Severe Infectious Complications Research Articles

Risk factors associated to infectious complications in children with febrile neutropenia induced by chemotherapy: A cohort study.

e22535 Background: Children cancer is the second cause of mortality, most of deaths are related to infectious complications due to immunosuppression provoked by chemotherapy. Febrile neutropenia is one of the most common issues in oncological patients and it’s considered an emergency. Studies have tried risk predicting models implementation, although they still need to be validated, updated and reproducible in different scenarios. The aim of this study was the early identification of conditioning factors to severe infectious complications in patients with febrile neutropenia that would allow taking decisions for diagnosis and treatment. Methods: We present a prospective cohort study that estimated the risk associated to clinical and paraclinical factors and the development of infectious complications in pediatric patients with febrile neutropenia induced by chemotherapy on their admission of an emergency room (ER). The clinical features analyzed were: age, type of cancer, chemotherapy regime, time between chemotherapy administration and ER admission, use of colony-stimulating factors, presence of central venous catheter, highest temperature registered, tachycardia, polypnea, hypoxemia and hypotension. The paraclinical features included were leucocyte, neutrophil and monocyte count, and C-reactive protein levels. Results: From 186 febrile neutropenia events, 101 cases reported infectious complications (54%). Clinical infection was the most frequent issue (38%). On the multivariate analysis we found that the features independently associated to infectious complication were tachycardia (OR1.07, CI95% 1.70-6.99) and highest temperature level reported in the ER (OR1.07, CI95% 1.00-1.13). Conclusions: Febrile neutropenia is the most common complication in pediatric oncological patients and it is related to life-threatening infections and high mortality rate. Risk prediction during the initial assessment in the ER is important to stratify patients and offer target therapy to decrease complications and prolonged hospitalization.

Risk of hospitalization and death from COVID-19 infection in patients with chronic plaque psoriasis receiving a biologic treatment and renal transplant recipients in maintenance immunosuppressive treatment

Risk of hospitalization and death from COVID-19 infection in patients with chronic plaque psoriasis receiving a biologic treatment and renal transplant recipients in maintenance immunosuppressive treatment

Failure to Prevent Severe Graft-Versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide in Chronic Granulomatous Disease.

Haploidentical related donor (HRD) transplantation was performed in 7 recipients with chronic granulomatous disease (CGD) who had no matched-related or unrelated donor. Peripheral blood cell (PBC) products were used with a conditioning regimen consisting of low-dose cyclophosphamide, fludarabine, total body irradiation, and busulfan. Graft-versus-host disease (GVHD) prophylaxis consisted of high-dose post-transplant cyclophosphamide and sirolimus. Recipients were ages 14-26years, and 3 had severe infections active at transplant. All 7 recipients achieved full engraftment with complete donor chimerism early in the post-transplant period. Acute GVHD occurred in all cases and was grade 3 or steroid refractory in 3. Two patients with steroid-refractory GVHD died. Three patients with severe infectious complications active at transplant, 1 Nocardia pneumonia and 2 extensive invasive fungal infections), survived and were cured of their infection at last follow-up. Bacterial disease occurred post-transplant in all recipients, and viral infections/reactivation were common, including 4 cases of BK virus-associated hemorrhagic cystitis. Seven patients with CGD achieved rapid and full-donor engraftment from HRDs utilizing PBCs and a conditioning regimen with PTCy and sirolimus GVHD prophylaxis. However, the incidence of grade 3 and steroid-refractory GVHD was high and led to 2 deaths. Patients with active infections at transplant had successful transplant courses and were cured of their disease. Although there was an initial success with this regimen, the cumulative experience does not support its use in CGD due to an unacceptable rate of severe GVHD.

