A Safe Framework for Quantitative In Vivo Human Evaluation of Image Guidance.

Goal: We present a new framework for in vivo image guidance evaluation and provide a case study on robotic partial nephrectomy. Methods: This framework (called the "bystander protocol") involves two surgeons, one who solely performs the therapeutic process without image guidance, and another who solely periodically collects data to evaluate image guidance. This isolates the evaluation from the therapy, so that in-development image guidance systems can be tested without risk of negatively impacting the standard of care. We provide a case study applying this protocol in clinical cases during robotic partial nephrectomy surgery. Results: The bystander protocol was performed successfully in 6 patient cases. We find average lesion centroid localization error with our IGS system to be 6.5 mm in vivo compared to our prior result of 3.0 mm in phantoms. Conclusions: The bystander protocol is a safe, effective method for testing in-development image guidance systems in human subjects.

Are 3D Image Guidance Systems Ready for Use? A Comparative Analysis of 3D Image Guidance Implementations in Minimally Invasive Partial Nephrectomy.

Introduction: Three-dimensional image-guided surgical (3D-IGS) systems for minimally invasive partial nephrectomy (MIPN) can potentially improve the efficiency and accuracy of intraoperative anatomical localization and tumor resection. This review seeks to analyze the current state of research regarding 3D-IGS, including the evaluation of clinical outcomes, system functionality, and qualitative insights regarding 3D-IGS's impact on surgical procedures. Methods: We have systematically reviewed the clinical literature pertaining to 3D-IGS deployed for MIPN. For inclusion, studies must produce a patient-specific 3D anatomical model from two-dimensional imaging. Data extracted from the studies include clinical results, registration (alignment of the 3D model to the surgical scene) method used, limitations, and data types reported. A subset of studies was qualitatively analyzed through an inductive coding approach to identify major themes and subthemes across the studies. Results: Twenty-five studies were included in the review. Eight (32%) studies reported clinical results that point to 3D-IGS improving multiple surgical outcomes. Manual registration was the most utilized (48%). Soft tissue deformation was the most cited limitation among the included studies. Many studies reported qualitative statements regarding surgeon accuracy improvement, but quantitative surgeon accuracy data were not reported. During the qualitative analysis, six major themes emerged across the nine applicable studies. They are as follows: 3D-IGS is necessary, 3D-IGS improved surgical outcomes, researcher/surgeon confidence in 3D-IGS system, enhanced surgeon ability/accuracy, anatomical explanation for qualitative assessment, and claims without data or reference to support. Conclusions: Currently, clinical outcomes are the main source of quantitative data available to point to 3D-IGS's efficacy. However, the literature qualitatively suggests the benefit of accurate 3D-IGS for robotic partial nephrectomy.

Practical Changes in Reference Services: A Case Study.

Between 2018 and 2019, the librarians at the Strauss Health Sciences Library improved the efficiency and reach of their reference service by implementing four small-scale changes. These changes included revising the method of collecting statistics, creating FAQs, utilizing an appointment scheduler, and launching proactive chat. This case study will provide the background and research to support these changes, details on how the changes were implemented using Springshare tools, as well as the results and implications. Finally, the librarians will share their lessons learned along with recommendations for institutions interested in adopting similar changes.

Orchestrating Opiate-Associated Memories in Thalamic Circuits.

Disrupting memories that associate environmental cues with drug experiences holds promise for treating addiction, yet accessing the distributed neural network that stores such memories is challenging. Here, we show that the paraventricular nucleus of the thalamus (PVT) orchestrates the acquisition and maintenance of opiate-associated memories via projections to the central nucleus of the amygdala (CeA) and nucleus accumbens (NAc). PVT→CeA activity associates morphine reward to the environment, whereas transient inhibition of the PVT→NAc pathway during retrieval causes enduring protection against opiate-primed relapse. Using brain-wide activity mapping, we revealed distributed network activities that are altered in non-relapsing mice, which enabled us to find that activating the downstream NAc→lateral hypothalamus (LH) pathway also prevents relapse. These findings establish the PVT as a key node in the opiate-associated memory network and demonstrate the potential of targeting the PVT→NAc→LH pathway for treating opioid addiction.

Dynamic salience processing in paraventricular thalamus gates associative learning.

