Resolution Of Acute Infection Research Articles

Respiratory Syncytial Virus Sequelae Among Adults in High-Income Countries: A Systematic Literature Review and Meta-analysis.

Respiratory syncytial virus (RSV) can cause severe respiratory infections in adults; however, information on associated sequelae is limited. This systematic literature review aimed to identify sequelae in adults within 1year following RSV-related hospitalization or resolution of acute infection. Studies were identified from Embase, MEDLINE, LILACS, SciELO, and grey literature. Random-effects meta-analyses using restricted maximum likelihood were used to calculate the proportions and relative risks of sequelae in patients with RSV compared with controls (patients with RSV-negative influenza-like illness, influenza, and parainfluenza) per follow-up period, population, and treatment setting, where possible. Twenty-one relevant studies covering the period from 1990 to 2019 were included. Among the general population, the most frequent clinical sequela was sustained function loss (33.5% [95%CI 27.6-39.9]). Decline in lung function and cardiovascular event or congestive heart failure were also identified. Utilization sequelae were readmission (highest at > 6months after discharge) and placement in a skilled nursing facility. The only subpopulation with data regarding sequelae was transplant patients. Among lung transplant patients, the most frequently reported clinical sequelae were decline in lung function, followed by graft dysfunction and bronchiolitis obliterans syndrome. Pooled relative risks were calculated for the following sequela with controls (primarily influenza-positive patients): cardiovascular event (general population) and pulmonary impairment (hematogenic-transplant patients) both 1.4 (95%CI 1.0-2.0) and for readmission (general population) 1.2 (95%CI 1.1-1.3). Although less data are available for RSV than for influenza or other lower respiratory tract infections, RSV infection among adults is associated with medically important sequelae, with a prevalence similar to other respiratory pathogens. RSV sequelae should be included in disease burden estimates.

COVID-19 and Long-COVID Thrombosis: From Clinical and Basic Science to Therapeutics.

Coronavirus infectious disease-19 (COVID-19) is a pandemic characterized by serious lung disease and thrombotic events in the venous and circulation trees, which represent a harmful clinical sign of poor outcome. Thrombotic events are more frequent in patients with severe disease requiring intensive care units and are associated with platelet and clotting activation. However, after resolution of acute infection, patients may still have clinical sequelae, the so-called long-COVID-19, including thrombotic events again in the venous and arterial circulation. The mechanisms accounting for thrombosis in acute and long COVID-19 have not been fully clarified; interactions of COVID-19 with angiotensin converting enzyme 2 or toll-like receptor family or infection-induced cytokine storm have been suggested to be implicated in endothelial cells, leucocytes, and platelets to elicit clotting activation in acute as well in chronic phase of the disease. In acute COVID-19, prophylactic or full doses of anticoagulants exert beneficial effects even if the dosage choice is still under investigation; however, a residual risk still remains suggesting a need for a more appropriate therapeutic approach. In long COVID-19 preliminary data provided useful information in terms of antiplatelet treatment but definition of candidates for thrombotic prophylaxis is still undefined.

Cytomegalovirus durably primes neutrophil oxidative burst.

Cytomegalovirus (CMV) is a ubiquitous herpes virus that infects most humans, thereafter persisting lifelong in tissues of the host. It is a known pathogen in immunosuppressed patients, but its impact on immunocompetent hosts remains less understood. Recent data have shown that CMV leaves a significant and long-lasting imprint in host immunity that may confer some protection against subsequent bacterial infection. Such innate immune activation may come at a cost, however, with potential to cause immunopathology. Neutrophils are central to many models of immunopathology, and while acute CMV infection is known to influence neutrophil biology, the impact of chronic CMV infection on neutrophil function remains unreported. Using our murine model of CMV infection and latency, we show that chronic CMV causes persistent enhancement of neutrophil oxidative burst well after resolution of acute infection. Moreover, this in vivo priming of marrow neutrophils is associated with enhanced formyl peptide receptor expression, and ultimately constitutive c-Jun N-terminal kinase phosphorylation and enhanced CD14 expression in/on circulating neutrophils. Finally, we show that neutrophil priming is dependent on viral load, suggesting that naturally infected human hosts will show variability in CMV-related neutrophil priming. Altogether, these findings represent a previously unrecognized and potentially important impact of chronic CMV infection on neutrophil responsiveness in immunocompetent hosts.

