MutSα expression predicts a lower disease-free survival in malignant salivary gland tumors: an immunohistochemical study.

BACKGROUND: Appropriate DNA replication is vital to maintain cell integrity at the genomic level. Malfunction on DNA repair mechanisms can have implications related to tumor behavior. Our aim was to evaluate the expression of key complexes of the DNA mismatch-repair system MutSα (hMSH2-hMSH6) and MutSß (hMSH2-hMSH3) in a panel comprising the most common benign and malignant salivary gland tumors (SGT), and to determine their association with disease-free survival. MATERIAL AND METHODS: Ten cases of normal salivary gland (NSG) and 92 of SGT (54 benign and 38 malignant) were retrieved. Immunohistochemistry was performed for hMSH2, hMSH3, hMSH6. Scanned slides were digitally analyzed based on the percentage of positive cells with nuclear staining. Cases were further classified in MutSαhigh and MutSßhigh based on hMSH2-hMSH6 and hMSH3-hMSH6 expression, respectively. RESULTS: hMSH3 expression was lower in malignant SGT compared to NSG and benign cases. Adenoid cystic carcinoma (ACC) cases with perineural invasion presented a lower percentage of hMSH3 positive cells. hMSH6 was downregulated in both benign and malignant SGT compared to NSG. Malignant SGT cases with MutSαhigh expression had lower disease-free survival compared to MutSαlow cases. A 10.26-fold increased risk of presenting local recurrence was observed. CONCLUSIONS: Our findings suggest that a lack of hMSH3 protein function is associated with a more aggressive phenotype (malignancy and perineural invasion) and that MutSα overexpression predicts a poor clinical outcome in malignant SGT.

Although it induces synchronized ovulation, hCG reduces the fertility of Santa Ines ewes submitted to TAI / Embora induza a ovulação sincronizada, hCG reduz a fertilidade de ovelhas Santa Inês submetidas à IATF

The aim of this study was to evaluate hCG treatment on ovarian response and on pregnancy rate using a 9-day oestrus synchronization protocol in Santa Ines ewes. On a random oestrus cycle day, ewes received an intravaginal progesterone device (Primer-PR®, Tecnopec, Brazil). Nine days later (Day 9), 30µg of d-cloprostenol (Prolise®, Syntex, Argentina) and 250IU of eCG (Folligon®, Intervet, Brazil) were administered and the progesterone device was removed. This moment, the ewes were randomly assigned on two groups: Control Group and hCG Group. In the hCG Group, the ewes received 500IU of hCG (Vetecor®, Hertape-Calier, Spain) 24h after device removal. In the Control Group, the ewes did not receive any ovulation inductor. Control and hCG Groups ewes were inseminated 60h and 48h after device removal, respectively. There was no difference between the groups regarding the first ovulatory follicle diameter and the second ovulatory follicle. hCG Group ewes had shorter interval between device removal and ovulation (Control: 79.9±15.4h and hCG: 54.7±4.9h; P=0.001) and more synchronized ovulations. However, the treatment with hCG decreased the pregnancy rate after TAI (P=0,009). In conclusion, hCG administration improves ovulatory synchronisation, but causes a decrease in the pregnancy rate.(AU)

Avaliou-se o tratamento com hCG na resposta ovariana e na taxa de prenhez utilizando protocolo de sincronização do estro de nove dias em ovelhas Santa Inês. As ovelhas receberam um dispositivo intravaginal de progesterona em fase aleatória do ciclo (dia zero= D0). No momento da remoção do dispositivo (D9), as fêmeas receberam 30µg de d-cloprostenol (Prolise®, Syntex, Argentina) e 250UI de eCG (Folligon®, Intervet, Brasil). Nesse momento, as ovelhas foram aleatoriamente distribuídas em dois grupos de tratamento: controle sem indução de ovulação e tratamento com 500UI hCG para indução de ovulação. As ovelhas dos grupos controle e hCG foram inseminadas 60h e 48h após a remoção do dispositivo, respectivamente. Não houve diferença entre os grupos para o diâmetro do primeiro e do segundo folículo pré-ovulatório. As avelhas do grupo hCG apresentaram menor intervalo entre a remoção do dispositivo e a ovulação (grupo controle: 79.9±15.4h e grupo hCG: 54.7±4.9h; P=0.001) e maior sincronização das ovulações. No entanto, o tratamento com hCG diminuiu a taxa de prenhez após a IATF (P=0,009). Conclui-se que, apesar de a administração de hCG aumentar a sincronização da ovulação, reduz a taxa de prenhez.(AU)

Biomass sorghum as a novel substrate in solid-state fermentation for the production of hemicellulases and cellulases by Aspergillus niger and A. fumigatus.

