Late-onset Complications Research Articles

Late-onset pulmonary complications among survivors of coronavirus Disease 2019.

To assess the late-onset pulmonary complications among survivors of coronavirus disease 2019. The cross-sectional analytical study was conducted in the department of Pulmonology, Sir Ganga Ram Hospital Lahore between October 2020 and March 2021. Total 288 patients visiting the hospital 12-week after recovery from COVID-19 enrolled using convenience sampling. After excluding patients (n=61) with a history of previous respiratory symptoms before the development of COVID-19, data from 227 patients was subjected to final analysis. Chest X-ray (CXR) was used to evaluate lung condition. Participation of middle-aged adults (54.6%) was higher than older (38.3%) and young adults (7.0%). The percentage of males was 55.5% and smokers was 29.1%. Dyspnea was the most common complication as 80.0% patients had moderate to severe dyspnea while chronic cough was 78.0% and lung fibrosis (LF) was 13.2%. The chances of LF increased with the rise in age (p-value 0.033). However, the distribution of LF was similar between males and females. The frequency of lung fibrosis in smokers was 3-time higher than among non-smokers (24.2 vs. 8.7%; p-value 0.003). The patients with LF were more dependent on O2 as compared to the patients without LF (p-value < 0.001). The frequency of tachycardia was significantly different between patients with and without LF (all p-values < 0.05). LF is a common late-onset pulmonary complication of COVID-19 and is associated with old age, smoking, O2 dependency, tachycardia, and severe dyspnea.

Late-onset vascular complications of radiotherapy for primary brain tumors: a case–control and cross-sectional analysis

PurposeRadiotherapy (RT) is a recognized risk factor for cerebrovascular (CV) disease in children and in adults with head and neck cancer. We aimed to investigate whether cerebral RT increases the risk of CV disease in adults with primary brain tumors (PBT).MethodsWe retrospectively identified adults with a supratentorial PBT diagnosed between 1975 and 2006 and with at least 10 years follow-up after treatment. We analyzed demographic, clinical, and radiological features with special attention to CV events. We also described CV events, vascular risk factors, and intracranial artery modifications in a cross-sectional study of irradiated patients alive at the time of the study.ResultsA total of 116 patients, treated with RT (exposed group), and 85 non-irradiated patients (unexposed group) were enrolled. Stroke was more frequent in irradiated PBT patients than in the unexposed group (42/116 (36%) vs 7/85 (8%); p < 0.001), with higher prevalence of both ischemic (27/116 (23%) vs 6/85 (7%); p = 0.004) and hemorrhagic (12/116 (10%) vs 1/85 (1%); p = 0.02) stroke. In the irradiated group, patients with tumors near the Willis Polygon were more likely to experience stroke (p < 0.016). Fourty-four alive irradiated patients were included in the cross-sectional study. In this subgroup, intracranial arterial stenosis was more prevalent (11/45, 24%) compared to general population (9%).ConclusionsStroke prevalence is increased in long-surviving PBT patients treated with cranial RT.Implications for cancer survivorsCV events are frequent in long survivors of PBT treated with cerebral RT. We propose a check list to guide management of late CV complications in adults treated with RT for PBT.

Genetic Polymorphisms of Vascular Endothelial Growth Factor in Neonatal Pathologies: A Systematic Search and Narrative Synthesis of the Literature

(1) Background: Vascular endothelial growth factor (VEGF) is essential in vasculo- and angiogenesis due to its role in endothelial cell proliferation and migration. As a vascular proliferative factor, VEGF is one of the hallmarks of cancer and, in adult populations, the relationship between genetic polymorphism and neoplasm was widely investigated. For the neonatal population, only a few studies attempted to uncover the link between the genetic polymorphism of VEGF and neonatal pathology, especially related to late-onset complications. Our objective is to evaluate the literature surrounding VEGF genetic polymorphisms and the morbidity of the neonatal period. (2) Methods: A systematic search was initially conducted in December 2022. The PubMed platform was used to explore MEDLINE (1946 to 2022) and PubMed Central (2000 to 2022) by applying the search string ((VEGF polymorphism*) and newborn*). (3) Results: The PubMed search yielded 62 documents. A narrative synthesis of the findings was undertaken considering our predetermined subheadings (infants with low birth weight or preterm birth, heart pathologies, lung diseases, eye conditions, cerebral pathologies, and digestive pathologies). (4) Conclusion: The VEGF polymorphisms seem to be associated with neonatal pathology. The involvement of VEGF and VEGF polymorphism has been demonstrated for retinopathy of prematurity.

