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The Lancet. Child & Adolescent Health Feb 2024A historic increase in paediatric invasive group A streptococcal (iGAS) infections was reported globally in 2022. iGAS infections can lead to severe manifestations (eg,...
Invasive group A streptococcal infections in children and adolescents in Denmark during 2022-23 compared with 2016-17 to 2021-22: a nationwide, multicentre, population-based cohort study.
BACKGROUND
A historic increase in paediatric invasive group A streptococcal (iGAS) infections was reported globally in 2022. iGAS infections can lead to severe manifestations (eg, pleural empyema, necrotising fasciitis, toxic shock syndrome, osteomyelitis, septic arthritis, and meningitis). We aimed to compare the incidence and severity of iGAS infections overall, for distinct clinical phenotypes, and for GAS emm variants in Denmark in 2022-23 with reference to the previous six seasons (ie, 2016-17, 2017-18, 2018-19, 2019-20, 2020-21, and 2021-22).
METHODS
In this nationwide, multicentre, population-based cohort study, we included all children and adolescents in Denmark aged 0-17 years with a positive culture of GAS or GAS confirmed through PCR-based methods from otherwise sterile sites in 2022-23 and the previous six seasons from 2016-17 to 2021-22. For all seven seasons, data were obtained from week 21 to week 20 of the next year. Patients at all 18 paediatric hospital departments in Denmark were identified through the Danish Microbiology Database, in which iGAS isolates from sterile sites are prospectively registered, including emm typing. We obtained electronic medical health records for each patient admitted with a diagnosis of iGAS. We calculated the incidence of iGAS per 1 000 000 inhabitants aged 0-17 years in each season from week 21 to week 20 of the next year and the risk ratios (RRs) for incidence of iGAS, distinct disease manifestations, and emm variants in 2022-23 versus the three pre-COVID-19 seasons in 2016-17, 2017-18, and 2018-19 using Fisher's exact test and Pearson's χ test.
FINDINGS
Among the Danish population of 1 152 000 children and adolescents aged 0-17 years, 174 with iGAS disease were included. 76 children and adolescents with iGAS during 2022-23 were identified; 31 (41%) of 76 were female and 45 (59%) were male. 98 children and adolescents with iGAS during 2016-17 to 2021-22 were identified; 41 (42%) of 98 were female and 57 (58%) were male. There was an increase in incidence of iGAS from mean 22·6 (95% CI 14·7-33·1) per 1 000 000 children and adolescents during 2016-17 to 2018-19 to 66·0 (52·0-82·6) per 1 000 000 during 2023-23 (RR 2·9, 95% CI 1·9-4·6; p<0·0001). During the COVID-19 pandemic in 2019-20, 2020-21, and 2021-22, the mean incidence of iGAS was 6·1 (95% CI 2·4-12·5) per 1 000 000 children and adolescents. In 2022-23, there was a 9·5-fold increase in emm-12 (95% CI 2·2-40·8; p=0·0002) and a 2·7-fold increase in emm-1 (1·3-5·5; p=0·0037). The most common clinical manifestations of iGAS in 2022-23 were soft-tissue infections, which increased by 4·5-fold (1·9-10·9; p=0·0003), and complicated pneumonia with parapneumonic effusion, which increased by 4·0-fold (1·4-11·4; p=0·0059), both compared with the three pre-COVID-19 seasons. Overall, there was no increased severity of iGAS in 2022-23 compared with the previous six seasons as measured by median duration of hospital stay (8 days, IQR 4-14 vs 9 days, 5-15; p=0·39), paediatric intensive care unit (PICU) admission (17 [22%] of 76 vs 17 [17%] of 98; p=0·53), duration of stay in PICU (4 days, IQR 2-10 vs 4 days, 2-11; p=0·84), or mortality (three [4%] of 76 vs three [3%] of 98; p=1·00). In 2022-23, there was a 3·6-fold (95% CI 1·8-7·3; p=0·0001) increase in children with a preceding upper respiratory tract infection and a 4·6-fold (1·5-14·1; p=0·0034) increase in children with a preceding varicella-zoster infection, both compared with the three pre-COVID-19 seasons.
