[Open questions with respect to extracorporeal circulatory support 2024]. / Offene Fragen zur extrakorporalen Kreislaufunterstützung 2024.

The use of extracorporeal circulatory support, both for cardiogenic shock and during resuscitation, still presents many unanswered questions. The inclusion and exclusion criteria for such a resource-intensive treatment must be clearly defined, considering that these criteria are directly associated with the type and location of treatment. For example, it is worth questioning the viability of an extracorporeal resuscitation program in areas where it is impossible to achieve low-flow times under 60 min due to local limitations. Additionally, the best approach for further treatment, including whether it is necessary to regularly relieve the left ventricle, must be explored. To find answers to some of these questions, large-scale, multicenter, randomized studies and registers must be performed. Until then this treatment must be carefully considered before use.

Reduction in pain: Is it worth the gain? The effect of opioids on the GI tract.

The use of opioid medications for acute and chronic pain has increased significantly in the past 20 years in the United States. Given the high density of opioid receptors in the gastrointestinal tract, side effects are common in these patients including constipation, dysphagia, bloating, nausea, and vomiting. These side effects, which are experienced by most patients who take opioids, can lead to significant impairment in quality of life. Unlike other side effects from opioids, gastrointestinal side effects do not diminish with continued use, often leading patients to reduce or discontinue their opioid treatment to relieve these side effects. Therefore, physicians must be aware and anticipate potential side effects in patients receiving opioids to ensure appropriate pain management.

Emergency department utilisation for inflammatory bowel disease in the United States from 2006 to 2014.

BACKGROUND: Despite advances in treatment, patients with inflammatory bowel disease (IBD) frequently require emergency department (ED) visits and hospitalisations. AIMS: To analyse trends in ED visits and subsequent hospitalisations for IBD in the United States (US). METHODS: Data were analysed from the Nationwide Emergency Department Sample (NEDS) years 2006-2014. The NEDS is the largest all-payer ED database in the US, weighted to represent 135 million visits/year. IBD was identified using ICD-9 codes for Crohn's disease (CD) or ulcerative colitis (UC). Surgeries were identified using procedure codes. RESULTS: The frequency of IBD-ED visits increased 51.8%, from 90 846 visits in 2006 to 137 946 in 2014, which was statistically significant in linear regression. For comparison, all-case ED use between 2006 and 2014 increased 14.8%. In-patient hospitalisations from the ED decreased 12.1% for IBD (from 64.7% rate of hospitalisation from the ED in 2006 to 52.6% in 2014), with a UC:CD ratio of 1.2:1 in 2006 and 1.3:1 in 2014. Chi-square analysis revealed that this was a significant decrease. Surgery rates also showed a statistically significant decrease. The mean ED charge per patient rose 102.5% and the aggregate national cost of IBD-ED visits increased 207.5%. CD accounted for over twice as many visits as UC in both years. UC, age, male gender, highest income quartile, private insurance, Medicaid/Medicare, and tobacco use were associated with in-patient admissions. CONCLUSIONS: The number of ED visits due to IBD and associated charges have continued to rise, while the rates of in-patient hospitalisations referred from the ED and surgeries have decreased.

A survey on general and temperature management of post cardiac arrest patients in large teaching and university hospitals in 14 European countries-The SPAME trial results.

