Platinum-Based Chemotherapy 'Rechallenge' in Advanced Non-ovarian Solid Malignancies.

Platinum-based chemotherapy forms the backbone of treatment for many solid cancers. However, resistance inevitably develops in those with advanced disease. Platinum rechallenge is a well-established concept in the management of ovarian cancer, small cell lung cancer and germ cell tumours. In other solid malignancies there is a lack of quality evidence to support platinum rechallenge, yet it is a widely adopted strategy. Often, patients are within the last year of life, making questions of efficacy, treatment-related toxicity and quality of life critical factors for treatment recommendations. In this overview we appraise the available evidence for platinum rechallenge and strategies being developed to attempt resensitisation of tumours to platinum-based chemotherapy.

A novel fuel cell design foroperandoenergy-dispersive x-ray absorption measurements.

A polymer electrolyte fuel cell has been designed to allowoperandox-ray absorption spectroscopy (XAS) measurements of catalysts. The cell has been developed to operate under standard fuel cell conditions, with elevated temperatures and humidification of the gas-phase reactants, both of which greatly impact the catalyst utilisation. X-ray windows in the endplates of the cell facilitate collection of XAS spectra during fuel cell operation while maintaining good compression in the area of measurement. Results of polarisation curves and cyclic voltammograms showed that theoperandocell performs well as a fuel cell, while also providing XAS data of suitable quality for robust XANES analysis. The cell has produced comparable XAS results when performing a cyclic voltammogram to an establishedin situcell when measuring the Pt LIII edge. Similar trends of Pt oxidation, and reduction of the formed Pt oxide, have been presented with a time resolution of 5 s for each spectrum, paving the way for time-resolved spectral measurements of fuel cell catalysts in a fully-operating fuel cell.

Stability of internal versus external fixation in osteoporotic pelvic fractures - a biomechanical analysis.

INTRODUCTION: Osteoporosis-related fragility fractures of the pelvic ring (FFP) differ fundamentally from pelvic fractures in younger patients. However, very little is known about biomechanical stability of different osteosynthesis procedures addressing the anterior pelvic ring in these fractures. The aim of this study was to compare standard external fixation with internal fixation using a novel screw-and-rod system in osteoporotic fractures of the pelvic ring in terms of stiffness, plastic deformation and maximum load under cyclic loading in a human cadaveric model. MATERIALS AND METHODS: A total of 18 embalmed osteoporotic cadaver pelvis specimens were randomized based on the T-score into a group for external fixation and a group for internal fixation. FFP type-IIB fractures were created. In addition to the external or internal fixator, a cement-augmented sacroiliac screw was implanted. Afterwards, axial cyclic loading was performed in a testing setup simulating one-leg stand. RESULTS: Mean plastic deformation and stiffness both were significantly better in the internal fixation group than in the external fixation group (plastic deformation: 0.37 mm (SD: 0.23) versus 0.71 mm (SD: 0.26), p = 0.011; stiffness: 43.69 N/mm (SD: 18.39) versus 26.52 N/mm (SD: 9.76), p = 0.029). Maximum load did not differ significantly between internal fixator (506.3 N; SD: 129.4) and external fixator (461.1 N; SD: 147.4) (p = 0.515). CONCLUSIONS: Submuscular internal fixation might be an interesting alternative to external fixation in clinical practice because of better biomechanical properties as well as several advantages in clinical use.

[Detection of malnutrition in geriatric trauma patients : A reassessment]. / Erfassung von Mangelernährung bei geriatrischen Traumapatienten : Eine erneute Bestandsaufnahme.

