bluuebunny/crossref_metadata_2025_split huggingface dataset:
#100: Disseminated Toxoplasmosis Presenting as Persistent Fevers in a Hematopoietic Stem Cell Transplant Recipient
Authors: Khan A , Nadimpalli S , Gans H 
Published: March 2021

Abstract

Background
Toxoplasma reactivation is a known concern in hematopoietic stem cell transplant (HSCT) patients with high mortality of approximately 40% and up to 100% if left untreated. The risk is highest when patients are most immunocompromised and presentation can vary from isolated fever to disseminated disease with CNS toxoplasmosis, pneumonitis, and myocarditis.

Case
The patient is a 10-year-old male with acute promyelocytic leukemia (APML) CNS1 status post-chemotherapy, secondary acute myeloid leukemia (AML), now status post 10/10 matched unrelated donor hematopoietic stem cell transplant (HSCT). He initially developed fever and neutropenia during conditioning chemotherapy with resolved fever prior to stem cell transplant. His transplant course was complicated by grade IV mucositis on day +4 with improvement on day +11. On day +19 he developed new fevers (Tmax 40.5oC) with a negative initial workup. He continued to have persistent fevers on broad-spectrum empiric therapy with meropenem and liposomal amphotericin B and also complained of daily headaches and abdominal pain, with worsening diffuse body pain. On day +26 the Pediatric Infectious Diseases team was consulted as a CT Chest demonstrated small scattered ground glass nodules in the right lung with minimal bibasilar atelectasis and small pleural effusions. Upon chart review, he was noted to be Toxoplasma IgG positive prior to transplant. Further infectious diseases studies were sent to evaluate for fungal etiologies, including a Toxoplasma PCR blood, and given persistent fever, he was empirically started on trimethoprim–sulfamethoxazole (TMP-SMX) by the primary team. Shortly after the initiation of TMP-SMX he became afebrile and testing confirmed Toxoplasma reactivation with positive PCR studies from the blood, cerebrospinal fluid (CSF), bronchoalveolar lavage (BAL), and bone marrow. He was treated with pyrimethamine, sulfadiazine, and folinic acid and developed sulfa crystalluria, requiring alteration of his therapy. He received multiple treatment regimens and continued on maintenance therapy without further complications.

Conclusion
This case highlights the importance of serial surveillance or empiric prophylaxis for Toxoplasma reactivation in HSCT recipients known to have prior infection. There is high associated mortality and patients may present with isolated fever or severe disseminated disease with multi-organ involvement. Toxoplasma disease requires the presence of organ involvement as demonstrated in our patient and treatment is typically 6 weeks at higher doses followed by maintenance therapy. The definite treatment course varies by clinical response and multiple options are available if toxicities occur.
#11: Metronidazole for the Treatment of Norovirus in Transplant Recipients
Authors: Soneji Maulin , Newman Alexander M , Toia Jacquie , Muller William J 
Published: March 2021

Abstract

Background
Norovirus is a common cause of gastroenteritis in both immunocompetent and immunocompromised hosts. In transplant recipients, it can lead to prolonged shedding and chronic diarrhea. Treatment with nitazoxanide, oral immunoglobulin, or mammalian target of rapamycin (mTOR) inhibitors have shown varying degrees of benefit in small studies. The commensal gastrointestinal bacterial flora may influence the pathogenesis of norovirus infection. Metronidazole is often used to modulate gastrointestinal flora, and improvement of an HIV patient with suspected Giardia infection subsequently identified to have norovirus suggested a possible use of this drug for other immune-suppressed patients with norovirus infection.

Methods
Solid-organ or stem cell transplant recipients testing positive for norovirus in stool from July 2014 to March 2019 were identified from the medical record. Patient characteristics, laboratory data, and medications were systematically reviewed to identify factors associated with clinical improvement.

Results
Thirty-eight patients met inclusion criteria. Almost 75% of the patients were male. Almost 80% of the patients were solid-organ transplant recipients: 40% heart, 24% kidney, and 15% liver. There were 85 positive norovirus tests among the 38 patients. Of these, 14 involved coinfections with another potential pathogen: 11 with adenovirus, 2 with Clostridioides difficile, and 1 with cytomegalovirus. In 25 of the 85 positive norovirus tests, nitazoxanide was given. Clinical improvement was documented in 15 of these episodes (60%), while no improvement was observed in 10 (40%). Eight positive tests were treated with metronidazole alone, with documented improvement observed during 6 (75%) courses. In 9 additional episodes, metronidazole was given within a week of the test result and 2 of these had improvement. When other antibiotics were used concurrently with metronidazole, 78% of episodes (7/9) did not lead to clinical response. Changes in immunosuppression were used for the treatment of 6 episodes, leading to clinical improvement in 5.

