Chromosomal complexity as a biomarker to de-escalate adjuvant imatinib treatment in high-risk gastrointestinal stromal tumor.

11535 Background: Gastrointestinal stromal tumors (GISTs) are characterized molecularly by oncogenic KIT or platelet-derived growth factor alpha ( PDGFRA) mutations. Malignant progression of primary GISTs occurs through stepwise accumulation of additional chromosomal aberrations, such as losses of chromosome arms 14q, 22q, 1p, 15q and Xp. After surgical resection of primary GIST, three years of adjuvant imatinib treatment is recommended for patients with an estimated high risk of recurrence. Still, nearly half of high-risk patients are cured by surgery alone, indicating that selection of patients could be improved. We hypothesized that high-risk GISTs with few chromosomal aberrations had a favorable outcome, and might not benefit from adjuvant therapy. The aim of the study was to investigate if chromosomal complexity could be used as a biomarker in de-escalation of adjuvant imatinib treatment. Methods: GIST patients undergoing surgical resection of their primary tumor between 1998 and 2020 were identified in the sarcoma database at Oslo University Hospital. All samples with available karyotype analysis made on fresh tumor tissue were included. Karyotypes were categorized as simple if they had ≤5 chromosomal changes, and complex if there were > 5 chromosomal aberrations. Results: Chromosomal aberrations were detected in 226 tumors, of which 181 (80.1 %) were gastric. The most frequent resulting imbalances were loss of 14q (75.9 %), 22q (43.5 %), 1p (36.6 %), and 15q (29.6 %). One-hundred and thirty-six tumors (60.2 %) had simple karyotypes whereas 90 (39.8 %) were complex. Cytogenetically complex tumors were larger ( P< 0.001), had a higher mitotic count ( P= 0.009), and were more often non-gastric ( P< 0.001). There was a strong association between chromosomal complexity and risk classification according to the modified NIH criteria ( P< 0.001). Thirty-eight of 58 (65.5 %) high-risk tumors were karyotypically complex compared to 37 of 144 (25.7 %) tumors that were not high-risk. In the high-risk group, 17 patients experienced disease recurrence, of whom one had a simple and 16 had a complex tumor karyotype. Estimated 5-year recurrence-free survival (RFS) for patients with simple tumor karyotypes was 94 % compared to 51 % for patients with cytogenetically complex tumors ( P= 0.004). Adjuvant and/or neoadjuvant imatinib treatment was administered to 40 high-risk patients with a median treatment duration of 33 months (range 2-60 months). A complex karyotype was associated with poor RFS both in patients with ( P= 0.016) and without ( P= 0.046) adjuvant imatinib. Conclusions: Chromosomal complexity was strongly associated with poor RFS in localized, high-risk GIST. Recurrences were infrequent for tumors with simple karyotypes, indicating that de-escalation of adjuvant imatinib treatment should be further explored in patients with cytogenetically simple GISTs.

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Post-operative Complications Following Emergency Laparotomy are Common and Associated with Increased Late Mortality – a Retrospective Multi-centre Study.

10.21203/rs.3.rs-428635/v1 ◽

2021 ◽

Author(s):

shivam sharma ◽

Joseph Alderman ◽

Dhruv Parekh ◽

David Thickett ◽

Jaimin Patel

Keyword(s):

