Long-term Sequelae Research Articles

SARS-CoV-2 Encephalitis versus Influenza Encephalitis: More Similarities than Differences.

From time to time, physicians face challenging diagnostic and therapeutic issues concerning the acute management of children with viral encephalitis. The aim of this article is to provide an updated narrative review on the similarities and differences between SARS-CoV-2 and influenza encephalitis. A PubMed search was performed with the function "Clinical Queries" using the key terms "SARS-CoV-2" OR "Influenza" AND "Encephalitis". The search strategy included metaanalyses, clinical trials, randomized controlled trials, reviews and observational studies. The search was restricted to the English literature and pediatric population. This article compares similarities and contrasts between SARS-CoV-2 and influenza-associated encephalitis. Encephalitis is an uncommon manifestation of both influenza and SARS-CoV-2. Both viruses are associated with fever and respiratory symptoms. However, SARS-CoV-2 patients may only have mild symptoms or be asymptomatic as silent carriers, rendering the disease spread difficult to control. Influenza patients usually have more severe symptomatology and are often bed bound for several days limiting its spread. Influenza is associated with seasonal and annual outbreaks, whereas SARS-CoV-2 has become endemic. Complications of encephalitis are rare in both viral infections but, when present, may carry serious morbidity and mortality. Many long-term sequelae of COVID- 19 infections (long COVID-19) have been described but not with influenza infections. Mortality associated with encephalitis appears higher with influenza than with SARS-CoV-2. Prophylaxis by immunization is available for both influenza and SARS-CoV-2. Specific efficacious antivirals are also available with oseltamivir for influenza and nirmatrelvir/ritonavir for SARS-CoV-2. Steroids are indicated with more severe SARS-CoV-2 but their role is not distinct in influenza disease. Encephalitis is a rare complication of influenza and SARS-CoV-2 infections. Both carry significant morbidity and mortality. Efficacious vaccines for prophylaxis and antivirals for treatment are available for both viruses.

Life After Invasive Meningococcal Disease: Insights from Survivors and Their Caregivers.

Invasive meningococcal disease (IMD) has a low incidence but is a life-threatening illness that is preventable via vaccination. Even with treatment, up to 10-15% of cases are fatal, and many survivors may experience severe long-term sequelae. Building upon the acute-phase findings presented in the Part1 manuscript for this study, we describe the long-term physical, social, psychological, and economic burden of IMD on US survivors and their caregivers in this Part2 manuscript. This was a novel, non-interventional, mixed-methods study among US survivors and their caregivers using a bespoke survey and qualitative interviews. Ten adult survivors, one adolescent survivor, and three caregivers participated in this study. Survivors described extensive physical, neurological, and systemic sequelae, including difficulty walking (11/11), repeat secondary infections (9/11), and numbness (6/11), among others, which were echoed by caregivers. Survivors shared that IMD had negatively impacted their long-term quality of life, citing long-term impacts including emotional impacts (11/11), social impacts (10/11), memory (7/11) and attention (5/11) problems, and difficulty with functional (10/11), self-care (7/11), and physical (6/11) activities. Caregivers were also impacted, describing emotional trauma (3/3), sleep problems (2/3), and day-to-day challenges (2/3). Long-term financial challenges related to healthcare resource utilization were substantial, with specialized care and rehabilitation therapy expenses (11/11), insurance challenges (8/11), and high out-of-pocket costs (6/11) for survivors. Productivity losses were also commonly described by survivors (9/11); sequelae hindered ability to attend school (9/11) or work full time (8/11). Caregivers (2/3) described taking leave from their employment, affecting family income. The humanistic burden of IMD on survivors and their caregivers is substantial and persistent. A comprehensive approach, including preventative measures (e.g., vaccination) and long-term medical, psychological, and financial support for those affected, is needed to mitigate the burden of IMD. A video abstract is available with this article. Video abstract (MP4 1,17,430kb).

