Disease-related Complications Research Articles

Early tumour necrosis factor antagonist treatment prevents perianal fistula development in children with Crohn’s disease: post hoc analysis of the RISK study

BackgroundOne in three children with Crohn’s disease develop perianal fistula complications (PFCs), among the most disturbing and difficult-to-treat disease-related complications. Retrospective evidence suggests PFCs may be preventable.ObjectiveWe aimed to determine...

Apixaban removal during emergency surgery for type A acute aortic dissection: a prospective cohort study.

Acute type A aortic dissection (ATAAD) has a high mortality, and acute aortic repair is the only curative treatment. In patients treated with factor Xa (FXa) inhibitors, the risk of severe disease-related complications such as cardiac tamponade and hemodynamic shock must be balanced against the potential for severe perioperative bleeding. The aim was to study intraoperative changes in plasma levels of the FXa inhibitor apixaban when using hemoadsorption during acute thoracic aortic repair. This is a single-center prospective cohort study. Eight apixaban-treated patients presenting with ATAAD underwent acute thoracic aortic repair with intraoperative hemoadsorption with CytoSorb. Apixaban concentrations were measured at the start of cardiopulmonary bypass (CPB) and after 5, 15, 30, 60, and 90min of CPB, at CPB weaning, 30min after CPB weaning and 24h postoperatively, using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). After 30min of CPB with hemoadsorption, mean apixaban concentration (±SD) was reduced by 59% from 108 (±69)µg/l to 44 (±20)µg/l (P=0.009). There was a further reduction to 37 (±17)µg/l at CPB weaning (P=0.008). Apixaban concentration displayed an increase to 56 (±29)µg/l 24h postoperatively (P=0.01). In-hospital mortality was 25%. The mean 24H chest tube drainage volume was 621 (±136)ml. Intraoperative hemoadsorption lowers apixaban levels in patients undergoing emergency surgery for ATAAD. Further research is needed to determine its impact on perioperative bleeding complications and mortality.

Aramchol attenuates fibrosis in mouse models of biliary fibrosis and blocks the TGFβ-induced fibroinflammatory mediators in cholangiocytes.

Fibroinflammatory cholangiopathies, such as primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), are characterized by inflammation and biliary fibrosis, driving disease-related complications. In biliary fibrosis, cholangiocytes activated by transforming growth factor-β (TGFβ) release signals that recruit immune cells to drive inflammation and activate hepatic myofibroblasts to deposit the extracellular matrix (ECM). TGFβ regulates stearoyl-CoA desaturase (SCD), an enzyme that catalyzes the synthesis of monounsaturated fatty acids, in stimulating fibroinflammatory lipid signaling. However, the role of SCD or its inhibitor, Aramchol, has not been investigated in biliary fibrosis or TGFβ-mediated cholangiocyte activation. 10-16-week-old multi-drug resistance 2 knockout (Mdr2 -/- ) and 3,5-diethoxycarboncyl-1,4-dihydrocollidine (DDC) diet-fed mice were orally gavaged daily with Aramchol at 12.5 mg/kg/day for 4 and 3 weeks, respectively. Liver and serum were harvested for the assessment of fibrosis and inflammation. Transformed human cholangiocyte cells (H69) and mouse large biliary epithelial cells (MLEs) were used to test the effects of the SCD inhibitor, Aramchol, at varying doses on TGFβ-mediated expression of fibroinflammatory signals and were confirmed in PSC-derived cholangiocytes (PSC-Cs) using ELISA, qPCR, and Western blot analyses. Aramchol treatment of Mdr2 -/- mice with established biliary fibrosis (treatment) and DDC diet-induced (prevention) models of cholestatic injury and fibrosis demonstrated significant reductions in both measures of ECM synthesis (mRNA expression of ECM components in the liver), collagen content of the liver (picrosirius red staining and hydroxyproline content) and myofibroblast activation (αSMA staining). Il6 and Tnfa were also reduced with Aramchol in the liver. RNA-seq analysis of H69 cells showed that Aramchol co-treatment led to significant inhibition of TGFβ-induced hepatic fibrosis pathways while upregulating peroxisome proliferator-activated receptor (PPAR) signaling. SCD expression was significantly increased in TGFβ-treated H69 cells (2-fold, p<0.05). Aramchol in a dose-dependent manner significantly attenuated the increased expression of the fibrotic marker, plasminogen activator inhibitor-1 (PAI-1/SERPINE1), and hepatic stellate cell-activating genes ( VEGFA and PDGFB ) in TGFβ-activated H69 and MLEs. Aramchol also markedly reduced the expression of the inflammatory cytokine, interleukin 6 (IL6). SCD siRNA knockdown produced similar results in H69 cells. Furthermore, in PSC-Cs, the expressions of SCD, VEGFA and IL6 were significantly reduced with Aramchol. The expression of the anti-fibroinflammatory factors PPARα and -γ were modestly increased in cholangiocyte cell lines with increased expression of PPAR-responsive genes and increased nuclear binding of DNA PPAR response elements with Aramchol co-treatment compared to TGFβ only. Aramchol, an SCD inhibitor, both attenuates and prevents biliary fibrosis in mouse models of cholestatic injury and fibrosis. This effect is partially due to Aramchol inhibiting TGFβ-induced fibroinflammatory mediators in cholangiocytes by upregulating PPARα and -γ expression and activity. These findings, along with Aramchol's excellent safety profile in clinical trials, provide the rationale for assessing Aramchol in further clinical studies in patients with biliary fibrosis, particularly PSC, where a treatment is desperately needed.

