Peer-to-peer validation of Ki-67 scoring in a pathology quality circle as a tool to assess interobserver variability: are we better than we thought?

Ki-67, a nuclear protein expressed in all stages of cellular proliferation, is a valuable tool to assess tumor proliferation and has been linked to more aggressive tumor behavior. However, interlaboratory staining heterogeneity and inter-observer variability challenge its reproducibility. Round Robin tests are a suitable tool to standardize and harmonize immunohistochemical and molecular analyses in histopathology. The study investigates the interrater and interlaboratory reproducibility of Ki-67-scoring using both manual and automated approaches. Unstained TMA slides comprising diverse tumor types (breast cancer, neuroendocrine tumors, lymphomas, and head and neck squamous cell carcinoma) were distributed to six pathology laboratories, each employing their routine staining protocols. Manual and automated scoring methods were applied, and interrater and interlaboratory agreement assessed using intraclass correlation coefficients (ICC). The results highlight good-to-excellent reliability overall, with automated scoring demonstrating higher consistency (ICC 0.955) than manual scoring (ICC 0.871). Results were more variable when looking at the individual entities. Reliability remained good for lymphomas (ICC 0.878) and breast cancer (ICC 0.784) and was poor in well-differentiated neuroendocrine tumors (ICC 0.354). This study clearly advocates standardized practices and training to ensure consistency in Ki-67-assessment, and it demonstrates that this can be achieved in a peer-to-peer approach in local quality-circles.

Pressure waveform analysis for occlusion assessment significantly reduces contrast medium use in cryoballoon pulmonary vein isolation.

BACKGROUND: Pulmonary vein (PV) occlusion is crucial for adequate lesion formation during cryoballoon-guided pulmonary vein isolation (CB-PVI). PV occlusion is usually confirmed by angiographies over the inflated balloon device. The aim of our study was to analyze the safety and efficacy of pressure waveform-based PV occlusion assessment during CB-PVI utilizing a novel fully integrated pressure analysis tool. METHODS: Consecutive patients with symptomatic atrial fibrillation (AF) scheduled for CB-PVI were prospectively enrolled for pressure waveform-based PV occlusion assessment. A patient cohort receiving conventional angiographies served as control group. Patients with common PV ostia were excluded. RESULTS: The study group consisted of 40 patients (16 females, mean age was 64.5 ± 9.7, 45% persistent AF). The control group consisted of 40 matched patients. All 160 PVs in the study group were successfully isolated without the use of additional venograms confirming PV occlusion. The mean procedure duration was 69 ± 12 min in the study group with a mean fluoroscopy duration of 11.5 ± 4.4 min. The mean contrast medium volume was 22 ± 9 ml in the study group and 36 ± 12 ml in the control group (p = 0.0001). Mean procedure duration, mean balloon temperatures, and mean ablation application durations did not differ significantly between the study and the control group. No periprocedural complications occurred. CONCLUSION: CB-PVI utilizing a fully integrated pressure waveform analysis tool to assess PV occlusion is feasible and safe and significantly reduces the amount of contrast medium without impact on procedural parameters and freedom from arrhythmia recurrence.

[Impact Analysis of a new, Cross-sector Service Provision of Gastroenterologic Endoscopic Services in Accordance with 115f SGB V (Hybrid-DRG): Allocation Matrix and Cost Analysis]. / Auswirkungsanalyse einer neuen, sektorenübergreifenden Erbringung bisher stationärer endoskopischer gastroenterologischer Leistungen entsprechend §115f SGB V (Hybrid-DRG): Zuordnungsmatrix und Kostenanalyse.

