Diagnostic Laparoscopy in Trauma Patients: Do We Need to Open and See if We Can See Without Opening?

BACKGROUND: Diagnostic laparoscopy (DL) has been advocated to reduce the incidence of nontherapeutic laparotomies (NL) among stable trauma patients. This study aimed to compare the outcomes of hemodynamically stable trauma patients undergoing DL versus NL. METHODS: This is a retrospective analysis of the American College of Surgeons Trauma Quality Improvement Program database over 4 y (2017-2020). Hemodynamically stable (systolic blood pressure >90 & heart rate < 120) adult (≥18 y) trauma patients undergoing DL or NL were included. Patients were stratified into DL and NL and substratified based on the mechanism of injury (blunt versus penetrating) and compared. RESULTS: Over 4 y, 3801 patients were identified, of which, 997 (26.2%) underwent DL. Overall, 25.6% sustained blunt injuries. The mean (SD) age was 39 (16) and 79.5% were male. The median injury severity score and abdominal abbreviated injury scale were 4 [4-9] and 1 [1-2], with no difference among study groups (P ≥ 0.05). The overall mortality and major complication rates were 2.8% and 13.2%, respectively. After controlling for potential confounding factors, DL was independently associated with lower odds of mortality (adjusted odds ratio: 0.10, 95% CI [0.04-0.29], P < 0.001) and major complications (adjusted odds ratio: 0.38, 95% CI [0.29-0.50], P < 0.001) and shorter hospital length of stay (ß: -1.22, 95% CI [-1.78 to -0.67], P < 0.001). The trends toward improved outcomes in the DL group remained the same in the subanalysis of patients with penetrating and blunt injuries. CONCLUSIONS: With advances in minimally invasive surgery, unnecessary exploratory laparotomy can be avoided in many trauma patients. Our study shows that hemodynamically stable patients undergoing DL had superior outcomes compared to those with NL.

Non-therapeutic laparotomies in military trauma (2009-2014).

BACKGROUND: Combat casualties are frequently injured in austere settings where modern imaging modalities are unavailable. Exploratory laparotomies are often performed in these settings when there is suspicion for intra-abdominal injury. Prior studies of combat casualties reported non-therapeutic laparotomy (NTL) rates as high as 32%. Given improvements in combat casualty care over time, we evaluated NTLs performed during later years of the wars in Iraq and Afghanistan. METHODS: Military personnel with combat-related injuries (6/1/2009-12/31/2014) who underwent exploratory laparotomy based on concern for abdominal injury (i.e. not performed for proximal vascular control or fecal diversion) and were evacuated to Landstuhl Regional Medical Center (Germany) before being transferred to participating U.S. military hospitals were assessed. An NTL was defined as a negative laparotomy without substantial intra-abdominal injuries requiring repair. Characteristics, indications for laparotomy, operative findings, and outcomes were examined. RESULTS: Among 244 patients who underwent laparotomies, 41 (16.8%) had NTLs and 203 (83.2%) had therapeutic laparotomies (i.e. positive findings). Patients with NTLs had more computed tomography scans concerning for injury (48.8% vs 27.1%; p = 0.006), less penetrating injury mechanisms (43.9% vs 71.9%; p < 0.001), and lower Injury Severity Scores (26 vs 33; p = 0.003) compared to patients with therapeutic laparotomies. Patients with NTLs were also less likely to be admitted to the intensive care unit (70.7 vs 89.2% for patients with therapeutic laparotomies; p = 0.007). No patients with NTLs developed abdominal surgical site infections (SSI) compared to 16.7% of patients with therapeutic laparotomies (p = 0.002). There was no significant difference in mortality between the groups (p = 0.198). CONCLUSIONS: Our proportion of NTLs was lower than reported from earlier years during the wars in Iraq and Afghanistan. No infectious complications from NTLs (i.e. abdominal SSIs) were identified. Nevertheless, surgeons should continue to have a low threshold for exploratory laparotomy in military patients in austere settings with concern for intra-abdominal injury.

Are we doing too many non-therapeutic laparotomies in trauma? An analysis of the National Trauma Data Bank.

