Validation of the efficacy of the NUTRISCORE for the nutritional screening of cancer patients in China.

BACKGROUND: Malnutrition is common in cancer patients. The NUTRISCORE is a newly developed cancer-specific nutritional screening tool and was validated by comparison with the Patient-Generated Subjective Global Assessment (PG-SGA) and Malnutrition Screening Tool (MST) in Spain. We aimed to evaluate the performance of the NUTRISCORE, MST, and PG-SGA in estimating the risk of malnutrition in Chinese cancer patients. METHODS: Data from an open parallel and multicenter cross-sectional study in 29 clinical teaching hospitals in 14 Chinese cities were used. Cancer patients were assessed for malnutrition using the PG-SGA, NUTRISCORE, and MST. The sensitivity, specificity, and areas under the receiver operating characteristic curve were estimated for the NUTRISCORE and MST using the PG-SGA as a reference. RESULTS: A total of 1000 cancer patients were included. The mean age was 55.9 (19 to 92 years), and 47.5% were male. Of these patients, 450 (45.0%) had PG-SGA B and C, 29 (2.9%) had a NUTRISCORE ≥5, and 367 (36.7%) had an MST ≥ 2. Using the PG-SGA as a reference, the sensitivity, specificity, and area under the curve values of the NUTRISCORE were found to be 6.2, 99.8%, and 0.53, respectively. The sensitivity, specificity, and area under the curve values of the MST were 50.9, 74.9%, and 0.63, respectively. The kappa index between the NUTRISCORE and PG-SGA was 0.066, and that between the MST and PG-SGA was 0.262 (P < 0.05). CONCLUSIONS: The NUTRISCORE had an extremely low sensitivity in cancer patients in China compared with the MST when the PG-SGA was used as a reference.

Efficacy of malnutrition screening tools in China for elderly outpatients.

BACKGROUND AND OBJECTIVES: Malnutrition in elderly individuals is extremely common. In China, Nutritional Risk Screening 2002 (NRS-2002) is often used to assess malnutrition in hospitalized elderly patients, although a gold standard for elderly outpatients is lacking. The Nutrition Screening Initiative Checklist (NSI) and Malnutrition Screening Tool (MST) have seldom been validated in elderly outpatients. This open, parallel, multi-center, cross-sectional study evaluated the performance of NRS-2002, the NSI, and the MST in estimating malnutrition risk in elderly outpatients. METHODS AND STUDY DESIGN: This study included 986 elderly outpatients, with 53.2% being women, from five clinical teaching hospitals in Beijing. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of the tools were estimated using a body mass index (BMI) of <18.5 kg/m2 as a reference. RESULTS: The mean (range) age of the patients was 69.6±6.8 (60-100) years. Overall, 4.3% had BMI <18.5 kg/m2, 16.8% scored ≥3 points in NRS-2002, 9.8% scored ≥2 points in the MST, and 37.0% scored ≥3 points in the NSI. NRS-2002 had the highest sensitivity and the best AUC (0.934 vs. 0.642 for the NSI and 0.660 for the MST, p<0.05), and the MST had the highest specificity. The sensitivity and specificity of the NSI were 0.64 and 0.64, respectively. CONCLUSIONS: NRS-2002 had the highest validity, and the MST had the highest specificity in estimating the risk of malnutrition in elderly outpatients. However, the accuracy of the NSI should be further verified with large samples.

Effects of an Intermittent Fasting 5:2 Plus Program on Body Weight in Chinese Adults with Overweight or Obesity: A Pilot Study.

