Cessation Of Therapy Research Articles

An ODEs multiscale model with cell proliferation for hepatitis C virus infection treated with direct acting antiviral agents

In a recent study, a mathematically identical ODE model is derived from a multiscale PDE model of hepatitis C virus infection, which helps to overcome the limitations of the PDE model in the analysis. Here, an extended proposed model is formulated for this transformed ODE model by including the hepatocyte proliferation of both uninfected and infected cells. Unlike the transformed model, the proposed model can predict the triphasic viral decline and the virus level after therapy cessation without oscillations. Numerical simulations are performed to investigate the effect of hepatocyte proliferation and therapy with direct-acting antivirals agents (DAAs). The basic reproduction number is obtained, the equilibrium points are specified, and their stability is analysed. A bifurcation analysis is performed to specify the bifurcation points and to study the effect of varying system parameters. Various viral load profiles generated by the model are confirmed to fit with reported data in the literature.

Prothrombotic Rebound After Discontinuation of Direct Oral Anticoagulants Therapy: A Systematic Review.

Background/Objectives: The practice of holding anticoagulation is a relatively common approach, with the aim of either preventing excessive bleeding in preparation for surgical procedures or managing acute bleeding episodes. Methods: To assess the relationship between the discontinuation of direct oral anticoagulants (DOACs) therapy and the condition of hypercoagulability, a systematic review of the literature was conducted, following PRISMA guidelines, in PubMed/MEDLINE, Cochrane, and Google Scholar. These databases were searched for all publications that described a rebound phenomenon or hypercoagulability state after DOACs discontinuation. Results: A total of 1494 articles were selected from searched databases, and 29 were eligible. A final total of 16 case reports and 14 original research articles were subjected to analysis. Conclusions: The results of this study indicate that the cessation of DOAC therapy may be associated with an increased risk of thrombotic events. More studies are required to ascertain whether DOACs treatment cessation can be linked to rebound phenomena associated with thromboembolic events. This will provide the data needed to determine the incidence and risk of this phenomenon.

Reply to: “Prediction of HBsAg loss after cessation of entecavir therapy”

Reply to: “Prediction of HBsAg loss after cessation of entecavir therapy”

A novel risk-stratification model that predicts long-term clinical outcomes in patients with recurrent pericarditis

Abstract Background Recurrent Pericarditis (RP) is condition associated with significant debility and morbidity. Previous studies have identified variables such as elevated C-Reactive protein, corticosteroid usage, and presence of delayed hyper-enhancement (DHE) on cardiac magnetic resonance imaging are associated with recurrence. To date however, there is no established model for risk stratifying outcomes in these patients, therefore we attempted to develop a model that could predict long-term outcomes in patients with RP and stratify them into groups based on risk. Methods A total of 365 consecutive patients with RP from 2012-2019 were retrospectively examined. Our primary outcome was clinical remission (CR) defined as symptom resolution in addition to complete cessation of all anti-inflammatory therapy. We employed 5 survival models: CoxPH, RSF, SSVM, GBSA and XGBoost with Cox loss function to determine the likelihood of achieving CR within 5 years and to stratify patients into specific risk groups. We divided the dataset into training (70%) and test (30%) sets. Model training and optimization of the training set occurred via 5-fold cross validation. Model evaluation and selection was based on C-index. Finally, we employed an explainable artificial intelligence approach, SHapley Additive exPlanations to generate both individual and global explanation of the models decision. Results Amongst the cohort, the mean age was 46 ± 15 years, 205 (56%) were female, and the main etiology was idiopathic in 223 (61%). CR was achieved in 118 (32%) patients. The final model included steroid dependency, total number of recurrences, pericardial DHE, age, etiology, gender, ejection fraction and heart rate as its most important parameters. We observed similar CR rates across three risk score ranges and accordingly stratified patients into low (n=62), intermediate (n=154), and high-risk (n=149) groups. Scores of 3 or lower were categorized as low risk, with CR rates exceeding 90%. Scores of 4 to 7 were associated with CR rates of 50%. Scores of 8 or higher were deemed high-risk, with CR rates notably below 10%. Overall, the model predicted the outcome with C-index of 0.800 on the test set and exhibited a significant ability in stratification of patients into low-, intermediate-, and high-risk groups (log-rank test; P <0.0001). Conclusion We created a novel risk prediction model that can aid in predicting rates clinical remission in patients with recurrent pericarditis as well as aid in stratification into low, medium, and high risk groups. This risk prediction model may be helpful in diagnosis and management of these complicated patients.Figure 1

