The Influence of Patient Exposure to Breast Reconstruction Approaches and Education on Patient Choices in Breast Cancer Treatment.

BackgroundThe landscape of surgical and medical management and patient choices for breast cancer treatment changes as breast reconstruction and oncoplastic approaches improve and diversify. Increased access to breast reconstruction, in addition to patient education, influences the breast cancer patient. Therefore, the examination of the possible impact of reconstructive surgery on all stages of the breast cancer management per se seemed timely.MethodsPlastic surgery consults were arranged for 520 new patients diagnosed with breast cancer (2012-2016) including patients with noninvasive breast cancer but at high risk of further cancer development. To test the plastic surgery impact on patient choices regarding the management of the cancer, a subset of 90 patients was identified to test the plastic surgery impact on patient choices. These patients were referred to plastic surgery, following the first round of consultations by surgical and medical oncologists with only the preliminary oncological management plan defined. After a plastic surgery consultation, but prior to finalization of the overall oncological management plan, they were surveyed on the subject of modification of their personal choices and requests pertaining to their cancer management.ResultsIn this subset of 90 patients 40 (44%) returned to their surgical or medical oncologist considering changes of the primary management plan after their plastic surgery consultation. Twenty-six (28%) ultimately altered their plan, and the following patient-driven changes were made: mastectomy as opposed to lumpectomy (18 patients [20%]), contralateral prophylactic mastectomy (11 patients [12%]), nipple/areola removal as opposed to nipple/areola sparing suggested by the oncologists (5 patients [6%]), oncoplastic breast reduction as part of lumpectomy (5 patients [6%]), and other modifications (3 patients [3%]).ConclusionsDecisions for altering the preliminary oncologic plan or choosing a specific alternative (eg, lumpectomy plus radiation vs mastectomy) resulted from patient education on (1) reconstructive options, (2) aesthetic pitfalls and results. and (3) their interfacing with the oncological outcomes. Ultimately, plastic surgeons influence the multispecialty breast cancer management and patient decision-making process. Therefore, oncological literacy for plastic surgeons is essential to provide state-of-the-art breast cancer care and avoidance of suboptimal patient decisions

Procalcitonin-Guided Antibiotic Therapy after Stroke

Background: Pneumonia is among the most common acute complications after stroke and is associated with poor long-term outcome. Biomarkers may help identifying stroke patients at high risk for developing stroke-associated pneumonia (SAP) and to guide early treatment. Aims: This trial investigated whether procalcitonin (PCT) ultrasensitive (PCTus)-guided antibiotic treatment of SAP can improve functional outcome after stroke. Methods: In this international, multicenter, randomized, controlled clinical trial with blinded assessment of outcomes, patients with severe ischemic stroke in the middle cerebral artery territory were randomly assigned within 40 h after symptom onset to PCTus-based antibiotic therapy guidance in addition to stroke unit care or standard stroke unit care alone. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale (mRS) and dichotomized as acceptable (≤4) or unacceptable (≥5). Secondary endpoints included usage of antibiotics, infection rates, days of fever, and mortality. The trial was registered with http://ClinicalTrials.gov (Identifier NCT01264549). Results: In the intention-to-treat-analysis based on 227 patients (112 in PCT and 115 in control group), 197 patients completed the 3-month follow-up. Adherence to PCT guidance was 65%. PCT-guided therapy did not improve functional outcome as measured by mRS (odds ratio 0.79; 95% confidence interval 0.45–1.35, p = 0.47). Pneumonia rate and mortality were similar in both groups. Days with fever tended to be lower (p = 0.055), whereas total number of days treated with antibiotics were higher (p = 0.004) in PCT compared to control group. A post hoc analysis including all PCT values in the intention-to-treat population demonstrated a significant increase on the first day of infection in patients with pneumonia and sepsis compared to patients with urinary tract infections or without infections (p < 0.0001). Conclusion: PCTus-guided antibiotic therapy did not improve functional outcome at 3 months after severe ischemic stroke. PCT is a promising biomarker for early detection of pneumonia and sepsis in acute stroke patients

Effects of a video game intervention on symptoms, training motivation, and visuo-spatial memory in depression

