Infrared flashing light through the cricothyroid membrane as guidance to awake intubation with a flexible bronchoscope: A randomised cross-over study.

BACKGROUND: In case of distorted airway anatomy, awake intubation with a flexible bronchoscope can be extremely difficult or even impossible. To facilitate this demanding procedure, an infrared flashing light source can be placed on the patient's neck superficial to the cricothyroid membrane. The light travels through the skin and tissue to the trachea, from where it can be registered by the advancing bronchoscope in the pharynx and seen as flashing white light on the monitor. We hypothesised that the application of this technique would allow more proximal and easier identification of the correct pathway to the trachea in patients with severe airway pathology. METHODS: As part of awake intubation, patients underwent insertion of a flexible video bronchoscope via the mouth into the trachea. The procedure was performed twice, in random order in each patient, with and without the aid of the transcutaneous flashing infrared light. All insertions were video recorded to determine at which anatomical landmark within the airway the correct pathway was identified. The videos are accessible via this link: https://airwaymanagement.dk/infrared_comparative. The predefined landmarks were in successive order: oral cavity, oro-pharynx, tip of epiglottis, arytenoid cartilages, false cords, vocal cords and trachea, as well as the spaces between them. RESULTS: Twenty-two patients had a total of 44 awake insertions with the flexible bronchoscope. The median anatomical level, at which correct identification of the trachea was obtained on the monitor, was, past the epiglottis, with the conventional technique, and at the level of the oropharynx, when using the infrared flashing light (p = .005). The time until the flashing light or the vocal cords were seen was 21 (22) S, mean (SD), and 48 (62) S, during the insertion with and without infrared flashing light activated, respectively (p = .005). Endoscopists rated it easier (p = .001) to recognise the entrance to the trachea in the infrared-group. CONCLUSION: During awake intubation of patients with airway pathology, the application of trans-cricothyroid infrared flashing light to guide the insertion of a flexible bronchoscope significantly facilitated the recognition of the pathway into the trachea and the correct advancement of the flexible endoscope. REGISTRATION OF CLINICAL TRIAL: NCT03930550.

Increased barium levels in recent marine sediments from the Norwegian and Barents Seas suggest impact of hydrocarbon drilling and production.

Barium (Ba) in recent marine sediments can originate from natural and anthropogenic sources including discharges from the oil and gas industry. In this study, we use data from the Norwegian and Barents Seas to assess whether Ba in recent marine sediments has increased due to these discharges. To account for Ba in detrital material, we normalise all samples with respect to aluminosilicate by calculating an enrichment factor. We use statistical modelling to control for parameters related to sedimentation. We present results that suggest increased Ba levels in recent sediments that coincide with the timing of hydrocarbon drilling and production. This is supported by geographical differences on a large scale that relate to proximity to hydrocarbon drilling and production. Among 243 sampling stations, we identify 73 locations exhibiting enrichment of Ba in the upper 6 of sediment. At these locations, Ba is 1.55 to 3.55 times higher than the levels that can be expected from the shale average when Ba in detrital matter is accounted for. Excess Ba is reported in sediment surface samples in areas important to fisheries like the Lofoten area and the western Barents Sea.

Psoriatic Spondylitis: A Disease Manifestation in Debate: Evidences to Know for the Clinical Rheumatologist.

ABSTRACT: With the advent of classification criteria for psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), patients with axial manifestations associated with psoriasis, initially described in the l950s as a specific entity termed psoriatic spondylitis (PS), are now categorized within PsA, ankylosing spondylitis (AS), and axSpA. Thus, different terms are used to describe axial disease in patients with PsA including PS, axial psoriatic arthritis (axPsA), and psoriatic spondyloarthritis. Patients with PS may present with inflammatory and/or mechanical back pain, but also may display axial disease on imaging despite not complaining of back pain. Cervical spondylitis has been reported in 35% to 75% of patients with PsA. Axial disease is silent in 20% and 25% of patients with axial PsA and PsA, respectively. The majority of axPsA patients have peripheral arthritis alongside the axial involvement, whereas only 2% to 5% of PsA patients have solely axial arthritis with no peripheral arthritis.A debate is currently underway as to whether inflammatory axial disease and psoriasis represent axSpA with psoriasis or a subset of PsA named axPsA. Studies have recognized that axial disease in PsA patients seems to be different demographically, genetically, clinically, and radiographically when compared with AS with or without psoriasis. This narrative review summarizes current knowledge regarding axial involvement of PsA in terms of history, terminology, classification, epidemiology, clinical presentation, imaging, diagnosis, and treatment, with the aim of providing advice for management of PS in clinical evidence-based practice. Data-driven studies are needed to develop clear, nonoverlapping classification criteria for spinal involvement in PsA.

