bluuebunny/crossref_metadata_2025 huggingface dataset:
Anterior Hippocampal–Cortical Functional Connectivity Distinguishes Antipsychotic Naïve First-Episode Psychosis Patients From Controls and May Predict Response to Second-Generation Antipsychotic Treatment
Authors: Blessing Esther M , Murty Vishnu P , Zeng Botao , Wang Jijun , Davachi Lila , Goff Donald C
Published: July 2019

Background

Converging evidence implicates the anterior hippocampus in the proximal pathophysiology of schizophrenia. Although resting state functional connectivity (FC) holds promise for characterizing anterior hippocampal circuit abnormalities and their relationship to treatment response, this technique has not yet been used in first-episode psychosis (FEP) patients in a manner that distinguishes the anterior from posterior hippocampus.

Methods

We used masked-hippocampal-group-independent component analysis with dual regression to contrast subregional hippocampal–whole brain FC between healthy controls (HCs) and antipsychotic naïve FEP patients (N = 61, 36 female). In a subsample of FEP patients (N = 27, 15 female), we repeated this analysis following 8 weeks of second-generation antipsychotic treatment and explored whether baseline FC predicted treatment response using random forest.

Results

Relative to HC, untreated FEP subjects displayed reproducibly lower FC between the left anteromedial hippocampus and cortical regions including the anterior cingulate and insular cortex (P < .05, corrected). Anteromedial hippocampal FC increased in FEP patients following treatment (P < .005), and no longer differed from HC. Random forest analysis showed baseline anteromedial hippocampal FC with four brain regions, namely the insular–opercular cortex, superior frontal gyrus, precentral gyrus, and postcentral gyrus predicted treatment response (area under the curve = 0.95).

Conclusions

Antipsychotic naïve FEP is associated with lower FC between the anterior hippocampus and cortical regions previously implicated in schizophrenia. Preliminary analysis suggests that random forest models based on hippocampal FC may predict treatment response in FEP patients, and hence could be a useful biomarker for treatment development.
Teaching mathematical modelling: a framework to support teachers’ choice of resources
Authors: Dunn Peter K , Marshman Margaret F
Published: July 2019

Mathematics teachers are often keen to find ways of connecting mathematics with the real world. One way to do so is to teach mathematical modelling using real data. Mathematical models have two components: a model structure and parameters within that structure. Real data can be used in one of two ways for each component: (a) to validate what theory or context suggests or (b) to estimate from the data. It is crucial to understand the following: the implications of using data in these different ways, the differences between them, the implications for teaching and how this can influence students’ perceptions of the real-world relevance of mathematics. Inappropriately validating or estimating with data may unintentionally promote poor practice and (paradoxically) reinforce in students the incorrect idea that mathematics has no relevance to the real world. We recommend that teachers approach mathematical modelling through mathematizing the context. We suggest a framework to support teachers’ choice of modelling activities and demonstrate these using examples.
Morphological evolution of the skull roof in temnospondyl amphibians mirrors conservative ontogenetic patterns
Authors: Pérez-Ben Celeste M , Báez Ana M , Schoch Rainer R
Published: July 2019

Addressing the patterns of ontogenetic allometry is relevant to understand morphological diversification because allometry might constrain evolution to specific directions of change in shape but also facilitate phenotypic differentiation along lines of least evolutionary resistance. Temnospondyl amphibians are a suitable group to address these issues from a deep-time perspective because different growth stages are known for numerous Palaeozoic and Mesozoic species. Herein we examine the patterns of ontogenetic allometry in the skull roof of 15 temponspondyl species and their relationship with adult morphological evolution. Using geometric morphometrics, we assessed ontogenetic and evolutionary allometries of this cranial part and the distribution of adult shapes in the morphospace to investigate whether these patterns relate to each other and/or to lifestyle and phylogeny. We found conspicuous stereotyped ontogenetic changes of the skull roof which are mirrored at the evolutionary level and consistency of the adult shape with phylogeny rather than lifestyle. These results suggest that the evolution of adult cranial shape was significantly biased by development towards pathways patterned by ontogenetic change in shape. The retrieved conserved patterns agree with a widespread evolutionary craniofacial trend found in amniotes, suggesting that they might have originated early in tetrapod evolutionary history or even earlier.
Management of Difficult Tracheal Intubation
Authors: Joffe Aaron M. , Aziz Michael F. , Posner Karen L. , Duggan Laura V. , Mincer Shawn L. , Domino Karen B.
Published: July 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Difficult or failed intubation is a major contributor to morbidity for patients and liability for anesthesiologists. Updated difficult airway management guidelines and incorporation of new airway devices into practice may have affected patient outcomes. The authors therefore compared recent malpractice claims related to difficult tracheal intubation to older claims using the Anesthesia Closed Claims Project database.

Methods

Claims with difficult tracheal intubation as the primary damaging event occurring in the years 2000 to 2012 (n = 102) were compared to difficult tracheal intubation claims from 1993 to 1999 (n = 93). Difficult intubation claims from 2000 to 2012 were evaluated for preoperative predictors and appropriateness of airway management.

