Major Determinants of Innovation Performance in the Context of Healthcare Sector.

Through the innovation network (IN) and the use of artificial intelligence (AI), this study aims to look into the innovation performance (IP) of the healthcare industry. Digital innovation (DI) is also tested as a mediator. For the collection of data, cross-sectional methods and quantitative research designs were used. To test the study hypotheses, the SEM technique and multiple regression technique were used. Results reveal that AI and the innovation network support the attainment of innovation performance. The finding demonstrates that the relationship between INs and IP links and AI adoption and IP links is mediated through DI. The healthcare industry plays a vital role in facilitating public health and improving the living standards of the people. This sector's growth and development are largely dependent on its innovativeness. This study highlights the major determinants of IP in the healthcare industry in terms of IN and AI adoption. This study adds to the literature's knowledge via an innovative proposal in which the mediation role of DI among IN-IP and AI adoption-innovation links is investigated.

Postoperative Echography for Optimization of Radiation Dosimetry in Patients with Uveal Melanoma Treated with Plaque Brachytherapy.

PURPOSE: (1) To describe the technique of postoperative echography to confirm the intended treatment dose to the tumor apex in patients with uveal melanoma treated with plaque brachytherapy. (2) To describe the local tumor control rate and visual outcomes with the brachytherapy strategies used at our institution. DESIGN: Retrospective review. SUBJECTS: Three hundred seventy-two consecutive patients with uveal melanoma (small, medium, and large) treated with plaque brachytherapy at the University of Iowa from August 2008 to February 2019. METHODS: Patient demographics and tumor characteristics were recorded for each patient. Patients with posterior tumors treated with plaque brachytherapy (n = 355) underwent intraoperative ultrasound to confirm plaque placement, and additional postoperative ultrasound on day 1 to 3 postplaque insertion. In cases where intratumor/episcleral plaque edema or hemorrhage shifted the dose to the prescription point to < 85 Gray (Gy), the duration of plaque brachytherapy was increased to compensate. Statistical analysis was performed to compare variables associated with the need for plaque adjustment. MAIN OUTCOMES MEASURES: Variables associated with plaque dose needing to be recalculated, local tumor control, and visual acuity outcomes. RESULTS: In 31 (8.3%) cases, postoperative echography showed that the tumor apex had shifted outside the 85 Gy isodose curve, requiring adjustment of the duration of brachytherapy (28 cases) or repositioning of the plaque (3 cases). Collaborative Ocular Melanoma Study tumor size was significantly associated with need to adjust the plaque prescription dose (P = 0.03), with large tumors having the highest rate of adjustment. Tumor thickness was larger in cases requiring plaque adjustment compared with those that were not adjusted (median 4.9 mm vs. 3.0 mm, P < 0.01). Local tumor control was 99% (95% confidence interval, 97%-100%) at 5 years and 99% (95% confidence interval, 97%-100%) at 10 years. The percentage of patients who had experienced a visual acuity decline of ≥ 3 lines of vision or had < 20/200 acuity was 14.9% at 1 year after brachytherapy, 35.3% at 3 years, and 51.6% at 5 years. CONCLUSIONS: Postoperative ultrasound performed on postoperative day 1 to 3 after plaque insertion for patients undergoing brachytherapy for uveal melanoma may result in improved local tumor control, particularly in the setting of thicker or larger tumors. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Neutropenic Enterocolitis: A Rare Complication of Sacituzumab Govitecan.

Neutropenic enterocolitis (NE) is a rare form of inflammatory colitis seen in severely neutropenic patients. Patients with NE typically have severe neutropenia (absolute neutrophil count [ANC] <500/mm3) in the setting of exposure to cytotoxic chemotherapy. Taxanes have traditionally been associated with NE, but there has been a growing amount of literature, linking a variety of other chemotherapeutic agents. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate comprising a topoisomerase I inhibitor component conjugated to an antibody targeting human trophoblast cell-surface antigen 2 (Trop-2). SG is approved for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) and urothelial cancer. We report a case of NE in a patient with mTNBC receiving SG and its successful management. Prompt diagnosis and management of NE in such patients can be potentially lifesaving.

Role of Natural Killer Cells in Uveal Melanoma.