AIMS: We investigated the role of carbon and nitrogen sources in the production of cellulase and hemicellulase by Aspergillus strains. METHODS AND RESULTS: The strains Aspergillus niger SCBM1 and Aspergillus fumigatus SCBM6 were cultivated under solid-state fermentation (SSF), with biomass sorghum (BS) and wheat bran (WB) as lignocellulosic substrates, in different proportions, along with variable nitrogen sources. The best SSF condition for the induction of such enzymes was observed employing A. niger SCBM1 in BS supplemented with peptone; maximum production levels were achieved as follows: 72 h of fermentation for xylanase and exoglucanase (300·07 and 30·64 U g-1 respectively), 120 h for ß-glucosidase and endoglucanase (54·90 and 41·47 U g-1 respectively) and 144 h for ß-xylosidase (64·88 U g-1 ). CONCLUSIONS: This work demonstrated the viability of the use of BS for the production of hemi- and cellulolytic enzymes; the high concentration of celluloses in BS could be associated with the significant production of cellulases, mainly exoglucanase. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study which presents the promising use of biomass sorghum (genetically modified sorghum to increase its biomass content) as an alternative carbon source for the production of enzymes by SSF.

The MSH2 c.388_389del mutation shows a founder effect in Portuguese Lynch syndrome families.

The MSH2 c.388_389del mutation has occasionally been described in Lynch families worldwide. At the Portuguese Oncology Institute in Porto, Portugal, we have identified 16 seemingly unrelated families with this germline mutation. To evaluate if this alteration is a founder or a recurrent mutation we performed haplotype analysis in the 16 Portuguese index cases and 55 relatives, as well as in four index cases and 13 relatives reported from Germany, Scotland, England, and Argentina. In the Portuguese families we observed a shared haplotype of approximately 10 Mb and all were originated from the north of Portugal. These results suggest that this alteration is a founder mutation in Portugal with a relatively recent origin. In the reported families outside Portugal with this mutation different haplotype backgrounds were observed, supporting the hypothesis that it occurred de novo on multiple occasions. We also conclude that the high proportion of families with the MSH2 c.388_389del mutation indicates that screening for this alteration as a first step may be cost-effective in the genetic testing of Lynch syndrome suspects of Portuguese ancestry, especially those originating from the north of Portugal.

Embryo production and quality of Holstein heifers and cows supplemented with beta-carotene and tocopherol.

The hypothesis was that the intramuscular injection (i.m.) of beta-carotene associated to tocopherol improves cow (n=86) and heifer (n=91) embryo production and quality. Time of estrus was synchronized in animals with an ear implant with 3 mg of norgestomet associated with an i.m. injection of 6 mg of norgestomet and 10mg of estradiol valerate (CRESTAR, Intervert International B.V., Boxmeer, Holland) and superovulated by 8 i.m. FSH/LHp injections (400 IU-heifers and 500 IU-cows) in decreasing concentrations at 12h intervals. Animals were inseminated 12 and 24h after observed onset of estrus and embryos recovered 7 days later. Animals were randomly allocated to one of three treatments: (1) vegetable oil vehicle (control), (2) 800 mg of beta-carotene and 500 mg of tocopherol (T800) and (3) 1200 mg of beta-carotene and 750 mg of tocopherol (T1200). Supplemental injections were given at the day norgestomet implants were inserted and at first superovulatory injection. An index (Embryo Quality Index or EQI) was proposed to more precisely evaluate embryo quality (excellent*1 + good*2 + regular*3 + poor*4 + degenerate*5 + unfertilized ova*5)/total. There was an interaction between physiological stage (heifer or cow) and treatment on EQI (P=0.01) and on the proportion of viable embryos (P=0.03), where both variables were improved in T1200 cows, but not in heifers. The average EQI for heifers and cows in control, T800 and T1200 were 2.6+/-0.3 and 3.6+/-0.3; 2.5+/-0.3 and 3.6+/-0.3; 2.9+/-0.3 and 2.7+/-0.3, respectively. The average total number of viable embryos was greater (P=0.01) in supplemented cows (3.5+/-1.1; 5.4+/-1.4 and 7.5+/-1.2 in control, T800 and T1200, respectively), but less (P=0.01) in heifers (7.5+/-1.2; 5.6+/-1.2 and 4.0+/-1.1 in control, T800 and T1200, respectively). Supplementation injections of beta-carotene associated to tocopherol improved embryo quality in superovulated Holstein cows, in the present experimental conditions and may be advantageous in similar embryo production systems. However, at dosages applied in the present experiment, this treatment should not be recommended for nulliparous heifers.