BACKGROUND: With the introduction of §115f SGB V, the prerequisites for "sector-equal remuneration" ('Hybrid DRG') have been created. In an impact analysis, we assigned inpatient gastroenterological endoscopic (GAEN) cases in a matrix of future hybrid DRG versus outpatient surgery (AOP) or inpatient treatment. METHODS: In selected DRGs (G47B, G67A, G67B, G67C, G71Z, H41D, H41E) an allocation matrix of GAEN cases was created on medical grounds. For this purpose, service groups from the DGVS service catalog ('Leistungskatalog') were assigned to the groups: 'Hybrid-DRG', 'AOP' and 'Inpatient' by a group of experts based on the DGVS position paper. Cost data from the DGVS-DRG project for the 2022 data year from 36 InEK calculation hospitals with a total of 232,476 GAEN cases were evaluated. RESULTS: 26 service groups from the DGVS service catalog were assigned to a "Hybrid-DRG", 24 to the "inpatient" group, and 12 to the "AOP" group. 7 performance groups were splitted "depending on the OPS code" and classified at this level. Cases with additional fees were excluded from a hybrid DRG because these cannot be agreed there.The cost analysis shows that services that are already in the AOP have a similar cost level to services that have been classified as 'Hybrid-DRG'. With the cost calculation, a cost level could be presented for the hybrid DRGs formed. CONCLUSION: Based on clearly defined structural, procedural and personnel requirements, services from suitable DRGs can be transferred to a hybrid DRG. Assigning services without the involvement of clinical experts seems extremely difficult. Case assignment based on arbitrary contextual factors increases complexity without demonstrably increasing the quality of the assignment and needs to be further developed. A cost analysis can be derived from the known inpatient costs and must serve as the basis for the 2025 Hybrid DRG catalog.

Peptide Receptor Radionuclide Therapy Is Effective for Clinical Control of Symptomatic Metastatic Insulinoma: A Long-Term Retrospective Analysis.

Metastatic insulinoma is a rare malignant neuroendocrine tumor characterized by inappropriate insulin secretion, resulting in life-threatening hypoglycemia, which is often difficult to treat. There is currently very limited information about the efficacy of peptide receptor radionuclide therapy (PRRT) for clinical control of hypoglycemia. The aim of this long-term retrospective study was to evaluate the therapeutic efficacy of PRRT for improving hypoglycemia, to evaluate the change of medication after PRRT, and to calculate progression-free survival (PFS) and overall survival (OS). Methods: Inclusion criteria were histologically proven somatostatin receptor-positive metastatic malignant insulinoma and at least 2 cycles of [90Y]Y-DOTATOC or [177Lu]Lu-DOTATOC therapy from early 2000 to early 2022. A semiquantitative scoring system was used to quantify the severity and frequency of hypoglycemic episodes under background antihypoglycemic therapy (somatostatin analog, diazoxide, everolimus, corticosteroids): score 0, no hypoglycemic episodes; score 1, hypoglycemic events requiring additional conservative treatment with optimization of nutrition; score 2, severe hypoglycemia necessitating hospitalization and combined medication or history of hypoglycemic coma. Hypoglycemic score before and after PRRT was analyzed. Time of benefit was defined as a time range of fewer hypoglycemic episodes in the observation period than at baseline. Information on antihypoglycemic medication before and after therapy, PFS, and OS was recorded. Results: Twenty-six of 32 patients with a total of 106 [90Y]Y-DOTATOC/[177Lu]Lu-DOTATOC cycles were included. The average observation period was 21.5 mo (range, 2.3-107.4 mo). Before therapy, 81% (n = 21) of the patients had a hypoglycemia score of 2 and 19% (n = 5) had a score of 1. After PRRT, 81% of patients (n = 21) had a decreased score, and the remaining 5 patients showed a stable situation. There was temporary worsening of hypoglycemia just after injection of [90Y]Y-DOTATOC/[177Lu]Lu-DOTATOC in 19% of patients. The average time of benefit in the observation period was 17.2 mo (range, 0-70.2 mo). Antihypoglycemic medication reduction was achieved in 58% (n = 15) of patients. The median OS and PFS after the start of PRRT were 19.7 mo (95% CI, 6.5-32.9 mo) and 11.7 mo (95% CI, 4.9-18.5 mo), respectively. Conclusion: To our knowledge, our study included the largest cohort of patients with malignant insulinoma to be evaluated. Long-lasting symptom control and reduction of antihypoglycemic medications were shown in most patients after late-line PRRT.

Cryolipolysis of the Arms and Inner Thighs Shows Similar Treatment Outcomes in Chinese Individuals Compared to White Individuals Treated in a Prior Study: The XinCOOL Study.