The salience of behaviorally relevant stimuli is dynamic and influenced by internal state and external environment. Monitoring such changes is critical for effective learning and flexible behavior, but the neuronal substrate for tracking the dynamics of stimulus salience is obscure. We found that neurons in the paraventricular thalamus (PVT) are robustly activated by a variety of behaviorally relevant events, including novel ("unfamiliar") stimuli, reinforcing stimuli and their predicting cues, as well as omission of the expected reward. PVT responses are scaled with stimulus intensity and modulated by changes in homeostatic state or behavioral context. Inhibition of the PVT responses suppresses appetitive or aversive associative learning and reward extinction. Our findings demonstrate that the PVT gates associative learning by providing a dynamic representation of stimulus salience.

Dopamine and opioid systems interact within the nucleus accumbens to maintain monogamous pair bonds.

Prairie vole breeder pairs form monogamous pair bonds, which are maintained through the expression of selective aggression toward novel conspecifics. Here, we utilize behavioral and anatomical techniques to extend the current understanding of neural mechanisms that mediate pair bond maintenance. For both sexes, we show that pair bonding up-regulates mRNA expression for genes encoding D1-like dopamine (DA) receptors and dynorphin as well as enhances stimulated DA release within the nucleus accumbens (NAc). We next show that D1-like receptor regulation of selective aggression is mediated through downstream activation of kappa-opioid receptors (KORs) and that activation of these receptors mediates social avoidance. Finally, we also identified sex-specific alterations in KOR binding density within the NAc shell of paired males and demonstrate that this alteration contributes to the neuroprotective effect of pair bonding against drug reward. Together, these findings suggest motivational and valence processing systems interact to mediate the maintenance of social bonds.

[Infective endocarditis]. / Mikrobiell verursachte Endokarditis.

Colonization of native cardiac valves or polymer implants, e.g. valves, conduits, rings, electrode leads and polymer-associated endocarditis (PIE), by microorganisms, primarily gram-positive bacteria (infective endocarditis), constitutes a severe, prognostically unfavorable disease. Fever and in the majority of cases development of a valve regurgitant murmur are clinical landmark findings. The white blood cell count, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are regularly elevated. With a normal CRP level, infective endocarditis is extremely unlikely. Irrespective of body temperature, at least three blood cultures (aerobic and anaerobic) should be taken and if initiation of antimicrobial therapy is urgent, 1 h apart before therapy is initiated. Identification of the pathogen to the species level and testing antimicrobial susceptibility to antibiotics by a quantitative hemodilution test, not with agar diffusion tests, are obligatory. A minimum inhibitory concentration should be administered for antibiotics and usual combinations of antibiotics with an expected synergistic potential. Streptococci, staphylococci and enterococci are the most frequent causative organisms. Immediate initiation of transthoracic echocardiography (TTE) is mandatory followed by transesophageal echocardiography if imaging quality is poor, involvement of intracardiac implants is possible or TTE is insufficient to establish the diagnosis. An insufficiently long antimicrobial therapy promotes recurrent infections, thus a 4-week treatment is standard, while in special cases (e.g. PIE) treatment for 6 weeks should be the rule. If typical complications of infective endocarditis, such as uncontrolled local infection, systemic thromboembolism, central nervous involvement, development of a severe valve incompetence or mitral kissing vegetation in primary aortic valve endocarditis occur, urgent surgical intervention should be considered. If cardiac implants are involved, early surgical removal followed by a 6-week antimicrobial treatment is the rule. Adequate and timely diagnosis and treatment are the key to improve the overall prognosis.

Metastatic castration-resistant prostate cancer: integrating new learnings to optimise treatment outcomes.

The approval or clinical evaluation of several new agents - cabazitaxel, abiraterone acetate, enzalutamide, sipuleucel-T, and radium-223 - has changed the management of patients with metastatic castration-resistant prostate cancer (mCRPC) prior to or after docetaxel-based chemotherapy significantly. All of these agents have resulted in a significant survival benefit as compared to their control group. However, treatment responses might differ depending on the associated comorbidities and the extent and the biological aggressiveness of the disease. Furthermore, treatment associated side effects differ between the various drugs. As new drugs become approved, new treatment strategies and markers to best select which patients will best respond to which drug are needed. It is the aim of the current article to: (1) summarize the data of established treatment options in mCRPC; (2) highlight new developments of medical treatment; (3) provide clinically useful algorithms for the daily routine and to (4) point out future developments of medical treatment.

