bluuebunny/crossref_metadata_2025 huggingface dataset:
Using a lipidomics approach to analyze the role of sphingomyelin in aging in C. elegans
Authors: McIntyre Grace E. , Radeny Joycelyn , Wang Lou , Chan Jason
Published: April 2020

Research breakthroughs on aging and diseases have helped extend life expectancy in the United States over the last 25 years. However, as individuals continue to age, they lose the ability to perform motor and cognitive functions and their risk of developing chronic diseases increases. Here, we used a lipidomic approach to identify important lipid mediators of aging in C. elegans. This study focuses on the bioactive lipid sphingomyelin (SM), whose abundance depends on metabolic enzymes including acid sphingomyelinase (ASM). In C. elegans, one ASM ortholog is coded by the asm‐3 gene, and loss of asm‐3 extends lifespan in C. elegans. To explore longitudinal changes in lipids between wildtype (wt) and mutant asm‐3 C. elegans during aging, we collected six samples of wt and asm‐3 animals, at ages 1, 5, and 10 days, for lipid analysis. Approximately 700 different lipids were abundant enough in concentration for analysis. We found that 10‐day old asm‐3 mutants have increased levels of two Omega‐3 fatty acids, docosahexaenoic acid (DHA/22:6) and docosapentaenoic acid (DPA/22:5); both are linked to increased lifespans and decreased mortality when present in higher concentrations. Previous studies show that SM accumulates later in life causing aging to accelerate, but less is known regarding changes in specific types of sphingomyelin. Therefore, we also sought to examine how chain length and saturation levels of SM change with age by comparing the SM of 1 and 10 day old wt worms. Future work plans to correlate lipid composition to physiological changes in old animals. Together, we hope that we can better understand the intrinsic biochemical lipid processes associated with late life conditions to better prevent illness care for our aging populations.

Support or Funding Information

Research reported in this publication was supported by the National Institute On Aging of the National Institutes of Health under Award Number R15AG052933. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The Intracranial baroreflex is attenuated in hypertension
Authors: Ramchandra Rohit , Guild Sarah-Jane , George Bindu , Vari Sydney
Published: April 2020

Background

We have previously shown that there is a novel control pathway between physiological levels of intracranial pressure (ICP) and blood pressure via the sympathetic nervous system. Increases in ICP of up to 20 mmHg over a 30‐minute infusion period were matched by increases in mean arterial pressure such that cerebral perfusion pressure remained constant. However, whether this ‘intracranial baroreflex’ is altered in hypertension is not known. Hence, in the present study we tested the hypothesis that the intracranial baroreflex is attenuated in a group of hypertensive animals.

Methods

Experiments were conducted in two groups of adult ewes which either underwent unilateral renal artery clipping for three weeks (n=6) or sham surgery (n=6). Three weeks later, the mean arterial pressure and renal blood flow response to intracerebroventricular infusion of saline was determined.

Results

Intracerebroventricular infusion of saline produced a ramped increase in ICP of up to 20 mmHg over a 30‐minute infusion period (baseline 4.3±1.1 mmHg) in the normotensive group of animals. The ICP increase was matched by an increase mean arterial pressure in the normal animals such that cerebral perfusion pressure remained constant. Direct recordings of renal blood flow indicated that renal blood flow did not change but renal vascular conductance decreased with increasing ICP. In the hypertensive group, while intracerebroventricular infusion of saline produced similar ramped increases in ICP, the increase in mean arterial pressure was significantly attenuated such that cerebral perfusion pressure decreased. Administration of the ganglionic blocker, hexamethonium, prior to the infusion of saline abolished the increase in blood pressure in both groups.

Discussion

In conclusion, we have shown that the ‘intracranial baroreflex’ ensures increases in mean arterial pressure during physiological increases in intracranial pressure to maintain cerebral perfusion. This reflex is attenuated in hypertension.

Support or Funding Information

Health Research Council of New Zealand
The Role of Proteoglycans in Glomerular Physiology and Pathophysiology
Authors: Ebefors Kerstin , Khramova Alina , Nyström Jenny
Published: April 2020

Background

Diabetic kidney disease (DKD) is the leading cause of renal failure in the world. Diabetes is associated with damage to the endothelial glycocalyx (eGCX), the layer of proteoglycans (PGs) and other negatively charged molecules covering the glomerular endothelial capillaries. The eGCX restrain the flow of charged molecules, such as albumin, over the filtration barrier in the kidney. Loss of the glomerular eGCX leads to proteinuria without other visible damage to the filtration barrier, but the detailed structure and composition is still largely unknown. The aim of this study was to gain new knowledge about the composition and role of the EGCX in health and DKD.

Methods

The negatively charged PGs in the eGCX was eluted from rat kidneys using 1 M NaCl solution (high salt, HS). In addition 1 M mannitol was used as osmotic control (HO) and 0.15 M NaCl to mimic physiological salt concentrations (NS). Solutions were introduced intra‐arterially to rat kidneys under anesthesia in vivo. Venous effluent was analyzed using mass spectrometry. Fractional clearance of albumin and GFR was measured. Electron microscopy (EM) was used to investigate morphological changes. Expression of PGs and PG related genes in glomeruli from patients with DKD was investigated using deep sequencing data from a Swedish DKD cohort (DKD, n=19, controls; pre‐transplant biopsies, n=20).

