Sonodynamic therapy and common head and neck cancers: in vitro and in vivo studies.

Carcinogenesis is a complex multi-stage process associated with abnormal oncogenic signals in various signaling pathways. HNSCC (Head and neck squamous cell carcinoma) includes the majority of head and neck cancers (HNC). Also, HNSCC indicates a tumors heterogeneous group that derives from the squamous epithelium of the oropharynx, hypopharynx, oral cavity, and larynx. The main cancer management approach contains chemotherapy, radiation, and surgery separately or in combination. Each therapeutic approach has a limitation that influences cancer therapy procedures. Different treatment manners, stimuli-responsive therapeutic methods can improve on-target responses and reduce side effects. Sonodynamic therapy (ST) shows promising potential as an alternative treatment for cancer in the last few years. There is a hypothesis that shows ST using sonosenitizer in combination with low-intensity ultrasound (LIUS) could be useful in all kinds of cancer without focusing on specific target proteins, molecules, and/or genes. This review study discussed the application of ST for the treatment, ST mechanisms, and also, advances in the treatment of HNCs approaches in the recent decades.

Intra-hospital dissemination of clinical and environmental isolates of Stenotrophomonas maltophilia from Tehran.

Stenotrophomonas maltophilia isolates are responsible for various hospital-acquired infections and are particularly increasing in the immunocompromised patients. The aim of this study was to determine the clonal relatedness between S. maltophilia isolates originating from the clinic and environment. A total of 150 S. maltophilia isolates from patients and 1108 environmental samples obtained in three hospitals from Tehran. Following molecular identification targeting 23S rRNA gene, the clonal relatedness of the environmental and clinical isolates was determined using pulsed field gel electrophoresis (PFGE). Of the 150 clinical and 18 environmental isolates identified using phenotypic tests, the speciation of 120 and 15 was confirmed by targeting the 23S rRNA gene. The 24 common pulsotypes (PTs) and 32 single PTs were identified by PFGE. Only a small cluster was shared among the clinic and environment within a hospital; therefore, the intra-hospital dissemination of certain isolates of S. maltophilia among the clinic and environment was demonstrated.

Serogroups, and drug resistance of nontyphoidal Salmonella in symptomatic patients with community-acquired diarrhea and chicken meat samples in Tehran.

BACKGROUND: Salmonella is considered as a main cause of community-acquired diarrhea in humans, however, sources of the multi-drug resistant (MDR) strains and their link with the disease are not well known. AIMS: This study aimed to investigate the frequency, serogroup diversity, and antimicrobial susceptibility patterns of Salmonella strains in poultry meat and stool samples of patients with community acquired diarrhea in Tehran. METHODS: We compared the frequency of non-typhoidal Salmonella serogroups, the similarities of their resistance patterns to 10 antimicrobial compounds, the prevalence of extended spectrum ß-lactamase (ESBL) and ampicillinase C (AmpC) genetic determinants, and class 1 and 2 integrons in 100 chicken meat and 400 stool samples of symptomatic patients in Tehran during June 2018 to March 2019. RESULTS: Salmonella was isolated from 75% and 5.5% of the chicken meats and human stool samples, respectively. The chicken meat isolates mainly belonged to serogroup C (88%, 66/75), while the human stool isolates were mainly related to serogroup D (59.1%, 13/22). The MDR phenotype and the most common rates of resistance to antibiotics, including tetracycline, trimethoprim/sulfamethoxazole (TS) and azithromycin, were detected in 4.5% and 45.3%, 59% and 13.6%, 43% and 9.1%, 42% and 9.1% of the human stool and chicken meat samples, respectively. Carriage of bla CTX, bla SHV, and bla PER genes in the meat isolate with ESBL resistance phenotype and bla ACC, bla FOX, and bla CMY-2 among the 7 meat strains with AmpC resistance phenotype was not confirmed using polymerase chain reaction (PCR). High prevalence of class 1 and 2 integrons was characterized and showed a correlation with resistance to TS and chloramphenicol. CONCLUSION: These findings showed a lack of association between chicken meats and human isolates due to discrepancy between the characterized serogroups and resistance phenotypes.

