Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers.

BACKGROUND: Germline variant evaluation in precision oncology opens new paths toward the identification of patients with genetic tumor risk syndromes and the exploration of therapeutic relevance. Here, we present the results of germline variant analysis and their clinical implications in a precision oncology study for patients with predominantly rare cancers. PATIENTS AND METHODS: Matched tumor and control genome/exome and RNA sequencing was carried out for 1485 patients with rare cancers (79%) and/or young adults (77% younger than 51 years) in the National Center for Tumor Diseases/German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER) trial, a German multicenter, prospective, observational precision oncology study. Clinical and therapeutic relevance of prospective pathogenic germline variant (PGV) evaluation was analyzed and compared to other precision oncology studies. RESULTS: Ten percent of patients (n = 157) harbored PGVs in 35 genes associated with autosomal dominant cancer predisposition, whereof up to 75% were unknown before study participation. Another 5% of patients (n = 75) were heterozygous carriers for recessive genetic tumor risk syndromes. Particularly, high PGV yields were found in patients with gastrointestinal stromal tumors (GISTs) (28%, n = 11/40), and more specifically in wild-type GISTs (50%, n = 10/20), leiomyosarcomas (21%, n = 19/89), and hepatopancreaticobiliary cancers (16%, n = 16/97). Forty-five percent of PGVs (n = 100/221) supported treatment recommendations, and its implementation led to a clinical benefit in 40% of patients (n = 10/25). A comparison of different precision oncology studies revealed variable PGV yields and considerable differences in germline variant analysis workflows. We therefore propose a detailed workflow for germline variant evaluation. CONCLUSIONS: Genetic germline testing in patients with rare cancers can identify the very first patient in a hereditary cancer family and can lead to clinical benefit in a broad range of entities. Its routine implementation in precision oncology accompanied by the harmonization of germline variant evaluation workflows will increase clinical benefit and boost research.

Regional analysis of inflammation and contractile function in reperfused acute myocardial infarction by in vivo 19F cardiovascular magnetic resonance in pigs.

Inflammatory cell infiltration is central to healing after acute myocardial infarction (AMI). The relation of regional inflammation to edema, infarct size (IS), microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and regional and global LV function is not clear. Here we noninvasively characterized regional inflammation and contractile function in reperfused AMI in pigs using fluorine (19F) cardiovascular magnetic resonance (CMR). Adult anesthetized pigs underwent left anterior descending coronary artery instrumentation with either 90 min occlusion (n = 17) or without occlusion (sham, n = 5). After 3 days, in surviving animals a perfluorooctyl bromide nanoemulsion was infused intravenously to label monocytes/macrophages. At day 6, in vivo 1H-CMR was performed with cine, T2 and T2* weighted imaging, T2 and T1 mapping, perfusion and late gadolinium enhancement followed by 19F-CMR. Pigs were sacrificed for subsequent ex vivo scans and histology. Edema extent was 35 ± 8% and IS was 22 ± 6% of LV mass. Six of ten surviving AMI animals displayed both MVO and IMH (3.3 ± 1.6% and 1.9 ± 0.8% of LV mass). The 19F signal, reflecting the presence and density of monocytes/macrophages, was consistently smaller than edema volume or IS and not apparent in remote areas. The 19F signal-to-noise ratio (SNR) > 8 in the infarct border zone was associated with impaired remote systolic wall thickening. A whole heart value of 19F integral (19F SNR × milliliter) > 200 was related to initial LV remodeling independently of edema, IS, MVO, and IMH. Thus, 19F-CMR quantitatively characterizes regional inflammation after AMI and its relation to edema, IS, MVO, IMH and regional and global LV function and remodeling.

Efficacy and safety of methylene blue in the treatment of malaria: a systematic review.