Uveal melanoma has a high mortality rate following metastasis to the liver. Despite advances in systemic immune therapy, treatment of metastatic uveal melanoma (MUM) has failed to achieve long term durable responses. Barriers to success with immune therapy include the immune regulatory nature of uveal melanoma as well as the immune tolerant environment of the liver. To adequately harness the anti-tumor potential of the immune system, non-T cell-based approaches need to be explored. Natural Killer (NK) cells possess potent ability to target tumor cells via innate and adaptive responses. In this review, we discuss evidence that highlights the role of NK cell surveillance and targeting of uveal melanoma. We also discuss the repertoire of intra-hepatic NK cells. The human liver has a vast and diverse lymphoid population and NK cells comprise 50% of the hepatic lymphocytes. Hepatic NK cells share a common niche with uveal melanoma micro-metastasis within the liver sinusoids. It is, therefore, crucial to understand and investigate the role of intra-hepatic NK cells in the control or progression of MUM.

Inquiring Voluntary Turnover For Female Nurses In Pakistan Through Focused Ethnography.

BACKGROUND: Pakistan is a country with very low nurses to population rate. This problem becomes more prominent due to voluntary turnover; especially among female nurses. This problem could be attributed to several social and demographic factors. PURPOSE: This study sought to identify the factors affecting voluntary turnover of female nurses in Pakistan. METHODS: This study is qualitative in nature. Focused ethnography was used for detailed exploration of the issue of voluntary turnover among female nurses. Ethnographic interviews of informants were conducted to identify the social and organizational determinants of voluntary turnover among female nursing staff. RESULTS: Social factors affecting voluntary turnover include religious beliefs, cultural values, lack of social respect, marital disruption, and lack of psychological support. While organizational factors affecting voluntary turnover include sexual harassment, work-family conflicts, workload and job stress, emotional labour, undefined career path and lack of promotion opportunities and bullying behaviour of co-workers. DISCUSSION: Both social and organizational issues affect voluntary turnover among female nursing staff. Policymakers at national and organizational level must identify and address these issues to provide congenial work environment and to reduce turnover of female nurses in Pakistan.

From envy to social anxiety and rumination: How social media site addiction triggers task distraction amongst nurses.

AIM: To investigate the effect of social networking site addiction on task distraction among nurses. BACKGROUND: Most of the existing literature focuses only on positive aspects of social networking site, while negative aspects thereof have rarely been highlighted. The current study focuses on finding the impact of social networking site addiction and mental states like envy, social anxiety and rumination on task distraction among nurses. METHOD: Data were collected through self-administrated questionnaires from 378 nurses in Pakistan. The study used descriptive and inferential statistics including correlation and structural equation modelling techniques to test the hypothesized model. RESULTS: The results suggest that social networking site addiction results in task distraction which is further enhanced by envy, social anxiety and rumination among nurses. CONCLUSION: The study contends that social networking site addiction stimulates various stressors among nurses such as envy, social anxiety and rumination that augment its negative effects on task distraction. IMPLICATIONS FOR NURSING MANAGEMENT: Findings of the study can be used develop strategies to control task distraction among nurses to limit its negative impact and to enhance work performance. Awareness campaigns can help nurses and other healthcare professionals to comprehend the effects of using social media at work.

Sequencing Ipilimumab Immunotherapy Before or After Chemotherapy (Nab-Paclitaxel and Bevacizumab) for the Treatment of BRAFwt (BRAF Wild-Type) Metastatic Malignant Melanoma: Results of a Study of Academic and Community Cancer Research United (ACCRU) RU261206I.

OBJECTIVES: With the introduction of novel immune therapeutics for the treatment of disseminated malignancies, we sought to evaluate whether deliberate sequencing of immunotherapy before/after conventional cytotoxic chemotherapy would have an impact on clinical outcomes in patients with previously treated metastatic melanoma. We sought to evaluate whether or not ipilimumab immunotherapy administered before or after cytotoxic chemotherapy (nab-paclitaxel+bevacizumab, AB) would impact clinical outcomes. METHODS: We conducted a randomized phase 2 clinical trial of patients with BRAF wild-type metastatic melanoma (up to 2 prior therapies) who received either: (A) AB followed by ipilimumab therapy at progression; or (B) ipilimumab followed by AB treatment at progression. The primary goal of the study was a comparison of AB versus ipilimumab progression-free survival, with secondary clinical and laboratory endpoints. RESULTS: This study did not reach full accrual due to concurrent Food and Drug Administration approval of anti-programmed cell death 1 agents. Nevertheless, the available data suggests a cumulative therapeutic advantage to the sequential use of ipilimumab followed by AB. Correlative laboratory data revealed a favorable effect on systemic immune homeostasis in patients receiving AB therapy, of potential interest in further investigations, especially in the context of chemotherapy/immunotherapy combinations. CONCLUSION: Albeit limited in scope, our data suggest that cytotoxic therapy with nab-paclitaxel and bevacizumab appear to favorably alter systemic parameters of immune function of potential benefit in combination T-cell directed immune checkpoint inhibitor therapy.

