Epidemiology of pediatric hematological malignancies in Kazakhstan: Data from Unified National Electronic Healthcare System 2014-2021.

We aimed to describe incidence and all-cause mortality of hematological pediatric malignancies (leukemia and lymphomas) in Kazakhstan based on nationwide large-scale healthcare data from the Unified National Electronic Healthcare System (UNEHS) for the 2014-2021 year period. The cohort included data of patients less than 18 years old with the diagnosis of hematological malignancies registered in the UNEHS (inpatient and outpatient registries) for the year period 2014-2021. Descriptive statistics were conducted to indicate socio-demographic characteristics of the cohort. Incidence and all-cause mortality were calculated per 100,000 population. Cox proportional hazard regression analysis was performed to investigate the association between determinants with the all-cause mortality. The total cohort consisted of 3357 children with leukemia and 1474 children with lymphomas. The mean age at diagnosis of leukemia and lymphomas was 7.3 ± 4.7 and 9.9 ± 4.9 years, respectively. The incidence rate of hematological malignancies was 6.8 per 100,000 in 2021. Patients with ALL had a higher incidence rate than patients with AML (3.4 and 1.2 per 100,000 in 2021, respectively). The incidence rate of HL and NHL was relatively similar which varied from 0.6 to 2.6 per 100,000 in 2014-2021. All-cause mortality of pediatric hematological malignancies varied from 1.1 to 1.5 per 100,000 in 2014-2021, with the peak in 2016 (1.7 per 100,000). Younger age is significantly associated with increased risk of all-cause mortality in children with AML. CONCUSION: Patients with ALL had a higher incidence rate than patients with AML. The incidence rate of HL and NHL was relatively similar. All-cause mortality rates for leukemia and lymphomas were quite stable during the study period. Younger age is significantly associated with increased all-cause mortality among AML patients. However, there is no significant association of age with all-cause mortality among ALL, HL and NHL. In order to obtain more reliable data and analysis on pediatric (hematological) malignancies, specific registries for childhood tumors (including detailed information on relapses, treatments, short and long-term side effects, and specific death causes) should be implemented. WHAT IS KNOWN: • Leukemias and lymphomas together account for around 45% of all pediatric malignancies. • Lymphoma accounts for 12% of all childhood malignancies; non-Hodgkin's lymphomas (NHL) are more frequent than Hodgkin's lymphomas (HL). WHAT IS NEW: • The incidence rate of ALL was higher than the incidence rate of AML throughout the whole study period, whereas all-cause mortality of ALL and AML was quite stable. • According to Cox PH analysis, younger age (0-5 years old) was associated with a higher risk of death among AML children compared to older children, and no significant association of age was observed with all-cause mortality among ALL and lymphomas.

Double-Negative T (DNT) Cells in Patients with Systemic Lupus Erythematosus.

Double-negative T (DNT) cells are a rare and unconventional T-lymphocyte subpopulation lacking both CD4 and CD8 markers. Their immunopathological roles and clinical relevance have yet to be elucidated. Beyond autoimmune lymphoproliferative syndrome (ALPS), these cells may also play a role in rheumatic disorders, including systemic lupus erythematosus (SLE); indeed, these two diseases share several autoimmune manifestations (including nephritis). Moreover, one of the main experimental murine models used to investigate lupus, namely the MRL/lpr mouse, is characterized by an expansion of DNT cells, which can support the production of pathogenic autoantibodies and/or modulate the immune response in this context. However, lupus murine models are not completely consistent with their human SLE counterpart, of course. In this mini review, we summarize and analyze the most relevant clinical studies investigating the DNT cell population in SLE patients. Overall, based on the present literature review and analysis, DNT cell homeostasis seems to be altered in patients with SLE. Indeed, most of the available clinical studies (which include both adults and children) reported an increased DNT cell percentage in SLE patients, especially during the active phases, even though no clear correlation with disease activity and/or inflammatory parameters has been clearly established. Well-designed, standardized, and longitudinal clinical studies focused on DNT cell population are needed, in order to further elucidate the actual contribution of these cells in SLE pathogenesis and their interactions with other immune cells (also implicated and/or altered in SLE, such as basophils), and clarify whether their expansion and/or immunophenotypic aspects may have any immunopathological relevance (and, then, represent potential disease markers and, in perspective, even therapeutic targets) or are just an unspecific epiphenomenon of autoimmunity.

