Fecal calprotectin and platelet count predict histologic disease activity in pediatric ulcerative colitis: results from a projection-predictive feature selection.

Especially for pediatric patients, proxies of mucosal inflammation are needed. The Pediatric Ulcerative Colitis Activity Index (PUCAI) has been established to predict clinical and endoscopic disease activity. However, histologic inflammation might persist. We applied a special variable selection technique to predict histologic healing in pediatric ulcerative colitis (UC) as parsimoniously (but still as precisely) as possible. The retrospective analysis included data from two study cohorts, comprising 91 visits from 59 pediatric patients with UC. A Bayesian ordinal regression model was used in combination with a projection-predictive feature selection (PPFS) to identify a minimal subset of clinical and laboratory parameters sufficient for the prediction of histologic disease activity. Following the PPFS, CEDATA-GPGE patient registry data were analyzed to investigate the relevance of the selected predictors in relation to PUCAI and Physician Global Assessment (PGA) in up to 6697 patient visits. Fecal calprotectin (FC) and platelet count were identified as the minimal subset of predictors sufficient for prediction of histologic disease activity in pediatric UC. FC and platelet count also appeared to be associated with increasing disease activity as measured by PUCAI and PGA in the CEDATA-GPGE registry. Based on the selected model, predictions can be performed with a Shiny web app.  Conclusion: Our statistical approach constitutes a reproducible and objective tool to select a minimal subset of the most informative parameters to predict histologic inflammation in pediatric UC. A Shiny app shows how physicians may predict the histologic activity in a user-friendly way using FC and platelet count. To generalize the findings, further prospective studies will be needed. What is Known: • Histologic healing is a major endpoint in the therapy of ulcerative colitis (UC). • The PUCAI score has been established to predict disease activity in pediatric UC but is not suitable for the prediction of histologic healing. What is New: • Our Bayesian ordinal regression model in combination with a projection-predictive feature selection is a reproducible and objective tool to select the minimal subset of clinical and laboratory parameters to predict histologic inflammation in pediatric UC. • Histologic inflammation in pediatric UC can be non-invasively predicted based on the combination of fecal calprotectin levels and platelet count.

Usability and preliminary effectiveness of an app-based physical activity and education program for people with hip or knee osteoarthritis - a pilot randomized controlled trial.

BACKGROUND: Hip and knee osteoarthritis (OA) are highly prevalent worldwide. The guidelines recommend physical activity and education as the core treatments for osteoarthritis. Digital health has the potential to engage people in physical activity and disease management. Therefore, we conducted a pilot trial to assess the usability and preliminary effectiveness of an app-based physical activity and education program (Join2Move) compared to usual care for people with hip and/or knee OA in Germany. METHODS: A randomized controlled pilot study was conducted. Individuals with diagnosed or self-reported knee and hip OA were included. Allocation to the intervention or control group was randomized. The intervention group received the Join2Move program. The Join2Move program was previously developed as a website and evaluated in the Netherlands. For the current study, the program was translated and adapted to the German context and adjusted from a website to an app. The control group received usual care. The primary outcomes were usability and preliminary effectiveness (pain and physical functioning). Measurements were taken at baseline and at twelve weeks. The data analysis was performed using SPSS (IBM SPSS Statistics 29.0). RESULTS: Sixty participants, with a mean age of 61.9 (SD ± 7.2) years, were allocated to the intervention (n = 32) or the control group (n = 28) and included in the analysis. The majority of participants had knee OA (68%), and 12% had hip and knee OA. The dropout rate was n = 11 (18%). No adverse events were reported. Usability was rated as acceptable (mean System Usability Scale = 71.3/100) with a wide range (32.5 to 100). Statistically significant between-group differences were found only for pain (mean difference 8.52 (95% CI 1.01 to 16.04), p = 0.027). CONCLUSIONS: Join2Move demonstrated acceptable usability. The preliminary results of the pilot trial indicate the potential of a stand-alone app for the treatment of patients with hip or knee OA. However, the acceptable usability of Join2Move limits its recommendation for everyone. There appears to be room for improvement in app usability and in identifying patients for whom the app is suitable and the right time to use a stand-alone app. TRIAL REGISTRATION: German Clinical Trials Register DRKS00027164 .

