FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction.

BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).

Unlocking New Topologies in Zr-Based Metal-Organic Frameworks by Combining Linker Flexibility and Building Block Disorder.

The outstanding diversity of Zr-based frameworks is inherently linked to the variable coordination geometry of Zr-oxo clusters and the conformational flexibility of the linker, both of which allow for different framework topologies based on the same linker-cluster combination. In addition, intrinsic structural disorder provides a largely unexplored handle to further expand the accessibility of novel metal-organic framework (MOF) structures that can be formed. In this work, we report the concomitant synthesis of three topologically different MOFs based on the same M6O4(OH)4 clusters (M = Zr or Hf) and methane-tetrakis(p-biphenyl-carboxylate) (MTBC) linkers. Two novel structural models are presented based on single-crystal diffraction analysis, namely, cubic c-(4,12)MTBC-M6 and trigonal tr-(4,12)MTBC-M6, which comprise 12-coordinated clusters and 4-coordinated tetrahedral linkers. Notably, the cubic phase features a new architecture based on orientational cluster disorder, which is essential for its formation and has been analyzed by a combination of average structure refinements and diffuse scattering analysis from both powder and single-crystal X-ray diffraction data. The trigonal phase also features structure disorder, although involving both linkers and secondary building units. In both phases, remarkable geometrical distortion of the MTBC linkers illustrates how linker flexibility is also essential for their formation and expands the range of achievable topologies in Zr-based MOFs and its analogues.

[Value of PET imaging in head and neck cancer]. / Stellenwert der PET-Bildgebung bei Kopf-Hals-Tumoren.

The combination of positron-emission tomography (PET) with cross-sectional imaging in particular is becoming increasingly important in the diagnosis of head and neck tumors because, in addition to pure anatomy, the metabolic activity of tissue can be visualized and assessed. The combination of PET and computed tomography (CT) is already an established procedure in head and neck tumor patients in some indications, e.g., for primary tumor detection in cancer of unknown primary (CUP) syndrome or also after completed primary radio(chemo)therapy for evaluation of response, especially also with regard to nodal status. In some cases, salvage neck dissection can thus be avoided in the case of PET-negative findings. In the context of primary diagnosis, PET/CT imaging can be used primarily to evaluate distant metastasis. According to current guidelines, PET-based imaging is not (yet) of value in determining the local extent at initial diagnosis. A challenge is the still limited reimbursement by health insurance companies, which currently allow only certain indications, and the still lack of nationwide coverage.

[Telemedicine in Otorhinolaryngology and Head and Neck Surgery - An universal remedy?] / Telemedizin in der HNO-Heilkunde ­ wirklich ein Allheilmittel?

Digitalization in healthcare has gained considerable importance in recent years and especially during the Covid19 pandemic. The pandemic has undeniably severely limited human interactions. In light of the risk of infection, and also in light of the decreasing number of physician consultations by patients due to fear of infection, the medical community has had to seek new platforms for physician-patient interaction and -communication and achieved these goals predominantly by accelerating the development of digitization processes and telemedicine. In otolaryngology, the term telemedicine usually refers to video consultation (VS) or teleconsultations. In principle, ENT physicians belong to the group of specialists who are allowed to perform and invoice video consultations. Data protection and legal aspects pose challenges with regard to offering telemedical services. From an ethical point of view, any telemedical consultation would also have to be preceded by a mandatory explanation of the risks and disadvantages of using these procedures, and the basis for liability would also have to be clarified here in principle. Telemedicine will also have to assert itself in view of the evidence. Thus, at least from the medical university side, accompanying studies should be initiated when new telemedical procedures are offered, in order to evaluate the corresponding advantages and disadvantages on the basis of evidence. In terms of professional policy, care should always be taken to ensure that telemedicine is only offered by players in the healthcare sector who can also guarantee personal treatment of the patient assessed by telemedicine.

Erythrocytes from patients with ST-elevation myocardial infarction induce cardioprotection through the purinergic P2Y13 receptor and nitric oxide signaling.