Results

Patients in 2000 to 2012 difficult intubation claims were sicker (78% American Society of Anesthesiologists [ASA] Physical Status III to V; n = 78 of 102) and had more emergency procedures (37%; n = 37 of 102) compared to patients in 1993 to 1999 claims (47% ASA Physical Status III to V; n = 36 of 93; P < 0.001 and 22% emergency; n = 19 of 93; P = 0.025). More difficult tracheal intubation events occurred in nonperioperative locations in 2000 to 2012 than 1993 to 1999 (23%; n = 23 of 102 vs. 10%; n = 10 of 93; P = 0.035). Outcomes differed between time periods (P < 0.001), with a higher proportion of death in 2000 to 2012 claims (73%; n = 74 of 102 vs. 42%; n = 39 of 93 in 1993 to 1999 claims; P < 0.001 adjusted for multiple testing). In 2000 to 2012 claims, preoperative predictors of difficult tracheal intubation were present in 76% (78 of 102). In the 97 claims with sufficient information for assessment, inappropriate airway management occurred in 73% (71 of 97; κ = 0.44 to 0.66). A “can’t intubate, can’t oxygenate” emergency occurred in 80 claims with delayed surgical airway in more than one third (39%; n = 31 of 80).

Conclusions

Outcomes remained poor in recent malpractice claims related to difficult tracheal intubation. Inadequate airway planning and judgment errors were contributors to patient harm. Our results emphasize the need to improve both practitioner skills and systems response when difficult or failed tracheal intubation is encountered.
Prediction Model for Audiological Outcomes in Patients With GJB2 Mutations
Authors: Chen Pey-Yu , Lin Yin-Hung , Liu Tien-Chen , Lin Yi-Hsin , Tseng Li-Hui , Yang Ting-Hua , Chen Pei-Lung , Wu Chen-Chi , Hsu Chuan-Jen
Published: July 2019

Objectives:

Recessive mutations in GJB2 are the most common genetic cause of sensorineural hearing impairment (SNHI) in humans. SNHI related to GJB2 mutations demonstrates a wide variation in audiological features, and there has been no reliable prediction model for hearing outcomes until now. The objectives of this study were to clarify the predominant factors determining hearing outcome and to establish a predictive model for SNHI in patients with GJB2 mutations.

Design:

A total of 434 patients confirmed to have biallelic GJB2 mutations were enrolled and divided into three groups according to their GJB2 genotypes. Audiological data, including hearing levels and audiogram configurations, were compared between patients with different genotypes. Univariate and multivariate generalized estimating equation (GEE) analyses were performed to analyze longitudinal data of patients with multiple audiological records.

Results:

Of the 434 patients, 346 (79.7%) were homozygous for the GJB2 p.V37I mutation, 55 (12.7%) were compound heterozygous for p.V37I and another GJB2 mutation, and 33 (7.6%) had biallelic GJB2 mutations other than p.V37I. There was a significant difference in hearing level and the distribution of audiogram configurations between the three groups. Multivariate GEE analyses on 707 audiological records of 227 patients revealed that the baseline hearing level and the duration of follow-up were the predominant predictors of hearing outcome, and that hearing levels in patients with GJB2 mutations could be estimated based on these two parameters: (Predicted Hearing Level [dBHL]) = 3.78 + 0.96 × (Baseline Hearing Level [dBHL]) + 0.55 × (Duration of Follow-Up [y]).

Conclusion:

The baseline hearing level and the duration of follow-up are the main prognostic factors for outcome of GJB2-related SNHI. These findings may have important clinical implications in guiding follow-up protocols and designing treatment plans in patients with GJB2 mutations.
Electro-Tactile Stimulation Enhances Cochlear-Implant Melody Recognition: Effects of Rhythm and Musical Training
Authors: Huang Juan , Lu Thomas , Sheffield Benjamin , Zeng Fan-Gang
Published: July 2019

Objectives:

Electro-acoustic stimulation (EAS) enhances speech and music perception in cochlear-implant (CI) users who have residual low-frequency acoustic hearing. For CI users who do not have low-frequency acoustic hearing, tactile stimulation may be used in a similar fashion as residual low-frequency acoustic hearing to enhance CI performance. Previous studies showed that electro-tactile stimulation (ETS) enhanced speech recognition in noise and tonal language perception for CI listeners. Here, we examined the effect of ETS on melody recognition in both musician and nonmusician CI users.

Design:

Nine musician and eight nonmusician CI users were tested in a melody recognition task with or without rhythmic cues in three testing conditions: CI only (E), tactile only (T), and combined CI and tactile stimulation (ETS).

Results:

Overall, the combined electrical and tactile stimulation enhanced the melody recognition performance in CI users by 9% points. Two additional findings were observed. First, musician CI users outperformed nonmusicians CI users in melody recognition, but the size of the enhancement effect was similar between the two groups. Second, the ETS enhancement was significantly higher with nonrhythmic melodies than rhythmic melodies in both groups.

Conclusions:

These findings suggest that, independent of musical experience, the size of the ETS enhancement depends on integration efficiency between tactile and auditory stimulation, and that the mechanism of the ETS enhancement is improved electric pitch perception. The present study supports the hypothesis that tactile stimulation can be used to improve pitch perception in CI users.
The Effect of Musical Training and Working Memory in Adverse Listening Situations
Authors: Escobar Jillian , Mussoi Bruna S. , Silberer Amanda B.
Published: July 2019

Objectives:

Speech-in-noise (SIN) perception is essential for everyday communication. In most communication situations, the listener requires the ability to process simultaneous complex auditory signals to understand the target speech or target sound. As the listening situation becomes more difficult, the ability to distinguish between speech and noise becomes dependent on recruiting additional cognitive resources, such as working memory (WM). Previous studies have explored correlations between WM and SIN perception in musicians and nonmusicians, with mixed findings. However, no study to date has examined the speech perception abilities of musicians and nonmusicians with similar WM capacity. The objectives of this study were to investigate (1) whether musical experience results in improved listening in adverse listening situations, and (2) whether the benefit of musical experience can be separated from the effect of greater WM capacity.

