Severe Infectious Complications Research Articles

Abstract 4121816: Viral Venture: A Case of Myocarditis and IgA Vasculitis from Adenovirus Infection

Case Description: A 19-year-old man presented to the emergency department for 3 days of shortness of breath, progressive bilateral lower extremity rash, generalized fatigue, and diffuse joint following an earlier visit to urgent care for pharyngitis symptoms. Physical exam was notable for tachycardia, pain with active wrist and ankle range of motion, pharyngeal erythema, cervical adenopathy, and confluent erythematous palpable purpura and petechiae noted on bilateral lower extremities with scattered lesions on his thighs, arms, and back. Laboratory workup notable for markedly elevated high-sensitivity troponin to 3398 ng/L, and elevated CRP. Further workup was notable for normal urinalysis, negative streptococcus antigen, negative ANCA antibodies, ANA, Hepatitis B and C, and cryoglobulins. Imaging and cardiac workup were notable for normal left ventricular function and cardiac MRI notable for late gadolinium enhancement in the anteroapical mid-myocardial region suggestive of myocarditis. Skin biopsy ultimately revealed immunodeposition of IgA on superficial capillaries compatible with a diagnosis of IgA vasculitis. The patient was started on steroids for IgA vasculitis with rapid improvement in his symptoms and he was discharged home in good condition. Discussion: Recognizing the severe complications of viral infection can lead to prompt treatment and prevention of progression to severe end organ damage. Our case highlights rarely reported cardiac involvement of IgA vasculitis secondary to adenovirus infection based on laboratory and imaging diagnosis with cardiac MRI. To date, only 16 cases of cardiac involvement in IgA vasculitis have been reported. This case adds to the limited body of published cases describing this presentation of IgA vasculitis and is also consistent with the results of prior cases suggesting that an immunosuppressive regimen including glucocorticoids may help to prevent disease progression and induce remission in cases with cardiac involvement without the need for endomyocardial biopsy.

Predictors and Profile of Severe Infectious Complications in Multiple Myeloma Patients Treated with Daratumumab-Based Regimens: A Machine Learning Model for Pneumonia Risk.

Daratumumab (Dara) is the first monoclonal antibody introduced into clinical practice to treat multiple myeloma (MM). It currently forms the backbone of therapy regimens in both newly diagnosed (ND) and relapsed/refractory (RR) patients. However, previous reports indicated an increased risk of infectious complications (ICs) during Dara-based treatment. In this study, we aimed to determine the profile of ICs in MM patients treated with Dara-based regimens and establish predictors of their occurrence. This retrospective, real-life study included MM patients treated with Dara-based regimens between July 2019 and March 2024 at our institution. Infectious events were evaluated using the Terminology Criteria for Adverse Events (CTCAE) version 5.0. The study group consisted of a total of 139 patients, including 49 NDMM and 90 RRMM. In the RR setting, the majority (60.0%) of patients received the Dara, bortezomib, and dexamethasone (DVd) regimen, whereas ND patients were predominantly (98%) treated with the Dara, bortezomib, thalidomide, and dexamethasone (DVTd) regimen. Overall, 55 patients (39.6%) experienced ICs. The most common IC was pneumonia (37.5%), followed by upper respiratory tract infections (26.8%). Finally, twenty-five patients had severe ICs (grade ≥ 3) and required hospitalization, and eight patients died due to ICs. In the final multivariable model adjusted for setting (ND/RR) and age, hemoglobin level (OR 0.77, 95% CI: 0.61-0.96, p = 0.0037), and Eastern Cooperative Oncology Group (ECOG) >1 (OR 4.46, 95% CI: 1.63-12.26, p = 0.0037) were significant factors influencing severe IC occurrence. Additionally, we developed predictive models using the J48 decision tree, gradient boosting, and random forest algorithms. After conducting 10-fold cross-validation, these models demonstrated strong performance in predicting the occurrence of pneumonia during treatment with daratumumab-based regimens. Simple clinical and laboratory assessments, including hemoglobin level and ECOG scale, can be valuable in identifying patients vulnerable to infections during Dara-based regimens, facilitating personalized prophylactic strategies.