Sex-related outcomes in patients receiving shortened or longer dual antiplatelet treatment after percutaneous coronary intervention: a systematic review and meta-analysis

Abstract Background There are known gender disparities in the pathophysiology, clinical presentation, and prognosis of coronary artery disease between male and female patients. Although antiplatelet therapy cessation is more frequent among women, female gender is an independent factor for major bleeding after percutaneous coronary interventions. Considering that the ischemic and bleeding risk of women undergoing PCI differ from men, it follows that the safety and efficacy of shortened, one or 3 months, DAPT (S-DAPT) compared to longer DAPT (L-DAPT) after PCI might differ between the sexes. Purpose Our systematic review and meta-analysis aims to explore the safety and efficacy of S-DAPT versus L-DAPT in men and women having undergone PCI. Methods Three major databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus) were screened for eligible randomized – controlled trials, or subgroup or post – hoc analyses of them. The studies should compare S-DAPT with L-DAPT in male and female patients undergoing PCI, providing separate data. The endpoints were Net Adverse Clinical Events (NACE), Major Adverse Cardiac Events (MACE), all-cause mortality, myocardial infarction and major bleeding. All endpoints were used as per trial defined and should be evaluated in 12-months. The effect of different DAPT regimens was assessed by calculating the risk ratio (RR) with 95% confidence intervals (CIs), using a random-effects model (Mantel-Haenzel). Results A total of eight studies and 46,476 patients were included; women were underrepresented being only the 26% (N=12,063) of the total participants. MACE did not differ significantly in the two arms in the total sample (RR: 0.94, 95%CI: 0.86-1.04); however, they were significantly reduced in women treated with S-DAPT (RR: 0.82, 95%CI: 0.70-0.97) (p-interaction: 0.049). (Figure 1) S-DAPT was associated with a significant reduction in both NACE (RR: 0.91, 95% CI: 0.85-0.99) (Figure 2A) and major bleeding (RR: 0.73, 95% CI: 0.57-0.95) (Figure 2C) in the total sample, without significant differences between male and female patients (p-interaction: 0.14 and 0.053, respectively). All-cause mortality (RR: 0.86, 95%CI: 0.73-1.01) (Figure 2B) and myocardial infarction rates (RR: 1.03, 95%CI: 0.86-1.24) (Figure 2D) were similar in both S-DAPT and L-DAPT in the total sample, without any significant subgroup differences (p-interaction: 0.13 and 0.051, respectively). Conclusions Shortened duration of DAPT significantly decreased MACE in women, in contrast with male patients, showing that women may benefit from abbreviated duration of DAPT. Further studies specifically investigating the optimal duration of DAPT in women are warranted and a sex-based approach could be considered in the management of antiplatelet treatment after PCI.A. NACE B. Mortality C. Bleedings D. MI

Baseline Clinical Factors Associated with Cessation of Growth Hormone Therapy in Patients with Severe Growth Hormone Deficiency - Real World Evidence

Background: Growth hormone replacement is indicated in adults with severe growth hormone (GH) deficiency, adult growth hormone deficiency assessment (AGHDA) score of at least 11 and are receiving treatment for other pituitary hormone deficiencies. There are no data looking at the cessation of GH replacement in adult patients with severe GH deficiency and the factors that predict the likelihood of patients continuing or stopping growth hormone replacement. Methods: We audited patients on the GH register between January 2006 and January 2023 in Hull University Teaching Hospitals NHS foundation Trust, a UK tertiary hospital. Baseline characteristics, the cause of GH deficiency, AGHDA score at diagnosis and the reason for stopping GH were collected. Proportions were compared between patients adhering to GH replacement and those who had ceased it. Logistic regression analysis was used to identify factors independently associated with cessation of GH. Results: The study comprised 141 adult patients with a mean age of 52 years, of which 75 (53%) were female. 54 (38%) individuals had discontinued GH replacement therapy. Predominant reasons for discontinuation were lack of therapeutic benefit (46%) and a change in clinical indication (26%). Among patients who discontinued GH therapy, the most frequent cause of GH deficiency was idiopathic (57%), while for those on GH replacement, pituitary surgery was the leading cause of GH deficiency (53%). Logistic regression analysis showed no baseline factor was statistically significantly associated with GH cessation, except female gender which had a borderline significance (P = 0.05). Conclusions: In this real-world investigation of patients with severe GH deficiency, over two in five individuals who discontinued GH therapy cited the absence of perceived benefits. We show a borderline association of female gender with GH cessation and large population-based studies will be needed to investigate this and other causes of GH cessation.

