Long-term Prognosis Research Articles

Assessing the Risk of Delirium and Death in Sepsis Using the Braden Score: A Retrospective Study.

To provide a viable tool for the early clinical identification of high-risk populations in patients with sepsis. Sepsis-associated delirium (SAD) has the potential to significantly impact the short- and long-term prognosis of patients. However, accurately predicting and effectively managing SAD remains a significant challenge. This study employed a retrospective analysis of adult sepsis patients admitted to the intensive care unit (ICU) for the first time. Patients were divided into two groups based on their initial Braden score upon admission to the ICU: a high-risk group (≤ 15 points) and a low-risk group (> 15 points). The relationship between Braden score and delirium was assessed using logistic regression and restricted cubic splines, while restricted mean survival time was employed to analyse the relationship between Braden scores and patients' 90- and 180-day mortality. Of the 28,312 patients included in the study, those in the high-risk group exhibited a significantly elevated risk of delirium (44.8% vs. 29.7%) and higher 90-day (28.7% vs. 19.4%) and 180-day (33.2% vs. 24.1%) mortality rates (all p < 0.001). After adjusting for confounding variables, logistic regression demonstrated that the risk of delirium was 1.54 times higher in the high-risk group (95% CI = 1.45-1.64, p < 0.001). Following propensity score matching, the difference in survival was statistically significant at both time points, with the high-risk group having a reduced survival rate of 7.50 days (95% CI = -8.24, -6.75; p < 0.001) and 15.74 days (95% CI = -17.40, -14.08; p < 0.001) at 90 days and 180 days, respectively. The Braden score is a simple and effective tool for the early identification of patients at increased risk of adverse outcomes in sepsis. Retrospective study. The Braden score can be employed by clinical nurses for the purpose of early identification of poor prognostic risk in patients with sepsis. This study was conducted according to the Strengthening Research in Observational Studies in Epidemiology (STROBE) guidelines. Patients were involved in the sample of the study.

Efficacy of Doxorubicin in the Adjuvant Treatment of Canine Splenic Visceral Hemangiosarcoma

Introduction. Splenic hemangiosarcoma is a highly malignant neoplasm that affects geriatric patients. The incidence in dogs is 45–50% of all splenic tumours and about 2% of all oncological pathologies. The visceral form of splenic hemangiosarcoma is characterised by the most aggressive course of the disease and early metastasis to other organs. The average life expectancy of animals after splenectomy, according to various scientific data, is from 20 to 90 days. The article studies the efficacy of additional doxorubicin-based adjuvant chemotherapy to increase the life expectancy of dogs at different stages of the disease.Materials and Methods. To compare the life expectancy, the patients were divided into 4 groups receiving different treatments for splenic hemangiosarcoma. Examination of patients, visual diagnostics and pathomorphological diagnostics were used for making a diagnosis, determining the stage of the disease and prescribing treatment. Treatment efficacy was assessed based on the median relapse-free period, median life expectancy and survival rate of patients after 3, 6, and 12 month periods. Statistical analysis was performed using the Fisher's exact test.Results. The obtained data demonstrated a more favourable course of disease in dogs with the stage I tumour process. Splenectomy made it possible to increase the life expectancy of patients to 243 days with a 6–month survival rate in 62.5% of patients. Postoperative chemotherapy treatment combined with doxorubicin significantly improved the longterm prognosis and led to more than twofold increase in life expectancy of dogs (up to 475 days) with a one-year survival rate in 83.3% of patients. However, no substantial statistical significance was determined in the studied groups (p=0.7).Discussion and Conclusion. The results of the research have revealed the efficacy of adjuvant doxorubicin-based chemotherapy in dogs with the visceral forms of splenic hemangiosarcoma. In animals with early stages of the disease, a significant increase in life expectancy has been discovered. The development of hemagdomain and/or the presence of metastasis to abdominal organs indicate the unfavourable course of the disease and, as a consequence, early metastasis. Nevertheless, even at these stages, doxorubicin can increase the life expectancy of patients.

CYSLTR1 antagonism displays potent anti-tumor effects in uveal melanoma

Uveal Melanoma (UM) is the most common primary intraocular malignancy in adults. Although rare, it is a deadly tumor, with a long-term prognosis of death occurring in more than 50% of the cases. It is characterized by frequent (∼80%) driver mutations in GNAQ and GNA11 genes, both of which are activated by cysteinyl leukotriene receptors (CYSLTRs). CYSLTR1 is upregulated and participated in the progression of several cancers. In the present study, we sought to determine the expression levels of CYSLTR1 in 31 human UM specimens and cell lines (3 primary and 1 metastatic), and its role in the proliferation and viability of these cells by analyzing cell metabolic activity, cell confluence and apoptosis levels. We show that all analyzed UM specimens and cells expressed CYSLTR1 at high levels. Notably, the pharmacological blockage of this receptor, using the inverse agonist MK571, reduced the growth and metabolic activity, and increased the apoptotic cell death of all analyzed UM cell lines. We provide evidence that CYSLTR1 is expressed in human UM and plays a significant role in UM progression behavior. Our data highlight the potential beneficial effects of targeting CYSLTR1 in the control of UM progression.

