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Aim: To propose a framework for consistently applying the 2018 periodontal status classification scheme to epidemiological surveys (Application of the 2018 periodontal status Classification to Epidemiological Survey data, ACES). Proposed Framework: We specified data requirements and workflows for either completed or planned epidemiological surveys, utilizing commonly collected measures of periodontal status (clinical attachment levels [CAL], probing depths, bleeding on probing), as well as additional necessary variables for the implementation of the 2018 periodontal status classification (tooth loss due to periodontitis and complexity factors). Following detailed instructions and flowcharts, survey participants are classified as having periodontal health, gingivitis or periodontitis. Rates of edentulism must also be reported. In cases of periodontitis, instructions on how to compute the stage and extent are provided. Assessment of grade can be derived from CAL measurements (or from radiographic alveolar bone loss data) in relation to root length and the participant's age. Conclusions: ACES is a framework to be used in epidemiological studies of periodontal status that (i) have been completed, and in which stage and grade according to the 2018 classification are inferred retroactively, or (ii) are being planned. Consistent use of the proposed comprehensive approach will facilitate the comparability of periodontitis prevalence estimates across studies. [ABSTRACT FROM AUTHOR]

Background: Atrial arrhythmias are common in patients with implantable cardioverter-defibrillator (ICD). External shocks and internal cardioversion through commanded ICD shock for electrical cardioversion are used for rhythm-control. However, there is a paucity of data on efficacy of external versus internal cardioversion and on the risk of lead and device malfunction. We hypothesized that external cardioversion is noninferior to internal cardioversion for safety, and superior for successful restoration of sinus rhythm.Methods: Consecutive patients with ICD undergoing elective cardioversion for atrial arrhythmias at 13 centers were randomized in 1:1 fashion to either internal or external cardioversion. The primary safety end point was a composite of surrogate events of lead or device malfunction. Conversion of atrial arrhythmia to sinus rhythm was the primary efficacy end point. Myocardial damage was studied by measuring troponin release in both groups.Results: N=230 patients were randomized. Shock efficacy was 93% in the external cardioversion group and 65% in the internal cardioversion group (P<0.001). Clinically relevant adverse events caused by external or internal cardioversion were not observed. Three cases of pre-existing silent lead malfunction were unmasked by internal shock, resulting in lead failure. Troponin release did not differ between groups.Conclusions: This is the first randomized trial on external vs internal cardioversion in patients with ICDs. External cardioversion was superior for the restoration of sinus rhythm. The unmasking of silent lead malfunction in the internal cardioversion group suggests that an internal shock attempt may be reasonable in selected ICD patients presenting for electrical cardioversion.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03247738. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to compare approved first-line therapies for patients with multiple myeloma. Methods: A systematic literature search for phase III randomized controlled trials (RCTs) comparing first-line chemotherapies approved in Germany and recommended by guidelines at the time of study design was conducted. Random-effects meta-analysis (MA) was used for direct and the Bucher method for adjusted indirect treatment comparison. Results: One RCT comparing melphalan and prednisone plus bortezomib (VMP) vs. melphalan and prednisone (MP) and six RCTs comparing MP plus thalidomide (MPT) vs. MP were analysed. For MPT vs. MP, an individual patient data (IPD) MA was used for sensitivity analyses. VMP and MPT were superior to MP regarding efficacy endpoints (VMP vs. MP, overall survival (OS): hazard ratio (HR) 0.70, 95 % confidence interval (CI) 0.57-0.86; progression-free survival (PFS): HR 0.56, 0.39-0.79; complete response (CR), risk-ratio (RR) for non-response: 0.70, 0.65-0.75; MPT vs. MP, OS: HR 0.83, 0.66-1.03; PFS: HR 0.67, 0.56-0.81; CR, RR for non-response 0.92, 0.88-0.95); but had a higher risk of developing any grade 3-4 adverse events (AEs) (VMP vs. MP: RR 1.13, 1.06-1.20; MPT vs. MP: RR 2.06, 1.43-2.98). The indirect comparison of VMP vs. MPT via MP showed a statistically not significant advantage for VMP regarding survival outcomes (OS: HR 0.85, 0.63-1.14; PFS: HR 0.83, 0.56-1.23) and a significant advantage regarding CR (RR for non-response 0.76, 0.70-0.83) and AEs (RR 0.55, 0.38-0.80). Treatment comparisons using results of IPD MA yielded similar effect sizes. Conclusions: VMP and MPT seem more effective than MP, VMP was superior to MPT regarding response criteria and AEs. Our results may best be confirmed by a head-to-head trial of VMP vs. MPT. [ABSTRACT FROM AUTHOR]

