Acute kidney injury predicts mortality in very elderly critically-ill patients.

BACKGROUND: The increasing admissions of very elderly patients to intensive care units (ICUs) over recent decades highlight a growing need for understanding acute kidney injury (AKI) in this population. Although these individuals are potentially at high risk for AKI and adverse outcomes, data on AKI in this population is scarce. This study investigates the AKI incidence and outcomes of critically-ill patients aging at least 90 years. METHODS: This retrospective cohort study conducted at the Department of Intensive Care Medicine, University Medical Centre Hamburg-Eppendorf, Germany (2008-2020), investigates AKI incidence and outcomes between 2008 and 2020 in critically-ill patients aged ≥ 90 years. AKI was defined according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria using creatinine dynamics and/or urine output. Primary endpoint was overall mortality after 1 year. Secondary endpoints were in-hospital mortality, length of ICU and hospital stay. RESULTS: During the study period 92,958 critically-ill patients were treated and 1108 were ≥ 90 years. Of these, 1054 patients had available creatinine values and were included in the present study. AKI occurred in 24.4%, mostly classified as mild (17.5%). AKI was independently associated with a significant increase in overall mortality (HR 1.21, 95 %-CI: 1.01-1.46), in-hospital mortality (OR 2, 1.41-2.85), length of ICU (+2.8 days, 2.3-3.3) and hospital stay (+2.3 days, 0.9-3.7). Severity escalated these effects, but even mild AKI showed significance. Introducing urine-based criteria increased incidence but compromised mortality prediction. CONCLUSIONS: AKI is a frequent complication in very elderly critically-ill patients. Occurrence of AKI at any stage was associated with increased mortality. Predictive ability applied to AKI defined by creatinine but not urine output. Careful attention of creatinine dynamics is essential in very elderly ICU-patients.

Evolution of Clinical Characteristics and Outcomes of Critically Ill Patients 90 Years Old or Older Over a 12-Year Period: A Retrospective Cohort Study.

OBJECTIVES: The global population is aging, and the proportion of very elderly patients 90 years old or older in the ICU is expected to increase. The changes in the comorbidities and outcomes of very elderly patients hospitalized in the ICU that have occurred over time are unknown. DESIGN: Retrospective observational cohort study. SETTING: ICUs at a single academic hospital in Germany. PATIENTS: Ninety years old or older and admitted to the ICU between January 1, 2008, and April 30, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 92,958 critically ill patients, 1,108 were 90 years old or older. The study period was divided into two halves: January 1, 2008-August 30, 2013, and September 1, 2013-April 30, 2019. The number of patients 90 years old or older increased from the first period ( n = 391; 0.90% of total admissions) to the second period ( n = 717; 1.44%). The patients' demographic characteristics were similar between the both time periods. The median Charlson Comorbidity Index was higher during the first period (1 [interquartile range, 1-3]) than compared with the second time period (1 [0-2]; p = 0.052). The Simplified Acute Physiology Score (SAPS) II was higher during the first time period (38 [29-49]) than during the second period (35 [27-45]; p = 0.005). Vasopressor therapy was necessary in 40% ( n = 158) and 43% ( n = 310) of patients in each time period, respectively ( p = 0.363). Invasive mechanical ventilation was administered in 37% ( n = 146) and 34% ( n = 243) of patients in each time period, respectively ( p = 0.250). The median length of the ICU stay was significantly lower in the first time period than in the second time period (1.4 vs. 1.7 d; p = 0.002). The ICU (18% vs. 18%; p = 0.861) and hospital (31% vs. 29%; p = 0.395) mortality rates were comparable between the two groups. The 1-year mortality was significantly lower during the second time period than during the first time period (61% vs. 56%; p = 0.029). Cox regression analysis revealed that the SAPS II, medical cause of admission, mechanical ventilation requirement, and vasopressor use were associated with 1-year mortality. CONCLUSIONS: The number of patients 90 years old or older who were treated in the ICU has increased in recent years. While the patients' clinical characteristics and short-term outcomes have not changed significantly, the long-term mortality of these patients has improved in recent years.

Outcomes in very elderly ICU patients surgically treated for proximal femur fractures.

