bluuebunny/crossref_metadata_2025 huggingface dataset:
Cultural Competence and Ethnic Diversity in Healthcare
Authors: Nair Lakshmi , Adetayo Oluwaseun A.
Published: May 2019

Today’s model of healthcare has persistent challenges with cultural competency, and racial, gender, and ethnic disparities. Health is determined by many factors outside the traditional healthcare setting. These social determinants of health (SDH) include, but are not limited to, education, housing quality, and access to healthy foods. It has been proposed that racial and ethnic minorities have unfavorable SDH that contributes to their lack of access to healthcare. Additionally, African American, Hispanic, and Asian women have been shown to be less likely to proceed with breast reconstructive surgery post-mastectomy compared to Caucasian women. At the healthcare level, there is underrepresentation of cultural, gender, and ethnic diversity during training and in leadership. To serve the needs of a diverse population, it is imperative that the healthcare system take measures to improve cultural competence, as well as racial and ethnic diversity. Cultural competence is the ability to collaborate effectively with individuals from different cultures; and such competence improves health care experiences and outcomes. Measures to improve cultural competence and ethnic diversity will help alleviate healthcare disparities and improve health care outcomes in these patient populations. Efforts must begin early in the pipeline to attract qualified minorities and women to the field. The authors are not advocating for diversity for its own sake at the cost of merit or qualification, but rather, these efforts must evolve not only to attract, but also to retain and promote highly motivated and skilled women and minorities. At the trainee level, measures to educate residents and students through national conferences and their own institutions will help promote culturally appropriate health education to improve cultural competency. Various opportunities exist to improve cultural competency and healthcare diversity at the medical student, resident, attending, management, and leadership levels. In this article, the authors explore and discuss various measures to improve cultural competency as well as ethnic, racial, and gender diversity in healthcare.
Stem Cells in Keloid Lesions: A Review
Authors: Lim Kim H. , Itinteang Tinte , Davis Paul F. , Tan Swee T.
Published: May 2019

Keloid disorder (KD) is a fibroproliferative condition caused by dysregulated wound healing following wounding of the skin. The pathogenesis of KD has not been fully elucidated and current treatment is unsatisfactory. There is increasing evidence of the role of stem cells in KD. This review discusses the role of embryonic stem (ESC)-like cells and mesenchymal stem cells in the pathogenesis of KD. It is proposed that dysfunction of the ESC-like population localized to the endothelium of the microvessels and perivascular cells within the keloid-associated lymphoid tissues may give rise to the aberrant fibroblasts and myofibroblasts via a mesenchymal stem cell intermediate in keloid lesions, by undergoing an endothelial-to-mesenchymal transition. We also discuss the role of the renin-angiotensin system (RAS), the immune system, and the inflammatory response, on stem cell proliferation and differentiation. The understanding of the precise roles of these stem cells and interplay of the associated regulatory pathways could lead to the development of targeted therapy for this enigmatic and challenging condition. The demonstration of the expression of components of the RAS and cathepsins B, D, and G that constitute bypass loops of the RAS, by the ESC-like population, suggests that the primitive population may be a therapeutic target by modulation of the RAS, using existing medications.
Efficacy of Local Anesthesia in the Face and Scalp: A Prospective Trial
Authors: Safran Tyler , Zammit Dino , Kanevsky Jonathan , Khanna Manish
Published: May 2019

Background:

The use of local anesthesia has allowed for the excision and repair of lesions of the head and neck to be done in an office-based setting. There is a gap of knowledge on how surgeons can improve operative flow related to the onset of action. A prospective trial was undertaken to determine the length of time for full anesthesia effect in the head and neck regions.

Methods:

Consecutive patients undergoing head and neck cutaneous cancer resection over a 3-month period were enrolled in the study. Local anesthesia injection and lesion excision were all done by a single surgeon. All patients received the standard of care of local anesthesia injection.

Results:

Overall, 102 patients were included in the prospective trial. The upper face took significantly longer (153.54 seconds) compared with the lower face and ears (69.37 and 60.2 seconds, respectively) (P < 0.001) to become fully anesthetized. In addition, there was no significant difference found when adjusting for the amount of local anesthesia used, type, and size of lesion (P > 0.05). Using the time to full anesthesia effect for each local injection, a heat map was generated to show the relative times of the face and scalp to achieve full effect.

Conclusions:

This prospective trial demonstrated that for the same local anesthetic and concentration, upper forehead and scalp lesions take significantly longer to anesthetize than other lesions in the lower face and ear. This can help surgeons tailor all aspects of their practice, which utilizes local anesthesia to help with patient satisfaction and operative flow.
Red blood cell distribution width for predicting significant liver inflammation in patients with autoimmune hepatitis
Authors: Wang Huali , Wang Jian , Huang Rui , Xia Juan , Zuo Lingyun , Yan Xiaomin , Yang Yongfeng , Wu Chao
Published: May 2019

Background

Red blood cell distribution width (RDW) was reported to be associated with the severity of liver diseases. We aimed to investigate the association between RDW and severity of liver inflammation in autoimmune hepatitis (AIH).

Patients and methods

Ninety-two consecutive AIH patients who underwent liver biopsy during 2016–2017 were included. Liver histology was evaluated using the Scheuer scoring system. Logistic regression analysis was used to analyze the risk factors for significant inflammation. The diagnostic accuracy was evaluated by the area under the receiver operating characteristic curve.

