Maxillary canine position of patients with non-syndromic craniofacial disorder: a retrospective evaluation of panoramic radiographs.

BACKGROUND: The study evaluates the position and displacement tendency of unerupted maxillary canines in orthodontic patients with non-syndromic craniofacial disorders (CD) compared to a control (C) group. METHODS: Canine position and displacement tendency were evaluated using panoramic radiographs (PAN) examined with parameters such as sector classification (sectors 1-5) and inclination angles (α and ß). The displacement tendency was defined as the positioning of the tip in sectors 1 or 2, as well as its combination with increased angles (α > 30° and ß > 39°). In addition, the correlation of the tooth position and agenesis, cleft side, and sex was assessed. RESULTS: A total of 116 pre-treatment PAN, divided into the CD group (n = 50; mean age 8.32 ± 2.27 years) and the C group (n = 66; mean age 10.80 ± 2.82 years), were evaluated in this study. The sector classification showed no displacement tendency in both groups. Inclination angles α/ß showed a statistically significant higher displacement tendency (p = 0.01) of the CD group (n = 5) on the right side, compared to healthy subjects (n = 1). Male CD patients had a statistically significant higher displacement tendency on the right side (p = 0.03). A statistically significant correlation between cleft and non-cleft-side (p = 0.03) was found. CONCLUSION: Patients with CD showed a statistically significant higher displacement tendency of the maxillary canine affected by the cleft side. The inclination angle was found to be the better predictor compared to the sector classification which should be considered in the orthodontic treatment planning.

Combined chemotherapy and pembrolizumab salvages multi-chemotherapy agent and avelumab resistant choriocarcinoma: A case report.

Introduction: Gestational trophoblastic neoplasia (GTN) including choriocarcinoma (CC) frequently requires multi-agent chemotherapy to achieve cure. In chemotherapy-resistant GTN, immunotherapy with the checkpoint inhibitors pembrolizumab, avelumab and camrelizumab are potential new treatment options previously described in small case series, phase 2 trials and case reports. Case description: A 32-year-old woman was diagnosed with gestational choriocarcinoma (FIGO score 5). Prior administered therapy regimes included methotrexate, actinomycin-D followed by open hysterectomy with bilateral salpingectomy (histology without GTN) as well as multi-agent chemotherapy and avelumab single-agent. After detection of a suspicious pulmonary mass video- assisted thoracoscopic left lung segmentectomy was performed confirming CC. The patient experienced an intracerebral haemorrhage and was treated with an emergency decompressive craniotomy. The cerebrospinal fluid showed an increased ratio of hCG compared to serum. Therapy with combined escalated etoposide and cisplatin with pembrolizumab was commenced followed by maintenance pembrolizumab achieving a complete hCG response and negative PET CT. Discussion: In the management of multi drug- resistant GTN, application of checkpoint inhibitor pembrolizumab is a new therapeutic strategy. In this heavily pre-treated patient incorporation of pembrolizumab resulted in complete long-term response in a patient who had also failed avelumab therapy.

[Topicality of the fundamental and determining importance of chronic critical ischemia of the extremities and its restorative treatment using crural/pedal bypasses in Germany and in Saxony-Anhalt]. / Aktualität der grundlegenden und determinierenden Bedeutung der chronisch-kritischen Extremitätenischämie sowie ihrer sich reetablierenden Behandlung mittels kruraler/pedaler Bypässe in Deutschland und in Sachsen-Anhalt.

