bluuebunny/crossref_metadata_2025 huggingface dataset:
The identification of the anthracycline aclarubicin as an effective cytotoxic agent for pancreatic cancer
Authors: Brouwer Thomas P. , van der Zanden Sabina Y. , van der Ploeg Manon , van Eendenburg Jaap D.H. , Bonsing Bert A. , de Miranda Noel F.C.C. , Neefjes Jacques J. , Vahrmeijer Alexander L.
Published: March 2022

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer, mainly due to its delayed diagnosis and lack of effective therapeutic options. Therefore, it is imperative to find novel treatment options for PDAC. Here, we tested a series of conventional chemotherapeutics together with anthracycline compounds as single agents or in combination, determining their effectivity against established commercial and patient-derived, low-passage PDAC cell lines. Proliferation and colony formation assays were performed to determine the anticancer activity of anthracyclines; aclarubicin and doxorubicin, on commercial and patient-derived, low-passage PDAC cell lines. In addition, the effect of standard-of-care drugs gemcitabine and individual components of FOLFIRINOX were also investigated. To evaluate which mechanisms of cell death were involved in drug response, cleavage of poly(ADP-ribose)polymerase was evaluated by western blot. Aclarubicin showed superior antitumor activity compared to other anthracyclines and standard of care drugs (gemcitabine and individual components of FOLFIRINOX) in a patient-derived, low-passage PDAC cell line and in commercial cell lines. Importantly, the combination of gemcitabine and aclarubicin showed a synergistic effect at a dose range where the single agents by themselves were ineffective. In parallel, evaluation of the antitumor activity of aclarubicin demonstrated an apoptotic effect in all PDAC cell lines. Aclarubicin is cytotoxic for commercial and patient-derived low-passage PDAC cell lines, at doses lower than peak serum concentrations for patient treatment. Our findings support a (re)consideration of aclarubicin as a backbone of new combination regimens for pancreatic cancer patients.
Poor response to selpercatinib plus crizotinib in a rearranged during transfection fusion-positive patient with acquired selpercatinib-resistant MNNG HOS transforming amplification: a case report
Authors: Meng Zhaoting , Zhang Cuicui , Zuo Ran , Zhu Fuyi , Wang Yajie , Mi Re , Zhang Meng , Chen Peng
Published: March 2022

Selpercatinib has been approved by most major regulatory bodies in 2020 and become the standard therapy for rearranged during transfection (RET)-rearranged nonsmall–cell lung cancer (NSCLC). Knowledge is limited regarding mechanisms of resistance to selpercatinib and effective treatment. One study identified MNNG HOS transforming (MET) amplification as intrinsic or secondary resistance mechanism from four patients, and three of them showed ~40% tumor reduction when treated with selpercatinib plus crizotinib. We report a 30-year-old female nonsmoker diagnosed in 2019 with stage IV lung adenocarcinoma harboring KIF5B-RET and a novel FOXD1-RET fusion. Frontline therapy consisted of bevacizumab combined with pemetrexed and carboplatin and achieved a progression-free survival (PFS) of 14 months with best response of stable disease. The patient then enrolled in the LIBRETTO-321 trial (NCT03157129) and started selpercatinib, which elicited a PFS of 9 months with best response of partial response. MNNG HOS transforming (MET) amplification was subsequently detected upon progression on selpercatinib, and the patient was placed on third-line treatment with selpercatinib plus crizotinib. However, her health deteriorated rapidly and died of cancer 4 months later. We provided additional evidence supporting MET amplification as an acquired mechanism of resistance to selective RET inhibition. In addition, the apparent lack of response to selpercatinib plus crizotinib in this case highlights the need for future cohort studies for examining the value of combining RET and MET inhibitors in treating RET-rearranged, MET-amplified NSCLC.
Hypoxia-inducible factor-1α inhibition augments efficacy of programmed cell death 1 antibody in murine prostatic cancer models
Authors: Shen Zhonghua , Pei Qiong , Zhang Huimin , Yang Chao , Cui Haijun , Li Bin , Liu Jian , Bo Zhiqiang , Wei Feng , Zhang Min , Liu Chuang
Published: March 2022

This study was designed to explore whether hypoxia-inducible factor-1α (HIF-1α) inhibitor could enhance immunotherapy efficacy in prostate cancer. Western blot was used to detect the expression of HIF-1α in the tumor and peritumor tissues from prostate cancer patients. The analysis from Cancer Genome Atlas database was used to show an association between HIF-1α expression and survival rate in prostate cancer patients. Murine prostate cell–derived xenograft (CDX) model was set up in both nude mice and BALB/c mice to observe the therapeutic effect of HIF-1α inhibitor IDF-11774. Protein expression of HIF-1α, as well as changes in the immune microenvironment, was detected. Moreover, the synergistic antitumor effect of IDF-11774 and PD-1 antibody was detected in another murine prostate cancer model. HIF-1α was found to have higher expression in prostate cancer tumor tissue than in peritumor tissue, and the expression level was negatively correlated with survival rate (P = 0.0157). HIF-1α inhibitor IDF-11774 reduced tumor volume and exhibited better efficacy in BALB/c mouse model (P < 0.0001) with normal immune system, with the same suppression level against HIF-1α. HIF-1α inhibitor reduced CD45+CD11b+Gr-1+ myeloid-derived suppressor cells (P = 0.0027) and CD45+ CD11b+F4/80+CD206hi M2 macrophages (P = 0.0059) but increased the abundance of CD45+CD3+CD8+ T cells (P = 0.0002) and CD45+CD3+CD4+ T cells (P = 0.0001) in tumor-infiltrating immune cells. The same synergistic effect was observed in RM-1 murine prostate CDX tumor model. HIF-1α inhibition augmented the antitumor efficacy of immune checkpoint inhibitor PD-1 antibody in murine prostate cancer models, probably through modulating the immunosuppressive microenvironment.
RNF185 antisense RNA 1 (RNF185-AS1) promotes proliferation, migration, and invasion in papillary thyroid carcinoma
Authors: Liu Dong , Zhang Mingchen , Song Yuanyuan , Yang Ning
Published: March 2022