Coronary covered stents in the management of late-onset arterial complications post-hepato-pancreato-biliary surgery.

To retrospectively evaluate the safety, efficacy, and late clinical outcome of coronary covered stent placement for the treatment of late-onset arterial complications after hepato-pancreato-biliary surgery. Consecutive patients presenting with post-hepato-pancreato-biliary surgery-related arterial lesions and subsequently treated with a covered coronary stent in the authors institution between January 2012 and November 2021 were included. Primary endpoints were technical and clinical success; secondary endpoints were covered stent patency and end-organ perfusion of the affected artery. The study included 22 patients (13 men and 9 women) with a mean age of 67years ± 9.6years. Initial surgery included pancreaticoduodenectomy (n = 15; 68%), liver transplantation (n = 2; 9%), left hepatectomy (n = 1; 5%), bile duct resection (n = 1; 5%), hepatogastrostomy (n = 1; 5%), and segmental enterectomy (n = 1; 5%). Technically, coronary covered stents were successfully placed in n = 22 patients (100%) without immediate complication. Definitive bleeding control was observed in n = 18 patients (81.1%) with recurrent bleeding within 30days postintervention in n = 5 patients (23%). No ischemic liver or biliary complications occurred during the follow-up period. The 30-day mortality rate was 0%. Coronary covered stents are a safe and efficient treatment option in most of the patients presenting with late-onset postoperative arterial injuries following hepato-pancreato-biliary surgery and are associated with an acceptable recurrent bleeding rate and no late, ischemic, parenchymal complications.

Model for predicting early and late-onset postoperative pulmonary complications in perioperative patients receiving neuromuscular blockade: a secondary analysis

Pulmonary complications continue to be the most common adverse event after surgery. The main objective was to carry out two independent predictive models, both for early pulmonary complications in the Post-Anesthesia Care Unit and late-onset pulmonary complications after 30 postoperative days. The secondary objective was to determine whether presenting early complications subsequently causes patients to have other late-onset events. This is a secondary analysis of a cohort study. 714 patients were divided into four groups depending on the neuromuscular blocking agent, and spontaneous or pharmacological reversal. Incidence of late-onset complications if we have not previously had any early complications was 4.96%. If the patient has previously had early complications the incidence of late-onset complications was 22.02%. If airway obstruction occurs, the risk of atelectasis increased from 6.88 to 22.58% (p = 0.002). If hypoxemia occurs, the incidence increased from 5.82 to 21.79% (p < 0.001). Based on our predictive models, we conclude that diabetes mellitus and preoperative anemia are two risk factors for early and late-onset postoperative pulmonary complications, respectively. Hypoxemia and airway obstruction in Post-Anesthesia Care Unit increased four times the risk of the development of pneumonia and atelectasis at 30 postoperative days.

Wellens’ syndrome following severe COVID-19 infection, an innocent coincidence or a deadly association: two case reports

BackgroundCoronavirus disease 2019 (COVID-19) has been associated with late-onset cardiovascular complications primarily due to a hypercoagulable state. Its association with Wellens’ syndrome, which reflects a stenosis in the proximal left anterior descending coronary artery, is not well established. We present two cases diagnosed with this syndrome following their COVID-19 acute phase despite taking adequate anticoagulation.Case presentationWe present two patients with incidental electrocardiography (ECG) showing the typical Wellens’-related changes, with an underlying severe triple-vessel coronary artery disease a few weeks following a severe COVID-19 infection associated with high inflammatory markers. The stenotic lesions were diagnosed by cardiac catheterization, and both patients underwent Coronary Artery Bypass Grafting successfully. Notably, patients’ baseline ECGs were normal, and they were maintained on Rivaroxaban 10 mg following their viral illness.ConclusionDespite advances in the preventive measures for COVID-19 complications, its pathophysiologic impact on vasculature and atherosclerosis is still incompletely understood. Further clinical trials must be conducted to study this association between Wellens’ syndrome and this virus to prevent life-threatening complications.

