Social determinants of Health and Google Trends: a worldwide infodemiological report.

OBJECTIVE: Several sociodemographic variables are essential to the complete comprehension of people's health conditions. Also, social determinants of health are decisive in influencing people's health and healthcare strategy outcomes. Nevertheless, the level of awareness of the general population about the social determinants of health still seems poorly investigated. In this scenario, using an infodemiological approach, Google Trends represents a handy tool for monitoring internet-related search activities concerning this specific topic. This study aimed to assess the general population's consciousness about social determinants of health, testing widespread knowledge of these items and evaluating the association of the results obtained through Google-specific search volumes. MATERIALS AND METHODS: Data were collected using the Google Trends tool using several search terms related to food, social problems, and economic issues, which are useful for defining some social determinants of health variables. Descriptive data analysis was performed to show the worldwide Relative Search Volume variations from 1 September 2013 to 31 August 2023. Pearson's correlation analysis tested Relative Search Volumes and later logarithmic transformation. The K-Nearest Neighbors analysis was used to define and assess Relative Search Volumes (RSV) associations. RESULTS: The results have shown that the general population was mainly interested in topics such as "social support" and "economic burden", showing frequent peaks during the 10 years of the study. According to Pearson's coefficients test, other specific interests and relative correlations emerged regarding social variables (i.e., social support and social problems), food, and financial distress. Moreover, the K-Nearest Neighbors analysis showed that searching activities for "social support", "lack of food", and "social problems" were highly related; for "economic burden", "financial burden", and "out of pocket" suggested the existence of financial distress. CONCLUSIONS: The results of this study underline that social determinants of health are significant barriers to health and well-being and that non-medical factors should be considered more. Healthcare professionals involved in public health should study and understand more about the social determinants of health in relation to health outcomes to provide patient-centered care. Finally, this research suggests that we should encourage and maintain a more comprehensive approach to addressing the health needs of patients and communities, also by an infodemiological assessment.

Elderly patients with multimorbidity in the home setting: umbrella review on therapeutic non-adherence causes.

OBJECTIVE: The elderly population is the most at risk regarding adherence, especially in the coexistence of multiple diseases. This study aims to detect factors contributing to therapeutic non-adherence in elderly patients in home settings. MATERIALS AND METHODS: A review protocol was developed to conduct the umbrella review using the methodological framework of the Richardson et al study. The search strategy was developed in December 2022 to conduct a systematic search and to perform an Umbrella Review of systematic reviews, meta-analyses and integrative reviews published from 2012 to 2022 in English. RESULTS: A total of 26,038 articles were identified and screened. 18 relevant articles were included in the study. CONCLUSIONS: Therapeutic adherence in elderly patients with comorbidities in polypharmacotherapy at home is a significant problem in public health and health care. Several factors of non-adherence have been identified in the studies reviewed, confirming that the problem is multifactorial. Reducing the number of medications prescribed would appear optimal, although often not possible, as this has been seen to have an immediate positive impact. A multidisciplinary approach makes it possible not to fragment care, ensuring positive feedback on therapeutic adherence.

Comparison across 12 countries on knowledge, attitude, and behavior scores about medication errors in Intensive Care Units: an international study.

OBJECTIVE: The aim of the study was to explore the degree of agreement of intensive care unit nurses working on a set of medication error preventive strategies and to examine possible predictors of nurses' knowledge, attitude and behavior. MATERIALS AND METHODS: Observational, international, and cross-sectional study. Iran, Malta, Spain, Pakistan, Nepal, Qatar, Ecuador, Australia, Finland, Italy, Egypt, and Jordan were the countries included in this survey. To collect data, the Knowledge, Attitude and Behavior in Medication Errors questionnaire was used. A descriptive statistical analysis was performed for the socio-demographic characteristics of the sample and three multiple logistic regressions were performed. RESULTS: The international sample consists of 1383 nurses, of whom 478 (34.6%) were men and 900 (65.1%) were women and their mean age was 35.61 years with a range of 19-61. Descriptive statistics conducted on the international sample show a medium to high degree of agreement among participants concerning some preventive strategies of medication error. In addition, the results of the present study show a strong relationship between positive nurses' attitudes and correct behaviors and/or adequate knowledge, as well as between adequate knowledge and correct behaviors (p< 0.01). CONCLUSIONS: Further studies are needed to explore the issue of medication error concerning nurses' cultural backgrounds, as well as to assess similarities and disparities among international nurses.