Proximal femur fractures (PFF) are a common injury in elderly patients that significantly impact mobility and daily living activities. Mortality rates in this population are also high, making effective treatment essential. Recent advances in intensive and geriatric care have enabled complex surgical interventions that were previously not feasible. However, there is a lack of studies focusing on outcome parameters in very elderly patients (≥ 90 years) who receive intensive care treatment following PFFs. In this retrospective study, we analyzed multi-layered data of 148 patients who were 90 years or older and received intensive care after trauma and orthopedic surgical treatment for PFFs or periprosthetic fractures between 2009 and 2019. All patients received a 365-day follow-up. To identify potential predictors of mortality, all deceased and surviving patients were subjected to multiple logistic regression analyses. We found that 22% of patients deceased during in-hospital care, and one-year survival was 44%. Independent predictors of one-year all-cause mortality included higher CCI and SOFA scores at ICU admission. Overall, 53% of patients who resided in private dwellings prior to admission were able to return home. Our study highlights the utility of using CCI and SOFA scores at ICU admission as prognostic indicators in critically ill very elderly patients who undergo surgical treatment for PFFs. These scores can provide valuable insight into the severity of illness and potential outcomes, which can inform resource allocation, prioritize endangered patients, and aid in end-of-life discussions and planning with patients and their families. Our findings can help improve the management of PFFs in very elderly patients and contribute to optimized patient care.

Association between Red Cell Distribution Width and Outcomes of Nonagenarians Admitted to the Intensive Care Unit-A Retrospective Cohort Study.

The red cell distribution width (RDW) measures the heterogeneity of the erythrocyte volume. Different clinical conditions are associated with increased RDW, and high levels (>14.5%) have been described as a predictive marker for unfavorable outcomes and mortality in critically ill patients. However, there is a lack of data on very elderly critically ill patients. Therefore, we aimed to investigate the association of RDW with outcomes in critically ill patients ≥ 90 years. A retrospective analysis was conducted for all consecutive critically ill patients ≥ 90 years who were admitted to the Department of Intensive Care Medicine of the Medical University Centre Hamburg-Eppendorf (Hamburg, Germany) with available RDW on admission. Clinical course and laboratory were analyzed for all patients with eligible RDW. High RDW was defined as (>14.5%). We clinically assessed factors associated with mortality. Univariable and multivariable Cox regression analysis was performed to determine the prognostic impact of RDW on 28-day mortality. During a 12-year period, we identified 863 critically ill patients ≥ 90 years old with valid RDW values and complete clinical data. In total, 32% (n = 275) died within 28 days, and 68% (n = 579) survived for 28 days. Median RDW levels on ICU admission were significantly higher in non-survivors compared with survivors (15.6% vs. 14.8%, p < 0.001). Overall, 38% (n = 327) had low, and 62% (n = 536) had high RDW. The proportion of high RDW (>14.5%) was significantly higher in non-survivors (73% vs. 57%, p < 0.001). Patients with low RDW presented with a lower Charlson Comorbidity Index (p = 0.014), and their severity of illness on admission was lower (SAPS II: 35 vs. 38 points, p < 0.001). In total, 32% (n = 104) in the low and 35% (n = 190) in the high RDW group were mechanically ventilated (p = 0.273). The use of vasopressors (35% vs. 49%, p < 0.001) and renal replacement therapy (1% vs. 5%, p = 0.007) was significantly higher in the high RDW group. Cox regression analysis demonstrated that high RDW was significantly associated with 28-day mortality [crude HR 1.768, 95% CI (1.355-2.305); p < 0.001]. This association remained significant after adjusting for multiple confounders [adjusted HR 1.372, 95% CI (1.045-1.802); p = 0.023]. High RDW was significantly associated with mortality in critically ill patients ≥ 90 years. RDW is a useful simple parameter for risk stratification and may aid guidance for the therapy in very elderly critically ill patients.

The Independent Impact of Peripheral Arterial Disease on Mortality in Nonagenarians and Centenarians Who Were Treated in an Intensive Care Unit: A Consecutive Cohort of 1 108 Patients.