BACKGROUND: Methylene blue (MB) was the first synthetic antimalarial to be discovered and was used during the late 19th and early 20th centuries against all types of malaria. MB has been shown to be effective in inhibiting Plasmodium falciparum in culture, in the mouse model and in rhesus monkeys. MB was also shown to have a potent ex vivo activity against drug-resistant isolates of P. falciparum and P. vivax. In preclinical studies, MB acted synergistically with artemisinin derivates and demonstrated a strong effect on gametocyte reduction in P. falciparum. MB has, thus, been considered a potentially useful partner drug for artemisinin-based combination therapy (ACT), particularly when elimination is the final goal. The aim of this study was to review the scientific literature published until early 2017 to summarise existing knowledge on the efficacy and safety of MB in the treatment of malaria. METHODS: This systematic review followed PRISMA guidelines. Studies reporting on the efficacy and safety of MB were systematically searched for in relevant electronic databases according to a pre-designed search strategy. The search (without language restrictions) was limited to studies of humans published until February 2017. RESULTS: Out of 474 studies retrieved, a total of 22 articles reporting on 21 studies were eligible for analysis. The 21 included studies that reported data on 1504 malaria patients (2/3 were children). Older studies were case series and reports on MB monotherapy while recent studies were mainly controlled trials of combination regimens. MB was consistently shown to be highly effective in all endemic areas and demonstrated a strong effect on P. falciparum gametocyte reduction and synergy with ACT. MB treatment was associated with mild urogenital and gastrointestinal symptoms as well as blue coloration of urine. In G6PD-deficient African individuals, MB caused a slight but clinically non-significant haemoglobin reduction. CONCLUSIONS: More studies are needed to define the effects of MB in P. falciparum malaria in areas outside Africa and against P. vivax malaria. Adding MB to ACT could be a valuable approach for the prevention of resistance development and for transmission reduction in control and elimination programs. SYSTEMATIC REVIEW REGISTRATION: This study is registered at PROSPERO (registration number CRD42017062349 ).

Prevention of mother-to-child transmission of HIV: a cross-sectional study in Malawi.

OBJECTIVE: To estimate the use and outcomes of the Malawian programme for the prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). METHODS: In a cross-sectional analysis of 33 744 mother-infant pairs, we estimated the weighted proportions of mothers who had received antenatal HIV testing and/or maternal antiretroviral therapy and infants who had received nevirapine prophylaxis and/or HIV testing. We calculated the ratios of MTCT at 4-26 weeks postpartum for subgroups that had missed none or at least one of these four steps. FINDINGS: The estimated uptake of antenatal testing was 97.8%; while maternal antiretroviral therapy was 96.3%; infant prophylaxis was 92.3%; and infant HIV testing was 53.2%. Estimated ratios of MTCT were 4.7% overall and 7.7% for the pairs that had missed maternal antiretroviral therapy, 10.7% for missing both maternal antiretroviral therapy and infant prophylaxis and 11.4% for missing maternal antiretroviral therapy, infant prophylaxis and infant testing. Women younger than 19 years were more likely to have missed HIV testing (adjusted odds ratio, aOR: 4.9; 95% confidence interval, CI: 2.3-10.6) and infant prophylaxis (aOR: 6.9; 95% CI: 1.2-38.9) than older women. Women who had never started maternal antiretroviral therapy were more likely to have missed infant prophylaxis (aOR: 15.4; 95% CI: 7.2-32.9) and infant testing (aOR: 13.7; 95% CI: 4.2-83.3) than women who had. CONCLUSION: Most women used the Malawian programme for the prevention of MTCT. The risk of MTCT increased if any of the main steps in the programme were missed.

[Poliomyelitis--Challenges for the Last Mile of the Eradication Programme]. / Poliomyelitis--Herausforderungen in der Endphase des globalen Eradikationsprogramms.

The World Health Organisation initiated the Global Polio Eradication Initiative in the year 1988. With the large-scale application of routine and mass vaccinations in children under the age of 5 years, polio disease has become restricted to only 3 endemic countries (Afghanistan, Pakistan and Nigeria) by today. However, since the beginning of the 21st century, increasing numbers of secondary polio epidemics have been observed which were triggered through migration, political turmoil and weak health systems. In addition, there emerged serious technical (e. g., back-mutations of oral vaccine virus to wild virus) and socio-political (refusal of vaccinations in Muslim populations of Nigeria and Pakistan) problems with the vaccination in the remaining endemic countries. It thus appears questionable if the current eradiation initiative will reach its goal in the foreseeable future.

Characteristics of TPT initiation and completion among people living with HIV.

