bluuebunny/crossref_metadata_2025 huggingface dataset:
What Is the Actual 3D Representation of the Rib Vertebra Angle Difference (Mehta Angle)?
Authors: Brink Rob C. , Schlösser Tom P.C. , van Stralen Marijn , Vincken Koen L. , Kruyt Moyo C. , Chu Winnie C.W. , Cheng Jack C.Y. , Castelein René M.
Published: May 2017

Study Design.

Cross-sectional study.

Objective.

To establish the relevance of the conventional two-dimensional (2D) rib vertebra angle difference (RVAD) and the relationship with the complex three-dimensional (3D) apical morphology in scoliosis.

Summary of Background Data.

The RVAD, also known as Mehta angle, describes apical rib asymmetry on conventional radiographs and was introduced as a prognostic factor for curve severity in early onset scoliosis, and later applied to other types of scoliosis as well.

Methods.

An existing idiopathic scoliosis database of high-resolution computed tomography scans used in previous work, acquired for spinal navigation, was used. Eighty-eight patients (Cobb angle 46°–109°) were included. Cobb angle and 2D RVAD, as described by Mehta, were measured on the conventional radiographs and coronal digitally reconstructed radiographs (DRR) of the prone computed tomography scans. A previously validated, semiautomatic image processing technique was used to acquire complete 3D spinal reconstructions for the measurement of the 3D RVAD in a reconstructed true coronal plane, axial rotation, and sagittal morphology.

Results.

The 2D RVAD on the x-ray was on average 25.3° ± 11.0° and 25.6° ± 12.8° on the DRR (P = 0.990), but in the true 3D coronal view of the apex, hardly any asymmetry remained (3D RVAD: 3.1° ± 12.5°; 2D RVAD on x-ray and DRR vs. 3D RVAD: P < 0.001). 2D apical rib asymmetry in the anatomical coronal plane did not correlate with the same RVAD measurements in the 3D reconstructed coronal plane of the rotated apex (r = 0.155; P = 0.149). A larger 2D RVAD was found to correlate linearly with increased axial rotation (r = 0.542; P < 0.001) and apical lordosis (r = 0.522; P < 0.001).

Conclusion.

The 2D RVAD represents a projection-based composite radiographic index reflecting the severity of the complex 3D apical morphology including axial rotation and apical lordosis. It indicates a difference in severity of the apical deformation.

Level of Evidence: 4
Hyperchloremia Is Associated With Acute Kidney Injury in Patients With Subarachnoid Hemorrhage
Authors: Sadan Ofer , Singbartl Kai , Kandiah Prem A. , Martin Kathleen S. , Samuels Owen B.
Published: May 2017

Objective:

To assess the prevalence of acute kidney injury in patients with subarachnoid hemorrhage patients.

Design:

Retrospective analysis of all subarachnoid hemorrhage admissions.

Settings:

Neurocritical care unit.

Patients:

All patients with a diagnosis of subarachnoid hemorrhage between 2009 and 2014.

Interventions:

None.

Measurements and Main Results:

Of 1,267 patients included in this cohort, 16.7% developed acute kidney injury, as defined by Kidney Disease Improving Global Outcome criteria (changes in creatinine only). Compared to patients without acute kidney injury, patients with acute kidney injury had a higher prevalence of diabetes mellitus (21.2% vs 9.8%; p < 0.001) and hypertension (70.3% vs 50.5%; p < 0.001) and presented with higher admission creatinine concentrations (1.21 ± 0.09 vs 0.81 ± 0.01 mg/dL [mean ± sd], respectively; p < 0.001). Patients with acute kidney injury also had higher mean serum chloride and sodium concentrations during their ICU stay (113.4 ± 0.6 vs 107.1 ± 0.2 mmol/L and 143.3 ± 0.4 vs 138.8 ± 0.1 mmol/L, respectively; p < 0.001 for both), but similar chloride exposure. The mortality rate was also significantly higher in patients with acute kidney injury (28.3% vs 6.1% in the non-acute kidney injury group [p < 0.001]). Logistic regression analysis revealed that only male gender (odds ratio, 1.82; 95% CI, 1.28–2.59), hypertension (odds ratio, 1.64; 95% CI, 1.11–2.43), diabetes mellitus (odds ratio, 1.88; 95% CI, 1.19–2.99), abnormal baseline creatinine (odds ratio, 2.48; 95% CI, 1.59–3.88), and increase in mean serum chloride concentration (per 10 mmol/L; odds ratio, 7.39; 95% CI, 3.44–18.23), but not sodium, were associated with development of acute kidney injury. Kidney recovery was noted in 78.8% of the cases. Recovery reduced mortality compared to non-recovering subgroup (18.6% and 64.4%, respectively; p < 0.001).

Conclusions:

Critically ill patients with subarachnoid hemorrhage show a strong association between hyperchloremia and acute kidney injury as well as acute kidney injury and mortality.
Tackling immunomonitoring in gastrointestinal cancer
Authors: Anciaux Maëlle , Vandeputte Caroline , Hendlisz Alain
Published: May 2017

Purpose of review

The growing awareness that the immune system is a key player in the antitumoral response and the excellent clinical results achieved in some settings with anti-programmed cell death 1 (PD1)/programmed death ligand 1 (PDL1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) drugs has led to the rise of immunotherapy as a supplement or an alternative to conventional cancer treatment. The high costs associated with these therapies, their significant toxicity and the need to understand and circumvent immune escape mechanisms raise the urgent need for immunological assessment of therapy response. The study of the immunological parameters before, during and after treatment is referred to as immunomonitoring. This review discusses the current knowledge of immunomonitoring markers in gastrointestinal cancers.

