Tight Versus Liberal Blood Glucose Control in Patients With Diabetes in the ICU: A Meta-Analysis of Randomized Controlled Trials.

Introduction: Glycemia is an important factor among critically ill patients in the intensive care unit (ICU). There is conflicting evidence on the preferred strategy of blood glucose control among patients with diabetes in the ICU. We aimed to conduct a meta-analysis comparing tight with liberal blood glucose in critically ill patients with diabetes in the ICU. Methods: We systematically searched PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) comparing tight versus liberal blood glucose control in critically ill patients with diabetes from inception to December 2023. We pooled odds-ratios (OR) and 95% confidence intervals (CI) with a random-effects model for binary endpoints. We used the Review Manager 5.17 and R version 4.3.2 for statistical analyses. Risk of bias assessment was performed with the Cochrane tool for randomized trials (RoB2). Results: Eight RCTs with 4474 patients were included. There was no statistically significant difference in all-cause mortality (OR 1.11; 95% CI 0.95-1.28; P = .18; I² = 0%) between a tight and liberal blood glucose control. RoB2 identified all studies at low risk of bias and funnel plot suggested no evidence of publication bias. Conclusion: In patients with diabetes in the ICU, there was no statistically significant difference in all-cause mortality between a tight and liberal blood glucose control. PROSPERO registration: CRD42023485032.

Impact of PVC microplastics in photodynamic inactivation of Staphylococcus aureus and MRSA.

Photodynamic processes have found widespread application in therapies. These processes involve photosensitizers (PSs) that, when excited by specific light wavelengths and in the presence of molecular oxygen, generate reactive oxygen species (ROS), that target cells leading to inactivation. Photodynamic action has gained notable attention in environmental applications, particularly against pathogens and antibiotic-resistant bacteria (ARB) that pose a significant challenge to public health. However, environmental matrices frequently encompass additional contaminants and interferents, including microplastics (MPs), which are pollutants of current concern. Their presence in water and effluents has been extensively documented, highlighting their impact on conventional treatment methods, but this information remains scarce in the context of photodynamic inactivation (PDI) setups. Here, we described the effects of polyvinyl chloride (PVC) microparticles in PDI targeting Staphylococcus aureus and its methicillin-resistant strain (MRSA), using curcumin as a PS under blue light. The presence of PVC microparticles does not hinder ROS formation; however, depending on its concentration, it can impact bacterial inactivation. Our results underscore that PDI remains a potent method for reducing bacterial concentrations in water and wastewater containing ARB, even in highly contaminated scenarios with MPs.

Multiplex PCR to Streptococcus pneumoniae serotype identification directly in cerebrospinal fluid samples.

Streptococcus pneumoniae causes invasive diseases of significant public health concern, such as meningitis. The culture of cerebrospinal fluid (CSF) samples, the standard technique for meningitis diagnoses, is not always positive. Consequently, meaningful information about the etiological agent is lost, which can compromise effective epidemiological surveillance and the improvement of immunization policies. This study aims to standardize a method to genotype pneumococcus in the CSF samples which could mitigate the absence of isolated strains, and also evaluate the prediction of this assay. We applied eight multiplex PCR (mPCR) assays to CSF samples paired with the Quellung reaction applied to the isolated strains. We also compared different master mix kits in the mPCR. Moreover, a retrospective study was conducted with CSF samples considered pneumococcus positive due to the presence of the lytA gene. Results showed that genotyping by the mPCR correlated 100% with the Quellung reaction, and genotyping was dependent on the master mix applied. In the retrospective study (2014-2020), 73.4% were successfully genotyped. The analyses of the receiver operating characteristic curve showed that the cycle threshold (Ct value) around 30 for the lytA gene had a 75% positive chance of successful genotyping, whereas with a Ct value > 35, the chance was 12.5%. Finally, we observed that genotype 19A was prevalent in the period (12%), information unknown until now due to the lack of isolated strains. Therefore, the mPCR of CSF samples can efficiently predict S. pneumoniae serotypes, especially in the absence of isolated strains, which can be a great tool for pneumococcal serotype surveillance.

Spread of Mycobacterium tuberculosis in Southern Brazilian persons deprived of liberty: a molecular epidemiology study.