Left prefrontal intermittent theta burst stimulation ameliorates tinnitus distress and symptoms of depression - A feasibility study.

Tinnitus remains a notoriously difficult to treat clinical entity. 1-2% of the entire population report relevant emotional distress due to tinnitus, and causal treatments are lacking. Repetitive transcranial magnetic stimulation (rTMS), most commonly of auditory cortical areas, has shown mixed results in the past. Prefrontal rTMS, including intermittent theta burst stimulation (iTBS) has shown more promising results in the treatment of depression, and clinical data suggests a meaningful overlap between tinnitus and depression. Therefore, we performed a feasibility study of 28 consecutive patients with tinnitus treated with an iTBS protocol over the left dorsolateral prefrontal cortex for three weeks. After treatment, we observed significant ameliorations of tinnitus distress as measured by the Tinnitus Handicap Inventory Questionnaire (THI), the Tinnitus Functional Index (TFI), the Mini-Tinnitus Questionnaire (Mini-TQ) and also of depression as measured by the Major Depression Inventory (MDI). Effect sizes were small to moderate and short-lived. Treatment response rates, defined as improvement of the THI of at least 7 points, were 35.7%. At follow-up twelve weeks after end of treatment, severity of tinnitus and depression returned to approximately baseline level on a descriptive level. Amelioration of depressive symptoms correlated only with TFI change, but not that of other measures of tinnitus distress. The data suggest that a prefrontal iTBS protocol might be applied in the treatment of tinnitus and open avenues for future neurostimulatory treatments other than those of auditory regions.

Manifestation of acute appendicitis as known but paradox visceral side effect of ulcerative colitis anti-inflammatory therapy with januskinase-inhibitor Tofacitinib (Xeljanz™).

BACKGROUND: The etiopathogenesis of accompanying inflammatory phenomena and consequences of immunomodulation constitute a challenging and innovative field in the medical treatment of patients with autoimmune diseases. AIM: Based on i) clinical management experience gained from this challenging clinical case and ii) selective references of reports published in the scientific medical literature, we present an unusual counterfactual scientific case report. A patient diagnosed with ulcerative colitis undergoing januskinase (JAK)-inhibitor therapy developed acuteappendicitis as an unusual complication or as a visceral side effect of immunosuppressive/anti-inflammatory therapy. METHOD: Scientific case report. RESULTS: (case description): Medical history: A 52-year-old male presented with spasmodic pain in the right lower abdomen lasting for two days (no fever, no bowel movement changes (no stool irregularities), no vomiting). MEDICATION USED TO DATE: Steroid-resistant ulcerative colitis treated with immunosuppressive therapy (Adalimumab administered for 10 months [next generation anti-TNFα mAb], Vendolizumab for 9 months [α4ß7 integrin antagonist], Tofacitinib for 6 months); fructose intolerance, no previous abdominal surgery; medication: XeljanzTM (Tofacitinib, 5 mg 2x1; JAK-inhibitor; PFIZER PHARMA GmbH, Berlin,Germany); MutaflorTM (1x1; Ardeypharm GmbH, Herdecke, Germany). CLINICAL FINDINGS: Pressure pain in the right lower abdomen with local muscular defense (Mc-Burney's/Lanz's point positive), no peritonism, Psoas-muscle sign positive. DIAGNOSTIC MEASURES: Laboratory parameters: standard value of white blood cell count, CrP: 25 mg/l.-Transabdominal ultrasound revealed hypertrophic 'appendix vermiformis' with detectable target-phenomenon and surrounding fluid. DECISION-MAKING: Indication for laparoscopic exploration. THERAPY: Under perioperative single-shot antibiotic administration with UnacidTM, the patient underwent emergency laparoscopic appendectomy due to confirmed acute appendicitis with additional lavage and placement of local drainage. CLINICAL COURSE: The postoperative phase was uneventful (sufficient analgetic therapy, removal of local drainage on the 2nd postoperative day). The patient was discharged four days after surgery. Histopathology confirmed ulcero-phlegmonous, acute purulent appendicitis with fibrinous purulent mesenteriolitis. FURTHER MEASURES: Immunosuppressive therapy was continued. CONCLUSION: Based on the paradoxon of an acute inflammatory disease (acute appendicitis) seen in the case of a patient undergoing immunosuppressive/anti-inflammatory treatment using a JAK-Inhibitor for ulcerative colitis, we consider this case worthy of publication although this side effect has previously been described in patients with rheumatoid arthritis. This might be the manifestation of i) an immunomodulatory effect that reduced or at least altered mucosal defense, including an increased risk of opportunistic infections, presenting as a specific visceral 'side effect' of the JAK-Inhibitor and/or as a consequence; ii) an induced alternative inflammatory mechanism/proinflammatory signal transduction and - theoretically - an intestinal drainage defect in the segment of right colic artery with consecutive collection of necrotic cells and activation of inflammatory mediators.

