bluuebunny/crossref_metadata_2025 huggingface dataset:
Adherence to Hepatitis C Therapy in a Shelter-Based Education and Treatment Model Among Persons Experiencing Homelessness
Authors: Powell Jesse , Ricco Margaret , Naugle Jessica , Magee Catherine , Hassan Hayat , Masson Carmen , Braimoh Grace , Zevin Barry , Khalili Mandana
Published: September 2021

Background

Medication adherence is a common reason for treatment deferment in persons experiencing homelessness. We evaluated adherence to hepatitis C virus (HCV) therapy following HCV education in a shelter-based care model.

Methods

Prospective study conducted at 4 homeless shelters in Minneapolis, Minnesota and San Francisco, California from November 2018 to January 2021. Sixty-three patients underwent HCV education and treatment. Multivariable modeling evaluated factors associated with (1) medication and (2) overall (composite score of medication, laboratory, and clinic visit) adherence.

Results

Median age was 56 years; 73% of participants were male, 43% were Black, 52% had psychiatric illness, and 81% used illicit drugs and 60% used alcohol in the past year. Following education, 52% were extremely confident in their ability to be adherent to HCV therapy. Medication adherence by patient and provider report was 88% and 48%, respectively, and 81% achieved HCV cure. Active alcohol use was associated with less confidence in medication adherence (43% vs 78%, P = .04). Older age was positively (coefficient = 0.3) associated with overall adherence to HCV treatment whereas prior therapy was associated with both medication (odds ratio, 0.08) and overall treatment (coefficient = –0.87) nonadherence.

Conclusions

Despite imperfect adherence, sustained virologic response rates were still high. Expanding opportunities to treat persons experiencing homelessness in a structured and supportive setting is critical to HCV elimination efforts.
Three-Dimensionally Printed Surgical Simulation Tool for Brain Mapping Training and Preoperative Planning
Authors: Colaguori Faith , Marin-Mera Maité , McDonnell Megan , Martínez Jaime , Valero-Moreno Fidel , Damon Aaron , Domingo Ricardo A , Clifton William , Fox W Christopher , Chaichana Kaisorn , Middlebrooks Erik H , Sabsevitz David , Forry Rebecca , Quiñones-Hinojosa Alfredo
Published: September 2021

BACKGROUND

Brain mapping is the most reliable intraoperative tool for identifying surrounding functional cortical and subcortical brain parenchyma. Brain mapping procedures are nuanced and require a multidisciplinary team and a well-trained neurosurgeon. Current training methodology involves real-time observation and operation, without widely available surgical simulation.

OBJECTIVE

To develop a patient-specific, anatomically accurate, and electrically responsive biomimetic 3D-printed model for simulating brain mapping.

METHODS

Imaging data were converted into a 2-piece inverse 3D-rendered polyvinyl acetate shell forming an anatomically accurate brain mold. Functional and diffusion tensor imaging data were used to guide wire placement to approximate the projection fibers from the arm and leg areas in the motor homunculus. Electrical parameters were generated, and data were collected and processed to differentiate between the 2 tracts. For validation, the relationship between the electrical signal and the distance between the probe and the tract was quantified. Neurosurgeons and trainees were interviewed to assess the validity of the model.

RESULTS

Material testing of the brain component showed an elasticity modulus of 55 kPa (compared to 140 kPa of cadaveric brain), closely resembling the tactile feedback a live brain. The simulator's electrical properties approximated that of a live brain with a voltage-to-distance correlation coefficient of r2 = 0.86. Following 32 neurosurgeon interviews, ∼96% considered the model to be useful for training.

CONCLUSION

The realistic neural properties of the simulator greatly improve representation of a live surgical environment. This proof-of-concept model can be further developed to contain more complicated tractography, blood and cerebrospinal fluid circulation, and more in-depth feedback mechanisms.
Resection of Clival Chordoma Through the Anterior Clivectomy: 2-Dimensional Operative Video
Authors: Kadri Paulo A S , Arnautović Kenan I , Ibn Essayed Walid , Al-Mefty Ossama
Published: September 2021

Clival chordomas are rare malignant behaving tumors that grow, locally invade, metastasize, and seed, and they have a high recurrence rate.
1,2
The longest disease control is achieved by radical resection followed by high doses of radiation therapy, commonly proton beam.
3

 To achieve radical tumor removal, multiple surgical procedures through different approaches might be required.
4
Since the chordoma's origin is, and remains, extradural, an extradural approach is preferred, and can lead to intradural extension. Anterior approach is frequently utilized to remove the midline-located tumor and the eroded clivus.
5

 Several midline approaches were utilized, including the transbasal, transfacial, transcervical, open door, and Lefort's maxillotomies
1
; however, the same tumor removal can be achieved with a simple extension of the trans-sphenoidal approach, by resecting the anterior maxillary wall, of the contralateral to the lesion preponderant side.
5
This approach coupled with the use of neuronavigation on mobile head and endoscopic-assisted technique allowed to achieve a wide and direct exposure, with the ability to resect extra- and intradural tumors.
2,5
Lately, the endonasal endoscopic technique became popular as an alternative
4
; however, we found a great advantage in the ability to combine the stereoscopic microsurgical technique with the endoscopic dissection, in addition to avoiding the extensive nasal dissection and its complications.