Comparative study of clinical characteristics of neutropenic and non-neutropenic adult cancer patients with bloodstream infections.

A total of 399 consecutive episodes of bloodstream infections in adult patients with haematologic malignancies and solid tumours were evaluated prospectively over a 26-month period, with the aim of determining the clinical characteristics and the microbiological profile of the patients relative to neutrophil count. The overall 30-day mortality rate was 32% (35% in non-neutropenic patients vs. 26% in neutropenic patients, p=0.05). Main diagnoses were solid tumours (33%) and lymphoma (29%). Most of the episodes of bloodstream infection (58%) occurred in non-neutropenic patients. Acute leukaemia and bone marrow transplantation predominated in the neutropenic group. Non-neutropenic patients tended to be older and to have a higher frequency of solid tumours and advanced or uncontrolled diseases. Indwelling central venous catheters were present in 51% of the episodes, with a predominance of long-term catheters in neutropenic haematologic patients. Concomitant infections were observed more frequently in non-neutropenic patients. There were 1,040 noninfectious comorbid conditions, most of which were present in non-neutropenic patients. The causative pathogens were predominantly gram-negative bacilli (56%). Escherichia coli and Klebsiella pneumoniae were isolated more frequently from neutropenic patients, while Staphylococcus aureus and Acinetobacter spp. were more frequent in non-neutropenic patients. Seventy-four percent of the episodes of candidaemia occurred in patients with central venous catheters, with non-albicans strains predominating. The results of this study highlight the heterogeneity of cancer patients with bloodstream infections and the value of stratifying risk factors and aetiologic agents according to neutrophil count.

Prospective evaluation of the epidemiology, microbiology, and outcome of bloodstream infections in adult surgical cancer patients.

The aim of this study was to describe the epidemiology and microbiology of bloodstream infections (BSIs) among adult surgical cancer patients and to determine independent factors that influence in-hospital mortality. The study enrolled 112 consecutive episodes of BSIs in adult surgical cancer patients during a 26-month period. The median age of the patients was 64.5 years, and crude in-hospital mortality was 19.6%. The median time from surgery to the index blood culture was 11 days and from index blood culture to death was 4.5 days. Seventy-five percent of the patients had an advanced tumor disease, 36.6% were under intensive care, and 68.7% had a central venous catheter in place at the time the bloodstream infection was diagnosed. Associated infected sites were present in 57.1% of the episodes. There were 328 noninfectious co-morbid conditions. Poor performance status, weight loss, hypoalbuminemia, and ventilatory support accounted for 67.4% of them. There was a predominance of aerobic gram-negative bacilli (62%), followed by gram-positive cocci (26.6%) and fungi (9.3%). The observed mortality rates associated with these organism groups were similar (23.6% vs 15% vs 28.6%, respectively; P=0.44). The most frequent organisms were Enterobacter spp., coagulase-negative staphylococci, Klebsiella spp., Acinetobacter spp., and fungi. Nonfermentative strains predominated in patients with catheters. Thirty-five (30.2%) pathogens were considered resistant. There was no significant difference in the mortality rate between patients with resistant and those with nonresistant organisms (20% vs 26%, respectively; P=0.49). Logistic regression analysis showed > or = 4 co-morbid conditions, advanced tumor, thoracic surgery, catheter retention, and pulmonary infiltrates as independent predictors of mortality. Medical and infection control measures addressing certain variables amenable to intervention might reduce the negative impact of postoperative infectious morbidity and mortality of BSIs in adult surgical cancer patients.

Prospective evaluation of the epidemiology, microbiology, and outcome of bloodstream infections in hematologic patients in a single cancer center.

