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Introduction: Bacterial infections are a leading cause of morbidity and mortality in patients receiving solid-organ transplants. Extended-spectrum beta-lactamases (ESBL) pathogens are the most important pathogenic bacteria infecting these patients. Aim: This study aims to evaluate for the incidence and characteristics of ESBL-positive organism, to look for the clinical outcomes in ESBL-positive infected cases, and to evaluate and draft the antibiotic policy in posttransplant patients during the first 28 days posttransplant. Materials and Methods: This is a retrospective data analysis of liver transplant recipients infected with ESBL culture-positive infections. All the culture sites such as blood, urine, and endotracheal tube aspirates were screened for the first ESBL infection they had and noted. This data were collected till day 28 posttransplant. The antibiotic susceptibility pattern and the most common organism were also noted. Results: A total of 484 patients was screened and 116 patients had ESBL-positive cultures. Out of these, 54 patients had infections and 62 patients were ESBL colonizers. The primary infection site was abdominal fluid (40.7%), with Klebsiella accounting for most of the ESBL infections. Colistin was the most sensitive antibiotic followed by tigecycline. The overall mortality was 11.4% and 31 out of 54 ESBL-infected patients died. Conclusions: Infections with ESBL-producing organism in liver transplant recipients has a high mortality and very limited therapeutic options. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) are a promising cell type for cancer vaccines due to their high immunostimulatory capacity. However, improper maturation of DC prior to treatment may account for the limited efficacy of DC vaccine clinical trials. Latent Membrane Protein-1 (LMP1) of Epstein-Barr virus was examined for its ability to mature and activate DC as a gene-based molecular adjuvant for DC vaccines. DC were transduced with an adenovirus 5 vector (Ad5) expressing LMP1 under the control of a Tet-inducible promoter. Ad5-LMP1 was found to mature and activate both human and mouse DC. LMP1 enhanced in vitro migration of DC toward CCL19, as well as in vivo migration of DC to the inguinal lymph nodes of mice following intradermal injection. LMP1-transduced DC increased T cell proliferation in a Pmel-1 adoptive transfer model and enhanced survival in B16-F10 melanoma models. LMP1-DC also enhanced protection in a vaccinia-Gag viral challenge assay. LMP1 induced high levels of IL-12p70 secretion in mouse DC when compared to standard maturation protocols. Importantly, LMP1-transduced human DC retained the capacity to secrete IL-12p70 and TNF in response to DC restimulation. In contrast, DC matured with Monocyte Conditioned Media-Mimic cocktail (Mimic) were impaired in IL-12p70 secretion following restimulation. Overall, LMP1 matured and activated DC, induced migration to the lymph node, and generated high levels of IL-12p70 in a murine model. We propose LMP1 as a promising molecular adjuvant for DC vaccines. [ABSTRACT FROM AUTHOR]

Atorvastatin and ticagrelor combination is a widely accepted therapy for secondary prevention of ischaemic heart disease. However, rhabdomyolysis is a well-known rare side effect of statins which should be considered when treatments are combined with cytochrome P450 3A4 enzyme inhibitors. We report a case of atorvastatin and ticagrelor associated severe rhabdomyolysis that progressed to multiorgan failure requiring renal replacement therapy, inotropes, intubation, and mechanical ventilation. Despite withdrawal of the precipitating cause and the supportive measures including renal replacement therapy, creatinine kinase increased due to ongoing rhabdomyolysis rapidly progressing to upper and lower limbs weakness. A muscle biopsy was performed to exclude myositis which confirmed extensive myonecrosis, consistent with statin associated rhabdomyolysis. After a prolonged ventilatory course in the intensive care unit, patient’s condition improved with recovery from renal and liver dysfunction. The patient slowly regained her upper and lower limb function; she was successfully weaned off the ventilator and was discharged for rehabilitation. To our knowledge, this is a second case of statin associated rhabdomyolysis due to interaction between atorvastatin and ticagrelor. However, our case differed in that the patient was also on amlodipine, which is considered to be a weak cytochrome P450 3A4 inhibitor and may have further potentiated myotoxicity. [ABSTRACT FROM AUTHOR]

The term phaeohyphomycosis (PHM) means dark-pigmented fungal hyphae. Cerebral PHM (CPHM) with onychomycosis is extremely rare; very few have been reported so far. The authors report a case of CPHM with onychomycosis in a 37-year-old male from a rural background in Haryana, India, with involvement of the left frontal lobe. The mass was resected and biopsy was sent for histopathological examination. He was given antifungal drugs in the postoperative period. The patient responded very well to the treatment, and there were no signs of recurrence at the 6-month follow-up visit. The clinical features, imaging and histopathological investigations, and management of this rare entity are discussed, and the available literature is also reviewed. [ABSTRACT FROM AUTHOR]