Background: Studies of predominantly White participants show that cryolipolysis reduces subcutaneous fat in the arms and inner thighs, but none have specifically tested for similar outcomes in participants of Chinese descent. Objectives: This study assessed the safety and effectiveness of cryolipolysis treatment for noninvasive subcutaneous fat reduction of arms and inner thighs in participants of Chinese descent to assess equivalence to results seen in a prior study of White participants. Methods: Replicating a similar study design, participants of first- or second-generation Chinese descent underwent cryolipolysis treatment of arms and/or inner thighs. Effectiveness was assessed using pretreatment and posttreatment photographic review by blinded, independent experts, investigator-assessed caliper measurements, and participant satisfaction 12 weeks posttreatment. Safety was assessed throughout. Results: Among 50 enrolled participants, 48 completed the study. The majority of participants (97.9%) were female, with a mean age of 36.0 years and mean BMI of 24.16 kg/m2 (range 19.3-29.9 kg/m2). Overall, 76.4% and 70.0% of pretreatment photographs of arms and pairs of inner thighs, respectively, were correctly identified by at least 2 of 3 reviewers. The mean reduction from baseline in caliper-measured fat thickness was 6.5 mm for arms and 6.6 mm for inner thighs, and the majority of participants (>60%) were satisfied with the treatment. No adverse events were reported. Conclusions: Cryolipolysis is a well-tolerated, effective means of noninvasive fat reduction of arms and inner thighs in participants of Chinese descent. The results from this study show similar effectiveness and safety in Chinese participants compared with White participants treated in a prior study.

An international multi-institutional validation study of the algorithm for prostate cancer detection and Gleason grading.

Pathologic examination of prostate biopsies is time consuming due to the large number of slides per case. In this retrospective study, we validate a deep learning-based classifier for prostate cancer (PCA) detection and Gleason grading (AI tool) in biopsy samples. Five external cohorts of patients with multifocal prostate biopsy were analyzed from high-volume pathology institutes. A total of 5922 H&E sections representing 7473 biopsy cores from 423 patient cases (digitized using three scanners) were assessed concerning tumor detection. Two tumor-bearing datasets (core n = 227 and 159) were graded by an international group of pathologists including expert urologic pathologists (n = 11) to validate the Gleason grading classifier. The sensitivity, specificity, and NPV for the detection of tumor-bearing biopsies was in a range of 0.971-1.000, 0.875-0.976, and 0.988-1.000, respectively, across the different test cohorts. In several biopsy slides tumor tissue was correctly detected by the AI tool that was initially missed by pathologists. Most false positive misclassifications represented lesions suspicious for carcinoma or cancer mimickers. The quadratically weighted kappa levels for Gleason grading agreement for single pathologists was 0.62-0.80 (0.77 for AI tool) and 0.64-0.76 (0.72 for AI tool) for the two grading datasets, respectively. In cases where consensus for grading was reached among pathologists, kappa levels for AI tool were 0.903 and 0.855. The PCA detection classifier showed high accuracy for PCA detection in biopsy cases during external validation, independent of the institute and scanner used. High levels of agreement for Gleason grading were indistinguishable between experienced genitourinary pathologists and the AI tool.

Impact of pulmonary vein anatomy and ostial dimensions on long-term outcome after single-shot device-guided cryoablation for paroxysmal atrial fibrillation.

BACKGROUND: Cryoballoon (CB)-guided pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). This observational study aimed to assess the role of individual anatomical characteristics to predict long-term freedom from arrhythmia recurrence after CB-guided PVI for paroxysmal AF (PAF). METHODS: Three hundred fifty three consecutive patients (58 ± 11 years, 56% males), undergoing PVI between 2012 and 2018 were analysed. Individual pulmonary vein (PV) anatomy was assessed using preprocedural cardiac magnetic resonance imaging (MRI). For each PV, the cross-sectional area (CSA) was calculated. The impact of PV characteristics and CSA on long-term AF-free survival was evaluated. RESULTS: Acute PVI was achieved in all patients. Two hundred twenty-three patients (63%) had a normal PV anatomy (2 left- and 2 right-sided PV). Variant PV anatomy was present in 130 patients (37%). During the observation period of 48 months, AF-recurrence was documented in 167 patients (47 %). Patients with AF-recurrence presented with significantly enlarged right-sided PVs and left superior PVs (LSPVs) (p < 0.001). The presence of left common PVs (LCPVs) (n = 75, Log-rank p < 0.001) as well as right variant PVs (n = 35, Log rank p < 0.001) was associated with a significantly impaired long-term AF-free survival rate as compared to patients with normal PV characteristics. CONCLUSION: Variant PV anatomy is a good predictor for AF-recurrence. A correlation between an enlarged CSA of right-sided PVs as well as LSPVs and AF-recurrence was documented.