BACKGROUND: TB preventive treatment (TPT) reduces morbidity and mortality among people living with HIV (PLHIV). Despite the successful scale-up of TPT in Malawi, monitoring and evaluation have been suboptimal. We utilized the Malawi Population-Based HIV Impact Assessment (MPHIA) 2020-2021 survey data to estimate TPT uptake and completion among self-reported HIV-positive persons. METHODS: We estimated the proportion of HIV-positive respondents who had ever undergone TPT, and determined the percentage of those currently on TPT who had completed more than 6 months of treatment. Bivariate and multivariable logistic regression were performed to calculate the odds ratios for factors associated with ever-taking TPT. All variables were self-reported, and the analysis was weighted and accounted for in the survey design. RESULTS: Of the HIV+ respondents, 38.8% (95% CI 36.4-41.3) had ever taken TPT. The adjusted odds of ever taking TPT were 8.0 and 5.2 times as high in the Central and Southern regions, respectively, compared to the Northern region; 1.9 times higher among those in the highest wealth quintile, and 2.1 times higher for those on antiretroviral therapy >10 years. Of those currently taking TPT, 56.2% completed >6 months of TPT. CONCLUSION: These results suggest low TPT uptake and >6 months' completion rates among self-reported HIV+ persons. Initiatives to create demand and strengthen adherence would improve TPT uptake.

CONTEXTE: Le traitement préventif de la TB (TPT) réduit la morbidité et la mortalité chez les personnes vivant avec le VIH (PVVIH). Malgré l'extension réussie du TPT au Malawi, le suivi et l'évaluation n'ont pas été optimaux. Nous avons utilisé les données de l'enquête MPHIA (Malawi Population-Based HIV Impact Assessment) 2020­2021 pour estimer l'adoption et l'achèvement du TPT parmi les personnes se déclarant séropositives. MÉTHODES: Nous avons estimé la proportion de répondants séropositifs qui avaient déjà subi un TPT et déterminé le pourcentage de ceux qui sont actuellement sous TPT et qui ont terminé plus de 6 mois de traitement. Une régression logistique bivariée et multivariable a été effectuée pour calculer les rapports de cotes des facteurs associés au fait d'avoir déjà pris un TPT. Toutes les variables étaient autodéclarées et l'analyse a été pondérée et prise en compte dans la conception de l'enquête. RÉSULTATS: Parmi les répondants séropositifs, 38,8% (IC 95% 36,4­41,3) avaient déjà pris du TPT. Les probabilités ajustées de prise de TPT étaient 8,0 et 5,2 fois plus élevées dans les régions du centre et du sud, respectivement, que dans la région du nord ; 1,9 fois plus élevées chez les personnes appartenant au quintile de richesse le plus élevé, et 2,1 fois plus élevées chez les personnes suivant une thérapie antirétrovirale depuis plus de 10 ans. Parmi ceux qui prennent actuellement un TPT, 56,2% ont terminé >6 mois de TPT. CONCLUSION: Ces résultats suggèrent un faible taux d'utilisation du TPT et des taux d'achèvement de >6 mois parmi les personnes déclarées séropositives. Des initiatives visant à créer une demande et à renforcer l'adhésion permettraient d'améliorer l'utilisation du TPT.

Malnutrition in young children of rural Burkina Faso: comparison of survey data from 1999 with 2009.

OBJECTIVE: For measurement of progress towards the Millennium Development Goal (MDG) 1, reliable data on nutrition indicators of specific countries are essential. Malnutrition is also the main determinant for childhood mortality, which is addressed in MDG 4. METHODS: In the health and demographic surveillance area of Kossi Province in north-western Burkina Faso, nutritional parameters were compared in two cohorts of young children of the same age range from eight villages. Surveys took place in June and December of the year 1999 and 2009. A multivariate model was used to control for confounding variables. RESULTS: For the 1999 study, data were analysed for 179 and 197 children who took part in the June and December survey respectively. In 2009, corresponding data were analysed for 460 and 409 children. Prevalence of underweight was highest in December 1999 (42.6%) and lowest in December 2009 (34.1%). After adjustment for age, sex and village, there was a slight but not always significant improvement in the z-scores of weight-for-age, weight-for-length, length-for-age, and mid-arm circumference over time. CONCLUSIONS: The findings from this study confirm the still unacceptable high prevalence of malnutrition in young children of rural sub-Saharan Africa (SSA). Progress in the reduction of malnutrition remains slow on this continent making it rather unlikely that the corresponding MDGs will be achieved. Large-scale multi-sectoral community-based interventions are urgently needed for a sustainable improvement of child health in SSA.

