bluuebunny/crossref_metadata_2025 huggingface dataset:
Adult exposure to ocean acidification and warming remains beneficial for oyster larvae following starvation
Authors: Gibbs Mitchell C , Parker Laura M , Scanes Elliot , Byrne Maria , O’Connor Wayne A , Ross Pauline M
Published: March 2021

Climate change is expected to warm and acidify oceans and alter the phenology of phytoplankton, creating a mismatch between larvae and their food. Transgenerational plasticity (TGP) may allow marine species to acclimate to climate change; however, it is expected that this may come with elevated energetic demands. This study used the oysters, Saccostrea glomerata and Crassostrea gigas, to test the effects of adult parental exposure to elevated pCO2 and temperature on larvae during starvation and recovery. It was anticipated that beneficial effects of TGP will be limited when larvae oyster are starved. Transgenerational responses and lipid reserves of larvae were measured for 2 weeks. Larvae of C. gigas and S. glomerata from parents exposed to elevated pCO2 had greater survival when exposed to elevated CO2, but this differed between species and temperature. For S. glomerata, survival of larvae was greatest when the conditions experienced by larvae matched the condition of their parents. For C. gigas, survival of larvae was greater when parents and larvae were exposed to elevated pCO2. Larvae of both species used lipids when starved. The total lipid content was dependent on parental exposure and temperature. Against expectations, the beneficial TGP responses of larvae remained, despite starvation.
Sublobar resection with intraoperative brachytherapy versus sublobar resection alone for early-stage non-small-cell lung cancer: a meta-analysis
Authors: Chen Enli , Wang Juan , Jia Chenfei , Min Xueya , Zhang Hongtao
Published: March 2021

OBJECTIVES

The purpose of this study was to compare the clinical outcomes for sublobar resection (SR) or SR plus intraoperative brachytherapy (SRB) for clinical stage I non-small-cell lung cancer.

METHODS

A systematic search was performed in the EMBASE, PubMed and Cochrane Library databases to identify related studies comparing SR to SRB. Data were collected on local recurrence (LR) as a primary outcome and regional or distant recurrence, overall survival and disease-free survival (DFS) as secondary outcomes. Meta-analysis was carried out using Stata 12.0.

RESULTS

A total of 476 patients received SRB, and 617 received SR across 5 studies. Meta-analysis of LR, regional or distant recurrence, overall survival and disease-free survival rates showed no significant difference between SRB and SR groups. However, when biologically effective dose (BED) was >100 Gy, LR rate was lower in the SRB group than in the SR group (Relative risk [RR] = 0.143, 95% confidence interval [CI]: 0.051-0.397) (p < 0.001). When BED was <100 Gy, no significant difference was found in LR rate between SRB and SR groups (SRB versus SR: RR = 1.132, 95%CI: 0.704-1.821) (p = 0.608).

CONCLUSIONS

Intraoperative brachytherapy was not associated with reduced risk of regional or distant metastasis or improved outcomes for patients with clinical stage I non-small-cell lung cancer; however, it might reduce the LR rate when BED was >100 Gy.
Duals of Semisimple Poisson–Lie Groups and Cluster Theory of Moduli Spaces of G-local Systems
Authors: Shen Linhui
Published: March 2021

We study the dual $\textrm{G}^{\ast }$ of a standard semisimple Poisson–Lie group $\textrm{G}$ from a perspective of cluster theory. We show that the coordinate ring $\mathcal{O}(\textrm{G}^{\ast })$ can be naturally embedded into a quotient algebra of a cluster Poisson algebra with a Weyl group action. The coordinate ring $\mathcal{O}(\textrm{G}^{\ast })$ admits a natural basis, which has positive integer structure coefficients and satisfies an invariance property under a braid group action. We continue the study of the moduli space $\mathscr{P}_{\textrm{G},{{\mathbb{S}}}}$ of $\textrm{G}$-local systems introduced in [ 16] and prove that the coordinate ring of $\mathscr{P}_{\textrm{G}, {{\mathbb{S}}}}$ coincides with its underlying cluster Poisson algebra.
Uniform Rectifiability, Elliptic Measure, Square Functions, and ε-Approximability Via an ACF Monotonicity Formula
Authors: Azzam Jonas , Garnett John , Mourgoglou Mihalis , Tolsa Xavier
Published: March 2021