Results

The RDW level was higher in AIH patients with significant inflammation (14.6%, interquartile range: 13.2–16.3%) than in patients with mild inflammation (13.2%, interquartile range: 12.6–13.8%). The RDW level was correlated positively with the grades of liver inflammation (r=0.356, P < 0.001). The area under the receiver operating characteristic curve of RDW in predicting significant inflammation was 0.739 (95% confidential interval: 0.634–0.843, P < 0.001), with 67.80% sensitivity and 75.76% specificity. The diagnostic performance of RDW for significant inflammation was better than alanine aminotransferase (P = 0.003) and immunoglobulin G (P = 0.049). RDW (odds ratio = 1.702, P = 0.001) was identified as an independent predictor for significant inflammation by logistic multivariable analysis.

Conclusion

The RDW level was correlated positively with the severity of liver inflammation in AIH patients. RDW can be a promising indicator for predicting significant liver inflammation in AIH.
Case Report: Adaptation of a Telescope with a Minus Lens Cap for Highly Myopic Patient
Authors: Matchinski Tracy L. , Rimkus John J. , Theisen Kelli M.
Published: May 2019

SIGNIFICANCE

This case report demonstrates a novel approach of using the optical principle of vergence amplification to correct for a visually impaired patient's ametropia while using a telescope system. This approach is easy to apply clinically.

PURPOSE

The purpose of this study was to present a novel approach of correcting high myopia for a patient with visual impairment using a spectacle-mounted telescope.

CASE REPORT

A 51-year-old man desired improved distance vision for television viewing and facial recognition. His refractive error was −18.00 diopter sphere in each eye with best-corrected acuities of 5/225 (20/900 Snellen equivalent) for the right eye and 10/225 (20/450) for the left eye. Over the years, multiple attempts at contact lens use were unsuccessful, and the patient used spectacle prescription. After evaluating telescope systems, the patient was successful with a 7 × 30 Beecher Mirage Keplerian telescope system. This system cannot be worn over glasses. To correct his ametropia, a −0.25-diopter minus lens cap was applied in front of the objective lens of the telescope, capitalizing on the property of vergence amplification. In addition, the tube length was adjusted. Adding lenses in front of the telescope and focusing the telescope can both affect the angular magnification of the system. Depending on the lenses used, type of telescope, and refractive error, there can be an increase or decrease in angular magnification. In this case, the minus lens at the front of the telescope decreased the power of the objective lens, and the focusing for the remaining uncorrected myopia increased the power of the ocular lens. Both of these factors contributed to increased resultant angular magnification for this patient. The patient achieved 10/30 (20/60) vision and reported success with his distance vision.

CONCLUSIONS

Minus-powered lens caps over the objective lens are a viable option for highly myopic individuals who wish to use premanufactured spectacle-mounted telescopes.
Limited Resection Is Associated With a Higher Risk of Locoregional Recurrence than Lobectomy in Stage I Lung Adenocarcinoma With Tumor Spread Through Air Spaces
Authors: Kadota Kyuichi , Kushida Yoshio , Kagawa Seiko , Ishikawa Ryou , Ibuki Emi , Inoue Kosuke , Go Tetsuhiko , Yokomise Hiroyasu , Ishii Tomoya , Kadowaki Norimitsu , Haba Reiji
Published: May 2019

A growing number of independent studies have validated spread through air spaces (STAS) to be a predictor of worse prognosis in lung adenocarcinoma. To investigate the prognostic significance of STAS according to types of surgery and locations of recurrence, and the association between STAS and anti-anaplastic lymphoma kinase (ALK) expression, we analyzed a series of 735 Japanese patients with resected lung adenocarcinoma, which was restaged according to the 8th edition of TNM staging system. STAS was defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. Tumors were classified according to the 2015 WHO lung tumor classification. Recurrence-free probability and overall survival were analyzed using the log-rank test and the Cox proportional hazards model. STAS was observed in 247 patients. STAS was more frequently identified in ALK-positive tumors (P=0.020). STAS was an independent prognostic factor of a worse recurrence-free probability in all patients (hazard ratio [HR]=5.33, P<0.001) and in stage I patients (HR=6.87, P<0.001). STAS was an independent prognostic factor of a worse overall survival in all patients (HR=2.32, P<0.001) and in stage I patients (HR=2.85, P<0.001). In stage I patients with STAS, compared with lobectomy, limited resection was associated with a significantly higher risk of any recurrence (P=0.010) and locoregional recurrence (P=0.002). We have demonstrated that, in lung adenocarcinoma with STAS, limited resection was associated with a significantly higher risk of recurrence (especially locoregional recurrence) than lobectomy was.
The Use of Prophylactic Antibiotics before Primary Palatoplasty Is Not Associated with Lower Fistula Rates: An Outcome Study Using the Pediatric Health Information System Database
Authors: Jodeh Diana S. , Nguyen Anh Thy H. , Cray James J. , Rottgers S. Alex
Published: May 2019

Background:

Previous attempts to study the effect of prophylactic antibiotics on the outcomes of cleft palate surgery have been hampered by the need for a very large sample size to provide adequate power to discern a potentially small therapeutic effect. This limitation can be overcome by querying large databases created by health care governing bodies.

