bluuebunny/crossref_metadata_2025 huggingface dataset:
Precision medicine in transplantation and hemodialysis
Authors: Oberbauer Rainer , Meyer Timothy W
Published: December 2020

In kidney transplantation, precision medicine has already entered clinical practice. Donor and recipient human leucocyte antigen (HLA) regions are genotyped in two class 1 and usually three class 2 loci, and the individual degree of sensitization against alloimmune antigens is evaluated by the detection of anti-HLA donor-specific antibodies. Recently, the contribution of non-HLA mismatches to outcomes such as acute T- and B-cell-mediated rejection and even long-term graft survival was described. Tracking of specific alloimmune T- and B-cell clones by next generation sequencing and refinement of the immunogenicity of allo-epitopes specifically in the interaction with HLA and T- and B-cell receptors may further support individualized therapy. Although the choices of maintenance immunosuppression are rather limited, individualization can be accomplished by adjustment of dosing based on these risk predictors. Finally, supplementing histopathology by a transcriptomics analysis allows for a biological interpretation of the histological findings and avoids interobserver variability of results. In contrast to transplantation, the prescription of hemodialysis therapy is far from precise. Guidelines do not consider modifications by age, diet or many comorbid conditions. Patients with residual kidney function routinely receive the same treatment as those without. A major barrier hitherto is the definition of ‘adequate’ treatment based on urea removal. Kt/Vurea and related parameters neither reflect the severity of uremic symptoms nor predict long-term outcomes. Urea is poorly representative for numerous other compounds that accumulate in the body when the kidneys fail, yet clinicians prescribe treatment based on its measurement. Modern technology has provided the means to identify other solutes responsible for specific features of uremic illness and their measurement will be a necessary step in moving beyond the standardized prescription of hemodialysis.
The long-term caregiver burden in World Health Organization grade I and II meningioma: It is not just the patient
Authors: Zamanipoor Najafabadi Amir H , van der Meer Pim B , Boele Florien W , Taphoorn Martin J B , Klein Martin , Peerdeman Saskia M , van Furth Wouter R , Dirven Linda ,   Dutch Meningioma Consortium, Moojen Wouter A , Reijneveld Jaap C
Published: December 2020

Background

Little is known about long-term caregiver burden in meningioma patients. We assessed meningioma caregiver burden, its association with informal caregiver’s well-being and possible determinants.

Methods

In this multicenter cross-sectional study, informal caregivers completed the Caregiver Burden Scale (five domains and total score). Patients completed a disease-specific health-related quality of life (HRQoL) questionnaire focusing on symptoms (EORTC QLQ-BN20) and underwent neurocognitive assessment. Both groups completed a generic HRQoL questionnaire (SF-36) and the Hospital Anxiety, and Depression Scale. We assessed the association between caregiver burden and their HRQoL, anxiety and depression. Furthermore, we assessed determinants for the caregiver burden. Multivariable regression analysis was used to correct for confounders.

Results

One hundred and twenty-nine informal caregivers were included (median 10 years after patients’ treatment). Caregivers reported burden in ≥1 domain (34%) or total burden score (15%). A one-point increase in total caregiver burden score was associated with a clinically relevant decrease in caregiver’s HRQoL (SF-36) in 5/8 domains (score range: −10.4 to −14.7) and 2/2 component scores (−3.5 to −5.9), and with more anxiety (3.8) and depression (3.0). Patients’ lower HRQoL, increased symptom burden, and increased anxiety and depression were determinants for higher caregiver burden, but not patients’ or caregivers’ sociodemographic characteristics, patients’ neurocognitive functioning, or tumor- and treatment-related characteristics.

Conclusions

Ten years after initial treatment, up to 35% of informal caregivers reported a clinically relevant burden, which was linked with worse HRQoL, and more anxiety and depression in both patients and caregivers, emphasizing the strong interdependent relationship. Support for meningioma caregivers is therefore warranted.
Replication, pathogenicity, and transmission of SARS-CoV-2 in minks
Authors: Shuai Lei , Zhong Gongxun , Yuan Quan , Wen Zhiyuan , Wang Chong , He Xijun , Liu Renqiang , Wang Jinliang , Zhao Qinjian , Liu Yuxiu , Huo Ningning , Deng Junhua , Bai Jingjing , Wu Hongchao , Guan Yuntao , Shi Jianzhong , Tian Kegong , Xia Ningshao , Chen Hualan , Bu Zhigao
Published: December 2020