High Risk ◽

Length Of Stay ◽

Pulmonary Complications ◽

High Risk Group ◽

University Hospital ◽

Emergency Laparotomy ◽

Multi Centre Study ◽

Mortality And Morbidity ◽

High Risk Patients ◽

Risk Patients

Abstract BackgroundThe ﬁrst National Emergency Laparotomy Audit (NELA) highlighted that morbidity and mortality from emergency surgery remains elevated especially in high-risk patients deﬁned as a P-POSSUM mortality ≥ 5% and ASA ≥ 3. The incidence of postoperative pulmonary complications (PPCs) are thought to be high following emergency laparotomy but no recent studies have evaluated the incidence or consequences of PPC following emergency laparotomy in the UK.MethodsA retrospective cohort study was conducted at University Hospital Birmingham and Heartlands Hospital, Birmingham, to investigate the incidence of PPCs following emergency laparotomy. The NELA databases from the two Trusts were used to identify patients. Patients were retrospectively screened for the development of PPCs using the validated Melbourne Group Scale. Data was analysed using Chi-squared test for categorical data and continuous data displayed as medians with statistical analysis from a Mann–Whitney U test. Results A total of 362 correctly coded patients were identified. High-risk patients accounted for 62% (226) of the cohort. These patients were older (p < 0.001) and had higher baseline lactate (p = 0.04) and creatinine levels (p = 0.003). Median P-POSSUM mortality was 10.6% (5.6–31.4%) with 76.4% of patients having an ASA ≥ 3. These patients had an increased length of stay (p < 0.001) and accounted for nearly all the deaths (42 vs. 2; p < 0.001). The incidence of PPCs was 37%, again the incidence was greater in the high-risk group (37% vs. 6% p < 0.001). Development of a PPC was associated with an increased length of stay (17 d vs. 9 d; p < 0.001) as well as a 90, 180 and 360 day mortality.DiscussionThis study demonstrates that the sub-group of patients deemed ‘high-risk’ are at greatest risk of developing a PPC and consequently have an increased length of stay and an increased 90, 180 and 360 day mortality. This allowed us to identify a group of patients at high risk of PPC who we can target with potential novel therapies such as high-ﬂow nasal cannulae oxygen in clinical trials to reduce mortality and morbidity.

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Outcome of carotid endarterectomy under local anaesthesia with respect to the patients’ risk profile

VASA ◽

10.1024/0301-1526.38.3.225 ◽

2009 ◽

Vol 38 (3) ◽

pp. 225-233 ◽

Cited By ~ 2

Author(s):

Aleksic ◽

Luebke ◽

Brunkwall

Keyword(s):

Myocardial Infarction ◽

High Risk ◽

Carotid Endarterectomy ◽

Complication Rate ◽

Local Anaesthesia ◽

High Risk Group ◽

High Risk Patients ◽

Hostile Neck ◽

Risk Patients ◽

Angioplasty And Stenting

Background: In the present study the perioperative complication rate is compared between high- and low-risk patients when carotid endarterectomy (CEA) is routinely performed under local anaesthesia (LA). Patients and methods: From January 2000 through June 2008 1220 consecutive patients underwent CEA under LA. High-risk patients fulfilled at least one of the following characteristics: ASA 4 classification, “hostile neck”, recurrent ICA stenosis, contralateral ICA occlusion, age ≥ 80 years. The combined complication rate comprised any new neurological deficit (TIA or stroke), myocardial infarction or death within 30 days after CEA, which was compared between patient groups. Results: Overall 309 patients (25%) were attributed to the high-risk group, which differed significantly regarding sex distribution (more males: 70% vs. 63%, p = 0,011), neurological presentation (more asymptomatic: 72% vs. 62%, p = 0,001) and shunt necessity (33% vs. 14%, p < 0,001). In 32 patients 17 TIAs and 15 strokes were observed. In 3 patients a myocardial infarction occurred. Death occurred in one patient following a stroke and in another patient following myocardial infarction, leading to a combined complication rate of 2,9% (35/1220). In the multivariate analysis only previous neurological symptomatology (OR 2,85, 95% CI 1,38-5,91) and intraoperative shunting (OR 5,57, 95% CI 2,69-11,55) were identified as independent risk factors for an increased combined complication rate. Conclusions: With the routine use of LA, CEA was not associated with worse outcome in high-risk patients. Considering the data reported in the literature, it does not appear justified to refer high-risk patients principally to carotid angioplasty and stenting (CAS) when LA can be chosen to perform CEA.

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P3609Temporal trends of the management and outcomes of patients after myocardial infarction according to the risk for recurrent cardiovascular events

European Heart Journal ◽

10.1093/eurheartj/ehz745.0468 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T Grinberg ◽

T Bental ◽

Y Hammer ◽

A R Assali ◽

H Vaknin-Assa ◽

...

Keyword(s):

Myocardial Infarction ◽

High Risk ◽

Cardiovascular Events ◽

Risk Group ◽

Temporal Trends ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

High Risk Patients ◽

Risk Patients

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.

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Finding of Kinase Domain Mutations at Diagnosis IN PATIENTS with Chronic PHASE Chronic Myeloid Leukemia (CP-CML) MAY Identify Those at High RISK of Disease Progression.

Blood ◽

10.1182/blood.v114.22.4251.4251 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4251-4251

Author(s):

Angelo Michele Carella ◽

Gabriella Cirmena ◽

Gioacchino Catania ◽

Gianmatteo Pica ◽

Germana Beltrami ◽

...