Methods:

Data from the Pediatric Health Information System database were used for this analysis. Patients, aged 6 to 18 months, who had undergone primary palatoplasty (International Classification of Diseases, Ninth Revision, code 27.62) between 2004 and 2009 were included. Subsequent repair of an oronasal fistula between 2004 and 2015 was identified by International Classification of Diseases, Ninth Revision, procedure code 21.82. Pharmacy billing records were used to determine antibiotic administration. Associations between antibiotic administration and fistula repair were assessed using random-intercept logistic regression adjusting for age, sex, race, and cleft type.

Results:

Seven thousand one hundred sixty patients were available for analysis; of these, 460 (6.4 percent) had a subsequent repair of an oronasal fistula. Fistula rates were 5.9, 11.4, and 5.2 percent among patients given preoperative antibiotics, only postoperative antibiotics, and no antibiotics, respectively (p < 0.001). Multivariable analysis results showed that the odds of having an oronasal fistula among patients who were administered preoperative antibiotics did not differ significantly (statistically) from patients who did not receive antibiotics (OR, 0.88; 95 percent CI, 0.59 to 1.31).

Conclusions:

The treatment goal of primary palatoplasty is the successful repair of the cleft without an oronasal fistula. Administration of preoperative antibiotics did not significantly reduce the odds of subsequent fistula repair within the same Pediatric Health Information System institution following primary palatoplasty.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Minimal-Invasive Robot-Assisted Image-Guided Resection of Prostate-Specific Membrane Antigen–Positive Lymph Nodes in Recurrent Prostate Cancer
Authors: van Leeuwen Fijs W. B. , van Oosterom Matthias N. , Meershoek Philippa , van Leeuwen Pim J. , Berliner Christoph , van der Poel Henk G. , Graefen Markus , Maurer Tobias
Published: May 2019

With the rapid expansion of robot-assisted surgical procedures, the need for robot-compliant image guidance technologies has also increased. Examples hereof are the integrated firefly fluorescence camera, the drop-in ultrasound probe, and the recently introduced DROP-IN gamma probe. Combined with 68Ga–prostate-specific membrane antigen–(PSMA)–11 PET/CT (staging) and 99mTc-PSMA-I&S SPECT/CT (preoperative imaging), the latter DROP-IN gamma probe technology recently allowed us to perform the first clinical cases of robot-assisted PSMA-guided salvage surgery of lymphatic metastases.
Compressed Central Zone Uptake on PSMA PET/CT—A Potential Pitfall in Interpretation
Authors: Ganeshalingam Rueben , Hsiao Edward
Published: May 2019

The case of a 66-year-old man undergoing a staging PSMA PET/CT after a recent diagnosis of prostate carcinoma is presented. In addition to uptake within the prostate consistent with primary tumor activity, mild symmetrical and diffuse uptake is also noted within central zone. The appearance is not consistent with likely tumor activity. Comparison is made with histopathology after a radical prostatectomy, and no correlating tumor is noted in the region of central zone uptake. Increased PSMA uptake within the compressed central zone of the prostate may represent a potential pitfall in PSMA PET/CT imaging.
Complete Metabolic Response Assessed by FDG PET/CT to FOLFIRI-Aflibercept in Second-Line Treatment of Metastatic Colorectal Cancer
Authors: Amrane Karim , Ollivier Luc , Salaun Pierre-Yves , Metges Jean-Philippe , Abgral Ronan
Published: May 2019

FOLFIRI-aflibercept chemotherapy is indicated in second-line treatment of metastatic colorectal cancer (mCRC) after progression under FOLFOX (±bevacizumab). Nevertheless, its proven therapeutic efficacy in clinical trials was based on partial responses. And to date, only 2 cases of complete response assessed by CT were reported in literature. We report a complete metabolic response assessed by FDG PET/CT in a 50-year-old woman with mCRC treated by FOLFIRI-aflibercept. This also confirms that FDG PET/CT is emerging as a useful approach for therapeutic assessment of targeted drugs in mCRC.
Benign High-Flow Priapism With a Diffuse and Intense 18F-FDG Uptake on 18F-FDG PET/CT Scanning
Authors: Nasiri Zakieh , Zarehparvar Moghadam Soroush , Kiamanesh Zahra , Emami Farshad , Sadeghi Ramin
Published: May 2019

We present benign high-flow priapism with intensive 18F-FDG uptake as an unusual finding in a case of testicular teratocarcinoma with a history of left orchiectomy and chemotherapy. 18F-FDG PET/CT scan showed pulmonary metastases, left obturator node involvement, and intense 18F-FDG uptake in the penis. Upon examination, the patient had a painless erection that lasted for couple of days. Because of pulmonary metastases, second-line chemotherapy regimen was started by his physician. The patient's priapism resolved spontaneously, with no episode of recurrence at 2 years' follow-up.
68Ga-DOTA-Exendin PET-MRI Fusion Imaging in a Case of Insulinoma
Authors: Sood Apurva , Basher Rajender Kumar , Kang Mandeep , Shukla Jaya , Behera Arunanshu , Walia Rama , Nada Rithambhra , Mittal Bhagwant Rai , Bhattacharya Anish
Published: May 2019