Heterogeneity in IgG-CD16 signaling in infectious disease outcomes.

In this review, we discuss how IgG antibodies can modulate inflammatory signaling during viral infections with a focus on CD16a‐mediated functions. We describe the structural heterogeneity of IgG antibody ligands, including subclass and glycosylation that impact binding by and downstream activity of CD16a, as well as the heterogeneity of CD16a itself, including allele and expression density. While inflammation is a mechanism required for immune homeostasis and resolution of acute infections, we focus here on two infectious diseases that are driven by pathogenic inflammatory responses during infection. Specifically, we review and discuss the evolving body of literature showing that afucosylated IgG immune complex signaling through CD16a contributes to the overwhelming inflammatory response that is central to the pathogenesis of severe forms of dengue disease and coronavirus disease 2019 (COVID‐19).

AB1092 INFLAMMATORY ARTHRITIDES IN POST-COVID-19 PATIENTS: AN ALBANIAN EXPERIENCE.

BackgroundCOVID-19 is a disease caused by the new pathogen SARS-CoV2 (severe acute respiratory syndrome coronavirus 2) typically presenting with pneumonia but also other systemic manifestation has been reported worldwide [1]. Different reports have described the appearance of inflammatory arthritis (IA) after resolution of acute infection from COVID-19 [2].ObjectivesTo observe the frequency of Inflammatory Arthritis in an Albanian cohort of post-COVID-19 patients.MethodsPost-Covid-19 patients, having two consecutive negative PCR (real-time reverse transcription polymerase chain reaction), discharged from the Pulmonology Department (January – July 2021) were invited to enter in a 6 (six) month multidisciplinary observational study. Data regarding post-COVID-19 inflammatory arthritis are presented in this study. Descriptive statistical analysis was used to express data.ResultsFrom 154 post-COVID-19 patients (F/M = 62/92) enrolled, 14 (9.09%) patients didn’t follow regularly the dedicated ambulatory thus were excluded from this study. Considering the remaining 140 patients (F/M = 58/82), only 21 (15%) patients were diagnosed with IA where the most common were, respectively: Reactive Arthritis (ReA) 11 (52.3%) patients; Rheumatoid Arthritis (RA) 4 (19.09%) patients; Ankylosing Spondylitis (AS) 3 (14.2%) patients; Gout Arthritis (GA) 3 (14.2%) patients. All rheumatic conditions were more frequent in male than in female post-COVID-19 patients. Data summarized in Table 1. All patients that developed a post COVID-19 IA, had fever during the period of SARS-CoV2 infection. Arthralgia was a typical symptom that have been reported by patients that have developed RA and AS. All RA post-Covid-19 patients reported having had even symptoms like cough, dispnea and fatigue. None of the AS patients neither GA reported symptoms of dysguesia or anosmia. Only 9% of ReA patients reported having had abdominal pain during acute infection with SARS-Cov2. Data summarized in Figure 1.Table 1.Inflammatory ArthritisPatients (N, %)Age (mean ± SD)Male (N, %)Days after COVID-19 (mean ± SD)ReA11 (52.3)48.2 ± 12.57 (63.6)15.8 ± 9.9RA4 (19,09)55.7 ± 8.72 (50)32.3 ± 11.3AS3 (14.2)50.5 ± 9.72 (14.2)18.8 ± 5.5GA3 (14.2)55.3 ± 1.23 (100)10.6 ± 0.9ConclusionIA is another manifestation that follows acute infection from COVID-19. In this regard increased awareness and further investigations are needed in order to better understand weather SARS-Cov2 infection can accelerate the development of a rheumatic autoimmune disease.

Foot-and-mouth disease virus localisation on follicular dendritic cells and sustained induction of neutralising antibodies is dependent on binding to complement receptors (CR2/CR1).

Previous studies have shown after the resolution of acute infection and viraemia, foot-and-mouth disease virus (FMDV) capsid proteins and/or genome are localised in the light zone of germinal centres of lymphoid tissue in cattle and African buffalo. The pattern of staining for FMDV proteins was consistent with the virus binding to follicular dendritic cells (FDCs). We have now demonstrated a similar pattern of FMDV protein staining in mouse spleens after acute infection and showed FMDV proteins are colocalised with FDCs. Blocking antigen binding to complement receptor type 2 and 1 (CR2/CR1) prior to infection with FMDV significantly reduced the detection of viral proteins on FDCs and FMDV genomic RNA in spleen samples. Blocking the receptors prior to infection also significantly reduced neutralising antibody titres, through significant reduction in their avidity to the FMDV capsid. Therefore, the binding of FMDV to FDCs and sustained induction of neutralising antibody responses are dependent on FMDV binding to CR2/CR1 in mice.

