Withdrawal Of Therapy Research Articles

Abstract Su701: The Influence of Public Assistance Among Patients Who Received Extracorporeal Cardiopulmonary Resuscitation after Cardiac Arrest in Japan

Background: This study aimed to evaluate the influence of public assistance on patients with out-of-hospital cardiac arrest (OHCA) who received extracorporeal cardiopulmonary resuscitation (ECPR) in Japan. Methods: We conducted a secondary analysis of data from the SAVE-J II study, a retrospective, multicenter registry study involving 36 participating institutions in Japan. Patients with cardiac arrest who received ECPR were divided into two groups depending on whether or not they had received public assistance. The primary outcome was 30-day survival. Secondary outcomes were as follows: 30-day favorable neurological outcomes (cerebral performance category scores 1-2); survival at discharge; favorable neurological outcome at discharge; number of intensive care unit, hospital, ventilator, and extracorporeal membrane oxygenation days; medical expenses; proportion of percutaneous coronary intervention; target temperature management; mechanical circulatory support (MCS) device use; and withdrawal of life-sustaining therapy. Results: Of 2,157 patients registered in the SAVE-J II study, 1,885 patients were enrolled in this study; 99 patients (5.3%) received public assistance and 1,786 patients (94.7%) did not. Multivariable logistic regression analysis did not show a significant difference in 30-day survival (OR 1.22, 95% CI 0.77-1.95, p=0.40). The log-rank test for the Kaplan-Meiercurve on 30-day survival did not demonstrate a significant difference (p=0.46). Except for the use of MCS devices, there were no significant differences in secondary outcomes. Conclusions: The use of public assistance did not influence the prognoses of OHCA patients receiving ECPR. Treatment option during hospitalization may be affected by the use of public assistance.

Diagnostic utility of testosterone priming prior to dynamic tests to differentiate constitutional delay in puberty from isolated hypogonadotropic hypogonadism in boys

BackgroundDifferentiation between isolated hypogonadotropic hypogonadism (IHH) and constitutional delay in puberty (CDP) throughout adolescence can be challenging for doctors. This study examines the withdrawal effects of short-term, low-dose testosterone treatment (testosterone priming) on the ability of dynamic testing to distinguish between CDP and IHH based on activation of the hypothalamo-pituitary–testicular axis.MethodsA case–control study included 20 boys with delayed puberty (group A) and 20 patients with IHH (group B). Both groups underwent Triptorelin and human chorionic gonadotropin (hCG) stimulation tests before and 2 months after testosterone injections (100 mg) intramuscularly every 4 weekly for 3 months.ResultsThe triptorelin-stimulated 4-h LH with a cutoff of 2.4 IU/L and the hCG-stimulated testosterone with a cutoff of 1.160 ng/mL had sensitivities of 65% each, and specificities of 90% and 95%, respectively, to diagnose CDP. After testosterone withdrawal, the cut-off values for 4-h LH were 8.850 IU/L and 3.190 ng/mL for hCG-stimulated testosterone. Basal inhibin B > 88.25 pg/ml was found to be a differentiating factor in diagnosing CDP after testosterone withdrawal.Conclusionsfollowing the withdrawal of testosterone therapy, Inhibin B levels or 4-h stimulated LH are the most effective discriminant assays to distinguish CDP from IHH.

Long-term follow-up of the TRED-HF trial

Abstract Background The TRED-HF trial (1) found that 44% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short term after withdrawal of medical therapy. The longer-term risk of relapse is uncertain. Purpose This follow-up aims to investigate the longer-term risk of relapse in patients with recovered DCM and any possible predictive factors. Methods TRED-HF trial participants were followed until May 2023. The primary outcome was DCM relapse defined as >10% reduction in left ventricular (LV) ejection fraction to <50%, doubling in N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) to >400ng/L, or clinical recurrence of heart failure (HF). Therapy intensity for HF was calculated using QUAD scores. The incidence of relapse was calculated using Kaplan-Meier estimates. Predictors of relapse were investigated using Cox proportional hazard modelling. Results For all fifty-one patients, median follow-up from enrolment was 6 (IQR: 6-7) years. Overall, thirty-three patients (65%) relapsed with an estimated 5-year relapse rate of 61% (95% CI 45-73). Twenty patients relapsed during the randomised trial, nine of whom had a recurrent relapse during follow-up (Figure 1). Thirteen patients relapsed for the first time after completion of the trial; of those, one patient did not have therapy withdrawn during the trial, 8 had restarted low intensity HF therapy and 4 patients stayed on no therapy. Five patients stayed off HF therapy and did not relapse. The overall mean intensity of HF therapy was lower after the trial compared to enrolment (mean difference in QUAD score -6 [-8 to -4]; p<0.001). A mean reduction in medication intensity was also seen at the point of relapse during the trial and during follow-up (Figure 2). Of relapses during follow-up, seven had identifiable triggers (arrhythmia (n=4), pregnancy (n=1), hypertension (n=1), infection (n=1)). Patients taking more HF medications at baseline or with higher baseline NT-pro-BNP were more likely to relapse. Corrected atrial fibrillation was associated with reduced future risk of relapse. Conclusions In patients with recovered DCM, the risk of relapse after therapy withdrawal increased with longer follow-up. Lower doses of HF medications and recurrent external triggers contributed to relapse. Few patients who stopped medications had sustained remission. Recovery of DCM after correction of AF was associated with a low risk of relapse provided atrial fibrillation did not recur.

