Miracle-dz/UniFAR-FTUs huggingface dataset:
Letermovir for the prevention of cytomegalovirus infection and disease in transplant recipients: an evidence-based review

Abstract Cytomegalovirus (CMV) is a leading opportunistic infection in immune compromised patients, including allogeneic hematopoietic stem cell (HSCT) or solid organ transplant (SOT) recipients, where primary infection or reactivation is associated with increased morbidity and mortality. Antiviral drugs are the mainstay for the prevention of CMV infection and disease, most commonly with valganciclovir. However, valganciclovir use is often associated with adverse drug reactions, most notably leukopenia and neutropenia, and its widespread use has led to emergence of antiviral resistance. Foscarnet and cidofovir, however, are associated with nephrotoxicity. Letermovir, a novel CMV viral terminase inhibitor drug, was recently approved for CMV prophylaxis in allogeneic HSCT recipients. It has a favorable pharmacokinetic and tolerability profile. The aim of this paper is to review the evidence supporting the use of letermovir in allogeneic HSCT recipients, and how the drug impacts our contemporary clinical practice. In addition, we discuss the ongoing clinical trial of letermovir for the prevention of CMV in SOT recipients. The use of letermovir for treatment of CMV infection and disease is not yet approved. However, because of a unique mechanism of activity, we provide our perspective on the potential role of letermovir in the treatment of ganciclovir-resistant CMV infection and disease. Furthermore, drug-resistant CMV has emerged during use of letermovir for prophylaxis and treatment. Caution is advised on its use in order to preserve its therapeutic lifespan.
Phase II study of chemoradiotherapy combined with gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic ductal adenocarcinoma (NUPAT 05 Trial): study protocol for a single arm phase II study

ABSTRACT The efficacy of nab-paclitaxel combined with gemcitabine (GnP) and of chemoradiotherapy (CRT) for unresectable locally advanced pancreatic ductal adenocarcinoma (UR-LA PDAC) is still unclear. We previously conducted a phase I study of CRT using GnP and determined the recommended dose and have now designed a phase II trial to evaluate the efficacy of CRT incorporating GnP for UR-LA PDAC. Eligibility criteria are chemotherapy-naïve patients with UR-LA PDAC as defined by the NCCN guidelines version 2. 2016. Study patients will receive 100 mg/m2 nab-paclitaxel and 800 mg/m2 gemcitabine on Days 1, 8, and 15 per 4-week cycle with concurrent radiation therapy (total dose of 50.4 Gy in 28 fractions of 1.8 Gy per day, 5 days per week). Treatment will be continued until disease progression or surgery, which is to be performed only for patients in whom the disease is well-controlled at 8 months from beginning the protocol treatment. Primary endpoint is 2-year overall survival rate and co-primary endpoint is resection rate. Secondary endpoints are overall survival, progression free survival, time to treatment failure, response rate, disease control rate, early tumor shrinkage, depth of response, reduction of SUV-max on PET–CT, serum tumor markers, relative dose intensity, safety, and Quality of life. This study will show the efficacy and safety of chemoradiotherapy combined with GnP.
An evaluative study of objective structured clinical examination (OSCE): students and examiners perspectives