Impact of nursing students on the quality of care perceived by patients: a systematic review of the literature.

OBJECTIVE: The quality assessment process, based on customer satisfaction, is fundamental in the delivery of the best care services. This is most evident in care settings where trainee students are allowed to assist the patients. The purpose of this review is to clarify whether nursing students have an impact on patients' assessment of the quality of their nursing care. MATERIALS AND METHODS: A systematic literature search was carried out using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines in six databases: PubMed, CINAHL, Cochrane, Web of Science, Scopus, and PsycInfo. Two co-authors independently screened titles, abstracts, and full-text articles, following explicit exclusion and inclusion criteria. Analyses included non-randomized and non-homogeneous samples, involving both selected patients and methods for assessing their satisfaction. RESULTS: After full-text screening, 30 articles were identified, but only 11 were considered pertinent to the topic of the review. The trainee-patient relationship is based on mutual help and can improve the patient experience and trainee learning. The instruments used to measure perceived quality were found to be valid and reliable. CONCLUSIONS: The studies under review show high levels of satisfaction among patients when nursing care is delivered through training, particularly when the patients who agree to be treated by nursing trainees have previous experience of hospitalization and relationships with trainees. Educational background and the empathy and communication skills of both professional nurses and trainees influence patients' perception of the quality of care and their satisfaction with it.

Risk of medication errors and nurses' quality of sleep: a national cross-sectional web survey study.

OBJECTIVE: We aimed to evaluate quality of sleep and self-perception risk of medication errors, in a significantly-sized sample of nurses in Italy, using a web survey. SUBJECTS AND METHODS: An anonymous questionnaire about self-perception of quality of sleep (Pittsburgh Sleep Quality Index - PSQI) and risk of medication errors (based on the 7 R-rule), was made up and delivered by social media, i.e., Facebook and Instagram. Risk of medication errors was intended as near misses, i.e., accidents that do not cause the patient harm. RESULTS: A poor quality of sleep stated by PSQI score >5, was present in 87.9% of subjects and the risk of medication errors during the last shift was reported in 76% of them. However, more than half of nurses' sample (60.1%) reported a good or excellent self-perception quality of sleep. Risk of medication errors was associated with poor quality of sleep and it was independently associated with short resting time after night shift and bad self-perception quality of sleep (OR 3.165, 95% CI 1.468-6.827, p=0.003). CONCLUSIONS: Absence of proper resting is crucial on performance even if nurses perceived a good quality sleep. The relationship between shift work, poor sleep quality, and risk of medication errors represents crucial point for all health professionals' community, and web-survey represents a valuable information in order to capture the risk of medication errors. Health care organizations should encourage such a type of research in order to show a more proactive approach towards patient safety.

Measuring knowledge, attitudes and behavior of nurses in medication management: cross-cultural comparisons in Italy and Malta.

OBJECTIVE: Medication errors are one of the most common causes of negative events affecting patient safety all over the world.  Scientific literature divides the factors that contribute to the occurrence of harmful events into factors related to the characteristics of the healthcare workers and factors related to the organization of the drug management process. The aim of the study was to examine the knowledge, attitudes and behaviours related to medication errors among Italian and Maltese nurses. SUBJECTS AND METHODS: Cross-sectional survey of nurses working in Intensive Care settings in Italian and Maltese hospitals was conducted. A valid and reliable questionnaire used in previous studies was adapted for online use. Despite improved reporting, The Strengthening the Reporting of Observational Studies in Epidemiology was used. RESULTS: Findings showed good psychometric properties and reliability. MANOVA demonstrated significant differences in nurses' perception of the pharmacist presence during medication process and of the use of computerized provider order entry. MANOVA also demonstrated significant differences in the control of vital parameters and the application of the 8 right. CONCLUSIONS: These findings support the contention that knowledge, attitude and behaviour of nurses is similar across different contexts in different countries wherein nurse training is harmonised and regulated through a transnational directive.

Contact precaution procedures in healthcare facilities.

BACKGROUND: Multidrug resistance is an established and growing worldwide public health problem, since few therapeutic options remain available. MRSA is the leading Gram-positive organism which has spread both in the community and healthcare environment. Gram-negative bacteria, either fermenter (enterobacteriaceae) or nonfermenter, pose a major challenge to the healthcare providers because they can express a wide multidrug resistance. METHODS: Specific keywords combinations were analitically searched in PubMed and Scopus databases. Publications concerning contact precaution procedures were reviewed. RESULTS: The review on infection control and isolation precautions was carried out focusing on bundles that could help healthcare personnel to improve their action. CONCLUSIONS: This paper clearly refers to measures in order to control the spread of infectious disease. We provided some synthetic tables that could improve healthcare workers knowledge and help them to apply all fundamental concepts in infection control.