[The "asymptomatic" patient with chronic acquired heart valve disease]. / Der "asymptomatische" Patient mit chronischem Herzklappenfehler.

An intervention for chronic acquired valvular heart disease may either be indicated in symptomatic patients to relieve symptoms and improve quality of life or in asymptomatic patients to improve long-term prognosis, e.g., by preventing disease-related complications like chronic heart failure or arrhythmias. For proper action according to current guidelines, the systematic evaluation of symptoms related to the underlying valve disease is of utmost importance. If a discrepancy between symptoms reported or not reported by the patients and the severity of the valve disease is supposed, true absence of symptoms and exercise tolerance should be verified by spiroergometry. In the truly asymptomatic patient with a severe valvular lesion, preservation of myocardial adaption to the chronic volume or pressure overload should be tested utilizing appropriate imaging techniques like radionuclide ventriculography under exercise conditions. The proper evaluation of the functional status is of growing importance in our aging population with its sedentary lifestyle. In this context, the results of a survey should be kept in mind, which indicated that a significant proportion of patients still have interventions too late during the natural history of their valve disease with symptoms of congestive heart failure, arrhythmias, and the risk of sudden cardiac death persisting after a primarily successful valve repair or replacement.

[Metastasectomy for renal cell cancer]. / Metastasenresektion beim Nierenzellkarzinom.

BACKGROUND: Metastasectomy prior to or after systemic medical cancer treatment is performed within a multimodal therapeutic approach in metastatic renal cell cancer (mRCC) to improve the prognosis. The role of metastasectomy in mRCC is controversially discussed and the potential therapeutic benefit is unquantifiable. The purpose of the current review is to critically discuss the available data. METHODS: A systematic literature search was carried out in the MedLinedatabase to identify original publications, review articles and editorials with respect to metastasectomy in mRCC and the current European guidelines were also taken into consideration. RESULTS: Metastasectomy is one of the approaches for mRCC recommended in the guidelines in cases of stable disease for at least 3 months, complete resectability of all metastatic lesions independent of the anatomic localization and a good performance status of the patient. The median survival time varies between 35 and 55 months. CONCLUSIONS: In mRCC metastasectomy is an indiviudal therapeutic approach which might be considered for limited metastatic disease and the presence of good prognostic risk factors to improve average survival time. Especially in renal cell cancer metastasectomy should be considered early.

[Organ-preserving renal tumor surgery for renal cell carcinoma ≥T1b: operative technique, complications and oncological control]. / Organerhaltende Nierentumorchirurgie bei Nierenzellkarzinomen ≥T1b : Operationstechnik, Komplikationen und onkologische Kontrolle.

BACKGROUND: Nephron sparing surgery (NSS) represents the recommended treatment of choice in guidelines for T1a and T1b renal tumors. Current data, however, suggest that approximately 60% of patients with T1b tumors are treated by radical nephrectomy. PATIENTS AND METHODS: We performed a retrospective analysis of 320 patients with renal cell cancer who underwent organ sparing procedures: NSS for renal tumors ≤4 cm (n=196, group 1) and 4.1-7 cm (n=92, group 2) as well as radiofrequency ablation (RFA, n=32, group 3). We analysed the indications, surgical techniques, perioperative complications and oncological outcome of the three groups. RESULTS: There were significant differences between groups 1 and 2 with regard to mean tumor size (2.9 cm versus 8.6 cm, p=0.03), necessity for warm ischemia (15.1% versus 51%, p=0.001), mean time of warm ischemia (3.5 min versus 10.2 min, p=0.002), necessity for endoluminal stenting due to involvement of the renal collecting system (0.5% versus 24.2%, p=0.001) and the number of pT2 (12.7% versus 29.7%, p=0.03) and pT3 tumors (8.7% versus 12%, p=0.05). In group 3 the mean age was 69.2 years and the mean Charlson comorbidity score was 7.7 (range 3-12) as compared to 3.4 (1-6) in groups 1 and 2. After a mean follow-up of 32 (2-71) months, 2 (6.2%) local recurrences developed and 8 patients died, 6 patients due to comorbidities and 2 patients due to metastatic renal cell carcinoma (RCC). CONCLUSIONS: Nephron sparing surgery can be safely performed for T1a to T2a renal cell carcinoma with equivalent oncological outcomes as compared to radical nephrectomy. Nephron sparing surgery should represent the standard surgical approach for localized RCCs independent of size and RFA should be reserved for patients with significant comorbidities.

