bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Conversion of a Failed IPAA to a Continent Ileostomy a Risk Factor for Long-term Failure?
Authors: Aytac Erman , Dietz David W. , Ashburn Jean , Remzi Feza H.
Published: November 2018

BACKGROUND:

A continent ileostomy may be offered to patients in hopes of avoiding permanent ileostomy. Data on the outcomes of continent ileostomy patients with a history of a failed IPAA are limited.

OBJECTIVE:

This study aimed to assess whether a history of previous failed IPAA had an effect on continent ileostomy survival and the long-term outcomes.

DESIGN:

This was a retrospective cohort study.

SETTINGS:

This investigation took place in a high-volume, specialized colorectal surgery department.

PATIENTS:

Patients who underwent continent ileostomy construction after IPAA failure between 1982 and 2013 were evaluated and compared with patients who have no history of IPAA surgery.

MAIN OUTCOME MEASURES:

Functional outcomes and long-term complications were compared.

RESULTS:

A total of 67 patients fulfilled the case-matching criteria and were included in the analysis. Requirement of major (52% vs 61%; p = 0.756) and minor (15% vs 19%; p = 0.492) revisions were comparable between patients who had continent ileostomy after a failed IPAA and those who had continent ileostomy without having a previous restorative procedure. Intubations per day (5 vs 5; p = 0.804) and per night (1 vs 1; p = 0.700) were similar in both groups. Our data show no clear relationship between failure of continent ileostomy and history of failed IPAA (p = 0.638). The most common cause of continent ileostomy failure was enterocutaneous/enteroenteric fistula (n = 14). Six patients died during the study period because of other causes unrelated to continent ileostomy.

LIMITATIONS:

This study was limited by its retrospective and nonrandomized nature.

CONCLUSIONS:

Converting a failed IPAA to a continent ileostomy did not worsen continent ileostomy outcomes in this selected group of patients. When a redo IPAA is not feasible, continent ileostomy can be offered as an alternative to conventional end ileostomy in highly motivated patients. See Video Abstract at http://links.lww.com/DCR/A803.
Spanish Linguistic Validation of the Velopharyngeal Insufficiency Effects on Life Outcomes: VELO-Spanish
Authors: Skirko Jonathan R. , Santillana Rosario M. , Roth Christina T. , Dunbar Chance , Tollefson Travis T.
Published: November 2018

Background:

Quality of life (QOL) assessments are useful tools that measure a patient’s health status and monitor patient-reported outcome measures. This study highlights the process of linguistic validation of a QOL assessment to serve Spanish-speaking families and ultimately help decrease language barriers in the treatment of velopharyngeal insufficiency (VPI).

Methods:

The standardized linguistic validation process included forward and backward translation, reconciliation, and cognitive interviews with patients and families. Preliminary instrument test-retest measurement was assessed. Eligibility for cognitive interviews included families with familiarity of velopharyngeal insufficiency. Exclusion criteria included illiteracy and parent and child respondents who do not speak Spanish. Reliability was tested by intraclass correlation (ICC) on VPI Effects on Life Outcomes (VELO)–Spanish instruments completion on 2 measurements from the medical record.

Results:

The instrument was optimized through a standardized forward and backward translation process. Further problematic language was identified during cognitive interviews with families and their children. In the second interview, only minimal changes were needed. Twenty-one patients (8 males and 13 females) were included. Mean (SD) age was 8.0 (5.3) years (range, 3–21 years). The mean (SD) Velo-Spanish score was 65 (22.1); range 32.7–100. The VELO-Spanish instrument demonstrated excellent test–retest reliability [ICC = 0.91; n = 21 and internal consistency (α = 0.96)].

Conclusions:

The Spanish VELO has been developed and refined for use in Spanish-speaking populations as a VPI-specific QOL instrument. The linguistic validation process including cognitive interviews and initial reliability testing. The instrument may improve the understanding of patient-reported outcomes and potential disparities from linguistic and cultural barriers in VPI treatment
Mouse Magnetic-field Nystagmus in Strong Static Magnetic Fields Is Dependent on the Presence of Nox3
Authors: Ward Bryan K. , Lee Yoon H. , Roberts Dale C. , Naylor Ethan , Migliaccio Americo A. , Della Santina Charles C.
Published: November 2018

Hypothesis:

Magnetic vestibular stimulation (MVS) elicits nystagmus in C57BL/6J mice but not head tilt mice lacking Nox3, which is required for normal otoconial development.

Background:

Humans have vertigo and nystagmus in strong magnetic fields within magnetic resonance imaging machines. The hypothesized mechanism is a Lorentz force driven by electrical current entering the utricular neuroepithelium, acting indirectly on crista hair cells via endolymph movement deflecting cupulae. We tested an alternate hypothesized mechanism: Lorentz action directly on crista hair cell stereocilia, driven by their currents independent of the utricle.

Methods:

Before MVS, vestibulo-ocular reflex responses of eight C57BL/6J mice and six head tilt mice were measured during whole-body sinusoidal rotations and tilts using video-oculography. Mice were then placed within a 4.7 Tesla magnetic field with the horizontal semicircular canals approximately Earth-horizontal for ≥1 minute in several head orientations, while eye movements were recorded via infrared video in darkness.