Treatment of depression and borderline personality disorder with 1 Hz repetitive transcranial magnetic stimulation of the orbitofrontal cortex - A pilot study.

Borderline personality disorder (BPD) is characterised by impairments in emotional regulation, impulse control and interpersonal interaction. Comorbid depression is common. The orbitofrontal cortex (OFC) plays a crucial role in the biological substrate of BPD. We investigated the effects of 1 Hz repetitive transcranial magnetic stimulation (rTMS) targeting the OFC on depressive symptoms and symptoms of BPD in 15 patients suffering from both conditions to assess feasibility and effectiveness. Target treatment intensity was 120% of resting motor threshold (RMT) and intended duration four weeks. Treatment improved both symptoms of depression as measured by the Hamilton Depression Rating Scale and of BPD as measured by Borderline Symptom List-23 and Barratt Impulsivity Scale. Drop-out rates were high with 7/15 patients not completing the full course of rTMS, but only two drop-outs were related to treatment. Only a minority of patients tolerated target treatment intensity. Despite the limitations, the results suggest efficacy of treatment and welcome further research.

[Hemithyroidectomy or total thyroidectomy for low-risk papillary thyroid cancer? : Surgical criteria for primary and secondary choice of treatment in an interdisciplinary treatment concept]. / Hemithyreoidektomie oder totale Thyreoidektomie beim papillären Niedrigrisikokarzinom der Schilddrüse? : Chirurgische Kriterien der primären und sekundären Therapiewahl im interdisziplinären Behandlungskonzept.

The increase in small intrathyroid papillary thyroid cancer (PTC) observed worldwide over the past two decades, with no increase in cancer-specific mortality, has challenged the previous concept of total thyroidectomy as a one-size-fits-all panacea. After exclusion of papillary microcarcinomas, a systematic review of 20 clinical studies published since 2002, which compared hemithyroidectomy (HT) to total thyroidectomy (TT), found comparable long-term oncological outcomes for low-risk papillary thyroid cancer (LRPTC) 1-4 cm in diameter, whereas postoperative complication rates were markedly lower for HT. To refine individual treatment plans, HT should be combined with ipsilateral central lymph node dissection and intraoperative frozen section analysis for staging. Based on recent evidence from studies and in consideration of individual risk factors, patients with LRPTC can be offered the concept of HT as an alternative to the standard TT. A prerequisite for the treatment selection and decision is a comprehensive patient clarification of the possible advantages and disadvantages of both approaches.

[Repeated drenching of calves - -Ultra-sonographic findings of the -reticulum and abomasum and -short-term -effects on pH and -D-lactate in rumen fluid and blood]. / Wiederholtes Drenchen von Kälbern ­ Ultraschallbefunde an Haube und Labmagen sowie kurzfristige Auswirkungen auf pH-Wert und D-Laktat in Pansensaft und Blut.