Let $\Omega \subset{{\mathbb{R}}}^{n+1}$, $n\geq 2$, be an open set with Ahlfors regular boundary that satisfies the corkscrew condition. We consider a uniformly elliptic operator $L$ in divergence form associated with a matrix $A$ with real, merely bounded and possibly nonsymmetric coefficients, which are also locally Lipschitz and satisfy suitable Carleson type estimates. In this paper we show that if $L^*$ is the operator in divergence form associated with the transpose matrix of $A$, then $\partial \Omega $ is uniformly $n$-rectifiable if and only if every bounded solution of $Lu=0$ and every bounded solution of $L^*v=0$ in $\Omega $ is $\varepsilon $-approximable if and only if every bounded solution of $Lu=0$ and every bounded solution of $L^*v=0$ in $\Omega $ satisfies a suitable square-function Carleson measure estimate. Moreover, we obtain two additional criteria for uniform rectifiability. One is given in terms of the so-called “$S<N$” estimates, and another in terms of a suitable corona decomposition involving $L$-harmonic and $L^*$-harmonic measures. We also prove that if $L$-harmonic measure and $L^*$-harmonic measure satisfy a weak $A_\infty $-type condition, then $\partial \Omega $ is $n$-uniformly rectifiable. In the process we obtain a version of the Alt-Caffarelli-Friedman monotonicity formula for a fairly wide class of elliptic operators which is of independent interest and plays a fundamental role in our arguments.
Modeling Optimal Laboratory Testing Strategies for Bacterial Meningitis Surveillance in Africa
Authors: Walker Joseph , Soeters Heidi M , Novak Ryan , Diallo Alpha Oumar , Vuong Jeni , Bicaba Brice Wilfried , Medah Isaie , Yaméogo Issaka , Ouédraogo-Traoré Rasmata , Gamougame Kadidja , Moto Daugla Doumagoum , Dembélé Assétou Y , Guindo Ibrehima , Coulibaly Souleymane , Issifou Djibo , Zaneidou Maman , Assane Hamadi , Nikiema Christelle , Sadji Adodo , Fernandez Katya , Mwenda Jason M , Bita Andre , Lingani Clément , Tall Haoua , Tarbangdo Félix , Sawadogo Guetwende , Paye Marietou F , Wang Xin , McNamara Lucy A
Published: March 2021

Since 2010, the introduction of an effective serogroup A meningococcal conjugate vaccine has led to the near-elimination of invasive Neisseria meningitidis serogroup A disease in Africa’s meningitis belt. However, a significant burden of disease and epidemics due to other bacterial meningitis pathogens remain in the region. High-quality surveillance data with laboratory confirmation is important to monitor circulating bacterial meningitis pathogens and design appropriate interventions, but complete testing of all reported cases is often infeasible. Here, we use case-based surveillance data from 5 countries in the meningitis belt to determine how accurately estimates of the distribution of causative pathogens would represent the true distribution under different laboratory testing strategies. Detailed case-based surveillance data was collected by the MenAfriNet surveillance consortium in up to 3 seasons from participating districts in 5 countries. For each unique country-season pair, we simulated the accuracy of laboratory surveillance by repeatedly drawing subsets of tested cases and calculating the margin of error of the estimated proportion of cases caused by each pathogen (the greatest pathogen-specific absolute error in proportions between the subset and the full set of cases). Across the 12 country-season pairs analyzed, the 95% credible intervals around estimates of the proportion of cases caused by each pathogen had median widths of ±0.13, ±0.07, and ±0.05, respectively, when random samples of 25%, 50%, and 75% of cases were selected for testing. The level of geographic stratification in the sampling process did not meaningfully affect accuracy estimates. These findings can inform testing thresholds for laboratory surveillance programs in the meningitis belt.
Real communities of virtual plants explain biodiversity on just three assumptions
Authors: Hunt Roderick , Colasanti Ric L
Published: March 2021

To illuminate mechanisms supporting diversity in plant communities, we construct 2D cellular automata and ‘grow’ virtual plants in real experiments. The plants are 19 different, fully validated functional types drawn from universal adaptive strategy theory. The scale of approach is far beyond that of even the most ambitious investigations in the physical world. By simulating 496 billion plant–environment interactions, we succeed in creating conditions that sustain high diversity realistically and indefinitely. Our simulations manipulate the levels of, and degree of heterogeneity in the supply of, resources, external disturbances and invading propagules. We fail to reproduce this outcome when we adopt the assumptions of unified neutral theory. The 19 functional types in our experiments respond in complete accordance with universal adaptive strategy theory. We find that spatial heterogeneity is a strong contributor to long-term diversity, but temporal heterogeneity is less so. The strongest support of all comes when an incursion of propagules is simulated. We enter caveats and suggest further directions for working with cellular automata in plant science. We conclude that although (i) the differentiation of plant life into distinct functional types, (ii) the presence of environmental heterogeneity and (iii) the opportunity for invasion by propagules can all individually promote plant biodiversity, all three appear to be necessary simultaneously for its long-term maintenance. Though further, and possibly more complex, sets of processes could additionally be involved, we consider it unlikely that any set of conditions more minimal than those described here would be sufficient to deliver the same outcome.
Ancient grains as novel dietary carbohydrate sources in canine diets
Authors: Traughber Zachary T , He Fei , Hoke Jolene M , Davenport Gary M , Rodriguez-Zas Sandra L , Southey Bruce R , de Godoy Maria R C
Published: March 2021

