Sequelae Of Infection Research Articles

Outcomes and Complications of Sole Reconstruction Using Lateral Thoracic Free Tissue Transfer.

The complex structure of the sole of the foot makes the repair of extensive defects challenging. The present study, therefore, aimed to address a gap in current research by evaluating the potential of the lateral thoracic free flap, including perforator options and chimeric configurations, to be used as an advanced solution for comprehensive sole reconstruction. We retrospectively collected the following data from the charts of patients with sole defects, due to various causes, who underwent lateral thoracic free tissue transfers: patient demographics; etiologies; comorbidities; flap types and dimensions; pedicle length; operative time; follow-up period; complications; and management. The present study included 54 patients who underwent lateral thoracic free tissue transfer, citing infection, trauma, tumor, and posttraumatic sequelae as the major etiologies. We used the following techniques for the reconstruction of sole defects: thoracodorsal artery perforator free flap (83.3%); latissimus dorsi musculocutaneous free flap (1.9%); and various chimeric pattern flaps (14.8%). Free tissue transfer in the lateral thoracic region offers versatility for reconstruction, as well as low donor site morbidity. Complications observed in the present study included wound dehiscence (9.3%), partial necrosis (9.3%), and pressure ulcers (22.2%), although most patients healed favorably without flap loss. The lateral thoracic free flap is a viable option for the reconstruction of the sole of the foot and allows for the effective reconstruction of complex defects. It contains a sustainable skin paddle, and multiple components can be easily included as a chimeric type. Further studies should seek to identify ways to prevent pressure ulcers, which was the only known long-term complication in the present study.

Conservative management of complicated retropharyngeal abscess with Antitubercular Therapy

Retropharyngeal abscess, the infection of deep neck spaces, extends from the base of the skull to the posterior mediastinum. It develops as a sequela of dental infection, upper respiratory tract infection, or any interventional procedure like laryngoscopy, endotracheal intubation, etc. Retropharyngeal abscess is a rare presentation of Tuberculosis (TB), with an annual incidence rate of 2.64 per 100,000 population, and gender-based incidence rates of 3.34 for males, and 1.94 for females per 100,000 population.1 It, as a part of head and neck TB, has a prevalence of 0.1-1% among all forms of TB. If not managed timely, it may lead to the spread of its infection to the mediastinum, which can be life-threatening at times, owing to airway compromission and other catastrophic complications like mediastinitis, mediastinal abscess, pericarditis, pyopneumothorax pleuritis and empyema. We hereby present a case of a middle-aged woman diagnosed with a complicated retropharyngeal abscess but managed conservatively with Antitubercular Therapy (ATT).

From Psychostasis to the Discovery of Cardiac Nerves: The Origins of the Modern Cardiac Neuromodulation Concept.

This review explores the historical development of cardiology knowledge, from ancient Egyptian psychostasis to the modern comprehension of cardiac neuromodulation. In ancient Egyptian religion, psychostasis was the ceremony in which the deceased was judged before gaining access to the afterlife. This ritual was also known as the "weighing of the heart" or "weighing of the soul". The Egyptians believed that the heart, not the brain, was the seat of human wisdom, emotions, and memory. They were the first to recognize the cardiocentric nature of the body, identifying the heart as the center of the circulatory system. Aristotle (fourth century BC) considered the importance of the heart in human physiology in his philosophical analyses. For Galen (third century AD), the heart muscle was the site of the vital spirit, which regulated body temperature. Cardiology knowledge advanced significantly in the 15th century, coinciding with Leonardo da Vinci and Vesalius's pioneering anatomical and physiological studies. It was William Harvey, in the 17th century, who introduced the concept of cardiac circulation. Servet's research and Marcello Malpighi's discovery of arterioles and capillaries provided a more detailed understanding of circulation. Richard Lower emerged as the foremost pioneer of experimental cardiology in the late 17th century. He demonstrated the heart's neural control by tying off the vagus nerve. In 1753, Albrecht von Haller, a professor at Göttingen, was the first to discover the heart's automaticity and the excitation of muscle fibers. Towards the end of the 18th century, Antonio Scarpa challenged the theories of Albrecht von Haller and Johann Bernhard Jacob Behrends, who maintained that the myocardium possessed its own "irritability", on which the heartbeat depended, and was independent of neuronal sensitivity. Instead, Scarpa argued that the heart required innervation to maintain life, refuting Galenic notions. In contemporary times, the study of cardiac innervation has regained prominence, particularly in understanding the post-acute sequelae of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection (PASC), which frequently involves cardiorespiratory symptoms and dysregulation of the intrinsic cardiac innervation. Recently, it has been recognized that post-acute sequelae of acute respiratory infections (ARIs) due to other pathogens can also be a cause of long-term vegetative and somatic symptoms. Understanding cardiac innervation and modulation can help to recognize and treat long COVID and long non-COVID-19 (coronavirus disease 2019) ARIs. This analysis explores the historical foundations of cardiac neuromodulation and its contemporary relevance. By focusing on this concept, we aim to bridge the gap between historical understanding and modern applications. This will illuminate the complex interplay between cardiac function, neural modulation, cardiovascular health, and disease management in the context of long-term cardiorespiratory symptoms and dysregulation of intrinsic cardiac innervations.