Bloodstream infections (BSIs) have an important impact on the outcome of cancer patients. A prospective cohort study was undertaken at a referral cancer center in order to describe the clinical and microbiological characteristics of patients with hematologic malignancies and BSIs and to identify independent predictors associated with mortality. The study enrolled 110 consecutive BSI episodes during an 18-month period. Patients were monitored for 30 days after the last positive blood culture. There were 10.24 BSI episodes per 1,000 patient-days. The median age of the patients was 25 years. Most patients had acute leukemia ( n=72). The origin of the BSI was unknown in 43.6% of the episodes and was associated with known sites in 32.7%. There were 58 concomitant infectious sites (lungs, 43%, and soft tissue, 22.4%) and 195 noninfectious comorbid factors (poor performance status, 30.2%; undernourishment, 14.3%). The median neutrophil count was 215 cells/mm(3). Indwelling catheters were present in 70% of the episodes. The majority of isolates obtained within the first 48 h of the BSI episode (61%) were gram-negative rods. Overall mortality was 24.5%. Multivariate analysis using logistic regression showed relapsed leukemia, poor performance status, recent weight loss, and ventilatory failure requiring ventilatory support as independent predictors of mortality. Hematologic cancer patients with BSIs should be regarded as a distinct group of patients at high risk of death. The knowledge of variables amenable to intervention would help diminish or prevent serious medical complications.

Epidemiology of bloodstream infections at a cancer center.

CONTEXT: Cancer patients are at unusually high risk for developing bloodstream infections (BSI), which are a major cause of in-hospital morbidity and mortality. OBJECTIVE: To describe the epidemiological characteristics and the etiology of BSI in cancer patients. DESIGN: Descriptive study. SETTING: Terciary Oncology Care Center. PARTICIPANTS: During a 24-month period all hospitalized patients with clinically significant BSI were evaluated in relation to several clinical and demographic factors. RESULTS: The study enrolled 435 episodes of BSI (349 patients). The majority of the episodes occurred among non-neutropenic patients (58.6%) and in those younger than 40 years (58.2%). There was a higher occurrence of unimicrobial infections (74.9%), nosocomial episodes (68.3%) and of those of undetermined origin (52.8%). Central venous catheters (CVC) were present in 63.2% of the episodes. Overall, the commonest isolates from blood in patients with hematology diseases and solid tumors were staphylococci (32% and 34.7%, respectively). There were 70 episodes of fungemia with a predominance of Candida albicans organisms (50.6%). Fungi were identified in 52.5% of persistent BSI and in 91.4% of patients with CVC. Gram-negative bacilli prompted the CVC removal in 45.5% of the episodes. Oxacillin resistance was detected in 26.3% of Staphylococcus aureus isolates and in 61.8% of coagulase-negative Staphylococcus. Vancomycin-resistant enterococci were not observed. Initial empirical antimicrobial therapy was considered appropriate in 60.5% of the cases. CONCLUSION: The identification of the microbiology profile of BSI and the recognition of possible risk factors in high-risk cancer patients may help in planning and conducting more effective infection control and preventive measures, and may also allow further analytical studies for reducing severe infectious complications in such groups of patients.

Argon plasma coagulation therapy for hemorrhagic radiation proctosigmoiditis.

BACKGROUND: Radiation-induced proctosigmoiditis is a serious complication of pelvic radiation therapy. Rectal bleeding occurs among 6% to 8% of these patients and is extremely difficult to manage. Pharmacotherapy is generally ineffective, whereas surgical treatment is associated with high morbidity and mortality. Argon plasma coagulation is a new method of noncontact electrocoagulation well suited for hemostasis of large bleeding areas. METHODS: From December 1996 through March 1998, we used argon plasma coagulation to treat 28 patients with hemorrhagic radiation-induced proctosigmoiditis. Indications for treatment were anemia (n = 18) and persistent bleeding despite pharmacotherapy (n = 10). Argon flow and electrical power were set at 1.5 L/min and 50 W. The severity of rectal bleeding was graded from 0 to 4 (highest), and hemoglobin levels were recorded before and after treatment. RESULTS: Eighty-two therapeutic sessions were performed (median 2.9 sessions per patient). The severity score for rectal bleeding dropped at least 1 point for all but 2 patients, and the mean value decreased from 2.96 to 0.68. Average hemoglobin level increased 1.2 gm/dL (1.9 gm/dL among anemic patients). No serious complications were observed. CONCLUSIONS: Argon plasma coagulation appears to be a simple, safe, and effective technique in the management of hemorrhagic radiation-induced proctosigmoiditis.