Diagnostic utility of procalcitonin in children with infectious complications during chemotherapy-induced neutropenia: single center experience, literature review

Background. Infectious complications cause significant mortality in children with oncological diseases during chemotherapy-induced neutropenia. The absence of sensitive and specific signs and symptoms of infectious conditions as well as its microbiological identification, leads to inappropriate antibiotic exposure. The use of laboratory biomarkers (procalcitonin (PCT) and C-reactive protein (CRP)) may be helpful for differential diagnostics of inflammatory conditions and for rational antimicrobial therapy.Objective: to assess the current value of PCT as an additional marker for differentiating inflammatory conditions in children with chemotherapy-induced neutropenia.Materials and methods. We presented the analysis of infectious complications in pediatric patients with oncological and onco- / hematological diseases between 2017–2020 (54 patients from 2 mnths – 17 years). PCT and CRP with clinical and instrumental diagnostic data were used for differential diagnosis of fever and development of antimicrobial therapy decision rules. Literature review concerning the discussed theme from 2006–2018 was done.Results. Eighty-five infectious episodes in 36 months were registered, among them 42 in pts with onco- / hematological diseases and 43 – with solid tumors. In the group of bacterial infectious complications mean CRP and PCT values were significantly higher than in group of nonbacterial, moreover the discriminative value was higher for PCT. We revealed the correlation between severity of infectious complications and values of markers of acute-phase reactions. In case of non-severe bacterial complications and other types of infections significant difference was revealed only for PCT mean values.Conclusion. Specificity of PCT concentration in bacterial infections exceeds that of CRP, which confirms the hypothesis of advantages in using PCT as differential marker of inflammatory conditions in children with malignancies.

Dextrose-Containing Carrier Solution for Hyperthermic Intraperitoneal Chemotherapy: Increased Intraoperative Hyperglycemia and Postoperative Complications.

Intraoperative hyperglycemia is associated with infectious complications in general surgery patients. This study aimed to determine if the use of lactated Ringer's (LR) carrier solution during hyperthermic intraperitoneal chemotherapy (HIPEC) would lower the incidence of intraoperative hyperglycemia and improve postoperative outcomes when compared with a standard 1.5% dextrose peritoneal dialysate carrier solution. This is a retrospective cohort study of 134 patients who underwent HIPEC at the University of Colorado. Perioperative glucose levels and outcomes were compared between patients who were perfused with 1.5% dextrose peritoneal dialysate carrier solution (n = 68) versus LR carrier solution (n = 66). The study population consisted of patients undergoing HIPEC for appendiceal (50%), colorectal (34%), mesothelioma (8%), and ovarian cancer (5%). Intraoperative severe hyperglycemia (glucose ≥ 180mg/dL) was significantly more common among patients perfused with a dextrose-containing carrier solution versus those perfused with LR (88% vs. 21%; p < 0.001). Patients in the dextrose cohort had significantly more severe complications (39% vs. 12%; p = 0.034), infectious complications (35% vs. 15%; p = 0.011), and organ space infections (18% vs. 5%: p = 0.026) than the LR cohort. On multivariable analysis, dextrose-containing carrier solution was significantly associated with an increased risk of postoperative infectious complications (HR 5.16; p = 0.006). Intraoperative hyperglycemia is common when dextrose-containing carrier solution is used during HIPEC, and severe intraoperative hyperglycemia is strongly associated with an increased risk for infectious of complications following HIPEC. LR carrier solution should be routinely used to reduce intraoperative hyperglycemia and its associated risks.