INTRODUCTION: Currently, there is an increase in severe stages of peripheral arterial occlusive disease (PAOD) with critical ischemia. This seems to correspond to the general demographic change as well as a consequence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic of the last 3 years. The now established and accepted interventional/endovascular approach for severe lower leg PAOD in experienced hands is still considered the first-line treatment but from the authors' perspective crural/pedal venous bypass is experiencing a renaissance. MATERIAL AND METHODS: Compact narrative review of the current state of crural/pedal bypass surgery in Germany and Saxony-Anhalt (SA) combined with selective references from the current scientific medical literature and own clinical experiences. RESULTS: The current statistics of case-related diagnosis-related groups (DRG) data show that, especially with the occurrence of the corona pandemic, a decrease in inpatient case numbers of patients with PAOD stage IIB can be observed nationwide and also in SA. The severe PAOD stages have remained approximately the same in case numbers but increased in SA. The risk stratification based on the wound, ischemia and foot infection (WIFI) classification offers the possibility to be able to make statements about the risk of amputation, benefits and type of revascularization measures. The length of the occlusion, occlusion site of the affected vessels and degree of calcification are taken into account in the global limb anatomic staging system (GLASS) to assess the prognosis. The evaluation of the case-based hospital statistics from 2015 to 2020 showed a constant use of femorocrural/femoropedal bypass surgery in Germany as well as a slight increase in reconstruction using femorocrural bypasses in SA, which seems to correlate with the tendency for an increase in the number of cases of severe PAOD. Parameter-based objectification of the severity of critical limb ischemia should be included in the indications for placement of a crural/pedal bypass. The WIFI classification and GLASS are suitable for this purpose as a relative prognosis of success is also possible. The treatment of critical limb ischemia by crural/pedal bypass surgery continues to find a constant application in Germany and SA.

[Statutory provisions, aims, motives, attitudes and thinking on the outpatient operation profile of general and abdominal surgery]. / Vorgaben, Zielvorstellungen, Motive, Haltungen und Denken zum ambulanten Operationsprofil der Allgemein- und Viszeralchirurgie.

AIM: The aim of the manuscript is to discuss and assess the implications and opportunities as well as dangers of "outpatientization" of surgical and inpatient services for general and abdominal surgery. METHOD: Narrative overview with literature reference based on a PubMed search with the search terms: outpatient operations and inpatient interventions, AOP catalog, hybrid DRG, outpatient hernia surgery, outpatient proctological surgery, selective sector-equal reimbursement and day-care forms of care. RESULTS (KEY POINTS): - In the Anglo-American area, the treatment of inguinal hernias is predominantly carried out on an outpatient clinic basis. In the USA, Sweden and Denmark, for example, over 70% of all hernias are treated in an outpatient clinic setting, in Germany it is only 20%. In Germany, the catalog of operations that can be performed on an outpatient basis and other department-replacing interventions in hospitals defines outpatient interventions in accordance with § 115b Social Security Code (SGB) V (Germany). - The conversion from inpatient to outpatient hernia surgery has also failed so far due to an enormous difference in revenues. According to the will of the Federal Ministry of Health, the planned forms of semistationary care are intended to relieve the nursing staff in the hospitals and thus relieve the tense situation of nursing professionals. By the end of March 2023, a special industry-specific reimbursement, so-called hybrid DRGs, is to be agreed, which applies regardless of whether a paid service is provided on an outpatient or inpatient basis. - According to § 115b SGB V, whether a hernia can be performed under inpatient or outpatient conditions is also decided according to the location of the hernia. In the new AOP catalog, frailty is operationalized in the context factors via the degree of care and the Barthel index. If one compares the number of encryption procedures for the 5­530 procedure (closure of an inguinal hernia) in 2005 (184,679) with the pre-corona year 2019 (179,851), it can be seen that the proportion of hernias treated in hospital remained approximately the same over a period of 14 years. - Most elective proctological procedures can be performed on an outpatient basis. For reasons of safety (bleeding) and practicality (pain management, dressing change of large abscesses), inpatient surgery is preferred: extensive hemorrhoidectomy in the case of massive findings, large abscesses, extensive perianal fistula corrections, particularly high transsphincteric or suprasphincteric fistulas. - Guidelines based on the British Guidelines for Ambulant Surgery should be required for comprehensive outpatient treatment in surgery. The introduction of corresponding hybrid DRGs seems to be the right way to cover the costs of outpatient surgery in hospitals. CONCLUSION: The restructuring of the hospital landscape and the nationwide expansion of outpatient operations is an unavoidable requirement in view of rising costs in the healthcare system and impending financing bottlenecks, which will pose challenges for the surgical disciplines in the years to come. Outpatient surgery is already practiced in many areas but has not become established due to the different remuneration. The flat rates for the same branches can be a starting point here. Furthermore, evidence-based framework conditions must be created along the lines of the British Guidelines for Ambulant Surgery.

Impact of a novel multilayer imager on metal artifacts in MV-CBCT.