INTRODUCTION: International guidelines recommend a bundle of care, including targeted temperature management (TTM), in post cardiac arrest survivors. Aside from a few small surveys in different European countries, adherence to the European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) recommendations are unknown. METHODS: This international European telephone survey was conducted to provide an overview of current clinical practice of post cardiac arrest management with a main focus on TTM. We targeted large teaching and university hospitals within Europe as leading facilities and key opinion leaders in the field of post cardiac arrest care. Selected national principal investigators conducted the survey, which was based on a predefined questionnaire, between December 2014 and March 2015, before the publication of the ERC Guidelines 2015. RESULTS: The return rate was 94% from 268 participating intensive care units (ICU). The majority had a predefined standard operating procedure (SOP) protocol for post cardiac arrest patients. Altogether, 68% of the ICUs provided TTM at a target temperature of 32-34°C for 24h, and 33% had changed the target temperature to 36°C. The minority provided a written SOP for neurological prognostication, which was generally initiated 72h after return of spontaneous circulation (ROSC). Electroencephalography and somatosensory evoked potentials were used by most ICUs for early prognostication. Treating more than fifty patients a year was significantly associated with providing written SOPs for TTM and prognostication (p<0.01), as well as the use of a computer feedback device (p=0.03) for TTM. CONCLUSION: This international European telephone survey revealed a high rate of implementation of TTM in post cardiac arrest patients in university and teaching hospitals. Most participants also provided a SOP, but only a minority had a SOP for neurological prognostication.

Gender differences in chronic constipation on anorectal motility.

BACKGROUND: The epidemiology of chronic constipation (CC) skews toward female predominance, yet men make up an important component of those suffering from CC. We sought to determine whether there are sex-specific differences in symptoms and physiologic parameters on anorectal manometry (ARM). METHODS: We performed a case-control analysis of sequential men and age-matched women (2:1 ratio) presenting for ARM as part of the evaluation of CC. We collected physiologic parameters derived from 3D high-resolution ARM in addition to the ROME III constipation module and the Pelvic Floor Distress Inventory 20 (PFDI-20) questionnaires. We analyzed univariate, sex-specific differences in ARM physiologic parameters and PFDI-20 parameters and adjusted for putative confounders using multivariate logistic regression. KEY RESULTS: Our study enrolled 80 men and 165 age-matched women. Men had a higher median sphincter resting pressure (81.2 vs 75.2 mm Hg, P=.01) and mean squeeze pressure (257.0 vs 170.5 mm Hg, P<.0001) than women. Although men reported significantly less severe straining and incomplete evacuation, they had greater mean rectoanal pressure differential (-106.7 vs -71.1 mm Hg, P<.0001), smaller mean defecation index (0.17 vs 0.27, P=.03) and higher volume threshold for urgency (115.2 v. 103.4 mL, P=.03). However, women were more likely to have abnormal balloon expulsion time (BET) than men (52.7% vs 35.0%, P=.01). After multivariate analysis, male gender was the only independent predictor of a normal BET (OR: 0.48, 95% CI: 0.27-0.86, P=.01). CONCLUSIONS & INFERENCES: Men and women with CC differ with regard to symptom severity and physiologic parameters derived from ARM suggesting differences in their pathophysiology.

Regional cerebral oxygen saturation after cardiac arrest in 60 patients--a prospective outcome study.

INTRODUCTION: Non-invasive near-infrared spectroscopy (NIRS) offers the possibility to determine regional cerebral oxygen saturation (rSO2) in patients with cardiac arrest. Limited data from recent studies indicate a potential for early prediction of neurological outcome. METHODS: Sixty cardiac arrest patients were prospectively enrolled, 22 in-hospital cardiac arrest (IHCA) and 38 out-of-hospital cardiac arrest (OHCA) patients respectively. NIRS of frontal brain was started after return of spontaneous circulation (ROSC) during admission to ICU and was continued until normothermia. Outcome was determined at ICU discharge by the Pittsburgh Cerebral Performance Category (CPC) and 6 months after cardiac arrest. RESULTS: A good outcome (CPC 1-2) was achieved in 23 (38%) patients, while 37 (62%) had a poor outcome (CPC 3-5). Patients with good outcome had significantly higher rSO2 levels (CPC 1-2: rSO2 68%; CPC 3-5: rSO2 58%; p<0.01). For good and poor outcome median rSO2 within the first 24h period was 66% and 59% respectively and for the following 16h period 68% and 59% (p<0.01). Outcome prediction by area of rSO2 below a critical threshold of rsO2=50% within the first 40h yielded 70% specificity and 86% sensitivity for poor outcome. CONCLUSION: On average, rSO2 within the first 40h after ROSC is significantly lower in patients with poor outcome, but rSO2 ranges largely overlap between outcome groups. Our data indicate limited potential for prediction of poor outcome by frontal brain rSO2 measurements.