To evaluate the genetic diversity and clustering rates of M. tuberculosis strains to better understand transmission among persons deprived of liberty (PDL) in Rio Grande do Sul (RS), southern Brazil. This is a cross-sectional study, including strains of M. tuberculosis isolated from PDL, stored at the Central Laboratory of RS, in the period from 2013 to 2018. The molecular characterization was performed using the MIRU-VNTR 15 loci method. A total of 598 M. tuberculosis strains were genotyped, and 37.5% were grouped into 53 clusters. Cluster sizes ranged from 2 to 34 strains. The largest cluster of the study had strains from 34 PDL, and 58.8% of the PDL of this cluster were in P01. Among the clusters formed, in 60.3%, there was at least one strain from P01. The most common strains in RS were LAM (53.2%) and Haarlem (31.1%). The LAM strain was the most likely to form clusters, and Haarlem was associated with anti-TB drug resistance. This was translational research, and the results can collaborate with the TB control programs, leading to improved strategies that allow the reduction of the TB burden in prisons.

Hydrogen peroxide preoxidation as a strategy for enhanced antimicrobial photodynamic action against methicillin-resistant Staphylococcus aureus.

Antimicrobial photodynamic treatment (aPDT) is a photooxidative process based on the excitation of a photosensitizer (PS) in the presence of molecular oxygen, under specific wavelengths of light. It is a promising method for advanced treatment of water and wastewater, particularly targeting disinfection challenges, such as antibiotic-resistant bacteria (ARB). Research in improved aPDT has been exploring new PS materials, and additives in general. Hydrogen peroxide (H2O2) a widely applied disinfectant, mostly in the food industry and clinical settings, present environmentally negligible residuals at the usually applied concentrations, making it friendly for the water and wastewater sectors. Here, we explored the effects of preoxidation with H2O2 followed by blue light-mediated (450 nm) aPDT using curcumin (a natural-based PS) against methicillin-resistant Staphylococcus aureus (MRSA). Results of the sequential treatment pointed to a slight hampering in aPDT efficiency at very low H2O2 concentrations, followed by an increasing cooperative effect up to a deleterious point (≥7 log10 inactivation in CFU mL-1), suggesting a synergistic interaction of preoxidation and aPDT. The increased performance in H2O2-pretreated aPDT encourages studies of optimal operational conditions for the assisted technology and describes potentials for using the described strategy to tackle the issue of ARB spread.

Predictive validity of the EVARUCI scale to evaluate risk for pressure injury in critical care patients.

OBJECTIVE: To compare the predictive capacity of the current risk assessment scale for pressure ulcers in intensive care (EVARUCI), translated into Brazilian Portuguese, using the Braden scale. METHOD: This cross-sectional study collected prospective data from adult patients in three intensive care units. The receiver operating characteristic (ROC) and precision-recall curve (PR curve) were used to analyse the predictive capacity for pressure injury (PI) using both predictive values and odds ratios (ORs). RESULTS: The incidence of PIs in the study sample of 324 patients was 14.2%. The area under the ROC curve was 0.807 for EVARUCI and 0.798 for the Braden scale. At a cutoff point of 10 on the EVARUCI scale, sensitivity was 69.6%; specificity 78.4%; positive predictive value 34.8%; and OR 8.3. At a cutoff point of 11 on the Braden scale, sensitivity was 76.1%; specificity 75.9%; positive predictive value 34.3%; and OR 10. The area under the PR curve was 0.396 for the EVARUCI scale and 0.348 for the Braden scale, reflecting a smaller area for both. The F1 score value was 0.476 with 37.5% precision and 65.2% recall for the EVARUCI scale, and 0.473 with 34.3% precision and 76.1% recall for the Braden scale. CONCLUSION: The EVARUCI scale predictive capacity was similar to that of the Braden scale. However, the precision of both scales was low for the accurate prediction of patients at risk of developing PIs.

Volatile compounds for biotechnological applications produced during competitive interactions between yeasts and fungi.

Fungi, yeasts and bacteria produce volatile compounds during their metabolism. In this study, the volatile compounds produced by yeast strains (Saccharomyces cerevisiae and Rhodotorula mucilaginosa) and fungal strains (Aspergillus carbonarius and Aspergillus ochraceus) during competitive interactions were investigated by solid-phase microextraction coupled with gas chromatography-mass spectrometry. Fifty-six volatile compounds were identified representing alcohols, aldehydes, esters, ketones, aromatic compounds, acids, furans, phenols, and nitrogen compounds, being the largest amount in the class of esters and alcohols. Eight compounds were identified only in interactive culture conditions such as 2-amino-1-propanol, isopropylamine, dimethylamine, pentyl propanoate, ethyl-2-aminopropanoate, acetone, oxalic acid, and ß-elemene and five of these were produced in cocultures including A. carbonarius. These will be developed for future biotechnological applications such as in the pharmaceutical and biological industry to produce drugs. Antimicrobial and antifungal activities; Solvent and herbicide; flavoring ingredient; solvent, plastic synthesis, nail polish remover and thinner, pesticide and herbicide; important in the complexation of minerals in the soil; and plant-environment interactions, defending predators, pathogens, and competitors.