Objective. Megavoltage cone-beam computed tomography (MV-CBCT) imaging offers several advantages including reduced metal artifacts and accurate electron density mapping for adaptive or emergent situations. However, MV-CBCT imaging is limited by the poor efficiency of current detectors. Here we examine a new MV imager and compare CBCT reconstructions under clinically relevant scenarios.Approach. A multilayer imager (MLI), consisting of four vertically stacked standard flat-panel imagers, was mounted to a clinical linear accelerator. A custom anthropomorphic pelvis phantom with replaceable femoral heads was imaged using MV-CBCT and kilovoltage CBCT (kV-CBCT). Bone, aluminum, and titanium were used as femoral head inserts. 8 MU 2.5 MV scans were acquired for all four layers and (as reference) the top layer. Prostate and bladder were contoured on a reference CT and transferred to the other scans after rigid registration, from which the structural similarity index measure (SSIM) was calculated. Prostate and bladder were also contoured on CBCT scans without guidance, and Dice coefficients were compared to CT contours.Main results. kV-CBCT demonstrated the highest SSIMs with bone inserts (prostate: 0.86, bladder: 0.94) and lowest with titanium inserts (0.32, 0.37). Four-layer MV-CBCT SSIMs were preserved with bone (0.75, 0.80) as compared to titanium (0.67, 0.74), outperforming kV-CBCT when metal is present. One-layer MV-CBCT consistently underperformed four-layer results across all phantom configurations. Unilateral titanium inserts and bilateral aluminum insert results fell between the bone and bilateral titanium results. Dice coefficients trended similarly, with four-layer MV-CBCT reducing metal artifact impact relative to KV-CBCT to provide better soft-tissue identification.Significance. MV-CBCT with a four-layer MLI showed improvement over single-layer MV scans, approaching kV-CBCT quality for soft-tissue contrast. In the presence of artifact-producing metal implants, four-layer MV-CBCT scans outperformed kV-CBCT by eliminating artifacts and single-layer MV-CBCT by reducing noise. MV-CBCT with a novel multi-layer imager may be a valuable alternative to kV-CBCT, particularly in the presence of metal.

The subjective perception of the association between psychotic experiences and suicidal behavior among young adults.

OBJECTIVES: Psychotic experiences such as hallucinations and delusions are reported by approximately 7.2% of the general population, even in the absence of a psychotic disorder. Individuals who report such psychotic experiences are significantly more likely to endorse suicidal ideation and behavior across several large epidemiological samples. This study aimed to determine whether individuals who reported psychotic experiences and suicidal behavior would subjectively endorse a causal relationship between these two clinical phenomena. METHODS: Five open-ended questions were asked via online survey to 12 college students who had previously reported both hallucination-like experiences and suicidal behavior in a quantitative survey. Thematic analysis was used to analyze open-ended responses. RESULTS: The majority of respondents, n (%) = 11 (91.6), did not endorse a notable subjective relationship between psychosis and suicidal ideation or suicide attempts. However, respondents did spontaneously report that stigma and fear may drive suicidal ideation among people who report psychotic experiences and other symptoms of psychological distress. CONCLUSIONS: These findings are generally inconsistent with the hypothesis that psychotic experiences are directly related to suicidal behavior, and are consistent with the alternative hypothesis that both psychotic experiences and suicidal behavior are indicators of common underlying factors such as general psychological distress, potentially exacerbated by stigma.

Photosensitisation and green egg yolks in laying hens caused by the feeding of ensiled alfalfa leaves.

1. The present study was carried out to determine the effects of feeding ensiled alfalfa leaves (ALS) as an alternative protein source to laying hens under the terms of an organic diet. Due to the occurrence of unexpected negative health effects and undesirable egg yolk pigmentation in the test groups the trial was prematurely stopped and further analysis was conducted to evaluate the responsible substances.2. Body weights of the test groups decreased significantly already in week 2 of the trial. Performance variables dropped. Olive green pigmented egg yolks were found in groups fed diets containing ALS. Severe comb necrosis occurred in the experimental group receiving the highest level of ALS (20%) combined with the option of free-range access and therefore natural light exposure.3. The noxious agent found in ALS, blood serum and egg yolk was the photosensitising chlorophyll derivate pheophorbid a (PPBa), deriving from a strong depletion of chlorophyll contained in the alfalfa leaves. PPBa caused the olive-green pigmentation found in yolks and led to photosensitivity in groups with the highest level of ALS in the diet in combination with light exposure.4. By aiming for high protein and amino acid levels, harvesting and processing have, unintentionally and initially unnoticed, led to a strong accumulation of phototoxic PPBa. From these results it is strongly advised not to include ensiled alfalfa leaves as a protein source in organic laying hen diets.