One-Year and Five-Year Outcomes in Medication Overuse Headache: A Real-World Study.

Medication overuse headache (MOH) is one of the global health-related problems that imposes significant morbidity. Effective management requires the abrupt cessation of the overused medications, transition therapy in the initial days, and initiation of preventive treatment. The objective of this study is to provide one-year and five-year follow-ups of study participants diagnosed with chronic migraine and MOH. The study will examine the efficacy of withdrawal therapy, the use of conventional preventive medication, and the use of anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies. We conducted a single-center, prospective, and descriptive study at a tertiary center in Brazil. The population was included by convenience sampling of consecutive subjects diagnosed with chronic migraine and MOH. Demographics and clinical data at baseline and one-year and five-year follow-ups were collected in the clinical records. Among 142 subjects, 116 were females and 26 were males, with a mean age of 42.1±14.3. They were followed for five years. The diagnosis was performed at the mean age of 24.9±14.7 years after the headache onset, and the time with headache ≥15 days per month was 6.3±7.6 years. On baseline, the average number of headache days per month (HDM) was 25.2±5.9. There was a reduction in HDM. At one-year and five-year follow-ups, a ≥75% reduction in HDM was observed, respectively, in 51.4% and 70.4% of the sample. The five-year follow-up of chronic migraine and MOH treated with the discontinuation of excessive medication, the use of preventative pharmacological agents, and the optional inclusion of anti-CGRP pathway monoclonal antibody led to a significant decrease in the initial occurrence of HDM.

Triple Therapy De-Escalation and Withdrawal of Inhaled Corticosteroids to Dual Bronchodilator Therapy in Patients with Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis.

Background/Objectives: The interpretation of evidence on the de-escalation of triple therapy with the withdrawal of inhaled corticosteroids (ICSs) to dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA) in patients with chronic obstructive pulmonary disease (COPD) is conflicting. We evaluated the efficacy and safety of ICS discontinuation from LABA-LAMA-ICS triple therapy compared to its continuation. Methods: We searched PubMed, Embase, Scopus, Web Of Science, clinicaltrial.gov, and CENTRAL for RCTs and observational studies from inception to 22 March 2024, investigating the effect of triple therapy de-escalation with the withdrawal of ICSs to dual therapy on the risk of COPD exacerbation, pneumonia, and lung function. This study was registered with PROSPERO, CRD42024527942. Results: A total of 3335 studies was screened; 3 RCTs and 3 real-world non-interventional studies were identified as eligible. The analysis of the time to the first moderate or severe exacerbation showed a pooled HR of 0.96 (95% CI, 0.80-1.15; I2 = 77%) for ICS withdrawal compared to triple therapy continuation. The analysis according eosinophil levels showed that COPD subjects with ≥300 eosinophils/µL had a significant increase in the incidence of moderate or severe exacerbations when de-escalated to LABA/LAMA (pooled HR: 1.35, 95% CI: 1.00-1.82; I2: 56%). ICS withdrawal did not significantly affect the risk of mortality and pneumonia. Conclusions: The de-escalation of triple therapy with ICS withdrawal does not affect the main outcomes evaluated (moderate or severe exacerbations, change in trough FEV1). COPD patients with high blood eosinophils (≥2% or ≥300 cells/µL) are most likely to benefit from continuing triple therapy.

