High Risk Of Infectious Complications Research Articles

PROSPECTS FOR THE USE OF MESENCHYMAL STEM CELLS IN THE TREATMENT OF CONGENITAL EPIDERMOLYSIS BULLOSA

Epidermolysis bullosa (EB) is a hereditary orphan pathology caused by mutations in genes encoding structural cellular proteins necessary for the integrity of the skin and mucous membranes. As a result of minor mechanical stress, blisters with serous and/or hemorrhagic contents, long-term non-healing wounds and scars form on the skin. Such injuries have a high risk of infectious complications and often lead to disability of the patient. Current treatment methods are primarily palliative in nature and aimed at preventing complications, which emphasizes the relevance in new therapeutic strategies. Mesenchymal stem cells (MSCs) offer a promising therapeutic approach. MSCs are known for their multipotency, immunomodulatory properties, and ability to promote tissue repair, a potential treatment for epidermolysis bullosa. This literature review evaluates the therapeutic potential of MSCs in the treatment of VEB, highlighting key findings from recent studies.

TREC and KREC values in patients with congenital heart defects — neonatal screening data

Relevance. Children with congenital heart disease (CHD) are at high risk of infectious complications with unfavorable outcomes, which is associated with inadequate immune responses. TREC and KREC are recognized biomarkers of T- and B-cell lymphopoiesis.Objective of the study: to evaluate the number of circular DNA segments — TREC and KREC in children with congenital heart defects.Materials and methods. The study used data from neonatal screening for primary immunodeficiencies in the Stavropol region from January 1, 2023, to June 30, 2024. An analysis of TREC and KREC was conducted in 43 newborns with CHD compared to healthy infants.Results. The levels of TREC and KREC in children with CHD were lower than in healthy children. A correlation was established between TREC levels and absolute lymphopenia, as well as the development of infectious complications. A decrease in KREC was identified in infants with CHD and genetic syndromes. It was shown that a TREC level of less than 650 copies per 105 cells may be a predictor of the development of infectious complications in newborns with CHD.Conclusions. The reduction in the number of TREC and KREC copies in neonatal screening allows for the identification of children with CHD at high risk of infection, opening potential opportunities for preventive therapy.

Procalcitonin level threshold and antibiotic use in patients receiving chimeric antigen receptor T-cell therapy

ABSTRACT Background: Patients undergoing chimeric antigen receptor (CAR) T-cell therapy are vulnerable to infection and sepsis. Treatment course is frequently complicated by cytokine release syndrome which is often clinically and biochemically indistinguishable from sepsis. Procalcitonin (PCT) levels have been examined as a promising biomarker for infection in this cohort of patients. Methods: In this study, we measured daily PCT levels for patients for fourteen days (or hospital discharge) after receiving CAR T-cells to determine threshold PCT values specific for infection compared to those without infection. Results: We present preliminary results of our enrolled cohort to date (sixteen patients). Infection was present in only 12.5% of patients. However, those diagnosed with sepsis had elevated PCT levels with a peak mean of 2.6 µg/L observed on the seventh day post-treatment compared to those without infection remaining below 0.5 µg/L. Furthermore, we observed a trend for early and liberal antibiotic administration within our cohort. Conclusion: Our study highlights the challenges of antimicrobial stewardship in managing CAR T-cell therapy recipients. Our preliminary results underscore the utility of PCT in the risk-stratification and diagnosis of those patients at high risk for infectious complications after receiving CAR T-cell therapy and continue to advocate for a PCT threshold of 1.5 µg/L for diagnosing sepsis. Additionally, in the setting of CRS and lymphodepletion, where white cell count and CRP value are unreliable, a PCT value of < 0.5 µg/L may help exclude sepsis.

Sex-related differences in periprosthetic joint infection research.

Introduction: Periprosthetic joint infections (PJIs) have emerged as a focal point in the realm of orthopedics, garnering widespread attention owing to the escalating incidence rates and the profound impact they impose on patients undergoing total joint arthroplasties (TJAs). Year after year, there has been a growing trend in the analysis of multiple risk factors, complication rates, and surgical treatments in the field. This study aims to illuminate the status of the sex-related differences in periprosthetic joint infections and advance research in this field. Methods: A systematic review was carried out following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. The final reference list comprised longitudinal studies (both retrospective and prospective) and randomized controlled trials. A sex-based analysis was conducted to assess differences between males and females. Results: A total of 312 studies were initially identified through online database searches and reference investigations. Nine studies were subsequently included in the review. Eight out of nine studies examined the risk of developing PJI after total joint replacement. Notably, only half of these studies demonstrated a statistically significant value, with a value , indicating a higher risk of infectious complications in males compared to females. Conclusion: According to the current literature, there appears to be a propensity for males to develop periprosthetic joint infection after total joint arthroplasty at a higher rate than the female population. Enhancing sex-related analysis in this field is imperative for gathering more robust evidence and insights.