Treatment Patterns and Glycaemic Control Between 2015 and 2019 in Tianjin, China: A Real-World Study of Adults with Type 2 Diabetes.

Diabetes is associated with a high economic burden in China; therefore, strategies to prevent diabetes, improve glycaemic control, delay disease-related complications and maintain quality of life are essential. This study was conducted to evaluate trends in treatment patterns and glycaemic control in people with type 2 diabetes (T2D) in real-world clinical practice in Tianjin, China. This retrospective, cross-sectional, multicentre study analysed data from adults with T2D living in Tianjin, China between 2015 and 2019, based on information obtained from a regional electronic medical record database. Temporal trends in treatment patterns and glycaemic control were assessed using linear regression (continuous variables), and Cochran-Armitage (two categories) or Cochran-Mantel-Haenszel (≥ 3 categories) tests. Between 2015 and 2019, data from 312,203 individuals treated at 75 hospitals were included. Over this period, there was an upward trend in the prevalence of hypertension, hyperlipidaemia, obesity, cardiovascular disease, stroke and retinopathy each year (all P < 0.001). The use of metformin or dipeptidyl peptidase-4 inhibitors increased, while thiazolidinedione, alpha-glucosidase inhibitor and glinide use decreased; the use of basal insulin (BI), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), GLP-1 RAs + BI, bolus insulin and BI + bolus insulin increased, whereas the use of premixed insulin showed a downward trend (all P < 0.001). From 2015 to 2019, an increased proportion of individuals achieved glycated haemoglobin (HbA1c) < 7% (< 53 mmol/mol; 28.1-33.7%), fasting plasma glucose (FPG) < 7 mmol/l (21.7-26.9%) and postprandial glucose (PPG) < 10 mmol/l (22.0-48.2%; all P < 0.001). There was no change in the proportion of individuals with an FPG ≥ 7 mmol/l and a PPG ≥ 10 mmol/l, while the prevalence of residual hyperglycaemia increased (P < 0.001). Glycaemic control improved between 2015 and 2019 in people with T2D in Tianjin, China; however, there is an unmet need for more effective glycaemic control.

Clinical Burden and Healthcare Resource Utilization Associated With Managing Transfusion-dependent β-Thalassemia in England