Infodemiological patterns in searching medication errors: relationship with risk management and shift work.

INTRODUCTION: Western world health care systems have been trying to improve their efficiency and effectiveness in order to respond properly to population aging and non-communicable diseases epidemic. Treatment of the elderly population is becoming complex due to the high number of prescribed drugs because of multimorbidity. Errors in drugs administration in different health care related settings are an actual important issue due to different causes. Aim of this observational study is to measure the online interest in seeking medication errors information related to risk management and shift work. MATERIALS AND METHODS: We investigated Google Trends® for popular search relating to medication errors, risk management and shift work. Relative search volumes (RSVs) were evaluated from 2008 to 2018. A comparison between RSV curves related to medication errors, risk management and shift work was carried out. Then, we compared the world to Italian search. RESULTS: RSVs were persistently higher for risk management than for medication errors (mean RSVs 069 vs. 48%) and RSVs were stably higher for medication errors than shift work (mean RSVs 48 vs. 22%). In Italy, RSVs were much lower compared to the rest of the world, and RSVs for medication errors during the study period were negligible. Mean RSVs for risk management and shift work were 3 and 25%, respectively. RSVs related to medication errors and clinical risk management were correlated (r=0.520, p<0.0001). CONCLUSIONS: Google Trends® search query volumes related to medication errors, risk management and shift work are different. RSVs for risk management are higher, and they are correlated with medication errors. Also, shift work search appears to be lower. These results should be interpreted in order to correctly evaluate how to decrease the number of medication errors in different health care related setting.

Can nurses' shift work jeopardize the patient safety? A systematic review.

OBJECTIVE: Medication administration accounts for 40% of the nursing clinical activity in hospitals and nurses play a central role in granting the patient safety, as they are directly responsible for the patient care. This review aims at analyzing the correlation between the clinical risk management and the occurrence of medication errors and the effects of the shift work (such as excessive fatigue and sleep deprivation after a shift in hospital) on inpatient nurses. MATERIALS AND METHODS: This paper adheres to the relevant EQUATOR guidelines. A systematic review was conducted according to the PRISMA statement and pertinent articles were selected based on inclusion criteria and quality assessment factors. Two reviewers searched the bibliographic databases PubMed, Scopus, Cochrane, CINAHL to collect all the available articles in English and Italian issued between 1992 and August 2017. RESULTS: The reviewers analyzed 19 of the 723 initially extracted references, as they focused on the impact of workload, shifts and sleep deprivation on the probability of making medication errors. CONCLUSIONS: The main reasons behind medication errors are stress, fatigue, increased workload, night shifts, nurse staffing ratio and workflow interruptions. These factors can have a significant negative impact on the health and the performance of the employees. It is desirable to extend and deepen the research to identify appropriate measures to minimize medication errors.

Perioperative nutritional support or perioperative fasting? A narrative review.

Traditionally, overnight fasting before elective surgery has been Romathe routine in medical practice for risk reduction of pulmonary aspiration of gastric contents. Several original study and international societies recommend a 2h preoperative fast for clear fluids and a 6h fast for solids in most elective patients. We conducted a narrative review of the literature, searching electronic databases (Medline and CINAHL). We used PICO approach. The results of our review suggest that nutrition support in the perioperative period is very important to reduce length of hospital stay and reduced postoperative complication.

Serum transforming growth factor ß1 during diabetes development in non-obese diabetic mice and humans.

Recent data show that regulatory cells with transforming growth factor (TGF)-ß1-dependent activity are able to restore self-tolerance in overtly diabetic non-obese diabetic (NOD) mice. Thus, TGF-ß1 seems to have a relevant role in protection from autoimmune diabetes. Our aim was to investigate the possible significance of serum TGF-ß1 measurement in the natural history of diabetes in NOD mice, as well as in children positive for at least one islet-related antibody. Serum TGF-ß1 (both total and active) was measured by enzyme-linked immunosorbent assay at monthly intervals in 26 NOD mice during the spontaneous development of diabetes and, on a yearly basis, in nine siblings of patients with type 1 diabetes (T1D) with a follow-up of 4 years. Diabetes appeared between the 12th week of age and the end of the study period (36 weeks) in 17 mice. TGF-ß1 serum level variations occurred in the prediabetic period in both NOD mice and humans and diabetes diagnosis followed a continuing reduction of active TGF-ß1 (aTGF-ß1) serum levels. In mice, aTGF-ß1 serum levels measured at 4 weeks of age correlated positively with severity of insulitis, and negatively with percentage of insulin-positive cells. Our findings suggest that in NOD mice serum TGF-ß1 levels during the natural history of the diabetes reflect the course of islet inflammation. The measurement of aTGF-ß1 in islet-related antibody-positive subjects may provide insights into the natural history of prediabetic phase of T1D.

