bluuebunny/crossref_metadata_2025 huggingface dataset:
LASER PHOTOCOAGULATION FOR THE TREATMENT OF OPTIC NERVE HEAD PIT–RELATED MACULOPATHY IN A PATIENT WITH BILATERAL CHORIORETINAL COLOBOMA
Authors: Weinberger Yehonatan , Weinberger Dov , Priel Ethan , Gal-Or Orly , Ehrlich Rita
Published: February 2021

Purpose:

To report a case of laser photocoagulation for the treatment of a combined coloboma and optic nerve head pit–related maculopathy in a patient with bilateral chorioretinal coloboma.

Methods:

A case report.

Results:

A 15-year-old woman, presented with the visual acuity of 20/100 in her right eye for six weeks. She was diagnosed with macular detachment secondary to optic nerve head pit in her right eye and bilateral chorioretinal coloboma. Multimodal imaging, including color photography, fluorescein angiography, and spectral-domain optical coherence tomography, was used to identify and demonstrate the location of the tract of fluid from the optic nerve head pit, isolated from the coloboma. Optical coherence tomography–guided laser photocoagulation treatment at the location of the tract resulted in complete resolution of macular fluid with visual recovery to 20/25.

Conclusion:

Our case stresses the value of correct diagnosis directing photocoagulation treatment of combined optic nerve head pit–related maculopathy in eyes with chorioretinal coloboma using multimodal imaging.
Spinal nociceptive sensitization and plasma palmitoylethanolamide levels during experimentally induced migraine attacks
Authors: De Icco Roberto , Greco Rosaria , Demartini Chiara , Vergobbi Pietro , Zanaboni Annamaria , Tumelero Elena , Reggiani Angelo , Realini Natalia , Sances Grazia , Grillo Valentina , Allena Marta , Tassorelli Cristina
Published: February 2021

Migraine pathophysiology has been suggested to include dysregulation of the endocannabinoid system (ES). We simultaneously evaluated plasma anandamide (AEA) and palmitoylethanolamide (PEA) levels and spinal sensitization in a validated human model of migraine based on systemic nitroglycerin (NTG) administration. Twenty-four subjects with episodic migraine (MIG) and 19 healthy controls (HC) underwent blood sampling and investigation of nociceptive withdrawal reflex thresholds (RTh: single-stimulus threshold; TST: temporal summation threshold) before and 30 (T30), 60 (T60), and 120 (T120) minutes after sublingual NTG administration (0.9 mg). At baseline, the MIG and HC groups were comparable for plasma AEA (P = 0.822) and PEA (P = 0.182) levels, and for RTh (P = 0.142) and TST values (P = 0.150). Anandamide levels increased after NTG administration (P = 0.022) in both groups, without differences between them (P = 0.779). By contrast, after NTG administration, PEA levels increased in the MIG group at T120 (P = 0.004), while remaining stable in the HC group. Nitroglycerin administration induced central sensitization in the MIG group, which was recorded as reductions in RTh (P = 0.046) at T30 and T120, and in TST (P = 0.001) at all time points. In the HC group, we observed increases in RTh (P = 0.001) and TST (P = 0.008), which suggest the occurrence of habituation. We found no significant correlations between the ES and neurophysiological parameters. Our findings suggest a role for PEA in the ictal phase of episodic migraine. The ES does not seem to be directly involved in the modulation of NTG-induced central sensitization, which suggests that the observed PEA increase and spinal sensitization are parallel, probably unrelated, phenomena.
Astrocytes mediate migraine-related intracranial meningeal mechanical hypersensitivity
Authors: Zhao Jun , Blaeser Andrew S. , Levy Dan
Published: February 2021

The genesis of the headache phase in migraine with aura is thought to be mediated by cortical spreading depression (CSD) and the subsequent activation and sensitization of primary afferent neurons that innervate the intracranial meninges and their related large vessels. Yet, the exact mechanisms underlying this peripheral meningeal nociceptive response remain poorly understood. We investigated the relative contribution of cortical astrocytes to CSD-evoked meningeal nociception using extracellular single-unit recording of meningeal afferent activity and 2-photon imaging of cortical astrocyte calcium activity, in combination with 2 pharmacological approaches to inhibit astrocytic function. We found that fluoroacetate and l-α-aminoadipate, which inhibit astrocytes through distinct mechanisms, suppressed CSD-evoked afferent mechanical sensitization, but did not affect afferent activation. Pharmacological inhibition of astrocytic function, which ameliorated meningeal afferents' sensitization, reduced basal astrocyte calcium activity but had a minimal effect on the astrocytic calcium wave during CSD. We propose that calcium-independent signaling in cortical astrocytes plays an important role in driving the sensitization of meningeal afferents and the ensuing intracranial mechanical hypersensitivity in migraine with aura.
Applying Lean Six Sigma to Improve Depression Screening and Follow-Up in Oncology Clinics
Authors: Gerard Bethlyn , Robbins Mona , Putra Joseph , Ram Mythili , Boukhari Mounia , Mutz Jacqueline , Coffie Sharron , Martin-Cook Kristin , Huffman Alexandra , Bryant Donna M. , Myers Lynn , Bajaj Puneet , Froehlich Thomas , Fish Jason
Published: February 2021