The role of stroke-induced immunosuppression as a predictor of functional outcome in the neurorehabilitation setting

Stroke affects the interconnection between the nervous and immune systems, leading to a down-regulation of immunity called stroke-induced immunosuppression (SII). The primary aim of this study is to investigate SII role as a predictor of functional, neurological, and motor outcomes in the neurorehabilitation setting (NRB). We conducted a prospective observational study enrolling post-acute stroke patients hospitalized for neurorehabilitation. At NRB admission (T0) and discharge (T1), we assessed presence of SII (defined by a neutrophil-to-lymphocyte ratio ≥ 5) and we evaluated functional independence (Functional Independence Measure-FIM, Barthel Index-BI), motor performances (Tinetti Score, Hauser Ambulation Index) and neurological impairment (NIHSS). We enrolled 96 patients (45.8% females, 70.6 ± 13.9 years, 88.5% ischemic stroke). At T0, 15.6% of patients (15/96) had SII. When compared to immunocompetent patients (IC), the SII group was characterized by worse baseline functional independence, motor performances and neurological disability. The same was confirmed at T1 (FIM p = 0.012, BI p = 0.007, Tinetti p = 0.034, NIHSS p = 0.001). Neurological disability demonstrated a less pronounced improvement in SII (ΔNIHSS: SII: − 2.1 ± 2.3 vs. IC: − 3.1 ± 2.5, p = 0.035). SII group presented a higher percentage of infectious complications during the neurorehabilitation period (SII 80% vs. IC 25.9%; p = 0.001). SII may represent a negative prognostic factor in the neurorehabilitation setting. SII patients were characterized by poorer functional, motor, neurological performances and higher risk of infectious complications. ClinicaTrial registration: NCT05889169.

Effectiveness and safety of primary prophylaxis with G-CSF after induction therapy for acute myeloid leukemia: a systematic review and meta-analysis of the clinical practice guidelines for the use of G-CSF 2022 from the Japan society of clinical oncology

Although granulocyte colony-stimulating factor (G-CSF) reduces the incidence, duration, and severity of neutropenia, its prophylactic use for acute myeloid leukemia (AML) remains controversial due to a theoretically increased risk of relapse. The present study investigated the effects of G-CSF as primary prophylaxis for AML with remission induction therapy. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis of pooled data was conducted, and the risk ratio with corresponding confidence intervals was calculated in the meta-analysis and summarized. Sixteen studies were included in the qualitative analysis, nine of which were examined in the meta-analysis. Although G-CSF significantly shortened the duration of neutropenia, primary prophylaxis with G-CSF did not correlate with infection-related mortality. Moreover, primary prophylaxis with G-CSF did not affect disease progression/recurrence, overall survival, or adverse events, such as musculoskeletal pain. However, evidence to support or discourage the use of G-CSF as primary prophylaxis for adult AML patients with induction therapy remains limited. Therefore, the use of G-CSF as primary prophylaxis can be considered for adult AML patients with remission induction therapy who are at a high risk of infectious complications.

Association of iron overload with infectious complications in liver transplant recipients: a systematic review and meta-analysis.

This study was performed to examine the possible association of iron overload with infectious complications and survival among liver transplant recipients. We conducted a systematic review and meta-analysis of studies published in the PubMed, Embase, Web of Science, and Cochrane Library databases up to September 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted to estimate the association of iron overload with infectious outcomes and overall survival after liver transplantation. Eight studies involving 2817 recipients met the inclusion criteria. Iron overload was strongly associated with an increased risk of infection after liver transplantation (HR, 1.66; 95% CI, 1.03-2.68). An increase in the serum ferritin level was associated with an increased risk of infection after liver transplantation (HR, 1.44; 95% CI, 1.09-1.91). Iron overload was a significant predictor of worse overall survival (HR, 1.35; 95% CI, 1.11-1.64). In addition, a high serum ferritin level was significantly associated with an increased risk of death (HR, 1.34; 95% CI, 1.10-1.64). Iron overload may be associated with a higher risk of infectious complications and a worse prognosis among liver transplant recipients.