Impact of bacterial co-isolation on treatment initiation and long-term prognosis of patients with nontuberculous mycobacterial pulmonary disease: analysis of a prospective cohort study.

Nontuberculous mycobacterial pulmonary disease (NTM-PD), a chronic respiratory condition, presents a growing challenge globally. Uncertainties exist regarding the impact of concurrent bacterial co-isolation on treatment initiation and long-term prognosis. This study analysed data from participants enrolled in an ongoing prospective observational cohort study on NTM-PD (NCT01616745) between 1 July 2011, and 31 December 2022, who provided sputum samples for bacterial culture at enrolment. Identification of potential pathogenic microorganisms (PPMs) was defined as a positive bacterial culture. Clinical characteristics were compared between NTM-PD patients with Pseudomonas, non-pseudomonal PPMs, and those without PPM co-isolation. Cox proportional hazard regression models were employed to assess the association of bacterial co-isolation with rates of NTM-PD treatment initiation and all-cause mortality. Overall, 453 patients (median age, 62 years; 30% male) were included in the analysis. PPMs were co-isolated in 77 patients (17%), including 13 with Pseudomonas species. Co-isolation of Pseudomonas was associated with a significantly higher erythrocyte sedimentation rate (P = 0.02) and St. George's Respiratory Questionnaire score (P = 0.01). Non-pseudomonal PPM co-isolation was significantly associated with a higher likelihood of NTM-PD treatment initiation (adjusted hazards ratio [aHR], 1.56, 95% confidence interval [CI], 1.03-2.36, P = 0.036), whereas co-isolation of Pseudomonas was independently correlated with increased all-cause mortality (aHR, 3.25, 95% CI, 1.08-9.84, P = 0.037). Our findings emphasize the importance of microbial surveillance, as bacterial co-isolation affects treatment initiation and prognosis in patients with NTM-PD.

Long-Term Outcomes in Antibody-Negative Autoimmune Encephalitis: A Retrospective Study.

To characterize the long-term outcomes of patients with "possible only" or "probable" autoimmune encephalitis (AE). Despite comprising one-third of AE cases, antibody-negative cases lacking typical AE-defining features are understudied. We conducted a retrospective analysis of adult patients evaluated at a tertiary center neuroimmunology practice from 2006 to 2020, meeting diagnostic criteria for "possible only" or "probable but antibody-negative" AE, with at least one year of follow-up. All patients underwent neural antibody testing. Forty-five patients (median age, 61 years [range, 20-88]; female, 21 [47%]) were included, with a median follow-up of 36 months (range, 12-174). A change in diagnosis was noted in six additional patients, who were excluded from further analysis, with only two receiving a non-autoimmune diagnosis during follow-up. The majority (41/45 [91%]) presented with significant disability (modified Rankin Scale [mRS] ≥3) at baseline. CSF was inflammatory in 20/44 (45%) and MRI was abnormal in 21/45 (47%). Unclassified neural-specific IgG staining on tissue-based assay was detected in five (11%). Two cases (4%) had a paraneoplastic cause. The median time from onset to immunotherapy initiation was two months (range, 0-21), resulting in at least partial improvement in all 44 (98%) treated cases. Clinical relapses occurred in 14/45 (31%). At last follow-up, the most common symptoms were memory dysfunction (31/45 [69%]), attention deficits (17/45 [38%]), gait instability (13/45 [29%]), and visuospatial dysfunction (10/45 [22%]). Most patients achieved independence (median mRS, 2 [range, 0-6]); however, 11 patients had poor neurological outcome (mRS ≥3). Higher mRS score and gait assistance requirement at three months were predictive of poor outcome (P ≤0.01). Despite significant disability at initial stages, patients with antibody-negative but clinically presumed AE show potential for improvement with immunotherapy, highlighting the importance of early intervention. Early functional status and gait assistance requirements may assist in predicting long-term prognosis.

Multidimensional analysis of the impact of Gemmatimonas, Rhodothermus, and Sutterella on drug and treatment response in colorectal cancer.