Oral probiotic administration induces interleukin-10 production and prevents spontaneous autoimmune diabetes in the non-obese diabetic mouse.

AIMS/HYPOTHESIS: Recent observations suggest the involvement of the gastrointestinal tract in the pathogenesis of islet autoimmunity. Thus, the modulation of gut-associated lymphoid tissue may represent a means to affect the natural history of the disease. Oral administration of probiotic bacteria can modulate local and systemic immune responses; consequently, we investigated the effects of oral administration of the probiotic compound VSL#3 on the occurrence of diabetes in non-obese diabetic (NOD) mice. METHODS: VSL#3 was administered to female NOD mice three times a week starting from 4 weeks of age. A control group received PBS. Whole blood glucose was measured twice a week. IFN-gamma and IL-10 production/expression was evaluated by ELISA in culture supernatants of mononuclear cells isolated from Peyer's patches and the spleen, and by real-time PCR in the pancreas. Insulitis was characterised by immunohistochemistry and histomorphometric studies. RESULTS: Early oral administration of VSL#3 prevented diabetes development in NOD mice. Protected mice showed reduced insulitis and a decreased rate of beta cell destruction. Prevention was associated with an increased production of IL-10 from Peyer's patches and the spleen and with increased IL-10 expression in the pancreas, where IL-10-positive islet-infiltrating mononuclear cells were detected. The protective effect of VSL#3 was transferable to irradiated mice receiving diabetogenic cells and splenocytes from VSL#3-treated mice. CONCLUSIONS/INTERPRETATION: Orally administered VSL#3 prevents autoimmune diabetes and induces immunomodulation by a reduction in insulitis severity. Our results provide a sound rationale for future clinical trials of the primary prevention of type 1 diabetes by oral VSL#3 administration.

[Male osteoporosis: current treatments and future options]. / L'osteoporosi maschile: possibilità terapeutiche attuali e prospettive future.

PURPOSE: To provide indications for currently approved treatments and future options for male osteoporosis, based on the pathogenetic mechanisms of bone loss in the male sex. DESIGN: Review of the most significant data reported in the literature. RESULTS: Unhealthy lifestyle habits should be modified. Testosterone replacement is indicated only in patients with diagnosis of hypogonadism. Based on the demonstrated pathogenetic role of estrogen lack in bone loss in men, either low doses of this hormone or selective androgen receptor modulators have been proposed for the treatment of male osteoporosis. Bisphosphonates are the only medications approved by Food and Drug Administration for idiopathic and glucocorticoid-induced osteoporosis in men. As far as anabolic treatments are concerned, there is not agreement on clinical utility of sodium fluoride. Short-term treatment with parathyroid hormone (PTH) seems to be safe and effective in patients with idiopathic osteoporosis, due to its anabolic action. Therapeutic use of growth hormone (GH) and insulin-like growth factor type I (IGF-I), both considered as potential anabolic agents, is still limited because of the high incidence of side effects and relatively transient efficacy, particularly of IGF-I. CONCLUSIONS: Treatments should be selected on the basis of anti-fracture efficacy of various medications, which has been demonstrated so far only for alendronate and risedronate. Although anabolic agents produce noticeable increase of bone mineral density, is still debated if they also reduce fracture incidence in males with osteoporosis.

Uneven deficits in vertebral bone density in postmenopausal patients with primary hyperparathyroidism as evaluated by posterior-anterior and lateral dual-energy absorptiometry.