Long-Term Follow-up of Patients With Cytomegalovirus Retinitis Treated With a Ganciclovir Implant.

Purpose: To assess the long-term safety and clinical outcomes of a ganciclovir intravitreal implant in patients with cytomegalovirus (CMV) retinitis. Methods: A retrospective study was performed of patients with CMV retinitis treated with a ganciclovir intravitreal implant. Results: The study included 13 patients (16 eyes) previously treated with a ganciclovir intravitreal implant. The mean time since the last implant placement was 21.3 years and the mean total duration of follow-up, 22.7 years. Visual acuity (VA) ranged from 20/25 to light perception, with 56% of eyes maintaining a VA of 20/60 or better at the most recent follow-up examination. Common ocular complications included epiretinal membrane (38%), macular fibrosis/scarring (25%), retinal detachment (RD) (25%), implant dislocation (25%), and immune reactivation uveitis (19%). Intraocular surgery was required in 10 eyes (63%), with the most frequent being cataract extraction (31%), pars plana vitrectomy (PPV) for implant removal (19%), and PPV for RD (13%). Conclusions: Results show the long-term safety of the ganciclovir intravitreal implant despite its residual inactive inert shell. Complication rates are consistent with those expected from infectious sequelae.

Frequency and Risk Factors for Post-COVID-19 Functional Gastrointestinal Disorders After One Year

Objectives: In light of the global COVID-19 pandemic and the subsequent emergence of functional gastrointestinal disorders (FGIDs) post-recovery, this study aimed to evaluate the frequency and risk factors associated with FGIDs one year after recovering from COVID-19. Methods: This cross-sectional study included a total of 357 patients who had recovered from COVID-19 for a year and were seen at Al-Zahra Hospital in 2021. Participants were chosen through simple random sampling. The ROME questionnaire, alongside patients' clinical histories regarding irritable bowel syndrome (IBS) and its variants, functional dyspepsia (FD), and other GI symptoms, was utilized for data collection. Results: Findings indicated that one year post-COVID-19, the prevalence rates of IBS, GI symptoms, and FD stood at 15.4%, 44.9%, and 9.5%, respectively. It was observed that women had a higher propensity than men to develop these FGIDs (P-value = 0.044). Anxiety was linked to a 1.910-fold increase in IBS risk (P-value = 0.039), a 2.225-fold surge in GI symptoms (P-value < 0.001), and a 1.110-fold rise in FD risk (P-value = 0.042). Moreover, depression was associated with a 1.772-fold and 3.753-fold elevated risk of developing IBS (P-value = 0.040) and FD (P-value < 0.001), respectively. Conclusions: The findings suggest that FGIDs such as IBS, FD, and other GI symptoms are significant long-term sequelae of COVID-19 infection. Anxiety and depression appear to be key risk factors for these conditions, with a more pronounced impact observed in women than in men.

Long COVID-19 and Peripheral Serotonin: A Commentary and Reconsideration.

