A systematic review of artificial intelligence algorithms for predicting acute kidney injury.

OBJECTIVE: Acute kidney injury (AKI) increases mortality and costs in hospitalized patients. New methods for early AKI identification have been developed with targeted biomarkers and electronic health records data analysis. Machine learning (ML) use in diagnostics and health data analysis has recently increased. We performed a systematic review to analyze the use of ML for AKI prediction in hospitalized adults. MATERIALS AND METHODS: Tubmed, EMBASE, Cochrane, and Web of Science databases were searched until 31st March of 2023. English-language studies using ML in adults for AKI prediction were included using predetermined eligibility search terms such as acute kidney injury, machine learning, and artificial intelligence. Two reviewers evaluated the publications' titles, abstracts, and full texts separately and obtained appropriate data. The main outcome was an area under the curve (AUC) result of at least 0.70. RESULTS: Ten studies in 102 articles were included involving 242,251 patients. Deep learning (AUC 0.907 in critical care AKI; AUC 0.797 in hospitalized patients AKI) was similar to Logistic regression (AUC 0.877 in critical care AKI; AUC 0.789 in hospitalized patients). Decision tree constructions had similar AUC. CONCLUSIONS: In this review, most ML models analyzed fulfilled the main outcome. AKI is multifactorial; however, ML performed well with different etiologies, such as cardiac-related AKI, drug-related AKI, and critical care patients. Overfitting data and constructing black box models are limitations that might jeopardize the generalization and comprehension of the results. Most studies were single-center, and three manuscripts used the same database with a predominantly Caucasian population, resulting in a lack of diversity and reducing external generalization. In conclusion, ML could effectively predict AKI in hospitalized adults. Future directions rely on including a more diverse population and completing prospective and controlled trials.

Decreased levels of cathepsin Z mRNA expressed by immune blood cells: diagnostic and prognostic implications in prostate cancer.

Cathepsin Z (CTSZ) is a cysteine protease responsible for the adhesion and migration of both immune and tumor cells. Due to its dual role, we hypothesized that the site of CTSZ expression could be determinant of the pro- or anti-tumorigenic effects of this enzyme. To test this hypothesis, we analyzed CTSZ expression data in healthy and tumor tissues by bioinformatics and evaluated the expression levels of CTSZ mRNA in the blood cells of prostate cancer (PCa) patients by qRT-PCR compared with healthy subjects, evaluating its diagnostic and prognostic implications for this type of cancer. Immune cells present in the blood of healthy patients overexpress CTSZ. In PCa, we found decreased CTSZ mRNA levels in blood cells, 75% lower than in healthy subjects, that diminished even more during biochemical relapse. CTSZ mRNA in the blood cells had an area under the curve for PCa diagnosis of 0.832, with a 93.3% specificity, and a positive likelihood ratio of 9.4. The site of CTSZ mRNA expression is fundamental to determine its final role as a protective determinant in PCa, such as CTSZ mRNA in the blood cells, or a malignant determinant, such as found for CTSZ expressed in high levels by different types of primary and metastatic tumors. Low CTSZ mRNA expression in the total blood is a possible PCa marker complementary to prostate-specific antigen (PSA) for biopsy decisions, with the potential to eliminate unnecessary biopsies.

Decreased levels of cathepsin Z mRNA expressed by immune blood cells: diagnostic and prognostic implications in prostate cancer

Cathepsin Z (CTSZ) is a cysteine protease responsible for the adhesion and migration of both immune and tumor cells. Due to its dual role, we hypothesized that the site of CTSZ expression could be determinant of the pro- or anti-tumorigenic effects of this enzyme. To test this hypothesis, we analyzed CTSZ expression data in healthy and tumor tissues by bioinformatics and evaluated the expression levels of CTSZ mRNA in the blood cells of prostate cancer (PCa) patients by qRT-PCR compared with healthy subjects, evaluating its diagnostic and prognostic implications for this type of cancer. Immune cells present in the blood of healthy patients overexpress CTSZ. In PCa, we found decreased CTSZ mRNA levels in blood cells, 75% lower than in healthy subjects, that diminished even more during biochemical relapse. CTSZ mRNA in the blood cells had an area under the curve for PCa diagnosis of 0.832, with a 93.3% specificity, and a positive likelihood ratio of 9.4. The site of CTSZ mRNA expression is fundamental to determine its final role as a protective determinant in PCa, such as CTSZ mRNA in the blood cells, or a malignant determinant, such as found for CTSZ expressed in high levels by different types of primary and metastatic tumors. Low CTSZ mRNA expression in the total blood is a possible PCa marker complementary to prostate-specific antigen (PSA) for biopsy decisions, with the potential to eliminate unnecessary biopsies.