Background: Anemia is a major cause of morbidity in cancer. Erythropoiesis stimulating agents (ESA) are a mainstay of treatment, although some patients lack response for unknown reasons. Recently, ESA dosing recommendations have changed and iron is increasingly used as an adjunct. Due to these changes, potential laboratory predictors of response were re-evaluated. Methods: This was a multi-center, observational study in cancer outpatients developing anemia under standard chemotherapy without absolute iron deficiency. For up to 12 weeks, laboratory data was collected while patients were treated with darbepoetin α (DA) either alone or along with intravenous iron. Baseline erythropoietin (Epo), changes in soluble transferrin receptor (sTfR) and in hemoglobin (Hb) early after treatment initiation were re-evaluated as response predictors, based on logistic regression models. Results: Overall, 279 patients (mean age 66.1 years, 59.5% female) entered the study; 171 (61%) received at least one iron dose along with DA. Response and its predictability hardly increased through adjunct iron, although baseline ferritin <100 mg/L resulted in a 10 times higher probability of response to the combination than to ESA alone. Baseline Epo had low predictive value, regardless of tumor type or use of adjunct iron, although it varied with sex and age. If criteria for all three - Epo, sTfR, and Hb - were met, probability of preventing transfusions was 97%, dropping to 44%, if all three failed. Conclusions: Changes in ESA treatment recommendations had no impact on the predictability of response. Best prediction is still based on the immediacy of Hb increase. [ABSTRACT FROM AUTHOR]

We thank Drs Sugimoto and Taniguchi for their interest in our publication.[1] In their letter to the editor, they express 2 concerns about the findings of our study. Second, Drs Sugimoto and Taniguchi criticize our findings on shock efficacy as potentially misleading and hypothesize that a comparison based on single shock efficacy may have led to a different result. Why low-voltage shock impedance measurements fail to reliably detect insulation breaches in transvenous defibrillation leads. [Extracted from the article]

Introduction: The determination of the electrolytes sodium and potassium is essential in critical care. In daily clinical practice, both the blood gas analyzer (ABG) and the laboratory autoanalyzer (AA) are generally applied. However, there is still uncertainty regarding the convergence of the prementioned assays, and data about the comparability dependent on the pH value are still lacking.Materials and Methods: One hundred samples from intensive care unit patients with a range in pH values between 7.20 and 7.49 were evaluated in this retrospective cohort study. All patients suffered an infarct-related cardiogenic shock and were intubated and not under therapeutical hypothermia at the time of blood collection. We used scatter plots to compare different distributions of sodium and potassium values between the methods. Comparability of the analyses was assessed using the Bland-Altmann approach, and intraclass correlations (ICC) as estimates of interrater reliability were calculated.Results: The mean potassium level measured on ABG was 4.33 mmol/L (SD 0.48 mmol/L), and the value obtained using the AA was 4.40 mmol/L (SD 0.55 mmol/L). A Bland-Altman comparison for total potassium measurements revealed that the limits of agreement were small (-0.241 to 0.391 mmol/L). Total ICC displayed a very good correlation of 0.949. For sodium, we found average values of 140 mmol/L (SD 5.20 mmol/L) in the AA and 140 mmol/L (SD 5.80 mmol/L) in the ABG assessment. Contrarily, the Bland-Altman comparison for sodium displayed that the 95% limits of agreement were very wide (-5.99 to 6.59 mmol/L) for total measurements as well as in every pH subgroup. Total ICC only reached a value of 0.830.Conclusion: Data from our single-center study indicate that urgent and vital decisions based on potassium measurements can be made by trusting the value obtained on the ABG machine irrespective of pH values. [ABSTRACT FROM AUTHOR]

Regularly reported patient surveys are an important dimension of hospital quality management. This study investigates whether providing hospital staff with interim feedback on patient survey results following a best practices workshop can help hospitals improve patient centeredness. Standardized surveys with consecutive patient samples were administered in accredited breast cancer center (BCC) hospitals in one German state (18 million inhabitants), over a 6-month period, in 2012. Two studies were conducted by applying a combination of regression point displacement (RPD) and interrupted time series (ITS) designs. In Study 1, 2 of the 27 hospitals that had previously participated in a best practices workshop to discuss patient-centeredness issues were randomly chosen and were provided interim feedback of patient survey results and workshop minutes. In Study 2, 4 randomly chosen hospitals of 32 that had not participated in the workshop also received interim feedback but no workshop minutes. Control hospitals in both studies neither received feedback nor workshop minutes. The impact of interim feedback was evaluated by applying graphical assessments and multiple regression analyses. Both graphical assessments (locally weighted scatterplot smoothing (LOESS) lines, RPD plots) suggested an effect of interim feedback. Multiple regression results did not unambiguously support these findings. The suggested design approach may prove particularly useful to assess effects in pilot studies, when resources are not available to conduct a randomized study or when its conduct is contingent on initial, positive evidence. [ABSTRACT FROM AUTHOR]

Objectives: To systematically review the prevalence of bacteraemia, triggered by dental intervention and home oral hygiene practices, in children. The network meta‐analysis (NMA) quantitatively compared the risk of bacteraemia triggered by dental extractions and home and professional cleaning procedures. Materials and Methods: Clinical trials with the outcome "bacteraemia in children" were searched. The NMA was performed using the frequentist weighted least‐squares approach comparing the odds ratios (OR) of different interventions. Results: Among 11 of 13 studies, dental treatment was performed under general anaesthesia. In 2,381 patients, bacteraemia occurred in 38.7%–56% patients following single‐tooth extractions, in 22%–46% after manual toothbrushing (MTB), and in 26%–78% after power toothbrushing (PTB). When MTB was set as the reference (OR 1), rubber cup polishing showed a slightly higher risk (OR 1.26) of bacteraemia. PTB presented a higher risk (OR 1.79–2.27) than with single‐tooth extractions (OR 1.55) but lower than that with multiple extractions (OR 2.55). Conclusion: Daily use of MTB and routine professional cleaning were associated with the lowest risk of developing bacteraemia in children with gingivitis, almost as much as with a single‐tooth extractions. Improved plaque control with PTB increased the risk of bacteraemia. There is limited evidence on gingivitis‐free and systemically‐diseased children. [ABSTRACT FROM AUTHOR]

