Potential of FX06 to prevent disease progression in hospitalized non-intubated COVID-19 patients - the randomized, EU-wide, placebo-controlled, phase II study design of IXION.

BACKGROUND: More than 2.7 million hospitalizations of COVID-19-infected patients have occurred in Europe alone since the outbreak of the coronavirus in 2020. Interventions against SARS-CoV-2 are still in high need to prevent admissions to ICUs worldwide. FX06, a naturally occurring peptide in humans and other mammals, has the potential to reduce capillary leak by improving endothelial dysfunction and thus preventing the deterioration of patients. With IXION, we want to investigate the potential of FX06 to prevent disease progression in hospitalized, non-intubated COVID-19 patients. METHODS: IXION is an EU-wide, multicentre, placebo-controlled, double-blinded, parallel, randomized (2:1) phase II clinical study. Patient recruitment will start in September 2022 (to Q2/2023) in Germany, Italy, Lithuania, Spain, Romania, Portugal, and France. A total of 306 hospitalized patients (≥ 18 years and < 75 years) with a positive SARS-CoV-2 PCR test and a COVID-19 severity of 4-6 according to the WHO scale will be enrolled. After randomization to FX06 or placebo, patients will be assessed until day 28 (and followed up until day 60). FX06 (2 × 200 mg per day) or placebo will be administered intravenously for 5 consecutive days. The primary endpoint is to demonstrate a difference in the proportion of patients with progressed/worsened disease state in patients receiving FX06 compared to patients receiving placebo. Secondary endpoints are lung function, oxygen saturation and breathing rate, systemic inflammation, survival, capillary refill time, duration of hospital stay, and drug accountability. DISCUSSION: With IXION, the multidisciplinary consortium aims to deliver a new therapy in addition to standard care against SARS-CoV-2 for the clinical management of COVID-19 during mild and moderate stages. Potential limitations might refer to a lack of recruiting and drop-out due to various possible protocol violations. While we controlled for drop-outs in the same size estimation, recruitment problems may be subject to external problems difficult to control for. TRIAL REGISTRATION: EudraCT 2021-005059-35 . Registered on 12 December 2021. Study Code TMP-2204-2021-47.

Establishment and Characterization of a Unilateral UV-Induced Photoreceptor Degeneration Model in the C57Bl/6J Mouse.

Purpose: To investigate whether UV irradiation of the mouse eye can induce photoreceptor degeneration, producing a phenotype reminiscent of the rd10 mouse, left eyes of female C57Bl/6J mice were irradiated with a UV LED array (370 nm). A lens was placed between the cornea and LED, allowing illumination of about one-third of the retina. The short-term and long-term effects on the retina were evaluated. Methods: First, a dose escalation study, in which corneal dosages between 2.8 and 9.3 J/cm2 were tested, was performed. A dosage of 7.5 J/cm2 was chosen for the following characterization study. Before and after irradiation slit-lamp examinations, full-field electroretinography, spectral domain optical coherence tomography and macroscopy were performed. After different time spans (5 days to 12 weeks) the animals were sacrificed and the retinae used for immunohistochemistry or multielectrode array testing. Right eyes served as untreated controls. Results: In treated eyes, spectral domain optical coherence tomography revealed a decrease in retinal thickness to 53%. Full-field electroretinography responses decreased significantly from day 5 on in treated eyes. Multielectrode array recordings revealed oscillatory potentials with a mean frequency of 5.2 ± 0.6 Hz in the illuminated area. Structural changes in the retina were observed in immunohistochemical staining. Conclusions: UV irradiation proved to be efficient in inducing photoreceptor degeneration in the mouse retina, while leaving the other retinal layers largely intact. The irradiated area of treated eyes can be identified easily in spectral domain optical coherence tomography and in explanted retinae. Translational Relevance: This study provides information on anatomic and functional changes in UV-treated retina, enabling the use of this model for retinitis pigmentosa-like diseases in animals suited for experimental retinal surgery.

