Persistent Morbidity Research Articles

Receiving a Pathogenic Variant in a Population Breast Cancer Screening Trial: A Mixed Method Study

Introduction: Risk-based breast cancer screening aims to address persistent high morbidity and mortality. This study examined the experience of participants in the Women Informed to Screen Depending on Measures of Risk (WISDOM) trial who received a pathogenic variant in one of nine high or moderate penetrance breast cancer genes. Methods: Participants completed a brief survey (n = 181) immediately following the results disclosure and 1 year later. Descriptive statistics were computed and comparisons between participants at different risk levels were performed using Fisher’s exact and McNemar’s tests. Analysis of qualitative interviews (n = 42) at 2–4 weeks and 6 months post-results disclosure compared responses at the 2 time points and explained and elaborated on the survey data. Results: 66.3% of survey respondents felt very or moderately prepared to receive genomic results. At the T1 survey, 80.7% of participants had shared the genetic result with a blood relative, increasing to 88.4% at T2; providing information and encouraging cascade testing were the most common reasons for sharing. Communication with a blood relative, other healthcare providers beyond the primary care provider, and cascade testing were higher for participants with a high risk than low or moderate risk genomic finding. Qualitative interviews elucidated varied reasons why participants felt (un)prepared for the results, including whether or not they had a family history of breast cancer, and illustrated the complexity of decision-making about sharing results. Conclusions: Although most participants communicated results with family members and healthcare providers in accordance with their risk level, questions remain about how to adequately prepare individuals to receive pathogenic results, ensure timely and accessible follow-up care, and facilitate genetic counseling and cascade testing of at-risk relatives in the setting of population risk-based screening.

Reported impact and protective factors of the care partner role during persistent critical illness: a content analysis

BackgroundPatients with persistent critical illness experience prolonged multi-system morbidity, functional impairments, and chronic conditions. As a result, these patients have prolonged intensive care unit admissions. If discharged, they return home with long-term medical dependencies. Care partners take on a variety of physical, mental health, cognitive, and social roles to support the provision of care for these patients. There is limited evidence, however, of the impact of being a care partner for this patient population during hospitalization.MethodsA qualitative descriptive study was conducted to explore the impact care provision on care partners for patients experiencing persistent critical illness. Patients who have or have had persistent critical illness and care partners were recruited from two inpatient units in a single community academic hospital in Toronto, Canada to participate in semi-structured interviews. Data was analyzed using a team-based inductive content analysis.ResultsSeven (43.8%) participants were patient survivors, and nine (56.3%) were care partners. Patients and care partners reported physical, socio-emotional, and social stress as impacts of care provision during persistent critical illness hospitalization. Care partners identified several protective strategies that they used to mitigate the impacts of care provision on them such as seeking external mental health support and boundary setting. Features of formalized and care partner programs were also identified and suggest that these programs can be protective of care partner values, mitigate feelings of helplessness and stress, and may improve relationships between the family members who are in the care partner role and the healthcare team.ConclusionsThis study identified physical, socio-emotional, and social stress related impacts of care provision on care partners of patients with persistent critical illness during hospitalization. Additionally, this study identified protective factors initiated by care partners to mitigate the reported stresses of the role, as well as protective features of a care partner program. The results provide a better understanding supportive features of care partner programs that are specific to the experiences and needs of persistent critical illness and add to the growing body of evidence about how to provide equitable access to care during and post hospitalization.

Unveiling potent inhibitors for schistosomiasis through ligand-based drug design, molecular docking, molecular dynamics simulations and pharmacokinetics predictions.