To retrospectively review the efficacy of intermittent fasting 5:2 plus program (30% of energy requirements on fast days and 70% of energy requirements on nonfasting days) in Chinese patients with overweight or obesity. This retrospective cohort study evaluated weight loss outcomes of patients treated with 12 weeks weight loss program in clinic. Adults with overweight or obesity participated in intermittent fasting 5:2 plus, daily calorie restriction (70% of energy requirements every day) or daily calorie restriction with meal replacement (70% of energy requirements every day, partly provided with high-protein meal replacement) programs for 12 weeks. The primary objective was to compare the weight loss of three groups. The primary outcome measure was the change in the % total weight loss. A total of 131 patients (35.3 ± 10.1 years; 81.7% female) were included, and the mean weight loss was 7.8 ± 4.4% after 12 weeks. The intermittent fasting 5:2 plus group (n = 42) achieved 9.0 ± 5.3% weight loss, compared with 5.7 ± 3.7% in the daily calorie restriction group (n = 41) (p < 0.001) and 8.6 ± 3.5% in the meal replacement group (n = 48) (p = 0.650). A total of 85.7% of patients in the intermittent fasting 5:2 plus group lost more than 5% body weight, vs. 58.5% in the daily calorie restriction group (p = 0.008), and 45.2% lost more than 10% body weight, vs. 14.6% in the daily calorie restriction group (p = 0.005). No serious adverse events were reported in the three groups. The intermittent fasting 5:2 plus program more effectively led to weight loss than daily calorie restriction in the short-term in Chinese patients with overweight or obesity. A longer-term prospective randomized controlled trial is needed.

[Analysis of maltose clearance in plasma and urine of healthy volunteers with high-performance liquid chromatography].

OBJECTIVE: To analyze the maltose clearance in plasma and urine of healthy volunteers with high-performance liquid chromatography. METHODS: Maltose solution was infused to 12 healthy volunteers during a 4-hour period at an infusion rate of 0.2, 0.3, and 0.5 g/(kg x h), Plasma and urine specimens were collected at different time points before and after infusion, and then analyzed with high-performance liquid chromatography. RESULTS: The coefficients of variation of the precision and accuracy of the analysis method ranged 3.68%-4.58% and 0.44%-4.83% for plasma, respectively, and 2.91%-7.62% and 0.95%-8.27% for urine, respectively. The plasma maltose concentration increased in a dose-dependent manner (r > 0.99). The plasma maltose concentrations returned to the baseline levels 12 hours later. Two hours after injection, the urinary excretion of maltose increased, reached the peak value within 2-4 hours, began to decrease 6 hours later, and became zero 24 hours later. CONCLUSIONS: An infusion rate of 0.2-0.5 g/(kg x h) of maltose will not remarkably increase the blood glucose level in healthy people. The routine infusion rate should below 0.3 g/(kg x h), unless an emergency exists.

Microarray analysis of gene expression profile of multidrug resistance in pancreatic cancer.

BACKGROUND: Chemotherapy is the most frequently adopted adjuvant therapy of pancreatic ductal adenocarcinoma (PDAC), but the development of drug resistance reduces its effectiveness. Clarification of the mechanism of multidrug resistance (MDR) development in PDAC is needed to improve the therapeutic effect of chemotherapy. This study was aimed to investigate the molecular mechanism of MDR of PDAC and to identify genes associated with MDR development. METHODS: The gene expression profiles of cell line SW1990 and three drug-selected pancreatic chemoresistant sub-lines, SW1990/5-Fu, SW1990/ADM and SW1990/GEM, were obtained using an oligonucleotide microarray (Affymetrix HG U133 2.0 plus) that contained approximately 38,000 human genes. The microarray results were validated by real-time quantitative polymerase chain reaction and Western blot analysis. RESULTS: There were 165 genes and expressed sequence tags, some of which have never been linked to drug resistance, that were up- or down-regulated at least 2-fold in all resistant sub-lines when compared with SW1990. According to Gene Ontology annotation, differentially expressed genes related to MDR in pancreatic cancer belong to many functional families and with diverse biological processes. Genes related to antioxidant activity, apoptosis, the cell cycle, signal transduction and intracellular adhesion may undergo epigenetic changes preceding MDR development. A hierarchical clustering was conducted and several interesting clusters were discovered that may be primarily related to cell cycle and developmental regulation. A prediction rule was built from the expression profiles of 117 genes after support vector machine (SVM) analysis, and the prediction result was examined by cytotoxic testing. As a result, a differential gene expression pattern was constructed in multidrug resistant pancreatic cancer cells. CONCLUSIONS: The findings of this study prove that construction of a chemoresistance prediction rule, based on gene expression patterns, is practical. These data provide new insights into the molecular mechanism of pancreatic cancer MDR development and may be useful for the detection and treatment of MDR in pancreatic cancer patients.

Peripherally inserted central catheter-related complications in cancer patients: a prospective study of over 50,000 catheter days.