Diagnostic superiority of a combined assessment of the systolic and early diastolic mitral annular velocities by tissue Doppler imaging for the differentiation of restrictive cardiomyopathy from constrictive pericarditis.

BACKGROUND AND AIMS: Echocardiographic tissue Doppler imaging (TDI) has been proposed as diagnostic tool for the differentiation between constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM). The aim of this study was a comprehensive TDI analysis of systolic (S') and early diastolic (E') velocities of the septal and lateral mitral annulus (MA) in patients (pts) with severe diastolic dysfunction caused either by CP or RCM. METHODS AND RESULTS: Sixty consecutive pts (34 men, mean age 61 +/- 11 years), 34 pts with proven CP and 26 pts with RCM due to cardiac amyloidosis, were included in the study. Forty-two of the 60 pts were in NYHA class III (70%). In pts with RCM systolic longitudinal velocity (S') was significantly decreased when compared to CP (septal MA 4.1 +/- 1.5 vs. 7.3 +/- 2.1 cm/s, p < 0.001; lateral MA 4.3 +/- 1.9 vs. 7.0 +/- 1.9 cm/s, p < 0.001). In addition, the RCM group showed a significantly decreased early diastolic longitudinal velocity (E'), both on the septal (4.1 +/- 1.6 vs. 12.9 +/- 4.9 cm/s, p < 0.001) and lateral side (4.8 +/- 1.9 vs. 11.3 +/- 3.7 cm/s; p < 0.001) of the mitral annulus. ROC analysis demonstrated an area under the curve of 0.889 (S' septal), 0.823 (S' lateral), 0.974 (E' septal), and 0.915 (E' lateral) for the differentiation of RCM and CP with a cutoff value of <8 cm/s. The combined use of an averaged S' cutoff value <8 cm/s as well as an E' cutoff value <8 at the lateral and septal MA demonstrated 93% sensitivity and 88% specificity for the diagnosis of RCM. CONCLUSION: TDI provides a diagnostic superiority and an accurate discrimination between RCM and CP by using the combined cutoff value of <8 cm/s for S' and E' at both sides of the MA.

[Management of patients with heart valve diseases in 2008. What has changed in the last three decades?]. / Management von Herzklappenpatienten 2008. Was hat sich in den letzten drei Jahrzehnten geändert?

In Central Europe, the vast majority of patients with valvar heart disease today suffer from degenerative aortic valve stenosis or mitral regurgitation. Due to the aging population, the prevalence of both diseases is rapidly increasing. Despite older age at the time of intervention and more co-morbidities, perioperative mortality has been constantly low (about 3.5 % in Germany). Clinical symptoms reported by patients are often inappropriate to chose the optimal time for intervention. Myocardial contractility reserve is yet the most appropriate measure to assess myocardial adaption to the chronic pressure and/or volume overload. Awaiting myocardial maladaption is hampered by a significant worsening in prognosis. This is especially true for mitral regurgitation, where imaging techniques regularly fail to assess LV pump function due to the low left ventricular impedance. For patients with valvar heart disease requiring therapy with vitamin K antagonists, stability of oral anticoagulation therapy is essential to avoid thromboembolic as well as bleeding complications. For the majority of these patients, a target INR of 2.5 is optimal. INR point of care self management results in a more than 30 % reduction of adverse events.

[Constrictive pericarditis or restrictive cardiomyopathy? Echocardiographic tissue Doppler analysis]. / Konstriktive Perikarditis oder restriktive Kardiomyopathie? Die echokardiografische Gewebedoppler-Analyse.