Clinical case of treatment of true drowning in fresh water

Drowning is the third leading cause of unintentional injury death worldwide. The largest number of victims of drowning falls on the young able- bodied population.Objective. There are no recent intensive care protocols for drowning, it is relevant to formulate guidelines for the treatment of drowning. Clinical observation. A 25-year-old female patient was taken by an ambulance team to the intensive care unit with a directional diagnosis ‘drowning in fresh water’ of three degree of severity. The patient had got on ventilator with closed aspiration system. Emergency bronchoscopy was performed during which 200 ml of fluid aspirated into the lungs was removed. Respiratory support was determined by stepwise increase of the PEEP level and decrease in FiO2 level taking into account respiratory index. Given the development of a pro-inflammatory mediator response, lactatacidosis, hemolysis, hyperhydration, a high risk of infectious complications, it was decided to start extracorporeal treatment early by continuous veno-venous hemodiafiltration and de-escalation of systemic antibacterial therapy with meropenem by prolonged infusion. Against the background of the ongoing treatment, we managed to achieve target respiratory parameters and stabilize central hemodynamic parameters by the end of the first day, prevent the development of renal damage, correct water-electrolyte and metabolic disorders, and avoid severe septic complications. Vasopressor support was discontinued on the 4th day, and on the 5th day the patient was switched to independent breathing. The patient`s stay in the intensive care unit was 6 days.Conclusions. Stepwise respiratory therapy using closed suction systems and urgent bronchoscopy prevent direct damage to the alveoli and ongoing translocation of fluid into the vascular bed. Prescribing broad-spectrum antibiotics prior to the growth of clinical and laboratory signs of infectious lung lesions allows to reduce the risk of severe septic complications with pulmonary destruction parenchyma. Early onset extracorporeal treatment by CVVHDF allows to correct homeostasis disorders, eliminate hypervolemia, prevent the development of acute renal damage as a result of hemolysis.

Clinical impact of preservation fluid contamination on kidney transplant patients.

Kidney transplantation is associated with a high risk of infectious complications due to immunosuppressive therapy. Although infections may be transmitted from donor to transplant recipient through contaminated preservation solution (PS), the clinical impact of this is not well-understood. We retrospectively evaluated PS contamination rates in a series of 339 patients who underwent cadaveric renal transplant at our centre. All patients with a positive culture received targeted preemptive therapy (PET). Of the 339 PS samples, 136 (40.1%) were positive for a microorganism, mainly coagulase-negative staphylococci (CoNS; n = 89;60.5%), gram-negative bacilli (n = 31;21.1%), non-CoNS gram-positive cocci (n = 18;12.2%), and Candida spp (n = 2;1.4%). Of the 136 positive cases, 42 (30.9%) received PET (12.4% of the cohort). No cases of urinary tract infection, surgical site infection, or graft loss were observed. Overall, our findings indicate that PS contamination, mainly by saprophytic skin flora (CoNS) is common. Only 8% of patients required antibiotic or antifungal therapy. The infection transmission rate from donors to recipients was negligible (0%), perhaps due to the early initiation of a targeted PET after isolation of a recognized pathogen. More data from large, prospective studies are needed to confirm these findings.

BCMA-Directed CAR-T Cell Therapy Is Associated with a Higher Risk of Infections: A Systematic Review and Meta-Analysis

Background: Chimeric antigen receptor (CAR) T-cell therapy is a rapidly evolving immunotherapy for hematological malignancies. With increasing access to this modality, there is an urgent need for a comprehensive understanding of infectious complications to optimize prophylaxis and improve clinical outcomes. We conducted a systematic review and meta-analysis to assess the incidence and characteristics of infectious complications in adult patients receiving CAR T-cell therapy. Methods: The study was registered on PROSPERO and we searched 5 electronic databases from inception to 2022. Each author independently screened titles, reviewed full texts to identify eligible studies and extracted data from included studies using Covidence, a data extraction tool for conduction of standard systematic reviews. A random effects model was used, and proportions were used as a measure of outcome. We assessed heterogeneity using I^2 statistic. Risk of bias assessments were conducted using the RoB 2.0 for RCTs and ROBINS I tool for non-RCTs. Results: Our search identified 12,441 studies of which 363 underwent full-text review (Figure 1). 33 studies were eligible for inclusion in the analysis and enrolled a total of 2866 patients. The pooled incidence of an infectious event in adult patients after CAR T-cell therapy was 38% (95%CI 0.31, 0.46; p&amp;lt;0.01; I2 = 98%]. No significant difference was noted in the incidence among studies with a longer follow up duration compared to studies with follow up of £ 30 days [40% (95% CI 0.30-0.50) vs 32% (95% CI 0.24-0.40), p=0.20 respectively]. BCMA-directed CAR T-cell therapies used for management of multiple myeloma had a significantly higher incidence of infectious complications compared to CD19 targeted agents, 64% (95% CI 0.53-0.74, I2 = 65%) versus 39% (95% CI 0.30-0.49; I2 = 98%; p &amp;lt;0.01) respectively, Figure 2. Clostridium difficile and Escherichia coli were the most common pathogens causing bacterial infections, while cytomegalovirus was the most commonly identified viral pathogen affecting these patients. Conclusion: In this study, BCMA-directed CAR T-cell therapies were associated with a significantly higher risk of infectious complications. The results of this study can guide the development of strategies to prevent and manage infectious complications in this patient population.