INTERPRETATION
In Denmark, the incidence of paediatric iGAS increased in 2022-23 compared with the three pre-COVID-19 seasons of 2016-17, 2017-18, and 2018-19. However, the course of iGAS disease in children and adolescents in 2022-23 was not more severe than in previous seasons. The high morbidity across all seasons highlights iGAS as a major invasive bacterial infection in children and adolescents.
FUNDING
Innovation Fund Denmark.
Topics: Child; Humans; Male; Female; Adolescent; Cohort Studies; Pandemics; Streptococcal Infections; Streptococcus pyogenes; COVID-19; Denmark
PubMed: 38103567
DOI: 10.1016/S2352-4642(23)00295-X -
Scientific Reports Dec 2023Characterization of the pathophysiology of ARDS following chlorine gas inhalation in clinically relevant translational large animal models is essential, as the...
Characterization of the pathophysiology of ARDS following chlorine gas inhalation in clinically relevant translational large animal models is essential, as the opportunity for clinical trials in this type of trauma is extremely limited. To investigate Cl concentration and gender-dependent ARDS severity. Sheep (n = 54) were exposed to air or Cl premixed in air at a concentration of 50, 100, 200, and 300 ppm for 30 min under anesthesia/analgesia and monitored for an additional 48 h in a conscious state. Cardiopulmonary variables and survival endpoints were compared between male and female sheep. Overall there were no significant differences in the responses of female and male sheep except pulmonary oxygenation tended to be better in the male sheep (300 ppm group), and the pulmonary arterial pressure was lower (200 ppm group). The onset of mild ARDS (200 < PaO/FiO ≤ 300) was observed at 36 h post exposure in the 50 ppm group, whereas the 100 ppm group developed mild and moderate (100 ≤ PaO/FiO ≤ 200) ARDS by 12 and 36 h after injury, respectively. The 200 ppm and 300 ppm groups developed moderate ARDS within 6 and 3 h after injury, respectively. The 300 ppm group progressed to severe (PaO/FiO ≤ 100) ARDS at 18 h after injury. Increases in pPeak and pPlateau were noted in all injured animals. Compared to sham, inhalation of 200 ppm and 300 ppm Cl significantly increased lung extravascular water content. The thoracic cavity fluid accumulation dose-dependently increased with the severity of trauma as compared to sham. At necropsy, the lungs were red, heavy, solidified, and fluid filled; the injury severity grew with increasing Cl concentration. The severity of ARDS and mortality rate directly correlated to inhaled Cl concentrations. No significant sex-dependent differences were found in measured endpoint variables.
Topics: Male; Female; Animals; Sheep; Chlorine; Lung; Administration, Inhalation; Respiratory Distress Syndrome
PubMed: 38102196
DOI: 10.1038/s41598-023-48720-2 -
Cell Dec 2023The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19...
The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of "local" when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation.
Topics: Humans; COVID-19; Genomics; Pandemics; Public Health; SARS-CoV-2; Infection Control; Geography
PubMed: 38101407
DOI: 10.1016/j.cell.2023.11.024 -
Clinical Infectious Diseases : An... Apr 2024Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active...
BACKGROUND
Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear.
METHODS
We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality.
RESULTS
CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10-6.19] and 2.03 [95% CI 1.24-3.33], respectively). CD4 cell counts below 350 cells/μL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies.
CONCLUSIONS
In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM.