Minks are raised in many countries and have transmitted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to humans. However, the biologic properties of SARS-CoV-2 in minks are largely unknown. Here, we investigated and found that SARS-CoV-2 replicates efficiently in both the upper and lower respiratory tracts, and transmits efficiently in minks via respiratory droplets; pulmonary lesions caused by SARS-CoV-2 in minks are similar to those seen in humans with COVID-19. We further found that a spike protein-based subunit vaccine largely prevented SARS-CoV-2 replication and lung damage caused by SARS-CoV-2 infection in minks. Our study indicates that minks are a useful animal model for evaluating the efficacy of drugs or vaccines against COVID-19 and that vaccination is a potential strategy to prevent minks from transmitting SARS-CoV-2.
Follow-up observations for IceCube-170922A: Detection of rapid near-infrared variability and intensive monitoring of TXS 0506+056
Authors: Morokuma Tomoki , Utsumi Yousuke , Ohta Kouji , Yamanaka Masayuki , Kawabata Koji S , Inoue Yoshiyuki , Tanaka Masaomi , Yoshida Michitoshi , Itoh Ryosuke , Sasada Mahito , Tominaga Nozomu , Mori Hiroki , Kawabata Miho , Nakaoka Tatsuya , Chogi Maiko , Abe Taisei , Huang Ruochen , Kawahara Naoki , Kimura Hiroki , Nagashima Hiroki , Takagi Kengo , Yamazaki Yuina , Liu Wei , Ohsawa Ryou , Sako Shigeyuki , Murata Katsuhiro L , Morihana Kumiko , Gilligan Christina K , Isogai Keisuke , Kimura Mariko , Wakamatsu Yasuyuki , Ohnishi Ryuhei , Takayama Masaki , Honda Satoshi , Matsuoka Yoshiki , Yamashita Takuji , Nagataki Shigehiro , Tanaka Yasuyuki T
Published: December 2020

We present our follow-up observations to search for an electromagnetic counterpart of the IceCube high-energy neutrino IceCube-170922A. Monitoring observations of a likely counterpart, TXS 0506+056, are also described. First, we quickly took optical and near-infrared images of seven flat-spectrum radio sources within the IceCube error region right after the neutrino detection and found a rapid flux decline of TXS 0506+056 in Kanata/HONIR J-band data. Motivated by this discovery, intensive follow-up observations of TXS 0506+056 were continuously performed, including our monitoring imaging observations, spectroscopic observations, and polarimetric observations in optical and near-infrared wavelengths. TXS 0506+056 showed a large-amplitude (∼1.0 mag) variability in a time scale of several days or longer, although no significant variability was detected in a time scale of a day or shorter. TXS 0506+056 also showed a bluer-when-brighter trend in optical and near-infrared wavelengths. Structure functions of the variabilities were examined and indicate that TXS 0506+056 is not a special blazar in terms of optical variability. Polarization measurement results of TXS 0506+056 are also discussed.
Learning Gait Modifications for Musculoskeletal Rehabilitation: Applying Motor Learning Principles to Improve Research and Clinical Implementation
Authors: Charlton Jesse M , Eng Janice J , Li Linda C , Hunt Michael A
Published: December 2020

Gait modifications are used in the rehabilitation of musculoskeletal conditions like osteoarthritis and patellofemoral pain syndrome. While most of the research has focused on the biomechanical and clinical outcomes affected by gait modification, the process of learning these new gait patterns has received little attention. Without adequate learning, it is unlikely that the modification will be performed in daily life, limiting the likelihood of long-term benefit. There is a vast body of literature examining motor learning, though little has involved gait modifications, especially in populations with musculoskeletal conditions. The studies that have examined gait modifications in these populations are often limited due to incomplete reporting and study design decisions that prohibit strong conclusions about motor learning. This perspective draws on evidence from the broader motor learning literature for application in the context of modifying gait. Where possible, specific gait modification examples are included to highlight the current literature and what can be improved on going forward. A brief theoretical overview of motor learning is outlined, followed by strategies that are known to improve motor learning, and finally, how assessments of learning need to be conducted to make meaningful conclusions.
Higher prevalence of non-skeletal comorbidity related to X-linked hypophosphataemia: a UK parallel cohort study using CPRD
Authors: Hawley Samuel , Shaw Nick J , Delmestri Antonella , Prieto-Alhambra Daniel , Cooper Cyrus , Pinedo-Villanueva Rafael , Javaid M Kassim
Published: December 2020

Objectives

X-Linked hypophosphataemic rickets (XLH) is a rare multi-systemic disease of mineral homeostasis that has a prominent skeletal phenotype. The aim of this study was to describe additional comorbidities in XLH patients compared with general population controls.

Methods

The Clinical Practice Research Datalink (CPRD) GOLD was used to identify a cohort of XLH patients (1995–2016), along with a non-XLH cohort matched (1 : 4) on age, sex and GP practice. Using the CALIBER portal, phenotyping algorithms were used to identify the first diagnosis (and associated age) of 273 comorbid conditions during patient follow-up. Fifteen major disease categories were used and the proportion of patients having ≥1 diagnosis was compared between cohorts for each category and condition. Main analyses were repeated according to the Index of Multiple Deprivation (IMD).

Results

There were 64 and 256 patients in the XLH and non-XLH cohorts, respectively. There was increased prevalence of endocrine [OR 3.46 (95% CI: 1.44, 8.31)] and neurological [OR 3.01 (95% CI: 1.41, 6.44)] disorders among XLH patients. Across all specific comorbidities, four were at least twice as likely to be present in XLH cases, but only depression met the Bonferroni threshold: OR 2.95 (95% CI: 1.47, 5.92). Distribution of IMD among XLH cases indicated greater deprivation than the general population.