Major clinical outcomes and discussions of the impacts of religiousity/spirituality in patients with palliative care and nutrology therapy: a concise systematic review

Introduction: In the scenario of nutritional therapy and religiosity/spirituality (R/S), several factors can impact the nutritional status of patients in palliative care. These include knowledge of nutrition, the level of emotional support required for the patient, their motivation, and the nature, impact, and severity of the illness. A diet suitable for weight stabilization provides patients with the energy necessary to meet physical, psychological, social, and R/E aspects. Objective: It was to carry out a concise systematic review to present the main clinical outcomes and discussions about the impacts of religiosity/spirituality in patients with palliative care undergoing nutritional therapy. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from August to October 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 91 articles were found, and 24 articles were evaluated in full, and 17 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 15 studies with a high risk of bias and 25 studies that did not meet GRADE and AMSTAR-2. Most studies showed homogeneity in their results, with X2=72.8%>50%. It was concluded that when the natural oral intake of food and liquids is disturbed, the role of caregivers is to assist the patient in covering the individual's nutritional needs through nutritional therapy and religiosity and spirituality as metabolic and immunological stimuli. Nutritional therapy requires indication to achieve a treatment goal and informed consent from the patient. The suspension and withdrawal of nutritional therapy and artificial hydration must be evaluated in specific situations (terminally ill, palliative care, dementia, elderly patients) and always on a case-by-case basis, according to the cultural and spiritual needs of the patients. Caregivers must emphasize the right to self-determination and therefore respect the patient's autonomy, and also the particular vulnerability of the patient who suffers from or is at risk of malnutrition.

Bioethics at the bedside: considering the adolescent voice in withdrawal of life-sustaining therapy.

Durable mechanical circulatory devices are commonly used to support children and adolescents in end-stage heart failure. However, these patients remain at high risk of acute medical complications, which may lead to significant impairment in functional capacity, altered quality of life, or death. We explore the incorporation of adolescent directives into medical decision-making in this scenario through a clinical case vignette.

New onset of Graves' disease after controlled ovarian stimulation: A case report and brief literature review.

De novo onset of Graves' disease (GD) after controlled ovarian stimulation (OS) is exceptional. Only one case of progression to GD after OS in a patient with pre-existing subclinical hyperthyroidism has been reported. We describe the case of a patient with neither previous thyroid disorders nor autoimmunity who developed GD after OS for primary infertility. A 40-year-old woman with primary infertility underwent four cycles of OS. Her thyroid function performed before the last cycle was unremarkable (thyroid stimulating hormone [TSH] 1.9 mU/L, fT4 1.3 ng/dL, fT3 2.4 pg/mL), and thyroid autoimmunity was negative (anti-thyroperoxidase antibodies and anti-thyroglobuline antibodies). Six weeks after the last cycle she developed overt thyrotoxicosis (TSH < 0.005 mU/L, fT4 4.79 ng/dL, fT3 15.6 pg/mL) with anti-thyrotropin receptor antibodies (TRAb) positivity (9.2 IU/L). She was diagnosed with GD and anti-thyroid therapy was instituted. After 1 year of treatment, thyroid function was still suboptimal (TSH 0.2 mU/L, fT4 1.04 ng/dL, fT3 2.2 pg/mL), and TRAb titer still elevated (8.75 IU/L). Despite her desire to achieve pregnancy, a further cycle of OS was postponed until complete remission of thyroid dysfunction and withdrawal of anti-thyroid therapy. Although TSH assay after OS is not recommended in euthyroid women without autoimmunity, in the presence of hyperthyroid symptoms throughout OS it is advisable to evaluate thyroid function and TRAb. It is advisable to carefully evaluate the course of GD before proceeding with further courses of OS that could lead to its exacerbation or recurrence. In cases where a strong desire for pregnancy persists, thyroidectomy may be proposed.

