bluuebunny/crossref_metadata_2025 huggingface dataset:
Exosomal circ_0007385 enhances non-small cell lung cancer cell proliferation and stemness via regulating miR-1253/FAM83A axis
Authors: Ning Zhiqiang , Tian Yue , Li Yufeng , Zhao Xinfei , Zhang Jing , Wang Chunmei , Hu Jin , Shen Hua , Wu Weibing
Published: October 2021

Exosomes are critical mediators of intercellular communication in the tumor microenvironment. Exosomal circular RNAs (circRNAs) can act as biomarkers and play crucial roles in many cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to explore the functions and regulatory mechanism of exosomal circ_0007385 in NSCLC. The expression levels of circ_0007385, microRNA-1253 (miR-1253), family with sequence similarity 83, member A (FAM83A) mRNA were determined by quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2′-deoxyuridine (Edu), and colony formation assays were utilized to determine cell proliferation ability. Sphere formation efficiency was determined by sphere formation assay. All protein levels were detected by western blot assay. Exosomes were detected using transmission electron microscopy analysis. Size distribution of exosomes was analyzed by nanoparticle tracking analysis. The interaction between miR-1253 and circ_0007385 or FAM83A was confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Mice xenograft model was established to verify the function of circ_0007385 in vivo. Circ_0007385 was upregulated in NSCLC tissues and cells. Knockdown of circ_0007385 inhibited NSCLC cell proliferation and stemness, while exosomal circ_0007385 facilitated NSCLC cell proliferation and stemness. In addition, miR-1253 was a direct target of circ_0007385, and miR-1253 reversed the inhibitory effects of circ_0007385 on cell proliferation and stemness in NSCLC cells. Moreover, FAM83A was a direct target of miR-1253, and miR-1253 suppressed NSCLC cell proliferation and stemness by targeting FAM83A. Furthermore, circ_0007385 knockdown inhibited tumor growth in vivo. Exosomal circ_0007385 promoted NSCLC cell proliferation and stemness by regulating miR-1253/FAM83A axis.
Partial response of metastatic cardia neuroendocrine carcinoma with the combined therapy involving PD-1 blockade after failed multi-line chemotherapies: a case report and literature review
Authors: Yang Yang , Xu Huan , Zhang Li , Bai Liangliang , Zhu Hong , Li Qiu
Published: October 2021

Cardia neuroendocrine cancer is a rare malignant tumor. The treatment regimens mainly refer to the small-cell lung cancer diagnosis and treatment guidelines and there is no standard treatment guideline specifically for neuroendocrine cancer. The use of albumin paclitaxel plus carboplatin combined with sintilimab for refractory cardia neuroendocrine carcinoma (NEC) has never been reported. This article reported a case that a 68-year-old man presented with belching without obvious reasons who was diagnosed with refractory cardia NEC by gastroscopy and pathological results. After failure of multi-line therapy including etoposide plus cisplatin as the first-line therapy, surufatinib plus toripalimab as the second-line therapy, FOLFIRI combined with bevacizumab as the third-line therapy, he received three cycles of albumin paclitaxel plus carboplatin combined with sintilimab as the fourth-line therapy and still obtained partial response of good efficiency. After the patient received this treatment regimen, the symptoms of dysphagia disappeared and the change trends of neuron-specific enolase were decreased. The computed tomography (CT) examination after three cycles of treatment was performed to show that the measured lesions have shrunk by more than 30% compared to the baseline CT. Additionally, there were no other adverse events such as nausea, vomiting, and diarrhea, except for grade III bone marrow suppression. At present, the patient is still being treated. This is the first case report that the albumin paclitaxel plus carboplatin combined with sintilimab has achieved good efficacy after failure of multi-line treatment of cardia NEC. It is very necessary to further explore the effectiveness and safety of this regimen in the treatment of NEC.
LncRNA PCAT6 activated by SP1 facilitates the progression of breast cancer by the miR-326/LRRC8E axis
Authors: Zhu Qiannan , Wang Shui , Shi Yuenian
Published: October 2021

Breast cancer is an aggressive malignancy with high morbidity in females worldwide. Extensive studies reveal that long noncoding RNAs (lncRNAs) are abnormally expressed and act as key regulators in various cancers, including breast cancer. In this work, we investigated the role and regulatory mechanism of lncRNA prostate cancer-associated transcript 6 (PCAT6) in breast cancer progression. Our findings revealed that PCAT6 was overexpressed in breast cancer tissues and cell lines. Furthermore, elevation of PCAT6 reflected an adverse prognosis of patients. Functional experiments indicated that PCAT6 knockdown hampered cell proliferation, facilitated apoptosis and cell cycle arrest in vitro, and inhibited tumor growth in vivo. We also found that the transcription factor SP1 could bind to the PCAT6 promoter and promoted its expression. Subsequently, it was verified that PCAT6 was a molecular sponge for microRNA-326 (miR-326), and the leucine-rich repeat containing the eight family member E (LRRC8E) was a direct target of miR-326. Rescue assays revealed that LRRC8E overexpression attenuated the suppressive effect of PCAT6 knockdown on cellular progression of breast cancer. In summary, this study demonstrated that SP1-activated PCAT6 promoted the malignant behaviors of breast cancer cells by regulating the miR-326/LRRC8E axis.
Safety of Prolonged Inhalation of Hydrogen Gas in Air in Healthy Adults
Authors: Cole Alexis R. , Sperotto Francesca , DiNardo James A. , Carlisle Stephanie , Rivkin Michael J. , Sleeper Lynn A. , Kheir John N.
Published: October 2021

BACKGROUND:

Ischemia-reperfusion injury is common in critically ill patients, and directed therapies are lacking. Inhaled hydrogen gas diminishes ischemia-reperfusion injury in models of shock, stroke, and cardiac arrest. The purpose of this study was to investigate the safety of inhaled hydrogen gas at doses required for a clinical efficacy study.

