bluuebunny/crossref_metadata_2025 huggingface dataset:
New systemic agents for hepatocellular carcinoma: an update 2020
Authors: von Felden Johann
Published: February 2020

Purpose of review

Despite major therapeutic improvements in most cancer entities, hepatocellular carcinoma (HCC) has remained a dismal disease. In fact, incidence and mortality are increasing in many parts of the world, including the United States. Given that a number of systemic agents has recently been tested positive in phase 3 clinical trials, the objective of this review is to summarize the current treatment landscape for advanced HCC.

Recent findings

Following the positive SHARP trial in 2008, sorafenib has been the only systemic agent for advanced HCC for almost a decade. However, in first line, lenvatinib was tested noninferior to sorafenib, and most recently, the combination of atezolizumab with bevacizumab was tested superior to sorafenib. In second line, regorafenib, cabozantinib, and ramucirumab (the latter for patients with AFP ≥400 ng/ml) have shown prolonged overall survival compared with placebo.

Systemic treatment options for advanced HCC have substantially increased over the past years. The combination of atezolizumab and bevacizumab will likely become the new standard of care as it is the first treatment to report improved overall survival compared with sorafenib and the first, and so far only, positive phase 3 clinical trial for an immune-checkpoint inhibitor-containing regimen in advanced HCC.
Comparison of International Growth Standards for Assessing Nutritional Status in Cystic Fibrosis
Authors: Poulimeneas Dimitrios , Grammatikopoulou Maria G. , Petrocheilou Argyri , Kaditis Athanasios G. , Troupi Evgenia , Doudounakis Stavros E. , Laggas Dimitrios , Vassilakou Tonia
Published: February 2020

Objective:

The aim of the study was to compare 3 international growth references and explore their differences in assessing growth in Greek school‐aged patients with cystic fibrosis (CF).

Methods:

Sample included 114 patients (50 boys, age 11.5 ± 3.9 years), provided care at Aghia Sofia Children's Hospital, Greece. Anthropometrics and predicted forced expiratory volume in 1 second (FEV1%) were measured. Body mass index (BMI) and height z scores were computed according to the Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), and International Obesity Task Force (IOTF) references. Agreement between methods was analyzed with kappa statistics, repeated‐measures analysis of variance, and Bland‐Altman analysis. The relationship between FEV1% and BMI was explored with linear regression.

Results:

Mean CDC BMI z score was the lowest (0.06 ± 1.08), followed by WHO (0.17 ± 1.14) and IOTF (0.35 ± 1.05) (P ≤ 0.001 for all). The CDC and WHO growth references highly agreed for most weight status strata and stunting; all other comparisons produced lower agreements. Except for CDC and IOTF BMI z scores, all other comparisons produced wide levels of agreement and proportional bias. CDC reference classified more children as attaining low or normal weight, against WHO or IOTF (P ≤ 0.001 for all). Lowest prevalence of ideal and excess weight was recorded by CDC, compared to all other standards (P ≤ 0.001 for all). All BMI z scores provided moderate associations with FEV1%.

Conclusion:

Large variations across weight status classification were present when employing 3 growth standards in school‐aged patients . Given than BMI z‐scores from all references provided comparable associations with pulmonary function, our data indicate that no studied reference is better than others in assessing growth in CF.
An Usual Presentation of Pneumocystis jirovecii Pneumonia in a Woman Treated With Immune Checkpoint Inhibitor
Authors: Si Stephanie , Erickson Kelley , Evageliou Nicholas , Silverman Michael , Kersun Leslie
Published: February 2020

We describe a case of Pneumocystis jirovecii pneumonia in an 18-year-old female individual with refractory primary mediastinal B-cell lymphoma treated with the immune checkpoint inhibitor pembrolizumab. She received 11 doses of pembrolizumab without immune-related adverse events (irAEs) before the diagnosis of P. jirovecii pneumonia. However, prophylactic trimethoprim/sulfamethoxazole was discontinued 6 months of postautologous stem cell transplant per standard guidelines. This case report highlights the importance of judicious infectious disease evaluation while on immune checkpoint inhibitor therapy as symptoms can often mimic irAEs. Furthermore, the benefits of immunosuppressive therapy for the treatment of presumptive irAEs must be weighed against the possible increased risk for opportunistic infections.
Nosocomial Infection Following Severe Traumatic Injury in Children
Authors: Sribnick Eric A. , Hensley Josey , Moore-Clingenpeel Melissa , Muszynski Jennifer A. , Thakkar Rajan K. , Hall Mark W.
Published: February 2020

Objectives:

Nosocomial infection is a common source of morbidity in critically injured children including those with traumatic brain injury. Risk factors for nosocomial infection in this population, however, are poorly understood. We hypothesized that critically ill pediatric trauma patients with traumatic brain injury would demonstrate higher rates of nosocomial infection than those without traumatic brain injury.

Design:

Retrospective case-control study.

Setting:

PICU, single institution.

Patients:

Patients under 18 years old who were admitted to the PICU for at least 48 hours following a traumatic injury were included. Patients were admitted between September 2008 and December 2015. Patients with the following injury types were excluded: thermal injury, drowning, hanging/strangulation, acute hypoxic ischemic encephalopathy, or nonaccidental trauma. Data collected included demographics, injury information, hospital and PICU length of stay, vital signs, laboratory data, insertion and removal dates for invasive devices, surgeries performed, transfusions of blood products, and microbiology culture results. Initial Pediatric Risk of Mortality III and Pediatric Logistic Organ Dysfunction-2 scores were determined. Patients were classified as having: 1) an isolated traumatic brain injury, 2) a traumatic injury without traumatic brain injury, or 3) polytrauma with traumatic brain injury.