Tensions between end-of-life care and organ donation in controlled donation after circulatory death: ICU healthcare professionals experiences

BackgroundThe development of controlled donation after circulatory death (cDCD) is both important and challenging. The tension between end-of-life care and organ donation raises significant ethical issues for healthcare professionals in the intensive care unit (ICU). The aim of this prospective, multicenter, observational study is to better understand ICU physicians’ and nurses’ experiences with cDCD.MethodsIn 32 ICUs in France, ICU physicians and nurses were invited to complete a questionnaire after the death of end-of-life ICU patients identified as potential cDCD donors who had either experienced the withdrawal of life-sustaining therapies alone or with planned organ donation (OD(-) and OD( +) groups). The primary objective was to assess their anxiety (State Anxiety Inventory STAI Y-A) following the death of a potential cDCD donor. Secondary objectives were to explore potential tensions experienced between end-of-life care and organ donation.ResultsTwo hundred six ICU healthcare professionals (79 physicians and 127 nurses) were included in the course of 79 potential cDCD donor situations. STAI Y-A did not differ between the OD(-) and OD( +) groups for either physicians or nurses (STAI Y-A were 34 (27–38) in OD(-) vs. 32 (27–40) in OD( +), p = 0.911, for physicians and 32 (25–37) in OD(-) vs. 39 (26–37) in OD( +), p = 0.875, for nurses). The possibility of organ donation was a factor influencing the WLST decision for nurses only, and a factor influencing the WLST implementation for both nurses and physicians. cDCD experience is perceived positively by ICU healthcare professionals overall.ConclusionscDCD does not increase anxiety in ICU healthcare professionals compared to other situations of WLST. WLST and cDCD procedures could further be improved by supporting professionals in making their intentions clear between end-of-life support and the success of organ donation, and when needed, by enhancing communication between ICU physician and nurses.Trial registrationThis research was registered in ClinicalTrials.gov (Identifier: NCT05041023, September 10, 2021).

Hypercholesterolemia and laboratory reports: joint document from the Italian Society of Cardiology (SIC) and the Italian Society of Clinical Biochemistry and Clinical Molecular Biology - Lab Medicine (SIBioC)

Dyslipidemia is one of the most important risk factors for the development of atherosclerotic disease and its control, through well-proven therapies, allows an optimal risk management over time. LDL-cholesterol targets are well defined by international guidelines and based on individual cardiovascular risk. As guidelines evolve, also laboratory reports need to do the same, including lipid reference values by cardiovascular risk classes, to avoid misunderstandings and inappropriate lipid-lowering therapy withdrawal. The aim of the present joint document from the Italian Society of Cardiology (SIC) and the Italian Society of Clinical Biochemistry and Clinical Molecular Biology - Lab Medicine (SIBioC) is to analyze the importance of cardiovascular risk estimation, therapeutical targets, and crucial elements about dyslipidemia in laboratory tests, as well as to suggest a shared proposal for the report of lipid profile parameters to be applied to all clinical scenarios of our daily practice.

Long-term follow-up of the TRED-HF trial: Implications for therapy in patients with dilated cardiomyopathy and heart failure remission.

In TRED-HF, 40% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short term after therapy withdrawal. This follow-up investigates the longer-term effects of therapy withdrawal. TRED-HF was a randomized trial investigating heart failure therapy withdrawal in patients with recovered DCM over 6 months. Those randomized to continue therapy subsequently withdrew treatment between 6 and 12 months. Participants were recommended to restart therapy post-trial and were followed until May 2023. Clinical outcomes are reported in a non-randomized fashion from enrolment and from the end of the trial. The primary outcome was relapse defined as ≥10% reduction in left ventricular ejection fraction to <50%, doubling in N-terminal pro-B-type natriuretic peptide to >400 ng/L, or clinical features of heart failure. From enrolment to the last follow-up (median 6 years, interquartile range 6-7), 33 of 51 patients (65%) relapsed. The 5-year relapse rate from enrolment was 61% (95% confidence interval [CI] 45-73) and from the end of the trial was 39% (95% CI 19-54). Of 20 patients who relapsed during the trial, nine had a recurrent relapse during follow-up. Thirteen relapsed for the first time after the trial; seven had restarted low intensity therapy, four had not restarted therapy and two did not have therapy withdrawn. The mean intensity of therapy was lower after the trial compared to enrolment (mean difference -6 [-8 to -4]; p < 0.001). One third of relapses during follow-up had identifiable triggers (arrhythmia [n = 4], pregnancy [n = 1], hypertension [n = 1], infection [n = 1]). Corrected atrial fibrillation was associated with reduced risk of relapse (hazard ratio 0.33, 95% CI 0.12-0.96; p = 0.042). The risk of relapse in the 5 years following the TRED-HF trial remained high. Restarting lower doses of heart failure medications at the end of the trial, external triggers and disease progression are likely to have contributed to relapse.

Kidney Transplant Outcome Following Donation After Euthanasia.

