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Hypertension is an immense challenge in public health. As one of the most prevalent medical conditions worldwide, it is a major cause of premature death. At present, the detection, diagnosis and monitoring of hypertension are subject to several limitations. In this review, we conducted a literature search on blood pressure measurement using only a smartphone, which has the potential to overcome current limitations and thus pave the way for long-term ambulatory blood pressure monitoring on a large scale. Among the 333 articles identified, we included 25 relevant articles over the past decade (November 2011–November 2021) and analyzed the described approaches to the types of underlying data recorded with smartphone sensors, the signal processing techniques applied to construct the desired signals, the features extracted from the constructed signals, and the algorithms used to estimate blood pressure. In addition, we analyzed the validation of the proposed methods against reference blood pressure measurements. We further examined and compared the effectiveness of the proposed approaches. Among the 25 articles, 23 propose an approach that requires direct contact between the sensor and the subject and two articles propose a contactless approach based on facial videos. The sample sizes in the identified articles range from three to 3000 subjects, where 8 articles used sample sizes of 85 or more subjects. Furthermore, 10 articles include hypertensive subjects in their participant pools. The methodologies applied for the evaluation of blood pressure measurement accuracy vary considerably among the analyzed articles. There is no consistency regarding the methods for blood pressure data collection and the reference blood pressure measurement and validation. Moreover, no established protocol is currently available for the validation of blood pressure measuring technologies using only a smartphone. We conclude the review with a discussion of the results and with recommendations for future research on the topic. [ABSTRACT FROM AUTHOR]

Background: Recent scientific work proved that knowledge about body composition beyond the body mass index is essential. Both adipose tissue and muscular status are determining risk factors of morbidity and mortality. Analysis of single cross-sectional computed tomography (CT) images, acquired during routine care only to prevent additional radiation exposure, provide a detailed insight into the body composition of chronically and critically ill patients. Methods: This retrospective study included 490 trauma patients of whom a whole-body multiple detector CT scan was acquired at admission. From a single cross-sectional CT, we compared eight diametric and planimetric techniques for the assessment of core muscle mass as well as visceral and subcutaneous adipose tissue. Furthermore, we derived formulas for converting the measurement results of various techniques into each other. Results: For intra- and interobserver reliability, we obtained intraclass correlation coefficients (ICCs) ranging from 0.947 to 0.997 (intraobserver reliability) and from 0.850 to 0.998 (interobserver reliability) for planimetric measurements. Diametric techniques conferred lower ICCs with 0.851–0.995 and 0.833–0.971, respectively. Overall, area-based measurements of abdominal adipose tissue yielded highly correlated results with diametric measures of obesity. For example, the Pearson correlation of visceral adipose tissue and sagittal abdominal diameter was 0.87 for male and 0.82 for female patients. Planimetric and diametric muscle measurements correlated best for lean psoas area and bilateral diametric measurement of the psoas with a Pearson correlation of 0.90 and 0.93 for male and female patients, respectively. Conclusion: Planimetric measurements should remain the gold standard to describe fat and muscle compartments. Diametric measurements could however serve as a surrogate if planimetric techniques are not readily available or feasible as for example in large registries. [ABSTRACT FROM AUTHOR]

Background: Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application.Methods: A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCRCG). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets (100%T>MIC, 50%T>4×MIC) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCRCG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non-attainment.Results: Large inter- and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100%T>MIC was merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50%T>4×MIC. A hyperbolic relationship between CLCRCG (25-255 ml/minute) and meropenem serum concentrations at the end of the dosing interval (C8h) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was identified as a risk factor for target non-attainment (for MIC 8 mg/L, additionally, moderate renal impairment).Conclusions: The investigated standard meropenem dosing regimen appeared to result in insufficient meropenem exposure in a considerable fraction of critically ill patients. An easy- and free-to-use tool (the MeroRisk Calculator) for assessing the risk of target non-attainment for a given renal function and MIC value was developed.Trial Registration: Clinicaltrials.gov, NCT01793012 . Registered on 24 January 2013. [ABSTRACT FROM AUTHOR]