Background: The objective structured clinical examination (OSCE) is the gold standard and universal format to assess the clinical competence of medical students in a comprehensive, reliable and valid manner. The clinical competence is assessed by a team of many examiners on various stations of the examination. Therefore, it is found to be a more complex, resource- and time-intensive assessment exercise compared to the traditional examinations. Purpose: The objective of this study was to determine the final year MBBS students’ and OSCE examiners’ perception on the attributes, quality, validity, reliability and organization of the Medicine and Therapeutics exit OSCE held at the University of the West Indies (Cave Hill) in June 2017. Methods: At the end of the OSCE, students and examiners were provided with a questionnaire to obtain their views and comments about the OSCE. Due to the ordinal level of data produced by the Likert scale survey, statistical analysis was performed using the median, IQR and chi-square. Results: A total of 52 students and 22 examiners completed the questionnaire. The majority of the students provided positive views regarding the attributes (eg, fairness, administration, structure, sequence, and coverage of knowledge/clinical skills), quality (eg, awareness, instructions, tasks, and sequence of stations), validity and reliability (eg, true measure of essential clinical skills, standardized, practical and useful experiences), and organization (eg, orientation, timetable, announcements and quality of examination rooms) of the OSCE. Similarly, majority of the examiners expressed their satisfaction with organization, administration and process of OSCE. However, students expressed certain concerns such as stressful environment and difficulty level of OSCE. Conclusion: Overall, the OSCE was perceived very positively and welcomed by both the students and examiners. The concerns and challenges regarding OSCE can be overcome through better orientation of the faculty and preparation of the students for the OSCE.
Lymph node mapping helps in R0 resection for anaplastic thyroid carcinoma—report of a case with prolonged survival

Abstract Anaplastic thyroid carcinoma is a rare tumor, consisting 1–2% of all thyroid malignancies and presenting a high mortality rate. Median survival for patients undergoing primary surgery is approximately 6.6 months. We present a case of a patient treated with R0 resection, including total thyroidectomy and lymphadenectomy of levels III, IV, VI and VII after cervical lymph node mapping, oral 131I administration, and radiotherapy. Proper preoperative research, R0 resection and relatively early diagnosis, led to good prognosis, as the patient is currently totally disease-free, twelve months postoperatively.
Chronic prostatitis: current treatment options

Abstract Male chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is represented by a heterogeneous group of symptoms that can cause an important impairment of daily quality of life for patients. Diagnosis of CP/CPPS is often not clear and treatment can be challenging, as it varies according to the different causative factors and derived symptoms. Differently from approaches used in the past, the diagnosis and subsequent treatment rely on separating this entity from chronic bacterial prostatitis and considering it as a multifactorial disease. Autoimmunity and inflammation, myofascial tenderness, neuroinflammation, and psychological causes have been clearly related to this disease, and therefore CPPS should not only be considered as related to benign prostatic enlargement. A multitude of different symptoms related to urinary, genital, rectal, and perineal areas can be attributed to this condition and therefore should be routinely investigated in patients, as well as possible differential diagnoses which can cause the same symptoms, such as pudendal nerve entrapment syndrome. The aim of this narrative review is to focus on CPPS after an infectious cause has been excluded.
Simvastatin improves the eradication rate of Helicobacter pylori: upper Egypt experience

Background: Helicobacter pylori infection is one of the most prevalent chronic bacterial human infections worldwide. Helicobacter pylori colonizes the gastric mucosa and causes persistent gastritis that may progress to gastric cancer. Increased resistance of H. pylori presents a major problem in most countries. Statins, including simvastatin, which are currently used to treat hypercholesterolemia, appear to have potential synergistic role to antibiotics. This study aimed to assess the value of adding simvastatin as adjuvant to standard triple therapy in patients infected with H. pylori. Methods: This study was conducted on 100 patients diagnosed with H. pylori by the presence of antigen in stools. All patients were randomly subjected either to the standard triple regimen (clarithromycin 500 mg bid + amoxicillin 1 g bid + omeprazole 20 mg bid) (group 1, N=50) or to the standard triple regimen plus simvastatin (clarithromycin 500 mg bid + amoxicillin 1 g bid + omeprazole 20 mg bid + simvastatin 20 mg bid) (group 2, N=50). Both groups were treated for 14 days and eradication of H. pylori was assessed by a stool antigen test 4 weeks after therapy. Results: Eradication of H. pylori infection was significantly higher in patients treated with the standard triple therapy plus simvastatin (n=41, 82%) than in patients treated with the standard triple therapy (n=31, 62%) (P<0.022). Conclusion: Simvastatin significantly improves the H. pylori eradication rate.
Clinical utility of daylight photodynamic therapy in the treatment of actinic keratosis – a review of the literature