Endomyocardial biopsy in the diagnosis of cardiac sarcoidosis

Abstract Background Definite diagnosis of cardiac sarcoidosis (CS) requires proof of sarcoid granulomas in the heart. Endomyocardial biopsy (EMB) is considered a risky procedure with poor sensitivity (<25%) in CS (1), although comprehensive studies on its diagnostic performance are not available. Purpose We investigated the sensitivity, complications, and prognostic significance of EMB in a large cohort of patients with CS to help to choose diagnostic strategy when the disease is suspected. Methods We analysed the data of 260 consecutive patients diagnosed with CS in 1988-2022 at our institution. All met the diagnostic criteria of the Heart Rhythm Society (1). The use, findings, and complications of EMB were retrospectively noted in addition to patients’ demographics, presenting phenotype, diagnostic examinations, and future serious cardiac events. The data were retrieved from hospital records and an ongoing CS registry (2). Advanced imaging studies (cardiac magnetic resonance, positron emission tomography) were re-analysed and the follow-up information was updated until June 2023. EMB’s performance was assessed also in 30 cardiac transplant recipients having CS at the histopathologic study of the explanted heart. Results Of the 260 patients (mean age 49, 60% females), 216 (83%) underwent diagnostic EMB, 48 with repeat procedures. The sensitivity of EMB was 38%, rising to 49% after repeats. The predictors of positive EMB (Table 1) included the presenting phenotype and characteristics of the activity, extent, and location of myocardial involvement. Presentation with ventricular tachyarrhythmia, left ventricular (LV) ejection fraction ≤45%, elevation of cardiac troponins, and presence of middle or apical LV septal late gadolinium enhancement on magnetic resonance imaging were independent predictors (p<0.05) of positive biopsy. The sensitivity of EMB was directly related to the count of the predictors present (Figure 1). The rate of procedural complications was 9.7% overall and 0.7% for major events. One pericardial effusion needed drainage, but no deaths or long-term sequels followed the biopsies. Minor complications included 10 paroxysms of ventricular tachycardia and 6 small pericardial effusions. The 10-year rate (95% CI) of the composite of cardiac death, end-stage heart failure, or ventricular tachyarrhythmia was 55% (44-67%) with positive EMB vs 29% (17-44%) with negative EMB (p<0.001). When adjusted for the presenting phenotype and LV ejection fraction, EMB did not predict outcome events. In the 30 patients with CS in explanted hearts, the sensitivity of EMB, including the repeats, was 60%. Conclusion The sensitivity of EMB is better than usually presented in CS and the higher the more extensive myocardial involvement is. Risk of serious complications is <1%. In patients with suspect CS, the pre-test likelihood and value of positive EMB should be weighed against the procedural risks in shared decision-making when choosing the diagnostic pathway.

Intracranial inoculation rapidly induces Nipah virus encephalitis in Syrian hamsters.

Nipah virus (NiV) is a highly pathogenic Paramyxovirus associated with outbreaks in Malaysia, Bangladesh, and India with high mortality rates. NiV infection causes fatal respiratory and neurological disease. The majority of survivors suffer from long-term neurological sequelae or late onset and relapsed encephalitis. The pathogenesis of neurological disease is complex and has not been able to be studied in current animal models as they are skewed towards the development of lethal respiratory disease rather than neurological disease. Although NiV neurological disease can be observed in animal models, there is currently no model where the majority of animals consistently develop neurological disease. Here, we developed a new Syrian hamster (Mesocricetus auratus) model to mimic neurological disease in humans. Hamsters were inoculated intracranially in the cerebellomedullary cistern with different doses of NiV, strain Malaysia. Intracranial NiV inoculation in the cerebellomedullary cistern resulted in a rapid progression towards severe neurological disease requiring euthanasia. High Nipah viral loads were detected in the brains, and NiV spread from the CNS to the lungs. Histopathologic examination of the brain showed ischemic necrosis, often accompanied by marked edema and hemorrhage. NiV antigen was detected primarily in meninges and cerebellum, but rarely observed in brain parenchyma. These histological lesions were different from the typical lesions observed in NiV-infected humans. Thus, despite the consistent development of neurological disease, intracranial inoculation does not result in a model representative of NiV neurological disease.

Experiences of access to care, diagnosis and rehabilitation among a multiethnic patient population with long-COVID in Denmark

Abstract Background and aim The aim of the study was to explore the experiences of accessing care, diagnosis, and rehabilitation among patients with long-COVID in a multiethnic population in Denmark. Methods Qualitative research using semi-structured interviews among a purposive sample of 18 people diagnosed with long-COVID, according to the NICE guideline, in the Capital Region of Denmark. Participants were sampled to secure variation in sex, age, ethnicity, migration status and education. Our interview guide was developed using the theoretical framework of candidacy. Interviews were transcribed verbatim, and member checked, and subsequently analyzed using thematic framework analysis and NVivo software. Results The analysis generated four categories: i) living with long-COVID, ii) access to care, iii) experiences in the healthcare system, and iv) experiences with rehabilitation. A main category was identified from these categories: limited knowledge of COVID resulting in uncertainty, which challenged nearly all aspects of access to diagnosis, care and rehabilitation among the informants. In particular, ethnic minorities experienced that their motives for seeking care were questioned or had the experience of differential treatment. In general, participants perceived to be themselves responsible of recovering, while also struggling with the mental, social and work-related consequences of their long-COVID. Conclusions Our study demonstrated how the emergence of a new viral disease with unknown long-term sequelae results in a group of patients who to a great extend carry the burden of getting better themselves. More research into relevant diagnosis, care and support for long-COVID patients is needed, especially among ethnic minorities.