PURPOSE: To evaluate incidence and risk factors of peripherally inserted central catheter (PICC)-related complications in cancer patients. METHODS: A prospective, multicenter, cohort study of cancer patients with PICC insertion was performed from February 1, 2013 to April 24, 2014. All patients were monitored in clinic until PICCs were removed. The primary endpoint was PICC removal due to complications. Patient-, catheter- and insertion-related factors were analyzed in univariable and multivariable logistic regression analysis to identify significant independent risk factors for PICC-related complications. RESULTS: There were 477 cancer patients included, for a total of 50,841 catheter-days. Eighty-one patients (17.0%) developed PICC-related complications, with an incidence of 1.59 per 1000 catheter days. Thirty-six (7.5%) PICCs were removed because of complications. The most common complications were skin allergy (4.6%), catheter occlusion (3.4%) and accidental withdrawal (2.3%). Nine (1.9%) patients developed symptomatic upper extremity deep venous thrombosis (UEDVT) and central line associated bloodstream infection (CLABSI) was shown in six (1.3%) PICCs with an infection rate 0.12 per 1000 catheter days. In multivariable analysis, body mass index (BMI) >25 (odds ratio, 2.09; 95% confidence interval, 1.26-3.47, p = 0.004) was shown to be a significant risk factor for PICC complications. CONCLUSIONS: Cancer patients with BMI greater than 25 were more likely to have PICC complications.

Health-related quality of life of cancer patients with peripherally inserted central catheter: a pilot study.

INTRODUCTION: This pilot exploratory study aimed to compare the health-related quality of life (HRQOL) among patients diagnosed with different types of cancer receiving peripherally inserted central catheters (PICCs). METHODS: A multicenter cross-section study of cancer patients with PICCs was performed from February 1, 2013 to April 24, 2014. The primary objective of this study was to compare HRQOL in different cancer type patients with PICC. HRQOL was examined based on European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30). Multiple linear regression models were conducted for coping with potential confounding variables. We also examined PICC-related quality of daily life with a self-made questionnaire. RESULTS: Three hundred and fifty-seven cancer patients with PICC completed the survey in nine teaching hospitals. Lung cancer patients with PICC reported the worst dyspnea. Digestive tract cancer patients reported the worst appetite loss. Patients with hematologic malignancy reported the worst emotional, social function, fatigue and financial impact. Breast cancer patients reported better HRQOL. Baseline variables were proven not significant predictors of EORTC QLQ-C30 global health status. In self-made survey, pain after PICC insertion was null or a little in 98.6% of cancer patients. Limitation of upper extremity activity was null or a little in 94.1% of patients. CONCLUSIONS: HRQOL varies in different types of cancer patients with PICC. PICC may have a low impact on cancer patients' HRQOL. Further large sample studies are needed.

Peripherally inserted central catheter-related vein thrombosis in breast cancer patients.

PURPOSE: To identify clinical incidence, risk factors and treatment of peripherally inserted central venous catheters (PICCs)-related upper extremity venous thrombosis (UEVT) in breast cancer patients undergoing chemotherapy. METHODS: We performed a retrospective cohort study of breast cancer patients with PICC insertion undergoing chemotherapy. PICC-related UEVT was diagnosed by ultrasound. Patient-, catheter- and insertion-related factors were analyzed in univariable and multivariable logistic regression to identify significant independent risk factors for PICC-related UEVT. The incidence and treatment of PICC-related UEVT were also analyzed. RESULTS: A total of 568 breast cancer patients with PICC undergoing chemotherapy were included, for a total of 54,769 catheter days; 8 patients (1.4%) developed PICC-related UEVT. The median time of developing UEVT was 11 days (range of 3 to 79 days). In multivariable analysis, metastasis (p = 0.002) and malposition (p = 0.013) were shown to be significant risk factors for PICC-related UEVT. All patients were treated with low-molecular-weight heparin (LMWH) and followed until PICCs were removed. None of the patients developed pulmonary embolus. CONCLUSIONS: Metastasis and malposition were significant risk factors for PICC-related UEVT in breast cancer patients. With early diagnosis and standardized anticoagulant treatment, a better clinical outcome could be achieved. Further prospective and large sample studies are needed.

Nutrition Therapy for Mitochondrial Neurogastrointestinal Encephalopathy with Homozygous Mutation of the TYMP Gene.