PurposePatients with transfusion-dependent β-thalassemia (TDT) have reduced levels of β-globin, leading to ineffective erythropoiesis and iron overload. Patients with TDT depend on regular red blood cell transfusions (RBCTs) and iron chelation therapy for survival and management of disease- and treatment-related clinical complications. This study describes the clinical and economic burden in patients with TDT in England. MethodsThis longitudinal, retrospective study linked the Clinical Practice Research Datalink (CPRD) database with secondary care data from the Hospital Episode Statistics database to identify patients with a diagnosis of β-thalassemia between July 1, 2008, and June 30, 2018. Included patients had a diagnosis of β-thalassemia prior to the index date, ≥8 RBCTs per year for ≥2 consecutive years, and ≥1 year of follow-up data available from the index date. Each eligible patient was exact matched with up to 5 controls in the CPRD. Proportions of deaths and rates of mortality, acute and chronic complications, and healthcare resource utilization (HCRU) were calculated during the follow-up period. FindingsOf 11,359 identified patients with β-thalassemia, 237 patients with TDT met the eligibility criteria and were matched with 1184 controls. The mean age at the index date was approximately 25 years in the patient and control groups. The proportion of deaths (7.17% vs 1.18%; P < 0.05) and mortality rate (1.19 deaths per 100 person-years vs 0.20 deaths per 100 person-years) were higher among patients with TDT compared to controls. Endocrine complications and bone disorders were the most prevalent complications among patients with TDT (58.23%) and included osteoporosis (29.11%), diabetes mellitus (28.27%), and hypopituitarism (28.27%). Patients with TDT had a mean of 13.62 RBCTs per patient per year (PPPY). HCRU was substantially higher among patients with TDT, wherein patients with TDT had higher rates of prescriptions recorded in primary care (24.09 vs 8.61 PPPY), outpatient visits (16.69 vs 1.31 PPPY), and inpatient hospitalizations (17.41 vs 0.24 PPPY) than controls. Inpatient hospitalizations were primarily <1 day, with 16.62 events PPPY lasting <1 day and 0.79 events PPPY lasting ≥1 day. Patients with TDT aged ≥18 years had increased rates of mortality, clinical complications, and HCRU than those aged <18 years. ImplicationsPatients with TDT in England have higher mortality than matched controls, substantial disease-related clinical complications, and substantial HCRU. High mortality and clinical complications highlight the need for additional innovative therapies for TDT.

End-of-life management of multiple myeloma patients in the era of CD38 and immunotherapy.

In spite of spectacular advances in the treatment of multiple myeloma, a majority of patients will die from this disease or related complications. While a great amount of focus has been dedicated to the development of novel therapies, little attention has been paid to latter stages of patient follow-up. In order to describe patient management during this critical period as well as the immediate causes and circumstances of death, we have analyzed a single center series of 100 patients diagnosed with myeloma who died between 2016 and 2021. Patients received a median of 3 lines of treatment, including 2 during their last year of life. Sixty per cent of patients had received daratumumab. Fifty patients had obtained complete remission or very good partial response at some time during the course of disease but 75 were refractory to the last treatment line. Eighteen patients died while their disease was stable or in remission while 77 had confirmed progressive disease at time of death. Thirty six patients had uncontrolled sepsis, 49 were in renal failure and 24 had hypercalcemia at the time of death. Seventy three patients presented with lymphopenia. Disease progression was documented in a majority of MM patients at the time of death and was associated with disease-related complications in a significant number of patients. Disease progression remains the main cause of death in patients with multiple myeloma.

A rare presentation of stress cardiomyopathy in a patient with ulcerative colitis

Stress cardiomyopathy is a reversible cause of acute left ventricular dysfunction that can cause disease-related complications in the acute phase. Due to overlapping symptoms and investigation findings, stress cardiomyopathy can be misdiagnosed as an acute myocardial infarction. Hence correct identification of the condition is of great importance. It is increasingly being described with several medical conditions, which are associated with increased catecholamine surge like inflammatory bowel disease. Although the disease is reversible, due to the disease-related severe complications it is important to promptly identify and treat accordingly to prevent morbidity and mortality.

Comparing the Effects of Healthy Lifestyle Education Through Peer Group and mHealth App on Self-esteem in Patients with Diabetes Mellitus: A Randomized Controlled Trial