Successful year-round mainstream partial nitritation anammox: Assessment of effluent quality, performance and N2O emissions.

For two decades now, partial nitritation anammox (PNA) systems were suggested to more efficiently remove nitrogen (N) from mainstream municipal wastewater. Yet to date, only a few pilot-scale systems and even fewer full-scale implementations of this technology have been described. Process instability continues to restrict the broad application of PNA. Especially problematic are insufficient anammox biomass retention, the growth of undesired aerobic nitrite-oxidizers, and nitrous oxide (N2O) emissions. In this study, a two-stage mainstream pilot-scale PNA system, consisting of three reactors (carbon pre-treatment, nitritation, anammox - 8 m3 each), was operated over a year, treating municipal wastewater. The aim was to test whether both, robust autotrophic N removal and high effluent quality, can be achieved throughout the year. A second aim was to better understand rate limiting processes, potentially affecting the overall performance of PNA systems. In this pilot study, excellent effluent quality, in terms of inorganic nitrogen, was accomplished (average effluent concentrations: 0.4 mgNH4-N/L, 0.1 mgNO2-N/L, 0.9 mgNO3-N/L) even at wastewater temperatures previously considered problematic (as low as 8 °C). N removal was limited by nitritation rates (84 ± 43 mgNH4-N/L/d), while surplus anammox activity was observed at all times (178 ± 43 mgN/L/d). Throughout the study, nitrite-oxidation was maintained at a low level (<2.5% of ammonium consumption rate). Unfortunately, high N2O emissions from the nitritation stage (1.2% of total nitrogen in the influent) were observed, and, based on natural isotope abundance measurements, could be attributed to heterotrophic denitrification. In situ batch experiments were conducted to identify the role of dissolved oxygen (DO) and organic substrate availability in N2O emission-mitigation. The addition of organic substrate, to promote complete denitrification, was not successful in decreasing N2O emission, but increasing the DO from 0.3 to 2.9 mgO2/L decreased N2O emissions by a factor of 3.4.

Tooth agenesis in German orthodontic patients with non-syndromic craniofacial disorder: a retrospective evaluation of panoramic radiographs.

OBJECTIVES: The study objective was to evaluate the tooth agenesis in German orthodontic patients with non-syndromic cleft lip and/or palate and Robin sequence compared to a control group without craniofacial disorder. MATERIALS/METHODS: A total of 108 panoramic radiographs were examined using the binary system of Tooth Agenesis Code (TAC) (excluding the third molar). Patients were divided into the craniofacial disorder group 1 (n = 43) and the healthy control group 2 (n = 65). Parameters such as skeletal class malformation, sex, localization of the cleft, craniofacial disorder, and interobserver reliability were assessed. RESULTS: Permanent tooth agenesis was observed in 44% of group 1 and 14% in group 2 with a statistically significant higher prevalence (p = 0.00162 (χ2)). Fourteen different TAC patterns were observed in group 1, ten of these occurring only once in separate patients. The distribution of the TAC codes in group 2 showed nine different possibilities of TAC code patterns; seven TACs were unique. In group 1, the most frequently absent teeth were the maxillary lateral incisor of the left side (30%); in group 2, the second premolar of the lower jaw on the right side (9%). Male patients with craniofacial disorder showed a higher percentage of tooth agenesis than female. CONCLUSION: The data presented here shows a statistically significant higher prevalence of tooth agenesis in German patients with non-syndromic craniofacial disorder. CLINICAL RELEVANCE: Radiographic evaluation enables the diagnosis of tooth agenesis. Recognizing early on the higher prevalence of tooth agenesis in patients exhibiting a craniofacial disorder is an important issue when developing long-term and comprehensive interdisciplinary treatment.

