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1.
Eur J Obstet Gynecol Reprod Biol ; 268: 48-55, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34800817

ABSTRACT

OBJECTIVE: Uterine artery embolization is an attractive option for the management of postpartum haemorrhage, however it is not available in every hospital. We compared the clinical characteristics and haemodynamic state of patients with postpartum haemorrhage, before and after helicopter transfer to a tertiary hospital for possible uterine artery embolization. We also analysed whether the type of treatment could modify the outcome. STUDY DESIGN: Between 1999 and 2019 in Switzerland, we retrospectively found 82 consecutive patients with postpartum haemorrhage who were transferred by a physician-staffed helicopter emergency medical service to the tertiary hospital for potential uterine artery embolization. The collected data included the type of delivery, estimated blood loss, shock index and blood lactate levels before transfer and at destination, uterine artery embolization rate and hospital mortality rate. Our primary outcome was to describe the clinical characteristics, outcomes and haemodynamic state of the patients with postpartum haemorrhage before and after helicopter transfer. Our secondary outcome was to report the treatments performed at the tertiary hospital. The collected data were analysed with Stata version 14 (Stata Corporation, College Station, TX, USA). Continuous data are compared by using the Student's t-test or the Mann-Whitney U test, as appropriate. RESULTS: We included 69 patients. Postpartum haemorrhage occurred after vaginal delivery in 38 cases (55%). Blood loss prior to transfer exceeded 2 L in 34% of cases. The median shock index was 1 (IQR 0.8-1.1) before transfer and 0.9 (IQR 0.8-1.1) after transfer (p = 0.41). The median lactate level was 2.9 mmol/L (IQR 2.1-6.8) before, and 2.1 mmol/L (IQR 1.55-3.5) after transfer (p = 0.90). Forty-four patients underwent uterine artery embolization (64%), with an overall success rate of 93%. One patient died (1.4%), from a haemorrhagic shock of abdominal origin. CONCLUSIONS: Interhospital helicopter transfer of patients with postpartum haemorrhage to a tertiary hospital seems to be safe in our setting, despite a significant proportion of patients exhibiting signs of haemodynamic instability. Decision criteria would be helpful to better guide choices regarding the transfer of patients with postpartum haemorrhage.


Subject(s)
Emergency Medical Services , Postpartum Hemorrhage , Aircraft , Female , Hemodynamics , Humans , Postpartum Hemorrhage/therapy , Retrospective Studies , Treatment Outcome
2.
Anaesthesist ; 70(3): 247-249, 2021 Mar.
Article in German | MEDLINE | ID: mdl-32968843

ABSTRACT

BACKGROUND: Due to SARS-CoV­2 respiratory failure, prone positioning of patients with respiratory and hemodynamic instability has become a frequent intervention in intensive care units (ICUs), and even in patients undergoing transfer in an ambulance or helicopter. It has become increasingly important how to perform safe and effective CPR in prone position, achieving both an optimal outcome for the patient and optimal protection of staff from infection. MATERIALS AND METHODS: We conducted feasibility tests to assess the effects of CPR with an automatic load-distributing band (AutoPulse™) in prone position and discussed different aspects of mechanical chest compression (mCPR) in prone position. RESULTS: In supine position, AutoPulse™ generated a constant pressure depth of 3cm at a frequency of 84/min. In prone position, AutoPulse™ generated a constant pressure depth of 2.6cm at a frequency of 84/min. CONCLUSION: We found mCPR to be feasible in manikins in both prone and supine positions.