Colorectal cancer is the third most prevalent cancer across the globe. Despite a diversity of treatment methods, the recurrence and mortality rates of the disease remain high. Recent studies have revealed a close association of the gut microbiota with the occurrence, development, treatment response, and prognosis of colorectal cancer. This study aims to integrate transcriptome and microbiome data to identify colorectal cancer subtypes associated with different gut microbiota and evaluate their roles in patient survival prognosis, tumor microenvironment (TME), and drug treatment response. An integrated analysis of microbiome data was conducted on samples of colorectal cancer from public databases. Based on this, two tumor subtypes (C1 and C2) closely associated with patient survival prognosis were identified and a risk score model was constructed. The survival status, clinical parameters, immune scores, and other features were analyzed in-depth, and the sensitivity of various potential drugs was examined. A thorough examination of microbiome information obtained from colorectal cancer patients led to the identification of two primary tumor clusters (C1 and C2), exhibiting notable variations in survival outcomes. Patients with the C1 subtype were closely associated with better prognosis, while those with the C2 subtype had higher gut microbial richness and poorer survival prognosis. A predictive model utilizing the microbiome data was developed to accurately forecast the survival outcome of patients with colorectal cancer. The TME scores provided a biological basis for risk assessment in high-risk (similar to the C2 subtype) patient cohorts. Evaluation of the sensitivity of different subtypes to various potential drugs, indicated the critical importance of personalized treatment. Further analysis showed good potential of the developed risk-scoring model in predicting immune checkpoint functions and treatment response of patients, which may be crucial in guiding the selection of immunotherapy strategies for patients with colorectal cancer. This study, through a comprehensive analysis of colorectal cancer microbiome, immune microenvironment, and drug sensitivity, enhances the current understanding of the multidimensional interactions of colorectal cancer and provides important clinical indications for improving future treatment strategies. The findings offer a new perspective on improving treatment response and long-term prognosis of patients with CRC through the regulation of microbiota or the utilization of biomarkers provided by it.

Survival benefit of adjuvant TACE for patients with hepatocellular carcinoma and child-pugh B7 or B8 after hepatectomy.

The benefit of postoperative adjuvant transcatheter arterial chemoembolization (pTACE) for patients with hepatocellular carcinoma (HCC), especially those with Child-Pugh (CP) B, remains controversial. This study aimed to assess the survival benefit of pTACE for HCC patients with CP B. Data from 297 HCC patients with CP B7 or B8 were analyzed, dividing them into groups with and without pTACE (70, 23.6% vs. 227, 76.4%). Propensity score matching (PSM) was used to control for confounding bias, and competing-risk regression was applied to address bias from non-cancer-specific death (NCSD). Preliminary findings suggest that pTACE did not increase the incidence of severe complications in HCC patients with CP B7 or B8. Survival analysis indicated that the group receiving pTACE had better overall survival and recurrence-free survival than the group without pTACE after PSM. Furthermore, competitive risk analysis revealed that pTACE was an independent prognostic factor associated with reduced cancer-specific death incidence (subdistribution hazard ratio [SHR] 0.644, 95%CI: 0.378-0.784, P = 0.011) and recurrence (SHR 0.635, 95% CI: 0.379-0.855, P = 0.001). Importantly, pTACE did not increase NCSD. Subgroup analysis corroborated these results. Adjuvant TACE demonstrates the potential to significantly enhance the long-term prognosis of HCC patients with CP B7 or B8 following hepatectomy, particularly those with multiple tumors, large tumor size, macrovascular or microvascular invasion, and narrow resection margin. Hence, pTACE should be considered for patients at high risk of recurrence following thorough evaluation.

Identification of an immune cell infiltration-related gene signature for prognosis prediction in triple-negative breast cancer.

Triple-negative breast cancer TNBC with higher immunogenicity and tumor-infiltrating lymphocyte (TIL) enrichment can benefit from immunotherapy relative to other breast cancer subtypes. Our work was designed to identify the TIL-related hub genes in TNBC and construct a prognostic signature for TNBC. TNBC gene expression files were obtained from the TCGA database. CIBERSORT algorithm and random forest risk model were used for immune infiltration group division. The TIL-related differentially expressed genes (DEGs) were then selected and subject to GO, KEGG analyses and GSEA. Next, Lasso cox regression analyses were adopted for constructing a prognostic risk model, followed by evaluation using time-dependent ROC curves. The copy number variation between the two risk groups was also analyzed, and major genomic mutation types were identified. Additionally, the nomogram was constructed with calibration curve for clinical prognosis analysis. Our results showed that totally 113 TNBC samples were allocated into the high or low-immune risk groups. We identified 243 DEGs between groups, namely TIL-related DEGs, with 128 upregulated and 115 downregulated genes. Among the TIL-related DEGs, 6 hub genes (SLITRK3, PCDHGB3, NELL2, SRRM4, ASIC2 and B4GALNT2) were screened out and constructed a prognostic risk signature, which had good performance for long-term prognosis prediction. Analysis of genomic mutation showed that the TP53, PIK3CA, TTH, etc. showed high mutation frequency in the two prognostic risk groups. Moreover, the higher risk score of the prognostic risk model predicted poor overall survival in TNBC patients, and nomogram and calibration curve confirmed the potent prediction ability of this model. To sum up, six TIL-related biomarkers (SLITRK3, PCDHGB3, NELL2, SRRM4, ASIC2 and B4GALNT2) were identified and used for the construction of the prognostic risk model, which might provide novel insight for the clinical decisions.