A Machine Learning Approach to Identifying Risk Factors for Long COVID-19

Long-term sequelae of coronavirus disease 2019 (COVID-19) infection are common and can have debilitating consequences. There is a need to understand risk factors for Long COVID-19 to give impetus to the development of targeted yet holistic clinical and public health interventions to reduce its associated healthcare and economic burden. Given the large number and variety of predictors implicated spanning health-related and sociodemographic factors, machine learning becomes a valuable tool. As such, this study aims to employ machine learning to produce an algorithm to predict Long COVID-19 risk, and thereby identify key predisposing factors. Longitudinal cohort data were sourced from the UK’s “Understanding Society: COVID-19 Study” (n = 601 participants with past symptomatic COVID-19 infection confirmed by serology testing). The random forest classification algorithm demonstrated good overall performance with 97.4% sensitivity and modest specificity (65.4%). Significant risk factors included early timing of acute COVID-19 infection in the pandemic, greater number of hours worked per week, older age and financial insecurity. Loneliness and having uncommon health conditions were associated with lower risk. Sensitivity analysis suggested that COVID-19 vaccination is also associated with lower risk, and asthma with an increased risk. The results are discussed with emphasis on evaluating the value of machine learning; potential clinical utility; and some benefits and limitations of machine learning for health science researchers given its availability in commonly used statistical software.

Sudden cardiac death in acute coronary occlusion: potential roles of sino-atrial nodal artery and conus artery

Abstract An estimated 80% of sudden cardiac death (SCD) is due to coronary artery disease1. Ventricular arrhythmia (VA) is most commonly associated with LAD infarctions, likely due to the larger extent of affected myocardium, but non-LAD territory infarctions also present with VA. We propose two potential contributors, the sinoatrial nodal artery (SANa) and conus artery (CA). We retrospectively analyzed 2 cohorts of patients presenting with STEMI complicated by SCD due to VA, and whether these arteries were compromised in non-LAD territory STEMI, compared with uncomplicated STEMI. In the first, cohort A, we compared 127 consecutive STEMI patients presenting with cardiac arrest, with 100 uncomplicated STEMI. SANa and CA involvement was assessed in patients presenting with non-LAD territory STEMI. In the second, cohort B, we looked at patients presenting with inferior STEMI involving the RCA only, 20 complicated by aborted SCD due to VA compared with 24 uncomplicated patients. Cohort A (see table) showed a preponderance of single vessel and proximal LAD culprits in the arrest group and a significant number of non-LAD culprits. The extent and complexity of coronary disease and amount of myocardium at risk, reflected in SYNTAX and modified Jeopardy scores, were not significantly different between arrest and non-arrest groups. In those with RCA or Circumflex culprits, 77% in the Arrest group had the SANa arising from the culprit vessel, with only 33% of patients in the Control group, p<0.005. In cohort B, 70% of arrest and 21% of non-arrest patients had SANa involvement, p<0.005. In this cohort, we also observed that 74% of the arrest patients had CA involvement, compared with only 21% of Control patients, p<0.005. There were no significant differences in heart rate nor incidence of complete heart block and atrial arrhythmia in either cohort. There was significantly more ST elevation in standard leads V1-V2, suggesting RVOT ischemia, in those with aborted SCD and RCA culprit in both cohorts (cohort B: Arrests 85% vs non-arrest 21%, p<0.005. The SANa arises from the proximal RCA in 60% of people, and 40% from the left system. Transient ischemia leading to sinus bradycardia may not result in as marked QT prolongation compared with AV block at comparable heart rates, but in the ischemic environment, with hypotension provoking sympathetic upregulation, may lead to enough repolarization heterogeneity to induce VA. The CA arises from the RCA in 50% or more, and otherwise from the right coronary sinus, supplying the RVOT, a region prone to arrhythmogenesis, even in structurally normal hearts, more so if ischemic. Recognizing the potential role of these arterial branches in the VA mechanism would alert operators into preserving their patency. Transient disturbances may not translate into long term adverse outcomes, but whereas permanent damage to the SAN is more readily remedied, further study is needed to assess any long-term sequelae of RVOT infarction.