Mechanisms of coronavirus infectious disease 2019-related neurologic diseases.

As of January 8, 2022, a global pandemic caused by infection with severe acute respiratory syndrome coronavirus (SARS-CoV)-2, a new RNA virus, has resulted in 304,896,785 cases in over 222 countries and regions, with over 5,500,683 deaths (www.worldometers.info/coronavirus/). Reports of neurological and psychiatric symptoms in the context of coronavirus infectious disease 2019 (COVID-19) range from headache, anosmia, and dysgeusia, to depression, fatigue, psychosis, seizures, delirium, suicide, meningitis, encephalitis, inflammatory demyelination, infarction, and acute hemorrhagic necrotizing encephalopathy. Moreover, 30-50% of COVID-19 survivors develop long-lasting neurologic symptoms, including a dysexecutive syndrome, with inattention and disorientation, and/or poor movement coordination. Detection of SARS-CoV-2 RNA within the central nervous system (CNS) of patients is rare, and mechanisms of neurological damage and ongoing neurologic diseases in COVID-19 patients are unknown. However, studies demonstrating viral glycoprotein effects on coagulation and cerebral vasculature, and hypoxia- and cytokine-mediated coagulopathy and CNS immunopathology suggest both virus-specific and neuroimmune responses may be involved. This review explores potential mechanistic insights that could contribute to COVID-19-related neurologic disease. While the development of neurologic diseases during acute COVID-19 is rarely associated with evidence of viral neuroinvasion, new evidence suggests SARS-CoV-2 Spike (S) protein exhibits direct inflammatory and pro-coagulation effects. This, in conjunction with immune dysregulation resulting in cytokine release syndrome (CRS) may result in acute cerebrovascular or neuroinflammatory diseases. Additionally, CRS-mediated loss of blood-brain barrier integrity in specific brain regions may contribute to the expression of proinflammatory mediators by neural cells that may impact brain function long after resolution of acute infection. Importantly, host co-morbid diseases that affect vascular, pulmonary, or CNS function may contribute to the type of neurologic disease triggered by SARS-COV-2 infection. Distinct effects of SARS-CoV-2 S protein and CNS compartment- and region-specific responses to CRS may underlie acute and chronic neuroinflammatory diseases associated with COVID-19.

Chronotropic Incompetence in Non-Hospitalized Patients with Post-COVID-19 Syndrome

Patients recovering from COVID-19 commonly report persistence of dyspnea, exertional fatigue, and difficulties in carrying out their daily activities. However, the nature of these symptoms is still unknown. The purpose of the study was to identify limiting causes of cardiopulmonary origin for the performance of physical exercise in post-COVID-19 condition that could explain the symptomatic persistence of dyspnea or fatigue-related symptoms. Thirty-two non-hospitalized patients with post-COVID-19 condition (i.e., still presenting a chronic symptomatic phase lasting >90 days since debut of symptoms that lasted for at least 2 months and cannot be explained by an alternative diagnosis) completed a clinical examination including echocardiography, submaximal and maximal cardiorespiratory fitness tests (Ekblom-Bak and Bruce’s protocols), and a battery of validated questionnaires about fatigue and exercise intolerance. Four participants (12.5%) reported an abnormal cardiac response to exercise during the submaximal test, which aroused suspicion of the presence of chronotropic incompetence. All of them were confirmed with a positive diagnosis maximal exercise test after cardiology screening, even with a comprehensive clinical examination, resting ECG, and echocardiogram, without other findings. No statistical differences were found in any physiological variables or questionnaire values, between patients with positive and negative diagnoses. Chronotropic incompetence and other autonomic disorders may appear in patients with mild forms of COVID-19 presentation and may persist in the long term, being responsible for exercise intolerance after resolution of acute infection. Clinicians should be aware that chronotropic incompetence and other autonomic disorders may be a complication of COVID-19 and should consider appropriate diagnostic and therapeutic interventions in these patients, especially when early exercise-related fatigability is reported.