Long noncoding RNA (lncRNA) plays an important role in multiple cancers. So far, the exact function of lncRNAs in papillary thyroid carcinoma (PTC) is unclear. The purposes of this work were to investigate the function and underlying mechanisms of RNF185 antisense RNA 1 (RNF185-AS1) in PTC. The expression of RNF185-AS1 was analyzed by quantitative real-time PCR (qRT-PCR). Colony formation, 5-ethynyl-2′-deoxyuridine, and Cell Counting Kit-8 assays were utilized to determine cell proliferation. Cell migration and invasion were tested using wound healing and transwell assays. A mouse transplantation tumor model was used for tumor growth analyses in vivo. The regulation of RNF185-AS1 on the downstream miR-429/lipoprotein receptor-related protein (LRP4) axis was predicted and identified through bioinformatic analysis, dual-luciferase reporter assay, and RNA immunoprecipitation (RIP) assay. RNF185-AS1 was dramatically overexpressed in PTC tumors and cells. High RNF185-AS1 expression was associated with bigger tumor size, lymph node metastasis, and advanced tumor-node-metastasis stage in PTC patients. Silencing of RNF185-AS1 impeded the proliferation, migration, and invasion in vitro and constrained tumorigenesis in vivo. Mechanistically, RNF185-AS1 could act as a sponge of miR-429 to regulate the expression of LRP4. In addition, downregulation of miR-429 or upregulation of LRP4 could relieve the proliferation, migration, and invasion of IHH-4 and TPC-1 cells that inhibited by RNF185-AS1 knockdown. Downregulation of RNF185-AS1 may suppress PTC progression through functioning as a sponge of miR-429 to hinder the expression of LRP4. The RNF185-AS1/miR-429/LRP4 axis will lay the groundwork for future therapeutic strategies in PTC.
Oncolytic viral therapy engenders a clinical response in a recurrent ovarian cancer patient
Authors: Micha John , Rettenmaier Mark , Giuliano Peter , Bohart Randy , Goldstein Bram
Published: March 2022

Platinum-resistant ovarian cancer frequently develops in response to multiple lines of chemotherapy, whereupon the disease becomes relatively intractable and clinical recourse is limited. We document a 58-year-old, advanced-stage, platinum-resistant ovarian cancer patient who previously failed numerous cytotoxic and targeted therapy regimens. She was referred to our gynecologic oncology service with a California (CA)-125 of 3194 U/mL and underwent a modified vaccinia virus coinciding with an Institutional Review Board-approved clinical trial. Following the oncolytic therapy and cycle 8 chemotherapy, the patient’s CA-125 declined to 440 U/mL; a computerized tomography scan of the abdomen and pelvis revealed a partial response to therapy. The favorable clinical benefit encountered in our case study indicates that the combination of oncolytic viral therapy and chemotherapy should be considered as a therapeutic option for heavily pretreated ovarian patients.
Mitochondrial protein LETM1 and its-mediated CTMP are potential therapeutic targets for endometrial cancer
Authors: Niu Feifei , Duan Yan , Man Ying , Liu Wei , Dai Tianyu , Zhang Hui , Li Changzhong , Wei Deying
Published: March 2022

Leucine zipper/EF hand-containing transmembrane-1 (LETM1) is an important mitochondrial protein, while its function in endometrial cancer remains unknown. This study aimed to explore the function of LETM1 in endometrial cancer and reveal the underlying mechanisms involving carboxy-terminal modulator protein (CTMP). Immunohistochemistry was performed to detect the expression of LETM1 and CTMP in normal, atypical hyperplastic and endometrial cancer endometrial tissues. LETM1 and CTMP were silenced in two endometrial cancer cell lines (ISK and KLE), which were verified by western blot. Cell viability, colony number, migration and invasion were detected by cell counting kit-8, colony formation, wound healing and trans-well assays, respectively. A xenograft mouse model was established to determine the antitumor potential of LETM1/CTMP silencing in vivo. In addition, CTMP was overexpressed to evaluate its regulatory relationship with LETM1 in endometrial cancer cells. The expression of LETM1 and CTMP proteins were higher in endometrial cancer tissues than atypical hyperplastic tissues and were higher in atypical hyperplastic tissues than normal tissues. LETM1 and CTMP were also upregulated in ISK and KLE cells. Silencing of LETM1 or CTMP could decrease the viability, colony number, migration and invasion of endometrial cancer cells and the weight and volume of tumor xenografts. In addition, CTMP was downregulated by LETM1 silencing in KLE cells, and its overexpression enhanced the malignant characteristics of si-LETM1-transfected KLE cells. Silencing of LETM1 inhibits the malignant progression of endometrial cancer through downregulating CTMP.
Rapid and durable response to fifth-line lorlatinib plus olaparib in an ALK-rearranged, BRCA2-mutated metastatic lung adenocarcinoma patient with critical tracheal stenosis: a case report
Authors: Jin Chang’e , He Zhengqiang , Guo Min , Liu Shengguo , Wang Yan , Qiu Jinfan , Li Chenhui , Wu Di
Published: March 2022