Recent findings

The last decade has seen a collaborative effort to standardize the assays performed in clinical trials to assess response to immunotherapy. Since then, multiple studies have been conducted on blood samples, biopsies and surgical specimens to determine their immunological profiles leading to the identification of several immunological markers possessing a predictive value of response to treatment.

Future research will focus on detangling the predictive value of immune markers in different therapeutic models, and also to develop new noninvasive means to monitor the immune response of patients.

Video abstract

http://links.lww.com/COON/A20.
DISEASE EXPRESSION IN NONEXUDATIVE AGE-RELATED MACULAR DEGENERATION VARIES WITH CHOROIDAL THICKNESS
Authors: Spaide Richard F.
Published: May 2017

Purpose:

To investigate the relationship between subfoveal choroidal thickness and disease manifestation in a series of eyes with nonexudative age-related macular degeneration (AMD).

Methods:

Retrospective study of eyes with nonexudative AMD. The extracellular deposits present, drusen and subretinal drusenoid deposits (SDD, pseudodrusen) along with a newly recognized form of drusen, pachydrusen, were graded and compared with choroidal thickness as determined by optical coherence tomography. Demographic and imaging information was evaluated with descriptive statistics and generalized estimating equations.

Results:

There were 94 eyes of 71 patients, who had a mean age of 78.1 years. Soft drusen alone were found in 45 eyes (47.9%) and subretinal drusenoid deposit with or without drusen in 38 (40.4%). Pachydrusen, which were typically larger than 125 μm, often had an irregular outer contour, showed a scattered distribution over the posterior pole and occurred in isolation or in groups of only a few drusen were found in 11 (11.7%). The mean subfoveal choroidal thickness in the soft drusen group was 227.9 μm, in the subretinal drusenoid deposit group 167.3 μm, and in the pachydrusen group 419 μm. The differences between the groups were highly significant.

Conclusion:

Extracellular deposits, subretinal drusenoid deposits and drusen, which are on either side of the retinal pigment epithelium, respectively, are common in nonexudative AMD. A new form of drusen presentation could be differentiated from typical soft drusen and was associated with thicker choroids. Disease manifestation in nonexudative AMD seems to be associated with choroidal thickness. Each of these has potential to lead to specific forms of late AMD.
Pharmaceutical Dosing Errors at a Pediatric HIV Clinic in Mwanza, Tanzania
Authors: Naik Neel Mahesh , Mbwanji Ruth Nicholas , Mgawe Mwajuma , Ongoa Richard , Gesase Anthony E. , Schutze Gordon E. , Minde Mercy , Mwita Lumumba Francis
Published: May 2017

The outpatient medication dosing error rate at a pediatric HIV clinic in Mwanza, Tanzania, was about 1 in every 34 prescriptions. Young children were at highest risk of a dosing error likely because of dose changes with growth and also the inconsistent supply of pediatric formulations. Majority of errors occurred at consecutive visits suggesting clinicians reordered medication without double checking dosing.
Impact of Higher Vancomycin Troughs on Vancomycin-Induced Nephrotoxicity
Authors: Bulloch Marilyn Novell , Paumen Lyndsi , Eure Stephen , Stewart Joseph Grier
Published: May 2017

Background

Guidelines published in 2009 by the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists recommended targeting vancomycin troughs of 15 to 20 mg/L. No previous studies exist examining the effect of implementing these guidelines on kidney function. The objective of this study was to evaluate the effect of a dosing nomogram that incorporated recommendations for higher vancomycin goal trough vancomycin-induced nephrotoxicity (VIN).

Methods

This study evaluated 300 adult inpatients with a pharmacokinetics consultation for vancomycin dosing. Two periods were evaluated: phase I (2008) assessed practice preguideline vancomycin dosing nomogram change, and phase II (2012) assessed practice postguideline vancomycin dosing nomogram change reflecting the higher trough targets. Groups were compared using χ2 or Fisher exact tests for categorical variables and Mann-Whitney U tests for continuous variables. The a priori level of significance was set at 0.05.

Results

A total of 300 inpatients (150 in 2008 and 150 in 2012) were included in the analysis. More patients from the 2012 group experienced VIN, according to the guideline definition (P = 0.03), but not per the 2007 Acute Kidney Injury Network definition (P = 0.88). There was no change in other adverse outcomes, including dialysis initiation (2 vs 0; P = 0.16), discharge on dialysis (1 vs 0; P = 0.32), transfer to another hospital for higher level of care (33 vs 34; P = 0.89), or death (15 vs 11; P = 0.41).

Conclusions

Targeting higher vancomycin troughs resulted in transient VIN but did not cause adverse sequelae.
Novel OFD1 frameshift mutation in a Chinese boy with Joubert syndrome: a case report and literature review
Authors: Zhang Kaihui , Meng Chen , Ma Jing , Gao Min , Lv Yuqiang , Liu Yi , Gai Zhongtao
Published: May 2017

Joubert syndrome (JBTS) is a clinically and genetically heterogeneous group of ciliopathy with a key diagnostic feature of ‘molar tooth sign’ in brain MRI. So far, over 20 causative genes have been identified, but only one gene (OFD1) results in X-linked Joubert syndrome 10 (JBTS10). Six mutations in the OFD1 gene have been found to cause JBTS10. In this study, we identified a novel OFD1 mutation of c.2843_2844 delAA (p.Lys948ArgfsX) in a 3-month-old boy with a ‘molar tooth sign’ and clinical features of JBTS using targeted exome next-generation sequencing. The de-novo OFD1 mutation in exon 21 leads to a frameshift mutation generating a prematurely truncated protein and is predicted to partly reduce the function of the OFD1 protein. Our study expands the genotype–phenotype spectrum in JBTS and will have applications in prenatal and early diagnosis of the disorder. This is the first report of the OFD1 mutation causing JBTS in a Chinese population.
Secondary reconstruction of maxillofacial trauma
Authors: Castro-Núñez Jaime , Van Sickels Joseph E.
Published: May 2017