Conclusion

We describe a higher risk of mental illness in XLH patients compared with matched controls, and greater than expected deprivation. These findings may have implications for clinical practice guidelines and decisions around health and social care provision for these patients.
ASSESSMENT OF RADIOFREQUENCY RADIATION WITHIN THE VICINITY OF SOME GSM BASE STATIONS IN GHANA: A FOLLOW-UP
Authors: Deatanyah Philip , Amoako Joseph K , Amoatey Edith , Osei Samuel , Azah Collins K , Dogbey Richard , Fuseini Abdul-Razak , Quarshie Emmanuel , Owusu-Banahene John
Published: December 2020

A follow-up of radiofrequency (RF) electromagnetic radiation safety survey at public access points had been carried out in 46 towns on 76 Global Systems for Mobile Communications and Universal Mobile Telecommunication System cell sites in two major cities in Ghana. The core objective was to determine the RF field levels in residential areas, schools and marketplaces and compare the measured results with the guidelines set by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). Measurements were made with calibrated log-periodic antenna coupled with a spectrum analyzer. The results obtained varied from 0.0008 to 182 mW m −2, which generally shows compliance with the ICNIRP reference levels. The highest value was 1.39 % of the reference.
Cyclic AMP response element-binding protein is required in excitatory neurons in the forebrain to sustain wakefulness
Authors: Wimmer Mathieu E , Cui Rosa , Blackwell Jennifer M , Abel Ted
Published: December 2020

The molecular and intracellular signaling processes that control sleep and wake states remain largely unknown. A consistent observation is that the cyclic adenosine monophosphate (AMP) response element-binding protein (CREB), an activity-dependent transcription factor, is differentially activated during sleep and wakefulness. CREB is phosphorylated by the cyclic AMP/protein kinase A (cAMP/PKA) signaling pathway as well as other kinases, and phosphorylated CREB promotes the transcription of target genes. Genetic studies in flies and mice suggest that CREB signaling influences sleep/wake states by promoting and stabilizing wakefulness. However, it remains unclear where in the brain CREB is required to drive wakefulness. In rats, CREB phosphorylation increases in the cerebral cortex during wakefulness and decreases during sleep, but it is not known if this change is functionally relevant to the maintenance of wakefulness. Here, we used the Cre/lox system to conditionally delete CREB in the forebrain (FB) and in the locus coeruleus (LC), two regions known to be important for the production of arousal and wakefulness. We used polysomnography to measure sleep/wake levels and sleep architecture in conditional CREB mutant mice and control littermates. We found that FB-specific deletion of CREB decreased wakefulness and increased non-rapid eye movement sleep. Mice lacking CREB in the FB were unable to sustain normal periods of wakefulness. On the other hand, deletion of CREB from LC neurons did not change sleep/wake levels or sleep/wake architecture. Taken together, these results suggest that CREB is required in neurons within the FB but not in the LC to promote and stabilize wakefulness.
Scaling up measurement to confront food insecurity in the USA
Authors: Byker Shanks Carmen , Calloway Eric E , Parks Courtney A , Yaroch Amy L
Published: December 2020

It is necessary to scale up measurement in order to confront the persisting problem of food insecurity in the United States (USA). The causes and consequences around food insecurity are briefly described in order to frame the complexity of the public health issue and demonstrate need for expanded measurement approaches. We assert that measurement of food security in the USA is currently based upon a core set of rigorous metrics and, moving forward, should also constitute a supplemental registry of measures to monitor and address variables that are associated with increased risk for food insecurity. Next, we depict dietary quality as a primary example of the power of measurement to make significant progress in our understanding and management of food insecurity. Finally, we discuss the translational implications in behavioral medicine required to make progress on achieving food security for all in the USA.
Transforming Growth Factor Beta-Induced Foxo3a Acts as a Profibrotic Mediator in Hepatic Stellate Cells
Authors: Kim Seung Jung , Kim Kyu Min , Yang Ji Hye , Cho Sam Seok , Jeong Eun Hee , Kim Jae Hoon , Lee Ji Hyun , Seo Kyu Hwa , Park Eun Young , Ki Sung Hwan
Published: December 2020

Hepatic stellate cells (HSCs) are major contributors to hepatic fibrogenesis facilitating liver fibrosis. Forkhead box O 3a (FoxO3a) is a member of the forkhead transcription factor family, which mediates cell proliferation and differentiation. However, the expression and function of FoxO3a during HSC activation remain largely unknown. FoxO3a overexpression was related to fibrosis in patients, and its expression was colocalized with desmin or α-smooth muscle actin, representative HSC markers. We also observed upregulated FoxO3a levels in two animal hepatic fibrosis models, a carbon tetrachloride-injected model and a bile duct ligation model. In addition, transforming growth factor beta (TGF-β) treatment in mouse primary HSCs or LX-2 cells elevated FoxO3a expression. When FoxO3a was upregulated by TGF-β in LX-2 cells, both the cytosolic and nuclear levels of FoxO3a increased. In addition, we found that the induction of FoxO3a by TGF-β was due to both transcriptional and proteasome-dependent mechanisms. Moreover, FoxO3a overexpression promoted TGF-β-mediated Smad activation. Furthermore, FoxO3a increased fibrogenic gene expression, which was reversed by FoxO3a knockdown. TGF-β-mediated FoxO3a overexpression in HSCs facilitated hepatic fibrogenesis, suggesting that FoxO3a may be a novel target for liver fibrosis prevention and treatment.
Crossroads of highly pathogenic H5N1: overlap between wild and domestic birds in the Black Sea-Mediterranean impacts global transmission
Authors: Hill Nichola J , Smith Lacy M , Muzaffar Sabir B , Nagel Jessica L , Prosser Diann J , Sullivan Jeffery D , Spragens Kyle A , DeMattos Carlos A , DeMattos Cecilia C , El Sayed Lu’ay , Erciyas-Yavuz Kiraz , Davis C Todd , Jones Joyce , Kis Zoltan , Donis Ruben O , Newman Scott  H , Takekawa John Y
Published: December 2020