Schistosomiasis is a neglected tropical disease which imposes a considerable and enduring impact on affected regions, leading to persistent morbidity, hindering child development, diminishing productivity, and imposing economic burdens. Due to the emergence of drug resistance and limited management options, there is need to develop additional effective inhibitors for schistosomiasis. In view of this, quantitative structure-activity relationship studies, molecular docking, molecular dynamics simulations, drug-likeness and pharmacokinetics predictions were applied to 39 Schistosoma mansoni Thioredoxin Glutathione Reductase (SmTGR) inhibitors. The chosen QSAR model demonstrated robust statistical parameters, including an R2 of 0.798, R2adj of 0.767, Q2cv of 0.681, LOF of 0.930, R2test of 0.776, and cR2p of 0.746, confirming its reliability. The most active derivative (compound 40) was identified as a lead candidate for the development of new potential non-covalent inhibitors through ligand-based design. Subsequently, 12 novel compounds (40a-40l) were designed with enhanced anti-schistosomiasis activity and binding affinity. Molecular docking studies revealed strong and stable interactions, including hydrogen bonding, between the designed compounds and the target receptor. Molecular dynamics simulations over 100 nanoseconds and MM-PBSA free binding energy (ΔGbind) calculations validated the stability of the two best-designed molecules. Furthermore, drug-likeness and pharmacokinetics prediction analyses affirmed the potential of these designed compounds, suggesting their promise as innovative agents for the treatment of schistosomiasis.

Digital health interventions for remote follow-up after mild traumatic brain injury

Background After a mild traumatic brain injury (mild TBI,) a significant number of patients may experience persistent symptoms and disabilities for months to years. Early identification and timely management of persistent symptoms may help to reduce the long-term impacts of mild TBIs. There is currently no formalised method for identifying patients with persistent symptoms after mild TBI once they are discharged from emergency department. Objective Assess the feasibility of a remote monitoring tool for early identification of persistent symptoms after mild TBI in the outpatient setting using digital tools. Methods Electronic surveys were sent to patients with mild TBI who presented to the emergency department at a Major Trauma Centre in England. The surveys were completed at three different timepoints (within days of injury (S1), 1 month (S2), and 3 months (S3) after injury). The indicators used to assess feasibility were engagement, number of eligible patients for follow-up evidence of need for the intervention, and consistency with the literature. Feedback was sought from participants. Results Of the 200 people invited to participate, 134 (67.0%) completed S1, 115 (57.5%) completed S2, and 95 (47.5%) completed S3. The rates of persistent symptoms ranged from 17.9%–62.6% depending on the criteria used, and we found a significant proportion of the participants experienced morbidity 1 and 3 months after injury. The electronic follow-up tool was deemed an acceptable and user-friendly method for service delivery by participants. Conclusion Using digital tools to monitor and screen mild TBI patients for persistent symptoms is feasible. This could be a scalable, cost-effective, and convenient solution which could improve access to healthcare and reduce healthcare inequalities. This could enable early identification of patients with further medical needs and facilitate timely intervention to improve the clinical workflows, patient satisfaction, and health outcomes for people with persistent morbidities after mild TBIs.

A Scoping Review of the Epidemiology, Management, and Outcomes of Golf-Related Fractures.

Golf is a popular sport; however, there is a paucity of data in relation to golf-associated fractures, and the rate and timing of returning to golf. The aim of this review is to describe golf-associated fractures, including epidemiology, management, and timing of returning to golf following treatment. A literature search was performed using MEDLINE/PubMed, Embase, and Web of Science. Data were extracted and summarized in a narrative synthesis. A total of 436 articles were identified with an initial search of which 58 met the inclusion criteria. Twelve anatomical sites of golf swing-related fractures were identified, of which 10 sites were specific for stress fractures. The most common sites of golf swing-related stress fractures were the ribs followed by the hook of hamate. There was a common theme of delay to diagnosis, being initially assigned to a soft tissue injury. Most golfers with swing-related stress fractures were able to return to golf with the exception of osteoporotic associated vertebral stress fractures. Timing of returning to golf was between 4 and 12 months for most of the golfers with stress fractures following conservative management. Operative intervention was an option of hook of hamate nonunion, following a stress fracture, and tibial shaft stress fractures. Golf equipment-related fractures were not rare and were associated with major trauma and in some cases associated with significant persistent morbidity. Golf-related stress fractures commonly involve the ribs and hook of hamate; knowledge of this may aid in early diagnosis and appropriate treatment when symptomatic golfers are encountered. Although golf is a noncontact sport, fractures associated with golf equipment can be life changing, and safety training guidelines should be established.