Results:

Outside the magnet, both C57BL/6J and head tilt mice had intact horizontal vestibulo-ocular reflex, but only C57BL/6J mice exhibited static counter-roll responses to tilt (normal utiruclo-ocular reflex). When placed in the magnet nose-first, C57BL/6J mice had left-beating nystagmus, lasting a median of 32.8 seconds. When tail-first, nystagmus was right-beating and similar duration (median 28.0 s, p > 0.05). In contrast, head tilt mice lacked magnetic field-induced nystagmus (p < 0.001).

Conclusions:

C57BL/6J mice generate nystagmus in response to MVS, while mice deficient in Nox3 do not. This suggests 1) a normal utricle is necessary, and 2) functioning semicircular canals are insufficient, to generate MVS-induced nystagmus in mice.
Vestibular Testing: Patient Perceptions, Morbidity, and Opportunity Costs
Authors: Kelly Elizabeth A. , Stocker Catherine , Kempton Carly M. , Dierking Darcia M. , Fehlberg Hannah E. , Adams Meredith E.
Published: November 2018

Objective:

To characterize patient tolerance and nonmonetary cost burdens of vestibular testing. Rigorously acquired data are essential for patient counseling and to determine if proposed additions/modifications to current protocols improve quality, experience, and efficiencies of care.

Study Design:

Prospective observational study.

Setting:

Tertiary center.

Patients:

130 adults (67% women, mean age 55 yr), referred to audiology clinic for vestibular testing.

Intervention(s):

Surveys administered to patients and audiologists immediately and 1 week following videonystagmography (VNG) with caloric and/or rotary chair (RC) testing.

Main Outcome Measure(s):

Symptoms, visual analog scale ratings of dizziness, distress, and nausea during testing; test completion; and opportunity costs (time, missed work).

Results:

Seventy-five patients (58%) experienced undesirable symptoms during testing, including nausea (50%), vomiting (5%), and headaches (12%). Distress and nausea ratings during testing were low (<3/10), with RC ratings lower than VNG. Nineteen patients (15%) discontinued testing early, rating distress and nausea two to three times higher than those who completed testing (p < 0.05). Greater dizziness was associated with younger age and female sex, not migraine and total eye speed. Women had increased distress. Test times were 71 [23] and 26 [13] minutes for VNG with calorics and RC, respectively. Testing required 48% to miss work (range 2–120 h) and 78% obtained assistance to/from testing. Posttest symptoms included drowsiness/fatigue (44%), nausea (31%), and headache (33%).

Conclusions:

This work provides baseline patient tolerance data for vestibular testing. While eliciting distress ratings comparable to other in-office otolaryngology procedures, there are high frequencies of undesirable symptoms, posttest morbidity, and opportunity costs.
Cell biology of activated protein C
Authors: Shahzad Khurrum , Kohli Shrey , Al-Dabet Moh’d Mohanad , Isermann Berend
Published: November 2018

Purpose of review

The serine protease activated protein C (aPC) was initially characterized as an endogenous anticoagulant, but in addition conveys anti-inflammatory, barrier-protective, and pro cell-survival functions. Its endogenous anticoagulant function hampered the successful and continuous implantation of aPC as a therapeutic agent in septic patients. However, it became increasingly apparent that aPC controls cellular function largely independent of its anticoagulant effects through cell-specific and context-specific receptor complexes and intracellular signaling pathways. The purpose of this review is to outline the mechanisms of aPC-dependent cell signaling and its intracellular molecular targets.

Recent findings

With the advent of new therapeutic agents either modulating directly and specifically the activity of coagulation proteases or interfering with protease-activated receptor signaling a better understanding not only of the receptor mechanisms but also of the intracellular signaling mechanisms controlled by aPC in a disease-specific and context-specific fashion, is required to tailor new therapeutic approaches based on aPC's anti-inflammatory, barrier-protective, and pro cell-survival functions.

This review summarizes recent insights into the intracellular signaling pathways controlled by aPC in a cell-specific and context-specific fashion. We focus on aPC-mediated barrier protection, inhibition of inflammation, and cytoprotecting within this review.
Adolescent idiopathic scoliosis for the primary care physician: frequently asked questions
Authors: Ghanem Ismat , Rizkallah Maroun
Published: November 2018

Purpose of review

Provide primary care physicians with the best available evidence to support answers to frequently asked questions by caregivers of patients with adolescent idiopathic scoliosis (AIS).

Recent findings

A review of best available evidence shows that schoolbag design and weight are not associated with higher odds of developing AIS. However, patients with AIS are more prone to balance problems with asymmetric backpack carrying and with rising weights. In patients with AIS, the backpack should be worn in a symmetric way and should never exceed 10% of the child's body weight. Although no relationship was found between systematic exercising in general and development of AIS, classical ballet and professional swimming in skeletally immature adolescents were associated to higher odds of having AIS. Since AIS affects adolescent girls mainly, women health issues are of paramount importance in this disease. Except for limited sexual activity and higher need for infertility treatment, patients with AIS perform similar to controls in marriage rates, age at first pregnancy, gestational age, offspring, labor and delivery. Best available evidence shows that adults with AIS diagnosed during adolescence have similar physical activity level compared with controls. In patients with AIS, adults with surgically treated idiopathic scoliosis have slightly lower physical activity level than previously braced and untreated patients.