Anti-CD20 immunosuppressive disease-modifying therapies and COVID-19

Anti-CD20 immunosuppressive disease-modifying therapies and COVID-19

INFECTIOUS COMPLICATIONS IN A PATIENT WITH SYSTEMIC SCLERODERMA AND MULTIPLE ORGAN DYSFUNCTION: A CASE REPORT

Systemic scleroderma is an autoimmune connective tissue disease with characteristic lesions of the skin, blood vessels, musculoskeletal system and internal organs (kidneys, heart, lungs, and digestive tract) based on impaired microcirculation, inflammation and generalized fibrosis. At the stage of provisional diagnosis, the triad of the initial signs of the disease is especially important including Raynaud’s syndrome, characteristic skin lesions, and joint syndrome. Subsequently, multiple organs and tissues are involved in the process. Infectious complications are one of the major threats to patients with systemic connective tissue disease, along with cardiovascular and cancerous diseases. Based on retrospective analysis, it has been found out that the incidence of comorbid infections in the in-patients with rheumatic diseases made up 9.7%; with predominant damage to respiratory organs was 44%, urinary tract – 29.2%, and skin and soft tissues – 18.9%. Comorbid infections were the most common in patients with systemic lupus erythematosus (28.4%) and rheumatoid arthritis (13.2%). Infections constitute 2-9% of overall causes of mortality in patients with systemic scleroderma. Cases of serious infections (pneumonia, sepsis, bacterial arthritis, skin and soft tissues lesions, etc.) have been recorded, including those with fatal outcomes. The problem of differential diagnosis of systemic infectious process and rheumatic diseases with high activity is extremely important. The paper presents a clinical case of subacute course of systemic scleroderma with multiple organ dysfunction affecting lungs (pneumofibrosis, pulmonary hypertension), heart (restrictive cardiomyopathy, atrial flutter), kidneys (nephritis) conjoined with severe infectious complications (septicemia, phlegmon of the soft tissues of the left leg). The present clinical case clearly demonstrates a severe subacute course with multiple organ dysfunction affecting lungs, heart, kidneys, digestive tract. Immunodeficiency was accompanied by severe infectious complications, in particularly, septicemia, soft tissue phlegmon, having complex pathogenesis that required prolonged intensive care.

The COVID-19 pandemic and the use of MS disease-modifying therapies

The COVID-19 pandemic and the use of MS disease-modifying therapies

The impact of nephrostomy drainage prior to mini-percutaneous nephrolithotomy in patients with ESBL-positive Escherichia coli.

Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is one of the most frightening multidrug-resistant bacteria that usually causes sepsis. Herein we explored the benefits of nephrostomy drainage prior to percutaneous nephrolithotomy (PCNL) on infection outcomes in patients with ESBL-EC. Between June 2016 and April 2019, 43 consecutive patients with ESBL-EC who received nephrostomy drainage for > 24h prior to PCNL were retrospectively evaluated as group 1. 86 patients were randomly selected from patients with ESBL-EC who received concurrent percutaneous access during PCNL as group 2. The postoperative infection complications were compared. Although the total infection complications were not statistically different (11.6% vs. 25.6%, p = 0.066), the severity seemed to be worse among group 2 subjects. Severe infections, including urosepsis (4.7% vs.13.9%) and septic shock (2.3% vs 4.6%), were observed at twice or greater rates in group 2. Blood transfusions were also more frequent (2.3% vs. 13.9%, p = 0.039). Multivariate analysis demonstrated that preoperative drainage was an independent risk factor for postoperative infection events (OR 2.31 CI 1.14-3.48, p = 0.017). Subgroup analyses indicated that preoperative drainage may largely reduce the incidence of urosepsis in patients with hydronephrosis or without receiving preoperative carbapenem therapy. Because of the high rate of severe infection after PCNL in patients with ESBL‑positive E. coli, preoperative nephrostomy drainage for > 24h is an effective measure to reduce the risk of severe infection complications, especially in patients with hydronephrosis or those without preoperative carbapenem therapy.

Parasite histones mediate blood–brain barrier disruption in cerebral malaria

Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection. Despite effective antimalarial drugs, 10–20% of children developing CM die, contributing to 400,000 malarial deaths per year, mostly in children in sub-Saharan Africa.[1,2][1] A defining feature of CM is the

Nonhome Discharge as an Independent Risk Factor for Adverse Events and Readmission in Patients Undergoing Anterior Cervical Discectomy and Fusion.

