Miracle-dz/UniFAR-FTUs huggingface dataset:
Balanced Scorecard for performance assessment in healthcare settings: a review of literature

The Balanced-Scorecard (BSC) is a management tool developed in the early 1990s to balance the impact of financial and non-financial parameters and analyse the organisational performance in private companies according to four determinants. The original BSC has spread to different sectors in the last decades, including healthcare services, in numerous amended versions. The aim of our project was to identify potential indicators of BSC for performance evaluation in general hospitals. We performed a systematic review of literature on Pubmed and Web of Science using the search string “balanced scorecard AND healthcare AND indicators”. We found 102 papers; 80 papers were removed for irrelevance, absence of full text or performance indicators. We only considered articles that followed the classic structure of BSC (Customer, Internal Processes, Financial, and Learning and Growth). The indicators listed in them were classified according to the four determinants of organisational performance. Eight articles out of 22 followed the classic structure of the BSC. The most represented category was Internal Processes (59 indicators), followed by Learning and Growth (52), Customer (40) and Financial (33). The number of common/overlapping indicators was low (5 for Internal Processes and 4 for the three other categories). While BSC has spread to different settings, the list of indicators used in the classic four determinants for performance evaluation is heterogeneous. While common points can be identified between indicators, our review highlighted that every BSC is developed in a unique way which makes it difficult to identify a general framework adaptable to different hospital settings. The use of the Balanced Scorecard as management tool has spread to healthcare settings in the last decade. Indicators in BSC for healthcare settings are heterogeneous and only a limited number follow the standard structure of BSC.
Novel KMT2A Partner Gene NUTM2A Revealed By Anchored Multiplex PCR in ALL

Objectives Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric and adult acute leukemias. Such rearrangements are more frequent in infants, in whom they are found in 60% - 80% of acute lymphoblastic leukemias (ALL). KMT2A-r group itself is genetically heterogeneous. KMT2A-r can occur with at least 94 partner genes previously described in «THE MLL RECOMBINOME <…> IN 2017». Detection of KMT2A-r is an essential part of AL initial diagnostics. Also, the accurate detection of all KMT2A-r types is crucial in order to perform minimal residual disease (MRD) monitoring, as it is clear now that MRD-based therapy adjustment has a very strong impact on outcome. Here we report a case of novel KMT2A partner in pediatric ALL - NUT family member 2A (NUTM2A). Methods The patient is 8 y.o. girl with T-cell acute lymphoblastic leukemia with pleural effusion. Bone marrow and pleural fluid aspirates were analyzed by G-banded karyotyping and FISH with KMT2A breakapart probe. Pleural fluid aspirates were also analyzed by real-time RT-PCR for 8 most common KMT2A rearrangements screening, long-distance inversed PCR and targeted RNA-seq with FusionPlex Myeloid kit (ArcherDX, CO, USA). Sanger sequencing was used for validation. Results Conventional cytogenetics and FISH showed 47,XX,t(10;11)(q22;q23),+mar[5] karyotype with 100% KMT2A-rearranged nuclei. Gene fusion analysis identified novel fusion KMT2A-NUTM2A with exon 11 - exon 1 breakpoint junction. NUTM2A is a gene at 10q23.2. This gene is not fully described in the literature. Rearrangements of this gene were identified in endometrial stromal sarcomas (ESS) (Cheng-Han Lee et al. 2012) and small round cell sarcoma (SRCS) (Sugita et al. 2017). In case of ESS, this rearrangement results in an in-frame fusion between YWHAE and NUTM2A (or highly homologous gene NUTM2B), and in case of SRCS it results in an in-frame fusion between NUTM2A and CIC. To our knowledge, KMT2A-NUTM2A fusion in our study is the first case demonstrating NUTM2A rearrangement in hematological malignancies. Conclusions Here we for the first time show the novel KMT2A-NUTM2A fusion transcript, which was found in pediatric T-cell acute lymphoblastic leukemia. Anchored multiplex PCR is one of the most sensitive way to detect rare variants of KMT2A rearrangements. It also allows selecting patient-specific primers for further PCR detection of MRD. No relevant conflicts of interest to declare.
Treatment of colon cancer with multiple liver metastases