Treatment options for heavily treated anaplastic lymphona kinase (ALK)-positive nonsmall cell lung cancer (NSCLC) patients, who typically bear-resistant mechanisms to ALK tyrosine kinase inhibitors (TKIs), are usually limited to chemotherapy, which elicits limited clinical benefit and may incur severe toxicity. It is clinically relevant to explore other revenues for these patients. poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib are currently approved to treat BReast CAncer gene 1/2 (BRCA1/2)-mutated patients in a few tumor types. There have been a trial and two case reports of an olaparib-containing regimen in treating epidermal growth factor receptor (EGFR)-positive or driver-negative NSCLC. We report a case of a 27-year-old female nonsmoker diagnosed with ALK-rearranged metastatic lung adenocarcinoma. She was treated with alectinib and acquired ALK p.I1171N and p.V1180L mutations. Germline BRCA2 p.F2801fs was also identified. After sequential lines of ceritinib and chemotherapy, lorlatinib was chosen as the fourth-line therapy and maintained control for 6 months. Shortly after progression, the patient was admitted to the ICU due to critically severe stenosis caused by a tracheal mass and soon relieved by embolization and stenting. Afterward lorlatinib plus olaparib was started and elicited a rapid response within 1 month. The progression-free survival was 6 months as of the latest follow-up, with the best response of partial response. To the best of our knowledge, this case is the first to provide clinical evidence of antitumor activity of olaparib plus ALK TKI in ALK-positive, gBRCA-mutated metastatic NSCLC. Together with previous reports in EGFR-positive or driver-negative patients, our finding warrants further studies on PARP inhibition in BRCA1/2-mutated NSCLC.
The marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol suppresses growth, migration and invasion and stimulates death of metastatic human prostate cancer cells: targeting diverse signaling processes
Authors: Yamaguchi Masayoshi , Yosiike Kenji , Watanabe Hideaki , Watanabe Mitsugu
Published: March 2022

Prostate cancer is metastatic cancer and is the second leading cause of cancer-related death in men. It is needed to develop more effective treatment for metastatic prostate cancer. The present study investigates whether the novel factor 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), which was isolated from marine oyster, suppresses the activity of metastatic human prostate cancer PC-3 or DU-145 cells. Culture of DHMBA (1 or 10 µM) suppressed colony formation and growth of PC-3 or DU-145 cells in vitro. Suppressive effects of DHMBA on cell proliferation were not occurred by culturing with intracellular signaling inhibitors. Mechanistically, DHMBA (10 µM) reduced the levels of key proteins linked to promotion of cell growth, including Ras, PI3K, Akt, MAPK, and mTOR in PC-3 cells. Interestingly, DHMBA increased the levels of cancer suppressor p53, p21, Rb, and regucalcin. Moreover, culture of DHMBA simulated the death of PC-3 and DU-145 cells. This effect was implicated to caspase-3 activation in cells. Interestingly, the effects of DHMBA on cell proliferation and death were blocked by culturing with an inhibitor of aryl hydrocarbon receptor linked to transcriptional regulation. Furthermore, culture of DHMBA inhibited production of reactive oxygen species in PC-3 or DU-145 cells. Of note, DHMBA blocked migration and invasion by diminishing their related protein levels, including NF-κB 65, caveolin-1 and integrin β1. The novel marine factor DHMBA was demonstrated to suppress metastatic prostate cancer cells via targeting diverse signaling pathways. This study may provide a new strategy for prostate cancer therapy with DHMBA.
MicroRNA hsa-miR-657 promotes retinoblastoma malignancy by inhibiting peroxisome proliferator-activated receptor alpha expression
Authors: He Xiumei , Feng Yueyue
Published: March 2022

Retinoblastoma is a familial inherited embryonic neuroretinal malignancy with a low survival rate and poor prognosis. Our study aimed to evaluate the potential interaction between microRNA miR-657 and the peroxisome proliferator-activated receptor alpha (PPARA) in retinoblastoma. Expression of miR-657 and PPARA was analyzed in retinoblastoma tissues and cells using RT-qPCR. Cell proliferation, apoptosis, and migration were measured in retinoblastoma cell lines, and xenografting experiments were performed using nude mice. Our study showed that miR-657 expression was markedly increased, whereas that of PPARA was markedly decreased in retinoblastoma. Additionally, PPARA knockdown enhanced the development of retinoblastoma. miR-657 enhanced the retinoblastoma tumorigenesis by directly inhibiting PPARA expression, suggesting that PPARA targeting by miR-657 facilitates retinoblastoma development by enhancing cell growth. This study provides novel insights into the miR-657- and PPARA-mediated mechanisms underlying retinoblastoma progression and suggests that the interaction between miR-657 and PPARA may serve as an effective target for therapeutic intervention.
Ubiquitin-specific protease 1 inhibition sensitizes hepatocellular carcinoma cells to doxorubicin by ubiquitinated proliferating cell nuclear antigen–mediated attenuation of stemness
Authors: Lu Zhe , Zhang Zhuo , Yang Min , Xiao Meifang
Published: March 2022