Impact of baseline body mass index on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy.

Primary liver cancer is the sixth most common cancer worldwide, with hepatocellular carcinoma (HCC) being the most prevalent form. Despite the current availability of multiple immune or immune combination treatment options, the prognosis is still poor, so how to identify a more suitable population is extremely important. To evaluate the clinical effectiveness of combining lenvatinib with camrelizumab for patients with hepatitis B virus (HBV)-related HCC in Barcelona Clinic Liver Cancer (BCLC) stages B/C, considering various body mass index (BMI) in different categories. Retrospective data were collected from 126 HCC patients treated with lenvatinib plus camrelizumab. Patients were divided into two groups based on BMI: The non-overweight group (BMI < 25 kg/m2, n = 51) and the overweight/obese group (BMI ≥ 25 kg/m2, n = 75). Short-term prognosis was evaluated using mRECIST criteria, with subgroup analyses for non-overweight (BMI: 18.5-24.9 kg/m2), overweight (BMI: 25-30 kg/m2), and obese (BMI ≥ 30 kg/m2) patients. A Cox proportional hazards regression analysis identified independent prognostic factors for overall survival (OS), leading to the development of a column-line graph model. Median progression-free survival was significantly longer in the obese/overweight group compared to the non-overweight group. Similarly, the median OS was significantly prolonged in the obese/overweight group than in the non-overweight group. The objective remission rate and disease control rate for the two groups of patients were, respectively, objective remission rate (5.88% vs 28.00%) and disease control rate (39.22% vs 62.67%). Fatigue was more prevalent in the obese/overweight group, while other adverse effects showed no statistically significant differences (P > 0.05). Subgroup analysis based on BMI showed that obese and overweight patients had better progression-free survival and OS than non-overweight patients, with obese patients showing the best outcomes. Multifactorial regression analysis identified BCLC grade, alpha-fetoprotein level, portal vein tumor thrombosis, and BMI as independent prognostic factors for OS. The column-line graph model highlighted the importance of BMI as a major predictor of patient prognosis, followed by alpha-fetoprotein level, BCLC classification, and portal vein tumor thrombosis. BMI is a long-term predictor of the efficacy of lenvatinib plus camrelizumab, and obese/overweight patients have a better prognosis.

Minimal intervention in pulpal and periapical pathology

Root canal treatment has been shown to be a predictable procedure with a favourable outcome in the case of pulpitis and apical periodontitis. The most important outcome measure is retention of an asymptomatic and functional tooth. When teeth are lost after root canal treatment, this is often the result of fracture due to weakening. By preventing or postponing root canal treatment, the long-term prognosis of the tooth may be better. Minimal interventions in endodontics are vital pulp therapy (indirect pulp therapy and pulpotomy), postponing and monitoring, and partial revision.

12270 Adolescent PCOS With Unexpected, Sudden-onset GAD And MDD: A Call For Vigilance In Longitudinal PCOS Care

Abstract Disclosure: K.I. Sarkisian: None. T. Aliabadi: None. F.Z. Stanczyk: None. Background: Polycystic Ovary Syndrome (PCOS) is a multifaceted endocrine disorder often associated with psychiatric disorders, yet the integration of psychiatric monitoring and multidisciplinary care following diagnosis remains understated as a guideline of clinical management of PCOS post-diagnosis. Historically, psychiatric comorbidities in PCOS have been attributed to social and personal factors such as self-image and self-esteem. However, the present patient’s denial of thoughts of disordered eating and lack of self-esteem related to acne or hirsutism challenges these assumptions.Clinical Case: A 13-year-old girl presented with classic symptoms of PCOS, including hirsutism, irregular and painful periods, and premature adrenarche. Laboratory investigations revealed an elevated total testosterone level (58 ng/dL, normal&amp;lt;38 ng/dL), consistent with PCOS. Previously, the patient had not expressed any concerns about mood. However psychological symptoms emerged alongside the physical symptoms. A psychological assessment performed by a licensed therapist revealed moderate-to-severe generalized anxiety disorder (GAD), which had rapidly worsened in a matter of weeks. Both the patient and the patient’s parents denied prior symptoms of moderate-to-severe anxiety before the onset of PCOS symptoms. Over the course of follow-up spanning 47 months, the patient documented symptoms, tracking both mood and PCOS fluctuations. During the follow-up period, the patient’s mood worsened, leading to the formal diagnosis of Major Depressive Disorder (MDD), despite a low assessed risk, no family history, and no symptoms prior to her PCOS development. The diagnoses of GAD and MDD were later confirmed through neuropsychiatric testing by a licensed psychologist.Clinical Lessons: While this presentation may not be considered novel in the context of PCOS, its overwhelming prevalence underscores the need for heightened awareness and research on the topic. The patient, previously considered low-risk for psychiatric conditions, experienced an unexpected onset of GAD and MDD concurrently with the diagnosis of PCOS. It is imperative to recognize that PCOS patients defy the conventional categorization of ‘healthy’ individuals concerning psychiatric care. This notion holds significance not only in clinical practice but also in research endeavors. Merely attributing psychiatric comorbidities in PCOS patients to social factors overlooks the unforeseen presentations of psychiatric disorders, as demonstrated in this patient. These manifestations cannot be solely attributed to social aspects of identity-insecurity, emphasizing the need for a more nuanced, proactive approach to psychiatric care in PCOS. This is crucial for achieving the best long-term prognosis and quality of life in affected individuals. Presentation: 6/1/2024