Cellular Mechanisms Associated with Suboptimal Immune Responses to Sars-Cov-2 Bivalent Booster Vaccination in Patients with Multiple Myeloma

Background: In response to the ever-evolving challenges posed by the antigenically diverse Omicron variants, the deployment of bivalent mRNA booster vaccines encompassing both the ancestral (WA1) and Omicron BA.5 spike components was initiated in fall of 2022. The real-world impact of these bivalent vaccines is largely unknown in patients with Multiple Myeloma (MM). We characterize the humoral and cellular immune responses in patients with MM before and after receiving the bivalent booster implementing cutting edge methodologies to identify patterns associated with continuing vulnerability in the current post-pandemic era. Methods: We studied the humoral and cellular immune responses before and after bivalent booster immunization in 48 MM patients. Spike binding IgG antibody levels were measured by SARS-CoV-2 spike binding ELISA and neutralization capacity was assessed by a SARS-CoV-2 multi-cycle microneutralization assay. We measured spike specific T cell function using the QuantiFERON SARS-CoV-2 (Qiagen) assay as well as flow cytometry-based T cell assays quantifying interferon-gamma (IFNg) production. In a subset of 38 patients, immune profiling was performed using high-dimensional flow cytometry. The frequencies of dendritic cells (DCs), B cells, Natural Killer (NK) cells and T follicular helper cells (TFH) were compared between responders and non-responders. Results: The serological effect of the bivalent vaccination in MM patients is nuanced with the overall cohort not demonstrating a significant increase post bivalent vaccination (median 196 AU/mL prior to bivalent to median 276 post bivalent p=0.11). The lack of antibody response was driven by patients undergoing anti-CD38 and anti-BCMA antibody therapy as compared to MM patients undergoing other therapies who demonstrated a significant increase in antibody levels post vaccination (p=0.021). Patients on anti-CD38 and anti-BCMA antibody therapy also did not significantly increase neutralizing capacity to WA1 (p=0.42) or BA.5 omicron strain (p=0.48) while MM patients on other therapies benefitted significantly, as illustrated by the increased neutralizing capacity of WA1 (p=0.024) and BA.5 (p=0.0055 Figure 1A). In addition to quantifying antibody responses, we profiled T cell responses using our published flow cytometry method using WA1 anti-S peptides as well as the QuantiFERON SARS-CoV-2 RUO assay (Qiagen). Spike reactive T cell responses significantly correlated with anti-Spike IgG levels in MM patients (r 2=0.49, p&amp;lt;0.001), WA1 neutralizing ID50 (R 2 = 0.6, p&amp;lt;0.01) and BA.5 neutralizing ID50 (R 2= 0.54, p=0.01) reinforcing the fact that T cell compensation is lacking in MM patients. We separated the lowest quantile (patients with Anti-S IgG &amp;lt;156 AU/mL) to delineate suboptimal producing patients compared to the remaining MM anti-S producing patients. Non-responders exhibited deficiencies in immune populations involved in robust antibody production including lower frequency of CD1c+ DCs (p=0.02 Figure 1B), B Cells (p&amp;lt;0.01 Figure 1B) and circulating CXCR3-CCR4+TFH cells (p&amp;lt;0.01 Figure 1B). Furthermore, immature NK cells were the predominant population in non-responders, while responders had more cytotoxic mature NK phenotype (p&amp;lt;0.01 Figure 1B) after bivalent vaccination. Conclusions: Our study highlights the varying immune responses observed in MM patients after receiving bivalent COVID-19 vaccination. Specifically, a subgroup of MM patients undergoing anti-CD38 and anti-BCMA therapy experience impairments in immune cells such DCs, B cells, NK cells and TFH cells, leading to an inability to generate adequate antibody and T cell responses to vaccinations. Our results indicate that the QuantiFERON SARS-CoV-2 assay could be deployed for clinical use bridging the need for suitable laboratory tests to measure SARS-CoV-2 specific T cell responses. Ongoing research will further investigate whether the compromised immune machinery and diminished T cell activity identified in this study can serve as discriminators for identifying MM patients at high risk of infectious complications stemming from anti-BCMA therapies. Such insights will aid in developing targeted strategies to address these challenges and improve patient outcomes.