Conclusion
Metronidazole treatment was associated with clinical improvement of norovirus gastroenteritis in transplant recipients at rates similar to those seen with nitazoxanide therapy. Reduction in immunosuppression also led to clinical improvement but in situations where that cannot be done safely, metronidazole may be an alternative to nitazoxanide. In this cohort, metronidazole was only used as a therapy after nitazoxanide, suggesting that a trial of metronidazole as rescue therapy in comparison to a repeat course of nitazoxanide after the initial failure of nitazoxanide is justified.
#94: BK Virus (BKV) Infections in Pediatric Allogeneic Hematopoietic Cell Transplant (Allo-HCT) Patients: A Single-center Experience
Authors: Halford K , Suliman A , Ferrolino J A , Dallas R H , Maron-Alfaro G , Hijano D R 
Published: March 2021

Abstract

Background
BK virus infection in Allo-HCT pediatric patients is associated with the development of hemorrhagic cystitis (HC) leading to increased morbidity and prolonged hospitalization. We described the baseline characteristics, clinical presentation, and outcomes associated with recent BK virus infections at St. Jude Children’s Research Hospital.

Methods
We identified all pediatric Allo-HCT recipients with a positive blood or urine test for BKV at St. Jude between 2010 and 2018. A retrospective review of the electronic medical records (EMR) was conducted for demographics, signs, and symptoms associated with BKV infection, complications, and outcomes. Descriptive statistics were used to summarize the cohort.

Results
Of 475 patients who received an Allo-HCT during the study period, 209 (44%) had at least one positive test for BKV. Most were male (60%) and mean age was 12.4 years. BKV was most common in haploidentical transplants (n = 65), followed by match unrelated donor and matched sibling donor. Sixty-seven (32%) had only viruria, 5 (2%) had only viremia, and 137 (66%) had both. Of those with a positive result for BKV, 169 (80%) presented with hematuria or were diagnosed with HC. Urologic interventions were required by 22% of the patients; 40 required continuous bladder irrigation and 9 underwent cystoscopy. Despite having BKV detected in urine and/or blood, 17% had no symptoms.

Conclusions
A large proportion of Allo-HCT patients developed BKV associated HC. Morbidity associated with HC is important, with 1 in 5 patients requiring urology intervention.
#85: Nutrient Availability Drives Community Dynamics in the Vaginal Microbiota
Authors: Hood-Pishchany M Indriati , Rakoff-Nahoum Seth 
Published: March 2021

Abstract

Background
Nutrient utilization is both critical for niche occupation and is the driver of competitive and cooperative interactions in microbial communities. The FRT is replete with host-associated glycans in the form of glycoproteins, epithelial glycogen stores, and the breakdown products of these glycans. I hypothesized that host-associated glycans drive environment, microbe–microbe and host–microbe interactions in the FRT.

Methods
We have developed robust, scalable, high-throughput culturing systems to empirically define the substrate utilization traits from more than 60 unique bacterial species capable of colonizing the vagina. In addition, we are using batch and continuous culture in vitro cultivation of multispecies communities to study vaginal bacteria within the complex community, that closely recapitulate key dynamics observed in vivo.

Results
Demonstrating the power of these in vitro models, I have defined the carbohydrate utilization profiles of hundreds of unique FRT isolates, identifying species and strain-level variation in utilization of host-derived carbohydrates. Given the known abundance of glycogen in the vaginal epithelium, I hypothesized that the utilization of host-associated glycogen represents an adaptation to the vaginal environment. Indeed, we identify glycogen degradation enzymes in diverse species resident in the reproductive tract, and find enrichment in genes encoding glycogen-degrading enzymes in L. crispatus strains derived from vaginal as opposed to intestinal sites. Metatranscriptomic analyses from human samples demonstrate that bacterial glycogen and maltose (a breakdown product of glycogen) utilization genes are highly expressed in the vagina and elucidate patterns of gene expression suggestive of context-dependent competition and cooperation for glycogen utilization in vivo. To empirically investigate the impact of glycogen availability and glycogen utilization in FRT microbiota communities, I assembled type strains or co-resident consortia into model, polymicrobial communities in vitro. These studies demonstrate that among health-associated L. crispatus strains, those that use glycogen have a competitive advantage during growth in a complex community. However, preliminary results suggest that some strains may benefit from cross-fed nutrients liberated by other members of the consortium.

