Acute TMS/fMRI response explains offline TMS network effects - An interleaved TMS-fMRI study.

BACKGROUND: Transcranial magnetic stimulation (TMS) is an FDA-approved therapeutic option for treatment resistant depression. However, exact mechanisms-of-action are not fully understood and individual responses are variable. Moreover, although previously suggested, the exact network effects underlying TMS' efficacy are poorly understood as of today. Although, it is supposed that DLPFC stimulation indirectly modulates the sgACC, recent evidence is sparse. METHODS: Here, we used concurrent interleaved TMS/fMRI and state-of-the-science purpose-designed MRI head coils to delineate networks and downstream regions activated by DLPFC-TMS. RESULTS: We show that regions of increased acute BOLD signal activation during TMS resemble a resting-state brain network previously shown to be modulated by offline TMS. There was a topographical overlap in wide spread cortical and sub-cortical areas within this specific RSN#17 derived from the 1000 functional connectomes project. CONCLUSION: These data imply a causal relation between DLPFC-TMS and activation of the ACC and a broader network that has been implicated in MDD. In the broader context of our recent work, these data imply a direct relation between initial changes in BOLD activity mediated by connectivity to the DLPFC target site, and later consolidation of connectivity between these regions. These insights advance our understanding of the mechanistic targets of DLPFC-TMS and may provide novel opportunities to characterize and optimize TMS therapy in other neurological and psychiatric disorders.

Physical exertion exacerbates decline in the musculature of an animal model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a genetic disorder caused by loss of the protein dystrophin. In humans, DMD has early onset, causes developmental delays, muscle necrosis, loss of ambulation, and death. Current animal models have been challenged by their inability to model the early onset and severity of the disease. It remains unresolved whether increased sarcoplasmic calcium observed in dystrophic muscles follows or leads the mechanical insults caused by the muscle's disrupted contractile machinery. This knowledge has important implications for patients, as potential physiotherapeutic treatments may either help or exacerbate symptoms, depending on how dystrophic muscles differ from healthy ones. Recently we showed how burrowing dystrophic (dys-1) C. elegans recapitulate many salient phenotypes of DMD, including loss of mobility and muscle necrosis. Here, we report that dys-1 worms display early pathogenesis, including dysregulated sarcoplasmic calcium and increased lethality. Sarcoplasmic calcium dysregulation in dys-1 worms precedes overt structural phenotypes (e.g., mitochondrial, and contractile machinery damage) and can be mitigated by reducing calmodulin expression. To learn how dystrophic musculature responds to altered physical activity, we cultivated dys-1 animals in environments requiring high intensity or high frequency of muscle exertion during locomotion. We find that several muscular parameters (e.g., size) improve with increased activity. However, longevity in dystrophic animals was negatively associated with muscular exertion, regardless of effort duration. The high degree of phenotypic conservation between dystrophic worms and humans provides a unique opportunity to gain insight into the pathology of the disease as well as the initial assessment of potential treatment strategies.

Proximal tibial osteophyte volumes are correlated spatially and with knee alignment: a quantitative analysis suggesting the influence of biochemical and mechanical factors in the development of osteophytes.

OBJECTIVE: To characterize the differences and correlations in osteophyte volumes between and within proximal tibial compartments, and to assess the correlations between osteophyte volumes and the femorotibial angle. DESIGN: CT scans of 73 knees with predominantly medial femorotibial osteoarthritis (21 K/L2, 28 K/L3, 24 K/L4) were retrospectively analyzed using a new, reproducible method measuring total and subregional osteophyte volumes in the medial and lateral compartments. Non-parametric statistics was used for comparison and correlation analyses. RESULTS: Total osteophyte volumes were larger in the medial than in the lateral compartment for all severity groups (p < 0.05). Additionally, statistically significant differences were observed among subregions of the lateral compartment in K/L3 and K/L4 knees. Statistically significant positive correlations were found between the medial and lateral total osteophyte volumes in K/L3 and K/L4 knees (ρ ≥ 0.44, p = 0.03), and among most subregional osteophyte volumes within each compartment in K/L3 knees. Markedly fewer statistically significant correlations were present in K/L2 and K/L4 knees. In K/L3 knees, the femorotibial angle was statistically significantly positively correlated with the total osteophyte volume in the medial compartment (ρ = 0.50, p = 0.01), with osteophyte volumes in most medial subregions, and with the osteophyte volume in the lateral posterior subregion (ρ = 0.40, p = 0.05). CONCLUSIONS: Quantitative assessment of osteophytes may bring insight on factors influencing their development. Positive correlations of osteophyte volumes found between and within compartments suggest the influence of biochemical mediators acting on the entire joint, while positive correlations between the femorotibial angle and osteophyte volumes suggest a role of mechanical factors. These hypotheses are to be further confirmed.