Persistent hyperinsulinemic hypoglycemia in adults is most commonly caused by insulinomas, which pose a diagnostic challenge to physicians, surgeons, and radiologists and require multimodality imaging for precise localization and staging. PET tracers such as 18F-FDOPA and glucagon-like peptide 1 receptor analogs have been used for imaging insulinomas. Glucagon-like peptide 1 receptor analogs have recently shown promising results in preoperative localization of these tumors, as all insulinomas express glucagon-like peptide 1 receptors. 68Ga-DOTA-Exendin PET and MRI done in the present case helped in precise localization and management of the culprit lesion, whereas contrast-enhanced CT and 18F-FDOPA PET failed to do so.
FDG PET/CT of Gardnerella vaginalis Infection
Authors: Foret Thibault , Dhomps Anthony , Dauwalder Olivier , Skanjeti Andrea , Tordo Jeremie
Published: May 2019

We report the case of a 23-year-old woman with a history of cystic fibrosis and bilung transplantation, who presented clinically cervical swollen lymph nodes with alteration of her general state. 18F-FDG PET/CT was performed because of lymphoma suspicion and showed cervical and pelvic hypermetabolic lymphadenopathies, with linear vaginal hypermetabolism. There was an increase of lactate dehydrogenase, and Epstein-Barr virus detection was negative. A right cervical lymph node biopsy was performed, with no lymphoma involvement. Complementary microbiological investigations showed positive results for Gardnerella vaginalis.
18F-FDG PET/CT lymphatic node hypermetabolism is not specific to lymphoma, particularly in immunocompromised patients.
Bilateral Adrenal Extremely Intense Metabolic Activity on 18F-FDG PET/CT in a Patient With Pheochromocytomas
Authors: Chen Xueqi , Chen Guoqian , Fu Zhanli , Li Qian
Published: May 2019

Bilateral adrenal masses were found by ultrasound on a 55-year-old man with sudden onset of chest distress and palpitation after drinking alcohol. After the negative laboratory tests of plasma catecholamine and urinary vanillylmandelic acid, the 18F-FDG PET/CT revealed extremely intense metabolic activity in the bilateral adrenal lesions, and the subsequent 131I-meta-iodobenzylguanidine scintigraphy also showed increased radioactivity in the lesions. The pathology of surgery confirmed the diagnosis of bilateral pheochromocytomas.
Standardized Laparoscopic Sphincter-preserving Total Mesorectal Excision For Rectal Cancer: Median of 10 Years’ Long-term Oncologic Outcome in 217 Unselected Consecutive Patients
Authors: Bademler Suleyman , Koza Kadir B. , Ucuncu Muhammed Z. , Tokmak Handan , Bakir Baris , Oral Ethem N. , Asoglu Oktar
Published: May 2019

This study was designed to evaluate the impact of a standardized laparoscopic total mesorectal excision (TME) on the long-term oncologic outcome. Unselected consecutive patients with rectal cancer underwent a standardized laparoscopic TME with medial to lateral approach encompassing 9 sequential steps. From 2005 to June 2012, laparoscopic sphincter-preserving TME was attempted in 217 patients. Mean follow-up of all patients was a median of 91 months (range, 3 to 164 mo). The local recurrence rate was 6.5%, and the distant recurrence rate was 19.8%. The 10-year disease-free survival (DFS) rates were 76.4% and overall survival (OS) was 67.1%. In the converted group, DFS and OS were 50% and 46.7%, respectively. In the laparoscopic group, DFS and OS were 78.3% and 68.5%, respectively. A standardized laparoscopic sphincter-preserving TME resulted in a favorable long-term oncologic outcome in unselected patients with rectal cancer. Conversion to open surgery has impaired OS and DFS.
The Effect of Laparoscopic Sleeve Gastrectomy on Nonalcoholic Fatty Liver Disease
Authors: Batman Burcin , Altun Hasan , Simsek Binnur , Aslan Ekrem , Namli Koc Sule
Published: May 2019

Obesity is associated with nonalcoholic fatty liver disease which is one of the most common causes of chronic liver disease. FibroScan is a noninvasive tool for liver stiffness measurement and controlled attenuation parameter to evaluate liver steatosis and fibrosis. We aimed to demonstrate the effect of laparoscopic sleeve gastrectomy on liver steatosis and fibrosis. Of the 120 consecutive patients screened, 72 were enrolled in this study. FibroScan M probe and XL probe were used for the evaluation of liver steatosis and fibrosis. Fifty-two patients (72.2%) were female individuals and 20 (27.8%) were male individuals; the mean age was 37.9±10.4 years. Percentage of excess weight loss was significant at the third and sixth months: 57.2±18.3 (P<0.05) and 81.4±24.6 (P<0.05), respectively. Mean preoperative controlled attenuation parameter and liver stiffness measurement values were 309.2±68.7 dB/m and 7.5±5.0 kPa, respectively, and significantly declined to 217.4±56.4 dB/m and 5.6±2.5 kPa, respectively, at sixth postoperative month (P<0.001 and <0.01, respectively). These results suggest that laparoscopic sleeve gastrectomy is associated with significant improvement in liver steatosis and fibrosis. Bariatric surgery has a beneficial effect on nonalcoholic fatty liver disease in morbidly obese patients.
Outcome Comparison of Single-port Versus Multiport Versus Under Direct View Completion Proctectomy With Ileal-Pouch Anal Anastomosis for Patients With Ulcerative Colitis
Authors: Li Wanglin , Rencuzogullari Ahmet , Costedio Meagan , Benlice Cigdem , Kessler Hermann , Stocchi Luca , Gorgun Emre
Published: May 2019

Purpose:

Whether the reported theoretical benefits of single-port laparoscopic (SPL) approach can be converted to superior clinical outcomes is still unknown for ulcerative colitis (UC) patients undergoing second-stage proctectomy. This study aimed to compare the short-term postoperative and long-term pouch-related functional outcomes of SPL, multiport laparoscopic (MPL), and direct view (DV) completion proctectomy with ileal-pouch anal anastomosis (CP/IPAA).