Red blood cells (RBCs) are suggested to play a role in cardiovascular regulation by exporting nitric oxide (NO) bioactivity and ATP under hypoxia. It remains unknown whether such beneficial effects of RBCs are protective in patients with acute myocardial infarction. We investigated whether RBCs from patients with ST-elevation myocardial infarction (STEMI) protect against myocardial ischemia-reperfusion injury and whether such effect involves NO and purinergic signaling in the RBCs. RBCs from patients with STEMI undergoing primary coronary intervention and healthy controls were administered to isolated rat hearts subjected to global ischemia and reperfusion. Compared to RBCs from healthy controls, RBCs from STEMI patients reduced myocardial infarct size (30 ± 12% RBC healthy vs. 11 ± 5% RBC STEMI patients, P < 0.001), improved recovery of left-ventricular developed pressure and dP/dt and reduced left-ventricular end-diastolic pressure in hearts subjected to ischemia-reperfusion. Inhibition of RBC NO synthase with L-NAME or soluble guanylyl cyclase (sGC) with ODQ, and inhibition of cardiac protein kinase G (PKG) abolished the cardioprotective effect. Furthermore, the non-selective purinergic P2 receptor antagonist PPADS but not the P1 receptor antagonist 8PT attenuated the cardioprotection induced by RBCs from STEMI patients. The P2Y13 receptor was expressed in RBCs and the cardioprotection was abolished by the P2Y13 receptor antagonist MRS2211. By contrast, perfusion with PPADS, L-NAME, or ODQ prior to RBCs administration failed to block the cardioprotection induced by RBCs from STEMI patients. Administration of RBCs from healthy subjects following pre-incubation with an ATP analog reduced infarct size from 20 ± 6 to 7 ± 2% (P < 0.001), and this effect was abolished by ODQ and MRS2211. This study demonstrates a novel function of RBCs in STEMI patients providing protection against myocardial ischemia-reperfusion injury through the P2Y13 receptor and the NO-sGC-PKG pathway.

A fully human anti-BMP6 antibody reduces the need for erythropoietin in rodent models of the anemia of chronic disease.

Recombinant erythropoietin (EPO) and iron substitution are a standard of care for treatment of anemias associated with chronic inflammation, including anemia of chronic kidney disease. A black box warning for EPO therapy and concerns about negative side effects related to high-dose iron supplementation as well as the significant proportion of patients becoming EPO resistant over time explains the medical need to define novel strategies to ameliorate anemia of chronic disease (ACD). As hepcidin is central to the iron-restrictive phenotype in ACD, therapeutic approaches targeting hepcidin were recently developed. We herein report the therapeutic effects of a fully human anti-BMP6 antibody (KY1070) either as monotherapy or in combination with Darbepoetin alfa on iron metabolism and anemia resolution in 2 different, well-established, and clinically relevant rodent models of ACD. In addition to counteracting hepcidin-driven iron limitation for erythropoiesis, we found that the combination of KY1070 and recombinant human EPO improved the erythroid response compared with either monotherapy in a qualitative and quantitative manner. Consequently, the combination of KY1070 and Darbepoetin alfa resulted in an EPO-sparing effect. Moreover, we found that suppression of hepcidin via KY1070 modulates ferroportin expression on erythroid precursor cells, thereby lowering potentially toxic-free intracellular iron levels and by accelerating erythroid output as reflected by increased maturation of erythrocyte progenitors. In summary, we conclude that treatment of ACD, as a highly complex disease, becomes more effective by a multifactorial therapeutic approach upon mobilization of endogenous iron deposits and stimulation of erythropoiesis.

[PSMA-PET-MRI and radio-guided surgery in cervical lymphadenectomy]. / PSMA-PET und "radio-guided surgery" bei zervikaler Lymphadenektomie.