Although schoolbag weight isn’t associated with higher odds of developing AIS, classical ballet and professional swimming in adolescents are. Except for limited sexual activity, patients with AIS perform similar to controls in remaining women health issues. Adults with AIS diagnosed during adolescence have similar physical activity level compared with controls.
Clinical Safety and Utility of Pediatric Balloon‐assisted Enteroscopy
Authors: Hagiwara Shin‐ichiro , Kudo Takahiro , Kakuta Fumihiko , Inoue Mikihiro , Yokoyama Koji , Umetsu Shuichiro , Iwama Itaru , Yodoshi Toshifumi , Tatsuki Maiko , Shimizu Toshiaki , Nakayama Yoshiko
Published: November 2018

Objectives:

The benefit of balloon‐assisted enteroscopy (BAE) had been recently documented in pediatric patients, but previous reports are based on single institution experiences. We evaluated the feasibility of pediatric BAE in 8 tertiary referral hospitals throughout Japan.

Methods:

This was a prospective, multi‐institutional study. Patients younger than 18 years were enrolled between April 2014 and March 2017 to undergo double‐balloon or single‐balloon enteroscopy. Data were collected prospectively using a standardized questionnaire.

Results:

We enrolled 79 pediatric patients (96 procedures, 70 boys, 26 girls; median age 12.7 years, range 1–17 years). Antegrade (oral‐route) BAE was performed in 20 procedures (lowest body weight 12.9 kg, youngest age 3.7 years), and retrograde (anal‐route) BAE in 76 (lowest body weight 10.8 kg, youngest age 1.6 years). Severe adverse events were associated with BAE in 2 patients: 1 with hemorrhage due to polypectomy and 1 with pancreatitis after double‐balloon endoscopic retrograde cholangioscopy. No intestinal perforation was reported. Procedure duration of oral‐route BAE for diagnosis was significantly longer than anal‐route for diagnosis (P < 0.001). The overall diagnostic yield for rectal bleeding/positive fecal occult blood test and abdominal pain was 48%. Among 40 patients referred for diagnosis who did not undergo capsule endoscopy, diagnoses were confirmed in 17 (42.5%) patients after BAE.

Conclusions:

This prospective multicenter observational study documents the efficacy of BAE in pediatric patients.
Support for Young Black Urban Women After Perinatal Loss
Authors: Fenstermacher Kimberly H. , Hupcey Judith E.
Published: November 2018

Purpose:

To describe the bereavement support needs of black urban women in late adolescence after perinatal loss.

Study Design and Methods:

Eight black women aged 18 to 21 years who had experienced recent perinatal loss were interviewed in person or by telephone at three points in the 12 weeks that followed their loss to describe their perinatal bereavement experience and support needs. Data from the interviews were analyzed using constant comparative analysis.

Results:

Black adolescent women need culturally appropriate bereavement support targeted at key transition points along the bereavement trajectory. They need accurate information, compassionate and respectful communication, and support from their mothers, grandmothers, and other women from their community of faith who have experienced perinatal loss. They value mementos, such as photographs and footprints.

Clinical Implications:

Nurses are well-positioned to be consistent caregivers and to provide clear, compassionate communication and anticipatory guidance to young black women experiencing perinatal loss. Attending to spiritual needs, harnessing family support, providing mementos, and encouraging reflection through journaling may help adolescent women find meaning and new perspectives on their bereavement experience.
The Nurse Leader’s Pivotal Role in Retaining Millennial Nurses
Authors: Ulep Kate
Published: November 2018

With increasing patient acuity and a significant nursing shortage expected in the near future, understanding and gaining the commitment of the new generation of novice nurses are important for nursing leaders. This article provides a review of recent literature and presents innovative strategies that nurse leaders can use to improve the engagement and commitment of millennials. The benefit of expanding mentoring to 3 years, involvement in department committees, quality initiatives, or unit-based councils and opportunities for lateral movement are also discussed.
Snapping Hip Syndrome
Authors: Badowski Elizabeth
Published: November 2018

Coxa saltans, or snapping hip syndrome, is a common orthopaedic problem that can easily be diagnosed and treated when the proper evaluation and management are utilized. It is often seen in growing adolescents, athletes, and people with sudden increase in physical activity. A thorough physical examination will help decipher whether the snapping hip is intra-articular or extra-articular and will help guide treatment options. This article reviews how to perform a physical assessment and treatment options such as medications, stretching, physical therapy, articular injections, and possible surgical interventions. Complications from conservative treatments are rare, but weakness, infection, nerve damage, and atrophy may occur following surgical procedures.
The Impact of a Phone Assistance Nursing Program on Adherence to Home Exercises and Final Outcomes in Patients Who Underwent Shoulder Instability Surgery
Authors: Martinez-Rico Sandra , Lizaur-Utrilla Alejandro , Sebastia-Forcada Emilio , Vizcaya-Moreno Maria F. , de Juan-Herrero Joaquin
Published: November 2018

PURPOSE:

The purpose of this study was to assess the impact of a phone assistance nursing program as an adjunct to conventional physiotherapy to increase adherence to a home exercise program on functional outcomes of patients who underwent shoulder instability surgery.

METHODS:

A randomized controlled study of 70 patients allocated to a phone assistance program (study group, n = 36 patients) or conventional postoperative management (control group, n = 34 patients) was conducted. All patients in both groups received conventional rehabilitation at the outpatient clinic after surgery. In addition, patients in the study group received phone calls from a nurse (who had access to a physiotherapist) 3 days per week. During the calls these patients received a coaching session about self-care and support with the home exercise program. Evaluations were performed during a follow-up of 12 months for range of motion (ROM), pain (visual analog scale [VAS] score), Disability of the Arm, Shoulder, and Hand (DASH) score, Oxford Shoulder Instability Score (OSIS), and Rowe score.