A qualitative content analysis of the experience of hypospadias care: The importance of owning your own narrative.

There is a lack of studies on men's individual experiences of living with hypospadias. We aimed to explore the personal experiences of having hypospadias in relation to healthcare and surgery. Purposive sampling was used to include men (aged 18 and over) with hypospadias representing different phenotypes (from distal to proximal) and ages in order to maximise the variation and richness of our data. Seventeen informants, aged 20-49, were included in the study. In-depth semi-structured interviews were conducted between 2019 and 2021. Inductive qualitative content analysis was used to analyse the data. We identified three categories: (1) Having surgery, which comprised the decision to operate, the experience of having surgery, and the outcomes of surgery; (2) Going to the doctor, which focused on follow-up care, re-entering care in adolescence or adulthood, and the experience of healthcare interactions; (3) Being informed, both about hypospadias in general, as well as about your specific body and medical history. There was overall a large variation in experiences. The latent theme across the data was the importance of owning your own narrative. The experience of men with hypospadias in healthcare is complex and varied, highlighting the difficulty of fully standardised care. Based on our results, we suggest that follow-up should be offered in adolescence, and that ways of accessing care for late onset complications be made clear. We further suggest clearer consideration for the psychological and sexual aspects of hypospadias. Consent and integrity in all aspects and all ages of hypospadias care should be adapted to the maturity of the individual. Access to trustworthy information is key, both directly from educated healthcare staff and if possible, from websites or patient-led forums. Healthcare can play a key role in providing the growing individual with tools to understand and address concerns that may develop relating to their hypospadias through life, giving them ownership over their own narrative.

Hepatitis C Virus Exposure and Infection in the Perinatal Period.

Hepatitis C virus infection is a leading cause of blood-borne hepatitis disease worldwide. Hepatitis C is a silent liver disease that, without treatment, leads to late-onset complications, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, in 10-40% of patients. This study aimed to review the epidemiology, clinical features, diagnosis, treatment, and prevention of hepatitis C among perinatally exposed children. Public databases, including MEDLINE and PubMed, and websites from the Centers for Disease Control and Prevention, the Food and Drug Administration, the World Health Organization, and the National Institutes of Health were searched for relevant articles published between 2006 and 2021. The prevalence of hepatitis C has increased among women of childbearing age in the United States and is associated with risk factors, such as intravenous drug use, health inequities, and low socioeconomic background. Infants born to hepatitis C virus-infected mothers have a 6% risk of vertical transmission, and among those infected, 75% will develop chronic hepatitis C and late complications. However, hepatitis C-exposed infants are frequently lost to follow-up, and those infected have delayed diagnosis and treatment and are at high risk for late-onset complications. Direct- acting antivirals and the establishment of effective treatment guidelines cure hepatitis C virus infections. Hepatitis C predominantly affects underserved communities. Early screening of mothers and infants is critical for the diagnosis, treatment, and prevention of chronic infections and lateonset complications. New policies are needed to address hepatitis C health care inequities affecting mothers and infants in the United States.

Technical and Clinical Complications of Cosmetic Tattooing.

Cosmetic tattooing and medical tattooing of the face share basic principles and to some degree types and spectrum of technical and clinical complications known from decorative tattooing of other parts of the body. Cosmetic tattoos recently have grown exponentially in popularity in industrialized countries all over the world. The different complications and their clinical symptoms, pathophysiology, diagnosis, treatment, and prevention are analyzed versus culprit pigments and updated. Eyeliner tattooing is associated with special complications because of the subtle anatomy and the closeness to the eye, and the risk of meibomian gland damage. The spectrum of cosmetic tattoo complications includes early-onset complications (infections particularly with herpes simplex, healing issues, aesthetic and technical mistakes with regret), and late-onset complications (color fading and color shift, "blowout" pigment escape to surrounding skin, papules, nodules, granulomas associated with sarcoidosis, allergic reactions in lip tattoos with lichenoid dermatitis, eye irritation, and fibrosis and scaring especially after microblading); miscellaneous complications include severe burn sensation in tattoos during magnetic resonance imaging later in life. Corneal tattooing and subconjunctival/episcleral tattooing performed on medical indication by ophthalmologists, and for decoration by tattooists carry special risk of intraocular complications. It is recommended for the purpose of research harmonization that terms and diagnostic classification of tattoo adverse events follow the system introduced by the Tattoo Clinic of Copenhagen and already accepted in specialized tattoo clinics in other centers.