Pediatric erythema ab igne: clinical aspects and diagnostic issues.

Erythema ab igne is a dermatological condition resulting from repeated low-grade heat exposure (below the burning point), which can variably manifest with reticulated erythema and skin hyperpigmentation. Not infrequently, the cause of such a skin disorder is not immediately evident or reported by patients, especially if these are children. Compared to adults, erythema ab igne is rare in children and, if the general practitioners and pediatricians are not aware of this disorder, pediatric patients are often addressed to rheumatologists and/or undergo useless immunological investigations. Here, we performed a systematic case-based review, which finally included 32 cases of pediatric erythema ab igne (in addition to our new clinical report), and discussed the main clinical aspects and issues of this clinical entity in children. In detail, similarities of erythema ab igne with livedo reticularis and/or vasculitis-related rashes sometimes can lead to perform a panel of immunological investigations, which could be avoided. Indeed, our analysis emphasizes the importance of a careful and complete patient's anamnesis, including active questioning about the potential exposure to any physical agents (including heat sources) that may cause dermatological lesions. We also highlight some peculiarities in terms of location and heat injury in children developing erythema ab igne, based on the presence or absence of comorbidities. CONCLUSION: The occurrence of erythema ab igne in children (and especially in adolescents) is likely to increase in the next years because of the greater and sometimes inappropriate use of technological devices. Physicians should be aware of this condition in order to prevent patients from useless investigations, especially in the differential diagnosis of rheumatic disorders. A careful and complete patient's history with active questioning about the potential exposure to heating source is often decisive to diagnose erythema ab igne. WHAT IS KNOWN: • Erythema ab igne is a dermatological condition which is mainly described in adults exposed to heating source at the workplace. WHAT IS NEW: • The occurrence of erythema ab igne in children is likely to increase in the next years because of the greater and sometimes inappropriate use of technological devices. • Erythema ab igne in children can be classified in two main categories, based on the presence or absence of comorbidity. • A careful and complete anamnesis (including the active questioning about potential exposure to any heating source) is the mainstay for diagnosing erythema ab igne in children.

Pediatric Extra-Renal Nephroblastoma (Wilms' Tumor): A Systematic Case-Based Review.

Wilms Tumor (WT) is one of the most common renal tumors in the pediatric population. Occasionally, WT can primarily develop outside the kidneys (Extra-Renal Wilms Tumor, ERWT). Most pediatric ERWTs develop in the abdominal cavity and pelvis, whereas the occurrence of this tumor in other extra-renal sites represents a minor part of ERWT cases. In addition to describing a case of spinal ERWT (associated with spinal dysraphism) in a 4-year boy (to add a further clinical experience on this very rare pediatric tumor), we performed a case-based systematic literature review on pediatric ERWT. We retrieved 72 papers providing enough information on the diagnosis, treatment, and outcomes of 98 ERWT pediatric patients. Our research highlighted that a multimodal approach involving both chemotherapy and radiotherapy, after partial or complete tumor resection in most cases, was typically used, but there is no standardized therapeutic approach for this pediatric malignancy. However, this tumor may be potentially treated with a better success rate if the diagnostic confirmation is not delayed, the mass can be totally resected, and an appropriate and, possibly, tailored multimodal treatment can be promptly established. In this regard, an international agreement on a unique staging system for (pediatric) ERWT is definitely needed, as well as the development of international research, which may be able to gather several children diagnosed with ERWT and, possibly, lead to clinical trials which should also include developing countries.

Case report: Atypical teratoid/rhabdoid tumor of the lateral ventricle in a male adolescent (case-based review and diagnostic challenges in developing countries).

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and highly malignant central nervous system (CNS) embryonal neoplasm: it accounts for <2% of all pediatric CNS tumors and occurs mainly in infants and young children. The primary site of this tumor is usually the posterior cranial fossa. Supratentorial and, in detail, latero-ventricular location is extremely uncommon, especially in adolescents. This tumor is characterized by rapid growth and spread in cerebrospinal fluid and, therefore, it is characterized by a poor prognosis. Neurological signs and symptoms are related the location of the tumor. The radiological features of AT/RT are nonspecific. Immunohistochemical staining for loss of nuclear integrase interactor 1 (INI1) expression is considered a reliable criterion for the diagnosis of this type of tumor. AT/RT has been linked to mutations of SMARCB1 or, rarely, SMARCA4 genes, which function as tumor suppressor genes. Currently, there is no validated protocol of treatment for children with AT/RT, and multimodality treatment (consisting of surgery, chemotherapy, and radiation therapy) is considered. In this case report, we describe a 15-year-old adolescent with an AT/RT of the left lateral ventricle. Despite the late diagnosis, the multimodal therapeutic approach provided a good outcome for our patient at 21 months' follow-up. Based on our case-based review, early diagnosis and a multimodal approach to treatment play a key role in improving the survival of patients with this diagnosis. Implementing a system supporting pathological and molecular analyses for developing countries and, in general, for non-academic centers is of primary importance to timely diagnose and treat rare tumors, such as AT/RT.