A 75-year-old male patient with suspicious cervical lymph nodes in level IV on the left side is presented. The cervical mass was detected in PSMA-PET-MRI as part of a restaging examination conducted due to an increase of PSA levels in the context of the patient's known prostate cancer. We conducted a selective cervical level IV lymphadenectomy with the aid of a gamma probe subsequent to radiolabelling with 99mTc-PSMA. Two visibly enlarged lymph nodes with high gamma probe signals could be extracted. Histopathological examination revealed lymph node metastases of the known prostate cancer. Using an adequate tracer radio-guided surgery helps to detect pathological lymph nodes in the head and neck region allowing for supraselective resection.

[Centralization, Specialization, and Outpatient Care for Head and Neck Tumor Patients]. / Zentralisierung, Spezialisierung und Ambulantisierung der Versorgung von Kopf-Hals-Tumorpatienten.

Demographically, the German population is aging and becoming more morbid. At the same time, urbanization trends, medical overcapacities, and increasing care costs are being observed in association with a tight healthcare budget. Centralization, specialization, and outpatient care are intended to provide a remedy and can be controlled by modifications to remuneration. This upheaval poses new challenges for patients and physicians, which were analyzed exemplarily at the Head and Neck Tumor (HNC) Center of the University Hospital Ulm. This is a retrospective, monocentric cohort study on the development of patient volume, catchment area, treatment modality, and demographics including 2070 HNC patients at the ENT clinic between the years 2011 and 2020. It was observed that the number (new diagnoses 2011: 134 vs. 2020: 204) and the average age (2011: 61.5 years vs. 2020: 65.8 years; p < 0.0001) of HNC patients increased over time. In addition, patients tended to travel longer distances (2011: 54.4 km vs. 2020: 64.4 km; p = 0.05). At the same time, the mean number of consultations and treatments per patient per 5-year follow-up interval grew (at initial diagnosis in 2011: 7.8 vs. 2016: 10.4; p = 0.0003), with the proportion of outpatient contacts increasing from 58.9 % to 62.4 % (p = 0.09) from 2011 to 2020. Accordingly, clinical centers are expected to become more important in the care of HNC patients as the healthcare system becomes more specialized, and centralized with a growing outpatient setting. The following consequences for patient care should be considered in restructuring strategies.

Arginase 1 is upregulated at admission in patients with ST-elevation myocardial infarction.

BACKGROUND: The mechanisms underlying rupture of a coronary atherosclerotic plaque and development of myocardial ischemia-reperfusion injury in ST-elevation myocardial infarction (STEMI) remain unresolved. Increased arginase 1 activity leads to reduced nitric oxide (NO) production and increased formation of reactive oxygen species due to uncoupling of the NO-producing enzyme endothelial NO synthase (eNOS). This contributes to endothelial dysfunction, plaque instability and increased susceptibility to ischemia-reperfusion injury in acute myocardial infarction. OBJECTIVE: The purpose of this study was to test the hypothesis that arginase gene and protein expression are upregulated in patients with STEMI. METHODS: Two cohorts of patients with STEMI were included. In the first cohort (n = 51), expression of arginase and NO-synthases as well as arginase 1 protein levels were determined and compared to a healthy control group (n = 45). In a second cohort (n = 68), plasma arginase 1 levels and infarct size were determined using cardiac magnetic resonance imaging. RESULTS: Expression of the gene encoding arginase 1 was significantly elevated at admission and 24-48 h after STEMI but not 3 months post STEMI, in comparison with the control group. Expression of the genes encoding arginase 2 and endothelial NO synthase (NOS3) were unaltered. Arginase 1 protein levels were elevated at admission, 24 h post STEMI and remained elevated for up to 6 months. No significant correlation between plasma arginase 1 protein levels and infarct size was observed. CONCLUSION: The markedly increased gene and protein expression of arginase 1 already at admission indicates a role of arginase 1 in the development of STEMI.

The Full Revasc (Ffr-gUidance for compLete non-cuLprit REVASCularization) Registry-based randomized clinical trial.