Large-Scale Post-Transplant TCR Deep Sequencing Reveals a Major T Cell Diversity Bottleneck with Post-Transplant Cyclophosphamide with Implications for Both Efficacy and Toxicity: Results of the BMT CTN 1801 Study

Background: BMT CTN 1703 was a Phase 3 trial comparing Tac/MTX (n = 217) to post-transplant cyclophosphamide (PT-Cy)/Tac/MMF (n = 214) GVHD prophylaxis after reduced intensity conditioning unrelated donor hematopoietic cell transplant (HCT). PT-Cy significantly improved GVHD-free Relapse-Free Survival (Bolanos-Meade et al NEJM 2023). However overall survival was not significantly different and the # of Grade 2 infections was higher with PT-Cy. To investigate its biologic underpinnings 1703 was linked to a mechanistic study, BMT CTN 1801, which co-enrolled 324 pts (159 CNI/MTX 165 PT-Cy). The resulting dataset enabled an analysis of post-HCT T cell reconstitution at an unprecedented level of detail. Methods: Samples were collected from the HCT infusion and on D+7, 14, 28, 63, 98, 180, 270, 1- and 2-yr. We extracted DNA (2,225 samples) and performed Adaptive Biotech β-strand T Cell Receptor (TCR) Immunosequencing (TCR-Seq). We profiled 44,077 (median) TCRs/sample resulting in 215,155,719 T cells analyzed. We evaluated multiple TCR diversity measures longitudinally and before/after cGVHD and infections. Each measure evaluates a specific aspect of TCR diversity, including Simpsons Clonality (focuses on the most expanded clones) Diversity Slope (mid-range clones) Richness (both mid-range and less-expanded clones) and Singletons (the TCR-Seq equivalent of naïve T cells). This analysis was robust to the full range (1000-50,000) of down-sampled TCRs sequenced. Results: We identified major differences in TCR reconstitution in Tac/MTX vs PT-Cy that begin early and persist through 2 yr post-HCT. These resulted in a significantly less diverse TCR repertoire with PT-Cy with substantial implications for its efficacy and toxicity. The most salient differences are: (1) PT-Cy caused significant in-vivo T cell depletion early post-HCT (% T cells/total WBC at D+28: 8.2% (Tac/MTX) vs 2.2% (PT-Cy) p=2.2x10 -23). (2) The remaining donor T cells in PT-Cy undergo substantial clonal expansion ( Fig 1) resulting in significantly constrained TCR diversity measured by Clonality, Slope, Richness, Singletons (not shown) and Singletons/Richness ( Fig 2) which began early (D+14) and persisted for 2 yr. (3) Linked T cell depletion and clonal expansion resulted in a TCR diversity bottleneck after PT-Cy ( Fig 1). Due to the bottleneck, while the fraction of T cells originating from the transplant infusion at =/&amp;gt; 1 yr was similar between arms (18% vs 24%, p=0.7) there were significantly fewer Singleton TCRs in PT-Cy, suggesting a reduction in naïve T cells ( Fig 2), an outcome that has critical consequences for both cGVHD and infection. Thus while cGVHD onset with Tac/MTX was linked to a significant drop in TCR diversity due to singleton clonal expansion (median log-2 fold change in singletons with Tac/MTX = -0.25 p = 0.01) this drop was not observed with PT-Cy (log-2 fold change = -0.05, p = 0.1). Along with the significantly decreased # singletons at all time-points in PT-Cy ( Fig 2) this suggests that while cGVHD after Tac/MTX is linked to substantial naïve T cell expansion, the same is not true with PT-Cy, identifying a novel mechanism for cGVHD control with PT-Cy. The substantially fewer singletons in PT-Cy vs Tac/MTX may also increase the risk of Grade 2+ infections. T cell responses to new infections rely on antigen recognition/effector maturation of naïve (singleton TCR) T cells. After infection, the TCR repertoire became less diverse for both Tac/MTX and PT-Cy (log-2-fold singleton change -0.17 and -1.2 p = 0.0006 and 0.01) indicating that singletons in both cohorts were capable of expanding to pathogens. However the markedly decreased # singletons in PT-Cy at all timepoints was associated with significantly fewer singletons prior to infection (mean 3979 at 5K read-depth for Tac/MTX vs 2820 for PT-Cy p&amp;lt;0.001). This singleton deficit would place PT-Cy patients at higher risk of missing the critical mass of TCRs required to respond effectively to infections, consistent with their increased rate of Gr 2 infections. Conclusions: We performed longitudinal TCR-Seq on &amp;gt;200 million T cells from 324 HCT patients, representing the largest post-HCT TCR-Seq analysis in the history of the field, and enabling novel insights into TCR dynamics. These data identify a previously unappreciated global TCR diversity bottleneck with PT-Cy that simultaneously protects patients from cGVHD and places them at higher risk of infectious complications.