Materials and Methods:

Patients who underwent either SPL, MPL, or under DV CP/IPAA for UC between August 2009 and August 2014 were identified from an institutional review board-approved, prospectively maintained institutional database and reviewed. Demographics, patient characteristics, short-term and long-term complications, and morbidity were compared between the 3 groups. Multivariate logistic or Cox regression analysis was conducted for covariate adjustments.

Results:

Groups (SPL: n=36; MPL: n=67; DV: n=97) were comparable in terms of preoperative characteristics and demographics except for age. The SPL group was associated with reduced estimated blood loss, reduced length of stay compared with the MPL and DV groups, and shorter operating time compared with the MPL group (P<0.001). Similar short-term postoperative and long-term pouch-related functional outcomes were noted without significant differences in quality of life scores among the 3 groups.

Conclusions:

SPL CP/IPAA for UC can be safely performed with superior short-term outcomes such as reduced intraoperative blood loss and length of hospital stay compared with MPL and under direct view approaches, and shorter operating time compared with MPL.
Adverse Effects on the Postoperative Urinary Function After Combined Resection of Inferior Vesical Artery in Laparoscopic Lateral Pelvic Lymph Node Dissection: Retrospective Analysis of Consecutive 95 Series
Authors: Manabe Tatsuya , Koga Yasuo , Kubo Hiroshi , Baba Koichi , Nagayoshi Kinuko , Nagai Shuntaro , Ueki Takashi , Nakamura Masafumi , Noshiro Hirokazu
Published: May 2019

Background:

The combined resection of the vesical artery (VA) in laparoscopic lateral pelvic lymph node dissection (L-LPLD) was reported to facilitate the safe dissection of metastatic lymph nodes. However, whether or not the combined VA resection affects the urinary function remains controversial.

Purpose:

The purpose of the present study was to examine the risk factors for the postoperative urinary dysfunction (PUD) after L-LPLD followed by total mesorectal excision and to clarify the effects of the combined VA resection in L-LPLD on PUD.

Patients and Methods:

L-LPLD was performed in 95 patients with advanced rectal cancer at Saga University Hospital and Kyushu University Hospital from January 2013 to December 2017. The risk factors for PUD after L-LPLD were investigated.

Results:

The univariate analysis revealed that the combined resection of the inferior vesical artery (IVA) was a risk factor for PUD. To examine by the type of IVA resection, the incidence of PUD significantly increased with the bilateral IVA resection, but the unilateral IVA resection induced PUD on the same level with the preservation of IVA.

Conclusions:

Bilateral IVA resection in L-LPLD could increase the incidence of PUD. Thus, if possible, the preservation of the unilateral IVA through L-LPLD should be considered.
Living Donor Liver Transplant for Alcoholic Liver Disease: Data from the Adult-to-adult Living Donor Liver Transplantation Study
Authors: Braun Hillary J. , Dodge Jennifer L. , Grab Joshua D. , Syed Shareef M. , Roll Garrett R. , Freise Chris E. , Roberts John P. , Ascher Nancy L.
Published: May 2019

Background.

Alcoholic liver disease (ALD) accounts for 15%–30% of transplants performed in the United States and Europe; however, the data on living donor liver transplantation (LDLT) for ALD remain sparse. The purpose of this study was to examine the outcomes following LDLT for ALD using data from the adult-to-adult living donor liver transplantation (A2ALL) study, which represents the largest Western experience with adult-to-adult LDLT.

Methods.

A retrospective review of A2ALL data collected between 1998 and 2014 was performed. Patients were excluded if they received a deceased donor liver transplant. Demographic data, postoperative outcomes and complications, graft and patient survival, and predictors of graft and patient survival were assessed.

Results.

Of the 1065 patients who underwent LDLT during the study time period, 168 (15.8%) were transplanted for a diagnosis of ALD. Comparing patients who underwent transplant for ALD with those who were transplanted for other etiologies of liver disease, there was no significant difference in graft survival at 1 (88% versus 84%), 5 (76% versus 74%), or 10 years following transplant (55% versus 61%, P = 0.29). Similarly, there was no difference in patient survival at 1 (94% versus 91%), 5 (83% versus 79%), or 10 years following transplant (61% versus 66%, P = 0.32).

Conclusions.