Comparing methods for estimation of heterogeneous treatment effects using observational data from health care databases.

There is growing interest in using routinely collected data from health care databases to study the safety and effectiveness of therapies in "real-world" conditions, as it can provide complementary evidence to that of randomized controlled trials. Causal inference from health care databases is challenging because the data are typically noisy, high dimensional, and most importantly, observational. It requires methods that can estimate heterogeneous treatment effects while controlling for confounding in high dimensions. Bayesian additive regression trees, causal forests, causal boosting, and causal multivariate adaptive regression splines are off-the-shelf methods that have shown good performance for estimation of heterogeneous treatment effects in observational studies of continuous outcomes. However, it is not clear how these methods would perform in health care database studies where outcomes are often binary and rare and data structures are complex. In this study, we evaluate these methods in simulation studies that recapitulate key characteristics of comparative effectiveness studies. We focus on the conditional average effect of a binary treatment on a binary outcome using the conditional risk difference as an estimand. To emulate health care database studies, we propose a simulation design where real covariate and treatment assignment data are used and only outcomes are simulated based on nonparametric models of the real outcomes. We apply this design to 4 published observational studies that used records from 2 major health care databases in the United States. Our results suggest that Bayesian additive regression trees and causal boosting consistently provide low bias in conditional risk difference estimates in the context of health care database studies.

Using self-reported data on the social determinants of health in primary care to identify cancer screening disparities: opportunities and challenges.

BACKGROUND: Data on the social determinants of health can help primary care practices target improvement efforts, yet relevant data are rarely available. Our family practice located in Toronto, Ontario routinely collects patient-level sociodemographic data via a pilot-tested survey developed by a multi-organizational steering committee. We sought to use these data to assess the relationship between the social determinants and colorectal, cervical and breast cancer screening, and to describe the opportunities and challenges of using data on social determinants from a self-administered patient survey. METHODS: Patients of the family practice eligible for at least one of the three cancer screening types, based on age and screening guidelines as of June 30, 2015 and who had answered at least one question on a socio-demographic survey were included in the study. We linked self-reported data from the sociodemographic survey conducted in the waiting room with patients' electronic medical record data and cancer screening records. We created an individual-level income variable (low-income cut-off) that defined a poverty threshold and took household size into account. The sociodemographic characteristics of patients who were overdue for screening were compared to those who were up-to-date for screening for each cancer type using chi-squared tests. RESULTS: We analysed data for 5766 patients for whom we had survey data. Survey participants had significantly higher screening rates (72.9, 78.7, 74.4% for colorectal, cervical and breast cancer screening respectively) than the 13, 036 patients for whom we did not have survey data (59.2, 65.3, 58.9% respectively). Foreign-born patients were significantly more likely to be up-to-date on colorectal screening than their Canadian-born peers but showed no significant differences in breast or cervical cancer screening. We found a significant association between the low-income cut-off variable and cancer screening; neighbourhood income quintile was not significantly associated with cancer screening. Housing status was also significantly associated with colorectal, cervical and breast cancer screening. There was a large amount of missing data for the low-income cut-off variable, approximately 25% across the three cohorts. CONCLUSION: While we were able to show that neighbourhood income might under-estimate income-related disparities in screening, individual-level income was also the most challenging variable to collect. Future work in this area should target the income disparity in cancer screening and simultaneously explore how best to collect measures of poverty.

Duplex sonography of the mesenteric vessels--a critical evaluation of inter-observer variability.