Objectives: Insufficient linezolid levels, which are associated with a poorer outcome, are often observed in ICU patients who receive standard dosing. Although strategies to overcome these insufficient levels have been discussed, appropriate alternative dosing regimens remain to be identified.Methods: Various infusion regimens (1200-3600 mg/day; q6h, q8h, q12h and continuous) were simulated in 67 000 ICU patients. The probability of attaining pharmacodynamic targets ( T >MIC ≥85%, AUC/MIC ≥100, cumulative fraction of response for Staphylococcus aureus and Enterococcus spp., PTA for an MIC of 0.5-4 mg/L) as well as the avoidance of toxic concentrations and concentrations constantly below the MIC (lack of antibiotic effect) or inside a mutant selection window (resistance development) were evaluated.Results: Best target attainment according to T >MIC was observed for continuous infusions, followed by q6h, q8h and q12h. A substantially reduced target attainment was observed in patients with acute respiratory distress syndrome (ARDS). In patients without ARDS, 1200 mg/day was insufficient irrespective of the regimen, while a dose of 1400 mg/day administered q6h or by continuous infusions provided an acceptable target attainment (e.g. cumulative fraction of response with regards to T >MIC  ≥93%). Higher rates of potentially toxic trough concentrations (28% versus 12%) and concentrations constantly inside the mutant selection window (15% versus <0.1%) were observed with continuous infusions compared with q6h infusions (1400 mg/day, patients without ARDS).Conclusions: Irrespective of the regimen, 1200 mg/day linezolid might be insufficient for the treatment of ICU patients. Patients without ARDS might particularly benefit from q6h infusions with increased daily doses (e.g. 1400 mg/day). [ABSTRACT FROM AUTHOR]

Purpose: Postoperative complications may have not only immediate but also long-term effects on the outcomes. Here, we analyzed the effect of postoperative complications requiring a reoperation (grade 3b) within the first 30 days on patients' and graft survival following liver transplantation. Methods: Graft and patient survival in relation to donor and recipient variables and the need of reoperation for complications of 277 consecutive liver transplants performed from January 2007 to December 2012 were analyzed. Results: Two hundred seventy-seven liver transplants were performed in 252 patients. Overall patient and graft survival at 1, 2, and 3 years were significantly reduced in patients requiring a reoperation. The labMELD score was significantly elevated ( p = 0.04) and cold ischemia time was prolonged ( p = 0.03) in recipients undergoing reoperations. Kaplan-Meier curves indicate that complications impact the outcome primarily within the first 3 months after transplantation. In multivariate analyses, the actual need of reoperation ( p < 0.001), the labMELD score ( p = 0.05), cold ischemia time ( p = 0.02), and the need for hemodialysis pre-transplant ( p = 0.05) were the only variables which correlated with the overall survival. Conclusion: Postoperative complications resulting in reoperations have a significant impact on the outcome primarily in the early phase after liver transplantation. Successful management of postoperative complications is key to every successful liver transplant program. [ABSTRACT FROM AUTHOR]

Background: Although therapeutic drug monitoring (TDM) for antibiotics in critically ill patients is recommended by expert panels, no commercial tests are available for most antibiotics. Therefore, we previously developed a multianalyte method for the quantification of piperacillin, tazobactam, cefepime, meropenem, ciprofloxacin and linezolid in serum. However, limited stability data were available, and the relevant studies did not address the coefficients of variation of the methods applied, which may be important for verifying the storage dependency of the observed effects. Here we aimed to evaluate the storage effects of antibiotics by applying a novel evaluation protocol. Methods: Serum-based test samples were aliquoted and stored at room temperature, 4 °C, -20 °C or -80 °C for up to 180 days. Using an innovative evaluation protocol (considering the coefficient of variation, p-value, and criterion of monotony of observed changes), we assessed whether relevant changes (defined as ≥ 15% in comparison with baseline) were storage dependent (defined as substantial changes). Results: Storage at -80 °C for up to 180 days did not lead to substantial changes for any analyte. In contrast, storage at -20 °C induced substantial decreases after ≥ 7 days for piperacillin, tazobactam, cefepime and meropenem; after 90 days at -20 °C, only ≤ 23% of the initial concentrations were found for these parameters. No substantial changes were observed for linezolid and ciprofloxacin at any storage condition. All of the observed substantial changes were monotonic decreases. Conclusions: We recommend a storage temperature of -80 °C for β-lactam antibiotics. The applied evaluation protocol yielded conclusive results and may be generally useful for stability studies. [ABSTRACT FROM AUTHOR]