BACKGROUND: Exploratory laparotomy (EL) has been the definitive diagnostic and therapeutic modality for operative abdominal trauma in the US. Recently, many trauma centers have started using diagnostic laparoscopy (DL) in stable trauma patients in an effort to reduce the incidence of non-therapeutic laparotomy (NL). We aim to evaluate the incidence of NL in the trauma population in the US and compare the outcomes between DL and NL. METHODS: Using ICD-9 codes, the National Trauma Data Bank (2010-2015) was queried for patients undergoing any abdominal surgical intervention. Patients were divided into two groups: diagnostic laparoscopy (DL) and exploratory laparotomy (EL). Hemodynamically unstable patients on arrival and patients with abbreviated injury score (AIS) > 3 were excluded. Patients in EL group without any codes for gastrointestinal, diaphragmatic, hepatic, splenic, vascular, or urological procedures were considered to have undergone NL. After excluding patients who were converted to open from the DL group, multivariate regression models were used to analyze the outcomes of DL vs NL group with respect to mortality, length of stay, and complications. RESULTS: A total of 3197 patients underwent NL vs 1323 patients who underwent DL. Compared to DL group, the NL group were older (mean age: 35 vs. 31, P < 0.01). Rate of penetrating injury was 77% vs 86% for patients in NL vs DL. On multivariate analysis, NL was associated with increased mortality (OR 4.5, 95% CI 2.1-9.7), higher rate of complications (OR 2.2, 95% CI 1.4-3.3), and a longer hospital stay (OR 2.7, 95% CI 2.1-3.5). NL was also associated with higher rates of pneumonia, VTE, ARDS, and cardiac arrest. CONCLUSION: With increasing experience in minimally invasive surgery, DL should be a part of the armamentarium of trauma surgeons. This study supports that in well-selected trauma patients DL has favorable outcomes compared to NL. These findings warrant further investigation.

What is the best age to circumcise? A medical and ethical analysis.

Circumcision is often claimed to be simpler, safer and more cost-effective when performed in the neonatal period as opposed to later in life, with a greater benefit-to-risk ratio. In the first part of this paper, we critically examine the evidence base for these claims, and find that it is not as robust as is commonly assumed. In the second part, we demonstrate that, even if one simply grants these claims for the sake of argument, it still does not follow that neonatal circumcision is ethically permissible absent urgent medical necessity. Based on a careful consideration of the relevant evidence, arguments and counterarguments, we conclude that medically unnecessary penile circumcision-like other medically unnecessary genital procedures, such as 'cosmetic' labiaplasty-should not be performed on individuals who are too young (or otherwise unable) to provide meaningful consent to the procedure.

[Complications of cosmetic piercings and tattoos in the head and neck region]. / Komplikationen bei kosmetischen Piercings und Tätowierungen im Kopf-Hals-Bereich.

Piercings and tattoos have gained popularity across all cultural environments during the past century, and one in ten Europeans are now pierced. While tattoos are often restricted to the rest of the body, piercings are common at facial sites such as ears, nose, lips, and tongue. Complications following piercings are not uncommon. Infections can rapidly spread across the auricular cartilage and require antibiotic and often surgical treatment. Mild trauma (i.e., piercing the earlobe) can lead to excessive scar formation due to fibroblast proliferation. Keloids have a particularly high rate of recurrence and are therefore difficult to treat. Due to recent developments in the field of permanent makeup, tattooing techniques are also increasingly applied in the head and neck region. Here, complications such as infection or allergic reactions can occur. Topical medication or laser procedures are the usual therapeutic options.

Non-therapeutic intensive care for organ donation: A healthcare professionals' opinion survey.

BACKGROUND AND PURPOSE: Providing non-therapeutic intensive care for some patients in hopeless condition after cerebrovascular stroke in order to protect their organs for possible post-mortem organ donation after brain death is an effective but ethically tricky strategy to increase organ grafting. Finding out the feelings and opinion of the involved healthcare professionals and assessing the training needs before implementing such a strategy is critical to avoid backlash even in a presumed consent system. PARTICIPANTS AND METHODS: A single-centre opinion survey of healthcare professionals was conducted in 2013 in the potentially involved wards of a French University Hospital: the Neurosurgical, Surgical and Medical Intensive Care Units, the Stroke Unit and the Emergency Department. A questionnaire with multiple-choice questions and one open-ended question was made available in the different wards between February and May 2013. ETHICAL CONSIDERATIONS: The project was approved by the board of the Lorraine University Diploma in Medical Ethics. RESULTS: Of a total of 340 healthcare professionals, 51% filled the form. Only 21.8% received a specific education on brain death, and only 18% on potential donor's family approach and support. Most healthcare professionals (93%) think that non-therapeutic intensive care is the continuity of patient's care. But more than 75% of respondents think that the advance patient's consent and the consent of the family must be obtained despite the presumed consent rule regarding post-mortem organ donation in France. CONCLUSION: The acceptance by healthcare professionals of non-therapeutic intensive care for brain death organ donation seems fairly good, despite a suboptimal education regarding brain death, non-therapeutic intensive care and families' support. But they ask to require previously expressed patient's consent and family's approval. So, it seems that non-therapeutic intensive care should only remain an ethically sound mean of empowerment of organ donors and their families to make post-mortem donation happen as a full respect of individual autonomy.