First clinical experience using a visualized sheath for atrial fibrillation ablation.

INTRODUCTION: Recently, a novel steerable sheath allowing its real-time visualization within a 3D-mapping system was introduced to facilitate atrial fibrillation (AF) ablation. AIM: This study aimed to assess safety and efficacy of AF ablation using the visualized sheath and to compare its performance with a matched control group of patients who received ablation with conventional and non-visualized sheaths. METHODS: The study included consecutive patients between 09/2019 and 02/2021 who underwent routine AF ablation using the visualized sheath. Patients were regularly followed-up in our outpatient's clinic. Arrhythmia recurrence was defined as any atrial fibrillation (AF)/ atrial tachycardia (AT) episode lasting > 30 s after a blanking period of 3 months. RESULTS: A total number of 100 patients undergoing ablation using the visualized sheath were compared to a group of 99 matched patients. No major complications were observed. Total procedure duration (108 ± 22 min vs. 112 ± 12 min; p = 0.045), fluoroscopy time (7 ± 3 min vs. 10 ± 5 min; p < 0.001) and -dose (507 ± 501 cGy*cm2 vs. 783 ± 433 cGy*cm2 ; p < 0.001) were significantly lower using the visualized sheath. The benefit in terms of procedure duration was mainly driven by a shortened left atrial dwell time (73 ± 13 min vs. 79 ± 12 min; p = 0.001). During a mean follow-up of 12 months, the overall procedural success was 85% in the visualized sheath group versus 83% in the control group (p = 0.948). CONCLUSION: AF ablation using the novel visualized sheath is safe and effective and leads to a measurable decrease of procedure duration and radiation exposure. The integration of the novel sheath might help to further improve safety and efficacy of AF ablation.

Impact of pulmonary vein variant anatomy and cross-sectional orifice area on freedom from atrial fibrillation recurrence after cryothermal single-shot guided pulmonary vein isolation.

BACKGROUND: Cryoballoon (CB)-guided pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). This study aimed to evaluate ablation efficacy and freedom from arrhythmia recurrence using the novel POLARx compared to the Arctic Front Advance Pro (AFA) CB system including the analysis of individual PV characteristics. METHODS: A total of 687 patients underwent CB-guided ablation for AF. Arrhythmia recurrence was defined as an ECG documented episode of any AF/atrial tachycardia (AT) > 30 s. Anatomical characteristics were assessed using magnetic resonance imaging (MRI). For each PV, the cross-sectional orifice area (CSOA) was determined. Follow-up examinations were scheduled after 3, 6, and 12 months. RESULTS: Acute PVI was achieved in all patients. Twelve-month AF-free survival was similar between the groups (POLARx 43/86 (50%) vs. AFA 318/601 (53%), Log-rank (LR) p = 0.346). MRI found a comparable percentage of patients with normal PV anatomy (POLARx 71/86 (83%) vs. AFA 530/601 (85%), p = 0.162). Patients with variant PV characteristics presented with a significantly impaired 12-month AF-free survival (normal PVs 326/585 (56%) vs. variant PVs 27/102 (27%), LR p < 0.001) independent of the applied CB ablation system. PAF patients with AF recurrence presented with significantly larger CSOA of the left-sided PVs and the right superior PVs (LSPV: p < 0.001; LIPV: p < 0.001; RSPV: p < 0.001). In PERS AF, no association between CSOA and ablation outcome was observed. Multivariate analyses identified PERS AF (hazard ratio (HR) 2.504, confidence interval (CI), 1.900-3.299, p < 0.001) and variant PV anatomy (HR 2.124, CI 1.608-2.805, p < 0.001) as independent predictors for AF recurrence. CONCLUSIONS: Both CB ablation systems are associated with comparable 12-month AF-free survival rates. Variant PV anatomy seems to be predictive for AF recurrence. An association between CSOA and the outcome after CB-guided PVI was demonstrated for PAF.

A frozen decade: Ten years outcome of atrial fibrillation ablation using a single shot device for pulmonary vein isolation.