 We present a case of a 63-yr old woman with an upper clivus chordoma compressing the brainstem who underwent a gross total resection by endoscopic-assisted microscopic techniques through an anterior clivectomy approach. Patient consented to the procedure and publication of her images.
Robotic-Assisted Digital Exoscope for Resection of Cerebral Metastases: A Case Series
Authors: Schupper Alexander J , Price Gabrielle , Hadjipanayis Constantinos G
Published: September 2021

BACKGROUND

Surgical resection is the primary treatment for cerebral metastases with safe complete resection as the goal. The robotically assisted digital surgical exoscope is a novel system with advanced visualization methods with recent applications in neurosurgery.

OBJECTIVE

To evaluate the outcomes for patients with cerebral metastases undergoing resection with the surgical exoscope.

METHODS

Data were retrospectively collected from patients with cerebral metastases where resection was achieved with using the surgical exoscope from 2016 to 2020. Demographics, clinical, imaging, and operative and outcome findings were collected. The relationship between perioperative data and discharge disposition as well as progression-free survival (PFS) and 12 mo overall survival (OS) was assessed.

RESULTS

A total of 31 patients (19 males) with a median patient age 63 yr (range 38-80) were included. Average pre- and postoperative volumes were 18.1 cc and 0.75 cc, respectively. Mean depth of the resected lesions was 0.6 cm (range 0-3.6 cm). Complete resection was achieved in 64.5% of patients. The mean extent of resection was 96.7%, with 71.0% achieving PFS at 6 mo. Overall PFS rate was 58.1% and the OS rate at 12 mo was 83.9%. Neurological complications included motor (35.5%) and sensory (12.9%) deficits, with 12 patients reporting no postoperative symptoms.

CONCLUSION

The surgical exoscope can delineate tumor tissues with high resolution, as shown by a gross total resection achieved for the majority of cases in our series. Postoperative complications and patient outcomes were similar to those reported with use of the operative microscope. Use of the exoscope can provide optimal visualization and delineation of cerebral metastases.
First-line Medications for the Outpatient Treatment of Alcohol Use Disorder: A Systematic Review of Perceived Barriers
Authors: Gregory Caroline , Chorny Yelena , McLeod Shelley L. , Mohindra Rohit
Published: September 2021

Objectives

Alcohol use disorder (AUD) is a common illness with significant health and economic consequences. Although three pharmacotherapeutic agents have been shown to decrease heavy drinking days among individuals with AUD, they are vastly underutilized in clinical practice. The objective of this review was to elucidate barriers that may prevent patients from obtaining medication for addiction treatment (MAT) for AUD in an outpatient or residential setting.

Methods

Electronic searches of Medline and EMBASE were conducted, and reference lists were hand-searched. All study designs which discussed the use of MAT for AUD in an outpatient or residential setting were eligible for inclusion. Two reviewers independently screened the search output to identify potentially eligible articles, the full texts of which were retrieved and assessed for inclusion.

Results

After eliminating duplicate citations and articles that did not meet eligibility criteria, 23 articles were included in the review. Perceived barriers to obtaining pharmacotherapy for the treatment of AUD in an outpatient or residential setting were grouped into 3 themes: lack of knowledge and concerns about efficacy and complexity of prescribing; treatment philosophy and stigma; medication accessibility including formulary restrictions, geographical and socioeconomic barriers.

Conclusions

Although evidence-based pharmacotherapeutics have been approved for the treatment of AUD, our findings suggest patients continue to experience barriers to the use of these medications. Efforts should be made to increase rates of prescribing by providers and the use of medications by patients. More research is needed to further elucidate perceived barriers to MAT use, along with strategies to overcome them.
Effectiveness of Positive Psychology Skills Training on Life Expectancy of Addicts in Tehran
Authors: Rad Meysam , Seifi Zahra
Published: September 2021

Introduction:

The aim of this study was the effectiveness of positive psychology skills training on increasing the life expectancy of addicts referred to addiction treatment centers in Tehran.

Methods:

The research method was quasiexperimental with pretest, post-test, and follow-up design with a control group. In this study, 60 addicts were selected who were randomly assigned to experimental (n=30) and control (n=30) groups. Group therapy sessions consisted of 10 sessions, twice a week for 90 minutes each time. The research tool was Snyder Hope Questionnaire. Analysis of variance with repeated measures was used to analyze the data.

Results:

The results showed that there was a statistically significant difference in the mean score of hope in the experimental and control groups (P<0.001). The results showed that teaching positive psychology skills as a group can significantly increase hope in addicts.

Conclusions:

Therefore, positive psychology with a strong theoretical and research background is an appropriate strategy to increase life expectancy and can be used as an effective intervention method to increase life expectancy in addicts.
What happens to the patella height in patients with cerebral palsy as they age
Authors: Min Jae Jung , Kwon Soon-Sun , Sung Ki Hyuk , Lee Kyoung Min , Lee Hansang , Chung Chin Youb , Park Moon Seok
Published: September 2021

We aimed to investigate the progression of patella alta (PA) in patients with cerebral palsy (CP) using the Koshino–Sugimoto (KS) index and assess associated risk factors. Participants in our retrospective study met the following inclusion criteria: patients with CP who visited our institute from May 2003 to December 2019, were ≤18 years of age, were followed up for >2 years and had at least two lateral knee radiographs. KS indices of both knee radiographs were measured for each patient. A linear mixed model was implemented. Our participants included 222 CP patients. KS index values were measured via 652 knee radiographs. Reference values of the KS index for those between 4 and 18 years of age were determined according to Gross Motor Function Classification System (GMFCS) levels. In all GMFCS levels, the KS index decreased with patients’ ages (P < 0.0001). In groups where the KS index increased, GMFCS levels IV (P = 0.0045) and V (P = 0.0040) were statistically significant. Change in the KS index values indicates that PA improves as patients age within all GMFCS levels. However, in patients with GMFCS levels of IV and V, progressive PA is expected.
Variability in evaluation and treatment of tibial tubercle fractures among pediatric orthopedic surgeons
Authors: Fields Michael W. , Kaushal Neil K. , Patel Neeraj M. , McCormick Sekinat K. , Eberson Craig P. , Schmitz Michael L. , Swarup Ishaan , Blanco John S. , Crawford Lindsay M. , Edobor-Osula O. Folorunsho
Published: September 2021