Conclusions
Taken together, these data establish that strain-level variability in glycan utilization contributes to competitive fitness during growth in community, and suggest that these traits may influence community stability or persistence in vivo. Moreover, the methods we have developed provide a scalable system in which to empirically study ecological dynamics within complex community ex vivo.
#31: Risk Factors Associated with Mortality due to Multidrug-Resistant Organisms in Pediatric Oncology Patients with Febrile Neutropenia
Authors: Minero Miguel A , Castro Asia , Avilés-Robles Martha 
Published: March 2021

Abstract

Background
Infectious processes are frequent complications presented in pediatric patients with cancer. Currently, the indiscriminate use of antibiotics induces resistance to available treatments, creating the emergence of multi-drug-resistant organisms (MDROs). Due to the impact in morbidity and mortality secondary to MDRO infection, we aimed to identify risk factors associated with mortality in infections due to MDROs in pediatric patients with cancer.

Methods
Case–control study nested in a prospective cohort of pediatric oncology patients with febrile neutropenia (FN) at Hospital Infantil de México Federico Gómez (HIMFG) in Mexico City from March 2015 to September 2017. MDRO was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories. Patients with FN episodes who died from an infection due to MDROs were defined as cases and patients with FN episodes of an infection due to MDROs who did not die were defined as controls. Mucositis, septic shock, PICU stay, and bacterial prophylaxis (Trimethoprim/Sulfamethoxazole) were compared between groups. Descriptive statistics was performed and Pearson χ 2 or Student’s t-test were used to compare risk factors between groups.

Results
A total of 929 FN episodes were documented, 44.4% episodes occurred in male patients, mean age was 7.9 years, with the population under 5 years being the most represented (68.2%). The most frequent diagnosis was acute lymphoblastic leukemia in 75% followed by rhabdomyosarcoma in 10.5% and acute myeloid leukemia in 9.6%. Prophylaxis (trimethoprim/sulfamethoxazole) was used in 86%, mucositis was present in 9.2% of episodes. 12.1% had septic shock and 4.7% were admitted to PICU. In 148 FN episodes (15.9%) a microorganism was identified, of these 50 (33.7%) were due to an MDROs. Urinary tract infection was the most frequent site (49%), followed by bloodstream infections (47%). K. pneumoniae was the most frequent MDRO in 22.8%, followed by E. coli in 19.2% and P. aeruginosa in 14%. Septic shock was presented in 26% of MDROs infections. Overall mortality was 1.94% and only 0.86% (8) were secondary to MDROs. Of patients with MDRO isolated mortality was 30% (15/50). Mortality associated with bloodstream infection due to MDROs was 25% compared with other source of MDROs infections (3%) (P = 0.01). Septic shock was present in 40% of patients with death due to MDROs infection (P = 0.001).

Conclusions
In our population of children with FN episodes who had an isolated microorganism, infection due to MDROs are high (33.7%) and MDROs infection-directed mortality was as high as 30%. Bloodstream infections and septic shock were risk factors associated with mortality due to MDROs.
#59: Children as Sentinels for Active Transmission of Tuberculosis: Disease Mapping Modeling of Programmatic Data in a High-Burden Setting
Authors: Kenneth Gunasekera , Joshua Warren , Ted Cohen 
Published: March 2021

Abstract

Background
To meet the transmission reduction goals of the End TB strategy, there is a growing interest in identifying and targeting case-finding efforts to tuberculosis“hotspots,” geographic regions of active transmission. Collecting and interpreting spatial and pathogenic genetic information, the most reliable evidence of active transmission, is prohibitively resource-intensive under routine conditions in high-burden settings. Many countries maintain case-notification registers under routine conditions, representing an attractive source of data to investigate for transmission. However, notification data are imperfect. Areas of high incidence may reflect other underlying patterns, and individual-level covariate information and other information that may aid in its interpretation, such as baseline census data or other healthcare utilization data, is often unavailable. Despite imperfections, the accessibility of notification data demands further investigation. We examined notification data from 2005 to 2007 in a South American, high-burden setting where the household address of each case was geocoded. Subsequent investigation of notification data in the same setting from 2009 to 2012 additionally provided pathogen genetic evidence from all culture-positive cases suggesting regions of active transmission of tuberculosis. We investigated a disease mapping modeling approach leveraging only age-specified tuberculosis notification data to suggest hotspots of active tuberculosis transmission.