Management of biliary obstruction in patients with newly diagnosed alveolar echinococcosis: a Swiss retrospective cohort study.

Alveolar echinococcosis, an orphan zoonosis affecting the liver, is of increasing concern worldwide. Most symptomatic cases present at an advanced and inoperable stage, sometimes with biliary obstruction prompting biliary tract interventions. These are, however, associated with a high risk of infectious complications. The aim of this retrospective study was to compare the effectiveness and safety of conservative and interventional treatment approaches in patients with newly diagnosed alveolar echinococcosis and biliary obstruction. Alveolar echinococcosis patients treated at two referral centres in Switzerland, presenting with hyperbilirubinaemia (total bilirubin >1.5 Upper Limit of Normal) at diagnosis were included, unless another underlying aetiology, i.e. common bile duct stones or decompensated cirrhosis, was identified. Patients were divided into two groups, according to whether they initially received a biliary tract intervention. The primary endpoint was normalisation of bilirubin levels within a 6-month period. Secondary endpoints included, among others, the occurrence of early and late biliary complications, the need for biliary tract interventions during follow-up and overall duration of hospital stays for treatment initiation and for biliary complications. 28 patients were included in this study, of whom 17 received benzimidazole therapy alone and 11 additionally received a biliary tract intervention. Baseline characteristics did not differ between groups. All but one patient in each group achieved the primary endpoint (p=0.747). Biliary tract intervention was associated with faster laboratory improvement (t1/21.3 vs 3.0 weeks), but also with more frequent early biliary complications (7/11 vs 1/17, p=0.002) and longer initial hospital stay (18 days vs 7 days, p=0.007). Biliary obstruction in patients with newly diagnosed alveolar echinococcosis can be treated effectively with benzimidazole therapy alone. Biliary tract intervention, on the other hand, is associated with a high complication rate and should probably be reserved for patients with insufficient response to benzimidazole therapy.

Сепсис-асоційоване ураження нервової системи в передчасно народжених дітей із дуже малою масою тіла

The immaturity of the organs and systems of preterm born children significantly complicates the differentiation between physiological and pathological changes in the brain. The etiology of brain damage in premature babies is complex and multifactorial, and even with the most favorable course of the neonatal period, they require additional respiratory support, a large number of invasive medical interventions and have a high risk of infectious complications. Sepsis-associated encephalopathy (SAE) is defined as diffuse or multifocal cerebral damage that is caused by a systemic response to infection even without clinical or laboratory evidence of direct brain infection. Purpose - to determine the clinical features of sepsis-associated brain damage in prematurely born children &lt;32 weeks gestation with a birth weight &lt;1500 g. Materials and methods. 38 prematurely born children, who were divided into two groups, were examined. The Group I (n=14) included children who were diagnosed with sepsis in the early neonatal period. The Group II (n=24) included prematurely born, in which no septic lesions were observed. Results. Children of both groups were born in a state of severe and moderate asphyxia. Analysis of associations between maternal, obstetric, and antenatal factors showed a significant prevalence of such factors as prelabor rupture of membranes, сervical weakness, rupture of the fetal bladder, and placement of an obstetric pessary in children with sepsis. All children with sepsis had pneumonia, acute kidney injury, and brain injury in the neonatal period. In the neurological status of children with very low birth weight who underwent SAE, the seizure syndrome, 3-4 grade intraventricular hemorrhages, periventricular leukomalacia, complications in the form of post-hemorrhagic ventriculomegaly were significantly more common. Conclusions. In children with very low birth weight who underwent SAE, convulsive syndrome, 3-4 grade intraventricular hemorrhages, and periventricular leukomalacia were significantly more common. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Postoperative infections associated with microvascular free flaps in head and neck reconstruction: Analysis of risk factors and results with a standardized prophylaxis protocol