Results

We identified 15 PGs in the eluate from rats. PGs were found in highest yields in the HS samples. EM demonstrated that the eGCX thickness was significantly reduced in the HS rats −28% (p<0.05) compared to NS. Rats perfused with HS had increased fractional clearance of albumin and reduced GFR, compared to NS and HO, 10 minutes after perfusion. In glomeruli from patients with DKD 12 PGs were found to be significantly regulated, and 4 of these PGs were also identified in the eGCX eluates from rats. There was an overall decrease in expression of enzymes responsible for building up PG side chains, as well as an increase in proteins involved in PG degradation.

Conclusion

The eGCX itself represents a dynamic structure with significant molecular turnover. In our study, we identified several PGs novel to the glomerular eGCX. We show that loss of eGCX leads to proteinuria and reduced GFR, strongly supporting that the eGCX is important for preventing proteinuria. In glomeruli from patients with DKD we found significant alterations in the gene expression of PGs and the enzymes regulating their composition. Further investigation is needed to clarify in detail when and how these alterations appear in DKD.
Role of CO2 in the Expression of TRPV1 in Vascular Smooth Muscle Cells
Authors: Nishimura Naoki , Sugimoto Naotoshi , Nakamura Taichi , Wada Taizo
Published: April 2020

Objectives

Carbon dioxide (CO2) is known to affect thermal sensation and vasodilatation in human skin immersed in CO2‐rich water. However, the role that CO2 plays in these mechanisms is unclear. Transient receptor potential vanilloid 1 (TRPV1) is a member of a non‐selective cationic channel family expressed in human sensory neurons. Activation of TRPV1 is induced by heat and chemical agonists such as H+. This study aimed to clarify the role of CO2 in regulating TRPV1 expression in vascular smooth muscle cells.

Methods

A7r5 rat smooth muscle cells were maintained in Dulbecco’s modified Eagle’s medium supplemented with 10% fetal bovine serum at 37°C in a 5% CO2 incubator. The cells were exposed to 20% CO2 for 24 hours. The expression of TRPV1 and TRPV4 were subsequently evaluated by real time PCR.

Results

The expression levels of TRPV1, but not TRPV4, were significantly increased ( P =0.013) in the vascular smooth muscle cells following exposure to 20% CO2 for 24 hours.

Conclusions

These results suggest that exposure to CO2 may regulate the expression of TRP family proteins in cultured vascular smooth muscle cells.

Support or Funding Information

none
Open Heart Surgery with Cardiopulmonary Bypass using Dexmedetomidine‐based Monitored Anesthesia Care without Endotracheal intubation Improves Postoperative Recovery
Authors: Chen Wenting , Yuan Lan , Wang Yongqiang , Tang Wei , Guo Feng , Xia Zhengyuan , Song Jiangang
Published: April 2020

Background

Studies have demonstrated the feasibility of performing awake cardiac surgery (ACS) in non‐intubated patients with consciousness and spontaneous breathing using epidural anesthesia. However, major concerns about severe complications of epidural anesthesia, such as epidural hematoma, have seriously hampered the development of ACS. Monitored anesthesia care (MAC) is a planned procedure during which the patients undergo local anesthesia together with sedation and analgesia. Dexmedetomidine (Dex), a highly selective α‐2 agonist, can facilitate fast recovery in patient undergoing cardiac surgery. We aimed to evaluate the feasibility and safety of Dex‐based MAC without intubation and the potential of achieving enhanced recovery after surgery (ERAS).

Methods

With patients’ consent, 11 patients scheduled to undergo cardiac surgeries under cardiopulmonary bypass (CPB) were arranged for MAC. Surgery was performed with a conventional median sternotomy. MAC composed of continuous Dex infusion (0.2 – 0.5 g/kg/hour) supplemented with low‐dose remifentanil/sufentanil, regional anesthesia and electroacupuncture was applied to satisfy the need for analgesia and sedation during cardiac surgery while avoid significant respiratory depression. 11 patients who routinely underwent general anesthesia (GA) that matched for age, gender and types of operation were used as controls. Intraoperative respiration and hemodynamics, postoperative vasoactive‐inotropic score (VIS), serum troponin I, complications and recovery after surgery were evaluated.

Results

11 cardiac surgeries including mitral valve replacements, valvoplasty, valve replacement plus valvoplasty, resection of atrial myxoma, and repair of atrial septal defect, were uneventfully accomplished under MAC. None of them required conversion to GA. The whole process of surgery was accompanied by adequate spontaneous breathing, stable hemodynamics, satisfactory surgical conditions, good patient satisfaction and no anesthesia awareness. Compared with GA group, intraoperative dosage of opioids and general anesthetics, VIS at 6 hours after entry into intensive care unit (ICU), serum cardiac troponin I concentrations, the time to drink and duration of ICU stay were significantly reduced in the MAC group (all p<0.05).

Conclusion

The minimally invasive Dex‐based MAC for heart surgery with CPB is safe and feasible. Moreover, it shows the potential of cardioprotection and enhanced recovery after surgery.

Support or Funding Information

Study supported in part by a NSFC grant(81774108)
Perceptions of Pain Treatment in Pediatric Patients With Functional Gastrointestinal Disorders
Authors: Hale Amy E. , Smith Allison M. , Christiana Julie Snyder , Burch Elizabeth , Schechter Neil L. , Beinvogl Beate C. , Paul Fiona , Henaghan Amelia S. , Logan Deirdre , Nurko Samuel
Published: April 2020

Objectives:

Individual understanding of and expectations for chronic pain treatment can influence treatment adherence and thus success, but little is known about these critical factors in parents and children presenting with pain-predominant functional gastrointestinal disorders. The aim of this study was to identify parent and patient understanding of pain-predominant functional gastrointestinal disorders, expectations for treatment, and interventions utilized before presenting to a multidisciplinary clinic.