Aims: The impact of type of first medical contact (FMC) in the setting of a guideline conform metropolitan ST-elevation myocardial infarction (STEMI) network providing obligatory primary percutaneous coronary intervention (PCI) is unclear. Methods and Results: 3,312 patients were prospectively included between 2006 and 2012 into a registry accompanying the “Cologne Infarction Model” STEMI network, with 68.4% primarily presenting to emergency medical service (EMS), 17.6% to non-PCI-capable hospitals, and 14.0% to PCI-capable hospitals. Median contact-to-balloon time differed significantly by FMC with 89 minutes (IQR 72–115) for EMS, 107 minutes (IQR 85–148) for non-PCI- and 65 minutes (IQR 48–91) for PCI-capable hospitals (p < 0.001). TIMI-flow grade III and in-hospital mortality were 75.7% and 10.4% in EMS, 70.3% and 8.6% in non-PCI capable hospital and 84.4% and 5.6% in PCI-capable hospital presenters, respectively (p both < 0.01). The association of FMC with in-hospital mortality was not significant after adjustment for baseline characteristics, but risk of TIMI-flow grade < III remained significantly increased in patients presenting to non-PCI capable hospitals. Conclusion: Despite differences in treatment delay by type of FMC in-hospital mortality did not differ significantly. The increased risk of TIMI-flow grade < III in patients presenting to non PCI-capable hospitals needs further study. [ABSTRACT FROM AUTHOR]

Introduction: Selective serotonin and norepinephrine reuptake inhibitors (SNRI) are among the most prescribed antidepressants, and dose escalation is a frequently applied strategy after non-response to an initially prescribed dose. Objective: This meta-analysis aimed to find evidence of a dose-response relationship or to the contrary in direct comparisons of different SNRI doses in patients with major depressive disorder. Methods: A systematic literature search for RCTs comparing at least two doses of SNRIs was carried out in CENTRAL, PubMed, PsycINFO, and EMBASE. Doses were classified as high, medium, and low according to manufacturers' product monographs and analyses at the level of SNRIs as a group and for single substances, accompanied by sensitivity network meta-analyses (Prospero CRD42018081031). Results: From 2,070 studies screened, we included 26 studies with a total of 10,242 patients. Comparisons of medium versus low and high versus medium doses resulted in clinically and statistically non-significant standardized mean differences of –0.06 (–0.16 to 0.04) and –0.06 (–0.16 to 0.03) in favor of higher doses. In the analyses of single substances, no statistically significant results emerged, and many contrasts yielded very small effect sizes. Dropouts due to side effects tended to be more frequent with higher doses. Heterogeneity was low. Network meta-analyses of direct comparisons supported the findings, as did a risk of bias analysis. Conclusion: Based on the lack of positive evidence for a dose-response relationship in SNRIs as a group and in single SNRIs, we recommend prescribing medium doses. In case of insufficient response, we do not recommend increasing the dose of SNRIs. [ABSTRACT FROM AUTHOR]

Purpose: Esophageal perforation is associated with high morbidity and mortality. In addition to surgical treatment, endoscopic endoluminal stent placement and endoscopic vacuum therapy (EVT) are established methods in the management of this emergency condition. Although health-related quality of life (HRQoL) is becoming a major issue in the evaluation of any therapeutic intervention, not much is known about HRQoL, particularly in the long-term follow-up of patients treated for non-neoplastic esophageal perforation with different treatment strategies. The aim of this study was to evaluate patients' outcome after non-neoplastic esophageal perforation with focus on HRQoL in the long-term follow-up. Methods: Patients treated for non-neoplastic esophageal perforation at the University Hospital Cologne from January 2003 to December 2014 were included. Primary outcome and management of esophageal perforation were documented. Long-term quality of life was assessed using the Gastrointestinal Quality of Life Index (GIQLI), the Health-Related Quality of Life Index (HRQL) for patients with gastroesophageal reflux disease (GERD), and the European Organization for Research and Treatment of Cancer (EORTC) questionnaires for general and esophageal specific QoL (QLQ-C30 and QLQ-OES18). Results: Fifty-eight patients were included in the study. Based on primary treatment, patients were divided into an endoscopic (n = 27; 46.6%), surgical (n = 20; 34.5%), and a conservative group (n = 11; 19%). Short- and long-term outcome and quality of life were compared. HRQoL was measured after a median follow-up of 49 months. HRQoL was generally reduced in patients with non-neoplastic esophageal perforation. Endoscopically treated patients showed the highest GIQLI overall score and highest EORTC general health status, followed by the conservative and the surgical group. Conclusion: HRQoL in patients with non-neoplastic esophageal perforation is reduced even in the long-term follow-up. Temporary stent or EVT is effective and provides a good alternative to surgery, not only in the short-term but also in the long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to show differences between breast cancer patients ≤35 and >35 years with regard to tumor characteristics and to present the patient-relevant outcomes overall survival (OAS) and recurrence-free survival (RFS). Methods: We analyzed data from 119 women aged 35 years or younger with breast cancer and compared multiple parameters against breast cancer patients between 36 and 55 ( n = 1,097), all pre-menopausal. Data were adjusted for tumor characteristics and therapy. Results: There was no statistically significant difference in tumor size, axillary lymph node involvement, and histological subtypes. On the contrary, grading lymphovascular invasion and receptor negativity showed statistically significant differences. Unadjusted hazard ratio are 2.11 (1.32–3.39) (OAS) and 1.92 (1.35–2.73) (RFS). Multi-adjusted hazard ratio are 2.97 (1.70–5.18) (OAS) and 2.11 (1.42–3.13) (RFS). Conclusions: In conclusion, young breast cancer patients still have a poor prognosis. Even after adjustment of the data, OAS and RFS showed a worse prognosis. Normal prognostic factors like tumor size, axillary lymph node involvement, and grading can therefore be not the explanation for the more aggressive disease progress within early onset breast cancer patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article by S. Schrodi et al published in the journal.