Histologic Patterns of Ribociclib-induced Liver Injury

Abstract Introduction/Objective Ribociclib, a cyclin dependent kinase (CDK) 4/6 inhibitor, used in the treatment of advanced breast carcinomas, can cause liver injury, often manifesting as elevated liver enzymes. However, the histologic patterns of liver injury caused by Ribociclib have not been well-documented. Our study aims to explore these patterns in patients undergoing Ribociclib treatment. Methods/Case Report Five female patients receiving Ribociclib treatment for breast carcinomas and undergoing liver biopsy post-transaminitis in the past seven years (2017-2024) were identified using our institution’s electronic medical record. Clinical information was collected, and liver biopsies were reviewed for histologic injury patterns. Results (if a Case Study enter NA) The mean age of the patients was 47 years (range 38-68). All patients had liver enzyme abnormalities after starting with Ribociclib: mean time to peak of ALT and AST was 75 days (range 36-125). Mean peak enzyme levels (IU/L) for ALT and AST were 685 and 420, respectively. Liver biopsy showed an acute hepatitis pattern of injury in all five patients: centrizonal confluent necrosis (n=3) and lobular spotty necrosis (n=2). Other findings included: mild cholestasis (n=1), interface hepatitis (n=2), focal bile duct injury (n=2), and mild macrovesicular steatosis without steatohepatitis (n=1). Portal inflammation was mild to moderate, comprising a mixed lymphoplasmacytic infiltrate. One patient had moderate periportal fibrosis without bridging. Ribociclib was withdrawn in all patients; three patients received prednisolone treatment. Three patients were rechallenged with Abemaciclib and two with Palbociclib. All patients had resolution of liver function tests after cessation of Ribociclib therapy. Mean time to normalization of ALT and AST was 46 days (range 30-72) and 62 days (range 30-96), respectively, after holding Ribociclib. Conclusion Ribociclib predominantly causes an acute hepatitis pattern of liver injury and of varying severity. Drug cessation, with or without steroid therapy, and switching to a less hepatotoxic CDK 4/6 inhibitor can be sufficient to restore normal liver function. Screening for liver dysfunction with baseline enzyme tests prior to Ribociclib treatment, as well as serial testing to trend enzyme levels, may help prevent severe liver injury.

Discontinuation of maintenance therapy in multiple myeloma guided by multimodal measurable residual disease negativity (MRD2STOP)

MRD2STOP is a pragmatic trial evaluating maintenance therapy cessation guided by measurable residual disease (MRD) negativity in multiple myeloma (MM). Eligible patients had previous MRD < 10−5, received ≥1 year of maintenance, and were prospectively confirmed to have undetectable disease by positron emission tomography, bone marrow (BM) flow cytometry (limit of detection [LoD] 10−5), and BM clonoSEQ (LoD 10−6). BM aspirates enriched for CD138+ cells were analyzed by clonoSEQ to achieve MRD 10−7 sensitivity. We evaluated the incidence of disease resurgence and progression-free survival (PFS), stratified by 10−7 status. Forty-seven patients discontinued maintenance after a median of 36 months. Baseline MRD ≥ 10−7 was observed in 19% (9/47). The median follow-up post-discontinuation was 30 months. Disease resurgence (MRD 10 ≥ −6) occurred in 11 patients, including 5 disease progressions. One patient died from a second cancer. The estimated 3-year cumulative incidence of disease resurgence was 20% for patients with baseline MRD < 10−7 compared to 75% for MRD ≥ 10−7 (HR 7.8, 95% CI 2.2-27.6, p = 0.001). Baseline MRD ≥ 10−7 was associated with inferior PFS compared to MRD < 10−7 (HR 10.1, 95% CI 1.6–62.3; 3-year PFS 49% vs 92%). Maintenance discontinuation in patients with MM and MRD < 10−6 led to low rates of disease resurgence. MRD < 10−7 may be a superior cessation threshold, requiring further validation.