Methods
Given the absence of baseline population data at a comparable spatial resolution, we aggregated the point-referenced cases reported to the Peruvian National Tuberculosis Program from 2005 to 2007 within two of Lima’s four health districts into a grid with 400 m × 400 m cells. We used Bayesian hierarchical spatial modeling methodology to model the proportion of children cases of the total number of adult and child cases in each cell. Where the modeled proportion of child cases is higher than expected, we suggest that case notification is driven primarily by active transmission.

Results
This method identified several grid cells in which the proportion of child cases is higher than expected. The location of these grid cells was found to approximate the location of active transmission evidenced by a later genotyping study.

Conclusions
This evidence suggests that age-specified notification data, with all its limitations, may be sufficient to suggest hotspots of active transmission of tuberculosis. We additionally provide the first spatial evidence to support the long-cited belief that with respect to tuberculosis transmission, childhood cases may truly be “the canary in the coal mine.”
#95: Clinical Profile and Outcome of Pediatric Acute Lymphoblastic Leukemia Patients with Tuberculosis at the Philippine General Hospital
Authors: Mortel Maika Kamille , Alcasabas Ana Patricia , Ong-Lim Anna Lisa 
Published: March 2021

Abstract

Background
The Philippines remains one of the countries on the WHO list of high-burden countries for tuberculosis (TB), and malignancy has long been recognized as a risk factor for this disease. This report describes the clinical profile and outcomes of pediatric patients with acute lymphoblastic leukemia (ALL) diagnosed with tuberculosis.

Methods
Medical records of pediatric patients with ALL consulting at the University of the Philippines – Philippines General Hospital diagnosed from January 2015 to December 2017 (excluding those with concomitant HIV infection) were reviewed. Those diagnosed with tuberculosis infection were further analyzed, obtaining demographic data, results of diagnostics, and treatment.

Results
Out of 102 patients, 5 were found to have tuberculosis, all of them being male, with an average age of 7.2 years old. All cases were pulmonary, with one patient having multi-drug-resistant TB. PPD was positive in 4 cases, with indurations measuring &gt;10mm, while chest radiographs showed nonspecific findings for 3 patients. Of 3 patients who underwent sputum AFB testing, one had a positive result. While 1 patient was diagnosed with TB and ALL concurrently, majority of patients were diagnosed after entering remission. Three patients completed 6 months of TB treatment, while 1 patient is still on medication for multi-drug-resistant tuberculosis. One patient abandoned treatment.

Conclusion
In this group of ALL patients, malnutrition and corticosteroid use were not found to be independent risk factors for TB. As TB disease may be due to reactivation of latent TB infection (LTBI) during immunosuppression, screening for LTBI may be a worthwhile strategy to decrease morbidity. Transmission precautions are emphasized to reduce acquired TB infection in immunocompromised populations.
#23: Survival Analysis of Childhood Acute Myeloblastic Leukemia in a Limited Resource Center: Do Infection and Lymphocyte-Mediated Immune Response Play a Role?
Authors: Ardianto Bambang ,   Christine, Triasih Rina , Supriyadi Eddy , Widjajanto Pudjo Hagung , Mulatsih Sri , Pangarso Alexandra Widita Swipratami , Armytasari Inggar , Purwanto Ignatius ,   Sutaryo
Published: March 2021

Abstract

Background
Acute myeloblastic leukemia (AML) is the second most prevalent cancer among Indonesian children. In contrast to those of acute lymphoblastic leukemia (ALL), a number of studies reported unfavorable outcomes following the initiation of cytostatic protocols for childhood AML. In addition, our previous study showed that Gram-negative bacterial infection constitutes the major cause of treatment-related mortality in children with AML. These findings raised a question on the prognostic role of diagnostic lymphopenia, which represents the immunosuppressive state, as demonstrated in adult patients with solid tumors.