AIMS: Cryoballoon-guided pulmonary vein isolation (CB-PVI) for symptomatic atrial fibrillation (AF) has become an established treatment option with encouraging results in terms of safety and efficacy. Data reporting on long-term data beyond a follow-up (FU) period of 5 years is scarce. This prospective study aimed to evaluate very long-term outcome after CB-PVI for AF. METHODS: Data from consecutive patients treated with CB-PVI for symptomatic and drug refractory AF between 2005 and 2012 were analyzed. Patients with a FU of ≥9 years after index CB-PVI were included. All patients were continuously followed-up in our outpatient clinic. Arrhythmia recurrence was defined as AF or atrial tachycardia (AT) lasting >30 s beyond a 3-month blanking period. RESULTS: A total of 385 patients (71% male) were included. Mean age was 58 ± 10 years and paroxysmal AF was present in 93% of patients. Mean FU duration was 124 ± 24 months. At the end of the observational period, 73% of all patients were in stable sinus rhythm after a mean of 2 ± 0.8 ablation procedures. Patients with AF/AT recurrence were older (60 ± 8 vs. 57 ± 10 years; p = .019), had a higher CHA2 DS2 -Vasc Score (2.47 ± 1.46 vs. 1.98 ± 1.50; p = .01) and presented with a larger left atrium (LA)-diameter (43 ± 5.6 vs. 40 ± 5.1 mm; p = .002). The LA-diameter was also a significant predictor for AF/AT recurrence after CB-PVI (odds ratio: 0.939, 95% confidence interval: [0.886, 0.992], p = .03). CONCLUSIONS: CB-PVI as index procedure for AF ablation resulted in favorable long-term outcome in symptomatic AF. CB-PVI might be recommended as interventional therapy in patients with lower LA remodeling.

The Arrhythmogenic Face of COVID-19: Brugada ECG Pattern in SARS-CoV-2 Infection.

In 1992, Brugada syndrome (BS) was first described; an often unrecognized cardiac conduction disorder mainly associated with unexplained sudden cardiac arrest and consecutive syncope. Nevertheless, the pathomechanism of BS and sudden cardiac death remains mainly explained. Mutations in the cardiac sodium channels, which cause a reduction or functional loss of these channels, are associated with characteristic electrocardiographic (ECG) abnormalities and malignant arrhythmia. The majority of affected people are previously healthy and unaware of their genetic predisposition for BS and might experience ventricular tachyarrhythmias and cardiac arrest potentially triggered by several factors (e.g., alcohol, sodium channel blockers, psychotropic drugs, and fever). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was firstly identified in Wuhan in early December 2019 and rapidly spread worldwide as coronavirus disease (COVID-19). COVID-19 is typically characterized by a severe inflammatory response, activation of the immune system, and high febrile illness. Due to this condition, symptomatic COVID-19 infection or vaccination might serve as inciting factor for unmasking the Brugada pattern and represents a risk factor for developing proarrhythmic complications. The aim of this narrative review was to detail the association between virus-related issues such as fever, electrolyte disturbance, and inflammatory stress of COVID-19 infection with transient Brugada-like symptoms and ECG-pattern and its susceptibility to proarrhythmogenic episodes.

High Participant Satisfaction Achieved Using Cryolipolysis for Fat Reduction of the Abdomen and Flanks.

BACKGROUND: Patient-reported outcome (PRO) data evaluating the physical and psychosocial impact of cryolipolysis (CoolSculpting) treatment are limited. OBJECTIVES: The aim of this study was to assess, by means of PRO instruments, multidimensional aspects of satisfaction following cryolipolysis treatment of the flanks and abdomen. METHODS: This was a multinational, prospective, single-cohort, interventional study. The primary endpoint was the proportion of participants stating they were "satisfied" or "very satisfied" with treatment at 12 weeks post final treatment. Secondary endpoints included satisfaction categorized by treatment area, total number of treatment cycles, baseline BMI, and fat volume reduction measured by 3-dimensional photography at 12 weeks post final treatment. Exploratory endpoints assessed the physical and psychosocial impacts of treatment. Safety was monitored throughout the study. RESULTS: Of 112 participants who were treated, 74.1% were female. The mean age and BMI were 42.5 years and 24.9 kg/mg2, respectively. Of the 106 evaluable participants, 89.6% were "satisfied" or "very satisfied" with treatment results. Satisfaction was high regardless of body area(s), total number of treatment cycles, or baseline BMI. Mean [standard deviation] fat volume reduction was 264.8 [411.4] mL. Overall, 90.6% reported "noticeable" or "very noticeable" fat reduction, 89.6% were "likely" or "very likely" to treat additional areas, and 93.4% would recommend cryolipolysis to a friend. Twenty-four (21.4%) participants reported treatment-emergent adverse events; 23 (20.5%) reported these as adverse device effects. No serious device-related or unanticipated adverse effects occurred. CONCLUSIONS: Cryolipolysis (CoolSculpting) for fat reduction of the flanks and/or abdomen was well-tolerated and associated with high levels of satisfaction across multidimensional PROs.