Subject(s)
COVID-19 , Cardiopulmonary Resuscitation , Humans , Manikins , Prone Position , SARS-CoV-2
3.
Am J Surg ; 218(6): 1138-1142, 2019 12.
Article in English | MEDLINE | ID: mdl-31563275

ABSTRACT

OBJECTIVE: This study examined the indications for prehospital needle thoracostomy (pNT), the need for tube thoracostomy (TT) following pNT, and the outcomes of patients who underwent pNT. METHODS: This study is a retrospective chart review of patients who underwent pNT prior to trauma center arrival. Patients were identified from the trauma registry and a quality improvement (QI) database from 9/2014-9/2018. RESULTS: 59 patients underwent 63 pNTs during the time period. The indication for pNT was "hypotension" in only 5 patients (7.9%). A CT chest was obtained on 51 NT attempts with the catheter in place. In 48 (94.1%) NT attempts, the catheter was not in the pleural space. 44 (69.4%) TTs were placed on admission date. CONCLUSION: In patients undergoing pNT, hypotension was rarely the indication. Additionally, CT identified the catheter within the pleural space in only 3 (5.8%) NT attempts. TT placement was performed in 79.3% of NT attempts.


Subject(s)
Chest Tubes , Emergency Treatment , Needles , Pneumothorax/surgery , Thoracostomy/instrumentation , Adult , Female , Humans , Male , Retrospective Studies , Trauma Centers , Treatment Failure
4.
Chirurg ; 90(4): 307-317, 2019 Apr.
Article in German | MEDLINE | ID: mdl-30255373

ABSTRACT

AIM: To investigate the perioperative management and outcome of patients undergoing abdominal surgery with additional vascular (comorbid) alterations for internal quality assurance of the clinical results. METHODS: Over a defined study period all consecutive cases of the aforementioned profile were documented and retrospectively analyzed as part of an ongoing prospective monocentric observational study to reflect the daily surgical practice. RESULTS: Over 10 years (from January 1999 to December 2008), a total of 113 cases were registered. Pancreas resection including vascular reconstruction showed the highest percentage (30.1%). Within the target patient groups, similar outcome data were found compared with international reports. An exception was in the case of mesenteric ischemia, where open surgery was more frequently used in comparison to the study situation (included together were patients treated by surgery and interventions). The majority of vascular alterations during the postoperative course and iatrogenic lesions occurred following pancreas resection. In the therapeutic profile there are two particularly important measures, namely open surgery on one hand and image-guided radiology as well as endoscopy on the other hand. The majority of patients with a rare visceral artery aneurysm (considerable potential for rupture or erosion) were more frequently treated with image-guided interventional radiology versus open surgery. This conforms to the current well-established sequential patient (individual), results, and, in particular, risk-adapted staged treatment approach. CONCLUSION: Additional vascular surgical treatment of problematic situations during abdominal surgery or in emergency cases is not daily routine; however, it is a challenging field including a considerable potential for complications (morbidity) and definitely mortality. This requires an experienced surgeon with high expertise, if possible in a center for vascular medicine.


Subject(s)
Aneurysm , Vascular Surgical Procedures , Aneurysm/surgery , Humans , Prospective Studies , Retrospective Studies , Tertiary Care Centers
5.
Anaesthesia ; 73(6): 719-729, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29411358

ABSTRACT

Tranexamic acid is used both pre-hospital and in-hospital as an antifibrinolytic drug to treat or prevent hyperfibrinolysis in trauma patients; dosing, however, remains empirical. We aimed to measure plasma levels of tranexamic acid in patients receiving pre-hospital anti-hyperfibrinolytic therapy and to build a population pharmacokinetic model to propose an optimised dosing regimen. Seventy-three trauma patients were enrolled and each received tranexamic acid 1 g intravenously pre-hospital. A blood sample was drawn after arrival in the emergency department, and we measured the plasma tranexamic acid concentration using liquid chromatography-mass spectrometry, and modelled the data using non-linear mixed effect modelling. Tranexamic acid was administered at a median (IQR [range]) time of 43 (30-55 [5-135]) min after trauma. Plasma tranexamic acid levels were determined on arrival at hospital, 57 (43-70 [20-148]) min after pre-hospital administration of the drug. The measured concentration was 28.7 (21.5-38.5 [8.7-89.0]) µg.ml-1 . Our subjects had sustained severe trauma; injury severity score 20 (16-29 [5-75]), including penetrating injury in 2.8% and isolated traumatic brain injury in 19.7%. The pharmacokinetics were ascribed a two-compartment open model with body-weight as the main covariate. As tranexamic acid concentrations may fall below therapeutic levels during initial hospital treatment, we propose additional dosing schemes to maintain a specific target blood concentration for as long as required. This is the first study to investigate plasma level and pharmacokinetics of tranexamic acid after pre-hospital administration in trauma patients. Our proposed dosing regimen could be used in subsequent clinical trials to better study efficacy and tolerance profiles with controlled blood concentrations.