BACKGROUND AND OBJECTIVE: Malnutrition in geriatric trauma patients is associated with an increased risk of complications and mortality and is therefore a key risk factor. The assessment of the affected patients plays an important role in improving the outcome of this growing patient group. MATERIAL AND METHODS: In 2016 a questionnaire was sent to 571 departments specialized in traumatology and orthopedics throughout Germany. The following were recorded: level of care, expertise in geriatric trauma, nutrition-based screening procedures and nutritional ward round procedures. RESULTS: The response rate was 57% (n = 325) and closely reflected the treatment reality in Germany with respect to the level of care (superregional, regional or local trauma center and those without special qualifications). In 14% (n = 45) the participants were German Society for Trauma Surgery(DGU)-certified centers for age-related traumatology, while a further 5% (n = 15) were in the process of certification. The nutritional status was assessed in 56% (n = 181) of the clinics. Most frequently used was the body mass index (74%) followed by the mini nutritional assessment (30%), laboratory parameters (29%) and nutritional risk screening 2002 (19%). Some additional methods were specified. In approximately half of the departments nutritional ward rounds took place in regular wards (50%) and intensive care units (57%). DISCUSSION: The high response rate of this study seems to show the particular interest for malnutrition in geriatric trauma patients. This is reflected in an increase in the participating clinics compared to past surveys and also the more regularly performed assessment of nutritional status and implementation of nutritional visits. CONCLUSION: The establishment of suitable and time-effective screening instruments and their implementation are still a challenge.

Cement-augmented sacroiliac screw fixation with cannulated versus perforated screws - A biomechanical study in an osteoporotic hemipelvis model.

INTRODUCTION: Cement-augmentation is a well-established way to improve the stability of sacroiliac screw fixation in osteoporosis-associated fragility fractures of the posterior pelvic ring. However, to date little is known about the influence of different techniques of cement augmentation on construct stability. The aim of this study was to evaluate the primary stability of cement-augmented sacroiliac screw fixation with cannulated versus perforated screws under cyclic loading. MATERIALS AND METHODS: A total of eight fresh-frozen human cadaveric hemipelvis specimens with osteoporosis were used. After generating ventral osteotomies on both sides of the sacrum, each specimen was treated using a cement-augmented cannulated screw on one side and a cement-augmented perforated screw on the other side. Afterwards, axial cyclic loading was performed. RESULTS: No statistically significant difference was found between cannulated and perforated screws concerning maximum load (356.25 N versus 368.75 N, p = 0.749), plastic deformation (1.95 mm versus 1.43 mm, p = 0.798) and stiffness (27.04 N/mm versus 40.40 N/mm, p = 0.645). CONCLUSIONS: Considering the at least equivalent results for perforated screws, cement augmentation via perforated screws might be an interesting option in clinical practice because of potential advantages, e.g. radiological control before cement application, reduced risk of cement displacement and time saving.

[Advance directives in clinical practice : Living will, healthcare power of attorney and care directive]. / Vorausverfügungen im klinischen Alltag : Patientenverfügung, Vorsorgevollmacht und Betreuungsverfügung.

In clinical practice, situations continuously occur in which medical professionals and family members are confronted with decisions on whether to extend or limit treatment for severely ill patients in end of life treatment decisions. In these situations, advance directives are helpful tools in decision making according to the wishes of the patient; however, not every patient has made an advance directive and in our experience medical staff as well as patients are often not familiar with these documents. The purpose of this article is therefore to explain the currently available documents (e.g. living will, healthcare power of attorney and care directive) and the possible (legal) applications and limitations in the routine clinical practice.

[Advance directives in clinical practice : Living will, healthcare power of attorney and care directive]. / Vorausverfügungen im klinischen Alltag : Patientenverfügung, Vorsorgevollmacht und Betreuungsverfügung.

In clinical practice, situations continuously occur in which medical professionals and family members are confronted with decisions on whether to extend or limit treatment for severely ill patients in end of life treatment decisions. In these situations, advance directives are helpful tools in decision making according to the wishes of the patient; however, not every patient has made an advance directive and in our experience medical staff as well as patients are often not familiar with these documents. The purpose of this article is therefore to explain the currently available documents (e.g. living will, healthcare power of attorney and care directive) and the possible (legal) applications and limitations in the routine clinical practice.