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is characterized by significant gastrointestinal dysmotility. Early and long-term nutritional therapy is highly recommended. We report a case of MNGIE in a patient who was undergoing long-term nutrition therapy. The patient was diagnosed with a serious symptom of fatty liver and hyperlipidemia complications, along with homozygous mutation of the thymidine phosphorylase (TYMP) gene (c.217G > A). To our knowledge, this is the first report of such a case. Herein, we describe preventive measures for the aforementioned complications and mitochondrial disease-specific nutritional therapy.

Omega-3 polyunsaturated fatty acids inhibit the increase in cytokines and chemotactic factors induced in vitro by lymph fluid from an intestinal ischemia-reperfusion injury model.

OBJECTIVE: To investigate the active factors and the intervention effect of ω-3 polyunsaturated fatty acids (PUFAs) during intestinal ischemia-reperfusion (I/R) injury, which causes the inflammation of monocytes-macrophages cultured in lymph fluid and stimulated with ω-3 PUFAs. METHODS: Forty-eight Sprague-Dawley male rats were randomly divided into the following two groups: A. (N + D) group and B. (I/R + D) group. The rats in the (N + D) group were drained of lymph for 180 min; the rats in the (I/R + D) group were subjected to 60 min ischemia by clamping the superior mesenteric artery followed by 120 min reperfusion and 180 min of lymph draining. Lymph fluid from each group was further divided into 4 subgroups, respectively: lymph group (A1, B1); eicosopentaenoic acid (EPA)-treated group (A2, B2); EPA + docosahexaeonic acid (DHA)-treated group (A3, B3); and DHA-treated group (A4, B4), then cultured monocyte-macrophage cell line. RESULTS: The levels of tumor necrosis factor-α, interleukin (IL)-1 ß, IL-6, soluble cell adhesion molecule-1, chemotactic factors macrophage chemoattractant protein-1, macrophage inflammatory protein-2, and high mobility group box protein 1 in the B1 group were significantly higher than in the A1 group. Importantly, addition of EPA, EPA + DHA, and DHA to the culture media significantly reduced the levels of the above-mentioned factors. Cell stimulation with EPA, EPA + DHA, and DHA also significantly decreased the expression of Toll-like receptor 4, nuclear factor-κB p65, macrophage chemoattractant protein-1, and macrophage inflammatory protein-2 with the combined treatment of EPA and DHA showing the strongest effect. CONCLUSIONS: The factors induced in lymph during intestinal I/R injury can cause inflammation in vitro. These data provide in vitro evidence that ω-3 PUFAs provide a protective effect by reducing the inflammatory response caused by intestinal I/R lymph. Moreover, the synergism of EPA and DHA had the greatest effect, which is possibly mediated through Toll-like receptor 4 and nuclear factor-κB p65.

The effect of supplemental enteral glutamine on plasma levels, gut function, and outcome in severe burns: a randomized, double-blind, controlled clinical trial.