Subject(s)
Antifibrinolytic Agents/administration & dosage , Antifibrinolytic Agents/pharmacokinetics , Tranexamic Acid/administration & dosage , Tranexamic Acid/pharmacokinetics , Wounds and Injuries/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antifibrinolytic Agents/adverse effects , Brain Injuries, Traumatic/drug therapy , Drug Administration Schedule , Emergency Medical Services , Female , Humans , Injury Severity Score , Male , Middle Aged , Prospective Studies , Tranexamic Acid/adverse effects , Young Adult
6.
Chirurg ; 88(12): 1040-1045, 2017 Dec.
Article in German | MEDLINE | ID: mdl-28660327

ABSTRACT

AIM AND METHODS: By means of a matched-pair analysis comparing data obtained from laparoscopic cholecystectomy (LC) and robot-assisted laparoscopic cholecystectomy (RAC), the value of both methods as well as the advantages and disadvantages of both approaches were elucidated. The consideration was carried out by evaluation of postoperative surgical results, a cost analysis and a subjective survey of the patients using a questionnaire. Thus, from the 35 consecutive RAC, 35 (parallel) retrospectively matched pairs were established. RESULTS: Postoperative surgical results did not show any significant differences between LC and RAC. In the individual assessment by each patient, there were also no significant differences; however, there was a tendency towards the assessment of the RAC to be slightly worse. A striking difference was found with respect to the cost analysis at the time of surgery. CONCLUSION: The RAC operation alone is significantly more expensive compared to LC with respect to maintenance and acquisition costs. In addition, RAC can at present not be completely reimbursed under the current German diagnosis-related system. The postulated advantages of RAC comprise mainly the precise preparation within narrow confinements and the favorable ergonomic handling for the surgeon. The basic prerequisites are control of the costs and a reasonable reflection in the current reimbursement system.


Subject(s)
Cholecystectomy, Laparoscopic , Robotic Surgical Procedures , Cholecystectomy/methods , Cholecystectomy, Laparoscopic/methods , Humans , Retrospective Studies
7.
Chirurg ; 88(8): 687-693, 2017 Aug.
Article in German | MEDLINE | ID: mdl-27995299

ABSTRACT

BACKGROUND: The aim of treatment of patients with colovesical fistulas should be prompt elimination of the infection and the social burden. We focused on the question whether a minimally invasive surgical approach as a cooperation between surgeons and urologists is possible. This requires effective diagnostics prior to the operation. METHODS: Since 2007 a total of 32 patients with the clinical suspicion of colovesical fistula have undergone extensive preoperative diagnostics. Operative treatment aimed primarily for a minimally invasive approach. In particular, the validity of preoperative diagnostics was analyzed and surgical results were characterized by clinical success, complications and long-term effects. RESULTS: The medical history significant for colovesical fistula and detected urinary infection provided the best evidence for the specific diagnosis. Cystoscopy, computed tomography (CT) scan and colonoscopy were only partially effective for predicting a fistula as subsequently diagnosed by histopathological investigations. Fistulas due to diverticulitis of the sigmoid colon occurred in 28 cases, while in 3 subjects there was a gynecological and inflammatory cause (malignant tumor growth, n = 1). A laparoscopic approach achieving repair and healing of the fistula was possible in 29 cases including conversion in 3 subjects because of intraoperative complications. The remaining patients underwent conventional treatment. The disease-related complication rate as revealed during follow-up was 10%. DISCUSSION: Laparoscopic repair and healing of a colovesical fistula is possible in the majority of cases by the recommended preoperative ureteral stenting. As part of diagnostic measures, the medical history significant for a fistula and detection of urinary infections are the most reliable aspects. In the case of this combination together with a further diagnostic measure, a laparoscopic approach is always recommended. The recurrency rate is 0%.