Purpose of review

Craniomaxillofacial trauma is one of the most complex clinical conditions in contemporary maxillofacial surgery. Vital structures and possible functional and esthetic sequelae are important considerations following this type of trauma and intervention. Despite the best efforts of the primary surgery, there are a group of patients that will have poor outcomes requiring secondary reconstruction to restore form and function. The purpose of this study is to review current concepts on secondary reconstruction to the maxillofacial complex.

Recent findings

The evaluation of a posttraumatic patient for a secondary reconstruction must include an assessment of the different subunits of the upper face, middle face, and lower face. Virtual surgical planning and surgical guides represent the most important innovations in secondary reconstruction over the past few years. Intraoperative navigational surgery/computed-assisted navigation is used in complex cases. Facial asymmetry can be corrected or significantly improved by segmentation of the computerized tomography dataset and mirroring of the unaffected side by means of virtual surgical planning. Navigational surgery/computed-assisted navigation allows for a more precise surgical correction when secondary reconstruction involves the replacement of extensive anatomical areas. The use of technology can result in custom-made replacements and prebent plates, which are more stable and resistant to fracture because of metal fatigue.

Careful perioperative evaluation is the key to positive outcomes of secondary reconstruction after trauma. The advent of technological tools has played a capital role in helping the surgical team perform a given treatment plan in a more precise and predictable manner.
Current opinion in otolaryngology and head and neck surgery: frontal sinus fractures
Authors: Chouake Robert J. , Miles Brett A.
Published: May 2017

Purpose of review

The purpose of this manuscript is to review the current literature regarding the management of frontal sinus fractures and offer the authors opinion on the current management of these traumatic injuries. We evaluate recently proposed management algorithms as well as novel surgical approaches reported within the last few years.

Recent findings

Patient selection for sinus sparing treatment modalities is balanced between fracture severity, involved structures, and reliable patient surveillance. Minimally invasive, aesthetically favorable approaches grow in diversity for anterior table fractures. For fractures of the posterior sinus wall and nasofrontal outflow tract, the literature focuses on sinus sparing surgery, as well as better defining the patients in which obliteration and/or cranialization is appropriate.

Lack of large patient cohorts and follow-up limits generalizability of frontal sinus fracture research, and the ability to develop national guidelines of management. Evidence-based literature shows growing support for conservative management and sinus preservation. Improvements in frontal sinus fracture classification schemes, surgical technique, and patient selection direct this treatment paradigm shift.
Complications in facial Mohs defect reconstruction
Authors: Berens Angelique M. , Akkina Sarah R. , Patel Sapna A.
Published: May 2017

Purpose of review

To review the recent literature in regards to complications after reconstruction of Mohs defects, outline common pitfalls and to discuss the literature on avoiding complications as outlined per aesthetic subunit.

Recent findings

Complications in facial Mohs reconstruction commonly consist of infection, wound necrosis and dehiscence, hematoma and suboptimal scarring. However, site-specific complications such as hairline or eyebrow distortion, eyelid retraction or ectropion, nasal contour abnormality, alar retraction, nasal valve compromise, significant facial asymmetry or even oral incompetence must also be considered.

A successful reconstruction mimics the premorbid state and maintains function. The use of perioperative antibiotics, sterile technique, meticulous hemostasis, subcutaneous dissection and deep sutures to minimize wound tension should be considered for all Mohs reconstructions. Cartilage grafting can minimize nasal deformity and obstruction. Reconstruction near the lower eyelid should employ periosteal suspension sutures to minimize downward tension and lid retraction. Perioral complications, such as microstomia and oral incompetence, typically improve with time and therapy. Always consider secondary procedures such as dermabrasion, steroid injection, scar revision and laser resurfacing to help optimize aesthetic outcome.
AL Amyloidoma of the Skin/Subcutis
Authors: Walsh Noreen M. , Lano Ian Marie , Green Peter , Gallant Christopher , Pasternak Sylvia , Ly Thai Yen , Requena Luis , Kutzner Heinz , Chott Andreas , Cerroni Lorenzo
Published: May 2017