Vaginal cysts: An important differential diagnosis in the anterior compartment.

INTRODUCTION: Benign anterior-vaginal-wall cysts (0.5-1% prevalence) often mimic other structures (e.g. cystoceles). No algorithm for their diagnosis, treatment, recurrence or complication prediction can be derived from existing data. Careful preoperative diagnosis can minimize intraoperative surprises and complications due to differences in cyst origin. METHODS: This retrospective study was performed with data from consecutive patients with anterior vaginal cysts who underwent surgery at the Pelvic Floor Centre, University Women's Hospital of Jena, within a period of 7 years. Data on patient age, symptoms, history of previous surgery, lesion characteristics, preoperative imaging findings, surgeries, postoperative stays, complications and histological and microbiological findings were collected. RESULTS: Out of 797 consecutive anterior vaginal prolapse repairs 19 (2.4%) anterior vaginal cystic lesions were found, mean age 47 [standard deviation (SD) 14, range 22-72] years. Symptoms reported were pressure (58%), voiding dysfunction (26%), dyspareunia (5%) and inflammation signs (37%); 26% of cases were asymptomatic. Two patients had received prolapse pessary treatment before. Two patients had history of previous vaginal surgery. Five cases were diagnosed preoperatively by ultrasound. Cysts were located on the medial anterior vaginal wall (42%), suburethral (42%) and the vaginal apex (16%). The mean lesion size was 2.6 (SD 0.9) cm. Eleven percent of cases showed microbiological positivity. Most (89%) vaginal cysts were excised; 11% were fenestrated, biopsied and drained. Twenty-six percent of patients underwent outpatient procedures; for inpatient procedures, the median stay was 2.7 days. Postoperative hemorrhage with no transfusion requirement occurred in one patient. All lesions were benign. CONCLUSIONS: Anterior-compartment vaginal cysts can be found incidentally during pelvic organ prolapse assessment and surgery, as they can mimic anterior-vaginal-wall prolapse. In this cohort, all excised lesions were benign.

Background concentrations of polycyclic aromatic hydrocarbons (PAHs) in deep core sediments from the Norwegian Sea and the Barents Sea: A proposed update of the OSPAR Commission background values for these sea areas.

Geochemical studies of 174 sediment cores collected by the MAREANO mapping program in Norwegian waters of the North Atlantic Ocean give new sets of values of background concentrations (BCs) for polycyclic aromatic hydrocarbons (PAHs) for the studied regions. The study is based on deep core sediment samples representing background levels of PAHs. The samples selected were only from the deeper parts of undisturbed sediment cores with low, stable concentrations of petrogenic and pyrogenic PAHs, with low variation for individual PAH compounds between the samples within the same core, and from below the parts of the cores dated with 210Pb to approximately the last 100-150 years. The results show that the main part of the studied area has BCs different from those previously established by OSPAR Commission (OSPAR) for the North-East Atlantic. Another area in central Barents Sea has a separate set of BCs of pyrogenic PAHs, apparently due to the influence from marginal ice zone mechanisms. A third area with its own set of BCs has been established for north-western Barents Sea off the coast of Svalbard, due to high natural contents of PAHs in this area. BCs for several PAHs not included in the present OSPAR list are also provided.

Can serum GAD65 antibody levels predict neurological disease or cancer?