Abstract Treatment of patients with colorectal cancer and synchronous liver metastases is challenging. We present the case of a 34-year-old woman who had about 50 liver metastases from an adenocarcinoma of the sigmoid colon. Neoadjuvant chemotherapy led to a remarkable response of the hepatic metastases. The patient was subjected to sigmoidectomy with primary anastomosis and synchronous treatment of all liver metastases. The number of liver lesions should not in itself present a contraindication to resection. This is the first report of successful concomitant surgical treatment of sigmoid adenocarcinoma and multimetastatic liver disease.
Transcanal Computed Tomography Views for Transcanal Endoscopic Lateral Skull Base Surgery: Pilot Cadaveric Study

Abstract Objective Transcanal endoscopic operative approaches provide for a minimally invasive surgical portal to the lateral skull base. Traditional preoperative imaging evaluation involves computed tomography (CT) acquisition in the axial and coronal planes that are not optimized for the transcanal surgical corridor. Herein, we describe a novel CT-based “transcanal view” for preoperative surgical planning and intraoperative navigation. Study Design Present study is a cadaveric imaging study. Methods Cadaveric temporal bones (n = 6) from three specimens underwent high-resolution CT (0.625 mm slice thickness). Using three-dimensional (3D) Slicer 4.8, reformatted “transcanal” views in the plane of the external auditory canal (EAC) were created. Axial and coronal reformats were used to compare and measure distances between anatomic structures in the plane of the EAC. Results The degree of oblique tilt for transcanal CT reformats was 6.67 ± 1.78 degrees to align the EAC in axial and coronal planes. Anticipated critical landmarks were identified easily using the transcanal view. Mean values were 8.68 ± 0.38 mm for annulus diameter, 9.5 ± 0.93 mm for isthmus diameter, 10.27 ± 0.73 mm for distance between annulus and isthmus, 2.95 ± 0.13 mm for distance between annulus and stapes capitulum, 5.12 ± 0.35 mm for distance between annulus and mastoid facial nerve, and 19.54 ± 1.22 mm for EAC length. Conclusion This study is the first to illustrate a novel “transcanal” CT sequence intended for endoscopic lateral skull base surgery. Future studies may address how incorporation of a transcanal CT reformat may influence surgical decision making.
Invasive Aspergillosis in Transplant Recipients

Patients with hematological malignancies and recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) as well as solid organ transplant recipients are the groups of patients with the highest risk of invasive fungal infections (IFI). Neutropenia, lymphopenia, chemotherapy of malignancies, radiation therapy, immunosuppressive therapy, administration of glucocorticosteroids, use of central venous catheters, dialysis therapy, liver and kidney failure, and diabetes are diseases and medical conditions which foster invasive fungal infections. In recent years, it has been observed that the most common etiological agents of these infections are yeastlike fungi of the genus Candida, and the second most common is moulds Aspergillus spp. Antifungal agent recommended for therapy of IFI caused by Aspergillus is voriconazole, according to the present guidelines. A combined therapy using voriconazole and caspofungin may not be effective. According to numerous publications, in case of infections caused by strains resistant to voriconazole, a therapeutic success is possible after a switch to the liposomal form of amphotericin B. Due to nonspecific clinical symptoms of IFI caused by Aspergillus spp. , histopathological as well as mycological and serological tests, echocardiographic examination, magnetic resonance imaging (MRI) and computer tomography (CT) may contribute to an early and reliable diagnosis of invasive aspergillosis.
Poor Prognosis With Coexistence Of EGFR T790M Mutation And Common EGFR-Activating Mutation In Non- Small Cell Lung Cancer

Purpose Previous studies have shown that the presence of EGFR T790M mutation may reduce the treatment efficacy of tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung cancer. However, little is known about the clinical features and outcomes of EGFR T790M mutation in pretreated patients with NSCLC. Patients and methods The clinical features of EGFR-activating and T790M mutations were assessed in a large cohort of patients with EGFR-TKI-naïve NSCLC (all/EGFR mutations, n=16,347/7,687). The correlation between the pretreatment T790M mutation status and clinical outcomes was evaluated using univariate and multivariate analyses. Results Pretreatment T790M mutation was reported in 1.39% of the patients and coexisted with an EGFR-activating or uncommon mutation. The dual EGFR T790M and common EGFR-activating mutations were more likely to be detected in lung adenocarcinoma, whereas single T790M mutation was more prevalent in non-adenocarcinomas. The presence of de novo T790M mutation correlated with reduced recurrence-free survival (RFS) in patients with NSCLC (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.67–6.79, P = 0.001). After molecular stratification, T790M mutation was shown to exert adverse effects on the RFS of EGFR 19-del group (OR 2.89, 95% CI 1.10–7.91, P = 0.028) and EGFR L858R group (OR 3.43, 95% CI 1.33–8.88, P = 0.013). Furthermore, pretreatment T790M mutation promoted tumor metastasis to different sites. Conclusion T790M-positive tumors presented special clinical features, and the coexistence of T790M and common EGFR-activating mutations was associated with poor prognosis in patients with NSCLC.
Inhibition of CML Stem Cell Growth By Targeting WNT Signaling Using a Porcupine Inhibitor