Interventions:

None.

Measurements and Main Results:

Two hundred three patients were included in the analyses, and 27 patients developed a nosocomial infection. Patients with polytrauma with traumatic brain injury demonstrated a significantly higher infection rate (30%) than patients with isolated traumatic brain injury (6%) or traumatic injury without traumatic brain injury (9%) (p < 0.001). This increased rate of nosocomial infection was noted on univariate analysis, on multivariable analysis, and after adjusting for other risk factors.

Conclusions:

In this single-center, retrospective analysis of critically ill pediatric trauma patients, nosocomial infections were more frequently observed in patients admitted following polytrauma with traumatic brain injury than in patients with isolated traumatic brain injury or trauma without traumatic brain injury.
Impact of Personal Protective Equipment on the Performance of Emergency Pediatric Tasks
Authors: Adler Mark D. , Krug Steven , Eiger Carmel , Good Grace L. , Kou Maybelle , Nash Mark , Henretig Fred M. , Hornik Christoph P. , Gosnell Leigh , Chen Jia-Yuh , Debski Julie , Sharma Gaurav , Siegel David , Donoghue Aaron J. ,   on behalf of the Best Pharmaceuticals for Children Act–Pediatric Trials Network
Published: February 2020

Objectives

Personal protective equipment (PPE) is worn by health care providers (HCPs) to protect against hazardous exposures. Studies of HCPs performing critical resuscitation tasks in PPE have yielded mixed results and have not evaluated performance in care of children. We evaluated the impacts of PPE on timeliness or success of emergency procedures performed by pediatric HCPs.

Methods

This prospective study was conducted at 2 tertiary children's hospitals. For session 1, HCPs (medical doctors and registered nurses) wore normal attire; for session 2, they wore full-shroud PPE garb with 2 glove types: Ebola level or chemical. During each session, they performed clinical tasks on a patient simulator: intubation, bag-valve mask ventilation, venous catheter (IV) placement, push-pull fluid bolus, and defibrillation. Differences in completion time per task were compared.

Results

There were no significant differences in medical doctor completion time across sessions. For registered nurses, there was a significant difference between baseline and PPE sessions for both defibrillation and IV placement tasks. Registered nurses were faster to defibrillate in Ebola PPE and slower when wearing chemical PPE (median difference, −3.5 vs 2 seconds, respectively; P < 0.01). Registered nurse IV placement took longer in Ebola and chemical PPE (5.5 vs 42 seconds, respectively; P < 0.01). After the PPE session, participants were significantly less likely to indicate that full-body PPE interfered with procedures, was claustrophobic, or slowed them down.

Conclusions

Personal protective equipment did not affect procedure timeliness or success on a simulated child, with the exception of IV placement. Further study is needed to investigate PPE's impact on procedures performed in a clinical care context.
Deep Neck Abscesses in Children
Authors: Donà Daniele , Gastaldi Andrea , Campagna Marta , Montagnani Carlotta , Galli Luisa , Trapani Sandra , Pierossi Nicola , De Luca Maia , D'Argenio Patrizia , Tucci Filippo Maria , De Vincentiis Giovanni , Grotto Paolo , Da Mosto Maria Cristina , Frigo Anna Chiara , Volo Tiziana , Emanuelli Enzo , Martini Alessandro , Da Dalt Liviana
Published: February 2020

Background

Retropharyngeal and parapharyngeal abscesses (RPAs, PPAs) usually affect young children. Surgical drainage and/or antibiotic therapy are treatment of choice, but no specific guidelines exist. In order to reduce the risk of severe complications, appropriate diagnosis and therapy are necessary. The aims of the study were to review diagnosis and management of children with RPAs/PPAs and to compare surgical versus medical approach.

Methods

This is a multicenter retrospective study including all patients younger than 15 years admitted at 4 Italian pediatric hospitals of Florence, Padua, Rome, and Treviso, with International Classification of Diseases, Ninth Revision discharge diagnosis code of RPAs and PPAs, from January 1, 2008, to December 31, 2016.

Results

One hundred fifty-three children were included. The median age was 4.4 years, with overall male predominance. Heterogeneous signs and symptoms (fever, neck cervical, lymphadenopathy, pain, and stiff neck most frequently) and a large mixture of bacteria from pus cultures were detected. Computer tomography (66.7%) and magnetic resonance imaging (27.5%) were performed to confirm the presence of abscess. Fifty-one percent of abscesses were greater than 3 cm. Eighty-seven patients (56.9%) underwent surgery, and 66 (43.1%) were treated with antibiotics alone (mostly ceftriaxone, metronidazole, amikacin, and clindamycin) with median days of therapy of 26.5 days and length of therapy of 16.0 days of median. Median length of stay was 11 days. None had severe complications. Multivariate analysis indicated as independent predictive factors of surgery abscess of 3 cm or greater, high white blood cell count, and—most of all—the hospital of admission.