An outbreak of Bacillus species in a cancer hospital.

Bacillus species were recovered from the blood cultures of 39 oncology patients over 14 weeks. A matched case-control study showed a strong association of Bacillus species bacteremia with use of calcium gluconate solution (odds ratio=25.0) and of central venous lines (odds ratio=8.8). Stopping use of the implicated calcium gluconate vials controlled the outbreak.

Risk factors for bloodstream infections at a cancer center.

A hospital-based matched case-control study was conducted in order to identify risk factors for the development of bloodstream infections in adult hospitalized patients. Between January 1993 and December 1994, 264 episodes of bloodstream infection were evaluated. Significant variables identified by univariate analysis were included in a multivariate model that showed that central venous catheter [odds ratio (OR), 6.71], poor performance status (OR, 3.40), weight loss (OR, 2.47), hematologic diseases (OR, 2.24), and previous antimicrobial therapy (OR, 2.12) independently influenced the outcome. The knowledge of modifiable risk factors is useful in the development of strategies that may contribute to the prevention of bloodstream infections.

Risk index for prediction of surgical site infection after oncology operations.

INTRODUCTION: Several studies have shown that surgical site infections represent most hospital-acquired infections, with the major impact being on average hospital stay and cost of hospitalization. METHODS: To develop a risk model for prediction of surgical site infections in cancer patients undergoing operative procedures and identify those with high probability of infection we performed a prospective cohort study in a tertiary cancer care hospital in Rio de Janeiro, Brazil. Risk factors were studied in single and multivariate analyses. RESULTS: Over a 24-month period, 1205 patients underwent operations for malignant disease. The overall surgical site infection rate was 17.3%. A multivariate stepwise logistic regression model identified six independent predictive risk factors: contaminated and infected operations, surgical duration greater than 280 minutes, male sex, prior radiotherapy, American Society of Anesthesiology class III to V, and antimicrobial prophylaxis not according to protocol. On the basis of individual risk scores, two groups of patients were identified: a low-risk (score < or = 8; surgical site infection rate 10%) and a high-risk group (score > or = 9; surgical site infection rate 33.6%; relative risk 3.4; 95% confidence interval 2.6 to 4.4). CONCLUSION: The oncology risk model allowed for the identification of a high-risk score group of patients and implementation of a more efficient and selective intervention program.

[Antibiotic prophylaxis in oncologic surgery]. / Profilaxia antimicrobiana em cirurgias oncológicas.

Perioperative antibiotic administration can decrease surgical morbidity, shorten hospitalization, while lowering the overall costs attributable to infections. Its use in surgery is widespread and often inappropriate. In this study, the authors evaluate the guidelines for selection and use of prophylactic antibiotics in surgical cancer patients at the Hospital of Cancer in Rio de Janeiro, Brazil. During 36 non-consecutive months, 1681 cancer patients submitted to surgical procedures were prospectively followed-up by members of the Hospital Infection Control Committee. The overall surgical site infection (SSI) and mortality rates were 17.7% and 4.8% respectively. Prophylactic antibiotics were used in 1262 elective surgeries (75.1%), and their use was not considered to be in accordance with the recommended protocol in 37.6% of the cases. The inadequate antimicrobial prophylaxis resulted in higher incidence of SSI than did prophylaxis in according to the protocol (21.7% vs. 16.4, Relative Risk 1.32; 95% Confidence Internal 1.05-1.67; p0.01). This study calls the attention for the need of a more strict and determined educational program in order to provide mechanisms for an adequate administration of prophylactic antibiotics to patients submitted to high-risk surgeries.

Nosocomial infections in an oncology intensive care unit.