INTRODUCTION: The number of publications concerning mesenteric Doppler sonography (mesDS) is immense and does not correlate with the frequency of its use in clinical practice. This is astonishing since it provides real time blood flow (perfusion) information without side effects. Despite uncontrollable parameters like the technical limitations in some situations the optimization of (possibly) controllable parameters like standardization, production of normal values and reduction of the investigator variability by evaluating stable parameters could change the situation. PATIENTS AND METHODS: 10 investigators experienced in abdominal sonography ("DEGUM-Seminarleiter") performed mesenteric Doppler sonography in 5 healthy subjects with 5 different machines. RESULTS: The portal vein at the confluence and the common hepatic artery provide a significant portion of investigations with intromission angles of more than 60°. Values of diameter, resistance index and pulsatility index of the celiac trunc could be obtained with inter-observer variability values below 25 %. The proper and the common hepatic artery show no differences in inter-observer variability values, whereas the intrahepatic measure point of the portal vein showed a higher reproducibility. DISCUSSION: We define frame conditions for future mesenteric Doppler studies: the portal vein should be investigated at the intrahepatic measure point. Pathophysiological studies should refrain from velocity parameters except in the case of larger vessels running in a straight course towards the probe.

Evaluation of Strain Elastography for Differentiation of Thyroid Nodules: Results of a Prospective DEGUM Multicenter Study.

PURPOSE: Many patients with thyroid nodules are presently referred to surgery for not only therapeutic but also diagnostic purposes. The aim of noninvasive diagnostic methods is to optimize the selection of patients for surgery. Strain elastography (SE) enables the ultrasound-based determination of tissue elasticity. The aim of the present study was to evaluate the value of SE for the differentiation of thyroid nodules in a prospective multicenter study. MATERIALS AND METHODS: The study was registered at clinicaltrials.gov and was approved by the local ethics committees of all participating centers. All patients received an ultrasound (US) of the thyroid gland including color Doppler US. In addition, all nodules were evaluated by SE (Hitachi Medical Systems) using qualitative image interpretation of color distribution (SE-ES), strain value and strain ratio. RESULTS: Overall, 602 patients with 657 thyroid nodules (567 benign, 90 malignant) from 7 centers were included in the final analysis. The sensitivity, specificity, NPV, PPV, +LR were 21 %, 73 %, 86 %, 11 %, 0.8, respectively, for color Doppler US; 69 %, 75 %, 94 %, 30 %, 2.9, respectively, for SE-ES; 56 %, 81 %, 92 %, 32 %, 2.9, respectively, for SE-strain value; and 58 %, 78 %, 92 %, 30 %, 2.6, respectively, for SE-strain ratio. The diagnostic accuracy was 71 % for both strain value and strain ratio of nodules. CONCLUSION: SE as an additional ultrasound tool improves the value of ultrasound for the work-up of thyroid nodules. It might reduce diagnostic surgery of thyroid nodules in the future.

[Contrast-enhanced ultrasound for characterisation of focal liver lesions, practical advice]. / Kontrastmittelsonografie zur Charakterisierung von Lebertumoren: Praktische Aspekte.

This review article reports on evidence-based and clinical aspects of contrast-enhanced ultrasound of liver masses. The advanced possibilities of contrast-enhanced ultrasound to detect and characterise liver tumors are described as well as limitations and pitfalls of the method. The choice of the ultrasound device and contrast agents as well as the qualifications of the examiners according to guidelines are discussed.

Importance of Abdominal Ultrasound in 17 Patients with Histologically Confirmed Autoimmune Pancreatitis (AIP).

PURPOSE: Autoimmune pancreatitis (AIP) is an independent, underdiagnosed, rare form of chronic pancreatitis. The goal of this study is to document ultrasound findings in histologically confirmed AIP in order to determine the diagnostic value of ultrasound. MATERIALS AND METHODS: 6 of 74 DEGUM instructors for internal medicine (level 3 and 2) provided anonymized clinical and sonographic data from 17 patients with histologically confirmed AIP. RESULTS: 9/17 patients had diffuse AIP, 8/17 had focal AIP, 14/17 suffered from upper abdominal pain, 9/17 had jaundice, and 3/9 had an elevated IgG4 level. Ultrasound showed diffuse hypoechoic organ enlargement in 9/17 cases and a hypoechoic tumor with an unclear border in 8/17 cases. AIP was verified by ultrasound-guided percutaneous core biopsy in 14 cases, by biopsy of the bile duct in 1 case, and by surgical biopsy in 2 cases. Involvement of the hepatobiliary system was present in 7/17 patients and autoimmune cholangitis was verified in 5 cases. All patients experienced remission after immunosuppressive treatment. The pancreatic duct had a normal width in 11 cases, was dilated in 5 cases, and was stenosed over a long stretch in 3 cases. Contrast-enhanced ultrasound did not show uniform signal increase but also no significantly reduced or absent perfusion. CONCLUSION: Ultrasound can be diagnostically useful if the clinical manifestations of AIP are known. While the diffuse form allows an ad-hoc suspected diagnosis, the focal form can only be suspected in the case of additional extrapancreatic involvement. Contrast-enhanced ultrasound (CEUS) contributes greatly to the differentiation from ductal adenocarcinoma in the case of focal AIP.