The purpose of this study was to determine the variability in clinical management of tibial tubercle fractures among a group of pediatric orthopedic surgeons. Nine fellowship-trained academic pediatric orthopedic surgeons reviewed 51 anteroposterior and lateral knee radiographs with associated case age. Respondents were asked to describe each fracture using the Ogden classification (type 1–5 with A/B modifiers), desired radiographic workup, operative vs. nonoperative treatment strategy and plans for post-treatment follow-up. Fair agreement was reached when classifying the fracture type using the Ogden classification (k = 0.39; P < 0.001). Overall, surgeons had a moderate agreement on whether to treat the fractures operatively vs. nonoperatively (k = 0.51; P < 0.001). Nonoperative management was selected for 80.4% (45/56) of type 1A fractures. Respondents selected operative treatment for 75% (30/40) of type 1B, 58.3% (14/24) of type 2A, 97.4% (74/76) of type 2B, 90.7% (39/43) of type 3A, 96.3% (79/82) of type 3B, 71.9% (87/121) of type 4 and 94.1% (16/17) of type 5 fractures. Regarding operative treatment, fair/slight agreement was reached when selecting the specifics of operative treatment including surgical fixation technique (k = 0.25; P < 0.001), screw type (k = 0.26; P < 0.001), screw size (k = 0.08; P < 0.001), use of washers (k = 0.21; P < 0.001) and performing a prophylactic anterior compartment fasciotomy (k = 0.20; P < 0.001). Furthermore, surgeons had fair/moderate agreement regarding the specifics of nonoperative treatment including degree of knee extension during immobilization (k = 0.46; P < 0.001), length of immobilization (k = 0.34; P < 0.001), post-treatment weight bearing status (k = 0.30; P < 0.001) and post-treatment rehabilitation (k = 0.34; P < 0.001). Significant variability exists between surgeons when evaluating and treating pediatric tibial tubercle fractures.
Fixation of open, unstable tuft fractures in toddlers and preschool-aged children using a 25-gauge hypodermic needle
Authors: Kilincoglu Volkan , Gonder Nevzat , Demir Ibrahim Halil , Acikgoz Irfan , Karsli Burcin
Published: September 2021

This study aimed to assess the treatment process of open, unstable tuft fractures occurring in toddlers and preschool-aged children treated using a 25-gauge hypodermic needle in the emergency department, and the cosmetic and functional results achieved by this treatment. This retrospective cohort study included a total of 72 patients. Children aged two to six years were included in the study. Van Beek classification was used for the evaluation of nail bed injuries. Cosmetic results were evaluated on the basis of Zook classification whereas functional results were evaluated according to the Buck-Gramko score simplified by Nietosvaara et al. The patient population consisted of 52 men and 20 women. The mean age was 4 ± 1.33 years. The operating time was 19.17 ± 3.66 minutes and the time to union was 46.68 ± 4.84 days. While excellent and good functional results were obtained in 65 (90.2%) of the patients, excellent and very good cosmetic results were obtained in 51 (70.8%) patients. Unless there is an accompanying extremity fracture, unstable pediatric tuft fractures can be successfully fixed with a hypodermic needle in the emergency department. Gentle and precise repair of the nail bed may provide cosmetically and functionally satisfactory results.
Outcome of Gastrocnemius Soleus Facial Lengthening in Ambulatory Patients With Cerebral Palsy
Authors: Stotts Alan K. , Carroll Kristen L. , Naatz Emma , MacWilliams Bruce A.
Published: September 2021

Background:

Treatment of equinus contractures in children with cerebral palsy (CP) varies across centers. Existing literature utilizes mixed study populations with a variety of procedures. As such, there is limited knowledge regarding recurrence rates and efficacy of a single procedure performed on a homogenous cohort. Here we retrospectively evaluate outcomes from gastroc soleus fascial lengthenings (GSFL) performed at 2 centers with consistent approaches in both patient selection and operative technique.

Methods:

Subjects meeting inclusion criteria including CP diagnosis, ambulation status, and minimum follow-up criteria were identified. Revision rate was reported based on need for additional calf lengthening procedures. Functional outcomes were evaluated using physical exam measures and selected variables from computational gait analysis. Outcomes factors were identified by comparing revised subjects to unrevised. Longitudinal outcomes of index surgeries were assessed by comparing preoperative functional data to short-term, mid-term, and long-term data.

Results:

A total of 64 subjects with 87 limbs met inclusion criteria. In all, 25% of subjects and 21% of limbs went on to revision. Factors influencing revision were age at index surgery and gross motor function classification system (GMFCS) level. More than half of revised limbs had index surgery before age 7. Revision rates for subjects less than 7 were 44% compared with a 17% revision rate for ages 7 to 12, and a 4% revision rate on children older than 12. GMFCSIII subjects had significantly higher revision rates (43%) compared with GMFCSII (18%) and GMFCSI (11%) subjects. Ankle range of motion measures improved significantly with GSFL and most maintained improvements at all time periods. GSFL did not lead to significant calcaneal gait or crouch.