It is unclear whether AL amyloidoma of the skin/subcutis represents a distinct entity, an indolent precursor of systemic amyloidosis, or a manifestation of cutaneous marginal zone lymphoma (cMZL). We collected 10 cases of cutaneous AL amyloidoma in order to better characterize the clinicopathologic features of this elusive entity (M:F=4:6; median age: 62.5 y, range: 31 to 82 y). Nine patients had a solitary nodule or plaque on the lower extremity (n=7), upper extremity (n=1), or chin (n=1). One patient had an AL amyloidoma on the right thigh and a second lesion on the right arm showing histopathologic features of cMZL without amyloid deposits. Clinical investigations excluded relevant systemic disease in all cases. Microscopically, dermal/subcutaneous deposits of amyloid were associated with sparse to moderate perivascular infiltrates of lymphocytes and monotypic plasma cells (7 with kappa and 3 with lambda light chain restriction). The plasma cells expressed CD56 in one of 9 studied cases. One case was characterized by a t(14;18)(q32;q21)/IGH-MALT1 translocation. Follow-up was available in 8 cases. All remain systemically well after a median time of 86.5 months (range: 40 to 144 mo). Local recurrence of disease was observed in 3 patients. A fourth patient presented with a cMZL without amyloid deposits 8 years after excision of the cutaneous AL amyloidoma. Although our series is small, careful categorization and follow-up of the cases, together with updated information in the literature, show clinical and biological links between AL amyloidomas of the skin/subcutis and cMZL, suggesting that at least a subset of cutaneous AL amyloidoma may represent an unusual manifestation of cMZL (cutaneous mucosa-associated lymphoid tissue lymphomas).
Immunohistochemical Classification of Ampullary Carcinomas
Authors: Xue Yue , Reid Michelle D. , Balci Serdar , Quigley Brian , Muraki Takashi , Memis Bahar , Xia Jun , Hacihasanoglu Ezgi , Bedolla Gabriela , Pehlivanoglu Burcin , Kim Grace E. , Tajiri Takuma , Ohike Nobuyike , Aneja Ritu , Krasinskas Alyssa M. , Adsay Volkan
Published: May 2017

Recently, immunohistochemistry-based classifications of ampullary carcinomas have been proposed (Ang and colleagues [PMID: 24832159]; Chang and colleagues [PMID: 23439753]). In this study, the prognostic value of Ang/Chang panel markers (CK20, MUC1, MUC2, CDX2) as well as other markers (CK7, MUC5AC, and MUC6) were tested on full-faced sections of 136 ampullary carcinoma resections with substantial (>5 mm) invasion. Immunohistochemistry was correlated with both histologic classification (intestinal [INT], pancreatobiliary [PB], or nontubular based on ≥3/5 observer agreement) and clinical outcome. No prognostic correlation was found with MUC1, CDX2, MUC2 or CK20 despite testing with different quantitative cutoffs. CK7 and CK20 were nonspecific. Ang classification had reasonable correlation with histologic subclassification of tubular cases as INT versus PB with high specificity but low sensitivity and ambiguous category was large (29%) and included also some classical cases. Prognostically, Ang classification approached but did not reach statistical significance, even when their large “ambiguous” group was eliminated and only tubular cases were analyzed (Ang-INT vs. Ang-PB; P=0.08). The Chang panel, in which the definition of the INT subcategory is not clearly defined, only marginally reached prognostic significance when tested as MUC1+/CDX2− versus MUC1−/CDX2+ and only by Wilcoxon test (P=0.0485) but 31% of the cases were “unclassifiable.” The only individual marker that was found to have direct and strong correlation with the clinical outcome was MUC5AC (not used in the Ang or Chang panels), with statistically significant survival differences found with various cutoffs tested (for 20% cutoff, 5-y survival, 68% vs. 31%; P=0.0002). In addition, MUC5AC significantly stratified the histologically PB and INT cases (P=0.01 and 0.03, respectively), as well as Ang’s ambiguous and Chang’s unclassified cases (P=0.006 and 0.007, respectively). In conclusion, the widely used putative lineage markers, MUC1/MUC2/CK7/CK20/CDX2, do not seem to have direct/significant prognostic correlation either individually or in combination of Ang and Chang panels. Ang panel is helpful as an adjunct in determining the cell lineage with a few caveats. MUC5AC proves to be a significant independent prognosticator and should be incorporated into evaluation of ampullary carcinomas.
A Novel Grading System Based on Tumor Budding and Cell Nest Size Is a Strong Predictor of Patient Outcome in Esophageal Squamous Cell Carcinoma
Authors: Jesinghaus Moritz , Boxberg Melanie , Konukiewitz Björn , Slotta-Huspenina Julia , Schlitter Anna M. , Steiger Katja , Specht Katja , Wieczorek Kathrin , Warth Arne , Schmidt Thomas , Hartmann Arndt , Demir Ihsan E. , Feith Markus , Ott Katja , Weichert Wilko
Published: May 2017

The determination of prognosis in patients with esophageal squamous cell carcinoma (ESCC) is primarily based on staging according to the TNM-classification, whereas conventional grading is of minor clinical importance because of its deficiencies in prognostic patient stratification. Recently, a novel, highly prognostic grading scheme based on budding activity and cell nest size has been proposed for squamous cell carcinoma (SCC) of both pulmonary as well as oral origin. In order to investigate the utility and transferability of this approach to ESCC, we evaluated budding activity and cell nest size, as well as other histomorphologic characteristics, in a cohort of 135 primarily resected tumors and correlated the results with clinicopathologic and outcome parameters. High budding activity and small cell nest size showed a strong association with reduced overall, disease-specific, and disease-free survival (P<0.001, respectively) in ESCC. The combination of both markers in a 3-step grading system showed excellent prognostic separation of well-differentiated (G1), moderately differentiated (G2), and poorly differentiated (G3) carcinomas (P<0.001). The hazard ratio for disease-free survival in multivariate analysis under inclusion of stage was 2.97 for G2 and 5.42 for G3 ESCC (P<0.001). World Health Organization–based grading had no prognostic impact. Taken together, our data prove the value of tumor budding and cell nest size as excellent outcome predictors in ESCC and validate the utility of a previously established grading scheme proposed for oral and pulmonary SCC in this tumor entity. Ultimately, these combined efforts may result in a universal grading system for SCC regardless of the site of origin.
The Adequacy of Core Biopsy in the Assessment of Smooth Muscle Neoplasms of Soft Tissues
Authors: Schneider Nina , Strauss Dirk C. , Smith Myles J. , Miah Aisha B. , Zaidi Shane , Benson Charlotte , van Houdt Winan J. , Jones Robin L. , Hayes Andrew J. , Fisher Cyril , Thway Khin
Published: May 2017