RESULTS:

All scores significantly improved from preoperative to the final follow-up in both groups (p = .001). At the final follow-up, there were no significant differences between groups in VAS, DASH, or Rowe scores. However, those in the study group had significantly better OSIS (p = .013) and ROM (p = .001), particularly for anterior forward motion (p = .001). Likewise, the study group achieved full motion and function significantly faster than the control group (p = .002). The amount of rehabilitation sessions at the outpatient clinic was 1.7 times higher in the control group (p = .004) than in the study group.

CONCLUSION:

The phone assistance nursing program was an effective procedure to significantly improve the outcomes of conventional physiotherapy in patients who have undergone an operation for shoulder instability.
Hepatitis B Vaccination Induces Mucosal Antibody Responses in the Female Genital Tract, Indicating Potential Mechanisms of Protection Against Infection
Authors: Simpson Samuel J. , Wiggins Rebecca , Fox James M. , Mthethwa Jabu , Cai Chun , Lacey Charles J.N.
Published: November 2018

Vaccines against hepatitis B virus confer effective protection. Enzyme-linked immunosorbent assay was developed to test for specific antibodies in female genital tract secretions. Anti–hepatitis B IgG and IgA were detected in the cervicovaginal secretions of women after hepatitis B vaccination, indicating a potential genital tract role for neutralizing antibodies against sexually transmitted hepatitis B virus.
Suicide Decapitation by a Detonating Cord
Authors: Khara Maliha , Herath Jayantha C.
Published: November 2018

In the field of forensic pathology, suicides consist of a considerable portion of the workload. Among the many methods used to commit suicide, using a detonation cord explosive is quite unique. We report the case of a man who committed suicide by detonation cord resulting in decapitation. This case report highlights the fact that the injury patterns observed in explosion-related deaths can be highly variable and that in cases with isolated injuries postmortem imaging and histology are an important adjunct to the standard death investigation. The ultimate goal of explosion-related investigations should be geared toward a well-documented and complete postmortem examination with the appropriate use of ancillary studies that provide a clear interpretation of the mechanism, cause, and manner of death.
Zygomatic Nonunion: A Misunderstood Complication of Reduction Malarplasty
Authors: Fu Xi , Mao Xiaoyan , Gui Lai , Niu Feng , Liu Jianfeng , Jia Qiao , Chen Ying
Published: November 2018

Reduction malarplasty is a popular facial skeletal contour surgery in East Asia. Zygomatic nonunion is a reported complication. However, it is often misunderstood and misdiagnosed. Here we present typical misdiagnosed zygomatic nonunion cases, propose and preliminarily clarify 4 major misunderstandings of zygomatic nonunion: diagnostic standard, the cause, the incidence, and the prognosis of zygomatic nonunion.
Bony Orbital Decompression Following Lateral Canthotomy and Cantholysis for Traumatic Orbital Compartment Syndrome
Authors: Kitaguchi Yoshiyuki , Takahashi Yasuhiro , Sabundayo Maria Suzanne , Kakizaki Hirohiko
Published: November 2018

Purpose:

To describe the clinical course of patients with traumatic orbital compartment syndrome who underwent bony orbital decompression due to persistently abnormal pupillary light reflex after lateral canthotomy and cantholysis.

Methods:

Four consecutive patients were retrospectively reviewed. The authors performed bony orbital decompression as there was no improvement in the pupillary light reflex and a tight orbit persisted even after lateral canthotomy and cantholysis.

Results:

The median interval between injury and bony decompression was 8.8 hours (range, 7–12 hours). All patients showed a preoperative intraocular pressure of 40 mm Hg or greater, which decreased to 20 mm Hg or less the next day. Two patients showed globe tenting with a posterior globe angle of 110° or less, which was resolved on the following day. Two patients with initial visual acuity of counting fingers or better showed complete visual recovery. By contrast, only 1 of the 2 patients with no light perception slightly improved to light perception while the other showed no improvement after surgery.

Conclusions:

Bony orbital decompression is effective for the treatment of traumatic orbital compartment syndrome in patients whose preoperative visual acuity is counting fingers or better.
Ulnar Artery Thrombosis Following Tranexamic Acid Administration for Craniosynostosis Repair
Authors: Chung Eugene , Karlberg Helena I.
Published: November 2018

Pediatric craniosynostosis repair with cranial vault reconstructive surgery can be associated with significant blood loss. Tranexamic acid (TXA), an antifibrinolytic agent, has been shown to decrease blood loss and transfusion volume in craniofacial surgery. Nonetheless data regarding the safety of TXA remains limited. The authors describe a case of ulnar artery thrombosis following ulnar arterial line placement in a patient who received TXA for cranial vault reconstructive surgery.
Fibromyxoma of the Orbit
Authors: Hwang Sungsoon , Kim Yoon-Duck , Siapno Debrelle Lou , Suh Yeon-Lim , Woo Kyung In
Published: November 2018