Conclusions:

This study evaluates long term efficacy of GSFL to address equinus in ambulatory children with CP. Overall revision rates are similar to previous reports for GSFL and other calf lengthening procedures. This information may be useful in setting expectations and counselling families. Younger subjects and those with more severe involvement are more likely to need revision surgery, with these factors compounding the likelihood in the younger GMFCSIII child.

Level of Evidence:

Level III—retrospective comparative study.
Tiered Guidelines in a Pediatric Orthopaedic Practice Reduce Opioids Prescribed at Discharge
Authors: Baker Courtney E. , Larson A. Noelle , Ubl Daniel S. , Shaughnessy William J. , Rutledge John D. , Stans Anthony A. , Habermann Elizabeth B. , Milbrandt Todd A.
Published: September 2021

Background:

Data regarding opioid prescribing patterns following pediatric orthopaedic procedures is limited. The aim of this work was to evaluate the effects of tiered guidelines for discharge opioid prescriptions following common pediatric orthopaedic procedures.

Methods:

Quality improvement project conducted at a single academic institution. Guidelines for discharge opioid prescriptions were implemented January 2018 and established 4 tiers of increasing invasiveness for 28 common pediatric orthopaedic procedures. Patients who underwent these procedures in 2017 comprised the preguideline cohort (N=258), while patients treated in 2019 comprised the postguideline cohort (N=212). Opioid prescriptions were reported as oral morphine equivalents (OMEs). Univariate tests were performed to assess statistically significant differences before and after implementation of the guidelines.

Results:

There was a significant decrease in OME prescribed between preguideline and postguideline cohorts (median OME 97.5 vs. 37.5). When analyzed according to procedure tiers, tiers 1, 2, and 4 showed significant decreases in OME prescribed between 2017 and 2019. The rate of no opioids prescribed at discharge increased from 13% to 23% between preguideline and postguideline cohorts. The 30-day refill rate did not significantly change. After implementation of guidelines, 91% of all prescriptions were within the guideline parameters, and there was a significant reduction in prescription variability. In tier 4 procedures, median OME prescribed decreased from 375 preguideline to 188 postguideline, but was associated with greater opioid refills within 30 days of discharge (10.2% preguideline vs. 28.8% postguideline).

Conclusions:

Tiered guidelines for discharge opioid prescriptions following pediatric orthopaedic procedures can significantly decrease the quantity of opioids prescribed. Furthermore, we noted excellent adherence and no overall increase in the rates of narcotic refills. Such guidelines may improve pediatric orthopaedists’ ability to responsibly treat postoperative pain while limiting the distribution of unneeded opioids.

Level of Evidence:

Level IV—quality improvement project.
Primary Septic Arthritis in Children Demonstrates Presumed and Confirmed Varieties Which Require Age-specific Evaluation and Treatment Strategies
Authors: Klosterman Mary M. , Villani Mary C. , Hamilton Elizabeth C. , Jo Chanhee , Copley Lawson A.
Published: September 2021

Background:

There is uncertainty involved in the evaluation and treatment of children suspected to have septic arthritis particularly when no causative pathogen is confirmed. This study evaluates children with primary septic arthritis to refine the processes of evaluation and treatment and improve the rate of pathogen confirmation.

Methods:

Children suspected to have septic arthritis from 2009 to 2019 were retrospectively studied. Diagnosis of primary septic arthritis, defined as hematogenous joint infection without associated osteomyelitis, was established by clinical evaluation, radiology and laboratory results, including joint fluid analysis. Excluded cases were categorized by etiology. Children with primary septic arthritis were divided into confirmed and presumed cohorts for statistical comparison.

Results:

A total of 355 children (average age 4.4 y, range 0.05 to 18 y) were initially treated as septic arthritis. Eighty-seven (24.5%) were excluded due to other conditions, including 34 (9.6%) with noninfectious conditions. Among 268 children with primary septic arthritis, 134 were confirmed and 134 were presumed. A higher rate of 16S polymerase chain reaction (PCR) acquisition (71.6% vs. 45.5%) occurred in the confirmed cohort. Overall yield for various methods of pathogen identification were 27 of 239 (11.3%) by blood culture, 83 of 268 (31.0%) by joint fluid culture and 85 of 157 (54.1%) by PCR. PCR identified a pathogen in 87.5% of children with confirmed septic arthritis. Antibiotic pretreatment was associated with a lower rate of joint fluid culture positivity. Pathogens aggregated within specific age groups. The 4 to 9-year-old age group displayed the widest spectrum of pathogens with limited predictability.

Conclusions:

This study emphasizes the need for systematic processes of evaluation and treatment for children suspected to have primary septic arthritis, including minimization of antibiotic pretreatment, age-based empiric antibiotic selection, and sufficient follow-up to ensure noninfectious conditions are distinguished in culture-negative cases. Extended observation, before intervention, may be appropriate for some children.

Level of Evidence:

Level III—retrospective control study.
Interobserver and Intraobserver Reliability in the Salter Classification of Avascular Necrosis of the Femoral Head in Developmental Dysplasia of the Hip
Authors: Schaeffer Emily K. , Ponton Ethan , Sankar Wudbhav N. , Kim Harry K.W. , Kelley Simon P. , Cundy Peter J. , Price Charles T. , Clarke Nicholas M.P. , Wedge John H. , Mulpuri Kishore
Published: September 2021

Background:

Avascular necrosis (AVN) of the femoral head is a concerning complication that can result from treatments for developmental dysplasia of the hip (DDH). AVN can lead to degenerative osteoarthritis, persistent acetabular dysplasia, reduced function, and continuing hip pain. The incidence of AVN reported in the DDH literature is widely varied (0% to 73%). This variability may arise from lack of consensus on what constitutes true AVN in this patient population, and lack of clear criteria provided in studies reporting incidence rates.