BACKGROUND: This research was conducted to evaluate the effect of enterally administered glutamine (gln) dipeptide on metabolic, gastrointestinal, and outcome parameters after severe burn injury. METHODS: Forty thermally injured patients with total body surface burns ranging between 50% and 80%, and third-degree burns ranging between 20% and 40% and without respiratory injuries, were randomized into a prospective, double-blind, controlled clinical trial. One group received gln-enriched enteral nutrition and the other group received the standard enteral formulation. Tube feedings were initiated on postburn day 1 (PBD +1), and isocaloric and isonitrogenous feedings were administered to both groups until PBD +12. The gln was given as the dipeptide of alanyl-gln (Ajinomoto, Tokyo, Japan), which provided 0.35 g gln/kg body weight/d. Plasma amino acid profiles, serum endotoxin concentrations, and the lactulose/mannitol absorption ratio (which reflects gut permeability) were measured at specific times throughout the clinical course. Wound healing at day 30 was assessed, and length of hospital stay and total costs were determined at discharge. RESULTS: The 2 groups were similar in terms of age and extent of injury. Plasma gln concentrations were approximately 300 umol/L in both groups on PBD +1 and remained low in the control group (399 +/- 40 umol/L, mean +/- SD) but increased toward normal in the supplemented group to 591 +/- 74 (p = .048). Lactulose/mannitol ratios were increased above normal on POD +1 (control, 0.221 +/- 0.169; gln, 0.268 +/- 0.202; not significant), reflecting increased intestinal permeability after burn injury. On POD +3, the ratio in the gln group was lower than control (0.025 +/- 0.008 versus 0.049 +/- 0.016; p = .0001), and both groups returned toward normal ratios with time. Endotoxin levels on PBD +1 were elevated in both groups (control, 0.089 +/- 0.023 EU/mL; gln, 0.103 +/- 0.037 EU/mL; NS) but decreased significantly on PBD +3 in the patients receiving gln. Hospital stay was significantly shorter in the gln group than controls (67 +/- 4 days versus 73 +/- 6; p = .026). On day 30, wound healing was 86% +/- 2% complete in the gln group compared with 72% +/- 3% in controls (p = .041). Total cost of hospitalization was 62794 +/- 6178 RMB (dollar 7593 +/- 747 US dollars) in the gln group and 68996 +/- 8620RMB (dollar 8343 +/- 1042, p = .031) in controls, although the cost of the enteral nutrition was higher in the gln-supplemented patients. CONCLUSION: Enteral gln supplementation using a commercially available dipeptide supported plasma gln levels, improved gut permeability, and initially decreased plasma endotoxin levels in severely thermally injured patients. These alterations were associated with a reduction in the length of hospitalization and lower costs.

[A randomized, double blind, and controlled clinical trial of the non-addictive propacetamol in postoperative analgesia].

OBJECTIVE: To compare the postoperative analgesic efficacy and safety of the non-addictive propacetamol hydrochloride (Pro-Bufferin) injection and dolantin in a prospective, randomized, double blind and controlled clinical trial. METHODS: After the pain intensity was assessed when the patients were undergone thoracic and abdominal selective surgery became fully conscious, 40 consecutive patients with moderate to severe postoperative pain (equivalent to Pain Grade I and II of American Anesthesia Association classification) were randomized into the study against the control groups. The two groups were similar for age, sex, height/weight, disease categories, operation categories, anesthesia methods and duration, vital signs, hepatorenal function, and blood cell count (P = 0.06-0.93). In the study group, 2 g propacetamol in 100 ml normal saline (NS) intravenously with 1.0 ml NS intramuscularly as the placebo control to dolantin were administered. In the control group, 1.6 g mannitose in 100 ml NS intravenously as the placebo control to propacetamol with 50 mg dolantin (1.0 ml) intramuscularly as the positive control to propacetamol were administered. The intensity change of postoperative pain was then evaluated 10 times with visual analog scale and verbal describing scale during 6 h from the beginning of propacetamol infusion. Vital signs and adverse reactions were also documented. After all data were put into the computer, the blinding codes were decoded and the statistic analysis was then made. RESULTS: There was no significant difference (P = 0.93) about the area under the curve of "Pain Relieve Score vs. Time". The "starting to effect" time (15-30 min), analgesic duration (6 h) and the percentage of excellent or good analgesic effect (90%) in the two groups were the same. Adverse reactions didn't reached the statistic different level (P = 0.35). CONCLUSIONS: Propacetamol HCL injection 2 g intravenously could be an alternative to dolantin 50 mg intramuscularly for moderate to severe postoperative pain with its advantage of being non-addictive.

[The role of nutritional status on serum immunoglobulins, body weight and postoperative infectious-related complications in patients with Crohn's disease receiving perioperative parenteral nutrition].