Perfusion-related changes in intestinal diffusion detected by NMR-MOUSE® monitoring in minipigs.

OBJECTIVE: The aim was to investigate perfusion-related changes in the intestinal diffusion assessed by NMR-MOUSE monitoring in minipigs. This was a follow-up study of previous experiments on landrace pigs demonstrating the feasibility of NMR-MOUSE monitoring in large animals. METHODS: 5 mature female minipigs (mean body weight 50 ±â€¯2 kg) underwent laparotomy with exposition of several small intestinal loops and their feeding vessels. The loops were examined consecutively using NMR-MOUSE monitoring for assessment of intestinal proton diffusion (fast diffusion component [FC] and slow diffusion component [SC]) and oxygen to see monitoring (O2C, LEA Medizintechnik GmbH, Giessen, Germany) for microcirculatory evaluation. Following a baseline measurement on each loop under physiological perfusion, measurements were continued as one of the following main treatments were performed per loop: method 1 - ischemia; method 2 - flow reduction; method 3 - intraluminal glucose followed by ischemia; method 4 - intraluminal glucose followed by flow reduction. Perioperative monitoring was supplemented by blood gas analyses and histopathological assessment of H.E. stained intestinal biopsies. RESULTS: The NMR-MOUSE measurement showed a significant difference in the change to baseline values in the FC during flow reduction compared to the other treatments according to the unadjusted (pM2 vs. M1 < 0.0001, pM2 vs. M3 = 0.0005, pM2 vs. M4 = 0.0005) and the adjusted p-values (pM2 vs. M1 < 0.0001, pM2 vs. M3 = 0.0030, pM2 vs. M4 = 0.0030). In the SC, the difference between ischemia and flow reduction was significant according to the unadjusted p-values (pM2 vs. M1 = 0.0397). Whereas the FC showed a trend towards ongoing increase during ischemia but towards ongoing decrease during flow reduction, the SC showed contrary trends. These effects seemed to be attenuated by prior glucose application. According to the results of O2C monitoring, ischemia as well as flow reduction caused a significant decrease of microcirculatory oxygen saturation (inner probe: methods 1-4 and outer probe methods 1, 2: p < 0.0001; outer probe: pM2 = 0.0001), velocity (inner probe: pM1 < 0.0001, pM2 = 0.0155, pM3 = 0.0027; outer probe: pM1 < 0.0001, pM2 = 0.0045, pM3 = 0.0047, pM4 = 0.0037) and serosal flow (outer probe, methods 1 and 2: p < 0.0001; pM3 = 0.0009, pM4 = 0.0008). The histopathological analysis showed a significant association with time (p = 0.003) but not with the experimental method (p = 0.1386). CONCLUSIONS: Intestinal diffusion is affected significantly by perfusion changes in mature minipigs. As shown by NMR-MOUSE monitoring, ischemia and flow reduction have contrary effects on intestinal diffusion and, additionally, the fast and slow diffusion components show opposite trends during each of those pathological perfusion states. Prior intraluminal glucose application seems to attenuate the effects of malperfusion on intestinal diffusion.