INTRODUCTION: Treatment of cancer has contributed to a growing number of immunocompromised patients with life-threatening nosocomial infections (NI). High mortality with considerable cost is observed when they are admitted to the intensive care unit (ICU). Few studies on infection control and surveillance have been undertaken in this population group. METHODS: All patients treated at a six-bed medical-surgical oncology ICU for > 48 hours were prospectively observed for the development of an NI and the influence of device utilization on infection rates. The analysis used the standard definitions of the National Nosocomial Infection Surveillance System Intensive Care Unit surveillance component. RESULTS: From September 1993 through November 1995, 370 infections occurred in 623 patients during 4034 patient-days, for an overall rate of 50.0 per 100 patients or 91.7 per 1000 patient-days. Pneumonia (28.9%), urinary tract infections (25.6%), and bloodstream infections (24.1%) were the main types of infection. The most common microorganisms isolated were Enterobacteriaceae (29.7%), fungi (22.2%), and Pseudomonas aeruginosa (13.2%). The median device utilization ratios were 0.63, 0.83, and 0.86 for ventilator, indwelling urinary catheter, and central venous catheter, respectively. The highest median device-specific associated infection rate was 41.7 for ventilator. The median for the average length of stay was 8.8 days, and the average severity of illness score was 4.0. There was a strong positive correlation between the overall NI patient rate and device utilization (r = 0.56, p < 0.01), average severity of illness score (r = 0.54, p < 0.01), and average length of stay (r = 0.67, p < 0.01). No correlations were statistically significant when patient-days were used in the denominator. Among the devices only the number of central venous catheter days was significantly correlated with infections (r = 0.51, p = 0.01). The NI patient-day rates were progressively higher the longer the patients stayed in the ICU. CONCLUSIONS: The high rates reported in this study may reflect a combination of several factors related to the underlying illness, neutrophil count, and exposure to invasive procedures. The adjusted infection rates described here provide specific surveillance data for further interhospital comparisons and also to assess the influence of invasive medical interventions, allowing the implementation of preventable measures to control infections.

Risk factors for infectious complications after abdominal surgery for malignant disease.

BACKGROUND: The emergence of nosocomial infection as a serious complication after intraabdominal operations for cancer prompted us to identify major independent risk factors associated with postoperative infection. METHODS: Risk factors were studied in single and multivariate analyses. Variables considered were remote infection, antimicrobial prophylaxis, preoperative stay, chemotherapy, radiotherapy, weight loss, elective versus emergency operation, wound class, duration of operation, drains, sex, age, and physical status. RESULTS: During 24 months, 236 patients were entered in the study. The overall postoperative infection rate was 45.7%; the surgical site infection rate was 22.4%. Multivariate analysis identified three independent variables: duration of operation longer than 5 hours (odds ratio 6.41, 95% confidence interval 3.28 to 12.54), presence of remote infection at operation (odds ratio 3.76, 95% confidence interval 1.76 to 8.03), and preoperative stay longer than 22 days (odds ratio 2.03, 95% confidence interval 1.04 to 3.95). The relative risk of infection increased from 3.0 when one risk factor was present to 7.3 when all three risk factors were present. CONCLUSIONS: The predictive power of our final multivariate risk index clearly groups these patients according to differing risk for postoperative infection. This classification contributes substantially to the effectiveness of infection control strategies to prevent the occurrence of postoperative infection in the high-risk population of patients with cancer.

[Risk factors for surgical wound infection development in head and neck cancer surgery]. / Fatores de risco para o desenvolvimento de infecção da ferida operatória em cirurgias oncológicas de cabeça e pescoço.

Over a period of 24 months, patients undergoing surgical procedures for head and neck cancer at the Cancer Hospital in Rio de Janeiro, Brazil were followed-up prospectively for identification of surgical wound risk factors. A total of 273 patients fulfilling the National Nosocomial Infection Surveillance (NNIS) surgical criteria completed the analysis. The overall wound infection rate was 25.3%. Of the 11 potential risk factors for postoperative wound infections analysed by stepwise multiple logistic regression, the five variables that were independent of each other and highly predictive were patient undergoing an operation classified as either contaminated or infected, a surgery lasting longer than 5 hours, an American Society of Anesthesiologist (ASA) preoperative assessment score of 4 and 5, age over 50 years and prior radiotherapy. The preoperative stay, antibiotic prophylaxis, surgical drains, preoperative nutritional status, sex and the presence of prior infection did not have an independent significant contribution to the risk of infection. This study reports specific risk factors for head and neck cancer surgeries and contributes substantially to the effectiveness of infection control strategies to prevent their occurrence in this high-risk group of patients.