Assessment of vitamin D status in common variable immunodeficiency or ataxia-telangiectasia patients.

INTRODUCTION AND OBJECTIVES: Vitamin D plays a role in the immune system, however studies regarding this are scarce. This study aimed to evaluate the nutritional status of vitamin D in patients with Common Variable Immunodeficiency (CVID) or Ataxia-Telangiectasia (A-T) and to relate it to body composition, inflammatory and bone metabolism markers. PATIENTS AND METHODS: This is a cross-sectional and controlled study involving 24 patients of both sexes (59.3% male), aged 8-56 years, with CVID (n=15) or A-T (n=9). The following variables were evaluated: body mass index (BMI), 25-hydroxyvitamin D (25 (OH) D), hepatic profile, parathormone, calcium, phosphorus, alkaline phosphatase, interleukin 6 and high-sensitivity C-reactive protein. RESULTS: The median age was 26.0 years. A deficiency of 25 (OH) D was found in four A-T patients (44%) and two CVID patients (13%). Nine patients with CVI (60%) and six with A-T (66.7%) were overweight and underweight, respectively. There was a negative correlation between vitamin D and fat mass in the CVID group, and vitamin D and BMI in the A-T group. Vitamin D was negatively associated with the percentage of total fat among the patients (ß - 0.842, 95% CI: -1.5-0.17, p=0.015), R2=0.21, after adjusting for sex and age. CONCLUSION: Vitamin D deficiency occurred in a quarter of the patients although there was no difference between the patient and the control group; without association with bone and inflammation biomarkers. The percentage of fat and BMI were negatively associated with the concentrations of 25 (OH) D.

The use of Z-scan technique for determination of biochemical parameters in children with solid tumors or leukemias supplemented or not with selenium.

Cancer is a disease that effects cell metabolism causing an imbalance in the health of the patient. On the other hand, malnutrition, presented by oncological patients, is caused by both the disease and its treatment. Some serum biochemical parameters cannot be determined by the traditional method of laboratory blood analysis (spectrophotometry). Among the various techniques that could be used for blood biochemical analysis, we opted for the Z-scan technique, due to its sensitivity to the reading of blood components. Our objective in this work was to compare the data obtained by the Z-scan technique and the spectrophotometry of the serological samples of children with solid tumors and leukemia under treatment, receiving or not selenium supplementation in a randomized, double-blind clinical trial. The biochemical parameters were read based on blood. These blood sampling made at different stages of chemotherapy and selenium supplementation. At each of these stages, the cholesterol, glucose and triglycerides parameters were read using the Z-scan and spectrophotometry techniques. We observed that selenium helps in balancing the health of these patients, and corroborates with our hypothesis that the Z-scan technique may be an alternative for the determination of biochemical parameters.

Quality of life on hemodialysis and inflammation: a descriptive analysis.

Chronic kidney disease (CKD) is highly prevalent worldwide. Patients with CKD on hemodialysis are more likely to present behavioral changes and worse quality of life as a result of their routine and complications. They also have higher levels of cytokines. The aim of this study is to assess the relationship between the inflammatory profile and quality of life measured by KDOQL-SF36 in hemodialysis outpatients. Patients older than 21 years of age and on routine hemodialysis for at least 6 months with treatment on a regular weekly basis were included and their anthropometric parameters and serum inflammatory markers were evaluated. Thirty patients consented to participate. Homocysteine (Hcy) levels were correlated with worse glomerular filtration rate (GFR; P=0.003) and creatinine (P=0.002). IL-6 was not correlated with worse nutritional status taking into account body mass index (BMI; kg/m2; P=0.83). On the other hand, TNF-alpha was positively correlated with albumin (P=0.008), nutritional status by BMI (P=0.04), and nutritional status by arm circumference area (P=0.04). IL-6 was correlated with activity limitation (P=0.02) and Hcy with work status (P=0.04). Hcy was correlated with nutritional status and inflammatory markers. In this population, the majority of the sections in KDOQL-SF36 were not correlated with cytokines levels.