Background: The increasing prevalence of diabetes mellitus has become a global public health challenge in recent decades. However, disease-related complications can be minimized through innovative educational programs. Objectives: This study aimed to compare the effects of healthy lifestyle education delivered via peer group and the mHealth app on self-esteem in patients with type 2 diabetes mellitus (T2DM). Methods: This three-group randomized controlled trial was conducted in 2022. A total of 135 patients living with T2DM were recruited using purposive sampling from two hospitals in Kermanshah Province, Iran, and then divided into three groups: Peer education, virtual education, and control groups, via replacement randomization. Peer patients with T2DM, previously trained by the researchers, provided education to those in the peer education group in four 35-minute sessions over two days. Simultaneously, patients in the virtual education group were trained by the researchers using the mHealth app, specifically designed for this purpose, in three 1-hour sessions over three days. Data were collected using the Patient Profile Form and the self-reported Rosenberg’s Self-Esteem Scale. The data were analyzed using IBM SPSS Statistics software, employing paired-sample t-tests, chi-square tests, Fisher’s exact tests, and one-way analysis of variance (ANOVA) for comparisons. Results: Before the intervention, there were no significant differences in the self-esteem mean scores between the study groups (P = 0.665). However, post-intervention, the self-esteem scores differed significantly between all groups (P = 0.002). The self-esteem mean scores of patients in the peer education group (100.36 ± 15.9 vs. 106.87 ± 9.08, P = 0.011) and the virtual education group (100.80 ± 24.72 vs. 116.91 ± 10.67, P = 0.018) significantly increased after the intervention, while no significant difference was observed in the control group (106.87 ± 9.08 vs. 105.60 ± 10.84, P = 0.134). Virtual education via the mHealth app was more effective than peer education in improving self-esteem in patients with T2DM. Conclusions: The healthy lifestyle education program delivered through virtual education via the mHealth mobile app led to higher self-esteem among patients with T2DM compared to peer education. It is suggested that future studies investigate the impact of virtual education using mobile-based apps and artificial intelligence capabilities on self-esteem in other patient populations. These results can serve as guidelines for the optimal use of distance education and educational apps for patients with chronic diseases.

6702 Management And Complications Of Metastatic Adrenocortical Carcinoma Presenting With Severe Cushing Syndrome

Abstract Disclosure: S. Rodrigues: None. A.K. Sumal: None. Background: Metastatic adrenocortical carcinoma (ACC) presenting with Cushing syndrome (CS) is a complicated, aggressive disease that commonly requires multiple adrenal steroidogenesis inhibitors and chemotherapy to achieve hormonal and tumor control. Clinical Case: A 66-year-old man with a history of prostate cancer and hypertension presented with right flank and back pain, worsening type 2 diabetes, profound proximal muscle weakness, and 3+ lower extremity edema to his thighs. CT and PET-CT revealed a 10.9 cm right adrenal mass with pericaval lymphadenopathy and metastatic disease at the L2 vertebral body. Laboratory testing demonstrated evidence of hypercortisolism with elevated 24-hour urinary cortisol excretion (449 mcg/24h; n&amp;lt;45 mcg/24h), and abnormal 1 mg dexamethasone suppression test (cortisol 15 mcg/dL; n&amp;lt; 1.8 mcg/dL) with suppressed ACTH (&amp;lt;6 pg/mL; n=7-63 pg/mL). Surgical resection of the primary tumor was aborted intraoperatively given the discovery of new peritoneal metastases, which were confirmed by biopsy to be metastatic ACC. He was started on mitotane and osilodrostat to manage his severe CS. He was also started on dexamethasone, both to prevent adrenal insufficiency and to avoid influencing serum cortisol measurements used to assess disease control. However, given his significant peripheral edema and weakness, he was functionally unable to receive chemotherapy. Despite rapid uptitration of mitotane and osilodrostat over three weeks, his CS remained uncontrolled, and he was ultimately hospitalized for lower extremity paralysis and septic shock due to pyelonephritis. Repeat imaging revealed severe spinal canal stenosis from an L2 pathologic fracture, as well as worsening hepatic, osseous, peritoneal, and retroperitoneal metastases. After recovery from his septic shock, he was started on chemotherapy with carboplatin and etoposide while hospitalized, but his mitotane was intermittently held due to elevated transaminases. His hospital course was complicated by hypotension requiring pressor support, atrial fibrillation, hemoperitoneum, worsening anasarca, and acute kidney injury requiring continuous renal replacement therapy. Given his worsening condition that precluded him from further chemotherapy or palliative radiation, he elected to pursue comfort care measures and expired shortly thereafter. Conclusion: This case highlights the therapeutic challenges of metastatic ACC presenting with life-threatening CS. Simultaneous use of multiple adrenal steroidogenesis inhibitors is often required for control of hypercortisolism, and chemotherapy is equally necessary to manage tumor burden. However, as in this case, disease-related complications can limit treatment management and result in rapid deterioration. Thus, early diagnosis and prompt treatment of metastatic ACC presenting with CS is critical to prevent morbidity and mortality. Presentation: 6/3/2024

Quantitative MRI in children with Crohn's disease - where do we stand?