[Advance directives in clinical practice : Living will, healthcare power of attorney and care directive]. / Vorausverfügungen im klinischen Alltag : Patientenverfügung, Vorsorgevollmacht und Betreuungsverfügung.

In clinical practice, situations continuously occur in which medical professionals and family members are confronted with decisions on whether to extend or limit treatment for severely ill patients in end of life treatment decisions. In these situations, advance directives are helpful tools in decision making according to the wishes of the patient; however, not every patient has made an advance directive and in our experience medical staff as well as patients are often not familiar with these documents. The purpose of this article is therefore to explain the currently available documents (e.g. living will, healthcare power of attorney and care directive) and the possible (legal) applications and limitations in the routine clinical practice.

[Advance directives in clinical practice : Living will, healthcare power of attorney and care directive]. / Vorausverfügungen im klinischen Alltag : Patientenverfügung, Vorsorgevollmacht und Betreuungsverfügung.

In clinical practice, situations continuously occur in which medical professionals and family members are confronted with decisions on whether to extend or limit treatment for severely ill patients in end of life treatment decisions. In these situations, advance directives are helpful tools in decision making according to the wishes of the patient; however, not every patient has made an advance directive and in our experience medical staff as well as patients are often not familiar with these documents. The purpose of this article is therefore to explain the currently available documents (e.g. living will, healthcare power of attorney and care directive) and the possible (legal) applications and limitations in the routine clinical practice.

Patient factors associated with increased acute care costs of hip fractures: a detailed analysis of 402 patients.

The aim of the present study was to identify patient factors associated with higher costs in hip fracture patients. The mean costs of a prospectively observed sample of 402 patients were 8853 €. The ASA score, Charlson comorbidity index, and fracture location were associated with increased costs. PURPOSE: Fractures of the proximal end of the femur (hip fractures) are of increasing incidence due to demographic changes. Relevant co-morbidities often present in these patients cause high complication rates and prolonged hospital stays, thus leading to high costs of acute care. The aim of this study was to perform a precise cost analysis of the actual hospital costs of hip fractures and to identify patient factors associated with increased costs. METHODS: The basis of this analysis was a prospectively observed single-center trial, which included 402 patients with fractures of the proximal end of the femur. All potential cost factors were recorded as accurately as possible for each of the 402 patients individually, and statistical analysis was performed to identify associations between pre-existing patient factors and acute care costs. RESULTS: The mean total acute care costs per patient were 8853 ± 5676 € with ward costs (5828 ± 4294 €) and costs for surgical treatment (1972 ± 956 €) representing the major cost factors. The ASA score, Charlson comorbidity index, and fracture location were identified as influencing the costs of acute care for hip fracture treatment. CONCLUSION: Hip fractures are associated with high acute care costs. This study underlines the necessity of sophisticated risk-adjusted payment models based on specific patient factors. Economic aspects should be an integral part of future hip fracture research due to limited health care resources.

[Operative interventions of urologic traumata in severe injured patients in the acute phase]. / Operative Interventionen urologischer Verletzungen beim schwerverletzten Patienten in der Akutphase.

INTRODUCTION: The frequency of urological traumata and the need for interventions in severely injured patients in Germany are unknown. The aim of this study was to determine the frequency of urological traumata in about 90,000 severely injured patients (Injury Severity Score, ISS ≥ 16). MATERIALS AND METHODS: Data of 90,000 patients from the TraumaRegister DGU® were retrospectively analyzed. All patients with an ISS of ≥ 16 were included. The kind of urological traumata and the need for urological intervention within 24 hours were assessed, as well as the kind of accident, additional traumata and the clinical course. RESULTS: 48,797 patients fulfilled the inclusion criteria. Urological trauma was existent in 7.1 %, especially in men (78 %). Kidneys were affected most frequently (4.8 %) compared to ureters (0.2 %), urinary bladder (1.2 %), urethra (0.5 %) and genitals (0.4 %). Traffic accidents and falls from higher levels represented the main cause for urological traumata (> 90 %). It was associated with additional pelvis, thorax and abdomen traumata (each 7.1 %) and showed a distinct increase dependent on the abbreviated injury scale (AIS). Ureter (10.6%) and urethra (6.3%) trauma was deferred diagnosed most, this was associated with a higher rate of urological operations. The general duration of hospital stay and that in the intensive care unit were prolonged by urological traumata. DISCUSSION: The data showed the prevalence of urological trauma in severely injured patients analyzed in a huge patient cohort of the TraumaRegister DGU®. For the first time the number, degree and medical care in the reality of urological traumata in severely injured patients were available.