INTRODUCTION: An oesophageal tube feeder was used to administer milk to six clinically healthy calves every 12 hours for a total of three feedings. The calves were seven to nine days of age, and each feeding consisted of a volume of milk that was 6 % of the body weight of the calves. The reticulum and abomasum were scanned ultrasonographically before, during and after drenching. Blood samples for D-lactate determination and venous blood gas analysis were collected at -12, 0 (first drenching), 6, 12 (second drenching), 18, 24 (third drenching), 30 and 36 hours. Ruminal fluid was collected for measurement of pH and D-lactate concentration at -12 and 36 hours. Based on simultaneous ultrasonographic examinations of the reticulum and abomasum, some of the force-fed milk flowed into the reticulum and some directly into the abomasum; both organs contained milk immediately after drenching. Drenching led to ruminal acidosis evidenced by a significant decrease in median pH from 7,0 (6,0 - 7,0) to 4,5 (3,0 - 5,0) and a 93-fold increase in median D-lactate concentration from 0,39 (0,14 - 1,33) to 36,3 (17,9 - 53,3) mmol/l but it did not cause metabolic acidosis. Based on these findings, we concluded that milk administered to calves via an oesophageal tube feeder flows into the reticulum and abomasum simultaneously and three force feedings 12 hours apart cause acute ruminal acidosis, which was not accompanied by metabolic acidosis in the short term.

INTRODUCTION: Une sonde d'alimentation œsophagienne a été utilisée pour administrer par trois fois du lait à six veaux cliniquement sains toutes les 12 heures. Les veaux étaient âgés de sept à neuf jours, et chaque repas comprenait un volume de lait correspondant à 6 % de leur poids corporel. Le réticulum et la caillette ont été examinés par ultrasons avant, pendant et après le drenchage. Des échantillons de sang pour la détermination du D-lactate et pour l'analyse des gaz du sang veineux ont été prélevés à ­12, 0 (premier drenchage), 6, 12 (deuxième drenchage), 18, 24 (troisième drenchage), 30 et 36 heures. Le jus de panse a été prélevé pour mesurer le pH et la concentration de D-lactate à ­12 et 36 heures. D'après les examens ultrasonographiques simultanés du réticulum et de la caillette, une partie du lait administré s'est écoulée dans le réticulum et une autre directement dans la caillette : les deux organes contenaient du lait immédiatement après le drenchage. Le drenchage a entraîné une acidose ruminale mise en évidence par une diminution significative du pH médian de 7,0 (6,0 ­ 7,0) à 4,5 (3,0 ­ 5,0) et une concentration médiane de D-lactate 93 fois plus élevée de 0,39 (0,14 ­ 1,33) à 36,3 (17,9 ­ 53,3) mmol/l, mais il n'a pas provoqué d'acidose métabolique. Sur la base de ces résultats, nous avons conclu que le lait administré aux veaux par l'intermédiaire d'une sonde d'alimentation œsophagienne s'écoule simultanément dans le réticulum et la caillette et que trois gavages à 12 heures d'intervalle provoquent une acidose ruminale aiguë qui ne s'est pas accompagnée d'une acidose métabolique à court terme.

Rationale and study design of a randomized, placebo-controlled, double-blind phase 2b trial to evaluate efficacy, safety, and tolerability of an oral glutaminyl cyclase inhibitor varoglutamstat (PQ912) in study participants with MCI and mild AD-VIVIAD.

BACKGROUND: Varoglutamstat (formerly PQ912) is a small molecule that inhibits the activity of the glutaminyl cyclase to reduce the level of pyroglutamate-A-beta (pGluAB42). Recent studies confirm that pGluAB42 is a particular amyloid form that is highly synaptotoxic and plays a significant role in the development of AD. METHODS: This paper describes the design and methodology behind the phase 2b VIVIAD-trial in AD. The aim of this study is to evaluate varoglutamstat in a state-of-the-art designed, placebo-controlled, double-blind, randomized clinical trial for safety and tolerability, efficacy on cognition, and effects on brain activity and AD biomarkers. In addition to its main purpose, the trial will explore potential associations between novel and established biomarkers and their individual and composite relation to disease characteristics. RESULTS: To be expected early 2023 CONCLUSION: This state of the art phase 2b study will yield important results for the field with respect to trial methodology and for the treatment of AD with a small molecule directed against pyroglutamate-A-beta. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04498650.