The clinical relevance of antibodies that bind to glutamic acid decarboxylase 65 (GAD65) is controversial regarding diagnostic utility in screening for neurological disease or cancer. We did a retrospective study of 3152 GAD65 antibody-positive patients to examine whether analysis of the antibody levels could predict neurological disease or cancer. Serum GAD65 antibody levels were not associated with any of the following groups: neurological disease, neurological disease and diabetes, diabetes only, no neurological diagnosis and no diabetes mellitus, or cancer. Analysis of serum GAD65 antibody levels had no prognostic value in neurological disease or cancer. GAD65 antibodies should therefore be measured in selective cases of autoimmune neurological diseases.

Auguste Renoir, Sculptor With Hired Hands: A Masterful Artistic Cooperation Overshadowed by Legal Issues and Copyright Infringement.

The coping with rheumatoid arthritis of the famous French impressionist painter Pierre-Auguste Renoir (1841-1919) is described in former publications. The heavily handicapped painter has in his last years created sculptures in cooperation with the sculptor Richard Guino (1890-1973). The extraordinary genesis of the sculptures through a masterful artistic cooperation, as well as the resulting legal issues and shameful copyright infringements, is reported. Renoir's decision to create sculptures with the help of Guido can be attributed to his remarkable artistic vision, vitality, optimistic nature, and strong will and is also a further testimonial of creative coping of an artist overcoming the physical handicap due to rheumatoid arthritis of his final years, so far not described in detail in the medical literature.

LAVH superior to TVH when concomitant salpingo-oophorectomy is intended in prolapse hysterectomy: a comparative cohort study.

PURPOSE: This comparative cohort study evaluated the influence of surgical route for prolapse hysterectomy (vaginal or laparoscopically assisted) on the achievement of intended elective salpingo-oophorectomy, which was a procedural goal planned with the patient before primary vaginal native-tissue prolapse surgery. METHODS: Consecutive patients who underwent total vaginal hysterectomy (TVH; n = 163) or laparoscopically assisted vaginal hysterectomy (LAVH; n = 144) and vaginal native-tissue repair for pelvic organ prolapse at Jena University Hospital were enrolled. RESULTS: Peri- and postoperative parameters, including Clavien-Dindo (CD) classification of surgical complications, were compared between groups using Student's t test, Fisher's exact test, and multivariable regression. Patient characteristics were similar, except that grade IV prolapse was more common in the LAVH group (p < 0.001). The following parameters differed between the TVH and LAVH groups: concomitant salpingectomy (1.2% vs. 34%) and salpingo-oophorectomy (45% vs. 66%), non-performance of intended salpingo-oophorectomy (36% vs. 0% OR 0.006, 95% CI < 0.001-0.083), adhesiolysis (0% vs. 44%), CD II-III complications (51% vs. 14.6% p < 0.001), operating time (153 ± 61 vs. 142 ± 27 min), and postoperative in-patient days (9.02 ± 4.9 vs. 4.99 ± 0.96; all p < 0.001). CONCLUSIONS: LAVH enabled the safe performance of planned concomitant salpingo-oophorectomy in all cases. To achieve the procedural goal in such cases, laparoscopic assistance in prolapse hysterectomy should be considered.

Optimisation of quality indicators for lipid-lowering treatment of type 2 diabetes mellitus.

INTRODUCTION: The Danish Adult Diabetes Database (DADD) annually reports a quality indicator for lipid-lowering treatment of type 2 diabetes mellitus (T2DM) patients. This retrospective cohort study aims to A) investigate the reasons for inadequate or lacking lipid-lowering treatment and to B) assess the validity of the DADD indicator as a measure of quality of care. METHODS: A) A pop-up questionnaire enquiring about reasons for lack of treatment was added to the clinicians' data entry tool in the Central Denmark Region. B) The DADD indicator was compared on a per-clinic basis with the achieved median low-density lipoprotein (LDL) cholesterol level and with an internationally widely used indicator of lipid-lowering treatment quality. RESULTS: A) A total of 3,491 patients were registered from 1 January 2013 to 28 February 2015. For 170 (62%) of 309 patients with an LDL level > 2.5 mmol/l who were not receiving lipid-lowering treatment, there was no "good" explanation for lacking treatment. Among 518 patients with an LDL level > 2.5 mmol/l despite lipid-lowering treatment, 259 (50%) did not receive high-intensity treatment. B) The DADD quality indicator was neither associated with the international quality indicator nor with the median per-clinic LDL level for T2DM patients. CONCLUSIONS: A) We found substantial potential for improvement of lipid management among T2DM patients in Denmark by initiating and/or intensifying lipid-lowering treatment. B) The current DADD indicator is not a valid measure of lipid-lowering quality of care. FUNDING: supported by the Rosa and Asta Jensen Foundation. TRIAL REGISTRATION: not relevant.