Efficacy and safety of first-line high-dose cytarabine in patients with primary CNS lymphoma ineligible for high-dose methotrexate: a case series

Abstract Introduction Despite recent significant advances, the treatment of elderly patients with primary central nervous system lymphoma (PCNSL) is still challenging due to comorbidities, poor baseline performance status (PS), and drug toxicities. There are proposals to use high-dose cytarabine (HD-araC) in these patients. Results Our retrospective study aimed to assess the efficacy and toxicity of HD-araC as an upfront treatment for patients with PCNSL who are ineligible for high-dose methotrexate (HD-MTX). Methods We identified 12 consecutive patients with newly diagnosed PCNSL (out of a total of 68) who received first-line treatment with HD-araC, with or without rituximab (R). Most of them had poor PS and relevant comorbidities. Six patients received this treatment upfront, while the other six received it after discontinuing HD-MTX-(based) therapy. Treatment with HD-araC resulted in poor outcome, limited response, and severe hematological and infectious complications. Patients who had previously received at least one cycle of HD-MTX appeared to have slightly better outcomes, highlighting the importance of HD-MTX in the treatment of PCNSL. Conclusion Our case series showed limited efficacy and substantial toxicity of (R)-HD-araC in patients with PCNSL ineligible for HD-MTX. This treatment should be omitted in elderly/frail patients to avoid further compromising their quality of life.

Ivermectin-Based Mass Drug Administration for Scabies in Northern India: A Single-Arm Community Intervention Trial.

Scabies and impetigo cause direct health effects and contribute to severe infectious and immune-mediated complications. Ivermectin-based mass drug administration can reduce scabies and impetigo prevalence in island settings with high prevalence, but the effectiveness in moderate-prevalence settings is not known. We conducted a single-arm, before-after community intervention trial. Mass drug administration was offered to the entire population of 4 villages in Uttarakhand, India. The treatment consisted of 2 doses, given 7 days apart, of oral ivermectin (∼200 μg/kg), or topical 5% permethrin if ivermectin was contraindicated. The primary outcome was the prevalence of scabies at 12 months compared with baseline, as diagnosed using clinical assessment and the 2020 International Alliance for the Control of Scabies criteria. Secondary outcomes included the prevalence of impetigo at each time point. The trial was registered with the Australian and New Zealand Trials Registry (ACTRN12619001712190). In January 2020, 1211 participants were enrolled (100% of the estimated village population). Treatment coverage was high-1204 (99.4%) and 1177 (97.2%) received 1 and 2 doses, respectively. Scabies was diagnosed in 91 participants (7.5%) and impetigo in 15 (1.2%). In February 2021, 1190 (98.3% of baseline) participants re-enrolled, and of these 11 had scabies (0.9%; relative risk reduction, 87.7%; 95% CI, 77.1%-93.4%) and 5 had impetigo (0.4%; relative risk reduction, 66.1%; 95% CI, 7.0%-87.6%). A single round of ivermectin-based mass drug administration substantially reduced the prevalence of scabies and impetigo in this setting with moderate scabies prevalence in northern India.

Sarcopenia As a Determinant Prognostic Factor After Surgery Among Patients with Colorectal Cancer.

Surgery for colorectal cancer (CRC) is not risk-free; therefore, preoperative evaluation must be done to predict and prevent surgical complications. Sarcopenia, a loss of muscle mass and function, was shown to be associated with surgical complications. Our study evaluates the effects of sarcopenia on short-term patient outcomes after CRC resection. Our retrospective study included patients with histologically proven CRC between 2018 and 2020 who underwent surgical resection. Skeletal muscle mass (cm2) was evaluated on a preoperative CT scan at the level of L3 vertebrae then standardized using stature (m2) to obtain the skeletal mass index (SMI) (cm2/m2). Patients received proper adjuvant care if needed and were followed up 90 days post surgery. Descriptive statistics were presented in percentage for categorical variables and in mean for continuous variables. Multivariate was made by linear regression. 113 patients were included, and 15% were sarcopenic. A statistically non-significant association was found between sarcopenia and severe complications (grade III-IV) (23.53% in sarcopenic vs. 9.38% non-sarcopenic, p=0.02, multivariate p=0.675). Sarcopenia was not associated with anastomotic leakage, infectious complications, or ileus or intra-abdominal bleeding (p>0.05). In literature, some studies showed an association between sarcopenia and postoperative complications while others showed no relationship between the two. Most studies used SMI. A non-statistically significant association was found between sarcopenia and postoperative complications in CRC patients. Sarcopenia does not predict postoperative severe complications, anastomotic leakage, infectious complications, or ileus or intra-abdominal bleeding. Emergent surgeries and age >60 years were associated with more postoperative complications.