Cool enough? Lessons learned from cryoballoon-guided catheter ablation for atrial fibrillation in young adults.

INTRODUCTION: Cryoballoon (CB)-guided ablation of atrial fibrillation (AF) is established in symptomatic AF patients. This study sought to determine the safety and efficacy of CB pulmonary vein isolation (PVI) in young adults. METHODS AND RESULTS: A total of 93 consecutive patients aged <45 years referred to our center for AF ablation were included in this observational study. All patients received CB-guided PVI according to a standardized institutional protocol. Follow-up was performed in our outpatient clinic using 72-h Holter monitoring and periodic telephone interview. Recurrence was defined as any AF/atrial tachycardia (AT) episode >30 s following a 3-month blanking period. A propensity matched control group consisting of patients older than 45 years were used for further evaluation. Mean age was 35 ± 7 years, 22% suffered from persistent AF, 85% were male. Mean follow-up was 2.6 ± 2 years. At the end of the observational period, 83% of patients were free of any AF/AT episodes. There was an excellent overall 12-month success rate of 92%. In comparison to a matched group the overall recurrence rate was noticeably lower in the young group (15% vs. 27%). Increasing age was associated with a hazard ratio of 1.16 for recurrence. In a multivariate analysis model, left atrial diameter remained as significant predictor of AF/AT recurrence. The complication rate was low, no permanent phrenic nerve palsy was observed. CONCLUSION: CB-guided PVI in young adults is safe and effective with favorable long-term results. It may be considered as first-line therapy in this relatively healthy population.

Comparison of Single- Versus Dual-Vector Technique Using Facial Suspension Threads: A Cadaveric Study Using Skin Vector Displacement Analysis.

BACKGROUND: Facial suspension threads have been successfully used for facial soft-tissue repositioning. When using facial suspension threads, it is unclear which technique and/or material has the greatest lifting effect for the middle and lower face or which technique/material best reduces the appearance of the jowls. MATERIAL AND METHODS: Three female and 2 male cephalic specimens of Caucasian ethnicity (65.2 ± 8.3 years; 20.72 ± 2.6 kg/m) were analyzed in an upright secured position. Polydioxanone and polycaprolactone bidirectional barbed facial suspension threads were introduced by an 18 G, 100 mm cannula. The single-vector technique aimed toward the labiomandibular sulcus, and the dual-vector technique aimed toward the labiomandibular sulcus and the mandibular angle. Computation of vertical lifting, horizontal lifting, and volume reduction at the jowls and along the jawline were calculated using 3D imaging. RESULTS: The dual-vector technique effected a greater vertical lifting effect (4.45 ± 2.78 mm vs 2.99 ± 2.23 mm) but a reduced horizontal lifting effect (0.33 ± 1.34 mm vs 0.49 ± 1.32 mm). The dual-vector technique effected less volume reduction at the jowls 0.32 ± 0.24 cc versus 0.41 ± 0.46 cc and less volume reduction along the jawline 0.46 ± 0.48 cc versus 0.87 ± 0.53 cc (dual-vector vs single-vector). CONCLUSION: This study provides evidence resulting from cadaveric observations for the overall nonsuperiority of the dual-vector technique compared with the single-vector technique.

The Influence of the Insertion Angle on Middle and Lower Face Tissue-Mechanics When Treating the Nasolabial Folds with Facial Suspension Threads-An Experimental Split-Face Cadaveric Study.