BCR-ABL tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML). However, TKIs are unable to eradicate the leukemia stem cells (LSCs) from which CML arises, despite effective inhibition of BCR-ABL kinase activity in this population. There is evidence that extrinsic signals from the bone marrow (BM) microenvironment play an important role in the resistance of CML LSC to TKI treatment. Our previous studies have shown a role for Wnt signaling in protecting CML LSC from TKI treatment (Blood. 2013; 121(10):1824-38). Palmitoylation of Wnts by the Porcupine acyltransferase (PORCN) is required for their secretion and activity. LGK974, a potent PORCN inhibitor, has recently been shown to inhibit Wnt signaling and shows in vivo efficacy against several Wnt-dependent tumors (PNAS. 2013; 110(50):20224-9). In this study, we investigated whether inhibition of Wnt secretion using LGK974 could sensitize CML stem/progenitor cells to TKI treatment. CML and normal CD34+ cells and purified CD34+CD38- stem cells and CD34+CD38+ committed progenitors were treated with LGK974 with or without addition of the BCR-ABL TKI (nilotinib), and in the presence and absence of human BM mesenchymal stromal cells (MSC). CML CD34+ cells showed enhanced Wnt signaling following exposure to recombinant Wnt3a (200ng/ml) compared to normal CD34+ cells as evidenced by increased phospho-LRP6 (ser1490) and β-catenin protein levels. Analysis of all 10 frizzled receptors expression by qRT-PCR revealed a significant upregulation of FZD4 (p=0.026, n=10), and FZD5 (p=0.003, n=10), but downregulation of FZD8 (p=0.009, n=10), in CML compared to normal CD34+ cells. Co-culture with MSC was associated with increased Wnt signaling in CML CD34+ cells as detected by increased expression and nuclear translocation of β-catenin protein, and increased expression of Wnt target genes including c-Myc, Cyclin-D1, PPARδ, and Axin2. Treatment with LGK974 reduced Wnt secretion from MSC measured in a TCF/LEF reporter assay (LGK 0.5μM, 0.74 fold reduction compared to control, p=0.016, n=5, LGK 1μM, 0.62 fold reduction, p=0.007, n=5) and potently inhibited Wnt signaling in CML CD34+ cells both in the absence and presence of MSC. Treatment with LGK974 (1μM) in combination with nilotinib (1μM) resulted in significantly increased inhibition of CML CFC growth compared to nilotinib alone, both in the presence and absence of MSC (34+38- cells LGK alone 82.75±6.38% inhibition of control, Nil alone 43.12±15.32%, combination 23.17±6.48%, p Disclosures Wang:Novartis Institute for Biomedical Research: Employment. McLaughlin:Novartis Institute for Biomedical Research: Employment.
Blended Learning Compared to Traditional Learning in Medical Education: Systematic Review and Meta-Analysis