Subject(s)
Colonic Diseases/surgery , Interdisciplinary Communication , Intersectoral Collaboration , Intestinal Fistula/surgery , Laparoscopy/methods , Urinary Bladder Fistula/surgery , Aged , Colonic Diseases/diagnosis , Colonic Diseases/etiology , Colonoscopy , Conversion to Open Surgery/methods , Cystoscopy , Female , Follow-Up Studies , Humans , Intestinal Fistula/diagnosis , Intestinal Fistula/etiology , Male , Middle Aged , Operative Time , Risk Factors , Tomography, X-Ray Computed , Urinary Bladder Fistula/diagnosis , Urinary Bladder Fistula/etiology
8.
Z Gastroenterol ; 54(7): 634-41, 2016 Jul.
Article in German | MEDLINE | ID: mdl-27429100

ABSTRACT

PURPOSE: In hepatic resections, there has been a high quality demand. The aim of this systematic clinical, prospective, unblinded unicenter observational study with two arms in an unselected patient cohort was to investigate whether hemostat device can significantly improve outcome in resective liver surgery, in particular, in high risk patients. METHODS: All consecutive patients (mean age, 60.5 [range, 17 - 96] years) who underwent hepatic resection (ntotal = 770) were prospectively documented in a computer-based registry at a university hospital (tertiary center) over a time period of 10 years and retrospectively evaluated specifically with regard to the use (-/+; in daily practice and intraoperative decision-making) of hemostat device (Tissucol(®), n = 59/Tachocomb(®), n = 202/combination, n = 55) indicated (among others) by drainage volume, inflammatory parameters and rate of specific complications (nvalidated = 541 [100 %]). RESULTS: Most frequently, (a-)/typical segmental resections were used: n = 192/90 (3-segment resection, only n = 38). 1) For the assignment of patients to the two different groups (-/+ hemostat device), weight loss and type of resection were found as significant factors (trend: ASA, cirrhosis), for the amount of drainage volume, ASA, sex, Karnofsky Performance Scale and also type of resections using independent distributed statistical tests (such as χ(2), U test [Mann/Whitney]; H test [Kruskal-Willis]; correlation coefficient by Spearman) - no impact: smoking, diabetes, BMI, ethanol. 2) Not taking into account these parameters, the use of hemostat device was characterized by an increased drainage volume (negative control < Tissucol = Tachocomb < combination). 3) Using multifactorial analysis of variance, it was found even under correction by the factors with significant impact elucidated in the single test that the application of hemostat device onto the hepatic resection area resulted unexpectedly rather in an increase than a decrease of the drainage volume but 4) under accompanying more pronounced increase of the white blood cell count (leucocytosis). 5) General and specific complications such as postoperative bleeding, biliary fistula and subhepatic abscess were not further lowered in a significant manner using hemostat device. CONCLUSION: Adequate surgery in the operative management of hepatic resection area cannot further be improved or optimized using hemostat device. In this context, drainage volume may not be considered a sufficient rather an orienting parameter. However, there is an inflammatory response detectable most likely indicated by a(n un-)specific effusion and increase of white blood cell count, which can be interpreted as a) being characteristic for the problematic group of patients, in whom hemostat device was decided to be useful and was finally used in daily prectice, or b) reactive inflammation to foreign material.