Terminations of pregnancy in the European Union.

OBJECTIVE: To study the current legislation and trends in terminations of pregnancy in the European Union (EU). DESIGN: Data were collected on legislation and statistics for terminations of pregnancy. SETTING: Population-based statistics from the EU member states. POPULATION: Women in reproductive age in the 27 EU member states. METHODS: Information on legislation was collected for all 27 EU member states. Statistical information until 2008 was compiled from international (n = 24) and national sources (n = 17). Statistical data were not available for Austria, Cyprus and Luxembourg. MAIN OUTCOMES MEASURES: Terminations of pregnancy per 1000 women aged 15-49 years. RESULTS: Ireland, Malta and Poland have restrictive legislation. Luxembourg permits termination of pregnancy on physical and mental health indications; Cyprus, Finland, and the UK further include socio-economic indications. In all other EU member states termination of pregnancy can be performed in early pregnancy on a women's request. In general, the rates of termination of pregnancy have declined in recent years. In total, 10.3 terminations were reported per 1000 women aged 15-49 years in the EU in 2008. The rate was 12.3/1000 for countries requiring a legal indication for termination, and 11.0/1000 for countries allowing termination on request. Northern Europe (10.9/1000) and Central and Eastern Europe (10.8/1000) had higher rates than Southern Europe (8.9/1000). Northern Europe, however, had substantially higher rates of termination of pregnancy among teenagers. CONCLUSION: A more consistent and coherent reporting of terminations of pregnancy is needed in the EU. The large variation of termination rates between countries suggests that termination of pregnancy rates may be reduced in some countries without restricting women's access to termination. Sexual education and provision of access to reliable and affordable contraception are essential to achieve low rates of termination of pregnancy.

Determinants of the use of insecticide-treated mosquito nets in pregnant women: a mixed-methods study in Ghana.

BACKGROUND: Malaria in pregnancy remains a significant cause of morbidity and mortality, affecting the highly endemic countries of sub-Saharan Africa (SSA). Insecticide-treated nets (ITNs) are effective for malaria prevention. However, poor adherence in SSA remains a challenge. METHODS: We conducted a standard questionnaire survey among 710 pregnant women from 37 primary care clinics in the Upper West Region of Ghana from January through May 2019. Using a sequential explanatory design, we integrated the survey data from six focus group discussions with pregnant women. RESULTS: While 67% of women had some general knowledge about malaria prevention, only 19% knew the specific risks in pregnancy. Determinants of ITN use included ITN ownership (odds ratio [OR] 2.4 [95% confidence interval {CI} 1.3 to 4.4]), good maternal knowledge of the risks of malaria in pregnancy (OR 2.4 [95% CI 1.3 to 4.3]) and more antenatal care (ANC) contacts (OR 1.3 [95% CI 1.0 to 1.5)]. Focus group discussions showed that non-use of ITNs resulted from inappropriate hanging infrastructure, a preference for other malaria prevention alternatives, allergy and heat. CONCLUSIONS: Specific maternal knowledge of malaria risks in pregnancy was low and influenced the regular use of ITNs. Community and ANC-based malaria interventions should prioritize increasing knowledge of the specific risks of malaria.

Hydroclimate footprint of pan-Asian monsoon water isotope during the last deglaciation.

Oxygen isotope speleothem records exhibit coherent variability over the pan-Asian summer monsoon (AM) region. The hydroclimatic representation of these oxygen isotope records for the AM, however, has remained poorly understood. Here, combining an isotope-enabled Earth system model in transient experiments with proxy records, we show that the widespread AM δ18Oc signal during the last deglaciation (20 to 11 thousand years ago) is accompanied by a continental-scale, coherent hydroclimate footprint, with spatially opposite signs in rainfall. This footprint is generated as a dynamically coherent response of the AM system primarily to meltwater forcing and secondarily to insolation forcing and is further reinforced by atmospheric teleconnection. Hence, widespread δ18Op depletion in the AM region is accompanied by a northward migration of the westerly jet and enhanced southwesterly monsoon wind, as well as increased rainfall from South Asia (India) to northern China but decreased rainfall in southeast China.