Evaluating the effects of social networking sites addiction, task distraction, and self-management on nurses' performance.

AIMS: The purpose of this study was to explore the relationship of social networking sites (SNSs) addiction on nurses' performance and how this relationship was mediated by task distraction and moderated by self-management. DESIGN: This cross-sectional study is designed to empirically test the relationship of SNSs addiction, task distraction, and self-management with the nurses' performance. METHODS: Data were collected by conducting an online survey on nurses across the world using a web-based questionnaire developed through 'Google Docs' and distributed through Facebook from 13 August 2018 - 17 November 2018. The Facebook groups were searched using the selected key terms. In total, 45 groups were found to have relevance to this research; therefore, request was made to the admins of these groups to participate in this research and to post a link in their groups. Only 19 group admins responded positively by uploading a link of the research instrument on their respective group pages and 461 members of these groups participated in the research. RESULTS: Results of the data collected from 53 different countries indicated that SNSs addiction results in lowering the nurses' performance. This relationship is further strengthened by task distraction introduced as a mediating variable. The results show that self-management mediates the relationship between SNSs addiction and employees' performance. Moreover, the results of the study confirm that self-management reduces the negative impact of SNSs addiction on nurses' performance. CONCLUSION: Social networking sites (SNSs) addiction and task distraction reduce the nurses' performance, whereas self-management enhances nurses' performance. IMPACT: This study addresses the problem of using SNSs at the workplace and its potential effect on nurses' performance. Results demonstrate that SNSs addiction reduces the performance which is further decreased by task distraction; however, self-management of nurses can enhance the nurses' performance. The research has numerous theoretical and practical implications for hospital administration, doctors, and nurses.

Role of one, two and three doses of high-dose chemotherapy with autologous transplantation in the treatment of high-risk or relapsed testicular cancer: a systematic review.

Approximately 20-30% of patients with metastatic germ cell cancers (GCCs) can develop relapsed or refractory (RR) disease, about 40-50% of patients who relapse after salvage chemotherapy may reach long-term remission. The goal of this review was to identify patients who appear to benefit from high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). To access this, we performed a systematic medical literature review to evaluate the effectiveness of HDCT in the frontline setting, as well as in patients with RR testicular cancer. We searched databases for interventional clinical studies and identified 5883 studies. We selected 49 studies for inclusion, which included a total of 5985 patients. Seventeen studies reported results of newly diagnosed poor-risk GCC patients and 32 studies reported results of RR patients. For newly diagnosed patients with poor prognostic predictors, a risk adjusted strategy using unfavorable tumor marker decline with initial standard chemotherapy regimen and upfront HDCT demonstrated improved outcomes. Our data suggest a minimum of two HDCT cycles with ASCT should be standard of care for patients with RR GCC. Failure of HDCT results in a poor prognosis with only 10% of patients achieving lasting remission with salvage therapy.

PD-L1 expression in tumor metastasis is different between uveal melanoma and cutaneous melanoma.

AIM: To compare PD-L1 expression between metastatic uveal melanoma (MUM) and metastatic cutaneous melanoma (MCM). MATERIALS & METHODS: A total of 295 MCM and 78 MUM specimens were analyzed for tumor cell PD-L1 expression. Additionally, 91 MCM and 45 MUM specimens were analyzed for PD-1 expression on tumor-infiltrating lymphocytes. RESULTS: A total of 77/295 (26.1%) MCM specimens expressed PD-L1 as compared to 4/78 (5.1%) MUM specimens (p < 0.0001). PD-1 expression on tumor-infiltrating lymphocytes was greater in MCM (73.6%; 67/91) than in MUM (51.1%; 23/45), respectively (p = 0.009). CONCLUSION: Significant differences exist in PD-L1 expression between MCM and MUM. The lower PD-L1 expression in MUM may provide a rationale for failure of PD-1 inhibitor therapy and suggests that immune evasion in this disease may occur via alternative mechanisms.

Autologous melanoma cell vaccine using monocyte-derived dendritic cells (NBS20/eltrapuldencel-T).

Targeted therapy and immunotherapy have revolutionized the treatment of advanced melanoma. Despite recent advances, lack of long-term efficacy from targeted therapy and serious immune-related toxicity are major concerns. There is unmet need for 'durable' and 'safe' treatment options for advanced melanoma. Cancer vaccine therapy in melanoma has been investigated for many years with modest clinical efficacy. More recently, dendritic cell-based vaccine products have become available for clinical use and have been the focus of investigation. CLBS20 (NBS20/eltrapuldencel-T) is a novel dendritic cell-based vaccine product that has shown promising results in early phase trials in advanced melanoma. This cancer vaccine approach could play an important role in providing a sustainable survival benefit, targeting cancer cells themselves and avoiding off-target immune-related toxicity.