The grading of soft tissue sarcomas is one of the most important prognostic factors and determines patient management. Although grading of most adult-type soft tissue sarcomas on biopsies correlates highly with the final grading on the excision specimen, it appears less reliable for tumors of smooth muscle. We assessed the pathologic findings for smooth muscle neoplasms diagnosed by core biopsy at our tertiary sarcoma center, and compared them with those in the subsequent excision specimens. A total of 100 patients with leiomyosarcoma first diagnosed on core biopsy and with a subsequent excision were identified and the accuracy of the biopsy grade determined by comparison with the excision grade. Differences in other salient histologic parameters were also noted. A grade difference between biopsy and excision specimens of leiomyosarcomas was found in 68% of cases, with all these cases showing an increase in grade from biopsy to excision specimen. Of the 3 parameters used for grading using the French Federation of Cancer Centers Sarcoma Group Grading System (FNCLCC), necrosis was the score that most commonly differed between biopsy and excision specimen (55%), closely followed by the mitotic count (51%). The grading of soft tissue smooth muscle tumor biopsies has a lower accuracy compared with other adult soft tissue sarcomas and should therefore be taken with caution, particularly as this may be an underrepresentation of the true tumor grade.
Gastric Cancer With Primitive Enterocyte Phenotype
Authors: Yamazawa Sho , Ushiku Tetsuo , Shinozaki-Ushiku Aya , Hayashi Akimasa , Iwasaki Akiko , Abe Hiroyuki , Tagashira Amane , Yamashita Hiroharu , Seto Yasuyuki , Aburatani Hiroyuki , Fukayama Masashi
Published: May 2017

A primitive cell-like gene expression signature is associated with aggressive phenotypes of various cancers. We assessed the expression of phenotypic markers characterizing primitive cells and its correlation with clinicopathologic and molecular characteristics in gastric cancer. Immunohistochemical analysis of a panel of primitive phenotypic markers, including embryonic stem cell markers (OCT4, NANOG, SALL4, CLDN6, and LIN28) and known oncofetal proteins (AFP and GPC3), was performed using tissue microarray on 386 gastric cancers. On the basis of the expression profiles, the 386 tumors were clustered into 3 groups: group 1 (primitive phenotype, n=93): AFP, CLDN6, GPC3, or diffuse SALL4 positive; group 2 (SALL4-focal, n=56): only focal SALL4 positive; and group 3 (negative, n=237): all markers negative. Groups 1 and 2 predominantly consisted of intestinal-type adenocarcinoma, including 13 fetal gut-like adenocarcinomas exclusively in group 1. Group 1 was significantly associated with higher T-stage, presence of vascular invasion and nodal metastasis when compared with groups 2 and 3. Group 1 was associated with patients’ poor prognosis and was an independent risk factor for disease-free survival. Group 1 showed frequent TP53 overexpression and little association with Epstein-Barr virus or mismatch repair deficiency. Further analysis of the Cancer Genome Atlas data set validated our observations and revealed that tumors with primitive phenotypes were mostly classified as “chromosomal instability” in the Cancer Genome Atlas’ molecular classification. We identified gastric cancer with primitive enterocyte phenotypes as an aggressive subgroup of intestinal-type/chromosomal instability gastric cancer. Therapeutic strategies targeting primitive markers, such as GPC3, CLDN6, and SALL4, are highly promising.
Effects of Preoperative Psychological Interventions on Catecholamine and Cortisol Levels After Surgery in Coronary Artery Bypass Graft Patients: The Randomized Controlled PSY-HEART Trial
Authors: Salzmann Stefan , Euteneuer Frank , Laferton Johannes A.C. , Auer Charlotte J. , Shedden-Mora Meike C. , Schedlowski Manfred , Moosdorf Rainer , Rief Winfried
Published: May 2017

Objective

The aim of the study was to examine whether preoperative psychological interventions targeting patients' expectations are capable of influencing the biological stress response after coronary artery bypass graft (CABG) surgery and could thus improve recovery after heart surgery.

Methods

Randomized controlled trial with assessments 10 days before surgery, after psychological intervention (day of hospital admission, but before surgery), postoperative (6–8 days later), and at follow-up (6 months after surgery). Eligible patients (N = 124) scheduled for elective on-pump CABG or CABG with valve replacement surgery were approached before hospital admission. Standard medical care (SMC) was compared with two additional preoperative psychological interventions: (a) an expectation manipulation intervention to optimize patients' expectations about course and outcomes or (b) supportive therapy, containing the same amount of therapeutic attention, but without specifically focusing on expectations. Postoperative plasma adrenaline, noradrenaline, and cortisol levels were a secondary outcome of our study (primary outcome patients' disability 6 months after surgery and other secondary patient-reported or clinical outcomes were reported elsewhere).

Results

Expectation manipulation intervention (3.68 ln pg/mL, 95% confidence interval = 3.38–3.98, p = .015) and supportive therapy (3.70 ln pg/mL, 95% confidence interval = 3.38–4.01, p = .026) led to significantly lower postoperative adrenaline levels compared with SMC (4.26 ln pg/mL, 95% confidence interval = 3.99–4.53) only. There were no treatment effects of the preoperative intervention for noradrenaline (p = .90) or cortisol (p = .30). Higher postoperative adrenaline levels predicted disability 6 months after surgery (r = .258, p = .018).