Evolution Characterization and Pathogenicity of an NADC34-like PRRSV Isolated from Inner Mongolia, China.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that causes severe abortions in sows and high piglet mortality, resulting in huge economic losses to the pig industry worldwide. The emerging and novel PRRSV isolates are clinically and biologically important, as there are likely recombination and pathogenic differences among PRRSV genomes. Furthermore, the NADC34-like strain has become a major epidemic strain in some parts of China, but the characterization and pathogenicity of the latest strain in Inner Mongolia have not been reported in detail. In this study, an NADC34-like strain (CHNMGKL1-2304) from Tongliao City, Inner Mongolia was successfully isolated and characterized, and confirmed the pathogenicity in pigs. The phylogenetic tree showed that this strain belonged to sublineage 1.5 and had high homology with the strain JS2021NADC34. There is no recombination between CHNMGKL1-2304 and any other domestic strains. Animal experiments show that the CHNMGKL1-2304 strain is moderately virulent to piglets, which show persistent fever, weight loss and high morbidity but no mortality. The presence of PRRSV nucleic acids was detected in both blood, tissues, nasal and fecal swabs. In addition, obvious pathological changes and positive signals were observed in lung, lymph node, liver and spleen tissues when subjected to hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). This report can provide a basis for epidemiological investigations and subsequent studies of PRRSV.

Translational Research on Orthobiologics in the Treatment of Rotator Cuff Disease: From the Laboratory to the Operating Room.

Rotator cuff disease is one of the most common human tendinopathies and can lead to significant shoulder dysfunction. Despite efforts to improve symptoms in patients with rotator cuff tears and healing rates after rotator cuff repair, high rates of failed healing and persistent shoulder morbidity exist. Increasing interest has been placed on the utilization of orthobiologics-scaffolds, cell-based augmentation, platelet right plasma (platelet-rich plasma), and small molecule-based strategies-in the management of rotator cuff disease and the augmentation of rotator cuff repairs. This is a complex topic that involves novel treatment strategies, including patches/scaffolds, small molecule-based, cellular-based, and tissue-derived augmentation techniques. Ultimately, translational research, with a particular focus on preclinical models, has allowed us to gain some insights into the utility of orthobiologics in the treatment of rotator cuff disease and will continue to be critical to our further understanding of the underlying cellular mechanisms moving forward.

Difference of Knee Strength Recovery Between Revision and Primary ACL Reconstruction.

Different grafting procedures are available to restore knee stability after revision anterior cruciate ligament (ACL) reconstruction. We compared knee strength recovery between ACL revision surgery and primary reconstruction. One hundred and ten patients with ACL revision surgery were matched with 110 patients with primary reconstruction based on the graft procedure. The isokinetic knee strength had been assessed for the first 9 months post-surgery. Knee laxity, function, and activity score were also evaluated. Limb symmetry index for knee extensor and flexor strength was not different at 4-, 6- and 9-months post-surgery between revision surgery and primary reconstruction. These results depended on ipsilateral or contralateral graft choice. Ipsilateral hamstring tendon (HT) and contralateral bone-patellar-tendon-bone (BPTB) graft procedures were similar for a revision of a BPTB graft failure. Contralateral HT procedure was better than ipsilateral BPTB procedure for a revision of a HT graft failure. The early recovery of isokinetic knee strength after ACL revision surgery regardless of the HT or BPTB procedures, was similar to the recovery after primary ACL reconstruction with the same graft technique. These results apparently depended on a temporary quadriceps arthrogenic muscle inhibition and on a persistent donor site morbidity, concerning the new and the previous grafts, respectively.

Carotid stenosis and cryptogenic stroke

ObjectivesCryptogenic stroke represents a type of ischemic stroke with an unknown origin, presenting a significant challenge in both stroke management and prevention. According to the Trial of Org 10,172 in Acute Stroke Treatment criteria, a stroke is categorized as being caused by large artery atherosclerosis only when there is >50% luminal narrowing of the ipsilateral internal carotid artery. However, nonstenosing carotid artery plaques can be an underlying cause of ischemic stroke. Indeed, emerging evidence documents that some features of plaque vulnerability may act as an independent risk factor, regardless of the degree of stenosis, in precipitating cerebrovascular events. This review, drawing from an array of imaging-based studies, explores the predictive values of carotid imaging modalities in the detection of nonstenosing carotid plaque (<50%), that could be the cause of a cerebrovascular event when some features of vulnerability are present. MethodsGoogle Scholar, Scopus, and PubMed were searched for articles on cryptogenic stroke and those reporting the association between cryptogenic stroke and imaging features of carotid plaque vulnerability. ResultsDespite extensive diagnostic evaluations, the etiology of a considerable proportion of strokes remains undetermined, contributing to the recurrence rate and persistent morbidity in affected individuals. Advances in imaging modalities, such as magnetic resonance imaging, computed tomography scans, and ultrasound examination, facilitate more accurate detection of nonstenosing carotid artery plaque and allow better stratification of stroke risk, leading to a more tailored treatment strategy. ConclusionsEarly detection of nonstenosing carotid plaque with features of vulnerability through carotid imaging techniques impacts the clinical management of cryptogenic stroke, resulting in refined stroke subtype classification and improved patient management. Additional research is required to validate these findings and recommend the integration of these state-of-the-art imaging methodologies into standard diagnostic protocols to improve stroke management and prevention.