In the Netherlands, organ donation after euthanasia (donation after circulatory death type V [DCD-V]) has been increasingly performed since 2012. However, the outcomes of DCD-V kidney grafts have not been thoroughly investigated. It is critical to assess the outcomes of these kidney grafts to ascertain whether DCD-V is a safe and valuable way to increase the kidney donor pool. To investigate the outcomes of DCD-V kidney transplantation and compare them with outcomes of kidney transplantation after circulatory death after withdrawal of life-sustaining therapies (DCD type III [DCD-III]) and donation after brain death (DBD). A retrospective cohort study was conducted using the database from the Dutch Transplant Foundation. All kidney transplants in the Netherlands between January 2012 (start of the euthanasia program) and July 2023 were included. Follow-up was obtained through 5 years after transplantation. Data analysis was performed from November 2023 until February 2024. Kidney transplantation with a DCD-V graft compared with DCD-III and DBD grafts. The primary outcome was death-censored graft survival until 5 years after transplantation. Secondary outcomes were the incidence of delayed graft function (DGF), permanent nonfunction (PNF), serum creatinine concentration, and patient survival until 5 years after kidney transplantation. A total of 145 DCD-V kidney transplants were compared with 1936 DCD-III and 1255 DBD kidney transplants. Median (IQR) recipient age was 59 (46-66) years in the DCD-V cohort, compared with 61 (50-68) years in the DCD-III cohort and 61 (50-68) years in the DBD cohort. The incidence of DGF with DCD-V kidney transplants (26%) was significantly less than that with DCD-III kidney transplants (49%; P < .001) and similar to that with DBD kidney transplants (22%; P = .46). PNF occurrence with DCD-V kidneys (6%) was similar to that with DCD-III kidneys (6%; P = .79) and higher than in DBD kidneys (4%; P < .001). There was no difference in 5-year death-censored graft survival between DCD-V grafts (82%) and DCD-III (86%; P = .99) or DBD (84%; P = .99) grafts. There was no difference in 5-year patient survival between DCD-V kidney transplants (69%) and DCD-III (76%; P = .45) or DBD (73%; P = .74) kidney transplants. A propensity score analysis was performed to match the DCD-V and DCD-III cohort, showing results similar to those of the unmatched cohort. This study found that DCD-V kidney transplantation yielded a lower incidence of DGF compared with DCD-III kidney transplantation and yielded long-term results similar to those of DCD-III and DBD kidney transplantation. The findings suggest that DCD-V is a safe and valuable way to increase the kidney donor pool.

Prognosis After Withdrawal of Cardioprotective Therapy in Patients With Improved Cancer Therapeutics–Related Cardiac Dysfunction

BackgroundThe long-term prognosis after the discontinuation of cardioprotective therapy (CPT) in patients with cancer therapeutics–related cardiac dysfunction (CTRCD) that has shown improvement remains unclear. ObjectivesThis study aims to assess the prognosis after CPT withdrawal in patients exhibiting improved CTRCD. MethodsIn this retrospective analysis of a single-center prospective cohort study, patients with improved CTRCD, defined as an increase in left ventricular ejection fraction (LVEF) ≥10 percentage points from the time of CTRCD diagnosis, were included. We analyzed their clinical outcomes, which included hospitalization for heart failure or a decrease in LVEF ≥10 percentage points within 2 years after CTRCD improvement, alongside echocardiographic changes. ResultsThe cohort comprised 134 patients with improved CTRCD. The median follow-up duration after CTRCD diagnosis was 368.3 days (Q1-Q3: 160-536 days). After improvement, 90 patients continued CPT (continued group [CG]) and 44 withdrew CPT (withdrawn group [WG]). Among patients whose baseline LVEF at CTRCD diagnosis ranged from 45% to 55%, the final mean LVEF was comparable between both groups (CG: 64.9% ± 4.4% vs WG: 62.9% ± 4.2%; P = 0.059). However, for patients with a baseline LVEF <45%, the final mean LVEF was significantly lower in the WG (CG: 53.3% ± 6.4% vs WG: 48.2% ± 6.9%; P < 0.001). The occurrence of composite major clinical events was notably higher in the WG (HR: 3.06; 95% CI: 1.51-7.73; P = 0.002). ConclusionsPatients who withdrew CPT after demonstrating improvement in CTRCD experienced worse clinical outcomes. Notably, a significant decrease in LVEF was observed after CPT withdrawal in patients with a baseline LVEF <45%.