DESIGN:

Prospective, single-arm study.

SETTING:

Tertiary care hospital.

PATIENTS/SUBJECTS:

Eight healthy adult participants.

INTERVENTIONS:

Subjects underwent hospitalized exposure to 2.4% hydrogen gas in medical air via high-flow nasal cannula (15 L/min) for 24 (n = 2), 48 (n = 2), or 72 (n = 4) hours.

MEASUREMENTS AND MAIN RESULTS:

Endpoints included vital signs, patient- and nurse-reported signs and symptoms (stratified according to clinical significance), pulmonary function testing, 12-lead electrocardiogram, mini-mental state examinations, neurologic examination, and serologic testing prior to and following exposure. All adverse events were verified by two clinicians external to the study team and an external Data and Safety Monitoring Board. All eight participants (18–30 yr; 50% female; 62% non-Caucasian) completed the study without early termination. No clinically significant adverse events occurred in any patient. Compared with baseline measures, there were no clinically significant changes over time in vital signs, pulmonary function testing results, Mini-Mental State Examination scores, neurologic examination findings, electrocardiogram measurements, or serologic tests for hematologic (except for clinically insignificant increases in hematocrit and platelet counts), renal, hepatic, pancreatic, or cardiac injury associated with hydrogen gas inhalation.

CONCLUSIONS:

Inhalation of 2.4% hydrogen gas does not appear to cause clinically significant adverse effects in healthy adults. Although these data suggest that inhaled hydrogen gas may be well tolerated, future studies need to be powered to further evaluate safety. These data will be foundational to future interventional studies of inhaled hydrogen gas in injury states, including following cardiac arrest.
ICU Mortality in Patients With Coronavirus Disease 2019 Infection: Highlighting Healthcare Disparities in Rural Appalachia
Authors: Sharma Sunil , Badami Varun , Rojas Edward , Mittal Abhinav , Stansbury Robert , Rana Bilal , Wilson Alison , Wen Sijin
Published: October 2021

OBJECTIVES:

To assess 30-day mortality in coronavirus disease 2019 acute respiratory distress syndrome patients transferred from rural Appalachian hospitals.

DESIGN:

Retrospective case controlled, based on consecutive patients transferred and admitted from rural hospitals to a tertiary-care ICU. The primary outcome was all-cause 30-day mortality. Kaplan-Meier method and log-rank test were used in the survival data analysis.

SETTING:

Medical ICU, West Virginia University Hospital, Morgantown, WV.

PATIENTS:

All adult patients admitted to the ICU for coronavirus disease 2019 disease between September 30, 2020, and December 2, 2020.

INTERVENTION:

Not applicable.

MEASUREMENTS AND MAIN RESULTS:

Seventy-nine consecutive coronavirus disease 2019 patients were admitted to the ICU during the defined period. Overall mortality of the cohort was 54%. Of the 79 patients, 50 were transferred from critical access hospitals/rural facilities with coronavirus disease 2019–induced acute respiratory distress syndrome. A control group consisted of 39 patients admitted to the ICU with noncoronavirus disease 2019 acute respiratory distress syndrome who were intubated and mechanically ventilated. Thirty-day mortality in patients with coronavirus disease 2019 admitted to the ICU was significantly higher than the control group (68% vs 42%) (p = 0.034). Mean Sequential Organ Failure Assessment scores were similar in both coronavirus disease 2019 acute respiratory distress syndrome group and controls. Intubation in patients 70 years or older and mechanical ventilation for over 5 days was associated with significantly higher mortality.

CONCLUSIONS:

Our data on critically ill and mechanically ventilated coronavirus disease 2019 acute respiratory distress syndrome patients transferred from critical access hospitals/rural facilities have increased mortality compared with noncoronavirus disease 2019 acute respiratory distress syndrome controls. These data suggest that lack or delay in access to tertiary care may impact coronavirus disease 2019 outcome in rural areas. Intubated patients 70 years old or more and mechanical ventilation for over 5 days may be a risk factor for increased mortality. These data may help physicians and hospital administrators in rural areas for optimal utilization of limited resources.
Allogeneic Hematopoietic Stem Cell Transplant Infusion During Venovenous Extracorporeal Membrane Oxygenation Support
Authors: Qutob Rayan , Ji Xinyu , Assanangkornchai Nawaporn , Sapon-Cousineau Vladimir , Tam May , Larotonda Rita , Routy Jean-Pierre , Popradi Gizelle , Samoukovic Gordan
Published: October 2021

BACKGROUND:

Management of hematopoietic stem cell transplant complicated by respiratory failure has been facilitated by the use of extracorporeal membrane oxygenation as a bridge to curative chemotherapeutic options. This is the first report of hematopoietic stem cell transplantation on extracorporeal membrane oxygenation in the adult population.

CASE SUMMARY:

A 28-year-old woman diagnosed with idiopathic aplastic anemia complicated by acute respiratory distress syndrome secondary to pneumonia required venovenous extracorporeal membrane oxygenation to supplement oxygenation and ventilation. She received hematopoietic stem cell transplantation while she was on extracorporeal membrane oxygenation support.