Comparison of urine and serum neutrophil gelatinase-associated lipocalin after open and endovascular thoraco-abdominal aortic surgery and their meaning as indicators of acute kidney injury.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) has been described as a potential biomarker of acute kidney injury (AKI) in different settings, but its behaviour under influence of open and endovascular repair of thoraco-abdominal aortic aneurysms (TAAA) has not been assessed yet. In this study, the course of NGAL was observed and differences of serum- (sNGAL) and urine-NGAL (uNGAL) levels following TAAA repair, especially with regard to AKI, were evaluated. PATIENTS AND METHODS: In this retrospective single centre study, 52 patients (mean age 64.5 years, [43-85 years]), including 39 (75 %) men, were enrolled (2014-2015, 13.2 months mean follow-up). Levels of sNGAL and uNGAL were measured perioperatively for 48 hours on intensive care unit. Twenty-three patients were treated by endovascular and 29 by open TAAA-repair. RESULTS: Logistic regression revealed an increase in NGAL (sNGAL p = 0.0263, uNGAL p = 0.0080) corresponding with an increase in serum creatinine within the first 48 hours. Fourteen patients (26.9 %) developed AKI and 11 (21.1 %) required dialysis. The course of NGAL differed significantly (uNGAL p < .0001, sNGAL p = 0.0002) between patients suffering from AKI requiring dialysis and patients without AKI. The predictive power of uNGAL was three times higher than that of sNGAL (estimate of the regression slope 0.1382 vs. 0.0460). No significant difference between patients undergoing open or endovascular TAAA repair regarding the perioperative course of sNGAL and uNGAL was observed. CONCLUSION: serum-NGAL and urine-NGAL correlate with serum creatinine levels and AKI requiring dialysis. Furthermore, the postoperative course of sNGAL and uNGAL after open and endovascular TAAA repair is not significantly different. Taken together, the results indicate that uNGAL and, to a lesser extent, sNGAL could be considered biomarkers for early detection of perioperative AKI after open and endovascular TAAA surgery.

Oxidation-Reduction Potential in Patients undergoing Transcatheter or Surgical Aortic Valve Replacement.

BACKGROUND: Aortic valve stenosis has gained increasingly more importance due to its high prevalence in elderly people. More than two decades ago, transcatheter aortic valve replacement emerged for patients who were denied surgery, and its noninferiority has been demonstrated in numerous studies. Oxidative stress has generated great interest because of its sensitivity to cell damage and the possibility of offering early hints of clinical outcomes. The aim of the present study was to investigate whether there is a significant difference between transcatheter (TAVR) or surgical aortic valve replacement (SAVR) in terms of the changes in oxidation-reduction potential (ORP) and antioxidant capacity. Therefore, we investigated perioperative oxidative stress levels and their influence on clinical outcomes. METHODS: A total of 72 patients (50% TAVR versus 50% SAVR) were included in the present study. Static oxidation-reduction potential (sORP) and antioxidant capacity were measured using the RedoxSys™ Diagnostic System (Luoxis Diagnostics, USA) in serum samples drawn before and after surgery, as well as on the first postoperative day. In addition, clinical data were obtained to evaluate the clinical outcome of each case. RESULTS: TAVR patients had higher preoperative sORP levels compared to the SAVR patients and more severe comorbidities. Unlike the TAVR cohort, patients in the SAVR group showed a significant difference in sORP from the pre- to postoperative levels. Capacity demonstrated higher preoperative levels in the SAVR cohort and also a greater difference postoperatively compared to the TAVR cohort. Regression analysis revealed a significant correlation between pre- and postoperative capacity levels (r = -0.9931, p < 0.0001), providing a method of predicting postoperative capacity levels by knowing the preoperative levels. According to the multivariable analysis, both sORP and antioxidant capacity are dependent on time point, baseline value, and type of surgery, with the largest variations observed for time effect and surgery method. CONCLUSION: A high preoperative sORP level correlated to more severe illness in the TAVR patients. As the TAVR patients did not show significant differences in their preoperative levels, we assume that there was a smaller production of oxidative agents during TAVR due to the less invasive nature of the procedure. Baseline values and development of antioxidant capacity values strengthen this hypothesis. The significant correlation of pre- and postoperative capacity levels might allow high risk patients to be detected more easily and might provide more adequate and individualized therapy preoperatively. This trial is registered with clinicaltrials.gov, identifier: NCT 02488876.

Evaluation of the NMR-MOUSE as a new method for continuous functional monitoring of the small intestine during different perfusion states in a porcine model.