OBJECTIVE: To investigate the clinical characteristics, risk factors, and outcomes of inpatients with peripheral arterial disease (PAD) including lower extremity PAD, abdominal aortic aneurysm (AAA), and carotid artery disease in a large cohort of critically ill patients aged ≥ 90 years. METHODS: A retrospective analysis was conducted of all adult patients aged ≥ 90 years consecutively admitted to the intensive care unit at a tertiary care centre in Hamburg, Germany, between 1 January 2008 and 30 April 2019. Multivariable regression and Kaplan-Meier methods were used to determine the independent impact of PAD on short and long term mortality endpoints. The analyses were adjusted for confounding by several sociodemographic and clinical parameters including Charlson Comorbidity Index (CCI) and established clinical risk scores. RESULTS: A total of 1 108 eligible patients were identified (92.3 years, 33% men). Of these, 24% had PAD (9% lower extremity PAD, 2% AAA, 15% coronary artery disease) and 76% did not have any history of PAD and were used as a comparison group. When compared with the comparison group, patients with PAD had a higher CCI (2 vs. 1, p < .001), more often had chronic kidney disease (28% vs. 21%, p = .019), and renal replacement therapy (5% vs. 2%, p = .016). Furthermore, they needed vasopressors (48% vs. 40%, p = .027) and parenteral nutrition (10% vs. 6%, p = .041) more often. After adjusting for confounding, PAD was independently associated with increased in hospital (hazard ratio [HR] 1.97, 95% confidence interval [CI] 1.39 - 2.81, p < .001) and long term mortality rates (HR 1.32, 95% CI 1.05 - 1.66, p = .019). CONCLUSION: One of four critically ill nonagenarians and centenarians in an ICU in Germany had PAD. PAD was associated with both higher short and long term mortality rates while its impact outweighed higher age. Future studies should address this increasingly important population beyond 89 years of age.

Occurrence, Characteristics, and Outcome of Hypoxic Liver Injury among Patients Aged ≥90 Years Admitted to the Intensive Care Unit: A Retrospective Cohort Study.

INTRODUCTION: Hypoxic liver injury (HLI) is a frequent and life-threatening complication occurring in up to 10% of critically ill patients. Heart failure and age were previously identified as risk factors for occurrence of HLI. However, there is lack of data on incidence of HLI and its clinical implications on outcome in very old (≥90 years) patients. The aim of this study was to investigate occurrence, clinical characteristics, and outcome of HLI in critically ill patients ≥90 years. METHODS: This is a retrospective analysis of all consecutive critically ill patients ≥90 years admitted to the intensive care unit (ICU) of a tertiary care university hospital in Hamburg, Germany. Clinical course and laboratory data were analyzed for all patients. HLI was defined according to established criteria as elevation of aminotransferase levels (>20-fold upper limit of normal). Predictors of HLI occurrence, clinical course, and outcome were assessed and compared to those of patients without HLI. RESULTS: In total, 1,065 critically ill patients ≥90 years were included. During the ICU stay, 3% (n = 35) developed HLI. Main causes of HLI were cardiogenic shock (51%, n = 18), septic shock (23%, n = 8), and cardiac arrest (20%, n = 7). Presenting characteristics including age, gender, and BMI were comparable between patients with and without HLI. The admission cause was primary medical (HLI: 49% vs. No-HLI: 34%, p = 0.07), surgical - planned (9% vs. 38%, p < 0.001), and surgical - emergency (43% vs. 28%, p = 0.06). The median Charlson Comorbidity Index (CCI) and the median updated CCI were 2 (1-3) and 2 (1-2) points in patients with HLI and 1 (0-2) and 1 (0-2) in patients without HLI (p < 0.01 and p = 0.08). Patients with HLI presented with higher SAPS II (55 vs. 36 points p < 0.001) score on admission and required mechanical ventilation (66% vs. 34%, p < 0.001), vasopressor therapy (91% vs. 40%, p < 0.001), renal replacement therapy (20% vs. 2%, p < 0.001), and parenteral nutrition (29% vs. 7%, p < 0.001). The ICU mortality and hospital mortality in patients with HLI were 66% (n = 23) and 83% (n = 29) compared with 17% (n = 170) and 28% (n = 292) in patients without HLI, respectively (both p < 0.001). Regression analysis identified SAPS II (OR 1.05, 95% CI: [1.02-1.07]; p < 0.001) and vasopressor therapy (OR 9.21, 95% CI: [2.58-32.86]; p < 0.01) as factors significantly associated with new onset of HLI. Occurrence of HLI was independently associated with mortality (HR 2.23, 95% CI: [1.50-3.30]; p < 0.001). CONCLUSION: HLI is an uncommon but not rare condition in critically ill patients aged ≥90 years. Occurrence of HLI is associated with high mortality and is mainly caused by cardiogenic or septic shock. HLI may serve as early prognostic marker in critically ill patients aged ≥90 years.