MAIN RESULTS AND CONCLUSION:

Delivery of the stem cell through extracorporeal membrane oxygenation circuit was successful in the described patient. There was no sequestered stem cell in extracorporeal membrane oxygenation circuit, and she was found to have 90% donor chimerism suggesting successful engraftment. This report showed that infusion of stem cell through extracorporeal membrane oxygenation circuit is safe and feasible, and our results suggest that successful engraftment is possible.
Induced pluripotent stem cell-derived motor neurons from amyotrophic lateral sclerosis (ALS) patients carrying different superoxide dismutase 1 mutations recapitulate pathological features of ALS
Authors: Liu Wen-Chao , Liu Na , Wang Yan , Huang Chen , Li Yan-Fang , Wang Hao , Li Xiao-Gang , Deng Min
Published: October 2021

Background:

Investigations of the pathogenic mechanisms in motor neurons (MNs) derived from amyotrophic lateral sclerosis (ALS) disease-specific induced pluripotent stem (iPS) cell lines could improve understanding of the issues affecting MNs. Therefore, in this study we explored mutant superoxide dismutase 1 (SOD1) protein expression in MNs derived from the iPS cell lines of ALS patients carrying different SOD1 mutations.

Methods:

We generated induced pluripotent stem cell (iPSC) lines from two familial ALS (FALS) patients with SOD1-V14M and SOD1-C111Y mutations, and then differentiated them into MNs. We investigated levels of the SOD1 protein in iPSCs and MNs, the intracellular Ca2+ levels in MNs, and the lactate dehydrogenase (LDH) activity in the process of differentiation into the MNs derived from the controls and ALS patients’ iPSCs.

Results:

The iPSCs from the two FALS patients were capable of differentiation into MNs carrying different SOD1 mutations and differentially expressed MN markers. We detected high SOD1 protein expression and high intracellular calcium levels in both the MN and iPSCs that were derived from the two SOD1 mutant patients. However, at no time did we observe stronger LDH activity in the patient lines compared with the control lines.

Conclusions:

MNs derived from patient-specific iPSC lines can recapitulate key aspects of ALS pathogenesis, providing a cell-based disease model to further elucidate disease pathogenesis and explore gene repair coupled with cell-replacement therapy. Incremental mutant expressions of SOD1 in MNs may have disrupted MN function, either causing or contributing to the intracellular calcium disturbances, which could lead to the occurrence and development of the disease.
Selective elimination of host cells harboring replication-competent human immunodeficiency virus reservoirs: a promising therapeutic strategy for HIV cure
Authors: Zaongo Silvere D. , Wang Yue , Ma Ping , Song Fang-Zhou , Chen Yao-Kai
Published: October 2021

Many seminal advances have been made in human immunodeficiency virus (HIV)/AIDS research over the past four decades. Treatment strategies, such as gene therapy and immunotherapy, are yielding promising results to effectively control HIV infection. Despite this, a cure for HIV/AIDS is not envisioned in the near future. A recently published academic study has raised awareness regarding a promising alternative therapeutic option for HIV/AIDS, referred to as “selective elimination of host cells capable of producing HIV” (SECH). Similar to the “shock and kill strategy,” the SECH approach requires the simultaneous administration of drugs targeting key mechanisms in specific cells to efficiently eliminate HIV replication-competent cellular reservoirs. Herein, we comprehensively review the specific mechanisms targeted by the SECH strategy. Briefly, the suggested cocktail of drugs should contain (i) latency reversal agents to promote the latency reversal process in replication-competent reservoir cells, (ii) pro-apoptotic and anti-autophagy drugs to induce death of infected cells through various pathways, and finally (iii) drugs that eliminate new cycles of infection by prevention of HIV attachment to host cells, and by HIV integrase inhibitor drugs. Finally, we discuss three major challenges that are likely to restrict the application of the SECH strategy in HIV/AIDS patients.
Discriminative stimulus properties of the 5-HT1A receptor biased agonists NLX-101 and F13714, in rats trained to discriminate 8-OH-DPAT from saline
Authors: Broadbear Jillian H. , Depoortere Ronan Y. , Vacy Kristina , Ralph David , Tunstall Brendan J. , Newman-Tancredi Adrian
Published: October 2021

NLX-101 and F13714 are selective, full efficacy, biased agonists of the serotonin (5-HT1A) receptor. NLX-101 preferentially activates cortical postsynaptic 5-HT1A receptors, whereas F13714 preferentially activates raphe nuclei presynaptic 5-HT1A receptors. We compared NLX-101 and F13714 for their efficacy and potency to substitute for the discriminative cue produced by the prototypical, nonbiased 5-HT1A receptor agonist 8-OH-DPAT (racemate). Male and female Sprague–Dawley rats were trained to discriminate 8-OH-DPAT (0.1 mg/kg i.p., 20 min pretreatment) from saline using a classical two-lever drug-discrimination procedure. 8-OH-DPAT (0.01 and 0.05 mg/kg i.p.) dose-dependently substituted for the training dose, with about 50% responding on the 8-OH-DPAT-associated lever at 0.05 mg/kg. F13714 fully and very potently substituted for the training dose of 8-OH-DPAT from 0.018 mg/kg i.p., whereas NLX-101 only achieved full substitution at 0.5 mg/kg i.p., a dose which is known to also activate presynaptic 5-HT1A receptors. The 5-HT1A receptor partial agonist, buspirone, partially substituted (~80%) at 1 and 2 mg/kg i.p., doses which also decreased response rates. F13714 decreased response rates at 0.05 mg/kg. The selective 5-HT1A receptor antagonist WAY-100 635 (1 mg/kg s.c., 40 min pretreatment) elicited almost no responding on the 8-OH-DPAT-associated lever by itself, but blocked the discriminative stimulus effects produced by administration (20 min pretreatment) of 8-OH-DPAT (0.1 mg/kg), F13714 (0.025 mg/kg), NLX-101 (0.5 mg/kg) or buspirone (1 mg/kg). These data suggest that the discriminative cue produced by 0.1 mg/kg i.p. 8-OH-DPAT results from activation of presynaptic 5-HT1A receptors. They also further demonstrate the distinct profiles in behavioral models of 5-HT1A receptor-biased agonists.
Phencynonate hydrochloride exerts antidepressant effects by regulating the dendritic spine density and altering glutamate receptor expression
Authors: Zhu Yingqi , Qu Yishan , Zhang Jing , Hou Jun , Fang Jie , Shen Jingxuan , Xu Chang , Huang Minyi , Qiao Hui , An Shucheng
Published: October 2021

