The Power and Promise of Angiotensin Receptor Neprilysin Inhibitor (ARNI) in Heart Failure Management: National Consensus Statement.

;Heart failure (HF) is a huge global public health task due to morbidity, mortality, disturbed quality of life, and major economic burden. It is an area of active research and newer treatment strategies are evolving. Recently angiotensin receptor-neprilysin inhibitor (ARNI), a class of drugs (the first agent in this class, Sacubitril-Valsartan), reduces cardiovascular mortality and morbidity in chronic HF patients with reduced left ventricular ejection fraction (LVEF). Positive therapeutic effects have led to a decrease in cardiovascular mortality and HF hospitalizations (HFH), with a favorable safety profile, and have been documented in several clinical studies with an unquestionable survival benefit with ARNI, Sacubitril-Valsartan. This consensus statement of the Indian group of experts in cardiology, nephrology, and diabetes provides a comprehensive review of the power and promise of ARNI in HF management and an evidence-based appraisal of the use of ARNI as an essential treatment strategy for HF patients in clinical practice. Consensus in this review favors an early utility of Sacubitril-Valsartan in patients with HF with reduced EF (HFrEF), regardless of the previous therapy being given. A lower rate of hospitalizations for HF with Sacubitril-Valsartan in HF patients with preserved EF who are phenotypically heterogeneous suggests possible benefits of ARNI in patients having 40-50% of LVEF, frequent subtle systolic dysfunction, and higher hospitalization risk.

A Review on a Deep Learning Perspective in Brain Cancer Classification.

A World Health Organization (WHO) Feb 2018 report has recently shown that mortality rate due to brain or central nervous system (CNS) cancer is the highest in the Asian continent. It is of critical importance that cancer be detected earlier so that many of these lives can be saved. Cancer grading is an important aspect for targeted therapy. As cancer diagnosis is highly invasive, time consuming and expensive, there is an immediate requirement to develop a non-invasive, cost-effective and efficient tools for brain cancer characterization and grade estimation. Brain scans using magnetic resonance imaging (MRI), computed tomography (CT), as well as other imaging modalities, are fast and safer methods for tumor detection. In this paper, we tried to summarize the pathophysiology of brain cancer, imaging modalities of brain cancer and automatic computer assisted methods for brain cancer characterization in a machine and deep learning paradigm. Another objective of this paper is to find the current issues in existing engineering methods and also project a future paradigm. Further, we have highlighted the relationship between brain cancer and other brain disorders like stroke, Alzheimer's, Parkinson's, and Wilson's disease, leukoriaosis, and other neurological disorders in the context of machine learning and the deep learning paradigm.

Barriers and enablers to meticillin-resistant Staphylococcus aureus admission screening in hospitals: a mixed-methods study.

BACKGROUND: To reduce the risk of transmission of meticillin-resistant Staphylococcus aureus (MRSA), international guidelines recommend admission screening to identify hospital patients at risk of colonization. However, routine monitoring indicates that optimum screening compliance levels are not always achieved. In order to enhance compliance, we must better understand those factors which influence staff screening behaviours. AIM: To identify factors which influence staff compliance with hospital MRSA screening policies. METHODS: A sequential two-stage mixed-methods design applied constructs from normalization process theory and the theoretical domains framework to guide data collection and analysis. Initial qualitative findings informed subsequent development of a national cross-sectional survey of nursing staff (N = 450). Multiple regression modelling identified which barriers and enablers best predict staff compliance. FINDINGS: Three factors were significant in predicting optimum (>90%) compliance with MRSA screening: having MRSA screening routinized within the admission process; category of clinical area; feedback of MRSA screening compliance within the clinical area. Integration of data-sets indicated that organizational systems which 'make doing the right thing easy' influence compliance, as does local ward culture. Embedded values and beliefs regarding the relative (de)prioritization of MRSA screening are important. CONCLUSION: To our knowledge, this is the first study to provide original evidence of barriers and enablers to MRSA screening, applying both sociological and psychological theory. As antimicrobial resistance is a global health concern, these findings have international relevance for screening programmes. Future policy recommendations or behaviour change interventions, based on the insights presented here, could have significant impact upon improving screening compliance.

Implementation of failure mode and effective analysis for high dose rate brachytherapy at Tata Memorial Hospital, Mumbai, India.