Effects of Different Lengths of a Nucleic Acid Binding Region and Bound Nucleic Acids on the Phase Behavior and Purification Process of HBcAg Virus-Like Particles.

Virus-like particles (VLPs) are macromolecular structures with great potential as vehicles for the targeted administration of functional molecules. Loaded with nucleic acids, VLPs are a promising approach for nanocarriers needed for gene therapy. There is broad knowledge of the manufacturing of the truncated wild-type lacking a nucleic acid binding region, which is mainly being investigated for vaccine applications. Whereas for their potential application as a nanocarrier for gene therapy, hepatitis B core antigen (HBcAg) VLPs with a nucleic acid binding region for efficient cargo-loading are being investigated. VLP structure, loading, and phase behavior are of central importance to their therapeutic efficacy and thereby considerably affecting the production process. Therefore, HBcAg VLPs with different lengths of the nucleic acid binding region were produced in E. coli. VLP attributes such as size, zeta potential, and loading with host cell-derived nucleic acids were evaluated. Capsid's size and zeta potential of the VLP constructs did not differ remarkably, whereas the analysis of the loading with host cell-derived nucleic acids revealed strong differences in the binding of host cell-derived nucleic acids dependent on the length of the binding region of the constructs, with a non-linear correlation but a two-zone behavior. Moreover, the phase behavior and purification process of the HBcAg VLPs as a function of the liquid phase conditions and the presence of host cell-derived nucleic acids were investigated. Selective VLP precipitation using ammonium sulfate was scarcely affected by the encapsulated nucleic acids. However, the disassembly reaction, which is crucial for structure homogeneity, separation of encapsulated impurities, and effective loading of the VLPs with therapeutic nucleic acids, was affected both by the studied liquid phase conditions, varying pH and concentration of reducing agents, and the different VLP constructs and amount of bound nucleic acids, respectively. Thereby, capsid-stabilizing effects of the bound nucleic acids and capsid-destabilizing effects of the nucleic acid binding region were observed, following the two-zone behavior of the construct's loading, and a resulting correlation between the capsid stability and disassembly yields could be derived.

[The Role of Partnership Status and Relationship Satisfaction in Inpatient Mother-Child Treatment in Postpartum Mental Disorders]. / Die Bedeutung von Partnerschaftsstatus und -zufriedenheit für den Outcome stationärer Mutter-Kind-Behandlungen bei postpartalen psychischen Krisen.

The Role of Partnership Status and Relationship Satisfaction in Inpatient Mother-Child Treatment in Postpartum Mental Disorders The study examines the partnership status and satisfaction in connection with symptoms of postpartum mental disorders, mother-child attachment and outcome of inpatient mother-child treatment. Two sub-studies were carried out. In the first study, N = 126 mothers with postpartum mental disorders who went to a preliminary consultation for inpatient mother-child treatment stated their symptom burden (SCL-90), mother-child attachment (PBQ) and satisfaction with their partner relationship (PFB-K). Mothers with stressed relationships showed the highest level of symptom burden and impaired attachment. Mothers without a partner reported the least amount of impairment in mother-child attachment. In the second study, N = 41 mothers were examined over the course of inpatient treatment (within-subject design with a waiting-list). The initial relationship satisfaction was not predictive of symptom reduction or improvement in mother-child attachment. An increase in satisfaction during the treatment was though correlated with an improvement in mother-child attachment.

Effects of COVID-19 on in-hospital cardiac arrest: incidence, causes, and outcome - a retrospective cohort study.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), an emerging virus, has caused a global pandemic. Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has led to high hospitalization rates worldwide. Little is known about the occurrence of in-hospital cardiac arrest (IHCA) and high mortality rates have been proposed. The aim of this study was to investigate the incidence, characteristics and outcome of IHCA during the pandemic in comparison to an earlier period. METHODS: This was a retrospective analysis of data prospectively recorded during 3-month-periods 2019 and 2020 at the University Medical Centre Hamburg-Eppendorf (Germany). All consecutive adult patients with IHCA were included. Clinical parameters, neurological outcomes and organ failure/support were assessed. RESULTS: During the study period hospital admissions declined from 18,262 (2019) to 13,994 (2020) (- 23%). The IHCA incidence increased from 4.6 (2019: 84 IHCA cases) to 6.6 (2020: 93 IHCA cases)/1000 hospital admissions. Median stay before IHCA was 4 (1-9) days. Demographic characteristics were comparable in both periods. IHCA location shifted towards the ICU (56% vs 37%, p < 0.01); shockable rhythm (VT/VF) (18% vs 29%, p = 0.05) and defibrillation were more frequent in the pandemic period (20% vs 35%, p < 0.05). Resuscitation times, rates of ROSC and post-CA characteristics were comparable in both periods. The severity of illness (SAPS II/SOFA), frequency of mechanical ventilation and frequency of vasopressor therapy after IHCA were higher during the 2020 period. Overall, 43 patients (12 with & 31 without COVID-19), presented with respiratory failure at the time of IHCA. The Horowitz index and resuscitation time were significantly lower in patients with COVID-19 (each p < 0.01). Favourable outcomes were observed in 42 and 10% of patients with and without COVID-19-related respiratory failure, respectively. CONCLUSION: Hospital admissions declined during the pandemic, but a higher incidence of IHCA was observed. IHCA in patients with COVID-19 was a common finding. Compared to patients with non-COVID-19-related respiratory failure, the outcome was improved.