Currently, resistance to the chemotherapeutic agent doxorubicin (Dox) in hepatocellular carcinoma (HCC) cells is an obstacle in developing effective Dox-targeted clinical therapies. Ubiquitin-specific protease 1 (USP1) plays a crucial role in the progression of multiple cancers. In this study, the purpose was to investigate the effect of USP1 depletion with chemotherapeutant Dox on the HCC cells. Flow cytometry was used to detect the ratio of apoptosis. The expression levels of selected proteins were evaluated by western blotting. In addition, the expression of genes was quantitated by quantitative real-time PCR assay. Coimmunoprecipitation was performed to confirm the interaction between USP1 and proliferating cell nuclear antigen (PCNA). Sphere formation assay was carried out to investigate the cancer stemness. Subcutaneous xenograft and orthotopic liver tumor models were established to examine the growth of tumor. Knockdown of USP1 increased the rate of Dox-induced apoptosis in stem-like and nonstem-like HCC cells. The combination of Dox and the USP1 inhibitor SJB3-019A (SJB3) markedly enhanced apoptosis in the primary liver carcinoma/PRF/5 and MHCC-97H cell lines. Notably, Dox/SJB3-induced tumor inhibition was further determined in vivo using a xenograft and orthotopic liver tumor model. Mechanically, USP1 inhibition via SJB3 or short hairpin RNA significantly decreased cancer stemness, including sphere formation ability and the expression of Nanog, Sox2, and c-Myc. The sensitization of HCC to Dox by SJB3 is attributed to the upregulation of PCNA ubiquitylation. Thus, genetic or pharmacological inhibition of USP1 restored the sensitivity of HCC cells to Dox in vitro and in vivo, representing a new potential therapeutic strategy for HCC.
The association between shift work exposure and the variations in age at natural menopause among adult Canadian workers: results from the Canadian Longitudinal Study on Aging (CLSA)
Authors: Khan Durdana , Rotondi Michael , Edgell Heather , Tamim Hala
Published: March 2022

Objective

A wide range of negative health outcomes have been associated with shift work (SW) particularly night and rotating SW. However, little is known about effects of SW exposure on reproductive health outcomes. The objective of our study is to prospectively investigate the association between SW exposure and the variations in age at natural menopause among adult Canadian workers.

Methods

Secondary data analyses were performed using the Canadian Longitudinal Study on Aging database. Premenopausal women (N = 3,688) at baseline were followed prospectively for 3 years. Three derived variables were used to measure SW primary exposure: 1) ever exposed to SW, 2) SW exposure in current job, and 3) SW exposure in the longest job. Cox proportional hazard regression models were used to evaluate risk of variations in age at natural menopause after adjusting for potential confounders.

Result

One out of five women (20%) reported to be ever exposed to SW during their jobs. Overall, women who were ever exposed to SW were significantly associated with a delayed onset of menopause compared with daytime workers (hazard ratios [HR] = 0.77, 95% CI, 0.61-0.98). Particularly, when compared with daytime workers, rotating shift worker in the current and longest job were significantly related to delayed onset of menopause (HR = 0.64, 95% CI, 0.46-0.89 and HR = 0.65, 95% CI, 0.49-0.86), respectively.

Conclusion

Our results suggest a relationship between rotating shift and delayed onset of menopause. We speculate that disruptive circadian stimuli may play a role in menopausal onset and this warrants further investigation.

Video Summary:

http://links.lww.com/MENO/A940.
Physical function trends and their association with mortality in postmenopausal women
Authors: Laddu Deepika R. , Saquib Nazmus , Manson JoAnn E. , Arena Ross , Shadyab Aladdin H. , Weitlauf Julie C. , Hovey Kathleen M. , Andrews Christopher , Banack Hailey , Stefanick Marcia L. , LaMonte Michael J. ,   for the Women’s Health Initiative Investigators
Published: March 2022

Objective

Research is limited regarding the predictive utility of the RAND-36 questionnaire and physical performance tests in relation to all-cause, cardiovascular disease (CVD), and total-cancer mortality in older women.

Methods

Data on the RAND-36 questionnaire, gait speed, and chair stand performance were assessed in 5,534 women aged ≥65 years at baseline. A subset (n = 298) had physical function assessments additionally at follow-up (years 1, 3, or 6). Multivariable Cox proportional hazards regression models estimated associations (HR) for a 1-standard deviation (SD) difference in baseline RAND-36 scores and performance tests (alone and combined) with mortality outcomes in the overall cohort and in models stratified by enrollment age (<70 and ≥ 70 y). The relative prognostic value of each physical function exposure was assessed using the Uno concordance statistic.

Results

A total of 1,186 deaths from any cause, 402 deaths from CVD, and 382 deaths from total-cancer were identified during a mean follow-up of 12.6 years. Overall, each 1-SD unit higher baseline RAND-36 score was associated with significantly lower all-cause mortality (HR =0.90) and discriminatory capacity (Uno = 0.65) that was comparable to each performance exposure (HRs 0.88-0.91; Uno = 0.65). These findings were consistent in women aged <70 and ≥ 70 years. The associations of RAND-36 and performance measures with CVD mortality and total-cancer mortality were not significant in multivariable models nor in age-stratified models.

Conclusions

The RAND-36 questionnaire is a reasonable substitute for tracking physical functioning and estimating its association with all-cause mortality in older adults when clinical performance testing is not feasible.
Increasing Dorsal Tilt in Distal Radius Fractures Does Not Increase Median Nerve Strain
Authors: Obiofuma Chukwuka , Dy Christopher , Iannucci Leanne E. , Lake Spencer P. , Brogan David
Published: March 2022

Background:

Although extensive research shows an association between distal radius fractures and the development of median nerve related pathologies such as carpal tunnel syndrome, none directly track how the resulting angular deformity relates to likelihood of development of median nerve pathology.