Tympanic temperature during therapeutic hypothermia.

OBJECTIVE: Prehospital induction of therapeutic hypothermia after cardiac arrest may require temperature monitoring in the field. Tympanic temperature is non-invasive and frequently used in clinical practice. Nevertheless, it has not yet been evaluated in patients undergoing mild therapeutic hypothermia (MTH). Therefore, a prospective observational study was conducted comparing three different sites of temperature monitoring during therapeutic hypothermia. METHODS: Ten consecutive patients admitted to our medical intensive care unit after out-of-hospital cardiac arrest were included in this study. During MTH, tympanic temperature was measured using a digital thermometer. Simultaneously, oesophageal and bladder temperatures were recorded in a total of 558 single measurements. RESULTS: Compared with oesophageal temperature, bladder temperature had a bias of 0.019°C (limits of agreement ± 0.61°C (2SD)), and tympanic measurement had a bias of 0.021°C (± 0.80°C). Correlation analysis revealed a high relationship for tympanic versus oesophageal temperature (r = 0.95, p < 0.0001) and also for tympanic versus bladder temperature (r = 0.96, p < 0.0001). CONCLUSIONS: That tympanic temperature accurately indicates both oesophageal and bladder temperatures with a very small discrepancy in patients undergoing MTH after cardiac arrest is demonstrated in this study. Although our results were obtained in the hospital setting, these findings may be relevant for the prehospital application of therapeutic hypothermia as well. In this case, tympanic temperature may provide an easy and non-invasive method for temperature monitoring.

The association between course of illness and subsequent morbidity in bipolar I disorder.

OBJECTIVE: We examined the relationship between certain bipolar I disorder clinical course variables over 5 years with outcome over the subsequent 5-year period. METHODS: Prospective observational follow-up data of 123 bipolar I subjects were analyzed. Predictive clinical variables included the frequency and direction of switches, and the quantity, polarity and length of affective periods. Outcome variables were an affective burden index (ABI) accounting for week-by-week severity and weeks hospitalized. Bivariate analyses guided the selection of predictors for multivariable analyses against the outcome variables. RESULTS: Affective burden index: while the number and direction of switches, the number of polyphasic episodes, weeks in hypomania/mania/mixed state, weeks in minor/major depression, weeks in at least marked affective syndrome, and weeks in any affective syndrome all had bivariate correlation (p<0.01) with the ABI, only weeks in hypomania/mania/mixed state and weeks in minor/major depression made significant contributions in the multivariable analysis (p<0.01) with the ABI. Weeks hospitalized: weeks in at least marked affective syndrome were significantly correlated with weeks hospitalized in bivariate analysis (p<0.01), and maintained a contribution to weeks hospitalized in the multivariable analysis (p<0.01). CONCLUSIONS: The quantity and severity of weeks in symptomatic affective states are possibly greater predictors of affective burden in bipolar I patients than the quantity and direction of affective switches.

Genome-wide linkage scan in a large bipolar disorder sample from the National Institute of Mental Health genetics initiative suggests putative loci for bipolar disorder, psychosis, suicide, and panic disorder.