Purpose: Baroreflex activation therapy (BAT) has been shown to lower blood pressure in patients with resistant hypertension. The purpose of this study was to analyze whether this translates into a reduction of more relevant clinical endpoints. Methods: Patients with resistant hypertension were treated with the second-generation BAT system. Records on hospitalization (dates of admission and discharge, main diagnosis) were obtained from medical insurance companies. Results: Records on hospitalization were available for a period of 1 year before BAT in two patients and 2 years in 22 patients. The total number of hospitalizations per patient was 3.3 ± 3.5/year before BAT and 2.2 ± 2.7/year after BAT (p = 0.03). Hospitalizations related to hypertension were significantly decreased from 1.5 ± 1.6/year before BAT to 0.5 ± 0.9/year after BAT (p < 0.01). The cumulative duration of hypertension-related hospital stays was significantly reduced from 8.0 ± 8.7 days/year before BAT to 1.8 ± 4.8 days/year after BAT (p < 0.01). Office cuff blood pressure was 183 ± 27 mmHg over 102 ± 17 mmHg under 6.6 ± 2.0 antihypertensive drugs before BAT and 157 ± 32 mmHg over 91 ± 20 mmHg (both p < 0.01) under 5.9 ± 1.9 antihypertensive drugs (p = 0.09 for number of drugs) at latest follow-up. Daytime ambulatory blood pressure was 164 ± 21 mmHg over 91 ± 14 mmHg before BAT and 153 ± 21 mmHg (p = 0.03) over 89 ± 15 mmHg (p = 0.56) at latest follow-up. Heart rate was 75 ± 16 bpm before BAT and 72 ± 12 bpm at latest follow-up (p = 0.35). Conclusions: Rate and duration of hypertension-related hospitalizations in patients with severe resistant hypertension were lowered after BAT. Whether the response is mediated through improvements in blood pressure control requires further studies. [ABSTRACT FROM AUTHOR]

Study Design: Prospective cohort study.Objective: We aimed to determine the 2-year survival and to identify clinical and microbiological characteristics of patients with native vertebral osteomyelitis (VO) as compared to postoperative VO to find further strategies for improvement of the management of VO.Summary Of Background Data: A relevant subgroup (20%-30%) of patients with VO has a history of spine surgery. Infection in these patients might be clinically different from native VO. However, clinical, microbiological, and outcome characteristics of this disease entity have not been well studied as most trials either excluded these patients or are limited by a small cohort and short observation period.Methods: Between 2008 and 2013, patients who presented at a tertiary care center with symptoms and imaging findings suggestive of VO were reviewed by specialists in infectious diseases, clinical microbiology, and orthopedics to confirm the diagnosis and followed prospectively for a period of 2 years. Statistical analysis for group comparisons, survival analysis, and uni- and multivariable Cox regression models were performed.Results: Thirty percent of the patients with VO (56/189) reported a history of spine surgery in the same segment. Patients with postoperative infection had a lower ASA score (American Society of Anesthesiologists) (P = 0.01) and were less likely to suffer from comorbidities compared to native cases (P = 0.003). Infections caused by coagulase-negative staphylococci (33.3 vs. 6.5%, P < 0.001) and other bacteria of the skin flora (15.2 vs. 0%, P = 0.002) were more prevalent in postoperative patients. Suffering from native VO increased the 2-year mortality risk 3-fold, also when adjusted for the remaining risk factors ASA score and number of comorbidities (hazard ratio 2.916 [95% confidence interval 1.215 -6.999], P = 0.017).Conclusion: Beside clear microbiological differences, the significant better 2-year survival supports the concept of postoperative VO presenting a distinct disease entity. The subtle disease presentation of patients with postoperative VO should not attenuate clinical suspicion of physicians.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