Methods:

Median nerve strain was measured with a custom-built system using a camera, optical markers, and a proprietary segmentation algorithm. After initial validation of the system in a cadaver model, our system was used to assess strain in 10 cadaver arms with a simulated distal radius fracture and increasing dorsal angulation. The measured strain at each angle was then analyzed using a linear regression model.

Results:

The linear regression model in the validation experiment demonstrated a regression coefficient of 1.00067 (P < 0.0001) with r2 = 0.899, thus validating the use of the optical tracking system. The average strain at maximum dorsal angulation (50 degrees) across all specimens was −0.2%. Linear regression analysis of the effect of increasing dorsal angulation on strain in the osteotomy model yielded a regression coefficient of −0.000048 (P = 0.714), r2 = 0.00129, suggesting no significant correlation between increasing dorsal tilt and median nerve strain.

Conclusions:

Increases in median nerve strain at the wrist are negligible with increasing dorsal tilt in a distal radius fracture model. It is therefore likely that other factors, such as increased pressure within the carpal tunnel, are the primary cause of median neuropathy in distal radius malunions. Therefore, correction of dorsal tilt may not be required to improve neurologic symptoms.
Lateral Tarsal Strip Complications With and Without Conjunctiva Stripping
Authors: Clauss Kevin D. , Ohana Oded , Patel Annika , Wester Sara T. , Lee Bradford , Alabiad Chrisfouad R. , Tse Brian C. , Lee Wendy W.
Published: March 2022

Purpose:

The lateral tarsal strip (LTS) procedure is commonly used to correct eyelid malposition. When performing LTS, some surgeons elect to remove conjunctiva from the tarsal strip, while others do not. It has been hypothesized that without conjunctival stripping, the buried conjunctival tissue can cause complications such as inclusion cysts and granulomas. However, there is limited data comparing LTS cases with and without conjunctiva removal. The authors sought to evaluate whether conjunctival stripping had any impact on complication rates with LTS.

Methods:

LTS operations for ectropion correction were retrospectively reviewed and were separated into 2 cohorts, Con (conjunctiva not removed) or Coff (conjunctival removed). Charts were reviewed for outcomes and complications including inclusion cyst formation, granuloma formation, wound dehiscence, infection, and focal rim tenderness.

Results:

The complication rate was 10% versus 8% for Con versus Coff respectively (p = 0.54). The common complications of LTS surgery were granuloma (4%), wound dehiscence (3%), focal rim tenderness (3%), and infection requiring antibiotics (<1%). There was no significant difference in these complications between the Con and Coff cohorts.

Conclusions:

Complications in both groups were minimal, similar to prior studies, and there was no difference between the 2 cohorts. While it has been suggested that buried conjunctiva may result in increased complication rates, the author’s findings suggest that removing the tarsal conjunctiva is a superfluous step in the LTS surgery and does not affect complication rates.
Orbital Sarcoidosis Masquerading as Late Postoperative Blepharoplasty Complication: A Case Report
Authors: Stevens Shanlee M. , Maeng Michelle M. , Dubovy Sander R. , Fagien Steve , Lee Wendy W.
Published: March 2022

Orbital sarcoid is a rare entity and may be the first manifestation of systemic sarcoidosis. We report a case of orbital sarcoidosis where diagnosis was complicated by a history of lower eyelid blepharoplasty. The patient presented with progressive swelling of the left lower eyelid, which was assumed to be a late complication of her surgery. After failing multiple treatments, MRI orbits was obtained and revealed an enhancing lesion in the left orbit inseparable from the lacrimal gland and inferior oblique muscle. Biopsy showed noncaseating granulomatous inflammation, and the patient was eventually diagnosed with sarcoidosis.
A prospective, double-blind, pilot, randomized, controlled trial of an “embodied” virtual reality intervention for adults with low back pain
Authors: Eccleston Christopher , Fisher Emma , Liikkanen Sammeli , Sarapohja Toni , Stenfors Carina , Jääskeläinen Satu K. , Rice Andrew S.C. , Mattila Leena , Blom Taru , Bratty J. Raymond
Published: March 2022

Adults with chronic low back pain, disability, moderate-to-severe pain, and high fear of movement and reinjury were recruited into a trial of a novel, automated, digital therapeutics, virtual reality, psychological intervention for pain (DTxP). We conducted a 3-arm, prospective, double-blind, pilot, randomized, controlled trial comparing DTxP with a sham placebo comparator and an open-label standard care. Participants were enrolled for 6 to 8 weeks, after which, the standard care control arm were rerandomized to receive either the DTxP or sham placebo. Forty-two participants completed assessments at baseline, immediately posttreatment (6-8 weeks), 9-week, and 5-month follow-up. We found that participants in the DTxP group reported greater reductions in fear of movement and better global impression of change when compared with sham placebo and standard care post treatment. No other group differences were noted at posttreatment or follow-up. When compared with baseline, participants in the DTxP group reported lower disability at 5-month follow-up, lower pain interference and fear of movement post treatment and follow-up, and lower pain intensity at posttreatment. The sham placebo group also reported lower disability and fear of movement at 5-month follow-up compared with baseline. Standard care did not report any significant changes. There were a number of adverse events, with one participant reporting a serious adverse event in the sham placebo, which was not related to treatment. No substantial changes in medications were noted, and participants in the DTxP group reported positive gaming experiences.
Serum level and clinical significance of vitamin E in pregnant women with allergic rhinitis
Authors: Wu Sihai , Wang Aiping
Published: March 2022

Background:

Allergic rhinitis is a frequent disorder during pregnancy, while in children it is triggered by significantly lower serum vitamin E level. This research aimed to investigate whether serum vitamin E level exhibited clinical significance in pregnant women with allergic rhinitis.