Epidemiology of intensive care unit cardiac arrest: Characteristics, comorbidities, and post-cardiac arrest organ failure - A prospective observational study.

BACKGROUND: Critically ill patients in intensive care units can frequently suffer from cardiac arrest (ICU-CA), the incidence of ICU-CA is associated with high mortality. Most studies on ICU-CA focused on risk factors and intra-arrest determinants. However, there is a lack of data on organ failure after ICU-CA and its clinical implications for outcome. This study aimed to investigate ICU-CA incidence, outcome and the occurrence of organ failure after ICU-CA. METHODS: We conducted a prospective observational study over a 1-year at 12 intensive care units of a tertiary care university hospital. We included all consecutive adult patients suffering cardiac arrest (CA) during the ICU stay. Incidence, clinical and neurological outcome, as well as organ failure and support were assessed. RESULTS: Out of 7690 patients, 176 (2%) with ICU-CA were identified during the study period. Male patients comprised 63% and the median age was 70 (58-78) years. The median ICU stay before ICU-CA was 3 (1-8) days. The initial cardiac rhythm was shockable (VT/VF) in 23% of patients; defibrillation during CPR was performed in 19%. The presumed cause of CA was cardiac in 24%, and sustained ROSC was observed in 80% of patients. Before CA 57% (n = 100) of patients were sedated, 63% (n = 110) mechanically ventilated, 70% needed vasopressor therapy and renal replacement therapy was necessary in 27% (n = 48) of patients. Organ failure after ICU-CA was common, 70% suffered from post-CA cardiac failure, renal replacement therapy was newly initiated in 26% of patients and liver failure occurred in 24% of patients. Mortality at ICU-discharge and at hospital discharge was 66 % and 68 %, respectively. Multivariate regression analysis identified the SOFA score [HR 1.09, 95% CI (0.92-3.18); p < 0.05] and liver failure [HR 2.44, 95% CI (1.39-4.26); p < 0.001] after ICU-CA as independent predictors of mortality. CONCLUSION: The incidence of ICU-CA is rare in critically ill patients. Organ failure before and after ICU-CA is common; liver failure incidence and severity of illness after ICU-CA are independent predictors of mortality and should be considered in further decisions on ICU therapy.

The chronic ICU patient: Is intensive care worthwhile for patients with very prolonged ICU-stay (≥ 90 days)?

BACKGROUND: Due to medical advances, an increasing number of patients are surviving the acute critical illness. However, some patients require a prolonged critical care treatment. Data on outcome and functional status of patients with an ICU-stay ≥90 days are scarce. METHODS: Single-center retrospective study including all adult patients with ICU stay ≥90 days treated at the department of intensive care medicine at the university medical center Hamburg-Eppendorf, Germany, between January 1st 2008 and December 31st 2016. RESULTS: Out of 65,249 patients, we identified 96 (0.1%) patients with a very prolonged ICU stay. Median age was 61 (49.8-67) years, 30 (31%) patients were female. Patients were admitted to ICU due to abdominal (28%) reasons, followed by sepsis (23%) and transplantation (15%). Fourteen patients received organ-transplantation: 9 received liver-, 4 lung- and 1 heart-transplantation. All patients needed mechanical ventilation (MV), median duration was 74.1 (55-95.1) days. Sixty-Three (66%) patients survived the ICU-stay and 1-Year survival rate was 28%. Overall eight (8%) patients had a favourable outcome after 1-Year. Severity of illness (SOFA, SAPS II) on admission were comparable. Length of MV, use of renal replacement therapy (both p < .01) and maximum lactate (5.3 vs 11.5 mmol/l; p < .001) were significantly higher in ICU non-survivors. ICU-stay was significantly longer in ICU non-survivors (137 vs 107 days; p < .05). Cox-regression-model revealed age (HR 1.02, 95% CI 1.00-1.04, p < .05) and surgical admission (HR 0.50, 95% CI 0.28-0.90, p < .05) as independent predictors of 1-year mortality. CONCLUSIONS: Only a small number of patients requires a very prolonged ICU stay. Two-third of patients survive the ICU stay and about one-third 1-Year. However, about 10% of patients have a remarkable recovery with a favourable overall outcome after 1-Year.