Methods:

A multicentre, prospective database of infants diagnosed with DDH between 2010 and 2014 from 0 to 18 months of age was analyzed for patients treated by closed reduction (CR). Twelve pediatric orthopaedic surgeons completed 2 rounds of AVN assessments. Deidentified anteroposterior radiographs at most recent follow-up were provided to surgeons along with patient age at radiographic assessment, length of follow-up, ands affected hip. Ten of 12 surgeons completed a third round of assessments where they were provided with 1 to 2 additional radiographs within the follow-up period. Radiographic criteria for total AVN described by Salter and colleagues were used. Surgeons rated the presence of AVN as “yes” or “no” and kappa values were calculated within and between rounds.

Results:

A total of 69 hips in 60 patients were assessed for AVN a median of 22 months (range: 12 to 36) post-CR. Interobserver kappa values for rounds 1, 2, and 3 were 0.52 (range: 0.11 to 0.90), 0.61 (range: 0.21 to 0.90), and 0.53 (range: 0.10 to 0.79), respectively. Intraobserver agreement for AVN diagnosis was an average of 0.72 (range: 0.31 to 0.96).

Conclusions:

Despite using the most commonly referenced diagnostic criteria, radiographic diagnosis of AVN following CR in DDH patients demonstrated only moderate agreement across surgeons. The addition of sequential radiographs did not improve cross-observer reliability, and while substantial agreement was seen within observers, the range of intraobserver kappa values was large.

Level of Evidence:

Level I—diagnostic study.
Natural products inducing nucleolar stress: implications in cancer therapy
Authors: Wu Mi , Lu Lu , Chen Sisi , Li Ying , Zhang Qiuting , Fu Shujun , Deng Xiyun
Published: September 2021

The nucleolus is the site of ribosome biogenesis and is found to play an important role in stress sensing. For over 100 years, the increase in the size and number of nucleoli has been considered as a marker of aggressive tumors. Despite this, the contribution of the nucleolus and the biologic processes mediated by it to cancer pathogenesis has been largely overlooked. This state has been changed over the recent decades with the demonstration that the nucleolus controls numerous cellular functions associated with cancer development. Induction of nucleolar stress has recently been regarded as being superior to conventional cytotoxic/cytostatic strategy in that it is more selective to neoplastic cells while sparing normal cells. Natural products represent an excellent source of bioactive molecules and some of them have been found to be able to induce nucleolar stress. The demonstration of these nucleolar stress-inducing natural products has paved the way for a new therapeutic approach to more delicate tumor cell-killing. This review provides a contemporary summary of the role of the nucleolus as a novel promising target for cancer therapy, with particular emphasis on natural products as an exciting new class of anti-cancer drugs with nucleolar stress-inducing properties.
Oxaliplatin facilitates tumor-infiltration of T cells and natural-killer cells for enhanced tumor immunotherapy in lung cancer model
Authors: Xin Min , Lin Dan , Yan Nahan , Li Huiling , Li Jieping , Huang Zongming
Published: September 2021

Platinum is reported to have adjuvant immune properties, whether oxaliplatin (OXA) could be utilized to synergize with anti-programmed cell death-1 (PD-1) antibody or anti-NKG2D (natural-killer group 2, member D) antibody is investigated. Subcutaneous A549 lung cancer and murine Lewis lung carcinoma (LLC) models were constructed, which were further intravenously injected with platinum-based drugs or concomitant administrated with anti-PD-1 antibody and or anti-NKG2D antibody. The tumor volume and the proportion of myeloid cells (CD45+CD11b+), CD3+T cells and NK (NK1.1+) cells were detected. The relative expression of chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10 and CXCL11 and C-X-C motif chemokine receptor 3 (CXCR3) was detected with the ELISA, western blot and flow cytometry. The three platinum drugs (cisplatin, DDP; carboplatin, CBP; OXA) showed similar effects to inhibit A549 tumor growth in immune-deficient mice. While OXA exhibited better antitumor efficacy in wild-type mice bearing LLC with downregulated myeloid cells proportion, upregulated concentration of CXCL9, CXCL10 and CXCL11, and upregulated proportion and CXCR3 expression on T cells and NK cells. OXA combined with anti-PD1 or anti-NKG2D synergistically improved tumor growth inhibition and survival. The combination of OXA to anti-PD1 and anti-NKG2D antibodies will provide the most appropriate treatment benefit. Oxaliplatin promotes T cells and NK cells infiltration through the CXCL9/10/11-CXCR3 axis to enhance anti-PD1 or anti-NKG2D immunotherapy in lung cancer.
Nucleolar protein 6 promotes cell proliferation and acts as a potential novel prognostic marker for hepatocellular carcinoma
Authors: Meng Lei , Xu Kai-Xuan , Zhao Ming-Xi , Li Kang , Zhu Kun , Yuan Da-Wei , Wang Hao-Nan , Dai Peng-Gao , Yan Rong
Published: September 2021

Background:

Nucleolar protein 6 (NOL6) is a nucleolar RNA-associated protein that is highly conserved between species. It has been proved to be associated with the prognosis of liver cancer. However, the underlying mechanism has not been fully established. This study aimed to assess the relationship between NOL6 and liver cancer prognosis.