Methods:

In this study, 37 pregnant women with allergic rhinitis and 35 healthy pregnant women were recruited. Allergic rhinitis severity was analyzed by the Total Nasal Symptom Score (TNSS) questionnaire. Blood samples were collected to evaluate serum vitamin E, interleukin (IL), and total IgE levels.

Results:

In pregnant women with allergic rhinitis, serum level of vitamin E was significantly lower than in healthy pregnant women. Serum vitamin E level in pregnant women with allergic rhinitis showed a negative correlation with TNSS, IL-13, IL-4, and total IgE levels.

Conclusion:

In conclusion, this research has demonstrated that pregnant women with allergic rhinitis showed significantly lower serum level of vitamin E. The decreased vitamin E showed a correlation with the pathogenesis of allergic rhinitis in pregnant women.
Partners' Experience of Informal Caregiving for Patients With Heart Failure
Authors: Wang Zequan , Tocchi Christine
Published: March 2022

Background

Individuals with heart failure (HF), a debilitating disease with ongoing adaptation and management, are often cared for by partner caregivers whose needs and voices are overshadowed by the demands of HF management. With multidimensional needs and complex challenges for individuals with HF, partner caregivers have to deal with uncertainty and need guidance. Given the vital role of partners, attention should be drawn toward understanding the experience of HF partner caregivers.

Objective

The aim of this study was to synthesize existing qualitative evidence related to caregivers' views and experiences of caring for their partners with HF. This knowledge would assist healthcare providers to better meet the demand of partners and provide them with effective guidance.

Methods

A meta-ethnography of qualitative evidence was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations for reporting systematic reviews. A comprehensive search of PubMed, Scopus, ISI Web of Science, CINAHL, PsycINFO, and EMBASE, as well as hand searches of the reference lists from included articles, was conducted. A combination of subject terms including MeSH and keywords related to HF, partner experience, and qualitative methods was used to identify studies. Studies were included if they were published in English between January 2000 and December 2020 and examined caregivers' experiences in providing care for their partner with HF by using qualitative methods.

Results

Ten articles were included, with 178 participants, and most partners were female. Five studies were conducted in the United States, and 4 studies were conducted in Sweden. Five studies reported partners' health problems; 8 of the studies delineated the inclusion and exclusion criteria for partners. Five overarching themes emerged: shouldering the responsibility, being overloaded, bearing emotional burdens, staying positive, and “left in the dark,” craving support from others.

Conclusions and Clinical Implications

Given the complex roles in caring for individuals with HF, more qualitative research is strongly warranted to enhance caregivers' support and education. A deeper and more comprehensive understanding of the experiences of caregivers for partners with HF is essential for developing tailored interventions. Healthcare providers should be aware of the importance of ongoing assessment and evaluate partner caregivers' needs and assist them in providing more information and formulating coping strategies as required.
Comparative Efficacy of Endoscopic Assist Devices on Colonic Adenoma Detection
Authors: Weissman Simcha , Mehta Tej I. , Stein Daniel J. , Tripathi Kartikeya , Rosenwald Nathan , Kolli Sindhura , Aziz Muhammad , Feuerstein Joseph D.
Published: March 2022

Background and Aims:

Numerous endoscopic assist devices exist, yet data surrounding their comparative efficacy is lacking. We conducted a systematic review with network meta-analysis to determine the comparative efficacy of endoscopic assist devices on colonic adenoma detection.

Methods:

A systematic search was performed using multiple electronic databases through July 2020, to identify all randomized controlled trials and dual-arm observational studies compared with either other endoscopic assist devices and/or standard colonoscopy. The primary outcome was adenoma detection rate (ADR). Secondary outcomes included polyp detection rate (PDR), serrated adenoma detection rate (SADR), right-sided adenoma detection rate (RADR), and proximal adenoma detection rate (PADR).

Results:

Fifty-seven studies (31,051 patients) met inclusion criteria and were analyzed. Network meta-analysis identified an enhanced ADR among (clear) cap [odds ratio (OR): 2.69, 95% confidence interval (CI): 1.45-4.99], endocuff, (OR: 4.95, 95% CI: 3.15-7.78), and endoring (OR: 3.68, 95% CI: 1.47-9.20)—with no significant difference amongst any particular device. Similar findings for PDR were also seen. Enhanced SADR was identified for endocuff (OR: 9.43) and endoring (OR: 4.06) compared with standard colonoscopy. Enhanced RADR (OR: 5.36) and PADR (OR: 3.78) were only identified for endocuff. Endocuff comparatively demonstrated the greatest ADR, PDR, and SADR, but this was not significant when compared with the other assist devices. Subgroup analysis of randomized controlled trials identified enhanced PDR and ADR for both cap and endocuff.

Conclusions:

Endoscopic assist devices displayed increased ADR and PDR as compared with standard colonoscopy and thus should be widely adopted. A nonsignificant trend was seen toward higher efficacy for the endocuff device.
Diagnostic Accuracy of the Proton Pump Inhibitor Test in Gastroesophageal Reflux Disease and Noncardiac Chest Pain
Authors: Ghoneim Sara , Wang Jiasheng , El Hage Chehade Nabil , Ganocy Stephen J. , Chitsaz Ehsan , Fass Ronnie
Published: March 2022

Background:

Response to a trial of proton pump inhibitors (PPIs) is currently accepted as a first step in the management of gastroesophageal reflux disease (GERD). However, information on the diagnostic performance of the PPI test is limited.