Unleaded gasoline as a significant source of Pb emissions in the Subarctic.

After the phasing out of leaded gasoline, Pb emissions to the atmosphere dramatically decreased, and other sources became more significant. The contribution of unleaded gasoline has not been sufficiently recognized; therefore, we evaluated the impact of Pb from unleaded gasoline in a relatively pristine area in Subarctic NE Norway. The influence of different endmembers (Ni slag and concentrate from the Nikel smelter in Russia, PM10 filters, and traffic) on the overall Pb emissions was determined using various environmental samples (snow, lichens, and topsoils) and Pb isotope tracing. We found a strong relationship between Pb in snow and the Ni smelter. However, lichen samples and most of the topsoils were contaminated by Pb originating from the current use of unleaded gasoline originating from Russia. Historical leaded and recent unleaded gasoline are fully distinguishable using Pb isotopes, as unleaded gasoline is characterized by a low radiogenic composition (206Pb/207Pb = 1.098 and 208Pb/206Pb = 2.060) and remains an unneglectable source of Pb in the region.

Coxiella burnetii immunogenic proteins as a basis for new Q fever diagnostic and vaccine development.

Coxiella burnetii is the etiological agent of the zoonosis Q fever, which can cause an acute or a chronic, life-threatening disease in humans. It presents a highly stable cell form, which persists in the environment and is transmitted via contaminated aerosols. Ruminants are considered as the main reservoir for human infections but are usually asymptomatic. Subclinical infection in these animals and the occurrence of serologically negative shedders hamper the identification of infected animals with the currently used diagnostic techniques. This suboptimal sensitivity limits reliable identification of infected animals as well as the well-timed implementation of countermeasures. This review summarizes compounds, focusing on C. burnetii seroreactive proteins, which were discovered in recent immunoproteomic studies. We analyzed these proteins regarding their localization, function, frequency of citation, differences seen in various host species as well as sensitivity and specificity. Finally, proteins useful for the development of new diagnostic test systems as well as subunit vaccines were discussed.

Serological evidence of Francisella tularensis in febrile patients seeking treatment at remote hospitals, northeastern Kenya, 2014-2015.

Tularaemia is a highly contagious infectious zoonosis caused by the bacterial agent Francisella tularensis. The aim of this study was to investigate the presence of antibodies to F. tularensis in febrile patients in northeastern Kenya. During 2014-2015, 730 patients were screened for anti-F. tularensis antibodies using a combination of ELISA and Western blot. Twenty-seven (3.7%) individuals were positive for F. tularensis. Tularaemia was not suspected by the treating clinicians in any of them. Our results suggest that tularaemia may be present in Kenya but remain unreported, and emphasizes the need for local clinicians to broaden their diagnostic repertoire when evaluating patients with undifferentiated febrile illness.

Stable isotope tracing of Ni and Cu pollution in North-East Norway: Potentials and drawbacks.