Ancient grains are becoming an increasingly abundant carbohydrate source in the pet food market as a result of their popularity and novelty in the human market. Thus, it is imperative to evaluate the characteristics of these ingredients in vivo. Ten adult intact female beagles were used in a replicated 5 × 5 Latin square design. Five dietary treatments were evaluated containing either: rice (CON), amaranth (AM), white proso millet (WPM), quinoa (QU), or oat groats (OG). All diets were formulated to include 40% of the test grain and to be isonitrogenous, isocaloric, and nutritionally complete and balanced for adult dogs at maintenance. The objectives were 1) to evaluate the effects of the novel carbohydrate sources on total apparent total tract digestibility (ATTD), fecal microbiota, and fermentative end-product concentrations and 2) to evaluate the effects of novel carbohydrate sources on the postprandial glycemic and insulinemic responses in healthy adult dogs. All diets were well accepted by the dogs and fecal scores remained within the ideal range for all treatments. In terms of ATTD, all diets were well digested by the dogs; WPM had the highest digestibility of dry and organic matter in contrast with dogs fed the other treatments (P < 0.05). Additionally, ATTD of total dietary fiber was highest for WPM (72.6%) in contrast with QU (63.5%) and CON (50.8%) but did not differ from AM (65.7%) and OG (66.6%). Dogs fed AM or OG had greater (P < 0.05) fecal concentrations of total short-chain fatty acids, as well as propionate and butyrate concentrations, than CON. Ancient grain inclusion appears to beneficially shift fecal microbial populations, with increases in relative abundances of butyrogenic bacteria (i.e., members of the Lachnospiraceae family) observed for OG and reductions in Fusobacteriaceae for both AM and OG when compared with CON. Postprandial glycemic and insulinemic responses did not differ among treatments. Together, these data suggest that ancient grains can be included up to 40% of the diet while eliciting beneficial effects on the overall host health without detrimentally affecting nutrient digestibility.
Regulation of HP1 protein by phosphorylation during transcriptional repression and cell cycle
Authors: Oki Masaya , Masai Hisao
Published: March 2021

HP1 (heterochromatin protein 1), a key factor for the formation of heterochromatin, binds to the methylated lysine 9 of histone H3 (H3K9me) and represses transcription. While the H3K9me mark and HP1 binding are thought to be faithfully propagated to daughter cells, the heterochromatin structure could be dynamically regulated during cell cycle. As evidenced by the well-known phenomenon called position effect variegation (PEV), heterochromatin structure is dynamically and stochastically altered during developmental processes, and thus the expression of genes within or in the vicinity of heterochromatin could be affected by mutations in factors regulating DNA replication as well as by other epigenetic factors. Recent reports show that HP1 also plays an important role in the maintenance and transmission of chromosomes. Like many other factors ensuring faithful chromosome segregation, HP1 family proteins are subjected to posttranslational modifications, most notably phosphorylation, in a cell cycle-dependent manner. Recent studies identified a conserved phosphorylation site that profoundly affects the functions of HP1 during mitotic phase. In this commentary, we discuss dynamic regulation of HP1 protein by phosphorylation during transcriptional repression and cell cycle.
Adjuvant radiotherapy for cervical cancer in South Korea: a radiation oncology survey of the Korean Radiation Oncology Group (KROG 20-06)
Authors: Kim Nalee , Park Won
Published: March 2021

Objective

Radiation therapy plays an important role in adjuvant treatment for surgically treated cervical cancer with adverse pathological findings. This was the first study to evaluate current practices of adjuvant radiation therapy among centres affiliated with the Korean Radiation Oncology Group.

Methods

A survey containing specific questions on the demographics in 2019, indications of adjuvant treatment, radiation therapy field, prescription radiation therapy dose, boost radiation therapy and chemotherapy was sent out by e-mail to 93 centres.