BACKGROUND: Complete revascularization in ST elevation myocardial infarction (STEMI) patients with multivessel disease has resulted in reduction in composite clinical endpoints in medium sized trials. Only one trial showed an effect on hard clinical endpoints, but the revascularization procedure was guided by angiographic evaluation of stenosis severity. Consequently, it is not clear how Fractional Flow Reserve (FFR)-guided percutaneous coronary intervention (PCI) affects hard clinical endpoints in STEMI. METHODS AND RESULTS: The Ffr-gUidance for compLete non-cuLprit REVASCularization (FULL REVASC) - is a pragmatic, multicenter, international, registry-based randomized clinical trial designed to evaluate whether a strategy of FFR-guided complete revascularization of non-culprit lesions, reduces the combined primary endpoint of total mortality, non-fatal MI and unplanned revascularization. 1,545 patients were randomized to receive FFR-guided PCI during the index hospitalization or initial conservative management of non-culprit lesions. We found that in angiographically severe non-culprit lesions of 90-99% severity, 1 in 5 of these lesions were re-classified as non-flow limiting by FFR. Considering lesions of intermediate severity (70%-89%), half were re-classified as non-flow limiting by FFR. The study is event driven for an estimated follow-up of at least 2.75 years to detect a 9.9%/year>7.425%/year difference (HR = 0.74 at 80% power (α = .05)) for the combined primary endpoint. CONCLUSION: This large randomized clinical trial is designed and powered to evaluate the effect of complete revascularization with FFR-guided PCI during index hospitalization on total mortality, non-fatal MI and unplanned revascularization following primary PCI in STEMI patients with multivessel disease. Enrollment completed in September 2019 and follow-up is ongoing.

Long-term effect of remote ischemic conditioning on infarct size and clinical outcomes in patients with anterior ST-elevation myocardial infarction.

BACKGROUND: Conflicting evidence exists concerning the cardioprotective efficacy of remote ischemic conditioning as an adjunct to primary percutaneous intervention (PCI) in ST-elevation myocardial infarction (STEMI) and data on long-term outcomes are scarce. We evaluated final infarct size by cardiac magnetic resonance (CMR) performed 6 months after anterior STEMI treated with remote ischemic conditioning and clinical outcomes up to 3 years after the event. METHODS: One hundred and fifteen patients with anterior STEMI were randomized to remote ischemic per-postconditioning (RIperpostC) or sham procedure as adjunct to primary PCI. The primary outcome was myocardial salvage index (MSI) on CMR 6 months after the event. Secondary outcomes were absolute infarct size, left ventricular function, cardiac mortality, major adverse cardiac and cerebrovascular events (MACCE-composite of all-cause mortality, myocardial infarction, readmission for heart failure, ischemic stroke, and target lesion revascularization) and all the individual components of MACCE. RESULTS: There was no difference in MSI or left ventricular function between the RIperpostC and the control group after 6 months. Nor did clinical outcomes at 6 months or 3 years differ between the groups. CONCLUSIONS: RIperpostC as an adjunct to PCI in anterior STEMI did not result in better MSI or left ventricular function 6 months after the event. Furthermore, clinical outcomes at 6 months and 3 years were not altered.

[Primary small cell neuroendocrine carcinoma of the larynx: a review of literature and case series]. / Kleinzelliges neuroendokrines Karzinom des Kopf-Hals-Bereichs: eine Übersichtsarbeit und Fallserie.