The effect of nutritional intervention on the lipid profile and dietary intake of adolescents with juvenile systemic lupus erythematosus: a randomized, controlled trial.

Objective This study sought to evaluate the effects of a nutritional intervention on the lipid metabolism biomarkers associated with cardiovascular risk, and their variation over time, in juvenile systemic lupus erythematosus (JSLE) patients. This study also investigated the relationships between these biomarkers and dietary intake, nutritional status, disease variables, and medication used. Methods A total of 31 10- to 19-year-old female adolescents with JSLE for at least six months were analyzed. The participants were randomly allocated to two groups: nutritional intervention or control. The intervention group received verbal and printed nutritional instructions once per month over nine months. Before and after the intervention, the participants underwent assessments of anthropometry; dietary intake; physical activity; socioeconomic status; total cholesterol and fractions; triglycerides; apolipoprotein A (Apo A-I); apolipoprotein B (Apo B); paraoxonase (PON) activity (a) and amount (q); myeloperoxidase (MPO); and small, dense LDL-c (sdLDL) particles. Results After nine months, we found significant reductions in the calorie, carbohydrate, total fat, saturated fat, and trans fat intakes in the intervention compared with the control group over time. The PONa/HDL-c ratio increased by 3.18 U/ml/mg/dl in the intervention group and by 0.63 U/ml/mg/dl in the control group ( p = 0.037). Unlike the intervention group, the sdLDL levels of the control group worsened over time ( p = 0.018). Conclusion The present study detected a reduction in calorie and fat intake, which indicates an improvement of HDL-c function and possible protection against cardiovascular risk for the intervention group.

IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients

Community-acquired pneumonia (CAP) is amongst the leading causes of death worldwide. As inflammatory markers, cytokines can predict outcomes, if interpreted together with clinical data and scoring systems such as CURB-65, CRB, and Acute Physiology and Chronic Health Evaluation II (APACHE II). The aim of this study was to determine the impact of inflammatory biomarkers on the early mortality of hospitalized CAP patients. Twenty-seven CAP patients needing hospitalization were enrolled for the study and samples of interleukin-1 (IL-1) and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and homocystein were collected at the time of admission (day 1) as well as on the seventh day of the treatment. There was a significant reduction in the levels of IL-6 between the first and the second collections. Median IL-6 values decreased from 24 pg/mL (day 1) to 8 pg/mL (day 7) (P=0.016). The median levels of TNF-α were higher in patients: i) with acute kidney injury (AKI) (P=0.045), ii) requiring mechanical ventilation (P=0.040), iii) with short hospital stays (P=0.009), iv) admitted to the intensive care unit (ICU) (P=0.040), v) who died early (P=0.003), and vi) with worse CRB scores (P=0.013). In summary, IL-6 and TNF-α levels were associated with early mortality of CAP patients. Longer admission levels demonstrated greater likelihood of early death and overall mortality, necessity of mechanical ventilation, and AKI.

The use of vancomycin with its therapeutic and adverse effects: a review.

OBJECTIVE: Vancomycin (VCM) is a tricyclic glycopeptide antibiotic produced by Streptococcus orientalis. Widely used in hospitals, it is indicated to fight severe infections caused by Gram-positive bacteria, especially with the advent of MRSA (methicillin-resistant Staphylococcus aureus), penicillin-resistant pneumococci among others. Furthermore, it is indicated for the treatment of patients allergic to penicillins and cephalosporins. Dose recommendations, dilution rates and types of infusion are controversial and also result in toxic effects. Aim of this paper was to perform a literature review showing the therapeutic and adverse effects of vancomycin. MATERIALS AND METHODS: This is a literature review of recent articles published on MEDLINE and SciELO databases in English, Portuguese and Spanish. RESULTS: The main adverse effects of vancomycin are: hypotension, phlebitis, nephrotoxicity, ototoxicity, hypersensitivity reactions, red man syndrome, neutropenia, chills, fever, interstitial nephritis. CONCLUSIONS: The use of vancomycin is still very common; however, inadequate doses and prolonged therapy pose a risk of increasing minimum inhibitory concentrations (MICs), resulting in subtherapeutic levels, treatment failures and toxicity. Therefore, further studies should be conducted to optimize the administration of vancomycin, monitoring treatments from the beginning in order to ensure a safe and effective use of the drug.

IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients.

Community-acquired pneumonia (CAP) is amongst the leading causes of death worldwide. As inflammatory markers, cytokines can predict outcomes, if interpreted together with clinical data and scoring systems such as CURB-65, CRB, and Acute Physiology and Chronic Health Evaluation II (APACHE II). The aim of this study was to determine the impact of inflammatory biomarkers on the early mortality of hospitalized CAP patients. Twenty-seven CAP patients needing hospitalization were enrolled for the study and samples of interleukin-1 (IL-1) and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and homocystein were collected at the time of admission (day 1) as well as on the seventh day of the treatment. There was a significant reduction in the levels of IL-6 between the first and the second collections. Median IL-6 values decreased from 24 pg/mL (day 1) to 8 pg/mL (day 7) (P=0.016). The median levels of TNF-α were higher in patients: i) with acute kidney injury (AKI) (P=0.045), ii) requiring mechanical ventilation (P=0.040), iii) with short hospital stays (P=0.009), iv) admitted to the intensive care unit (ICU) (P=0.040), v) who died early (P=0.003), and vi) with worse CRB scores (P=0.013). In summary, IL-6 and TNF-α levels were associated with early mortality of CAP patients. Longer admission levels demonstrated greater likelihood of early death and overall mortality, necessity of mechanical ventilation, and AKI.

Survinin expression in patients with breast cancer during chemotherapy.

Breast cancer (BC) is the second most common cancer worldwide and the first among women. If early diagnosed and treated, this disease has a good prognosis. However, it is believed that 90 % of all patients who have had cancer died due to metastatic disease, which highlights the need for a marker which allows the detection of latent cancer cells spread from the primary tumor. The objective of this study was to investigate the expression of survinin in peripheral blood of patients with breast cancer at diagnosis and during chemotherapy aiming correlation with minimal residual disease, clinical and pathological findings. The study included 40 patients with breast cancer and 12 healthy donors as a comparison group. Survinin expression was verified by real-time PCR. For diagnosis, survinin expression cutoff point was 1.05; considering this cutoff point, we obtained a test sensitivity of 85.3 %, specificity of 75.0 %, positive predictive value of 90.6 %, negative predictive value of 64.3 %, and accuracy of 82.6 %. There was statistical significance between groups (patients × control group), presenting to patients a significantly higher value than the control group (p < 0.001). Patients that presented at the diagnosis a survinin gene expression ≥ 1.05 are 17 times more likely to develop metastatic disease.

Erythropoietin reduces the expression of myostatin in mdx dystrophic mice

Erythropoietin (EPO) has been well characterized as a renal glycoprotein hormone regulating red blood cell production by inhibiting apoptosis of erythrocyte progenitors in hematopoietic tissues. EPO exerts regulatory effects in cardiac and skeletal muscles. Duchenne muscular dystrophy is a lethal degenerative disorder of skeletal and cardiac muscle. In this study, we tested the possible therapeutic beneficial effect of recombinant EPO (rhEPO) in dystrophic muscles in mdx mice. Total strength was measured using a force transducer coupled to a computer. Gene expression for myostatin, transforming growth factor-β1 (TGF-β1), and tumor necrosis factor-α (TNF-α) was determined by quantitative real time polymerase chain reaction. Myostatin expression was significantly decreased in quadriceps from mdx mice treated with rhEPO (rhEPO=0.60±0.11, control=1.07±0.11). On the other hand, rhEPO had no significant effect on the expression of TGF-β1 (rhEPO=0.95±0.14, control=1.05±0.16) and TNF-α (rhEPO=0.73±0.20, control=1.01±0.09). These results may help to clarify some of the direct actions of EPO on skeletal muscle.

Erythropoietin reduces the expression of myostatin in mdx dystrophic mice.