67 A population-based cohort study of endocrine outcomes within the first 5 years of life in children born preterm

Abstract Background Preterm birth (<37 weeks’ gestational age [GA]) occurs in 8% of live births in Canada. While advancements in neonatal medicine have led to increased survival in preterm births, infants born preterm continue to sustain short- and long-term health sequelae. There is paucity of large population studies evaluating childhood health care outcomes, including endocrine-related outcomes, in recent birth cohorts. Objectives To evaluate the rates of endocrine conditions during the first 5 years of life in children born preterm and term. Design/Methods The study cohort included liveborn infants at 22-44 weeks’ GA in British Columbia, Canada between 2004-2014. Follow-up data to December 2019 included linked health services use information from four BC provincial databases (perinatal database, hospitalizations, outpatient services, and outpatient prescriptions). Rates of outcomes were compared by GA at birth (37-44 weeks reference category) using robust Poisson regression. Results There were 455,960 children included in this study with 42,820 (9.4%) born at <37 weeks GA. Results are summarized in Table 1 and Table 2. Compared to children born at 37-44 weeks’ gestations, infants born at 36 weeks’ gestation or younger have an increased rate of thyroid disorders between 0 months and 5 years (rate ratio [RR]: 1.45, 95% confidence interval [CI]: 0.78-2.43; RR: 1.83, 95% CI 1.51-2.20; RR: 1.41 95% CI 1.26-1.57 for 22-27 weeks, 28-33 weeks and 34-36 weeks GA, respectively). Similarly, infants born at 36 weeks’ gestation or younger have a higher rate of conditions in growth and development (RR: 3.05, 95% CI: 0.76-7.96; RR: 3.20, 95% CI 2.04-4.76; RR: 1.42 95% CI 1.02-1.94 for 22-27 weeks, 28-33 weeks and 34-36 weeks gestations, respectively) and bone health conditions (RR: 1.38, 95% CI: 1.27-1.49; RR: 1.04, 95% CI 1.00-1.08; RR: 1.05 95% CI 1.03-1.07 for 22-27 weeks, 28-33 weeks and 34-36 weeks gestations, respectively). There was no difference in rates of conditions related to glucose metabolism such as diabetes mellitus or hypoglycemia. Conclusion Children born preterm have increased rates of endocrine conditions by age 5. Disorders of thyroid, growth and development are increased in infants born preterm. Children born preterm have an increase rate of bone-related disorders, including those born late-preterm. These results provide useful prognostic information for follow-up care for preterm children and for healthcare resource planning. Furthermore, these results highlight areas of future research in endocrine health among preterm infants.

Epidemiological profile of patients hospitalized with Crohn’s disease due to severe acute respiratory infection during the COVID-19 pandemic: a 2-year report from Brazil

Background and aimsThe novel coronavirus-induced severe acute respiratory syndrome (COVID-19) led to one of the most significant global pandemics of the 21st century, causing substantial challenges for healthcare systems worldwide, including those in Brazil. This study aimed to investigate the demographic and clinical profiles of hospitalized patients in Brazil who had both COVID-19 and Crohn’s disease (CD) over a 2-year period.MethodsAn epidemiological analysis was conducted using data from Open-Data-SUS. The study focused on describing the demographic characteristics, clinical manifestations, comorbidities, and hospitalization details of patients afflicted with severe acute respiratory syndrome due to COVID-19 and CD, with the aim of predicting mortality risk.ResultsThe states of São Paulo, Paraná, and Minas Gerais accounted for 50% of the reported COVID-19 cases. The most affected racial group consisted of individuals who self-declared as mixed race. Common comorbidities included heart disease, diabetes mellitus, and obesity. The age group most affected was 25 to 60 years old, particularly among hospitalized patients with both CD and COVID-19 who ultimately succumbed to the illness. A multivariable analysis was conducted to identify the following significant risk factors for death: (a) the presence of neurological disorder (OR = 6.716; 95% CI = 1.954–23.078), (b) the need for intensive care (OR = 3.348; 95% CI = 1.770–6.335), and (c) the need for invasive mechanical ventilation (OR = 59.017; 95% CI = 19.796–175.944).ConclusionThere was no discernible gender-based prevalence among hospitalized patients with CD and COVID-19; however, individuals of mixed race were disproportionately affected. The 25 to 60 age group emerged as the most vulnerable demographic group, with high risks of hospitalization and mortality. Moreover, the study highlights the potential for COVID-19 to induce systemic pathologies that may result in long-term degenerative effects and sequelae.

Association Between Body Composition Measured by Artificial Intelligence and Long-Term Sequelae After Acute Pancreatitis.