We believe there are serious problems with a recently published and highly publicized paper entitled "Serotonin reduction in post-acute sequelae of viral infection." The blood centrifugation procedure reportedly used by Wong et al would produce plasma that is substantially (over 95%) depleted of platelets. Given this, their published mean plasma serotonin values of 1.2 uM and 2.4 uM for the control/contrast groups appear to be at least 30 to 60 times too high and should be disregarded. The plasma serotonin values reported for the long COVID and viremia patients also should be disregarded, as should any comparisons to the control/contrast groups. We also note that the plasma serotonin means for the two control/contrast groups are not in good agreement. In the "Discussion" section, Wong et al state that their results tend to support the use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of COVID-19, and they encourage further clinical trials of SSRIs. While they state that, "Our animal models demonstrate that serotonin levels can be restored and memory impairment reversed by precursor supplementation or SSRI treatment", it should be noted that no data are presented showing an increase or restoration in circulating serotonin with SSRI administration. In fact, one would expect a marked decline in platelet serotonin due to SSRIs' effective inhibition of the platelet serotonin transporter. Wong et al hypothesize that problems of long COVID arise from too little peripheral serotonin. However, given the frequent presence of a hyperaggregation state in long COVID, and the known augmenting effects of platelet serotonin on platelet aggregation, it is plausible to suggest that reductions in platelet serotonin might be associated with a lessening of the cardiovascular sequelae of COVID-19.

ETIOLOGICAL REVIEW OF BRAIN INJURIES ON CT SCANNING IN THE ASSESSMENT OF PSYCHOMOTOR DEVELOPMENT DELAY IN CHILDREN UNDER FIVE (5) YEARS OF AGE AT THE LUXEMBOURG MOTHER-CHILD CHU

Objective: Our workaimed to describe the scan semiology of lesionsencountered in delayedpsychomotordevelopment (DPMD) in childrenunder 5 yearsold at the Mother-Child University Hospital Center Le Luxembourg Methodology:This is a prospective analytical and descriptive studycarried out over a period of 18 months (from April 15, 2021 to September 15, 2022) in the radiologydepartment of the CHU-ME Mère et Enfant Le Luxembourg. It concerned all patients aged 0 to 5 yearsadmitted to the medicalimagingdepartment of the Luxembourg Mother and Child University Hospital for psychomotordelaywhohadundergone a brain scan. Childrenwithoutpsychomotordelaywereexcludedfromourstudy. Results:Weretained 150 cases of psychomotordelayduringourstudyperiod. The age group of 0 to 02 yearswas the majority (67%) with an average of 1.33 years, an extreme of 1 month to 5 years and standard deviation of 5.807. The male genderwas in the majoritywith (55%) with a sex ratio of 1.22.The mostcommon type of deliverywas normal deliverywith a frequency of 62.0%. Prematuritywas the mostrepresentedobstetricrisk factor (18.0%).Convulsion was the mostrepresentedneonatalrisk factor (16.7%).Epilepsywas the mostcommon postnatal neurologicalantecedent (6.7%). The scan resultwasabnormalin 75% of our patients. The lesionsfoundwere:anoxo-ischemicleukoencephalopathy (47%), hydrocephalus (17%), malformative lesions (7%), sequelae of brain infections(3%) and tuberoussclerosis of Bourneville (1%) Conclusion: ChildhoodDPMDrepresents a major healthproblemwith a relatively high prevalence. This studydemonstrates the diagnostic value of CT in the exploration of RPM in children. Of the 150 patients explored, brain CT revealed a lesionin 75.0% of cases.

Immunocompetent isolated cerebral mucormycosis presenting with obstructive hydrocephalus: illustrative case.

Isolated cerebral mucormycosis is rare in immunocompetent adults and is only sparsely reported to be associated with obstructive hydrocephalus. Here, the authors report a case of obstructive hydrocephalus secondary to central nervous system mucormycosis without other systems or rhino-orbital involvement and its technical surgical management. A 23-year-old, incarcerated, immunocompetent patient with history of intravenous (IV) drug use presented with syncope. Although clinical and radiographic findings failed to elucidate an infectious pathology, endoscopy revealed an obstructive mass lesion at the level of the third ventricle, which, on microbiological testing, was confirmed to be Rhizopus fungal ventriculitis. Perioperative cerebrospinal fluid diversion, endoscopic third ventriculostomy, endoscopic biopsy technique, patient outcomes, and the literature are reviewed here. The patient received intrathecal and IV amphotericin B followed by a course of oral antifungal treatment and currently remains in remission. The patient's unique presentation and diagnosis of isolated cerebral mucormycosis reveal this pathogen as a cause of ventriculitis and obstructive hydrocephalus in immunocompetent adult patients, even in the absence of infectious sequelae on neuroimaging.