Erythropoietin (EPO) has been well characterized as a renal glycoprotein hormone regulating red blood cell production by inhibiting apoptosis of erythrocyte progenitors in hematopoietic tissues. EPO exerts regulatory effects in cardiac and skeletal muscles. Duchenne muscular dystrophy is a lethal degenerative disorder of skeletal and cardiac muscle. In this study, we tested the possible therapeutic beneficial effect of recombinant EPO (rhEPO) in dystrophic muscles in mdx mice. Total strength was measured using a force transducer coupled to a computer. Gene expression for myostatin, transforming growth factor-ß1 (TGF-ß1), and tumor necrosis factor-α (TNF-α) was determined by quantitative real time polymerase chain reaction. Myostatin expression was significantly decreased in quadriceps from mdx mice treated with rhEPO (rhEPO = 0.60 ± 0.11, control = 1.07 ± 0.11). On the other hand, rhEPO had no significant effect on the expression of TGF-ß1 (rhEPO = 0.95 ± 0.14, control = 1.05 ± 0.16) and TNF-α (rhEPO = 0.73 ± 0.20, control = 1.01 ± 0.09). These results may help to clarify some of the direct actions of EPO on skeletal muscle.

AMH: An ovarian reserve biomarker in assisted reproduction.

Ovarian reserve tests provide knowledge of a possible response to controlled ovarian hyperstimulation in patients undergoing assisted reproduction treatment, allowing management and alteration of treatment protocol with the appropriate dose of gonadotrophin. Several parameters have been used as predictors of ovarian response. The basal FSH serum level on the third day of the menstrual cycle seemed to be the best predictor, but with significant intraindividual variability from one cycle to another. Thus, the anti-Müllerian hormone (AMH) emerges as a new ovarian test marker. AMH is produced exclusively in the gonads, by the granulosa cells, and plays an important role in folliculogenesis, acting on the modulation of follicular recruitment in the granulosa cells in order to limit the number of recruited oocytes and to regulate the number of growing follicles and their selection for ovulation. It has been suggested that AMH is strongly associated with oocyte yield after ovarian stimulation and could therefore be capable of predicting the ovarian response and the quality of oocytes and embryos. In this review, we discuss the role of AMH in assisted reproduction outcomes.

Diagnosis of the infection by the Helicobacter pylori through stool examination: method standardization in adults.

OBJECTIVES: Infection caused by Helicobacter pylori (H. pylori) is one of the most common causes of chronic infection in the world. The presence of the infection is strongly associated with the neoplasia of the gastrointestinal tract, and its diagnosis is easily made by means of invasive or non-invasive methods. Among such methods, the H. pylori antigen detection in stool through ELISA technique is easily performed and it is an alternative to endoscopy in children, since this exam is not usually indicated in this age group. The aim of the current study is to establish the standardization of the ELISA method for the detection of H. pylori in stool specimens in Brazil. DESIGN AND METHODS: Patients between 18 and 70 years of age were randomly selected in the gastroenterology ambulatory center at Faculdade de Medicina do ABC between 2007 and 2009. They all answered a questionnaire to investigate possible dyspeptic symptoms and then underwent endoscopy and detection of H. pylori through no more than 4 methods. Besides the gastric biopsy, established as the gold standard test, the urease test, the stool ELISA test and serology were also methods applied. RESULTS: The sensitivity and specificity of the exams in this sample were respectively 87.2% and 44% for the stool ELISA test, 41.9% and 64% for serology, 65.6% and 58.8% for the urease test and 100% and 80.8% for the clinical analysis. CONCLUSIONS: The ROC curve showed a good correlation between the compared methods. In Brazil the standardization of the ELISA test for the detection of H. pylori in stool specimens constitutes a non-invasive diagnostic alternative.

Safety and efficacy analysis of liposomal insulin-like growth factor-1 in a fluid gel formulation for hair-loss treatment in a hamster model.

Insulin-like growth factor (IGF)-1 has shown some interesting results in studies examining its use as a hair-loss treatment. IGF-1 works by regulating cellular proliferation and migration during the development of hair follicles. Hepatotoxicity and myelotoxicity were evaluated in hamsters (Mesocricetus auratus) after topical application of the liquid gel vehicle (placebo), 1% IGF-1 or 3% IGF-1. No significant difference in the levels of aspartate aminotransferase or alanine aminotransferase was found between the control and treated groups. ELISA did not shown any increase in the plasma level of IGF-1. A haematopoietic niche was found, but it was not associated with myelotoxicity. Efficacy was determined by dermatoscopy analysis of hair density and microscopy analysis of hair diameter, with hair found to be thicker and with more rapid growth in the 3% group than in either the 1% group or the control group. These results strongly suggest that liposomal IGF-1 in a liquid gel formulation is a safe and efficient treatment for hair loss.