[Living will, durable power of attorney and legal guardianship in the trauma surgery routine : Data from a geriatric trauma center]. / Patientenverfügung, Vorsorgevollmacht und gesetzliche Betreuung im unfallchirurgischen Alltag : Zahlen aus einem alterstraumatologischen Zentrum.

BACKGROUND: Due to the increasing number of elderly patients, trauma surgeons are often confronted with end-of-life treatment decisions. Advance directives can help reduce the lack of clarity in those situations. OBJECTIVES: The aim of this study was to identify the presence of living wills, durable power of attorney, legal guardianship and appointment of guardianship in the geriatric trauma center of a university hospital. MATERIALS AND METHODS: The data of all patients treated in our geriatric trauma center from 01/01/2013 to 03/31/2014 were analyzed regarding the presence of a living will, durable power of attorney, legal guardianship and appointment of guardianship as well as the procedure of documenting those items. RESULTS: Out of 181 patients, 63 % (n = 114) had one or more of these documents. Most frequently used was the durable power of attorney in 33 % (n = 59), followed by a living will in 27 % (n = 48), legal guardianship in 20 % (n = 37) and appointment of guardianship in 7 % (n = 12). The existence of those documents was recorded in 88 % (n = 100) of patients within 24 h after admission; documentation in the medical records was found in 58 % (n = 66). CONCLUSION: A large proportion of patients had one or more of the documents named above. In this respect, standardized documentation of advance directives in the medical record is an important issue for all persons involved.

An international surgical collaboration: humanitarian surgery in Brazil.

PURPOSE: Brazil is the fifth most populous country in the world with widespread regional and social inequalities. Regional disparities in healthcare are unacceptably large, with the remote and poor regions of the north and northeast having reduced life expectancy compared to the south region, where life expectancy approaches that of rich countries. We report our experience of a humanitarian surgery mission to the Amazonas state, in the northwest part of Brazil. METHODS: In August 2014, a team of seven consultant surgeons, and two trainees with the charity 'International Hernia', visited three hospitals in the Amazonas state to provide hernia surgery and training. RESULTS: Eighty-nine hernias were repaired in 74 patients (female = 22, male = 52) with a median age of 44 years (range 2-83 years). Nine patients underwent more than one type of hernia repair, and there were 9 laparoscopic inguinal and ventral incisional hernia repairs. Local doctors were trained in hernia repair techniques, and an International Hernia Symposium was held at the University of the State of Amazonas, Manaus. CONCLUSION: The humanitarian mission provided hernia surgery to an underserved population in Brazil and training to local doctors, building local sustainability. Continued cooperation between host and international surgeons for future missions to Brazil will ensure continuing surgical training and technical assistance.

[10-Year Follow-Up of the NexGen CR Total Knee Prosthesis]. / Zehn-Jahres-Ergebnisse nach bikondylärem Kniegelenksersatz mit der kreuzbanderhaltenden Knietotalendoprothese NexGen CR.

