Metabolic Impact of Rapamycin (Sirolimus) and B-Estradiol Using Mouse Embryonic Fibroblasts as a Model for Lymphangioleiomyomatosis

Introduction

Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease that predominantly affects women of childbearing age. Exogenous rapamycin (sirolimus) has been shown to improve clinical outcomes and was recently approved to treat LAM, whereas estrogen (E₂) is implicated in disease progression. No consistent metabolic model currently exists for LAM, therefore wild-type mouse embryonic fibroblasts (MEF +/+) and TSC2 knockout cells (MEF ?/?) were used in this study as a model for LAM.

Methods

Oxygen consumption rates (OCR) and redox potential were measured to determine metabolic state across control cells, MEF +/+ and ?/? cells treated with rapamycin (Rapa), and MEF +/+ and ?/? cells treated with E₂. An XF96 extracellular flux analyzer from Seahorse Bioscience^® was used to measure OCR, and a RedoxSYS? ORP was used to measure redox potential.

Results

OCR of MEF ?/? cells treated with rapamycin (MEF ?/? Rapa) versus MEF ?/? control were significantly lower across all conditions. The static oxidation reduction potential of the MEF ?/? Rapa group was also lower, approaching significance. The coupling efficiency and ratio of ATP-linked respiration to maximum respiration were statistically lower in MEF ?/? Rapa compared to MEF +/+ Rapa. There were no significant metabolic findings across any of the MEF cells treated with E₂. MEF ?/? control cells versus MEF +/+ control cells were not found to significantly differ.

Conclusion

MEF cells are thought to be a feasible metabolic model for LAM, which has implications for future pharmacologic and biologic testing.

     

Op.-Simulation in der Chirurgie

Background

Patient safety during operations hinges on the surgeon’s skills and abilities. However, surgical training has come under a variety of restrictions. To acquire dexterity with decreasingly “simple” cases, within the legislative time constraints and increasing expectations for surgical results is the future challenge.

Objectives

Are there alternatives to traditional master–apprentice learning?

Materials and methods

A literature review and analysis of the development, implementation, and evaluation of surgical simulation are presented.

Results

Simulation, using a variety of methods, most important physical and virtual (computer-generated) models, provides a safe environment to practice basic and advanced skills without endangering patients. These environments have specific strengths and weaknesses.

Conclusions

Simulations can only serve to decrease the slope of learning curves, but cannot be a substitute for the real situation. Thus, they have to be an integral part of a comprehensive training curriculum. Our surgical societies have to take up that challenge to ensure the training of future generations.

     

Hepatosplenic T-cell lymphoma in a 47-year-old Crohn’s disease patient on thiopurine monotherapy

Hepatosplenic T-cell lymphoma (HSTCL) is a rare non-Hodgkin lymphoma with a high mortality rate. Higher incidence is reported in patients with inflammatory bowel disease, specifically in male patients that are younger than 35 years, and have been treated with thiopurine and tumor necrosis factor (TNF)-α inhibitor combination therapy for over 2 years. In this case report we describe a 47-year-old patient with Crohn’s disease (CD) who developed HSTCL after having been treated with thiopurine monotherapy for 14 years. To our best knowledge, only eleven cases exist of patients with CD who developed HSTCL while on thiopurine monotherapy. We report the first patient with CD, older than 35 years, who developed HSTCL while on thiopurine monotherapy. This emphasizes that HSTCL risk is not limited to young men receiving both thiopurines and TNF-α inhibitors.     

Predictive value of cytokines for developing complications after polytrauma

AIM: To investigate posttraumatic cytokine alterations and their value for predicting complications and mortality in polytraumatized patients. METHODS: Studies on the use of specific cytokines to predict the development of complications and mortality were identified in MEDLINE, EMBASE, Web of Science and the Cochrane Library. Of included studies, relevant data were extracted and study quality was scored. RESULTS: Forty-two studies published between 1988 and 2015 were identified, including 28 cohort studies and 14 “nested” case-control studies. Most studies investigated the cytokines interleukin (IL)-6, IL-8, IL-10 and tumor necrosis factor (TNF-α). IL-6 seems related to muliorgan dysfunction syndrome, multiorgan failure (MOF) and mortality; IL-8 appears altered in acute respiratory distress syndrome, MOF and mortality; IL-10 alterations seem to precede sepsis and MOF; and TNF-α seems related to MOF. CONCLUSION: Cytokine secretion patterns appear to be different for patients developing complications when compared to patients with uneventful posttraumatic course. More research is needed to strengthen the evidence for clinical relevance of these cytokines.     