INTRODUCTION: Small cell neuroendocrine carcinoma (SCNC) of the larynx is a rare tumor entity with a 5-year overall survival (OS) of only 5 % after treatment with chemoradiotherapy. METHODS: A systematic review of the literature was performed for "SCNC" and "SCNC in head and neck". Our hospital's own electronic patient file database was investigated for patients diagnosed with a SCNC over the last 12 years. RESULTS: The effectiveness of chemoradiotherapy in SCNC is still unclear since randomized clinical trials are missing for the evaluation of standard of care treatment. Common therapy approaches are based on experiences with small cell lung cancer. 0.5 % of all SCNC occur in the head and neck region. In the last 12 years, we diagnosed 9 patients with SCNC, two of which were located in the larynx. Exemplarily, we report the case of a 29-year-old male with the initial diagnosis of a SCNC of the larynx with concurrent lymph node metastasis. This case is particularly interesting due to the young age at disease onset and the lack of major risk factors. Treatment was modified to nivolumab due to progressive disease after treatment with chemoradiotherapy. After an OS of 22 months, the patient deceased due to a tumor-associated major bleeding with airway obstruction. CONCLUSION: So far there are no clinical reports evaluating the use of nivolumab in third-line-therapy of SCNC. NTRK fusion (neurotrophic tyrosine receptor kinase gene fusion) or the folate receptor expression analysis should be considered to evaluate the potential use of a tropomyosin receptor kinase inhibitor or a folate receptor targeting therapy.

Effects Of Endothelin-1 On Intracellular Tetrahydrobiopterin Levels In Vascular Tissue.

OBJECTIVE: Tetrahydrobiopterin (BH4) is the essential cofactor of endothelial nitric oxide synthase (eNOS) and intracellular levels of BH4 is regulated by oxidative stress. The aim of this paper was to describe the influence of exogenous endothelin-1 on intracellular BH4 and its oxidation products dihydrobiopterin (BH2) and biopterin (B) in a wide range of vascular tissue. DESIGN: Segments of internal mammary artery (IMA) and human saphenous vein (SV) from 41 patients undergoing elective surgery were incubated in ET-1 (0.1 µM). Aorta and lung from transgenic mice overexpressing ET-1 in the endothelium (ET-TG) were analysed with regards to intracellular biopterin levels. Human umbilical vein endothelial cells (HUVEC) were incubated in ET-1 (0.1 µM) and intracellular biopterin levels were analysed. From 6 healthy women undergoing caesarean section, subcutaneous fat was harvested and the resistance arteries in these biopsies were tested for ET-mediated endothelial dysfunction. RESULTS: In HUVEC, exogenous ET-1 (0.1 µM) did not significantly change intracellular BH4, 1.54 ± 1.7 vs 1.68 ± 1.8 pmol/mg protein; p = .8. In IMA and SV, exogenous ET-1(0.1 µM) did not change intracellular BH4 n = 10, p = .4. In aorta from wild type vs ET-TG mice there was no significant difference in intracellular BH4 between the groups: 1.3 ± 0.49 vs 1.23 ± 0.3 pmol/mg protein; p = .6. In resistance arteries (n = 6) BH4 together with DTE (an antioxidant) was not able to prevent ET-mediated endothelial dysfunction. CONCLUSION: ET-1 did not significantly alter intracellular tetrahydrobiopterin levels in IMA, SV, HUVEC or aorta from ET-TG mice. These findings are important for future research in ET-1 mediated superoxide production and endothelial dysfunction.

Sgarbossa criteria used to identify cardiac ischemia in patient with ventricular paced rhythm.

There is a paucity of research on how the Sgarbossa criteria perform in patients with ventricular pacing. However, the limited research that exists suggests that the criteria are specific, but not sensitive, for myocardial ischemia in this population. We present the case of a 73-year-old man who presented to the ED with acute chest pain. His previous medical history was significant for hypertension and a pacemaker due to type 2 s-degree AV block. His initial ECG fulfilled all three Sgarbossa criteria and subsequent coronary angiography identified a culprit lesion in the posterior descending artery. In this case, awareness of the Sgarbossa criteria's applicability in patients with ventricular paced rhythm facilitated earlier identification of ischemia and subsequent intervention.

Effect of remote ischemic conditioning on infarct size in patients with anterior ST-elevation myocardial infarction.