Keyword(s):

High Risk ◽

Conflicts Of Interest ◽

Prognostic Significance ◽

Chronic Phase ◽

Kinase Domain ◽

Imatinib Treatment ◽

Intermediate Risk ◽

High Risk Patients ◽

Risk Patients ◽

Kinase Domain Mutations

Abstract Abstract 4251 Kinase domain (KD) mutations are associated with resistance to Imatinib in CP-CML but their incidence and prognostic significance before any treatment are unclear. To assess if KD mutations at diagnosis may have prognostic significance, we have recently reviewed (before treatment with Imatinib) the mutation status of 45 patients,of whom low risk: 24 patients; intermediate risk: 8 patients; high risk: 13 patients, according to Sokal/Euro. We found that a) no patient with low and intermediate risk showed KD mutations at diagnosis; b) 4/13 high risk patients showed the following mutations at diagnosis: S265R, E255K, F359Y and E255V/E258V; other 5 patients developed mutations during Imatinib treatment (E255V, T315I, E255V/E258V, H396R and D248-274). All patients with low-intermediate risk are alive and well at a median of 44 months (range, 15-71 months). On the contrary, 3/4 high risk patients with KD mutations at diagnosis progressed and died of blastic evolution at 23, 33 and 69 months despite Nilotinib and Dasatinib therapy. Other 3/5 high risk patients who developed mutations under Imatinib, died of blastic evolution at 22, 23 and 43 months despite Nilotinib and Dasatinib treatment. Seven high risk patients are alive under Imatinib between 4 and 51 months. In conclusion, the KD mutations at diagnosis were frequent in high Sokal/Euro risk group supporting the concept that such mutations could be related to the basic biology of the disease. These data, if confirmed, could modify our approach to high risk patients with KD mutation at diagnosis, i.e. utilizing second/third TKI generation earlier during the disease and, in selected cases, reconsidering allografting earlier before leukemic evolution make such procedure useless. Disclosures: No relevant conflicts of interest to declare.

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A comprehensive characterization of anatomical and molecular risk factors in gastric gastrointestinal stromal tumor.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e23522 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e23522-e23522

Author(s):

Kjetil Boye ◽

Anne Marit Wiedswang ◽

Leonardo A. Meza-Zepeda ◽

Ivar Hompland ◽

Ingvild Lobmaier ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Tumor Growth ◽

Large Population ◽

Population Based ◽

Gastric Gist ◽

Imatinib Treatment ◽

High Risk Patients ◽

Risk Patients ◽

Upper Third

e23522 Background: Gastric gastrointestinal stromal tumors (GISTs) demonstrate a remarkable diversity in clinical behavior. Established risk criteria identify patients prone to recurrence with high sensitivity, but factors that could add specificity are needed. The aim of this study was to give a comprehensive picture of localized, gastric GIST and to investigate prognostic factors in a large population-based series. Methods: Patients with primary gastric GISTs completely resected between 2000 and 2018 were identified in the sarcoma database at Oslo University Hospital. Gastric subsite was divided into the upper, middle and lower thirds. Macroscopic growth pattern was coded as luminal, exophytic or transmural based on imaging and surgical reports. Mutation analysis was performed by Sanger sequencing of selected exons in KIT and PDGFRA and by targeted next-generation sequencing. Results: The cohort comprised 295 patients, representing 98% of patients in the region reported to the Cancer Registry of Norway. Of 292 tumors suitable for anatomical classification, 122 were located in the upper third of the stomach (41.8%), 120 in the middle (41.1%), and 50 in the lower third (17.1%). The number of luminal, exophytic and transmural tumors were 100 (34.1%), 94 (32.1%) and 99 (33.8%), and 2 tumors were not possible to classify. KIT mutations were detected in 183 of 256 tumors (71.5%), PDGFRA mutations in 62 (24.2%), whereas only 11 patients (4.3%) had KIT and PDGFRA wild-type tumors. Transmural tumors were larger, more often located in the upper third, had higher mitotic activity, and more frequently had KIT del557/558 mutations. KIT mutated tumors had a predilection for the upper two thirds and PDGFRA mutated tumors for the lower two thirds. Recurrences were rare among patients with luminal or exophytic tumors, with a 5-year RFS of 96% versus 71% with transmural tumors (HR 8.45; 95% CI 3.69-19.36; P< 0.001). RFS was inferior with transmural tumor growth also among high-risk patients, 46% versus 83% at 5 years ( P= 0.001). Excluding patients with tumor rupture, there was only one recurrence among 24 high-risk patients with luminal or exophytic primaries, of whom 11 did not receive adjuvant therapy. Conclusions: This study provides a comprehensive, population-based description of the anatomical and molecular landscape of gastric GIST, with findings of potential clinical relevance. Transmural tumor growth was a predictor of poor outcome and could supplement established risk factors in selecting patients for adjuvant imatinib treatment.