Dynamic Changes of Growth and Thyroid Function in Young Children With Chronic Hepatitis B Treated With Peginterferon Monotherapy.

Peginterferon (PegIFN) has shown promising results in the treatment of chronic hepatitis B (CHB). This study aimed to evaluate the effects of PegIFN α-2b on growth and thyroid function in young children with CHB. A retrospective study was performed by extracting clinical data from children with CHB who received PegIFN α-2b monotherapy at the Public Health Clinical Center of Chengdu between June 2017 and December 2020. Mean, SD, independent samples t test and 1-way repeated analysis of variance were used to evaluate relevant data. A total of 62 children were included in this study. Overall, significant differences were observed in the weight-for-age z score (WAZ), height-for-age z score (HAZ) and body mass index-for-age z score (BAZ) at different time points ( P < 0.001). WAZ, HAZ and BAZ were not affected by PegIFN α-2b at 24 weeks of treatment (all P > 0.05). WAZ, HAZ and BAZ at the end of treatment and 48 weeks after treatment; WAZ at 96 weeks after treatment were lower than baseline levels (all P < 0.05). No statistical differences were found in HAZ and BAZ at 96 weeks after treatment compared with baseline. Thyroid dysfunction developed in 17.7% of children during the treatment. Thyroid dysfunction was transient and had no effect on growth. PegIFN α-2b has inhibitory effects on growth and can increase the incidence of thyroid dysfunction in young children with CHB. These effects are generally reversible with the cessation of therapy, although WAZ had not returned to baseline after 96 weeks of observation.

8407 Baseline Clinical Factors Associated with Cessation of Growth Hormone Therapy in Patients with Severe Growth Hormone Deficiency: Real World Evidence

8407 Baseline Clinical Factors Associated with Cessation of Growth Hormone Therapy in Patients with Severe Growth Hormone Deficiency: Real World Evidence

Real-World Experience of the Association of HLADQA1*05 Allele With Loss of Response to Anti-TNF Inhibitors.

Antitumor necrosis factor (anti-TNF) biologics have revolutionized the treatment of inflammatory bowel disease (IBD). Previously, studies have shown an association between the HLADQA1*05 allele and the development of antibodies and were predictive of loss of response. We sought to investigate the rate of the HLADQA1*05 allele in patients with IBD at a New England center and its association with antibody development and discontinuation of anti-TNF therapy. A single center retrospective cohort study with patients on anti-TNF inhibitor therapy being followed at our IBD clinic who had testing performed for the HLADQA1*05 allele were identified and separated into 2 different groups: HLADQA1*05 positive (HLA carriers) or HLADQA1*05 negative (HLA noncarriers). Persistence of remaining on anti-TNF therapy, measurement of drug/antibody levels, and need for dose escalation were collected and stratified amongst the 2 groups. The prevalence of the HLADQA1*05 allele among all IBD patients followed was 53%. We identified 67 IBD patients being treated with anti-TNF medications, 46 (69%) patients with Crohn's disease and 21 (31%) with ulcerative colitis. Most of the HLA carriers (85%) and HLA noncarriers (92%) remained on anti-TNF therapy at the end of the study period. Thirty-six (84%) patients had therapeutic drug monitoring performed during maintenance therapy. Three patients in the HLA carrier group had meaningful antidrug antibody levels necessitating cessation of therapy compared to one patient in the HLA noncarrier group (P = .61). Only 3 (13%) of HLA carriers and 4 (21%) of HLA noncarriers were on combination therapy with an immunomodulator. 65% of HLA carriers required dose escalation compared to 50% of HLA noncarriers (P = .70). The prevalence of the HLADQA1*05 allele was 53% in our New England IBD patient population, similar to what has previously been reported in European studies. The majority of patients remained on anti-TNF therapy at the end of the study period despite carrier status. While there was a trend toward increased need for dose escalation among HLA carriers, this was not statistically significant. Future studies are needed to determine if the presence of the HLADQA1*05 allele leads to antibody development against anti-TNF inhibitors and treatment failure in patients with IBD.