BACKGROUND: Previous studies indicate that remote ischemic conditioning performed before percutaneous coronary intervention (PCI) reduces infarct size in patients with ST-elevation myocardial infarction (STEMI). It remains unclear whether remote conditioning affords protection when performed in adjunct to primary PCI. We aimed to study whether remote ischemic per-postconditioning (RIperpostC) initiated after admission to the catheterization laboratory attenuates myocardial infarct size in patients with anterior STEMI. METHODS: In this prospective multicenter trial 93 patients with anterior STEMI were randomized to RIperpostC or sham procedure as adjunct to primary PCI. RIperpostC was started on arrival in the catheterization laboratory by 5-minute cycles of inflation and deflation of a blood pressure cuff around the left thigh and continued throughout the PCI procedure. Infarct size and myocardium at risk were determined by cardiac magnetic resonance at day 4 to 7. The primary outcome was myocardial salvage index. RESULTS: There was no significant difference in myocardial salvage index between the RIperpostC and control group (median 48.5% and interquartile range 30.9%-60.8% vs 49.2% [42.1%-58.8%]). Neither did absolute infarct size in relation to left ventricular myocardial volume differ significantly (RIperpostC 20.6% [14.1%-31.7%] vs control 17.9% [13.4%-25.0%]). The RIperpostC group had larger myocardial area at risk than the control group (43.1% (35.4%-49.7%) vs 37.0% (30.8%-44.1%) of the left ventricle, P=.03). Peak value and area under the curve for troponin T did not differ significantly between the study groups. CONCLUSIONS: RIperpostC initiated after admission to the catheterization laboratory in patients with anterior STEMI did not confer protection against reperfusion injury.

Implementation of an extracorporeal resuscitation (ECPR) program for out-of-hospital cardiac arrest in Stockholm, Sweden: Feasibility, safety, and outcome.

Background: The aim of this study was to evaluate the implementation of a novel extra corporeal cardiopulmonary (ECPR) program in the greater Stockholm area with focus on feasibility, safety aspects and clinical outcomes. Methods: Prospective observational study of ECPR program including patients with OHCA from January 2020 to December 2022, fulfilling ECPR criteria: age 18-65 years, initial shockable rhythm or pulseless electrical activity, witnessed arrest, bystander cardiopulmonary resuscitation and refractory arrest after three cycles of advance cardiac life support. The predefined time threshold from collapse to extracorporeal membrane oxygenation (ECMO) initiation was set at 60 min. Results: We included 95 patients. Of these, 22/95 (23%) had return of spontaneous circulation before ECMO initiation, 39/95 (41%) were excluded for ECMO and 34/95 (36%) had ECMO initiated out of which 23 patients were admitted alive to the ICU. ECMO-initiation within 60 min was met in 9%. In 6 patients vascular access was complicated, 2 patients had severe bleeding at access site requiring intervention. Survival to discharge among all cases was 25% (24/95). Among patients admitted to ICU on ECMO 39% (9/23) survived to discharge, of these 78% had cerebral performance category scale score 1-2 within 12 months. 8 out of 9 survivors had time from OHCA to ECMO-initiation >60 min. Conclusion: The implementation of an ECPR protocol was feasible without any major, unexpected safety aspects but did not meet the intended target time intervals. Despite this, survival rates were similar to previous studies although most survivors had >60 min to ECMO-initiation.

Arginase inhibition improves endothelial function in patients with coronary artery disease and type 2 diabetes mellitus.