Benefit of Contrast-Enhanced Ultrasound (CEUS) in the Follow-Up Care of Patients with Colon Cancer: A Prospective Multicenter Study.

PURPOSE: According to the German guidelines on colorectal cancer, unenhanced ultrasound is recommended for follow-up. On the other hand, ultrasound and radiology societies specify the use of contrast-enhanced ultrasound for ruling out liver metastases. Studies focusing on the follow-up of cancer patients are lacking. The goal of this multicenter study initiated by the German Ultrasound Society (DEGUM) was to determine the potential benefit of contrast-enhanced ultrasound in the follow-up of patients with colon cancer. MATERIALS AND METHODS: Follow-up patients with colon cancer (UICC > IIa) were investigated. As scheduled according to the German guidelines, unenhanced ultrasound was performed followed by contrast-enhanced ultrasound. All liver lesions were recorded. In case of additional metastases detected on contrast-enhanced ultrasound, contrast-enhanced CT, MRI or biopsy was performed to confirm additional liver metastases. RESULTS: A total of 45 liver metastases were detected in 26/290 patients (= 9 %) using unenhanced ultrasound. A further 28 metastases were detected on contrast-enhanced ultrasound in these 26 patients. In 18 patients showing no liver metastases, 40 additional metastases were detected on unenhanced ultrasound. This means that 44 patients with a total of 113 liver metastases were detected on contrast-enhanced ultrasound (p = 0.0006). CONCLUSION: Contrast-enhanced ultrasound should be recommended in the follow-up of patients with colon cancer in addition to unenhanced ultrasound - the up-to-date standard.

Incidence of bleeding in 8172 percutaneous ultrasound-guided intraabdominal diagnostic and therapeutic interventions - results of the prospective multicenter DEGUM interventional ultrasound study (PIUS study).

PURPOSE: To analyse the incidence of bleeding after percutaneous ultrasound guided diagnostic and therapeutic intraabdominal interventions in a prospective multicentre study (DEGUM percutaneous interventional ultrasound study). MATERIALS AND METHODS: Within a time period of 2 years diagnostic and therapeutic intraabdominal interventions (with the exclusion of ascites paracentesis) performed percutaneously under continuous ultrasound (US) guidance were prospectively assessed using a pseudonymized standardized web site entry form. Number and type of intervention, operator experience, patient characteristics, medication, lab data as well as technical aspects of the procedure and bleeding complications were analysed according to the interventional radiology standards. RESULTS: 8172 US-guided intraabdominal interventions (liver n = 5903; pancreas n = 501, kidney n = 434, lymph node = 272, biliary system n = 153, spleen n = 63, other abdominal organs and extra-organic targets n = 999) were analysed in 30 hospitals. The majority were diagnostic biopsies including 1780 liver parenchyma, 3400 focal liver lesions and 404 pancreatic lesions. 7525 interventions (92.1 %) were performed in hospitalized patients (mean age 62.6 years). Most operators were highly experienced in US-guided interventions (> 500 interventions prior to the study n = 5729; 70.1 %). Sedation was administered in 1131 patients (13.8 %). Needle diameter was ≥ 1 mm in 7162 punctures (87.9 %) with main focus on core needle biopsies (18 G, n = 4185). Clinically relevant bleeding complications with need of transfusion (0.4 %), surgical bleeding control (0.1 %) and radiological coiling (0.05 %) were very rare. Bleeding complications with fatal outcome occurred in four patients (0.05 %). The frequency of major bleeding complications was significantly higher in patients with an INR > 1.5 (p < 0.001) and patients taking a medication potentially interfering with platelet function or plasmatic coagulation (p < 0.0333). CONCLUSION: This prospective multicentre study confirms the broad spectrum of percutaneous US-guided intraabdominal interventions. However diagnostic liver biopsies dominate with the use of core needle biopsies (18 G). Percutaneous US-guided interventions performed by experienced sonographers are associated with a low bleeding risk. Major bleeding complications are very rare. A pre-interventional INR < 1.5 and individual medication risk assessment are recommended.