Unilateral Diaphragmatic Weakness After Stereotactic Radiotherapy of The Lung: A Case Report

Stereotactic body radiation therapy (SBRT) is the treatment of choice for patients with stage 1 non-small cell lung cancer (NSCLC) who are medically unfit or those refusing surgery. SBRT is a modality which is well tolerated with respect to limitations on surrounding organs and contra-indications. With improving techniques and cancer treatments, patients have a longer life span, but it is known that radiotherapy can cause late-onset complications. We are reporting the case of a 77-year-old woman who was treated with SBRT because of stage 1 NSCLC. She received a total dose of 51 Gy in three fractions, prescribed to the 78% isodose line. Eight months after SBRT she developed progressive dyspnea and the CT scan showed an elevated left hemi-diaphragm. Potential causes were ruled out. The SBRT treatment was performed without other complications. To our knowledge this complication has not previously been described after SBRT. With constant improving cancer treatments and radio-therapeutic techniques, and better longevity, we could see an increase in long term toxicity in the future.

Pleuroparenchymal fibroelastosis after hematopoietic stem cell transplantation in children: a propensity score-matched analysis.

To investigate the incidence, risk factors, and clinical outcomes of pleuroparenchymal fibroelastosis (PPFE) in pediatric hematopoietic stem cell transplantation (HSCT) recipients. This single-center, retrospective, case-control study included 738 consecutive patients who underwent chest CT more than 3 months after HSCT. We identified patients who fulfilled the diagnostic criteria for PPFE and assessed their clinical characteristics and radiologic findings. Propensity score-matched analysis was performed using four covariates (age, sex, HSCT type, and primary disease). The risk factors and clinical outcomes of PPFE were analyzed using the Fine and Gray regression model and stratified log-rank test in the matched groups. PPFE was identified in 4% (31/738, 8.3 ± 3.1 years, 15 males) of the pediatric HSCT recipients with a median time of 2.7 years after HSCT, and it occurred following allogeneic (5%, 15/317), autologous (4%, 15/379), or both (2%, 1/42). Matching yielded 30 and 130 cases in the PPFE and control groups, respectively. The PPFE group showed more frequent late-onset noninfectious pulmonary complications (LONIPCs) and pneumonia more than 3 months after HSCT (p < 0.05). Multivariable analysis showed a significantly higher risk of PPFE in HSCT recipients who had pneumonia more than 3 months after HSCT (hazard ratio = 10.78 [95% confidence interval: 4.29, 27.13], p < 0.001). The PPFE group showed higher mortality (73%, 22/30) and poorer median overall survival (6.8 years [95% confidence interval: 4.1, 9.5]) than the control group (p < 0.001). PPFE represents a severe type of LONIPC after HSCT. HSCT recipients with pneumonia after HSCT may have an increased risk of PPFE. • The incidence of pleuroparenchymal fibroelastosis is not negligible (4%), and it can occur after either allogeneic or autologous hematopoietic stem cell transplantation. • Pleuroparenchymal fibroelastosis after hematopoietic stem cell transplantation showed poor outcome with a high mortality rate of 73% and median overall survival of 6.8 years. • After hematopoietic stem cell transplantation, pneumonia may increase the risk of pleuroparenchymal fibroelastosis development in children. • Lung biopsy should not be indicated in patients with pleuroparenchymal fibroelastosis findings on chest CT as it can cause refractory pneumothorax without helping the diagnosis.

Frequency, Risk Factors, and Clinical Outcomes of Late-Onset Atrial Flutter in Patients after Heart Transplantation.