Background Blended learning, which combines face-to-face learning and e-learning, has grown rapidly to be commonly used in education. Nevertheless, the effectiveness of this learning approach has not been completely quantitatively synthesized and evaluated using knowledge outcomes in health education. Objective The aim of this study was to assess the effectiveness of blended learning compared to that of traditional learning in health education. Methods We performed a systematic review of blended learning in health education in MEDLINE from January 1990 to July 2019. We independently selected studies, extracted data, assessed risk of bias, and compared overall blended learning versus traditional learning, offline blended learning versus traditional learning, online blended learning versus traditional learning, digital blended learning versus traditional learning, computer-aided instruction blended learning versus traditional learning, and virtual patient blended learning versus traditional learning. All pooled analyses were based on random-effect models, and the I2 statistic was used to quantify heterogeneity across studies. Results A total of 56 studies (N=9943 participants) assessing several types of learning support in blended learning met our inclusion criteria; 3 studies investigated offline support, 7 studies investigated digital support, 34 studies investigated online support, 8 studies investigated computer-assisted instruction support, and 5 studies used virtual patient support for blended learning. The pooled analysis comparing all blended learning to traditional learning showed significantly better knowledge outcomes for blended learning (standardized mean difference 1.07, 95% CI 0.85 to 1.28, I2=94.3%). Similar results were observed for online (standardized mean difference 0.73, 95% CI 0.60 to 0.86, I2=94.9%), computer-assisted instruction (standardized mean difference 1.13, 95% CI 0.47 to 1.79, I2=78.0%), and virtual patient (standardized mean difference 0.62, 95% CI 0.18 to 1.06, I2=78.4%) learning support, but results for offline learning support (standardized mean difference 0.08, 95% CI –0.63 to 0.79, I2=87.9%) and digital learning support (standardized mean difference 0.04, 95% CI –0.45 to 0.52, I2=93.4%) were not significant. Conclusions From this review, blended learning demonstrated consistently better effects on knowledge outcomes when compared with traditional learning in health education. Further studies are needed to confirm these results and to explore the utility of different design variants of blended learning.
Thoracic Unilateral Spinal Cord Syndrome Following Neuraxial Anaesthesia for Periprosthetic Knee Fracture: A Case Report

Neuraxial anaesthesia is widely used in surgical procedures; overall, epidural and intrathecal techniques. Nevertheless, several outcomes should be considered. The incidence of neurologic complications after neuraxial anaesthesia is not perfectly clear (0% - 0.08%), although there are several described cases of spinal cord ischemia. We present a case of thoracic unilateral spinal cord syndrome following lumbar spinal anaesthesia for periprosthetic knee fracture. Our patient suffered monoparesis in her left lower limb as well as decreasing of muscle strength and loss of tendon reflexes. The MNR showed left hyperintense intra-cord images from T7 to T12 attributed to spinal cord oedema and a lineal hypointensity related to minimal haematic component. What made this case surprising was the fact that spinal anaesthesia was performed between L3 and L4 and the patient did not suffer paraesthesia associated with local anaesthetic injection. She was treated with glucocorticoids, gabapentin and amitriptyline. She also was checked by physical rehabilitators, neurologists and Pain Unit physicians. We have found another case reported in the literature about thoracic cord injury after lumbar spinal puncture. In this paper, we report possible aetiologies according to a review and neurological evolution of the patient seven months later.
Cardiac Arrest Secondary to Short-Coupled TdP: A Case Report

Background: The short-coupled variant of Torsade de Pointes (Sc-TdP) is rare and causes Torsade-like polymorphic ventricular tachycardia (VT) without the classical QT-prolongation. It is initiated by a remarkably short coupling interval (<300 ms). The arrhythmia is important to identify as the treatment differs from another traditional polymorphic VT. Case summary: A 76 years old male was transferred to our coronary care unit after surviving an out of hospital cardiac arrest. Apart from frequent premature ventricular beats, the electrocardiogram was normal. In the acute phase, left ventricular function was decreased, but quickly normalized. The coronary angiography (CAG) revealed normal coronary arteries. The first night after the CAG was performed, the patient experienced a new episode of cardiac arrest with successful resuscitation. The telemetry revealed Sc-Tdp. He was initially treated with intravenous amiodarone, later changed to oral metoprolol. An implantable cardioverter defibrillator (ICD) was inserted, metoprolol was replaced by verapamil and the patient was discharged. A 3-month follow-up visit revealed two episodes of short-lasting VT but no therapy was delivered by the ICD. Conclusion: Data on the clinical management of patients with Sc-TdP during the acute phase and long-term clinical outcome remain minimal. In our present case, verapamil seems to be an effective drug in suppressing the arrhythmias, but it does not eliminate the need of an ICD to reduce the risk of sudden cardiac death.
DELIRIUM E CORRELAÇÕES CLÍNICAS OBSERVADAS EM PESSOAS DA TERCEIRA IDADE INTERNADAS EM UM HOSPITAL GERAL