OBJECTIVE: To evaluate the role of nutritional status on serum immunoglobulins, body weight and postoperative infectious-related complications in patients with Crohn's disease receiving perioperative parenteral nutrition (PN). METHODS: 32 patients with Crohn's disease receiving perioperative parenteral nutrition in our department between 1984 and 1994 were enrolled in this survey. 16 patients with loss of body weight in the range of 15%-30% were assigned to the malnutrition group, the other 16 patients with normal weight or loss of body weight less than 15% to the control group. Serum IgM, IgG and IgA levels were measured before and after PN by enzyme-linked immunosorbent assays. Liver function, body weight changes and postoperative complications were also analyzed. RESULTS: IgM levels were elevated before PN in both groups [control group: (133 +/- 16) mg/dl, malnutrition group: (139 +/- 41) mg/dl; normal value: (110 +/- 35) mg/dl; P = 0.04], decreased to normal value [(105 +/- 29) mg/dl, P = 0.02] in the malnutrition group while having no obvious changes in the control group [(129 +/- 13) mg/dl, P = 0.34]. No significant changes in concentrations of IgG and IgA were found (P in the range of 0.20-0.57). The average weight gain was 1.862 kg in malnutrition group [before PN: (45.8 +/- 8.9) kg, after PN: (48.0 +/- 8.8) kg; P = 0.005] and no significant changes in the control group [before PN: (55.6 +/- 6.1) kg, after PN: (56.3 +/- 6.0) kg; P = 0.46]. There was an increase in infectious complications in the control group (control group: 4 cases, 25%, malnourished group: 2 cases, 12.5%; P = 0.13). CONCLUSIONS: Perioperative parenteral nutrition ameliorated the humoral immunity, increased the body weight in patients with obvious malnutrition, whereas it had little value for those without or with mild malnutrition.

Association of Birth Weight with Health and Long-Term Survival up to Middle and Old Ages in China.

This study is based on an unique dataset of birth records of 11,693 persons born in Beijing, China from 1921-54 and from clinical examinations (May 2003-April 2005) of 2,085 tracked surviving cohort members (aged 50-82) to diagnose seven major chronic diseases. Data were analyzed using the extended Fixed Attribute Dynamics (FAD) method and multivariate regressions. The results of our FAD analysis have shown that, as compared to the persons with low birth weight (<2,500 g), the probability of survival from age 0 to ages 50-56, 63-67 and 68-82 for persons with higher birth weight (2,500-2,999 g, 3,000-3499 g, or ≥3,500 g) was 16-31, 62-104, and 52-108% higher respectively. These estimates display similar patterns for both genders, with somewhat stronger effects in men. Of the 27 estimates of the Odds Ratio of Survival in the FAD analysis, 21 are statistically significant. Controlling for 14 confounding factors, multivariate binary logistic regressions have demonstrated that the risk of having cardiovascular disease and diabetes is negatively associated birth weight; ordinal logit regressions have shown that the number of major chronic diseases at ages 50-82 is significantly associated with birth weight: the lower the birth weight, the higher the risk of having more chronic diseases. We conclude that low birth weight is negatively associated with 1) long-term survival probability from age 0 to ages 50-82, and 2) overall health at middle and old ages. Further research is needed to understand the mechanisms of these effects.

Moxifloxacin is non-inferior to combination therapy with ceftriaxone plus metronidazole in patients with community-origin complicated intra-abdominal infections.

Management of community-origin complicated intra-abdominal infections (cIAIs) requires surgical intervention and antimicrobial therapy. This multinational, randomised, double-blind clinical trial carried out in Asia compared the efficacy and safety of moxifloxacin monotherapy and ceftriaxone/metronidazole combination therapy in adults with confirmed or suspected cIAI. Patients received surgical intervention and either intravenous (i.v.) moxifloxacin 400 mg once daily or i.v. ceftriaxone 2 g once daily plus i.v. metronidazole 500 mg twice daily. A total of 364 patients were randomised [intent-to-treat (ITT), moxifloxacin N=180, comparator N=181; per-protocol (PP), moxifloxacin N=174, comparator N=171]. The most common cIAI diagnosis was complicated appendicitis. Moxifloxacin was non-inferior to ceftriaxone/metronidazole in terms of clinical response at test-of-cure in the PP population [clinical cure, 90.2% for moxifloxacin vs. 96.5% for ceftriaxone/metronidazole; 95% confidence interval (CI) of the difference -11.7 to -1.7] and in the ITT population (87.2% for moxifloxacin vs. 91.2% for ceftriaxone/metronidazole; 95% CI -10.7 to 1.9). Bacteriological cure rates in the microbiologically evaluable population support the clinical results (89.4% for moxifloxacin vs. 95.9% for ceftriaxone/metronidazole; 95% CI -13.3 to -0.6). The incidence of treatment-emergent adverse events was similar for both treatment groups (moxifloxacin 31.7% vs. comparator 24.3%). These results confirm previous findings that moxifloxacin plus adequate source control is an appropriate treatment of cIAI.