Cognitive behavioral therapy for psychosis (CBT) is an effective treatment in adult patients with schizophrenia. However, no randomized controlled and blinded trial in adolescents with early-onset psychosis (EOP) has been conducted. Therefore, the present pilot study explores the acceptance, tolerability, feasibility, and safety of a modified CBT in adolescents with EOP. Twenty-five adolescents with EOP were randomized to either 9 months (20 sessions) of CBT + treatment as usual (TAU) or TAU alone. The primary endpoint was the PANSS-positive subscale (P1-7). Secondary endpoints included psychopathology, global functioning, and quality of life (QoL). Acceptance, tolerability, feasibility, and safety were assessed. Blinded assessments took place by the end of the treatment (9 months) and at 24-month follow-up. Despite improvements in both groups and lack of statistical significance between CBT + TAU and TAU regarding the primary endpoint, we observed between-group effect sizes of at least d = 0.39 in favor of CBT + TAU at post-treatment for delusions, negative symptoms, functioning and QoL after the intervention and effect sizes of at least d = 0.35 after 24 months. CBT in EOP was highly acceptable (73.5% agreed to randomization), well-tolerated (83.1% attendance rate, no drop-outs), and safe (one serious adverse event (SAE) in CBT + TAU in comparison with six SAEs in TAU). These findings suggest that CBT adapted to the needs of adolescents with EOP is a promising approach regarding negative symptoms, functioning, and QoL. CBT is a safe and tolerable treatment. However, due to the small sample size and the pilot character of the study, these conclusions are limited, and should be tested in a larger, adequately powered randomized controlled trial. [ABSTRACT FROM AUTHOR]

Aim: Psychological interventions, such as cognitive behavioural therapy (CBT) and supportive counselling (SC), are used to treat people with schizophrenia and people at clinical high risk (CHR) of psychosis. However, little information is available on predictors of treatment response. This study aims to identify such predictors of psychological interventions in CHR. Methods: A total of 128 help‐seeking CHR outpatients were randomized into two groups—integrated psychological intervention (IPI), including CBT, and SC—for 12 months. Multiple regression analysis was used to identify demographic, symptomatic and functional variables that predict improvement in positive (PANSS Positive), negative (PANSS Negative) and basic symptoms (Basic symptom total score) and improvement in functioning (GAF) at 1‐year follow up. Results: In the merged group (IPI + SC), people who lived independently, were younger and presented with higher baseline functioning showed more improvement in symptomatic outcomes at follow up. Negative symptoms at baseline predicted less improvement in positive and basic symptoms. Being married or cohabiting and living in the primary family were found to correlate with good functioning at 1‐year follow up. Conclusions: Younger CHR individuals and those who are functioning well may particularly benefit from early intervention. Treatment might need to be modified for low‐functioning CHR and those who already display higher scores of negative symptoms. Registration number: NCT00204087 [ABSTRACT FROM AUTHOR]

For nasal application of neurotrophins and mesenchymal stem cells, successful delivery to the brain and therapeutic effects are known from experimental data in animals. Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. This is a first exploration on additional nasal breast milk and neuromorphological outcome after severe neonatal brain injury. We present a retrospective summary of 31 very low birth weight preterm infants with intraventricular hemorrhage °3/4 from one third-level neonatal center. All were breast milk fed. Sixteen infants additionally received nasal drops of fresh breast milk daily with informed parental consent for at least 28 days. Cerebral ultrasound courses were reviewed by a pediatric radiologist blinded to the intervention. The main outcome measure was severity of porencephalic defects before discharge. Clinical covariates were comparable in both groups. With nasal breast milk, a trend to a lower incidence for severe porencephalic defects (21% vs. 58%) was detected. Incidences were lower for progressive ventricular dilatation (71% vs. 91%) and surgery for posthemorrhagic hydrocephalus (50% vs. 67%).Conclusion: The hypothesis is generated that early intranasal application of breast milk could have a beneficial effect on neurodevelopment in preterm infants. Controlled investigation is needed. What is Known:• Successful delivery to the brain and therapeutic effects are known for nasal application of neurotrophins and mesenchymal stem cells from experimental data in animal studies.• Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. What is New:• This is the first report on additional nasal breast milk application in very low birth weight preterm infants with severe brain injury observing a trend for less severe porencephalic defects.• The hypothesis is generated that nasal breast milk might exert neuroprotective effects in preterm infants. [ABSTRACT FROM AUTHOR]

Background This study evaluates whether preoperative statin therapy improves clinical outcomes in patients referred to coronary artery bypass grafting (CABG) for acute coronary syndrome (ACS). Methods A total of 1,151 patients undergoing CABG for ACS were prospectively entered into the North-Rhine-Westphalia surgical myocardial infarction registry and subdivided into two groups according to their preoperative statin status (statin naive vs. statin group). A logistic regression model was employed to analyze the impact of a statin therapy and dose for the endpoints in-hospital mortality and major adverse cardiac events (MACE). Results Demographics, pre- and intraoperative data of the statin-naive group (n = 208; 18%) and statin-treated group (n = 943, 82%) did not differ. In-hospital mortality (12.6 vs. 6.3%, p = 0.002) and MACE rates (22.1 vs. 9.7%, p < 0.001) were significantly higher in statin naive when compared with statin-treated patients with ACS, respectively. Mevalonic acid revealed that both low- and high-dose statin treatment was associated to a reduction in in-hospital mortality and MACE, without a dose-dependent statin effect. Conclusion Statin therapy in patients with ACS undergoing CABG reduces in a dose-independent manner in-hospital mortality and MACE. [ABSTRACT FROM AUTHOR]