Background: Recent studies have demonstrated highly variable blood concentrations of piperacillin, tazobactam, cefepime, meropenem, ciprofloxacin and linezolid in critically ill patients with a high incidence of sub-therapeutic levels. Consequently, therapeutic drug monitoring (TDM) of these antibiotics has to be considered, requiring robust and reliable routine analytical methods. The aim of the present work was to develop and validate a multi-analyte ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous quantification of the above mentioned antibiotics. Methods: Sample preparation included a manual protein precipitation step followed by two-dimensional ultra high performance liquid chromatography (2D-UHPLC). Corresponding stable isotope-labeled substances were used as internal standards for all of the analytes, with the exception of tazobactam. The injected sample volume was 7 μL. The run time was 5.0 min. Results: Inaccuracy was ≤8% and imprecision coefficient of variation (CV) was <9% for all analytes. Only minor matrix effects and negligible carry-over was observed. The method was found to be robust during the validation period. Conclusions: We were able to develop a reliable 2D-UHPLC-MS/MS method addressing analytes with highly heterogeneous physico-chemical properties. The novel assay may be an efficient tool for an optimized process workflow in clinical laboratories for important antibiotics in regards to TDM. [ABSTRACT FROM AUTHOR]

Patients with terminal lung failure may be bridged to lung transplantation ( LTX) by extracorporeal membrane oxygenation ( ECMO). With the present shortage of donor organs and the high level of invasiveness of ECMO treatment, appropriate selection criteria for bridge to transplant need to be defined. We report retrospective data from 26 patients on ECMO listed for LTX. Seven patients were successfully transplanted ( LTX-s). Six patients survived until transplantation, but died intra- or post-operatively ( LTX-ns). Thirteen patients died before transplantation (Fail). There was no difference between LTX-s and the 19 overall non-survivors ( NS) prior to ECMO initiation with regard to demographic data or ventilator parameters except for higher Pa O2/ Fi O2 in the LTX-s. Time on ECMO pre- LTX did not differ in the LTX-s and LTX-ns groups. SOFA score was lower in LTX-s when compared to LTX-ns before ECMO (p = 0.0155), during bridging (p = 0.028), and right before transplantation (p = 0.0038). Maximal bilirubin during bridging and bilirubin prior to transplantation was markedly elevated in the LTX-ns group [4.2 (2.4-4.7) vs. 1.1 (0.8-2.0) mg/dL; p = 0.0266 and 1.6 (1.2-3.0) vs. 0.5 (0.5-0.5) mg/dL; p = 0.0047). Bridging to LTX is a challenging but viable option for selected patients. Special consideration should be given to hepatic function. [ABSTRACT FROM AUTHOR]

Huppmann P, Neurohr C, Leuschner S, Leuchte H, Baumgartner R, Zimmermann G, Meis T, von Wulffen W, Überfuhr P, Hatz R, Frey L, Behr J for the Munich Lung Transplant Group (MLTG). The Munich-LTX-Score: predictor for survival after lung transplantation. Clin Transplant 2012: 26: 173-183. © 2011 John Wiley & Sons A/S. Abstract: Background: The purpose of this study was to create a prognostic score calculated one yr after LTX based on post-transplant factors inclusive of donor and recipient characteristics that could be used to predict long-term survival in patients after lung transplantation (LTX). Methods: Uni- and multivariate analysis in 206 consecutive LTX patients identified independent risk factors for post-transplant mortality and onset of bronchiolitis obliterans syndrome. Munich-LTX-Score is devised by summing up each identified risk factor. Results: Multivariate analyses revealed acute rejection, lymphocytic bronchiolitis, donor age ≥55 yr, and HLA-A ≥ 2-/DR ≥ 2 mismatch and single LTX to be independent negative predictors for long-term survival (p < 0.05). Munich-LTX-Score identified three discrete groups: low-, moderate-, and high risk. The actuarial five-yr survival after score calculation one yr after LTX of the entire cohort was 58%, compared with 91% in low-, 54% in moderate-, and 0% in the high-risk group (p < 0.001). Conclusion: Within our cohort of patients calculation of the Munich-LTX-Score, consisting of donor-, recipient-, and post-transplant characteristics, one yr after LTX allowed to predict long-term survival of lung transplant recipients. After prospective validation, this score could identify patients who may benefit from intensified surveillance after LTX. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a frequent indication for lung transplantation (LTX) with pulmonary hypertension (PH) negatively affecting outcome. The optimal procedure type remains a debated topic. The aim of this study was to evaluate the impact of pretransplant PH in IPF patients. Single LTX (SLTX, n = 46) was the standard procedure type. Double LTX (DLTX, n = 30) was only performed in cases of relevant PH or additional suppurative lung disease. There was no significant difference for pretransplant clinical parameters. Preoperative mean pulmonary arterial pressure was significantly higher in DLTX recipients (22.7 ± 0.8 mmHg vs. 35.9 ± 1.8 mmHg, P < 0.001). After transplantation, 6-min-walk distance and BEST-FEV1 were significantly higher for DLTX patients (6-MWD: 410 ± 25 m vs. 498 ± 23 m, P = 0.02; BEST-FEV1: 71.2 ± 3.0 (% pred) vs. 86.2 ± 4.2 (% pred), P = 0.004). Double LTX recipients demonstrated a significantly better 1-year-, overall- and Bronchiolitis obliterans Syndrome (BOS)-free survival ( P < 0.05). Cox regression analysis confirmed SLTX to be a significant predictor for death and BOS. Single LTX offers acceptable survival rates for IPF patients. Double LTX provides a significant benefit in selected recipients. Our data warrant further trials of SLTX versus DLTX stratifying for potential confounders including PH. [ABSTRACT FROM AUTHOR]