PURPOSE: To report our experience of failure mode and effective analysis for high dose rate brachytherapy of gynaecological cancer carried out in our hospital. MATERIALS AND METHODS: Failure mode and effective analysis process described in AAPM TG 100 was followed: a multidisciplinary team consisting of two physicians, physicists, dosimetrists, a medical resident, a nurse, and a secretary was formed. A weekly meeting was held for four months. A process tree was created based on the overview of the entire process, with the main branches as follows: procedure in the operating room, patient imaging, contouring, treatment planning, machine quality assurance and treatment delivery. Each team member assigned the risk probability numbers based on the predefined scoring system. For a particular failure mode, if the risk probability number assigned by one member differed from the other, the highest risk probability number was taken into consideration. RESULTS: The process tree consisted of 185 nodes, with risk probability numbers ranging from 1-220, with 77 possible failure modes. Four nodes were found with risk probability numbers greater than 200, which were considered for immediate process improvements. Twenty-four nodes were found to be with risk probability numbers ranging from 100 to 200. All 24 processes were considered for process improvement, out of which 12 were found effective and feasible, which includes failure nodes with high severity score at least 8. The processes with high-risk probability numbers (greater than 200) were reduced after the introduction of process improvements. For the other processes, standard procedures were modified. The common causes of failure, were found to be due to lack of attention, human error and work pressure. CONCLUSIONS: Failure mode and effective analysis is a useful tool that uses a systematic approach for quality management of a specific process.

Clinical outcomes and the role of adjuvant therapy sequencing in Type II uterine cancer following definitive surgical treatment.

PURPOSE OF INVESTIGATION: Because of rarity, consensus on adjuvant therapies for Type II endometrial cancers (BC) remains undefined. Reporting their institutional outcomes, the present authors assessed the impact of adjuvant therapies on recurrence and overall survival in women with 2009 FIGO Stage I-III Type II BC. MATERIAL AND METHODS: The authors identified 108 women, treated with definitive surgery between 2000-2013, with pathologically-confirmed Type II EC (non-endometrioid [NEM, n=801 and high grade endometrioid [G3EEC, n=28]) Cox proportional hazard models were used to assess the effect of prognostic variables on disease-free (DFS) and overall survival (OS). Kaplan-Meier method was used to assess survival. RESULTS: Of the 108 women, 83 (77%) were African American (AA). Fifty-nine (55%), 12 (11%), and 37 (34%) were Stage I, II, and III, respectively. Ninety-seven patients received adjuvant therapy: 52 (radiation only), four (chemotherapy only), and 40 (combined). During follow-up (median 41 months), 44 patients (41%) recurred. Five-year DFS was 53% overall (48% [NEM], 80% [G3EEC]). Five-year OS was 75% overall (68% [NEM], 95% [G3EEC]). On multivariate analysis, lower stage and adjuvant radiation improved DFS. Higher stage, NEM, and increasing age were poor prognostic indicators of OS. CONCLUSION: Representing a large single institutional cohort for Type II BC, the present study's observed sur- vival rates are consistent with previous studies, despite the relatively high frequency of carcinosarcoma and Stage III/nodal disease. The protective effect on recurrence was not lost when radiation was delayed for chemotherapy. The present results support a multimodal adjuvant approach for treating all stages of invasive NEM EC.

Long-term remission of clear cell carcinoma of the cervix after chemoradiation with 109 cycles of paclitaxel: a case report and literature review.

BACKGROUND: Clear cell carcinoma of cervix (CCCC) is a rare cervical neoplasm that is usually associated with diethylstilbestrol (DES) exposure in utero as a primary risk factor. Advanced stage disease typically has poor outcomes and no evidence-based approach exists to guide clinicians in treating this rare disease. CASE: The authors report a case of locally advanced CCCC in a 37-year-old Caucasian female. She underwent chemoradiation therapy that included 109 courses of paclitaxel chemotherapy until no disease could be detected on imaging studies. She is now disease-free 13 years after discontinuing chemotherapy. CONCLUSION: A prolonged course of single agent paclitaxel after completing standard radiation therapy was successful in achieving remission in a patient with this rare disease.

Histopathologic review of 400 biopsies and resection specimens of trunk and extremity-based soft tissue tumors.