Purpose: Hyponatremia is a common electrolyte abnormality seen in hospitalized patients. It may cause a variety of symptoms and is associated with longer hospitalizations and higher mortality. However, to date, only little is known about the extent of hyponatremia in patients with incurable diseases and whether it is associated with physical symptoms in this patient group. This study aims to describe the prevalence of hyponatremia, associated symptoms, and symptom intensity in inpatients with hyponatremia receiving specialist palliative care (SPC).Methods: This is a retrospective study. Demographic and clinical data as well as symptoms, scored symptom intensity, and laboratory values were collected. All inpatients of a large German University Hospital receiving SPC in 2013 with documented sodium values were included.Results: In 2013, 789 inpatients received SPC of which 710 had documented sodium values. The prevalence of hyponatremia was 38.7% (275/710). A mild degree showed 220 (31,0%), 44 (6.2%) had a moderate, and 11 (1.6%) a severe form. Hyponatremia patients experienced significantly more symptoms than normonatremic patients (mean = 7.71 vs 6.63; p < 0.001). Breathlessness, depressiveness, nausea, vomiting, poor appetite, constipation, and weakness were significantly more frequent in patients with hyponatremia. Furthermore, hyponatremia severity was associated with higher symptom intensity (mean = 13.29 vs 11.28; p < 0.001).Conclusions: More than one third of all SPC patients showed a hyponatremia, and the hyponatremia grade was associated with symptom burden and symptom intensity. A prospective analysis is needed to further examine this association and the possible influence of hyponatremia correction on symptom burden reduction. [ABSTRACT FROM AUTHOR]

The present study was conducted to assess the diagnostic accuracy of Acoustic Structure Quantification (ASQ) ultrasound software in liver biopsy of patients with liver fibrosis and cirrhosis. Eighty patients (47 ± 14 y, 41 men) with chronic liver diseases underwent ultrasound examination of the liver and liver biopsy. In addition to the standard-care ultrasound examination, three valid gray-scale images were obtained for each patient. With the ASQ software, the average and peak values ( C m 2 ) of each ultrasound gray-scale image were calculated and then compared with histologic fibrosis staging (F0–F4). No correlation was found between ASQ values and histologic fibrosis stage ( p > 0.05). Areas under the curve for the diagnosis of no or mild fibrosis (F0 and F1), moderate/severe fibrosis (F2 and F3) and cirrhosis (F4) using average/peak C m 2 values of small regions of interest were 0.46/0.43, 0.62/0.68 and 0.38/0.33. Determination of liver fibrosis with ASQ in its present form as an alternative approach to liver biopsy is too imprecise. [ABSTRACT FROM AUTHOR]

Background: Thrombotic microangiopathies (TMA) in adults such as thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are life-threatening disorders if untreated. Clinical presentation is highly variable and prognostic factors for clinical course and outcome are not well established. Methods: We performed a retrospective observational study of 62 patients with TMA, 22 males and 40 females aged 16 to 76 years, treated with plasma exchange at one center to identify clinical risk factors for the development of renal insufficiency. Results: On admission, 39 of 62 patients (63%) had acute renal failure (ARF) with 32 patients (52%) requiring dialysis treatment. High systolic arterial pressure (SAP, p = 0.009) or mean arterial pressure (MAP, p = 0.027) on admission was associated with acute renal failure. Patients with SAP>140 mmHg on admission had a sevenfold increased risk of severe kidney disease (OR 7.464, CI 2.097-26.565)> MAP.100 mmHg indicated a fourfold increased risk for acute renal failure (OR 4.261, CI 1.400-12.972). High SAP, diastolic arterial pressure (DAP), and MAP on admission were also independent risk factors for persistent renal insufficiency with the strongest correlation for high MAP. Moreover, a high C-reactive protein (CRP) level on admission correlated with renal failure in the course of the disease (p = 0.003). At discharge, renal function in 11 of 39 patients (28%) had fully recovered, 14 patients (23%) remained on dialysis, and 14 patients (23%) had non-dialysisdependent chronic kidney disease. Seven patients (11%) died. We identified an older age as risk factor for death. Conclusions: High blood pressure as well as high CRP serum levels on admission are associated with renal insufficiency in TMA. High blood pressure on admission is also a strong predictor of sustained renal insufficiency. Thus, adult TMA patients with high blood pressure may require special attention to prevent persistent renal failure. [ABSTRACT FROM AUTHOR]