Crohn's disease (CD) is a chronic inflammatory condition that affects the gastrointestinal tract, particularly the ileum and colon. This disease is characterized by recurrent bouts of intestinal inflammation with subsequent bowel wall damage, including scarring (i.e., fibrosis) and abnormal smooth muscle proliferation. MR enterography, an MRI examination tailored to assess the small bowel, is a first-line diagnostic tool for diagnosing CD in children, characterization and monitoring of disease severity and extent, and assessment of disease-related complications. To date, such MRI evaluations have been mostly qualitative, which can adversely impact diagnostic performance and inter-radiologist agreement. Quantitative MRI methods have been shown to aid in the evaluation of a variety of medical conditions and have been increasingly investigated in children and adults with CD. In CD, such objective techniques have been used to assist with diagnosis, assess treatment response, and characterize bowel wall histologic abnormalities. In the current work, we will review quantitative MRI methods for detecting and measuring intestinal active inflammation (MRI-based scoring systems, T1 relaxation mapping, diffusion-weighted imaging, intra-voxel incoherent motion, mesenteric phase contrast), bowel wall damage (magnetization transfer), and motility (quantitative cine imaging) in small bowel CD, with an emphasis on the pediatric population.

Risk Prediction in Diverticulitis

AbstractAcute diverticulitis is a common sequela of colonic diverticulosis that often poses a significant dilemma for surgeons and patients considering surgical management of the disease. Importantly, the decision to recommend surgery for patients with diverticular disease hinges on identifying those who will benefit most in terms of preventing future disease-related complications. This review focuses on identifying patient risk factors that are predictive of onset of diverticulitis, recurrence of disease, and progression to complicated disease, such as abscess, fistula, or stricture, and aims to assist clinicians with counseling patients who are considering surgery versus medical management. Specifically, a variety of modifiable and nonmodifiable risk factors have been identified across several studies that have strong associations with the development of diverticulitis, recurrence of uncomplicated disease, and progression to complicated disease. A handful of clinical scores have been described to guide surgeons and patients on their individual risk; however, none have been adopted into wider clinical practice. A novel polygenic risk score does show promise in potentially fulfilling this role. Nevertheless, there is significant room for innovation and development of new methods to risk-stratify patients presenting with the spectrum of diverticular disease.

SP4.14 - Mild acute biliary pancreatitis: still a surgical disease. A post-hoc analysis of the MANCTRA-1 international study

Abstract Aims The current standard of care for mild acute biliary pancreatitis (MABP) involves early laparoscopic cholecystectomy (ELC) reducing the risk of early recurrence. The MANCTRA-1 project disclosed a discrepancy in translating this evidence into clinical practice, estimating a 35 to 70% probability of narrowing this gap within 2025. This study assesses the safety of suboptimal ELC implementation in MABP, looking for risk factors for recurrent acute biliary pancreatitis (ABP) in patients awaiting interval cholecystectomy after an uneventful episode of MABP. Methods We conducted a post hoc analysis of the MANCTRA-1 registry. Clinicaltrials.gov ID NCT04747990. We included MABP patients who did not undergo ELC during the index hospitalization, excluding those who experienced disease-related complications. The primary outcome was the 30-day hospital readmission rate due to ABP recurrence. We performed univariable and multivariable logistic regression to identify risk factors for 30-day ABP recurrence. Results Between January 2019 and December 2020, a total of 2,253 MABP patients from 150 centres were included. The 30-day readmission rate due to ABP recurrence was 6%. The multivariable logistic regression showed that admission to a medical ward (internal medicine or gastroenterology) odds ratio (OR) 1.62 (95%[CI] 1.1;2.37), p=0.01 was an independent risk factor for 30-day ABP recurrence. Conclusion Our real-world analysis provides valuable insights to manage MABP, particularly in centres where ELC strategies cannot be fully implemented due to organizational and clinical constraints. Despite the admitting ward, it underscores the importance of timely access to surgical care in reducing the risk of early recurrence, disclosing the need to implement surgical consultation pathways in ABP care bundles.