Outcome of laparotomy and conservative treatment of patients with acute mesenteric venous ischemia with viable bowel.

BACKGROUND: Acute mesenteric ischemia (AMI) is one of the most serious abdominal emergencies. Predicting the onset of bowel necrosis that warrants surgical intervention is of paramount importance in AMI. The present study aimed to investigate the outcome of patients with AMI secondary to mesenteric venous occlusion (MVO) and the consequence of non-therapeutic exploratory laparotomy. METHODS: The records of 132 patients with AMI were retrospectively reviewed. The outcome of patients with acute mesenteric venous ischemia (AMVI) and viable bowel was analyzed based on the method of treatment: conservative versus surgical. The impact of non-therapeutic laparotomy on the outcome of patients with AMVI in terms of morbidity, readmission, and mortality was analyzed. RESULTS: Forty-seven patients (34 male) with AMVI had viable bowel. Of the 47 patients with viable bowel, 8 (17%) had an exploratory non-therapeutic laparotomy, whereas 39 patients were treated conservatively. Patients who had non-therapeutic laparotomy had significantly higher complication (50 vs 5.1%, p = 0.005) and readmission rates (37.5 vs 5.1%, p = 0.03) and longer hospital stay (8.5 vs 7 days, p = 0.02) than those treated conservatively. Patients with bowel necrosis who had a therapeutic laparotomy had slightly lower rates of morbidity and mortality as compared to patients with viable bowel who underwent a non-therapeutic laparotomy. CONCLUSION: Careful assessment and informed decision-making in patients with AMVI are crucial to avoid unnecessary surgical intervention that can result in higher rates of complications and readmission and extended hospital stay.

A multicenter evaluation on the impact of non-therapeutic transfer in rural trauma.

INTRODUCTION: Trauma transfers are a common occurrence in rural areas, where critical access and lower-level trauma centers routinely transfer to tertiary care centers for specialized care. Transfers are non-therapeutic (NTT) when no specialist intervention occurs, leading to transfer that were futile (FT) or secondary overtriage (SOT). This study aimed to evaluate the prevalence of NTT among four trauma centers providing care to rural Appalachia. METHODS: This retrospective review was performed at four, ACS verified, Level 1 trauma centers. All adult trauma patients, transferred during 2018 were included for analysis. Transfers were considered futile if in <48 h the patient died or was discharged to hospice, without operative intervention. SOT transfers were discharged in <48 h, without major intervention, with an ISS< 15. Cost analysis was performed to describe the impact of NTT on EMS use. RESULTS: 4,189 patients were analyzed during the study period. 105 (2.5%) met criteria for futility. Futile patients had a median ISS of 25 (IQR 9-26), and 48% had an AIS head ≥4. These were significantly greater (p<0.001) than non-futile transfers, median ISS 5 (IQR 2-9), 3% severe head injury. SOT occurred in 1371 (33%), median ISS of 5, and lower AIS scores by region. Isolated facial injuries resulted in 165 transfers. 13% of FT+SOT were admitted to the ICU. Only 22% of FT+SOT came from a trauma center. 68% were transported by ALS and 13% transported by air transport. FT+SOT traveled on average 70 miles from their home to receive care. CONCLUSIONS: Non-therapeutic transfers account for more than 1/3 of transfers in this rural environment. There was a significant use of advanced life support and aeromedical transport. The utility of these transfers should be questioned. With the recent increases in telehealth there is an opportunity for trauma systems to improve regional care and decrease transfers for futile cases.

Intralesional microbleeding in resected thymic cysts indeterminate on imaging.