Depression is a common and serious illness that impairs the health of individuals and societies globally. It is associated with a significant economic burden, with productivity losses exceeding $40 billion dollars annually in the United States (U.S.) alone. This project focused on the use of a systematic, data-driven approach to improve the screening rate for depression in an academic, metropolitan cancer center located in North Texas. A multidisciplinary team collaboratively applied Lean Six Sigma education, methods, and tools within oncology and psychiatry clinics to address the increased risk of depression among oncology patients. Improving the standardization of screening and follow-up processes, resulted in a 44% sustained increase in the depression screening and follow-up performance rate. This improvement was verified to be statistically significant through the use of control charts toward the end of the project.
Three-dimensional (3D) Printed Vestibular Schwannoma for Facial Nerve Tractography Validation
Authors: Epprecht Lorenz , Qureshi Ahad , Kozin Elliott D. , McInturff Stephen , Remenschneider Aaron , Huber Alexander M. , Brown Merrit Christian , Barker Frederick G. , Reinshagen Katherine L. , Lee Daniel J.
Published: February 2021

Objectives:

Predicting the course of cranial nerve (CN) VII in the cerebellopontine angle (CPA) on preoperative imaging for vestibular schwannoma (VS) may help guide surgical resection and reduce complications. Diffusion MRI based tractography has been used to identify cranial nerve trajectory, but intraoperative validation of this novel approach is challenging. Currently, validation is based on operative report descriptions of the course of cranial nerves, but yields a simplified picture of the three-dimensional (3D) course of CN VII. In this study, we investigate the accuracy of tractography with detailed patient-specific 3D-printed VS tumors.

Design:

Retrospective case review.

Setting:

Tertiary referral center.

Participants:

Twenty adult VS surgical candidates.

Main Outcome Measures:

We compared tractography with intraoperative 3D course of CN VII. The surgeons were blinded to tractography and drew the intraoperative course of the CN VII on a patient specific 3D-printed tumor model for detailed comparison with tractography.

Results:

Of 20 patients, one was excluded due to subtotal removal and inability to assess CN VII course. In the remaining 19 patients, 84% (16/19) tractography was successful. In 94% of tumors with tractography (15/16), the intraoperative description of CN VII course matched the tractography finding. The maximum distance, however, between tractography and intraoperative course of CN VII was 3.7 mm ± 4.2 mm.

Conclusion:

This study presents a novel approach to CN VII tractography validation in VS. Although descriptions of CN VII intraoperatively match tractography, caution is warranted as quantitative measures suggest a clinically significant distance between tractography and CN VII course.
A Compliant Model of the Ventricular Apex to Study Suction in Ventricular Assist Devices
Authors: Rocchi Maria , Fresiello Libera , Meyns Bart , Jacobs Steven , Gross Christoph , Pauls Jo P. , Graefe Roland , Stecka Anna , Kozarski Maciej , Zieliński Krzysztof
Published: February 2021

Ventricular suction is a frequent adverse event in patients with a ventricular assist device (VAD). This study presents a suction module (SM) embedded in a hybrid (hydraulic-computational) cardiovascular simulator suitable for the testing of VADs and related suction events. The SM consists of a compliant latex tube reproducing a simplified ventricular apex. The SM is connected on one side to a hydraulic chamber of the simulator reproducing the left ventricle, and on the other side to a HeartWare HVAD system. The SM is immersed in a hydraulic chamber with a controllable pressure to occlude the compliant tube and activate suction. Two patient profiles were simulated (dilated cardiomyopathy and heart failure with preserved ejection fraction), and the circulating blood volume was reduced stepwise to obtain different preload levels. For each simulated step, the following data were collected: HVAD flow, ventricular pressure and volume, and pressure at the inflow cannula. Data collected for the two profiles and for decreasing preload levels evidenced suction profiles differing in terms of frequency (intermittent vs. every heart beat), amplitude (partial or complete stoppage of the HVAD flow), and shape. Indeed different HVAD flow patterns were observed for the two patient profiles because of the different mechanical properties of the simulated ventricles. Overall, the HVAD flow patterns showed typical indicators of suctions observed in clinics. Results confirmed that the SM can reproduce suction phenomena with VAD under different pathophysiological conditions. As such, the SM can be used in the future to test VADs and control algorithms aimed at preventing suction phenomena.
Left Ventricular Assist Device Implantation in Patients with Preoperative Severe Mitral Regurgitation
Authors: Tang Paul C. , Duggal Neal M. , Haft Jonathan W. , Romano Matthew A. , Bolling Steven F. , Abou El Ela Ashraf , Wu Xiaoting , Colvin Monica M. , Aaronson Keith D. , Pagani Francis D.
Published: February 2021

We examined cardiac features associated with residual mitral regurgitation (MR) following continuous-flow left ventricular assist device (cfLVAD) implant. From 2003 to 2017, 134 patients with severe MR underwent cfVLAD implant without mitral valve (MV) intervention. Echocardiographic (echo) assessment occurred pre-cfLVAD, early post-cfLVAD, and at last available echo. Ventricular and atrial volumes were calculated from established formulas and normalized to be predicted. Cluster analysis based on preoperative normalized left ventricular and atrial volumes, and MV height identified grades 1, 2, and 3 with progressively larger cardiac chamber sizes. Median early echo follow-up was 0.92 (0.55, 1.45) months and the last follow-up was 15.12 (5.28, 38.28) months. Mitral regurgitation improved early after cfLVAD by 2.10 ± 1.16 grades (
p
< 0.01). Mitral regurgitation severity at the last echocardiogram positively correlated with the preoperative left ventricular volume (
p
= 0.014, R = 0.212), left atrial volume (
p
= 0.007, R = 0.233), MV anteroposterior height (
p
= 0.032, R = 0.185), and MV mediolateral diameter (
p
= 0.043, R = 0.175). Morphologically, smaller grade 1 hearts were correlated with MR resolution at the late follow-up (
p
= 0.023). Late right ventricular failure (RVF) at the last clinical follow-up was less in grade 1 (4/48 [8.3%]) compared with grades 2 and 3 (26/86 [30.2%]),
p
= 0.004). Grade 1 cardiac dimensions correlates with improvement in severe MR and had less late RVF.
Essentials of Advocacy in Case Management: Part 2
Authors: Tahan Hussein M.
Published: February 2021

Purpose/Objectives:

This article describes a client advocacy model for use by case managers. It delineates necessary competencies for the case manager and shares important strategies for effective client advocacy.