7316 A Unique Presentation of Diabetes Mellitus in an 8-Year-Old Male Positive For 3 Different Mutations Related to MODY

Abstract Disclosure: R. Senguttuvan: None. A. Pamfil: None. Background: Maturity-Onset Diabetes of the Young (MODY) is the most common form of inherited non-autoimmune diabetes mellitus, characterized by autosomal dominant inheritance, young age at onset and beta cell dysfunction. There are at least 14 MODY mutations and we present a pediatric case not meeting criteria for type 1[T1DM] or type 2 diabetes mellitus[T2DM], who tested positive for mutations in 3 different genes known to cause MODY. Case: An 8-year-old male, born full term, 2776 grams and 48.3 cm, without history of neonatal hypoglycemia or hyperglycemia, was referred for new onset diabetes mellitus management. While undergoing evaluation for abdominal pain and constipation, he was found to have a fasting glucose of 126 mg/dL (7 mmol/L) and hemoglobin A1C of 6.5%. He endorsed polyuria, but no polydipsia. He had no clinical signs of insulin resistance (e.g., acanthosis nigricans) and a BMI of 23.65 kg/m2, at the 97th percentile. Family history is positive for diabetes mellitus requiring insulin, in father (diagnosed at 11 years) and paternal grandmother and T2DM in paternal aunt. Laboratory evaluation was negative for all 5 antibodies (GAD, IA-2, Anti-islet cell antibody, Zinc Transporter 8 and Insulin antibodies) and revealed an insulin level of 15.9 uIU/mL (RR: &amp;lt;2.0-13.0) and C peptide: 2.3 ng/mL (RR: 1.1-4.4). Lacking diagnostic criteria for T1DM or T2DM, genetic testing was performed. Patient tested heterozygous for mutations in 3 genes known to cause MODY: GCK [(c.350 G&amp;gt;T p. (G117V)], ABCC8 [(c.2270 C&amp;gt;G p.(T757R)], and HNF1B [(c.68A&amp;gt;G p.(K23R)], all variant of uncertain significance. Over an 8-month period, patient's weight decreased from 98 lbs. (44.9 kg) to 90 lbs. (41.1 kg) after meeting with our dietician and implementing healthy dietary changes, and his beta cell function markers improved from diagnosis: Fasting insulin (4.5 uIU/mL), C peptide (1.3 ng/mL), and glucose 119 mg/dL; Hemoglobin A1C remained relatively stable at 6.1%. A kidney ultrasound was normal. No medical intervention were started yet, and patient is being monitored clinically and biochemically every 3-4 months. Discussion: Clinical monitoring over time, genetic testing in the parents, are critical in this patient’s long-term treatment plan and prognosis. To our knowledge, this may be the first case of diabetes mellitus in a pediatric patient, positive for mutations in 3 different genes known to cause MODY. South Texas has one of the highest incidences of T2DM in the USA. In addition to screening for genetic forms of diabetes, in patients with negative T1DM antibodies and atypical phenotype for T2DM, we should consider genetic screening in mildly obese pediatric and young adult patients without significant acanthosis nigricans, who were already diagnosed as T2DM. Presentation: 6/1/2024

7483 The Pharmacokinetic Profile of Lanreotide Autogel® Improved Long-Term Arrhythmia Fluctuations in Acromegalic Cardiomyopathy