Materials and Methods:

This was a prospective study of patients evaluated in a Multidisciplinary Functional Abdominal Pain Program. Before the clinic visit, parents and patients completed questionnaires regarding their understanding of chronic pain, perceptions of abdominal pain contributors, expectations regarding treatment, and identification of previous interventions utilized.

Results:

Participants were knowledgeable regarding the biology of chronic pain. Perceptions of contributors to abdominal pain included a sensitive stomach, general stress, and nerves/worry. Most had attempted to treat their pain with medication, exercise or physical therapy, or a psychological treatment. Participants reported that receiving a definite diagnosis would be the most helpful intervention, followed by psychological treatment.

Discussion:

Participants were knowledgeable regarding chronic pain, but still indicated that receiving a definite diagnosis would be the most helpful intervention. Most had tried multiple interventions and did not believe that further medication, testing, or surgery would solve their pain. Instead, parents presenting at this Functional Abdominal Pain Program appeared most hopeful about the benefits of multidisciplinary treatment approaches including psychological interventions, a focus on activity and functioning, and complementary and alternative medicine interventions.
Wnt Signaling Pathway Proteins in Scar, Hypertrophic Scar, and Keloid: Evidence for a Continuum?
Authors: Chaudet Kristine M. , Goyal Amrita , Veprauskas Katy R. , Nazarian Rosalynn M.
Published: April 2020

Hypertrophic scars and keloids are fibroproliferative lesions characterized by excessive collagen deposition. It is unclear whether these entities represent distinct disorders or share a common pathogenesis and the molecular underpinnings of these lesions are poorly understood. Accumulating evidence suggests that the Wnt signaling pathway is a key regulator of wound healing. In this study, tissue microarray was used to evaluate the protein expression profile for Wnt3a, phosphorylated glycogen synthase kinase 3 alpha (pGSK-3α), WNT1-inducible-signaling pathway protein 1 (WISP1), and WISP2 in normal skin, scars, hypertrophic scars, and keloids. Analysis revealed significantly increased fibroblast expression of pGSK-3α in scars (27.2%), hypertrophic scars (30.4%), and keloids (57.3%) compared with normal skin (16.4%) (all differences statistically significant; P < 0.01). Analysis of WISP2 showed 94% of fibroblasts in normal skin expressing WISP2 and significantly decreased expression in scars (46.8%), hypertrophic scars (27.0%), and keloids (61.3%) (all differences statistically significant; P < 0.01). The parallel patterns of expression of pGSK-3α and WISP2 in scars and hypertrophic scars and significantly increased expression in keloids may support the notion that keloids are a truly distinct fibrosing disorder and may provide further evidence for targeting the Wnt signaling pathway in the treatment of keloids.
Results of a 2-Year Prospective Multicenter Study Evaluating Long-term Audiological and Clinical Outcomes of a Transcutaneous Implant for Bone Conduction Hearing
Authors: Kruyt Ivo J. , Monksfield Peter , Skarzynski Piotr H. , Green Kevin , Runge Christina , Bosman Arjan , Blechert Johan I. , Wigren Stina , Mylanus Emmanuel A. M. , Hol Myrthe K. S.
Published: April 2020

Objective(s):

To evaluate 2-year audiological and clinical outcomes of a transcutaneous implant for bone conduction hearing of a previously published 6-month evaluation.

Design:

Fifty-four unilaterally implanted adult patients with conductive or mild mixed hearing loss or single-sided sensorineural deafness were included in this prospective multicenter study. Follow-up visits were scheduled post-surgery at 10 days; 4, 6, and 12 weeks; 6, 12, and 24 months. Main outcomes were audiological benefit, patient-reported outcomes (PROs), soft tissue status, pain, numbness, implant survival, and daily usage.

Results:

In the study population, the transcutaneous implant resulted in statistically significant improvement in objective hearing test and PROs compared with the unaided situation. Soft tissue complications were observed in 4.6% of the patients per visit. Pain/discomfort and numbness were initially reported in the majority of the patients, but declined over time; approximately 9% of patients reported some degree of numbness and 15% (slight) pain/discomfort after 2 years. During the 24-month period, two implant magnets were removed (3.7%), while two other implants were converted to the percutaneous counterpart (3.7%). At the final visit, 89.6% (n = 42 out of 47) of the patients used their sound processor, with a median daily usage of 6 h/d (range, 0–18 h/d).

Conclusions:

After 24 months, the transcutaneous implant provided statistically significant mean improvement in objective and subjective hearing performance as well as PROs compared with the preoperative unaided condition and had a low soft tissue complication rate. The test device could be considered as an alternative treatment option for appropriately selected and counseled patients.
Frequency of daily tooth brushing and subsequent cardiovascular events
Authors: Kobayashi Daiki , Mizuno Atsushi , Mitsui Rie , Shimbo Takuro
Published: April 2020

Objective

Although previous studies have shown an inverse association between the frequency of daily tooth brushing and cardiovascular risk factors, research on cardiovascular events is limited. This study aimed to evaluate the association between the frequency of daily tooth brushing and subsequent cardiovascular events.