Long-term neurological outcomes in patients aged over 90 years who are admitted to the intensive care unit following cardiac arrest.

BACKGROUND: The number of cardiac arrests (CA) in the group of very elderly patients (≥ 90 years) is expected to increase markedly due to the world`s rapidly ageing population. However, only little is known about long term outcome, CA- and intensive care unit (ICU) characteristics of patient's ≥ 90 years (nonagenarians) suffering from CA. METHODS: This single-center retrospective study included all adult patients ≥ 90 years after CA and return of spontaneous circulation (ROSC) which were treated at our ICU between January 1st 2008 and September 15th 2016. Patients were followed at least 1-Year after ICU discharge for assessment of survival and neurological outcome. Aim of the study was to evaluate CA- and patients characteristics, as well as ICU- and neurological outcome after CA in patient's ≥ 90 years. RESULTS: 657 patients ≥ 90 years were treated at our ICU during the study period, of these we could identify 48 patients with CA and successful resuscitation. 27 (56%) were female and the median age was 91.7 (90.7 - 92.6) years. 41 (85%) patient suffered from in-hospital CA. Cardiac events leading to CA were observed in 19 (40%) patients. Initial rhythm was shockable (VT/VF) in 12 (25%) patients and time to ROSC was median 4 (1.6 - 9.5) minutes. Patients after CA who survived the ICU stay had significantly lower SAPS II score (44 (36 - 55) vs. 58 (46.5 - 75.5), p < 0.05), lower maximum lactate (2.8 (1.9 - 4.3) mmol/l vs. 6.2 (4 - 9) mmol/l, p < 0.001) and higher pH (7.29 (7.26 - 7.38) vs. 7.23 (7.12 - 7.32), p < 0.05) on admission compared to patients with CA who did not survive the ICU stay. Overall, after CA, 39 (81%) patients needed mechanical ventilation, 44 (92%) received catecholamine support, 17 (35%) received red blood cell transfusion and 4 (8%) received renal replacement therapy. Mechanical ventilation and red blood cell transfusion was significantly more common in ICU non-survivors (both p < 0.05). 19 (46%) patients survived the ICU-stay, of these 86% had favourable neurological outcome (CPC I/II) at ICU discharge. One year survival rate was 23% (n = 11), of these 55% (n = 6) had favorable neurological outcome. CONCLUSIONS: 46% of successfully resuscitated nonagenarians survived the ICU stay, the majority with favourable neurological outcome at ICU discharge. Resuscitation and post-CA care, in the highly selected group of very elderly patients (≥ 90 years), seems to be justified.

Attachment Patterns Affect Spiritual Coping in Palliative Care.

Research has shown that spiritual coping is essential for palliative care patients in enhancing quality of life and that attachment patterns affect the emotional well-being of the terminally ill. This is the first study evaluating how spiritual coping and attachment are associated in palliative care patients. Four different attachment patterns-secure, dismissive, preoccupied, and unresolved-were examined, as well as how they relate to three different spiritual coping strategies-search, trust, and reflection. In a cross-sectional, correlative design, 80 patients were recruited from German palliative care wards and hospices. Attachment patterns were determined using the Adult Attachment Projective System and spiritual coping strategies by SpREUK questionnaire, measuring spiritual and religious attitudes in dealing with illness. The results indicate that there is an association between attachment style and spiritual coping. Preoccupied patients had the lowest score in spiritual coping, with the strategy "reflection" being significantly lowest (t = 2.389, P = .019). Securely and dismissively attached patients presented equally high scores, raising the question of what mechanisms underlie spiritual coping. Furthermore, the unresolved group scored high in spiritual coping. Heightening awareness for ways in which attachment styles influence spiritual coping can contribute significantly to the quality of life in terminally ill patients, enabling health care professionals to tailor to individual needs in this vulnerable stage of life.