We conducted a 9-cM genome scan in a large bipolar pedigree sample from the National Institute of Mental Health genetics initiative (1060 individuals from 154 multiplex families). We performed parametric and nonparametric analyses using both standard diagnostic models and comorbid conditions thought to identify phenotypic subtypes: psychosis, suicidal behavior, and panic disorder. Our strongest linkage signals (genome-wide significance) were observed on chromosomes 10q25, 10p12, 16q24, 16p13, and 16p12 using standard diagnostic models, and on 6q25 (suicidal behavior), 7q21 (panic disorder) and 16p12 (psychosis) using phenotypic subtypes. Several other regions were suggestive of linkage, including 1p13 (psychosis), 1p21 (psychosis), 1q44, 2q24 (suicidal behavior), 2p25 (psychosis), 4p16 (psychosis, suicidal behavior), 5p15, 6p25 (psychosis), 8p22 (psychosis), 8q24, 10q21, 10q25 (suicidal behavior), 10p11 (psychosis), 13q32 and 19p13 (psychosis). Over half the implicated regions were identified using phenotypic subtypes. Several regions - 1p, 1q, 6q, 8p, 13q and 16p - have been previously reported to be linked to bipolar disorder. Our results suggest that dissection of the disease phenotype can enrich the harvest of linkage signals and expedite the search for susceptibility genes. This is the first large-scale linkage scan of bipolar disorder to analyze simultaneously bipolar disorder, psychosis, suicidal behavior, and panic disorder.

Daily Record of Severity of Problems (DRSP): reliability and validity.

The Daily Record of Severity of Problems (DRSP) form was developed to aid in the diagnosis and evaluation of DSM-IV Premenstrual Dysphoric Disorder (PMDD). The reliability and validity of the procedure was tested in two studies. Study A included 27 subjects who ranged from having few or no premenstrual problems to those who met criteria for PMDD. Study B included 243 subjects, all of whom met criteria for PMDD. Individual items and Summary Scores had high test-retest reliability in both studies. Internal consistency of Summary Scores was also high in both studies. Summary Scores had moderate to high correlations with other measures of severity of illness. In addition, items and Summary Scores have been shown to be sensitive to change and to treatment differences in Study B. The DRSP provides sensitive, reliable, and valid measures of the symptoms and impairment criteria for PMDD.

Linkage analysis of psychosis in bipolar pedigrees suggests novel putative loci for bipolar disorder and shared susceptibility with schizophrenia.

The low-to-moderate resolution of linkage analysis in complex traits has underscored the need to identify disease phenotypes with presumed genetic homogeneity. Bipolar disorder (BP) accompanied by psychosis (psychotic BP) may be one such phenotype. We previously reported a genome-wide screen in a large bipolar pedigree sample. In this follow-up study, we reclassified the disease phenotype based on the presence or absence of psychotic features and subgrouped pedigrees according to familial load of psychosis. Evidence for significant linkage to psychotic BP (genome-wide P<0.05) was obtained on chromosomes 9q31 (lod=3.55) and 8p21 (lod=3.46). Several other sites were supportive of linkage, including 5q33 (lod=1.78), 6q21 (lod=1.81), 8p12 (lod=2.06), 8q24 (lod=2.01), 13q32 (lod=1.96), 15q26 (lod=1.96), 17p12 (lod=2.42), 18q21 (lod=2.4), and 20q13 (lod=1.98). For most loci, the highest lod scores, including those with genome-wide significance (at 9q31 and 8p21), occurred in the subgroup of families with the largest concentration of psychotic individuals (> or =3 in a family). Interestingly, all regions but six--5q33, 6q21, 8p21, 8q24, 13q32 and 18q21--appear to be novel; namely, they did not show notable linkage to BP in other genome scans, which did not employ psychosis for disease classification. Also of interest is possible overlap with schizophrenia, another major psychotic disorder: seven of the regions presumed linked in this study--5q, 6q, 8p, 13q, 15q, 17p, and 18q--are also implicated in schizophrenia, as are 2p13 and 10q26, which showed more modest support for linkage. Our results suggest that BP in conjunction with psychosis is a potentially useful phenotype that may: (1) expedite the detection of susceptibility loci for BP and (2) cast light on the genetic relationship between BP and schizophrenia.

First-episode major depression. Few sex differences in course.