Abstract Disclosure: M. Iwabuchi: None. Background: The prognosis of acromegaly is related to the status of cardiac complications. Ventricular premature contractions (VPC) are frequently observed in acromegaly, and it is very important to suppress fatal arrhythmias to improve long-term prognosis. Somatostatin analogs are widely used as pharmacotherapy for acromegaly, and they have been reported to improve cardiac prognosis. In comparison to LAR, lanreotide Autogel® has a unique property of self-aggregation under favorable conditions, leading to a stable structure of highly organized nanotubules and has a long half-life after subcutaneous injection determined by pseudo-first order kinetics. CASE: 55-year-old man visited a cardiologist for the treatment of PVCs and heart failure. Because of his acromegalic features, endocrinological and image examinations were performed, and diagnosis of acromegaly was confirmed. His GH was 7.17 ng/mL, IGF-1 566 ng/mL (Normal range: 59-215). Concerning excess of GH may cause nonischemic cardiomyopathy, administration of 20 mg of LAR once a month was started. GH and IGF-1 improved to1.52 ng/mL and 217 ng/mL respectively. The dose of LAR was increased to 30mg because of a remaining fluctuation of VPCs. Considering a possibility of the problem of bioavailability due to method of injection and the pharmacokinetics of LAR, administration of lanreotide Autogel® was started instead of LAR, with the result that an improvement of the fluctuation of the symptom was observed without remarkable change in GH and IGF-1. Arrhythmia status was assessed over time using Holter electrocardiography. Pretreatment Holter electrocardiogram showed 18% of total heart rates in PVCs. After LAR injection, the frequency of PVCs decreased to 3%, and 6 years after changing LAR to lanreotide, the frequency of PVCs decreased to 2%. Clinical Lessons: Simulated steady state pharmacokinetic profiles of LAR and lanreotide Autogel® differ significantly. During LAR treatment, serum concentrations of the drug are approximately stable, whereas the characteristic first-order kinetics of lanreotide Autogel® is superimposed on levels just before the next administration. The pharmacokinetic differences indicate that LAR can be better tailored to therapeutic levels, whereas serum levels of lanreotide must be high for part of the interval between injections to be effective in the period before the next administration. Lanreotide Autogel® has similar clinical effects compared to LAR for the treatment of cardiomyopathy of acromegaly and has the advantage of being available in a convenient pre-filled syringe and no necessity of injection by healthcare professionals. It is suggested that the pharmacokinetic profile of Lanreotide Autogel® resulted in decreased arrhythmia fluctuation in acromegalic hearts, which has been maintained for the past 6 years. Presentation: 6/3/2024

Association of hemoglobin glycation index with clinical outcomes in patients with coronary artery disease: a prospective cohort study

BackgroundTo analyze the association between the hemoglobin glycation index (HGI) and the long-term prognosis of patients with coronary artery disease (CAD).MethodsHGI represented the difference between laboratory measured Hemoglobin A1c (HbA1c) and predicted HbA1c based on a liner regression between Hb1Ac and fasting plasma glucose (FPG). A total of 10 598 patients who treated with percutaneous coronary intervention (PCI) were stratified into three groups (low HGI group: HGI<-0.506, medium HGI group: -0.506 ≤ HGI < 0.179, and high HGI group: HGI ≥ 0.179). The primary endpoints includes all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs).ResultsA total of 321 ACMs, 243 CMs, 774 MACEs, and 854 MACCEs were recorded during a 60-month follow-up period. After adjusting for confounders using a multivariate Cox regression analysis, the patients in the low HGI group had a significantly increased risk of ACM (adjusted HR = 1.683, 95%CI:1.179–2.404, P = 0.004) and CM (HR = 1.604, 95%CI:1.064–2.417, P = 0.024) as compared with patients in the medium HGI group. Similarly, the patients in the high HGI group had an increased risk of MACEs (HR = 1.247, 95% CI: 1.023–1.521, P = 0.029) as compared with patients in the medium HGI group. For ACM, CM, and MACEs, a U-shaped relation were found among these three groups. However, we did not find significant differences in the incidence of MACCEs among these three groups.ConclusionThe present study indicates that HGI could be an independent predictor for the risk of mortality and MACEs in patients with CAD.

Therapeutic advances for the management of adult T cell leukemia: Where do we stand?

Adult T cell leukemia (ATL) is an aggressive blood malignancy secondary to chronic infection with the human T cell leukemia virus type I (HTLV-1) retrovirus. ATL encompasses four subtypes (acute, lymphoma, chronic, and smoldering), which exhibit different clinical characteristics and respond differently to various treatment strategies. Yet, all four subtypes are characterized by a dismal long-term prognosis and a low survival rate. While antiretroviral therapy improves overall survival outcomes in smoldering and chronic subtypes, survival remains poor in lymphoma subtypes despite their good response to intensive chemotherapy. Nonetheless, acute ATL remains the most aggressive form associated with profound immunosuppression, chemo-resistance and dismal prognosis. Targeted therapies such as monoclonal antibodies, epigenetic therapies, and arsenic/IFN, emerged as promising therapeutic approaches in ATL. Allogeneic hematopoietic cell transplantation is the only potentially curative modality, alas applicable to only a small percentage of patients. The recent findings demonstrating the expression of the viral oncoprotein Tax in primary ATL cells from patients with acute or chronic ATL, albeit at low levels, and their dependence on continuous Tax expression for their survival, position ATL as a virus-addicted leukemia and validates the rationale of anti-viral treatment strategies. This review provides a comprehensive overview on conventional, anti-viral and targeted therapies of ATL, with emphasis on Tax-targeted therapied in the pre-clinical and clinical settings.