Maternal Aneurysmal Subarachnoid Hemorrhage During Pregnancy as an Interdisciplinary Task.

Maternal aneurysmal subarachnoid hemorrhage (aSAH) during pregnancy presents a challenge regarding treatment and management. Due to the limited number of cases there are no treatment guidelines available. Thus, treatment is usually done on a case-by-case basis. Here we report on four cases of aSAH during pregnancy, describing the different management strategies and suggesting a possible treatment algorithm. Patients treated between 2003 and 2013 in our center were included in this retrospective study. Clinical data focused on time management concerning gestation week (GW), microsurgical or endovascular treatment, and outcome of the patients and the fetuses. Results were compared to the present literature on this issue. Mean age was 30.8 years, initial Hunt & Hess (H&H) grade ranged from III to V. All patients suffered from aSAH during the 3rd trimester of pregnancy. In the four cases, two emergency Caesarean sections (CS) were performed. Two aneurysms were occluded by microsurgical clipping and one was treated endovascularly. One patient died before definitive treatment of the aneurysm could be achieved, whereas fetal mortality was 0%. The mean follow-up was 83 months. aSAH during pregnancy needs individualized interdisciplinary management. Efforts must focus on the mother so that a delay in the best available treatment for the pregnant patient is avoided. Therefore treatment modality should be primarily determined by the aneurysm itself. However, timing in terms of delivery of the fetus and aneurysm treatment is a crucial point.

LIL3, a Light-Harvesting Complex Protein, Links Terpenoid and Tetrapyrrole Biosynthesis in Arabidopsis thaliana.

The LIL3 protein of Arabidopsis (Arabidopsis thaliana) belongs to the light-harvesting complex (LHC) protein family, which also includes the light-harvesting chlorophyll-binding proteins of photosystems I and II, the early-light-inducible proteins, PsbS involved in nonphotochemical quenching, and the one-helix proteins and their cyanobacterial homologs designated high-light-inducible proteins. Each member of this family is characterized by one or two LHC transmembrane domains (referred to as the LHC motif) to which potential functions such as chlorophyll binding, protein interaction, and integration of interacting partners into the plastid membranes have been attributed. Initially, LIL3 was shown to interact with geranylgeranyl reductase (CHLP), an enzyme of terpene biosynthesis that supplies the hydrocarbon chain for chlorophyll and tocopherol. Here, we show another function of LIL3 for the stability of protochlorophyllide oxidoreductase (POR). Multiple protein-protein interaction analyses suggest the direct physical interaction of LIL3 with POR but not with chlorophyll synthase. Consistently, LIL3-deficient plants exhibit substantial loss of POR as well as CHLP, which is not due to defective transcription of the POR and CHLP genes but to the posttranslational modification of their protein products. Interestingly, in vitro biochemical analyses provide novel evidence that LIL3 shows high binding affinity to protochlorophyllide, the substrate of POR. Taken together, this study suggests a critical role for LIL3 in the organization of later steps in chlorophyll biosynthesis. We suggest that LIL3 associates with POR and CHLP and thus contributes to the supply of the two metabolites, chlorophyllide and phytyl pyrophosphate, required for the final step in chlorophyll a synthesis.

GAP promoter-based fed-batch production of highly bioactive core streptavidin by Pichia pastoris.

Streptavidin is a homotetrameric protein binding the vitamin biotin and peptide analogues with an extremely high affinity, which leads to a large variety of applications. The biotin-auxotrophic yeast Pichia pastoris has recently been identified as a suitable host for the expression of the streptavidin gene, allowing both high product concentrations and productivities. However, so far only methanol-based expression systems have been applied, bringing about increased oxygen demand, strong heat evolution and high requirements for process safety, causing increased cost. Moreover, common methanol-based processes lead to large proportions of biotin-blocked binding sites of streptavidin due to biotin-supplemented media. Targeting these problems, this paper provides strategies for the methanol-free production of highly bioactive core streptavidin by P. pastoris under control of the constitutive GAP promoter. Complex were superior to synthetic production media regarding the proportion of biotin-blocked streptavidin. The optimized, easily scalable fed-batch process led to a tetrameric product concentration of up to 4.16 ± 0.11 µM of biotin-free streptavidin and a productivity of 57.8 nM h(-1) based on constant glucose feeding and a successive shift of temperature and pH throughout the cultivation, surpassing the concentration in un-optimized conditions by a factor of 3.4. Parameter estimation indicates that the optimized conditions caused a strongly increased accumulation of product at diminishing specific growth rates (µ ≈ D < 0.01 h(-1) ), supporting the strategy of feeding. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:855-864, 2016.