Methods and results

A retrospective longitudinal study was conducted at a hospital in Tokyo, Japan. We included all participants who underwent health check-ups from 2005 to 2011 and followed up to 2018. Our outcomes were the development of cardiovascular events. Outcomes were compared by the frequency of daily tooth brushing with a generalized estimating equation, adjusting for potential confounders. A total of 71 221 participants were included. The mean age was 45.6 years and 50.3% were male. During a median follow-up of 2061 (interquartile range: 933–3311) days, 1905 participants developed cardiovascular events. The adjusted odds ratios (ORs) of cardiovascular events increased in a dose-dependent manner as the frequency of tooth brushing decreased. Even those who brushed their teeth once in a day had a higher adjusted OR of stroke (1.22; 95% confidence interval, 1.01–1.48) than did those who brushed after every meal.

Conclusions

Frequent tooth brushing was inversely associated with subsequent cardiovascular events in a dose-dependent manner. Even brushing one’s teeth once a day may be related to an increased likelihood of stroke than brushing one’s teeth after every meal. Less frequent tooth brushing may be considered to be a marker for subsequent cardiovascular disease and coronary heart disease, rather than a risk factor.
Interarterial course of anomalous right coronary artery: role of symptoms and surgical outcomes
Authors: Saleem Sameer , Syed Mubbasher , Elzanaty Ahmed M , Nazir Salik , Changal Khalid , Gul Sajjad , Sheikh Mujeeb
Published: April 2020

Anomalous origin of right coronary artery with interarterial course (ARCA-IA) is a risk factor for sudden death and other cardiac complications. Surgical correction remains its gold standard treatment. We describe clinical characteristics, workup, surgical techniques and outcomes of ARCA-IA at our center. A retrospective analysis of cardiovascular database was performed. From March 2005 through January 2011, 11 patients with mean age of 53 ± 18 years were diagnosed with ARCA-IA. Reported symptoms included chest pain (64%), arrhythmia [27%; i.e. atrial flutter (9%), recurrent supraventricular tachycardia (9%), ventricular tachycardia (9%)], syncope (18%), dyspnea (9%) and aborted sudden cardiac death (9%). Chest pain (n = 7) was episodic and lasted longer than 6 months before diagnosis. Initial diagnosis was made at coronary computed tomography in two patients and at cardiac catheterization in nine patients. Four patients had positive stress test and were subsequently found to have ARCA-IA at cardiac catheterization. There was no operative mortality. Surgery (bypass with ligation of native vessel or translocation and reimplantation) was performed in seven patients. Three patients refused surgery, and in one patient, surgery was not considered due to comorbidities. Symptom relief was noted in all surgical patients. At mean follow-up of 36 months, two patients had noncardiac-related deaths whereas nine were asymptomatic. There were no deaths reported in patients treated surgically. Definitive surgery is indicated in symptomatic ARCA-IA and is associated with excellent long-term outcome. RCA dominance in ARCA-IA is an adverse marker with increased symptoms; this hypothesis should be tested in larger studies.
Internal mammary artery: the primary conduit for surgical revascularization
Authors: Harky Amer , Sankaranarayanan Vissagan , Kong Qiu Ginj
Published: April 2020

Internal mammary artery, by far, is the gold standard and first conduit for surgical revascularization especially when it comes to bypassing a lesion in the left anterior descending coronary artery. Several factors behind using this artery have been established, including but not limited to, the anatomical location, the course and flow, the elastic nature of the artery as well as the physiological characteristics that make this conduit to yield excellent long-term patency rates. This review aims to thoroughly examine current literature and establish the facts behind using this conduit in our daily surgical revascularization practice.
Vildagliptin vs. insulin treatment alone in diabetic acute coronary syndrome patients
Authors: Dobrecky-Mery Idit , Sommer Adir
Published: April 2020

Background

Vildagliptin, an oral antidiabetic of the dipeptidyl peptidase-4 (DPP-4) inhibitor drugs, exhibits an overall low risk of hypoglycemia with less frequent hypoglycemic events in type 2 diabetes mellitus (T2DM) patients than other antidiabetic drugs. We hypothesized that among hospitalized acute coronary syndrome (ACS) patients, the addition of vildagliptin to subcutaneous insulin therapy would reduce the risk of hypoglycemic events.

Methods

One hundred ACS T2DM adult patients naive to DPP-4 inhibitors were enrolled during admission to the ICCU. Patients were divided into two randomized controlled groups: a subcutaneous rapid-acting insulin-only therapy group and an oral vildagliptin plus subcutaneous insulin group. The trial was open label with no placebo arm. Mean glucose values, insulin values given for correction per hospitalization, and the number of hypoglycemic events (glucose < 70 mg/dL) were documented.

Results

Eight hypoglycemia events occurred in the insulin-only group and none in the insulin plus DPP-4 inhibitor group (P < 0.001). Patients with acute myocardial infarction experienced a higher number of hypoglycemic events compared with unstable angina diagnosed patients. No significant differences were found regarding glucose level (P = 0.462) and administered insulin units (P = 0.639).