Fibromyxomas are rare tumors that are not commonly seen in the orbit. The authors present a case of orbital fibromyxoma. A 42-year-old male presented with proptosis of the right eye that began 1 month prior. Magnetic resonance imaging revealed the presence of an orbital mass in the right eye, with low signal intensity on T1-weighted images and heterogeneous high-signal intensity on T2-weighted images. The patient underwent excisional biopsy of the orbital tumor through a Krönlein approach. The tumor originated from the inferior rectus muscle. Histopathologic analysis demonstrated scattered spindle cells, with both fibrous and myxoid stroma. Immunohistochemical staining was positive for Vimentin and negative for S-100 protein and CD34. The tumor was diagnosed as orbital fibromyxoma. The patient showed no evidence of recurrence over 18 months of follow-up after operation.
Comparison of Nasal Symmetry Between Presurgical Nasal Stenting and Postsurgical Nasal Retainer Placement in Unilateral Clefts
Authors: Funayama Emi , Yamamoto Yuhei , Oyama Akihiko , Furukawa Hiroshi , Murao Naoki , Hayashi Toshihiko , Maeda Taku , Osawa Masayuki
Published: November 2018

The timing of cleft lip nose surgery remains controversial. The less invasive the procedure at the time of primary cleft lip repair, the less the growth and development of the nose is affected. Therefore, the nasal-stenting component of presurgical nasoalveolar molding has increasingly been used. However, not all cleft centers use such treatment. Conventional postsurgical placement of silicone nasal retainers remains popular. No report has yet compared presurgical nasal stenting (preNS) and postsurgical nasal retainer placement (postNR). In this study, postoperative nasal form outcomes after primary lip repair using preNS or postNR in patients with complete unilateral cleft lips, alveoli, and palates were compared. Patients in whom preNS alone was used for 6 months (group I) were compared with those receiving postNR (no preNS) for 6 months after primary nasal cartilage dissection (group II) and controls with no appliance (group III). Nasal anthropometric distances and angular relationships were measured photographically to assess nasal symmetry at 4 years of age in all groups. Compared to group III, groups I and II exhibited significantly greater nostril heights (P = 0.0075, P = 0.0015 respectively) and columellar deviation angles (P = 0.0020, P = 0.0221). Groups I and II did not differ significantly. No significant between-treatment difference in terms of nasal symmetry between preNS and postNR was observed. However, both treatments afforded significantly better results than no treatment. Since older infants tend to resist the placement of nasal devices, preNS is more feasible in this age group.
Modified Posterolateral Approach for Pterygium Colli
Authors: Komatsu Seiji , Shinaoka Akira , Kimata Yoshihiro
Published: November 2018

Pterygium colli is a congenital deformity associated with malformation syndromes. Various surgical procedures have been reported, but these procedures have advantages and disadvantages. The modified posterolateral approach has been reported as a new surgical procedure for pterygium colli. However, there has been no confirmatory report. In this study, a case of pterygium colli that was treated with the modified posterolateral approach was reported.

An 11-year-old girl with Turner syndrome was referred with chief complaints of web neck deformity and an abnormal hairline. The modified posterolateral approach was selected. Hairy excessive skin was excised at the posterolateral and posterior neck. An inferior skin incision was made parallel to the hairline, and a superior skin incision was made along the desired hairline. Hairless excessive skin was excised along the posterior midline of the neck. Undermining was extended over the sternocleidomastoid muscle, and flaps were rotated upward and inward. Z-plasty was performed at the posterior midline of the neck to prevent hypertrophic scar formation. The web neck deformity disappeared, but the patient expressed concern for excessive skin at the posterior midline. Thus, secondary surgery was performed 12 months later. The operative scar was opened 2 months after secondary surgery owing to suture abscess, and the wound was closed directly. The web neck deformity had not recurred, and the natural hairline was maintained at 65 months after the primary surgery.

The modified posterolateral approach is beneficial for pterygium colli, because it allows the correction of the web neck deformity and abnormal hairline without a noticeable scar.
Future Trends in Demand for Liver Transplant: Birth Cohort Effects Among Patients With NASH and HCC
Authors: Shingina Alexandra , DeWitt Peter E. , Dodge Jennifer L. , Biggins Scott W. , Gralla Jane , Sprague David , Bambha Kiran
Published: November 2018

Background

With increasing US adiposity, nonalcoholic steatohepatitis (NASH) is now a leading liver transplant (LT) indication. Given its association with hepatocellular carcinoma (HCC), the burden of NASH is substantial. We analyzed birth cohort effects among NASH LT registrants, with and without HCC.

Methods

All new LT registrants in United Network for Organ Sharing (1995-2015) were identified. Birth cohorts were defined as: 1936-1940, 1941-1945, 1946-1950, 1951-1955, 1956-1960, 1961-1965, 1966-1970, 1971-2015. Poisson regression examined trends in LT registration, by disease etiology (NASH, hepatitis C virus [HCV], other liver disease etiologies [OTHER]), and HCC.

Results

We identified 182 368 LT registrants with median age of 52 years (range, 0-86 years). Nine percent (n = 16 160) had NASH, 38% (n= 69 004) HCV, 53% (n = 97 204) OTHER. HCC was present in: 13% (n = 2181), 27% (n = 18 295), and 11% (n = 10 902), of NASH, HCV, and OTHER, respectively. Liver transplant registration for HCC increased significantly from 2002 to 2015 across all etiologies (NASH, 6%-18%; HCV, 19%-51%; OTHER, 9%-16%; P < 0.0001 for all). NASH LT registrations, with and without HCC, increased sharply in patients born from 1945 to 2015. This upward NASH trend is in stark contrast to HCV LT registrations, which showed a general decline. Notably, a sharp rise in LT registrations is occurring among younger NASH patients (35-55 years), mirroring the increasing adiposity across all age groups in the US population.