Covid Reinfection versus Asymptomatic Carrier State: A Case Report

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first discovered in China in December 2019, has been implicated in the current coronavirus disease 2019 (COVID-19) pandemic. Although much has been learned about the virus which peaked with the development of the vaccine, there is still a lot of unanswered questions. Maximum duration of positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction (RT-PCR) from symptom onset may be up to 3 months [1], however it is not known if the continued detection of the viral genome implies prolonged infectivity or presence of a non-viable virus [2]. Most people with COVID-19 develop antibodies after resolution of acute infection [2]. The exact duration of these antibodies in the body is unknown, but some studies have shown that both memory T-cells and B-cells can persist up to 6 to 8 months after acute SARS-CoV-2 infection [3]. These SARS-CoV-2 antibodies may confer some immunity to the person after the acute infection and have been associated with protection against subsequent infection in nonhuman primates by the same viral strain during the early recovery phase [4]. In humans, however, it is unknown to what extent this immune response indicates a protective immunity to subsequent infection with SARS-CoV-2 [5]. Few cases of reinfection have been documented worldwide with varying symptom severity; the first case in the US was published in January 2021 (reinfection occurred in June 2020) [5]. None of the initial cases reported the presence of SARS-CoV-2 antibodies at the time of reinfection. We present a patient who tested positive to SARS-CoV-2 RT-PCR twice in 10 months (Table 1). At both times, she was asymptomatic and the second time, she had coexisting SARS-CoV-2 antibodies.

Long COVID-19: A Primer for Cardiovascular Health Professionals, on Behalf of the CCS Rapid Response Team

It is now widely recognized that COVID-19 illness can be associated with significant intermediate and potentially longer-term physical limitations. The term, “long COVID-19” is used to define any patient with persistent symptoms after acute COVID-19 infection (ie, after 4 weeks). It is postulated that cardiac injury might be linked to symptoms that persist after resolution of acute infection, as part of this syndrome. The Canadian Cardiovascular Society Rapid Response Team has generated this document to provide guidance to health care providers on the optimal management of patients with suspected cardiac complications of long COVID-19.

Etiology, diagnosis, and surgical management of obstructive salivary gland disease

: Obstructive salivary gland disease (OSGD) represents a large subset of salivary gland entities that affect a significant number of patients every year. Many different pathologic processes such as sialoliths, mucous plugs, strictures, and ductal stenosis can present with nearly identical obstructive symptoms, making diagnosis and treatment challenging. Current management of OSGD revolves around resolution of acute infection, targeted imaging, and definitive surgical management of the causal obstruction. Technological advances and improved diagnostic methods over the last two decades have led to a paradigm shift in management of these disorders, with an emphasis on gland-sparing and minimally-invasive therapies. Imaging for obstructive salivary gland disorders has shifted away from traditional sialography and plain film radiography in favor of ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). Rehydration, gland massage, and antibiotics continue to be the mainstay of medical management. The use of sialendoscopy represents a minimally-invasive method to treat most OSGD without the morbidity associated with sialoadenectomy or other open procedures. The development of multiple adjunct treatment methods such as mechanical lithotripsy, laser lithotripsy, and extracorporeal shock wave lithotripsy have added to the overall effectiveness of minimally-invasive treatments for OSGD. This paper presents a review on the four main etiologies of salivary gland obstruction, appropriate diagnostic workup, and medical and surgical management of these disorders.