O objetivo com esse estudo e identificar alguma associacao entre pacientes internados em um hospital geral e o desenvolvimento de delirium, uma sindrome neuropsiquiatrica grave, caracterizada por disturbio da consciencia e rebaixamento cognitivo, considerando variaveis como: idade, sexo, tempo e local de internamento, grupo de medicamentos em uso, sitio orgânico da patologia de base que motivou o internamento e dados laboratoriais como hemoglobina, creatinina e glicemia. O estudo transversal observacional foi realizado durante o mes de maio de 2014, atraves da entrevista de pacientes internados na enfermaria e na unidade de terapia intensiva (UTI) de um hospital geral, em Santa Rita-PB, apos aprovacao do Comite de Etica em Pesquisa sob o protocolo no 59/14. Sessenta pacientes com idade igual ou superior a 60 anos, internados pelas mais variadas causas, foram submetidos ao chamado de Metodo de Avaliacao da Confusao (Confusion Assessment Method - CAM). Concluiu-se que, entre os pacientes que apresentaram o diagnostico de delirium segundo CAM, apenas os na setima decada e os com anemia atingiram significância estatistica. As doencas gastrointestinais, os glicocorticoides e os opioides foram o grupo de doencas e os farmacos, respectivamente, mais implicados na genese do deficit de atencao, apesar de nao apresentarem significância estatistica.
Encapsulating Peritoneal Sclerosis: A Rare Devastating Peritoneal Disease: Case Series and Literature Review

Background: Encapsulating peritoneal sclerosis is a rare but life-threatening condition in peritoneal dialysis. It is associated with extensive thickening and fibrosis of the peritoneum resulting in recurrent small bowel obstructions and malnutrition. Herein we present case series of encapsulating peritoneal sclerosis diagnosed and treated in a large center of peritoneal dialysis in the State of Qatar followed by literature review to increase the awareness of physicians to it. Case Presentation: The data were collected retrospectively from 180 peritoneal dialysis patients at Hamad General Hospital, Doha, Qatar, between 2008 and 2016. The diagnosis of encapsulating peritoneal sclerosis was based on clinical and radiological features. Seven patients (3.8%) were diagnosed with encapsulating peritoneal sclerosis. The mean age of the patients was 49 years (range, 23 to 65 years). The mean duration of peritoneal dialysis was 6 years (range, 3 to 7 years). The mean peritonitis episodes were 1.8 (range 1 to 4 episodes). Five patients were diagnosed with encapsulating peritoneal sclerosis after stopping peritoneal dialysis, and two patients diagnosed while they were on peritoneal dialysis treatment. Five patients are still alive and were treated with oral prednisolone and tamoxifen. Two patients underwent adhesiolysis surgery, one of them died due to recurrent sepsis and malnutrition. Another patient died because of cardiac arrest during hemodialysis. The overall mortality rate was 28.5% in our series. Conclusions: Encapsulating peritoneal sclerosis is a rare and life-threatening peritoneal disease in chronic peritoneal dialysis patients. It requires high index of suspicion for early diagnosis and treatment.
May Tigit (T cell Ig and ITIM domain) Expression be a New Target for Hodgkin Lymphoma?

Introduction: The use of immune-checkpoints (anti PD-1/PD-L1) resulted very effective in the treatment of relapsed/refractory classical Hodgkin Lymphoma (cHL). T cell Ig and ITIM domains (TIGIT) is another immune checkpoint receptor known to negatively regulate T cell functions. Methods: In this study, we investigated the expression of TIGIT in cHL microenvironment in order to find a potential new target for inhibitor therapy. TIGIT, PD-1 and PD-L1 expression was evaluated in 34 consecutive patients with cHL referred to Campus Bio-Medico University Hospital for diagnosis and treatment during the last eight years. Results: TIGIT positivity was observed in 19/34 patients (56%), of these 11 (58%) had advanced stages and 10 (52%) B symptoms. Among the 8 patients with IPS ≥ 4, 6 (75%) were TIGIT +. Out of the 19 TIGIT + (score 1 to 3) peritumoral T lymphocytes, 16 (84%) were also PD-1+. While out of 15 TIGIT- peritumoral T lymphocytes only 4 (27%) were PD-1+ and 11 (73%) were PD1- (P=0.001). Moreover all 15 TIGIT- patients were PD-L1+ (100%) while out of 19 TIGIT + patients, 11 (58%) were PD-L1+ and 8 (42%) PD-L1- (P=0.004). Conclusion: This study indicate that the great majority of TIGIT+ patients are also PD-1+, while those who are TIGIT- are all PD-L1+. These results may offer a new therapeutic possibility in the treatment of Relapsed/Refractory (R/R) cHL by the use of anti-TIGIT monoclonal antibodies. Figure