Declining child mortality in northern Malawi despite high rates of infection with HIV.

OBJECTIVE: To determine whether routine surveys, such as the Demographic and Health Surveys (DHS), have underestimated child mortality in Malawi. METHODS: Rates and causes of child mortality were obtained from a continuous-registration demographic surveillance system (DSS) in Malawi for a population of 32 000. After initial census, births and deaths were reported by village informants and updated monthly by project enumerators. Cause of death was established by verbal autopsy whenever possible. The likely impact of human immunodeficiency virus (HIV) infection on child mortality was also estimated from antenatal clinic surveillance data. Overall and age-specific mortality rates were compared with those from the 2004 Malawi DHS. FINDINGS: Between August 2002 and February 2006, 38 617 person-years of observation were recorded for 20 388 children aged < 15 years. There were 342 deaths. Re-census data, follow-up visits at 12 months of age and the ratio of stillbirths to neonatal deaths suggested that death registration by the DSS was nearly complete. Infant mortality was 52.7 per 1000 live births, under-5 mortality was 84.8 per 1000 and under-15 mortality was 99.1 per 1000. One-fifth of deaths by age 15 were attributable to HIV infection. Child mortality rates estimated with the DSS were approximately 30% lower than those from national estimates as determined by routine surveys. CONCLUSION: The fact that child mortality rates based on the DSS were relatively low in the study population is encouraging and suggests that the low mortality rates estimated nationally are an accurate reflection of decreasing rates.

Paclitaxel and carboplatin vs gemcitabine and vinorelbine in patients with adeno- or undifferentiated carcinoma of unknown primary: a randomised prospective phase II trial.

Platinum/taxane combinations are widely used in patients with carcinoma of unknown primary (CUP), yielding response rates of 30% and median overall survival of 9-11 months in selected patients. Yet these combinations have not been subject to a randomised trial to overcome selection bias, a major problem in CUP. We randomised 92 patients to either paclitaxel/carboplatin (arm A) or the non-platinum non-taxane regimen gemcitabine/vinorelbine (arm B). The primary endpoint was rate of practicability as defined: application of >or=2 cycles of therapy (1) with a maximal delay of 1 week (2) and survival of >or=8 months (3). Practicability was shown in 52.4% (95% CI 36-68%) in arm A and in 42.2% (95% CI 28-58%) in arm B, respectively. The median overall survival, 1-year survival -rate and response rate of patients treated in arm A was 11.0 months, 38, and 23.8%, arm B 7.0 months, 29, and 20%. In conclusion, the paclitaxel/carboplatin regimen showed clinically meaningful activity in this randomised trial (Clinical trial registration number 219, 'Deutsches KrebsStudienRegister', German Cancer Society.)

Peripheral neuropathy in HIV-positive patients at an antiretroviral clinic in Lilongwe, Malawi.

Peripheral neuropathy (PN) is common in the setting of antiretroviral (ARV) programmes in resource-limited settings and poses significant challenges in assessment and management. A retrospective analysis was undertaken of prevalence and management of PN in a cohort of 3341 patients on highly active antiretroviral therapy. A first line ARV regimen containing stavudine (D4T) is used for clinically eligible patients. Amitriptyline is prescribed for symptom relief and in cases of persistent or escalating symptoms zidovudine (AZT) is substituted for D4T. Leg pain or numbness was reported in 1173 patients (35%). However, only 428 (13%) were given a diagnosis of PN, 228 (7%) were prescribed amitriptyline and 200 (6%) were switched to AZT. A recent pharmokinetic study in this population showed a high Cmax of D4T with the generic combination triomune (D4T 40 mg). This could account for the high prevalence of PN. The optimum time for switch to a non-D4T containing regimen is unknown.

[The phenomenology of cervical dystonia]. / Zur Phänomenologie der zervikalen Dystonien.