Integration of basic sciences in health's courses.

Concepts from disciplines such as Biochemistry, Genetics, Cellular and Molecular Biology are essential to the understanding and treatment of an elevated number of illnesses, but often they are studied separately, with no integration between them. This article proposes a model for basic sciences integration based on problem-based learning (PBL) and compares failure rate, global final grade, approved student final grade, grade distribution and students' satisfaction with teacher conduction between integrated curriculum and traditional learning in health courses from Anhembi Morumbi University-a private institution from Brazil. Comparison between integrated and traditional curriculum was based on students' records obtained from first-year health sciences students. A total of 1,697 records from 2005 to 2007 (nonintegrated curriculum) and 785 records from 2008 (integrated curriculum) were selected for this study and they were necessary to get information about students' grades. Moreover, a questionnaire was applied in order to cover student's satisfaction with teacher conduction. The data presented in this study indicated that the integrated curriculum based on PBL was related to an improvement in student's grades and satisfaction compared with traditional teaching. We believe that the effectiveness in health education will be a combination of "classical" presentation of contents associated to actively involved students in the educational process and methodology based on problems in order to create the stimulus for the undergraduates continue to integrate basic and clinical investigation.

Bisphosphonate therapy in patients under androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis.

The objective of this study was to clarify the role of bisphosphonates in the treatment of osteoporosis in patients with prostate adenocarcinoma under androgen deprivation therapy (ADT). The Medline, EMBASE, Cancerlit and the American Society of Clinical Oncology abstract databases were searched for published randomized, placebo-controlled trials evaluating the usage of bisphosphonates in patients with prostate cancer (PC) under ADT. The outcomes assessed were fracture, osteoporosis, incidence of adverse events and changes in bone mineral density (BMD) during treatment. A total of 15 articles (2634 participants) were included in the meta-analysis. Treatment with bisphosphonates showed a substantial effect in preventing fractures (risk ratio (RR), 0.80; P = 0.005) and osteoporosis (RR, 0.39; P <0.00001). Zoledronic acid showed the best number needed to treat (NTT), compared with placebo, in relation to fractures and osteoporosis (NNT = 14.9 and NNT = 2.68, respectively). The between-group difference (bisphosphonates vs placebo) in the lumbar spine and femoral neck BMD were 5.18 ± 3.38% and 2.35 ± 1.16%, respectively. This benefit of bone loss prevention could be reached without major side effects (cardiovascular or gastrointestinal events). Bisphosphonates are effective in preventing bone loss in patients with PC who are under ADT.

Bone and total alkaline phosphatase for screening skeletal metastasis in patients with solid tumours.

Alkaline phosphatase (AP) has several isoforms including bone alkaline phosphatase (BAP). We evaluated BAP and AP for screening for bone metastasis (BM) in patients with solid tumours. This is a prospective non-blinded study conducted at ABC Foundation School of Medicine Oncology clinics. A total of 40 subjects without a history of cancer and 62 patients with various solid tumours referred for a bone scan had serum drawn for BAP and AP determination. Bone alkaline phosphatase and AP levels in patients with cancer and BM, without BM and with no cancer, were 70.32 +/- 3.65 and 310.21 +/- 16.87 U/L; 41.40 +/- 2.80 and 113.23 +/- 12.95 U/L; 21.19 +/- 2.76 and 148.05 +/- 12.79 U/L respectively (P < 0.0001 for both AP and BAP). For BAP and AP sensitivity, specificity, positive and negative predictive values were 0.86 and 0.52; 0.69 and 1; 0.45 and 1; 0.94 and 0.87 respectively. ROC AUC value for BAP was 0.89 and for AP was 0.93. We conclude that BAP is more sensitive than AP, whereas AP had a remarkable specificity of 100%. In screening for BM in patients with solid tumours, obtaining initially BAP and then selecting for further investigation only patients with an abnormal AP may be a cost and resource saving strategy.