Characterization of Competitive Inhibitors of Plasmodium falciparum cGMP-Dependent Protein Kinase.

Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) is an enticing antimalarial drug target. Novel chemotypes are needed because existing inhibitors have safety issues that may prevent further development. This work demonstrates isoxazole-based compounds are potent ATP competitive inhibitors of PfPKG and discloses a new analogue in this series. Isoxazoles 3 and 5 had Ki values that are comparable to a known standard, 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1H pyrrol-3-yl] pyridine. They also exhibited excellent selectivity for PfPKG over the human orthologue and the gatekeeper mutant T618Q PfPKG, which mimics the less accessible binding site of the human orthologue. The human orthologue's larger binding site volume is predicted to explain the selectivity of the inhibitors for the P. falciparum enzyme.

Genetic patterns in Montipora capitata across an environmental mosaic in Kane'ohe Bay, O'ahu, Hawai'i.

Spatial genetic structure (SGS) is important to a population's ability to adapt to environmental change. For species that reproduce both sexually and asexually, the relative contribution of each reproductive mode has important ecological and evolutionary implications because asexual reproduction can have a strong effect on SGS. Reef-building corals reproduce sexually, but many species also propagate asexually under certain conditions. To understand SGS and the relative importance of reproductive mode across environmental gradients, we evaluated genetic relatedness in almost 600 colonies of Montipora capitata across 30 environmentally characterized sites in Kane'ohe Bay, O'ahu, Hawaii, using low-depth restriction digest-associated sequencing. Clonal colonies were relatively rare overall but influenced SGS. Clones were located significantly closer to one another spatially than average colonies and were more frequent on sites where wave energy was relatively high, suggesting a strong role of mechanical breakage in their formation. Excluding clones, we found no evidence of isolation by distance within sites or across the bay. Several environmental characteristics were significant predictors of the underlying genetic variation (including degree heating weeks, time spent above 30°C, depth, sedimentation rate and wave height); however, they only explained 5% of this genetic variation. Our results show that asexual fragmentation contributes to the ecology of branching corals at local scales and that genetic diversity is maintained despite strong environmental gradients in a highly impacted ecosystem, suggesting potential for broad adaptation or acclimatization in this population.

Alternative instrument for the evaluation of handgrip strength in Duchenne muscular dystrophy.

BACKGROUND: The commonly used dynamometers can be ineffective in evaluating handgrip in patients with Duchenne muscular dystrophy (DMD), especially children with generalized muscle weakness. The aim of this study was to analyze whether the modified sphygmomanometer is an effective instrument for handgrip strength evaluation in patients with DMD, during different stages of the disease. METHOD: The handgrip strength of 33 patients was evaluated by the Jamar dynamometer and the modified sphygmomanometer. Motor function was evaluated by the Motor Function Measurement (MFM) scale. Four evaluations, with a six-month interval between each, were performed: Evaluation 1 (N = 33), Evaluation 2 (N = 24), Evaluation 3 (N = 15), and Evaluation 4 (N = 8). A linear regression model with mixed effects was used for the longitudinal data and descriptive analysis of strength for all four evaluations. RESULT: The first evaluation data presented very high correlations between the dynamometer and the modified sphygmomanometer (r = 0.977; p < 0.001). The longitudinal analysis showed a significant difference between Evaluation 1 and the other handgrip strength evaluations obtained using the dynamometer (p < 0.05) but not the modified sphygmomanometer (p > 0.05). Null values were obtained only when using the dynamometer device. CONCLUSION: The modified sphygmomanometer seems to be more suitable than the dynamometer for measuring handgrip strength in all stages of DMD.

Basidiocarp structures of Lentinus crinitus: an antimicrobial source against foodborne pathogens and food spoilage microorganisms.