Conclusions

In addition to SMC, preoperative psychological interventions seem to buffer psychobiological stress responses and could thus facilitate recovery from CABG surgery. Patients' postoperative stress responses could be an important factor for explaining trajectories of long-term outcomes.

Clinical Trial Registration

www.clinicaltrials.gov (NCT01407055).
Influence of Uncertain Anticipation on Brain Responses to Aversive Rectal Distension in Patients With Irritable Bowel Syndrome
Authors: Kano Michiko , Muratsubaki Tomohiko , Morishita Joe , Kono Keiji , Mugikura Shunji , Takase Kei , Ly Huynh Giao , Dupont Patrick , Van Oudenhove Lukas , Fukudo Shin
Published: May 2017

Objective

We investigated whether certainty and uncertainty of impending aversive visceral sensation differently modulate regional brain activity, both during anticipation and visceral sensation in irritable bowel syndrome (IBS) patients compared with healthy controls.

Methods

Twenty-six IBS patients (14 women) and 29 healthy controls (15 women) were enrolled in a functional magnetic resonance imaging study. Participants received rectal distention at an individually titrated severe discomfort level that was preceded by visual cues to induce certain (100% chance of distention), uncertain (50% chance), and safe (0% chance) anticipation.

Results

Subjective ratings of anticipatory fear before and discomfort during distention were similar between IBS and control participants under cued certainty and uncertainty (p > .05). Uncertain anticipation compared with certain anticipation induced greater activation of anterior midcingulate cortex, thalamus, and visual processing areas in IBS patients compared with controls. Rectal distention after the uncertain, but not certain, cue induced higher activity in the posterior- and midcingulate cortices and the precuneus in IBS compared with controls. Controls exhibited bilateral insula activation during the nondistention period after the uncertain cue compared with the safe cue. IBS patients failed to produce this response, which was possibly due to elevated bilateral insular responses during nondistention after the safe cue. Brain data were significant at a voxel-level threshold of p
uncorrected value of less than .005 combined with a cluster-level threshold of p
FWE-corrected value of less than .05.

Conclusions

Preceding uncertainty differentially modulates the brain processing of physiologically identical rectal stimulation in IBS patients. Cue-dependent alterations in brain responses may underlie hypervigilance to visceral sensations in IBS patients.
Impact of Point-of-Care CD4 Testing on Retention in Care Among HIV-Positive Pregnant and Breastfeeding Women in the Context of Option B+ in Zimbabwe: A Cluster Randomized Controlled Trial
Authors: Joseph Jessica , Gotora Tendai , Erlwanger Alison S. , Mushavi Angela , Zizhou Simukai , Masuka Nyasha , Boeke Caroline E. , Mangwiro Alexio-Zambezi
Published: May 2017

Introduction:

Scale-up of Option B+ in Zimbabwe has increased antiretroviral therapy (ART) coverage but patient loss-to-follow-up remains high; thus, effective strategies to improve retention in care are needed. Evidence for Elimination, a cluster randomized controlled trial, evaluated the impact of point-of-care (POC) CD4 testing with CD4 count-specific adherence counseling on rates of retention among 1150 HIV-positive pregnant women initiating ART in Zimbabwe.

Methods:

Thirty-two primary care health facilities were randomized to offer either standard-of-care (SOC) or POC CD4 testing plus CD4-specific counseling to clients (POC Plus). The primary outcome was the proportion of HIV-positive pregnant women retained on ART after 12 months, calculated by cluster-adjusted proportions, unadjusted and adjusted relative risks (RR and aRR, respectively).

Results:

Retention in care 12 months after initiation was 50.7% and 54.5% in the POC Plus and SOC arms, respectively (RR 0.93, 95% confidence interval [CI]: 0.78 to 1.11; aRR 0.91, 95% CI: 0.77 to 1.07). Although considered not retained, 9.7% transferred to another facility and 0.2% died. Most women, 95.3% in POC Plus and 92.9% in SOC, initiated ART within 1 month of antenatal booking (RR 1.03, 95% CI: 0.97 to 1.08).

Discussion:

Although patient retention was similar in both arms, women in the POC Plus arm were more likely to have received a CD4 test at booking and a repeat CD4 test later in care. CD4 is no longer required for treatment initiation but is still recommended in national guidelines and is of value in clinical management. Further work is needed to identify effective strategies to increase patient retention in ART care.
Long-term Outcomes of Carotid Endarterectomy Versus Stenting in a Multicenter Population-based Canadian Study
Authors: Hussain Mohamad A. , Mamdani Muhammad , Tu Jack V. , Saposnik Gustavo , Aljabri Badr , Bhatt Deepak L. , Verma Subodh , Al-Omran Mohammed
Published: May 2017

Objective:

To compare the long-term outcomes of patients treated with carotid endarterectomy and carotid-artery stenting.

Background:

Evidence for the long-term safety and efficacy of carotid-artery stenting compared with endarterectomy is accumulating from randomized trials. However, comparative data on the long-term outcomes of carotid revascularization strategies in real world practice are lacking.

Methods:

We conducted a population-based, multicenter, observational cohort study using validated linked databases from Ontario, Canada. We identified all individuals treated with carotid endarterectomy and stenting (2002–2014), and followed them up to 2015. We compared long-term (up to 13 years) and 30-day outcomes of each strategy using multilevel multivariable Cox proportional-hazards models, and conducted confirmatory analyses using propensity-score matching methods.