Deleterious effects of plasma-derived cellular debris in a porcine model of hemorrhagic shock.

BACKGROUND: Recent studies identify large quantities of inflammatory cellular debris within Fresh Frozen Plasma (FFP). As FFP is a mainstay of hemorrhagic shock resuscitation, we used a porcine model of hemorrhagic shock and ischemia/reperfusion to investigate the inflammatory potential of plasma-derived cellular debris administered during resuscitation. METHODS: The porcine model of hemorrhagic shock included laparotomy with 35 % hemorrhage (Hem), 45 min of ischemia from supraceliac aortic occlusion with subsequent clamp release (IR), followed by protocolized resuscitation for 6 h. Cellular debris (Debris) was added to the resuscitation phase in three groups. The four groups consisted of Hem + IR (n = 4), Hem + IR + Debris (n = 3), Hem + Debris (n = 3), and IR + Debris (n = 3). A battery of laboratory, physiologic, cytokine, and outcome data were compared between groups. RESULTS: As expected, the Hem + IR group showed severe time dependent decrements in organ function and physiologic parameters. All animals that included both IR and Debris (Hem + IR + Debris or IR + Debris) died prior to the six-hour end point, while all animals in the Hem + IR and Hem + Debris survived. Cytokines measured at 30-60 min after initiation of resuscitation revealed significant differences in IL-18 and IL-1ß between all groups. CONCLUSIONS: Ischemia and reperfusion appear to prime the immune system to the deleterious effects of plasma-derived cellular debris. In the presence of ischemia and reperfusion, this model showed the equivalency of 100 % lethality when resuscitation included quantities of cellular debris at levels routinely administered to trauma patients during transfusion of FFP. A deeper understanding of the immunobiology of FFP-derived cellular debris is critical to optimize resuscitation for hemorrhagic shock.

Patterns of progression on first line osimertinib in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC): A Swiss cohort study.

AIM: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved for patients with EGFR mutated non-small cell lung cancer as first-line treatment. However, treatment resistance inevitably emerges and may present as oligo-progressive disease (OPD) or systemic progressive disease (SPD). The incidence of OPD on first-line osimertinib is unknown. METHODS: We retrospectively analyzed patients who received first-line osimertinib at 13 Swiss centers. The rate of OPD (PD in ≤ 5 lesions) and treatment outcomes were analyzed. RESULTS: The median age of the 148 patients was 68.2 years (range. 38.0-93.3). There were 62 % females, 83 % with a PS ≤ 1, 59 % never smokers, 57 % of patients with an EGFR exon 19 deletion and 37 % with EGFR p.L858R exon 21. 77 % experienced OPD. Median overall survival (OS) was 51.6 months (95 % CI, 38.4-65.0). Median progression-free survival (PFS) was 19.2 (95 % CI, 14.3-23.5) and 8.7 (95 % CI, 2.8-15.6) months for patients with common and uncommon EGFR mutations. Patients with OPD compared to SPD had a significantly longer time to treatment failure and longer OS of (22.9 vs. 10.8 months, p < 0.001 and 51.6 vs. 26.4 months, p = 0.004, respectively). The most common organ sites of PD were lung (62 %), brain (30 %), lymph nodes (30 %), bone (27 %) and pleura (27 %). Twenty-six patients (45 %) with OPD received local ablative treatment (LAT). The OS of OPD patients with LAT was 60.0 (95 % CI, 51.6-NA) vs. 51.4 (95 % CI 38.4-65.3) months (p = 0.43) without LAT. CONCLUSION: The rate of OPD of patients receiving first line osimertinib was 77 %. Patients with OPD had a significantly better OS compared to patients with SPD (51.6 vs. 26.4 months). Patients with OPD receiving LAT had the longest median OS (60.0 months).

[Liver segment anatomy in ultrasound--examinations to define the frontier between segment II/III and literature review]. / Die Segmenteinteilung der Leber im Ultraschall--Untersuchungen zur Grenzdefinition zwischen Segment II/III und Literaturvergleich.