Primary Practice Setting(s):

All practice settings across the continuum of health and human services and case managers of diverse professional backgrounds.

Findings and Conclusion:

Advocacy is a primary role and necessary competency of professional case managers functioning in various care settings. It is rooted in ethical theory and principles. Successful case managers apply ethical principles of advocacy at every step of the case management process and in the decisions they make. Part II of this two-part article presents a client advocacy model for case managers to apply in their practice, describes the role of advocacy in client engagement, and identifies important strategies and a set of essential competencies for effective case management advocacy. Part I already explored the ethical theories and principles of advocacy, the perception of case management-related professional organizations of advocacy, and the common types of advocacy based on scope, complexity, impact, and reach.

Implications for Case Management:

Acquiring foundational knowledge, skills, and competencies in what advocacy is and how to effectively enact its related behaviors is essential for success of case managers and for achieving desired outcomes for both the clients and health care agencies/providers alike. Case management leaders are urged to use the knowledge shared in this article to develop advocacy training and competency management programs for their case managers.
Baclofen Toxicity Mimicking Brain Death
Authors: Pearson Rachel P. , Hoang LeAnn K. , Roufail John , Muhonen Michael G. , Galion Anjalee W.
Published: February 2021

Background

Baclofen is commonly used in both pediatric and adult patients to treat spasticity secondary to spinal cord and cerebral pathology. A broad range of symptoms and severity of baclofen toxicity have been described. However, to our knowledge, there are no reports to date of baclofen toxicity mimicking brain death in pediatric patients.

Objective

We reviewed the presentation, clinical course, diagnostic studies including imaging and electroencephalography, and outcome of a patient with transient coma and loss of brainstem reflexes mimicking brain death secondary to baclofen toxicity.

Methods

During a baclofen pump refill, a 12-year-old boy with cerebral palsy had inadvertent injection of 12,000 μg of baclofen into the pocket around his pump. Within an hour, he presented with acute altered mental status that rapidly progressed to a comatose state with absent brainstem reflexes.

Results

After appropriate management, the patient returned to his neurological baseline by hospital day 3.

Discussion

We reviewed the literature for varying presentations of baclofen toxicity and associated electroencephalography findings, mechanism of overdose, and different management options. In this case, the mechanism of baclofen toxicity was suspected to be secondary to extravasation from the pump pocket and subsequent systemic absorption.

Conclusions

Patients with baclofen toxicity may have a dramatic presentation and an initial examination mimicking brain death. Given its rarity, this clinical entity may not be readily recognized, and there is potential for misinterpretation of diagnosis and prognosis. It is important for physicians to be familiar with this clinical scenario to avoid false declaration of brain death.
MLH1/PMS2-deficient Endometrial Carcinomas in a Universally Screened Population: MLH1 Hypermethylation and Germline Mutation Status
Authors: Kurpiel Brett , Thomas Martha S. , Mubeen Mansoor , Ring Kari L. , Modesitt Susan C. , Moskaluk Christopher A. , Mills Anne M.
Published: February 2021

MLH1/PMS2 loss due to epigenetic hypermethylation of the MLH1 promoter is the most common cause of mismatch repair deficiency in endometrial carcinoma, and typically provides reassurance against an associated germline mutation. To further characterize the genetic features of MLH1/PMS2-deficient endometrial cancers, the departmental database was searched for cases with dual MLH1/PMS2 loss and retained MSH2/6 expression which underwent MLH1 hypermethylation testing. Genetic testing results were obtained when available. One hundred seventeen endometrial cancers met inclusion criteria: 100 (85%) were MLH1-hypermethylated, 3 (3%) were low-level/borderline, 7 (6%) were nonmethylated, and 7 (6%) were insufficient for testing. Sixteen cases (12 MLH1-hypermethylated, 3 nonmethylated, and 1 insufficient for testing) underwent germline testing, 6 of which (37.5%) demonstrated germline variants of unknown significance (VUS) (MSH6, PMS2, POLD1, BRIP1, RAD51D, CHEK2) but no known deleterious mutations. Notably, however, the patients harboring the MSH6 and PMS2 germline VUS had clinical features concerning for Lynch syndrome. One nonmethylated, germline-normal case underwent somatic tumor testing, and demonstrated a somatic MLH1 mutation. In summary, MLH1-hypermethylation accounts for the vast majority of MLH1/PMS2-deficient cancers in a universally screened population, although MLH1 somatic and germline mutations can occur. Occasionally, patients with MLH1-hypermethlated tumors also bear germline VUS in other mismatch repair genes as well as genes implicated in other hereditary cancer syndromes, but their clinical relevance is unclear. Family and personal cancer histories must always be evaluated to determine the need for germline testing in women with loss of MLH1/PMS2, even in the setting of hypermethylation.
Hepatitis C Knowledge and Recent Diagnosis Affect Hepatitis C Treatment Willingness in Persons Living With HIV
Authors: Cachay Edward R. , Torriani Francesca J. , Hill Lucas , Rajagopal Amutha , Yin Jeffrey , Bamford Laura , Mathews William C.
Published: February 2021

Background:

We assessed the impact of health literacy and hepatitis C (HCV) knowledge on HCV treatment willingness among people living with HIV (PLWH) at an academic HIV clinic.