Generation of a humanized mAce2 and a conditional hACE2 mouse models permissive to SARS-COV-2 infection.

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) remains a public health concern and a subject of active research effort. Development of pre-clinical animal models is critical to study viral-host interaction, tissue tropism, disease mechanisms, therapeutic approaches, and long-term sequelae of infection. Here, we report two mouse models for studying SARS-CoV-2: A knock-in mAce2F83Y,H353K mouse that expresses a mouse-human hybrid form of the angiotensin-converting enzyme 2 (ACE2) receptor under the endogenous mouse Ace2 promoter, and a Rosa26 conditional knock-in mouse carrying the human ACE2 allele (Rosa26hACE2). Although the mAce2F83Y,H353K mice were susceptible to intranasal inoculation with SARS-CoV-2, they did not show gross phenotypic abnormalities. Next, we generated a Rosa26hACE2;CMV-Cre mouse line that ubiquitously expresses the human ACE2 receptor. By day 3 post infection with SARS-CoV-2, Rosa26hACE2;CMV-Cre mice showed significant weight loss, a variable degree of alveolar wall thickening and reduced survival rates. Viral load measurements confirmed inoculation in lung and brain tissues of infected Rosa26hACE2;CMV-Cre mice. The phenotypic spectrum displayed by our different mouse models translates to the broad range of clinical symptoms seen in the human patients and can serve as a resource for the community to model and explore both treatment strategies and long-term consequences of SARS-CoV-2 infection.

Comparison of the Damage Results of Bullet and Pellet Ammunition in Firearm Injuries Causing Bone Fractures in the Extremities

Objective
 The spectrum of firearm injuries (FI) is broad and challenging for physicians in terms of diagnosis and treatment. The bullets and pellet ammunition used in FI exhibit different ballistic patterns and cause quite different damage to the body. The aim of this study was to compare the outcomes of bullet and pellet injuries causing bone fractures in the extremities.
 Methods
 The files of patients who were injured in their extremities due to civilian FI between 2016 and 2020 and who were followed up by the orthopedic clinic due to bone fractures were retrospectively analyzed. Age, gender, injured extremity, presence of infection, presence of vascular injury, presence of nerve injury, total number of operations, length of hospital stay and permanent sequelae were evaluated. Cases with missing files were excluded from the study. Evaluation criteria were compared under two main headings for bullet and pellet ammunition types.
 Results
 There were a total of 40 cases with a mean age of 43.5 years. The mean follow-up period was 41.5(24-61) months. 39 of the cases were male and 1 was female. There were 28 bullet injuries and 12 pellet injuries. Thirty-two of the cases were lower extremity injuries and 8 were upper extremity injuries. There were significant differences between ammunition type and number of operations (p=0.032).The length of hospital stay was significantly higher in the pellet group (p=0.024, p=0.024. Overall, 12.5% infection, 10% vascular damage, 17.5% nerve damage and 30% permanent sequelae occurred as a result of treatments. There were no significant differences between the groups in terms of infection, vascular injury, nerve injury and permanent sequelae.
 Conclusion
 When comparing the clinical outcomes of bullets and pellet ammunition, there were many differences in the severity of the injury and the treatment process.

Shoulder arthroplasty in the management of native shoulder joint infections has a high complication rate and poor functional outcome - a systematic review.

Shoulder arthroplasty is a treatment option of the sequelae of native shoulder joint infections. However, the functional outcomes and re-infection rates are unknown. The aim of this review was to analyse the outcome of shoulder arthroplasty in patients with native shoulder infections. A review of the online databases MEDLINE and Embase was conducted according to PRISMA guidelines. The review was registered prospectively in the PROSPERO database. Studies reporting either primary or secondary infections of native shoulder joints treated with any form of arthroplasty were included and appraised using the methodological index for non-randomised studies (MINORS) tool. Fourteen studies were eligible for inclusion. Mean age ranged from 56 to 72 years and the mean follow-up from 20.5 months to 8.2 years. Primary shoulder infections were present in 50 patients and secondary infections in 86. 76 patients underwent a two stage: 46 patients a single-stage procedure whilst 14 refused second-stage surgery. Mean post-operative Constant score ranged from 38 to 56.2. The overall reported re-infection rate was 2.3% and complication rate was 26%. Shoulder arthroplasty in the management of either primary or secondary native shoulder infections has a high complication rate and low functional outcome but low re-infection rates at short-term follow-up.