INTRODUCTION: Liver segment definition due to Couinaud is the basis for localisation of focal liver lesions in imaging, in the follow-up or for planning operations. A literature review shows variety in segment definition and the frontier between segment II and III in the left liver lobe, in the course of the portal vein level and in variations of liver veins. The aim of this study is to demonstrate liver segment anatomy in sonography compared to anatomic preparations and the literature. This leads to a proposal for a unique nomenclature and illustration. MATERIAL AND METHODS: 152 liver healthy persons (77 F, 75 M, mean age 63.3 years (18 - 91 years) were examined with standardised abdominal ultrasound in longitudinal, transversal and axis planes. (Angle) measurements were taken to define the left hepatic vein (Fissura sinistra), the Ramus umbilicalis of the portal vein (Fissura umbilicalis), the portal vein level and the amount and variations of the liver veins. RESULTS: The left hepatic vein was found with a mean angle of 24° (0 - 70°) left to the median axis, the Pars umbilicalis of the portal vein wasalmost strictly in the mid axis. The portal vein level was located with a mean angle of 61° (5 - 110°) right to the median with no variations of the two main branches. 27 (18 %) out of the remaining 151 patients showed variations of the liver veins: 7 × (4.6 %) a doubled mid hepatic vein, 12 × (8 %) a doubled left hepatic vein, 4 × (2.7 %) 3 left liver veins were found with a short (≤ 1 cm) common trunk, 1 × each (0.7 %) four left liver veins with a short common trunk, one trifurcation of the mid hepatic vein, one doubled right liver vein and one common trunk (2 cm) of all 3 main liver veins leading to the inferior V. cava. DISCUSSION: The surgical functional liver segment definition by Couinaud is the basis for localisation of focal liver lesions. The frontier between segment II and III is mainly described as a horizontal plane in the literature. The course of the left liver vein (fissura sinistra) has a mean angle of 24° left to the median and not like the umbilical fissure, which is found almost strictly in the median plane. The left hepatic vein(s), their course and liver vein variations are well demonstrated by sonography (99.3 % in this study). Anatomic landmarks as well as variations and a unique nomenclature should be well known and considered in the localisation of focal liver lesions, their feeding vessels and liver segment anatomy.

[How safe is sedation in gastrointestinal endoscopy? A multicentre analysis of 388,404 endoscopies and analysis of data from prospective registries of complications managed by members of the Working Group of Leading Hospital Gastroenterologists (ALGK)]. / Wie sicher ist die Sedierung in der gastrointestinalen Endoskopie? Eine multizentrische Auswertung von 388 404 Endoskopien und Auswertung der Daten aus prospektiv geführten Komplikationsregistern von Mitgliedern der Arbeitsgemeinschaft leitender Gastroenterologen im Krankenhaus (ALGK).

BACKGROUND: Gastrointestinal endoscopies are increasingly being carried out with sedation. All of the drugs used for sedation are associated with a certain risk of complications. Data currently available on sedation-associated morbidity and mortality rates are limited and in most cases have substantial methodological limitations. The aim of this study was to record severe sedation-associated complications in a large number of gastrointestinal endoscopies. METHODS: Data on severe sedation-associated complications were collected on a multicentre basis from prospectively recorded registries of complications in the participating hospitals (median documentation period 27 months, range 9 - 129 months). RESULTS: Data for 388,404 endoscopies from 15 departments were included in the study. Severe sedation-associated complications occurred in 57 patients (0.01 %). Forty-one percent of the complications and 50 % of all complications with a fatal outcome (10/20 patients) occurred during emergency endoscopies. In addition, it was found that 95 % of the complications and 100 % of all fatal complications affected patients in ASA class ≥ 3. CONCLUSIONS: Including nearly 400,000 endoscopies, this study represents the largest prospective, multicenter record of the complications of sedation worldwide. The analysis shows that sedation is carried out safely in gastrointestinal endoscopy. The morbidity and mortality rates are much lower than previously reported in the literature in similar groups of patients. Risk factors for the occurrence of serious complications include emergency examinations and patients in ASA class ≥ 3.

[Secondary implantation of retropupillary fixated iris-claw intraocular lenses]. / Sekundärversorgung mit retropupillar fixierten Irisklauenlinsen.