COVID Re-Infection or Something Else? A Case Report

<strong>Introduction:</strong> Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 100 million people so far globally with few cases of reinfection reported [1, 2]. Most people with coronavirus disease 2019 (COVID-19) develop antibodies after resolution of acute infection, however the exact duration of these antibodies and the extent to which it may indicate a protective immunity to SARS-CoV-2 in humans is unknown [2, 3]. We report an unusual case of probable asymptomatic reinfection with SARS-CoV-2 while still having antibodies present. <strong>Case Presentation:</strong> A 39-year-old healthy female healthcare professional in New York City had severe myalgia, generalized body weakness, cough, and subjective fever (maximum axillary temperature 99.8F) in March of 2020. The patient was not tested for COVID-19 initially because there was no documentation of fever ≥100F and restriction of testing due to limited availability. Conservative management with analgesics and hydration was done and symptoms subsided after 7 days. One week later (April 2020), multiple family members became sick with COVID-like symptoms and tested positive to SARS-CoV-2 by polymerase chain reaction (PCR). Patient was then screened with SARS-CoV-2 RT-PCR (Roche Cobas 6800) due to close household contact and was positive. Routine COVID-19 antibody testing (Roche Cobas Elecsys) offered to hospital staff on a voluntary basis a month later and again 4 months later (September 2020) during annual employee health screening were both positive. In January 2021, the patient was tested due to mandatory return-to-work screening after out-of-state travel and was found to be positive by both PCR and antibody (<em><strong>Table 1</strong></em>). At that time, patient was completely asymptomatic but was required to quarantine. Six days later, she repeated both tests in an urgent care facility at which time SARSCoV-2 RNA PCR (Roche Cobas) was negative while the IgG antibodies (Abbott Alinity i) remained positive. A respiratory viral panel for SARS-CoV-2 RNA PCR and influenza A and B (Roche Cobas) done three weeks later as part of the prerequisites for clinical rotation in a different hospital was also negative. <strong>Conclusion:</strong>The asymptomatic index case had antibodies at the time she re-tested positive to SARS-CoV-2 10 months after first testing positive. This may be a case of re-infection in which the presence of antibodies kept the patient symptom-free. Less likely, she may have been carrying viral particles in her nose for 10 months as there was no documented negative test in the interim. There are no published reports of such prolonged carriage of virus [4]. Furthermore, prolonged detection of viral particles does not translate to infectivity [4, 5]. The repeat positive test could also have been a false positive. Polymerase chain reaction cycle thresholds may prove helpful to clinicians to determine the significance of a positive PCR test.

Immune response to respiratory syncytial virus infection (&lt;i&gt;Orthopneumovirus&lt;/i&gt;)

Respiratory syncytial virus (RSV) infects children as well as elderly and immunocompromised subjects. In 2016, RSV was renamed to Orthopneumovirus owing to virus taxonomy latinization and was also included into the Pneumoviridae family. However, in this review we will use the old and more common RSV name. RSV infection may occur throughout human lifetime as it does not induce sterilizing immunity. During RSV infection, diverse immune cells such as dendritic cells, macrophages, T cells, B cells and eosinophils are involved in the antiviral response. Some of them play an important role in eliminating RSV, while the others can provoke tissue damage. An interaction between these cells occurs through the induced cytokines and chemokines, some of which emerge at early disease stages, whereas the others — at later stages. In addition, the mentioned cells can affect the course of both primary and secondary RSV infection. A prolonged or persistent RSV infection is observed in children with T-cell immunodeficiency, emphasizing the importance of T cells in resolution of acute infection as well as for virus-specific immunological memory development. Almost all the adults and children bear RSV-specific antibodies, but that doesn't protect against the repeated infection. It was shown that high mucosal rather than serum IgG level correlated better with reduced RSV load. A growing body of RSV vaccine candidates has emerged: live-attenuated, protein-based, whole-inactivated, particle-based, subunit antigens, and nucleic acid-based vaccines. While developing vaccines, there should be taken into consideration features of anti-RSV immune response as well as age of subjects to be vaccinated. In particular, to avoid vaccine-associated aggravation of RSV infection it is justified to use live attenuated vaccines in children, whereas middle-aged and the elderly subjects might be applied with subunit vaccines. Currently, no licensed vaccine for RSV infection is available. In this review, we will detail an interaction of the RSV with diverse immune cells as well as our contemporary understanding regarding preventive vaccines in RSV infection.

Neurological Sequelae Resulting from Encephalitic Alphavirus Infection.