OBJECTIVE: The study aim was to evaluate a small low-field NMR (nuclear magnetic resonance) scanner, the NMR-MOUSE®, for detecting changes in intestinal diffusion under different (patho-) physiological perfusion states. METHODS: Laparotomy was performed on 8 female landrace pigs (body weight 70±6 kg) and the feeding vessels of several intestinal loops were dissected. Successively, the intestinal loops were examined using O2C (oxygen to see, LEA Medizintechnik GmbH, Giessen, Germany) for microcirculatory monitoring and the NMR-MOUSE® for diffusion measurement (fast and slow components). On each loop the baseline measurement (physiological perfusion) was followed by one of the following main procedures: method 1 -ischemia; method 2 -flow reduction; method 3 -intraluminal glucose followed by ischemia; method 4 -intraluminal glucose followed by flow reduction. Additionally, standard perioperative monitoring (blood pressure, ECG, blood gas analyses) and histological assessment of intestinal biopsies was performed. RESULTS: There was no statistical overall time and method effect in the NMR-MOUSE measurement (fast component: ptime = 0.6368, pmethod = 0.9766, slow component: ptime = 0.8216, pmethod = 0.7863). Yet, the fast component of the NMR-MOUSE measurement showed contrary trends during ischemia (increase) versus flow reduction (decrease). The slow-to-fast diffusion ratio shifted slightly towards slow diffusion during flow reduction. The O2C measurement showed a significant decrease of oxygen saturation and microcirculatory blood flow during ischemia and flow reduction (p < .0001). The local microcirculatory blood amount (rHb) showed a significant mucosal increase (pClamping(method 1) = 0.0007, pClamping(method 3) = 0.0119), but a serosal decrease (pClamping(method 1) = 0.0119, pClamping(method 3) = 0.0078) during ischemia. The histopathological damage was significantly higher with increasing experimental duration and at the end of methods 3 and 4 (p < .0001,Fisher-test). CONCLUSION: Monitoring intestinal diffusion changes due to different perfusion states using the NMR-MOUSE is feasible under experimental conditions. Despite the lack of statistical significance, this technique reflects perfusion changes and therefore seems promising for the evaluation of different intestinal perfusion states in the future. Beforehand however, an optimization of this technology, including the optimization of the penetration depth, as well as further validation studies under physiological conditions and including older animals are required.

Perioperative safety and complications in treatment of oral and maxillofacial surgery patients under general anesthesia with obstructive sleeping disorders.

Patients with sleeping disorders, such as obstructive sleep apnea, (OSA) have a higher risk for postoperative complications after maxillofacial surgery under general anesthesia. The aim of this study was to detect specific complications after oral and maxillofacial surgery. Sixty-nine cases of patients with middle or severe sleep apnea who underwent an operation under general anesthesia in the oral and maxillofacial region were retrospectively analyzed. This group was compared with an age and diagnosis matched group without sleep apnea receiving the same operative treatment. We found a significant difference between the two groups concerning body mass index, the ASA-Index, the Cormack-Mallampati Index, the number of pre-existing conditions, and home medication (p < 0.05). Concerning the length of stay, overrun of estimated mean length of stay, and number of surgical complications and hypertonic events, no difference could be detected. Almost 28% of the patients with OSA in our study suffered a substantial respiratory complication even under intensive care observation. The number of patients with oxygen desaturation was 9% in the control group, which differed significantly (p = 0.0093) from the number of such patients in the OSA group. In this study, we have shown that the presence of OSA in patients undergoing elective maxillofacial surgery is associated with a considerable number of comorbidities in the postoperative period. Through preoperative OSA screening and OSA evaluation, an improvement in management of surveillance resources could be achieved and the OSA-specific risk could be assessed more precisely and also reduced.

Are elevated serum haemolysis markers a harbinger of adverse events in HeartMate II patients?