A retrospective study of a prospectively collected cohort. To characterize a cohort of patients who underwent anterior cervical discectomy and fusion (ACDF) and examine whether nonhome discharge (NHD) is associated with postdischarge adverse events (AEs) and readmission. Predictors of NHD have been elucidated in the spine surgery literature, and NHD has been tied to poor outcomes in the joint arthroplasty literature, but no such analysis exists for patients undergoing ACDF. All patients who underwent ACDF from 2012 to 2015 in the National Surgical Quality Improvement Program were identified. Those who underwent concomitant posterior cervical operations were excluded. Patients who were discharged to home were compared with those discharged to nonhome destinations on the basis of demographics and outcomes. Multivariable models were created to assess whether NHD was an independent risk factor for postdischarge AEs and readmission. NHD patients were significantly older (63.96 vs. 53.57 y; P<0.0001), more functionally dependent (13.87% vs. 1.09%; P<0.0001), more likely to have body mass index >40 (9.38% vs. 7.51%; P=0.004), and more likely to have ASA Class >2 (77.89% vs. 39.57%; P<0.0001). Patients who underwent NHD were significantly more likely to suffer severe AEs (14.44% vs. 0.93%; P<0.0001), minor AEs (7.22% vs. 0.24%; P<0.0001), and infectious complications (3.58% vs. 0.13%; P<0.0001) before discharge. When examining AEs after discharge, patients who underwent NHD were more likely to suffer severe AEs (6.37% vs. 1.34%; P<0.0001), minor AEs (4.09% vs. 0.74%; P<0.0001), death (1.25% vs. 0.07%; P<0.0001), and unplanned readmission (10.12% vs. 3.06%; P<0.0001). In adjusted analysis, NHD was found to independently predict severe AEs after discharge (odds ratio, 2.40; 95% confidence interval, 1.87-3.07; P<0.0001) and readmission (odds ratio, 1.77; 95% confidence interval, 1.46-2.14; P<0.0001). NHD patients were significantly sicker than those discharged home. In addition, NHD is associated with higher rates of postdischarge complications.

Ceftazidime/Avibactam and Ceftolozane/Tazobactam for Multidrug-Resistant Gram Negatives in Patients with Hematological Malignancies: Current Experiences.

Patients suffering from hematological malignancies are at high risk for severe infections, including in particular bloodstream infections, which represent one of the most frequent life-threatening complications for these patients, with reported mortality rates reaching 40%. Furthermore, a worrisome increase in antimicrobial resistance of Gram-negative bacteria (e.g., cephalosporin- and/or carbapenem-resistant Enterobacteriaceae and multidrug-resistant (MDR) Pseudomonas aeruginosa) involved in severe infectious complications among patients with hematological malignancies has been reported during the last years. The two novel combination of cephalosporins and β-lactamase inhibitors, ceftolozane/tazobactam and ceftazidime/avibactam, were recently approved for treatment of complicated intra-abdominal and urinary tract infections and nosocomial pneumonia and display activity against several MDR Gram-negative strains. Although not specifically approved for neutropenic and/or cancer patients, these drugs are used in this setting due to increasing rates of infections caused by MDR Gram-negative bacteria. The aim of this review is to describe the actual evidence from scientific literature about the “real-life” use of these two novel drugs in patients with hematological malignancies and infections caused by MDR Gram-negative bacteria.

Pathogenic functions and diagnostic utility of cytokines/chemokines in EHEC-HUS.

Hemolytic-uremic syndrome (HUS) is a severe complication of infection by Shiga toxin (STx)-producing enterohemorrhagic Escherichia coli. Hemolytic-uremic syndrome is defined clinically as a triad of non-immune microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injuries. Neurologic complications such as acute encephalopathy are also observed. In humans, endothelial cells, proximal tubular epithelial cells, mesangial cells, podocytes, intestinal epithelial cells, and monocytes / macrophages are susceptible to STx-mediated injury. Shiga toxin induces the secretion of inflammatory cytokines and chemokines from susceptible cells, including tumor necrosis factor-α interleukin (IL)-1, IL-6, and IL-8. These cytokines and chemokines contribute to the pathogenesis of HUS and encephalopathy by enhancing STx-induced cytotoxicity and inducing inflammatory cell infiltration. Serum cytokine/chemokine levels are therefore useful as indicators of disease activity and predictors of progression from acute kidney injury to chronic kidney disease. Anti-inflammation therapy combined with apheresis to remove excessive cytokines / chemokines and methylprednisolone pulse therapy to suppress cytokine/chemokine production may be an effective treatment regimen for severe E. coli-associated HUS. However, this regimen requires careful monitoring of potential side effects, such as infections, thrombus formation, and hypertension.

Air flight barotrauma and meningitis: causality seems real.