AIMS: To review various pathologic parameters in diagnosed cases of trunk and extremity-based soft tissue tumors (STTs), in order to identify concordance rate between initial biopsy and resection specimen and discrepancies between initial and review diagnosis, by a specialist pathologist. MATERIALS AND METHODS: Over a 2-year-period, 400 retrospectively diagnosed STTs (553 specimens) including referral and "in-house" cases were studied. The reviewing specialist pathologist was blinded to the initial diagnoses. Discordances including discrepancies and deficiencies were defined as major and minor. Major discrepancies included those that could lead to significant treatment changes. True discrepancies were those related to sampling issues between the biopsies and resection specimens. Deficiencies relating to tumor subtyping, sarcoma grading, documentation of tumor size, and marginal status (in resections) were subdivided as major and minor. RESULTS: Most cases (328, 82%) were sarcomas (most common, synovial sarcoma; most common Stage, III), followed by benign tumors (36, 9%) (most common, schwannoma) and intermediate malignancies (32, 8%) (most common, fibromatosis). Within STTs, liposarcomas, neural tumors, and undifferentiated pleomorphic sarcomas were relatively more frequently associated with discrepancies. Percentage of cases with major discordances between the referral reports (100 cases) and review diagnosis was 60%. Percentage of cases with major discordances between the specialist and other oncopathologists was 11%. True discrepancies were observed in 20 (5%) cases. The association of type of specimen with the rate of discordance was not significant (P = 0.114). CONCLUSIONS: Diagnoses of STTs are fraught with errors mostly from general pathologists, followed by nonspecialist oncopathologists. These findings reinforce the need for reporting of STTs, especially sarcomas, by specialist pathologists.

Intracranial Applications of MR Imaging-Guided Focused Ultrasound.

Initially used in the treatment of prostate cancer and uterine fibroids, the role of focused ultrasound has expanded as transcranial acoustic wave distortion and other limitations have been overcome. Its utility relies on focal energy deposition via acoustic wave propagation. The duty cycle and intensity of focused ultrasound influence the rate of energy deposition and result in unique physiologic and biomechanical effects. Thermal ablation via high-intensity continuous exposure generates coagulative necrosis of tissues. High-intensity, pulsed application reduces temporally averaged energy deposition, resulting in mechanical effects, including reversible, localized BBB disruption, which enhances neurotherapeutic agent delivery. While the precise mechanisms remain unclear, low-intensity, pulsed exposures can influence neuronal activity with preservation of cytoarchitecture. Its noninvasive nature, high-resolution, radiation-free features allow focused ultrasound to compare favorably with other modalities. We discuss the physical characteristics of focused ultrasound devices, the biophysical mechanisms at the tissue level, and current and emerging applications.

Local therapy in non-metastatic primary Ewing sarcoma of the mandible and maxilla in children.

Ewing sarcoma (ES) of the jaw bones comprises a small fraction of ES at all sites. Due to their rarity, a specific policy for local treatment is lacking. The aim of this study was to evaluate the local therapy for ES and recommend measures to individualize treatment options. Patients with primary non-metastatic ES of the jaw bones treated between August 2005 and February 2015 were analyzed. All patients received primary induction chemotherapy, following which lesions amenable to resection based on specific radiological criteria were resected; those with unresectable lesions were offered definitive radiotherapy. The maxilla was the primary site in 13 patients and the mandible in eight. The median age of patients was 11.6 years (range 5-17 years). Overall, surgery was performed in 17 patients and definitive radiotherapy was used in four patients. Postoperative radiotherapy was administered to 12 patients and was avoided in five patients with 100% tumour necrosis. The 3-year overall survival, event-free survival, and local control were 68.1%, 63.6%, and 80.2%, respectively. Mandible primary and a histological response to chemotherapy were significant prognostic factors. The stratification of patients based on radiological criteria aids in selecting local therapy. In eligible patients, surgery with contemporary reconstruction results in optimal oncological and functional outcomes. Surgery also has the added advantage of identifying patients who may not need radiotherapy.

Combination therapy for multidrug-resistant cytomegalovirus disease.

Multidrug-resistant (MDR) cytomegalovirus (CMV) emerged after transient responses to ganciclovir, foscarnet, and cidofovir in a CMV-seropositive recipient who underwent allogeneic hematopoietic stem cell transplantation from a CMV-seronegative donor. Experimental treatments using leflunomide and artesunate failed. Re-transplantation from a CMV-seropositive donor supported by adoptive transfer of pp65-specific T cells and maribavir was followed by lasting suppression. This case illustrates that successful MDR CMV therapy may require individualized multidisciplinary approaches.

Risk-assessment-based approach to patients exposed to endoscopes contaminated with Pseudomonas spp.

Patients exposed to bronchoscopes contaminated with Pseudomonas aeruginosa are at increased risk of pseudomonal infection. The optimal methods for management and mitigation of risk following exposure are controversial. This article describes a two-phase risk assessment following pseudomonal contamination of a family of 75 endoscopes, detected through routine surveillance and attributed to one endoscope washer-disinfector. An initial risk assessment identified 18 endoscopes as high risk, based on the presence of lumens used for irrigation or biopsy. Exposure was communicated to the patients' clinical teams and a further clinical risk assessment of the exposed patients was performed. No patients developed complications due to pseudomonal infection.