Severe relapse after cessation of immunosuppressive therapy in a patient with co‐occurrence of neuromyelitis optica spectrum disorder and Sjögren's syndrome: A case report

Severe relapse after cessation of immunosuppressive therapy in a patient with co‐occurrence of neuromyelitis optica spectrum disorder and Sjögren's syndrome: A case report

T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma: Optimal Dosing Schedule and Duration of Treatment.

T cell-redirecting bispecific antibodies (BsAb) induce significant responses in heavily pretreated multiple myeloma. BsAbs are currently administered in a dose-dense manner until disease progression. However, continuous therapy is associated with safety concerns, including a high risk of infections and high costs. In addition, chronic exposure to BsAbs, and thus long-term T-cell stimulation, induces T-cell exhaustion, which may contribute to relapse. There is increasing evidence that the strategy of induction treatment followed by maintenance with longer intervals between BsAb doses, or limited treatment duration with cessation of therapy in patients who achieve deep remission, improves the balance between toxicity and efficacy. Significance: There is increasing evidence that after initial debulking, less-frequent BsAb administration mitigates T-cell exhaustion and minimizes the potential for chronic or cumulative toxicity while maintaining durable clinical responses. In addition, specific patient subsets may experience an extended treatment-free period following fixed-duration treatment. Fixed-duration treatment may, therefore, decrease cumulative toxicities and the burden on patients and healthcare systems.

Ileoanal pouch salvage rates with endoluminal vacuum therapy for early vs late anastomotic leaks

BackgroundAnastomotic leaks after ileal pouch-anal anastomosis (IPAA) significantly compromise patient outcomes and increase healthcare resource utilization. The aim of this study was to evaluate the outcomes of endoluminal vacuum therapy (EndoVac) for pouch leaks. We hypothesized that EndoVac for early compared with late leaks was associated with a higher pouch survival rate. MethodsWe retrospectively reviewed consecutive pouch anastomotic leaks treated with EndoVac therapy at our institution between 2013 and 2023. Patients were stratified into early (≤30 days) and late (>30 days) leak groups. Anastomotic healing was defined as complete closure of the leak site and resolution of symptoms. Pouch failure was defined as a permanent ileostomy or pouch excision. The probability of pouch survival was estimated using the Kaplan-Meier method. ResultsA total of 14 patients with IPAA were included: median age, 34 years; 71% were males; and median body mass index, 23.46 kg/m2. The following were the diagnoses made: ulcerative colitis (n = 12) and familial adenomatous polyposis (n = 2). The median (IQR) time from pouch construction to leak was 44.5 (12−192) days; of these, 6 (43%) were early, and 8 (57%) were late. All (100%) leaks were at the anastomosis; all (100%) were diverted at the time of EndoVac therapy: 10 (71%) still diverted, and 4 (29%) rediverted. Patients underwent a median of 5.5 EndoVac changes (3−7) over a 13.5 (6−21) day period from initiation of treatment to cessation of therapy. After EndoVac therapy, healing was observed in 10 (71%) patients; 2 of whom required a minor handsewn anastomotic revision but healed completely, and 4 did not heal; 3 had pouch excision, and 1 underwent redo pouch surgery. Anastomotic healing (66.7% vs 75%, P = .7) and pouch survival (83.3% vs 75%, P = .73) were not significantly different between the early and late leak groups. The overall pouch salvage rate was 78.5%. ConclusionEndoVac therapy was effective in achieving high rates of pouch salvage and anastomotic healing in patients with ileoanal pouch leaks, irrespective of the timing of intervention postoperatively. This supports the use of EndoVac as a viable treatment option for both early and late anastomotic leaks.