The use of Ni and Cu isotopes for tracing contamination sources in the environment remains a challenging task due to the limited information about the influence of various biogeochemical processes influencing stable isotope fractionation. This work focuses on a relatively simple system in north-east Norway with two possible endmembers (smelter-bedrock) and various environmental samples (snow, soil, lichens, PM10). In general, the whole area is enriched in heavy Ni and Cu isotopes highlighting the impact of the smelting activity. However, the environmental samples exhibit a large range of δ60Ni (-0.01 ± 0.03‰ to 1.71 ± 0.02‰) and δ65Cu (-0.06 ± 0.06‰ to -3.94 ± 0.3‰) values which exceeds the range of δ60Ni and δ65Cu values determined in the smelter, i.e. in feeding material and slag (δ60Ni from 0.56 ± 0.06‰ to 1.00 ± 0.06‰ and δ65Cu from -1.67 ± 0.04‰ to -1.68 ± 0.15‰). The shift toward heavier Ni and Cu δ values was the most significant in organic rich topsoil samples in the case of Ni (δ60Ni up to 1.71 ± 0.02‰) and in lichens and snow in the case of Cu (δ65Cu up to -0.06 ± 0.06‰ and -0.24 ± 0.04‰, respectively). These data suggest an important biological and biochemical fractionation (microorganisms and/or metal uptake by higher plants, organo-complexation etc.) of Ni and Cu isotopes, which should be quantified separately for each process and taken into account when using the stable isotopes for tracing contamination in the environment.

Systematic review and meta-analysis of dietary carbohydrate restriction in patients with type 2 diabetes.

OBJECTIVE: Nutrition therapy is an integral part of self-management education in patients with type 2 diabetes. Carbohydrates with a low glycemic index are recommended, but the ideal amount of carbohydrate in the diet is unclear. We performed a meta-analysis comparing diets containing low to moderate amounts of carbohydrate (LCD) (energy percentage below 45%) to diets containing high amounts of carbohydrate (HCD) in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: We systematically reviewed Cochrane library databases, EMBASE, and MEDLINE in the period 2004-2014 for guidelines, meta-analyses, and randomized trials assessing the outcomes HbA1c, BMI, weight, LDL cholesterol, quality of life (QoL), and attrition. RESULTS: We identified 10 randomized trials comprising 1376 participants in total. In the first year of intervention, LCD was followed by a 0.34% lower HbA1c (3.7 mmol/mol) compared with HCD (95% CI 0.06 (0.7 mmol/mol), 0.63 (6.9 mmol/mol)). The greater the carbohydrate restriction, the greater the glucose-lowering effect (R=-0.85, p<0.01). At 1 year or later, however, HbA1c was similar in the 2 diet groups. The effect of the 2 types of diet on BMI/body weight, LDL cholesterol, QoL, and attrition rate was similar throughout interventions. LIMITATIONS: Glucose-lowering medication, the nutrition therapy, the amount of carbohydrate in the diet, glycemic index, fat and protein intake, baseline HbA1c, and adherence to the prescribed diets could all have affected the outcomes. CONCLUSIONS: Low to moderate carbohydrate diets have greater effect on glycemic control in type 2 diabetes compared with high-carbohydrate diets in the first year of intervention. The greater the carbohydrate restriction, the greater glucose lowering, a relationship that has not been demonstrated earlier. Apart from this lowering of HbA1c over the short term, there is no superiority of low-carbohydrate diets in terms of glycemic control, weight, or LDL cholesterol.

Systematic review of brucellosis in Kenya: disease frequency in humans and animals and risk factors for human infection.

BACKGROUND: Brucellosis is a debilitating zoonotic disease affecting humans and animals. A comprehensive, evidence-based assessment of literature and officially available data on animal and human brucellosis for Kenya are missing. The aim of the current review is to provide frequency estimates of brucellosis in humans, animals and risk factors for human infection, and help to understand the current situation in Kenya. METHODS: A total of accessible 36 national and international publications on brucellosis from 1916 to 2016 were reviewed to estimate the frequency of brucellosis in humans and animals, and strength of associations between potential risk factors and seropositivity in humans in Kenya. RESULTS: The conducted studies revealed only few and fragmented evidence of the disease spatial and temporal distribution in an epidemiological context. Bacteriological evidence revealed the presence of Brucella (B.) abortus and B. melitensis in cattle and human patients, whilst B. suis was isolated from wild rodents only. Similar evidence for Brucella spp infection in small ruminants and other animal species is unavailable. The early and most recent serological studies revealed that animal brucellosis is widespread in all animal production systems. The animal infection pressure in these systems has remained strong due to mixing of large numbers of animals from different geographical regions, movement of livestock in search of pasture, communal sharing of grazing land, and the concentration of animals around water points. Human cases are more likely seen in groups occupationally or domestically exposed to livestock or practicing risky social-cultural activities such as consumption of raw blood and dairy products, and slaughtering of animals within the homesteads. Many brucellosis patients are misdiagnosed and probably mistreated due to lack of reliable laboratory diagnostic support resulting to adverse health outcomes of the patients and routine disease underreporting. We found no studies of disease incidence estimates or disease control efforts. CONCLUSION: The risk for re-emergence and transmission of brucellosis is evident as a result of the co-existence of animal husbandry activities and social-cultural activities that promote brucellosis transmission. Well-designed countrywide, evidence-based, and multidisciplinary studies of brucellosis at the human/livestock/wildlife interface are needed. These could help to generate reliable frequency and potential impact estimates, to identify Brucella reservoirs, and to propose control strategies of proven efficacy.