Phencynonate hydrochloride (PCH) is a drug that crosses the blood–brain barrier. Cellular experiments confirmed that PCH protects against glutamate toxicity and causes only weak central inhibition and limited side effects. As shown in our previous studies, PCH alleviates depression-like behaviours induced by chronic unpredictable mild stress (CUMS). Here we administered PCH at three different doses (4, 8 and 16 mg/kg) to male rats for two continuous days after CUMS and conducted behavioural tests to assess the dose-dependent antidepressant effects of PCH and its effects on the neuroplasticity in the hippocampus and medial prefrontal cortex (mPFC). Meanwhile, we measured the spine density and expression of related proteins to illustrate the mechanism of PCH. PCH treatment (8 mg/kg) significantly alleviated depression-like behaviours induced by CUMS. All doses of PCH treatment reversed the spine loss in prelimbic and CA3 regions induced by CUMS. Kalirin-7 expression was decreased in the hippocampus and mPFC of the CUMS group. The expression of the NR1 and NR2B subunits in the hippocampus, and NR2B in mPFC are increased by CUMS. PCH treatment (8 and 16 mg/kg) reversed all of these changes of Kalirin-7 in PFC and hippocampus, as well as NR1 and NR2B expression in the hippocampus. PCH is expected to be developed as a new type of rapid antidepressant. Its antidepressant effect may be closely related to the modulation of dendritic spine density in the prelimbic and CA3 regions and the regulation of Kalilin-7 and N-methyl-D-aspartic acid receptor levels in the hippocampus.
Direct comparison of the reproducibility of in-office and self-measured home blood pressures
Authors: Asayama Kei , Ohkubo Takayoshi , Rakugi Hiromi , Miyakawa Masaaki , Mori Hisao , Katsuya Tomohiro , Ikehara Yumi , Ueda Shinichiro , Ohya Yusuke , Tsuchihashi Takuya , Kario Kazuomi , Miura Katsuyuki , Ito Sadayoshi , Umemura Satoshi
Published: October 2021

Objective:

The aim was to compare short-term and long-term reproducibilities of in-office unattended blood pressure (BP), namely automated office blood pressure (AOBP), conventionally measured attended office BP, and self-measured home BP.

Methods:

A multicentre, clinical study was conducted in Japan, and 287 Japanese outpatients on antihypertensive drug medication were followed-up for 1 year.

Results:

The intensity of drug treatment was sustained consistently throughout the study period (defined daily doses, 1.62–1.68; P = 0.12). The mean SBP differences between baseline and 1 month later, as well as baseline and 1 year later, were less than 1.5 mmHg, whereas the standard deviations of the differences for home, AOBP, and attended office measurements for the 1-year interval were 7.7, 14.5, and 15.3 mmHg, respectively. The coefficients of variation were significantly smaller for home BP than for AOBP among all patients at both 1-month and 1-year intervals (P < 0.0001). In the 1-month interval, partial correlation coefficients of home BP (r, 0.73/0.88 for systolic/diastolic measures) were significantly higher than of conventional BP (r, 0.47/0.69). However, the correlations converged to the modest level regardless of BP information (r, 0.49–0.54/0.63–0.73) when the 1-year interval was assessed. Results were confirmatory when patients on the same drug regimen (n = 167) were analysed.

Conclusion:

A higher reproducibility of home BP was demonstrated compared with in-office BP, including AOBP. However, the modest correlations for the 1-year interval support the importance of regular assessment of BP, regardless of in-office or home measurements for treatment of hypertension.
PARACENTRAL ACUTE MIDDLE MACULOPATHY IN BEHCET DISEASE
Authors: Song Delu , Choi Daniel J. , Bhatt Nirali
Published: October 2021

Purpose:

To report a novel presentation of bilateral paracentral acute middle maculopathy and peripheral vascular occlusions in Behcet disease.

Methods:

A retrospective case report with multimodal imaging studies of a patient with Behcet's disease.

Results:

A 58-year-old Chinese man presented with a paracentral scotoma, fever, arthralgias, and skin rash. Human leukocyte antigen (HLA) typing revealed HLA-B51 positivity. Ophthalmic examination showed peripheral retinal hemorrhages and fluorescein angiography (FA) demonstrated vascular occlusions in the peripheral retina bilaterally. Optical coherence tomography showed classic acute paracentral acute middle maculopathy lesions in both eyes.

Conclusions:

Paracentral acute middle maculopathy and peripheral vascular occlusion are infrequent and unconventional presentations of Behcet disease. To the best of our knowledge, this is the first report in the ophthalmic literature of paracentral acute middle maculopathy and peripheral vascular occlusion in Behcet disease.
Long-Term Outcomes of Bowman Layer Inlay Transplantation for the Treatment of Progressive Keratoconus
Authors: van der Star Lydia , van Dijk Korine , Vasiliauskaitė Indrė , Dapena Isabel , Oellerich Silke , Melles Gerrit R. J.
Published: October 2021

Purpose:

To report long-term clinical outcomes and estimated success rates after Bowman layer (BL) inlay transplantation in eyes treated for progressive keratoconus (KC).