Methods:

We constructed an NOL6-short hairpin RNA (shRNA)-expressing lentivirus. Through viral transfection, cell growth assay and fluorescence-activated cell sorting, we evaluated the effect of shRNA-mediated NOL6 knockdown on the proliferation, colony formation, and apoptosis of hepatocellular carcinoma (HCC) cells. The relationship between NOL6 expression and HCC patient survival has been established through bioinformatics analysis. We also explored the downstream molecular regulatory network of NOL6 in HCC by performing an Ingenuity Pathway Analysis in the database.

Results:

Increased NOL6 expression was detected in HCC cells compared to normal controls; HCC patients with high NOL6 expression had poorer prognoses than those with low expression. NOL6 knockdown inhibited HCC cell proliferation, apoptosis, and colony formation. Also, MAPK8, CEBPA, and FOSL1 were selected as potential downstream genes of NOL6.

Conclusions:

NOL6 up-regulates HCC cell proliferation and affects downstream expression of related genes. Moreover, NOL6 is considered to be associated with poor prognosis in HCC patients.
In vitro fertilization-embryo transfer in patients with unexplained recurrent pregnancy loss
Authors: Li Tai-Yang , Li Rong , Zeng Lin , Li Li , Qiao Jie , Liu Ping , Wang Hai-Yan
Published: September 2021

Background:

Empiric therapy for patients with unexplained recurrent pregnancy loss (URPL) is not precise. Some patients will ask for assisted reproductive technology due to secondary infertility or advanced maternal age. The clinical outcomes of URPL patients who have undergone in vitro fertilization-embryo transfer (IVF-ET) require elucidation. The IVF outcome and influencing factors of URPL patients need further study.

Methods:

A retrospective cohort study was designed, and 312 infertile patients with URPL who had been treated during January 2012 to December 2015 in the Reproduction Center of Peking University Third Hospital were included. By comparing clinical outcomes between these patients and those with tubal factor infertility (TFI), the factors affecting the clinical outcomes of URPL patients were analyzed.

Results:

The clinical pregnancy rate (35.18% vs. 34.52% in fresh ET cycles, P = 0.877; 34.48% vs. 40.27% in frozen-thawed ET cycles, P = 0.283) and live birth rate (LBR) in fresh ET cycles (27.67% vs. 26.59%, P = 0.785) were not significantly different between URPL group and TFI group. URPL group had lower LBR in frozen-thawed ET cycles than that of TFI group (23.56% vs. 33.56%, P = 0.047), but the cumulative LBRs (34.69% vs. 38.26%, P = 0.368) were not significantly different between the two groups. The increased endometrial thickness (EMT) on the human chorionic gonadotropin day (odds ratio [OR]: 0.848, 95% confidence interval [CI]: 0.748–0.962, P = 0.010) and the increased number of eggs retrieved (OR: 0.928, 95% CI: 0.887–0.970, P = 0.001) were protective factors for clinical pregnancy in stimulated cycles. The increased number of eggs retrieved (OR: 0.875, 95% CI: 0.846–0.906, P < 0.001), the increased two-pronucleus rate (OR: 0.151, 95% CI: 0.052–0.437, P < 0.001), and increased EMT (OR: 0.876, 95% CI: 0.770–0.997, P = 0.045) in ET day were protective factors for the cumulative live birth outcome.

Conclusion:

After matching ages, no significant differences in clinical outcomes were found between the patients with URPL and the patients with TFI. A thicker endometrium and more retrieved oocytes increase the probability of pregnancy in fresh transfer cycles, but a better normal fertilization potential will increase the possibility of a live birth.
Chromosomal microarray analysis vs. karyotyping for fetal ventriculomegaly: a meta-analysis
Authors: Sun Yan , Zhang Weiyuan , Wang Zhiwen , Guo Likui , Shi Shaowen
Published: September 2021

Background:

Chromosomal abnormalities are important causes of ventriculomegaly (VM). In mild and isolated cases of fetal VM, obstetricians rarely give clear indications for pregnancy termination. We aimed to calculate the incidence of chromosomal abnormalities and incremental yield of chromosomal microarray analysis (CMA) in VM, providing more information on genetic counseling and prognostic evaluation for fetuses with VM.

Methods:

The Chinese language databases Wanfang Data, China National Knowledge Infrastructure, and China Biomedical Literature Database (from January 1, 1991 to April 29, 2020) and English language databases PubMed, Embase, and Cochrane Library (from January 1, 1945 to April 29, 2020) were systematically searched for articles on fetal VM. Diagnostic criteria were based on ultrasonographic or magnetic resonance imaging (MRI) assessment of lateral ventricular atrium width: ≥10 to <15 mm for mild VM, and ≥15 mm for severe VM. Isolated VM was defined by the absence of structural abnormalities other than VM detected by ultrasonography or MRI. R software was used for the meta-analysis to determine the incidence of chromosomal abnormalities and incremental yield of CMA in VM, and the combined rate and 95% confidence interval (CI) were calculated.

Results:

Twenty-three articles involving 1635 patients were included. The incidence of chromosomal abnormalities in VM was 9% (95% CI: 5%–12%) and incremental yield of CMA in VM was 11% (95% CI: 7%–16%). The incidences of chromosomal abnormalities in mild, severe, isolated, and non-isolated VM were 9% (95% CI: 4%–16%), 5% (95% CI: 1%–11%), 3% (95% CI: 1%–6%), and 13% (95% CI: 4%–25%), respectively.