Methods:

Cross-sectional analysis of PLWH coinfected with HCV who completed health literacy, HIV literacy, and HCV knowledge inventories. We estimated the prevalence of low health literacy, HIV knowledge, and HCV knowledge sampled from 3-comparison groups: PLWH not referred for HCV, referred but who “not showed” to the HCV clinic, and referred and attended the HCV clinic. We used mixed-model linear and logistic regression to ascertain predictors of low health literacy, HIV knowledge, HCV knowledge, and predictors of willingness to start HCV treatment.

Results:

We enrolled 151 PLWH; 17% were female, 38% non-White, and 60% without a high-school education. Approximately, 68% were men who have sex with men, of whom 62% used intravenous drugs. The prevalence of low health, HIV knowledge, and HCV knowledge was 10%, 32%, and 29%, respectively. Predictors of low health literacy were being Hispanic, cirrhotic, and not completing high-school education. Low HCV knowledge was observed in female, non-White, and those diagnosed with HCV for a decade. In adjusted analyses, PLWH living with HCV for a decade (OR: 0.23) were less likely to be very willing to be treated for HCV. By contrast, those with high HCV knowledge were more likely to be very willing to receive treatment (OR: 1.27).

Conclusion:

Low HCV knowledge and living with HCV for at least a decade are under-recognized negative predictors for PLWH's willingness to receive HCV treatment.

Clinical Trials Registration:

ClinicaTrials.gov identifier: NCT20170991.
Illustration of the Added Value of 18F-DOPA PET to Multimodal MRI to Distinguish Low- and High-Grade Gliomas
Authors: Louarn Nicolas , Kauv Paul , Capelle Laurent , Mokhtari Karima , Itti Emmanuel
Published: February 2021

18F-DOPA PET-MRI was performed on a 38-year-old man referred for complementary imaging after a brain tumor was discovered, according to EANM/RANO recommendations. We performed a simultaneous PET with 3-T brain MRI, which revealed 2 high 18F-DOPA uptakes, with no multimodal MRI sign of aggressiveness. An awake surgery was performed and found a grade III anaplastic astrocytoma IDH1-R132L mutant, according to the 2016 WHO classification. This was probably the aggressive transition of a grade II diffuse astrocytoma. This case illustrates the added value of 18F-DOPA PET to multimodal MRI to distinguish low- and high-grade gliomas.
Temporal Trends and Geographical Variation in Dupuytren Disease Surgery in England
Authors: Alser Osaid , Abram Simon G. F. , Craig Richard S. , Lane Jennifer C. E. , Shaw Abigail V. , Prats-Uribe Albert , Rees Jonathan L. , Prieto-Alhambra Daniel , Furniss Dominic
Published: February 2021

Background

Dupuytren disease (DD) is a common fibroproliferative disease of the palmar fascia. The mainstay of DD treatment in England is surgery with either percutaneous needle fasciotomy, limited fasciectomy, or dermofasciectomy. This study aimed to investigate the temporal trends and geographical variation of primary DD surgery in England.

Methods

A longitudinal population-based cohort study was perfomed using the Hospital Episode Statistics database from April 1, 2007, to March 31, 2017. Directly standarized rates were estimated over time (between financial years 2007–2008 and 2016–2017) and by geographic region (by clinical commissioning groups [CCGs]; financial years 2010–2011, 2013–2014, and 2016–2017). The Office for National Statistics midyear population estimates were used as the reference population.

Main Findings

Primary DD surgery was undertaken at a steadily increasing rate from financial year 2007 to 2008, to 2016 to 2017 in England. There was a striking 3.6-fold variation in the rates of primary DD surgery among National Health Service CCGs in England place of residence.

Conclusions

This significant variation in DD surgical treatment in England suggests a need for the development of standardized surgical practice across all CCGs and National Health Service hospitals, promoting equality of access to cost-effective health care.
Our Strategy in Management of Maxillonasal Dysplasia in Pediatric Patients
Authors: Afifi Tarek , Saleh Dalia , Shaker Ayman
Published: February 2021

Maxillonasal dysplasia or Binder syndrome is an uncommon condition. It is a congenital disease characterized by undergrowth of the central face and may include elements of the nose and upper jaw. The hallmark of the deformity is a retruded mid-face and an extremely flat nose. The timing and the surgical approaches for management of such deformity are still controversial. In this paper, we are going to present our experience in management of Binder syndrome in children. Seven children ranging in age from 6 to 13 years with classic features of Binder syndrome were operated upon in this study. The surgical approach was done at an early age and included 3 main components; nasal dorsum augmentation by costal cartilage graft, maxillary augmentation by rib grafts and columellar reconstruction by VY-plasty and strut grafts. Patients were followed for up to 6 years. Excellent results were obtained in all patients with this surgical procedure. Half of our patients required more than 1 surgery but none of them required any secondary orthognathic surgery. Therefore, we recommend that children with Binder syndrome should be managed at an early age at least for correction of their nasal deformities. Maxillary augmentation can also be done simultaneously or delayed for a second stage. During the second stage, further nasal augmentation can be accomplished. Definitive orthognathic surgeries have to be postponed to adolescence. This strategy can dramatically improve the patient aesthetic and alleviate the psychological upset without much disturbance of the facial growth.
Modified Z-Epicanthoplasty Based on the Movement and Tension of Medial Canthal Area in Asian Females
Authors: Tong Jing , Wang Rongrong , Sun Jiaming , Yang Jie
Published: February 2021

Background:

Z-epicanthoplasty is a popular method of correcting mild to moderate epicanthal folds. However, it has some limitations, such as, under correction, recurrence, and leaving of a visible scar. This study aimed to modify the traditional Z-epicanthoplasty to optimize its application in correcting severe cases of epicanthal fold.