Long-COVID-19 autonomic dysfunction: An integrated view in the framework of inflammaging

The recently identified syndrome known as Long COVID (LC) is characterized by a constellation of debilitating conditions that impair both physical and cognitive functions, thus reducing the quality of life and increasing the risk of developing the most common age-related diseases. These conditions are linked to the presence of symptoms of autonomic dysfunction, in association with low cortisol levels, suggestive of reduced hypothalamic-pituitary-adrenal (HPA) axis activity, and with increased pro-inflammatory condition. Alterations of dopamine and serotonin neurotransmitter levels were also recently observed in LC. Interestingly, at least some of the proposed mechanisms of LC development overlap with mechanisms of Autonomic Nervous System (ANS) imbalance, previously detailed in the framework of the aging process. ANS imbalance is characterized by a proinflammatory sympathetic overdrive, and a concomitant decreased anti-inflammatory vagal parasympathetic activity, associated with reduced anti-inflammatory effects of the HPA axis and cholinergic anti-inflammatory pathway (CAP). These neuro-immune-endocrine system imbalanced activities fuel the vicious circle of chronic inflammation, i.e. inflammaging. Here, we refine our original hypothesis that ANS dysfunction fuels inflammaging and propose that biomarkers of ANS imbalance could also be considered biomarkers of inflammaging, recognized as the main risk factor for developing age-related diseases and the sequelae of viral infections, i.e. LC.

Dengue Fever with Hemolysis: Unmasking Beta-Thalassemia

Intravascular hemolysis is a rare but known complication of Dengue infection. Following is the description of a patient who presented with features of intravascular hemolysis with other sequelae of Dengue infection. Clinical stigmata of chronic iron overload led to a search for the aetiology of chronic hemolysis, which resulted in a diagnosis of non-transfusion-dependent beta-thalassemia.

SARS-CoV-2 Infection is Associated with Age- and Gender-Specific Changes in the Nasopharyngeal Microbiome.

The recent Coronavirus Disease 2019 (COVID-19) pandemic has dramatically exposed our gap in understanding the pathogenesis of airborne infections. Within such a context, it is increasingly clear that the nasal cavity represents a critical checkpoint not only in the initial colonization phase but also in shaping any infectious sequelae. This is particularly relevant to COVID-19 in that the nasal cavity is characterized by high-level expression of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) receptor, Angiotensin-Converting Enzyme 2 (ACE2), all along the respiratory tract. As part of the nasal mucosa, commensal microbes harbored by the nasal cavity likely are far more than just innocent bystanders in the interaction between SARS-CoV-2 and the local microenvironment. Yet the role of the qualitative composition of the nasal microbiome is unclear, as is its function, whether protective or not. In this study, individuals undergoing SARS-CoV-2 molecular testing at the Hospital of Perugia (Italy) were recruited, with their residual material from the nasopharyngeal swabs being collected for microbiome composition analysis and short-chain fatty acid (SCFA) measurements (by 16S rRNA sequencing and gas chromatography-mass spectrometry), respectively. After stratification by age, gender, and viral load, the composition of the nasopharyngeal microbiome appeared to be influenced by age and gender, and SARS-CoV-2 infection further determined compositional changes. Notwithstanding this variability, a restricted analysis of female subjects-once SARS-CoV-2-infected-unraveled a shared expansion of Lachnospirales-Lachnospiraceae, irrespective of the viral load and age. This was associated with a reduction in the branched SCFA isobutanoic acid, as well as in the SCFAs with longer chains. Our results indicate that the nasopharyngeal microbiome is influenced by age, gender, and viral load, with consistent patterns of microbiome changes being present across specific groups. This may help in designing a personalized medicine approach in COVID-19 patients with specific patterns of nasal microbial communities.

The lucky polyp: an unusual manifestation of chronic schistosomiasis.

A 23-year-old male from Brazil presented with bright red hematochezia. Proctological examination revealed grade II internal hemorrhoids, but flexible sigmoidoscopy uncovered a 6 mm-pedunculated polyp in the sigmoid colon, which was found to result from inflammatory reaction to Schistosoma mansoni egg deposition. The patient had no signs of portal hypertension and was successfully treated with praziquantel. This case underscores a rare presentation of chronic intestinal schistosomiasis and emphasizes the role of early diagnosis in preventing severe hepatic sequelae of chronic Schistosoma infection.