LDLT for ALD results in excellent 1-, 5-, and 10-year graft and patient survival. Patients with ALD and impaired renal function have a higher risk of graft loss and death. These findings support the notion that early LDLT for patients with ALD may help optimize outcomes.
Translating surveillance data into incidence estimates
Authors: Bourhis Y. , Gottwald T. , van den Bosch F.
Published: May 2019

Monitoring a population for a disease requires the hosts to be sampled and tested for the pathogen. This results in sampling series from which we may estimate the disease incidence, i.e. the proportion of hosts infected. Existing estimation methods assume that disease incidence does not change between monitoring rounds, resulting in an underestimation of the disease incidence. In this paper, we develop an incidence estimation model accounting for epidemic growth with monitoring rounds that sample varying incidence. We also show how to accommodate the asymptomatic period that is the characteristic of most diseases. For practical use, we produce an approximation of the model, which is subsequently shown to be accurate for relevant epidemic and sampling parameters. Both the approximation and the full model are applied to stochastic spatial simulations of epidemics. The results prove their consistency for a very wide range of situations. The estimation model is made available as an online application.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.
New methodologies for the estimation of population vulnerability to diseases: a case study of Lassa fever and Ebola in Nigeria and Sierra Leone
Authors: Kajero Olumayowa , Del Rio Vilas Victor , Wood James L. N. , Lo Iacono Giovanni
Published: May 2019

Public health practitioners require measures to evaluate how vulnerable populations are to diseases, especially for zoonoses (i.e. diseases transmitted from animals to humans) given their pandemic potential. These measures would be valuable to support strategic and operational decision making and allocation of resources. Although vulnerability is well defined for natural hazards, for public health threats the concept remains undetermined. Here, we develop new methodologies to: (i) quantify the impact of zoonotic diseases and the capacity of countries to cope with these diseases, and (ii) combine these two measures (impact and capacity) into one overall vulnerability indicator. The adaptive capacity is calculated from estimations of disease mortality, although the method can be adapted for diseases with no or low mortality but high morbidity. As an example, we focused on the vulnerability of Nigeria and Sierra Leone to Lassa Fever and Ebola. We develop a simple analytical form that can be used to estimate vulnerability scores for different spatial units of interest, e.g. countries or regions. We show how some populations can be highly vulnerable despite low impact threats. We finally outline future research to more comprehensively inform vulnerability with the incorporation of relevant factors depicting local heterogeneities (e.g. bio-physical and socio-economic factors).

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.
Transmission routes of rare seasonal diseases: the case of norovirus infections
Authors: Rushton Stephen P. , Sanderson Roy A. , Reid William D. K. , Shirley Mark D. F. , Harris John P. , Hunter Paul R. , O'Brien Sarah J.
Published: May 2019

Norovirus (NoV) is the most commonly recognized cause of acute gastroenteritis, with over a million cases globally per year. While usually self-limiting, NoV poses a substantial economic burden because it is highly contagious and there are multiple transmission routes. Infection occurs through inhalation of vomitus; faecal-oral spread; and food, water and environmental contamination. While the incidence of the disease is predictably seasonal, much less is known about the relative contribution of the various exposure pathways in causing disease. Additionally, asymptomatic excretion and viral shedding make forecasting disease burden difficult. We develop a novel stochastic dynamic network model to investigate the contributions of different transmission pathways in multiple coupled social networks representing schools, hospitals, care-homes and family households in a community setting. We analyse how the networks impact on transmission. We used ward-level demographic data from Northumberland, UK to create a simulation cohort. We compared the results with extant data on NoV cases from the IID2 study. Connectivity across the simulated cohort was high. Cases of NoV showed marked seasonality, peaking in early winter and declining through the summer. For the first time, we show that fomites and food appear to be the most important exposure routes in determining the population burden of disease.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.
Applying optimal control theory to complex epidemiological models to inform real-world disease management
Authors: Bussell E. H. , Dangerfield C. E. , Gilligan C. A. , Cunniffe N. J.
Published: May 2019

Mathematical models provide a rational basis to inform how, where and when to control disease. Assuming an accurate spatially explicit simulation model can be fitted to spread data, it is straightforward to use it to test the performance of a range of management strategies. However, the typical complexity of simulation models and the vast set of possible controls mean that only a small subset of all possible strategies can ever be tested. An alternative approach—optimal control theory—allows the best control to be identified unambiguously. However, the complexity of the underpinning mathematics means that disease models used to identify this optimum must be very simple. We highlight two frameworks for bridging the gap between detailed epidemic simulations and optimal control theory: open-loop and model predictive control. Both these frameworks approximate a simulation model with a simpler model more amenable to mathematical analysis. Using an illustrative example model, we show the benefits of using feedback control, in which the approximation and control are updated as the epidemic progresses. Our work illustrates a new methodology to allow the insights of optimal control theory to inform practical disease management strategies, with the potential for application to diseases of humans, animals and plants.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.
Rigorous surveillance is necessary for high confidence in end-of-outbreak declarations for Ebola and other infectious diseases
Authors: Thompson Robin N. , Morgan Oliver W. , Jalava Katri
Published: May 2019

The World Health Organization considers an Ebola outbreak to have ended once 42 days have passed since the last possible exposure to a confirmed case. Benefits of a quick end-of-outbreak declaration, such as reductions in trade/travel restrictions, must be balanced against the chance of flare-ups from undetected residual cases. We show how epidemiological modelling can be used to estimate the surveillance level required for decision-makers to be confident that an outbreak is over. Results from a simple model characterizing an Ebola outbreak suggest that a surveillance sensitivity (i.e. case reporting percentage) of 79% is necessary for 95% confidence that an outbreak is over after 42 days without symptomatic cases. With weaker surveillance, unrecognized transmission may still occur: if the surveillance sensitivity is only 40%, then 62 days must be waited for 95% certainty. By quantifying the certainty in end-of-outbreak declarations, public health decision-makers can plan and communicate more effectively.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’. This issue is linked with the earlier theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.
A global to local genomics analysis of Clostridioides difficile ST1/RT027 identifies cryptic transmission events in a northern Arizona healthcare network
Authors: Williamson Charles H. D. , Stone Nathan E. , Nunnally Amalee E. , Hornstra Heidie M. , Wagner David M. , Roe Chandler C. , Vazquez Adam J. , Nandurkar Nivedita , Vinocur Jacob , Terriquez Joel , Gillece John , Travis Jason , Lemmer Darrin , Keim Paul , Sahl Jason W.
Published: May 2019