Understanding transmission dynamics that link wild and domestic animals is a key element of predicting the emergence of infectious disease, an event that has highest likelihood of occurring wherever human livelihoods depend on agriculture and animal trade. Contact between poultry and wild birds is a key driver of the emergence of highly pathogenic avian influenza (HPAI), a process that allows for host switching and accelerated reassortment, diversification, and spread of virus between otherwise unconnected regions. This study addresses questions relevant to the spillover of HPAI at a transmission hotspot: what is the nature of the wild bird–poultry interface in Egypt and adjacent Black Sea-Mediterranean countries and how has this contributed to outbreaks occurring worldwide? Using a spatiotemporal model of infection risk informed by satellite tracking of waterfowl and viral phylogenetics, this study identified ecological conditions that contribute to spillover in this understudied region. Results indicated that multiple ducks (Northern Shoveler and Northern Pintail) hosted segments that shared ancestry with HPAI H5 from both clade 2.2.1 and clade 2.3.4 supporting the role of Anseriformes in linking viral populations in East Asia and Africa over large distances. Quantifying the overlap between wild ducks and H5N1-infected poultry revealed an increasing interface in late winter peaking in early spring when ducks expanded their range before migration, with key differences in the timing of poultry contact risk between local and long-distance migrants.
A survey of the most common methods of group randomization and distribution in pre‐clinical in vivo studies (1053.7)
Authors: Kumer Jeffrey , Ibsen Eric
Published: December 2020

To closely emulate clinical research methodology and improving clinical relevance, researchers are utilizing clinically‐similar group randomization and distribution methods for pre‐clinical studies in animals. One common approach, random number generator in a spreadsheet, is paradoxically the least clinically‐relevant and subject to manual and transcription errors. This method provides no easy way to exclude animals from distribution based on other parameters. Due to limitations in spreadsheet software, commercially available pre‐clinical trial applications can be used to perform the most accepted randomization and distribution methods: deterministic and matched distribution, pure randomization, stratified sampling randomization and block randomization across multiple numeric parameters. Subjects may be excluded initially based on recorded qualitative observations, and then by acceptable value ranges for numerical parameters. Animals can be randomized iteratively in rolling enrollment studies and previously randomized subjects can be re‐randomized into new groups for drug‐resistance studies. ANOVA results are displayed instantly to ensure similarity between groups. Standardizing randomization and distribution using clinically relevant methods improves the efficiency, clinical relevance, and outcome of animal studies relative to spreadsheet‐based methods.
National Metrics Improved Timeliness of Antibiotic Administration for Open Extremity Fractures
Authors: Shieh Alvin K. , Lucas Justin F. , Shelton Trevor J. , Wright Aaron J. , Steffner Robert J. , Wolinsky Philip R.
Published: December 2020

Introduction:

Antibiotics have been shown to be an essential component in the treatment of open extremity fractures. The American College of Surgeons' Trauma Quality Improvement Program, based on a committee of physician leaders including orthopaedic trauma surgeons, publishes best-practice guidelines for the management of open fractures. Accordingly, it established the tracking of antibiotic timing as a metric with a plan to use that metric before trauma center site reviews. Our hypothesis was that this physician-led effort at the national level would provide the necessary incentive to effect change within our institution.

Methods:

A retrospective review of all patients treated at our institution for open extremity fractures was performed over 3 periods separated by 2 quality initiatives. The first initiative was an institution-driven effort to increase awareness and educate specific departments about the importance of prompt antibiotic administration. The second initiative was the tracking of antibiotic order and administration times with quarterly audits following newly published guidelines.

Results:

Neither antibiotic order placement within 1 hour nor administration within 1 hour improved after our first institution-specific initiative. Both outcome measures significantly improved after the second quality initiative, as did median times from arrival to antibiotic order and administration.

Conclusions:

Metrics developed and measured by a physician-led national organization led to practice changes at our hospital. Tracking of antibiotic timing for open fracture treatment was more effective than institutional education of healthcare providers alone. This study suggests that nationally published guidelines, developed and measured by physician leaders, will be found to be relevant by other physicians and can be a powerful tool to drive change.
Determining Thresholds for Three Indices of Autoregulation to Identify the Lower Limit of Autoregulation During Cardiac Surgery*
Authors: Liu Xiuyun , Akiyoshi Kei , Nakano Mitsunori , Brady Ken , Bush Brian , Nadkarni Rohan , Venkataraman Archana , Koehler Raymond C. , Lee Jennifer K. , Hogue Charles W. , Czosnyka Marek , Smielewski Peter , Brown Charles H.
Published: December 2020

OBJECTIVES:

Monitoring cerebral autoregulation may help identify the lower limit of autoregulation in individual patients. Mean arterial blood pressure below lower limit of autoregulation appears to be a risk factor for postoperative acute kidney injury. Cerebral autoregulation can be monitored in real time using correlation approaches. However, the precise thresholds for different cerebral autoregulation indexes that identify the lower limit of autoregulation are unknown. We identified thresholds for intact autoregulation in patients during cardiopulmonary bypass surgery and examined the relevance of these thresholds to postoperative acute kidney injury.