GO/CaCO3/SiO2 nanocomposite incorporated Carrageenan/Chitosan injectable hydrogel for enhanced hemostasis

Every year, millions of civilian casualties are caused by excessive bleeding, often known as hemorrhage. Even if the initial bleeding is effectively controlled, wound sequelae such as infection remains a substantial cause for persistent morbidity. Numerous blood clotting materials have been found, tried, and used to stop the bleeding. Topical dressings such gauzes, as well as organic and bioinspired materials are used to stop bleeding. None of these substances, however, can accurately duplicate the intricate and dynamic characteristics of blood clotting and the body's natural ability for wound healing. In this research work we have synthesized GO/CaCO3/SiO2 nanocomposite and incorporated them in a polymeric hydrogel for blood clotting application. The nanocomposite is characterized with XRD, FTIR and TEM. The injectable hydrogel is characterized with FTIR and SEM. Colony count and growth curve analysis are done for the nanocomposite. The injectable hydrogel consisting of the GO/CaCO3/SiO2 nanocomposite enhances the blood clotting property. This hydrogels with graphene oxide nanocomposite will be an ideal choice for addressing the clear need for better blood clotting material.

Preventive treatment for latent tuberculosis from Indian perspective.

The persistent morbidity and mortality associated with tuberculosis (TB), despite our continued efforts, has been long recognized, and the rise in the incidence of drug-resistant TB adds to the preexisting concern. The bulk of the TB burden is confined to low-income countries, and rigorous efforts are made to detect, notify, and systematically treat TB. Efforts have been infused with renewed vigor and determination by the World Health Organization (WHO) to eliminate tuberculosis in the near future. Different health agencies worldwide are harvesting all possible strategies apart from consolidating ongoing practices, including prevention of the development of active disease by treating latent TB infection (LTBI). The guidelines for the same were already provided by the WHO and were then adapted in the Indian guidelines for the treatment of LTBI in 2021. While the long-term impact of TBI treatment is awaited, in this article, we aim to discuss the implications in the Indian context.

Keyhole Fenestration for Cerebrospinal Fluid Leaks in the Thoracic Spine: Quantification of Bone Removal and Microsurgical Anatomy

BACKGROUND AND OBJECTIVE: A safe working trajectory is mandatory for spinal pathologies, especially in the midline, anterior to the spinal cord. For thoracic cerebrospinal fluid (CSF) leaks, we developed a minimally invasive keyhole fenestration. This study investigates the necessary bone removal for sufficient exposure of different leak types particularly regarding weight-bearing structures. METHODS: In this retrospective case series between January 2022 and June 2023, the volume of bone resection and the axial and sagittal diameter of hemilamina defects after closure through keyhole fenestration were quantified. The involvement of facet joints and pedicles was qualitatively rated. Demographic (age, sex, body mass index, leak type) and surgical data (blood loss, surgery time, discharge after surgery) and complications were analyzed. RESULTS: Thirty-three patients with 34 approaches were included. The volume of resected bone was 1.5 cm3, and the diameter of the hemilamina defect was 17.8 mm in the sagittal and 15.1 mm in the axial plane. Facet joints were uninvolved in 24% and partly resected in 74%, and one facet joint was resected completely. Pedicles remained intact in 71% and were minimally involved in 29%. The median surgery time was 93 minutes, blood loss was 45 mL, and discharge was 4 days after surgery. Three patients (9%) needed revision surgery. No relevant and persisting morbidity occurred. Within the median follow-up period of 10 months, no stabilizing surgery was necessary. No permanent neurological deficit occurred. CONCLUSION: The keyhole fenestration leaves weight-bearing structures like facet joints and pedicles intact in most cases. The limited, penny-sized bone resection is sufficient to reach and close thoracic CSF leaks Type 1, 2, and 3 from the anterior midline to the ganglion. For experienced centers, it is a universal minimally invasive approach for treating all CSF leaks.