Molecular serotyping and genotyping of penicillin non-susceptible pneumococci: the introduction of new sequence types, Tehran, Iran.

The emergence of penicillin non-susceptible Streptococcus pneumoniae (PNSP) isolates can pose significant challenges to today's health-care system. Resistant clonal isolates are disseminated in different regions and countries, and this study was focused on the description of the epidemiological spread of these strains. Clinical samples were collected from individuals admitted to hospitals affiliated to the Tehran University of Medical Sciences, Iran. To investigate the molecular characteristics of PNSP isolates, they were subjected to molecular typing using multi-locus sequence typing (MLST). Serotype distributions of S. pneumoniae isolates were also evaluated by multiplex PCR assay. The most prevalent serotypes in the PNSP isolates were 23F, 19F, 14, 3 and 9V. Two isolates were considered as a non-vaccine serotype. The MLST analysis showed that PNSP isolates belonged to five different clonal complexes (CC180, CC217, CC81, CC63 and CC320) and 42% (5/12) of the sequence types were novel (12936, 12937, 12938, 12939 and 12940). This study indicates the high level of heterogeneity that is present among PNSP isolates. Unexpected high genetic diversity in small populations indicates consecutive diversification of resistant strains.

Diabetes, undernutrition, migration and indigenous communities: tuberculosis in Chiapas, Mexico.

We investigated the distribution of comorbidities among adult tuberculosis (TB) patients in Chiapas, the poorest Mexican state, with a high presence of indigenous population, and a corridor for migrants from Latin America. Secondary analysis on 5508 new adult TB patients diagnosed between 2010 and 2014 revealed that the most prevalent comorbidities were diabetes mellitus (DM; 19.1%) and undernutrition (14.4%). The prevalence of DM in these TB patients was significantly higher among middle aged (41-64 years) compared with older adults (⩾65 years) (38.6% vs. 23.2%; P < 0.0001). The prevalence of undernutrition was lower among those with DM, and higher in communities with high indigenous presence. Immigrants only comprised 2% of all TB cases, but were more likely to have unfavourable TB treatment outcomes (treatment failure, death and default) when compared with those born in Chiapas (29.5% vs. 11.1%; P < 0.05). Unfavourable TB outcomes were also more prevalent among the TB patients with undernutrition, HIV or older age, but not DM (P < 0.05). Our study in Chiapas illustrates the challenges of other regions worldwide where social (e.g. indigenous origin, poverty, migration) and host factors (DM, undernutrition, HIV, older age) are associated with TB. Further understanding of these critical factors will guide local policy makers and health providers to improve TB management.

Severity of Mitral Regurgitation before and after Kidney Transplantation.

BACKGROUND: Perivalvular and valve involvement are prevalent in patients with end-stage renal disease (ESRD), especially in younger patients compared with normal population. Kidney transplantation improves the prognosis of these patients. Patients with cardiac valvular disease is also be improved following kidney transplantation. OBJECTIVE: To evaluate the impact of renal transplantation on the severity of mitral regurgitation (MR). METHODS: We studied 95 kidney transplantation candidates in Sina Hospital. The patients underwent echocardiography preoperatively and at the 3rd, 6th, and 12th months post-operatively. RESULTS: Pre-operatively, the average MR fraction was 30%; MR volume 30 mL/beat; mitral valve mean gradient 1.8 mm Hg; mitral valve area 4.6 cm2; and mitral annular size 3 cm. No significant difference was observed among the measurements made at the 3rd, 6th, and 12th months post-operatively. CONCLUSION: There was no significant association between the variables measured pre- and post-operatively. The reason might be the fact that patients with ESRD in Iran do not have to expect long transplant waiting lists and dialysis cannot affect their heart adversely.