OBJECTIVES: Haemolysis during left ventricular assist device support is associated with thrombosis. In this retrospective study, we analysed whether low-level haemolysis (LLH) as defined by simultaneously elevated lactate dehydrogenase (LDH) and free haemoglobin (fHb) levels had an impact on thromboembolic and bleeding events and on von Willebrand factor levels in HeartMate II patients. METHODS: After exclusion of patients with LDH >700 U/l and fHb >40 mg/dl at hospital discharge, 79 HeartMate II patients were included. LDH and fHb levels were measured at discharge and in 3 months interval. von Willebrand factor activity and antigen activity were measured 3 months postoperatively. Outcomes regarding ischaemic stroke (IS), pump thrombosis (PT) and gastrointestinal bleeding were recorded. Patients with LLH (400 < LDH ≤ 700 U/l and 30 < fHb ≤ 40 mg/dl) at discharge (pre-Hemolyzers) were compared with the rest of the cohort (non-Hemolyzers). Competing risk analysis and Cox regression were applied for the comparison between groups. RESULTS: In all, 20% of the patients were identified as pre-Hemolyzers. Of these, 5 patients had PT and 3 patients had IS compared with 2 PT and 2 IS in the non-Hemolyzers group (P = 0.003 and P = 0.053, respectively). Fifty percent of the pre-Hemolyzers suffered gastrointestinal bleeding compared with 42% of the non-Hemolyzers (P = 0.399). The cumulative risk of thromboembolic events (IS or PT) in the pre-Hemolyzers group was significantly higher compared with the non-Hemolyzers group (hazard ratio 11.8, 95% confidence interval 3.7-37.7; P = 0.005). LLH did not have an impact on von Willebrand factor and the incidence of gastrointestinal bleeding. CONCLUSIONS: LLH as assessed by elevated fHb and LDH values at discharge during HeartMate II support is associated with thromboembolic events.

Changes in Distress Measured by the Distress Thermometer as Reported by Patients in Home Palliative Care in Germany.

AIM: To identify changes in distress as reported by patients in a home palliative care program over a 2-week period. METHODS: Prospective study in West Germany with consecutive patients cared for at home by a palliative care specialty team. Exclusion criteria were patients under 18 years of age, mentally or physically not able to complete the assessment questionnaires, or unable to comprehend German language. Distress was measured using the distress thermometer (DT); sociodemographic and medical data were collected from the patients' records. RESULTS: One hundred three participated in the study (response rate of 69%) and 39 participants completed DT at 2-week follow-up (T1; response rate = 38%; mean age = 67; female = 54.4%; married = 67%; living home with relatives = 60.2%; oncological condition = 91.3%; Karnofsky performance status [KPS] 0-40 = 18.9%, KPS 50-70 = 70.3%, KPS >80 = 10.8%). The mean DT score at the first visit (T0) was 5.9 (2.3), with 82.1% of the participants scoring DT ≥5. At the 2-week follow-up (T1), mean DT score was 5.0 (2.0), with 64.1% scoring DT ≥5, showing a statistically significant difference between T0 and T1. Comparing the single scores at T0 and T1 of each participant, the difference in DT scores was -0.9 (2.27). CONCLUSION: The DT is a useful tool for screening severity and changes in psychological distress as well as sources of distress. The DT detected change in self-reported distress within a short treatment period, indicating success or failure of the palliative care treatment approaches.

A non-language-specific speech test to evaluate the speech of cleft patients from different language and cultural backgrounds - A pilot study.

Cleft speech tests are not universally available. We developed a tool to fill this gap, especially in the context of a cleft mission setting. We performed a pilot study to evaluate the test's ability to differentiate between the speech of cleft patients and healthy individuals from three different language backgrounds. We used 78 made-up, nonsensical syllables to evaluate hypernasality, nasal emissions, and consonant errors. Cleft (n = 41) and non-cleft (n = 39) individuals from three countries were included in this study. Two speech and language pathologists, blinded to the examination, rated the audio recording independently. Patients from Germany (n = 12; mean age 15.2), Iran (n = 14; mean age 7), and India (n = 15; mean age 14.7 years) were evaluated. We observed a significant difference in each category (p < 0.05) between patients and control subjects of the same language and cultural background. Hypernasality was affected the most. The test proved to possess the correct phonetic characteristics to reveal and provoke relevant cleft speech pathologies independent of cultural and language backgrounds. The test sounds posed no articulatory difficulties to non-cleft individuals, with some exceptions regarding non-specific consonant errors. A comparison with other existing tests will further illuminate its value as a speech test.