BackgroundPeople with Major Depressive Disorder (MDD) often experience reduced affect, mood, and cognitive impairments such as memory problems. Although there are various treatments for MDD, many of them do not address the cognitive deficits associated with the disorder. Playing 3D video games has been found to improve cognitive functioning in healthy people, but it is not clear how they may affect depressed mood and motivation in people with MDD. The aim of this study was to investigate whether a six-week video game intervention leads to improvements in depressed mood, training motivation, and visuo-spatial (working) memory functions in patients with MDD.MethodsA total of 46 clinically depressed individuals were randomly assigned to one of three groups: an experimental “3D video gaming” group (n = 14) which played a video game, an active control group (n = 16) which trained with a computer program “CogPack,” and a treatment-as-usual group (n = 16) which received a standard clinical treatment including psychotherapy and/or pharmacotherapy. Participants performed a neuropsychological assessment, including self-report questionnaires asking for depressive symptoms, training motivation, and visuo-spatial (working) memory functions before and after the training intervention.ResultsRegarding depressive symptoms, a significant decrease in the proportion of participants who showed clinical levels of depressive symptoms as measured by the Beck Depression Inventory was only found in the 3D video gaming group. Additionally, mean motivational levels of performing the training were significantly higher in the 3D video gaming group when compared with the active control group. Moreover, whereas the 3D Video Gaming group only significantly improved on one visuo-spatial memory test, the active control group improved in all visuo-spatial memory functions. The 3D video gaming group did not perform significantly better than the CogPack group, and the TAU group.ConclusionBesides a standalone cognitive training, the current findings suggest that cognitive trainings using a video game have potential to increase subjective well-being, show higher levels of training motivation, and lead to improvements in visuo-spatial (working) memory functions in MDD. However, given the mixed and unblinded nature of this study, the results should be interpreted with caution. Further research with larger samples and follow-up measurements is needed

SKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration

High levels of proinflammatory cytokines induce neurotoxicity and catalyze inflammation-driven neurodegeneration, but the specific release mechanisms from microglia remain elusive. Here we show that secretory autophagy (SA), a non-lytic modality of autophagy for secretion of vesicular cargo, regulates neuroinflammation-mediated neurodegeneration via SKA2 and FKBP5 signaling. SKA2 inhibits SA-dependent IL-1β release by counteracting FKBP5 function. Hippocampal Ska2 knockdown in male mice hyperactivates SA resulting in neuroinflammation, subsequent neurodegeneration and complete hippocampal atrophy within six weeks. The hyperactivation of SA increases IL-1β release, contributing to an inflammatory feed-forward vicious cycle including NLRP3-inflammasome activation and Gasdermin D-mediated neurotoxicity, which ultimately drives neurodegeneration. Results from protein expression and co-immunoprecipitation analyses of male and female postmortem human brains demonstrate that SA is hyperactivated in Alzheimer's disease. Overall, our findings suggest that SKA2-regulated, hyperactive SA facilitates neuroinflammation and is linked to Alzheimer's disease, providing mechanistic insight into the biology of neuroinflammation

The Worker Honeybee Fat Body Proteome Is Extensively Remodeled Preceding a Major Life-History Transition

Honeybee workers are essentially sterile female helpers that make up the majority of individuals in a colony. Workers display a marked change in physiology when they transition from in-nest tasks to foraging. Recent technological advances have made it possible to unravel the metabolic modifications associated with this transition. Previous studies have revealed extensive remodeling of brain, thorax, and hypopharyngeal gland biochemistry. However, data on changes in the abdomen is scarce. To narrow this gap we investigated the proteomic composition of abdominal tissue in the days typically preceding the onset of foraging in honeybee workers

Etablierung des neuartigen Gewebeclearing-Verfahrens CLARITY zur Verbesserung der Immunmarkierung in der Elektronenmikroskopie