Design:

Forty-nine young musicians and nonmusicians were assigned to subgroups of high versus low WM, based on the performance on the backward digit span test. To investigate the effects of music training and WM on SIN perception, performance was assessed on clinical tests of speech perception in background noise. Listening effort (LE) was assessed in a dual-task paradigm and via self-report. We hypothesized that musicians would have an advantage when listening to SIN, at least in terms of reduced LE.

Results:

There was no statistically significant difference between musicians and nonmusicians, and no significant interaction between music training and WM on any of the outcome measures used in this study. However, a significant effect of WM on SIN ability was found on both the Quick Speech-In-Noise test (QuickSIN) and the Hearing in Noise Test (HINT) tests.

Conclusion:

The results of this experiment suggest that music training does not provide an advantage in adverse listening situations either in terms of improved speech understanding or reduced LE. While musicians have been shown to have heightened basic auditory abilities, the effect on SIN performance may be more subtle. Our results also show that regardless of prior music training, listeners with high WM capacity are able to perform significantly better on speech-in-noise tasks.
Long-term Impacts of Brace Treatment for Adolescent Idiopathic Scoliosis on Body Composition, Paraspinal Muscle Morphology, and Bone Mineral Density
Authors: Ohashi Masayuki , Watanabe Kei , Hirano Toru , Hasegawa Kazuhiro , Katsumi Keiichi , Shoji Hirokazu , Mizouchi Tatsuki , Endo Naoto
Published: July 2019

Study Design.

A retrospective, long-term follow-up study.

Objective.

We aimed to investigate the long-term impacts of brace treatment for adolescent idiopathic scoliosis (AIS) on the musculoskeletal system.

Summary of Background Data.

Although full-time brace treatment is the mainstay of conservative treatment for AIS, the restrictive nature of brace treatment for lumbosacral motion might negatively affect the musculoskeletal system.

Methods.

Of 319 patients treated nonoperatively for AIS, 80 patients completed clinical and imaging examinations. Body composition, including body fat mass, lean mass, fat percent, and muscle mass, was estimated via bioelectrical impedance analysis. Bone mineral density (BMD) was measured at the lumbar spine and left hip. In 73 patients, the measurement of cross-sectional area and fatty degeneration of paraspinal muscles at the superior endplate of L4 were performed using axial T2-weighted magnetic resonance imaging. Patients were divided into the full-time brace (FB; >13 hours per day) and nonfull-time brace (NFB; observation, part-time bracing, or drop out from FB within a year) groups.

Results.

There were 44 patients in the FB group and 36 in the NFB group. Patients in the FB group were significantly younger at the initial visit (12.7 ± 1.3 years) and older at the final follow-up (41.5 ± 5.6 years) than those in the NFB group (14.2 ± 3.2 and 37.4 ± 7.1 years, respectively; P < 0.01). The rate of patients engaging in mild or moderate sports activity in adulthood tended to be higher in the FB group (47.7%) than in the NFB group (25%) (P = 0.11). However, there were no significant differences in body composition, paraspinal muscle morphology, and BMD between the two groups both before and after adjusting for age.

Conclusion.

Full-time brace wearing during adolescence did not have any negative impacts on the musculoskeletal system in adulthood. This information will be helpful for improving the compliance of full-time bracing.

Level of Evidence: 4
Respiratory Complications After Posterior Spinal Fusion for Neuromuscular Scoliosis
Authors: Cohen Jacob L. , Klyce Walter , Kudchadkar Sapna R. , Kotian Ronak N. , Sponseller Paul D.
Published: July 2019

Study Design.

Retrospective cohort.

Objective.

To determine how respiratory failure rates and duration of intensive care unit (ICU) stay after posterior spinal fusion (PSF) for neuromuscular scoliosis compare between children with Rett syndrome (RS) versus cerebral palsy (CP).

Summary of Background Data.

Rett syndrome and CP are associated with high incidence of neuromuscular scoliosis and respiratory dysfunction.

Methods.

We included 21 patients with RS (mean age, 13 ± 3.1 yrs) and 124 with CP (mean age, 14 ± 3.2 yrs) who underwent PSF by one surgeon from 2004 to 2017. Preoperative motor function was assessed using the Gross Motor Function Classification System (GMFCS). Primary outcomes were respiratory failure and duration of ICU stay. Secondary outcomes were pneumonia and prolonged use of positive pressure ventilation (PPV). Using multivariate regression, we identified associations of age, intraoperative vital signs, duration of hospital stay, number of vertebral levels fused, anesthesia and surgery durations, and estimated blood loss with longer ICU stay and respiratory failure.

Results.

A greater proportion of CP patients (96%) than RS patients (66%) were in GMFCS IV or V (P < 0.01). Respiratory failure was more common in RS patients (43% vs. 19%; P = 0.02), as was PPV (67% vs. 31%; P < 0.01). RS patients had shorter median durations of anesthesia and surgery (P < 0.01). RS patients had a longer median (interquartile range) ICU stay (4 days [1–5] vs. 2 days [2–19]; P = 0.01). Incidence of pneumonia did not differ between groups (P = 0.69). Only RS diagnosis (P = 0.02) and prolonged PPV (P < 0.01) were associated with longer ICU stay.

Conclusion.

Despite better preoperative motor function and shorter anesthesia and surgery durations, patients with RS experienced more respiratory failure, prolonged PPV use, and longer ICU stays after PSF than did children with CP.