Subject(s)
Blood Loss, Surgical/prevention & control , Hemostatic Techniques/instrumentation , Hemostatic Techniques/statistics & numerical data , Hepatectomy/instrumentation , Hepatectomy/statistics & numerical data , Postoperative Complications/epidemiology , Vascular Closure Devices/statistics & numerical data , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Blood Loss, Surgical/statistics & numerical data , Equipment Design , Equipment Failure Analysis , Female , Hepatectomy/methods , Humans , Liver/surgery , Male , Middle Aged , Postoperative Complications/prevention & control , Prevalence , Retrospective Studies , Sex Distribution , Treatment Outcome , Young Adult
9.
Zentralbl Chir ; 141(2): 204-9, 2016 Apr.
Article in German | MEDLINE | ID: mdl-23824612

ABSTRACT

BACKGROUND: The surgical approach of choice in the treatment of symptomatic cholecystolithiasis is considered to be elective laparoscopic cholecystectomy (CCE) as the established gold standard. Today, approximately 80-90% of CCE are performed using a laparoscopic approach whereas the remaining portion undergoes primary conventional CCE, however, in 6% conversion is necessary. AIM: Since pathological aspects found intraoperatively and finally requiring conversion are correlated to an increased risk for complications, it appears reasonable to assess the risk factors prior to operation. PATIENTS AND METHODS: Through a well defined study period of 9 years, all consecutive patients who underwent CCE for cholecystolithiasis at the Municipal Hospital "HELIOS Klinikum Aue" were enrolled in a registry comparing laparoscopic and conversion CCE. Diverse parameters were tested as to whether they increase significantly the risk for conversion. The intensity of each factor-associated impact on a possible conversion was determined. RESULTS: From 2001 to 2009 1477 patients underwent CCE at the Municipal Hospital "Helios Klinikum Aue", out of them 131 (8.9%) cases were primarily treated by conventional CCE whereas in the vast majority (1346 subjects [91.1%]), laparoscopic CCE was the initial approach. However, conversion became necessary in 106 individuals resulting in a conversion rate of 7.9%. Comparing data obtained from laparoscopic CCE with those from open procedure after conversion, there were significant differences in operating time, complication rate and postoperative hospital stay (p = 0.01). Over the study period, there were 5 cases (0.37%) with iatrogenic injuries of the biliary system. Hospital mortality was 0.08% in the laparoscopic and 2.8% in the conversion group. The following parameters were found to have a significant impact on the risk for conversion (univariate analysis): elevation of CRP, preoperative ERCP, renal insufficiency, previous laparotomy, histological grade M3 (ulcerous, haemorrhagic necrotising cholecystitis, perforation of the gall bladder) and M4 (carcinoma of the gall bladder). While in the spectrum of preoperative factors former ERCP, elevation of CRP and terminal renal insufficiency were most relevant (2- to 3-fold each), histological grade M3 and M4, 7- and 14-fold, respectively, showed the greatest impact on conversion rate highlighting the profile of postoperative parameters. CONCLUSION: The main focus is directed to keep the conversion rate low. In case of diagnosing a severely inflamed gall bladder, a primarily open procedure or an early decision for conversion should be considered.


Subject(s)
Cholecystectomy, Laparoscopic/statistics & numerical data , Cholecystolithiasis/surgery , Conversion to Open Surgery/statistics & numerical data , Intraoperative Complications/surgery , Adult , Aged , Comorbidity , Cross-Sectional Studies , Female , Gallbladder Neoplasms/epidemiology , Gallbladder Neoplasms/surgery , Germany , Humans , Intraoperative Complications/epidemiology , Length of Stay/statistics & numerical data , Male , Middle Aged , Operative Time , Prospective Studies , Risk Factors
10.
Chirurg ; 86(8): 787-93, 2015 Aug.
Article in German | MEDLINE | ID: mdl-26070274