This investigation was undertaken to determine whether the preservation of bone mass in patients with mild primary hyperparathyroidism (PHPT) could be detected when measuring spine density in the lateral projection. We compared the bone mineral density (BMD) of L2-L4 utilizing the posterior-anterior (PA) and lateral projections in postmenopausal patients with PHPT and in a group of 27 postmenopausal normal women. Thirty-three consecutive postmenopausal patients with PHPT were studied; 25 were asymptomatic whereas the remaining 8 suffered complications related to the disease. Based upon the criteria established by the Consensus Conference on the Management of Asymptomatic PHPT, only 10 of the 25 asymptomatic patients could be considered affected by mild disease; the remaining patients were classified as having moderate disease. Patients with mild disease had mean lateral total BMD values (0.682 +/- 0.113 g/cm(2)) significantly higher than normal women (0.588 +/- 0.076, p<0.02) and patients with moderate disease (0.599 +/- 0.077, p<0.05). There were significant differences among the three groups in both PA L2-L4 and L1-L4 levels: patients with mild disease had significantly higher mean BMD values than patients with moderate disease and normal women, when either three or four vertebrae were considered. Interestingly, at this latter site, patients with moderate disease had significantly ( p<0.05) lower values than normal women. Our results indicate that patients with mild PHPT have a preservation of vertebral mass when compared with the other hyperparathyroid patients and normal women, when taking into account both the mainly trabecular portion and the whole vertebra. The finding that when the PA projection was assessed, BMD values of patients with moderate disease were significantly lower than those of normal women, might be attributed to the detrimental effect of raised parathyroid hormone levels on the cortical component of the vertebral body.

Gender differences in serum markers of bone resorption in healthy subjects and patients with disorders affecting bone.

To assess how two different serum markers of bone resorption may reflect changes in bone turnover, we compared age- and sex-related changes in serum C-terminal telopeptide of type I collagen (betaCTx) and tartrate-resistant acid phosphatase activity (TRAP) in 136 healthy men and 184 normal women. Serum levels of the two markers were also assessed in several groups of patients of both sexes presenting with the most common metabolic and endocrine bone diseases: established osteoporosis (n = 77), primary hyperparathyroidism (n = 44), glucocorticoid excess (n = 17), chronic renal failure (n = 39), active Paget's disease of bone (n = 5), humoral hypercalcemia of malignancy (n = 3), osteomalacia (n = 3), hyperthyroidism (n = 10), post-surgical hypoparathyroidism (n = 10), acromegaly (active disease, n = 8) and Cushing's syndrome (n = 10). In men the regression of betaCTx with age showed an initial decrease in bone resorption followed by an increase thereafter, starting from the sixth decade of life. No age-related change in serum TRAP activity was observed. In women, by contrast, a slight but significant linear correlation of both serum betaCTx and TRAP with age (r = 0.223, p<0.003 and r = 0.333, p<0.0001, respectively) was found, the two markers being positively correlated (r = 0.238, p<0.002). In each class of patients the mean Z-scores of betaCTx were significantly higher than those of TRAP activity. Moreover, compared with normal subjects, serum betaCTx seems to be characterized by a superior sensitivity relative to TRAP measurement, at least in the disorders studied.

Short-term effects of surgery in post-menopausal patients with primary hyperparathyroidism and normal bone turnover.

The most common clinical presentation of primary hyperparathyroidism (PHPT) is nowadays characterized by a slight skeletal involvement. We studied 5 consecutive female patients with PHPT presenting with bone turnover marker levels within the reference range of our Center and whose bone mineral density values were above the usual fracture risk threshold. In each patient we measured, both in basal conditions and daily, for the first 5 days after surgery, the following indexes: serum total (T-ALP) and bone-specific (B-ALP) alkaline phosphatase activity, osteocalcin (BGP, by two different assays), together with the 24-hour urinary excretions of total pyridinoline (Pyr/Cr) and deoxypyridinoline (DPyr/Cr), free deoxypyridinoline (FD-Pyr/Cr), cross-linked N-telopeptide of type I collagen (NTx/Cr), and type I C-telopeptide (CTx/Cr). The markers of both bone formation and resorption significantly decreased after surgery (p<0.001 by multiple ANOVA). Individual post-surgical markers changes were all significant but T-ALP and FD-Pyr, the most pronounced percent reductions being shown by NTx and CTx. The time-course of such variations substantially differed among the various indexes. These results show that bone formation and resorption markers are up-regulated also in PHPT patients with mild skeletal involvement; acute removal of parathyroid hormone excess differently affected the markers of bone turnover in terms of both entity and time-course.

Exogenous glucocorticoids affect in different way the various phases of bone formation in postmenopausal patients.