Management of primary and renal hyperparathyroidism: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: The purpose of this review is to provide updated recommendations for the surgical management of primary (pHPT) and renal (rHPT) hyperparathyroidism, formulating a new guideline of the German Association of Endocrine Surgeons (CAEK). METHODS: Evidence-based recommendations for the diagnosis and therapy of pHPT and rHPT were assessed by a multidisciplinary panel using PubMed for a comprehensive literature search together with a structured consensus dialogue (S2k guideline of the Association of the German Scientific Medical Societies, AWMF). RESULTS: During the last 20 years, a variety of new preoperative localization procedures, such as sestamibi-SPECT, 4D-CT, and various PET/CT procedures, were established for pHPT. High-resolution imaging, together with intraoperative parathyroid hormone (IOPTH) measurement, enabled focused or minimally invasive surgery to become the most favored surgical technique. Patients with pHPT and nonlocalizing imaging have a higher risk of multiglandular disease. Surgical therapy provides very high cure rates, with a clear relation to the surgeon's experience in parathyroid procedures. Reoperative parathyroidectomy, children with pHPT or familial forms, and parathyroid carcinoma are addressed and require special surgical expertise. A multidisciplinary team of experienced nephrologists, transplant, and endocrine surgeons should assess the diagnosis and treatment of renal HPT. CONCLUSION: Surgery is the only curative treatment for pHPT and should be considered for all patients with pHPT. For rHPT, a more selective approach is required, and parathyroidectomy is indicated only when conservative treatment options fail. In parathyroid carcinoma, the adequacy of local resection influences local disease control.

Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles in regenerative endodontics.

Regenerative endodontic procedures are an alternative to conventional root-canal treatment and apexification. There are two different tissue engineering approaches that are currently followed, both aiming at the colonisation of the cleaned pulp space by pluripotent cells and subsequent pulp regeneration. Firstly, the transplantation of mesenchymal stem cells (MSCs), and secondly a cell-free strategy that relies on bioactive molecules to trigger the recruitment of the patient's own cells. The first approach is hampered by costs and regulatory issues. Despite great initial enthusiasm with a clinically used cell-free approach that relies on induced bleeding into the pulp space, results have been revealed to be rather unpredictable, and mere repair rather than regeneration of the pulp-dentin complex is what is typically achieved. Moreover, the extent of further root development is variable, and the concept is limited to immature teeth. This article discusses a third possible way of regenerative endodontics that involves the application of MSC-derived exosomes. These are extracellular vesicles that contain proteins, lipids, and nucleic acids, reflecting the secretome of MSCs. Based on the first in vitro and in vivo studies, exosomes appear to be a potent tool to improve pulp regeneration. This narrative review aims to investigate the therapeutic use of human MSCs or dental pulp-derived exosomes in regenerative endodontics. Furthermore, the focus of this review is on targeting important questions that should be investigated in future in-vivo and clinical studies, such as the choice of scaffold material for exosome delivery into the pulp space.

DLL3 (delta-like protein 3) expression correlates with stromal desmoplasia and lymph node metastases in medullary thyroid carcinomas.

Medullary thyroid carcinomas (MTC) are rare and aggressive neuroendocrine tumors of the thyroid. About 70% of MTC are sporadic; approximately 50% of those harbor somatic RET mutation. DLL3 is widely expressed in many neuroendocrine tumors and has been evaluated as a potential therapeutic target. Since stromal desmoplasia in sporadic MTC has been identified as a reliable predictor of aggressive behavior and development of lymph node metastases, a possible correlation of DLL3 expression with the presence of stromal desmoplasia was of particular interest. 59 paraffin-embedded samples of sporadic MTC with (44 cases) and without (15 cases) stromal desmoplasia and known lymph node status were included. DLL3 expression was determined by immunohistochemistry; no expression (0%), low expression (1-49%) and high expression (≥50%) were correlated with clinicopathological data. The proportion of DLL3 positivity was significantly correlated with both stromal desmoplasia (P < 0.0001) and lymph node metastases (P < 0.0001). MTC without stromal desmoplasia consistently lack DLL3 expression. This is the first study to focus on MTC regarding DLL3 expression and the relationship to various factors. Our results demonstrate that expression of DLL3 in MTC represents a reliable surrogate marker for stromal desmoplasia and lymph node metastases and might be an indicator for aggressive clinical behavior. DLL3 expression in ≥50% of tumor cells virtually excludes MTC without stromal desmoplasia. DLL3 was discussed as a potential therapeutic target in malignant tumors of other locations with positive immunohistochemical reaction and might therefore be a new therapeutic option in MTC, as well.