Prevention of Recurrent Myocardial Infarction in an Outpatient Setting

The aim was to study the medical and social characteristics of patients with repeated myocardial infarction (MI), features of the course of the disease, as well as the degree of contribution of cardiovascular disease (CVD) risk factors (RFs) to its development, in order to optimize secondary prevention measures at the primary health care level. Material and methods. Part of the study was carried out on the basis of a retrospective analysis of the outpatient records of all patients registered at the dispensary who had suffered primary MI and recurrent MI. Clinical, laboratory, and instrumental studies were carried out. Results. The study population had both non-modifiable and modifiable risk factors, among which the most common were low levels of physical activity, excess body weight, dyslipidemia and hypertension. The study also revealed gender differences in the prevalence of risk factors for coronary artery disease, which must be taken into account when conducting secondary prevention at the outpatient stage. Clear correlations were revealed between RF, clinical, laboratory, hemodynamic, and morphological, as well as functional parameters in patients with recurrent MI. The most significant correlations in patients with recurrent MI were between the number of complications and the degree of systolic cardiac dysfunction, as well as lipid metabolism disorders. Effective management of patients who have had an MI on an outpatient basis will reduce the risks of recurrent cardiovascular complications and will positively affect the long-term prognosis and clinical endpoints of MI.

Pregnancy cholestasis typically occurs in the third trimester of pregnancy and is a significant clinical condition.

The aim of this study is to determine the albumin/bilirubin ratio index and the aspartate aminotransferase (AST)/alanine aminotransferase ratio (ALT) index in patients diagnosed with cholestasis during pregnancy, and to demonstrate their correlation with liver damage. Additionally, potential strategies to prevent liver damage will be elucidated. Our study is a retrospective study. A total of 4019 pregnant women aged between 18 and 40years, presenting with itching complaints at 32-36weeks of gestation, were screened at the Department of Obstetrics and Gynecology, Istanbul Training and Research Hospital of Health Sciences University between January 1, 2018, and December 31, 2023. Among them, 104 pregnant women without any other accompanying diseases were diagnosed with Gestational Cholestasis. Among the 104 diagnosed women, 78 met the inclusion criteria and were included in the study. Twenty-six women were excluded from the study due to missing albumin and total bilirubin values or due to blood samples being taken at different times. The serum albumin/bilirubin ratio index and the alanine aminotransferase/aspartate aminotransferase ratio index were calculated and statistically compared between pregnant women diagnosed with cholestasis and healthy pregnant women at the same gestational week. We found that AST, ALT, albumin, and total bilirubin levels were significantly higher in pregnant women diagnosed with cholestasis compared to the control group (p < 0.05). The AST/ALT index in the case group was significantly lower compared to the control group. However, there were no significant differences found between the case and control groups regarding the albumin/total bilirubin index and ALBI grade. When comparing ALBI grades in cases, no significant differences were found in terms of patients' age, gestational week, AST, ALT, and AST/ALT index. When compared according to ALBI grades, the albumin level was higher in patients with ALBI grade I compared to grade II, and in patients with grade II compared to grade III. The total bilirubin level was significantly higher in patients with ALBI grade III compared to grades I and II, but there was no significant difference between grades I and II. No significant differences were found among the groups separated according to ALBI grades when FBA values were compared. In this study, the negative correlation between lower AST/ALT ratio and FBA values in patients with severe cholestasis suggests the need for careful consideration regarding future liver damage. The lack of difference in ALBI score between the case and control groups, as well as the absence of correlation with FBA values, indicates the necessity to evaluate ALBI score based on patients' long-term prognosis.

Association of Self-Reported Improvement After 4 Weeks and Outcomes After 52 Weeks Among Adolescents With Patellofemoral Pain and Osgood-Schlatter Disease.