BACKGROUND: There is a sex difference in the prevalence of unipolar major depression. This study sought to determine whether there is a sex difference in its course. METHODS: The National Institute of Mental Health Collaborative Program on the Psychobiology of Depression-Clinical Studies provided data on 96 male and 101 female subjects who were diagnosed as having a first episode of unipolar major depressive disorder at intake and on whom prospective data were available. We looked for differences at intake in factors other than sex that might affect the course of illness: demographic factors, characteristic features of the first depressive episode, psychiatric history, and family history of depression. We then examined the course of depression of these subjects during the following 15 years. RESULTS: The subjects were similar at intake, enabling us to focus on sex when we looked for differences in the course. Most subjects recovered from their first episode of major depression, but the majority had at least 1 recurrence in the following 5 years. During the following 15 years, male and female subjects did not differ significantly in the time to recovery, the overall time to first recurrence, of the number or severity of recurrences of major depressive episodes. There was no evidence for a more chronic course of depression in women. CONCLUSION: There were few significant sex differences in the course of major depressive disorder in this study population.

Endicott Work Productivity Scale (EWPS): a new measure to assess treatment effects.

The Endicott Work Productivity Scale (EWPS) is a brief self-report questionnaire designed to enable investigators to obtain a sensitive measure of work productivity. The total score is based on the degree to which behaviors and subjective feelings or attitudes that are likely to reduce productivity and efficiency in work activities characterize the subject during the week before evaluation. The total score was found to be reliable and valid within a group of depressed outpatients and a group of nonpatients in the community. The EWPS score is related to, but not redundant with, measures of overall severity of illness and severity of depression in these samples. The EWPS shows considerable promise as an easily used, brief, and sensitive measure for assessing the effects on work performance of various disorders and the efficacy of different therapeutic interventions.

Voltage-gated calcium currents have two opposing effects on the secretion of aldosterone.

Using Ca2+ channel blockers with different specificities for L- and T-type Ca2+ channels, we have investigated the roles of these two channel types in K(+)-induced aldosterone secretion. In whole cell voltage-clamp experiments, the spider toxin omega-agatoxin-IIIA (omega-Aga-IIIA) completely blocks L-type Ca2+ channels but has no effect on T-type Ca2+ channels. In contrast, Ni2+ and 1,4-dihydropyridines block both L- and T-type Ca2+ channels. Secretion induced by 7 mM extracellular K+ concentration ([K+]o) is unaffected by omega-Aga-IIIA but is strongly inhibited by Ni2+ or the 1,4-dihydropyridine, nitrendipine. This suggests that physiological increases in [K+]o stimulate aldosterone secretion primarily by enhancing Ca2+ entry through T-type Ca2+ channels. Surprisingly, secretion induced by 60 mM [K+]o is enhanced by omega-Aga-IIIA or Ni2+ and is inhibited by the L-type Ca2+ channel activator BAY K 8644. Nitrendipine (1 nM) also stimulates such secretion, although higher concentrations are inhibitory (concentration inhibiting 50% of maximal response approximately 30 nM). If extracellular Ca2+ concentration is reduced from 1.25 to 0.5 mM, secretion induced by 60 mM [K+]o is enhanced, and Ni2+ or low nitrendipine become inhibitory. Together, these results that L-type Ca2+ currents can reduce steroidogenesis and that the role of these currents was previously misconstrued because 1,4-dihydropyridines modify secretion by multiple mechanisms. Thus Ca2+ entry can function as a negative modulator of steroid secretion.

An internist joins the surgery service: does comanagement make a difference?