Conclusions

NASH LT registrants, with and without HCC, have increased over time, and are projected to increase unabated in the future, notably among younger birth cohorts (“Adipose Wave Effect”). HCC LT registration patterns demonstrate that, compared with HCV, NASH patients encompass younger birth cohorts. These data illustrate that the full impact of NASH on demand for LT is yet to be realized.
Modified Technique of Total Hepatectomy in Polycystic Liver Disease With Caval Flow Preservation: The Exposure Left Lateral Sectionectomy
Authors: Le Roy Bertrand , Cauchy François , Sepulveda Ailton , Yoh Tomoaki , Dokmak Safi , Weiss Emmanuel , Cesaretti Manuela , Durand Francois , Francoz Claire , Dondéro Fédérica , Soubrane Olivier
Published: November 2018

Background.

Liver transplantation (LT) for polycystic liver disease (PLD) is rare, extremely challenging and hemorrhagic, without standard approach. Moreover, LT for PLD presents the highest mortality rate (12% to 18%) among all causes of LT. In this setting, the combination of difficult mobilization of a heavy polycystic native liver with narrow access to inferior vena cava and fragile venous wall may lead to venous tearing and cataclysmic bleeding during dissection. The aim of this study was to evaluate a modified technique of total hepatectomy to limit hazardous liver manipulation and improve exposure of inferior vena cava in patients with massive hepatomegaly related to PLD: the exposure left lateral sectionectomy (ELLS).

Methods.

From 2011 to 2018, ELLS was performed during LT for PLD. Key technical points for safe and fast ELLS include avoidance of left triangular ligament section and placement of a tape behind the left lateral section allowing its ascension and prior dissection of the hepatic pedicle to limit bleeding. The transection plane is mainly composed of cysts, with limited parenchyma, which allows for rapid and bloodless transection using electric scalpel.

Results.

Fifteen patients had ELLS with no postoperative death or intraoperative complication. Median ELLS duration was 16 minutes, and no massive bleeding occurred during this step. During total hepatectomy, median blood loss was 500 mL, and no patient required total caval clamping. All patients were alive at the end of the follow-up.

Conclusions.

ELLS during LT for PLD facilitates total hepatectomy with vena cava and caval flow preservation.
Endothelial Glycocalyx Shedding Predicts Donor Organ Acceptability and Is Associated With Primary Graft Dysfunction in Lung Transplant Recipients
Authors: Sladden Timothy M. , Yerkovich Stephanie , Grant Michelle , Zhang Fuming , Liu Xinyue , Trotter Michael , Hopkins Peter , Linhardt Robert J. , Chambers Daniel C.
Published: November 2018

Background.

The endothelial glycocalyx, a sieve-like structure located on the luminal surface of all blood vessels, has been found to be integral to regulation of capillary permeability and mechanotransduction. Given this, we investigated the role of endothelial glycocalyx breakdown products in organ donors and recipients in terms of acceptability for transplant and risk of primary graft dysfunction (PGD).

Methods.

Endothelial glycocalyx breakdown products were measured in the peripheral blood of 135 intended and actual organ donors. Breakdown product levels were tested for association with donor demographic and clinical data, organ acceptability for transplant along with lung recipient outcomes (n = 35). Liquid chromatography mass spectrometry analysis was performed to confirm glycosaminoglycan levels and sulfation patterns on donor samples (n = 15). In transplant recipients (n = 50), levels were measured pretransplant and daily for 4 days posttransplant. Levels were correlated with PGD severity and intubation time.

Results.

Decreased hyaluronan levels in peripheral blood independently predicted organ acceptability in intended and actual donors (odds ratio, 0.96; [95% confidence interval, 0.93–0.99] P = 0.026). Furthermore, high donor syndecan-1 levels were associated with PGD in recipients (3142 [1575–4829] versus 6229 [4009–8093] pg/mL; P = 0.045). In recipient blood, levels of syndecan-1 were correlated with severe (grades 2–3) PGD at 72 hours posttransplant (5982 [3016–17191] versus 3060 [2005–4824] pg/mL; P = 0.01).

Conclusions.

Endothelial glycocalyx breakdown occurs in lung transplant donors and recipients and predicts organ acceptability and development of PGD. Glycocalyx breakdown products may be useful biomarkers in transplantation, and interventions to protect the glycocalyx could improve transplant outcomes.
Functionalized mesoporous silica nanoparticles for innovative boron-neutron capture therapy of resistant cancers
Authors: Vares Guillaume , Jallet Vincent , Matsumoto Yoshitaka , Rentier Cedric , Takayama Kentaro , Sasaki Toshio , Hayashi Yoshio , Kumada Hiroaki , Sugawara Hirotaka
Published: November 2018