BACKGROUND: The purpose of this study was to evaluate long-term clinical and radiological results as well as survival rates of the NexGen® CR posterior cruciate retaining prosthesis. PATIENTS AND METHODS: We evaluated a consecutive series of 761 total knee replacements performed on 716 patients from 1999 to 2001 at our institution. All patients had been recorded prospectively in our in-house arthroplasty register. Follow-up data were available for 379 patients at 10 years postoperatively. Functional outcome was evaluated using the Knee Society score. An additional radiographic evaluation was performed on 224 patients at 10 years. The mean age of the patients at the time of surgery was 71 years. 75 % of the patients were female, 25 % were male. Mean BMI of the patients was 29.2 kg/m(2). The preoperative diagnosis was osteoarthritis in 91 %, rheumatoid arthritis in 5,5 % and posttraumatic osteoarthritis in 2 %. Patella resurfacing was performed in 4 %. All components were cemented. RESULTS AND DISCUSSION: Mean Knee Society clinical score improved from 26.7 points preoperatively to 88.5 points at the time of the latest follow-up, and mean Knee Society function score improved from 48.3 to 55.2 points. Flexion improved from a mean of 106.7° preoperatively to 111.4° at 10 years. Patellofemoral pain was indicated by 66 % of the patients before surgery and 4 % at the latest follow-up. 96 % were satisfied with the result of the surgery at 10 years. Radiographic evaluation was performed on 224 patients at the time of the latest follow-up. 203 patients (91 %) had normal radiographic findings, 21 patients (9 %) showed pathological findings. Radiolucencies were seen in 18 patients on the AP view of the tibia, 1 patient had an additional femoral radiolucency. There was an osteolysis located in the lateral tibia seen in 1 patient and an occurrence of heterotopic ossification in another patient. One knee showed a patella subluxation. No patient had radiographic evidence of loosening. 17 knees had required revision surgery with exchange of at least one of the components up to 10 years after the index procedure. 5 of the patients had revision for a deep infection, 2 for periprosthetic fractures of the distal femur with loosening of the prosthesis, 1 for fracture of the proximal tibia due to osteoporosis, 4 for aseptic loosening, 3 for instability and 2 for severe pain. Kaplan-Meier survival of all components using revision for any reason as the end point was 97.8 % at 10 years. CONCLUSION: The good clinical and radiological long-term results as well as the satisfactory survival rate after total knee replacement with the NexGen CR® prosthesis are comparable with the results of other long-term studies using the NexGen CR® and assimilable prosthesis. Our results demonstrate that quality of life was improved by the implantation of the NexGen CR® prosthesis even a long time after the index procedure despite old age and comorbidity of the patients.

A Microfluidic Method for the Selection of Undifferentiated Human Embryonic Stem Cells and in Situ Analysis.

Conventional cell-sorting methods such as fluorescence-activated cell sorting (FACS) or magnetic-activated cell sorting (MACS) can suffer from certain shortcomings such as lengthy sample preparation time, cell modification through antibody labeling, and cell damage due to exposure to high shear forces or to attachment of superparamagnetic Microbeads. In light of these drawbacks, we have recently developed a label-free, microfluidic platform that can not only select cells with minimal sample preparation but also enable analysis of cells in situ. We demonstrate the utility of our platform by successfully isolating undifferentiated human embryonic stem cells (hESCs) from a heterogeneous population based on the undifferentiated stem-cell marker SSEA-4. Importantly, we show that, in contrast to MACS or FACS, cells isolated by our method have very high viability (~90%). Overall, our platform technology could likely be applied to other cell types beyond hESCs and to a variety of heterogeneous cell populations in order to select and analyze cells of interest.

Self dilation as a treatment for resistant benign esophageal strictures: outcome, technique, and quality of life assessment.

BACKGROUND: Resistant benign esophageal strictures can have a negative impact on patients' quality of life. A portion of these patients require frequent physician performed dilations, leading to numerous interactions with their attendant inconvenience and sense of dependence. This study demonstrates the efficacy, safety and effect on quality of life of this under-utilized technique. METHODS: A retrospective chart review was performed for all patients undergoing esophageal self dilation at our institution between January 2003 and November 2009. The impact on quality of life was evaluated using a telephone questionnaire specifically designed to explore emotional, social and financial impacts. RESULTS: Of the 11 patients who initially began self dilation for non-malignant strictures, nine are included in this study. Median follow-up was 35.4 months (range 6-168). No significant complications were reported. When asked to compare self dilation with physician performed dilation a large proportion of patients reported financial benefits, and a majority reported being more socially active. Overall quality of life improvement was reported by almost all of the participants in the study. Global scores for dysphagia and overall quality of life were significantly improved under conditions of self dilation versus physician performed dilation (P = 0.008 and P = 0.016, respectively). CONCLUSIONS: Our results suggest that esophageal self dilation can be a safe and effective treatment modality in motivated patients with benign resistant esophageal strictures. Esophageal self dilation has a positive impact on emotional, social, and financial aspects of patient's life. Self dilation should be considered a treatment option in all patients with benign resistant esophageal strictures.