Cardiologists' perspective on termination of pacemaker therapy-an anonymous survey among cardiologists in Germany.

The patient's right to refuse pacemaker therapy is mentioned in the relevant European consensus statement but additional information is only available on deactivation of implantable cardioverter deactivator and not on other cardiac implantable electronic devices such as pacemakers. Therefore, we were interested in opinions, concerns and attitudes of cardiologists, who are the primary contact persons for such requests, since the number of patients asking for withdrawal of pacemaker therapy is likely to increase leaving cardiologists and healthcare professionals with a difficult medical but also ethical problem. An anonymous questionnaire was sent to all German cardiology departments (N = 288). 48% of cardiology departments responded by sending back 247 completed questionnaires. Most participating cardiologists were experienced when considering the duration of their professional activity. Almost all of the respondents regularly perform check-ups of pacemakers. The majority of cardiologists answering our questionnaire were prepared to deactivate a pacemaker upon patients' request, and have done so. In pacemaker dependency, however, the willingness to withdraw decreases, even if death is imminent, for fear of causing distressing symptoms, sense of being responsible for patients possible immediate death, or fear of legal consequences. The survey could clearly show that uncertainties remain among cardiologists dealing with a patient's wish for withdrawal, especially in cases of pacemaker dependency. We suggest that official statements of cardiologic societies in Europe are issued to clarify ethical, legal and practical aspects of pacemaker withdrawal. Registered in the German Clinical Trials Register (DRKS00026168) on 30.08.2021.

Clinical analysis of immune reconstitution after chemotherapy in children with acute lymphoblastic leukemia

ObjectivesThe aim of this retrospective study was to investigate the influence of chemotherapy on the immune status of individual patients diagnosed with acute lymphoblastic leukemia (ALL) and to elucidate the clinical characteristics of immune reconstitution in ALL patients following chemotherapy.MethodsClinical data of children with ALL were gathered, including information on the number of lymphocyte subsets prior to chemotherapy, at the end of therapy, six months, and one year after the end of the treatment.ResultsA total of 146 children with ALL were included, and T cells, B cells, and NK cells all decreased to various degrees prior to treatment. The abnormal CD3 + T cell numbers group experienced a considerably higher mortality (21.9% vs. 6.1%) and recurrence rate (31.3% vs. 11.4%) compared to the normal group (P < 0.05). T cells, B cells, and NK cells were all significantly compromised at the end of therapy compared to the beginning of chemotherapy, with B cells being more severely compromised (P < 0.001). At the end of treatment, levels of B cells, CD4 + T cells, CD4/CD8, IgG and IgM in low risk (LR) group were significantly higher than those in intermediate risk (IR) group (P < 0.01), and levels of NK cells in LR group were evidently lower than those in IR group (P < 0.001). Six months after the end of therapy, all the above indicators recovered (P < 0.001) except CD4/CD8 ratio (P = 0.451).ConclusionsThe immune systems of the ALL patients were severely compromised upon therapy withdrawal, particularly the B cells. At six months after the therapy ended, the B cells were basically restored to normal level, while the T-cell compartment was not. The impaired numbers of CD3 + T cell may contribute to a weakened anti-tumor response, potentially leading to a poorer prognosis.

Cardiac sarcoidosis in patients with recurrent ventricular arrhythmias refractory to endocardial ablation.