Results:

In all, 15,525 patients received carotid-artery revascularization. Rate of the primary composite outcome of 30-day death, stroke, or myocardial infarction plus any stroke during 13-year follow-up was higher with stenting (16.3%) compared with endarterectomy (9.7%) [adjusted hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.43–1.73, P < 0.001). The increased risk with stenting was observed regardless of age, sex, intervention year, carotid-artery symptoms, or diabetes. The primary outcome was driven by higher rates of 30-day stroke (adjusted HR 1.59, 95% CI 1.29–1.95), 30-day death (adjusted HR 2.62, 95% CI 2.20–3.13), and long-term stroke >30 days after the procedure (adjusted HR 1.47, 95% CI 1.36–1.59) with stenting; 30-day myocardial infarction was lower with stenting (adjusted HR 0.70, 95% CI 0.57–0.86). These results were confirmed with 1:2 propensity-score matching (HR for primary composite outcome with stenting 1.55, 95% CI 1.31–1.83, P < 0.001).

Conclusions:

Compared with carotid endarterectomy, stenting was associated with an early and sustained approximately 55% increased hazard for major adverse events over long-term follow-up. Although nonrandomized, these results raise potential concerns about the interchangeability of carotid endarterectomy and stenting in the context of actual clinical practice.
Kidney Transplant Recipients' Perspectives on Cardiovascular Disease and Related Risk Factors After Transplantation: A Qualitative Study
Authors: Ballesteros Fabián , Allard Julie , Durand Céline , Cardinal Héloïse , Lalonde Lyne , Fortin Marie-Chantal
Published: May 2017

Background

Cardiovascular disease (CVD) is a major cause of mortality among kidney transplant recipients (KTRs). These patients have a high prevalence of risk factors, such as hypertension, diabetes, and dyslipidemia. Despite regular medical care, few of them reach the recommended therapeutic targets. The objective of this study is to describe KTRs' perspectives on CVD and related risk factors, as well as their priorities for posttransplant care.

Methods

Twenty-six KTRs participated in a semistructured interview about their personal experience and offered their perspectives on CVD risk factors posttransplant. The interview was digitally recorded and the transcripts were analyzed using a thematic and content methodology.

Results

CVD and related risk factors appear to be underestimated and trivialized. Only 2 of 26 patients identified CVD prevention and treatment as a priority. The most important posttransplant priorities identified by patients were related to immunosuppressive drugs (13 of 26), posttransplant follow-up (10) and graft survival (9). However, 21 of 26 patients stated they wanted to be better informed about posttransplant CVD risk factors.

Conclusions

CVD and related risk factors are not a priority for KTRs, and the importance of CVD is underestimated and trivialized. KTRs did recommend that tailored information be provided by various professionals and at several points in the transplantation process. This knowledge will help us develop a new approach to increase awareness of posttransplant CVD and related risk factors.
New neurosurgical approaches for tremor and Parkinson's disease
Authors: Fasano Alfonso , Lozano Andres M. , Cubo Esther
Published: May 2017

Purpose of review

The objective of this review is to gather the newest advances in the surgical treatment of tremor and Parkinson's disease. We will briefly discuss the potential applications of the new technologies of deep brain stimulation (DBS), and we will focus on MRI-guided focused ultrasound (MRgFUS).

Recent findings

Novel DBS devices are being progressively adopted, particularly electrodes allowing a longer stimulating surface (suitable for multiple targets stimulation) and current radial steering (to minimize side effects of stimulation). New implantable pulse generators are also able to record neurons and are generating enough knowledge to advance the implementation of adaptive (closed-loop) DBS.

Over the last years, ‘minimally-invasive’ neurosurgical approaches for the treatment of movement disorders have been developed: gamma knife radiosurgery and MRgFUS. Uncontrolled and recent controlled studies have shown the benefits of MRgFUS targeting the thalamus and pallidus for the treatment of tremor and Parkinson's disease.

The initial clinical data are certainly promising and have expanded the current portfolio of neurosurgical treatments of movement disorders. Many issues are yet to be addressed, particularly safety of MRgFUS-and how these new treatments compare with the existing ones.
Sir Paul Terence Callaghan FRS PCNZM. 19 August 1947 — 24 March 2012
Authors: Kelly Michael J.
Published: May 2017

Paul Callaghan will be remembered internationally for many seminal contributions to the foundations of magnetic resonance imaging as applied to the rheological analysis of a series of real world materials – paints, gels, polymer solutions – and at home in New Zealand as the leading physical scientist of his day, who became a familiar science communicator through popular books, a radio programme and the promotion of high technology as a part of the New Zealand economy. Apart from his time as a research student in Oxford (1970–75) and short stays abroad, Paul undertook all his research in New Zealand, and was a passionate and effective advocate for New Zealand science. His direct and continuing legacy for condensed matter science in New Zealand was his leadership in the foundation in 2002 of the multi-university MacDiarmid Institute devoted to research in advanced materials and nanotechnology, which he led through its first five years and into its second phase. In later life he was the founder of Magritek, a company manufacturing the specialist magnets needed for resonance imaging and spectroscopy.
Detection and perception of generic host volatiles by mosquitoes: responses to CO2constrains host-seeking behaviour
Authors: Majeed Shahid , Hill Sharon Rose , Dekker Teun , Ignell Rickard
Published: May 2017