Conclusions

Deep neck abscesses mostly affect patients in early childhood, with a combination of nonspecific signs and symptoms, and it still emerges as a heterogeneous approach in diagnosis and management of these infections. Thus, common shared protocols represent an essential tool in order to standardize care and improve patients' outcomes.
The Nonsurgical Rhinoplasty: A Retrospective Review of 5000 Treatments
Authors: Harb Ayad , Brewster Colin T.
Published: February 2020

Background:

Nonsurgical rhinoplasty with injectable dermal fillers has become an increasingly popular alternative to surgical procedures, in view of its relative low cost, convenience and rapid recovery, and low risk profile. The safety and efficacy of nonsurgical rhinoplasty remains a relatively contentious and ambiguous matter, given that there are few large-scale series reporting results or complications. This study reports the experience of a single clinician performing nonsurgical rhinoplasty in the largest cohort to date.

Methods:

Patient demographics, indications, treatment details, and outcomes of patients treated between March of 2016 and January of 2019 were reviewed. The nonsurgical rhinoplasty technique described previously by Harb was used using hyaluronic acid dermal filler.

Results:

Nonsurgical rhinoplasty was performed in 5000 patients. The commonest indication was dorsal hump (44 percent). Swelling and erythema were self-limiting side effects encountered in approximately half of patients. Infection was seen in two patients, and localized skin necrosis was observed in three patients.

Conclusions:

Nonsurgical rhinoplasty is a safe procedure with positive aesthetic results when performed by an experienced clinician. Knowledge of nasal anatomy, comprehensive training, and use of appropriate materials are key in ensuring safety and results.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Fat Graft Enrichment Strategies: A Systematic Review
Authors: Vyas Krishna S. , Vasconez Henry C. , Morrison Shane , Mogni Benjamin , Linton Samuel , Hockensmith Lindsay , Kabir Tanvir , Zielins Elizabeth , Najor Anna , Bakri Karim , Mardini Samir
Published: February 2020

Background:

Autologous fat grafting is a dynamic modality used in plastic surgery as an adjunct to improve functional and aesthetic form. However, current practices in fat grafting for soft-tissue augmentation are plagued by tremendous variability in long-term graft retention, resulting in suboptimal outcomes and repetitive procedures. This systematic review identifies and critically appraises the evidence for various enrichment strategies that can be used to augment and improve the viability of fat grafts.

Methods:

A comprehensive literature search of the Medline and PubMed databases was conducted for animal and human studies published through October of 2017 with multiple search terms related to adipose graft enrichment agents encompassing growth factors, platelet-rich plasma, adipose-derived and bone marrow stem cells, gene therapy, tissue engineering, and other strategies. Data on level of evidence, techniques, complications, and outcomes were collected.

Results:

A total of 1382 articles were identified, of which 147 met inclusion criteria. The majority of enrichment strategies demonstrated positive benefit for fat graft survival, particularly with growth factors and adipose-derived stem cell enrichment. Platelet-rich plasma and adipose-derived stem cells had the strongest evidence to support efficacy in human studies and may demonstrate a dose-dependent effect.

Conclusions:

Improved understanding of enrichment strategies contributing to fat graft survival can help to optimize safety and outcomes. Controlled clinical studies are lacking, and future studies should examine factors influencing graft survival through controlled clinical trials in order to establish safety and to obtain consistent outcomes.
Complications after Breast Augmentation with Fat Grafting: A Systematic Review
Authors: Ørholt Mathias , Larsen Andreas , Hemmingsen Mathilde N. , Mirian Christian , Zocchi Michele L. , Vester-Glowinski Peter V. , Herly Mikkel
Published: February 2020

Background:

Breast augmentation with fat grafting is used as an alternative to breast implants. However, a systematic evaluation of the complication rates after fat grafting using only studies with consecutive patients has not previously been performed. In this study, the authors compiled studies reporting complication rates and radiologic changes in consecutive patients undergoing cosmetic breast augmentation with fat grafting.

Methods:

Studies reporting on consecutive patients undergoing breast augmentation with fat grafting were included. Complication rates, radiologic changes, Breast Imaging Reporting and Data System assessments, and the number of patients undergoing revision surgery were extracted. Mean complication rates and radiologic changes were calculated with meta-analytical methods.

Results:

Twenty-two studies with 2073 patients were included. The rates of major complications were low (hematoma, 0.5 percent; infection, 0.6 percent; and seroma, 0.1 percent). None of these patients needed revision surgery. The most frequent minor complication was palpable cysts in 2.0 percent of the patients; 67 percent of these were treated with aspiration. The radiologic changes in the patients after fat grafting were as follows: oil cysts, 6.5 percent; calcifications, 4.5 percent; and fat necrosis, 1.2 percent. The risk of being referred for additional radiologic imaging (e.g., to exclude malignant changes) was 16.4 percent, and the risk of being referred for biopsy was 3.2 percent.

Conclusions:

The complication rates after breast augmentation with fat grafting are low and support fat grafting as an alternative to breast augmentation with implants. The rates of radiologic changes are high after fat grafting, but the changes do not seem to have any therapeutic consequences for the patients.
Effect of Parental English Proficiency on Psychosocial Functioning in Children with Craniofacial Anomalies
Authors: De Leon Fransia S. , Pfaff Miles J. , Volpicelli Elizabeth J. , Potemra Hi’ilani M. K. , Lin Johnny , Ayeroff Julia R. , Bradley James P. , Wilson Libby F. , Lee Justine C.
Published: February 2020

Background:

Psychosocial distress in children with craniofacial anomalies is multifactorial. A known cause of childhood psychosocial distress is parental limited English proficiency; however, its role as a psychosocial stressor in the craniofacial anomaly population remains unknown. The current study aimed to understand the potential influence of parental English proficiency in children with craniofacial anomalies.