ABSTRACT

BACKGROUND: Frequently, the first clinical sign of colorectal cancer is complete obstruction, which has to be considered an emergency situation. The treatment goal is to overcome ileus including reduction of the associated high morbidity and mortality. Therefore, alternative therapeutic options to emergency surgery have been sought in order to allow adequate preparation for elective surgery or stabilization of palliative patients and avoid colostoma. Therapeutic results of the placement of self-expanding metal stents (SEMS) are discussed in terms of a single-center, retrospective observational study. METHODS: In 35 patients with a clinically manifest stenosis of colonic cancer, it was attempted to insert SEMS to treat ileus as the first therapeutic step. Therapeutic results were investigated with regard to technical and clinical success, spectrum and rate of complications, and survival time, differentiating between a palliative and curative group of patients. RESULTS: Primary placement of a stent was achieved in 29 of 35 patients (82.9 %); 14 underwent the procedure with palliative and 15 with curative intention. Stent location was mainly the left hemicolon. In 2 of 15 patients (13.3 %), emergency surgery within 48 h was required because of complications, whereby in 13 patients (86.7 %), 6 patients (46.2 %) underwent elective open surgery and 7 patients (53.8 %) underwent a laparoscopic procedure. In all patients treated with curative intent, primary anastomosis was achieved, thus, avoiding a colostoma. Survival times of the palliative and curative patient groups were on average 7 and 28 months, respectively. CONCLUSION: In carefully selected cases, placement of SEMS in malignant stenosis of the left hemicolon with ileus can be considered a reasonable therapeutic alternative to emergency surgery since it allows surgical intervention with curative intention under more favorable conditions and also avoids a colostoma.


Subject(s)
Colonic Diseases/therapy , Colorectal Neoplasms/therapy , Emergency Medical Services , Intestinal Obstruction/therapy , Stents , Aged , Aged, 80 and over , Colorectal Neoplasms/complications , Colorectal Neoplasms/mortality , Elective Surgical Procedures , Female , Germany , Humans , Intestinal Obstruction/mortality , Laparoscopy , Male , Middle Aged , Palliative Care , Retreatment , Retrospective Studies , Risk Factors , Survival Analysis
11.
Unfallchirurg ; 118(3): 233-9, 2015 Mar.
Article in German | MEDLINE | ID: mdl-25783692

ABSTRACT

The influence of the transport mode, i.e. Helicopter Emergency Medical Service (HEMS) versus ground-based Emergency Medical Service (EMS) on the mortality of multiple trauma patients is still controversially discussed in the literature. In this study a total of 333 multiple trauma patients treated over a 1-year period in a level I trauma center in Switzerland were analyzed. Using the newly established revised injury severity classification (RISC) score there was a tendency towards a better outcome for patients transported by HEMS (standardized mortality ratio 1.06 for HEMS versus 1.29 for EMS). Overall a short preclinical time and the presence of an emergency physician (EP) were associated with a better outcome.


Subject(s)
Air Ambulances/statistics & numerical data , Automobiles/statistics & numerical data , Injury Severity Score , Multiple Trauma/mortality , Multiple Trauma/therapy , Trauma Centers/statistics & numerical data , Emergency Medical Services/statistics & numerical data , Female , Humans , Male , Middle Aged , Multiple Trauma/diagnosis , National Health Programs/statistics & numerical data , Outcome Assessment, Health Care , Prevalence , Risk Factors , Survival Rate , Switzerland
12.
Talanta ; 134: 453-459, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25618693

ABSTRACT

Given its high sensitivity and non-destructive nature, fluorescence excitation-emission matrix (EEM) spectroscopy is widely used to differentiate changes and transformations of dissolved or water-extracted organic matter (OM) in natural environments. The same technique applied directly on solid samples (solid-phase fluorescence spectroscopy, SPF-EEM) provides accurate results when used with pharmaceutical products or food samples, but only a few studies have considered natural OM. This study reports on the use of SPF-EEM on solid compost samples and emphasises the way the different maturation phases can be distinguished with fluorophores closely resembling those found in dissolved samples. A very good correlation has been found with data from Rock-Eval pyrolysis, nuclear magnetic resonance ((13)C CPMAS NMR), and humic-fulvic acid ratios determined by conventional NaOH-extraction. SPF-EEM appears as a much simpler method than the conventional ones to detect transformations in natural OM samples with low mineral contents. However, direct application to soil samples requires some additional studies.