Conclusions

In T2DM patients, the addition of DPP-4 inhibitors to routine subcutaneous insulin therapy may significantly reduce hypoglycemic events while maintaining acceptable recommended ranges of glucose. Further studies on a larger scale are required to verify these results and to support that DPP-4 inhibitors added to today’s standard insulin-only treatment in hospitalized diabetic ACS patients may improve overall glycemic control and provide a potential treatment option in this challenging clinical setting.
Frontostriatal Brain Activation Is Associated With the Longitudinal Progression of Cardiometabolic Risk
Authors: Allen Ben , Jennings John Richard , Muldoon Matthew F. , Gianaros Peter J.
Published: April 2020

Objective

Cardiometabolic risk refers to a set of interconnected factors of vascular and metabolic origin associated with both cardiovascular disease and various brain disorders. Although midlife cardiometabolic risk is associated with future brain dysfunction, emerging evidence suggests that alterations in autonomic and central nervous system function may precede increases in cardiometabolic risk.

Methods

The present study tested whether patterns of cerebral blood flow in brain areas associated with autonomic regulation were associated with increases in overall cardiometabolic risk. A community sample of 109 adults with resting systolic blood pressure between 120 and 139 mm Hg, diastolic blood pressure between 80 and 89 mm Hg, or both underwent pseudocontinuous arterial spin labeling to quantify cerebral blood flow responses to cognitively challenging tasks. Cardiometabolic risk and cerebral blood flow measurements were collected at baseline and at a 2-year follow-up.

Results

Regression analyses showed that greater frontostriatal cerebral blood flow responses to cognitive challenge were associated with higher cardiometabolic risk at follow-up (β = 0.26 [95% confidence interval = 0.07 to 0.44],t= 2.81,p= .006, ΔR2= 0.04). These findings were specific to frontostriatal brain regions, as frontoparietal, insular-subcortical, and total cerebral blood flow were not associated with progression of cardiometabolic risk. Moreover, cardiometabolic risk was not associated with frontostriatal cerebral blood flow responses 2 years later.

Conclusions

Frontostriatal brain function may precede and possibly forecast the progression of cardiometabolic risk.
Investigating the effect of antiretroviral switch to tenofovir alafenamide on lipid profiles in people living with HIV
Authors: Lacey Aoife , Savinelli Stefano , Barco Elena Alvarez , Macken Alan , Cotter Aoife G. , Sheehan Gerard , Lambert John S. , Muldoon Eavan , Feeney Eoin , Mallon Patrick W. , Tinago Willard
Published: April 2020

Background:

Whilst reporting improved renal and bone safety profiles, studies have noted changes in lipid profiles among people living with HIV (PLWH) receiving antiretroviral therapy (ART) switching away from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). We aimed to characterize changes in lipids observed after switching to TAF-containing ART in a real-world setting.

Methods:

A prospective study on PLWH enrolled in the UCD-ID Cohort study who switched to TAF-containing ART. Routine laboratory data [including lipids (total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides], ART history and use of lipid-lowering therapy (LLT) were analysed preswitch and postswitch to TAF. Dyslipidaemia was classified according to the National Cholesterol Education Program-Adult Panel III (NCEP-ATP III). Change in lipid parameters and change in the proportion of individuals with dyslipidaemia postswitch was assessed using the paired t-test and the Stuart--Maxwell test, respectively.

Results:

Of 775 PLWH enrolled in the cohort, 238 switched to TAF containing ART, of whom 194 had both preswitch and postswitch lipids measured a median (IQR) 24 (14–41) weeks postswitch to TAF. TC, LDL, HDL, triglycerides and TC : HDL ratio significantly increased postswitch [mean change (SE) mmol/l; +0.37 (0.06), P < 0.001; +0.25 (0.06), P < 0.001; +0.05 (0.02), P = 0.003, +0.13 (0.07), P = 0.02, and +0.16 (0.08), P = 0.013) respectively]. There were significant increases in the proportions of PLWH with more severe dyslipidaemia postswitch across TC and LDL (both P < 0.001).

Conclusion:

These data suggest clinically relevant, worsening lipid profiles postswitch to TAF, with a larger proportion of PLWH exceeding recommended lipid thresholds postswitch. How these changes will impact on cardiovascular risk or need for LLT remains to be determined.
Drug efflux transporters and metabolic enzymes in human circulating and testicular T-cell subsets: relevance to HIV pharmacotherapy
Authors: Whyte-Allman Sana-Kay , Hoque Md. Tozammel , Gilmore Julian C. , Kaul Rupert , Routy Jean-Pierre , Bendayan Reina
Published: April 2020

Objectives:

ATP-binding cassette (ABC) drug efflux transporters and drug metabolic enzymes could reduce antiretroviral concentrations in HIV target cells. The testis has been demonstrated to be a sanctuary site, displaying suboptimal antiretroviral concentrations and persistent HIV infection. Therefore, we compared the expression and function of ABC transporters and metabolic enzymes in CD4+ and CD8+ T cells isolated from human testis and peripheral blood mononuclear cells (PBMCs), and assessed their expression in circulating naive and memory CD4+ T-cell phenotypes.

Design:

Testicular tissue and blood were collected from 15 uninfected donors undergoing gender affirmation surgery. Testicular interstitial cells were isolated by enzymatic digestion, whereas PBMCs were isolated from blood by density gradient centrifugation. The expression and/or function of ABC transporters and metabolic enzymes were examined in blood and testicular T-cell subsets by flow cytometry.

Results:

ABC transporters (P-gp, BCRP, MRP1) and metabolic enzymes (CYP3A4, UGT1A1) were expressed in testicular and circulating CD4+ and CD8+ T cells, as well as in circulating naive, central, transitional, and effector memory T-cell phenotypes. MRP1 demonstrated lower frequencies in T cells from testis compared with PBMCs, as well as in circulating naive T cells compared with the memory T-cell phenotypes. Functional activity of P-gp and BCRP was detected in T-cell subsets from testis and PBMCs.