DESIGN:

A single-center retrospective analysis.

SETTING:

Tertiary academic medical center.

PATIENTS:

Data from 59 patients was used to determine precise cerebral autoregulation thresholds for identification of the lower limit of autoregulation. These thresholds were validated in a larger cohort of 226 patients.

METHODS AND MAIN RESULTS:

Invasive mean arterial blood pressure, cerebral blood flow velocities, regional cortical oxygen saturation, and total hemoglobin were recorded simultaneously. Three cerebral autoregulation indices were calculated, including mean flow index, cerebral oximetry index, and hemoglobin volume index. Cerebral autoregulation curves for the three indices were plotted, and thresholds for each index were used to generate threshold- and index-specific lower limit of autoregulations. A reference lower limit of autoregulation could be identified in 59 patients by plotting cerebral blood flow velocity against mean arterial blood pressure to generate gold-standard Lassen curves. The lower limit of autoregulations defined at each threshold were compared with the gold-standard lower limit of autoregulation determined from Lassen curves. The results identified the following thresholds: mean flow index (0.45), cerebral oximetry index (0.35), and hemoglobin volume index (0.3). We then calculated the product of magnitude and duration of mean arterial blood pressure less than lower limit of autoregulation in a larger cohort of 226 patients. When using the lower limit of autoregulations identified by the optimal thresholds above, mean arterial blood pressure less than lower limit of autoregulation was greater in patients with acute kidney injury than in those without acute kidney injury.

CONCLUSIONS:

This study identified thresholds of intact and impaired cerebral autoregulation for three indices and showed that mean arterial blood pressure below lower limit of autoregulation is a risk factor for acute kidney injury after cardiac surgery.
Inherited Chromosomally Integrated Human Herpesvirus 6: An Unexpected Finding in a Septic Neonate
Authors: Pugni Lorenza , Pietrasanta Carlo , Ronchi Andrea , Lunghi Giovanna , Pellegrinelli Laura , Mosca Fabio , Campanini Giulia , Baldanti Fausto
Published: December 2020

Human herpesvirus 6 (HHV-6) can integrate its genome in human chromosomes and be germline transmitted (inherited chromosomally integrated HHV-6). We report a case of chromosomally integrated HHV-6 inherited from the mother unexpectedly diagnosed in a septic neonate. Since HHV-6 has recently been included in multiplex polymerase chain reaction assays for meningitis/encephalitis, diagnosing inherited chromosomally integrated HHV-6 status is essential to avoid misdiagnosis of active HHV-6 infection and unnecessary antiviral treatment.
Role of rheology in tears and artificial tears
Authors: A. Arshinoff Steve , Hofmann Ilan , Nae Hemi
Published: December 2020

The study of viscoelastic fluids as artificial tears dates back to the late 1970s. Healon, the first ophthalmic viscosurgical device, was approved in 1980, but studied extensively before then, exhibits very interesting shear-thinning properties that were found to be beneficial in both ophthalmic surgery and somewhat later as a tear replacement solution. Unlike the previous tear film replacements, which were mainly viscous in nature, viscoelastic solutions, particularly those based on hyaluronan, exhibited very interesting, potentially beneficial, rheological properties, especially when slightly altered to become elastoviscous. This review examines the rheological properties that are significant in artificial tear solutions. We define herein the necessary parameters that need to be further studied to design and formulate rheologically better artificial tears, which should provide enhanced efficacy compared with their predecessors.
Using technology to assess nutritional status and optimize nutrition therapy in critically ill patients
Authors: Dong Victor , Karvellas Constantine J.
Published: December 2020

Purpose of review

Malnutrition is prevalent in critically ill patients and is linked to worse outcomes such as prolonged mechanical ventilation, length of intensive care unit (ICU) stay, and increased mortality. Therefore, nutritional therapy is important. However, it is often difficult to accurately identify those at high malnutrition risk and to optimize nutritional support. Different technological modalities have therefore been developed to identify patients at high nutritional risk and to guide nutritional support in an attempt to optimize outcomes.

Recent findings

Computed tomography (CT), ultrasound (US), and bioelectrical impedance analysis are tools that allow assessment of lean body mass and detection of sarcopenia, which is a significant marker of poor nutrition. The use of indirect calorimetry allows the determination of resting energy expenditure to serve as a guide to providing optimal nutrition intake in ICU patients.