Aims: Atrial flutter (AFL) is a common late-onset complication after heart transplantation (HTX) and is associated with worse clinical outcomes. Methods: This study investigated the frequency, risk factors, and outcomes of late-onset post-transplant AFL. We analyzed 639 adult patients undergoing HTX at the Heidelberg Heart Center between 1989 and 2019. Patients were stratified by diagnosis and type of late-onset post-transplant AFL (>90 days after HTX). Results: A total of 55 patients (8.6%) were diagnosed with late-onset post-transplant AFL, 30 had typical AFL (54.5%) and 25 had atypical AFL (45.5%). Patients with AFL were younger at HTX (p = 0.028), received more biatrial anastomosis (p = 0.001), and presented with moderate or severe tricuspid regurgitation (56.4%). Typical AFL was associated with graft rejection (p = 0.016), whereas atypical AFL was associated with coronary artery disease (p = 0.028) and stent implantation (p = 0.042). Patients with atypical AFL showed a higher all-cause 1-year mortality (p = 0.010) along with a higher rate of graft failure after diagnosis of AFL (p = 0.023). Recurrence of AFL was high (83.6%). Patients with catheter ablation after AFL recurrence had a higher 1-year freedom from AFL (p = 0.003). Conclusions: Patients with late-onset post-transplant AFL were younger at HTX, received more biatrial anastomosis, and showed a higher rate of moderate or severe tricuspid regurgitation. Typical AFL was associated with graft rejection, whereas atypical AFL was associated with myocardial ischemia, graft failure, and mortality. Catheter ablation represents a viable option to avoid further episodes of late-onset AFL after HTX.

AN UNUSUAL PRESENTATION OF A PULSATILE NECK MASS

AN UNUSUAL PRESENTATION OF A PULSATILE NECK MASS

How Safe Is Airline Travel 48 Hours After Open Septo-Rhinoplasty Surgery?

Objective: The aim of this study was to find out if patients can travel safely on a plane 48 hours after open septo-rhinoplasty (SRP) surgery. Also, to compare analgesic need, mobilization time, readmission rate, side effects, time out of work and routine life between travelling and nontravellingpatients. Materials and Methods: This study was conducted at Istanbul Florence Nightingale Hospitals in Istanbul/Turkey and Group Florence Hospitals in London/United Kingdom. A total of 120 patients who had SRP were included in the study. Sixty patients who traveled from London to Istanbul by plane (approximately 3 hours 40 minutes, 2520 km) for SRP surgery and returned home 48 hours after surgery were compared with 60 local patients. All patients were observed at 8, 12, 24, 36, and 48 hour intervals after surgery. Additionally, all patients who travelled from London to Istanbul were reviewed after 6 days, 14 days, 1 month, 3 months, 6 months and 1 year. The analgesia need, mobilization time, readmission rate, early and late complications patterns and incidence, time out of work and daily routine was compared between the two groups. Early onset side effects include pain, discomfort, bruising, ecchymosis, edema, oozing, bleeding, septal haematoma, and late onset complications like delayed septal haematoma, delayed bleeding, infection, excess edema, breathing problems were compared between travelling and nontravelling patients. Results: The hospital stay was 24 hours for all patients. No further analgesia was needed in both groups during their hospital stay, Mobilization time was in 8 hours in both groups and none of the patients needed readmission in both groups. Common early complications in travelling patients like pain, edema, bruising, ecchymosis, minor oozing, blocked nose, and pain after 48 hours were similar to the local patients and all travelling patients felt confident and strong enough to travel after 48 hours without additional medication or treatment during or after the surgery. Conclusion: People with no underlying medical conditions, who want to travel abroad for surgery and cannot or do not want to stay longer than 48 hours due to their personal or business lives, can consider travelling back to their countries, following SRP surgery, which is as safe as having the surgery locally without travelling abroad.

Cardiopulmonary Exercise Testing Characterizes Silent Cardiovascular Abnormalities in Asymptomatic Pediatric Cancer Survivors.