Conclusion:

Our findings demonstrate for the first time that antiretroviral drug efflux transporters and metabolic enzymes are functionally expressed in T-cell subsets infiltrating the human testis. These transporters and enzymes can reduce antiretroviral intracellular concentrations, potentially contributing to residual HIV replication in the testis, and negatively impact HIV cure strategies.
Outcomes of immunomodulatory and biologic therapy in people living with HIV
Authors: Peluso Michael J. , Chen Jessica , Munter Sadie , Reed Asia , Teraoka Justin , Eshun-Wilson Ingrid , Henrich Timothy J. , Chin-Hong Peter V.
Published: April 2020

Objectives:

Immunomodulatory drugs (IMDs) are crucial for treating autoimmune, inflammatory, and oncologic conditions. Data regarding the safety of IMDs in people living with HIV (PLWH) are limited. We describe outcomes in all PLWH prescribed these agents from 2000--2019 at two academic medical centers.

Design:

Retrospective cohort study.

Methods:

We systematically identified and reviewed charts of all PLWH receiving IMDs. We defined a treatment episode as an uninterrupted period on an IMD regimen. We quantified infections, blips (detectable plasma HIV RNA following an undetectable result), and virologic failure (progression from plasma HIV RNA <200 copies/ml to two consecutive values >200 copies/ml despite ART).

Results:

Seventy-seven patients contributed 110 treatment episodes. Rheumatologic comorbidities were the most frequent indication. The most common IMD classes were TNF inhibitors, antimetabolites, and checkpoint inhibitors. Ninety percent of treatment episodes involved concomitant ART. Median pretreatment CD4+ T-cell count was 609 cells/μl (IQR 375--861). Among 51 treatment episodes on ART with undetectable pretreatment plasma HIV RNA, HIV became detectable within 1 year in 21 of 51 cases (41.2%); there were no instances of virologic failure. Compared with other agents, treatment episodes involving checkpoint inhibitors were more likely to involve a blip (77.8 vs. 33.3%, P = 0.015). Thirteen treatment episodes (11.8%) were associated with concomitant infection; none was attributed to IMDs by the treating clinician.

Conclusion:

PLWH treated with IMDs should be monitored carefully for virologic blips and incident infections. Checkpoint inhibitors may be associated with a higher rate of viral blips, although the clinical significance is unclear.
Virtual Reality Haptic Simulator for Endoscopic Sinus and Skull Base Surgeries
Authors: Kim Do Hyun , Kim Hyun Mun , Park Jae-Sung , Kim Sung Won
Published: April 2020

Objective:

This paper proposes a virtual reality (VR) haptic simulator with realistic instruments, an exchangeable patient-specific three-dimensional (3D)–printed external nostril and a caudal septum model to facilitate real surgical motion for training in endoscopic sinus and skull–base surgery.

Study design and Setting:

industry-academy cooperation development model

Methods:

The VR simulator consists of the main simulator body, a monitor, an endoscope device, 2 haptic devices, an endoscope holder support fixture, and a pair of pedals. The location of the endoscope device is determined by an electromagnetic sensor. Two haptic devices are located so as to prevent mutual interference during application of the two-nostrils/four-hands technique for endoscopic skull-base surgery. The pedals were used for select surgical instrument and endoscopes, and operate microdebriders or microdrill. An exchangeable patient-specific external nostril and caudal septum model was created using material that mimics the texture of human tissue and a 3D printer. Graphics were rendered using Unity 3D, to which the Simulation Open Framework Architecture (SOFA) physics engine can be bolted on using the Unity3d plug-in.

Results:

This VR haptic simulator enables performance of basic endoscopic sinus surgeries (eg, maxillary sinus antrostomy, ethmoidectomy, and frontostomy), as well as endoscopic endonasal transsphenoidal (including sphenoidotomy) and transclival approaches.

Conclusion:

VR haptic simulators can improve the skill and confidence of surgical trainees by allowing them to accrue experience in various tasks under different conditions. The simulator introduced here comprises novel technologies and provides a realistic training environment for endoscopic sinus and skull–base surgery.
Free Dermal Fat Autografting for Complex Craniofacial Wounds
Authors: Dufresne Craig R. , Poling Mikaela I.
Published: April 2020

Complex craniofacial wounds (CCW) are those refractory to initial treatment and may involve chronic infection, exposed hardware, irradiated tissue, and soft tissue volume loss. Typical reconstruction with microvascular flaps involves considerable morbidity. While free dermal fat autografting (DFA) is used extensively in many applications, its use treating CCW remains an unexplored but attractive possibility. Data from a retrospective cohort of 34 consecutive patients (13 male; 21 female and aged 2–79-years), who underwent free DFA between 1985 and 2018 for CCW by a single plastic surgeon, were analyzed. Post-operative follow-up was 1–24 years (M = 6.53, SD = 7.91). Many patients had several concomitant wound complications. Primary pre-operative wound complications were dominated by infection (N = 20), of which over 75% (N = 15) were associated with non-autogenic material. Eighteen had resolution of their pre-operative infection. Of the total (N = 34), 79.41% had stable grafts at follow-up [X2(3) = 54, P < 0.001], with only 3 experiencing observable atrophy and 1 graft necrosis. Most of the cohort was complication free [X2(1) = 7.53, P = 0.006], with 73.53% experiencing no problems involving the graft. Twenty-nine (85.29%) of 34 patients had therapeutic success with free DFA [X2(1) = 28.65, P < 0.001]. Pre-operative wound status (β = 1.13, P < 0.001) predicted therapeutic success [R2 = 0.87, F(7,9) = 8.94, P = 0.002]. While 5 (14.71%) did not have therapeutic success, no additional problems arose related to grafts. Free DFA appears to be beneficial and show low morbidity. Future studies must evaluate these findings. In this context, their use should be considered in recalcitrant craniofacial wounds.
Cranial Reconstruction Using Antibiotic-Impregnated Calcium Phosphate Bone Cement With a Titanium Mesh Sheet
Authors: Ogino Akihiro , Nakamichi Miho , Takeda Kei , Onishi Kiyoshi
Published: April 2020