Dominant In-Plane Symmetric Elastoresistance in CsFe_{2}As_{2}.

We study the elastoresistance of the highly correlated material CsFe_{2}As_{2} in all symmetry channels. Neutralizing its thermal expansion by means of a piezoelectric-based strain cell is demonstrated to be essential. The elastoresistance response in the in-plane symmetric channel is found to be large, while the response in the symmetry-breaking channels is weaker and provides no evidence for a divergent nematic susceptibility. Rather, our results can be interpreted naturally within the framework of a coherence-incoherence crossover, where the low-temperature coherent state is sensitively tuned by the in-plane atomic distances.

Detection of antibodies against tick-borne encephalitis flaviviruses in breeding and sport horses from Spain.

Tick-borne encephalitis virus (TBEV) and louping-ill virus (LIV) are two closely related zoonotic flaviviruses leading to neurological diseases and belonging to the tick-borne encephalitis (TBE) serocomplex. Both viruses are transmitted by the same ixodid tick vector, Ixodes ricinus. Due to global warming affecting vector biology and pathogen transmission, the viruses pose an emerging threat for public health in Europe and Asia. These flaviviruses share some hosts, like sheep, goats and humans, although the main hosts for LIV and TBEV are sheep and small rodents, respectively. Whereas LIV has been detected in Spanish sheep and goat herds, circulating antibodies against TBEV have only been reported in dogs and horses from particular regions in this country. The limited available information about the prevalence of these viruses in Spain led us to investigate the serological evidence of TBE flaviviruses in horses from Spain. Serum neutralization tests (SNT) were performed using sera from 495 breeding and sport horses collected during two periods (2011-2013 and 2015-2016). A seroprevalence of 3.1 % (95 % CI 1.5-4.6) was found and cross-reactivity with West Nile virus was excluded in the positive samples. Sport horses showed a significantly higher TBE serocomplex seropositivity compared to breeding horses. An increased seroprevalence was observed in the second sampling period (2015-2016). Our results demonstrate for the first time the presence of antibodies against TBE flaviviruses in horses residing in mainland Spain; further epidemiological surveys are necessary in order to understand and monitor the active transmission of TBE flaviviruses in this country and rule out the presence of other flaviviruses co-circulating in Spain.

[Completion thyroidectomy after less than total resection for postoperatively diagnosed follicular thyroid cancer]. / Komplettierungsoperation nach nichttotaler Thyreoidektomie beim postoperativ diagnostizierten follikulären Schilddrüsenkarzinom.

As there are no reliable preoperative or intraoperative markers to identify follicular thyroid cancer (FTC), the postoperative histopathological diagnosis frequently raises the question of completion surgery. The oncological necessity must not be questioned by an allegedly increased morbidity. The operation is particularly indicated if there is evidence of distant or lymph node metastasis, the presence of a broadly invasive FTC, or evidence of extensive angioinvasion. Prophylactic lymphadenectomy is not indicated. There are no clear data that minimally invasive oncocytic FTC poses a special risk. Risk factors such as tumor size and age must be assessed as a biological continuum and require an individual assessment. Utilizing the technical options and thorough planning enables a completion thyroidectomy to be performed without increased risk.

Nematic Correlation Length in Iron-Based Superconductors Probed by Inelastic X-Ray Scattering.

Nematicity is ubiquitous in electronic phases of high-T_{c} superconductors, particularly in the Fe-based systems. We used inelastic x-ray scattering to extract the temperature-dependent nematic correlation length ξ from the anomalous softening of acoustic phonon modes in FeSe, underdoped Ba(Fe_{0.97}Co_{0.03})_{2}As_{2}, and optimally doped Ba(Fe_{0.94}Co_{0.06})_{2}As_{2}. In all cases, we find that ξ is well described by a power law (T-T_{0})^{-1/2} extending over a wide temperature range. Combined with the previously reported Curie-Weiss behavior of the nematic susceptibility, these results point to the mean-field character of the nematic transition, which we attribute to a sizable nematoelastic coupling that is likely detrimental to superconductivity.