Restoration of Type 17 immune signaling is not sufficient for protection during influenza-associated pulmonary aspergillosis.

Influenza-associated pulmonary aspergillosis (IAPA) is a severe complication of influenza infection that occurs in critically ill patients and results in higher mortality compared to influenza infection alone. Interleukin-17 (IL-17) and the Type 17 immune signaling pathway cytokine family are recognized for their pivotal role in fostering protective immunity against various pathogens. In this study, we investigate the role of IL-17 and Type 17 immune signaling components during IAPA. Wild-type mice were challenged with influenza A H1N1 (Flu) and then exposed to Aspergillus fumigatus ATCC42202 resting conidia on day 6 post-influenza infection, followed by the quantification of cytokines and chemokines at 48 hours post-fungal infection. Gene and protein expression levels revealed that IL-17 and Type 17 immune cytokines and antimicrobial peptides are downregulated during IAPA compared to mice singularly infected solely with A. fumigatus. Restoration of Type 17 immunity was not sufficient to provide protection against the increased fungal burden observed during IAPA. These findings contrast those observed during post-influenza bacterial super-infection, in which restoration of Type 17 immune signaling protects against exacerbation seen during super-infection. Our study highlights the need for future studies to understand the immune mechanisms that increase susceptibility to fungal infection.

Chikungunya encephalitis: A case report

Rationale: Transmitted to humans via the Aedes mosquito, Chikungunya virus (CHIKV) is associated with multi-system complications, sometimes collectively referred to as “atypical features.” However, a disorder of the nervous system appears to be the most common severe complication of CHIKV infection. Patient’s Concern: A seventy-five-year-old patient from India presented to the hospital with fever, chills, rigors, and multiple joint pains for which he was worked up. Diagnosis: CHIKV encephalitis. Interventions: The patient was treated initially on supportive therapy with antipyretics, intravenous fluids; however, during his hospital stay, the patient had altered sensorium during which he was managed in the intensive care unit; required mechanical ventilation. Outcomes: The patient sccumbed to his illness. Lessons: Treating clinicians should keep CHIKV disease in the differential diagnosis in cases of febrile exanthems associated with disabling arthritis, especially in a CHIKV-endemic country like India.

Midurethral sling infectious complications: A systematic review

BackgroundThe French Health Authority (Haute Autorité de santé) and French scientific societies (Collège national des gynécologues et obstétriciens français) recommend the use of midurethral slings as the surgical treatment of choice for stress incontinence due to urethral hypermobility and failure of hygienic diet and pelvic rehabilitation. Within a year of implantation, almost 90% of patients no longer experience stress urinary incontinence. Despite their recognized efficacy, retropubic and/or trans-obturator midurethral sling can expose patients to potentially severe infectious complications. MethodsA comprehensive literature review using Pubmed, Medline, Embase and Cochrane: “stress urinary incontinence”, and/or the following keywords “complications”, “infections”, “abscess”, “prosthetic exposures”, “fistula”, “erosion”, “cellulitis”, “fasciitis” in association with the keywords “midurethral slings”, “suburethral sling”, “tension free vaginal tape” and “trans-obturator tape. In the 330 articles, 61 really dealt with infectious complications following the implantation of synthetic midurethral slings in women. ResultsPreoperative urinalysis and intraoperative antibiotic prophylaxis were rarely reported (n=1 and n=11, respectively). We recorded thirty-six cases of abscess, twenty-one cases of cellulitis, sixteen cases of fistula and forty-one cases of prosthetic exposure. In 95.5% of cases, patients were treated with broad-spectrum antibiotics. Total explantation of the prosthesis was performed in 56% of patients at the initial management, with two-stage explantation performed in 23% of cases, partial explantation was carried out in 12% of cases, and the prosthesis was left in place in 9% of cases. No deaths were recorded. ConclusionTo limit the risk of urinary tract infections and potential prosthetic infections, a prophylactic approach should be adopted by performing a preoperative urinalysis and administering intraoperative antibiotic prophylaxis should be discussed. In the event of prosthetic and/or surgical site infection, broad-spectrum probabilistic antibiotic therapy should be initiated as early as possible until targeted antibiotic therapy. Total explantation of the prosthesis appears to be the most appropriate surgical strategy.