Clostridioides difficile

is a ubiquitous, diarrhoeagenic pathogen often associated with healthcare-acquired infections that can cause a range of symptoms from mild, self-limiting disease to toxic megacolon and death. Since the early 2000s, a large proportion of

C. difficile

cases have been attributed to the ribotype 027 (RT027) lineage, which is associated with sequence type 1 (ST1) in the

C. difficile

multilocus sequence typing scheme. The spread of ST1 has been attributed, in part, to resistance to fluoroquinolones used to treat unrelated infections, which creates conditions ideal for

C. difficile

colonization and proliferation. In this study, we analysed 27 isolates from a healthcare network in northern Arizona, USA, and 1352 publicly available ST1 genomes to place locally sampled isolates into a global context. Whole genome, single nucleotide polymorphism analysis demonstrated that at least six separate introductions of ST1 were observed in healthcare facilities in northern Arizona over an 18-month sampling period. A reconstruction of transmission networks identified potential nosocomial transmission of isolates, which were only identified via whole genome sequence analysis. Antibiotic resistance heterogeneity was observed among ST1 genomes, including variability in resistance profiles among locally sampled ST1 isolates. To investigate why ST1 genomes are so common globally and in northern Arizona, we compared all high-quality

C. difficile

genomes and identified that ST1 genomes have gained and lost a number of genomic regions compared to all other

C. difficile

genomes; analyses of other toxigenic

C. difficile

sequence types demonstrate that this loss may be anomalous and could be related to niche specialization. These results suggest that a combination of antimicrobial resistance and gain and loss of specific genes may explain the prominent association of this sequence type with

C. difficile

infection cases worldwide. The degree of genetic variability in ST1 suggests that classifying all ST1 genomes into a quinolone-resistant hypervirulent clone category may not be appropriate. Whole genome sequencing of clinical

C. difficile

isolates provides a high-resolution surveillance strategy for monitoring persistence and transmission of

C. difficile

and for assessing the performance of infection prevention and control strategies.
dearseq: a variance component score test for RNA-Seq differential analysis that effectively controls the false discovery rate
Authors: Gauthier Marine , Agniel Denis , Thiébaut Rodolphe , Hejblum Boris P.
Published: May 2019

RNA-seq studies are growing in size and popularity. We provide evidence that the most commonly used methods for differential expression analysis (DEA) may yield too many false positive results in some situations. We presentdearseq, a new method for DEA which controls the FDR without making any assumption about the true distribution of RNA-seq data. We show thatdearseqcontrols the FDR while maintaining strong statistical power compared to the most popular methods. We demonstrate this behavior with mathematical proofs, simulations, and a real data set from a study of Tuberculosis, where our method produces fewer apparent false positives.
High-throughput microfluidic micropipette aspiration device to probe time-scale dependent nuclear mechanics in intact cells
Authors: Davidson Patricia M. , Fedorchak Gregory R. , Mondésert-Deveraux Solenne , Bell Emily S. , Isermann Philipp , Aubry Denis , Allena Rachele , Lammerding Jan
Published: May 2019

The mechanical properties of the cell nucleus are increasingly recognized as critical in many biological processes. The deformability of the nucleus determines the ability of immune and cancer cells to migrate through tissues and across endothelial cell layers, and changes to the mechanical properties of the nucleus can serve as novel biomarkers in processes such as cancer progression and stem cell differentiation. However, current techniques to measure the viscoelastic nuclear mechanical properties are often time consuming, limited to probing one cell at a time, or require expensive, highly specialized equipment. Furthermore, many current assays do not measure time-dependent properties, which are characteristic of viscoelastic materials. Here, we present an easy-to-use microfluidic device that applies the well-established approach of micropipette aspiration, adapted to measure many cells in parallel. The device design allows rapid loading and purging of cells for measurements, and minimizes clogging by large particles or clusters of cells. Combined with a semi-automated image analysis pipeline, the microfluidic device approach enables significantly increased experimental throughput. We validated the experimental platform by comparing computational models of the fluid mechanics in the device with experimental measurements of fluid flow. In addition, we conducted experiments on cells lacking the nuclear envelope protein lamin A/C and wild-type controls, which have well-characterized nuclear mechanical properties. Fitting time-dependent nuclear deformation data to power law and different viscoelastic models revealed that loss of lamin A/C significantly altered the elastic and viscous properties of the nucleus, resulting in substantially increased nuclear deformability. Lastly, to demonstrate the versatility of the devices, we characterized the viscoelastic nuclear mechanical properties in a variety of cell lines and experimental model systems, including human skin fibroblasts from an individual with a mutation in the lamin gene associated with dilated cardiomyopathy, healthy control fibroblasts, induced pluripotent stem cells (iPSCs), and human tumor cells. Taken together, these experiments demonstrate the ability of the microfluidic device and automated image analysis platform to provide robust, high throughput measurements of nuclear mechanical properties, including time-dependent elastic and viscous behavior, in a broad range of applications.
Physiological determinants of the increase in oxygen consumption during exercise in individuals with stroke
Authors: Oyake Kazuaki , Baba Yasuto , Ito Nao , Suda Yuki , Murayama Jun , Mochida Ayumi , Kondo Kunitsugu , Otaka Yohei , Momose Kimito
Published: May 2019