The recent surge in viral clinical cases and associated neurological deficits have reminded us that viral infections can lead to detrimental, long-term effects, termed sequelae, in survivors. Alphaviruses are enveloped, single-stranded positive-sense RNA viruses in the Togaviridae family. Transmission of alphaviruses between and within species occurs mainly via the bite of an infected mosquito bite, giving alphaviruses a place among arboviruses, or arthropod-borne viruses. Alphaviruses are found throughout the world and typically cause arthralgic or encephalitic disease in infected humans. Originally detected in the 1930s, today the major encephalitic viruses include Venezuelan, Western, and Eastern equine encephalitis viruses (VEEV, WEEV, and EEEV, respectively). VEEV, WEEV, and EEEV are endemic to the Americas and are important human pathogens, leading to thousands of human infections each year. Despite awareness of these viruses for nearly 100 years, we possess little mechanistic understanding regarding the complications (sequelae) that emerge after resolution of acute infection. Neurological sequelae are those complications involving damage to the central nervous system that results in cognitive, sensory, or motor deficits that may also manifest as emotional instability and seizures in the most severe cases. This article serves to provide an overview of clinical cases documented in the past century as well as a summary of the reported neurological sequelae due to VEEV, WEEV, and EEEV infection. We conclude with a treatise on the utility of, and practical considerations for animal models applied to the problem of neurological sequelae of viral encephalopathies in order to decipher mechanisms and interventional strategies.

Lymphangiogenesis Is Induced by Mycobacterial Granulomas via Vascular Endothelial Growth Factor Receptor-3 and Supports Systemic T-Cell Responses against Mycobacterial Antigen

Granulomatous inflammation is characteristic of many autoimmune and infectious diseases. The lymphatic drainage of these inflammatory sites remains poorly understood, despite an expanding understanding of lymphatic role in inflammation and disease. Here, we show that the lymph vessel growth factor Vegf-c is up-regulated in Bacillus Calmette-Guerin- and Mycobacterium tuberculosis-induced granulomas, and that infection results in lymph vessel sprouting and increased lymphatic area in granulomatous tissue. The observed lymphangiogenesis during infection was reduced by inhibition of vascular endothelial growth factor receptor 3. By using a model of chronic granulomatous infection, we also show that lymphatic remodeling of tissue persists despite resolution of acute infection and a 10- to 100-fold reduction in the number of bacteria and tissue-infiltrating leukocytes. Inhibition of vascular endothelial growth factor receptor 3 decreased the growth of new vessels, but also reduced the proliferation of antigen-specific T cells. Together, our data show that granuloma-up-regulated factors increase granuloma access to secondary lymph organs by lymphangiogenesis, and that this process facilitates the generation of systemic T-cell responses to granuloma-contained antigens.

New Insights into how HBV Manipulates the Innate Immune Response to Establish Acute and Persistent Infection

The mechanisms by which HBV establishes and maintains chronic infection are poorly understood. Although adult acquired HBV is generally cleared by a robust immune response, most individuals infected at childbirth or in very early childhood develop lifelong chronic infection. In addition, acute infections are unresolved in approximately 5% of individuals infected in adulthood. The host cell mechanisms that ensure establishment and resolution of acute infection and persistent infection remain unclear. Currently, two schools of thought suggest that either HBV is a 'stealth' virus, which initially establishes infection by avoiding host innate immune responses, or that HBV facilitates initial infection and progression to persistence by actively manipulating the host innate immune response to its advantage. There is increasing evidence that activation of innate host cell signalling pathways plays a major role in limiting adult acquired HBV infection and that, in turn, HBV has evolved numerous strategies to counteract these defence mechanisms. In this review, we summarize current knowledge regarding innate immune responses to HBV infection and discuss how HBV regulates cell signalling pathways to its advantage, particularly in the setting of chronic HBV infection. In turn, we show how an intimate knowledge of innate immune responses is driving development of novel therapeutic agents to treat chronic HBV infection.