Clinical and radiological features of a cluster of immunocompetent adolescents with varicella pneumonia: a descriptive study.

Varicella pneumonia is one of the most common and severe complications of chickenpox infection. This study aimed to describe the clinical and radiological features of varicella pneumonia in a cluster of immunocompetent adolescents. A retrospective analysis was conducted on a cohort of adolescent patients diagnosed with varicella pneumonia at Wuhan Jinyintan Hospital between February 2023 and May 2023. The clinical and imaging data were collected and analyzed. A total of 116 patients were divided into two groups by the absence (group 1, n=57) or presence (group 2, n=59) of lower respiratory symptoms for data comparison. Among 116 patients (median age, 16 years; 60 males), rash (100%) was the most prevalent clinical symptom. The most common respiratory symptom and sign were fever (42.2%) and coarse breath sounds (41.4%). Chest computed tomography (CT) performed within five days of symptoms onset revealed multiple (89.7%), peripheral (51.7%), and ill-defined (73.3%) lung nodules in most patients, which gradually improved 6-10 days after symptom onset. Group 2 had higher levels of interleukin-6 (P<0.001), C-reactive protein (P=0.02), serum amyloid-A protein (P=0.002), longer hospital stays (P=0.04), more involved lung lobes (P=0.02), and a higher incidence of multiple nodules (P=0.043) than those of group 1. In immunocompetent adolescents, clustered varicella pneumonia often presents as mild and more uniform in clinical and radiological presentations than sporadic cases. The most common CT findings were multiple pulmonary nodules. Patients with lower respiratory symptoms exhibited more severe clinical and radiological manifestations. Generally, it is not recommended that patients undergo frequent CT scans in a short period.

Serum C-reactive protein and procalcitonin levels in patients with pneumonia and anastomotic leakage in the postoperative period after esophagectomy.

Despite being a less-invasive procedure, esophagectomy can cause severe infectious complications, such as pneumonia and anastomotic leakage. Herein, we aimed to clarify the inflammatory characteristics of pneumonia/anastomotic leakage after esophagectomy by assessing the difference between the postoperative trends of serum C-reactive protein (CRP) and procalcitonin (PCT) levels in patients with pneumonia/anastomotic leakage using the values on the consecutive postoperative day (POD). This study included 439 patients who underwent minimally invasive esophagectomy. Serum CRP and PCT levels were measured on PODs 1-7, 10, and 14. Pneumonia and anastomotic leakage were defined as Clavien-Dindo grades ≥ 2. Pneumonia and anastomotic leakage occurred in 96 and 51 patients, respectively. The CRP and PCT levels peaked on POD 3 (11.6 ± 6.8mg/dL) and POD 2 (0.69 ± 2.9ng/mL), respectively. Between PODs 3 and 14, CRP levels were significantly higher in patients with pneumonia and anastomotic leakage than in those without complications (P < 0.001). Between PODs 3 and 14, PCT levels were significantly higher in patients with pneumonia; however, on most PODs, there were no significant differences in PCT levels between patients with and without anastomotic leakage. Inflammatory reactions caused by pneumonia may be more intense than those caused by anastomotic leakage after esophagectomy. Postoperative trends in serum CRP and PCT levels may vary depending on the complication type. Pneumonia and anastomotic leakage after esophagectomy can be potentially distinguished by the postoperative trend of PCT values before detailed examinations, such as computed tomography and endoscopy.

Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era.

Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. In the current review, we provide an up-to-date summary of CGD pathophysiology, underpinning current methods of diagnostic testing for CGD and closely related disorders. We present an overview of the benefits of early diagnosis and when to suspect and test for CGD. We discuss current and historical methods for functional testing of NADPH oxidase activity, as well as assays for measuring protein expression of NADPH oxidase subunits. Lastly, we focus on genetic and genomic methods employed to diagnose CGD, including gene-targeted panels, comprehensive genomic testing and ancillary methods. Throughout, we highlight general limitations of testing, and caveats specific to interpretation of results in the context of CGD and related disorders, and provide an outlook for newborn screening and the future.