Lentinus crinitus basidiocarps are an alternative to antimicrobials, but the stipe (24% basidiocarp) is discarded even with potential antimicrobial activity. This study evaluated the antimicrobial activity of L. crinitus basidiocarp pileus and stipe extracts against foodborne pathogens and food spoilage microorganisms. Basidiocarps of L. crinitus were grown in sugarcane bagasse and rice husks and the pileus and stipe methanolic extract was analyzed by broth microdilution method for antimicrobial activity against eight bacteria and eight fungi. The minimum bactericidal concentration values for pileus and stipe ranged from 0.40 to 0.50 mg mL- 1, for streptomycin from 0.10 to 0.50 mg mL- 1, and for ampicillin from 0.40 to 1.20 mg mL- 1. The minimum fungicidal concentration values for pileus and stipe ranged from 0.06 to 0.60 mg mL- 1, for bifonazole from 0.20 to 0.25 mg mL- 1, and for ketoconazole from 0.30 to 3.50 mg mL- 1. Extracts had bacteriostatic, bactericidal, fungistatic and fungicidal activity against all microorganisms, but with greater efficiency and specificity for some microorganisms. Both pileus and stipe are promising and sustainable alternatives for use in food, agricultural, and pharmaceutical industries.

Spatial distribution of Mycobacterium bovis spoligotypes in cattle from the state of Minas Gerais, Brazil.

Genotyping methods have led to a better understanding of the epidemiology of Mycobacterium bovis (M. bovis) infection, and its transmission dynamics, as well as the possible phylogenetic relationships between Mycobacterium strains, thus making bovine tuberculosis control programs more efficient. The goal of this study was to characterize the main spoligotypes of M. bovis isolated from cattle in the State of Minas Gerais, Brazil. It was carried out in 28 municipalities of "Triângulo Mineiro" and "Alto Paranaíba" regions of the state. Viscera samples were obtained from 58 bovines positive for tuberculosis according to comparative cervical tests, and from another 100 bovines with lesions suggestive of tuberculosis, which were donated by the National Agricultural Laboratory of Pedro Leopoldo, Minas Gerais. Microbiological isolation was performed in Stonebrink medium, and molecular identification of mycobacteria was performed by PCR. Genotyping was performed using the spoligotyping method at the Agrobiotechnology and Molecular Biology Institute of National Agricultural Technology Institute-National Scientific and Technical Research Council, Buenos Aires, Argentina. Among the 158 viscera samples, we obtained 40 (25%) isolates of M. bovis, and detected 11 spoligotype patterns, with a predominance of SB1142 (37.5%), SB0121 (25.0%), and SB1145 (10.0%). Other standards, SB0295, SB1050, SB0881, SB1144, SB1802, SB0140, SB0120, and SB0849, varied from 2.5 to 7.5%, heterogeneously distributed among the municipalities. The presence of spoligotypes shared with other Brazilian states and different countries indicates their possible exchange through epidemiological relationships, such as the transit of live animals and/or genetic similarity between strains that share a common ancestor.

An Original Complex Rearrangement Involving Chromosomes 9, 11, and 14, Harboring a Complex KMT2A Gene Rearrangement in an Infant With Mixed-phenotype Acute Leukemia.

KMT2A gene rearrangements represent the most frequent group of abnormalities in childhood leukemia (~70% of cases), with over 120 rearrangements described. The investigation of KMT2A rearrangements is still a vast field to be explored. Several studies have been characterizing different outcomes and leukemogenic mechanisms, depending on the translocation partner gene involved in childhood KMT2A-r leukemias. Therefore, the detection of the translocation partner gene, including in the context of complex rearrangements, may help to better delineate the disease. Here, we describe clinical and molecular cytogenetic data of a new complex variant translocation, involving chromosomes 9, 11, and 14, presenting a KMT2A gene extra copy and rearrangements, in an infant with de novo mixed-phenotype acute leukemia.

Body Dysmorphic Disorder in Rhinoplasty Candidates: Prevalence and Functional Correlations.