Aim:

The aim of this study was to determine the diagnostic accuracy of the PPI test in GERD and noncardiac chest pain (NCCP) and to assess the test performance in erosive reflux disease (ERD) and nonerosive reflux disease (NERD).

Methods:

Web of Science, Cochrane Controlled Register of Trials (CENTRAL), and MEDLINE were searched for studies reporting the diagnostic accuracy of the PPI test in adult patients with typical GERD and NCCP who underwent evaluation using an accepted reference standard, from January 1, 1950, through February 1, 2021. Subgroup analyses were performed, and the risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool.

Results:

Nineteen studies (GERD=11, NCCP=8) involving 1691 patients were included. In GERD, the PPI test had 79% pooled sensitivity [95% confidence interval (CI), 72%-84%], and 45% pooled specificity (95% CI, 40%-49%). In NCCP, pooled sensitivity and specificity were 79% (95% CI, 69%-86%) and 79% (95% CI, 69%-86%), respectively. In ERD, the PPI test had 76% pooled sensitivity (95% CI, 66%-84%) and 30% pooled specificity (95% CI, 8%-67%). In NERD, the PPI test had 79% pooled sensitivity (95% CI, 70%-86%) and 50% pooled specificity (95% CI, 39%-61%).

Conclusions:

The PPI test was sensitive in GERD but with suboptimal specificity. The test performed better in GERD-related NCCP. Diagnostic accuracy was comparable in ERD and NERD.
Youtube videos for the most commonly applied radionuclide treatments: sufficient for patients as an information source?
Authors: Şan Hüseyin
Published: March 2022

Objectives

YouTube is one of the most popular online sources of information for patients. The purpose of the study is to analyze the quality of YouTube videos about the most commonly applied radionuclide treatments.

Method

Related radionuclide therapy videos were searched on YouTube in October 2021. The quality of the videos was assessed by using the Journal of the American Medical Association (JAMA) benchmark criteria, the DISCERN Scale and the Global Quality Scale (GQS).

Results

A total of 473 videos were assessed and 270 were included in the study according to inclusion and exclusion criteria. According to the GQS score, videos were categorized as high-quality (n:63, 23.33%), intermediate quality (n:118, 43.70%) and low-quality (n:89, 32.96 %) groups. The findings of our study showed that the highest number of video views and comments were in the low-quality group. In addition; the number of video likes, views and comments were the lowest in the high-quality video group. The most viewed and commented as well as most liked videos and the videos of highest video power index scores were nonphysician sourced videos. The most quality videos were the physician-sourced videos in terms of JAMA, DISCERN and GQS scores.

Conclusion

Although high-quality videos about radionuclide treatments on YouTube may enlighten and motivate patients positively; it should be kept in mind that improper information may also be uploaded to this platform. Under the guidance of the European Association of Nuclear Medicine, it is necessary to generate an official video in English with multilingual subtitles.
Neuropsychological Effects of Chemotherapy
Authors: Kim Hee-Ju , Kim Jung Eun Esther , Jung Sun Ok , Lee Dasuel , Abraham Ivo
Published: March 2022

Background

Findings from longitudinal studies can provide more conclusive evidence as to the impact of chemotherapy on cognitive functioning.

Objectives

This study aimed to (a) synthesize the evidence from longitudinal studies of the neuropsychological effects associated with chemotherapy in breast cancer patients, (b) identify associated factors, and (c) evaluate methodological issues.

Methods

Data were extracted from PubMed, EMBASE, CINAHL, PsycINFO, and the Cochrane Library. Inclusion criteria included the original study with the breast cancer sample, validated measure, and at least 1 baseline data point before and after chemotherapy began. Data accrued for sample characteristics, data-collection time points, statistical methods for longitudinal data analysis, outcome measures, and major findings (eg, longitudinal changes in cognitive function).

Results

We selected 42 articles for this review. The sample sizes ranged from 20 to 610, and most recruited were younger than 70 years. We found a trend across studies—statistically significant objective cognitive function deteriorations in severity and prevalence after initiating chemotherapy compared with a control group or relative to their baseline observations. A subsample, as high as 65%, experienced marked declines in cognitive function after initiating chemotherapy. The memory domain was most affected. The consistently associated factors were education, IQ, and regimen. Major methodological concerns were the measurement—the wide range of neuropsychological tests and a test’s unclear domains.

Conclusion

Chemotherapy affects objective cognitive function in some subsets. The highest-impact time point, mechanisms, and clinical significance of chemotherapy-associated cognitive impairment need additional evidence.

Implication for Practice

Clinicians must assess and manage cognitive impairment during and after chemotherapy.
Cultural Humility Toolkit
Authors: Foronda Cynthia , Prather Susan , Baptiste Diana-Lyn , Luctkar-Flude Marian
Published: March 2022

Background:

Diversity, equity, and inclusion (DEI) are increasingly recognized as core values for nursing education and practice.

Purpose:

The purpose of this article is to offer teaching tools and strategies to integrate cultural humility within the nursing curriculum and create a more inclusive learning environment.

Approach:

Various teaching tools, methods, and strategies are presented.

Outcomes:

Use of ground rules, an environmental assessment, examination of the curriculum landscape and teaching materials, bias awareness activity, modified privilege walk, Modified Monopoly, simulation, low-income community experiences, study abroad, debriefing, and evaluation with valid and reliable tools are suggested.