Airway breathing circulation dengue: a case of multifactorial shock due to major trauma and severe dengue infection

BackgroundDengue is the most common arboviral illness reported globally, endemic to most tropical and sub-tropical regions of the world. Dengue Shock Syndrome is a rare complication of severe Dengue infection resulting in haemorrhagic complications and refractory hypotension. We report on a case of severe dengue diagnosed in a patient with major trauma and illustrate some of the potential challenges and considerations in the clinical management of such cases.Case PresentationA 49-year-old female presented following a road trauma incident with multiple abdominal injuries requiring urgent laparotomy. Her recovery in Intensive Care Unit was complicated by the development of Dengue Shock Syndrome characterised by a falling haemoglobin and platelet count, multiorgan dysfunction and prolonged hospital stay.ConclusionsDengue Shock Syndrome may complicate fluid management and bleeding control in major trauma cases. Awareness of Dengue, particularly in endemic areas and returned travellers may help facilitate early diagnosis and management of complications.

A Single Large Center Experience of Medically Treating Impending Compartment Syndrome of Tibia with Deflazacort

Abstract Background: Acute compartment syndrome (ACS) is a rare condition characterized by increased pressure in the closed compartments of the limbs resulting in ischemic tissue necrosis. Most of the patients present following limb fractures. Apart from surgical options such as fasciotomy, which has inherent complication of myonecrosis and severe infection, conservative management with corticosteroids hasshown to be useful. We conducted this study to understand the changes in intra-compartment pressures in ACS after regular monitoring following corticosteroids treatment. Materials and Methods: Consecutive patients of ACS following closed fractures lower limb fractures of tibia or fibula from June 2021 to February 2022 were included. The intra-compartment pressure was measured using a manometer at the time of presentation and after 3, 6, 12, 24, 48, 72, and 96 h of treatment with tab Deflazacort 6 mg × 1 Tablet × Tds. The efficacy of treatment was assessed on the basis of changes in intra-compartmental pressure and improvement in the clinical signs and symptoms of ACS. Results: The study included 60 patients, most (63.3%) suffering from fracture of proximal tibia or fibula (36.7%), presenting with ACS. The mean age was 32.4 ± 8.6 years and most (53%) were males. We observed a statistically significant change (P &lt; 0.05) in the intra-compartment pressures from the baseline to 3 h, 24 h, 48 h, 72 h, and 96 h after corticosteroid treatment. None of these patients suffered from ischemic necrosis or any other complication of ACS. Conclusion: Our results suggest that the timely diagnosis of ACS in patients with lower limb fractures and early initiation of conservative management with corticosteroids can be a mainstay of treatment in these patients. This conservative approach can avoid surgical intervention and reduce the cost of management.

Vacation in Egypt associated with Shiga toxin-producing Escherichia coli infection in children and adolescents, northern Italy, 2023.

BackgroundHaemolytic uremic syndrome (HUS) is a severe complication of infection with Shiga toxin-producing Escherichia coli (STEC). Although the reservoirs of STEC are known, the source of the infection of sporadic cases is often unknown. In 2023, we observed several cases of bloody diarrhoea with STEC infection in children and adolescents returning from vacations.AimWe aimed to explore the association between travel and bloody diarrhoea with STEC infection in children and adolescents.MethodsWe included all children and adolescents with bloody diarrhoea with STEC infection identified in 2023 by the ItalKid-HUS Network surveillance system in northern Italy. We interviewed children's families and sent a questionnaire on recent travels abroad. The exposure time was between 3 days after arrival abroad and 5 days after return home. A self-controlled case series (SCCS) design was used in the analysis.ResultsOf the 43 cases, 11 developed HUS. Twenty-three cases did not travel abroad, while 20 had travelled to several destinations. The incidence rate ratio (IRR) associated with travel to Egypt was 88.6 (95% confidence interval (CI): 17.0-462). Serotype analysis excluded the possibility of a single strain causing the infections. We did not find the source of the infections.ConclusionThere is an elevated risk of acquiring STEC infection with bloody diarrhoea and HUS associated with travel to Egypt. Specific investigations to identify the source are needed to implement effective preventive measures.