Methods:

A total of 117 Asian female patients received the modified Z-epicanthoplasty between January 2018 and April 2018. The type and severity of epicanthal fold were evaluated preoperatively, whereas the intercanthal distance, interpupillary distance, and scar visibility and cosmetic results were evaluated preoperatively and one-year postsurgery.

Results:

A total of 142 eyes had epicanthus tarsalis, whereas 92 eyes had epicanthus palpebralis. Of these, 29 were mild, 95 were moderate, and 119 were severe. After the operation, the intercanthal distance ratio was decreased from 0.615 (range, 0.548–0.685) preoperatively to 0.564 (range, 0.500–0.632). The mean reduction was 5.1% (range, 1.2%–10.1%; P < 0.001, Wilcoxon signed-rank test). Also, 195 eyes (83.3%) had no apparent scar and 36 (15.4%) had visible scar only under close inspection. Three eyes (1.32%) had visible scar without the need for revision. No reoccurrence was observed. And the cosmetic outcomes were scored as either excellent or good.

Conclusions:

The modified Z-epicanthoplasty which released the medial canthus activity sufficiently and corrected epicanthal fold at its maximum displacement is an effective method for the treatment of all degrees of epicanthus tarsalis and epicanthus palpebralis in Asian females.
Carotid Ultrasound in Assessing Fluid Responsiveness in Patients with Hypotension and Suspected Sepsis
Authors: Liteplo Andrew S. , Schleifer Jessica , Marill Keith A. , Huang Calvin K. , Gouker Stacey K. , Ratanski Daniel , Diamond Eden , Filbin Michael R. , Shokoohi Hamid
Published: February 2021

Purpose:

We sought to assess whether ultrasound (US) measurements of carotid flow time (CFTc) and carotid blood flow (CBF) predict fluid responsiveness in patients with suspected sepsis.

Methods:

This was a prospective observational study of hypotensive (systolic blood pressure < 90) patients “at risk” for sepsis receiving intravenous fluids (IVF) in the emergency department. US measurements of CFTc and CBF were performed at time zero and upon completion of IVF. All US measurements were repeated after a passive leg raise (PLR) maneuver. Fluid responsiveness was defined as normalization of blood pressure without persistent hypotension or need for vasopressors.

Results:

A convenience sample of 69 patients was enrolled. The mean age was 65; 49% were female. Fluid responders comprised 52% of the cohort. CFTc values increased significantly with both PLR (P = 0.047) and IVF administration (P = 0.003), but CBF values did not (P = 0.924 and P = 0.064 respectively). Neither absolute CFTc or CBF measures, nor changes in these values with PLR or IVF bolus, predicted fluid responsiveness, mortality, or the need for intensive care unit admission.

Conclusion:

In patients with suspected sepsis, a fluid challenge resulted in a significant change in CFTc, but not CBF. Neither absolute measurement nor delta measurements with fluid challenge predicted clinical outcomes.
Outcomes of Kidney Donors With Impaired Fasting Glucose
Authors: Hebert Sean A. , Murad Dina N. , Nguyen Duc T. , Graviss Edward A. , Adrogue Horacio E. , Matas Arthur J. , Ibrahim Hassan N.
Published: February 2021

Background.

Many kidney donor candidates with impaired fasting glucose (IFG) and all candidates with diabetes are currently excluded from kidney donation, fearing the development of an accelerated course of diabetic kidney disease in the remaining kidney.

Methods.

We studied mortality, proteinuria, and end-stage kidney disease (ESKD) in 8280 donors who donated between 1963 and 2007 according to donation fasting plasma glucose (FPG): <100 mg/dL (n = 6204), 100–125 mg/dL (n = 1826), and ≥126 mg/dL (n = 250).

Results.

Donors with IFG and those with FPG ≥126 mg/dL were older, less likely to be non-Hispanic White, had a higher body mass index, and were more likely to be related to their recipient. After 15.7 ± 10.5 y from donation to study close, 4.4% died, 29.4% developed hypertension, 13.8% developed proteinuria, and 41 (0.5%) developed ESKD. In both the logistic and Cox models, IFG was associated with a higher diabetes risk (adjusted hazard ratio [aHR], 1.65; 95% confidence interval [CI], 1.18-2.30) and hypertension (aHR, 1.35; 95% CI, 1.10-1.65; P = 0.003 for both), but not higher risk of proteinuria or ESKD. The multivariable risk of mortality in donors with ≥126 mg/dL was higher than the 2 other groups, but risks of proteinuria, cardiovascular disease, and reduced estimated glomerular filtration rate were similar to those with FPG <126 mg/dL. Three cases of ESKD developed in the 250 donors with FPG ≥126 mg/dL at 18.6 ± 10.3 y after donation (aHR, 5.36; 95% CI, 1.0-27.01; P = 0.04).

Conclusions.