Conclusions:

Applying CMA in VM improved the detection rate of abnormalities. When VM is confirmed by ultrasound or MRI, obstetricians should recommend fetal karyotype analysis to exclude chromosomal abnormalities. Moreover, CMA should be recommended preferentially in pregnant women with fetal VM who are undergoing invasive prenatal diagnosis. CMA cannot completely replace chromosome karyotype analysis.
Hsp90-associated DNA replication checkpoint protein and proteasome-subunit components are involved in the age-related macular degeneration
Authors: Xing Chen , Liu Xiao-Feng , Zhang Chun-Feng , Yang Liu
Published: September 2021

Background:

Age-related macular degeneration (AMD) is the leading cause of vision loss worldwide. However, the mechanisms involved in the development and progression of AMD are poorly delineated. We aimed to explore the critical genes involved in the progression of AMD.

Methods:

The differentially expressed genes (DEGs) in AMD retinal pigment epithelial (RPE)/choroid tissues were identified using the microarray datasets GSE99248 and GSE125564, which were downloaded from the gene expression omnibus database. The overlapping DEGs from the two datasets were screened to identify DEG-related biological pathways using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The hub genes were identified from these DEGs through protein-protein interaction network analyses. The expression levels of hub genes were evaluated by quantitative real-time polymerase chain reaction following the induction of senescence in ARPE-19 with FK866. Following the identification of AMD-related key genes, the potential small molecule compounds targeting the key genes were predicted by PharmacoDB. Finally, a microRNA-gene interaction network was constructed.

Results:

Microarray analyses identified 174 DEGs in the AMD RPE compared to the healthy RPE samples. These DEGs were primarily enriched in the pathways involved in the regulation of DNA replication, cell cycle, and proteasome-mediated protein polyubiquitination. Among the top ten hub genes, HSP90AA1, CHEK1, PSMA4, PSMD4, and PSMD8 were upregulated in the senescent ARPE-19 cells. Additionally, the drugs targeting HSP90AA1, CHEK1, and PSMA4 were identified. We hypothesize that Hsa-miR-16-5p might target four out of the five key DEGs in the AMD RPE.

Conclusions:

Based on our findings, HSP90AA1 is likely to be a central gene controlling the DNA replication and proteasome-mediated polyubiquitination during the RPE senescence observed in the progression of AMD. Targeting HSP90AA1, CHEK1, PSMA4, PSMD4, and/or PSMD8 genes through specific miRNAs or small molecules might potentially alleviate the progression of AMD through attenuating RPE senescence.
The Challenge of Pregnancy in Women With Hypertrophic Cardiomyopathy
Authors: Lloji Amanda , Panza Julio A.
Published: September 2021

Hypertrophic cardiomyopathy is a genetic disease that frequently presents at a young age. Pregnancy represents a state of high physiological stress to the cardiovascular system. Thus, pregnant women with hypertrophic cardiomyopathy face the potential for higher morbidity and, therefore, their management may become a significant challenge when complications develop. Physiologic changes that occur during pregnancy, that is, decreased vascular resistance, increased blood volume, and increased heart rate can lead to worsening heart failure in women with hypertrophic cardiomyopathy. In addition, pregnant women with hypertrophic cardiomyopathy are at higher risk for arrhythmias. The hemodynamic effects of atrial fibrillation and ventricular tachycardia are significant and can be dangerous for the mother and the fetus. In addition, they can lead to heart failure exacerbation. Atrial fibrillation is of particular interest in this population subgroup. Pregnancy is a hypercoagulable state and atrial fibrillation is an arrhythmia associated with significant thromboembolic complications. Patients with hypertrophic cardiomyopathy that develop atrial fibrillation are especially at a higher risk of thrombosis. Anticoagulation is recommended regardless of CHA2DS2-VASc score. Anticoagulation during pregnancy is challenging not only because of the teratogenic effects of some drugs and the lack of evidence for some others, but also the differences in the plasma concentration of many anticoagulants. Overall, the potential for high morbidity in pregnant women with hypertrophic cardiomyopathy is not negligible. Major cardiac events such as arrhythmias and heart failure are common. However, early recognition and treatment of these complications can lead to full-term pregnancy and successful delivery.
Exercise, Physical Activity, and Cardiometabolic Health: Insights into the Prevention and Treatment of Cardiometabolic Diseases
Authors: Rao Prashant , Belanger Matthew J. , Robbins Jeremy M.
Published: September 2021

Physical activity (PA) and exercise are widely recognized as essential components of primary and secondary cardiovascular disease (CVD) prevention efforts and are emphasized in the health promotion guidelines of numerous professional societies and committees. The protean benefits of PA and exercise extend across the spectrum of CVD, and include the improvement and reduction of risk factors and events for atherosclerotic CVD (ASCVD), cardiometabolic disease, heart failure, and atrial fibrillation (AF), respectively. Here, we highlight recent insights into the salutary effects of PA and exercise on the primary and secondary prevention of ASCVD, including their beneficial effects on both traditional and nontraditional risk mediators; exercise “prescriptions” for ASCVD; the role of PA regular exercise in the prevention and treatment of heart failure; and the relationships between, PA, exercise, and AF. While our understanding of the relationship between exercise and CVD has evolved considerably, several key questions remain including the association between extreme volumes of exercise and subclinical ASCVD and its risk; high-intensity exercise and resistance (strength) training as complementary modalities to continuous aerobic exercise; and dose- and intensity-dependent associations between exercise and AF. Recent advances in molecular profiling technologies (ie, genomics, transcriptomics, proteomics, and metabolomics) have begun to shed light on interindividual variation in cardiometabolic responses to PA and exercise and may provide new opportunities for clinical prediction in addition to mechanistic insights.
Exercise, Physical Activity, and Cardiometabolic Health
Authors: Belanger Matthew J. , Rao Prashant , Robbins Jeremy M.
Published: September 2021