BACKGROUND: Rhinoplasty is one of the most commonly performed aesthetic/functional procedures worldwide. Among those who seek rhinoplasty are those whose aesthetic defect is interpreted by themselves disproportionately, leading to significant suffering. These are given the diagnosis of body dysmorphic disorder (BDD). They commonly have high expectations regarding the surgical outcome and are often not satisfied postoperatively. The present study aimed to correlate BDD with the patient's self-assessment of nasal function, analysing whether BDD would have any influence on it. In addition, we verified the prevalence of the disorder in our population. METHODS: Cross-sectional, comparative and analytical study. Eighty-eight patients participated in the trial, 57 of them being candidates for rhinoplasty, rhinoplasty group (RG), and 31 from a random population, control group (CG). Through self-assessment, the BDSS, The Utrecht, SNOT-22 and NOSE questionnaires were applied. Patients with BDSS score ≥ 6 were considered as positive for BDD. Comparisons were made between the groups and among the candidates for rhinoplasty with positive or negative BDD. RESULTS: The prevalence of the disorder was 35.1% in the RG and 3.2% in the CG. Significantly, higher NOSE and SNOT-22 scores, reflecting worse nasal function, were obtained by the RG, especially in those with positive screening for BDD, when compared to those with negative screening (p < 0.05). CONCLUSIONS: BDD affects about one-third of the rhinoplasty candidate population. Their presence seems to exert a negative influence on the patients' self-assessment regarding their nasal function. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Discovery of Potent, Reversible, and Competitive Cruzain Inhibitors with Trypanocidal Activity: A Structure-Based Drug Design Approach.

A virtual screening conducted with nearly 4 000 000 compounds from lead-like and fragment-like subsets enabled the identification of a small-molecule inhibitor (1) of the Trypanosoma cruzi cruzain enzyme, a validated drug target for Chagas disease. Subsequent comprehensive structure-based drug design and structure-activity relationship studies led to the discovery of carbamoyl imidazoles as potent, reversible, and competitive cruzain inhibitors. The most potent carbamoyl imidazole inhibitor (45) exhibited high affinity with a Ki value of 20 nM, presenting both in vitro and in vivo activity against T. cruzi. Furthermore, the most promising compounds reduced parasite burden in vivo and showed no toxicity at a dose of 100 mg/kg. These carbamoyl imidazoles are structurally attractive, nonpeptidic, and easy to prepare and synthetically modify. Finally, these results further advance our understanding of the noncovalent mode of inhibition of this pharmaceutically relevant enzyme, building strong foundations for drug discovery efforts.

From Inflammation to Cutaneous Repair: Topical Application of Lupeol Improves Skin Wound Healing in Rats by Modulating the Cytokine Levels, NF-κB, Ki-67, Growth Factor Expression, and Distribution of Collagen Fibers.

Skin wound healing is a highly complex event that involves different mediators at the cellular and molecular level. Lupeol has been reported to possess different biological activities, such as anti-inflammatory, antioxidant, antidiabetic, and in vitro wound healing properties, which motivated us to proceed with in vivo studies. We aimed to investigate the wound healing effect of lupeol-based cream for 3, 7, and 14 days. Wound excisions were induced on the thoraco-lumbar region of rats and topically treated immediately after injury induction. Macroscopic, histopathological, and immunohistochemical analyses were performed. Cytokine levels were measured by ELISA and gene expression was evaluated by real-time RT-qPCR. Our results showed a strong wound-healing effect of lupeol-based cream after 7 and 14 days. Lupeol treatment caused a reduction in proinflammatory cytokines (TNF-a, IL-1ß, and IL-6) and gene and protein NF-κB expression, and positively altered IL-10 levels, showing anti-inflammatory effects in the three treatment periods. Lupeol treatment showed involvement in the proliferative phase by stimulating the formation of new blood vessels, increasing the immunostaining of Ki-67 and gene expression, and immunolabeling of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and increasing gene expression of transforming growth factor beta-1 (TGF-ß1) after seven days of treatment. Lupeol was also involved in the tissue regeneration phase by increasing the synthesis of collagen fibers noted in the three treatment periods analyzed. Our findings suggest that lupeol may serve as a novel therapeutic option to treat cutaneous wounds by regulating mechanisms involved in the inflammatory, proliferative, and tissue-remodeling phases.

Correlation between carcass condemnations in slaughterhouses and official notifications of cattle testing positive for tuberculosis.

The objective of this study was to analyze the correlation between condemnations in slaughterhouses situated in Minas Gerais State and notifications to the Brazilian Official Veterinary Service of cattle that were positive for intradermal tuberculin tests. Data were obtained from three slaughterhouses under different surveillance conditions and from the Brazilian Agriculture and Livestock Health Agency for 2011 to 2017. During this period, there was an increase in the number of condemnations of females aged over 36 months, despite the number of females testing with intradermal tests and being reported as positive decreasing. Therefore, there is a discrepancy between the analyzed variables. Since there is a belief that slaughter condemnations can be used as tools for epidemiological surveys in beef and dairy farms, it is advisable for there to be a greater integration of the Brazilian Health Inspection Services in slaughterhouses and Brazilian Agriculture and Livestock defense department. This will ensure safe animal products.