Estimation of renal function immediately after cessation of continuous renal replacement therapy at the ICU

Estimating glomerular filtration (eGFR) after Continuous Renal Replacement Therapy (CRRT) is important to guide drug dosing and to assess the need to re-initiate CRRT. Standard eGFR equations cannot be applied as these patients neither have steady-state serum creatinine concentration nor average muscle mass. In this study we evaluate the combination of dynamic renal function with CT-scan based correction for aberrant muscle mass to estimate renal function immediately after CRRT cessation. We prospectively included 31 patients admitted to an academic intensive care unit (ICU) with a total of 37 CRRT cessations and measured serum creatinine before cessation (T1), directly (T2) and 5 h (T3) after cessation and the following two days when eGFR stabilized (T4, T5). We used the dynamic creatinine clearance calculation (D3C) equation to calculate eGFR (D3CGFR) and creatinine clearance (D3Ccreat) between T2-T3. D3Ccreat was corrected for aberrant muscle mass when a CT-scan was available using the CRAFT equation. We compared D3CGFR to stabilized CKD-EPI at T5 and D3CCreat to 4-h urinary creatinine clearance (4-h uCrCl) between T2-T3. We retrospectively validated these results in a larger retrospective cohort (NICE database; 1856 patients, 2064 cessations). The D3CGFR was comparable to observed stabilized CKD-EPI at T5 in the prospective cohort (MPE = − 1.6 ml/min/1.73 m2, p30 = 76%) and in the retrospective NICE-database (MPE = 3.2 ml/min/1.73 m2, p30 = 80%). In the prospective cohort, the D3CCreat had poor accuracy compared to 4-h uCrCl (MPE = 17 ml/min/1.73 m2, p30 = 24%). In a subset of patients (n = 13) where CT-scans were available, combination of CRAFT and D3CCreat improved bias and accuracy (MPE = 8 ml/min/1.73 m2, RMSE = 18 ml/min/1.73 m2) versus D3CCreat alone (MPE = 18 ml/min/1.73 m2, RMSE = 32 ml/min/1.73 m2). The D3CGFR improves assessment of eGFR in ICU patients immediately after CRRT cessation. Although the D3CCreat had poor association with underlying creatinine clearance, inclusion of CT derived biometric parameters in the dynamic renal function algorithm further improved the performance, stressing the role of muscle mass integration into renal function equations in critically ill patients.

Multi-omics analysis of SIV-specific CD8+ T cells in multiple anatomical sites.

CD8+ T cells exert immunological pressure against immunodeficiency lentiviruses. In previous studies, we examined the TCR repertoire of CD8+ T cells specific for a single SIV immunodominant epitope, Gag-CM9, throughout SIV infection or after vaccination, and across multiple anatomic sites. We identified both tissue specific TCR sequences and TCRs shared by multiple anatomical sites. Here we use single cell RNA sequencing to evaluate if the tissue localization or TCR sequence of a CM9-specific CD8+ T cell corresponds with unique transcriptomics. CM9-specific CD8+ T cells were sorted from blood, lymph nodes, spleen, and liver from SIV infected rhesus macaques with progressive SIV infection and in animals who spontaneously control SIV replication after cessation of antiretroviral therapy. The cells were processed through a single cell sequencing protocol, creating a TCR amplified library and an RNA gene expression library corresponding to individual cells. Gene set enrichment analysis revealed no distinct transcriptional profiles for CM9 specific CD8+ T cells between different anatomical sites and between cells with shared or tissue specific TCRs. Similarly, no clear transcriptional profiles were associated with clonotypes which were shared across individual animals. However, CM9 specific CD8+ T cells from posttreatment controllers did exhibit enrichment of pathways associated with cellular activation compared to progressively infected animals, suggesting that altered transcription in distinct cellular pathways in antigen specific CD8+ T cells may associate with viral control. Together, these studies represent a thorough analysis of the relationship between anatomical and clonal origin, and the transcriptional profile of antigen specific CD8+ T cells and unravel pathways that may be important for CD8+ T cell mediated control of SIV replication.