Methods:

Thirty-five eyes (29 patients) with progressive KC underwent BL inlay transplantation. Best-corrected spectacle and contact lens visual acuity, Scheimpflug-based corneal tomography [simulated and maximum keratometry (Kmax)], central corneal thickness, thinnest point thickness, complications, and success rate were evaluated up to 8 years postoperatively for the total group and 2 subgroups [group 1: preoperative Kmax > 69 diopter (D) (n = 26); group 2: preoperative Kmax < 69D (n = 9)].

Results:

Mean logarithm of the minimum angle of resolution best contact lens–corrected visual acuity for the total group and the 2 subgroups did not change from preoperative up to the last available follow-up (all P > 0.05), whereas best spectacle–corrected visual acuity improved for group 1 (P = 0.03). Group 1 showed an average Kmax reduction of 7D in the first month (P < 0.001) with no further changes up to 8 years postoperatively (P > 0.05), whereas no significant changes were observed in group 2 (all P > 0.05). Postoperative KC progression occurred in 4 eyes (n = 3 group 1, n = 1 group 2) and 1 eye (group 2) underwent retransplantation for unsatisfactory visual performance. Kaplan–Meier analysis showed an estimated success rate of 85% at the 5 to 8 years follow-up in group 1 and of 75% at the 5 to 7 years follow-up for group 2.

Conclusions:

BL inlay transplantation stabilized KC in most eyes along with preservation of contact lens tolerance up to 8 years postoperatively and may be a successful treatment option, in particular for eyes with progressive advanced KC (Kmax > 69D).
Acute Corneal Transplant Rejection After COVID-19 Vaccination
Authors: Shah Amar P. , Dzhaber Daliya , Kenyon Kenneth R. , Riaz Kamran M. , Ouano Dean P. , Koo Ellen H.
Published: October 2021

Purpose:

The purpose of this report was to describe 4 cases of acute corneal transplant rejection occurring in association with coronavirus disease 2019 (COVID-19) mRNA vaccination.

Methods:

Four patients with prior keratoplasty developed presumed immunologic rejection after the mRNA-1273 vaccination for coronavirus 2 (SARS-CoV-2). Case 1 had received Descemet membrane endothelial keratoplasty 6 months ago and presented with endothelial graft rejection 3 weeks after the first vaccine dose. Case 2 had undergone penetrating keratoplasty 3 years previously and presented with acute endothelial rejection 9 days after the second vaccine dose. Case 3 had prior Descemet stripping automated endothelial keratoplasty (DSAEK) and began experiencing symptoms of endothelial graft rejection 2 weeks after the second vaccine dose. Case 4 presented with endothelial rejection of the penetrating keratoplasty graft 2 weeks after the second vaccine dose.

Results:

Frequent topical corticosteroids alone were initiated in all 4 cases. In case 1, the endothelial rejection line appeared fainter with improvement in visual acuity and corneal edema 5 weeks after diagnosis. Case 2 experienced complete resolution of corneal stromal edema and rejection line 6 weeks after diagnosis. Cases 3 and 4 have both experienced initial improvement with steroid treatment as well.

Conclusions:

These cases suggest acute corneal endothelial rejection may occur soon after either dose of the COVID-19 mRNA vaccine. Prompt initiation of aggressive topical steroid therapy may result in complete resolution of clinical signs and symptoms. Further studies are needed to elucidate the causal mechanism of corneal graft rejection after COVID-19 vaccination.
Longitudinal Reciprocal Relationships Between the Psychosocial Work Environment and Burnout
Authors: Shahidi Faraz Vahid , Smith Peter M. , Oudyk John , Gignac Monique A.M.
Published: October 2021

Objective:

To examine longitudinal reciprocal relationships between the psychosocial work environment and burnout.

Methods:

We used two-wave cross-lagged panel models to estimate associations between a wide range of psychosocial work factors (ie, job demands, job control, job insecurity, coworker support, supervisor support, and organizational justice) and burnout in a broadly representative sample of the general working population in Canada (n = 453).

Results:

Bidirectional associations between the psychosocial work environment and burnout were observed. Results supported the causal predominance of psychosocial work factors over burnout. Higher job demands, lower job control, higher job insecurity, and lower organizational justice predicted burnout over time. Burnout only predicted lower supervisor support over time.

Conclusions:

Our findings suggest that stress at work is better understood as a cause rather than a consequence of burnout in the general working population.
Organizational Best Practices Supporting Mental Health in the Workplace
Authors: Wu Ashley , Roemer Enid Chung , Kent Karen B. , Ballard David W. , Goetzel Ron Z.
Published: October 2021

Objective:

To provide a narrative review of best and promising practices for achieving exemplary mental health in the workplace as the foundation for the inaugural Carolyn C. Mattingly Award for Mental Health in the Workplace.

Methods:

Research was drawn from peer-reviewed articles using the search terms associated with workplace mental health.

Results:

Eight categories of best practices were identified: (1) culture, (2) robust mental health benefits, (3) mental health resources, (4) workplace policies and practices, (5) healthy work environment, (6) leadership support, (7) outcomes measurement, and (8) innovation.

Conclusion:

The review provided the scientific backing to support criteria developed for the Carolyn C. Mattingly Award for Mental Health in the Workplace. By recognizing organizations that apply evidence-based practices in their health and well-being programs, the Mattingly Award may inspire employers to adopt best practices.
Exploring Factors Responsible for Delay in Pediatric Cochlear Implantation
Authors: DeVries Jacquelyn , Ren Yin , Purdy Julie , Carvalho Daniela , Kari Elina
Published: October 2021

Objective:

To identify and characterize demographic and socioeconomic factors associated with delays in cochlear implantation (CI) in children.

Study Design:

Retrospective.