The clinical utility of body composition in the development of complications of acute pancreatitis (AP) remains unclear. We aimed to describe the associations between body composition and the recurrence of AP. We performed a retrospective study of patients hospitalized with AP at three tertiary care centers. Patients with computer tomography (CT) imaging of the abdomen at admission were included. A previously validated and fully automated abdominal segmentation algorithm was used for body composition analysis. Hospitalization for a recurrent episode of AP was the primary endpoint. Secondary endpoints included the development of chronic pancreatitis (CP) or diabetes mellitus (DM) in patients who were evaluated. Cox Proportional Hazards regression was used. From a total of 347 patients, 89 (25.6%) were hospitalized for recurrent AP (median time: 219days). Thirty-four of 112 patients (30.4%) developed CP (median time: 311days) and 22 of 88 (25.0%) developed DM (median time: 1104days). After adjusting for age, male sex, first episode of AP, BUN, and severity of AP, we found that obesity, body mass index, alcohol pancreatitis, and gallstone pancreatitis were significantly associated with a recurrent episode of AP. Body composition was not associated with recurrent AP. In unadjusted analysis, subcutaneous adipose tissue (SAT) (HR 0.87 per 10 cm2, p = 0.002) was associated with CP. Skeletal muscle (SM) mass approached significance for CP (p = 0.0546). Intermuscular adipose tissue (IMAT) (HR 1.45 per 5 cm2, p = 0.0264) was associated with DM. Body composition was not associated with having a recurrent AP. At follow-up, 30% and 25% of evaluated patients developed CP and DM, respectively. A higher SAT and IMAT were associated with a lower incidence of CP and higher incidence of DM, respectively.

Mental health-related hospitalisations of adolescents and their contact with child protection services to age 11 years, South Australia: a whole-of-population descriptive study.

To investigate the number of mental health-related hospitalisations of adolescents (12-17 years) in South Australia by level of contact with the child protection system (0-11 years). Whole-of-population descriptive study; analysis of de-identified linked administrative data from the Better Evidence Better Outcomes Linked Data (BEBOLD) platform. Adolescents born in South Australia, 1991-1999; linked SA Department for Child Protection, Admitted Patient Care (SA Health), and South Australian Perinatal Statistics collection (SA Department for Health and Wellbeing) data. Proportion of adolescents (12-17 years) hospitalised with mental health-related diagnoses; proportion of mental health-related hospitalisations of adolescents, by level of child protection contact (0-11 years) (no contact, notification but not screened in, screened-in notification but not investigated, investigation but not substantiated, substantiation, and out-of-home care). Of 175 115 adolescents born during 1991-1999, 5646 (3.2%) had been hospitalised with mental health conditions, and 27 203 (15.5%) had histories of contact with child protection services. The proportion of adolescents admitted to hospital with mental health-related diagnoses increased with the level of prior child protection contact, from 3366 of 147 912 adolescents with no contact (2.3%), to 398 of 6645 with notifications (6.0%), to 209 of 1191 who had been placed in out-of-home care (17.5%). Contact with child protection services was recorded for 2280 of 5646 adolescents admitted to hospital with mental health-related diagnoses (40.4%); 4477 of 10 633 mental health-related hospitalisations (44.9%) were of adolescents with histories of child protection services contact, including 1285 hospitalisations (12.1%) of adolescents for whom substantiated maltreatment (but not out-of-home care) was recorded, and 568 hospitalisations (5.3%) of adolescents who had been placed in out-of-home care. About 45% of mental health-related hospitalisations of 12-17-year-old adolescents were of people who had had contact with child protection services by the age of 11 years, although only 15.5% of all adolescents had histories of child protection contact. The trauma associated with a history of child protection can have longer term sequelae, and this should be considered when adolescents are hospitalised with mental health conditions.

German general practitioners' experiences of managing post-COVID-19 syndrome: A qualitative interview study.

The management of the long-term sequelae of coronavirus disease 2019 (COVID-19) infection, known as post-COVID-19 syndrome (PCS), continues to challenge the medical community, largely owing to a significant gap in the understanding of its aetiology, diagnosis and effective treatment. To examine general practitioners' (GPs) experiences of caring for patients with PCS and to identify unmet care needs and opportunities for improvement. This study follows a qualitative design, using in-depth semi-structured telephone interviews with GPs (N = 31) from across Germany. Interviews were audio-recorded, transcribed verbatim and analysed using qualitative content analysis. GPs reported that they were often the first point of contact for patients with persistent symptoms following SARS-CoV-2 infection, with symptoms typically resolving within weeks. While ongoing symptomatic COVID-19 is perceived to be more common, the relevance of PCS to GP practices is considerable given its severe impact on patients' functioning, social participation and the substantial time required for patient care. GPs coordinate diagnosis and treatment but face challenges because of the unclear definition of PCS and difficulties in attributing symptoms, resulting in a cautious approach to ICD-10 coding. Interviewees highlight lengthy diagnostic pathways and barriers to accessing specialist care. The findings confirm the high functional limitations and psychosocial burden of PCS on patients, and the central role of GPs in their care. The study suggests a need for further research and health policy measures to support GPs in navigating diagnostic uncertainty, interprofessional communication and the limited evidence on effective treatments.