By using CT, US, or bioelectrical impedance analysis, detection of sarcopenia can be undertaken in patients admitted to the ICU. This allows for an accurate picture of underlying nutritional status to help clinicians focus on nutritional support for these patients. Subsequently, indirect calorimetry can be used to guide optimal nutrition therapy and caloric intake in critically ill patients. However, whether these methods result in improved outcomes in critically ill patients remains to be validated.
Novel therapies for familial hypercholesterolemia
Authors: Mohamed Farzahna , Seedat Faheem , Raal Frederick J.
Published: December 2020

Purpose of review

Familial hypercholesterolemia is a genetic disorder of defective clearance and subsequent increase in serum LDL cholesterol (LDL-C) with a resultant increased risk of premature atherosclerotic cardiovascular disease. Despite treatment with traditional lipid-lowering therapies (LLT), most patients with familial hypercholesterolemia are unable to achieve target LDL-C. We review current and future novel therapeutic options available for familial hypercholesterolemia.

Recent findings

The use of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are effective in lowering LDL-C in patients with familial hypercholesterolemia, with a reduction in LDL-C of 60% in heterozygous familial hypercholesterolemia (HeFH) and up to 35% in homozygous familial hypercholesterolemia (HoFH). Inclisiran, another novel agent, is a small-interfering ribonucleic acid that reduces hepatic production of PCSK9 to provide a prolonged and sustained reduction in LDL-C of nearly 50% in HeFH. However, both agents require LDL receptor (LDLR) activity. Evinacumab, a novel monoclonal antibody against angiopoetin-like 3 (ANGPTL3), reduces LDL-C by 50% independent of LDLR activity.

Achieving a target LDL-C in familial hypercholesterolemia can be challenging with standard LLT; however, novel therapeutic modalities show remarkable reductions in LDL-C allowing nearly all patients with HeFH and a significant proportion of patients with HoFH to achieve acceptable LDL-C levels.
Advances in the management of statin myopathy
Authors: Gallo Antonio , Perregaux Jeff , Bruckert Eric
Published: December 2020

Purpose of review

Statins are highly effective therapies for reducing low-density lipoprotein cholesterol and preventing cardiovascular events. However, many patients taking statins experience statin-associated muscle symptoms. In the current manuscript, we review algorithms to define statin intolerance and approaches to optimize cardiovascular risk reduction and reduce the nocebo effect among individuals reporting statin-associated muscle pain.

Recent findings

Patients with statin intolerance have a higher cardiovascular event risk. These data underscore the need to apply clinical strategies that improve treatment utilization and adherence of patients experiencing statin-related side effects. Recent data have shown that the nocebo effect is frequent with statin therapy. This may be explained by the high frequency of muscle symptoms in the general population and media misinformation. When statins even at a low dosage are not tolerated other therapies can be used such as fibrate, ezetimibe nutraceuticals and antiPCSK9 antibodies. Recent data have identified other alternative therapeutic strategies such as bempedoic acid.

There are multiple strategies for the management of statin-intolerance, both pharmacological and nonpharmacological. Patient involvement in the justification of statin treatment indication and therapeutic choice is the first step to overcome misbelief and reduce nocebo effect.
The role of the molecular circadian clock in human energy homeostasis
Authors: Dollet Lucile , Pendergrast Logan A. , Zierath Juleen R.
Published: December 2020

Purpose of review

The aim of this review is to present the latest findings on the role of the circadian clock in the control of metabolism, and the therapeutic potential of chronotherapy to regulate energy homeostasis in humans.

Recent findings

We summarized the recent advances related to circadian clock regulation of food intake and energy expenditure. In peripheral organs, mitochondrial oxidative capacity and lipolysis show circadian pattern in humans, and rhythms disruption may be involved in the pathogenesis of metabolic diseases. Indeed, circadian desynchrony affects food intake, insulin sensitivity, and increases the risk of developing metabolic disease. Time-targeted strategies, which aim to synchronize external cues with the molecular clock to improve metabolic outcomes, have positive effects on metabolism in humans, with several studies showing that time-targeted feeding improves body weight loss and glucose tolerance.

The interest in time-targeted strategies to prevent or manage metabolic disturbances has grown this past year with encouraging health benefits. To maximize the therapeutic effect of these strategies, further research is warranted to delineate the molecular regulation of metabolic processes controlled by the clock and especially its modulation in contexts such as aging, sex differences, or metabolic diseases.
Impact of metabolic dysfunction on cognition in humans
Authors: Juul Rasmussen Ida , Qvist Thomassen Jesper , Frikke-Schmidt Ruth
Published: December 2020

Purpose of review

The current review evaluates the recent literature on the impact of metabolic dysfunction in human cognition, focusing on epidemiological studies and meta-analyses of these.

Recent findings

Worldwide around 50 million people live with dementia, a number projected to triple by 2050. Recent reports from the Lancet Commission suggest that 40% of dementia cases may be preventable primarily by focusing on well established metabolic dysfunction components and cardiovascular risk factors.

There is robust evidence that type 2 diabetes and midlife hypertension increase risk of dementia in late life. Obesity and elevated levels of LDL cholesterol in midlife probably increase risk of dementia, but further research is needed in these areas. Physical activity, diet, alcohol, and smoking might also influence the risk of dementia through their effect on metabolic dysfunction. A key recommendation is to be ambitious about prevention, focusing on interventions to promote healthier lifestyles combating metabolic dysfunction. Only comprehensive multidomain and staff-requiring interventions are however efficient to maintain or improve cognition in at-risk individuals and will be unrealistic economic burdens for most societies to implement. Therefore, a risk score that identifies high-risk individuals will enable a targeted early intensive intervention toward those high-risk individuals that will benefit the most from a prevention against cardiovascular risk factors and metabolic dysfunction.
Osteogenesis imperfecta: treatment and surgical management
Authors: Hidalgo Perea Sofia , Green Daniel W.
Published: December 2020

Purpose of review

Osteogenesis imperfecta is a disease with many different causes and clinical presentations. Surgery at a young age is the often required in order to improve the patients’ growth development and quality of life. This manuscript highlights the current approach to treat children with osteogenesis imperfecta. The main purpose of this review is to compare and discuss the latest surgical techniques and procedures.