OBJECTIVE: To determine the effect of internist comanagement of cardiothoracic surgical patients on patient outcome and resource utilization. DESIGN: Before/after comparison. SETTING: Tertiary care university-affiliated Veterans Affairs hospital. PATIENTS: 165 patients (86 before the intervention and 79 after the intervention) undergoing cardiothoracic surgery. INTERVENTIONS: All patients were seen preoperatively and at least daily through discharge by a comanaging staff internist who was a full-time member of the surgical team. MAIN OUTCOME MEASURES: Length of stay, in-hospital mortality, and laboratory and radiology utilization. RESULTS: Significant shortening of postoperative length of stay (18.1 days before and 12.1 days after, p = 0.05) and total length of stay (27.2 days before and 19.7 days after, p = 0.03) was noted. The in-hospital mortality rate for the patients undergoing surgery was 8.1% before the intervention versus 2.5% afterward (p = 0.17). There were significant reductions in the total number of x-rays (p = 0.02) and nearly significant reductions in total laboratory test utilization (p = 0.06). Referring physicians and surgeons both believed that the contribution of the internist was important. CONCLUSIONS: The addition of an internist to the cardiothoracic surgery service at a tertiary care teaching center was associated with decreased resource utilization and possible improved outcomes. Before becoming more widely adopted, this intervention deserves further exploration at other sites using stronger study designs.

Ca(2+)-dependent activation of T-type Ca2+ channels by calmodulin-dependent protein kinase II.

The T-type Ca2+ channel is unique among voltage-dependent Ca2+ channels in its low threshold for opening and its slow kinetics of deactivation. Here, we evaluate the importance of intracellular Ca2+ (Cai2+) in promoting low-threshold gating of T-type channels in adrenal glomerulosa cells. We observe that 390 nM to 1.27 microM Cai2+ enhances T-type current by shifting the voltage dependence of channel activation to more negative potentials. This Ca(2+)-induced shift is mediated by calmodulin-dependent protein kinase II (CaMKII), because it is abolished by inhibitors of CaMKII but not of protein kinase C and is subsequently restored by exogenous calmodulin. This Ca(2+)-induced reduction in gating threshold would render T-type Ca2+ channels uniquely suited to transduce depolarizing stimuli of low amplitude into a Ca2+ signal sufficient to support a physiological response.

Atrial natriuretic peptide enhances activity of potassium conductance in adrenal glomerulosa cells.

Aldosterone secretion from the adrenal glomerulosa (AG) cells is inhibited by atrial natriuretic peptide (ANP). Inasmuch as alterations in K+ conductance can modulate aldosterone secretion, the effect of ANP on intracellular K+ homeostasis was investigated. Intracellular K+ concentration ([K+]i) of AG cells was assessed by spectrofluorometry using the K(+)-sensitive dye, K(+)-binding benzofuran isophthalate. The resting value of [K+]i in AG cells was determined to be 120 +/- 1.2 mM (n = 37) in a HCO3-free, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered medium. Exposure of AG cells to ANP led to a dose-dependent, transient decrease in [K+]i, from 21 +/- 3.2% (n = 7) at 100 pM to 31 +/- 2.3% at 1 microM (n = 7). In the continued presence of ANP, a rapid recovery to near basal values of [K+]i was attained within 90 s. Measurements of membrane voltage using the potential sensitive dye 1-3(-sulfonatopropyl)-4-[beta-(-(di-n-butylamino)-6-naphthyl)vinyl ]- pyridinium betaine documented an accompanying change in membrane potential. Pretreatment of AG cells with barium (0.5 mM), tetraethylammonium (0.1 mM), charybdotoxin (100 nM), or ethylene glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid (0.5 mM) blunted the ANP-induced decrease in [K+]i. ANP-(7-23), the ANP-C-receptor selective agonist, which does not elevate guanosine 3',5'-cyclic monophosphate (cGMP) did not alter [K+]i in contrast to cGMP (50 microM), which did. We conclude that ANP via the activation of the ANP A receptor alters K+ homeostasis through a Ca(2+)-activatable K(+)-conductive pathway likely to be the maxi-K channel.

Premenstrual changes: are they familial?

To investigate the potential familial component in premenstrual changes, 80 pairs of sisters were assessed with the Premenstrual Assessment Form, a retrospective measure, and the Daily Ratings Form, a prospective measure, for physical, behavioral and mood changes during the premenstrual phase of the menstrual cycle. Sisters were not found to be concordant for premenstrual changes on measures derived from either procedure, a finding contradictory to previous reports in the literature as well as to our own prior research.