EComment. Vacuum-assisted closure therapy in cardiac surgery

The retrospective study by Vos et al. has reported on the superiority of VAC-therapy compared to open packing in patients with post-sternotomy mediastinitis (PM) [1]. We have reviewed our experience regarding the management of deep sternal wound infections (also commonly called PM) in 85 patients over a period of 11 years (2000–2010) where the in-hospital mortality rate for this specific group was 7% vs. 3% . The higher logistic EuroSCORE for these patients (10.2% vs. 7.9%) indicates the higher rate of preoperative co-morbidities [2]. Our therapeutic approach is consistent with immediate application of VAC-therapy plus systemic antibiotics even when there is no clear distinction of whether there is an infective deep sternal wound or not [2]. This approach may improve the wound healing process through the early removal of the infective tissues and reduction of dead space. In case of sternal dehiscence, further surgical revision is required. Upon resolution of acute infection and confirmation of wound cultures as negative, a primary sternal closure technique is applied followed by insertion of closed irrigation - suction drains [2]. Bilateral myocutaneous pectoral flap reconstruction can be performed when necessary with particular emphasis on the preservation of its vascular supply. Six percent of these patients required a further plastic intervention [2]. In 2003, Luckraz et al. found that VAC-therapy combined with primary closure or myocutaneous flap is superior to VAC-therapy alone in patients with PM (VAC duration 13.5 days vs. 8 days, healed scar 77% vs. 64%, mortality rate 7.7% vs. 28.6%) [3]. The overall cost of the VAC-therapy per patient was regarded as nearly $4000 cheaper per patient than the single use of a closed irrigation system [3]. Pectoralis flaps can frequently be used for the definitive treatment of PM and the final sternal reconstruction. These flaps, as described by Jurkiewicz et al., allow early closure and healing of sternal wounds and are currently the conventional treatment for PM [4]. Alternatively, omental flaps can also be used for the treatment of PM specifically in the case of replacement of the ascending aorta with a prosthetic graft [4]. In 2007, Raja and Berg published their meta-analysis regarding the routine use of VAC-therapy in all patients with deep sternal wound infections post cardiac surgery. The authors identified 13 papers (out of 198) representing the best evidence in the use of VAC-therapy [5]. All the studies were retrospective or small cohort and the largest one was by Agarwal et al. with 103 patients (64% had the definitive diagnosis of PM) [5]. According to Agarwal et al., all the patients were treated with VAC-therapy (average period 11 days/patient) of whom 68% had definitive chest closure. The overall mortality rate was 28%, however, no deaths were related to VAC-therapy. Four deaths were due to PM sepsis [5]. This meta-analysis illustrates that VAC-therapy is a safe and effective additional method for the surgical management of PM. However, a prospective double-blinded randomized controlled trial is essential in order to validate the effectiveness, cost effectiveness and improvement of quality of life of patients undergoing VAC-therapy [5]. Conflict of interest: none declared.

Early severe inflammatory responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection.

Chronic infections are an increasing problem due to the aging population and the increase in antibiotic resistant organisms. Therefore, understanding the host-pathogen interactions that result in chronic infection is of great importance. Here, we investigate the molecular basis of chronic bacterial cystitis. We establish that introduction of uropathogenic E. coli (UPEC) into the bladders of C3H mice results in two distinct disease outcomes: resolution of acute infection or development of chronic cystitis lasting months. The incidence of chronic cystitis is both host strain and infectious dose-dependent. Further, development of chronic cystitis is preceded by biomarkers of local and systemic acute inflammation at 24 hours post-infection, including severe pyuria and bladder inflammation with mucosal injury, and a distinct serum cytokine signature consisting of elevated IL-5, IL-6, G-CSF, and the IL-8 analog KC. Mice deficient in TLR4 signaling or lymphocytes lack these innate responses and are resistant, to varying degrees, to developing chronic cystitis. Treatment of C3H mice with the glucocorticoid anti-inflammatory drug dexamethasone prior to UPEC infection also suppresses the development of chronic cystitis. Finally, individuals with a history of chronic cystitis, lasting at least 14 days, are significantly more susceptible to redeveloping severe, chronic cystitis upon bacterial challenge. Thus, we have discovered that the development of chronic cystitis in C3H mice by UPEC is facilitated by severe acute inflammatory responses early in infection, which subsequently are predisposing to recurrent cystitis, an insidious problem in women. Overall, these results have significant implications for our understanding of how early host-pathogen interactions at the mucosal surface determines the fate of disease.