Recent findings

Recent studies have indicated that telescoping intramedullary Faisser-Duval rods are one of the most suitable surgical devices to correct long bone deformities. The design permits elongation with growth and helps reduce the number of revision surgeries compared to previous static devices.

Osteogenesis imperfecta patients require an interdisciplinary and tailored treatment that involves both medical and surgical components. On the basis of the most recent surgical and medical findings, the authors recommend treating osteogenesis imperfecta patients early with bisphosphonates prior to surgical intervention and then utilizing Faisser-Duval rods in a surgical setting to correct lower extremity deformities and fractures.
Evaluation and selection of the liver transplant candidate: updates on a dynamic and evolving process
Authors: Kriss Michael , Biggins Scott W.
Published: December 2020

Purpose of review

Although conceptually unchanged, the evaluation and selection of the liver transplant candidate has seen significant recent advances. Expanding criteria for transplant candidacy, improved diagnostics for risk stratification and advances in prognostic models have paralleled recent changes in allocation and distribution that require us to revisit core concepts of candidate evaluation and selection while recognizing its now dynamic and continuous nature.

Recent findings

The liver transplant evaluation revolves around three interrelated themes: candidate selection, donor selection and transplant outcome. Introduction of dynamic frailty indices, bariatric surgery at the time of liver transplant in obese patients and improved therapies and prognostic tools for hepatobiliary malignancy have transformed candidate selection. Advances in hypothermic organ preservation have improved outcomes in marginal donor organs. Combined with expansion of hepatitis C virus positive and split donor organs, donor selection has become an integral part of candidate evaluation. In addition, with liver transplant for acute alcohol-related hepatitis now widely performed and increasing recognition of acute-on-chronic liver failure, selection of critically ill patients is refining tools to balance futility versus utility.

Advances in liver transplant candidate evaluation continue to transform the evaluation process and require continued incorporation into our clinical practice amidst a dynamic backdrop of demographic and policy changes.
Living donation – any news on the donor?
Authors: Haugen Anders J. , Mjøen Geir
Published: December 2020

Purpose of review

Living kidney donation has been an established practice for many years. Although studies from the past decade have uncovered risks to the donor, living kidney donation is still promoted. In this review, the most recent studies are summarized.

Recent findings

Retrospective studies with long follow-up have detected an increased risk of hypertension among donors. Donors with hypertension at the time of donation may be at increased risk of adverse outcomes, but results differ. Recent studies have not found increased long-term mortality, but follow-up is short and control groups are of different quality.

In all, the most recent findings more or less corroborate previous knowledge in the field of living donation. There is still a need for new studies on mortality with appropriate control groups and long enough follow-up.
An Exploratory Study on Physical Function in Stem Cell Transplant Patients Undergoing Corticosteroid Treatment for Acute Graft-Versus-Host-Disease
Authors: Ngo-Huang An , Yadav Rajesh , Bansal Swati , Williams Janet , Wu Jimin , Fu Jack B. , Alousi Amin M. , Bruera Eduardo
Published: December 2020

Acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation is treated with corticosteroids, placing patients at risk for steroid myopathy. In this single-arm cohort study, 23 patients who were started on high-dose corticosteroids for acute graft-versus-host disease underwent a series of functional tests (baseline and days 14, 28, and 56): 6-min walk test, hip flexor and knee extensor strength via dynamometry, five times sit-to-stand, Brooke scale for myopathy, modified Adult Myopathy Assessment Tool, and manual muscle testing. Participants were prescribed home exercises including walking and resistance exercises, with low adherence. Fifteen (63%) participants were male and median (range) age was 60 (36–70) yrs. Median (range) corticosteroid duration and cumulative equivalent methylprednisolone dose were 66 (22–165) days and 3625 (1020–11720) mg, respectively. At day 14, there was a significant decline in five times sit-to-stand (P = 0.0132), knee extensor (P = 0.0182), and manual muscle testing (P = 0.0466). Functional tests negatively associated with cumulative corticosteroid dose included 6-min walk test distance (P = 0.0103), hip flexor strength (P = 0.0262), knee extensor strength (P = 0.0369), and manual muscle testing strength (P = 0.0319). Five times sit-to-stand was positively associated with corticosteroid dose (P = 0.0003). In conclusion, stem cell transplant patients receiving high-dose corticosteroids for acute graft-versus-host disease are at risk for weakness detected as early as day 14. Increasing adherence to exercise may mitigate these changes.
Cotrimoxazole and clindamycin in skin and soft tissue infections
Authors: Montravers Philippe , Eckmann Christian
Published: December 2020

Purpose of review

The aim of this study was to present recent microbiological, experimental, clinical and tolerance data for cotrimoxazole and clindamycin in the specific field of skin and soft tissue infections (SSTIs).