Background and Aims: This study investigated the long-term clinical course of patients with Schatzki rings, who were treated by single bougie dilation. Furthermore, it analyzed possible predictors for the time of recurrence.Patients and Methods: A total of 133 patients (100 males, 33 females) with a mean age of 57 ± 14.6 years who were treated by single dilation with the use of Maloney bougies without the aid of fluoroscopy were prospectively registered and followed-up for a mean duration of 58.3 months (range 12-240 months). Duration of remission was evaluated by Kaplan-Meier estimates with regard to recurrence. Log-rank test was performed to analyze possible predictors for the time to second dilation (recurrence).Results: No complications occurred and all patients were symptom-free at the first follow-up examination 4 weeks after dilation. However, later on, 73 patients required a second dilation. The estimate remission rates were 63.8% (95% CI: 55.6-72.0%) after 2 years, 44.3% (95% CI: 35.4-53.4%) after 5 years, and 39.9% (95% CI: 30.5-49.3%) after 10 years. Neither the initial morphological findings, nor age or gender determined the need for repeated dilation. Only patients treated with a large bougie diameter (≥52 F) seemed to have a tendency for a longer time until symptomatic recurrence.Conclusions: Single dilation of symptomatic Schatzki rings is a safe and effective therapy. However, more than half of the patients will need a second treatment. Recurrences are unrelated to initial morphological findings, age, or gender. Only the treatment with a large bougie diameter (≥52 F) showed a tendency for a longer time of remission. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2010) : 786-792 Vascular endothelial growth factor (VEGF) plays an important role in promoting angiogenesis and is overexpressed in several malignancies. Polymorphisms of the VEGF gene can alter VEGF protein expression, which may be biologically significant and account for heterogeneity in disease risk and outcome. The aim of this case-control study was to evaluate potential associations between single nucleotide polymorphisms (SNP) of the VEGF gene with susceptibility of oral squamous cell carcinoma (OSCC). Five VEGF SNP (−1154 G/A, +405 G/C, +936 C/T, −2578 C/A and −460 C/T) were determined in peripheral blood isolated from 80 patients with OSCC and from 40 age- and gender-matched healthy volunteers (RT-PCR). The +936 T allele and the −2578 C/A SNP were expressed significantly more often in the OSCC-group ( P = 0.002; P < 0.0001) where three associations between two SNPs (+936 and +405, −2578 and −1154, −460 and −2578) were found. Our findings provide support that +936 T allele and −2578 C/A SNP of the VEGF gene alone or in combination with other SNP are associated with OSCC. The SNPs may be used as biomarker for the development of specialized anti-VEGF drugs. Further studies must confirm the value of preoperative genetic analysis for prognosis. [ABSTRACT FROM AUTHOR]

Summary: Costimulatory molecules have complementary effects on T-cell activation and their balance may control the development of oral cancer. The aim of this study was to determine the relevance of cytotoxic T-lymphocyte antigen 4 (CTLA-4), CD28 and inducible costimulator (ICOS) polymorphisms in oral squamous cell carcinoma (OSCC). Genotyping for CTLA-4 (−1661 A/G and +49 A/G), CD28 (0 C/G and +3160 G/T) and ICOS (+637 A/C and +1599 C/T) was performed in the 83 patients with OSCC, compared to the 40 unrelated healthy volunteers as controls. The genotype CTLA-4 −1661 was significantly different between the patient group and the control group. The allele CTLA-4 −1661 G was significantly found more frequent in patients with OSCC (p =0.001). In bivariate analysis, noticeable differences between OSCC and controls were seen. The combinations CTLA-4 −1661 G/G and CTLA-4 +49 A/G, ICOS +1559 C/T and ICOS +1559 C/C each with CTLA-4 −1661 G/G, ICOS +637 C/C and ICOS +637 A/C each with CTLA-4 −1661, CTLA-4 −1661 A/G and ICOS +637 C/C, CD28 +3160 G/T and CTLA-4 −1661 A/A and CD28 +3160 G/T and CTLA-4 −1661 A/G were seen in the patient group only. Especially the polymorphisms of the CTLA-4 −1661-genotype – alone and in combination with other T cell regulator polymorphisms – seem to be possible predisposing factors for OSCC. Therefore, they might be future targets for a primary prophylaxis or an individualised therapy. [Copyright &y& Elsevier]

For nasal application of neurotrophins and mesenchymal stem cells, successful delivery to the brain and therapeutic effects are known from experimental data in animals. Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. This is a first exploration on additional nasal breast milk and neuromorphological outcome after severe neonatal brain injury. We present a retrospective summary of 31 very low birth weight preterm infants with intraventricular hemorrhage °3/4 from one third-level neonatal center. All were breast milk fed. Sixteen infants additionally received nasal drops of fresh breast milk daily with informed parental consent for at least 28 days. Cerebral ultrasound courses were reviewed by a pediatric radiologist blinded to the intervention. The main outcome measure was severity of porencephalic defects before discharge. Clinical covariates were comparable in both groups. With nasal breast milk, a trend to a lower incidence for severe porencephalic defects (21% vs. 58%) was detected. Incidences were lower for progressive ventricular dilatation (71% vs. 91%) and surgery for posthemorrhagic hydrocephalus (50% vs. 67%).Conclusion: The hypothesis is generated that early intranasal application of breast milk could have a beneficial effect on neurodevelopment in preterm infants. Controlled investigation is needed. What is Known: • Successful delivery to the brain and therapeutic effects are known for nasal application of neurotrophins and mesenchymal stem cells from experimental data in animal studies. • Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. What is New: • This is the first report on additional nasal breast milk application in very low birth weight preterm infants with severe brain injury observing a trend for less severe porencephalic defects. • The hypothesis is generated that nasal breast milk might exert neuroprotective effects in preterm infants. [ABSTRACT FROM AUTHOR]