BACKGROUND AND OBJECTIVE: Echocardiographic tissue Doppler imaging (TDI) has been proposed for differentiating between constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM). The aim of this retrospective study was to analyse TDI in patients with severe diastolic dysfunction associated with proven constrictive pericarditis or restrictive cardiomyopathy. PATIENTS AND METHODS: The cohort included 34 consecutive patients (24 men. 10 women; mean age 58 12 years), 20 of whom had proven CP (pericardectomy) and 14 had RCM due to amyloidosis (proven by biopsy). Tissue Doppler Imaging was performed online by pulsed-wave TDI at the lateral and septal mitral annulus in the four-chamber view. Filling pressures were measured invasively. RESULTS: 20 of the 34 patients (60%) were in NYHA class III. 19 of the 34 patients were in sinus rhythm (56 %) and 15 had atrial fibrillation. Left ventricular systolic function was normal in all patients with CP. Eight patients with RCM had normal, 3 patients near normal and 3 patients slightly impaired left ventricular contractile function (EF 50-55% and EF 40%, respectively). Respiratory variation of the transmitral inflow was increased in 10 of 12 patients with CP and sinus rhythm. TDI of the early diastolic velocity across the mitral annulus E} was significantly higher in patients with CP than in those with RCM at the septal and at the lateral mitral annulus (13.8 4.2 cm/s vs. 4.0 1.2 cm/s; p < 0.01 and 11.4 3.4 cm/s vs. 4.4 1.7 cm/s; p < 0.01, respectively). A cut-off value 8 cm/s for the diagnosis of RCM showed a sensitivity of 100% and a specificity of 90% (septal) and 80% (lateral), respectively. The E/E}ratio also was significantly different between both groups (septal: 11.2 8.8 vs. 25.1 8.7; p < 0.01). CONCLUSION: TDI of the early diastolic velocity of the mitral annulus E} makes it possible to differentiate between constrictive pericarditis and restrictive cardiomyopathy and should be part of the echocardiographic work-up in clinical routine.

[Diagnosis and treatment of infective endocarditis]. / Diagnostik und Therapie der mikrobiell verursachten Endokarditis.

In infective endocarditis (IE) initial symptoms and clinical findings are unspecific. It is thus of the utmost importance that physicians primarily involved consider IE a potential diagnosis. Any delay in diagnosis and thus in adequate antimicrobial therapy has a significant negative prognostic influence. Any subject suspected of having IE should immediately have a transthoracic echocardiography (TTE) by an experienced examiner. If the TTE results are inconclusive, transoesophageal echocardiography (TEE) has to be performed without delay. Other steps in diagnosis, medical and surgical therapy follow established and evidence-based guidelines. Antimicrobial regimens are standardized for IE, for which demonstration of causative microorganisms from blood cultures or other microbiological sources are unavoidable. If there are problems in diagnosis, if difficult-to-treat microorganisms are isolated or difficult-to-treat situations (e.g. locally uncontrolled infections) complicate active IE, a reference centre should be involved.

New aspects of infective endocarditis.

The current incidence of infective endocarditis (IE) is estimated as 7 cases per 100,000 population per year and continues to increase. The prognosis is significantly influenced by proper diagnosis and adequate therapy. In cases with unconfirmed IE, transesophageal echocardiography is the imaging technique of choice. Culture-negative endocarditis requires either termination of antimicrobial treatment initiated without mircobiological test results and reevaluation of blood samples or serological/molecular biological techniques to identify the causative organism. Antimicrobial therapy should be established only after quantitative sensitivity tests of antibiotics (minimal inhibitory concentrations, MIC) and guided by drug monitoring. In the first 3 weeks after primary manifestation, an index embolism is frequently followed by recurrencies. If vegetations can still be demonstrated by echocardiography after an embolic event, a surgical intervention should seriously be considered. Cerebral embolic events are no contraindication for cardiac surgery, as long as a cerebral bleeding has been excluded by cranial computed tomography immediately preoperatively and the operation is performed before a significant disturbance of the blood-brain barrier (<72 hours) has manifested. A significant prognostic improvement has also been demonstrated for patients with early surgical intervention suffering from myocardial failure due to acute valve incompetence, acute renal failure, mitral kissing vegetations in primary aortic valve IE, and in patients with sepsis persisting for more than 48 hours despite adequate antimicrobial therapy.