Impact of Systemic Lupus Erythematosus on Conception: Insights into Infertility, Fertility Preservation, Assisted Reproductive Technology, and Pregnancy Outcomes.

Many individuals with systemic lupus erythematosus (SLE) face significant challenges manifesting their family planning goals due to numerous factors, including disease-related complications, treatment-induced effects, immunological factors, self-imposed limitations, and the socioeconomic impacts of having a chronic disease. Instances of unexplained infertility are also prevalent. Encouragingly, advancements in treatment modalities, risk factor management, specialized training within the medical community, and enhanced patient/provider education have contributed to an increase in successful pregnancies among SLE patients, fostering a safer, more promising reproductive landscape. However, despite advances, individuals with SLE continue to struggle with the complexities of family building. This review explores infertility and pregnancy outcomes in SLE, fertility preservation, the role of assisted reproductive technology, and considerations for tailoring these approaches to SLE patients.

Prognostic impact of disease-related complications in asymptomatic mitral regurgitation: a health insurance claims analysis.

The impact of mitral regurgitation (MR) in asymptomatic patients is not well defined. We aimed to determine the prevalence of MR-related complications and their association with 10-year survival in a large unselected asymptomatic MR cohort. Health insurance claims data from Germany's second largest health insurance fund, BARMER, which maintains longitudinal data on 8.7 million German residents, were retrospectively analyzed. All patients with an outpatient diagnosis of MR in a minimum of two quarters during a calendar year and first recorded diagnosis between 2008 and 2011 were included. Patients with any complication attributable to MR or mitral valve intervention at index were excluded. Outcomes were compared between study group and age- and sex-matched controls (i.e., without known cardiac disease). MR-related complications of interest were new congestive heart failure, new-onset atrial fibrillation, pulmonary hypertension, or cardiac decompensation. A total of 56,577 individuals (median age 68 years, 67% female) with asymptomatic MR were identified. At 10 years, MR-related complications were more frequent in the study group vs. control group (46.5% vs. 20.8%, OR 3.31, P < 0.0001). Furthermore, MR-related complications were more common in male vs. female patients with an asymptomatic MR (OR 2.65, P < 0.0001). The occurrence of at least one MR-related complication was associated with a reduced 10-year survival (OR 1.80, P < 0.0001). Almost half of patients with asymptomatic MR experience complications during a 10 year follow-up which result in impaired survival. These results imply the necessity of long-term disease management program. Furthermore, decision-making process and timing for mitral valve intervention in asymptomatic patients should be reevaluated.

Depression among people living with HIV at a district hospital in KwaZulu-Natal, South Africa.

Depression is a debilitating condition worldwide and a major contributor to the overall global burden of disease. The prevalence of depression is estimated to be higher in people living with HIV and AIDS (PLWHA) compared to the general population, with disease related complications increasing when mental health problems remain untreated. The aim of the study was to determine the prevalence of depression among PLWHA who attend a district hospital ART clinic in KwaZulu-Natal (KZN), South Africa (SA). Using strict systematic sampling, a descriptive cross-sectional study was employed with 121 adult outpatients attending an antiretroviral clinic at a district hospital in KZN, SA. Their biographical and clinical characteristics were obtained through a questionnaire and medical records, while depression was evaluated using the PHQ-9 scale. The data were analysed using descriptive and inferential statistics. A total of 121 participants were recruited for this study. The prevalence of depression was 19.8% and significantly associated with a poor support system (adjusted odds ratio [aOR] = 3.60,p= 0.010). Female patients were more likely to have depressive symptoms than males (aOR = 0.73; confidence interval: 0.28-1.90) although this was not statistically significant. Age, marital status and viral load were not contributors to depression. Routine screening for depression among PLWHA at primary health care (PHC) level may improve detection rates, earlier treatment and overall health outcomes.Contribution:The results emphasise the need for patient-centeredness and holistic care that involves addressing mental health for PLWHA, given that HIV is a lifelong condition.