Donors with IFG and the majority of donors with ≥126 mg/dL do well and perhaps should not be routinely excluded from donation.
CT-measured Cortical Volume Ratio Is an Accurate Alternative to Nuclear Medicine Split Scan Ratio Among Living Kidney Donors
Authors: Montgomery John R. , Brown Craig S. , Zondlak Allyse N. , Walsh Kevin W. , Kozlowski Julia E. , Pinsky Alexa M. , Herriman Emily A. , Sussman Jeremy , Lu Yee , Stein Erica B. , Shankar Prasad R. , Sung Randall S. , Woodside Kenneth J.
Published: February 2021

Background.

The 125I-iothalamate clearance and 99mTc diethylenetriamine-pentaacetic acid (99mTc-DTPA) split scan nuclear medicine studies are used among living kidney donor candidates to determine measured glomerular filtration rate (mGFR) and split scan ratio (SSR). The computerized tomography–derived cortical volume ratio (CVR) is a novel measurement of split kidney function and can be combined with predonation estimated GFR (eGFR) or mGFR to predict postdonation kidney function. Whether predonation SSR predicts postdonation kidney function better than predonation CVR and whether predonation mGFR provides additional information beyond predonation eGFR are unknown.

Methods.

We performed a single-center retrospective analysis of 204 patients who underwent kidney donation between June 2015 and March 2019. The primary outcome was 1-y postdonation eGFR. Model bases were created from a measure of predonation kidney function (mGFR or eGFR) multiplied by the proportion that each nondonated kidney contributed to predonation kidney function (SSR or CVR). Multivariable elastic net regression with 1000 repetitions was used to determine the mean and 95% confidence interval of R
2, root mean square error (RMSE), and proportion overprediction ≥15 mL/min/1.73 m2 between models.

Results.

In validation cohorts, eGFR-CVR models performed best (R
2, 0.547; RMSE, 9.2 mL/min/1.73 m2, proportion overprediction 3.1%), whereas mGFR-SSR models performed worst (R
2, 0.360; RMSE, 10.9 mL/min/1.73 m2, proportion overprediction 7.2%) (P < 0.001 for all comparisons).

Conclusions.

These findings suggest that predonation CVR may serve as an acceptable alternative to SSR during donor evaluation and furthermore, that a model based on CVR and predonation eGFR may be superior to other methods.
World Survey on Minimally Invasive Donor Hepatectomy: A Global Snapshot of Current Practices in 2370 Cases
Authors: Rotellar Fernando , Ciria Ruben , Wakabayashi Go , Suh Kyung-Suk , Cherqui Daniel
Published: February 2021

Background.

Having little evidence on the real extent of the minimally invasive donor hepatectomy (MIDH), a world survey was conducted aiming to picture the spread of MIDH and to identify geographical, institutional, and individual differences.

Methods.

A web-based survey was created with 5 sections (general, institutional, surgeon’s experience, technical, and spread and dissemination), comprising up to a total of 47 questions. A thorough search was carried out to identify all possible centers and surgeons performing MIDH.

Results.

A global MIDH experience of 2370 cases was collected: 1587 right hepatectomies (RHs; 48.9% pure laparoscopic), 471 left lateral sectionectomies (LLS; 81.1% pure laparoscopic), and 366 left hepatectomies (LHs; 77.6% laparoscopic-assisted). LLS and adult MIDH conversion rates were 5.4% and 3.9%, respectively. Median blood loss was 250 mL (100–600), 100 mL (50–250), and 150 mL (50–500) for RH, LLS, and LH, respectively. Intra- and postoperative transfusion rates were 0.5%, 0%, and 0.3%; and 1.3%, 1.6%, and 0% for RH, LLS, and LH, respectively. Geographically, Asia accounts up to 1730 cases (73% of the global experience, 49.6% pure lap), of which 1374 cases are RH; Europe and Middle East—395 cases—stands out for its experience in left lateral sectionectomy: 289 cases (93% pure lap). Finally, America accounts for 245 cases, using a laparoscopic-assisted technique in 72.6% of the cases (178).

Conclusions.

This world survey provides evidence and data on the global spread of MIDH and anticipates how in a near future a large-scale adoption of these techniques may be observed.
Impact of Donor and Recipient Clinical Characteristics and Hepatic Histology on Steatosis/Fibrosis Following Liver Transplantation
Authors: Shaked Oren , Demetris Jack , Levitsky Josh , Feng Sandy , Loza Bao-Li , Punch Jeff , Reyes Jorge , Klintmalm Goran , Jackson Whitney , DesMarais Michele , Sayre Peter , Shaked Abraham , Reddy K. Rajender
Published: February 2021

Background.

Deceased donor and recipient predictors of posttransplant steatosis/steatohepatitis and fibrosis are not well known. Our aim was to evaluate the prevalence and assess donor and recipient predictors of steatosis, steatohepatitis, and fibrosis in liver transplantation recipients.

Methods.

Using the immune tolerance network A-WISH multicenter study (NCT00135694), donor and recipient demographic and clinical features were collected. Liver biopsies were taken from the donor liver at transplant, and from recipients per protocol and for-cause (ie, abnormal transaminases and to rule out rejection) and were interpreted by a central pathologist.

Results.

One hundred eighty-three paired donor/recipients liver biopsies at the time of transplant and posttransplant follow-up (median time 582 d; average time to last biopsies was 704 d [SD ± 402 d]) were analyzed. Donor steatosis did not influence recipient steatosis or fibrosis. Ten of 183 recipients had steatohepatitis on the last biopsy. Recipient body mass index at the time of liver biopsy was the most influential factor associated with posttransplant steatosis. Both donor and recipient metabolic syndrome features were not associated with graft steatosis. Untreated hepatitis C viral (HCV) infection was the most influential factor associated with the development of allograft fibrosis.

Conclusions.