Febrile patients admitted to remote hospitals in Northeastern Kenya: seroprevalence, risk factors and a clinical prediction tool for Q-Fever.

BACKGROUND: Q fever in Kenya is poorly reported and its surveillance is highly neglected. Standard empiric treatment for febrile patients admitted to hospitals is antimalarials or penicillin-based antibiotics, which have no activity against Coxiella burnetii. This study aimed to assess the seroprevalence and the predisposing risk factors for Q fever infection in febrile patients from a pastoralist population, and derive a model for clinical prediction of febrile patients with acute Q fever. METHODS: Epidemiological and clinical data were obtained from 1067 patients from Northeastern Kenya and their sera tested for IgG antibodies against Coxiella burnetii antigens by enzyme-linked-immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA) and quantitative real-time PCR (qPCR). Logit models were built for risk factor analysis, and diagnostic prediction score generated and validated in two separate cohorts of patients. RESULTS: Overall 204 (19.1 %, 95 % CI: 16.8-21.6) sera were positive for IgG antibodies against phase I and/or phase II antigens or Coxiella burnetii IS1111 by qPCR. Acute Q fever was established in 173 (16.2 %, 95 % CI: 14.1-18.7) patients. Q fever was not suspected by the treating clinicians in any of those patients, instead working diagnosis was fever of unknown origin or common tropical fevers. Exposure to cattle (adjusted odds ratio [aOR]: 2.09, 95 % CI: 1.73-5.98), goats (aOR: 3.74, 95 % CI: 2.52-9.40), and animal slaughter (aOR: 1.78, 95 % CI: 1.09-2.91) were significant risk factors. Consumption of unpasteurized cattle milk (aOR: 2.49, 95 % CI: 1.48-4.21) and locally fermented milk products (aOR: 1.66, 95 % CI: 1.19-4.37) were dietary factors associated with seropositivity. Based on regression coefficients, we calculated a diagnostic score with a sensitivity 93.1 % and specificity 76.1 % at cut off value of 2.90: fever >14 days (+3.6), abdominal pain (+0.8), respiratory tract infection (+1.0) and diarrhoea (-1.1). CONCLUSION: Q fever is common in febrile Kenyan patients but underappreciated as a cause of community-acquired febrile illness. The utility of Q fever score and screening patients for the risky social-economic and dietary practices can provide a valuable tool to clinicians in identifying patients to strongly consider for detailed Q fever investigation and follow up on admission, and making therapeutic decisions.

Q fever is an old and neglected zoonotic disease in Kenya: a systematic review.