External validation of a smartphone app model to predict the need for massive transfusion using five different definitions.

BACKGROUND: Previously, a model to predict massive transfusion protocol (MTP) (activation) was derived using a single-institution data set. The PRospective, Observational, Multicenter, Major Trauma Transfusion database was used to externally validate this model's ability to predict both MTP activation and massive transfusion (MT) administration using multiple MT definitions. METHODS: The app model was used to calculate the predicted probability of MTP activation or MT delivery. The five definitions of MT used were: (1) 10 units packed red blood cells (PRBCs) in 24 hours, (2) Resuscitation Intensity score ≥ 4, (3) critical administration threshold, (4) 4 units PRBCs in 4 hours; and (5) 6 units PRBCs in 6 hours. Receiver operating curves were plotted to compare the predicted probability of MT with observed outcomes. RESULTS: Of 1,245 patients in the data set, 297 (24%) met definition 1, 570 (47%) met definition 2, 364 (33%) met definition 3, 599 met definition 4 (49.1%), and 395 met definition 5 (32.4%). Regardless of the outcome (MTP activation or MT administration), the predictive ability of the app model was consistent: when predicting activation of the MTP, the area under the curve for the model was 0.694 and when predicting MT administration, the area under the curve ranged from 0.695 to 0.711. CONCLUSION: Regardless of the definition of MT used, the app model demonstrates moderate ability to predict the need for MT in an external, homogenous population. Importantly, the app allows the model to be iteratively recalibrated ("machine learning") and thus could improve its predictive capability as additional data are accrued. LEVEL OF EVIDENCE: Diagnostic test study/Prognostic study, level III.

Predicting treatment failure, death and drug resistance using a computed risk score among newly diagnosed TB patients in Tamaulipas, Mexico.

The purpose of this study was to develop a method for identifying newly diagnosed tuberculosis (TB) patients at risk for TB adverse events in Tamaulipas, Mexico. Surveillance data between 2006 and 2013 (8431 subjects) was used to develop risk scores based on predictive modelling. The final models revealed that TB patients failing their treatment regimen were more likely to have at most a primary school education, multi-drug resistance (MDR)-TB, and few to moderate bacilli on acid-fast bacilli smear. TB patients who died were more likely to be older males with MDR-TB, HIV, malnutrition, and reporting excessive alcohol use. Modified risk scores were developed with strong predictability for treatment failure and death (c-statistic 0·65 and 0·70, respectively), and moderate predictability for drug resistance (c-statistic 0·57). Among TB patients with diabetes, risk scores showed moderate predictability for death (c-statistic 0·68). Our findings suggest that in the clinical setting, the use of our risk scores for TB treatment failure or death will help identify these individuals for tailored management to prevent these adverse events. In contrast, the available variables in the TB surveillance dataset are not robust predictors of drug resistance, indicating the need for prompt testing at time of diagnosis.

The impact of primer sets on detection of the gene encoding biofilm-associated protein (Bap) in Acinetobacter baumannii: in silico and in vitro analysis.

The Acinetobacter baumannii virulence protein Bap is encoded by a large gene and contains both variable sequence and repetitive modules. To date, four primer sets targeting different regions of bap have been designed, but no study has evaluated all these primers simultaneously for detection of bap. Here, we assessed the effect of primer sets Bap I-IV, on detection of bap both in silico and in vitro. Using the primer set Bap II, all 143 tested strains yielded an amplicon corresponding to the bap gene. This primer set showed the highest sensitivity (100, 95% CI: 97·9-100%) compared to the other primer sets. This study demonstrates that primer set Bap II performs with optimal efficiency for detection of the bap gene among different strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This study investigated the effect of nucleotide variation on PCR detection of the bap gene in various Acinetobacter baumannii strains. Since bap is the target gene for many detection assays, this variation can affect the detection efficiency. Here we present a primer set Bap II with optimal detection efficiency amongst 143 different strains, as shown by in silico and in vitro evidence.