14.
J Theor Biol ; 351: 47-57, 2014 Jun 21.
Article in English | MEDLINE | ID: mdl-24594370

ABSTRACT

Viral antagonism of host responses is an essential component of virus pathogenicity. The study of the interplay between immune response and viral antagonism is challenging due to the involvement of many processes acting at multiple time scales. Here we develop an ordinary differential equation model to investigate the early, experimentally measured, responses of human monocyte-derived dendritic cells to infection by two H1N1 influenza A viruses of different clinical outcomes: pandemic A/California/4/2009 and seasonal A/New Caledonia/20/1999. Our results reveal how the strength of virus antagonism, and the time scale over which it acts to thwart the innate immune response, differs significantly between the two viruses, as is made clear by their impact on the temporal behavior of a number of measured genes. The model thus sheds light on the mechanisms that underlie the variability of innate immune responses to different H1N1 viruses.


Subject(s)
Influenza A Virus, H1N1 Subtype/immunology , Influenza, Human/immunology , Models, Immunological , Dendritic Cells/immunology , Dendritic Cells/virology , Gene Expression/immunology , Host-Pathogen Interactions , Humans , Immune Evasion , Immunity, Innate/genetics , Immunity, Innate/immunology , Influenza A Virus, H1N1 Subtype/classification , Influenza A Virus, H1N1 Subtype/pathogenicity , Influenza, Human/genetics , Influenza, Human/virology , Interferon-beta/biosynthesis , Viral Nonstructural Proteins/physiology
17.
J Virol ; 87(19): 10435-46, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23903831

ABSTRACT

Current influenza virus vaccines contain H1N1 (phylogenetic group 1 hemagglutinin), H3N2 (phylogenetic group 2 hemagglutinin), and influenza B virus components. These vaccines induce good protection against closely matched strains by predominantly eliciting antibodies against the membrane distal globular head domain of their respective viral hemagglutinins. This domain, however, undergoes rapid antigenic drift, allowing the virus to escape neutralizing antibody responses. The membrane proximal stalk domain of the hemagglutinin is much more conserved compared to the head domain. In recent years, a growing collection of antibodies that neutralize a broad range of influenza virus strains and subtypes by binding to this domain has been isolated. Here, we demonstrate that a vaccination strategy based on the stalk domain of the H3 hemagglutinin (group 2) induces in mice broadly neutralizing anti-stalk antibodies that are highly cross-reactive to heterologous H3, H10, H14, H15, and H7 (derived from the novel Chinese H7N9 virus) hemagglutinins. Furthermore, we demonstrate that these antibodies confer broad protection against influenza viruses expressing various group 2 hemagglutinins, including an H7 subtype. Through passive transfer experiments, we show that the protection is mediated mainly by neutralizing antibodies against the stalk domain. Our data suggest that, in mice, a vaccine strategy based on the hemagglutinin stalk domain can protect against viruses expressing divergent group 2 hemagglutinins.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Genetic Vectors/administration & dosage , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Influenza A virus/physiology , Influenza Vaccines/administration & dosage , Orthomyxoviridae Infections/prevention & control , Animals , Antibody Specificity , Cells, Cultured , Cross Reactions , Enzyme-Linked Immunosorbent Assay , Female , Fluorescent Antibody Technique , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Humans , Influenza A virus/classification , Kidney/immunology , Kidney/metabolism , Kidney/virology , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/virology , Phylogeny
18.
Am J Transplant ; 13(5): 1134-48, 2013 May.
Article in English | MEDLINE | ID: mdl-23566221