Setting:

Tertiary pediatric CI referral center.

Patients:

All patients under 18 years of age receiving CI between March 2018 and February 2020.

Interventions:

CI.

Main Outcome Measures:

Primary outcome measures included age at implantation and time from hearing loss diagnosis and candidacy evaluation to CI.

Results:

Seventy-two patients were identified (44% women, average age at implantation 4.9 yr). Age at implantation was older in patients with public, rather than private, insurance (6.0 ± 0.8 yr versus 3.1 ± 0.7 yr, p = 0.007) and those from low-income areas (8.6 ± 7.6 yr versus 2.4 ± 3.0 yr, p = 0.007). Time between hearing loss diagnosis and implantation was longer in publicly insured patients (4.1 ± 0.6 yr versus 2.2 ± 0.5 yr, p = 0.014). Time between identification as a CI candidate and implantation was longer in publicly insured patients (721 ± 107d versus 291 ± 64 d, p = 0.001). Among children with congenital profound hearing loss, publicly insured patients continued to be older at implantation (1.9 ± 0.2 versus 1.0 ± 0.2 yr, p = 0.008). Latinx children were more often publicly insured whereas white children were more often privately insured (p < 0.05). Publicly insured patients had delays in the pre-CI workup, including, in no particular order, vestibular evaluation (621 ± 132 d versus 197 ± 67 d, p = 0.007), developmental evaluation (517 ± 106 d versus 150 ± 56 d, p = 0.003), speech evaluation (482 ± 107 d versus 163 ± 65 d, p = 0.013), and children's implant profile (ChIP) assessment (572 ± 107d versus 184 ± 59d, p = 0,002). On ChIP evaluation, concerns regarding educational environment and support were higher in Spanish-speaking children (p = 0.024; p = 2.6 × 10−4) and children with public insurance (p = 0.016; p = 0.002).

Conclusions:

Disparities in access to CI continue to affect timing of pediatric cochlear implantation.
A comparison between on-demand usage of rFVIIa vs prophylaxis use of emicizumab in high titer inhibitory hemophilia A patients in Iran
Authors: Saiyarsarai Parisa , Robabpour Derakhshan Atefeh , Khedmati Jamaleddin , Eshghi Peyman , Seyedifar Meysam
Published: October 2021

Background:

Hemophilia A (HA) is an inherited X-linked bleeding disease with costly treatment, especially for high titer inhibitory patients. Emicizumab, a new humanized bispecific antibody, has been approved for use to prevent or reduce the frequency of bleeding episodes in HA patients with inhibitors. This study evaluated the cost-utility of emicizumab prophylaxis (EP) in comparison with recombinant factor VII activated on-demand treatment in HA patients with inhibitors.

Methods:

A life-time Markov model with payer and societal perspectives was developed in different age groups with different annual bleeding rates (ABR). Efficacy of treatments were extracted from HAVEN trials. Utilities were retrieved from published evidence. Costs were calculated based on Iran food and drug administration official website, national tariff book for medical services and hospital data. One-way deterministic sensitivity analysis was performed.

Results:

EP was dominant choice in comparison with on-demand administration of recombinant factor VII activated in all age groups with ABR 20 and 25, and it remained dominant in patients with age 2 and age 12 at start point with ABR 16 and 17. The reported incremental cost-effectiveness ratio for the group with ABR 18 at the age 20, was 12,936 United States Dollars which is lower than the acceptable threshold of cost-effectiveness in Iran (1–3 gross domestic product per capita) and EP can be considered as cost-effective choice in this scenario.

Conclusion:

EP was found to be a dominant and cost-effective choice for Iranian HA patients with factor VIII inhibitors with ABR 18 and above with considerable cost saving.
Decreasing recurrence and increasing survival rates in patients of ethmoid or sphenoid intestinal-type adenocarcinomas
Authors: Huang Ethan I. , Lu Ang , Tsai Yao-Te , Wang Ting-Chung , Chuang Huei-Chieh , Chen Wen-Cheng , Chen Ping-Tsung
Published: October 2021

Background:

Ethmoid or sphenoid intestinal-type adenocarcinomas (ITACs) form a distinct subtype of sinonasal adenocarcinomas that occur less than 1 case/100,000/yr. They have obvious exposure relationship to hardwood or leather dusts, infrequent metastasis, but a relatively high local-recurrence rate. They locate at sinuses close to vital structures listed as high-risk areas in surgeries. Even in expert hands, a craniofacial resection is associated with non-negligible mortality and morbidity. Management of these tumors, first or recurrent, needs to weigh these consequences versus the survival, regional-recurrence, and distant-recurrence rates. Due to the rareness of ethmoid or sphenoid ITACs, accurate overall survival and local- or regional-recurrence rates across diverse treatments are unclear. The aim of this study is to report the overall statistics of this cancer and the relationship between enrollment year versus age, recurrence, and survival.

Methods:

Systemic review and meta-analysis with 1126 cases across various treatments in the literature.

Results:

Here, we show that patients of ethmoid or sphenoid ITACs had overall local-, regional-, and distant-recurrence rates of 32.2%, 2.2%, and 10.3%, respectively, with a 5-year overall survival rate of 66.2%. The results present a significant correlation between age, local-recurrent rate, or overall survival rate versus enrollment year.