BACKGROUND: Q fever is a neglected zoonosis caused by the bacterium Coxiella burnetii. The knowledge of the epidemiology of Q fever in Kenya is limited with no attention to control and prevention programs. The purpose of this review is to understand the situation of Q fever in human and animal populations in Kenya in the past 60 years, and help identify future research priorities for the country. METHODS: Databases were searched for national and international scientific studies or reports on Q fever. We included studies and reports published between 1950 and 2015 if they reported on Q fever prevalence, incidence, and infection control programs in Kenya. Data were extracted with respect to studies on prevalence of Coxiella infections, study design, study region, the study populations involved, and sorted according to the year of the study. RESULTS: We identified 15 studies and reports which qualified for data extraction. Human seroprevalence studies revealed evidence of C. burnetii infections ranging from 3 to 35.8% in all regions in which surveys were made and two Q fever outbreak episodes. Coxiella burnetii infections found in cattle 7.4-51.1%, sheep 6.7-20%, camels 20-46%, and goats 20-46% revealed variation based on ecoregions and the year of study. Farming and lack of protective clothing were associated with increased seropositivity among humans. However, high quality data is lacking on Q fever awareness, underlying cultural-economic factors influencing C. burnetii infection, and how the pathogen cycles may be embedded in livestock production and management systems in the economically and ecologically different Kenyan regions. We found no studies on national disease incidence estimates or disease surveillance and control efforts. CONCLUSION: Coxiella burnetii infections are common in human and in a wide range of animal populations but are still unrecognized and underestimated thus presenting a significant human and animal health threat in Kenya. The factors influencing pathogen transmission, persistence and spread are poorly understood. Integrated disease surveillance and prevention/control programs are needed in Kenya.

Bayesian Cure Rate Modeling of Local Tumor Control: Evaluation in Stereotactic Body Radiation Therapy for Pulmonary Metastases.

PURPOSE: Most radiobiological models for prediction of tumor control probability (TCP) do not account for the fact that many events could remain unobserved because of censoring. We therefore evaluated a set of TCP models that take into account this censoring. METHODS AND MATERIALS: We applied 2 fundamental Bayesian cure rate models to a sample of 770 pulmonary metastasis treated with stereotactic body radiation therapy at German, Austrian, and Swiss institutions: (1) the model developed by Chen, Ibrahim and Sinha (the CIS99 model); and (2) a mixture model similar to the classic model of Berkson and Gage (the BG model). In the CIS99 model the number of clonogens surviving the radiation treatment follows a Poisson distribution, whereas in the BG model only 1 dominant recurrence-competent tissue mass may remain. The dose delivered to the isocenter, tumor size and location, sex, age, and pretreatment chemotherapy were used as covariates for regression. RESULTS: Mean follow-up time was 15.5 months (range: 0.1-125). Tumor recurrence occurred in 11.6% of the metastases. Delivered dose, female sex, peripheral tumor location and having received no chemotherapy before RT were associated with higher TCP in all models. Parameter estimates of the CIS99 were consistent with the classical Cox proportional hazards model. The dose required to achieve 90% tumor control after 15.5 months was 146 (range: 114-188) Gy10 in the CIS99 and 133 (range: 101-164) Gy10 in the BG model; however, the BG model predicted lower tumor control at long (≳20 months) follow-up times and gave a suboptimal fit to the data compared to the CIS99 model. CONCLUSIONS: Biologically motivated cure rate models allow adding the time component into TCP modeling without being restricted to the follow-up period which is the case for the Cox model. In practice, application of such models to the clinical setting could allow for adaption of treatment doses depending on whether local control should be achieved in the short or longer term.

Local tumor control probability modeling of primary and secondary lung tumors in stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and between primary non-small cell lung cancer (NSCLC) and secondary lung tumors. MATERIALS AND METHODS: A retrospective multi-institutional (n=22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison. RESULTS: After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose-response relationship was observed in the primary NSCLC and metastatic cohort but dose-response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151-223) and 160 Gy (123-237) (n.s.), respectively. The dose-response relationship was not influenced by the primary cancer site within the metastatic cohort. CONCLUSIONS: Dose-response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases.

First Draft Genome Sequence of a Human Coxiella burnetii Isolate, Originating from the Largest Q Fever Outbreak Ever Reported, the Netherlands, 2007 to 2010.

In 2009, Coxiella burnetii caused a large regional outbreak of Q fever in South Limburg, the Netherlands. Here, we announce the genome draft sequence of a human C. burnetii isolate, strain NL-Limburg, originating from this outbreak, including a brief summary of the genome's general features.