Methods:

Two hundred ninety-six children were prospectively evaluated at the University of California, Los Angels and the Orthopaedic Institute for Children using the Pediatric Patient-Reported Outcomes Measurement Information System to assess anger, anxiety, depression, and peer relationships. Children were grouped by parental English proficiency based on the requirement or lack thereof for interpreting services during clinic appointments. Independent t tests, analyses of variance, and linear regressions were performed to compare groups and identify predictors for psychosocial functioning.

Results:

Although comparison children did not exhibit any differences in psychosocial scores with respect to parental English proficiency, craniofacial anomaly children with parents who have limited English proficiency demonstrated higher anger, anxiety, depression, and lower peer relationships compared with those with parents who are English proficient. Linear regression analyses demonstrated that limited English proficiency in parents was a significant predictor for anger (p = 0.005), anxiety (p = 0.002), depression (p < 0.001), and poor peer relationships (p < 0.001) in children with craniofacial anomalies.

Conclusions:

Parental English proficiency is associated with increased psychosocial distress in children with craniofacial anomalies. Future efforts toward identification of and assistance for parents with limited English proficiency to address barriers to care may improve psychosocial function in children with craniofacial anomalies.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Estimating the probability of diagnosis within 1 year of HIV acquisition
Authors: Xia Qiang , Lim Sungwoo , Wu Baohua , Forgione Lisa A. , Crossa Aldo , Balaji Alexandra B. , Braunstein Sarah L. , Daskalakis Demetre C. , Tsoi Benjamin W. , Harriman Graham , Torian Lucia V. , Song Ruiguang
Published: February 2020

Background:

Early diagnosis of HIV is important for the prevention of ongoing transmission and development of HIV-related illness. The purpose of this study is to develop an outcome indicator to monitor the progress in early HIV diagnosis.

Methods:

Persons diagnosed with HIV in New York City and their first CD4+test results were used to estimate the distribution of HIV diagnosis delay, based on a CD4+count depletion model. The distribution was then used to estimate the probability of diagnosis within 1 year of HIV acquisition, which is the number of cases diagnosed in a given calendar year for which diagnosis occurred within 1 year of acquisition divided by the number of incident cases in that calendar year.

Results:

In 2012–2016, the estimated annual probability of diagnosis within 1 year of HIV acquisition in New York City was 43.0% [95% confidence interval (CI): 37.9–48.2%), 42.5% (95% CI: 36.8--48.3%), 42.8% (95% CI: 36.3--49.2%), 42.9% (95% CI: 35.4--50.3%), and 42.2% (95% CI: 33.1--51.2%), respectively.

Conclusion:

National and local health jurisdictions should consider using this new outcome indicator, the probability of diagnosis within 1 year of HIV acquisition, to monitor their progress in early HIV diagnosis.
No Changes in T1 Relaxometry After a Mean of 11 Administrations of Gadobutrol
Authors: Deike-Hofmann Katerina , Reuter Julia , Haase Robert , Kuder Tristan , Paech Daniel , Bickelhaupt Sebastian , Forsting Michael , Schlemmer Heinz-Peter , Heußel Claus Peter , Radbruch Alexander
Published: February 2020

Objectives

Quantitative T1 relaxometry is the benchmark in imaging potential gadolinium deposition and known to be superior to semiquantitative signal intensity ratio analyses. However, T1 relaxometry studies are rare, commonly limited to a few target structures, and reported results are inconsistent.

We systematically investigated quantitative T1 relaxation times (qT1) of a variety of brain nuclei after serial application of gadobutrol.

Materials and Methods

Retrospectively, qT1 measurements were performed in a patient cohort with a mean number of 11 gadobutrol applications (n = 46) and compared with a control group with no prior gadolinium-based contrast agent administration (n = 48). The following target structures were evaluated: dentate nucleus, globus pallidus, thalamus, hippocampus, putamen, caudate, amygdala, and different white matter areas. Subsequently, multivariate regression analysis with adjustment for age, presence of brain metastases and previous cerebral radiotherapy was performed.

Results

No assessed site revealed a significant correlation between qT1 and number of gadobutrol administrations in multivariate regression analysis. However, a significant negative correlation between qT1 and age was found for the globus pallidus as well as anterior and lateral thalamus (P < 0.05 each).

Conclusions

No T1 relaxation time shortening due to gadobutrol injection was found in any of the assessed brain structures after serial administration of 11 doses of gadobutrol.
Cracking the Opium Den
Authors: Blinick Rachel , Chaya Nathan , Zalta Benjamin , Haramati Linda B. , Shmukler Anna
Published: February 2020

Recreational drug use is increasing worldwide, with emergency room visits and total deaths from drug overdose rising in recent years. Complications from prescription and recreational drug use may result from the biochemical effects of the drugs themselves, impurities mixed with substances, or from causes related to the method of drug administration. The presentation of drug overdose may be complex due to multisubstance abuse, including cigarette smoking and alcoholism, and can impact any organ system. Patients may present without history, and radiologists may be the first clinicians to suggest the diagnosis. We aim to explore the cardiothoracic manifestations of drug abuse and their multimodality imaging manifestations.
Reconstruction of Complex Oromandibular Defects in Head and Neck Cancer: Role of the Chimeric Subscapular Free Flap
Authors: Molteni Gabriele , Gazzini Luca , Plotegher Cristina , Lanaro Luca , Fior Andrea , Marchioni Daniele , Nocini Pier Francesco
Published: February 2020

The purpose of this study is to present the chimeric scapula tip-free flap as a reconstructive choice in composite head and neck defects and to highlight the experiences of the authors in this field.