Level of Evidence: 4
Clinical and Radiographic Outcome of Patients With Cervical Spondylotic Myelopathy Undergoing Total Disc Replacement
Authors: Pehlivanoglu Tuna , Wuertz-Kozak Karin , Heider Franziska , Sauer Daniel , Wanke-Jellinek Lorenz , Mayer Michael , Mehren Christoph
Published: July 2019

Study Design.

A nonrandomized, prospective, and single-center clinical trial.

Objective.

The aim of this study was to investigate the clinical and radiographic efficacy of ProDisc Vivo cervical total disc replacement (cTDR) in patients with clinical and radiographic documented cervical spondylotic myelopathy (CSM), due to degenerative changes at the index level.

Summary of Background Data.

Decompression and fusion is still the gold standard in patients with cervical myelopathy. Very limited data are available regarding the application of cTDR in patients with clinical and radiological documented CSM in context of clinical and radiographic outcomes.

Methods.

Clinical outcome scores included the Neck Disability Index (NDI), Visual Analogue Scale (VAS), arm and neck pain self-assessment questionnaires as well as the Nurick grade and the Japanese Orthopaedic Association (JOA) score. The radiological outcome included the range of motion (ROM), the segmental and global (C2-C7) lordosis, and the occurrence of heterotopic ossifications.

Results.

Eighteen consecutive patients (10 males, 8 females) with documented clinical and radiological signs of myelopathy were included in this investigation. The study population had a mean age of 52.4 years and a follow-up period of 20.3 months in average (range 3–48 months). The mean range ROM of the index level stayed consistent with 6.8° preoperatively and 7.2° (P = 0.578) at the last follow-up; the global lordosis in neutral position changed from 3.5° to 14.2° significantly (P = 0.005) in mean. The JOA score improved from 11.3 to 16.6 (P < 0.001) as well as the NDI 36.7 to 10.3 (P < 0.001) and the VAS score from 5.7/6.1 (arm/neck) to 1.3/2.0 (P < 0.001/P < 0.001). The mean Nurick grade was 1.33 preoperatively and dropped down in all cases to Nurick grade of 0 (P < 0.001).

Conclusion.

cTDR (with ProDisc Vivio) in patients with CSM yielded good clinical and radiographic outcomes and found as a reliable, safe, and motion-preserving surgical treatment option, although its indication is very limited due to numerous exclusion criteria.

Level of Evidence: 4
Clinical Efficacy of Frameless Stereotactic Radiosurgery in the Management of Spinal Metastases From Thyroid Carcinoma
Authors: Hariri Omid , Takayanagi Ariel , Lischalk Jonathan , Desai Kaniksha , Florence Timothy J. , Yazdian Pouria , Chang Steven D. , Vrionis Frank , Adler John R. , Quadri Syed A. , Desai Atman
Published: July 2019

Study Design.

A retrospective data review.

Objective.

To evaluate the efficacy of CyberKnife (CK) stereotactic radiosurgery (SRS) for thyroid spinal metastasis (SMs).

Summary of Background Data.

Thyroid carcinoma is an infrequent cause of SM. The absolute efficacy of SRS generally and CK in particular remains poorly characterized for thyroid SM. The current study is the first to specifically evaluate the efficacy of CK SRS for thyroid SMs.

Methods.

A retrospective review of patients at our institution between 2003 and 2013 was done. Details about tumor location, radiographic findings before and after CK SRS, tumor recurrence, prescription isodose level, total and maximum dose, number of fractions, and gross tumor volume coverage were similarly collected. For comparison with other studies, the biologically effective dose and the equivalent total dose in 2 Gy fractions were calculated. Each patient was assessed for survival and local disease control from the time of the first CK session and survival analysis was carried out using the Kaplan–Meier method. Risk factors for local failure were assessed using multivariate logistic regression.

Results.

A total of 12 patients with 32 spinal metastases from thyroid carcinoma that were treated with CK SRS were identified. Survival for 1, 2, and 3 years was 55%, 44%, and 33%, and local control was 67%, 56%, and 34% respectively. The study found that the single strongest factor associated with local control was prior radiotherapy (β-coefficient −27.72, P = 0.01). No complications occurred in the immediate or late follow-up period.

Conclusion.

This was the first study to specifically investigate the efficacy of CK for treatment of thyroid SMs. Our findings suggest that CK can be safely used to treat spinal SMs from thyroid cancer and is associated with a high rate of local control.

Level of Evidence: 4
Myasthenia Gravis Induced by Immune Checkpoint Inhibitors
Authors: Becquart Ondine , Lacotte Julie , Malissart Pauline , Nadal Jeremy , Lesage Candice , Guillot Bernard , Du Thanh Aurélie
Published: July 2019

Immune checkpoint inhibitors deeply improved the prognosis of metastatic melanoma or other types of cancer, but their related adverse effects (AEs) can be very severe, especially when the neurological system is touched, as in myasthenia gravis (MG). It is a rare immune AE that can be life-threatening and can be revealed by several symptoms. We report a case of our experience and review the current literature of MG exacerbated or occurring during immunotherapy to describe characteristics of this AE, warn the oncologist about this toxicity, and summarize the treatments conducted. Thirty-four cases of MG were reported, mostly with anti-programmed cell death protein 1 checkpoint inhibitor, and with melanoma. Onset was quick after the first or second infusion. Treatment comprised corticosteroids, prostigmine, and more or less plasmapheresis or immunoglobulins. Prognosis is poor, as 13 patients died after MG. MG is a rare immune-related AE that must be rapidly evoked and treated in case of neurological symptoms emerging after immunotherapy.
Anti-αFR CAR-engineered NK-92 Cells Display Potent Cytotoxicity Against αFR-positive Ovarian Cancer
Authors: Ao Xiang , Yang Yu , Li Weiqiang , Tan Yan , Guo Wei , Ao Luoquan , He Xiao , Wu Xiaofeng , Xia Jianchuan , Xu Xiang , Guo Jianxin
Published: July 2019