Successful mainstream nitritation through NOB inactivation.

The development of new wastewater treatment processes can assist in reducing the impact of wastewater treatment on the environment. The recently developed partial nitritation anammox (PNA) process, for example, consumes less energy for aeration and reduces nitrate in the effluent without requiring additional organic carbon. However, achieving stable nitritation (ammonium oxidation; NH4+ → NO2-) at mainstream conditions (T = 10-25 °C, C:N > 10, influent ammonium < 50 mgNH4-N/L and effluent < 1 mgNH4-N/L) remains challenging. This study explores the potential and mechanism of nitrite-oxidizing bacteria (NOB) suppression in a bottom-fed sequencing batch reactor (SBR). Two bench-scale (11 L) reactors and a pilot-scale reactor (8 m3) were operated for over a year and were fed with organic substrate depleted municipal wastewater. Initially, nitratation (nitrite oxidation; NO2- → NO3-) occurred occasionally until an anaerobic phase was integrated into the operating cycle. The introduction of the anaerobic phase effectively suppressed the regrowth of NOB while nitritation was stable over 300 days, down to 8 °C and at ammonium influent concentrations < 25 mgNH4-N/L. Batch experiments and process data revealed that parameters typically affecting NOB growth (e.g., dissolved oxygen, alkalinity, trace elements, lag-phase after anoxia, free nitrous acid (FNA), free ammonia (FA), pH, sulfide, or solids retention time (SRT)) could not fully explain the suppression of nitratation. Experiments in which fresh nitrifying microbial biomass was added to the nitritation system indicated that NOB inactivation explained NOB suppression better than NOB washout at high SRT. This study concludes that bottom-fed SBRs with anaerobic phases allow for stable nitritation over a broad range of operational parameters. Coupling this type of SBR to an anammox reactor can enable efficient mainstream anammox-based wastewater treatment.

The unknown third - Hydrogen isotopes in tree-ring cellulose across Europe.

This is the first Europe-wide comprehensive assessment of the climatological and physiological information recorded by hydrogen isotope ratios in tree-ring cellulose (δ2Hc) based on a unique collection of annually resolved 100-year tree-ring records of two genera (Pinus and Quercus) from 17 sites (36°N to 68°N). We observed that the high-frequency climate signals in the δ2Hc chronologies were weaker than those recorded in carbon (δ13Cc) and oxygen isotope signals (δ18Oc) but similar to the tree-ring width ones (TRW). The δ2Hc climate signal strength varied across the continent and was stronger and more consistent for Pinus than for Quercus. For both genera, years with extremely dry summer conditions caused a significant 2H-enrichment in tree-ring cellulose. The δ2Hc inter-annual variability was strongly site-specific, as a result of the imprinting of climate and hydrology, but also physiological mechanisms and tree growth. To differentiate between environmental and physiological signals in δ2Hc, we investigated its relationships with δ18Oc and TRW. We found significant negative relationships between δ2Hc and TRW (7 sites), and positive ones between δ2Hc and δ18Oc (10 sites). The strength of these relationships was nonlinearly related to temperature and precipitation. Mechanistic δ2Hc models performed well for both genera at continental scale simulating average values, but they failed on capturing year-to-year δ2Hc variations. Our results suggest that the information recorded by δ2Hc is significantly different from that of δ18Oc, and has a stronger physiological component independent from climate, possibly related to the use of carbohydrate reserves for growth. Advancements in the understanding of 2H-fractionations and their relationships with climate, physiology, and species-specific traits are needed to improve the modelling and interpretation accuracy of δ2Hc. Such advancements could lead to new insights into trees' carbon allocation mechanisms, and responses to abiotic and biotic stress conditions.

Improvements in beam's eye view fiducial tracking using a novel multilayer imager.