Conclusion:

This suggests that recent patients of ethmoid or sphenoid ITACs may present at an older mean age, have a lower local-recurrence rate, and have a better 5-year survival rate than before. There was a shifting trend of treating ethmoid ITACs from external approach to endoscopic resection. Clinicians may want to weigh mortality and morbidity rates of external surgeries and these data to share or decide a solution.
Rectal mixed adenoneuroendocrine carcinoma
Authors: Silva Diogo J. , dos Santos Joana , Vaz Ana Paula , Mesquita Alexandra
Published: October 2021

Rationale:

Colorectal mixed neuroendocrine–nonneuroendocrine neoplasms constitute a rare group of gastrointestinal tumors composed by both neuroendocrine and nonneuroendocrine components. Nondiagnostic macroscopic features, specific histological features, and poor awareness of the disease are responsible for the underestimated incidence and conflicting data available. Due to lack of randomized clinical trials and validated clinical guidelines, diagnostic and therapeutic approach are based on the standard of care for pure colorectal neuroendocrine carcinomas or adenocarcinomas.

Patient concerns:

A 76-year-old caucasian male, without relevant medical or familial history, presented a positive faecal occult blood test during colorectal cancer screening.

Diagnosis:

Total colonoscopy identified a rectal lesion with biopsy showing a moderate rectal adenocarcinoma staged as cT2N0M0.

Interventions:

Anterior resection of the rectum with right ileostomy followed by local radiotherapy with radio-sensitising chemotherapy and adjuvant chemotherapy with capecitabine 1000 mg bid plus oxaliplatin 130 mg/m2. Due to chronic nodular pulmonary aspergillosis and chemotherapy induced immunosuppression patient was on 400 mg/daily of oral voriconazole.

Outcomes:

Overall survival of 15 months after progression under first line treatment and under palliative chemotherapy with platinum plus etoposide regimen.

Lessons:

The reported case illustrates the challenge associated to the management of mixed neuroendocrine–nonneuroendocrine carcinomas due to lack of validated guidelines and scientific evidence. From diagnosis and staging to treatment, all steps must be tailored to individual clinical and histological features.
Risk of herpes zoster associated with biological therapies for psoriasis and psoriatic arthritis
Authors: Zou Ailing , Chen Yongjun , Shi Nian , Ye Yu
Published: October 2021

Background:

Biological therapy is effective for the treatment of psoriasis and psoriatic arthritis; however, adverse effects related to immunosuppression, such as viral infections, have been reported. Amongst these infections, herpes zoster (HZ) is common.

Objective:

To evaluate the risk of HZ in psoriasis and psoriatic arthritis patients treated with biological therapy.

Data sources:

A comprehensive literature search of PubMed, Embase, and Web of Science was performed using certain keywords until October 9, 2020. Nine studies were included after a detailed assessment.

Study eligibility criteria:

The eligibility criteria included randomized controlled trials (RCTs) and observational studies of patients with psoriasis or psoriatic arthritis treated with biological therapies; compared with non-biological therapies, non-biological systemic therapies, or controls; with the incidence of HZ reported in case and control groups. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of the RCTs and observational studies, respectively. Data were extracted from 9 eligible studies and then analyzed using Stata software (Version 12.0).

Results:

The risk of HZ in biological therapies was higher than that in non-biological (odds ratios [OR]: 1.48; 95% confidence interval [CI]: 1.18–1.86; I
2 = 0%) and non-biological systemic (OR: 1.32; 95% CI: 1.02–1.71; I
2 = 0%) therapies. Furthermore, the risk of HZ associated with tumor necrosis factor-α inhibitors increased significantly (OR: 1.50; 95% CI: 1.11–2.02; I
2 = 0%). Notably, infliximab (OR: 2.43; 95% CI: 1.31–4.50; I
2 = 0%) and etanercept (OR: 1.65; 95% CI: 1.07–2.56; I
2 = 0%) increased the risk of HZ, while adalimumab (OR: 1.21; 95% CI: 0.64–2.30; I
2 = 0%), ustekinumab (OR: 2.20; 95% CI: 0.89–5.44; I
2 = 0%), alefacept (OR: 1.46; 95% CI: 0.20–10.47; I
2 = 0%), and efalizumab (OR: 1.58; 95% CI: 0.22–11.34; I
2 = 0%) did not.

Limitations:

Few RCTs have reported HZ incidents; thus, our results require confirmation via large-scale RCTs.

Conclusions and implications of key findings:

Biological therapies, especially tumor necrosis factor-α inhibitors, may lead to the risk of HZ in psoriasis and psoriatic arthritis patients. Amongst these agents, infliximab and etanercept have been shown to significantly increase the risk of HZ. Additionally, younger age and female sex may be risk factors.

Systematic review registration number:

INPLASY202110027.
Efficacy and safety of Xinkeshu in the treatment of angina pectoris of coronary heart disease
Authors: Fan Maoxia , Guo Dong , Wang Yiming , Liu Yongcheng , Zhao Jisen , Yu Zhou
Published: October 2021

Background:

The incidence of angina pectoris (AP) of coronary heart disease (CHD) is increasing in the world, which seriously affects people's lives and brings a huge economic burden. The clinical research on Xinkeshu (XKS) in the treatment of AP of CHD has been increasing. However, there is no systematic review and meta-analysis. This study intends to provide a basis for systematically evaluating the efficacy and safety of XKS combined with conventional western medicine in the treatment of AP of CHD.

Methods:

CNKI, Wanfang, VIP, Web of Science, PubMed, Cochrane Library, and EMbase databases were searched for the period from the establishment of the database to August 31, 2021. The clinical randomized controlled trials of XKS in the treatment of AP of CHD were collected. Two systematic reviewers independently selected the literature, extracted the data, and evaluated the quality according to the inclusion and exclusion criteria. The methodological quality of the literature was evaluated using Cochrane Handbook 5.3.0 bias risk assessment tool, RevMan 5.3.0 software was used for meta-analysis and GRADE3.6 evidence quality grading system was used to evaluate the quality.