The optimal maintenance therapy after lung transplantation remains to be established. The aim of this study was to analyse the impact of tacrolimus and mycophenolate mofetil (MMF) as first line immunosuppression on long-term survival and Bronchiolitis Obliterans Syndrome (BOS). From January 1996 through December 2006, all 155 recipients receiving tacrolimus and MMF as maintenance immunosuppression were included in this study. Tacrolimus and MMF was discontinued in 36 patients (23.2%). The overall survival rates were 91.6% at 6 months, 86.4% at 1 year, 74.9% at 3 years, 60.3% at 5 years and 32.4% at 10 years. The overall freedom from acute rejection was 74.6%, 63.2% and 59.4% at 1, 3, and 5 years respectively. The overall BOS-free survival was 95.6% at 1 year, 88.4% at 3 years, 69.5% at 5 years and 30.5% at 10 years. The development of BOS ≥ 1 was associated with a significantly increased risk of death and reduced long-term survival. The combination of tacrolimus and MMF offers safe and reliable maintenance immunosuppression after lung transplantation. However, substantial improvements of long-term survival and freedom from BOS might only be achieved by a change in organ allocation policies and patient management beyond differential immunosuppressive protocols. [ABSTRACT FROM AUTHOR]

Acute rejection and diffuse alveolar damage are major problems during the early time after transplantation. Against this background, lung biopsies after allogeneic lung transplantation were studied using immunohistochemistry. Biopsies with acute rejection, diffuse alveolar damage and morphological inconspicuous biopsies were chosen. The objectives of this study were to ascertain: (a) if and how CD4 and CD8 T cells contribute to allograft rejection and diffuse alveolar damage, (b) whether there is a correlation of the chemoattractant regulated on activation normal T cells (RANTES) with the mononuclear infiltrate and (c) whether perforin/granzyme and Fas/FasL pathways contribute to lung injury after lung transplantation. Our results show that CD4(+) and CD8(+) T cells were increased in biopsies with acute rejection and, to a minor extent, also in biopsies with diffuse alveolar damage due to reperfusion injury. RANTES expression of T cells was increased in biopsies with acute rejection. Perforin seemed to have a dual role in the alloimmune response. In one regard, it had a cytolytic function in the acute rejection process, and, in contrast, it may be responsible for downregulating both CD4- and CD8-mediated alloimmune responses. The FasL/Fas pathway is not only important for induction of apoptosis during rejection but is also a mechanism of lung injury in the development of diffuse alveolar damage. [ABSTRACT FROM AUTHOR]

The article presents a case study of a patient with septic shock and multiple organ failure, characterized by excessive inflammatory responses. An initial laparotomy showed an ischaemic bowel with peritonitis, and the patient was given intravenous meropenem and segmental resection of the jejunum and colon. The patient was given with linezolid and meropenem. The case demonstrated the effect of cytokine adsorber treatment on antibiotic concentrations.

The article discusses a mentoring program for first-year law students, inaugurated in the 2012-2013 academic year at the Freie Universität (Free University) of Berlin, Germany. Information is provided about the qualifications and selection of mentors, the effect of a shortened time to a high school degree and the abolition of compulsory military service in Germany on the life experiences and attitudes of first-year students, and introductory courses in law.