Background:

The authors treated skin ulcer accompanied by cranial osteomyelitis using a combination of antibiotic-impregnated calcium phosphate bone cement (Biopex; Pentax, Tokyo, Japan) and a titanium mesh sheet (3D Mesh Plate; Bear Medic, Tokyo, Japan).

Method:

A 71-year-old male was treated with superficial temporal artery-middle cerebral artery bypass surgery for diffuse cerebral infarction and obstruction of the left internal carotid artery by a previous doctor. Skin necrosis and epidural abscess developed in the sutured region after surgery, and ulcer accompanied by temporal bone exposure remained. Thus, the patient transferred to our department. A bone defect formed by debridement and sequestrectomy was measured at 4.5 × 8 cm (30 cm2). Methicillin-resistant Staphylococcus aureus was detected on wound culture test. Cranioplasty with a combination of calcium phosphate bone cement impregnated with teicoplanin, to which the causative bacteria showed high sensitivity, and a titanium mesh sheet and scalp reconstruction with a free rectus abdominis musculocutaneous flap were performed.

Results:

As of 6 months after surgery, no infection has relapsed and no complication, such as resorption of the calcium phosphate bone cement and breakage of the titanium mesh sheet, was noted on postoperative computed tomography.

Conclusion:

The authors performed cranial reconstruction with a combination of teicoplanin-impregnated calcium phosphate bone cement and a titanium mesh sheet in a patient with Methicillin-resistant Staphylococcus aureus infection-induced skin ulcer accompanied by cranial osteomyelitis and achieved subsidence of infection. Drug-impregnated calcium phosphate bone cement has a problem with strength, but combination with a titanium mesh sheet as an auxiliary support material enables application to relatively extensive cranial full-thickness defects and it may be a useful treatment method.
Evaluation of Changes in Nasal Projection After Surgically Assisted Rapid Maxillary Expansion With 3dMD Face System
Authors: Büyükçavuş Muhammed Hilmi , Findik Yavuz , Baykul Timuçin
Published: April 2020

The most appropriate treatment option for maxillary expansion in adulthood due to increased cyanosis in sutures is surgically assisted maxillary expansion (SARME). Skeletal and dental changes are observed with SARME. Three-dimensional imaging techniques are gaining importance with the developing technology in evaluating the changes that occur as a result of the treatments applied. The aim of study was to evaluate the soft tissue changes occurring in the nasal projection after SARME in 3-dimensional analyzes during the expansion and post-retention processes. The study sample consisted of 19 patients with a transverse maxillary deficiency of more than 5 mm (11 female and 8 male). 3dMD Vultus software was used for measuring height and width of the philtrum, superior alar, nasal and subnasal width; nasal length, nasal projection, nasal bridge width, nasal tip protrusion and upper face height) before surgery (T0), after the expansion phase (T1), and 6 months postoperatively (T2). A significant difference was found only subnasal width between pre-treatment and post-retention values. Surgically assisted maxillary expansion operations alter the nasal projection and this study certified these results with 3dMD face system. 3dMD face technique is an effective imaging technique for evaluating the soft tissues changes after orthognathic surgeries.
Kenny-Caffey Syndrome Type 2: A Unique Presentation and Craniofacial Analysis
Authors: Turner Acara E. , Abu-Ghname Amjed , Davis Matthew J. , Shih Linden , Volk Angela S. , Streff Haley , Buchanan Edward P.
Published: April 2020

Kenny-Caffey Syndrome Type 2 (KCS2) is a rare genetic disorder characterized by short stature, skeletal dysplasia, primary hypoparathyroidism, and delayed closure of the anterior fontanelle. Patients with KCS2 typically require multidisciplinary management due to numerous craniofacial and skeletal anomalies. Craniosynostosis, however, has not yet been identified in a patient with KCS2 to the best of our knowledge. We present the first case of craniosynostosis in the setting of KCS2 and provide a comprehensive analysis of the associated craniofacial findings to date. The authors will describe the craniofacial features specific to our patient and review the characteristic morphological features in a manner relevant to early recognition and focused evaluation.
Relationship Between Visual Acuity and Corneal Curvature Change in Children After Epiblepharon Surgery
Authors: Suh Su Youn , Ahn Jung Hyo
Published: April 2020

Purpose:

To determine the relationship between visual acuity and corneal curvature change in children after epiblepharon correction surgery by corneal topography.