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SPECIFICS OF ANTIHYPERTENSION THERAPY IN HYPERTENSIVES OF VARIOUS CARDIOVASCULAR RISK (BY THE REGISTRY OF CHRONIC NON-COMMUNICABLE DISEASES IN TYUMENSKAYA OBLAST)

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2018-3-4-10 ◽

2018 ◽

Vol 17 (3) ◽

pp. 4-10

Author(s):

A. Yu. Efanov ◽

Yu. A. Vyalkina ◽

Yu. A. Petrova ◽

Z. M. Safiullina ◽

O. V. Abaturova ◽

...

Keyword(s):

Cardiovascular Risk ◽

High Risk ◽

Risk Group ◽

High Risk Group ◽

Risk Level ◽

Moderate Risk ◽

High Risk Patients ◽

Risk Patients ◽

Very High

Aim. To assess the specifics of antihypertension therapy (AHT) in hypertensives of various cardiovascular risk, in the registry of chronic non-communicable diseases in Tyumenskaya oblast.Material and methods. A random sample studied, of 1704 patients with hypertension, inhabitants of Tyumenskaya oblast (region), ascribed to dispensary follow-up. Mean age 62±7,5 y.o. Of those 31,5% (n=537) males. The prevalence and efficacy of AHT assessed according to cardiovascular risk level. The significance was evaluated with the criteria χ2.Results. AHT was characterized by the growth of the frequency of treatment approaches with cardiovascular risk consideration. Regular treatment took 33,9% patients of low and moderate risk vs 41,3% of high and very high (p<0,01). In the male group such tendency also took place. Gender specifics of AHT was characterized by that in the groups of high and very high risk females took medications significantly more commonly than males — 46,6% vs 29,1% in high risk group (p<0,01) and 47,5% vs 30% in very high risk group (p<0,01). With the increase of the risk level, there was decline of treatment efficacy — from 95% in low risk group to 32,5% in very high risk group; 53,1% of the participants were taking monotherapy, 32,9% — two drugs, 14,0% — ≥3 drugs. With the increase of risk grade there is tendency to increase of combinational AHT, however with no significant increase of efficacy. Treatment efficacy in high and very high risk patients comparing to patients with low and moderate risk was significantly lower — 33,1% vs 69,7% (p<0,01), respectively. Statins intake among the high and very high risk patients was 10,6-11,0% males and 7,8% females (p<0,05).Conclusion. AHT in hypertensives in Tymenskaya oblast, under dispensary follow-up, is characterized by insufficient usage of combinational drugs. With the raise of cardiovascular risk there is tendency to higher rate of combinational AHT. However there is no significant increase in efficacy of treatment with the increase of medications number. A very low rate of statins intake is noted. The obtained specifics witness for the necessity to optimize AHT among the high and very high risk patients — inhabitants of Tyumenskya oblast.

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Presence of a High Amount of Stroma and Downregulation of SMAD4 Predict for Worse Survival for Stage I–II Colon Cancer Patients

Analytical Cellular Pathology ◽

10.1155/2009/214085 ◽

2009 ◽

Vol 31 (3) ◽

pp. 169-178

Author(s):

Wilma E. Mesker ◽

Gerrit-Jan Liefers ◽

Jan M. C. Junggeburt ◽

Gabi W. van Pelt ◽

Paola Alberici ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Disease Free Survival ◽