Frequency of Diplopia in Zygomatic Complex Fractures-A Cross-Sectional Descriptive Study.

The zygomatic complex is the second most common fracture of the facial bones after the nasal bone. The prominent convex shape of the zygoma makes it vulnerable to traumatic injury. Diplopia is one of the serious complications of zygomatic complex fracture and is a common subjective complaint. To determine the frequency of diplopia in zygomatic complex fractures. Methodology. A cross-sectional descriptive study was conducted at the Oral and Maxillofacial Surgery Ward, Civil Hospital, Karachi, Pakistan. The duration of the study was 1 year (March 1, 2021 to February 28, 2022). A total of 126 patients having zygomatic complex fractures were included in this study. After recording the patient's complete history, like demographic details and cause for fracture, diplopia was examined clinically. If, during the examination, the patient complained of double vision, this was labeled as diplopia positive (Yes) and negative (No) if the patient did not have any such complain. Data were statistically analyzed. The mean (±SD) age of patients was 33.42 (±9.27), with 91 (72.2%) male patients and 35 (27.8%) female patients. The frequency of diplopia in zygomatic complex fractures was observed in 52 (41.3%) patients. The rate of diplopia was significantly high in patients aged between 31 and 40 years (P-value=0.0005). The frequency of diplopia among patients having zygomatic complex fractures was high in this study. Thus, forming a strategy to properly diagnose and treat it and to prevent persistent morbidity to improve patient's quality of life is recommended.

A CASE STUDY ON A COMPLEX FISTULA-IN-ANO BY AYURVEDIC MANAGEMENT

Fistula-in-ano can be a complicated disease to manage. An anal fistula is divided into simple and complex fistula. Managing complex fistula is even more challenging, which typically affects younger people and causes persistent morbidity. It is pertinent to define complex anal fistula. From a practical point of view, a fistula that is difficult to manage has a higher risk of recurrence, poses a greater threat to continence and is classified as a complex fistula. Due to its difficulty in treating medically and surgically, Bhagandara (fistula-in-ano) is one of the eight major disorders classified under Astamahagada in Ayurveda. Ayurvedic surgeons frequently use the effective fistula treatment known as Ksharasutra; however, cutting the passage takes a very long time. As a result, this procedure is now sometimes referred to as partial fistulectomy with Ksharasutra ligation, fibrin glue, fistula plug (FP), Fistula-tract Laser Closure (FiLaC), Seton techniques, video-assisted anal fistula treatment (VAAFT), LIFT (ligation of intersphincteric fistulous tract), and IFTAK (interception of fistulous tract with application of Ksharasutra), also known as window technique, where the Guggulu based Apamarg Ksharasutra is placed. This method shortens the healing time and allows repairing such a complicated fistula-in-ano with little tissue injury. Infected anal crypt, secondary extension and related conditions are the key factors that lead to the recurrence of complex anal fistulas. Surgery in complex anal fistula aims to prevent recurrence, avoid incontinence and avoid damaging the sphincter muscles (the ring of muscles that open and close the anus).

Elevated leukotriene B4 and 8-isoprostane in exhaled breath condensate from preterm-born infants