Anti-Inflammatory, Antioxidant, and Anti-Atherosclerotic Effects of Natural Supplements on Patients with FMF-Related AA Amyloidosis: A Non-Randomized 24-Week Open-Label Interventional Study.

We aimed to evaluate the effect of a combination of natural products on parameters related to inflammation, endothelial dysfunction, and oxidative stress in a cohort of familial Mediterranean fever (FMF) patients with Serum Amyloid A amyloidosis, in a non-randomized, 24-week open-label interventional study. Morinda citrifolia (anti-atherosclerotic-AAL), omega-3 (anti-inflammatory-AIC), and extract with Alaskan blueberry (antioxidant-AOL) were given to patients with FMF-related biopsy-proven AA amyloidosis. Patients were >18 years and had proteinuria (>3500 mg/day) but a normal estimated glomerular filtration rate (eGFR). Arterial flow-mediated dilatation (FMD), carotid intima media thickness (CIMT), and serum biomarkers asymmetric dimethylarginine (ADMA), high sensitivity C-reactive protein (hs-CRP), pentraxin (PTX3), malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and glutathione peroxidase (GSH-Px) were studied at baseline and after 24 weeks of treatment. A total of 67 FMF-related amyloidosis patients (52 male (77.6%); median age 36 years (range 21−66)) were enrolled. At the end of a 24-week treatment period with AAL, AIC, and AOL combination therapy, ADMA, MDA, PTX3, hsCRP, cholesterol, and proteinuria were significantly decreased compared to baseline, while CuZn-SOD, GSH-Px, and FMD levels were significantly increased. Changes in inflammatory markers PTX3, and hsCRP were negatively correlated with FMD change, and positively correlated with decreases in proteinuria, ADMA, MDA, cholesterol, and CIMT. Treatment with AAL, AIC and AOL combination for 24 weeks were significantly associated with reduction in inflammatory markers, improved endothelial functions, and oxidative state. Efficient control of these three mechanisms can have long term cardiovascular and renal benefits for patients with AA amyloidosis.

Assessment of Surrogate Markers for Cardiovascular Disease in Familial Mediterranean Fever-Related Amyloidosis Patients Homozygous for M694V Mutation in MEFV Gene.

Cardiovascular disease (CVD) remains underestimated in familial Mediterranean fever-associated AA amyloidosis (FMF-AA). We aimed to compare early markers of endothelial dysfunction and atherosclerosis in FMF-AA with a homozygous M694V mutation (Group 1 = 76 patients) in the Mediterranean fever (MEFV) gene and in patients with other genotypes (Group 2 = 93 patients). Measures of increased risk for future CVD events and endothelial dysfunction, including flow-mediated dilatation (FMD), pentraxin-3 (PTX3), and carotid intima-media thickness (cIMT), and fibroblast growth factor 23 (FGF23) as a marker of atherosclerotic vascular disease were compared between groups. The frequency of clinical FMF manifestations did not differ between the two groups apart from arthritis (76.3% in Group 1 and 59.1% in Group 2, p < 0.05). FMD was significantly lower in Group 1 when compared with Group 2 (MD [95% CI]: −0.6 [(−0.89)−(−0.31)]). cIMT, FGF23, and PTX3 levels were higher in Group 1 (cIMT MD [95% CI]: 0.12 [0.08−0.16]; FGF23 MD [95% CI]: 12.8 [5.9−19.6]; PTX3 MD [95% CI]: 13.3 [8.9−17.5]). In patients with FMF-AA, M694V homozygosity is associated with lower FMD values and higher cIMT, FGF23, and PTX3 levels, suggesting increased CVD risk profiles. These data suggest that a genotype−phenotype association exists in terms of endothelial dysfunction and atherosclerosis in patients with FMF-AA.