Topics: Humans; Acquired Immunodeficiency Syndrome; HIV; HIV Infections; Anti-Retroviral Agents; CD4 Lymphocyte Count; Neoplasms; CD4-CD8 Ratio; Viral Load; Anti-HIV Agents
PubMed: 38092042
DOI: 10.1093/cid/ciad671 -
BMC Pulmonary Medicine Dec 2023Usual Interstitial Pneumonia (UIP) is characterized by progression of lung parenchyma that may be observed in various autoimmune rheumatic diseases (ARDs), including... (Review)
Review
Usual Interstitial Pneumonia (UIP) is characterized by progression of lung parenchyma that may be observed in various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis and connective tissue diseases. From a diagnostic point of view, a UIP pattern related to ARDs may display imaging and pathological features able to distinguish it from that related to IPF, such as the "straight-edge" sign at HRCT and lymphoplasmacytic infiltrates at histologic specimens. Multidisciplinary approach (MDD), involving at least pulmonologist, rheumatologist and radiologist, is fundamental in the differential diagnosis process, but MDD is also required in the evaluation of severity, progression and response to treatment, that is based on the combination of changes in symptoms, pulmonary function trends, and, in selected patients, serial CT evaluation. Differently from IPF, in patients with ARDs both functional evaluation and patient-reported outcomes may be affected by systemic involvement and comorbidities, including musculoskeletal manifestations of disease. Finally, in regards to pharmacological treatment, immunosuppressants have been considered the cornerstone of therapy, despite the lack of solid evidence in most cases; recently, antifibrotic drugs were also proposed for the treatment of progressive fibrosing ILDs other than IPF. In ARD-ILD, the therapeutic choice should balance the need for the control of systemic and lung involvements with the risk of adverse events from multi-morbidities and -therapies. Purpose of this review is to summarize the definition, the radiological and morphological features of the UIP pattern in ARDs, together with risk factors, diagnostic criteria, prognostic evaluation, monitoring and management approaches of the UIP-ARDs.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung; Autoimmune Diseases; Rheumatic Diseases; Respiratory Distress Syndrome
PubMed: 38082233
DOI: 10.1186/s12890-023-02783-z -
Endocrine Connections Feb 2024Endometriosis and polycystic ovary syndrome (PCOS) are common gynecological disorders that constitute a significant burden of disease in women of fertile age. The... (Review)
Review
Endometriosis and polycystic ovary syndrome (PCOS) are common gynecological disorders that constitute a significant burden of disease in women of fertile age. The disorders share a link to female reproduction and infertility; however, divergent effects on menstrual cycle, related hormones, and body composition have been proposed. Disorders of the thyroid gland including abnormal thyroid dysfunction (hyperthyroidism or hypothyroidism) and/or markers of thyroid autoimmunity similarly show a female predominance and onset in younger age groups. We reviewed the literature on the association between endometriosis, PCOS, and thyroid disease up until July 1, 2023, and identified 8 original studies on endometriosis and thyroid disease and 30 original studies on PCOS and thyroid disease. The studies were observational and heterogeneous regarding the design, sample size, and definitions of exposure and outcome; however, a tendency was seen toward an association between hyperthyroidism and endometriosis. Especially an association between endometriosis and slightly elevated levels of thyroid-stimulating hormone receptor antibodies has been found and corroborated in studies from different populations. On the other hand, the literature review turned a focus toward an association between hypothyroidism and PCOS, however, with uncertainties as to whether the association is caused by hypothyroidism per se and/or the thyroid autoantibodies (thyroid peroxidase and thyroglobulin antibodies). More evidence is needed to substantiate an association between endometriosis, PCOS, and thyroid disease, and to differentiate between the role of thyroid function and thyroid autoimmunity. Furthermore, studies are warranted to extend knowledge on the different disease characteristics and underlying mechanisms.
PubMed: 38078917
DOI: 10.1530/EC-23-0431 -
PNAS Nexus Dec 2023Immunocompromised patients often fail to raise protective vaccine-induced immunity against the global emergence of severe acute respiratory syndrome coronavirus 2...
Immunocompromised patients often fail to raise protective vaccine-induced immunity against the global emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Although monoclonal antibodies have been authorized for clinical use, most have lost their ability to potently neutralize the evolving Omicron subvariants. Thus, there is an urgent need for treatment strategies that can provide protection against these and emerging SARS-CoV-2 variants to prevent the development of severe coronavirus disease 2019. Here, we report on the design and characterization of a long-acting viral entry-blocking angiotensin-converting enzyme 2 (ACE2) dimeric fusion molecule. Specifically, a soluble truncated human dimeric ACE2 variant, engineered for improved binding to the receptor-binding domain of SARS-CoV-2, was fused with human albumin tailored for favorable engagement of the neonatal fragment crystallizable receptor (FcRn), which resulted in enhanced plasma half-life and allowed for needle-free transmucosal delivery upon nasal administration in human FcRn-expressing transgenic mice. Importantly, the dimeric ACE2-fused albumin demonstrated potent neutralization of SARS-CoV-2 immune escape variants.