Interleukin-6 Serum Levels Correlate With Severity of Burn Injury but Not With Gender.

Gender-specific differences in the outcome of patients with burn injury have been recognized in the past with female patients being at a higher risk of mortality. We hypothesized that early post-burn interleukin-6 (IL-6) cytokine levels may contribute to the different gender-specific outcome. We retrospectively examined 94 burned patients who were treated in the Burn Intensive Care Unit at the University Hospital Aachen. Age, gender, presence of inhalation injury, depth, TBSA, and clinical outcome were documented. Serum samples for IL-6 analysis were collected within 24 hours posttrauma. The relationship between IL-6 levels, gender, survival, and abbreviated burn severity index score was investigated. Male patients (64.9%; n = 61) presented a higher median TBSA (26%) than female patients (20%). The mortality rate of male patients (27.9%; n = 17) and female patients (21.2%; n = 7) was similar. Deceased patients had significant higher TBSA (P = 0.0005) and IL-6 levels (P = 0.0007) than burn survivors. A moderate correlation between IL-6 levels and abbreviated burn severity index score was observed (r = 0.554; P < 0.0001). While TBSA showed a significant influence on IL-6 levels (P = 0.0003), gender did not (P = 0.7395) and inhalation injury indicated a minor influence (P = 0.0780). Only TBSA and age presented a significant influence on mortality (P = 0.0028 and P = 0.0031, respectively). All patients with burn trauma were characterized by elevated IL-6 levels with higher TBSA values resulting in more pronounced levels. Deceased patients had higher initial IL-6 serum levels reflecting higher TBSA and severity. In contrast to other defined trauma mechanisms, gender had no significant influence on postburn IL-6 serum levels and mortality in our patient population.

Influence of horizontal dimensions around single gap and adjacent zirconia implants on the papilla - a cross-sectional survey.

PURPOSE: To evaluate a possible association between the inter-implant distance and the papilla deficit. Additionally, the effect of high or low contact points of the crowns on the papilla deficit was investigated. MATERIALS AND METHODS: Periapical radiographs taken 1 year after loading were used to assess the distance from the shoulder of the implant to the adjacent tooth or implant. On the clinical images, the interdental papilla height, soft tissue deficit and crown length were evaluated. The papilla crown proportion and the proportion of the height of the contact point to the crown length were assessed. RESULTS: Eighty-one patients, with a total of 104 zirconia implants and 208 measurements were involved in this cross-sectional survey. Considering patient means, the correlation between the papilla deficit and the interproximal distance, respectively inter-implant distance, was very low (r = -0.05220; P = 0.6435, N = 81). Logistic regression at implant-level showed that there was no significant difference in the likelihood for a papilla deficit between a high and a low contact point of the crowns with P = 0.8191 (Odds ratio: 1.106 with 95%CI 0.461; 2.654). CONCLUSIONS: Horizontal interproximal dimensions around zirconia implants showed very weak influence on the papilla height. A high or a low contact point position of the crowns did not affect the papilla deficit. Conflict of Interest and sources of funding: All authors reported no conflict of interest. There were no sources of funding for the research.

Macrophage Migration Inhibitory Factor Predicts Outcome in Complex Aortic Surgery.