Background: The allocation of any scarce health care resource, especially a lifesaving resource, can create profound ethical and legal challenges. Liver transplant allocation currently is based upon urgency, a sickest-first approach, and does not utilize capacity to benefit. While urgency can be described reasonably well with the MELD system, benefit encompasses multiple dimensions of patients' well-being. Currently, the balance between both principles is ill-defined.Methods: This survey with 502 participants examines how urgency and benefit are weighted by different stakeholders (medical staff, patients on the liver transplant list or already transplanted, medical students and non-medical university staff and students).Results: Liver transplant patients favored the sickest-first allocation, although all other groups tended to favor benefit. Criteria of a successful transplantation were a minimum survival of at least 1 year and recovery of functional status to being ambulatory and capable of all self-care (ECOG 2). An individual delisting decision was accepted when the 1-year survival probability would fall below 50%. Benefit was found to be a critical variable that may also trigger the willingness to donate organs.Conclusions: The strong interest of stakeholder for successful liver transplants is inadequately translated into current allocation rules. [ABSTRACT FROM AUTHOR]

Background: Piperacillin levels after standard dosing have been shown frequently to be subtherapeutic, especially when renal clearance was augmented. Here, we aimed to determine if piperacillin was in its therapeutic range in a typically heterogeneous intensive care unit patient group, and also to describe target attainment dependent on daily dosage, creatinine clearance, and renal replacement therapy (RRT).Methods: Sixty patients with severe infections were included in this monocentric prospective observational study. Patients received 4.5 g of piperacillin-tazobactam two to three times daily by intermittent infusion depending on renal function according to clinical guidelines. Over 4 days, multiple serum samples (median per patient, 29; in total, 1627) were obtained to determine total piperacillin concentrations using ultra-high-performance liquid chromatography/tandem mass spectrometry.Results: A high heterogeneity of patient characteristics was observed (e.g., on day 1: creatinine clearance 2-233 mL/min and ten patients on RRT). Piperacillin trough levels showed inter-individual variation from 123 to >1785-fold on different study days. Each day, approximately 50% and 60% of the patients had piperacillin levels below the target ranges 1 and 2, respectively [defined for the calculated unbound piperacillin fraction according to the literature as 100% time above MIC (100%fT > MIC) (target range 1) and ≥ 50%fT > 4 × MIC (target range 2); MIC = 16 mg/L]. Whereas only the minority of patients who received piperacillin-tazobactam three times daily (TID) reached target 1 (38% on day 1), most patients who received piperacillin-tazobactam only twice daily (BID) because of severely impaired renal function reached this target (100% on day 1). Patients with RRT had significant higher percentages of fT > MIC. Zero percent, 55% and 100% of patients without RRT who received antibiotics TID reached target 1 when creatinine clearance was > 65 mL/min, 30-65 mL/min and < 30 mL/min, respectively. In patients with causative strains only sensitive to piperacillin-tazobactam of all antibiotics given to the patient, piperacillin levels negatively correlated with CRP concentrations of day 4 (p < 0.05).Conclusions: A dosage of 4.5 g piperacillin-tazobactam TID seems to be frequently insufficient in critically ill patients, and also in patients where renal function is mildly to moderately impaired. For these patients, prescription of 4.5 g piperacillin-tazobactam four times daily could be considered.Trial Registration: Clinicaltrials.gov NCT01793012. Registered 24 January 2013. [ABSTRACT FROM AUTHOR]

Introduction: Severe infections in intensive care patients show high morbidity and mortality rates. Linezolid is an antimicrobial drug frequently used in critically ill patients. Recent data indicates that there might be high variability of linezolid serum concentrations in intensive care patients receiving standard doses. This study was aimed to evaluate whether standard dosing of linezolid leads to therapeutic serum concentrations in critically ill patients.Methods: In this prospective observational study, 30 critically ill adult patients with suspected infections received standard dosing of 600 mg linezolid intravenously twice a day. Over 4 days, multiple serum samples were obtained from each patient, in order to determine the linezolid concentrations by liquid chromatography tandem mass spectrometry.Results: A high variability of serum linezolid concentrations was observed (range of area under the linezolid concentration time curve over 24 hours (AUC24) 50.1 to 453.9 mg/L, median 143.3 mg*h/L; range of trough concentrations (Cmin) < 0.13 to 14.49 mg/L, median 2.06 mg/L). Furthermore, potentially subtherapeutic linezolid concentrations over 24 hours and at single time points (defined according to the literature as AUC24 < 200 mg*h/L and Cmin < 2 mg/L) were observed for 63% and 50% of the patients, respectively. Finally, potentially toxic levels (defined as AUC24 > 400 mg*h/L and Cmin > 10 mg/L) were observed for 7 of the patients.Conclusions: A high variability of linezolid serum concentrations with a substantial percentage of potentially subtherapeutic levels was observed in intensive care patients. The findings suggest that therapeutic drug monitoring of linezolid might be helpful for adequate dosing of linezolid in critically ill patients.Trial Registration: Clinicaltrials.gov NCT01793012. Registered 24 January 2013. [ABSTRACT FROM AUTHOR]