BACKGROUND: Cervical dystonia is the most common form of focal dystonia. Most cases of cervical dystonia are idiopathic and generally it is a life-long disorder. In recent years, Botulinum toxin type A (BtA) has become the first line therapy. However, some patients are resistant to it. This problem leads to the study of the clinical forms of cervical dystonias with the help of CT and MRI. PATIENTS AND METHODS: 78 patients with diagnosed primary cervical dystonia were examined. All underwent CT of the soft tissues of the neck with the aid of slices at the level of cervical vertebra 3 and 7. The cervical spine and the soft tissues of the neck were examined using magnetic resonance tomography in T 1 and T 2 with a slice thickness of 2 mm and in T 1 tilted towards the deep neck muscles. For comparison the MRT image data of 50 patients who had no cervical dystonia was analysed. The largest diameters were measured and the shape of all muscles captured in the neck region was described, including the small neck muscles. RESULTS: It was shown that in lateral flexion and in rotation, in 1 / 5 of patients the disorder affected only muscles which work on atlanto-occipital joints (latero- or torticaput), and in a further 1 / 5 it affected only muscles which work on the cervical spine (latero- or torticollis). 3 / 5 showed both disorders, but with a different degree of caput and collis involvement. Thus a ration of 1:1:3 was obtained in relation to this. CONCLUSIONS: 1. In lateral tilt, differentiation between laterocollis and laterocaput is clinically possible. 2. Lateral shift always occurs when laterocollis is present on one side and laterocaput on the other. 3. In rotation, clinical differentiation between torticollis and torticaput is not always possible. In this case CT sections at levels C 3 and C 7 are recommended. By comparing the vertebral position at the two levels it is possible to differentiate reliably between torticollis and torticaput. 4. Anteflexion--differentiation between anterocollis and anterocaput--is analysed by lateral inspection of the angle between the cervical spine and the thoracic spine or between the cervical spine and the base of the skull. The same applies for the analysis of retroflexion, the differentiation between retrocollis and retrocaput. 5. A posteroanterior sagittal shift requires no further diagnosis: it is often caused by bilateral dystonic activity of the sternocleidomastoid muscles.

Holography and criticality in matchgate tensor networks.

The AdS/CFT correspondence conjectures a holographic duality between gravity in a bulk space and a critical quantum field theory on its boundary. Tensor networks have come to provide toy models to understand these bulk-boundary correspondences, shedding light on connections between geometry and entanglement. We introduce a versatile and efficient framework for studying tensor networks, extending previous tools for Gaussian matchgate tensors in 1 + 1 dimensions. Using regular bulk tilings, we show that the critical Ising theory can be realized on the boundary of both flat and hyperbolic bulk lattices, obtaining highly accurate critical data. Within our framework, we also produce translation-invariant critical states by an efficiently contractible tensor network with the geometry of the multiscale entanglement renormalization ansatz. Furthermore, we establish a link between holographic quantum error-correcting codes and tensor networks. This work is expected to stimulate a more comprehensive study of tensor network models capturing bulk-boundary correspondences.

Ascertainment of childhood vaccination histories in northern Malawi.

OBJECTIVE: To assess factors related to recorded vaccine uptake, which may confound the evaluation of vaccine impact. METHODS: Analysis of documented vaccination histories of children under 5 years and demographic and socio-economic characteristics collected by a demographic surveillance system in Karonga District, Malawi. Associations between deviations from the standard vaccination schedule and characteristics that are likely to be associated with increased mortality were determined by multivariate logistic regression. RESULTS: Approximately 78% of children aged 6-23 months had a vaccination document, declining to <50% by 5 years of age. Living closer to an under-5 clinic, having a better educated father, and both parents being alive were associated with having a vaccination document. For a small percentage of children, vaccination records were incomplete and/or faulty. Vaccination uptake was high overall, but delayed among children living further from the nearest under-5 clinic or from poorer socio-economic backgrounds. Approximately 9% of children had received their last dose of DPT with or after measles vaccine. These children were from relatively less educated parents, and were more likely to have been born outside the health services. CONCLUSIONS: Though overall coverage in this community was high and variation in coverage according to child or parental characteristics small, there was strong evidence of more timely coverage among children from better socio-economic conditions and among those who lived closer to health facilities. These factors are likely to be strong confounders in the association of vaccinations with mortality, and may offer an alternative explanation for the non-specific mortality impact of vaccines described by other studies.