The perioperative inflammatory response is associated with outcome after complex aortic repair. Macrophage migration inhibitory factor (MIF) shows protective effects in ischemia-reperfusion (IR), but also adverse pro-inflammatory effects in acute inflammation, potentially leading to adverse outcome, which should be investigated in this trial. This prospective study enrolled 52 patients, of whom 29 (55.7%) underwent open repair (OR) and 23 (44.3%) underwent endovascular repair (ER) between 2014 and 2015. MIF serum levels were measured until 72 h post-operatively. We used linear mixed models and ROC analysis to analyze the MIF time-course and its diagnostic ability. Compared to ER, OR induced higher MIF release perioperatively; at 12 h after ICU admission, MIF levels were similar between groups. MIF course was significantly influenced by baseline MIF level (P = 0.0016) and acute physiology and chronic health evaluation (APACHE) II score (P = 0.0005). MIF level at 24 h after ICU admission showed good diagnostic value regarding patient survival [sensitivity, 80.0% (28.4-99.5%); specificity, 51.2% (35.1-67.1%); AUC, 0.688 (0.534-0.816)] and discharge modality [sensitivity, 87.5% (47.3-99.7%); specificity, 73.7% (56.9-86.6%), AUC, 0.789 (0.644-0.896)]. Increased perioperative MIF-levels are related to an increased risk of adverse outcome in complex aortic surgery and may represent a biomarker for risk stratification in complex aortic surgery.

Is local anaesthesia a favourable approach for transcatheter aortic valve implantation? A systematic review and meta-analysis comparing local and general anaesthesia.

OBJECTIVES: We conducted a systematic review and meta-analysis to identify the potential favourable effects of local anaesthesia plus sedation (LAS) compared with general anaesthesia (GA) in transcatheter aortic valve implantation (TAVI). METHODS: Electronic databases (PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials) and the reference lists of eligible publications were screened for randomised controlled trials (RCTs) and observational studies published between 1 January 2006 and 26 June 2016 that compare LAS to GA in an adult study population undergoing TAVI. We conducted study quality assessments using the Cochrane risk of bias tool and structured the review according to PRISMA. A meta-analysis calculating the pooled risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) under the assumption of a random-effects model was performed. Statistical heterogeneity was evaluated using the I² statistic and Cochran's Q-test. RESULTS: After database screening, one RCT and 19 observational studies were included in the review. We found no differences between LAS and GA in terms of 30-day mortality, in-hospital mortality and other endpoints that addressed safety and complication rates. LAS was associated with a shorter ICU and hospital stay and with lower rates of catecholamine administration and red blood cell transfusion. New pacemaker implantations occurred more frequently under LAS. The overall conversion rate from LAS to GA was 6.2%. CONCLUSION: For TAVI, both LAS and GA are feasible and safe. LAS may have some benefits such as increased haemodynamic stability and shorter hospital and ICU stays, but it does not impact 30-day mortality. Since there is a paucity of randomised trial data and the findings are mainly based on observational study data, this review should be considered as a hypothesis-generating article for subsequent RCTs that are required to confirm the potential favourable effects we detected for LAS. REGISTRATION NUMBER: CRD42016048398 (PROSPERO).

Evaluation of bone resorption in fibula and deep circumflex iliac artery flaps following dental implantation: A three-year follow-up study.

Long-term results of dental implant treatment in fibula free and deep circumflex iliac artery (DCIA) free flaps are scarce. The purpose of this study was to assess and compare peri-implant bone resorption of vascularized bone flaps treated with dental implants. A total of 28 patients, 14 fibula and 14 DCIA flaps, respectively, underwent reconstruction of the lower and upper jaw by the use of vascularized bone flaps and were treated with dental implants. Peri-implant bone resorption was measured using digital panographs up to 3 years. Radiographic pictures were taken immediately after implant surgery before prosthetic rehabilitation (T0), the second after 6-12 months (T1), the third after 13-24 months (T2), and the fourth after 25-36 months (T3). Over a period of 3 years, implant resorption changed significantly over time (pD1 = 0.0113, pD2 = 0.0232, pD3 = 0.0143). However, a significant difference in overall resorption between implants with fibula flaps and DCIA could not be detected for the patient average or within the implant-level analysis. Flaps presented minimal resorption from beneath (mean resorption DCIA 0.65, fibula = 0.26). Strong peri-implant bone resorption changed significantly over time. However, no significant difference was observed between fibula and DCIA flaps.