A retrospective study and a literature review were conducted. Data about preoperative condition, intraoperative images, and radiological and clinical documentation were collected.

Excision of head and neck advanced cancers may result in large composite defects containing different types of soft tissue and bone. This topic is particularly challenging in salvage surgery after radiation therapy. In this setting, reconstructive techniques are very complex and traditionally require the use of multiple microvascular flaps. Chimeric free flaps, based on the subscapular system, allow complex reconstructions, providing both soft tissue and bone on a single vascular peduncle.

The regional anatomy of the subscapular system and the possible chimeric flaps that can be harvested will be discussed, together with the reconstructive surgical technique used and the positioning of the patient. Two representative clinical cases of complex head and neck reconstruction after radiotherapy are presented.

Different types of chimeric flap can be harvested from the subscapular system. These flaps can include different tissues: skin, bone, muscle on a single vascular peduncle. This characteristic is particularly useful in complex defects with different tissue types involved, following large en-bloc excision of advanced head and neck tumors.

Free flaps based on the subscapular system can be an excellent reconstructive choice in complex head and neck defects.
The Global Macroeconomic Burden of Breast Cancer
Authors: Ranganathan Kavitha , Singh Puneet , Raghavendran Krishnan , Wilkins Edwin G. , Hamill Jennifer B. , Aliu Oluseyi , Newman Lisa A. , Hutton David , Momoh Adeyiza O.
Published: February 2020

Objective:

In this study, we quantified the global macroeconomic burden of breast cancer to underscore the critical importance of improving access to oncologic surgical care internationally.

Summary Background Data:

Breast cancer mortality in many low and middle-income countries (LMICs) is dramatically higher than in high-income countries. Prior to identifying solutions, however, it is important to first define the burden of disease.

Methods:

Data from the Institute of Health Metrics and Evaluation (2005–2015) were used to assess epidemiologic trends for 194, middle, and low-income countries. Economic burden defined by Welfare Loss (WL) was calculated by measuring disability-adjusted-life-years lost to breast cancer alongside the dollar equivalent of a value of statistical life year and as a function of each country's gross domestic product (GDP).

Results:

Annual mortality rates among breast cancer patients were significantly greater in LMICs in South Asia (3.06 per 100 women) and Sub-Saharan Africa (2.76 per 100 women), compared with high-income countries like the United States (1.69 per 100 women). From 2005–2015, mortality in South Asia increased by 8.20% and decreased by 6.45% in Sub-Saharan Africa; mortality rates in 2015 were observed as 27.9 per 100,000 in South Asia and 18.61 per 100,000 in Sub-Saharan Africa. Countries in South Asia demonstrated the greatest rise in WL due to breast cancer, from 0.05% to 0.08% of GDP.

Conclusions:

The burden of disease and economic impact of breast cancer is intensifying in LMICs. Global efforts to improve access to surgical care for women with breast cancer could reduce mortality and mitigate the social and financial impact of this disease in LMICs.
Meta-analysis and Meta-regression of Survival After Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma
Authors: Cambridge William A. , Fairfield Cameron , Powell James J. , Harrison Ewen M. , Søreide Kjetil , Wigmore Stephen J. , Guest Rachel V.
Published: February 2020

Objective:

To systematically review studies reporting survival data following neoadjuvant chemoradiation and orthotopic liver transplantation (NCR-OLT) for unresectable perihilar cholangiocarcinoma (pCC).

Background:

Despite survival improvements for other cancers, the prognosis of pCC remains dismal. Since publication of the Mayo protocol in 2000, increasing numbers of series globally are reporting outcomes after NCR-OLT.

Methods:

MEDLINE, EMBASE, Scopus, and Web of Science databases were searched from January 2000 to February 2019. A meta-analysis of proportions was conducted, pooling 1, 3-, and 5-year overall survival and recurrence rates following NCR-OLT across centers. Per protocol and intention to treat data were interrogated. Meta-regression was used to evaluate PSC as a confounder affecting survival.

Results:

Twenty studies comprising 428 patients were eligible for analysis. No RCTs were retrieved; the majority of studies were noncomparative cohort studies. The pooled 1, 3-, and 5-year overall survival rates following OLT without neoadjuvant therapy were 71.2% (95% CI 62.2%–79.4%), 48.0% (95% CI 35.0%–60.9%), and 31.6% (95% CI 23.1%–40.7%). These improved to 82.8% (95% CI 73.0%–90.8%), 65.5% (95% CI 48.7%–80.5%), and 65.1% (95% CI 55.1%–74.5%) if neoadjuvant chemoradiation was completed. Pooled recurrence after 3 years was 24.1% (95% CI 17.9%–30.9%) with neoadjuvant chemoradiation, 51.7% (95% CI 33.8%–69.4%) without.