Trend of extensively drug-resistant Acinetobacter baumannii and the remaining therapeutic options: a multicenter study in Tehran, Iran over a 3-year period.

Comprehensive data on drug-resistant patterns of Acinetobacter baumannii isolates in developing countries is limited. We conducted a multihospital study to assess the rate and trend of drug-resistant phenotypes in Ac. baumannii using standardized definitions and to determine the remaining therapeutic options against resistant phenotypes. The 401 nonduplicate isolates were collected from six hospitals which are geographically distributed across Tehran, Iran over a 3-year period. Following PCR of blaOXA-51-like gene, susceptibility testing was performed against nine antimicrobial agent categories. Three hundred and ninety (97%) isolates were resistant to least two carbapenems; carbapenem-resistant Ac. baumannii. The majority of isolates (366, 91·3%) were extensively drug resistant (XDR) and the rest of the isolates were classified as multidrug resistant (26, 6·8%) and susceptible (9, 2·2%). The rate of XDR-AB slightly decreased from 93·8% in 2011 to 89·8% in 2013. A considerable decrease in resistance to doxycycline, minocycline and tigecycline was demonstrated. The XDR-AB isolates showed susceptibility to gentamicin (10·4%), tobramycin (23%), ampicilin-sulbactam (30·1%), minocycline (32·8%), tigecycline (10·7%), doxycycline (21·6%), colistin (100%) and polymixin B (100%). We demonstrated the rising trend of resistance to all antibiotic categories except tetracyclines and folate pathway inhibitors. We found that the treatment options against XDR-AB are extremely limited and each treatment alternative including even old, but safe, antibiotics might be considered. SIGNIFICANCE AND IMPACT OF THE STUDY: The high frequency of drug-resistant phenotypes including carbapenem-resistant Acinetobacter baumannii, multidrug-resistant, and extensively resistant has been demonstrated in Ac. baumannii isolates tested here. As the antibiotic resistance pattern of isolates varies in different geographical regions, this study can provide comprehensive information about the antibiotic resistance profile of Ac. baumannii isolates in Tehran. In addition, the resistance profiles could be effectively considered by clinicians to manage antibiotic therapy. This work also emphasizes on the prudent use of antibiotics and the monitoring of antibiotic susceptibility trend and rate.

Comparative in vitro activity of carbapenems against clinical isolates of Acinetobacter baumannii.

AIMS: The aim of this multi-hospital study was to assess the in vitro activity of doripenem and its comparators, imipenem and meropenem, using the new CLSI breakpoints against a large population of a frequently isolated nosocomial pathogen, Acinetobacter baumannii. METHODS AND RESULTS: During a 2-year period, four referral or tertiary hospitals submitted 400 isolates of Ac. baumannii for susceptibility testing using imipenem, meropenem and doripenem via disc diffusion and E-test methods. A subset of 390 isolates was resistant to all three tested carbapenems. Doripenem and meropenem (MIC50 , 32 µg ml(-1) ) had comparable activity, albeit doripenem's activity was greater than imipenem (MIC50 , >32 µg ml(-1) ). A significantly higher proportion of the isolates were inhibited by doripenem than by imipenem at MIC values of 12, 16, 24 and 32 µg ml(-1) (P < 0·05). The cumulative percentage of imipenem MICs was lower compared to its comparators. The comparison of resistance rate to imipenem and meropenem based on old and new breakpoints showed <1% difference. The overall agreement between the two susceptibility testing methods was ≥95%. CONCLUSION: Doripenem has a slightly greater in vitro activity than imipenem in terms of zone breakpoints and MIC values, but its activity is comparable to meropenem. SIGNIFICANCE AND IMPACT OF THE STUDY: Doripenem should be considered as a therapeutic option for monotherapy or combination therapy, particularly when the therapeutic options are limited.

Candida infection in the intensive care unit: A study of antifungal susceptibility pattern of Candida species in Milad hospital, Tehran, Iran.