Accuracy of the Distress Thermometer for home care patients with palliative care needs in Germany.

OBJECTIVE: Our aim was to examine the accuracy of the German version of the Distress Thermometer (DT) compared with the Hospital Anxiety and Depression Scale (HADS) in patients with palliative care needs living at home. METHOD: Ours was a 15-month cross-sectional study beginning in September of 2013 in Germany with consecutive patients cared for by a palliative home care service. The survey was implemented during the initial visit by a home care team. Patients were excluded if they were under 18 years of age, mentally or physically unable to complete the assessment questionnaires as judged by their healthcare worker, or unable to understand the German language. During the first encounter, the DT and HADS were applied, and sociodemographic and medical data were collected. RESULTS: A total of 89 persons completed both the HADS and DT questionnaires (response rate = 59.7%; mean age = 67 years; female = 55.1%; married = 65.2%; living home with relatives = 73.0%; oncological condition = 92.1%; Karnofsky Performance Scale [KPS] score: 0-40 = 30.3%, 50-70 = 57.3%, >80 = 6.7%). The mean DT score was 6.3 (±2.3), with 84.3% of participants scoring above the DT cutoff (≥4). The mean HADStotal score was 17.9 (±7.8), where 64% of participants had a total HADS score (HADStotal) ≥15, 51.7% reported anxiety (HADSanxiety ≥ 8), and 73% reported depression (HADSdepression ≥ 8). Using the HADS as a gold standard, a DT cutoff score ≥5 was optimal for identifying severe distress in patients with palliative care needs, with a sensitivity of 93.0%, a specificity of 34.4%, a positive predictive value (PPV) of 73.3%, and likelihood ratios LR+ = 1.42 (<3) and -LR = 0.203 (<0.3). SIGNIFICANCE OF RESULTS: The DT performed satisfactorily compared to the HADS in screening for distress in our study and can be employed as an instrument for identification of patients with distress. Consequent to the high prevalence of distress, we recommend its routine use for screening distressed persons at home with palliative care needs in order to offer adequate support.

Interleukin-6 predicts inflammation-induced increase of Glucagon-like peptide-1 in humans in response to cardiac surgery with association to parameters of glucose metabolism.

OBJECTIVE: Glucagon-like peptide-1 (GLP-1) is an incretin hormone, which gets secreted in response to nutritional stimuli from the gut mediating glucose-dependent insulin secretion. Interestingly, GLP-1 was recently found to be also increased in response to inflammatory stimuli in an interleukin 6 (IL-6) dependent manner in mice. The relevance of this finding to humans is unknown but has been suggested by the presence of high circulating GLP-1 levels in critically ill patients that correlated with markers of inflammation. This study was performed to elucidate, whether a direct link exists between inflammation and GLP-1 secretion in humans. RESEARCH DESIGN AND METHODS: We enrolled 22 non-diabetic patients scheduled for cardiac surgery as a reproducible inflammatory stimulus with repeated blood sampling before and after surgery. RESULTS: Mean total circulating GLP-1 levels significantly increased in response to surgery from 25.5 ± 15.6 pM to 51.9 ± 42.7 pM which was not found in a control population. This was preceded by an early rise of IL6, which was significantly associated with GLP-1 under inflammatory but not basal conditions. Using repeated measure ANCOVA, IL6 best predicted the observed kinetics of GLP-1, followed by blood glucose concentrations and cortisol plasma levels. Furthermore, GLP-1 plasma concentrations significantly predicted endogenous insulin production as assessed by C-peptide concentrations over time, while an inverse association was found for insulin infusion rate. CONCLUSION: We found GLP-1 secretion to be increased in response to inflammatory stimuli in humans, which was associated to parameters of glucose metabolism and best predicted by IL6.