In a large experience evaluating paired donor and recipient characteristics, recipient body mass index at the time of liver biopsy was most significantly associated with posttransplant steatosis. Untreated HCV etiology influenced graft fibrosis. Thus relative to untreated HCV, hepatic fibrosis in those with steatosis/steatohepatitis is less common though long-term follow-up is needed to determine the course of posttransplant fibrosis. Emphasis on recipient weight control is essential.
Mitochondrial Dysfunction and Oxidative Stress in Liver Transplantation and Underlying Diseases: New Insights and Therapeutics
Authors: Shi Shaojun , Wang Ling , van der Laan Luc J.W. , Pan Qiuwei , Verstegen Monique M. A.
Published: February 2021

Mitochondria are essential organelles for cellular energy and metabolism. Like with any organ, the liver highly depends on the function of these cellular powerhouses. Hepatotoxic insults often lead to an impairment of mitochondrial activity and an increase in oxidative stress, thereby compromising the metabolic and synthetic functions. Mitochondria play a critical role in ATP synthesis and the production or scavenging of free radicals. Mitochondria orchestrate many cellular signaling pathways involved in the regulation of cell death, metabolism, cell division, and progenitor cell differentiation. Mitochondrial dysfunction and oxidative stress are closely associated with ischemia-reperfusion injury during organ transplantation and with different liver diseases, including cholestasis, steatosis, viral hepatitis, and drug-induced liver injury. To develop novel mitochondria-targeting therapies or interventions, a better understanding of mitochondrial dysfunction and oxidative stress in hepatic pathogenesis is very much needed. Therapies targeting mitochondria impairment and oxidative imbalance in liver diseases have been extensively studied in preclinical and clinical research. In this review, we provide an overview of how oxidative stress and mitochondrial dysfunction affect liver diseases and liver transplantation. Furthermore, we summarize recent developments of antioxidant and mitochondria-targeted interventions.
clusTCR: a Python interface for rapid clustering of large sets of CDR3 sequences
Authors: Valkiers Sebastiaan , Van Houcke Max , Laukens Kris , Meysman Pieter
Published: February 2021

The T-cell receptor (TCR) determines the specificity of a T-cell towards an epitope. As of yet, the rules for antigen recognition remain largely undetermined. Current methods for grouping TCRs according to their epitope specificity remain limited in performance and scalability. Multiple methodologies have been developed, but all of them fail to efficiently cluster large data sets exceeding 1 million sequences. To account for this limitation, we developed clusTCR, a rapid TCR clustering alternative that efficiently scales up to millions of CDR3 amino acid sequences. Benchmarking comparisons revealed similar accuracy of clusTCR with other TCR clustering methods. clusTCR offers a drastic improvement in clustering speed, which allows clustering of millions of TCR sequences in just a few minutes through efficient similarity searching and sequence hashing.

clusTCR was written in Python 3. It is available as an anaconda package (https://anaconda.org/svalkiers/clustcr) and on github (https://github.com/svalkiers/clusTCR).
Household secondary attack rate of COVID-19 by household size and index case characteristics
Authors: Tibebu Semra , A. Brown Kevin , Daneman Nick , Paul Lauren A. , Buchan Sarah A.
Published: February 2021

In this population-wide study in Ontario, Canada, we investigated the household secondary attack rate (SAR) to understand its relationship to household size and index case characteristics. We identified all patients with confirmed COVID-19 between July 1 and November 30, 2020. Cases within households were matched based on reported residential address; households were grouped based on the number of household contacts. The majority of households (68.2%) had a SAR of 0%, while 3,442 (11.7%) households had a SAR ≥75%. Overall household SAR was 19.5% and was similar across household sizes, but varied across index case characteristics. Households where index cases had longer delays between symptom onset and test seeking, households with older index cases, households with symptomatic index cases, and larger households located in diverse neighborhoods, were associated with greater household SAR. Our findings present characteristics associated with greater household SARs and proposes immediate testing as a method to reduce household transmission and incidence of COVID-19.
The differential impact of the COVID-19 epidemic on Medicaid expansion and non-expansion states
Authors: Hussein Muhammad Ragaa , Morsi Islam , Awad Engy A. , Fayed Dina A. , AlSulaiman Thamer , Habib Mohamed , Herbold John R.
Published: February 2021

Medicaid expansion is a federally-funded program to expand health care access and coverage to economically challenged populations by increasing eligibility to Medicaid enrollment and investing in public health preventive services in the individual states. Yet, when the COVID-19 epidemic plagued the country, fourteen states were practicing their chosen decision not to enact the Medicaid expansion policy. We examined the consequences of this nationwide split in Medicaid design on the spread of the COVID-19 epidemic between the expansion and non-expansion states. Our study shows that, on average, the expansion states had 217.56 fewer confirmed COVID-19 cases per 100,000 residents than the non-expansion states [-210.41; 95%CI (−411.131) - (−2.05); P<0.05]. Also, the doubling time of COVID-19 cases in Medicaid expansion states was longer than that of non-expansion states by an average of 1.68 days [1.6826; 95%CI 0.4035-2.9617; P<0.05]. These findings suggest that proactive investment in public health preparedness was an effective protective policy measure in this crisis, unsurpassed by the benefits of COVID-19 emergency plans and funds. The study findings could be relevant to policymakers and healthcare strategists in non-expansion states considering their states’ preparations for such public health crises.
An integrated approach to identify environmental modulators of genetic risk factors for complex traits
Authors: Balliu Brunilda , -Orive Ivan Carcamo , Gloudemans Michael J. , Nachun Daniel C. , Durrant Matthew G. , Gazal Steven , Park Chong Y. , Knowles David A. , Wabitsch Martin , Quertermous Thomas , Knowles Joshua W. , Montgomery Stephen B.
Published: February 2021