Late-onset cardiovascular complications are serious concerns for pediatric cancer survivors (PCS) including those who are asymptomatic. We investigated whether cardiopulmonary exercise testing (CPET) can delineate the underlying pathophysiology of preclinical cardiovascular abnormalities in PCS. We examined CPET data via cycle ergometer in asymptomatic PCS with normal echocardiogram and age-matched controls. Peak and submaximal parameters were analyzed. Fifty-three PCS and 60 controls were studied. Peak oxygen consumption (VO2), peak work rate (WR), and ventilatory anaerobic threshold (VAT) were significantly lower in PCS than controls (1.86 ± 0.53 vs. 2.23 ± 0.61 L/min, 125 ± 45 vs. 154 ± 46W, and 1.20 ± 0.35 vs. 1.42 ± 0.43 L/min, respectively; all p < 0.01), whereas peak heart rate (HR) and ventilatory efficiency (a slope of minute ventilation over CO2 production or ∆VE/∆VCO2) were comparable. Peak respiratory exchange ratio (RER) was significantly higher in PCS (p = 0.0006). Stroke volume (SV) reserve was decreased in PCS, indicated by simultaneous higher dependency on HR (higher ∆HR/∆WR) and lower peak oxygen pulse (OP). Twelve PCS with high peak RER (≥ 1.3) revealed lower pVO2 and VAT than the rest of PCS despite higher ventilatory efficiency (lower ∆VE/∆VCO2), suggesting fundamental deficiency in oxygen utilization in some PCS. Poor exercise performance in PCS may be mainly attributed to limited stroke volume reserve, but the underlying pathophysiology is multifactorial. Combined assessment of peak and submaximal CPET parameters provided critical information in delineating underlying exercise physiology of PCS.

Two-dimensional ultrathin Ti3C2 MXene nanosheets coated intraocular lens for synergistic photothermal and NIR-controllable rapamycin releasing therapy against posterior capsule opacification.

Posterior capsule opacification (PCO) is one of the most frequent late-onset complications after cataract surgery. Several kinds of drug-eluting intraocular lenses (IOL) were designed for sustainable drug release to suppress ocular inflammation, the proliferation of lens epithelial cells (LECs) and the development of PCO after cataract surgery. Despite previous advances in this field, the drug-loaded IOLs were limited in ocular toxicity, insufficient drug-loading capacity, and short release time. To prevent PCO and to address these drawbacks, a novel drug-loaded IOL (Rapa@Ti3C2-IOL), prepared from two-dimensional ultrathin Ti3C2 MXene nanosheets and rapamycin (Rapa), was fabricated with a two-step spin coating method in this study. Rapa@Ti3C2 was prepared via electrostatic self-assembly of Ti3C2 and Rapa, with a loading capacity of Rapa at 92%. Ti3C2 was used as a drug delivery reservoir of Rapa. Rapa@Ti3C2-IOL was designed to have the synergistic photothermal and near infrared (NIR)-controllable drug release property. As a result, Rapa@Ti3C2-IOL exhibited the advantages of simple preparation, high light transmittance, excellent photothermal conversion capacity, and NIR-controllable drug release behavior. The Rapa@Ti3C2 coating effectively eliminated the LECs around Rapa@Ti3C2-IOL under a mild 808-nm NIR laser irradiation (1.0 W/cm−2). Moreover, NIR-controllable Rapa release inhibited the migration of LECs and suppressed the inflammatory response after photothermal therapy in vitro. Then, Rapa@Ti3C2-IOL was implanted into chinchilla rabbit eyes, and the effectiveness and biocompatibility to prevent PCO were evaluated for 4 weeks. The Rapa@Ti3C2-IOL implant exhibited excellent PCO prevention ability with the assistance of NIR irradiation and no obvious pathological damage was observed in surrounding healthy tissues. In summary, the present study offers a promising strategy for preventing PCO via ultrathin Ti3C2 MXene nanosheet-based IOLs with synergistic photothermal and NIR-controllable Rapa release properties.

Impact of lung function impairment after allogeneic hematopoietic stem cell transplantation

Late-onset noninfectious pulmonary complications (LONIPC) are a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). However, the clinical impact of lung function deterioration itself in long-term adult survivors of HSCT remains to be fully investigated. This retrospective, longitudinal study aimed to investigate pulmonary function following HSCT in terms of its change and the clinical significance of its decline. We examined 167 patients who survived for at least 2 years without relapse. The median follow-up period was 10.3 years. A linear mixed-effects model showed that the slope of pulmonary function tests values, including percent vital capacity (%VC), percent forced expiratory volume in one second (%FEV1), and FEV1/forced VC ratio (FEV1%), decreased over time. The cumulative incidence of newly obstructive and restrictive lung function impairment (LFI) at 10 years was 15.7% and 19.5%, respectively. Restrictive LFI was a significant, independent risk factor for overall survival (hazard ratio 7.11, P = 0.007) and non-relapse mortality (hazard ratio 12.19, P = 0.003). Our data demonstrated that lung function declined over time after HSCT and that the decline itself had a significant impact on survival regardless of LONIPC.