BACKGROUND: To determine the effect of glucocorticoid excess on the most important circulating markers of bone formation in postmenopausal treated patients. METHODS: The study included 15 postmenopausal women taking glucocorticoids for various medical conditions and two groups of 30 healthy premenopausal and 28 age-matched postmenopausal women as controls. Osteoblastic activity was assessed by measuring both serum levels of osteocalcin (BGP) (N-tact Osteo SP, Incstar Co.) and the bone-specific isoenzyme of alkaline phosphatase (BAP) (Alkphase-B, Metra Biosystems). RESULTS: The mean values of serum BGP found in patients taking steroids were significantly reduced as compared to those found in both fertile and postmenopausal women (p < 0.0001). The mean serum levels of BAP were significantly increased in treated patients as compared to premenopausal women (p < 0.0001), while no significant difference was found between patients and age-matched postmenopausal women. Similar results were also obtained when individual values of both serum BAP and BGP were expressed as standard units in comparison to values obtained in fertile subjects (T-score) or postmenopausal subjects (Z-score). CONCLUSIONS: Steroid therapy in postmenopausal patients differentially affects the various phases of bone formation. Measurement of serum BGP may represent a reliable parameter for monitoring bone formation in postmenopausal treated patients.

T-cell mediated autoimmunity to the insulinoma-associated protein 2 islet tyrosine phosphatase in type 1 diabetes mellitus.

The target molecules of the T-cell response in type 1 diabetes, despite their pathogenic importance, remain largely uncharacterized, especially in humans. Interestingly, molecules such as insulin and glutamic acid decarboxylase (GAD) have been shown to be a target not only of autoantibodies, but also of autoreactive T-lymphocytes both in man and in the non-obese diabetic (NOD) mouse. In the present study we aimed to determine the existence of a specific T-cell response towards the insulinoma-associated protein 2 (IA-2) islet tyrosine phosphatase, a recently identified autoantigen which is the target of autoantibodies strongly associated with diabetes development. Human recombinant IA-2 produced in Escherichia coli, was tested for its reactivity with peripheral blood lymphocytes obtained from 16 newly diagnosed type 1 diabetic patients and from 25 normal controls, 15 of whom were HLA-DR-matched. A T-cell proliferation assay was performed in triplicate employing freshly isolated cells in the absence or in the presence of the antigen to be tested (at two different concentrations: 2 microg/ml and 10 microg/ml). A specific T-cell proliferation (defined as a stimulation index (S.I.) >/=3) was observed against IA-2 used at a concentration of 10 microg/ml (but not of 2 microg/ml) in 8/16 diabetic patients, in 1/15 HLA-DR-matched control subjects (P<0.01 by Fisher exact test) and in 0/10 of the remaining normal individuals. A statistically significant difference (P<0.003 by Mann-Whitney U test) was also observed in S.I. values between patients (3.1+/-1.4) and HLA-DR-matched controls (1.7+/-0.54) employing IA-2 at a concentration of 10 microg/ml. However, when IA-2 was used at a concentration of 2 microg/ml, the difference in S. I. between patients (1.65+/-0.8) and controls (1.0+/-0.3) did not reach statistical significance. In conclusion, these data show the presence of a specific, dose-dependent T-lymphocyte response against the IA-2 islet tyrosine phosphatase at the onset of type 1 diabetes. Consequently, this molecule appears to be a target not only at the B-lymphocyte but also at the T-lymphocyte level, reinforcing the potential pathogenic role of this autoantigen in the islet destructive process.

The synergistic effect of simultaneous addition of retinoic acid and vitamin D3 on the in-vitro differentiation of human promyelocytic leukemia cell lines could be efficiently transposed in vivo.

Both human cell lines HL-60 and AML-193 exhibit a myeloblastic and promyelocytic morphology, respectively, but may be regarded as bipotent leukemic precursors. They can be triggered to differentiate to either granulocytes or monocytes upon retinoic acid (RA) or 1,25-dihydroxyvitamin D (D3) addition, respectively. We have investigated the effect of combined addition of these chemical inducers on the in-vitro differentiation of both cell lines. RA and D3 added together exert synergistic effects on the in-vitro maturation of these myeloid cell lines. Interestingly, the additive effects were lost if the cells were incubated with the inducers added at sequential times. The synergistic effect could be transposed in vivo and could be clinically significant in the treatment of the promyelocytic leukemia. This clinical strategy may help to prevent retinoic acid resistance or to overcome it in patients relapsed after RA therapy and usually unresponsive to a reinduction therapy with RA alone.