The Use of a Wheelchair Propulsion Field Test to Determine Peak Heart Rate in Children and Adolescents With Myelomeningocele.

PURPOSE: We analyzed the evolution and pattern of heart rate (HR) during the 12-minute wheelchair propulsion field test (WPFT) and compared the peak HR (HRpeak) from the WPFT to the HRpeak obtained in the progressive cardiopulmonary exercise test on arm cranking ergometer (ACT). We aimed to determine if the field test detects the HRpeak consistently and could be used in clinical practice. METHODS: Eleven wheelchair-using children and adolescents with myelomeningocele (aged 8-15 y) performed a maximal ACT and a 12-minute WPFT. HR was recorded continuously at rest, during each minute of the tests, and at recovery. Mixed analysis of variance was used to compare the variables at rest and peak. Bland-Altman plot and Lin's concordance correlation coefficient were used to show agreement between the tests. RESULTS: During minute 2 of the WPFT, participants reached 73%-96% of the HRpeak values recorded in the ACT. From minutes 4 to 12, participants reached HRpeak values ranging 86%-109% of the values recorded in the ACT. There is agreement between the ACT and the WPFT tests. CONCLUSION: WPFT with minimal duration of 4 minutes may be an alternative tool to obtain HRpeak in children and adolescents with myelomeningocele.

First molecular epidemiological study of Mycobacterium avium subsp. paratuberculosis in cattle and buffalo from different regions of Brazil.

Paratuberculosis is an incurable disease in ruminants with great worldwide economic impact, caused by Mycobacterium avium subsp. paratuberculosis (MAP). The objective of this study was to carry out a study of the molecular epidemiology of the MAP using the restriction enzyme analysis (REA) technique of IS1311 MAP region in biological samples of feces, intestinal tissue, and mesenteric lymph nodes of cattle and buffaloes from six Brazilian states. In total, 109 samples of feces and tissues of cattle and buffaloes were collected from animal paratuberculosis suspected. Twenty-five samples were positive in the detection of the DNA of the IS900 region of MAP and it was possible to type 18 strains in the analysis of the region IS1311, being 100% of them identified as belonging to subtype Bison MAP strain. This is the first epidemiological molecular study of MAP in Brazil. The results indicate that paratuberculosis is widespread in cattle and in buffaloes in several regions of Brazil, and the subtype Bison MAP strain was the only one identified in the samples analyzed in this study, demonstrating the similarity between the strains from different states tested. These results provide the necessary support for the implementation of paratuberculosis control strategies in cattle and buffaloes in Brazil.

GAS6 Oncogene and Reverse MLLT3-KMT2A Duplications in an Infant with Acute Myeloid Leukemia and a Novel Complex Hyperdiploid Karyotype: Detailed High-Resolution Molecular Cytogenetic Studies.

Pediatric acute myeloid leukemia (AML) is a highly heterogeneous disease, presenting cytogenetic and molecular abnormalities which turned out to be critical prognostic factors. Ploidy changes as gain or loss of individual chromosomes are rare in AML, occurring only in about 1-2% of the affected children. Hyperdiploid karyotypes are exceedingly rare in infants less than 12 months of age. In this age group, structural rearrangements involving the KMT2A gene occur in about 58% of the cases. Among them, the translocation t(9;11)(p22;q23), KMT2A-MLLT3, is the most common abnormality accounting for approximately 22% of KMT2A rearrangements in infant AML cases. Here, we describe a 7- month-old girl with a history of fever and severe diarrhea, and a physical examination remarkable for pallor and hepatosplenomegaly. A novel complex hyperdiploid karyotype 53,XX,+X,+6,t(9;11)(p21.3;q23.3),+der(9)t(9;11)(p21.3;q23.3),dup(13)(q31q34),+14,+19,+21,+22 was characterized by high-resolution molecular cytogenetic approaches. Fluorescence in situ hybridization, multiplex-FISH, and multicolor chromosome banding were applied, revealing 2 reverse MLLT3-KMT2A fusions and a duplication of the GAS6 oncogene. Our work suggests that molecular cytogenetic studies are crucial for the planning of a proper strategy for risk therapy in AML infants with hyperdiploid karyotypes.