HTA49 Determining Appropriate Health Economic Modeling Approaches in Fabry Disease

Fabry disease (FD) is a rare X-linked inherited multisystem disorder, caused by a deficiency of a lysosomal enzyme which can lead to progressive accumulation of glycolipids in different cells and multi-organ dysfunction over time. There are different health economic (HE) models that can be considered to simulate the clinical pathway in FD. However, including early-onset symptoms in addition to different late-onset complications of FD in HE models is a major challenge. Moreover, the availability of long-term data in FD is very limited.

Distribution and frequency of tyrosine kinase inhibitor-associated long-term complications in children with chronic myeloid leukemia.

Tyrosine kinase inhibitors (TKIs) improve outcomes for pediatric malignancies characterized by specific gene rearrangements and mutations; however, little is known about the long-term impact of TKI exposure. Our objective was to assess the incidence and type of late-onset TKI-related toxicities in children with chronic myeloid leukemia (CML). We reviewed medical records from patients diagnosed with CML between 2006 and 2019 at <21years of age and prescribed one or more TKIs. Patients treated with stem cell transplant were excluded. Outcomes were captured beginning at 1year after CML diagnosis. Outcome incidence was described overall and stratified by TKI exposure during the data-capture period. Twenty-two eligible TKI-exposed patients with CML were identified. The median follow-up was 6.0years (range: 2.2-14.3). All pericardial (n=3) or pleural (n=3) effusion outcomes occurred in patients treated with TKIs during the data-capture period. Other outcomes included hypertension (n=2), ectopy on electrocardiogram (n=2), and gastrointestinal bleed (n=1). All outcomes were graded as mild to moderate: some resulted in a temporary discontinuation of TKI, but none led to a change in TKI. No differences were noted in outcome incidence by type of TKI exposure. TKIs have substantially improved prognosis for subsets of childhood leukemia, but there are limited long-term data to inform exposure-based risk for late-onset complications and screening. Our results suggest that TKI-exposed survivors may be at risk for long-term outcomes that extend well into survivorship.

Retrospective, Landmark Analysis of Long-term Adult Morbidity Following Allogeneic HSCT for Inborn Errors of Immunity in Infancy and Childhood

PurposeAllogeneic hematopoietic stem cell transplant (HSCT) remains the treatment of choice for patients with inborn errors of immunity (IEI). There is little published medical outcome data assessing late medical complications following transition to adult care. We sought to document event-free survival (EFS) in transplanted IEI patients reaching adulthood and describe common late-onset medical complications and factors influencing EFS.MethodsIn this landmark analysis, 83 adults surviving 5 years or more following prior HSCT in childhood for IEI were recruited. The primary endpoint was event-free survival, defined as time post-first HSCT to graft failure, graft rejection, chronic infection, life-threatening or recurrent infections, malignancy, significant autoimmune disease, moderate to severe GVHD or major organ dysfunction. All events occurring less than 5 years post-HSCT were excluded.ResultsEFS was 51% for the whole cohort at a median of 20 years post HSCT. Multivariable analysis identified age at transplant and whole blood chimerism as independent predictors of long-term EFS. Year of HSCT, donor, conditioning intensity and underlying diagnosis had no significant impact on EFS. 59 events occurring beyond 5 years post-HSCT were documented in 37 patients (45% cohort). A total of 25 patients (30% cohort) experienced ongoing significant complications requiring active medical intervention at last follow-up.ConclusionAlthough most patients achieved excellent, durable immune reconstitution with infrequent transplant-related complications, very late complications are common and associated with mixed chimerism post-HSCT. Early intervention to correct mixed chimerism may improve long-term outcomes and adult health following HSCT for IEI in childhood.