Fed-batch production and secretion of streptavidin by Hansenula polymorpha: Evaluation of genetic factors and bioprocess development.

Streptavidin - a protein secreted by the filamentous bacterium Streptomyces avidinii - is applied in a variety of methods, leading to numerous studies on its heterologous production. Development and characterization of a novel expression system for streptavidin genes by Hansenula polymorpha is described utilizing different target gene variants along with the two methanol-inducible promoters PMOX and PFMD. Extracellular product concentrations were higher for cultivation at 30 instead of 37°C. The best performing strain carrying the full-length streptavidin gene under control of PFMD was characterized in the bioreactor applying a synthetic medium and oxygen-controlled feeding of glucose. Derepression resulted in an extracellular concentration of 1.31±0.07µM of tetrameric streptavidin after 48h (27.3nMh(-1)). Feeding of glycerol improved biomass formation, but lowered the product concentration. By combining derepression and methanol induction the final extracellular streptavidin concentration increased to 11.42±0.22µM (approx. 751mgL(-1)), yielding a productivity of 52.5nMh(-1). Despite supplementing biotin the proportion of biotin-blocked binding sites in the supernatant dropped from 54.4±5.0 % after 18h to 17.2±6.5 % towards the end of glucose feeding to a final value of 1.1±3.8 %, indicating a highly bioactive product. Thus, H. polymorpha proved to be a suitable host for the production of streptavidin.

Constitutive production and efficient secretion of soluble full-length streptavidin by an Escherichia coli 'leaky mutant'.

Due to its various applications the protein streptavidin is a highly interesting target for heterologous production. This study focuses on different Escherichia coli-based constructs targeting a high-level expression and secretion of streptavidin to the medium. The effect of various promoters, variants of the target gene, leader sequences and host strains on expression and secretion into the culture broth was analyzed. Constitutive production of full-length streptavidin fused with the leader sequence of the bglA gene from Bacillus amyloliquefaciens by the periplasmic 'leaky mutant' E. coli JW1667-5 (Δlpp-752:kan) at 30°C generated the highest yield of the conditions tested, surpassing the extracellular concentration of a conventional T7-based expression system. Supplementation of the medium by the non-ionic surfactants Triton(®) X-100 and X-45 led to an improved secretion of the protein to the culture supernatant. Tetrameric concentrations of streptavidin of 2790±166nM were reached in shake flasks at a productivity of 49.6nMh(-1). Optimization of conditions led to a successful transfer to the bioreactor, yielding a maximal concentration of 2608±169nM and a productivity of 65.2nMh(-1) in fed-batch operation. The proportion of biotin-blocked binding sites of 8.3±4.3% indicated a highly bioactive product.

[Attachment and psychosomatic health among Catholic pastoral professionals]. / Bindung und psychosomatische Gesundheit bei katholischen Seelsorgenden.

OBJECTIVES: The study examines attachment representations and psychosomatic symptoms of Catholic priests and other pastoral professionals in Germany. METHOD: We conducted structured biographical interviews with 83 Catholic pastoral professionals (47 priests, 36 lay pastoral workers). Attachment representations were diagnosed by use of the Adult Attachment Projective Picture System (AAP). Psychosomatic health data (Brief Symptom Inventory - BSI-18) were taken from the associated German Pastoral Ministry Study. RESULTS: In the sample, the proportion of secure attachment representations was 23%, of insecure- dismissing 39%, of insecure-preoccupied 18% and of unresolved attachment status 21%. Individuals with secure attachment representation were associated with lower values of psychosomatic stress, while individuals with insecure-dismissing and unresolved attachment status had higher values. DISCUSSION: The amount of insecure attachment representations and psychosomatic symptoms is higher than in data from the healthy samples, especially in the cohorts between 1933 and 1945. Data from biographical interviews indicate the significant role of institutional attachment to the Church, in many cases possibly compensating for dysfunctional parental relationships in personal history.