Folate receptor alpha (αFR) is overexpressed in 90% of ovarian cancers, one of the most lethal gynecologic cancers. Recent studies have suggested that natural killer (NK) cells may be better chimeric antigen receptor (CAR) drivers because of their favorable innate characteristics, such as directly recognizing and killing tumor cells. However, the therapeutic effects of CAR-engineered NK cells targeting αFR in ovarian cancer have not been reported. In this research, 3 generations of anti-αFR CAR were constructed, namely αFR-ζ (first generation), αFR-28ζ (second generation), and αFR-28BBζ (third generation), and were highly expressed on the surface of NK-92 cells by lentivirus gene transfection. Three anti-αFR CAR-engineered NK-92 cells can specifically kill αFR-positive tumor cells in vitro, especially ovarian cancer cells with high αFR expression. Compared with NK-92 cells expressing αFR-ζ or αFR-28ζ, NK-92 cells expressing αFR-28BBζ showed not only higher antigen-specific cytotoxicity and proliferation but also lower antigen-induced apoptosis. Moreover, stronger degranulation and cytokine secretion were detected in NK-92 cells expressing αFR-28BBζ cocultured with αFR-positive tumor cells. Real-time cell analysis and live cell imaging recorded the process of NK-92 cells expressing αFR-28BBζ killing ovarian cancer cells in vitro. Furthermore, NK-92 cells expressing αFR-28BBζ can effectively eliminate cancer cells in a mouse xenograft model of ovarian cancer and significantly prolong the survival of tumor-bearing mice. These results demonstrate that the anti-αFR CARs redirect NK-92 cells with specific antitumor activity, and the third-generation anti-αFR CAR-engineered NK-92 cells display more potent cytotoxicity against αFR-positive ovarian cancer, laying the foundation for future clinical research.
PD-L1 Expression in De Novo Metastatic Castration-sensitive Prostate Cancer
Authors: Iacovelli Roberto , Ciccarese Chiara , Brunelli Matteo , Bogina Giuseppe , Munari Enrico , Bimbatti Davide , Mosillo Claudia , Fantinel Emanuela , Bria Emilio , Martignoni Guido , Tortora Giampaolo
Published: July 2019

De novo metastatic castration-sensitive prostate cancer (mCSPC) is small subgroup of prostate cancer associated with poor prognosis. The aim of our study was to assess the expression of programmed death-ligand 1 (PD-L1) in tumor cells of de novo mCSPC patients. Patients referred to our institution from January 2007 to October 2017 with de novo mCSPC and available diagnostic tissue were included. We tested the PD-L1 pharmaDx qualitative immunohistochemical assay, a monoclonal rabbit anti-PD-L1, clone 28-8 intended for use in the detection of PD-L1 protein in formalin-fixed paraffin-embedded. Kaplan-Meier method was used to estimate survivals according to the expression of PD-L1. The study population included 32 de novo mCSPC patients, analyzed for PD-L1 expression using 2 cut-off values (1% and 5%) to define the positivity. Total of 46.9% of cases had tumor PD-L1 expression ≥1%, and 31.3% had expression ≥5%. No differences were found between the PD-L1 expression ≥1% and the involvement of liver, lung, and number of bone metastases, and the disease volume based on CHAARTED classification. PD-L1− tumors had higher incidence of Gleason score ≥8 compared with PD-L1+ tumors (P=0.037), while the incidence of lymph node metastases was higher in PD-L1+ tumors (P=0.044). No difference in the median overall survival (mOS) was observed between the PD-L1− population and the PD-L1+ patients (43.8 vs. 29.6 mo; P=0.88). The tumor PD-L1 expression cannot be considered a prognostic factor for de novo mCSPC, even if its prognostic and predictive significance have to be thoroughly investigated to better define the selected group of prostate cancer patients that might benefit from checkpoint blockade immunotherapy.
Linear IgA Disease of the Gingiva Following Nivolumab Therapy
Authors: Jonna Sushma , Neiders Mirdza , Lakshmanan Suresh , Khan Amir , DeKlotz Timothy , Lanasa Dominic , Gibney Geoffrey T. , Liu Stephen V.
Published: July 2019

Immunotherapy has advanced the treatment of solid organ malignancies. Although generally well tolerated, treatment with immune checkpoint inhibitors can be complicated by immune-related adverse events, some of which are relatively uncommon. We report the first case of gingival linear immunoglobulin A disease related to treatment with an antiprogrammed cell death protein 1 antibody. A 73-year-old male with advanced non–small cell lung cancer achieved a durable response to nivolumab monotherapy. After 1 year of treatment, he developed gingival swelling and pain. Biopsy revealed linear immunoglobulin A disease of the gingiva which was effectively treated with systemic steroids. Ongoing vigilance for immune-mediated toxicity is paramount during and after treatment with immune checkpoint inhibitors.
Perineal Pressure During Hip Arthroscopy Is Reduced by Use of Trendelenburg: A Prospective Study With Randomized Order of Positioning
Authors: Lall Ajay C. , Saadat Ardavan A. , Battaglia Muriel R. , Maldonado David R. , Perets Itay , Domb Benjamin G.
Published: July 2019

Background

The use of traction during hip arthroscopy is commonly used to provide safe joint access and to improve visualization. However, traction during hip arthroscopy has been associated with complications ranging from transient neuropraxias to devastating soft-tissue necrosis. Trendelenburg positioning may be helpful, but the degree to which this is true is not well understood.