BACKGROUND: There is no standard for the treatment of functional aphakia in cases with a compromised capsular system. Retropupillary fixation of an Artisan iris-claw IOL ("Intraokularlinse") is one of the established procedures. OBJECTIVE: Aim of this study was the evaluation of indications, visual and refractive long-term results and complication rates after retropupillary implantation of an iris-claw lens. MATERIAL AND METHODS: This retrospective study comprised 366 eyes that received a retropupillary Artisan intraocular lens (IOL) in a single center between January 2009 and December 2019. The mean follow-up period was 249 days (8 months) ±516 days. RESULTS: IOL dislocation (68%) was the most common reason for a retropupillary iris-claw implantation. Previous vitrectomy was a significant preoperative risk factor for IOL dislocation (p = 0.0001). Best corrected visual acuity improved from 0.65 ± 0.64 (logMAR) preoperatively to 0.57 ± 0.51 (logMAR) 4-6 weeks after the surgery. The mean deviation from the planned refraction was +0.40 ± 1.37 dpt and 73% of the patients had a deviation within ±1 dpt of the planned refraction. Relevant postoperative complications during the first 4 weeks were pupillary distortion (42%), ocular hypotony (15%) and transient hyphema (14%). Late complications (≥4 weeks after the surgery) included persistent pupillary distortion (20%), cystoid macular edema (13%) and iris-claw disenclavation (6%). CONCLUSION: The retropupillary Artisan implantation is an efficient method for treating aphakia without capsular support and provides good visual and refractive results with an acceptable surgical risk profile.

Frequency of tumor entities among liver tumors of unclear etiology initially detected by sonography in the noncirrhotic or cirrhotic livers of 1349 patients. Results of the DEGUM multicenter study.

AIM: Investigation of the frequency of various solid focal liver lesions (SFLL) in noncirrhotic and cirrhotic livers with focus on the frequency of metastasis in cirrhotic livers. MATERIAL AND METHODS: The patient collective in the DEGUM multicenter study (n = 1349) was reevaluated and divided in subcollective A without (n = 1067) and B with cirrhosis (n = 282). 74.6 % of the various tumor entities were confirmed histologically (n = 1006). RESULTS: In subcollective A there were 385 patients with metastases (36.4 %) and 65 with HCC (6.1 %), whereas the most common benign lesions were hemangioma, with 237 cases (22.4 %) and FNH, with 170 cases (16.1 %). In subcollective B there were 216 cases of HCC (76.6 %) and 12 metastases (4.3 %), as well as 42 benign lesions (14.9 %). CCC was rare in both subcollective A (3.3 %) and subcollective B (2.5 %). A positive oncological history increased the probability of a malignant SFLL in subcollective A by 1.8 times, but did not do so in subcollective B. CONCLUSION: The frequency of various tumor entities is different in patients with and without cirrhosis of the liver. In noncirrhotic livers, malignant and benign SFLL are equally common. The most common forms are metastases, hemangiomas and FNH, CCC is rare. A positive history of extrahepatic malignancy increases the probability of a malignant SFLL. In cirrhosis, HCC dominates, HCC is 18 times as common as metastases. Benign SFLL and CCC are rare.

Diagnostic accuracy of CEUS in the differential diagnosis of small (≤ 20  mm) and subcentimetric (≤ 10  mm) focal liver lesions in comparison with histology. Results of the DEGUM multicenter trial.

PURPOSE: To evaluate the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of small and subcentimetric liver tumors in clinical practice. MATERIALS AND METHODS: 1349 patients with a hepatic tumor lacking a definite diagnosis based on B-mode ultrasound and power Doppler ultrasound were examined at 14 hospitals by CEUS using a standardized protocol (pulse/phase inversion imaging, mechanical index < 0.4). Differential diagnosis was based on the vascularity pattern and contrast enhancement pattern during the arterial, portal, and late phase according to the EFSUMB guidelines. 335 patients with focal liver lesions (FLL) ≤ 20  mm were analyzed. The tumor status established after CEUS was compared to histology (73.2 %) or in some cases to CT or MRI. RESULTS: A definitive diagnosis based on the gold standard was possible in 329 FLLs, while 6 FLLs remained unclear even in the combined gold standard (histology and/or CT and/or MRI). The final diagnoses of ≤ 20  mm FLL with histological confirmation (n = 241) included 87 benign and 154 malignant entities. The overall diagnostic accuracy of CEUS in FLL ≤ 20  mm with histological confirmation was 83.8 %. CEUS correctly identified 144 /154 malignant FLLs (sensitivity 93.5 %) and 58 /87 benign FLLs (specificity 66.7 %). 24 /241 FLLs remained unclear after CEUS (9.9 %). CEUS misclassified 15 /241 FLLs (6.2 %; 12 benign and 3 malignant FLLs). The positive predictive value of CEUS for a malignant FLL was 92.3 % and the negative predictive value was 95.1 %. Out of 241 small FLLs with histological confirmation, 62  FLLs were ≤ 10  mm (diagnostic accuracy of CEUS 80.6 %) and 179 FLLs were > 10  mm and ≤ 20  mm (diagnostic accuracy of CEUS 84.9 %). CONCLUSION: CEUS has a high diagnostic accuracy for the differential diagnosis of small and subcentimetric FLLs in clinical practice.