Decompensated labyrinthine weakness presenting as de novo peripheral vertigo: a discrete clinical entity?

OBJECTIVE: A distinct subgroup of patients, presenting with apparently spontaneous onset of vertigo, is described. RESULTS: Although vestibular evaluation revealed caloric weakness, the proximate cause of vertigo was not labyrinthine dysfunction, but rather the loss of vestibular compensation for an older and previously compensated labyrinthine injury. CONCLUSION: Instead of addressing the vestibular weakness, effective management needs to focus on the condition that has caused the loss of compensation.

CMR-guidance of passively tracked endomyocardial biopsy in an in vivo porcine model.

Endomyocardial biopsy (EMB) is considered to be the diagnostic gold-standard in detection of myocardial-inflammation. EMB is usually conducted under fluoroscopy without any specific target information. Specific target-information provided by cardiovascular magnetic resonance (CMR) may improve specificity of EMB. The aim was to investigate feasibility and safety of CMR-guided and targeted EMB in a preclinical-model using passively-tracked devices. Procedures were performed on a MRI-System equipped with an Interventional Software-Platform for real-time imaging. Ex vivo experiments were conducted to optimize visibility of the guide-sheath. In vivo experiments were conducted in 2 pigs for technical feasibility assessment and in 4 pigs after acute myocardial infarction to test feasibility of guided and lesion targeted EMB. For anatomical real-time imaging a single-shot-balanced-SSFP-sequence was applied. Myocardial targets were identified under real-time imaging (single-shot-T2 (sshT2) and single-shot Late-Gadolinium-Enhancement (sshLGE) sequences). Ex vivo experiments demonstrated best visibility of continuously labelled guide-sheath. CMR-guided EMB was feasible in all cases without major complications. Likewise, lesion-targeting endomyocardial biopsy was feasible in two cases. Biopsies exhibited appropriate sizes and qualities. Real-time lesion sequences revealed comparable CNR values to clinical-protocols. Real-time imaging of lesions showed following signal- and contrast-to-noise ratios (SNR/CNR): SNR of sshT2- and sshLGE was 124 ± 35 and 67 ± 51 respectively, whereas CNR was 81 ± 30 and 57 ± 44. This study demonstrates feasibility and safety of CMR-guided and basically targeted EMB with passively-tracked devices. Signal-to-noise ratios of real-time sequences is non-inferior to standard sequences for lesion detection. CMR-guidance may improve diagnostic accuracy of EMB since CMR can detect myocardial-targets under real-time-imaging.

Benign positional vertigo and endolymphatic hydrops: what is the connection?

BACKGROUND: Although benign paroxysmal positional vertigo and endolymphatic hydrops are considered to be distinct diagnoses, a minority of vertiginous patients exhibit features of both conditions. This coincidence has been reported previously in the literature, and is reviewed here in terms of possible aetiology. RESULTS AND CONCLUSION: A new hypothesis to account for both conditions is offered, implicating free-floating degenerating debris from the otolithic apparatus. It is postulated that the gelatinous/proteinaceous component may account for an osmotically induced hydrops, while the calcified fragments may induce positional vertigo.

ENVIRONMENTAL DOSIMETRY WITH THE BeOSL PERSONAL DOSEMETER.

In the course of this work, a dosemeter for measurement of ambient dose equivalent H*(10) based on the BeOSL dosimetry system was designed. Calculations of the energy response of the two-element BeOSL personal dosemeter in terms of H*(10) showed that the response does not fulfil the requirements of IEC 62387 Especially, the response for photon energies of 60-100 keV is too low. It is possible to correct this under-response using a BeOSL two-element dosemeter, a linear algorithm and an additional cover for the dosemeter. The Hp(0.07) element is shielded with lead, and with the help of a linear algorithm, corrections of the energy response are possible. So, the national requirements for an H*(10) area dosemeter in Germany can be fulfilled. The requirements of IEC 62387 are fulfilled for angles of radiation incidence from 0° to 60° for a rotation around the vertical and horizontal axis through the dosemeter, whereas for angles of incidence from 75° to 90°, the requirements are only fulfilled for rotation around the vertical axis through both elements.