Stellungnahme zur Orbitotomie im Rahmen ophthalmoplastischer und rekonstruktiver operativer Ma?nahmen

Mitteilungen der DOG

Stellungnahme zur Orbitotomie im Rahmen ophthalmoplastischer und rekonstruktiver operativer Ma?nahmen     

Chemical Dependency and the Physician

Although the nature and scope of addictive disease are commonly reported in the lay press, the problem of physician addiction has largely escaped the public''s attention. This is not due to physician immunity from the problem, because physicians have been shown to have addiction at a rate similar to or higher than that of the general population. Additionally, physicians'' addictive disease (when compared with the general public) is typically advanced before identification and intervention. This delay in diagnosis relates to physicians'' tendency to protect their workplace performance and image well beyond the time when their life outside of work has deteriorated and become chaotic. We provide an overview of the scope and risks of physician addiction, the challenges of recognition and intervention, the treatment of the addicted physician, the ethical and legal implications of an addicted physician returning to the workplace, and their monitored aftercare. It is critical that written policies for dealing with workplace addiction are in place at every employment venue and that they are followed to minimize risk of an adverse medical or legal outcome and to provide appropriate care to the addicted physician.Approximately 10% to 12% of physicians will develop a substance use disorder during their careers, a rate similar to or exceeding that of the general population.^1,2 Although physicians'' elevated social status brings many tangible and intangible rewards, it also has an isolating effect when they are confronted with a disease such as addiction, which has a social stigma. This isolation can lead to disastrous consequences, both in delaying the recognition of and in intervening in the disease process, as well as in the attendant risk of death by inadvertent overdose or suicide.³Further causes for delay in diagnosis include fear on the part of the physician that disclosure of an addictive illness might cause loss not only of prestige but also of his or her license to practice medicine and thus livelihood. Additionally, a physician''s family members and coworkers will often participate in a “conspiracy of silence” in an effort to protect the family or practice workers from economic ruin by the loss of the physician''s job and income.McLellan et al² conducted a 5-year longitudinal cohort study of 904 physicians, 87% of whom were male, who were enrolled in 16 state physician health programs (PHPs). Alcohol was the primary drug of abuse in 50.3%, opioids in 35.9%, stimulants in 7.9%, and other substances in 5.9%; 50% reported abuse of multiple substances, 13.9% a history of intravenous drug use, and 17% previous treatment for addiction. The authors found that certain specialties, such as anesthesiology, emergency medicine, and psychiatry, appeared to be overrepresented in these programs relative to their numerical representation in the national physician pool. Indeed, other investigators have suggested that these specialties seem to have a disproportionate propensity toward addiction.^4,5 Contributing factors may include stresses of the work, ready access to narcotics and other psychotropic drugs in the workplace, and perhaps a selection bias in the type of physicians who seek these specialties.⁶Physicians in different specialties tend to abuse different classes of drugs. For example, although alcohol is the drug of choice for most physicians with addiction, only about 10% of anesthesiologists enter treatment for alcohol addiction. Instead, the vast majority of addicted anesthesiologists are addicted to potent intravenous opioids such as fentanyl and sufentanil. Often, addicted physicians divert these drugs from the workplace, indeed from their individual patients, and losing their job would cut their lifeline to their drug of abuse. Thus, they preserve their work performance above all other aspects of their life, and by the time a physician''s addictive illness becomes apparent in the workplace, the rest of his or her social, family, and personal life is in shambles.⁷For editorial comment, see page 576For a colleague who suspects addiction in a peer, the challenges of conclusively identifying and intervening can be daunting and include everything from a concern of “What right do I have to tell them how to live their life?” to a fear of retaliatory litigation. Additionally, the medical licensing boards in many states have included the risk of sanctions if a physician becomes aware of an addictive disease in a colleague and fails to intervene or notify the board or the state''s PHP. This aspect will be covered more fully in a later section.     

Schädelbasischondrosarkome

BACKGROUND: Chondrosarcoma is a rare differential diagnosis of malignant tumours of the skull base. The prognosis was rated as unfavourable in articles for many years. It has, however, improved considerably in recent years. The objective of this study was to evaluate and current, new optimised treatment strategies. PATIENTS AND METHODS: We retrospectively analysed the case histories and course of four patients whom we treated for chondrosarcoma of the skull base over the past 5 years at the Freiburg Skull Base Centre. RESULTS: Because of initially mild symptoms, the patients first came for examination at an advanced stage of the tumour. All patients underwent surgery, whereby an R0-resection was barely or only questionably present. Three patients underwent radiation therapy postoperatively. All patients are currently tumour free. CONCLUSIONS: Surgical treatment with curative intent is basically the therapy of choice. Due to the usually large size of the tumour and its close relationship to relevant structures, complete resection is, however, not always possible despite advances in surgical procedures. Taking the possibility of modern adjuvant radiotherapeutic procedures into account, an incomplete, function-preserving resection is preferred to a radical and mutilating resection.