Background: The propensity of thymic cysts to mimic solid thymic epithelial tumors (TETs) on computed tomography (CT), on account of attenuation values greater than water and thickened or calcified walls, can lead to non-therapeutic thymectomy. These lesions can fluctuate in volume, CT attenuation, and magnetic resonance imaging (MRI) signal over time. We hypothesized that spontaneous hemorrhage and resorption may contribute to their variable appearance over time. Methods: Completely excised thymic cysts were identified retrospectively over a 20-year period by their pathologic diagnosis. Cysts were excluded if they did not have available presurgical imaging, were not prevascular, were located within or contained an enhancing mass by imaging, or were of non-thymic origin upon microscopic review. Histopathological analysis of all available resected thymic cyst material and radiologic analysis of the cysts on pre-operative imaging were performed. Results: Upon application of exclusion criteria, we identified 18 thymic cysts from the initial 85 mediastinal cystic specimens. Most cysts were unilocular (11/15, 73%), showed turbid-to-semisolid, hemorrhagic fluid (10/12, 83%) and showed histopathological findings suggestive of intralesional microbleeding (14/18, 78%), remodeling (8/18, 44%), pathological wound healing/scarring of the capsule (16/18, 89%), and fat necrosis in the surrounding thymic tissue (12/18, 67%). On CT, 6/17 (35%) cysts demonstrated wall calcification. Sixty-five percent (11/17) had attenuation values ≥20 Hounsfield units (HU). Two of the 4 cysts imaged by MRI were T1-isointense, one was mixed hyper- and isointense, and one T1-hypointense to muscle, with iso- and hyperintensity indicating hemorrhagic or proteinaceous content. Twenty-five percent (1/4) of cyst walls imaged by MRI were T1/T2-hypointense, indicating presence of calcification, hemosiderin, and/or fibrosis. Conclusions: Resected thymic cysts in this cohort often showed features suggestive of intralesional microbleeding, inflammation, and fibrosis, which may explain their appearance and behavior over time on CT and MRI.

Public Anxiety, Attitudes, and Practices towards COVID-19 Infection in the Eastern Province of Saudi Arabia: A Cross-Sectional Study.

Coronavirus disease 2019, or COVID-19, still has a terrifying potential due to its continuous genetic variation. Although vaccines have been created, adherence to preventive measures remains a privileged choice to tackle the pandemic. This study aims to investigate the anxiety, attitudes, and practices (KAPs) towards COVID-19 infection in the Eastern Province of Saudi Arabia. In this cross-sectional study, data were collected from 400 participants via an online self-structured questionnaire. Anxiety, attitude, and practice scores were calculated by summing the points of the statements under the corresponding domain multiplied by 100 over 12, 21, or 15, respectively. Chi-square and one-way analysis of variance were used to investigate the relationships between vaccination, anxiety, attitude, practice scores, and demographic characteristics. More than half of the participants were female (58.5%; mean age of 29.5 years; the majority in the age groups of <20 years and 21-30 years). Only 21.5% of the participants were suffering from or previously had chronic diseases. Notably, 22.3% of the male participants were vaccinated (p = 0.000). The old age groups (41-50 years and >50 years) were more vaccinated (16.3% and 24.1%, respectively, p = 0.000), as well as the unemployed (36.4%; p = 0.000). The mean scores of anxiety, attitude, and practice were 66.8, 72.3, and 85.2, respectively. Females had an anxiety score of 68.5% (p = 0.008) and a higher attitude score of 68.5% (p = 0.008). Infected male participants had a lower practice score of 80% (p = 0.038), while females recorded higher practice scores (85.7 ± 11.6). The results highlight the importance of reliable communication from health representatives and legislators in educating the public and promoting their knowledge about non-therapeutic interventions. Efficient intervention approaches are required to fill the gap during the implementation of non-therapeutic measures. Also, it is recommended that awareness programs, during COVID-19 or any other similar pandemics, should be tailored to target Eastern Province inhabitants, especially males.

Feasibility and Tolerance of Fingertip Peripheral Arterial Tonometry Measurements in School-Aged Children.

Background: Assessment of the endothelial function of the microvasculature by peripheral arterial tonometry (PAT) has gained increasing popularity in pediatrics. Discomfort or experienced pain during fingertip PAT has only been studied in adolescents and adults. Methods: In 142 children (aged 4-11 years old), a fingertip PAT with a commercial device (EndoPAT 2000®) as well as a caliper and ultrasound examination of peripheral skinfolds were performed as part of a cross-sectional cohort study. In 110 children, Faces Pain Scale (FPS-R) data were collected after PAT and skinfold measurements by caliper and ultrasound. Results: In 111 out of the 142 PAT measurements (78.2%), a reactive hyperemia index (RHI) could be obtained. The most frequent error messages by the software was a "too noisy" and/or a "poor quality" signal. The success rate was higher in children aged older than 6 years (83.1 vs. 44.4%; p < 0.001). Median (range) FPS-R after PAT was 0 (range 0-6) but was significantly higher than the median pain experienced after caliper measurements of peripheral skinfolds (p < 0.001). No pain was experienced by 59 of the 110 children (54.1%). Conclusion: PAT testing is feasible in the great majority of school-aged children, and the procedure is well-tolerated.