ABSTRACT

The Food and Drug Administration (FDA) held an open public workshop in September 2011 to discuss the current state of science related to the effects of ischemia reperfusion injury (IRI) on outcomes in kidney transplantation. Topics included the development of IRI and delayed graft function (DGF), histology and biomarkers, donor factors, recipient factors, organ quality and organ preservation by means of cold storage solutions or machine perfusion. Various mechanisms of injury and maladaptive response to IRI were discussed as potential targets of intervention. Animal models evaluating specific pathophysiological pathways were presented, as were the limitations of extrapolating animal results to humans. Clinical trials of various drug products administered in the peri-transplant period were summarized; a few demonstrated early improvements in DGF, but none demonstrated an improvement in late graft function. Clinical trial design for IRI and DGF were also discussed.


Subject(s)
Congresses as Topic , Delayed Graft Function/etiology , Kidney Transplantation , Organ Preservation/methods , Reperfusion Injury/complications , Animals , United States , United States Food and Drug Administration
20.
Zentralbl Chir ; 138(3): 278-83, 2013 Jun.
Article in German | MEDLINE | ID: mdl-23208856

ABSTRACT

INTRODUCTION: By minimising the invasiveness of a surgical intervention, a reduction of operative trauma can be achieved. AIM AND METHODS: The aim of this study was based on a theoretical approach to investigate (i) the feasibility of the SP approach and its overall costs, and, furthermore, (ii) the patients' outcome based on simple perioperative parameters available in daily clinical practice. Therefore, single-port (SP) and laparoscopic appendectomies (LA) were compared using a matched-pair analysis. As a prediction, an absolute match between the criteria histology, sex and ASA stage was required. RESULTS: From 01/01/2009 to 12/31/2010, 196 (60 % were females) consecutive patients underwent appendectomy. Out of them, in 23 patients with either SP or LA appendectomy the predictions for matched-pair analysis (congruence in histopathological finding, sex and ASA criteria) were fulfilled. The operating time was the target criterion for the feasibility of the new surgical method (SP), which could be shortened as seen by comparing SP No. 1-10 with 11-23 (54.6 ± 19.8 min vs. 28.5 ± 18.9 min) expressing the typical effect of a learning curve. The times were similar to those for LA. The postoperative hospital stay and complication rate used to appropriately assess patient outcome did not show a significant difference if comparing SP and LA. Based on the use of single ports, which can be re-used (which has been also a further target) in SP (34.8 %) at the end of the investigation period, SP and LA can be considered comparable surgical techniques with regard to operating times, middle-term outcome and general costs. CONCLUSION: SP is (in case of well-developed laparoscopic expertise) a surgical method that can be easily inaugurated and considered as a feasible approach in daily surgical practice; it is comparable to LA with regard to outcome and general costs. Based on this, SP can be gradually added to the spectrum of surgical procedures in clinical practice and can be performed in suitable cases. A further systematic institutional or even country-wide case register appears to be recommendable to recruit a larger case number and, thus, to achieve a better knowledge on the perioperative management as well as the especially interesting long-term outcome for an appropriate assessment of treatment quality.


Subject(s)
Appendectomy/methods , Appendicitis/surgery , Laparoscopy/methods , Matched-Pair Analysis , Minimally Invasive Surgical Procedures/methods , Natural Orifice Endoscopic Surgery/methods , Abdominal Abscess/etiology , Abdominal Abscess/mortality , Adult , Appendectomy/mortality , Appendicitis/mortality , Cause of Death , Female , Germany , Humans , Laparoscopy/mortality , Male , Minimally Invasive Surgical Procedures/mortality , Multicenter Studies as Topic , Postoperative Complications/etiology , Postoperative Complications/mortality , Quality Assurance, Health Care/methods , Surgical Instruments , Surgical Stapling/methods , Survival Analysis , Suture Techniques
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