Die Untersuchung von Gewebe ist eine der wichtigsten Voraussetzungen für die Erforschung humaner Pathologien. Durch die Entwicklung der ersten Mikroskope vor ca. 300 Jahren ist es Wissenschaftlern möglich, Zellen und ihre kleinsten Strukturen, darunter Organellen und Proteine, zu analysieren. Physikalische Effekte wie Streuung, Reflexion oder Absorption erschweren die Gewebeuntersuchung jedoch erheblich. Hauptsächlich dafür verantwortlich sind die Biomembranen, die die Penetranz von Molekülen (Immunmarkierung) verhindern und Licht während der Mikroskopie streuen, was Unschärfe und Trübung zur Folge hat. Eine der erfolgreichsten Techniken der letzten Jahre, um Gewebe zu fixieren und für optische Aufnahmen vorzubereiten, ist das Gewebeclearing-Verfahren CLARITY (Clear, Lipid-exchanged, Anatomically Rigid, Imaging/immunostaining compatible, Tissue hYdrogel). Im Zentrum dieser Promotionsarbeit steht die Etablierung und die Verbesserung von CLARITY sowie die Kombination mit der Immuno-Elektronenmikroskopie (Immuno-EM). Zunächst wurde hierfür das passive Clearing optimiert und umgesetzt. Mit der Entwicklung einer Elektrophoresekammer konnte das Verfahren beschleunigt und damit verbessert werden. CLARITY steigert zudem die Permeablität des Gewebes für Antikörper und ermöglichte damit die Darstellung cerebellärer Synapsen in einem 100 µm dicken Mausgehirnschnitt. Ausgehend von diesen Ergebnissen wurde versucht, die Vorteile von CLARITY wie bessere Antikörper-Penetration und Anstieg der Immunogenität mit denen der Elektronenmikroskopie wie hohe Auflösung und Detailansicht der Ultrastruktur zu kombinieren. Zunächst konnte gezeigt werden, dass Gewebe nach Behandlung mit CLARITY generell mit dem Elektronenmikroskop dargestellt werden kann. Proteindichte Strukturen und Organellen konnten gut erhalten werden, bei gleichzeitigem Verlust der Biomembranen und Lipiden. Im nächsten Schritt wurden zwei Immunmarkierungsverfahren getestet: 1.) Die 3,3'-Diaminobenzidin (DAB)-Kontrastierung und 2.) die Immunogold-Markierung. Für ersteres Verfahren wurden zunächst verschiedene Hirnregionen u.a. der Hippocampus, das Cerebellum und das Striatum sowie unterschiedliche synaptische Antikörper gegen Synaptophysin, SHANK2 und SHANK3 getestet. Zur Auswertung der DAB-Reaktion wurde eine quantitative Analyse angewandt und zur Bestätigung der Immunogold-Markierung genügte ein positiver Nachweis der Gold-Kolloid-Partikel in der postsynaptischen Dichte. Methoden wie die Immunhistochemie oder die Darstellung kleinster Strukturen mit Hilfe der Elektronenmikroskopie haben eine große Bedeutung bei der Erforschung humaner Pathologien. Allen voran Erkrankungen an der Synapse wie beispielsweise Autismus-Spektrum-Störungen. Diese Arbeit leistet einen Beitrag zur Fusion bewährter Methoden mit neuartigen Verfahren

The Randomized Controlled STRAWINSKI Trial: Procalcitonin-Guided Antibiotic Therapy after Stroke

Background: Pneumonia is among the most common acute complications after stroke and is associated with poor long-term outcome. Biomarkers may help identifying stroke patients at high risk for developing stroke-associated pneumonia (SAP) and to guide early treatment. aims: This trial investigated whether procalcitonin (PCT) ultrasensitive (PCTus)-guided antibiotic treatment of SAP can improve functional outcome after stroke. Methods: In this international, multicenter, randomized, controlled clinical trial with blinded assessment of outcomes, patients with severe ischemic stroke in the middle cerebral artery territory were randomly assigned within 40 h after symptom onset to PCTus-based antibiotic therapy guidance in addition to stroke unit care or standard stroke unit care alone. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale (mRS) and dichotomized as acceptable (≤4) or unacceptable (≥5). Secondary endpoints included usage of antibiotics, infection rates, days of fever, and mortality. The trial was registered with http://ClinicalTrials.gov (Identifier NCT01264549). results: In the intention-to-treat-analysis based on 227 patients (112 in PCT and 115 in control group), 197 patients completed the 3-month follow-up. Adherence to PCT guidance was 65%. PCT-guided therapy did not improve functional outcome as measured by mRS (odds ratio 0.79; 95% confidence interval 0.45–1.35, p = 0.47). Pneumonia rate and mortality were similar in both groups. Days with fever tended to be lower (p = 0.055), whereas total number of days treated with antibiotics were higher (p = 0.004) in PCT compared to control group. A post hoc analysis including all PCT values in the intention-to-treat population demonstrated a significant increase on the first day of infection in patients with pneumonia and sepsis compared to patients with urinary tract infections or without infections (p < 0.0001). Conclusion: PCTus-guided antibiotic therapy did not improve functional outcome at 3 months after severe ischemic stroke. PCT is a promising biomarker for early detection of pneumonia and sepsis in acute stroke patients.peerReviewe