Tumor Stroma ◽

High Risk Group ◽

Stage I ◽

Prognostic Information ◽

Mesenchymal Transition ◽

High Risk Patients ◽

Risk Patients

Background: For stage I–II colon cancer a significant number (5–25%) of patients has recurrent disease within 5 years. There is need to identify these high-risk patients as they might benefit from additional treatment.Stroma-tissue surrounding the cancer cells plays an important role in the tumor behavior. The proportion of intra-tumor stroma was evaluated for the identification of high-risk patients. In addition, protein expression of markers involved in pathways related to stroma production and epithelial-to-mesenchymal transition (EMT) was analyzed: β-catenin, TGF-β-R2 and SMAD4.Methods: In a retrospective study of 135 patients with stage I–II colon cancer, the amount of stroma was estimated on routine haematoxylin–eosin stained histological sections. Sections were also immunohistochemically stained for β-catenin, TGF-β-R2 and SMAD4.Results: Of 135 analyzed patients 34 (25.2%) showed a high proportion of stroma (stroma-high) and 101 (74.8%) a low proportion (stroma-low). Significant differences in overall-survival and disease-free-survival were observed between the two groups, with stroma-high patients showing poor survival (OS p < 0.001, HZ 2.73, CI 1.73–4.30; DFS p < 0.001, HZ 2.43, CI 1.55–3.82). A high-risk group was identified with stroma-high and SMAD4 loss (OS p = 0.008, HZ 7.98, CI 4.12–15.44, DFS p = 0.005, HZ 6.57, CI 3.43–12.56); 12 of 14 (85.7%) patients died within 3 years. In a logistic-regression analysis a high proportion of stroma and SMAD4 loss were strongly related (HZ 5.42, CI 2.13–13.82, p < 0.001).Conclusion: Conventional haematoxylin–eosin stained tumor slides contain more prognostic information than previously fathomed. This can be unleashed by assessing the tumor–stroma ratio. The combination of analyzing the tumor–stroma ratio and staining for SMAD4 results in an independent parameter for confident prediction of clinical outcome.

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Diabetic foot and its serial treatment in high-risk patients: focusing on the individual

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.66.11.1542 ◽

2020 ◽

Vol 66 (11) ◽

pp. 1542-1547

Author(s):

Eli Ávila Souza Júnior ◽

Raul Silva Simões de Camargo ◽

Tiago Soares Baumfeld ◽

Daniel Soares Baumfeld ◽

Benjamin Dutra Macedo

Keyword(s):

High Risk ◽

Diabetic Foot ◽

Tertiary Hospital ◽

Cross Sectional Study ◽

High Risk Group ◽

Foot Care ◽

Cross Sectional ◽

High Risk Patients ◽

Risk Patients ◽

The Individual

SUMMARY Objectives: To assess knowledge about diabetic foot, care measures, and the importance attached to serial treatment in a group of high-risk diabetic foot patients. METHODS: This is a cross-sectional study, carried out in a tertiary hospital, with 25 patients undergoing serial treatment for diabetic foot. The tabulation of the data occurred through the use of three methodological figures: core idea, key expressions, and the collective subject discourse. RESULTS: It became evident that even among high-risk patients with diabetic foot, there is no complete knowledge about the definition of the disease. Despite this, all participants reported practicing daily care measures, including frequent inspection of the feet, food care, and attention to footwear. Regarding the importance of serial treatment, there was unanimous recognition of the relevance of this practice, which improves self-care discipline, optimizes the understanding of the disease, and helps to prevent progression. CONCLUSIONS: Authentic speeches in the context of a pathology of considerable prevalence manifested, in an unprecedented way, with conceptions about its definition, care measures, and importance of serial treatment in a high-risk group.

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Epidemiology and risk factors of rectal colonization of carbapenemase-producing Enterobacteriaceae among high-risk patients from ICU and HSCT wards in a university hospital

10.21203/rs.3.rs-21674/v1 ◽

2020 ◽

Author(s):

Li Yan ◽

Jide Sun ◽

Xiuyu Xu ◽

Shifeng Huang

Keyword(s):