Barotrauma to the middle-ear cavity and paranasal sinuses is a relatively common flight-related health problem. Occasionally, it may result in severe mechanical or infectious intracranial complications; these have been rarely reported to date. Four cases of acute bacterial meningitis following air travel are presented, and its pathogenesis is briefly described. Neurological symptoms occurring after air flight should prompt proper investigation. Otitis media and sinusitis are common primary focuses of bacterial meningitis. Severe complications of air flight barotrauma may be underreported.

Subconjunctival Loa Loa Worm: a First Native Case Report in a Moroccan Child

The loiasis is limited to, Western and Central Africa. Characteristic clinical features include Calabar swellings and subconjunctival migration of the adult parasite. Severe complications of infection, including cardiomyopathy, nephropathy, and fatal encephalitis, are rare, but do occur. So far, all Moroccan cases are seen in adult travelers. We report the first case of autochthone loiasis in a Moroccan child.

Evaluation of Cardiac Biomarkers in Dengue Myocarditis in a Tertiary Care Hospital in Eastern India

Introduction: Dengue, a vector borne viral infection transmitted by Aedes mosquito has recently become a major public health concern in the tropical regions of the world. In addition to the two major life threatening complications- Dengue Haemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS), a variety of cardiac complications have been recognised, the most common being myocarditis. Aim: To study and compare the quantity of different cardiac biomarkers in patients of Dengue Fever with and without myocarditis. Materials and Methods: This was a hospital-based retrospective observational study done in a Tertiary Care Hospital, Kolkata, West Bengal, India from June 2019 to November 2019. Dengue patients with diagnosed myocarditis on day 7 of fever based on electro and echocardiogram changes of left ventricular ejection fraction less than 50% were considered as cases (n=41). Age and sex matched dengue patients with normal electro and echocardiogram changes were considered as control (n=43). After obtaining Institutional Ethics Committee Clearance, laboratory data were collected from samples coded and assayed for markers of acute cardiac myocyte damage such as total Creatine Kinase (CK), CK-Muscle Brain (CK-MB), Troponin T (Trop T) and cardiac failure biomarker N-Terminal pro Brain Natriuretic Peptide (NT-proBNP). Statistical analysis of the data was performed using Statistical Package for Social Sciences (SPSS 20). Results: Cardiac biomarkers CK, CK-MB, Trop T and NT-proBNP levels in cases were higher compared to controls (p-value &lt;0.05). Trop T and NT-proBNP were positively correlated to each other (r-value: 0.44). Trop T changes could also predict significantly the rise in NT-proBNP in circulation (p&lt;0.05). Conclusion: It reconfirmed the need of routine monitoring of cardiac biomarkers in conjunction with other cardiac function tests in early diagnosis and or management of myocarditis, a severe complication of Dengue Viral Infection (DENV).

Gemtuzumab Ozogamicin in the Treatment of Critical Patients with Refractory Acute Myeloid Leukemia (3 Case Reports)

The treatment of refractory acute myeloid leukemia (AML) patients presents considerable challenges. They are often critically ill. The critical conditions of these patients are mainly associated with severe infectious complications resulting in sepsis as well as with the extramedullary lesions with organ dysfunctions. So far, the obtained data demonstrated the successful use of gemtuzumab ozogamicin, the mechanism of which is likely to be based not only on depletion of CD33-positive tumor cells but also on its immunomodulatory effect. The present article focuses on the fast-effect mechanisms of gemtuzumab ozogamicin and deals with clinical experience of successful use of this drug combined with hypomethylating agents in patients with refractory AML whose condition is critical by the time therapy begins. The use of this drug combination results in fast stabilization of health status, recovery of internal organs, and apyrexia with the decreasing systemic inflammatory response within the first days of therapy. All this together with significantly lower blast count in blood and in bone marrow can bring critically ill patients to recovery.

Dissociationsof oral foci of infections with infectious complications and survival after haematopoietic stem cell transplantation.