Hypothesis Explaining Development of Squamous Cell Carcinoma During Infection with Schistosoma Haematobium

Schistosome worms are blood-dwelling flukes that cause chronic infection in more than 200 million people and are thought to be responsible for 500,000 deaths annually. During infection with Schistosoma haematobium, eggs are deposited in the mucosa and submucosa of the bladder and lower ureters. Squamous cell carcinoma (SCC) of the bladder is a long-term sequela of chronic infection. The mechanisms underlying the association between S. haematobium and SCC of the bladder are largely unknown, with all reports to date exclusively demonstrating epidemiological evidence linking S. haematobium infection with SCC of the bladder. Scientists hypothesised that the parasite antigens might induce alterations in epithelial cells towards cancer. Scientists used Chinese Hamster Ovary (CHO) cells and treated the cells in culture with S. haematobium total antigen (Sh). Results showed increased proliferation, increased S-phase and decreased apoptosis, as well as down-regulation of tumor suppressor p27 and up-regulation of anti-apoptotic molecule Bcl-2 (Botelho et al., 2009). Angiogenesis is defined as the formation of new blood vessels from preexisting ones and is recognized as a key event in cell proliferation and carcinogenesis and spread of malignant lesions (Dematei et al., 2017). S. haematobium is classified as a Group 1 carcinogen by the World Health Organization’s International Agency for Research on Cancer (Hodderet al., 2000). Another factor that may play a major role in bladder carcinogenesis in schistosomiasis patients is the presence of continuous physical irritation and inflammation produced by Schistosoma eggs in the bladder mucosa. The adult S. haematobium worms inhabit the veins of the perivesical plexus, where the female lays eggs. Some eggs pass through the bladder mucosa and are excreted in the urine. Other eggs are trapped in the tissue. A chronic inflammatory reaction is initiated, with the invasion of histiocytes and other inflammatory cells into the bladder, the formation of granulomas and eventually fibrosis. In addition, the eruption of the eggs through the mucosa stimulates reparative urothelial hyperplasia and cell turnover (Rosin et al., 1994). In our article we try to explain possible mechanism of conversion normal cells into tumor cells from the position of karyogamic theory.

Serum detection of blood brain barrier injury in subjects with a history of stroke and transient ischemic attack

ObjectiveStroke and transient ischemic attack may have long-term negative effects on the blood-brain barrier (BBB) and promote endothelial inflammation, both of which could increase neurodegeneration and dementia risk beyond the cell death associated with the index event. MethodsSerum from 88 postmortem subjects in the Arizona Study of Aging and Neurodegenerative Disorders were analyzed by sandwich ELISA for specific biomarkers to investigate the effects of cerebrovascular accidents (CVAs) on BBB integrity and endothelial activation. Statistical analyses were performed using the Mann-Whitney U Test, Spearman rank correlation, and linear/logistic regressions adjusted for potential confounders; a P-value < .05 was considered significant for all analyses. ResultsSerum PDGFRẞ, a putative biomarker of BBB injury, was significantly increased in subjects with vs without a history of CVA who had similar cardiovascular risk factors (P < .01). This difference was stable after adjusting for age, hypertension, and other potential confounders in regression analysis (odds ratio, 27.02; 95% confidence interval, 2.61-411.7; P < .01). In addition, PDGFRẞ was positively associated with VCAM-1, a biomarker of endothelial inflammation (ρ = 0.42; P < .01). ConclusionsOur data suggest that patients with stroke or transient ischemic attack have lasting changes in the BBB. Still more, this demonstrates the utility of PDGFRẞ as a serum-based biomarker of BBB physiology, a potentially powerful tool in studying the role of the BBB in various neurodegenerative diseases and COVID infection sequelae. Clinical RelevanceOur data demonstrate the utility of serum PDGFRẞ, a putative biomarker of BBB integrity in the setting of stroke and TIA (CVA). A serum biomarker of BBB integrity could be a useful tool to detect early BBB damage and allow prospective work to study how such damage affects long-term neurodegenerative risk. Since BBB disruption occurs early in ADRD development, it could be monitored to help better understand disease progression and involvement of vascular pathways in ADRD.