Background

Understanding the physiological limitations of the increase in oxygen consumption (V̇O2) during exercise is essential to improve cardiorespiratory fitness in individuals with stroke. However, the physiological determinants of the increase in V̇O2 during exercise have not been examined using multivariate analysis in individuals with stroke. This study aimed to identify the physiological determinants of the increase in V̇O2 during a graded exercise in terms of the respiratory function, cardiac function, and ability of skeletal muscles to extract oxygen.

Methods

Eighteen individuals with stroke (60.1 ± 9.4 years of age, 67.1 ± 30.8 days poststroke) underwent a graded exercise test for the assessment of cardiorespiratory response to exercise. The increase in V̇O2 from rest to ventilatory threshold and that from rest to peak exercise were measured as a dependent variable. The increases in respiratory rate, tidal volume, heart rate, stroke volume, and arterial-venous oxygen difference from rest to ventilatory threshold and those from rest to peak exercise were measured as independent variables.

Results

From rest to ventilatory threshold, the increases in heart rate (β = 0.546) and arterial-venous oxygen difference (β = 0.398) were significant determinants of the increase in V̇O2 (adjusted R2 = 0.703, p < 0.001). From rest to peak exercise, the increases in tidal volume (β = 0.611) and heart rate (β = 0.353) were significant determinants of the increase in V̇O2 (adjusted R2 = 0.702, p < 0.001).

Conclusion

V̇O2 is well-known to increase nearly linearly with increasing heart rate; however, our results suggest that arterial-venous oxygen difference and tidal volume are also significant physiological determinants of the increase in V̇O2 from rest to ventilatory threshold and that from rest to peak exercise, respectively. Our findings could potentially contribute to the development of appropriate therapies to improve cardiorespiratory fitness in individuals with stroke.
Casilio-ME: Enhanced CRISPR-based DNA demethylation by RNA-guided coupling methylcytosine oxidation and DNA repair pathways
Authors: Taghbalout Aziz , Du Menghan , Jillette Nathaniel , Rosikiewicz Wojciech , Rath Abhijit , Heinen Christopher D. , Li Sheng , Cheng Albert W.
Published: May 2019

We have developed a methylation editing toolbox, Casilio-ME, that enables not only RNA-guided methylcytosine editing by targeting TET1 to genomic sites, but also by co-delivering TET1 and protein factors that couple methylcytosine oxidation to DNA repair activities, and/or promote TET1 to achieve enhanced activation of methylation-silenced genes. Delivery of TET1 activity by Casilio-ME1 robustly altered the CpG methylation landscape of promoter regions and activated methylation-silenced genes. We augmented Casilio-ME1 to simultaneously deliver the TET1-catalytic domain and GADD45A (Casilio-ME2) or NEIL2 (Casilio-ME3) to streamline removal of oxidized cytosine intermediates to enhance activation of targeted genes. Using two-in-one effectors or modular effectors, Casilio-ME2 and Casilio-ME3 remarkably boosted gene activation and methylcytosine demethylation of targeted loci. We expanded the toolbox to enable a stable and expression-inducible system for broader application of the Casilio-ME platforms. This work establishes an advanced platform for editing DNA methylation to enable transformative research investigations interrogating DNA methylomes.
Global distribution and evolution ofMycobacterium bovislineages
Authors: Zimpel Cristina Kraemer , Patané José Salvatore L. , Proença Guedes Aureliano Coelho , de Souza Robson F. , Silva-Pereira Taiana T. , Soler Camargo Naila C. , de Souza Filho Antônio F. , Ikuta Cássia Y. , Ferreira Neto José Soares , Setubal João Carlos , Heinemann Marcos Bryan , Sa Guimaraes Ana Marcia
Published: May 2019

Mycobacterium bovisis the main causative agent of zoonotic tuberculosis in humans and frequently devastates livestock and wildlife worldwide. Previous studies suggested the existence of genetic groups ofM. bovisstrains based on limited DNA markers (a.k.a. clonal complexes), and the evolution and ecology of this pathogen has been only marginally explored at the global level. We have screened over 2,600 publicly availableM. bovisgenomes and newly sequenced two wildlifeM. bovisstrains, gathering 823 genomes from 21 countries and 21 host-species, including humans, to complete a phylogenomic analyses. We propose the existence of four distinct global lineages ofM. bovis(Lb1, Lb2, Lb3 and Lb4) underlying the current disease distribution. These lineages are not fully represented by clonal complexes and are dispersed based on geographic location rather than host species. Our data divergence analysis agreed with previous studies reporting independent archeological data of ancientM. bovis[(South Siberian infected skeletons at ∼2,000 years BP (before present)] and indicates that extantM. bovisoriginated during the Roman period, subsequently dispersing across the world with the discovery and settlement of the New World and Oceania, directly influenced by trades among countries.