Association Study of Anticitrullinated Peptide Antibody Status with Clinical Manifestations and SNPs in Patients Affected with Rheumatoid Arthritis: A Pilot Study.

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology that leads to disability due to articular and extra-articular damage. RA prevalence is variable. The disease is most common among females with a 3 : 1 ratio. The interaction of environmental and host factors contributes to RA development. Currently, the genome-wide association studies (GWAS) give the opportunity to uncover the RA genetic background. Anticitrullinated peptide antibody (ACPA) is a highly specific RA antibody, associated with poor prognosis and severe course of RA, and regulated by numerous genes. Our study is aimed at investigating whether there are any clinical and genetic aspects correlate with ACPA presence in Kazakhstani patients with RA. Indeed, the available studies on this subject are focused on Caucasian and East Asian populations (mainly Japanese and Chinese), and there are scarce data from Central Asia. Methods: Our study included 70 RA patients. Patients' blood samples were collected and genotyped for 14 SNPs by real-time polymerase chain reaction (RT-PCR). General examination, anamnestic, and clinical and laboratory data collection were carried out. Statistical analysis was performed using R statistics. Results and Conclusion. Our study revealed a significant association of ACPA positivity with Fc receptor-like 3 (FCRL3) and ACPA negativity with signal transducer and activator of transcription 4 (STAT4) genes, but not with T cell activation Rho GTPase activating protein (TAGAP). In addition, ACPA positivity was associated with radiographic progression, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), age of RA onset, the patient global assessment, body mass index (BMI), and Gamma globulin. Conclusion: Remained 11 earlier identified significantly associated in Caucasian and Asian population SNPs were not replicated in our cohort. Further studies on larger cohorts are needed to confirm our findings with higher confidence levels and stronger statistical power.

Conventional and novel therapeutic options in children with familial Mediterranean fever: A rare autoinflammatory disease.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease and is usually diagnosed in childhood, especially in the first decade of life. Paediatric FMF is characterized by a protean clinical expression and a variable therapeutic response, which can make its medical management very challenging. However, even if long-term complications of untreated FMF (e.g. amyloidosis and related organ damage) are less frequent in children compared to adults, they are not uncommon. Colchicine is the mainstay of the therapy in paediatric FMF; however, if children develop colchicine intolerance and/or resistance, biologics, particularly interleukin-1 antagonists, must be considered. Other conventional or biological therapeutic options do not currently have appropriate evidence-based support, except for some specific clinical presentations (e.g., arthritis). In this review, we discuss the biological basis and the clinical evidence for the current pharmacological treatment options available for paediatric FMF.

Somatic Copy Number Alterations in Human Cancers: An Analysis of Publicly Available Data From The Cancer Genome Atlas.

Somatic copy number alterations (SCNAs) are a pervasive trait of human cancers that contributes to tumorigenesis by affecting the dosage of multiple genes at the same time. In the past decade, The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) initiatives have generated and made publicly available SCNA genomic profiles from thousands of tumor samples across multiple cancer types. Here, we present a comprehensive analysis of 853,218 SCNAs across 10,729 tumor samples belonging to 32 cancer types using TCGA data. We then discuss current models for how SCNAs likely arise during carcinogenesis and how genomic SCNA profiles can inform clinical practice. Lastly, we highlight open questions in the field of cancer-associated SCNAs.

Diagnostic Barriers in Children with Immunodeficiencies in Central Asia: A Case-Based Discussion.

Common variable immunodeficiency (CVID) is a primary immune deficit (PID) mainly characterized by hypogammaglobulinemia. In addition to increased susceptibility to infections and several immune-mediated manifestations, patients with CVID frequently develop bronchiectasis because of recurrent respiratory infections. This occurrence could be more likely if the diagnosis of CVID is delayed, as it often happens in less resourced clinical settings. A 15-year-old female patient was admitted to a tertiary hospital in Kazakhstan for consultation regarding a previous and established diagnosis of bronchiectasis. The clinical history was characterized by recurrent respiratory infections for several years, in addition to the development of a mixed restrictive-obstructive respiratory syndrome. Therefore, she underwent chest computerized tomography, which confirmed the presence of multiple and bilateral bronchiectasis. The clinical discussion on this patient highlighted that serum immunoglobulins were never measured previously and, thus, their assessment was strongly recommended. Based on that, a diagnosis of CVID was finally achieved, and the patient started the appropriate immunoglobulin replacement therapy. To our knowledge, this report is the first English-language publication on CVID and bronchiectasis from Central Asia. Bronchiectasis is currently an important medical problem in developing countries and populations with low socioeconomic status, where the diagnosis of the underlying cystic fibrosis and non-cystic fibrosis comorbidities can be delayed and more difficult than in countries with more accessible health care systems and facilities. This case report emphasized this important clinical issue in Central Asia and should raise the medical attention and awareness of this health problem, in order to improve the diagnostic timing and rate.