OBJECTIVE: The occurrence of Candida infections has improved during the past two decades as a result of increase in the number of immunocompromised patients. In this study the antifungal susceptibility patterns of Candida species isolated from sterile body sites of patients admitted in Milad Intensive Care Unit (ICU) during 6 months were determined. METHODS: Candidal isolates were obtained from 50 patients admitted in Milad ICUs from April to September 2013. Identification of the isolates was performed by using morphological and polymerase chain reaction assay. Resistance to the antifungal agents containing caspofungin, posoconazole, voriconazole and amphotericin B was determined using E-test method. RESULTS: Out of 67 Candida isolates 47.8% were Candida glabrata, 28.3% were C. albicans, 7.5% were C. tropicalis, 7% were C. guilliermondii, 3% were C. krusei and 2% were C. dubliniensis. C. glabrata was the least susceptible species, with 9.4% of the isolates resistant to amphotericin B and 6.3% resistant to posoconazole and voriconazole. No resistance to caspofungin was observed among C. glabrata isolates. One of the C. krusei isolates was resistant to amphotericin B while no resistance to voriconazole, caspofungin and posoconazole was detected among C. krusei strains. Increase in the prevalence of antifungal-resistant non-C. albicans species in recent years has become a problematic event amongst clinicians caring for ICU patients. C. glabrata as the most common species isolated from ICU patients in this study indicated higher levels of antifungal resistance in comparison with other species. This observation accentuates the importance of managing preventive treatments to avoid development of resistance to the current antifungal drugs.

Patient refusal of thrombolytic therapy for suspected acute ischemic stroke.

OBJECTIVE: To determine factors associated with patients refusing IV t-PA for suspected acute ischemic stroke (AIS), and to compare the outcomes of patients who refused t-PA (RT) with those treated with t-PA. METHODS: Patients who were treated with and refused t-PA at our stroke center were identified retrospectively. Demographics, clinical presentation, and outcome measures were collected and compared. Clinical outcome was defined as excellent (mRS: 0-1), good (mRS: 0-2), and poor (mRS: 3-6). RESULTS: Over 7·5 years, 30 (4·2%) patients refused t-PA. There were no demographic differences between the treated and RT groups. The rate of RT decreased over time (OR 0·63, 95% CI 0·50-0·79). Factors associated with refusal included a later symptom onset to emergency department presentation time (OR 1·02, 95% CI 1·01-1·03), lower NIHSS (OR 1·11, 95% CI 1·03-1·18), a higher proportion of stroke mimics (OR 17·61, 95% CI 6·20-50·02) and shorter hospital stay (OR 1·32, 95% CI 1·09-1·61). Among patients who were subsequently diagnosed with ischemic stroke, only length of stay was significantly shorter for refusal patients (OR 1·37, 95% CI 1·06-1·78). After controlling for mild strokes and stroke mimics, clinical outcome was not different between the groups (OR 1·61, 95% CI 0·69-3·73). CONCLUSION: The incidence of patients refusing t-PA has decreased over time, yet it may be a cause for t-PA under-utilization. Patients with milder symptoms were more likely to refuse t-PA. Refusal patients presented later to the hospital and had shorter hospital stays. One out of six refusal patients (16·6%) had a stroke mimic.

The Effect of Ignoring Statistical Interactions in Regression Analyses Conducted in Epidemiologic Studies: An Example with Survival Analysis Using Cox Proportional Hazards Regression Model.

OBJECTIVE: To demonstrate the adverse impact of ignoring statistical interactions in regression models used in epidemiologic studies. STUDY DESIGN AND SETTING: Based on different scenarios that involved known values for coefficient of the interaction term in Cox regression models we generated 1000 samples of size 600 each. The simulated samples and a real life data set from the Cameron County Hispanic Cohort were used to evaluate the effect of ignoring statistical interactions in these models. RESULTS: Compared to correctly specified Cox regression models with interaction terms, misspecified models without interaction terms resulted in up to 8.95 fold bias in estimated regression coefficients. Whereas when data were generated from a perfect additive Cox proportional hazards regression model the inclusion of the interaction between the two covariates resulted in only 2% estimated bias in main effect regression coefficients estimates, but did not alter the main findings of no significant interactions. CONCLUSIONS: When the effects are synergic, the failure to account for an interaction effect could lead to bias and misinterpretation of the results, and in some instances to incorrect policy decisions. Best practices in regression analysis must include identification of interactions, including for analysis of data from epidemiologic studies.