A novel treatment approach to address the nasolabial fold is the insertion facial suspension threads. However, there is a paucity of data available to guide insertion techniques and material selection. Three female and two male cephalic specimens of Caucasian ethnicity (73.6 ± 6.5 years; 21.41 ± 2.2 kg/m2) were included into this experimental split-face study. One facial side was treated with polycaprolactone (PCL) thread: 180 mm, bidirectional, 18G 100 mm cannula, 20 degrees trajectory, preauricular approach whereas the contralateral side was treated with polydioxanone (PDO) thread: 100 mm, bidirectional, 19G, 60 mm cannula, 50 degrees trajectory, infraorbital approach. Three-dimensional imaging outcome measures included vertical and horizontal skin displacement and volume changes at the nasolabial sulcus, at the labiomandibular sulcus, and along the jawline. Comparing PCL 180 mm 20 degrees to PDO 100 mm 50 degrees: vertical lifting effect 1.42 ± 2.63 mm versus 1.24 ± 1.88 mm (p = 0.906); horizontal lifting effect 3.42 ± 1.44 mm versus -2.02 ± 1.84 mm (p = 0.001); nasolabial volume change -0.80 ± 0.65 mL versus -0.52 ± 0.17 mL (p = 0.367); labiomandibular volume change -0.45 ± 0.42 mL versus -0.16 ± 0.16 mL (p = 0.191); jawline volume change 0.02 ± 0.43 mL versus -0.01 ± 0.21 mL (p = 0.892). The study provides objective evidence for the short-term effectiveness of facial suspension threads in treating the nasolabial folds. The results point toward a better aesthetic outcome when utilizing long facial suspension threads that can effect full-face changes as compared with short facial suspension threads.

Closing gaps, opening doors: an experimental collaboration in stem cell intervention.

Despite years of warnings by the academic community that for most of the stem cell-based therapies offered in the private arena little evidence of efficacy exists, these services have been increasingly offered by Canadian private clinics. Recently, as the culmination of years of clashes between stem cell researchers and therapy providers, Health Canada issued a statement prohibiting any type of cell therapy that is not specifically approved. In this climate of conflict, a small group representing both these communities as well as the government gathered in Vancouver to identify common values, and agree on principles to move forward constructively. This historic moment demonstrated that even in this contentious space a meeting-of-minds in between researchers, clinicians, ethicists, entrepreneurs and other stakeholders is possible.

Quantitative 99mTc-DPD SPECT/CT in patients with suspected ATTR cardiac amyloidosis: Feasibility and correlation with visual scores.

PURPOSE: While a visual interpretation of 99mTc-DPD scintigraphy by means of Perugini score can provide a reliable diagnosis of transthyretin-related (ATTR) cardiac amyloidosis (CA), a quantitative approach is expected to play a major role in risk stratification and therapy evaluation. The aim of our study was to test the feasibility of a quantitative assessment and to correlate various parameters to Perugini score. METHODS: in this retrospective study, consecutive patients underwent a 99mTc-DPD whole-body bone scintigraphy and a SPECT/CT of the thorax. XSPECT-QUANT software was used to quantify the DPD uptake in the heart. RESULTS: Thirteen patients were included. CA was confirmed in 8 and rejected in 5. Myocardial SUVmax and SUVpeak showed a fairly strong correlation with Perugini score (both ρ = .71, P = .006). Same held true for to-bone normalized values (both ρ = .75, P = .003). There was a great degree of overlap for quantitative values in patients with Perugini score 2 and 3. CONCLUSION: Quantitative 99mTc-DPD SPECT/CT in suspected ATTR CA patients is feasible and allows for a more accurate assessment of myocardial uptake.

Targeting Notch1 and IKKα Enhanced NF-κB Activation in CD133+ Skin Cancer Stem Cells.