Abstract Actinic keratosis (AK) is an early in situ squamous cell carcinoma that results from UV light exposure and has the potential to evolve into invasive tumor. Therefore, it is crucial that AKs are monitored and treated appropriately. Photodynamic therapy (PDT) is a treatment option that is minimally invasive and leaves patients with cosmetically superior results. However, disadvantages of PDT include pain and lengthy clinic visits. Accordingly, there has been much interest in the use of daylight photodynamic therapy (daylight-PDT) as a more convenient and less painful alternative to conventional photodynamic therapy (c-PDT). Current evidence shows that daylight-PDT is noninferior to c-PDT in the short and long term. Patients reported decreased pain with daylight-PDT and were more satisfied with the procedure (P<0.001). Current evidence suggests that 2 hrs of daylight exposure was sufficient for treatment, and its efficacy does not appear to be limited by weather conditions. Given the decreased intensity of treatment, daylight-PDT is better for mild disease, as it is less effective in moderate-to-thick AKs. Though further studies are still needed to refine the technique, daylight-PDT is a potential alternative to c-PDT for thin-to-moderate AKs and should be offered to patients with lower pain tolerance or busy schedules.
c-MYC expression in T (III/IV) stage oral squamous cell carcinoma (OSCC) patients

Purpose: c-MYC has been noted in many tumor types, but its functional significance and clinical utility in oral squamous cell carcinoma (OSCC) are not well known. Here we studied the expression of c-MYC in correlation to clinical outcome in patients with oral squamous cell carcinoma. Methods: The current study, using immunohistochemical staining, first examined c-MYC expression in OSCC patients and further correlated its expression with clinicopathological parameters. Results: c-MYC was expressed in the majority of OSCC patients (n=133). The c-MYC expression is associated with histological grade (P=0.0205) of patients with oral squamous cell carcinoma. Multivariate Cox regression analysis revealed that TN stage (P<0.001), American Joint Committee on Cancer (AJCC) stage (P<0.0001), and tumor differentiation (P=0.0025) were independent factors for overall survival in patients with OSCC except for c-MYC expression (P>0.05). Multiplicative-scale interaction between T stage (III/IV) and low c-MYC expression on mortality risk was identified (P=0.0233). Kaplan–Meier survival analysis demonstrated that oral cancer patients (T III/IV stage) with high c-MYC expression had better survival than those with low and medium c-MYC expression (P=0.0270). Conclusion: Our data indicate that c-MYC is a potential biomarker that can be used as a therapeutic target for treating OSCC patients with T stage (III/IV).
Prognostic factors in pediatric pneumococcal meningitis patients in mainland China: a retrospective multicenter study

Background: Prognosis of pneumococcal meningitis (PM) remains very poor, especially in less developed countries. Currently, few multi-centric studies on pediatric PM have been reported in mainland China. Objectives: This study aimed to explore the correlation of clinical and laboratory findings with complications and prognosis in pediatric PM. Methods: The pediatric PM patients were retrospectively recruited from ten pediatric tertiary hospitals across China between January 2013 and June 2018. Clinical, biochemical, and microbiological data and follow-up information were collected. Predictive factors for complications and prognostic factors for overall survival (OS) and sequelae-free survival (SFS) were analyzed. Results: A total of 132 pediatric PM patients were included. Seventy-one patients had complications, 25 patients died, and 39 patients had neurological sequelae. Multivariate logistic regression suggested that age less than 28 months (adjusted OR=2.654, 95%CI=1.067–6.600, P=0.036) and lower white blood cells in blood (aOR=3.169, 95%CI=1.395–7.202, P=0.006) were associated with high risk of complications. Multivariate Cox’s proportional hazard regression suggested that age less than 28 months (aHR=6.479, 95%CI=1.153–36.404, P=0.034), coma (aHR=9.808, 95%CI=2.802–34.323, P=0.000), and non-adjuvant steroid therapy (aHR=4.768 95%CI=1.946–11.678, P=0.001) were independent prognostic factors for poor OS; coma (aHR=5.841, 95%CI=2.652–12.864, P=0.000), septic shock on admission (aHR=2.949, 95%CI=1.049–8.290, P=0.040), and lower glucose level in cerebrospinal fluid (CSF) (aHR=2.523, 95%CI=1.336–4.765, P=0.004) were independent prognostic factors for poor SFS. Conclusion: Age, coma, and adjuvant steroid therapy were independent factors for OS, while coma, septic shock on admission, and lower glucose level in CSF were independent factors for SFS in pediatric PM patients. These factors might be used to identify PM patients with poor prognosis and guide individual treatment.
The effect of etomidate or propofol on brainstem function during anesthesia induction: a bispectral index-guided study