Natural selection has favoured specialization in anthropophilic mosquito host choice, yet in the absence of human hosts, females feed on a selected range of vertebrates. For host recognition, we hypothesize that mosquitoes primarily rely on generic host volatiles. Detection and perception of such compounds would provide the mosquito with a flexible, yet constrained, odour coding system that could delineate host preference. In this study, we show that the quintessential generic volatile for host-seeking, carbon dioxide, activates and attracts the malaria mosquito,Anopheles coluzzii, and the arbovirus vectors,Aedes aegyptiandCulex quinquefasciatus, within boundaries set by the dynamic range and coding capacity of the CO2-sensitive olfactory receptor neurons. These boundaries are sufficiently broad to elicit behavioural responses to various hosts within their preferred host range. This study highlights the significance of the sensitivity of the carbon dioxide detection system and its regulation of host seeking and recognition.
Characterization of amylase and protease activities in the digestive system ofConcholepas concholepas(Gastropoda, muricidae)
Authors: Gutierrez Alejandro P. , Cerda-Llanos Viviana , Forttes Diego , Carvajal Nelson , Uribe Elena A.
Published: May 2017

Concholepas concholepas(loco) is a carnivorous gastropod that inhabits the coast of Chile and Peru. Its fisheries showed a great importance in the past decades, however, now mainly relies on artisanal management of wild stocks. Feeding is one of the important factors that have restrained the establishment of large scale field rearing of loco.C. concholepasfood preferences consist of mytilids and cirripeds, however its digestive physiology has not been studied and its digestive enzymes have not been yet characterized. The purification of amylase and protease from the digestive gland and the gland of Leiblein ofC. concholepaswere performed by ionic exchange chromatography (DEAE-cellulose), and substrate-PAGE indicated the presence of the amylase and protease in the fractions collected from the column. Amylase enzymatic assays showed its maximum activity at pH 7.0 and 50°C in the digestive gland. Protease on the other hand showed a great acidic activity, specifically at pH 3.0 in both organs, also at 50°C. Inhibition of the amylolytic activity was observed in the presence of EDTA, and metal ions like MnCl2, MgCl2, ZnSO4, while it was enhanced in the presence of CaCl2, NaCl, KCl. Protease inhibition assays were also performed evidencing mainly the presence of aspartic proteases and a low but not inexistent presence of serine proteases. Our results provide evidence of important proteolytic but also amylolytic activities present in the digestive system of loco, providing evidence that this mollusc has wider digestive capabilities than initially though, which could potentially lead to the development of alternative food diets.
Epigenetic Transitions and Knotted Solitons in Stretched Chromatin
Authors: Michieletto D. , Orlandini E. , Marenduzzo D.
Published: May 2017

The spreading and regulation of epigenetic marks on chromosomes is crucial to establish and maintain cellular identity. Nonetheless, the dynamical mechanism leading to the establishment and maintenance of a given, cell-line specific, epigenetic pattern is still poorly understood. In this work we propose, and investigatein silico, a possible experimental strategy to illuminate the interplay between 3D chromatin structure and epigenetic dynamics. We consider a set-up where a reconstituted chromatin fibre is stretched at its two ends (e.g., by laser tweezers), while epigenetic enzymes (writers) and chromatin-binding proteins (readers) are flooded into the system. We show that, by tuning the stretching force and the binding affinity of the readers for chromatin, the fibre undergoes a sharp transition between a stretched, epigenetically disordered, state and a crumpled, epigenetically coherent, one. We further investigate the case in which a knot is tied along the chromatin fibre, and find that the knotted segment enhances local epigenetic order, giving rise to “epigenetic solitons” which travel and diffuse along chromatin. Our results point to an intriguing coupling between 3D chromatin topology and epigenetic dynamics, which may be investigated via single molecule experiments.
Neuronal upregulation of Prospero protein is driven by alternative mRNA polyadenylation and Syncrip-mediated mRNA stabilisation
Authors: Samuels Tamsin J. , Arava Yoav , Järvelin Aino I. , Robertson Francesca , Lee Jeffrey Y. , Yang Lu , Yang Ching-Po , Lee Tzumin , Ish-Horowicz David , Davis Ilan
Published: May 2017

DuringDrosophilaand vertebrate brain development, the conserved transcription factor Prospero/Prox1 is an important regulator of the transition between proliferation and differentiation. Prospero level is low in neural stem cells and their immediate progeny, but is upregulated in larval neurons and it is unknown how this process is controlled. Here, we use single molecule fluorescentin situhybridisation to show that larval neurons selectively transcribe a longprosperomRNA isoform containing a 15 kb 3’ untranslated region, which is bound in the brain by the conserved RNA-binding protein Syncrip/hnRNPQ. Syncrip binding increases the mRNA stability of the longprosperoisoform, which allows an upregulation of Prospero protein production. Our findings highlight a regulatory strategy involving alternative polyadenylation followed by differential post-transcriptional regulation.
Millisecond dynamics of BTK reveal kinome-wide conformational plasticity within the apo kinase domain
Authors: Sultan Mohammad M. , Denny Rajiah Aldrin , Unwalla Ray , Lovering Frank , Pande Vijay S.
Published: May 2017

Bruton tyrosine kinase (BTK) is a key enzyme in B-cell development whose improper regulation causes severe immunodeficiency diseases. Design of selective BTK therapeutics would benefit from improved,in-silicostructural modeling of the kinase’s solution ensemble. However, this remains challenging due to the immense computational cost of sampling events on biological timescales. In this work, we combine multi-millisecond molecular dynamics (MD) simulations with Markov state models (MSMs) to report on the thermodynamics, kinetics, and accessible states of BTK’s kinase domain. Our conformational landscape links the active state to several inactive states, connected via a structurally diverse intermediate. Our calculations predict a kinome-wide conformational plasticity, and indicate the presence of several new potentially druggable BTK states. We further find that the population of these states and the kinetics of their inter-conversion are modulated by protonation of an aspartate residue, establishing the power of MD & MSMs in predicting effects of chemical perturbations.