The clinical presentation of cardiac sarcoidosis is diverse. Detection of granuloma in histopathological evaluation proves the diagnosis, but endomyocardial biopsy (EMB) is associated with a high sampling error. However, prompt immunosuppressive therapy may significantly affect patient's prognosis. By analyzing our single center cohort of patients with recurrent ventricular arrhythmias (VA) and nonischemic cardiomyopathy after failure of endocardial ablation, we looked for additional markers supporting the diagnosis of cardiac sarcoidosis. In the last 4years, 135 patients (mean age 49 y, 63% male) were hospitalized for epicardial ventricular arrhythmia (VA) ablation after failure of endocardial ablation. Nineteen patients had either previously received a diagnosis of cardiac sarcoidosis or were newly diagnosed. The mean follow-up time was 4.3years. The ECG criteria, primary manifestation, histological findings in EMB, history of VT ablation, distribution of scars on MRI, electroanatomical mapping (EAM), PET CT findings, presence of atrial tachycardias, valve disease and comorbidities were analyzed. Six of 19 (32%) patients showed right bundle block; 6 of 19 (32%) had AV nodal disease, including 4 patients with AV-block III; and 14 patients (73%) primarily presented with ventricular arrhythmias (including 3 with cardiac arrest). In all 19 patients cardiac EMB revealed elevated CD68 macrophages and CD3 T lymphocytes, and 7 of 19 were positive for granuloma (36,8%). Six of 6 patients (100%) undergoing PET CT showed acute inflammation. By analyzing the scar distribution, the most common locations were basal anteroseptal, basal inferoseptal, mid inferoseptal, mid inferior and the septal RV/RVOT. (septal substrate in 100%). There was a high correlation between the findings on the MRIs and low voltage in the electroanatomical mapping EAM). All patients received an immunosuppressive therapy. No patient died during follow-up, 1 patient had a high urgent heart transplant after withdrawal of steroid therapy. Chronic untreated inflammation may be the underlying pathophysiology for patients with unspecific cardiomyopathy and recurrent VA refractory to endocardial and epicardial ablation. Septal substrate in the EAM/MRI, elevated CD3 lymphocytes in the EBM and inflammation in the PET CT may indicate the possible diagnosis of cardiac sarcoidosis. Initializing immunosuppressive therapy in patients with this dedicated constellation with should be taken into consideration.

Clinical characteristics, treatment and outcome of clindamycin induced acute generalized exanthematous pustulosis.

Acute generalized exanthematous pustulosis (AGEP) is a serious and rare adverse reaction to clindamycin. This study investigated the clinical features of clindamycin-induced AGEP and provided reference for the prevention and treatment of AGEP. Case reports, case series and clinical studies of clindamycin-induced AGEP were collected by retrieving English and Chinese database from inception until May 31, 2024. Of the 35 patients included, 25 (71.4%) were female, and the median age was 57 years (1.6-88 years). The duration of AGEP onset is 2 days (range 0.04,13) after initial administration. The main clinical morphology of AGEP is a non-follicular pustular on an erythematous base, which may be accompanied by fever (54.3%) and pruritus (40.0%). These lesions mainly involved extremities and trunk. The median elevated neutrophil count was 13.3 × 109/L (range 10.3, 31.4). Histologic features of AGEP are characterized by intracorneal, subcorneal, and/or intraepidermal pustules with papillary dermal edema containing neutrophilic, lymphocytic, andeosinophilic infiltrates. Patients gradually recovered after the withdrawal of clindamycin and supportive therapy with a median time of 9 days (range 2, 30). Clinicians should be aware of AGEP as a rare adverse effect of clindamycin. When clindamycin is prescribed, it should be stopped in time when AGEP occurs, and active systemic treatment should be given. AGEP is a self-limiting disease with a good prognosis.

Baricitinib Withdrawal and Retreatment in Patients With Severe Alopecia Areata

Baricitinib has demonstrated efficacy for treating severe alopecia areata in adults. There is currently limited information about the need for continuous therapy after achieving scalp hair regrowth. To report results from the randomized withdrawal period of the BRAVE-AA1 trial. BRAVE-AA1 was a randomized, placebo-controlled, phase 3 randomized clinical trial with a treatment withdrawal substudy that was conducted at 70 centers in 3 countries beginning in March 2019. It included 654 adults with severe alopecia areata (AA) (Severity of Alopecia Tool [SALT] score ≥50) who were randomized 3:2:2 to receive treatment with baricitinib, 4 mg; baricitinib, 2 mg; or placebo. Data were analyzed in August 2023. At week 52, 154 patients who were responders (SALT score ≤20) were rerandomized 3:1 to continue to take their current dose of baricitinib or transition to placebo (randomized withdrawal). Responders randomized to placebo who experienced a loss of treatment benefit (>20-point worsening in SALT score) at any time after week 52 were retreated with their original baricitinib dose. The proportion of patients who lost treatment benefit through week 152 and the proportion of patients who recaptured response after retreatment. The last observation carried forward was used to impute missing or censored data. Of 654 patients who received treatment, the mean (SD) age was 37.1 (13.0) years, and there were 383 women (58.6%). At week 52, 10 of 39 responders taking baricitinib, 2 mg, and 30 of 115 responders taking baricitinib, 4 mg, were rerandomized to placebo. At 4 and 8 weeks of treatment withdrawal, 0% and 10% to 11% of patients, respectively, lost treatment benefit regardless of dose. At week 152, 80% of patients had lost benefit compared with 7% for those who continued baricitinib therapy for both dose groups. Within the follow-up observation periods, 5 of 8 patients taking 2 mg (63%) and 21 of 24 patients taking 4 mg (87.5%) recaptured a SALT score of 20 or less response after retreatment. Severe AA is a chronic, relapsing condition, and this randomized clinical trial found that withdrawal of therapy for a patient population with severe AA who had achieved meaningful hair regrowth after 1 year of treatment with baricitinib resulted in loss of benefit for almost all patients, indicating that continued therapy is required to maintain hair regrowth. ClinicalTrials.gov Identifier: NCT03570749.