Results

The overall response rate was 62.4%. Regarding radiation therapy techniques, intensity-modulated radiation therapy was adopted in most institutions (41/58, 70.7%). Various risk group criteria were selected for adjuvant radiation therapy and concurrent chemoradiation therapy. One or two risk factors among tumour size, depth of invasion and lymphovascular invasion were considered for adjuvant radiation therapy by 20.7 and 60.3% of the respondents, respectively. The following criteria for concurrent chemoradiation therapy were considered by 60.3% of the respondents: parametrial extension, positive resection margin or lymph node metastasis. Various upper borders were preferred for pelvic radiation therapy by the institutions, and a total dose of 50.4 Gy in 28 fractions was the most prescribed dose scheme (37/58, 63.8%). Lymph node bed boost radiation therapy and vaginal cuff brachytherapy were considered for selected patients by 22.4% (13/58) and 60.3% (35/58) of the institutions.

Conclusion

This survey demonstrated the practice patterns of adjuvant treatment that are prevalent in the field of radiation oncology among members of the Korean Radiation Oncology Group. These findings warrant further consensus on radiation therapy guidelines in the context of adjuvant treatment for cervical cancer.
Nongenetic Determinants of Risk for Early-Onset Colorectal Cancer
Authors: Archambault Alexi N , Lin Yi , Jeon Jihyoun , Harrison Tabitha A , Bishop D Timothy , Brenner Hermann , Casey Graham , Chan Andrew T , Chang-Claude Jenny , Figueiredo Jane C , Gallinger Steven , Gruber Stephen B , Gunter Marc J , Hoffmeister Michael , Jenkins Mark A , Keku Temitope O , Marchand Loïc Le , Li Li , Moreno Victor , Newcomb Polly A , Pai Rish , Parfrey Patrick S , Rennert Gad , Sakoda Lori C , Sandler Robert S , Slattery Martha L , Song Mingyang , Win Aung Ko , Woods Michael O , Murphy Neil , Campbell Peter T , Su Yu-Ru , Zeleniuch-Jacquotte Anne , Liang Peter S , Du Mengmeng , Hsu Li , Peters Ulrike , Hayes Richard B
Published: March 2021

Background

Incidence of early-onset (younger than 50 years of age) colorectal cancer (CRC) is increasing in many countries. Thus, elucidating the role of traditional CRC risk factors in early-onset CRC is a high priority. We sought to determine whether risk factors associated with late-onset CRC were also linked to early-onset CRC and whether association patterns differed by anatomic subsite.

Methods

Using data pooled from 13 population-based studies, we studied 3767 CRC cases and 4049 controls aged younger than 50 years and 23 437 CRC cases and 35 311 controls aged 50 years and older. Using multivariable and multinomial logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess the association between risk factors and early-onset CRC and by anatomic subsite.

Results

Early-onset CRC was associated with not regularly using nonsteroidal anti-inflammatory drugs (OR = 1.43, 95% CI = 1.21 to 1.68), greater red meat intake (OR = 1.10, 95% CI = 1.04 to 1.16), lower educational attainment (OR = 1.10, 95% CI = 1.04 to 1.16), alcohol abstinence (OR = 1.23, 95% CI = 1.08 to 1.39), and heavier alcohol use (OR = 1.25, 95% CI = 1.04 to 1.50). No factors exhibited a greater excess in early-onset compared with late-onset CRC. Evaluating risks by anatomic subsite, we found that lower total fiber intake was linked more strongly to rectal (OR = 1.30, 95% CI = 1.14 to 1.48) than colon cancer (OR = 1.14, 95% CI = 1.02 to 1.27; P = .04).

Conclusion

In this large study, we identified several nongenetic risk factors associated with early-onset CRC, providing a basis for targeted identification of those most at risk, which is imperative in mitigating the rising burden of this disease.
#100: Disseminated Toxoplasmosis Presenting as Persistent Fevers in a Hematopoietic Stem Cell Transplant Recipient
Authors: Khan A , Nadimpalli S , Gans H
Published: March 2021

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

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

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

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

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

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

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 >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

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

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.
#50: Vancomycin Doses and Trough Concentrations in Pediatric Patients
Authors: Vilchez Medalit Luna , Gil César Ugarte , Alvarez Diana Portillo , Afaray Julio Maquera , Mesones Blanca Salazar , Huauya Emilio Aguilar , Revilla José López
Published: March 2021

Background

Vancomycin serum trough concentrations are monitored to reduce nephrotoxicity and optimize therapeutic efficacy. Vancomycin pharmacokinetics and trough levels used in pediatric patients are extrapolated from the adult population. The pediatric dosing strategies are empirical and there is limited evidence to suggest that these doses result in the recommended steady-state trough concentrations. The objective of the study was to determine the association between vancomycin dosing regimens and trough concentrations levels of 10 to 20 μg/mL in pediatric patients with complicated infections.