Results:

This study intended to evaluate the efficacy and safety of XKS in the treatment of AP of CHD from many aspects, including the frequency of AP, the duration of AP, the dosage of nitroglycerin, and the efficacy of ECG (total effective rate = markedly effective + effective). The secondary indicators included the efficacy of AP (total effective rate = significant + effective), blood lipids (triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), hemorheology (whole blood viscosity, plasma viscosity, and fibrinogen), serum factors (C-reactive protein, endothelin-1, homocysteine, and nitric oxide), and adverse drug reactions.

Conclusion:

The conclusion of the systematic review intended to provide clear evidence of clinical application of XKS combined with conventional western medicine in the treatment of AP of CHD, which can be widely used in the clinic.
Better discrimination of the concomitant peri-ankle fractures in the spiral tibial shaft fractures by thin-slice axial and three-dimensional CT
Authors: Suzuki Takashi , Kurozumi Taketo , Nakayama Yuhei , Matsui Kentaro , Watanabe Yoshinobu , Sakamoto Tetsuya , Morimura Naoto
Published: October 2021

The objective of this study was to examine the morphologic features of spiral tibial shaft as well as concomitant fibular and peri-ankle fractures on multidetector high-resolution CT and to speculate about the mechanisms underlying these combined fractures.

This is a retrospective cohort study. A total of 197 tibial shaft fractures underwent multidetector high-resolution CT before intramedullary nailing. The presence and location of peri-ankle fractures were recorded using thin-slice axial CT. Tibial shaft fractures were classified as spiral or non-spiral. The morphologies of spiral tibial fractures and concomitant lateral malleolar fractures were delineated using three-dimensional CT.

Seventy-five spiral and 122 non-spiral fractures were identified. Peri-ankle fractures excluding lateral malleolar fractures were found in 77.3% of spiral fractures and 18.9% of non-spiral fractures. The most frequent location of peri-ankle fractures in the spiral group was the posterior malleolus, followed by the anterolateral distal tibia, while the medial malleolus was the most frequent site in the non-spiral group. Of 75 spiral fractures, 72 showed a fracture morphology attributed to external rotation force. There were 13 lateral malleolar fractures that were defined as within 6 cm from the distal end of the fibula. No lateral malleolar fractures showed the typical morphology of isolated supination/external rotation-type ankle injuries. The displaced syndesmotic injuries commonly coexisting in pronation/external rotation-type ankle injuries were not observed.

Most spiral tibial shaft fractures were caused by external rotation force. However, the morphology of concomitant peri-ankle fractures was inconsistent with typical mechanisms of isolated external rotation ankle injuries.
Analysis of serum hepatitis B virus RNA levels among HBsAg and HBsAb copositive patients and its correlation with HBV DNA
Authors: Xiang Yu , Yang Yang , Chen Pu , Lai Xiaofei , Shi Shan , Li Shuang , You Wenxian
Published: October 2021

There are approximately 2 billion HBV-infected individuals worldwide, and approximately 1.87% to 7% of these individuals are copositive for HBsAg and HBsAb.

Our study detected hepatitis B virus pgRNA (HBV RNA) levels in HBsAg and HBsAb copositive patients and then analyzed the correlation with HBV DNA, HBsAg, ALT, and AST levels. A total of 149 HBsAg and HBsAb copositive patients were identified from 66,617 outpatients.

HBV RNA, HBV DNA, HBsAg, ALT, and AST serum levels were significantly different in different natural phases of HBV infection (immune tolerance phase, immune clearance phase, low replication phase, and reactivation phase) with statistical significance (P < .01). HBV RNA levels were positively correlated with HBV DNA, HBsAg, ALT, and AST levels. HBV RNA and HBV DNA levels were significantly increased in the HBeAg-positive group (66 patients) compared with the HBeAg-negative group (83 patients) (P < .01). In the HBeAg-positive group, HBV RNA levels were positively correlated with HBV DNA and HBsAg levels. In the HBeAg-negative group, HBV RNA levels were positively correlated with HBV DNA. Serum HBV RNA levels were positively correlated with HBV DNA, HBsAg, ALT, and AST levels.

HBV RNA could be used as a virological indicator for antiviral therapy in HBsAg and HBsAb copositive hepatitis B patients.
The prevention of postoperative port-site adhesion following single-port access (SPA) laparoscopic surgeries
Authors: Noh Joseph J. , Kim Myeong-Seon , Jeong Soo-Young , Kang Jun-Hyeok , Park Byung-Kwan , Kim Tae-Joong
Published: October 2021

No studies have examined the issue of intraabdominal port-site adhesion following single-port access (SPA) laparoscopic surgeries. The purpose of the present study was to investigate the clinical effects of temperature-sensitive adhesion barrier solution in preventing periumbilical adhesion in SPA laparoscopy. This was a prospective, single-arm study in which patients were given GUARDIX-SGTM after SPA laparoscopic surgery for benign gynecologic diseases. One gram of GUARDIX-SGTM was applied on the abdominal viscera just below the umbilical port site and adjacent abdominal wall prior to fascia closure. The primary endpoint was the incidence of postoperative adhesion evaluated by visceral sliding technique through transabdominal sonography after three months. Between June 2019 and March 2020, a total of 37 healthy patients without any history of previous abdominal surgery received SPA laparoscopic surgery by a single surgeon. No postoperative complications such as wound dehiscence or surgical site infection occurred during the follow-up period of three months. No postoperative adhesion around the umbilicus was noted in all 37 patients. The mean visceral movement measured by transabdominal sonography during maximal respiration was 4.9 cm (4.9 ± 1.9 cm). Using an adhesion barrier around the port site prior to fascia closure prevents postoperative adhesion in benign SPA laparoscopic gynecologic surgery.