Treatment resistance, relapse and metastasis remain critical issues in some challenging cancers, such as chondrosarcomas. Boron-neutron Capture Therapy (BNCT) is a targeted radiation therapy modality that relies on the ability of boron atoms to capture low energy neutrons, yielding high linear energy transfer alpha particles. We have developed an innovative boron-delivery system for BNCT, composed of multifunctional fluorescent mesoporous silica nanoparticles (B-MSNs), grafted with an activatable cell penetrating peptide (ACPP) for improved penetration in tumors and with Gadolinium for magnetic resonance imaging (MRI)in vivo. Chondrosarcoma cells were exposedin vitroto an epithermal neutron beam after B-MSNs administration. BNCT beam exposure successfully induced DNA damage and cell death, including in radio-resistant ALDH+ cancer stem cells (CSCs), suggesting that BNCT using this system might be a suitable treatment modality for chondrosarcoma or other hard-to-treat cancers.
Transient activation of the UPRER is an essential step in the acquisition of pluripotency during reprogramming
Authors: Simic Milos S. , Moehle Erica , Schinzel Robert T. , Lorbeer Franziska , Jullié Damien , Halloran Jonathan J. , Heydari Kartoosh , Sanchez Melissa , Hockemeyer Dirk , Dillin Andrew
Published: November 2018

Somatic cells can be reprogrammed into pluripotent stem cells by the forced expression of the OCT4, SOX2, KLF4 and c-MYC transcription factors. This process requires the reshaping of not only epigenetic landscapes, but the global remodeling of cell identity, structure, and function including such basic processes of metabolism and organelle form and function. Cellular reprogramming is a stochastic process with only a marginally measureable fraction of cells successfully crossing these, and many other, cellular epitomes to acquire the fully pluripotent state. We hypothesize that this variation is due, in part, by variable regulation of the proteostasis network and its influence upon the protein folding environment within cells and their organelles upon the remodeling process. We find that the endoplasmic reticulum unfolded protein response (UPRER), the heat-shock response (HSR) and the mitochondrial unfolded protein response (UPRmt), which monitor and ensure the quality of the proteome of, respectively, the ER, the cytosol and the mitochondria during stress, are activated during cellular reprogramming. Particularly, we find that the UPRER is essential for reprograming, and ectopic, transient activation of the UPRER, either genetically or pharmacologically, enhances the success of cells to reach a pluripotent state. Finally, and most revealing, we find that stochastic activation of the UPRER can predict the reprogramming efficiency of naïve cells. The results of these experiments indicate that the low efficiency and stochasticity of cellular reprogramming is partly the result of the inability to initiate a proper ER stress response for remodeling of the ER and its proteome during the reprogramming process. The results reported here display only one aspect of the proteostasis network and suggest that proper regulation of many more components of this network might be essential to acquire the pluripotent state.
Identifying native plants for coordinated habitat management of arthropod pollinators, herbivores and natural enemies
Authors: Lundin Ola , Ward Kimiora L. , Williams Neal M.
Published: November 2018

Providing noncrop flowering resources in agricultural landscapes is widely promoted as a strategy to support arthropods that deliver pollination and pest control services. However, management options have largely been developed separately for pollinators and natural enemies, whereas possible effects on insect herbivores, such as crop pests, have often been overlooked. A first critical step for design and implementation of multifunctional plantings that promote beneficial arthropods while controlling insect pests is to identify suitable plant species to use.

We aimed to identify California native plants and, more generally, plant traits suitable for the coordinated management of pollinators (wild bees and honeybees), insect herbivores and arthropod natural enemies (predators and parasitic wasps). We established 43 plant species in a common garden experiment and sampled arthropods by weekly netting (wild bees), observations (honeybees), or vacuum sampling (insect herbivores, arthropod predators, and parasitic wasps) during peak bloom of each plant species over 2 years.

Plant species differed in attractiveness for each arthropod functional group. Floral area of the focal plant species positively affected honeybee, predator, and parasitic wasp attractiveness. Later bloom period was associated with lower numbers of parasitic wasps. Flower type (actinomorphic, composite, or zygomorphic) predicted attractiveness for honeybees, which preferred actinomorphic over composite flowers and for parasitic wasps, which preferred composite flowers over actinomorphic flowers.

Across plant species, herbivore, predator, and parasitic wasp abundances were positively correlated, and honeybee abundance correlated negatively to herbivore abundance.

Synthesis and applications. We use data from our common garden experiment to inform evidence‐based selection of plants that support pollinators and natural enemies without enhancing potential pests. We recommend selecting plant species with a high floral area per ground area unit, as this metric predicts the abundances of several groups of beneficial arthropods. Multiple correlations between functionally important arthropod groups across plant species stress the importance of a multifunctional approach to arthropod habitat management.
Nonrandom RNAseq gene expression associated with RNAlater and flash freezing storage methods
Authors: Passow Courtney N. , Kono Thomas J. Y. , Stahl Bethany A. , Jaggard James B. , Keene Alex C. , McGaugh Suzanne E.
Published: November 2018

RNA sequencing is a popular next‐generation sequencing technique for assaying genome‐wide gene expression profiles. Nonetheless, it is susceptible to biases that are introduced by sample handling prior gene expression measurements. Two of the most common methods for preserving samples in both field‐based and laboratory conditions are submersion in RNAlater and flash freezing in liquid nitrogen. Flash freezing in liquid nitrogen can be impractical, particularly for field collections. RNAlater is a solution for stabilizing tissue for longer‐term storage as it rapidly permeates tissue to protect cellular RNA. In this study, we assessed genome‐wide expression patterns in 30‐day‐old fry collected from the same brood at the same time point that were flash‐frozen in liquid nitrogen and stored at −80°C or submerged and stored in RNAlater at room temperature, simulating conditions of fieldwork. We show that sample storage is a significant factor influencing observed differential gene expression. In particular, genes with elevated GC content exhibit higher observed expression levels in liquid nitrogen flash‐freezing relative to RNAlater storage. Further, genes with higher expression in RNAlater relative to liquid nitrogen experience disproportionate enrichment for functional categories, many of which are involved in RNA processing. This suggests that RNAlater may elicit a physiological response that has the potential to bias biological interpretations of expression studies. The biases introduced to observed gene expression arising from mimicking many field‐based studies are substantial and should not be ignored.
Severity, course trajectory, and within‐person variability of individual symptoms in patients with major depressive disorder
Authors: van Eeden W. A. , van Hemert A. M. , Carlier I. V. E. , Penninx B. W. , Giltay E. J.
Published: November 2018