Physical activity and its sustained and purposeful performance—exercise—promote a broad and diverse set of metabolic and cardiovascular health benefits. Regular exercise is the most effective way to improve cardiorespiratory fitness, a measure of one’s global cardiovascular, pulmonary and metabolic health, and one of the strongest predictors of future health risk. Here, we describe how exercise affects individual organ systems related to cardiometabolic health, including the promotion of insulin and glucose homeostasis through improved efficiency in skeletal muscle glucose utilization and enhanced insulin sensitivity; beneficial changes in body composition and adiposity; and improved cardiac mechanics and vascular health. We subsequently identify knowledge gaps that remain in exercise science, including heterogeneity in exercise responsiveness. While the application of molecular profiling technologies in exercise science has begun to illuminate the biochemical pathways that govern exercise-induced health promotion, much of this work has focused on individual organ systems and applied single platforms. New insights into exercise-induced secreted small molecules and proteins that impart their effects in distant organs (“exerkines”) highlight the need for an integrated approach towards the study of exercise and its global effects; efforts that are ongoing.
Retrievable Inferior Vena Cava Filters—Use, Removal, and Removal Techniques
Authors: Kim Chan W. , Babu Sateesh , Frishman William H. , Aronow Wilbert S.
Published: September 2021

The use of retrievable inferior vena cava filters is on the rise, but there is an inadequate number of these filters being removed even if their use as a prophylactic for venous thromboembolism is no longer indicated. Complications with retrievable filters that remain in the patient for an extended duration include examples such as filter tilt and embedding into the caval wall. This raises concerns for whether the filter is properly functioning and for consequent sequelae, including recurrent thrombosis, stenosis, or inferior vena cava perforation. With these complications, there are also challenges to retrieving these filters via the standard techniques and thus more advanced techniques are required. Both standard and advanced techniques, their uses, and possible risks of these methods are also discussed.
C4d as a Practical Marker for Cutaneous Amyloidosis
Authors: Yaman Banu , Kumbaracı Banu Sarsık , Gómez González Claudia A. , Akalın Taner , Şen Sait
Published: September 2021

Cutaneous amyloidosis (CA) is defined by the accumulation of amyloid in the dermis; it might be primary or secondary. The diagnosis is based on histopathological findings with the demonstration of amyloid deposits, confirmed by Congo red stain under the polarized light. Studies on other diagnostic markers are ongoing in the literature. The aim of this study was to demonstrate the utility of C4d staining in the recognition of amyloid in CA and using it as an alternative or substitute marker for the diagnosis. In this retrospective study, 199 skin biopsies with a clinical provisional diagnosis of CA were analyzed, the Congo red stain was performed, and, in a subgroup (n = 97) with histopathological findings probably for CA, C4d immunohistochemistry was assessed. Forty-eight cases of CA were detected. Congo red birefringence was positive in all cases, whereas in 14 cases, it was faded. In these 14 cases, the diagnosis of CA was made by means of Congo red fluorescence and Thioflavin T because the histopathological findings were highly suggestive for CA. All CA cases were positive with C4d, and in 12 of the 49 inflammatory dermatoses, C4d was positive. The interpretation of C4d immunohistochemistry can be performed more easily and rapidly than Congo red evaluation. The sensitivity and specificity of C4d were 100% and 75.5%, respectively. In our experience, C4d staining was a useful method for detecting amyloid deposits in CA. Although Congo red staining is the gold standard for amyloid detection, we propose C4d immunohistochemistry as a routine screening method or hybrid transition while further investigations are completed.
Utility of Cyclin D1 Immunostaining in Cutaneous Xanthogranuloma
Authors: Sharma Anurag , McAfee John , Wang Lin , Cook Eleanor , Ababneh Emad , Bergfeld Wilma F.
Published: September 2021

Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase pathway activation has recently been found to be associated with almost all Langerhans cell histiocytosis cases. In BRAF V600E mutation–positive cases, this activation is seen as a downstream activation. In addition, cyclin D1 is a downstream target of the MAPK pathway. Recent studies have argued in favor of using cyclin D1 as a potential neoplastic marker to differentiate Langerhans cell histiocytosis from other reactive Langerhans cell proliferations in the skin and lymph nodes. Therefore, we chose to study the immunohistochemical expression of cyclin D1 in cutaneous xanthogranuloma (XG) cases. Fifteen XG cases were retrieved and stained for cyclin D1, BRAF (v-raf murine sarcoma viral oncogene homolog B1), CD1a, and langerin (CD207). Twelve cases showed strong and diffuse nuclear positivity for cyclin D1, both in the XG cells and in the multinucleated osteoclast-like giant cells. Three cases showed focal weak nuclear staining for cyclin D1. All 15 cases showed negative immunoreactivity for BRAF, CD1a, and CD207. Although limited by small sample size, we conclude that most cases of cutaneous XG should show at least weak nuclear staining with cyclin D1. The histogenesis of XG is still largely unknown, and the finding of cyclin D1 positivity in a majority of cases may indicate a role for the MAPK/extracellular signal-regulated kinase pathway in cutaneous XG.