Questions/purposes

To determine whether there would be a reduction in perineal pressure at 5°, 10°, and 15° of Trendelenburg compared with baseline (0° of Trendelenburg) while in the modified supine position during hip arthroscopy.

Methods

A consecutive cohort of 50 patients treated with hip arthroscopy by a single, high-volume orthopaedic surgeon was analyzed. There were 30 females and 20 males in this study, with a mean age of 36 ± 16 years (range, 14 to 66 years); mean BMI was 26 kg/m2. In the operating room, patients were placed in the modified supine position on a traction extension table with a well-padded perineal post. A standard blood pressure cuff was secured to the post to measure pressure exerted on the perineum as traction was applied to distract the hip. For each patient, pressure against the perineum was measured at four different positions using a digital level: 0°, 5°, 10°, and 15° of Trendelenburg. These positions were tested in a random order for each patient. Mean pressure was compared within patients under the four-period crossover design using a repeated-measure (mixed) ANOVA model. Examination of the residual error quantile plot showed that the pressure data followed a normal distribution, making the use of a parametric model appropriate. Tests were made for period and order effects.

Results

Compared with baseline (0° or no Trendelenburg) there was a reduction in pressure of 4.4 (15.5%) at 5° of Trendelenburg (p = 0.203), 8 (28%) at 10° of Trendelenburg (p = 0.022) and 13.1 (46%) at 15° (p = 0.006). These results were maintained regardless of the sequence of positions used in each patient (0°, 5°, 10°, 15°).

Conclusions

Trendelenburg positioning of 10° and 15° during hip arthroscopy resulted in decreased perineal pressure compared with the neutral (0°) position. This technique is intended to harness gravity to exert the majority of countertraction while retaining the perineal post as a backup patient stabilizer. Routine introduction of Trendelenburg during hip arthroscopy reduces perineal pressure against the post, which may decrease complications related to traction and perineal pressure. Future studies should assess whether the observed differences in perineal pressure will reduce the frequency of post-related complications after hip arthroscopy.

Level of Evidence

Level II, therapeutic study.
Unique Uses of SPY: High-risk Facelift
Authors: Kislevitz Mikaela L. , Lu Karen B. , Sanniec Kyle , Amirlak Bardia
Published: July 2019

Skin flap necrosis occurs in 1–3% of facelift procedures. The SPY Elite Fluorescence Imaging System has been widely used in evaluating mastectomy skin flaps for breast reconstruction but has not been described in assessing skin flaps during facelifts. This case report describes the intraoperative use of SPY to assess flap perfusion during a high-risk facelift and static sling for the correction of facial paralysis. The use of intraoperative SPY during this high-risk facelift allowed for the timely assessment of perfusion, successful intervention of nitroglycerin paste to improve blood flow, and prevention of any additional surgical interventions. SPY may have a more widespread role in facelift patients with a higher risk of skin flap necrosis.
Meta-analysis Comparing Outcomes of Two Different Negative Pressure Therapy Systems in Closed Incision Management
Authors: Singh Devinder P. , Gabriel Allen , Silverman Ronald P. , Griffin Leah P. , McGowan Lucy D’Agostino , D’Agostino Ralph B.
Published: July 2019

Background:

Closed incision negative pressure therapy (ciNPT) is an emerging approach to managing closed incisions of patients at risk of postoperative complications. There are primarily 2 different commercially available ciNPT systems. Both systems consist of a single-use, battery-powered device and foam- or gauze-based peel-and-place dressing designed for closed incisions. These systems vary in design, and there are no data comparing outcomes between the 2 systems.

Methods:

We performed 2 separate meta-analyses to compare surgical site infection (SSI) rates postuse of (1) ciNPT with foam dressing (FOAM) versus conventional dressings and (2) ciNPT with multilayer absorbent dressing (MLA) versus conventional dressings.

Results:

Seven articles and 2 abstracts met inclusion criteria in the FOAM group (n = 489) versus the control group (n = 489) in meta-analysis 1; 7 articles and 1 abstract met inclusion criteria in the MLA group (n = 532) versus the control group (n = 540) in meta-analysis 2. Meta-analysis 1 showed that patients in the control group were 3.17 times more likely to develop an SSI compared with patients in the FOAM group [weighted mean odds ratios of FOAM group versus control group was 3.17 (P < 0.0001) with the 95% confidence intervals of 2.17–4.65]. Meta-analysis 2 showed no significant difference in SSI rates between patients in the MLA group and patients in the control group [weighted mean odds ratios of MLA group versus control group was 1.70 (P = 0.08) with the 95% confidence intervals of 0.94–3.08].

Conclusions:

Comparing outcomes of two different ciNPT systems with a common comparator (conventional dressings) may provide an interim basis for comparing ciNPT systems until further comparative evidence is available. More comparative research is required to determine outcomes in clinical practice.
Expression Profiles of lncRNAs and circRNAs in Keloid
Authors: Wang Jie , Wu Hao , Xiao Zhibo , Dong Xiaoqun
Published: July 2019

Background:

We hypothesized that crosstalk between noncoding RNAs, including microRNA (miRNA), lncRNA, and circRNA, might play a critical role in keloids development and physiology. To reveal the molecular mechanisms involved in the pathogenesis of keloids, we compared their gene expression profiles and differential expressions in keloid and normal skin tissues.