Mammalian Target of Rapamycin Complex 1 Activation in Macrophages Contributes to Persistent Lung Inflammation following Respiratory Tract Viral Infection

Respiratory virus infections cause millions of hospitalizations worldwide each year. Severe infections lead to lung damage that coincides with persistent inflammation and a lengthy repair period. Vaccination and anti-viral therapy help to mitigate severe infections prior to or during the acute stage of disease, but there are currently limited specific treatment options available to individuals suffering from the long-term sequelae of respiratory viral infection. C57BL/6 mice were infected with influenza A/PR/8/34 as a model for severe viral lung infection and allowed to recover for 21 days. Mice were treated with rapamycin, a well characterized mTORC1 inhibitor on days 12 to 20 post infection; a time period after viral clearance. Persistent inflammation following severe influenza infection in mice was primarily driven by macrophages and T cells. UMAP analysis of flow cytometry data revealed that lung macrophages had high activation of mTORC1, an energy sensing kinase involved in inflammatory immune cell effector functions. Rapamycin treatment reduced lung inflammation and the frequency of exudate macrophages, T cells, and B cells in the lung, while not impacting epithelial progenitor cells or adaptive immune memory. These data highlight mTORC1’s role in sustaining persistent inflammation following clearance of a viral respiratory pathogen and suggest a possible intervention for post-viral chronic lung inflammation.

COVID-19 in a Dutch Nursing Home: A Longitudinal Retrospective Care-Home-Level Case Study on Infection Rate, Survival Rate, and Daily Functioning.

During the pandemic, nursing homes in the Netherlands were heavily affected by COVID-19. This study assesses the impact of COVID-19 on infection rate, survival rate, and daily functioning over the course of two years among residents of a nursing home in the Netherlands that was amongst the first nursing homes to be affected by the pandemic. This retrospective study followed 70 residents during a two-year period, starting in March 2020. Data were collected on baseline characteristics of participants and the onset, duration, and sequelae of COVID-19 infections. Primary outcomes were mortality and infection rate. The secondary outcome was daily functioning using the Barthel Index at intervals of six months. Within two years, 44 (62.9%) residents were diagnosed with COVID-19. During this study, 72.7% (n = 32) of the COVID-positive residents died, of which 22 deaths were related to the COVID-19 infection. Overall mortality was 60% (n = 42), while COVID-related mortality was 31.4% (n = 22). COVID-19 and multimorbidity (>3 morbidities) were independent risk factors for mortality. Barthel Index scores showed no significant difference in daily functioning. Overall, a high COVID-19 infection rate was seen and was the most common cause of death. COVID-19 did not affect functional status over time.

Epidemiology of COVID-19 in Infants in the United States: Incidence, Severity, Fatality, and Variants of Concern.

The clinical spectrum of infant COVID-19 ranges from asymptomatic infection to life-threatening illness, yet epidemiologic surveillance has been limited for infants. Using COVID-19 case data (restricted to reporting states) and national mortality data, we calculated incidence, hospitalization, mortality and case fatality rates through March 2022. Reported incidence of COVID-19 was 64.1 new cases per 1000 infant years (95% CI: 63.3-64.9). We estimated that 594,012 infants tested positive for COVID-19 nationwide by March 31, 2022. Viral variant comparisons revealed that incidence was 7× higher during the Omicron (January-March 2022) versus the pre-Delta period (June 2020-May 2021). The cumulative case hospitalization rate was 4.1% (95% CI: 4.0%-4.3%). For every 74 hospitalized infants, one infant death occurred, but overall COVID-19-related infant case fatality was low, with 7.0 deaths per 10,000 cases (95% CI: 5.6-8.7). Nationwide, 333 COVID-19 infant deaths were reported. Only 13 infant deaths (3.9%) were the result of usually lethal congenital anomalies. The majority of infant decedents were non-White (28.2% Black, 26.1% Hispanic, 8.1% Asian, Indigenous or multiracial). More than half a million US infants contracted COVID-19 by March 2022. Longitudinal assessment of long-term infant SARS-CoV-2 infection sequelae remains a critical research gap. Extremely low infant vaccination rates (<5%), waning adult immunity and continued viral exposure risks suggest that infant COVID-19 will remain a persistent public health problem. Our study underscores the need to increase vaccination rates for mothers and infants, decrease viral exposure risks and improve health equity.