Currently, large defects of the head and neck regions are mainly reconstructed using microvascular free flap. Postoperative infections, including surgical site infections (SSIs) and medical postoperative infections (MPI), are important causes of morbidity and worsening of surgical outcomes. The authors aimed to analyze the results obtained using a standardized prophylaxis protocol in a series of 100 consecutive patients who underwent microvascular reconstruction surgery between 2016 and 2021 at a single institution, to identify the risk factors, which could be overcome, to minimize the incidence of infectious complications. In this study, 24 patients developed infectious complications. Higher American Society of Anesthesiologists(ASA) score was statistically associated with higher risk of infectious complications (p=0.01), need for postoperative transfusions (p=0.01), and higher T and N stage (p=0.03 and p=0.02, respectively) in patients with cancer. We also found a correlation between the increase in surgery duration, hospitalization, and intensive care unit (ICU) stay with higher risk of infection (p=0.03, p=0.01, and p=0.001, respectively). Nine patients reported partial or total flap necrosis and in this group of patients, a higher incidence of infectious complication was recorded (p=0.001). Our experience shows that SSIs and MPIs affect the global and surgical outcomes of patients and both their incidences can be reduced by correcting potential risk factors preoperatively (e.g., anemia), intraoperatively (amount of blood loss and duration of surgery), and postoperatively (duration of hospitalization and ICU stay and early elimination of potential sources of infection).

Expanding the scope of the infectious diseases pharmacist in HCT: Beyond antimicrobial stewardship.

Infectious disease (ID) pharmacists and antimicrobial stewardship (AMS) programs are integral to the infection management of hematopoietic cell transplant (HCT) recipients demonstrating effective implementation of clinical pathways, de-escalation of empirical antibiotics for febrile neutropenia (FN), allergy assessments, and use of rapid diagnostic testing. The HCT procedure is complex, dynamic, and a high risk for infectious complications. Therefore, there is an important role for an ID and AMS pharmacist to collaborate with the primary treating team, with ongoing care, involving the optimal individual patient prophylactic, pre-emptive and treatment management of infections in this high-risk population. This review highlights key factors for consideration of ID/AMS Pharmacists in relation to HCT, including important aspects in the evaluation of infection risk prior to transplant, risk from donor sources, length of, and changes in immunosuppression, and potential drug-drug interactions from other essential supportive care therapies.

Severe infections in peritoneal dialysis and home hemodialysis patients: An inception cohort study.

Infections are the most common non-cardiovascular cause of death among dialysis patients. Earlier studies have shown similar or higher risk of infectious complications in peritoneal dialysis (PD) compared to hemodialysis (HD) patients, but comparisons to home HD patients have been rare. We investigated the risk of severe infections after start of continuous ambulatory PD (CAPD) and automated PD (APD) as compared to home HD. All adult patients (n = 536), who were on home dialysis at day 90 from starting kidney replacement therapy (KRT) between 2004 and 2017 in Helsinki healthcare district, were included. We defined severe infection as an infection with C-reactive protein of 100 mg/l or higher. Cumulative incidence of first severe infection was assessed considering death as a competing risk. Hazard ratios were estimated using Cox regression with propensity score adjustment. The risk of getting a severe infection during the first year of dialysis was 35% for CAPD, 25% for APD and 11% for home HD patients. During five years of follow-up, the hazard ratio of severe infection was 2.8 [95% CI 1.6-4.8] for CAPD and 2.2 [95% CI 1.4-3.5] for APD in comparison to home HD. Incidence rate of severe infections per 1000 patient-years was 537 for CAPD, 371 for APD, and 197 for home HD patients. When excluding peritonitis, the incidence rate was not higher among PD than home HD patients. CAPD and APD patients had higher risk of severe infections than home HD patients. This was explained by PD-associated peritonitis.

#4793 DOES PRIOR ABDOMINAL SURGERY INFLUENCE TECHNIQUE SURVIVAL OF PERITONEAL DIALYSIS PATIENTS?