Cytomegalovirus presenting with abdominal pain and pyrexia of unknown origin

Dear EditorCytomegalovirus (CMV) is a member of the herpesvirus family with ubiquitous transmission. Infection is mostoften asymptomatic, with exceptions being the immuno-compromised and those in utero. Like other members ofthe herpesvirus family, CMV establishes latent infectionafter the resolution of acute infection. Seroprevalence ratesvary between 40 and 60%, increasing with age and areinversely proportional to socioeconomic status. A syn-drome resembling infectious mononucleosis is the mostcommon presentation of symptomatic CMV infection inimmunocompetent adults. Classic mononucleosis is anillness characterised by significant, often protracted feversand lassitude in the setting of absolute lymphocytosis withatypical lymphocytes. The mononucleosis syndrome asso-ciated with CMV infection has been described as‘‘typhoidal’’ in presentation, since systemic symptoms andfever predominate and signs of enlarged cervical nodes andsplenomegaly are not as commonly seen as they are inEpstein Barr Virus (EBV) [1]. Here, we present the case ofan acute CMV infection that presented as a surgicaladmission of abdominal pain with pyrexia.A 54-year-old Irish Caucasian farmer was referred to theaccident and emergency department by his general practi-tioner for an 18-day history of left iliac fossa (LIF) pain.He had a background history of a total colectomy forhereditary nonpolyposis colorectal cancer (HNPCC)3 years prior and a left-sided orchidectomy as a child. TheLIF pain was rated as mild to moderate in severity andintermittently crampy in nature. Radiation to his back wasnoted along with associated night sweats. The patientdenied any history of changes in bowel habit, blood perrectum, anorexia or weight loss.On examination, he was apyrexial with normal respira-tory parameters, blood pressure 150/80 mmHg and a sinustachycardia at 120 beats/min. Cardiovascular, respiratoryand neurological examinations were all unremarkable.Abdominal examination revealed a soft non-tender abdo-men with no masses or organomegaly. Bowel sounds werepresent and PR examination was unremarkable with anegative test for faecal occult blood. Preliminary investi-gations showed normal haematology and biochemistry,with the exception of an elevated C-reactive protein (CRP)at 43 mg/l. Urinary dipstick was unremarkable, as was thepresenting chest X-ray (CXR). Blood cultures and MSUwere taken.

HIV in children: take a moment to make a difference!

You may not know it, but there are 5.5 million HIV-infected people in Africa. More important for paediatric radiologists to know is that there are nearly 2 million HIV-infected children in sub-Saharan Africa. In my home country, South Africa, there are 360,000 HIV-infected children. Now you understand why we have dedicated seven articles in this minisymposium to HIV in children. You may not believe that this affects you as a European or North American radiologist, but if the resurgence of tuberculosis is anything to go by, HIV should be a major concern to you too. The mass migration from Africa, increasing urban poverty and worsening social conditions in parts of cities of many developed nations make Africa at your doorstep. The majority of adults with HIV infection are of childbearing age, and of these, three-quarters are women. This, in turn, translates to both a medical and a social disaster for children. Not only are the bread-winners ill and not able to care for their children, but mothers transmit the disease during pregnancy, delivery and breast feeding to their children. Additionally, parents who are not treated and die leave orphans behind (many of whom are infected with the virus). There are currently over 11 million AIDS orphans! Imaging in HIV infection and AIDS requires skills ranging from interpretation of plain radiographs to MRI scanning of the central nervous system. Children with HIV infection are susceptible to both common and unusual infections, sometimes simultaneously. The radiologist also needs to distinguish changes resulting from HIV infection itself, such as brain shrinkage or cardiomegaly. Furthermore, neurological damage, chronic illness and superinfection compound each other with a variety of complications, such as aspiration and cardiac failure. Neoplasms, such as lymphoma, present radiologically in similar ways to some infections such as TB, when lymphadenopathy can no longer be used as a distinguishing imaging feature. The patient’s condition also affects the diseases that they are most susceptible to, and depending on CD4 levels the composition of a radiological differential diagnosis changes. Moreover, the institution of highly active antiretroviral therapy further complicates image interpretation, especially when the body is able to mount an immune response, resulting in the phenomenon of immune reconstitution inflammatory syndrome (IRIS). Without information from the clinician, the radiologist can become lost in identifying multiple radiological signs without any coherent conclusion and without being able to assist the clinician to manage the patient. Children may be on prophylaxis for pneumocystis, making that an unlikely diagnosis. There may be newonset pyrexia and the suggestion of fungal disease. Coexistent skin lesions may allow the rare diagnosis of Kaposi sarcoma in the lung to be made on radiographic findings. The clinician may depend on radiological identification of lymphadenopathy to start anti-TB treatment. The CD4 count may make some infections or neoplasms less likely and others more likely. Imaging is also useful for follow-up. Disease progression, resolution of acute infections, response to treatment and success of interventions for some complications can be determined this way. Because HIV predominantly affects children in the developing world, imaging research should be geared towards low-cost solutions. However, high-end imaging in Pediatr Radiol (2009) 39:525–526 DOI 10.1007/s00247-009-1279-5