patients. In our study, we aimed to elucidate the effects of the concept of family, the most significant social support, on clinical characteristics, exercise capacity, echocardiographic, and laboratory features in HF cases.&#x0D; A multicenter cohort study was conducted, including 303 patients previously diagnosed with HF, following current guidelines and presenting for outpatient follow-up. Patients with a new diagnosis of HF, those with acute decompensated HF, and those with a history of malignancy were excluded from the study. Demographic data (age, gender), comorbidities (hypertension, diabetes mellitus, atrial fibrillation, etc.), HF treatments, laboratory tests, and detailed transthoracic echocardiography results were recorded.&#x0D; Patients were divided into two groups based on whether they lived with a spouse, parent, child, or without any of them, defining the presence or absence of family support. In the study, 303 patients with an average age of 62.1±13.0, of which 94 (31%) were female, were included. The mean left ventricular ejection fraction was 28.7±8.1. When the groups were compared in terms of comorbidities, there was no statistically significant difference in the presence of hypertension, diabetes mellitus, hyperlipidemia, chronic obstructive pulmonary disease, stroke, or atrial fibrillation (all p&gt;0.005). Coronary artery disease was more frequently observed in the group with family support, while chronic kidney disease was more common in the group without family support (p=0.008 and p=0.012, respectively). Smoking prevalence was significantly higher in the group without family support, while alcohol use showed no significant difference (p=0.046 and p=0.602, respectively). Analyzing the results, it was observed that patients with family support were more regularly monitored for HF reasons (71% vs. 59%, p=0.054).&#x0D; It has been observed that the social support provided by family members in individuals with HF can have positive effects on the clinical course of the disease and the patient's lifestyle.

Congenital fibrinogen disorders: a retrospective clinical and genetic analysis of the Prospective Rare Bleeding Disorders Database

AbstractCongenital fibrinogen deficiency (CFD) is a rare bleeding disorder caused by mutations in FGA, FGB, and FGG. We sought to comprehensively characterize patients with CFD using PRO-RBDD (Prospective Rare Bleeding Disorders Database). Clinical phenotypes, laboratory, and genetic features were investigated using retrospective data from the PRO-RBDD. Patients were classified from asymptomatic to grade 3 based on their bleeding severity. In addition, FGA, FGB, and FGG were sequenced to find causative variants. A total of 166 CFD cases from 16 countries were included, of whom 123 (30 afibrinogenemia, 33 hypofibrinogenemia, 55 dysfibrinogenemia, and 5 hypodysfibrinogenemia) were well characterized. Considering the previously established factor activity and antigen level thresholds, bleeding severity was correctly identified in 58% of the cases. The rates of thrombotic events among afibrinogenemic and hypofibrinogenemic patients were relatively similar (11% and 10%, respectively) and surprisingly higher than in dysfibrinogenemic cases. The rate of spontaneous abortions among 68 pregnancies was 31%, including 86% in dysfibrinogenemic women and 14% with hypofibrinogenemia. Eighty-six patients received treatment (69 on-demand and/or 17 on prophylaxis), with fibrinogen concentrates being the most frequently used product. Genetic analysis was available for 91 cases and 41 distinct variants were identified. Hotspot variants (FGG, p.Arg301Cys/His and FGA, p.Arg35Cys/His) were present in 51% of dysfibrinogenemia. Obstetric complications were commonly observed in dysfibrinogenemia. This large multicenter study provided a comprehensive insight into the clinical, laboratory, and genetic history of patients with CFDs. We conclude that bleeding severity grades were in agreement with the established factor activity threshold in nearly half of the cases with quantitative defects.