Methods

Retrospective cohort, 505 trough vancomycin serum concentrations of patients of 1 month to 18 years from hospital wards and the Intensive Care Unit of the Instituto Nacional de Salud del Niño San Borja during December 2015 to April 2019. It included only the first vancomycin trough level measured 30 minutes before the fourth doses and serum trough concentrations of 10 to 20 μg/mL were considered as therapeutic levels. A multinomial logistic regression model to estimate the relative risk ratio (RRR) with a 95% confidence interval was used, the comparator group was therapeutic vancomycin levels and it was adjusted by glomerular filtration rate, age group, hospital room, dose interval, and weight.

Results

Five hundred and five vancomycin dosages were analyzed. Infants and children were 43.12% and 39.22%, respectively, 45.17% were women. 56.77% had a high glomerular filtration rate and only 28.02% of the patients obtained therapeutic trough levels of vancomycin. The RRR of having sub-therapeutic levels in patients with low glomerular filtration rates compared with normal filtration rates was 0.31 (P = 0.049) and the RRR of having sub-therapeutic levels in patients from 2 to 12 years compared with patients under 2 years old was 2.38 (P = 0.007). There was no difference in having therapeutic levels using doses equal or greater than 60 mg/kg/day vs. less than 40 mg/kg/day comparing sub-therapeutic levels (P = 0.655) and supratherapeutic levels (P = 0.264).

Conclusions

The empirical vancomycin regimens used in pediatric patients did not reach the recommended therapeutic trough levels of 10 to 20 μg/mL. Patients of 2 to 12 years and low glomerular filtration rates were associated to have sub-therapeutic trough levels.
#69: Improving Communication About the Care and Prevention of Infections in a Pediatric Oncology Unit by Using Patient Daily Goals in Multidisciplinary Rounds
Authors: Griselda Escobedo-Melendez , Manuel Martinez-Albarran , Isadora Magaña-Saldivar , Norma Jimenez , Elizabeth Gomez-Huerta , Monserrat Pardo-Zepeda , Marcela Espinoza , Cuauhtli Acosta-Rubio , Dulce Inzunza-Valenzuela , Fernando Sanchez-Zubieta , Jeannette Kirby , Miguela Caniza
Published: March 2021

Background

In children with cancer infections are the most frequent complication, with fatal outcomes if not addressed promptly. Therefore, care and prevention of infections in these patients require multidisciplinary interventions, with effective communication among healthcare providers to reduce the morbidity, length of stay, and the inappropriate use of resources. We used the Institute of Healthcare Improvement (IHI) model for improving the communication among healthcare providers by using patient daily goals after the oncology pediatric unit multidisciplinary rounds.

Methods

A multidisciplinary team was identified in the pediatric oncology unit. The team received weekly coaching on the IHI methodology. The methodology used included the creation of a block diagram to understand the baseline processes and a key driver diagram. Then, after a literature review, a data collection plan and measures were identified. The team identified different ideas for changes and prioritized them using an impact-effort matrix. Finally, several rounds of Plan-Do-Study-Act (PDSA) cycles reached the desired changes that organized the patient daily goals for sharing in the form of a worksheet. This worksheet was shared with nurses and pharmacist staff, a chat group was created, and the routine use of the daily goals for patient management was taught and incorporated into the rest of the care team staff. The percentage of excellent communication among all multidisciplinary teams and outcomes (length of stay, intensive care unit admission, and mortality) were recorded at baseline and endline. We determined the statistical significance of the baseline vs. endline difference by using χ 2 and t-tests.

Results

A total of 105 patients with suspected infections were included over a 6-month period (June through November 2019). We found a significant increase per month in the percent of agreement in excellent communication in the patient daily goals between infectious diseases specialist faculty and fellows, nurses, pharmacist, and pediatric oncology faculty and fellows (33.3% vs. 91.3%) (P = 0.004). Length of stay decreased monthly after our interventions (baseline: mean 14.7 days [SD 12.4] vs. after intervention: mean 6.7 days [SD 2.7]) (P = 0.014). There were only one ICU admission and no deaths during the implementation period.

Conclusions

Our approach using patient daily goals improved communication among a multidisciplinary team, leading to decreased length of stay and supporting adequate outcomes.