Methods:

Expression profiles of mRNAs and lncRNAs and circRNAs in 2 pairs (identification set) of keloid and matched normal skin tissues were analyzed through sequencing. Real-time quantitative PCR was performed to validate the sequencing results using 5 pairs (validation set) of keloid and matched normal skin tissues. Presumed targets of differentially expressed lncRNAs and circRNAs were functionally annotated by bioinformatics approaches.

Results:

The differential expression of mRNAs in keloid and normal skin by high-throughput sequencing was 2,528, of which 1,271 were downregulated, whereas 1,257 were upregulated. In the meantime, sequencing identified 2,227 differentially expressed lncRNAs, including 1,224 upregulated and 1,003 downregulated in keloid tissue compared with normal skin tissue. Additionally, 154 differentially expressed circRNAs were identified, including 81 upregulated and 73 downregulated in keloid tissue compared with normal skin tissue. Functional annotations of differentially expressed circRNA targets revealed their enrichment in several signaling pathways important for scar wound healing.

Conclusions:

Expression profiles of mRNAs, lncRNAs, and circRNAs were altered in keloid tissue, which may partly contribute to the etiology of keloids by affecting several signaling pathways relevant to scar wound healing. A better understanding of keloids pathogenesis may identify new therapeutic targets for keloids.
Nerve Transfers—A Paradigm Shift in the Reconstructive Ladder
Authors: Domeshek Leahthan F. , Novak Christine B. , Patterson J. Megan M. , Hasak Jessica M. , Yee Andrew , Kahn Lorna C. , Mackinnon Susan E.
Published: July 2019

In this review, we present the current role of nerve transfers in the management of nerve injuries. The outcome of a literature review comparing the results of nerve graft versus nerve transfer and the experience of select surgical societies’ members regarding experience and adoption of nerve transfer are reported. Nerve transfer publications have increased more than nerve graft or repair articles. The surgeon survey revealed an increase in nerve transfers and that more motor nerve transfers have been adopted into practice compared to sensory nerve transfers. The meta-analyses and systematic reviews of motor nerve transfers for shoulder and elbow function presented variable outcomes related to donor nerve selection. Comprehensive patient assessment is essential to evaluate the immediate functional needs and consider future reconstruction that may be necessary. Optimal outcome following nerve injury may involve a combination of different surgical options and more than one type of reconstruction. Nerve transfer is a logical extension of the paradigm shift from nerve repair and nerve graft and offers a new rung on the reconstruction ladder.
Median Nerve Injury Caused by Screw Malpositioning in Percutaneous Scaphoid Fracture Fixation
Authors: Starnoni Marta , Colzani Giulia , De Santis Giorgio , Acciaro Andrea Leti
Published: July 2019

An unusual complication of percutaneous fixation of a schapoid fracture in a 36-year-old man is described. After this surgery, the patient complained of numbness and tingling within the median nerve distribution and thenar weakness. An Electromyography showing moderate CTS had led to carpal tunnel decompression, which resulted unsuccessful. When the patient presented to us, both sensory and motor median nerve impairment were present, interfering with his professional activity. A computed tomography scan performed to assess the scaphoid screw position, showed that the screw had been placed volar to the scaphoid, adjacent to the median nerve. Surgery confirmed median nerve compression by the screw, especially during complete wrist extension. The surgical removal of the screw led to immediate improvement of both the motor and sensory functions of the nerve, with complete clinical restoration of nerve function and resolution of the symptoms 2 months postoperatively.
Reconstruction of Congenital Microtia and Anotia: Analysis of Practitioner Epidemiology and Postoperative Outcomes
Authors: Cuccolo Nicholas G. , Zwierstra Myrthe J. , Ibrahim Ahmed M.S. , Peymani Abbas , Afshar Salim , Lin Samuel J.
Published: July 2019

Background:

Microtia refers to a congenital malformation of the external ear that is associated with a range of functional, psychosocial, aesthetic, and financial burdens. The aim of this study was to analyze the epidemiology and postoperative complication profile of microtia reconstruction.

Methods:

A retrospective review was conducted using data from the 2012–2017 the American College of Surgeons National Quality Improvement Program Pediatric databases. Patients with a diagnosis of microtia or anotia were identified using International Classification of Diseases codes. Demographics and postoperative complications were analyzed using Chi-square and t tests for categorical and continuous variables, respectively. Multivariable regression was performed to control for confounding variables.

Results:

A total of 466 cases were analyzed, of which 290 (62.2%) were performed by plastic surgeons and 176 (37.8%) by otolaryngologists (ear, nose, and throat physicians [ENT]). Autologous reconstruction was the predominant approach [76.2% of cases (n = 355)] in this cohort. ENT physicians operated on a significantly younger patient population (mean age 8.4 ± 3.2 years versus 10.0 ± 3.2 years, P< 0.001) and had higher rates of concurrent atresia/middle ear repair [21.0% (n = 37) versus 3.7% (n = 17)] compared with plastic surgeons. The rate of all-cause complications was 5.9% (n = 17) in the plastic surgery cohort and 4.0% (n = 7) in the ENT cohort (P= 0.372). Multivariable regression did not reveal any statistically significant predictors for all-cause complications.