[Gallbladder polyps: prevalence and risk factors]. / Gallenblasenpolypen: Prävalenz und Risikofaktoren.

PURPOSE: The objective of the present study was to investigate the prevalence of gallbladder polyps and possible risk factors in a random population sample of an urban population. MATERIAL AND METHODS: A total of 2099 subjects (1072 women, 1027 men; aged 19 - 65 years, mean age 42.1 (SD ± 12.8 years) were prospectively examined using ultrasound, a standardized questionnaire and laboratory studies. RESULTS: Gallbladder polyps were identified in 6.1 % (128 / 2099) of all subjects (women: 6.1 % [63 / 1027]); men: 6.1 % [65 / 1072]). Solitary polyps were found in 52.4 % (65 / 124), two polyps in 16.1 % (20 / 124), three polyps in 6.5 % (8 / 124), several polyps in 22.6 % (28 / 124) and multiple polyps in 2.4 % (3 / 124) of subjects. The mean polyp diameter was 4.7 mm (SD ± 2.2; range 2 - 20 mm). The polyp diameter was ≤ 7 mm in 94.5 % of subjects. The polyps were described as pedunculate in 82.3 % (102 / 124). The polyps were broad-based in 11.3 % of subjects (14 / 124; men: 18 % women: 4.8 %). The polyps were homogeneously echogenic in 100 % of cases and with irregular contours in only one male subject. Multiple logistic regression failed to demonstrate an influence on the increased occurrence of gallbladder polyps for the risk factors of male sex, age, body-mass index (BMI), alcohol, nicotine or caffeine consumption or diabetes mellitus. CONCLUSION: The prevalence of gallbladder polyps reported in the present study (6.1 %) is higher than figures previously published for populations in Germany or Europe. The majority of polyps were pedunculate and solitary. A typical risk factor profile for gallbladder polyps could not be identified in the present population sample.

Is the whole the sum of its parts? Agent-based modelling of wastewater treatment systems.

Agent-based models (ABMS) simulate individual units within a system, such as the bacteria in a biological wastewater treatment system. This paper outlines past, current and potential future applications of ABMs to wastewater treatment. ABMs track heterogeneities within microbial populations, and this has been demonstrated to yield different predictions of bulk behaviors than the conventional, "lumped" approaches for enhanced biological phosphorus removal (EBPR) completely mixed reactors systems. Current work included the application of the ABM approach to bacterial adaptation/evolution, using the model system of individual EBPR bacteria that are allowed to evolve a kinetic parameter (maximum glycogen storage) in a competitive environment. The ABM approach was successfully implemented to a simple anaerobic-aerobic system and it was found the differing initial states converged to the same optimal solution under uncertain hydraulic residence times associated with completely mixed hydraulics. In another study, an ABM was developed and applied to simulate the heterogeneity in intracellular polymer storage compounds, including polyphosphate (PP), in functional microbial populations in enhanced biological phosphorus removal (EBPR) process. The simulation results were compared to the experimental measurements of single-cell abundance of PP in polyphosphate accumulating organisms (PAOs), performed using Raman microscopy. The model-predicted heterogeneity was generally consistent with observations, and it was used to investigate the relative contribution of external (different life histories) and internal (biological) mechanisms leading to heterogeneity. In the future, ABMs could be combined with computational fluid dynamics (CFD) models to understand incomplete mixing, more intracellular states and mechanisms can be incorporated, and additional experimental verification is needed.