Autoimmune pancreatitis and pancreatic cancer: Epidemiological aspects and immunological considerations.

Ordinary chronic pancreatitis is a well-known risk factor for pancreatic cancer, whereas such an association with autoimmune pancreatitis (AIP) is widely debated. Due to the rarity of the latter disorder, there are few specific clinical and epidemiological studies investigating the relation between AIP and pancreatic cancer, which do not seem to support it. However, these studies are affected by several limitations and, therefore, a link between AIP (and, specifically, type 1 AIP) and pancreatic cancer cannot be ruled out definitively on this basis. Moreover, several immunopathological aspects of type 1 AIP and, in general, immunoglobulin G4-related disease can create an immunological context that may impair the tumoral immunosurveillance and promote the pancreatic carcinogenesis and its progression. In detail, Th2 immunological dominance, type 2 macrophage polarization and basophil infiltration observed in type 1 AIP, may play a permissive role in creating a favorable immunological environment for pancreatic carcinogenesis, in addition to the immunosuppressive therapies that can be used in these patients.

Case Series: Efficacy and Safety of Hemoadsorption With HA-330 Adsorber in Septic Pediatric Patients With Cancer.

Background: Sepsis is a frequent cause of death in hospitalized patients and, in detail, in neonatal, pediatric, and adult intensive care units (ICUs). Severe sepsis has a very poor prognosis. Indeed, the mortality rate varies between 30 and 70% during the first 7-14 days. Despite a timely and appropriate therapy, the prognosis of severe sepsis is too often negative. Therefore, new therapeutic resources are under investigation in order to further improve prognosis. Case series: Here, we reported three septic children in whom we used extracorporeal blood purification therapy with hemoadsorption device HA330 (Jafron Biomedical Co., Ltd., China), aiming to scavenge and eliminate bacterial toxins and inflammatory mediators from the blood. Discussion and Conclusion: This small case series first showed that hemoperfusion with HA330 cartridge may be an effective and relatively safe adjunctive treatment to counterbalance the cytokine storm in septic children with hematological disorders. Further studies are needed to confirm and further support its safety and efficacy in a large number of pediatric patients.

Staphylococcus aureus Infection and Persistence in Chronic Rhinosinusitis: Focus on Leukocidin ED.

Chronic rhinosinusitis (CRS) is thought to be a multifactorial disease that includes a direct involvement of bacteria that trigger inflammation and contribute to CRS pathogenesis. Staphylococcus aureus infection and persistence is associated with chronic rhinosinusitis (CRS), and it may be particularly relevant in the form with nasal polyps (CRSwNP). The large array of exotoxins deployed by S. aureus is instrumental for the bacterium to warrant its infection and dissemination in different human body districts. Here, we analyze the common Th2 environment in CRSwNP and prospect a possible dynamic role played by S. aureus leukocidins in promoting this chronic inflammation, considering leukocidin ED (LukED) as a strong prototype candidate worth of therapeutic investigation. CCR5 is an essential target for LukED to exert its cytotoxicity towards T cells, macrophages and dendritic cells. Therefore, CCR5 blockade might be an interesting therapeutic option for CRS and, more specifically, persistent and relapsing CRSwNP. In this perspective, the arsenal of CCR5 antagonists being developed to inhibit HIV-1 entry (CCR5 being the major HIV-1 co-receptor) could be easily repurposed for CRS therapeutic investigation. Finally, direct targeting of LukED by neutralizing antibodies could represent an important additional solution to S. aureus infection.

HLA-DQB1*02 allele in children with celiac disease: Potential usefulness for screening strategies.