BackgroundInflammation and oxidative stress play a key role in the development of bronchopulmonary dysplasia (BPD), possibly contributing to persistent respiratory morbidity after preterm birth. We aimed to assess if inflammatory markers were elevated in exhaled breath condensate (EBC) of infants born very prematurely (< 32 weeks gestation) at 12–16 corrected months of age, and if increased levels were associated with BPD diagnosis and respiratory morbidity.MethodsEBC samples and respiratory questionnaires were collected from 15 term-born infants and 33 preterm-born infants, 12 with a neonatal BPD diagnosis. EBC samples were analysed for leukotriene B4 (inflammation) and 8-isoprostane (oxidative stress) concentrations using enzyme-linked immune-assays. Differences between groups were analysed by Kruskal-Wallis Test with post-hoc comparisons, independent samples t-test or Mann-Whitney U test depending on normality of the data.ResultsLeukotriene B4 and 8-isoprostane levels were elevated in exhaled breath condensate of preterm-born infants compared to those born at term (mean difference [95% CI]; 1.52 [0.45, 2.59], p = 0.02; 0.77 [0.52, 1.02], p < 0.001, respectively). Leukotriene B4 and 8-isoprostane levels were independent of BPD diagnosis and respiratory morbidity over the first year of life.ConclusionsInfants born very prematurely exhibit elevated markers of airway neutrophilic inflammation and oxidative stress beyond the first year of life, regardless of a neonatal diagnosis of chronic lung disease or respiratory morbidity during infancy. These findings may have implications for future lung health.Trial RegistrationN/A.

MiR-455-3p inhibits gastric cancer progression by repressing Wnt/β-catenin signaling through binding to ARMC8

BackgroundGlobally, gastric cancer (GC) is one of the world’s most widespread malignancies, with persistent high mortality and morbidity rates. Increasing evidence now suggests that microRNAs (miRNAs) participate in many biological processes, with miR-455-3p having key roles in the progression of diverse cancers. Nevertheless, miR-455-3p function and expression in GC remain unclear.MethodsWe explored miR-455-3p expression in GC using quantitative polymerase chain reaction (qPCR). To further examine the effect of miR-455-3p in GC, after transfecting miR-455-3p mimics or inhibitors into GC cells, 5-ethynyl-2’-deoxyuridine (EdU) incorporation and colony formation assays were performed to examine cell proliferation. Flow cytometry was used to detect apoptosis, and expression levels of Bax, Bcl-2, Snail, N-cadherin, E-cadherin, and Caspase-3 were assessed by western blotting (WB). Using online databases and luciferase assays, we identified armadillo repeat-containing protein 8 (ARMC8) as a promising target of miR-455-3p. A mouse tumor model was established to investigate actions of miR-455-3p in vivo. Expression levels of C-myc, cyclinD1, and β-catenin were examined using WB and immunofluorescence.ResultsMiR-455-3p expression was attenuated in GC tissue and cell lines. MiR-455-3p overexpression inhibited GC cell proliferation, epithelial-mesenchymal transition (EMT), as well as facilitated apoptosis, while suppression of miR-455-3p had the opposite effects. From luciferase assays, we confirmed that ARMC8 was a novel and direct downstream target gene of miR-455-3p, and that the tumor suppressive role of miR-455-3p was in part reversed due to ARMC8 overexpression. Moreover, miR-455-3p inhibited GC growth in vivo via ARMC8. We also observed that miR-455-3p repressed canonical Wnt pathway activation by binding to ARMC8.ConclusionsMiR-455-3p exerted tumor inhibitory effects in GC by targeting ARMC8. Therefore, intervening in the miR-455-3p/ARMC8/Wnt/βcatenin axis could be a promising novel treatment strategy for GC.

The Healthcare Cost Burden of Asthma in Children: A Longitudinal Population-Based Study

ObjectivesThis study aimed to investigate the extent of healthcare cost increase at population level due to childhood asthma. We aimed to investigate the cross-sectional relationship between asthma and healthcare costs among children aged 2 to 18 years and, in longitudinal analyses, whether costs increase with an increase in the duration of asthma prevalence. MethodsStudy participants are 4175 and 4482 children of birth and kindergarten cohorts from the nationally representative Longitudinal Study of Australian Children for whom the linked Medicare cost data are available. The children were followed in all waves from the year 2004 to 2018. Generalized linear models were used to estimate the excess healthcare costs associated with asthma. The sum of Medicare Benefits Schedule and Pharmaceutical Benefits Scheme costs constitutes the total healthcare costs. ResultsTotal excess healthcare costs associated with asthma among the 2- to 18-year-old children were A$4316 per child. At the population level, the estimated total excess Medicare costs associated with current asthma treatment among 2- to 18-year-old children were, on average, A$190.6 million per year (2018 population and price). Compared with the non-asthmatic children, peers with persistent asthma morbidity and treatment requirements had excess costs up to A$20 727 for the B cohort children until 14 years of age, whereas excess costs for the K cohort children were A$19 571 until 18 years of age. ConclusionsAsthma in children imposes a significant financial burden on the public health system. Higher excess healthcare costs of all asthmatic children than the costs of nonasthmatic children provide further economic justification for promoting preventive efforts at early ages.