Purpose.Electronic portal image devices (EPIDs) have been investigated previously for beams-eye view (BEV) applications such as tumor tracking but are limited by low contrast-to-noise ratio and detective quantum efficiency. A novel multilayer imager (MLI), consisting of four stacked flat-panels was used to measure improvements in fiducial tracking during liver stereotactic body radiation therapy (SBRT) procedures compared to a single layer EPID.Methods.The prototype MLI was installed on a clinical TrueBeam linac in place of the conventional DMI single-layer EPID. The panel was extended during volumetric modulated arc therapy SBRT treatments in order to passively acquire data during therapy. Images were acquired for six patients receiving SBRT to liver metastases over two fractions each, one with the MLI using all 4 layers and one with the MLI using the top layer only, representing a standard EPID. The acquired frames were processed by a previously published tracking algorithm modified to identify implanted radiopaque fiducials. Truth data was determined using respiratory traces combined with partial manual tracking. Results for 4- and 1-layer mode were compared against truth data for tracking accuracy and efficiency. Tracking and noise improvements as a function of gantry angle were determined.Results. Tracking efficiency with 4-layers improved to 82.8% versus 58.4% for the 1-layer mode, a relative improvement of 41.7%. Fiducial tracking with 1-layer returned a root mean square error (RMSE) of 2.1 mm compared to 4-layer RMSE of 1.5 mm, a statistically significant (p < 0.001) improvement of 0.6 mm. The reduction in noise correlated with an increase in successfully tracked frames (r = 0.913) and with increased tracking accuracy (0.927).Conclusion. Increases in MV photon detection efficiency by utilization of a MLI results in improved fiducial tracking for liver SBRT treatments. Future clinical applications utilizing BEV imaging may be enhanced by including similar noise reduction strategies.

Clinical translation of a new flat-panel detector for beam's-eye-view imaging.

Electronic portal imaging devices (EPIDs) lend themselves to beams-eye view clinical applications, such as tumor tracking, but are limited by low contrast and detective quantum efficiency (DQE). We characterize a novel EPID prototype consisting of multiple layers and investigate its suitability for use under clinical conditions. A prototype multi-layer imager (MLI) was constructed utilizing four conventional EPID layers, each consisting of a copper plate, a Gd2O2S:Tb phosphor scintillator, and an amorphous silicon flat panel array detector. We measured the detector's response to a 6 MV photon beam with regards to modulation transfer function, noise power spectrum, DQE, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and the linearity of the detector's response to dose. Additionally, we compared MLI performance to the single top layer of the MLI and the standard Varian AS-1200 detector. Pre-clinical imaging was done on an anthropomorphic phantom, and the detector's CNR, SNR and spatial resolution were assessed in a clinical environment. Images obtained from spine and liver patient treatment deliveries were analyzed to verify CNR and SNR improvements. The MLI has a DQE(0) of 9.7%, about 5.7 times the reference AS-1200 detector. Improved noise performance largely drives the increase. CNR and SNR of clinical images improved three-fold compared to reference. A novel MLI was characterized and prepared for clinical translation. The MLI substantially improved DQE and CNR performance while maintaining the same resolution. Pre-clinical tests on an anthropomorphic phantom demonstrated improved performance as predicted theoretically. Preliminary patient data were analyzed, confirming improved CNR and SNR. Clinical applications are anticipated to include more accurate soft tissue tracking.

Research Note: Delay in sampling influences the profile of phytate in gizzard digesta and ileal digestibility of phosphorus in broilers.

The objective of this study was to investigate the effect of different durations of time delay when sampling digesta from the gizzard and ileum of broilers on the degradation of myo-inositol hexakisphosphate (InsP6) and digestibility of phosphorus (P). There was 1 experimental diet with a supplemental phytase activity of 1,212 phytase units/kg feed, which was provided to birds from day 13 to 18 after hatching. The diet was formulated to provide 6.6 g/kg Ca and 1.9 g/kg nonphytate P and fed to 24 cages of 6 birds. The 24 cages of birds were further randomly divided into 6 subgroups of 4 cages from which the digesta samples in the gizzard and ileum were collected at 0, 5, 10, or 20 min postmortem. The results showed that the concentration of InsP6 decreased linearly (P = 0.002), InsP5 decreased quadratically (P = 0.038), and the summation of concentrations of P in InsP6-4 decreased linearly (P = 0.028) in the gizzard digesta with the increasing delay of sampling. In the ileum, the digestibility of phytate P tended to decrease linearly (P = 0.087), and the digestibility of total P decreased linearly (P = 0.026) with prolonged delay. In conclusion, delay in sampling could alter the measured profile of InsP esters in gizzard digesta probably because of a continued effect of supplemental phytase, while the ileal digestibility of total P could diminish. Therefore, standard sampling procedures should be implemented to minimize variance.