Background

Depression shows a large heterogeneity of symptoms between and within persons over time. However, most outcome studies have assessed depression as a single underlying latent construct, using the sum score on psychometric scales as an indicator for severity. This study assesses longitudinal symptom‐specific trajectories and within‐person variability of major depressive disorder over a 9‐year period.

Methods

Data were derived from the Netherlands Study of Depression and Anxiety (NESDA). This study included 783 participants with a current major depressive disorder at baseline. The Inventory Depressive Symptomatology‐Self‐Report (IDS‐SR) was used to analyze 28 depressive symptoms at up to six time points during the 9‐year follow‐up.

Results

The highest baseline severity scores were found for the items regarding energy and mood states. The core symptoms depressed mood and anhedonia had the most favorable course, whereas sleeping problems and (psycho‐)somatic symptoms were more persistent over 9‐year follow‐up. Within‐person variability was highest for symptoms related to energy and lowest for suicidal ideation.

Conclusions

The severity, course, and within‐person variability differed markedly between depressive symptoms. Our findings strengthen the idea that employing a symptom‐focused approach in both clinical care and research is of value.
Harm reduction in opioid treatment: an established idea under threat
Authors: Kalk Nicola J.
Published: November 2018

Commentary to: What defines a clinically meaningful outcome in the treatment of substance use disorders: reductions in direct consequences of drug use or improvement in overall functioning?
Biodiversity responses to land‐use and restoration in a global biodiversity hotspot: Ant communities in Brazilian Cerrado
Authors: Dalle Laste Keila Caroline , Durigan Giselda , Andersen Alan N.
Published: November 2018

Given that land‐use change is the main cause of global biodiversity decline, there is widespread interest in adopting land‐use practices that maintain high levels of biodiversity, and in restoring degraded land that previously had high biodiversity value. In this study, we use ant taxonomic and functional diversity to examine the effects of different land uses (agriculture, pastoralism, silviculture and conservation) and restoration practices on Cerrado (Brazilian savanna) biodiversity. We also examine the extent to which ant diversity and composition can be explained by vegetation attributes that apply across the full land management spectrum. We surveyed vegetation attributes and ant communities in five replicate plots of each of 13 land‐use and restoration treatments, including two types of native vegetation as reference sites: cerrado sensu stricto and cerradão. Several land‐use and restoration treatments had comparable plot richness to that of the native reference habitats. Ant species and functional composition varied systematically among land‐use treatments following a gradient from open habitats such as agricultural fields to forested sites. Tree basal area and grass cover were the strongest predictors of ant species richness. Losses in ant diversity were higher in land‐use systems that transform vegetation structure. Among productive systems, therefore, uncleared pastures and old pine plantations had similar species composition to that occurring in cerrado sensu stricto. Restoration techniques currently applied to sites that were previously Cerrado have focused on returning tree cover, and have failed to restore ant communities typical of savanna. To improve restoration outcomes for Cerrado biodiversity, greater attention needs to be paid to the re‐establishment and maintenance of the grass layer, which requires frequent fire. At the broader scale, conservation planning in agricultural landscapes, should recognize the value of land‐use mosaics and the risks of homogenization.
Ecoregions within the Brazilian Pampa biome reflected in Odonata species assemblies
Authors: Renner Samuel , Périco Eduardo , Dalzochio Marina S. , Sahlén Göran
Published: November 2018

Based on vegetation composition, previous studies of the Pampa biome in southern Brazil have defined seven ecoregions within the area. Here, we test this ecoregion approach studying the semi‐aquatic insect group Odonata in five of these regions, aiming at comparing the ecoregions to the more traditional environmental predictors of water quality and land cover. Based on a data set of occupancy comprising 99 species distributed between 131 localities, a one‐way Permutational Multivariate Analysis of Variance was used to compare differences in the species composition between the ecoregions, followed by a Principal Component Analysis to visualize the variation. The composition varied significantly between all groups tested, and the ordination explained 61.8% of the variance. A partial redundancy analysis of ecoregions, land cover and water quality variables explained 71% of the variance in Odonata community structure. Ecoregion was the most important predictor, followed by water quality and land cover. Within these species assemblies, we could select certain species that were representative of a given ecoregion, to which their distribution within the Pampa biome was entirely or mainly confined. Of 24 representative species 41.7% were rare, while the rest were more abundant and, hence, easier to detect. We suspect that the differences found between the Pampa ecoregions might be due to geology, as such factors may be strong determinants of biodiversity. Specific ecological requirements at the family and genus levels also seemed to act selectively on the species compositions within the ecoregions. Today, the Pampa is highly fragmented due to agricultural activities such as rice cultivation, extensive cattle farming and forest plantations. We suggest that an ecoregion‐based approach to the implementation of conservation measures may be the best way to help these distinct species assemblies survive.