Background: Analgosedation is a cornerstone therapy for mechanically ventilated patients in intensive care units (ICU). To avoid inadequate sedation and its complications, monitoring of analgosedation is of great importance. The aim of this study was to investigate whether monitoring of analgosedative drug concentrations (midazolam and sufentanil) might be beneficial to optimize analgosedation and whether drug serum concentrations correlate with the results of subjective (Richmond Agitation-Sedation Scale [RASS]/Ramsay Sedation Scale) and objective (bispectral (BIS) index) monitoring procedures. Methods: Forty-nine intubated, ventilated, and analgosedated critically ill patients treated in ICU were clinically evaluated concerning the depth of sedation using RASS Score, Ramsay Score, and BIS index twice a day. Serum concentrations of midazolam and sufentanil were determined in blood samples drawn at the same time. Clinical and laboratory data were statistically analyzed for correlations using the Spearman’s rank correlation coefficient rho (ρ). Results: Average age of the population was 57.8 ± 16.0 years, 61% of the patients were males. Most frequent causes for ICU treatments were sepsis (22%), pneumonia (22%), or a combination of both (25%). Serum concentrations of midazolam correlated weakly with RASS (ρ = − 0.467) and Ramsay Scores (ρ = 0.476). Serum concentrations of sufentanil correlated weakly with RASS (ρ = − 0.312) and Ramsay Scores (ρ = 0.295). Correlations between BIS index and serum concentrations of midazolam (ρ = − 0.252) and sufentanil (ρ = − 0.166) were low. Conclusion: Correlations between drug serum concentrations and clinical or neurophysiological monitoring procedures were weak. This might be due to intersubject variability, polypharmacy with drug-drug interactions, and complex metabolism, which can be altered in critically ill patients. Therapeutic drug monitoring is not beneficial to determine depth of sedation in ICU patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES The aim of this retrospective study was to assess pre- and intraoperative factors leading to neurological complications and early death following repair of acute type A aortic dissection (ATAAD). METHODS There were 122 patients (85 male, age: 58.6 ± 12.5 years) with ATAAD, treated consecutively from August 2003 to August 2010. Pre- and intraoperative variables were analysed using a logistic regression model in order to identify risk factors for temporary neurological dysfunction (TND) and adverse outcome (AO), defined as stroke and 30-day mortality. RESULTS The 30-day mortality rate was 16.4%. Forty-one patients (33.6%) suffered transient neurological dysfunction and 20 (16.4%) had a postoperative stroke. Mean hypothermic circulatory arrest (HCA) temperature was 24 ± 4°C. Selective cerebral perfusion (SCP) was performed in 99 (82%) patients, with a mean SCP flow rate of 10.3 ml/kg/min. The duration of lower body ischaemia (LBI) was 36 ± 27 min, of HCA 8.7 ± 15.5 min and of SCP 34 ± 28 min, respectively. Male gender [odds ratio (OR): 3.30, 95% confidence interval (CI): 1.15–9.47], diabetes (OR: 3.95, 95% CI: 1.18–13.24), compromised consciousness (OR: 6.65, 95% CI: 1.41–31.48) and manifest arterial atherosclerosis (OR: 6.68, 95% CI: 1.31–34.09) were detected as risk factors for TND, whereas a high body mass index (OR: 1.14, 95% CI: 1.01–1.3), a preoperative malperfusion syndrome (OR: 2.28, 95% CI: 0.84–6.18) and left ventricular ejection fraction <50% (OR: 3.84, 95% CI: 1.41–10.43) were detected as independent predictors for an AO. A dissection entry localized in the aortic arch or the descending aorta independently increased the risk for a postoperative stroke. A prolonged LBI increased the risk for AO (OR: 1.02, 95% CI: 1.00–1.04), whereas femoral cannulation showed a trend to an increased stroke incidence (OR: 4.2, 95% CI: 0.8–21.3). CONCLUSIONS Regardless of standardized neuroprotective techniques, treatment of ATAAD remains a high-risk operation. Preoperatively, the presence of a reduced ejection fraction, a malperfusion syndrome or a high body mass index may increase the perioperative risk for an adverse outcome. A dissection ‘entry’ localized in the aortic arch or the descending aorta may increase the risk for postoperative stroke. Intraoperatively, cannulation of the femoral artery and extension of the LBI time over 45 min should be avoided. Especially in patients with manifest preoperative cerebral and/or end-organ malperfusion, the cannulation modality as well as the entire neuroprotective management should be chosen individually, respecting its limitations. [ABSTRACT FROM PUBLISHER]