Through a retrospective analysis of a real-life cohort of children with celiac disease (CD), who underwent HLA-DQ genotyping, we supported our previous findings indicating the presence of HLA-DQB1*02 allele in at least 90%-95% of pediatric patients. In the present study, reporting the HLA-DQ analysis from 184 children (age range: 1-16 years) diagnosed with CD in a single centre, we found that 97.29% of all these CD children (n = 179 out of 184 genotyped patients) resulted to be carriers of at least one copy of HLA-DQB1*02 allele. If a widened screening for CD should result to be appropriate in the pediatric population after further clinical research, this observation might be potentially exploited to consider a two-step screening strategy, starting with the HLA-DQB1*02 targeted analysis followed by the specific serology for CD in these predisposed patients only. However, additional and larger studies are needed to support our findings.

Adalimumab in the treatment of pediatric Behçet's disease: case-based review.

Behçet's disease (BD) is a systemic vasculitis affecting prominently the veins, which is usually diagnosed in adulthood, but can occur in children younger than 16 years in about 4-26% of cases. The therapy is based on several immune-suppressive drugs; in case of inadequate control and/or complications, the biologic therapy with anti-TNF drugs has been successfully used in adults. Here, we reported one pediatric case of BD with systemic (persistent/recurrent high fever), skin and mucosal manifestations (recurrent aphthous stomatitis, anal/penile ulcers, erythema nodosum and papulo-pustules), that were unresponsive to the conventional treatment with steroids and colchicine; however, he was successfully treated with adalimumab. Compared to adult patients, the experience with adalimumab in the treatment of pediatric BD is very limited. Indeed, through a systematic search in the medical literature, we retrieved 4 case reports and 2 case series, describing BD pediatric patients treated with adalimumab, in addition to three clinical studies including some BD children. The analysis and discussion of these available clinical experiences may indicate adalimumab as an effective and safe option to treat several forms of BD, in addition to BD-related chronic uveitis.

Ibuprofen for Pain Control in Children: New Value for an Old Molecule.

BACKGROUND: Acute pain is one of the major complaints reported in pediatric emergency departments and general wards. Recently, both the US Food and Drug Administration and European Medicine Agency emitted some warnings regarding the use of opioids, including codeine, in children. OBJECTIVE: The aims of this study were summarizing the main pharmacological aspects of ibuprofen, discussing the current evidence about the use of ibuprofen in different and specific clinical settings, and providing a comparison with acetaminophen and/or codeine, according to available studies. STUDY DESIGN AND METHODS: Studies evaluating ibuprofen for the management of acute pain in children were extracted from the PubMed and MEDLINE database within the period ranging from 1985 through 2017. After discussing safety of ibuprofen and its concomitant use with acetaminophen, the specific indications for the clinical practice were considered. RESULTS: Ibuprofen resulted to be more effective than acetaminophen, and comparable to the combination acetaminophen-codeine, for the control of acute pain related to musculoskeletal pain. Moreover, similar results have been reported also in the management of toothache and inflammatory diseases of the oral cavity and pharynx. Ibuprofen resulted to be useful as a first approach to episodic headache. Finally, the role of ibuprofen in the management of postoperative pain and, particularly, after tonsillectomy and/or adenoidectomy has been reconsidered recently. CONCLUSIONS: Ibuprofen resulted to be the most studied nonsteroidal anti-inflammatory drug in the management of acute pain in children; in general, it showed a good safety profile and provided evidence of effectiveness, despite some differences according to the specific clinical context.

Bacterial resistance in the intensive care unit of developing countries: Report from a tertiary hospital in Kazakhstan.

OBJECTIVES: The aim of this study was to describe the patterns of antimicrobial resistance (AMR) of bacterial isolates causing hospital-acquired infections (HAIs) in the intensive care unit (ICU) of a tertiary hospital in Kazakhstan. METHODS: This was a retrospective analysis of AMR in the ICU of the National Research Center for Oncology and Transplantation (Astana, Kazakhstan) during the year 2015. RESULTS: During the study period, 546 patients were admitted to the ICU, of whom 135 (24.7%) developed at least one HAI. Most HAIs caused by Gram-positive bacteria were due to Enterococcus faecalis, which were resistant to aminoglycosides in >70% cases. Gram-negative bacteria were isolated in ca. 50% of cases, thus representing the greatest burden of HAIs. Very high resistance rates to ceftriaxone, cefotaxime and cefuroxime were observed. Moreover, Pseudomonas aeruginosa and Acinetobacter baumannii were resistant to carbapenems in <20% and in ca. 45% of cases, respectively. CONCLUSION: This study demonstrates the urgent need to implement more rational use of antimicrobials in Kazakhstan, which can be done only by establishing a proactive surveillance system along with an appropriate infection control programme.