Concurrent Vogt-Koyanagi-Harada disease and impressive response to immune checkpoint blockade in metastatic melanoma.

Background: Vogt-Koyanagi-Harada disease (VKHD)-like symptoms have previously been reported in 11 melanoma patients treated with immune checkpoint inhibitors. Materials & methods: We report a female patient with multilocular metastatic melanoma who was treated with nivolumab. Results: Following the first nivolumab dose, she experienced bilateral blurry vision, hearing loss, vertigo and ataxia. Ocular ultrasound was consistent with the diagnosis of uveitis. Audiography revealed severe bilateral sensorineural hearing loss. A high-dose corticosteroid regimen was initiated under which the patient developed generalized vitiligo. Abdominal and thoracic CT scans showed an almost complete response to nivolumab therapy. This patient fulfilled all criteria of VKHD which is characterized pathogenetically by an antimelanocytic autoimmune process. Conclusion: The present case showed an impressive response to antimelanoma immunotherapy. Based on these data, the occurrence of VKHD in melanoma patients appears to be a strong indicator for immune checkpoint inhibitor efficacy.

Automated MV markerless tumor tracking for VMAT.

Tumor tracking during radiotherapy treatment can improve dose accuracy, conformity and sparing of healthy tissue. Many methods have been introduced to tackle this challenge utilizing multiple imaging modalities, including a template matching based approach using the megavoltage (MV) on-board portal imager demonstrated on 3D conformal treatments. However, the complexity of treatments is evolving with the introduction of VMAT and IMRT, and successful motion management is becoming more important due to a trend towards hypofractionation. We have developed a markerless lung tumor tracking algorithm, utilizing the electronic portal imager (EPID) of the treatment machine. The algorithm has been specifically adapted to track during complex treatment deliveries with gantry and MLC motion. The core of the algorithm is an adaptive template matching method that relies on template stability metrics and local relative orientations to perform multiple feature tracking simultaneously. Only a single image is required to initialize the algorithm and features are automatically added, modified or removed in response to the input images. This algorithm was evaluated against images collected during VMAT arcs of a dynamic thorax phantom. Dynamic phantom images were collected during radiation delivery for multiple lung SBRT breathing traces and an example patient data set. The tracking error was 1.34 mm for the phantom data and 0.68 mm for the patient data. A multi-region, markerless tracking algorithm has been developed, capable of tracking multiple features simultaneously without requiring any other a priori information. This novel approach delivers robust target localization during complex treatment delivery. The reported tracking error is similar to previous reports for 3D conformal treatments.

Non-memory cognitive symptom development in Alzheimer's disease.

BACKGROUND AND PURPOSE: Memory is known to be the most common first symptom in Alzheimer's disease (AD). Assessing non-memory cognitive symptom development in AD is important for understanding disease progression and the potential identification of treatment-responsive subtypes. METHODS: Data from the National Alzheimer's Coordinating Center were examined. Logistic regression models were fitted evaluating the development of judgement, language, visuospatial and attention symptoms at first and second visits to Alzheimer's Disease Centers. Predictors were age and prior symptoms, adjusting for symptom length and sex. The models were then refitted assessing apolipoprotein E ε4 (APOE-ε4) effects. RESULTS: Each decade reduction in presentation age increased the odds of language, visuospatial and attention symptom development at both visits by 8%-18% (P < 0.05, all tests), and judgement symptoms at the second visit by 13% (P < 0.05). Prior symptoms were not equally predictive of symptom development. For example, having first predominant language symptoms carried the lowest risk of developing other first-visit symptoms and having memory symptoms was a stronger predictor of developing judgement than other symptoms. The APOE-ε4 gene showed little impact on symptom development when included as a predictor. CONCLUSIONS: Our findings provide support for the concept that younger-onset AD is associated with the progressive development of more non-memory symptoms beyond the first time point. Associations between symptoms were evident, which may reflect that pathology can remain isolated in a network for some time. APOE-ε4 status had little influence on cognitive symptom development which may indicate that the effect it has occurs very early in the disease course.