Human metapneumovirus infection after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The clinical characteristics of human metapneumovirus (hMPV)-associated lower respiratory tract infection (LRTI) after allogeneic hematopoietic stem cell transplantation (HSCT) is not well described. We describe the clinical course in eight HSCT recipients suffering from hMPV infection. METHODS: We prospectively included all patients with hMPV-associated LRTI after allogeneic HSCT during a period of 1 year. hMPV was diagnosed by multiplex polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL). RESULTS: Eight patients with hMPV-associated LRTI were identified from 93 BAL samples. Three of the eight patients had co-infections with other pathogens. The median age of the patients was 45 years [interquartile range (IQR) 36.8-53.5], the median time posttransplant was 473 days (IQR 251-1,165), 5/8 patients had chronic graft-versus-host disease (cGvHD), and 6/8 patients received immunosuppression. Chest computed tomography (CT) scanning showed a ground-glass pattern in 7/8 patients. Seven of eight patients required hospitalization due to severe symptoms and hypoxemia. All were treated with intravenous immunoglobulin (IVIG), which was combined with oral ribavirin in six patients. The mortality rate was 12.5 % (1/8). CONCLUSIONS: hMPV-associated LRTI in allogeneic HSCT recipients are not uncommon and present with unspecific respiratory symptoms, ground-glass pattern in CT scanning, and co-infection.

An unusual infection in an injecting drug user.

Injecting drug users are prone to atypical infections. We present a case of septic thrombophlebitis secondary to Fusobacterium gonidiaformans infection in a heroin user, which demonstrates the frequently unusual nature of pathogens and presentations in this group of patients.

Nicotine dependence and depression among women smokers on methadone maintenance.

OBJECTIVE: Tobacco use and depression are highly prevalent among methadone maintenance (MM) treatment programme participants. Our aim was to study the relationship between nicotine dependence, depression, and readiness to change smoking behaviour among women smokers in MM compared to women smokers attending a primary care clinic (Control group). METHOD: We conducted a cross-sectional survey of 117 MM women smokers and 50 controls attending a family medicine clinic. All participants completed a computerized self-administered questionnaire, including demographic information, medical history, and drug and tobacco use history. Participants also completed the Fagerström Test for Nicotine Dependence (FTND), the Center for Epidemiologic Studies Depression Scale (CES-D), and the University of Rhode Island Change Assessment (URICA) instrument. RESULTS: In this study 83% African American women had an average age of 43 years. Of the women smokers in the MM group, 95% were daily smokers compared to 46% in the Control group (P <0.05). The MM women smokers had CES-D scores of 22.5 compared to 14.7 in women of the Control group (P <0.0001). Women smokers in MM were significantly more likely to be depressed, more dependent on nicotine, and more ready to change their smoking behaviour. CONCLUSIONS: Our data show a higher level of nicotine dependence and depression, and greater readiness to change among women smokers in methadone maintenance programmes compared to women smokers attending primary care clinics. Methadone treatment programmes present a need and an opportunity to assess and intervene in nicotine dependence and depression and in addressing and eliminating health disparities.

Potassium channel openers exhibit cross-tolerance with morphine in two experimental models of pain / Los abridores de canales de potasio exhiben tolerancia cruzada con la morfina en dos modelos experimentales de dolor

OBJECTIVE: The study was performed to assess the effect of potassium channel openers on morphine tolerance and vice-versa. METHODS: Swiss albino mice of either gender weighing between 25-30 g were used for the study. The study assesses the effect of potassium channel openers (cromakalim, diazoxide and minoxidil) on morphine tolerance and vice-versa, using formalin and tail-flick tests. RESULTS: The antinociceptive effect of cromakalim and minoxidil was significantly reduced when administered to morphine-tolerant mice, in both the behavioural tests. However, reduced analgesic effect of diazoxide was observed on morphine-tolerance in the formalin test but not in the tail-flick test. Tolerance was observed when morphine was administered to animals chronically treated with any of the potassium channel openers. The same effect was observed when morphine was injected into a group treated with a combination of morphine and any of the potassium channel openers. CONCLUSIONS: This study, therefore, suggests that both morphine and potassium channel openers are cross-tolerant. However, such interaction occurs at the level of potassium channels rather than at the level of receptors.