PubMed: 38077689
DOI: 10.1093/pnasnexus/pgad403 -
Journal of Medical Virology Dec 2023Ramsay Hunt syndrome (RHS) is a manifestation of reactivated varicella-zoster virus (VZV) from the geniculate ganglion. Data on clinical features and outcomes of...
Ramsay Hunt syndrome (RHS) is a manifestation of reactivated varicella-zoster virus (VZV) from the geniculate ganglion. Data on clinical features and outcomes of patients with RHS and concurrent VZV meningitis (henceforth RHS meningitis) are limited. Thus, we conducted a nationwide population-based cohort study of all adults hospitalized for RHS meningitis at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with VZV meningitis without cranial nerve palsies were included for comparison. In total, 37 patients with RHS meningitis (mean annual incidence: 1.6/1 000 000 adults) and 162 with VZV meningitis without cranial nerve palsies were included. In RHS meningitis, the median age was 52 years (interquartile range: 35-64), and in addition to peripheral facial nerve palsy (100%), dizziness (46%), and hearing loss (35%) were common symptoms. The triad of headache, neck stiffness, and photophobia/hyperacusis was less common in RHS meningitis than in VZV meningitis without cranial nerve palsies (0/27 [0%] vs. 24/143 [17%]; p = 0.02). At 30 days after discharge, 18/36 (50%) patients with RHS meningitis had persistent peripheral facial nerve palsy, with no statistically significant difference between those treated with and without adjuvant glucocorticoids (6/16 [38%] vs. 12/20 [60%]; p = 0.18). Additional sequelae of RHS meningitis included dizziness (29%), neuralgia (14%), tinnitus/hyperacusis (11%), hearing loss (9%), headache (9%), fatigue (6%), and concentration difficulties (3%). In conclusion, clinical features and outcomes of RHS meningitis were primarily related to cranial neuropathies.
Topics: Adult; Humans; Middle Aged; Herpes Zoster Oticus; Herpesvirus 3, Human; Cohort Studies; Dizziness; Hyperacusis; Facial Paralysis; Chickenpox; Hearing Loss; Headache; Denmark
PubMed: 38058258
DOI: 10.1002/jmv.29291 -
European Journal of Pediatrics Feb 2024Effective management of neonatal respiratory distress requires timely recognition of when to transition from non-invasive to invasive ventilation. Although the lung... (Observational Study)
Observational Study
Assessing the diagnostic accuracy of lung ultrasound in determining invasive ventilation needs in neonates on non-invasive ventilation: An observational study from a tertiary NICU in India.
Effective management of neonatal respiratory distress requires timely recognition of when to transition from non-invasive to invasive ventilation. Although the lung ultrasound score (LUS) is useful in evaluating disease severity and predicting the need for surfactants, its efficacy in identifying neonates requiring invasive ventilation has only been explored in a few studies. This study aims to assess the accuracy of LUS in determining the need for invasive ventilation in neonates on non-invasive ventilation (NIV) support. From July 2021 to June 2023, we conducted a prospective study on 192 consecutively admitted neonates with respiratory distress needing NIV within 24 h of birth at our NICU in Hyderabad, India. The primary objective was the diagnostic accuracy of LUS in determining the need for invasive ventilation within 72 h of initiating NIV. We calculated LUS using the scoring system of Brat et al. (JAMA Pediatr 169:e151797, [10]). Treating physicians' assessments of the need for invasive ventilation served as the reference standard for evaluating LUS effectiveness. Out of 192 studied neonates, 31 (16.1%) required invasive ventilation. The median LUS was 5 (IQR: 2-8) for those on NIV and 10 (IQR: 7-12) for those needing invasive ventilation. The LUS had a strong discriminative ability for invasive ventilation with an AUC (area under the curve) of 0.825 (CI: 0.75-0.86, p = 0.0001). An LUS > 7 had 77.4% sensitivity (95% CI: 58.9-90.8%), 75.1% specificity (95% CI: 67.8-81.7%), 37.5% positive