Conclusions:

In unresectable pCC, NCR-OLT confers long-term survival in highly selected patients able to complete neoadjuvant chemoradiation followed by transplantation. PSC patients appear to have the most favorable outcomes. A high recurrence rate is of concern when considering extending national graft selection policy to pCC.
Development and Validation of a Nomogram to Preoperatively Estimate Post-hepatectomy Liver Dysfunction Risk and Long-term Survival in Patients With Hepatocellular Carcinoma
Authors: Wang Yan-Yan , Xiang Bang-De , Ma Liang , Zhong Jian-Hong , Ye Jia-Zhou , Wang Kun , Xing Bao-Cai , Li Le-Qun
Published: February 2020

Objective:

To develop a nomogram to estimate the risk of SPLD (International Study Group of Liver Surgery definition grade B or C) and long-term survival in patients with HCC before hepatectomy.

Background:

SPLD is the leading cause of post-hepatectomy mortality. The decision to refer an HCC patient for hepatectomy is mainly based on the survival benefit and SPLD risk. Prediction of SPLD risk before hepatectomy is of great significance.

Methods:

A total of 2071 consecutive patients undergoing hepatectomy for HCC were recruited and randomly divided into the development cohort (n = 1036) and internal validation cohort (n = 1035). Five hundred ninety patients from another center were enrolled as the external validation cohort. A nomogram was developed based on independent preoperative predictors of SPLD determined in multivariable logistic regression analysis.

Results:

The SPLD incidences in the development, internal, and external validation cohorts were 10.1%, 9.5%, and 8.6%, respectively. Multivariable analysis identified total bilirubin, albumin, gamma-glutamyl transpeptidase, prothrombin time, clinically significant portal hypertension, and major resection as independent predictors for SPLD. Incorporating these variables, the nomogram showed good concordance statistics of 0.883, 0.851, and 0.856, respectively in predicting SPLD in the 3 cohorts. Its predictive performance in SPLD, 90-day mortality, and overall survival (OS) outperformed Child-Pugh, model for end-stage liver disease, albumin-bilirubin, and European Association for the Study of the Liver recommended algorithm. With a nomogram score of 137, patients were stratified into low and high risk of SPLD. High-risk patients also had decreased OS.

Conclusions:

The nomogram showed good performance in predicting both SPLD and OS. It could help surgeons select suitable HCC patients for hepatectomy.
The Incidence of Low Anterior Resection Syndrome as Assessed in an International Randomized Controlled Trial (MRC/NIHR ROLARR)
Authors: Bolton William S. , Chapman Stephen J. , Corrigan Neil , Croft Julie , Collinson Fiona , Brown Julia M. , Jayne David G.
Published: February 2020

Objective:

To investigate the incidence of LARS in patients undergoing elective anterior resection within the MRC/NIHR ROLARR trial and to explore perioperative variables that might be associated with major LARS.

Summary background data:

Sphincter-preserving rectal cancer surgery is frequently accompanied by defaecatory dysfunction known as Low anterior resection syndrome (LARS). This is distressing for patients and is an unmet clinical challenge.

Methods:

An international, retrospective cohort study of patients undergoing anterior resection within the ROLARR trial was undertaken. Trial participants with restoration of gastrointestinal continuity and free from disease recurrence completed the validated LARS questionnaire between August 2015 and April 2017. The primary outcome was the incidence of LARS and secondary outcome was severity (minor versus major).

Results:

LARS questionnaires were received from 132/155 (85%) eligible patients. The median time from surgery to LARS assessment was 1065 days (range 174–1655 d). The incidence of LARS was 82.6% (n = 109/132), which was minor in 26/132 (19.7%) and major in 83/132 (62.9%). The most common symptoms were incontinence to flatus (n = 86/132; 65.2%) and defaecatory clustering (88/132; 66.7%). In a multivariate model, predictors of major LARS were: 1 cm decrease in tumor height above the anal verge (OR = 1.290, 95% CI: 1.101,1.511); and an ASA grade greater than 1 (OR = 2.920, 95% CI: 1.239, 6.883). Treatment allocation (laparoscopic vs robotic) did not predict major LARS.

Conclusions:

LARS is a common after rectal cancer surgery and patients should be appropriately counselled preoperatively, particularly before surgery for low tumors or in comorbid populations.
Sacral Neuromodulation Lead Twisting Causes Migration and Loss of Efficacy
Authors: Guzman-Negron Juan M. , Derisavifard Samir , Goldman Howard B.
Published: February 2020

Objective

This study aimed to present 2 cases with unusual lead complications in InterStim devices implanted in patients with refractory overactive bladder symptoms.

Materials

Two patients with InterStim implants presented with loss of efficacy. Both patients required lead revision surgery with findings of a twisted lead with associated lead migration.

Results

In both cases, revision surgery revealed twisting of the InterStim lead causing retrograde lead displacement. Patients were managed with lead removal and placement of a new lead. At the time of revision, one patient had a seroma within a large pocket of the implantable pulse generator (IPG) site, which was managed with closure and development of a new IPG pocket. In both cases, revision with new lead placement resulted in significant symptom improvement.

Conclusions

Sacral neuromodulation lead complications are known to be among the most consequential adverse events. We report the first 2 cases, to our knowledge, of patients presenting with an InterStim device that lost efficacy due to lead twisting and subsequent retrograde lead migration, likely due to rotation of the IPG within the gluteal pocket. This finding is easily remedied with IPG pocket revision and lead replacement.
Linking mechanisms of periodontitis to Alzheimer's disease
Authors: Sadrameli Mahtab , Bathini Praveen , Alberi Lavinia
Published: February 2020

Purpose of review

The review article discusses the association between periodontal disease and the development of dementia.