The home-based breathing and chest mobility exercise improves cardiorespiratory functional capacity in long COVID with cardiovascular comorbidities: a randomized study

BackgroundBeyond the acute phase, a considerable proportion of patients recovering from the coronavirus disease 2019 (COVID-19) experience long-term sequelae that profoundly impact their quality of life, particularly their physical fitness. This study aims to assess the effect of home-based breathing and chest mobility exercise on the cardiorespiratory functional capacity of long COVID with cardiovascular comorbidity.MethodsIn this randomized, controlled, single-blind clinical trial, 46 long COVID with cardiovascular comorbidities were randomly assigned to either intervention or control group. The intervention group (n = 23) received additional home-based breathing and chest mobility exercise 3x/week for 12 weeks supervised by attending physicians, whereas the control group only received a home-based cardiac rehabilitation program. Baseline and post-intervention assessments consisted of laboratory (D-Dimer and CRP levels) and functional capacity, assessed through 6-minute walking test (6-MWT), exercise stress test’s metabolic equivalents (METS), and predicted peak oxygen consumption (VO2 peak), peak expiratory flow rate (PEFR), peak cough flow (PCF), chest expansion, and EuroQoL’s quality of life. Intention to treat analysis was performed.ResultsAt the 12th week, intervention subjects had significantly greater functional capacity with higher mean PEFR (p = .031) and PCF (p = .016). Similarly, 6-MWT was higher in the group receiving home-based breathing and chest mobility training (p = .032). The bottom part of the chest circumference was statistically different between the two groups (p = .01). METS and predicted VO2 peak were also higher in the intervention group. However, laboratory parameters and quality of life did not differ markedly (p > .05).ConclusionsHome-based respiratory and chest mobility exercise could be an adjunct to cardiac rehabilitation in long COVID with cardiovascular comorbidities for improving cardiorespiratory functional capacity.Trial registrationThe study protocol was registered at http://ClinicalTrial.gov.id NCT05077943 (14/10/2021).

Feasibility Study of Adverse Childhood Experiences, Treatment-Related Sequelae, and Inflammatory Markers in Breast Cancer Survivors.

To explore the incidence of adverse childhood experiences (ACEs) in breast cancer survivors and potential associations with long-term treatment-related sequelae. English-speaking breast cancer survivors three or more years from diagnosis with complete treatment response (N = 120) were recruited prior to scheduled survivorship clinic visits. Participants in this cross-sectional observational feasibility study rated anxiety, depression, fatigue, sleep disturbance, cognitive issues, resilience, and ACEs (experienced prior to age 18 years). Blood samples were analyzed for inflammatory and epigenetic biomarkers. ACEs assessment was feasible. Higher ACE scores correlated with greater fatigue, anxiety, and depression, and with lower cognitive function (p < 0.05). Resilience was positively associated with cognitive function and negatively associated with fatigue, anxiety, and depression. There is evidence for the impact of ACEs on long-term treatment-related sequelae in women with breast cancer. Oncology nurses should consider incorporating ACEs assessment into the workflow for women receiving survivorship care.

Endocrine Complications in Hepatic Glycogen Storage Diseases: A Long-term Perspective.

Patients with hepatic type of glycogen storage diseases (GSDs) can manifest endocrine features such as hypoglycemia, dyslipidemia, or osteoporosis. This study aimed to investigate the long-term endocrine consequences in patients with hepatic GSDs. This study included 64 patients from 52 families with hepatic GSDs including GSD type Ia (41 patients from 37 families), Ib (3 unrelated), III (8 from 6 families), IV (one patient), and IX (11 from 5 families). All patients were genetically confirmed. Clinical and endocrine findings were retrospectively analyzed. The median age at diagnosis and current age were 2.4 years (range, 0.1-42.4 years) and 17.6 years (range, 1.0-47.8 years), respectively. The mean height SDS at diagnosis was -3.5 ± 1.4, and short stature was observed in 35.6% of patients. Patients diagnosed after the age of 3.4 years exhibited a high risk of short stature (OR = 36.1; P-value < 0.001). Among 33 patients who reached final height, 23 (69.7%) showed delayed puberty. Hypertriglyceridemia was observed in 46 patients (71.9%), whereas 25 patients (39%) had elevated low-density lipoprotein cholesterol levels during the follow-up period. Among 24 patients who underwent dual energy X-ray absorptiometry, 22 showed a low bone mineral density Z-score of -3.0 ± 1.3 at the L-spine. This study described the long-term endocrine consequences in patients with hepatic GSDs. Pediatric endocrinologists should be aware of the presenting features and long-term endocrine sequelae of GSDs to provide proper management and decrease its morbidities.