Predicting Long-Term Clinical Outcomes of Patients With Recurrent Pericarditis

BackgroundRecurrent pericarditis (RP) is a complex condition associated with significant morbidity. Prior studies have evaluated which variables are associated with clinical remission. However, there is currently no established risk-stratification model for predicting outcomes in these patients. ObjectivesWe developed a risk stratification model that can predict long-term outcomes in patients with RP and enable identification of patients with characteristics that portend poor outcomes. MethodsWe retrospectively studied a total of 365 consecutive patients with RP from 2012 to 2019. The primary outcome was clinical remission (CR), defined as cessation of all anti-inflammatory therapy with complete resolution of symptoms. Five machine learning survival models were used to calculate the likelihood of CR within 5 years and stratify patients into high-risk, intermediate-risk, and low-risk groups. ResultsAmong the cohort, the mean age was 46 ± 15 years, and 205 (56%) were women. CR was achieved in 118 (32%) patients. The final model included steroid dependency, total number of recurrences, pericardial late gadolinium enhancement, age, etiology, sex, ejection fraction, and heart rate as the most important parameters. The model predicted the outcome with a C-index of 0.800 on the test set and exhibited a significant ability in stratification of patients into low-risk, intermediate-risk, and high-risk groups (log-rank test; P < 0.0001). ConclusionsWe developed a novel risk-stratification model for predicting CR in RP. Our model can also aid in stratifying patients, with high discriminative ability. The use of an explainable machine learning model can aid physicians in making individualized treatment decision in RP patients.

One-Stage Burr Hole Surgery and Middle Meningeal Arterial Embolization for Treating Chronic Subdural Hematoma in a Hybrid Operative Angiography Suite

BackgroundChronic subdural hematoma (CSDH) is a prevalent neurosurgical condition that is known to recur and that leads to unfavorable clinical outcomes. Middle meningeal artery embolization (MMAE) has emerged as an alternative treatment to prevent recurrence. This study investigated the efficacy of combined two therapies in a hybrid operative suite for high-risk patients. MethodsThis retrospective review provides evidence for the indications and benefits of one-stage combined therapy in a hybrid neurovascular operative suite. The procedures include burr hole craniostomy, irrigation, and drainage followed by adjuvant MMAE at the lesion site. Subsequently, routine cone beam computed tomography is conducted after the whole process. ResultsFive patients with symptomatic CSDH and mass effect were enrolled in this study. Among them, three patients had undergone burr hole surgery previously but experienced hematoma recurrence. Two patients presented with a history of recent cardiac stent placement due to coronary artery disease, precluding the cessation of antiplatelet or anticoagulant therapy. All patients experienced symptom resolution and demonstrated no evidence of CSDH recurrence during the follow-up period. ConclusionIn our initial case experiences, one-stage burr hole surgery and adjuvant MMAE for treating chronic subdural hematoma in a hybrid operative angiography suite could be a feasible and effective treatment modality.

Insulin-Related Suicides-3 Cases.

Insulin is a pancreas-produced hormone, which is essential for normal life. In persons with diabetes, who lack sufficient production of endogenous insulin, the availability of exogenously-produced and administered insulin represents an extremely valuable, life-preserving medical advancement. Unfortunately, as with many other medications, overdosage with insulin can and does occur, sometimes in an intentional suicidal manner. Another possible insulin-related suicidal action involves the intentional cessation of insulin therapy by someone who relies on insulin for survival. In this case series, we present 3 cases of insulin-related suicides, including two related to intentional insulin overdose and one where a known diabetic purposefully stopped taking insulin in order to commit suicide.

Combination blood pressure lowering therapy in patients with type 2 diabetes: messages from the ADVANCE trial.

The Action in Diabetes and Vascular disease: preterAx and diamicroN Controlled Evaluation (ADVANCE) trial investigated the effects of intensive blood pressure (BP) lowering using a fixed combination of perindopril-indapamide versus placebo in type 2 diabetes (T2D). The study showed that combination perindopril-indapamide had significant benefits in reducing cardiovascular, renal, and mortality events, with consistent relative risk reductions across different patient subgroups. Secondary analyses of ADVANCE have identified novel risk markers in T2D including cessation of BP lowering therapy, absent peripheral pulses and cardiac biomarkers to name a few. ADVANCE also shed light on practical aspects of hypertension management, including the limitations of office BP, tolerability of combination BP lowering therapy across the range of BP levels and the interpretation of changes in serum creatinine after treatment initiation. This review article summarizes the findings of ADVANCE and its subsequent substudies, which have been foundational in our understanding of BP management and the use of combination BP lowering therapy in T2D.