Abstract Background and Aims Prior abdominal surgery may result in peritoneal membrane adhesions and fibrosis, compromising the success of peritoneal dialysis (PD). The impact of this factor on peritoneal membrane function and PD technique survival has not been adequately investigated. The aim of our study was to disclosure the effect of prior abdominal surgical procedures on PD technique survival (main outcome), efficacy rates and also evaluate the risk of infectious complications (secondaries outcomes). Method We performed a retrospective, longitudinal study, that included 155 PD patients followed at our unit, since September 2018 to September 2022. Two groups were created: G1 (without previous abdominal surgery) and G2 (with previous abdominal surgery). Demographic and clinical characteristics, such as age, gender, chronic kidney disease (CKD) etiology, time on PD program, dialytic efficacy (Kt/V), peritoneal equilibration test results and episodes of peritonitis were registered from our unit database. Statistical analyses were performed using SPSS statistics version 23,0. The statistical hypothesis tests with p-value &amp;lt;0,05 were considered significant. Results One-hundred and fifty-five patients (female: 50,9%) with a mean age of 55,4 ± 7 years were selected. The main CKD cause was glomerular diseases (n = 43, 27,7%), followed by uncertain etiology (n = 32, 20,6%) and autosomal dominant polycystic kidney disease (n = 21, 13,5%). G1 (n = 87; 56,1%) and G2 (n = 68; 43,9%) had similar distributions of gender (female: 50,6% vs 47,1%, p = 0,061), age (50,4± 9 vs 55,4 ±10 years, p = 0,076) and dialysis vintage (27,9 vs 28,2 months, p = 0,081). In G1, 62,1% of patients were on continuous ambulatory peritoneal dialysis (vs 55,9% in G2). The majority of patients were high-average transporters in both groups (58,6% vs 54,4%, p = 0,066). Previous comorbidities were (G1 vs G2): arterial hypertension (95,4% vs. 98,5%, p = 0,87), diabetes (27,6% vs. 26,5%, p = 0,83), heart failure (25,3% vs. 26,5%, p = 0,64), peripheral arterial disease (28,7% vs 35,3%, p = 0,082), body mass index &amp;gt;30 kg/m2 (20,7% vs 29,4%, p = 0,072) and dyslipidemia (64,4% vs. 64,7%, p = 0,91). In G1, Kt/V was inferior a 1,7 in 36,8% of patients (vs 66,2% in G2, p&amp;lt;0,001). Seven patients (8,1%) have reported more than one peritonitis during time in PD in group 1 (vs 32,4% in G2, p&amp;lt;0,001). We found no differences in PD technique survival between both groups. Transition to hemodialysis happened in 26,4% of patients in G1 (vs 26,5% in G2, p = 0,092). Mortality rate was similar in both groups (6,9% vs 10,3%, p = 0,063). Conclusion According to our results, prior abdominal surgical procedures do not appear to compromise technique survival in patients on PD. Although, abdominal surgical events places PD patients in a higher risk of infectious complications and lower efficacy rates. Thus, this group of patients deserve a more detailed evaluation before starting PD, in order to understand if they are good candidates for the technique, as this may not be the most advantageous for them in the long term.

Oral antibiotic prophylaxis for infection in patients with vascular anomalies receiving sirolimus treatment: a multicenter retrospective study

ObjectivesPatients with vascular anomalies (VAs) who receive oral sirolimus may be at high risk of infectious complications. Antibiotic prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) has been advocated. However, there have been few evidence-based analyses on this topic. This study assessed the effect of prophylactic TMP-SMZ on the incidence of infections in VA patients receiving sirolimus monotherapy.MethodsA retrospective, multicenter chart review was performed on all VA patients receiving sirolimus treatment from August, 2013 to January, 2021.ResultsBefore January 2017, 112 patients were treated with sirolimus without antibiotic prophylaxis. In the subsequent period, 195 patients were treated with TMP-SMZ for at least 12 months during sirolimus therapy. The percentage of patients with at least one serious infection during the initial 12 months of sirolimus treatment did not differ between the groups (difference, 1.1%; 95% CI − 7.0–8.0%). We observed no difference in the incidence of individual infection or total adverse events between the groups. The rate of sirolimus discontinuation due to adverse events did not differ significantly between groups.ConclusionsWe demonstrated that prophylactic TMP-SMZ does not decrease the incidence of infection or improve tolerance in VA patients receiving sirolimus monotherapy.

SAFETY OF PERIOPERATIVE BIOLOGICS IN PATIENTS WITH IBD UNDERGOING RESECTIVE BOWEL SURGERY: THE MUNICH IBD CENTER EXPERIENCE

The risk of biologics in the peri-operative setting in IBD is still discussed controversially. Recently, the large prospective PUCCINI trial could demonstrate that direct exposure to TNF-blockers within 12 weeks before abdominal surgery was not associated with a higher risk of infectious complications. However, in daily clinical practice experiences on biological treatment perioperatively are limited. In our current retrospective trial, we addressed the safety of different biologicals in a peri-operative setting.