Cyclic AMP signaling contributes to neural plasticity and hyperexcitability in AH sensory neurons following intestinal Trichinella spiralis-induced inflammation.

Trichinella spiralis infection causes hyperexcitability in enteric after-hyperpolarising (AH) sensory neurons that is mimicked by neural, immune or inflammatory mediators known to stimulate adenylyl cyclase (AC)/cyclic 3',5'-adenosine monophosphate (cAMP) signaling. The hypothesis was tested that ongoing modulation and sustained amplification in the AC/cAMP/phosphorylated cAMP related element binding protrein (pCREB) signaling pathway contributes to hyperexcitability and neuronal plasticity in gut sensory neurons after nematode infection. Electrophysiological, immunological, molecular biological or immunochemical studies were done in T. spiralis-infected guinea-pigs (8000 larvae or saline) after acute-inflammation (7 days) or 35 days p.i., after intestinal clearance. Acute-inflammation caused AH-cell hyperexcitability and elevated mucosal and neural tissue levels of myeloperoxidase, mast cell tryptase, prostaglandin E2, leukotrine B4, lipid peroxidation, nitric oxide and gelatinase; lower level inflammation persisted 35 days p.i. Acute exposure to blockers of AC, histamine, cyclooxygenase or leukotriene pathways suppressed AH-cell hyperexcitability in a reversible manner. Basal cAMP responses or those evoked by forskolin (FSK), Ro-20-1724, histamine or substance P in isolated myenteric ganglia were augmented after T. spiralis infection; up-regulation also occurred in AC expression and AC-immunoreactivity in calbindin (AH) neurons. The cAMP-dependent slow excitatory synaptic transmission-like responses to histamine (mast cell mediator) or substance P (neurotransmitter) acting via G-protein coupled receptors (GPCR) in AH neurons were augmented by up to 2.5-fold after T. spiralis infection. FSK, histamine, substance P or T. spiralis acute infection caused a 5- to 30-fold increase in cAMP-dependent nuclear CREB phosphorylation in isolated ganglia or calbindin (AH) neurons. AC and CREB phosphorylation remained elevated 35 days p.i.. Ongoing immune activation, AC up-regulation, enhanced phosphodiesterase IV activity and facilitation of the GPCR-AC/cAMP/pCREB signaling pathway contributes to T. spiralis-induced neuronal plasticity and AH-cell hyperexcitability. This may be relevant in gut nematode infections and inflammatory bowel diseases, and is a potential therapeutic target.

ADOA3R as a therapeutic target in experimental colitis: proof by validated high-density oligonucleotide microarray analysis.

Adenosine A3 receptors (ADOA3Rs) are emerging as novel purinergic targets for treatment of inflammatory diseases. Our goal was to assess the protective effect of the ADOA3R agonist N(6)-(3-iodobenzyl)-adenosine-5-N-methyluronamide (IB-MECA) on gene dysregulation and injury in a rat chronic model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)--induced colitis. It was necessary to develop and validate a microarray technique for testing the protective effects of purine-based drugs in experimental inflammatory bowel disease. High-density oligonucleotide microarray analysis of gene dysregulation was assessed in colons from normal, TNBS-treated (7 days), and oral IB-MECA-treated rats (1.5 mg/kg b.i.d.) using a rat RNU34 neural GeneChip of 724 genes and SYBR green polymerase chain reaction. Analysis included clinical evaluation, weight loss assessment, and electron paramagnetic resonance imaging/spin-trap monitoring of free radicals. Remarkable colitis-induced gene dysregulation occurs in the most exceptional cluster of 5.4% of the gene pool, revealing 2 modes of colitis-related dysregulation. Downregulation occurs in membrane transporter, mitogen-activated protein (MAP) kinase, and channel genes. Upregulation occurs in chemokine, cytokine/inflammatory, stress, growth factor, intracellular signaling, receptor, heat shock protein, retinoid metabolism, neural, remodeling, and redox-sensitive genes. Oral IB-MECA prevented dysregulation in 92% of these genes, histopathology, gut injury, and weight loss. IB-MECA or adenosine suppressed elevated free radicals in ex vivo inflamed gut. Oral IB-MECA blocked the colitis-induced upregulation (90% of genes tested (33 of 37 genes). We conclude that our validated high-density oligonucleotide microarray analysis is a powerful technique for molecular gene dysregulation studies to assess the beneficial effects of purine-based or other drugs in experimental colitis. ADOA3R is new potential therapeutic target for inflammatory bowel disease.