Respiratory sequelae after COVID-19 infection in Thai healthy children.

The long-term respiratory sequelae of COVID-19 infection in children remain poorly understood and may differ across countries. This study aims to investigate the respiratory sequelae, including residual respiratory symptoms and pulmonary function in Thai children. The secondary aim is to identify factors associated with the respiratory sequelae. This is an observational study involving 56 healthy children, aged between 7 and 18 years, who were diagnosed with COVID-19 infection from July 2021 to February 2023. Clinical data relating to COVID-19 infection and persistent symptoms after the infection were assessed after the infection up to 6 months. Spirometry was performed to assess pulmonary function. Post-COVID-19 symptoms were identified in 14 patients (25%), with fatigue, cough, and dyspnea being common symptoms (28%-35%). A significant correlation was found between post COVID-19 symptoms and pneumonia (OR = 6.00, 95%CI [1.54,23.33], p = .01). Abnormal pulmonary function was identified in 10 patients (17.8%) with obstructive impairment being the most common. However, there was no significant association between clinical factors and pulmonary function impairment. Prolonged respiratory symptoms and abnormal pulmonary function following COVID-19 infection are not uncommon in children. The post-COVID-19 symptoms are possibly associated with COVID-19 pneumonia.

Post-Meningitic Syndrome: Pathophysiology and Consequences of Streptococcal Infections on the Central Nervous System.

Streptococcus species represent a significant global cause of meningitis, leading to brain damage through bacterial virulence factors and the host inflammatory response. Upon entering the central nervous system (CNS), excessive inflammation leads to various neurological and psychological complications. This review explores the pathophysiological mechanisms and associated outcomes of streptococcal meningitis, particularly its short- and long-term neurological sequelae. Neurological symptoms, such as cognitive impairment, motor deficits, and sensory loss, are shown to vary in severity, with children being particularly susceptible to lasting complications. Among survivors, hearing loss, cognitive decline, and cranial nerve palsies emerge as the most frequently reported complications. The findings highlight the need for timely intervention, including neurorehabilitation strategies that focus on optimizing recovery and mitigating long-term disabilities. Future recommendations emphasize improving early diagnosis, expanding vaccine access, and personalizing rehabilitation protocols to enhance patient outcomes. As a novel contribution, this review proposes the term "post-meningitic syndrome" to showcase the broad spectrum of CNS complications that persist following streptococcal meningitis, providing a framework for a future clinical and research focus.

Age-Related Differences in Clinical Characteristics and Outcomes of Aneurysmal Subarachnoid Hemorrhage: A Retrospective Study of 657 Patients

Aneurysmal subarachnoid hemorrhage (aSAH) has an incidence of 6-7 per 100,000 person-years. Despite advancements in treatment, 26% of patients die, and 19% remain dependent post-hemorrhage. Long-term neuropsychological sequelae affect about half of the survivors, significantly impacting their quality of life. This study aims to assess aSAH characteristics and identify predictive factors of clinical outcomes in young patients. A retrospective study analyzed 657 aSAH patients treated at two South Korean medical centers from January 2011 to December 2023. Data on demographics, comorbidities, smoking history, clinical grades, aneurysm size and location, and outcomes were collected. Outcomes were classified using the modified Rankin Scale (mRS), with scores ≤2 indicating good outcomes. The cohort included 233 men and 424 women (male-to-female ratio 1:1.8). Most patients were middle-aged (74.4%), followed by young (16.7%) and old (8.8%) groups. Young patients exhibited male predominance (56.8%), lower hypertension (12.7%) and diabetes (1.8%) rates, and higher smoking rates (39.6%). Older patients had higher hypertension (44.6%) and diabetes (23.3%) rates, and were predominantly female (69.1%). Aneurysms in young patients were smaller (p=0.04). Multivariate analysis identified poor Hunt-Hess grade, permanent cerebral infarction, and aneurysmal recurrence or rebleeding as predictors of poor outcomes in young patients. Middle-aged patients had additional predictors, including diabetes and hydrocephalus. In older patients, only poor Hunt-Hess grade was significant. Young aSAH patients exhibit distinct characteristics and prognostic factors compared to older patients. Despite higher post-operative complications, young patients generally have better outcomes, emphasizing the need for age-specific management strategies in aSAH.