Mucormycosis as a complication of COVID-19 coronavirus infection: eye symptoms

COVID-19 causes an immunosuppressive condition and increases the risk of secondary infections, including fungal diseases such as mucormycosis (MM), so doctors should be aware of the possibility of MM development in COVID-19 patients. Since no specific complaints or clinical symptoms exist and the disease is rare, especially in developed countries with a moderate climate, it is often impossible to diagnose MM at the initial examination. Therefore, the detection of the pathogen (mycelium zygomycetes) plays a key role in the diagnosis. Over 70 % of MM patients experience eye damages. According to the literature, the most common manifestations thereof are blepharoptosis, ophthalmoplegia, exophthalmos, injection and conjunctival chemosis. Quite often, the patients have eye pains, orbital cellulitis or phlegmon of the orbit, accompanied by a decrease in vision. For the effective treatment of this severe infectious COVID-19 complication, which takes the form of deep and aggressive mycosis, an interdisciplinary approach is necessary. The complex treatment should make use of antimycotic agents and symptomatic therapy, and, essentially, surgical rehabilitation of infection foci by removing the affected necrotic tissues. The prognosis is always very serious.

COVID-19 associated encephalopathy

Background. COVID-19 is a virus that affects the respiratory system most commonly. However, cases of widespread effects of COVID-19 on the human body have been emerging. During our search, we found that COVID-19 associated encephalitis has been reported in literature as a severe complication of COVID-19 infection. Case report. We report a case of COVID-19 associated encephalitis. Our patient had extensive inpatient morbidity because of this illness. Conclusions. We believe that COVID-19 associated encephalitis is a condition with high mortality and very limited data about risk factors, diagnosis and treatment, and, as such, more studies are needed to enhance medical knowledge regarding this disease.

Transcriptional responses of brain endothelium to Plasmodium falciparum patient-derived isolates in vitro.

Cerebral malaria (CM) is the most prevalent and deadly complication of severe Plasmodium falciparum infection. A hallmark of this disease is sequestration of P. falciparum-infected erythrocytes (IE) in brain microvasculature that ultimately results in breakdown of the blood-brain barrier. Here, we compared the effect of P. falciparum parasites derived from uncomplicated malaria (UM) and CM cases on the relative gene expression of human brain microvascular endothelial cells (HBMECs) for a panel of genes. We observed a significant effect on the endothelial transcriptional response in the presence of IE, yet there is no significant correlation between HBMEC responses and the type of clinical syndrome (UM or CM). Furthermore, there was no correlation between HBMEC gene expression and both binding itself and the level of IE binding to HBMECs. Our results suggest that interaction of IE with endothelial cells induces endothelial responses that are independent of clinical origin and not entirely driven by surface Plasmodium falciparum erythrocyte membrane protein 1 expression.

Usage of Meropenem Continuous Infusion for Treatment of Infectious Complications in Orthopedic Elderly Patients with Anemia: A Case Series.

Background and Objectives: The prolonged infusion of meropenem is recommended by guidelines for the treatment of sepsis. However, studies provide controversial data on the advantages of prolonged infusions over intermittent ones. In our opinion, this can be related to age, which possibly distorts the final data, as older people have age-related characteristics. In our study, we analyzed the ventilatory status, laboratory tests and vital signs of the patient and carried out microbiological cultures. Materials and Methods: This was a prospective single-center case series investigation conducted from June 2022 to June 2023. The objective of this study was to evaluate the effectiveness of continuous infusion in elderly patients with severe infectious complications after orthopedic interventions. The primary endpoints were 28-day survival and the emergence of new multidrug-resistant strains. Secondary endpoints were long-term mortality and length of stay in the ICU. Results: Three patients (median age 65, 100% female) received a continuous infusion of meropenem. Two patients were alive at hospital discharge, and one patient died on the 105th day of hospitalization. Multi-resistant bacteria were observed in one patient. Conclusions: The use of a continuous meropenem infusion in the complex treatment of purulent-septic complications in elderly patients with periprosthetic infection and anemia probably led to clinical improvement in these case reports. However, the emergence of new pan-resistant strains and overall mortality using this infusion technique remains unclear. Further, high-quality RCTs for the elderly are needed.