[Intensive care to facilitate organ donation. ONT-SEMICYUC recommendations]. / Cuidados intensivos orientados a la donación de órganos. Recomendaciones ONT-SEMICYUC.

Intensive care to facilitate organ donation (ICOD) is defined as the initiation or continuation of life-sustaining measures, such as mechanical ventilation, in patients with a devastating brain injury with high probability of evolving to brain death and in whom curative treatment has been completely dismissed and considered futile. ICOD incorporates the option to organ donation allowing a holistic approach to end-of-life care, consistent with the patients wills and values. Should the patient not evolve to brain death, life-supportive treatment must be withdrawal and controlled asystolia donation could be evaluated. ICOD is a legitimate practice, within the ethical and legal regulations that contributes increasing the accessibility of patients to transplantation, promoting health by increasing deceased donation by 24%, and with a mean of 2.3 organs transplanted per donor, and collaborating with the sustainability of health-care system. This ONT-SEMICYUC recommendations provide a guide to facilitate an ICOD harmonized practice in spanish ICUs.

COVID-19 and School: To Open or Not to Open, That Is the Question. The First Review on Current Knowledge.

The COVID-19 pandemic has led to an unprecedented closure of schools in terms of duration. The option of school closure, SARS-CoV-2 initially being poorly known, was influenced by the epidemiological aspects of the influenza virus. However, school closure is still under debate and seems unsupported by sure evidence of efficacy in the COVID-19 era. The aim of our narrative review is to discuss the available literature on SARS-CoV-2 spread among children and adolescents, in the school setting, trying to explain why children appear less susceptible to severe disease and less involved in viral spreading. We also tried to define the efficacy of school closure, through an overview of the effects of the choices made by the various countries, trying to identify which preventive measures could be effective for a safe reopening. Finally, we focused on the psychological aspects of such a prolonged closure for children and adolescents. SARS-CoV-2, children, COVID-19, influenza, and school were used as key words in our literature research, updated to 29 March 2021. To our knowledge, this is the first review summarizing the whole current knowledge on SARS-CoV-2 spreading among children and adolescents in the school setting, providing a worldwide overview in such a pandemic context.

How to Maximize Children's Involvement in Non-therapeutic Research-Lessons Learnt From EFFECTOR.

Background: Children are vulnerable study subjects, especially in non-therapeutic research. Nowadays more attention is paid to the children's voice in both decision-making on participation and their experience of clinical research procedures. Methods: We share our experiences from a long-term, cross-sectional, non-therapeutic follow-up study in the offspring of mothers who participated in scientific research during their pregnancy. Results: During the data collection process, different strategies were developed to achieve a satisfactory participation rate with a focus on the involvement of the children. All study documents and measurements were assembled into a superhero framework. This theme is flexible and attracts children of a wide age-span. In order to inform the children before the study visit, a visually attractive assent was created as well as a superhero video. During the study visit, a sticker diploma was used with similar visuals from the assent. The toddlers received a superhero-cape. The children were involved in the decision-making process during the whole process. Discussion and conclusion: From our experience during the EFFECTOR data collection process, parents and their children can be motivated to participate in a long-term, non-therapeutic, follow-up study when child friendly and adequate communication is used. Framing in a superhero theme is simple and suitable for children of a wide age-span.

COVID-19 and Bangladesh: Challenges and How to Address Them.

As the coronavirus outbreak quickly surges worldwide, many countries are adopting non-therapeutic preventive measures, which include travel bans, remote office activities, country lockdown, and most importantly, social distancing. However, these measures face challenges in Bangladesh, a lower-middle-income economy with one of the world's densest populations. Social distancing is difficult in many areas of the country, and with the minimal resources the country has, it would be extremely challenging to implement the mitigation measures. Mobile sanitization facilities and temporary quarantine sites and healthcare facilities could help mitigate the impact of the pandemic at a local level. A prompt, supportive, and empathic collaboration between the Government, citizens, and health experts, along with international assistance, can enable the country to minimize the impact of the pandemic.

[Urological and psychological approach of secondary complications to penile aesthetic modifications]. / Abordaje urológico y psicológico de las complicaciones secundarias a las modificaciones estéticas peneanas.