Medical complications among acute leukaemia patients receiving inward induction chemotherapy at haematooncology section of the National Cancer Institute, Sri Lanka

Introduction: Acute leukaemias are complicated with numerous disease and treatment related medical complications. Infection is one of the major complications and is related to chemotherapy associated-neutropaenia. This study aims to identify medical complications in acute leukaemia patients during the induction chemotherapy period. Results: Medical complications were observed in patients receiving induction chemotherapy N=50. Infections and electrolyte disturbances were the most frequently observed complications (74% each) followed by chemotherapy induced neutropaenia (38%), alteration of liver functions (32%), steroid induced hyperglycaemia (28%) and bleeding (16%). Thrombosis and tumour lysis were detected at lesser frequencies (4% each). Among infections, the majority showed evidence of blood stream infection (27%) followed by pulmonary infections (24.3%). Gram negative organisms were the most frequently identified pathogen. Among the electrolyte disturbances, hypokalaemia (48%), hyponatraemia (48%), and hypocalcaemia (44%) were more prevalent. Mean duration from initiation of chemotherapy to neutrophil nadir was 10.05 days.Conclusions: Patients with acute leukaemia encounter a multitude of disease and treatment related medical complications during induction chemotherapy. Infection is the most common complication with higher rates of bacteraemia and gram-negative sepsis. This is likely to be a result of treatment related neutropaenia. However, further focused studies on neutropaenic sepsis during induction chemotherapy are recommended. Clinical vigilance, strict and improved infection control strategies are necessary to improve the outcome of these patients.

Clinical and Economic Implications of Hydroxyurea Intolerance in Polycythemia Vera in Routine Clinical Practice.

Background/Objectives: Polycythemia vera (PV) is a chronic hematologic neoplasm commonly treated with hydroxyurea (HU). We utilized the advanced digitalized database of Maccabi Healthcare Services to retrospectively investigate the clinical and economic implications of HU intolerance in the routine clinical care of PV patients in Israel. Methods: We collected data on demographics, physician visits, hospitalizations, laboratory results, medication purchases, cardiovascular and thrombotic events, mental health, economic outcomes, and mortality. Outcomes included cardiovascular and other thrombotic events, disease progression, mental health events, economic outcomes, and overall mortality. Results: Of the 830 patients studied, 3 (0.4%) were resistant to HU treatment, 318 (38.3%) were intolerant to HU treatment, and 509 (61.3%) were stable on HU treatment. The venous thrombosis rate was significantly higher among HU-intolerant compared to HU-stable patients (1.58 vs. 0.47 per 100 person-years [PY], respectively; p < 0.001). The rate of progression to myelofibrosis was 6 vs. 0.9 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively (p < 0.001), and the rate of progression to acute myeloid leukemia (AML) was 1.16 vs. 0.2 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively (p < 0.001). The phlebotomy requirement, mortality rate, and total hospitalization days among HU-intolerant patients were significantly higher than in HU-stable patients (p = 0.049, p < 0.001, p < 0.001, respectively). More mental health-related events were noted in HU-intolerant patients vs. HU-stable patients (p = 0.007), and the total healthcare cost ratio was 2.65 for the HU-intolerant patients compared with HU-stable patients. Conclusions: This study suggests that HU-intolerant patients are more likely to have worse outcomes than HU-stable patients, highlighting the need for the close monitoring of these patients for disease-related complications or progression.

MIP vaccine in leprosy: A scoping review and future horizons.

Mycobacterium Indicus Pranii (MIP) vaccine is a killed vaccine developed in India for leprosy with immunotherapeutic as well as immunoprophylactic effects. MIP, earlier known as Mycobacterium welchii, is a rapidly growing non-pathogenic mycobacterium. The novelty of this bacterium is due to its translational application as an immunotherapeutic agent. When administered intradermally, the vaccine induces cell-mediated immunity in the host towards Mycobacterium leprae. It leads to faster clinical and histopathological improvement, rapid bacillary clearance, and also lepromin conversion in anergic leprosy patients. The beneficial role of the MIP vaccine in augmenting the therapeutic efficacy of Multidrug Therapy (MDT), particularly in highly bacillated leprosy patients, is well documented in various studies from India. The role of the vaccine in reactional states is controversial, with varied results in different studies. Overall, it is found to decrease the frequency of type 2 lepra reactions and is useful in recalcitrant erythema nodosum leprosum. Even though there may be an increased likelihood of type 1 reactions, no additional nerve function impairment is attributed to the vaccine in various studies. In household contacts of leprosy who are administered MIP, it is noted to confer protection from disease lasting up to 10 years. It may prove to be a cost-effective strategy in national leprosy programmes. Apart from local injection site reactions, the vaccine is relatively safe, but it is not recommended in pregnancy and lactation. This article provides an overview of the MIP vaccine's clinical application in the context of leprosy spanning over 40 years. It also considers the vaccine's possible future applications in the management of disease-related complications and achieving the long-term goal of zero leprosy.