Conclusions:

Reconstruction of the external ear for patients with microtia/anotia is a safe procedure, with low rates of postoperative complications, readmissions, and reoperations. Autologous reconstruction remains the preferred modality for repair of the external ear and simultaneous atresiaplasty/middle ear repair does not increase the risk of complications.
Structural Differences in Meibum From Donors After Hematopoietic Stem Cell Transplantations
Authors: Ramasubramanian Aparna , Blackburn Ryan , Yeo Heegook , Sledge Samiyyah M. , Gully Zahara N. , Singh Sharika , Mehta Sanya , Mehta Aakash , Yappert Marta C. , Borchman Douglas
Published: July 2019

Purpose:

Meibum is considered to be a key component of tears that serve to protect the eye, and conformational changes in meibum have not been studied extensively within the population of patients who had hematopoietic stem cell transplantation (HSCT). The aim of this study was to determine possible lipid conformational changes in the meibum of patients who had HSCT.

Methods:

Participants who had HSCT were randomly sampled for this prospective comparative study. Control participants did not have dry eye or had not undergone allogeneic or autologous stem cell transplantation. Fourier-transform infrared spectroscopy was used to measure meibum phase transition.

Results:

Meibum was collected from both eyes of 36 donors without dry eye (Mc) and from 22 patients who had undergone HSCT (MHSCT). There were no significant differences between the phase transition parameters based on gender or race. The following were the significant differences (P < 0.0001) between the parameters for Mc compared with MHSCT : lipid order (% trans) at 33.4°C increased from 40 (1) to 54 (2), cooperativity decreased from 7.9 (0.4) to 5.4 (0.3), the phase transition temperature (oC) increased from 30.3 (0.4) to 34.2 (0.9), and the magnitude of the phase transition (cm−1) increased from 4.0 (0.1) to 4.7 (0.5) (standard error of the mean).

Conclusions:

Conformational and thermodynamic differences were observed between Mc and MHSCT. The changes observed in the lipid conformation of meibum from patients receiving HSCTs suggest that meibum composition changes after stem cell transplantation, and clinicians should consider treating the meibomian glands to improve the ocular surface.
Pyuria as a Marker of Urinary Tract Infection in Neurogenic Bladder
Authors: Su Ruthie R. , Palta Mari , Lim Amy , Wald Ellen R.
Published: July 2019

Objective:

The utility of the urinalysis as a potential marker to diagnose urinary tract infection (UTI) in patients with neurogenic bladder is controversial. We assessed the baseline urine characteristics and intraindividual variance of pyuria in a cohort of asymptomatic children with neurogenic bladder followed longitudinally.

Study Design:

A cohort of 54 children with neurogenic bladder was followed from 2004 to 2015 at a single institution’s multidisciplinary clinic. Urine data obtained from 529 routine urology visits were reviewed. Urine obtained within 2 weeks before or after treatment for UTI were excluded. Bladder surgery was defined as any operation that altered the bladder as a closed or sterile system. The effects of age, gender, catheterization, and bladder surgery on pyuria were evaluated using mixed-model regression analysis.

Results:

Fifty patients with 305 urine samples had a mean length of follow-up of 3.2 years. Only 16/50 patients (32%) never had pyuria, and these patients had shorter follow-up compared with the group who ever had pyuria (≥5 white blood cells per high powered field) (1.7 vs. 3.8 years; P = 0.008). Catheterization was associated with a 15% increase in pyuria (P = 0.21). Surgery was associated with a 120% increase in pyuria (P < 0.001). The test-to-test variance of pyuria within an individual was consistently greater than between individuals (P < 0.001).

Conclusions:

Bladder surgery is associated with significant increases in pyuria among children with neurogenic bladder. The substantial test-to-test variation in pyuria in asymptomatic individuals indicates the low reliability of pyuria, when positive, as a marker for UTI in neurogenic bladder and the need to search for either methods to reduce this variability or alternative biomarkers of UTI in this population.
Strategic Trials to Define the Best Available Treatment for Neonatal and Pediatric Sepsis Caused by Carbapenem-resistant Organisms
Authors: Donà Daniele , Sharland Mike , Heath Paul T. , Folgori Laura
Published: July 2019

The optimal standard of care for carbapenem-resistant bloodstream infections in children is currently unknown. This systematic review, aiming to define the best available treatments to be compared with new antibiotics in clinical trials, clearly points out the paucity of available data. The simplification and a wider harmonization of study design are a global priority to inform the best strategies to treat these life-threatening infections in children.
Cancer cell-derived tissue factor-positive extracellular vesicles: biomarkers of thrombosis and survival
Authors: Hisada Yohei , Mackman Nigel
Published: July 2019

Purpose of review

Tissue factor (TF) is released from cancer cells and tumors in the form of extracellular vesicles (EVs). This review summarizes our current knowledge of the mechanisms of release of TF-positive EVs (TF+EVs) from cancer cells and the effect of these TF+EVs on cultured endothelial cells. In addition, we will summarize the contribution of TF+EVs to thrombosis in mice, and the association between plasma EVTF activity and venous thrombosis as well as survival of cancer patients.

Recent findings

The release of TF+EVs from cancer cells is regulated by multiple factors, including hypoxia, epithelial–mesenchymal transition, and various intracellular signaling pathways. Cancer cell-derived, TF+EVs confer procoagulant activity to endothelial cells and induce the expression of adhesion proteins and IL-8. In addition, they contribute to thrombosis by directly activating the coagulation system and by generating thrombin that activates platelets in mouse models. Finally, there is an association between EVTF activity and venous thrombosis in pancreatic cancer patients as well as mortality in cancer patients.

Cancer cell-derived TF+EVs bind to and activate endothelial cells. In addition, they serve as biomarkers of survival of cancer patients and venous thrombosis in pancreatic cancer patients.