Recent findings

In the last decade, increasing evidence has pointed to a microbial and inflammatory origin for Alzheimer's disease with the discovery of oral and airway bacteria, viruses, and fungal species in the brain of patients with Alzheimer's disease. Furthermore, recognized as the culprit of neural network dysfunction, β-amyloid oligomeric species have antimicrobial properties reinforcing the idea that dysbiosis in the host–microbiota interaction can be at the origin of dementia. Periodontitis (gum disease), a persistent low-grade inflammatory condition, caused by pathogenic microorganisms, has been linked to an increased β-amyloid burden and cognitive disabilities later in life.

The pathogens of periodontal disease and the subsequent chronic inflammatory responses have significant implications on the development of Alzheimer's disease. The exact molecular mechanism by which Porphyromonas gingivalis and periodontal disease are involved in the pathogenicity of Alzheimer's disease is not currently evident. Understanding this causality can be instrumental in the development of treatments for this yet uncurable disease.
Biarticular muscles in light of template models, experiments and robotics: a review
Authors: Schumacher C. , Sharbafi M. , Seyfarth A. , Rode C.
Published: February 2020

Leg morphology is an important outcome of evolution. A remarkable morphological leg feature is the existence of biarticular muscles that span adjacent joints. Diverse studies from different fields of research suggest a less coherent understanding of the muscles’ functionality in cyclic, sagittal plane locomotion. We structured this review of biarticular muscle function by reflecting biomechanical template models, human experiments and robotic system designs. Within these approaches, we surveyed the contribution of biarticular muscles to the locomotor subfunctions (stance,balanceandswing). While mono- and biarticular muscles do not show physiological differences, the reviewed studies provide evidence for complementary and locomotor subfunction-specific contributions of mono- and biarticular muscles. Instance, biarticular muscles coordinate joint movements, improve economy (e.g. by transferring energy) and secure the zig-zag configuration of the leg against joint overextension. These commonly known functions are extended by an explicit role of biarticular muscles in controlling the angular momentum forbalanceandswing. Human-like leg arrangement and intrinsic (compliant) properties of biarticular structures improve the controllability and energy efficiency of legged robots and assistive devices. Future interdisciplinary research on biarticular muscles should address their role for sensing and control as well as non-cyclic and/or non-sagittal motions, and non-static moment arms.
Mumia zhuanghuii sp. nov., isolated from the intestinal contents of plateau pika (Ochotona curzoniae) on the Qinghai–Tibet Plateau
Authors: Tian Zhi , Lu Shan , Jin Dong , Yang Jing , Pu Ji , Lai Xin-He , Li Junqin , Zhang Sihui , Dong Kui , Lei Wenjing , Huang Ying , Ren Zhihong , Zhang Dezhu , Wang Suping , Xu Jianguo
Published: February 2020

Two Gram-staining-positive, catalase-positive, oxidase-negative, aerobic, non-motile, irregular rod-shaped bacterial strains (Z350T and Z527) were isolated from intestinal contents of plateau pika (Ochotona curzoniae) from the Qinghai–Tibet Plateau, PR China. Results of phylogenetic analyses based on 16S rRNA gene sequences indicated that strain Z350T belongs to the genus

Mumia

(family

Nocardioidaceae

) but clearly differs from the currently recognized species

Mumia xiangluensis

DSM 101040T (98.4 % similarity) and

Mumia flava

DSM 27763T (97.4 %). Strain Z350T had a DNA G+C content of 70.7 mol% and shared 80.4 and 76.7 % average nucleotide identity values and 23.4 and 20.6 % in silico DNA–DNA hybridization relatedness with

M. xiangluensis

DSM 101040T and

M. flava

DSM 27763T, respectively. Further phylogenetic analyses based on 497 core genes indicated that our isolates were members of the genus

Mumia

but separated from all existing genera within the family

Nocardioidaceae

. The major cellular fatty acids were C18 : 1 ω9c and 10-methyl C18 : 0. The cell wall contained ll-diaminopimelic acid as the diamino acid, and rhamnose, ribose and glucose as whole cell-wall sugars. MK-9(H4) was detected as the major menaquinone. Polar lipids present were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside and one unidentified phospholipid. Based on distinct differences in the genotypic and phenotypic data from the two

Mumia

species, a novel species, Mumia zhuanghuii sp. nov., is proposed. The type strain is Z350T (=CGMCC 4.7464T=DSM 106288T).
Cryobacterium ruanii sp. nov. and Cryobacterium breve sp. nov., isolated from glaciers
Authors: Liu Qing , Tian Ji-Hui , Liu Hong-Can , Zhou Yu-Guang , Xin Yu-Hua
Published: February 2020

Strains Sr36T and TMT4-23T were isolated from No. 1 glacier in Xinjiang Uygur Autonomous Region and Toumingmengke glacier in Gansu Province, PR China, respectively. They were Gram-stain-positive and rod-shaped micro-organisms. The optimum growth temperature of the two strains was 10–14 °C. Phylogenetic analysis showed that the two strains were related to members of the genus

Cryobacterium

. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between strain Sr36T and its close relatives