A 14-year follow-up of ultrasound-detected urinary tract pathology associated with urogenital schistosomiasis in women living in the Msambweni region of coastal Kenya.

Complications of urogenital schistosomiasis include acute inflammatory and chronic fibrotic changes within the urogenital tract. Disease burden of this neglected tropical disease is often underestimated, as only active, urine egg-patent Schistosoma infection is formally considered. Previous studies have focussed on short-term effects of praziquantel treatment on urinary tract pathology, demonstrating that acute inflammation is reversible. However, the reversibility of chronic changes is less well studied. Our study compared, at two time points 14 y apart, urine egg-patent infection and urinary tract pathology in a cohort of women living in a highly endemic area having intermittent praziquantel treatment(s). In 2014 we matched 93 women to their findings in a previous study in 2000. Between 2000 and 2014 the rate of egg-patent infection decreased from 34% (95% confidence interval [CI] 25 to 44) to 9% (95% CI 3 to 14). However, urinary tract pathology increased from 15% (95% CI 8 to 22) to 19% (95% CI 11 to 27), with the greatest increase seen in bladder thickening and shape abnormality. Despite praziquantel treatment, fibrosis from chronic schistosomiasis outlasts the presence of active infection, continuing to cause lasting morbidity. We suggest that future efforts to eliminate persistent morbidity attributable to schistosomiasis should include intensified disease management.

Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID.

COVID-19 is associated with a dysregulated immune response but it is unclear how immune dysfunction contributes to the chronic morbidity persisting in many COVID-19 patients during convalescence (long COVID). We assessed phenotypical and functional changes of monocytes in COVID-19 patients during hospitalisation and up to 9 months of convalescence following COVID-19, respiratory syncytial virus or influenza A. Patients with progressive fibrosing interstitial lung disease were included as a positive control for severe, ongoing lung injury. Monocyte alterations in acute COVID-19 patients included aberrant expression of leukocyte migration molecules, continuing into convalescence (n=142) and corresponding with specific symptoms of long COVID. Long COVID patients with unresolved lung injury, indicated by sustained shortness of breath and abnormal chest radiology, were defined by high monocyte expression of C-X-C motif chemokine receptor 6 (CXCR6) (p<0.0001) and adhesion molecule P-selectin glycoprotein ligand 1 (p<0.01), alongside preferential migration of monocytes towards the CXCR6 ligand C-X-C motif chemokine ligand 16 (CXCL16) (p<0.05), which is abundantly expressed in the lung. Monocyte CXCR6 and lung CXCL16 were heightened in patients with progressive fibrosing interstitial lung disease (p<0.001), confirming a role for the CXCR6-CXCL16 axis in ongoing lung injury. Conversely, monocytes from long COVID patients with ongoing fatigue exhibited a sustained reduction of the prostaglandin-generating enzyme cyclooxygenase 2 (p<0.01) and CXCR2 expression (p<0.05). These monocyte changes were not present in respiratory syncytial virus or influenza A convalescence. Our data define unique monocyte signatures that define subgroups of long COVID patients, indicating a key role for monocyte migration in COVID-19 pathophysiology. Targeting these pathways may provide novel therapeutic opportunities in COVID-19 patients with persistent morbidity.

Persistent morbidity in Clade IIb mpox patients: interim results of a long-term follow-up study, Belgium, June to November 2022.

While mpox was well characterised during the 2022 global Clade IIb outbreak, little is known about persistent morbidity. We present interim results of a prospective cohort study of 95 mpox patients assessed 3-20 weeks post-symptom onset. Two-thirds of participants had residual morbidity, including 25 with persistent anorectal and 18 with genital symptoms. Loss of physical fitness, new-onset/worsened fatigue and mental health problems were reported in 36, 19 and 11 patients, respectively. These findings require attention by healthcare providers.