Short-term, self-reported changes in symptom severity for musculoskeletal pain disorders may be more strongly associated with long-term prognoses than baseline patient characteristics, because such changes describe a trajectory and not a state. To investigate whether short-term improvement in self-reported symptom severity is associated with long-term recovery among adolescents with nontraumatic knee pain (patellofemoral pain [PFP] or Osgood-Schlatter disease [OSD]). Cohort study; Level of evidence, 3. The authors evaluated data from 2 prospective clinical trials that included adolescents aged 10 to 14 years with either PFP (n = 151) or OSD (n = 51). Both groups underwent a self-management rehabilitation program including activity modification, education, and exercise. The primary outcome was a 7-point global rating of change (GROC) scale (from "much improved" to "much worse"); participants were considered to have improved symptoms if they reported being "much improved" or "improved." Outcomes were collected after 4 and 52 weeks. To investigate whether participants who improved according to GROC scores after 4 weeks were more likely to improve after 52 weeks compared with those who had not improved after 4 weeks, the authors calculated the relative risk (RR) of being improved. Among participants with PFP, reporting an improvement after 4 weeks increased the likelihood of an improvement after 52 weeks (RR = 1.26; 95% CI, 1.06-1.50; P = .008); among those with OSD, reporting an improvement after 4 weeks did not increase the likelihood of an improvement after 52 weeks (RR = 1.06; 95% CI, 0.88-1.28; P = .545). Among participants with PFP who did not improve after 4 weeks, 73% reported improvement after 52 weeks, whereas among participants with OSD who did not improve after 4 weeks, 89% reported improvement after 52 weeks. Self-reported improvement after 4 weeks of treatment was associated with better outcomes after 52 weeks among adolescents with PFP. This association was present only among adolescents with PFP, as almost all adolescents with OSD improved after 52 weeks, regardless of short-term results. Importantly, even among adolescents reporting no improvement after 4 weeks, a large proportion reported improvement after 52 weeks. This highlights the importance of following the rehabilitation program regardless of the short-term response.

Preoperative markers for identifying CT ≤2 cm solid nodules of lung adenocarcinoma based on image deep learning.

The solid pattern is a highly malignant subtype of lung adenocarcinoma. In the current era of transitioning from lobectomy to sublobar resection for the surgical treatment of small lung cancers, preoperative identification of this subtype is highly important for patient surgical approach selection and long-term prognosis. A total of 1489 patients with clinical stage IA1-2 primary lung adenocarcinoma were enrolled. Based on patient clinical characteristics and lung imaging features obtained via deep learning, highly correlated diagnostic factors were identified through LASSO regression and decision tree analysis. Subsequently, a logistic model and nomogram were constructed. A restricted cubic spline (RCS) was used to calculate the optimal inflection point of quantitative data and the differences between the groups. The three-dimensional proportion of solid component (PSC), sex, and smoking status was identified as being highly correlated diagnostic factors for solid predominant adenocarcinoma. The logistic model had good prediction efficiency, and the area under the ROC curve was 0.85. Decision curve analysis demonstrated that the application of diagnostic factors can improve patient outcomes. RCS analysis indicated that the proportion of solid adenocarcinomas increased by 4.6 times when the PSC was ≥72%. A PSC of 72% is a good cutoff point. The preoperative diagnosis of solid-pattern adenocarcinoma can be confirmed by typical imaging features and clinical characteristics, assisting the thoracic surgeon in developing a more precise surgical plan.

Clinical Features, Long-Term Prognosis, and Clinical Management of Genotype-Negative Long QT Syndrome Patients.

Approximately 15% to 20% of patients clinically diagnosed with long QT syndrome (LQTS) are genotype-negative (GEN-). Whether they have a different arrhythmic risk or should be managed differently remains unclear, often leading to incomplete treatment. The purpose of this study was to compare clinical aspects of GEN- and genotype-positive (GEN+) LQTS patients. We retrospectively evaluated 832 LQTS patients genetically screened in Japan (n=347) and Italy (n=485), including 698 with a disease-causing variant in the KCNQ1, KCNH2, and SCN5A genes (GEN+), and 134 without variants in these LQTS-related genes (GEN-). At diagnosis, the Japanese patients were more often probands (86% vs 60%), symptomatic (39% vs 18%), and of younger age than the Italian patients; conversely, they used less β-blockers (65% vs 95%), more rarely had a family history (FH) of LQTS (42% vs 73%), and had more cardiac events during follow-up (13% vs 4%) (P< 0.001 for all comparisons). Within the Japanese cohort, the GEN- had more cardiac arrests, used less β-blockers, and had much less FH for LQTS compared their GEN+ counterpart. The Italian cohort was more homogeneous, with just more LQTS FH among the GEN+. QTc shortening (close to 30ms in all groups) during follow-up was similar between Japanese and Italian patients, irrespective of their being GEN+ or GEN-. In both cohorts, during an average follow-up of 6 and 7 years, respectively, GEN+ and GEN- patients showed a comparable clinical outcome. Arrhythmic risk is similar between GEN+ and GEN- LQTS patients; they should be managed and treated in the same way.