BACKGROUND: Endothelial dysfunction plays an important role in the early development of atherosclerosis and vascular complications in type 2 diabetes mellitus. Increased expression and activity of arginase, metabolizing the nitric oxide substrate l-arginine, may result in reduced production of nitric oxide and thereby endothelial dysfunction. We hypothesized that inhibition of arginase activity improves endothelial function in patients with coronary artery disease (CAD) and type 2 diabetes mellitus. METHODS AND RESULTS: Three groups of subjects were included: 16 patients with CAD, 16 patients with CAD and type 2 diabetes mellitus (CAD+Diabetes), and 16 age-matched healthy control subjects. Forearm endothelium-dependent and endothelium-independent vasodilatation were assessed with venous occlusion plethysmography before and during intra-arterial infusion of the arginase inhibitor N(ω)-hydroxy-nor-l-arginine (nor-NOHA; 0.1 mg/min). Nor-NOHA was also coinfused with the nitric oxide synthase inhibitor (N(G)-monomethyl L-arginine). The expression of arginase was determined in the internal mammary artery of patients undergoing bypass surgery. Nor-NOHA markedly increased endothelium-dependent vasodilatation (up to 2-fold) in patients with CAD+Diabetes and CAD (P<0.001) but not in the control group. N(G)-monomethyl L-arginine completely inhibited the increase in endothelium-dependent vasodilatation induced by nor-NOHA. Endothelium-independent vasodilatation was slightly improved by nor-NOHA in the CAD+Diabetes group. Arginase I was expressed in vascular smooth muscle cells and endothelial cells, and arginase II was expressed in endothelial cells of patients with and without diabetes mellitus. CONCLUSIONS: Arginase inhibition markedly improves endothelial function in patients with CAD and type 2 diabetes mellitus suggesting that increased arginase activity is a key factor in the development of endothelial dysfunction.

A novel 3D-printed laryngoscope with integrated working channels for laryngeal surgery.

Background: For the surgical treatment of early-stage laryngeal cancer, the use of transoral laser microsurgery (TLM) has emerged as the gold standard. However, this procedure requires a straight line of sight to the operating field. Therefore, the patient's neck needs to be brought into a hyperextended position. In a considerable number of patients, this is not possible due to anomalies in the cervical spine anatomy or soft tissue scarring, e.g., after radiation. In these cases, adequate visualization of relevant laryngeal structures cannot be ensured using a conventional rigid operating laryngoscope, which may negatively affect the outcome of these patients. Methods: We present a system based on a 3D-printed prototype of a curved laryngoscope with three integrated working channels (sMAC). The curved profile of the sMAC-laryngoscope is specifically adapted to the nonlinear anatomy of the upper airway structures. The central working channel provides access for flexible video endoscope imaging of the operating field while the two remaining channels provide access for flexible instrumentation. In a user study (n = 11), visualization and reachability of relevant laryngeal landmarks as well as the feasibility of basic surgical procedures with the proposed system were examined in a patient simulator. In a second setup, the system was evaluated for its applicability in a human body donor. Results: All participants of the user study were able to visualize, reach and manipulate the relevant laryngeal landmarks. Reaching those took significantly less time in the second attempt compared to the first one (27.5 s ± 5.2 s vs. 39.7 s ± 16.5 s, p = 0.008) indicating a significant learning curve for handling the system. Instrument changes were performed quickly and reliably by all participants (10.9 s ± 1.7 s). All participants were able to bring the bimanual instruments into position for a vocal fold incision. Relevant laryngeal landmarks could be visualized and reached in the human body donor setup. Conclusion: Possibly, the proposed system may develop into an alternative treatment option for patients with early-stage laryngeal cancer and restricted mobility of the cervical spine in the future. Further improvements of the system could include finer end effectors and a flexible instrument with a laser cutting tool.

[Value of PET imaging in head and neck cancer]. / Stellenwert der PET-Bildgebung bei Kopf-Hals-Tumoren.

The combination of positron-emission tomography (PET) with cross-sectional imaging in particular is becoming increasingly important in the diagnosis of head and neck tumors because, in addition to pure anatomy, the metabolic activity of tissue can be visualized and assessed. The combination of PET and computed tomography (CT) is already an established procedure in head and neck tumor patients in some indications, e.g., for primary tumor detection in cancer of unknown primary (CUP) syndrome or also after completed primary radio(chemo)therapy for evaluation of response, especially also with regard to nodal status. In some cases, salvage neck dissection can thus be avoided in the case of PET-negative findings. In the context of primary diagnosis, PET/CT imaging can be used primarily to evaluate distant metastasis. According to current guidelines, PET-based imaging is not (yet) of value in determining the local extent at initial diagnosis. A challenge is the still limited reimbursement by health insurance companies, which currently allow only certain indications, and the still lack of nationwide coverage.