Race and Socio-Economic Status Impact Withdrawal of Treatment in Young Traumatic Brain Injury

ContextWithdrawal of life-sustaining therapies (WDLST) in young individuals with traumatic brain injury (TBI) is an overwhelming situation often made more stressful by socioeconomic factors that shape health outcomes. Identifying these factors is crucial to developing equitable and goal-concordant care for patients and families. ObjectivesWe aimed to identify predictors of WDLST in young patients with 1-TBI. We hypothesized uninsured payment method, race, and co-morbid status are associated with WDLST. MethodsWe queried the 2021 Trauma Quality Improvement Program database for patients <45 years with TBI. Patients with WDLST were compared to patients without WDLST. Multivariable logistic regression (MLR) was performed. Results61,115 patients were included, of whom 2,487 (4.1%) underwent WDLST. Patients in the WDLST cohort were older (29 vs 27, P<0.001), more likely to suffer from a penetrating mechanism (29% vs 11%, P<.0001), and have uninsured (22% vs 18%) or other payment method (5% vs 3%) when compared to the non-WDLST cohort. MLR identified age (AOR:1.019, 95% CI 1.014–1.024, P<.0001), non-Hispanic ethnicity (AOR:1.590, 95% CI 1.373–1.841, P<.0001), penetrating mechanism (AOR:3.075, 95% CI 2.727–3.467, P<.0001), systolic blood pressure (AOR: 0.992, 95% CI 0.990–0.993, P<0.0001), advanced directive (AOR:4.987, 95% CI 2.823–8.812, P<.0001), cirrhosis (AOR:3.854, 95% CI 2.641–5.625, P<.0001), disseminated cancer (AOR:6.595, 95% CI 2.370–18.357, P=0.0003), and interfacility transfer (AOR:1.457, 95% CI 1.295–1.640, P<0.0001) as factors associated with WDLST. Black patients were less likely to undergo WDLST when compared to white patients (AOR:0.687, 95% CI 0.603–0.782, P<.0001). ConclusionThe decision for WDLST in young patients with severe TBI may be influenced by cultural and socioeconomic factors in addition to clinical considerations.

Glucocorticoid Sensitivity Among Young Survivors of Childhood Acute Lymphoblastic Leukemia: What Does It Matter?

The aim of the study was to assess glucocorticoid sensitivity in survivors of childhood acute lymphoblastic leukemia using in vivo and in vitro tests. Thirty leukemia survivors of both sexes aged ≥18 years participated in the study and at least two years after therapy withdrawal. In vivo tests comprised: a) a very low dose intravenous dexamethasone suppression test for measurement of serum cortisol before, after, and % suppression, compared with 32 age-matched controls; and b) 0.25 mg overnight oral dexamethasone suppression test for assessment of salivary cortisol before, after, and % suppression. In vitro methods comprised: c) glucocorticoid receptor polymorphisms: BcI1-NR3C1 and A3669G; and d) splicing variant of glucocorticoid receptor GR-α mRNA by real-time quantitative polymerase chain reaction, compared with 32 controls. There was a reduction in salivary cortisol, and 73.3% of leukemia survivors showed high sensitivity according to % suppression after oral dexamethasone (p<0.05). Serum cortisol at baseline, after the test, % suppression after intravenous dexamethasone, and the percentage of high sensitivity were reduced in the leukemia group (%F=36.7; p<0.05). The BcI1-NR3C1 and A3669G polymorphisms were present in 11/30 (36.7%) and 5/30 (16.7%) patients, respectively. GR-α mRNA levels were lower in the leukemia group than in the controls (p<0.05). Survivors of acute lymphoblastic leukemia presented with reduced glucocorticoid sensitivity. Glucocorticoid sensitivity allows individualized treatment to avoid adverse effects and may be involved in cardiovascular disease risk among this particular group of cancer survivors.