Cryobacterium luteum

Hh15T,

Cryobacterium aureum

Hh31T,

Cryobacterium levicorallinum

Hh34T and

Cryobacterium flavum

Hh8T were 81.16–87.24 and 28.0–32.5 %, respectively. The ANI and dDDH values between strain TMT4-23T and its close relative

Cryobacterium psychrotolerans

0549T were 81.16 and 22.3 %. The polar lipids of strain Sr36T were diphosphatidylglycerol, phosphatidylglycerol, one unidentified glycolipid and three unidentified lipids. The polar lipids of strain TMT4-23T were diphosphatidylglycerol, phosphatidylglycerol, one unidentified glycolipid, one unidentified phospholipid and six unidentified lipids. The major fatty acids of strain Sr36T were anteiso-C15 : 0, iso-C16 : 0, anteiso-C17 : 0 and anteiso-C15 : 1. The major fatty acids of strain TMT4-23T were anteiso-C15 : 0, anteiso-C17 : 0, iso-C16 : 0, anteiso-C15 : 1 and iso-C15 : 1. Both strains contained 2,4-diaminobutyric acid and their predominant menaquinone was MK-10. On the basis of the phenotypic, phylogenetic and genotypic data, two novel species Cryobacterium ruanii sp. nov. (type strain = Sr36T=CGMCC 1.9275T=NBRC 113797T) and Cryobacterium breve sp. nov. (type strain =TMT4-23T=CGMCC 1.9556T=NBRC 113800T) are proposed.
Evaluation of protective immunity responses against pneumococcal PhtD and its C-terminal in combination with outer-membrane vesicles as adjuvants
Authors: Malekan Mohammadali , Siadat Seyed Davar , Aghasadeghi Mohammadreza , Shahrokhi Nader , Afrough Parviz , Behrouzi Ava , Ahmadi Khadijeh , Mousavi Seyed Fazlollah
Published: February 2020

Introduction.

Streptococcus pneumoniae

is a significant bacterial pathogen in humans. Currently, there are two types of pneumococcal vaccines, but there are concerns regarding their application.

Aim. Since many pneumococcal proteins are serotype-independent, polyhistidine triad protein D (PhtD) has been selected as a vaccine candidate.

Methodology. We prepared recombinant PhtD and its C-terminal fragment (PhtD-C) using alum and outer-membrane vesicles (OMVs) as adjuvants. The combinations were injected intraperitoneally into mice, and then total immunoglobulin G (IgG) and specific IgG, IgG1 and IgG2a were measured. A serum bactericidal assay and opsonophagocytosis were also performed as complementary tests. Meningococcal OMVs were used as an adjuvant.

Results. The levels of specific IgG and IgG1 against combinations of PhtD and its C-terminal with OMVs and alum as adjuvants increased at the time of the third mouse immunization on day 35. Forty per cent and 60% of

S. pneumoniae

ATCC 6303 (serotype 3) as a virulent pneumococcal strain, respectively, were killed in the opsonophagocytosis test and these results could also be observed in the serum bactericidal assay. Mice mmunized iwith PhtD and its C-terminal with OMVs and alum as adjuvants survived after 10 days of pneumococcal challenge.

Conclusion. The combination of PhtD and PhtD-C with alum produced optimal results, but the combination of PhtD and PhtD-C with OMVs produced minimal results by comparison. The survival rates were also measured, and these corresponded with the results of the immunological assessments. Our findings showed that mice receiving PhtD and PhtD-C plus OMV and alum had higher survival rates than the mice in the other groups.
Comparison of Shiga toxin-encoding bacteriophages in highly pathogenic strains of Shiga toxin-producing Escherichia coli O157:H7 in the UK
Authors: Yara Daniel A. , Greig David R. , Gally David L. , Dallman Timothy J. , Jenkins Claire
Published: February 2020

Over the last 35 years in the UK, the burden of Shiga toxin-producing

Escherichia coli

(STEC) O157:H7 infection has, during different periods of time, been associated with five different sub-lineages (1983–1995, Ia, I/IIa and I/IIb; 1996–2014, Ic; and 2015–2018, IIb). The acquisition of a stx2a-encoding bacteriophage by these five sub-lineages appears to have coincided with their respective emergences. The Oxford Nanopore Technologies (ONT) system was used to sequence, characterize and compare the stx-encoding prophages harboured by each sub-lineage to investigate the integration of this key virulence factor. The stx2a-encoding prophages from each of the lineages causing clinical disease in the UK were all different, including the two UK sub-lineages (Ia and I/IIa) circulating concurrently and causing severe disease in the early 1980s. Comparisons between the stx2a-encoding prophage in sub-lineages I/IIb and IIb revealed similarity to the prophage commonly found to encode stx2c, and the same site of bacteriophage integration (sbcB) as stx2c-encoding prophage. These data suggest independent acquisition of previously unobserved stx2a-encoding phage is more likely to have contributed to the emergence of STEC O157:H7 sub-lineages in the UK than intra-UK lineage to lineage phage transmission. In contrast, the stx2c-encoding prophage showed a high level of similarity across lineages and time, consistent with the model of stx2c being present in the common ancestor to extant STEC O157:H7 and maintained by vertical inheritance in the majority of the population. Studying the nature of the stx-encoding bacteriophage contributes to our understanding of the emergence of highly pathogenic strains of STEC O157:H7.