OBJETIVO: El estudio fue realizado para evaluar el efecto de los abridores de canales de potasio en la tolerancia a la morfina, y viceversa. MÉTODOS: Para el estudio, se usaron ratones albinos suizos de ambos sexos que pesaban entre 25-30 g. El estudio evalúa el efecto de los abridores de canales de potasio (cromacalina, diazóxido y minoxidil) en la tolerancia a la morfina, y viceversa, usando la prueba de la sacudida de la cola y la prueba de la formalina. RESULTADOS: El efecto antinociceptivo de la cromacalina y el minoxidil fue significativamente reducido cuando se le administró a los ratones tolerantes a la morfina, en ambas pruebas conductuales. Sin embargo, se observó un efecto analgésico reducido de diazóxido sobre la tolerancia a la morfina en la prueba de la formalina, pero no en la prueba de la sacudida de la cola. Se observó tolerancia al administrar morfina a animales crónicamente tratados con cualquiera de los abridores de canales de potasio. El mismo efecto fue observado cuando se inyectó la morfina al grupo tratado con una combinación de morfina y cualquiera de los abridores de canales de potasio. CONCLUSIONES: Por consiguiente, este estudio sugiere que tanto la morfina como los abridores de canales de potasio son tolerantes cruzados. Sin embargo, tal interacción ocurre a nivel de los canales de potasio más bien que a nivel de los receptores.

Hepatitis C virus coinfection and the risk of cardiovascular disease among HIV-infected patients.

BACKGROUND: Among HIV-infected patients, hepatitis C virus (HCV) coinfection is associated with lower cholesterol levels, but it remains unclear how it affects cardiovascular outcomes. METHODS: We performed logistic regression to evaluate acute myocardial infarction (AMI) and cerebrovascular disease (CVD) events by HCV status among HIV-infected US veterans in the highly active antiretroviral therapy (HAART) era (1996-2004). We then performed survival analyses to evaluate incident AMI and CVD, exploring antiretroviral therapy (ART) as a time-dependent variable. RESULTS: A total of 19 424 HIV-infected patients [31.6% of whom were HCV-coinfected (HIV/HCV)] contributed 76 376 patient-years of follow-up. HCV coinfection was associated with lower rates of hypercholesterolaemia (18.0% in HIV/HCV vs. 30.7% in HIV-only patients; P<0.001), but higher rates of hypertension (43.8%vs. 35.6%; P<0.0001), type 2 diabetes mellitus (16.2%vs. 11.1%; P<0.0001) and smoking (36.7%vs. 24.7%; P=0.009). Rates of AMI and CVD were significantly higher among HIV/HCV than HIV-only patients: 4.19 vs. 3.36 events/1000 patient-years, respectively (P<0.001), for AMI; and 12.47 vs. 11.12 events/1000 patient-years, respectively (P<0.001), for CVD. When analyses were controlled for diabetes mellitus, hypertension, age and duration of ART, hazard ratios (HRs) among those with HIV/HCV (vs. HIV only) were 1.25 [95% confidence interval (CI) 0.98-1.61; P=0.072] for AMI and 1.20 (CI 1.04-1.38; P=0.013) for CVD. Hypertension (HR 2.05; P<0.001), greater age (HR 1.79; P<0.001) and longer duration (cumulative years) of antiretroviral use (HR 1.12; P=0.0411) were also associated with increased risk of AMI in the adjusted model. CONCLUSIONS: In the HAART era, HCV coinfection was associated with a significantly increased risk of CVD and a trend towards an increased risk of AMI among HIV-infected patients.

Outcome of influenza infections in outpatients after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Influenza can cause significant morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). The diagnostic methods and antiviral treatment have scarcely been investigated. METHODS: We retrospectively identified influenza-infected patients with upper or lower respiratory tract infection (RTI) diagnosed by culture and polymerase chain reaction (PCR) testing between November 2007 and April 2008. Treatment with oseltamivir 75 mg twice daily and serial nasal swabs were performed at the discretion of the treating physician. RESULTS: We identified 21 influenza infections in 19 patients: 19 with upper RTI and 2 with lower RTI. At diagnosis, all 21 samples were positive for PCR with a median influenza load of 5.9 log(10) copies/mL. Culture was positive in 14 (67%) patients. Influenza A virus was diagnosed in 8 (38%) episodes and influenza B virus in 13 (62%) episodes. Two patients were sequentially infected by influenza A, followed by B after 38 and 47 days, respectively. Eighteen (86%) patients were treated with oseltamivir for 11 days (median, interquartile range [IQR]: 8-14). No progression to lower RTI or mortality occurred. Shedding persisted for 12 days (median, IQR: 8-13). Absolute lymphocyte count at diagnosis correlated inversely with shedding of the virus (P<0.001). CONCLUSIONS: Oseltamivir is well tolerated and may reduce mortality of influenza virus-infected patients after HSCT. PCR may help to optimize diagnosis and to monitor treatment strategies.