Recent findings

Staphylococcus aureus and streptococci remain the leading cause of SSTIs. Cotrimoxazole is a good anti-Gram-positive agent with preserved activity against methicillin-susceptible and methicillin-resistant S. aureus (MRSA) and streptococci. Although clindamycin has good methicillin-susceptible S. aureus activity, a growing number of resistant MRSA and streptococci have been reported. Strong experimental data support the antitoxin activity of clindamycin, but clinical observations remain scarce. Several recent randomized trials involving cotrimoxazole and/or clindamycin demonstrate the efficacy and tolerance of both drugs. The oral formulation of both drugs may facilitate the implementation of early switch and early discharge protocols in clinical practice.

Recent publications demonstrate that cotrimoxazole and clindamycin remain reliable and realistic therapeutic approaches for SSTIs.
Current management of necrotizing soft-tissue infections
Authors: Eckmann Christian , Montravers Philippe
Published: December 2020

Purpose of review

The aim of the article is to present recent epidemiological, microbiological, and clinical data for the surgical, antimicrobial, and adjunctive management of necrotizing soft-tissue infections (NSTI).

Recent findings

NSTI can be caused by a broad variety of organisms. Reports about NSTI caused by multidrug-resistant bacteria are increasing. Owing to the rareness of NSTI, general clinical awareness is low and prompt diagnosis is often delayed. New diagnostic instruments (scoring systems, MRI) have either a low accuracy or are time consuming and cannot guide clinicians reliable currently. The value of adjunctive measures (intravenous immunoglobulin, hyperbaric oxygen therapy) is uncertain as well. Morbidity and mortality in NSTI remain high, ranging from 20 up to over 30%.

Early radical surgical debridement and empirical broad-spectrum antimicrobial treatment remain the cornerstones of therapy in NSTI. Further clinical research is necessary to shorten diagnostic pathways and to optimize surgical, antimicrobial, and adjunctive treatment.
Transgender Scrotoplasty and Perineal Reconstruction With Labia Majora Flaps
Authors: Miller Travis J. , Lin Walter C. , Safa Bauback , Watt Andrew J. , Chen Mang L.
Published: December 2020

Purpose

Labia majora, the embryologic homologs of the scrotum, are ideal donor tissue for transgender scrotoplasty. The technique is detailed, and surgical outcomes are assessed for scrotoplasty using labia majora rotational advancement flaps.

Methods

We retrospectively reviewed the outcomes of phalloplasty patients who underwent either primary or secondary labia majora flap scrotoplasty and perineal reconstruction from October 1, 2017, to December 1, 2019. Bilateral elevation and rotational flap advancement from the posterior to anterior position formed a pouch-like scrotum. Perineal reconstruction involved multilayered closure with apposition of the inner thigh skin.

Results

The mean follow-up was 12.5 months (0.5–26 months). One hundred forty-seven scrotoplasties were performed. Of the 147 total scrotoplasty patients, 133 had labia majora flap scrotoplasty and perineal reconstruction with single-stage phalloplasty. Distal flap necrosis occurred in 6 patients (4.1%); 5 were ipsilateral to the groin dissection required for phalloplasty. Large (>1 cm diameter) perineoscrotal junction dehiscence occurred in 7 patients (4.7%). All wounds were managed conservatively except for 3 patients who developed urethrocutaneous fistulas at the perineoscrotal junction. All 3 patients required fistula repair. Two (1.4%) scrotal hematomas and 3 (2.0%) perineal hematomas were seen; all required operative intervention.

Conclusions

Labia majora flap scrotoplasty via the bilateral rotational advancement technique and perineal reconstruction can be safely performed during phalloplasty. Minor wound complications are common and frequently heal with conservative management. Wounds that do not heal may be associated with urethral complications. Hematomas are rare but usually require operative intervention.
Advances in ophthalmic structural and functional measures in multiple sclerosis: do the potential ocular biomarkers meet the unmet needs?
Authors: Jiang Hong , Delgado Silvia , Wang Jianhua
Published: December 2020

Purpose of review

Multiple sclerosis is a heterogeneous disorder. Biomarkers to monitor disease activities are highly desirable especially because of the recent shift toward personalized medicine that coincides with the expansion of disease-modifying therapy. The visual system is highly involved in multiple sclerosis, and the rapid advancement of ophthalmic techniques has boosted the development of potential ocular biomarkers for multiple sclerosis management.

Recent findings

Recent studies have found that the rapid thinning of the peripapillary retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) occurs in the progressive stage. Furthermore, the inter-eye thickness difference of the GCIPL could be used in identifying unilateral optic neuritis to facilitate the early diagnosis of multiple sclerosis. Moreover, the retinal microvascular alterations measured as vessel density were found to be related to the disability and visual function, although a standardized protocol to measure retinal microvascular alterations has not been well established. Additionally, aberrant ocular motility, such as fixation microsaccades, can be used to measure disability objectively.

The fast expansion of potential ocular biomarkers measured as retinal microstructural, microvascular, and ocular motility changes may facilitate the diagnosis and management of multiple sclerosis.