Complex traits and diseases can be influenced by both genetics and environment. However, given the large number of environmental stimuli and power challenges for gene-by-environment testing, it remains a critical challenge to identify and prioritize specific disease-relevant environmental exposures. We propose a novel framework for leveraging signals from transcriptional responses to environmental perturbations to identify disease-relevant perturbations that can modulate genetic risk for complex traits and inform the functions of genetic variants associated with complex traits. We perturbed human skeletal muscle, fat, and liver relevant cell lines with 21 perturbations affecting insulin resistance, glucose homeostasis, and metabolic regulation in humans and identified thousands of environmentally responsive genes. By combining these data with GWAS from 31 distinct polygenic traits, we show that heritability of multiple traits is enriched in regions surrounding genes responsive to specific perturbations and, further, that environmentally responsive genes are enriched for associations with specific diseases and phenotypes from the GWAS catalogue. Overall, we demonstrate the advantages of large-scale characterization of transcriptional changes in diversely stimulated and pathologically relevant cells to identify disease-relevant perturbations.
SnapKin: a snapshot deep learning ensemble for kinase-substrate prediction from phosphoproteomics data
Authors: Lin Michael , Xiao Di , Geddes Thomas A. , Burchfield James G. , Parker Benjamin L. , Humphrey Sean J. , Yang Pengyi
Published: February 2021

Mass spectrometry (MS)-based phosphoproteomics enables the quantification of proteome-wide phosphorylation in cells and tissues. A major challenge in MS-based phosphoproteomics lies in identifying the substrates of kinases, as currently only a small fraction of substrates identified can be confidently linked with a known kinase. By leveraging large-scale phosphoproteomics data, machine learning has become an increasingly popular approach for computationally predicting substrates of kinases. However, the small number of high-quality experimentally validated kinase substrates (true positive) and the high data noise in many phosphoproteomics datasets together impact the performance of existing approaches. Here, we aim to develop advanced kinase-substrate prediction methods to address these challenges. Using a collection of seven large phosphoproteomics datasets, including six published datasets and a new muscle differentiation dataset, and both traditional and deep learning models, we first demonstrate that a ‘pseudo-positive’ learning strategy for alleviating small sample size is effective at improving model predictive performance. We next show that a data re-sampling based ensemble learning strategy is useful for improving model stability while further enhancing prediction. Lastly, we introduce an ensemble deep learning model (‘SnapKin’) incorporating the above two learning strategies into a ‘snapshot’ ensemble learning algorithm. We demonstrate that the SnapKin model achieves overall the best performance in kinase-substrate prediction. Together, we propose SnapKin as a promising approach for predicting substrates of kinases from large-scale phosphoproteomics data. SnapKin is freely available athttps://github.com/PYangLab/SnapKin.
Studies on Biofilm Formation byPsuedomonas Aeruginosain Different Urinary Catheters
Authors: Asante Emmanuel
Published: February 2021

Urinary Catheters are the leading cause of healthcare –associated Urinary Tract Infections (UTIs) making their use a necessary evil. Various models and approaches had been developed to help reduce the complications associated with the use of these catheters. This study aimed at investigating how two different types of urinary catheters (Silicone Catheter and Latex Coated Catheter) support biofilm formation ofPseudomonas aeruginosaisolates. The growth rate of the bacteria and the rate of formation of biofilm on each urinary catheter was determined by preparing biofilm assays, ranking them using crystal violet satins and measuring their absorbance using UV-VIS spectrophotometer. A difference in the level of biofilm in the catheters were observed. The differences in the level of biofilm observed in the catheters imply that different catheters may have different susceptibility for the formation of biofilms. The study recommends the assessment of biofilm formation in the quality evaluation of catheters. Also further studies should be done to investigate how different catheter material support biofilm formation and the mechanisms involved.
cpn60 barcode sequences accurately identify newly defined genera within theLactobacillaceae
Authors: Shukla Ishika , Hill Janet E.
Published: February 2021

The cpn60 barcode sequence is established as an informative target for microbial species identification. Applications of cpn60 barcode sequencing are supported by the availability of “universal” PCR primers for its amplification and a curated reference database of cpn60 sequences, cpnDB. A recent reclassification of lactobacilli involving the definition of 23 new genera provided an opportunity to update cpnDB and to determine if the cpn60 barcode could be used for accurate identification of species consistent with the new framework. Analysis of 275 cpn60 sequences representing 258/269 of the validly named species inLactobacillus, Paralactobacillusand the 23 newer genera showed that cpn60-based sequence relationships were consistent with the whole-genome-based phylogeny. Aligning or mapping full length barcode sequences or a 150 bp subsequence resulted in accurate and unambiguous species identification in almost all cases. Taken together, our results show that the combination of available reference sequence data, “universal” barcode amplification primers, and the inherent sequence diversity within the cpn60 barcode make it a useful target for the detection and identification of lactobacilli as defined by the latest taxonomic framework.

Significance and Impact of the Study

The genusLactobacillusrecently underwent a major reorganization resulting in the definition of 23 new genera. Lactobacilli are widespread in environmental and host-associated microbiomes and are exploited in food and biotechnology applications, making methods for their accurate identification desirable. Here we show that the combination of a reference sequence database, “universal” barcode amplification primers, and the inherent sequence diversity within the cpn60 barcode make it a useful target for the detection and identification of lactobacilli as defined by the latest taxonomic framework.