Comparison of the impact of wireless versus catheter-based pH-metry on daily activities and study-related symptoms.

AIMS: To evaluate the variation in tolerance to wireless pH-metry compared with catheter-based pH-metry, and to determine clinical characteristics that might predict reduced tolerance to wireless pH-metry. METHODS: Consecutive outpatients (n=341) completing wireless (n=234) or catheter-based pH-metry (n=106) were evaluated. All patients completed the pH-Metry Impact Scale and the pH-Metry Symptoms Scale to assess the impact of the pH-metry on activities of daily living and pH-metry associated changes in study-related symptoms. All data are presented as mean (SD) or odds ratios (95% confidence interval). RESULTS: The impact of pH-metry on activities of daily living were modest, but wireless pH-metry had less impact than catheter-based pH-metry (P=0.01). A sense of foreign body in the chest, chest discomfort, and chest pain were reported more frequently during wireless pH-metry. Difficulty swallowing and painful swallowing were more common during catheter-based pH-metry. Noncardiac chest pain was associated with increased symptom severity. Patients with poor tolerance were twice as likely to have a diagnosis of noncardiac chest pain (odds ratio=2. 53; 95% confidence interval, 1.4-4.6). CONCLUSIONS: Wireless pH-metry has less of an impact on activities of daily living but is not associated with fewer study-related symptoms compared with catheter-based pH-metry. The prevalence of specific study-related symptoms does differ between the 2 groups and noncardiac chest pain seems to be the primary risk factor for more severe study-related symptoms and reduced tolerance for wireless pH-metry. This information may be useful in helping to decide which patients should undergo the wireless pH-metry or receive additional counseling on procedural expectations.

An Unusual Case of Colon Perforation Complicating Acute Pancreatitis.

Colonic complications of severe acute pancreatitis occur rarely. Although there have been several theories on how pancreatic pseudocysts rupture into the colon, the exact pathogenesis remains unknown. We report an unusual case of pseudocysts complicating severe acute pancreatitis presenting with colonic perforation in a 71-year-old man with a history of chronic mesenteric ischemia. Pressure effects from a giant pseudocyst and intravascular volume depletion with acute insult on chronic mesenteric ischemia are highlighted as possible etiologic factors.

A case of melioidosis of the breast present at screening mammography.

A previously well 54-year-old woman presented for screening mammography with a 3-day history of an inflamed lump in her right breast. She was subsequently admitted to hospital with acute melioidosis where right breast abscesses were drained. Following recovery and discharge, she was reviewed at the mammographic screening unit where her previous abnormal mammogram was found to be due to melioidosis. To our knowledge this is the first reported case of melioidosis of the breast and its appearance on mammography and ultrasound are described.

Hyperammonemia and coma without hepatic dysfunction induced by valproate therapy.

The authors report a case of a 41-year-old mentally disabled man with bipolar disorder who presented to the emergency department with altered mental status. He was found to have a significantly elevated ammonia level (377 microM/L) with no signs of hepatic insufficiency. His coma and hyperammonemia were attributed to his chronic valproate therapy. This patient had the highest serum ammonia level ever reported with a therapeutic valproate level in the absence of any other anticonvulsant therapy, metabolic abnormality, or hepatic dysfunction. The authors discuss this case and review the current literature on hyperammonemia in valproic acid therapy and the use of L-carnitine in these patients.