[Possibilities and limitations of palliative surgery in head and neck cancer patients]. / Möglichkeiten und Grenzen der Palliativchirurgie im Kopf-Hals-Bereich.

BACKGROUND: Incurable head and neck cancer causes distressing symptoms that significantly reduce patients' quality of life. OBJECTIVE: The aim of this article is to present the surgical possibilities and their limitations in a palliative setting. MATERIALS AND METHODS: A literature review was performed and supplemented with the authors' own experiences. RESULTS: Smaller endoscopic procedures for tumor debulking or hemostasis are possible to reduce symptoms and improving quality of life, which should be the aim of palliative care. To preserve swallowing function and breathing, the insertion of stents is a feasible alternative to tracheotomy. However, even larger tumor resections with reconstruction by pedicled or free grafts may be justified. CONCLUSION: Especially in the palliative setting, patients and their individual complaints are the primary focus. Therefore, the indications for surgery should be discussed with the patient and his relatives, preferentially interdisciplinarily. Due to considerable progress, particularly in the field of systemic tumor therapy, extended surgical procedures with reconstruction are losing some of their importance in the palliative situation.

Similar inductive effects of enamel and dentin matrix derivatives on osteoblast-like cell response over SLA titanium surface.

OBJECTIVES: The aim of this in vitro study was to investigate the behavior of osteoblasts on titanium discs under different concentrations of enamel matrix derivatives (EMD) and dentin matrix derivative (DMD). MATERIALS AND METHODS: MC3T3-E1 osteoblast-like cells were cultivated on coated titanium SLA discs with EMD or DMD at 100 µg/ml, 1 mg/ml, 10 mg/ml and 30 mg/ml or left uncoated. Cell viability, proliferation, adhesion and migration were assessed respectively with MTT, BrdU, DAPI and scratch wound healing assays. Messenger ribonucleic acid of different genes related to osteoblastic differentiation was quantified by means of real-time quantitative PCR. Data were analyzed using student t-test for adhesion and migration assay and ANOVA for proliferation assay (p < 0.05). RESULTS: BrdU incorporation was found in proliferative osteoblasts for both test solutions at all concentrations. Osteoblast migrated and covered approximately 70% of the wound area observed at time zero when exposed to EMD and DMD to all concentrations. The increase of gene expression was dependent on the concentration enhancement of EMD and DMD. Higher concentrations showed proliferation augmentation if compared to lower concentrations. CONCLUSIONS: Roughness surface of Ti SLA can limit cell adhesion independent of the presence EMD or DMD. DMD enhances cell migration of osteoblasts on SLA titanium implants in a concentration-dependent manner.

[Pheochromocytomatosis after adrenalectomy: metastasis or cell seeding?] / Phäochromozytomatose nach Adrenalektomie: Metastasierung oder Zellverschleppung?

Pheochromocytomatosis is defined as a multifocal cell dissemination limited to the operatively opened space with no signs of distant metastasis. After primary adrenalectomy due to a pheochromocytoma this is a rare and underrecognized manifestation of a tumor recurrence. Between 2010 and 2019 a total of 5 patients with the presentation of pheochromocytomatosis were treated in this center. Clinical and survival data were compared to 12 patients with a metastasized pheochromocytoma. Patients presenting with pheochromocytomatosis showed a better but not significant overall survival (136.8 vs. 107 months). Furthermore, patients with pheochromocytomatosis presented more often with a noradrenaline secretion type. Tumor recurrence in the pheochromocytomatosis group occurred on average 69.2 months after the initial diagnosis and was therefore much later than in patients with distant metastases from a pheochromocytoma (39 months, p = 0.13). This article outlines this special manifestation of recurrence of a pheochromocytoma based on this patient collective. Besides technical operative aspects there appears to be evidence for tumor-specific factors that promote the development of pheochromocytomatosis. Importantly, it seems that all patients with a pheochromocytoma should receive lifelong aftercare and that patients should be closely monitored during the first 5 years after surgery.