Risk Factors ◽

High Risk ◽

University Hospital ◽

Health Concern ◽

Urinary System ◽

Fecal Samples ◽

High Risk Patients ◽

Risk Patients ◽

Independent Risk Factors ◽

Rectal Colonization

Abstract Background: Nosocomial infections caused by carbapenemase-producing Enterobacterieceae (CPE) constitute a major global health concern and are associated with increased morbidity and mortality. Rectal colonization with CPE is a risk factor for bacterial translocation leading to subsequent endogenous CPE infections. This prospective observational study was aimed to investigate the prevalence and epidemiology of rectal colonization of CPE, the carbapenemase genotypes, and to identify the independent risk factors for the acquisition of CPE colonization in high-risk patients from ICU and HSCT wards in a university hospital in China. Methods: In a prospective cohort study, 150 fecal samples from rectal swabs were consecutively obtained for inpatients from the ICU and HSCT wards from November 2018 to May 2019, and screening test for CPE was conducted by using home-made trypsin soybean broth (TSB) selective media and MacConkey agar. Antimicrobial susceptibility was determined by the broth microdilution method and carbapenemase genes were characterized by both the GeneXpert Carba-R and PCR for blaKPC, blaNDM, blaIMP, blaVIM and blaOXA. In order to further investigate the risk factors and clinical outcomes of CPE colonization, a prospective case-control study was also performed.Results: 26 suspected CPE strains, including 17 Klebsiella pneumoniae, 6 Escherichia coli, 1 Citrobacter freundii, 1 Enterobacter Kobe, and 1 Raoultella ornithinolytica, were identified in 25 non-duplicated fecal samples from 25 patients, with a carriage rate of 16.67% (25/150). Through GeneXpert Carba-R and subsequent PCR and sequencing, all the suspected CPE isolates were identified to be positive for the carbapenemase genes, of which 17 were blaKPC-carriers, and another 9 were blaNDM-producers. Multivariate analysis indicated that urinary system diseases, operation of bronchoscopy, and combined use of antibiotics were independent risk factors for acquiring CPE colonization in high-risk patients from the ICU and HSCT wards. Conclusions: This study revealed a high prevalence of rectal CPE colonization in high-risk patients from ICU and HSCT wards, and a predominant colonization of the KPC-producing K. pneumoniae strains. Stricter infection control measures are urgently needed to limit the dissemination of CPE strains, especially in patients who were afflicted by urinary system diseases, have underwent bronchoscopy, and were previously exposed to combined antibiotic use.

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Epidemiology and risk factors of rectal colonization of carbapenemase-producing Enterobacteriaceae among high-risk patients from ICU and HSCT wards in a university hospital

Antimicrobial Resistance and Infection Control ◽

10.1186/s13756-020-00816-4 ◽

2020 ◽

Vol 9 (1) ◽

Author(s):

Li Yan ◽

Jide Sun ◽

Xiuyu Xu ◽

Shifeng Huang

Keyword(s):

Risk Factors ◽

High Risk ◽

University Hospital ◽

Health Concern ◽

Urinary System ◽

High Risk Patients ◽

Broth Microdilution Method ◽

Risk Patients ◽

Independent Risk Factors ◽

Rectal Colonization

Abstract Background Nosocomial carbapenemase-producing Enterobacterieceae (CPE) infections constitute a major global health concern and are associated with increased morbidity and mortality. Rectal colonization with CPE is a risk factor for bacterial translocation leading to subsequent endogenous CPE infections. This prospective observational study was aimed to investigate the prevalence and epidemiology of rectal colonization of CPE, the carbapenemase genotypes, and to identify the independent risk factors for the acquisition of CPE colonization in high-risk patients from ICU and HSCT wards in a university hospital in China. Methods In a prospective cohort study, 150 fecal samples from rectal swabs were consecutively obtained for inpatients from the intensive care unit (ICU) and hematopoietic stem cell transplantation (HSCT) wards from November 2018 to May 2019, and screening test for CPE was conducted by using prepared in-house trypsin soybean broth (TSB) selective media and MacConkey agar. Antimicrobial susceptibility was determined by the broth microdilution method and carbapenemase genes were characterized by both the GeneXpert Carba-R and PCR for blaKPC, blaNDM, blaIMP, blaVIM and blaOXA. Multi-locus sequence typing (MLST) was employed to characterize the genetic relationships among the carbapenemase-producing K. Pneumonia (CPKP) isolates. In order to further investigate the risk factors and clinical outcomes of CPE colonization, a prospective case-control study was also performed. Results Twenty-six suspected CPE strains, including 17 Klebsiella pneumoniae, 6 Escherichia coli, 1 Citrobacter freundii, 1 Enterobacter Kobe, and 1 Raoultella ornithinolytica, were identified in 25 non-duplicated rectal swab samples from 25 patients, with a carriage rate of 16.67% (25/150). Through GeneXpert Carba-R and subsequent PCR and sequencing, all the suspected CPE isolates were identified to be positive for the carbapenemase genes, of which 17 were blaKPC-carriers, and another 9 were blaNDM-producers. MLST designated all the CPKP isolates to be ST11 clone. Multivariate analysis indicated that urinary system diseases, operation of bronchoscopy, and combined use of antibiotics were independent risk factors for acquiring CPE colonization in high-risk patients from the ICU and HSCT wards. Conclusions This study revealed a high prevalence of rectal CPE colonization in high-risk patients from ICU and HSCT wards, and a predominant colonization of the KPC-producing K. pneumoniae clone ST11. Stricter infection control measures are urgently needed to limit the dissemination of CPE strains, especially in patients who were afflicted by urinary system diseases, have underwent bronchoscopy, and were previously exposed to combined antibiotic use.

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