Cancer stem-like cells are hypothesized to be the major tumor-initiating cell population of human cutaneous squamous cell carcinoma (cSCC), but the landscape of molecular alterations underpinning their signaling and cellular phenotypes as drug targets remains undefined. In this study, we developed an experimental pipeline to isolate a highly enriched CD133+CD31-CD45-CD61-CD24- (CD133+) cell population from primary cSCC specimens by flow cytometry. The CD133+ cells show enhanced stem-like phenotypes, which were verified by spheroid and colony formation in vitro and tumor generation in vivo Gene expression profiling of CD133+/- cells was compared and validated, and differentially expressed gene signatures and top pathways were identified. CD133+ cells expressed a repertoire of stemness and cancer-related genes, including NOTCH and NOTCH1-mediated NF-κB pathway signaling. Other cancer-related genes from WNT, growth factor receptors, PI3K/mTOR, STAT pathways, and chromatin modifiers were also identified. Pharmacologic and genetic targeting of NOTCH1, IKKα, RELA, and RELB modulated NF-κB transactivation, the CD133+ population, and cellular and stemness phenotypes. Immunofluorescent staining confirmed colocalization of CD133+ and IKKα expression in SCC tumor specimens. Our functional, genetic, and pharmacologic studies uncovered a novel linkage between NOTCH1, IKKα, and NF-κB pathway activation in maintaining the CD133+ stem SCC phenotypes. Studies investigating markers of activation and modulators of NOTCH, IKK/NF-κB, and other pathways regulating these cancer stem gene signatures could further accelerate the development of effective therapeutic strategies to treat cSCC recurrence and metastasis. Mol Cancer Ther; 17(9); 2034-48. ©2018 AACR.

Low BUB1 expression is an adverse prognostic marker in gastric adenocarcinoma.

Gastric adenocarcinomas are associated with a poor prognosis due to the fact that the tumor has often metastasized by the time of diagnosis and prognostic markers are urgently needed to tailor treatment. We examined the expression of the mitotic spindle checkpoint protein BUB1 (budding uninhibited by benzimidazoles 1) and Ki-67 protein expression by immunohistochemistry in 218 patients with primary gastric adenocarcinomas. Tumors with low frequency of BUB1 expression were associated with larger tumor size (pT) (p < 0.001), higher incidence of lymph node metastases (pN) (p = 0.027), distant metastases (pM) (p = 0.006) and higher UICC stage (p < 0.001). Furthermore, BUB1 expression was inversely correlated with residual tumor stage (p = 0.038). Abundant BUB1 protein expression correlated with frequent Ki-67 protein expression (p < 0.001) and low BUB1 expression was associated with shorter survival (p < 0.001). Univariate and multivariate analyses confirmed BUB1 to be an independent prognostic marker in gastric cancer (p = 0.021).

[Cost assessment for endoscopic procedures in the German diagnosis-related-group (DRG) system - 5 year cost data analysis of the German Society of Gastroenterology project]. / Kosten endoskopischer Leistungen der Gastroenterologie im deutschen DRG-System ­ 5-Jahres-Kostendatenanalyse des DGVS-Projekts.

Background In the German hospital reimbursement system (G-DRG) endoscopic procedures are listed in cost center 8. For reimbursement between hospital departments and external providers outdated or incomplete catalogues (e. g. DKG-NT, GOÄ) have remained in use. We have assessed the cost for endoscopic procedures in the G-DRG-system. Methods To assess the cost of endoscopic procedures 74 hospitals, annual providers of cost-data to the Institute for the Hospital Remuneration System (InEK) made their data (2011 - 2015; §â€Š21 KHEntgG) available to the German-Society-of-Gastroenterology (DGVS) in anonymized form (4873 809 case-data-sets). Using cases with exactly one endoscopic procedure (n = 274 186) average costs over 5 years were calculated for 46 endoscopic procedure-tiers. Results Robust mean endoscopy costs ranged from 230.56 € for gastroscopy (144 666 cases), 276.23 € (n = 32 294) for a simple colonoscopy, to 844.07 € (n = 10 150) for ERCP with papillotomy and plastic stent insertion and 1602.37 € (n = 967) for ERCP with a self-expanding metal stent. Higher costs, specifically for complex procedures, were identified for University Hospitals. Discussion For the first time this catalogue for endoscopic procedure-tiers, based on §â€Š21 KHEntgG data-sets from 74 InEK-calculating hospitals, permits a realistic assessment of endoscopy costs in German hospitals. The higher costs in university hospitals are likely due to referral bias for complex cases and emergency interventions. For 46 endoscopic procedure-tiers an objective cost-allocation within the G-DRG system is now possible. By international comparison the costs of endoscopic procedures in Germany are low, due to either greater efficiency, lower personnel allocation or incomplete documentation of the real expenses.