OBJECTIVES: Due to the scarcity of scientific articles that review the technical alternatives available for aesthetic modifications in the penis that are the cause of subsequent uro-andrological problems, the existing literature is reviewed after the assistance of a penile infection by injection of subcutaneous hyaluronic acid with aesthetic purposes. MATERIAL AND METHODS: A 38-year-old male patient with no medical or psychiatric remarkable reports who came to the emergency room due to inflammation and abscess in penile skin after injection of hyaluronic acid. Surgical treatment was required and degloving and excision of affected skin was performed, with subsequent satisfactory evolution. The psychological analysis showed a narcissistic personality possibly secondary to traumas in childhood. We have reviewed the literature present in medical databases as well as information available on-line. RESULTS: Enlargement of the penis is an important cultural and social concern, so that there are different devices in the market to meet this demand, among them: herbal medicine, stretching exercises, weights, vacuum pumps or extensor devices. Among the surgical techniques, there have been described the pubic liposuction, the section of the suspensory ligament of the penis or the injection of autologous material or synthetic substances among others. As for the aesthetic modifications of the penis, there is a wide variety of genital piercings, tattoos and subcutaneous implants also called "pocketing" or "3D implants". All of these techniques or modifications are described in this article along with their possible associated more frequent urological complications. CONCLUSIONS: Aesthetic manipulations in the penis are becoming increasingly popular, and both its terminology and its medical implications should be known by urologists and andrologists. community.

Born to donate: proposals for "savior sibling" regulation in Latin America.

A Savior Sibling is a child who is born to provide an organ, bone marrow or cell transplant, to a sibling that is affected with a fatal disease. There are created with the in vitro fertilization and pre-implantation genetic diagnosis and, in the process, the ethical standards for organ donation of children become less demanding. Therefore, we propose that the authorization of the technique considers, unavoidably, the opinion of an impartial third party that can guarantee the welfare of the child. We develop a critical analysis of the laws that regulate the creation of babies to serve as organ donors. We evaluate under what circumstances the organizations that play a part in the decisions, fulfill the ethical standards to allow the organ donation of children.

Inflammatory Reactions to Red Tattoo Inks: Three cases highlighting an emerging problem.

In recent years, tattoos have become more commonplace. However, this can result in various inflammatory processes, the management of which can be challenging in daily clinical practice. Tattoo-related inflammatory reactions can comprise different patterns, including acute and immediate reactions, foreign body granulomas, sarcoid granulomas, isomorphic lesions, allergic contact dermatitis and photosensitivity. We report three cases who were referred to the Dermatology Outpatient Clinic of the Hospital Universitario San Cecilio, Granada, Spain, in 2017 with various skin reactions in the red-ink areas of their tattoos. Screening was performed for infectious diseases like atypical mycobacterial infections and systemic processes such as sarcoidosis. A good therapeutic response was achieved in all cases. An adequate differential diagnosis is essential for the therapeutic management of this emerging health problem.

Fingolimod: a review of its mode of action in the context of its efficacy and safety profile in relapsing forms of multiple sclerosis.

Fingolimod is an orally administered, first-in-class therapy for the treatment of relapsing forms of multiple sclerosis. Data from pivotal clinical trials show that fingolimod has a robust, significant effect on annualized relapse rates and MRI outcomes. Fingolimod has a novel, well-characterized mechanism of action. It acts through a specific set of receptors, sphingosine 1-phosphate receptors, present on the surface of a wide range of human cells and tissues, including neural cells, neurons and lymphocytes. Here we review the current literature to describe the mechanism of action of fingolimod in the context of its well-established clinical efficacy and safety profile. Understanding of the mechanisms behind any non-therapeutic effects of fingolimod facilitates their prediction and management in the clinical setting.

Surrogate consent to non-beneficial research: erring on the right side when substituted judgments may be inaccurate.

Part of the standard protection of decisionally incapacitated research subjects is a prohibition against enrolling them unless surrogate decision makers authorize it. A common view is that surrogates primarily ought to make their decisions based on what the decisionally incapacitated subject would have wanted regarding research participation. However, empirical studies indicate that surrogate predictions about such preferences are not very accurate. The focus of this article is the significance of surrogate accuracy in the context of research that is not expected to benefit the research subject. We identify three morally relevant asymmetries between being enrolled and not being enrolled in such non-beneficial research, and conclude that when there is a non-negligible probability that surrogates' predictions are wrong, it will generally be better to err on the side of not authorizing enrollment.