Methods
A retrospective cohort study, which involved children younger than 18 years of age with the newly diagnosed, non-M3 AML, was conducted. These children were admitted to Dr. Sardjito General Hospital, Yogyakarta, Indonesia, during the period of 2011–2019 and received National Pilot Protocol (2011–2016), Pediatric AML Protocol (2016–2018), and International Society of Pediatric Oncology (SIOP) Pediatric Oncology in Developing Countries (PODC) Protocol with prephase (2018–2019). One-year overall survival (OS) was analyzed, using diagnostic absolute lymphocyte counts (ALC0) of more than 4.5 × 109/L and less than 4.5 × 109/L as the determinants, in accordance with those reported in a number of studies on adult AML.

Results
Sixty-five children, which consisted of 41 (63%) children with ALC0 of more than 4.5 × 109/L and 24 (37%) children with ALC0 of less than 4.5 × 109/L, were eligible for this study. In a multivariate logistic regression analysis, compared with those of diagnostic white blood cell and peripheral blood myeloblast counts, treatment-related pneumonia, gastrointestinal tract infection, and sepsis were the most responsible factors for the occurrence of death within the first year of treatment [relative risk (RR), 2.82; 95% confidence interval (95% CI), 0.99–8.04; P = 0.05]. OS analysis showed that 43% and 16% of children with ALC0 of more than 4.5 × 109/L and less than 4.5 × 109/L, respectively, were alive within the first year of treatment. Cox-regression analysis, however, failed to reach statistical significance [hazard ratio (HR), 0.63; 95% CI, 0.33–1.18; P = 0.15].

Conclusion
Despite lacked statistical significance, our study showed the superior one-year OS in children with ALC0 of more than 4.5 × 109/L. Our findings, therefore, might indicate the prognostic role of infection and lymphocyte-mediated immune response in childhood AML.
#43: Monotherapy Experience in Pediatric Patients with High-risk Febrile Neutropenia
Authors: Gutiérrez Valentina , Claverie Ximena 
Published: March 2021

Abstract

Background
Fever during neutropenia is a common occurrence in children with cancer. In a systematic review of RCTs of pediatric febrile neutropenia, compared monotherapy with aminoglycoside-containing combination therapy found no significant differences in failure rates, infection-related mortality, or overall mortality. The updated pediatric-specific guidelines recommend initiation of empirical antibiotic monotherapy using an antipseudomonal β-lactam, a fourth-generation cephalosporin, or a carbapenem for pediatric high-risk febrile neutropenia. However, local epidemiology and resistance patterns should be evaluated regularly. Our local hospital epidemiology does not have Pseudomonas aeruginosa isolates, therefore, we used ceftriaxone as monotherapy in patients with high-risk febrile neutropenia without other risk factors. The goal of our investigation is to describe the experience of using third-generation cephalosporins in these patients.

Methods
Descriptive study of high-risk febrile neutropenia episodes in patients admitted to the Pediatric Oncology Unit of Hospital Dr. Sótero del Río, Santiago, Chile. We included patients ≤15 years from June 2016 until November 2019.

Results
We found a total of 133 high-risk febrile neutropenia episodes corresponding to 50 patients, 78% were leukemia and 22% were solid tumor patients. Of the 133 episodes, 92 (69%) had clinical signs at admission, mostly respiratory in 46 (50%) of the cases, 18 (29%) had mucositis and 13 (14%) had diarrhea. Of 133 episodes, 41 (31%) did not have any source at clinical examination. Eighty-six (65%) cases started ceftriaxone at admission, 28 (33%) maintained ceftriaxone for 7 days of treatment with good clinical response. Of this group 58 (67%) patients changed treatment: 32 (37%) cases started second-line antibiotics for clinical worsening, 19 (22%) cases required second- and third-line antibiotics for persistent fever and clinical worsening, and 7 (8%) received third-line antibiotics from the start for past microbiological history. Sixteen (12%) cases of total evolved with sepsis requiring intensive care unit management. We had 30 (23%) episodes with positive blood culture, 11 (37%) due to gram-positive bacteria, 16 (53%) gram-negative bacteria, and 3 (10%) cases of fungal infections. Of the gram-negative bacteria, 7 (44%) were ESBL producers, without P. aeruginosa isolates. One case died (0.7%) for refractory sepsis due to gram-negative bacteria.

Conclusion
Although we did not have P. aeruginosa isolates, due to the spread of ESBL strains, monotherapy with ceftriaxone is not a good option as initial therapy for high-risk febrile neutropenia patients. The empiric therapy has to be evaluated regularly and should always be based on local epidemiology.