#2526 Sex differences in chronic kidney disease-related complications and mortality across levels of glomerular filtration rate

Abstract Background and Aims Chronic kidney disease (CKD) is a growing global health concern. In recent years, studies have increasingly focused on the differential risk profile of diseases between men and women. Current evidence suggests that sex-linked biological and behavioral differences may play a key role in influencing the incidence, prevalence, and outcomes of diseases. Similarly, previous studies have demonstrated a differential risk profile in the prevalence, progression, and outcomes of CKD between men and women. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented. Method We investigated sex-specific disparities in CKD-related complications and mortality according to eGFR levels. We analyzed NHANES data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150 ml/min per 1.73 m². The outcomes were CKD-related complications (hypertension, anemia, CV diseases, acidosis, hyperphosphatemia, hyperparathyroidism) and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios (ORs) and hazard ratios (HRs) for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance. Values of eGFR over which the log-odds (for CKD-related complications outcomes) or log-hazard (for all-cause and cause-specific mortality outcomes) was found to be significantly different from zero (i.e., 95% CI for the smooth term did not contain zero) were identified as thresholds of statistical significance. Results The study included 49, 562 participants (50.31% women, 49.68% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modeling eGFR as a natural spline revealed varied significance thresholds between sexes for anemia and hyperparathyroidism. We found a significantly (P &amp;lt; 0.05) higher proportion of women with anemia downstream an eGFR cut-off of 69 mL/min per 1.73 m2, which was lower than the cut-off in men; a significantly higher proportion of men with anemia was observed downstream an eGFR cut-off of 76 mL/min per 1.73 m2. However, the relationship was more pronounced in women than in men; thus, at an eGFR cut-off of 41 mL/min per 1.73 m2, the proportion of women with anemia was significantly higher (P &amp;lt; .05) (Figure). Similarly, a higher proportion of women with hyperparathyroidism were observed downstream an eGFR cut-off of 73 mL/min per 1.73 m2, which was lower than in men; a significantly higher proportion of men (P &amp;lt; .05) was observed downstream an eGFR cut-off of 89 mL/min per 1.73 m2 (Figure). Furthermore, although no sex differences were observed in terms of eGFR thresholds for hyperphosphatemia, a more pronounced relationship was observed in men. Thus, at an eGFR cut-off of 38 mL/min per 1.73 m2, the proportion of men with hyperphosphatemia was significantly higher (P &amp;lt; .05) than that of women (Figure). We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR Conclusion Research shows sex disparities in most CKD-related complications. Men develop anemia and hyperparathyroidism earlier, women show steeper anemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.

Acute Respiratory Failure in Autoimmune Rheumatic Diseases: A Review.

This review examines respiratory complications in autoimmune rheumatic diseases within intensive care units (ICUs). The respiratory system, primarily affected in diseases like rheumatoid arthritis, systemic lupus erythematosus, and scleroderma, often leads to respiratory failure. Common manifestations include alveolar hemorrhage, interstitial fibrosis, and acute respiratory distress syndrome. Early recognition and treatment of non-malignant conditions are crucial to prevent rapid disease progression, with ICU mortality rates ranging from 30% to 60%. Delayed immunosuppressive or antimicrobial therapy may result in organ system failure. Collaboration with rheumatic specialists is vital for accurate diagnosis and immediate intervention. Mortality rates for rheumatic diseases in the ICU surpass those of other conditions, underscoring the need for specialized care and proactive management. The review emphasizes comprehensive assessments, distinguishing disease-related complications from underlying issues, and the importance of vigilant monitoring to enhance patient outcomes.