#1654 Infectious complications after kidney transplantation: a retrospective study

Abstract Background and Aims Infection is a major cause of morbidity among kidney transplant recipients. Allograft rejection is a frequent cause of dysfunction and its treatment increases the risk for both common and opportunistic infections. Nevertheless, its exact impact on infection incidence and further worsening of allograft dysfunction is not fully known. We aimed to characterize the incidence, nature, and severity of infectious complications following kidney transplantation, their association with previous rejection and its impact on allograft function. Method This was a single center retrospective study covering all patients transplanted between July 2021 and June 2023 in a tertiary referral center. Demographic and clinical data were collected from patient records, including donor and patient features, graft function over time and occurrence of either infection or rejection. Logistic regressions were adjusted considering sex, age, blood type and presence of diabetes as independent variables. Results A total of 139 patients were considered, 49 (35.3%) were women and 90 (64.7%) were men. Mean age was 49.6 ± 13.0 years. Median follow-up time was 375 [194-596] days. The main cause of renal disease was diabetes (37 patients, 26.8%) and most patients (113; 81.9%) were on hemodialysis for a median vintage of 3 [2.3] years. Considering the 139 transplants performed, 113 (81.2%) were isolated kidney, 24 (17.4%) were simultaneous kidney-pancreas and 2 (1.4%) were simultaneous kidney-liver transplantation. Eleven (7.9%) were living donor. During follow-up time, in-hospital infection occurred in 34 (24.4%) patients, mostly urinary (13, 38%) and blood stream (11, 32%) infections. These events significantly delayed hospital discharge (15.88 ± 8.52 vs 26.05 ± 14.3 days, p-value=0.001). During the follow up, a total of 107 (77%) patients developed 220 infection episodes leading to 47 hospital admissions. Urinary infections (64, 28.8%) and cytomegalovirus (CMV) viremia (64, 28.8%) were the most common at median follow-up time of 85.5 [40.25-183.75] and 159 [43.25-258.5] days, respectively. Median timing of diagnosis was 400.8 [203-614] days after transplant. They were much more common during the first three months (0.014 vs 0.002 per follow-up day). There were no differences in infection incidence between type of donor (p=0.76), type of allograft (p=0.361), immunosuppression protocol (thymoglobulin or basiliximab, p=0.45), renal replacement therapy or presence of diabetes. Regarding urinary infections, days of urinary catheterization (p=0.905), need for catheter replacement (p=0.092) or presence of residual diuresis (p=0.375) had no impact on infection rates. A positive correlation was found, between the number of infection episodes and creatinine increase over the first year (r=0.386; p&amp;lt;0.000). Allograft rejection was diagnosed and treated through protocol biopsy in 25 (18%) cases. These patients presented 17 confirmed episodes of infection over the three following months. Nine of them (36%) were CMV detectable viremias. Patients with a history of rejection had significantly more infections (1.49 ± 1.22 vs 2.20 ± 1.26, p=0.01), even after adjustment (p=0.006). Conclusion Early infections after kidney transplantation negatively impact hospital length of stay and allograft function. Furthermore, immunosuppressive treatment of allograft rejection carries a higher risk of infection. Further research is needed to clarify the impact of specific subsets of allograft rejection and immunosuppression protocols on the incidence of various types of infectious complications which could impair short-term renal function.

Targeted rescue of synaptic plasticity improves cognitive decline in sepsis-associated encephalopathy

Sepsis-associated encephalopathy (SAE) is a frequent complication of severe systemic infection resulting in delirium, premature death, and long-term cognitive impairment. We closely mimicked SAE in a murine peritoneal contamination and infection (PCI) model. We found long-lasting synaptic pathology in the hippocampus including defective long-term synaptic plasticity, reduction of mature neuronal dendritic spines, and severely affected excitatory neurotransmission. Genes related to synaptic signaling, including the gene for activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and members of the transcription-regulatory EGR gene family, were downregulated. At the protein level, ARC expression and mitogen-activated protein kinase signaling in the brain were affected. For targeted rescue we used adeno-associated virus-mediated overexpression of ARC in the hippocampus invivo. This recovered defective synaptic plasticity and improved memory dysfunction. Using the enriched environment paradigm as a non-invasive rescue intervention, we found improvement of defective long-term potentiation, memory, and anxiety. The beneficial effects of an enriched environment were accompanied by an increase in brain-derived neurotrophic factor (BDNF) and ARC expression in the hippocampus, suggesting that activation of the BDNF-TrkB pathway leads to restoration of the PCI-induced reduction of ARC. Collectively, our findings identify synaptic pathomechanisms underlying SAE and provide a conceptual approach to target SAE-induced synaptic dysfunction with potential therapeutic applications to patients with SAE.