A Systematic Review and Meta-Analysis of the Efficacy of Antimicrobial Chemoprophylaxis for Recurrent Acute Otitis Media in Children.

Acute otitis media (AOM) is a common childhood infection. Recurrent AOM affects a subset of children, resulting in an adverse impact on quality of life, socioeconomic disadvantage, and risk of long-term sequelae. Antimicrobial chemoprophylaxis is used in some settings but is increasingly controversial due to an awareness of adverse long-term effects and contribution to global antibiotic resistance. A comprehensive literature search was undertaken using Medline (1946-October 2023) and Embase (1974-October 2023). The primary aim was to assess the efficacy of antimicrobial chemoprophylaxis on AOM episodes in children < 18 years of age. Bias and quality assessment was performed. Dichotomous data were analysed using risk ratio with 95% confidence intervals. Meta-analysis was carried out using random-effects models for pooled analysis, independent of heterogeneity. Heterogeneity was assessed using the I2 statistic. The effect of antimicrobial chemoprophylaxis in children with rAOM on the number of individual AOM episodes. assessment of antimicrobial agents and outcomes in children with risk factors. Assessment of qualitative data was performed on 20 studies (n = 2210). No controlled trials were identified post-multivalent pneumococcal conjugate vaccine (PCV) introduction, restricting current generalisability. Quantitative meta-analysis on nine pre-PCV studies (n = 1087) demonstrated antimicrobial chemoprophylaxis reduced any episode of AOM with a risk ratio 0.59 (95% CI 0.45-0.77). Families and clinicians must balance marginal short-medium term benefit (based on pre-PCV data), and the potential for adverse effects to that individual, and the societal risk of antimicrobial resistance with prolonged antibiotic use.

STI Rates Among High-Risk Youth Undeterred During Early COVID-19 In A HIV Care Clinic

Abstract Background In recent years, the United States has observed increasing rates of sexually transmitted infections (STIs). Rates are highest amongst the teen and young adult age groups. In addition to the immense healthcare costs associated with STIs, long-term sequelae can be severe on the individual level. The risk of infertility is particularly high for those with repeated or prolonged infection. Upon entering the COVID-19 pandemic, it was unclear if the widespread behavioral changes and disruptions in routine care practices to minimize the further spread of COVID-19 would cause an increase or decrease in the United States’ STI rates. This study sought to determine if there was a change in the incidence of STIs during the first year of the COVID-19 pandemic compared to the year prior in a population at high risk for STIs. Methods A retrospective chart review was performed for 330 patients aged 12 to 41 years (mean 20.2 years, median 20 years, standard deviation 3.75 years) with human immunodeficiency virus (HIV) or on pre-exposure prophylaxis (PrEP) to prevent the acquisition of HIV, who presented for preventative and acute care appointments at a multidisciplinary pediatric and young adult HIV Clinic in the year prior to and during the first year of the COVID-19 pandemic (March 22, 2019-March 21, 2021). Utilizing telehealth, rapid COVID-19 screening, and multimodal patient communication, increased efforts were made in this clinic during the pandemic to maintain appropriate STI screening, testing, treatment, and rescheduling of routine visits when appropriate to minimize COVID-19 exposure and spread. Comparisons were made between the two time periods, which evaluated the incidences of individual and overall STIs diagnosed per person-years, STIs per total tests performed, and time to treatment initiation. Results Between one year prior to and the first year during the COVID-19 pandemic, this clinic experienced no statistically significant rate changes of sexually transmitted infections. A non-significant decreased incidence of chlamydia (22 cases per 100 person-years and 18 cases per 100 person-years, respectively) and unchanged rates of gonorrhea (22 cases per 100 person-years and 22 cases per 100 person-years, respectively) and syphilis (16 cases per 100 person-years and 15 cases per 100 person-years, respectively) were observed. The median times to treatment remained largely unchanged. Conclusion This HIV care clinic experienced a decreased chlamydia infection rate, a trend similar to the CDC United States STI data during this time period. In contrast to the nationally reported increased rates of gonorrhea and syphilis, this clinic experienced unchanged rates. The lack of change in our cohort could reflect that the benefits of a multidisciplinary HIV care model persist despite a pandemic that disrupted routine medical care and behavior practices.