predictive value (PPV) (95% CI: 30.15-45.5%), 94.5% negative predictive value (NPV) (95% CI: 89.9-97.1%), 3.1 positive likelihood ratio (PLR) (95% CI: 2.2-4.3), 0.3 negative likelihood ratio (NLR) (95% CI: 0.15-0.58), and 75.5% overall accuracy (95% CI: 68.8-81.4%) for identifying invasive ventilation needs. In contrast, SAS, with a cutoff point greater than 5, has an AUC of 0.67. It demonstrates 62.5% sensitivity, 61.9% specificity, 24.7% PPV, 89.2% NPV, and an overall diagnostic accuracy of 61.9%. The DeLong test confirms the significance of this difference (AUC difference: 0.142, p = 0.04), underscoring LUS's greater reliability for NIV failure. Conclusion: This study underscores the diagnostic accuracy of the LUS cutoff of > 7 in determining invasive ventilation needs during the initial 72 h of NIV. Importantly, while lower LUS values typically rule out the need for ventilation, higher values, though indicative, are not definitive. What is known? • The effectiveness of lung ultrasound in evaluating disease severity and the need for surfactants in neonates with respiratory distress is well established. However, traditional indicators for transitioning from non-invasive to invasive ventilation, like respiratory distress and oxygen levels, have limitations, underscoring the need for reliable, non-invasive assessment tools. What is new? • This study reveals that a LUS over 7 accurately discriminates between neonates requiring invasive ventilation and those who do not. Furthermore, the lung ultrasound score outperformed the Silverman Andersen score for NIV failure in our population.
Topics: Infant, Newborn; Humans; Noninvasive Ventilation; Prospective Studies; Intensive Care Units, Neonatal; Reproducibility of Results; Lung; Respiratory Distress Syndrome; Surface-Active Agents; Ultrasonography; Respiratory Distress Syndrome, Newborn
PubMed: 38052734
DOI: 10.1007/s00431-023-05356-8 -
The Ocular Surface Jan 2024This double-blinded randomized clinical trial aimed to evaluate the efficacy of injecting allogeneic adipose-derived mesenchymal stem cells (ASCs) into the lacrimal... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
This double-blinded randomized clinical trial aimed to evaluate the efficacy of injecting allogeneic adipose-derived mesenchymal stem cells (ASCs) into the lacrimal gland (LG) for the treatment of dry eye disease (DED) secondary to Sjögren's syndrome (SS).
METHODS
Fifty-four participants with severe DED secondary to SS were included and allocated to either ASCs (n = 20), vehicle (n = 20), or a non-randomized observation group (n = 14). The intervention groups received a single injection of either ASCs or an active comparator (vehicle, Cryostor® CS10) into the LG in one eye, while the observation group received lubricating eye drops only. The primary outcome measure was changes in Ocular Surface Disease Index (OSDI) score and secondary outcome measures were non-invasive tear break-up time, tear meniscus height, Schirmer's test, and Oxford score within a 12-month follow-up.
RESULTS
A significant reduction in OSDI score was observed in the ASCs and vehicle groups compared to the observation group. In addition, the ASCs group demonstrated a significant increase in non-invasive tear break-up time compared to the vehicle group at the 4-week follow-up and to the observation group at the 12-month follow-up. A significant improvement in ocular surface staining, tear osmolarity, and Schirmer test score from baseline was also observed in the ASCs group; however, these changes were not significant compared to the other groups.
CONCLUSION
Improvement of subjective and objective signs and symptoms of DED was observed in both intervention groups following injection into the LG compared to the observation group. Future studies should investigate the mode-of-action of both injection treatments.
Topics: Humans; Sjogren's Syndrome; Mesenchymal Stem Cell Transplantation; Dry Eye Syndromes; Tears; Hematopoietic Stem Cell Transplantation
PubMed: 38049032
DOI: 10.1016/j.jtos.2023.11.007