IntroductionHaematopoietic stem cell transplantation (HSCT) recipients are at increased risk for severe infections. This study examined the associations of common oral infections with survival and infectious complications in HSCT recipients.Materials and methodsAll autologous and allogeneic HSCT recipients transplanted in the University Hospital of Basel, Switzerland, between 2008 and 2016 and referred to oral infection control pre-HSCT were included in this retrospective case-control study. All patients had a clinical and a panoramic radiological dental examination taken immediately prior to HSCT. Presence of acute or chronic oral foci of infections, decayed, missing or filled tooth index (DMFT) and radiological attachment loss (RAL) were examined. Survival and infections of the subjects were followed up for 6 months post-HSCT.ResultsAltogether 341 allogeneic and 125 autologous HSCT recipients were included in the study. Within 6 months post-HSCT, 47 (14%) of the allogeneic and 4 (3%) of the autologous recipients died. Oral foci of infections (acute or chronic), DMFT or periodontitis pre-HSCT were not associated with survival 6 months post-HSCT. Oral foci of infections were also not associated with hospital treated infectious diseases or blood culture positive bacteremia during the 6 month follow-up period. Untreated oral foci of infections were not associated with survival or severe infectious complications within 6 months post-HSCT.ConclusionThe results of this study suggest that radical dental interventions to chronic oral infections could be postponed until post-HSCT.

Clinical features, genetic background, and outcome in infants with urinary tract infection and type IV renal tubular acidosis.

Type IV renal tubular acidosis (RTA) is a severe complication of urinary tract infection (UTI) in infants. A detailed clinical and molecular analysis is still lacking. Infants with UTI who exhibited features of type IV RTA were prospectively enrolled. Clinical, laboratory, and image characteristics and sequencing of genes responsible for phenotype were determined with follow-up. The study cohort included 12 infants (9 males, age 1-8 months). All exhibited typical type IV RTA such as hyperkalemia with low transtubular potassium gradient, hyperchloremic metabolic acidosis with positive urine anion gap, hypovolemic hyponatremia with renal salt wasting, and high plasma renin and aldosterone levels. Seven had hyperkalemia-related arrhythmia and two of them developed life-threatening ventricular tachycardia. With prompt therapy, all clinical and biochemical abnormalities resolved within 1 week. Five had normal urinary tract anatomy, and three of them carried genetic variants on NR3C2. Three variants, c.1645T>G (S549A), c.538G>A (V180I), and c.1-2C>G, on NR3C2 were identified in four patients. During follow-up, none of them had recurrent type IV RTA, but four developed renal scaring. Genetic mutation on NR3C2 may contribute to the development of type IV RTA as a complication of UTI in infants without identifiable risk factors, such as urinary tract anomalies.

Results of CoALL 07-03 study childhood ALL based on combined risk assessment by in vivo and in vitro pharmacosensitivity

AbstractWe conducted a clinical trial and report the long-term outcome of 773 children with acute lymphoblastic leukemia upon risk-adapted therapy accrued in trial CoALL 07-03 (from the Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia). In a 2-step stratification, patients were allocated to receive either low- or high-risk treatment, based on initial white blood cell count, age, and immunophenotype. A second stratification was performed according to the results of in vitro pharmacosensitivity toward prednisolone, vincristine, and asparaginase (PVA score) and in vivo response after induction therapy (minimal residual disease [MRD]). Therapy was reduced for both risk groups in patients with a low PVA score or negative MRD result, and intensified in patients with a high PVA score. Overall outcome improved significantly compared with the predecessor CoALL 06-97 trial, with identical therapy backbone despite treatment reduction in 15.8% of patients (10-year probability of event-free survival, 83.5% vs 73.9%; overall survival, 90.7% vs 83.8%). Outcome for patients in the reduced treatment arms was superior to that of patients in the standard arms, associated with a profound reduction in frequency and severity of infectious complications. Importantly, we observed a lack of correlation between in vitro and in vivo drug response, as well as a lower predictive value of in vitro drug testing, reflecting an intrinsic limitation of this methodology that prevents its use for treatment stratification in future trials. In conclusion, it might be possible to reduce chemotherapy in children with acute lymphoblastic leukemia selected by stringent in vivo measurement of MRD without jeopardizing overall outcome.