Purpose To compare the effect of etomidate versus propofol infusion on hemodynamic profiles, spontaneous breathing, and corneal reflex during the induction of anesthesia. Methods Adult patients (n=80) were randomized to receive etomidate (Group E, n=40) or propofol (Group P, n=40) infusion during anesthesia induction. Throughout induction, mean blood pressure and heart rate were monitored. Time to loss of consciousness (LOC), bispectral index (BIS), existence of spontaneous breathing, and corneal reflex at LOC were recorded. Results Fewer changes in hemodynamic profile occurred in Group E compared with Group P during induction of anesthesia. The mean time to LOC was shorter with etomidate than propofol (129.5 s vs 189.5 s, P<0.0001). BIS was lower in Group E compared with Group P at LOC (46.3 vs 52.9, P=0.0141). More patients exhibited spontaneous breathing in Group E compared with Group P at LOC (80% vs 17.5%, P<0.0001). Similarly, more patients maintained corneal reflex in Group E compared with Group P (34 patients vs 4 patients, P<0.0001). The incidence of etomidate-induced myoclonus was 17.5%. Conclusion Compared with propofol infusion, etomidate infusion during anesthesia induction had fewer effects on the hemodynamic profile of patients. Among patients who received etomidate, the BIS value was lower at LOC, and more patients displayed spontaneous breathing and corneal reflex. Trial Registry Number China Clinical Research Information Service, ChiCTR-IOR-17011050
The natural flavonoid glycoside vitexin displays preclinical antitumor activity by suppressing NF-κB signaling in nasopharyngeal carcinoma

Background and objectives: Vitexin is a natural flavonoid glycoside mainly extracted from the leaves of vitex, which has a variety of physiological activities. For example, vitexin has antitumor and anti-inflammation activities, and it can also promote blood circulation in the body. However, the function and mechanism of vitexin in nasopharyngeal carcinoma (NPC) are still unclear. Materials and methods: Cell Counting Kit-8 assay and cell cycle analysis were performed to examine cell survival in response to vitexin. Immunoblotting was used to analyze relative proteins’ expression. NPC xenograft models were established to assess the effect of vitexin in vivo. The luciferase activity of pNFκB-Luc was analyzed by using Dual-Luciferase Reporter Assay System. Quantitative real-time polymerase chain reaction was performed to detect relative genes’ expression. Kinase activity of IKKβ was analyzed in a cell-free system. Results: In this study, vitexin was found to display significant antitumor activity in NPC in vitro and in vivo. In NPC cells, vitexin inhibited cell cycle progression in NPC cells and induced the cleavages of PARP and inhibited antiapoptotic proteins’ expression, including Bcl-2 and Mcl1. Further studies indicated that vitexin significantly suppressed the luciferase activity of pNF-κB-Luc and inhibited the activation of NF-κB key regulators, including p65, IκBα and IKKs in NPC cells. Moreover, the kinase activity of IKKβ could be suppressed by vitexin in a cell-free system, and overexpression of CA-IKKβ could attenuate the inhibitory effect of vitexin on p65 phosphorylation. Conclusion: These results indicated that vitexin displayed antitumor activity by suppressing NF-κB signaling in NPC, which suggested that vitexin could be as a potential drug for the treatment of NPC in the future.
Evaluation of patients’ needs to design and assess a patient education program in cancer pain