Methods:

The authors retrospectively reviewed the data of 62 children (121 eyes) who had epiblepharon surgery. The authors measured keratometric values of corneal curvature for 2 corneal zones: central 3 and 5 mm zone. Two zones were classified into 4 areas, including nasal, superior, temporal, and inferior area. Visual acuity and keratometric values were estimated preoperatively and at 1, 3, and 6 months postoperatively. The authors analyzed the correlation between visual acuity and corneal curvature change in 4 areas of the 2 zones.

Results:

There were statistically significant differences between preoperative and postoperative visual acuity 1 month after surgery. At postoperative 3 months, the inferior and superior areas of the 3 mm corneal zone were much flatter than before surgery (P < 0.05). Corneal curvature only at the inferior area of the 3 mm zone had significantly a negative correlation with postoperative visual acuity at 3 and 6 months (r =  −0.275, P = 0.02 and r = −0.351, P = 0.01, respectively). However, visual acuity had no significant correlation with corneal curvature change in any of the areas of the 5-mm corneal zone.

Conclusions:

The authors found that corneal curvature has significantly become flattened in the superior and inferior areas of the 3 mm corneal zone, postoperatively. Furthermore, inferior area in the 3 mm corneal zone affected only on the visual acuity improvement after postoperative 3 months.
Child and Caregiver Perspectives Towards Facial Appearance in Children With Microtia With or Without Craniofacial Microsomia Using a Newly Developed Likert Scale
Authors: Bradford Perry S. , Akinosun Moriyike , Danielson Kirstie K. , Monson Rebecca S. , Morris David. , Rosenberg Janine
Published: April 2020

Craniofacial microsomia (CFM) is the second most common congenital craniofacial malformation characterized by asymmetric malformation of the ear and mandible. Numerous studies have reported the importance of child perspective and psychosocial issues in patients with craniofacial abnormalities. However, clinical tools to evaluate child and caregiver perspectives in patients with microtia with or without CFM have been limited or not reported in the literature. The authors aimed to (1) To develop a tool for measuring patient and caregiver evaluation of facial appearance as it relates to microtia and craniofacial microsomia (CFM). (2) To utilize this tool in comparing children, between 7 and 20 years of age, and caregiver perspectives towards facial appearance in patients with microtia with or without craniofacial microsomia (CFM). A prospective single center study conducted from 2016 to 2017 using newly developed 13-item (Microtia) and 27-item (CFM) 5-point Likert scale Likert scale questionnaires given to patients with CFM and caregivers at a craniofacial center. Aged 7 to 20 (N = 25) and their caregivers. A total of 25 patients (13 male, 12 female; mean age at time of survey 13.2 ± 3.7) met criteria for the study. The Likert scale developed and presented in this study may be a useful tool for clinical use in investigating patient and caregiver perspectives for planning surgical timeline. Based on our pilot data it is important to incorporate all voices into decision-making on timing.
Successful Treatment of Full Thickness Frontal Skull Bone Defect With Dermal Fat Grafting and Artificial Bone Grafts
Authors: Yamauchi Daisuke , Rikimaru Hideaki , Rikimaru-Nishi Yukiko , Ueki Shoya , Hara Shigeru , Hashiguchi Shinichiro , Morinaga Keigo , Kiyokawa Kensuke
Published: April 2020

Rigid reconstruction for frontal bone defects not only improves function, but also approximates more normal appearance. However, in cases involving dural scar contractures, a concave deformation remains when rigid reconstruction is performed without compensating for dead space created by swelling of the brain. This study involved 4 cases in which a 2-stage reconstruction procedure was used to first eliminate dead space by grafting dermal fat, and subsequently carry out rigid reconstruction to achieve a natural forehead configuration. This method is advantageous and considered to be effective in allowing dead space to be easily filled with minimal invasiveness for concave deformations of the dura mater with bone defects. Furthermore, the risk of artificial bone exposure is reduced by adding the dermal component of dermal fat, which is grafted to thinned frontal skin.
Outcomes of Immediate Titanium Cranioplasty Following Post-Craniotomy Infection
Authors: Talwar Ankoor A. , Bhat Deepa K. , Heiman Adee J. , Ricci Joseph A.
Published: April 2020

When craniotomy complicated by secondary infection requires debridement and craniectomy, the bony defect is typically not reconstructed immediately. Due to concerns about placing a prosthetic material in an infected field, cranioplasty has traditionally been delayed by weeks or months after craniectomy. However, surgeons have begun performing single-stage cranioplasty after craniectomy in an effort to reduce the morbidity associated with multiple procedures and reduce overall healthcare costs. The purpose of this systematic review is to analyze outcomes of immediate cranioplasty performed after bone flap debridement secondary to infection. A literature review from January 1, 1998 through January 1, 2019 was conducted, examining the data on immediate titanium cranioplasty and its complication and reoperation rates. A meta-analysis of these articles was then performed. Variables studied included incidence of infection post-cranioplasty, wound healing complications, need for unplanned reoperation, and mortality. In total, there were 40 patients who underwent immediate cranioplasty after bone flap debridement. Overall, there was a 5% rate of postoperative infection, a 12.5% rate of unplanned return to the operating room, 7.5% rate of CSF fistula or leak, a 2.5% rate of hematoma, and a 2.5% rate of mortality within the immediate post-op period. Although there are insufficient data in the literature to rigorously compare these immediate cranioplasties in a direct way with the more traditional delayed type; the outcomes of immediate cranioplasty procedures secondary to craniectomy for infection were similar to the outcomes of delayed cranioplasty after craniectomy for any reason. Given these results, immediate titanium cranioplasty should be considered in select patients.