Molecular identification of Pseudomonas aeruginosa recovered from cystic fibrosis patients.

OBJECTIVE: Precise identification of various morphotypes of Pseduomonas aeruginosa which developed during cystic fibrosis (CF) is of prime importance. We aimed to identify the isolates of P. aeruginosa recovered from CF patients at the genus and species level through primers targeting oprI and oprL genes via PCR. METHODS: Sputum samples or throat swabs were taken from 100 CF patients and plated on cetrimide agar. All suspected colonies were primarily screened for P. aeruginosa by a combination of phenotypic tests. Molecular identification of colonies was performed using specific primers for oprI and oprL genes. RESULTS: Based on phenotypic tests, P. aeruginosa isolates were recovered from 40% of CF patients. Forty isolates yielded amplicon of oprI gene using genus-specific primers confirming the identity of fluorescent pseudomonads. However, 37 of 40 isolates yielded amplicon of oprL gene using species-specific primers, verifying the identity of P. aeruginosa. CONCLUSION: This study showed that the species-specific PCR targeting oprL gene can be used as accurate test for identification of highly adaptable P. aeruginosa in CF patients. This procedure may provide a simple and reliable method for identification of various morphotypes.

Intraperitoneal inoculation of Haemophilus influenzae local isolates in BALB/c mice model in the presence and absence of virulence enhancement agents.

PURPOSE: Haemophilus influenzae (Hi), predominantly type b accounts for approximately 4% of cases of community-acquired and nosocomial meningitis, in adults. The objective of this study was to evaluate the pathogenicity of local Hi isolates (type b, f and non-typable) in BALB/c mice in the presence of virulence enhancement agents. MATERIALS AND METHODS: Three different concentrations of the Hi isolates were inoculated intraperitoneally in BALB/c mice in the presence of 2% hemoglobin and 4% mucin as virulence enhancing agents (VEA). The ability of the isolates to produce bacteremia, the percent survival and lethal dose (LD50) were recorded in different challenge groups. RESULTS: The 3 Haemophilus influenzae type b (Hib) isolates used in study were able to show virulence in BALB/c mice model only in the presence of VEA and their LD50 decreased significantly when 2% hemoglobin and 4% mucin were used. All survived animals showed bacteremia within 4 h of inoculation which was cleared within 18 h. Significant differences (P<0.01) in the virulence and survival percentage of Hib challenge groups were observed based on their dose of inoculation and VEA. None of the isolates were able to induce infection in the absence of VEA. Non-type b isolates failed to produce disease in the mice models even at the highest inoculated dose (108 cfu) and in the presence of VEA. CONCLUSIONS: BALB/c mice appeared suitable for evaluating the virulence of Hib strains, and 2% hemoglobin with 4% mucin an appropriate concentration for inducing infection in this animal model.

Mortality causes in children 1-59 months in iran.

BACKGROUND: Mortality rate indicator for children under 5 years old is one of the important indicators in countries' development. Identifying the most common causes of mortality is one of the most important attempts to reduce mortality in children less than 5 years. The purpose of this study was to identify distribution of the mortality causes in Iranian children less than 5 years. METHODS: This cross-sectional study has been carried out based on the results of data from the Child Mortality Surveillance System since 2007 to 2008. To determine the causes of death questionnaires have been designed which include personal data of the deceased child, medical history, and information on procedures at the time of hospitalization or death. RESULTS: Of 5926 deaths on children under 5 years which the questionnaires were filled out, 63.2% were postneonatal deaths (1-11 month). Totally 60% of mortalities occurred in the rural areas and 52% of them had been among boys. The most common causes of mortality were the congenital and chromosomal abnormalities with 23.4%. The most incidences among diseases were respiratory system diseases. CONCLUSIONS: Carrying out more epidemiologic studies, providing health programs to control and prevent diseases with high incidences and delivering more specialized health facilities and services could be the proper strategies to reduce under 5 mortality rates in Iran.