Conclusions:

By threading cultural humility concepts throughout the curriculum, nurse educators have the potential to shape learner perspectives to better appreciate and value diversity.
Toward good governance for the prosthetics and orthotics sector in Iran: Evidence from a qualitative study
Authors: Shahabi Saeed , Pardhan Shahina , Shabaninejad Hosein , Teymourlouy Ahmad Ahmadi , Tabrizi Reza , Lankarani Kamran Bagheri
Published: March 2022

Background:

Prosthetics and orthotics (P&O) services are essential health services whose desired provision is considered as prerequisite to achieving universal health coverage. However, the P&O sector is sometimes not audited and governed, leading to groups that receive and offer the services to face challenges for benefits in Iran.

Objectives:

To identify common challenges of governance for the P&O sector and provide some potential policy recommendations to strengthen it.

Study design:

Qualitative study.

Methods:

This study was conducted using semistructured in-depth interviews with prosthetists and orthotists (n = 13), P&O academicians (n = 6), and healthcare policy-makers (n = 8). The interview guide was also established based on 10 dimensions of the Framework for Governance of Healthcare System.

Results:

Challenges identified included no legislation on P&O services, insufficient government support, uninformed policy-makers, and lack of interest by powerful stakeholders. In addition, nontransparent policy-making, inadequate distribution of workforce across the country, and lack of insurance coverage for P&O services were also raised as other challenges. The respondents identified the need for clear legislation to inform policy-makers and to seek advocacy from the government.

Conclusions:

The governance of the P&O sector in Iran has faced with a number of challenges that have made it unable to respond to existing demands desirably. Hence, it is important and necessary to adopt effective and comprehensive policies to reduce current challenges and barriers and improve the governance for P&O services.
Regarding Arthroscopy
Authors: Ike Robert W. , Kalunian Kenneth C.
Published: March 2022

Background/Objective

Rheumatologists' interest in arthroscopy began before the 1980s, when many era practitioners began to take up the procedure in earnest. Some of the important players in pre–World War II explorations of arthroscopy were rheumatologists, and the father of modern arthroscopy Makei Watanabe counted many rheumatologists among his postwar students, who were publishing about arthroscopic insights into rheumatic conditions in the 1960s and 1970s. We chose to review this evolution to demonstrate the diverging interests of rheumatologists and orthopedists in arthroscopy and emphasize the chances for reconciliation and cooperation. Methods involve our personal recollection and review of the literature.

Results

Guidelines for the practice of arthroscopy were published by the American Rheumatism Association (now the American College of Rheumatology) 7 years before similar guidelines appeared from the Arthroscopy Association of North America. American rheumatologists ceased arthroscopy when controlled trials showed no effect in osteoarthritis beyond placebo and biologics for synovitis virtually eliminated situations in which synovectomy might be considered. The research potential of arthroscopy has been realized mainly by European rheumatologists, although the ultrasound-guided biopsy is supplanting arthroscopy as means to secure synovium for investigation, despite the advantages of the latter, such as the ability to obtain larger amounts of tissue, select tissue based on macroscopic appearance, sample multiple area in the same joint, and deliver the potentially therapeutic effect of washout. New miniscopes suitable for office use could restore some of the lagging interest in arthroscopy for investigation. Orthopedists have generally been resistant to rheumatologists doing arthroscopy but would not be sharing any turf with rheumatologists using the miniscope.

Conclusions

We hope that we orthopedists and rheumatologists could be friends as we enter this new phase of arthroscopy as we use the technique for different purposes.
Bowel Dysfunction and Enteral Nutrition in Critically Ill Adult Patients
Authors: Blakeslee Paul A. , Hyrkäs Eira Kristiina , Corica Erin , Orff Sonja , Trottier Alana , Turner Elizabeth
Published: March 2022

This retrospective study investigated diarrhea, constipation, associations of enteral nutrition (EN), and medications in critically ill patients (n = 4118). Data were retrieved from electronic health records. Over half (68%) of patients had diarrhea and 8% had constipation. Diarrhea and constipation were more common in patients in the EN group (n = 799) than in the no-EN group (n = 802). Interestingly, patients who received EN were administered more medications with lower incidence of diarrhea than patients who did not receive EN. The findings of this study highlight the importance of reviewing medications (ie, opioids, prophylactic laxative regimens, and antibiotics) as well as formula composition for potential contributing etiologies to bowel movement abnormalities in critically ill patients.
Is There a Correlation Between NRS-2002 and EAT-10 Score?
Authors: Garipoğlu Gökçen , Andaç Öztürk Serap , Bursa Ayşe Gül
Published: March 2022

Dysphagia may play a significant role in the development and progression of malnutrition and may lead to prolonged hospital stay. A group of 187 patients was screened with the NRS-2002 to evaluate nutritional status and the EAT-10 for dysphagia screening. A statistically significant correlation was found between the EAT-10 and NRS scores at hospitalization (initial NRS score) and the final NRS score (P = .014 and P = .007, respectively). To prevent or minimize the adverse outcomes of dysphagia and malnutrition, it is necessary to perform routine dysphagia and malnutrition screening in hospitals.
Digital Learning
Authors: Chan Lauren , Brody Rebecca , Dobak Stephanie , Peterson Sarah
Published: March 2022

Nutrition and dietetics education content is uncommon on online platforms. This cross-sectional study evaluated learning preferences and YouTube usage for nutrition education via a Web-based survey of 185 members of Dietitians in Nutrition Support. In-person learning (43%) and video (33%) were preferred learning modalities. Age (P = .008) and practice years (P = .02) were significantly different between modality preference. More than one-half of respondents have used and recommended a video for nutrition education. Top barriers for using educational videos were lack of relevant content and challenges identifying valid resources. Nutrition organizations should prioritize building relevant, evidenced-based video content for education.