Purpose: Patient education constitutes a relevant strategy to improve pain management. In the field of therapeutic patient education (TPE), we aimed 1) to assess pain impact in cancer patients, 2) to identify patients’ educative needs in pain management, and 3) to refine research criteria for its future evaluation. Patients and methods: Pain intensity, relief and interference were assessed in 75 cancer patients with unbalanced background pain. Self-assessment questionnaire evaluated i) patients’ pain management and ii) their knowledge and needs in TPE. Results: Most patients experienced pain for more than 6 months and 41.6% reported adequate pain relief. Understanding pain and pain management were major patients’ preferences (>58%). Most patients declared they knew their pain treatments, but fewer than half of them were able to name them. However, education concerning pain treatment was considered as essential in <30% of patients. Almost all patients (97.1%) stated pain education as beneficial, with a preference for individualized sessions (41.2%). In addition, the assessment criteria for its future evaluation were refined. Conclusion: Targeted population mainly concerned patients with persistent pain. Only half of patients reported pain relief despite antalgics. Patient education was declared as beneficial for almost all participants. Practice implications: Tailoring a pain TPE on patients’ needs has the potential to help them to optimally manage their pain daily.
Physical activity programs for older people in the community receiving home care services: systematic review and meta-analysis

: The proportion of older adults is increasing around the world and most wish to live in their home until they die. To achieve this, many will require services in the home to remain living independently. To maintain function (ie, strength, balance, and endurance), physical activity needs to be undertaken on a regular basis, and is essential as a person ages. Unfortunately, as people age there is a tendency to reduce activity levels, which often leads to loss of function and frailty, and the need for home care services. This updated systematic review includes a mix of study methodologies and meta-analysis, and investigated the effectiveness of physical activity/exercise interventions for older adults receiving home care services. Eighteen studies including ten randomized controlled trials meeting the selection criteria were identi ﬁ ed. Many of the studies were multi-factorial interventions with the majority reporting aims beyond solely trying to improve the physical function of home care clients. The meta-analysis showed limited evidence for effectiveness of physical activity for older adults receiving home care services. Future exercise/physical activity studies working with home care populations should consider focusing solely on physical improvements, and need to include a process evaluation of the intervention to gain a better understanding of the association between adherence to the exercise program and other factors in ﬂ uencing effectiveness.
Stability and osteogenic potential evaluation of micro-patterned titania mesoporous-nanotube structures

Background: Although titanium dioxide nanotubes (TNTs) had great potential to promote osteogenesis, their weak bonding strength with titanium substrates greatly limited their clinical application. Purpose: The objective of this study was to maintain porosity and improve the stability of TNT coatings by preparing some micro-patterned mesoporous/nanotube (MP/TNT) structures via a photolithography-assisted anodization technology. Methods: The adhesion strength of different coatings was studied by ultrasonic cleaning machine and scratch tester. The early adhesion, spreading, proliferation and differentiation of MC3T3-E1 cells on different substrates were investigated in vitro by fluorescent staining, CCK8, alkaline phosphatase activity, mineralization and polymerase chain reaction assays, respectively. Results: Results of ultrasonic and scratch assays showed that the stability of TNTs (especially 125 nm) was significantly improved after being patterned with MP structures. In vitro cell assays further demonstrated that the insertion of MP structure into 125 nm TNT coating, which was denoted as MP125, could effectively improve the early adhesion, spreading and proliferation of surface MC3T3-E1 cells without damaging their osteogenic differentiation. Conclusion: We determined that the MP/TNT patterned samples (especially MP125) have excellent stability and osteogenesis properties, and may have better clinical application prospects.