KPC-producer gram negative bacteria among burned infants in Motahari Hospital, Tehran: first report from Iran.

To the best of our knowledge, this is the first report of Klebsiella, Acinetobacter and Pseudomonas-producing Klebsiella pneumoniae Carbapenemase (KPC) among burn infants in Iran. The objective of this study was to determine the phenotypic detection of these KPC among isolated Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella spp. A cross-sectional study was performed (February to September 2011) at a tertiary burn hospital in Tehran, Iran. Sixty-four strains were isolated from 20 patients. Strain and genus of isolates were confirmed, antibiotic susceptibility testing was implemented, and KPC determined by Modified Hodge Test. Fifteen of 36 strains (six Pseudomonas aeruginosa, six Acinetobacter baumannii, and three Klebsiella pneumoniae) were resistant to imipenem. Ten strains of 36 Gram negative isolates were resistant to all tested antibiotics except for Colistin. Thirteen of 15 resistant imipenem strains were confirmed as KPC-producer bacteria that isolated from nine patients. Six of 36 isolated strains were extended-spectrum ß-lactamase (ESBL)-producing bacteria, of which four strains were both KPC and ESBL. A high percentage of multidrug resistant (MDR) strains in our centre with positive KPC have created a major challenge in terms of mortality and morbidity. The findings of this study highlight the importance of implementing an effective infection control strategy to prevent and decrease the prevalence of KPC-producing organisms.

Bayesian adaptive trial design in acute heart failure syndromes: moving beyond the mega trial.

Over the last 2 decades, early treatment for patients presenting with acute heart failure syndromes (AHFS) has changed very little. Despite strikingly different underlying disease pathophysiology, presenting signs and symptoms, and precipitants of AHFS, most patients are treated in a homogeneous manner with intravenous loop diuretics. Inhospital studies of new therapies have produced disappointingly neutral results at best. Patients continue to be enrolled in trials long after initial therapy, at a time when vital signs have improved, symptoms have changed, and initiating pathophysiologic processes, such as myocardial and renal injury, have already begun. The "one-size-fits-all" approach to inhospital AHFS trials have been recognized as one potential contributor to the disappointing trial results seen to date. Studies designed to tailor the therapeutic approach to ascertain which treatment modalities are most effective depending on patient phenotypes have not been previously conducted in AHFS because this objective is not traditional in clinical trial design. Utilizing Bayesian adaptive designs in trials of early AHFS provides an opportunity to personalize therapy within the constraints of clinical research. Bayesian adaptive design is increasingly recognized as an efficient method for obtaining valid clinical trial results. At its core, this approach uses existing information at the time of trial initiation, combined with data accumulating during the trial, to identify treatments most beneficial for specific patient subgroups. Based on accumulating evidence, the study then "adapts" its focus to critical differences between treatments within patient subgroups. Bayesian adaptive design is ideally suited for investigating complex, heterogeneous conditions such as AHFS and affords investigators the ability to study multiple treatment approaches and therapies in multiple patient phenotypes within a single trial, while maintaining a reasonable overall sample size. Identifying specific treatment approaches that safely improve symptoms and facilitate early discharge in patients who traditionally are admitted, often for prolonged periods of time, are necessary if we aim to reverse the disappointing trend in clinical trial results. In this study, AHFS clinical researchers and biostatisticians with expertise and experience in designing "personalized medicine" trials describe the development of a Bayesian adaptive design for an emergency department-based AHFS trial.