Aim: The alpha-1 isoform of the calcium channel gene is expressed abundantly in neuronal tissue, especially within the cerebellum. Mutations in this gene may manifest with hemiplegic migraine, spinocerebellar ataxia type 6 (SCA6) and episodic ataxia type 2 (EA2) in adults. There are reports of children with CACAN1A mutations presenting with paroxysmal tonic upgaze, abnormal saccades and congenital nystagmus as well as severe forms of hemiplegic migraine. The aim of this study was to review the clinical presentation and subsequent course of all children with a CACNA1A mutation who presented to a tertiary children's hospital.Method: We reviewed retrospectively nine children with a proven CACNA1A mutation who presented to the Children's Hospital at Westmead between 2005-2015. The initial and subsequent clinical presentation, radiological features and molecular genetic profile of each child was reviewed.Results: Nine children presented to out institute over a 10 year period; six were female and three male. The median age of presentation was 1.2 years. Eye movement disorders were the presenting feature in eight children. Three of these children later presented with severe hemiplegic migraine episodes often requiring ICU care. Affected children also had developmental delay and developed classical hemiplegic migraine, episodic ataxia and seizures. Calcium channel blockers were used with some efficacy in preventing severe HM episodes.Interpretation: Eye movement disorders are an early manifestation of CACNA1A mutations in children. Improved recognition of the CACNA1A phenotype in childhood is important for early diagnosis, counselling and appropriate emergency management. There is some early evidence that calcium channel blockers may be an effective prophylactic agent for the severe hemiplegic migraine episodes. [ABSTRACT FROM AUTHOR]

Aim: This study compared the amount of aqueous-based and oil-based calcium hydroxide [Ca(OH)2] remaining in the canal, after removal with two different chelators 17% EDTA and 0.2% Chitosan in combination with ultrasonic agitation. Materials and Methods: Cleaning and shaping of root canals of 28 mandibular premolar was done and canals were filled either with Metapex or Ca(OH)2 mixed with distilled water. Volumetric analysis was performed utilizing cone beam-computed tomography (CBCT) after 7 days of incubation. Ca(OH)2 was removed using either 17% EDTA or 0.2% Chitosan in combination with ultrasonic agitation. Volumetric analysis was repeated and percentage difference was calculated and statistically analysed using Kruskal-Wallis and Mann-Whitney U test. Results: Both the chelators failed to remove aqueous-based as well as oil-based Ca(OH)2 completely from the root canal. Aqueous-based Ca(OH)2 was easier to be removed than oil-based Ca(OH)2. 0.2% Chitosan was significantly more effective for removal of oil-based Ca(OH)2 (P < 0.01) while both 17% EDTA and 0.2% Chitosan were equally effective in removing aqueous-based Ca(OH)2. Conclusion: Combination of 0.2% Chitosan and ultrasonic agitation results in lower amount of Ca(OH)2 remnants than 17% EDTA irrespective of type of vehicle present in the mix. [ABSTRACT FROM AUTHOR]

Trauma to primary tooth leads to abnormal variations in crown and root canals of permanent teeth that presents a challenge in diagnosis and clinical management to the practitioner. This article presents a detailed case report of the endodontic treatment of a three canalled maxillary central incisor and maxillary lateral incisor having single canal with open apex linked with periodontal defect. Root canals were prepared with hand files and canals were irrigated with 2.5% sodium hypochlorite solution. Calcium hydroxide was placed as an intracanal medicament. As the expected healing did not occur even after one month of calcium hydroxide therapy, so periapical endodontic surgery was performed using Platelet Rich Plasma (PRP). Satisfactory clinical and radiographic results were obtained at 12 months. Detailed knowledge of the anatomical variations in the root canal and awareness of their configuration is essential for the success of such cases. [ABSTRACT FROM AUTHOR]

CD40 ligand (CD40L, CD154) is a membrane protein that is important for the activation of dendritic cells (DCs) and DC-induced CD8+ T cell responses. To be active, CD40L must cluster CD40 receptors on responding cells. To produce a soluble form of CD40L that clusters CD40 receptors necessitates the use of a multitrimer construct. With this in mind, a tripartite fusion protein was made from surfactant protein D (SPD), HIV-1 Gag as a test antigen, and CD40L, where SPD serves as a scaffold for the multitrimer protein complex. This SPD-Gag-CD40L protein activated CD40-bearing cells and bone marrow-derived DCs in vitro. Compared to a plasmid for Gag antigen alone (pGag), DNA vaccination of mice with pSPD-Gag-CD40L induced an increased number of Gag-specific CD8+ T cells with increased avidity for major histocompatibility complex class I-restricted Gag peptide and improved vaccine-induced protection from challenge by vaccinia-Gag virus. The importance of the multitrimeric nature of the complex was shown using a plasmid lacking the N terminus of SPD that produced a single trimer fusion protein. This plasmid, pTrimer-Gag-CD40L, was only weakly active on CD40-bearing cells and did not elicit strong CD8+ T cell responses or improve protection from vaccinia-Gag challenge. An adenovirus 5 (Ad5) vaccine incorporating SPD-Gag-CD40L was much stronger than Ad5 expressing Gag alone (Ad5-Gag) and induced complete protection (i.e., sterilizing immunity) from vaccinia- Gag challenge. Overall, these results show the potential of a new vaccine design in which antigen is introduced into a construct that expresses a multitrimer soluble form of CD40L, leading to strongly protective CD8+ T cell responses. [ABSTRACT FROM AUTHOR]

Acute chest pain with very elevated troponin level and abnormal EKG in adult population is considered sine qua non to acute coronary syndrome (ACS) unless proved otherwise. Similar presentation in adolescent population is seen less often but raises suspicion for ACS. Most common etiology for chest pain with cardiac enzyme elevation in adolescent population is usually viral myopericarditis. The adolescent population presenting with chest pain and elevated cardiac enzymes should be carefully evaluated for ACS and other etiologies including myocarditis, myopericarditis, pulmonary embolism, acute rheumatic fever, and trauma. We report one Japanese adolescent male with mycoplasma pneumoniae myocarditis who presented to the ER with chest pain, elevated cardiac enzymes, and abnormal EKG. [ABSTRACT FROM AUTHOR]

Management of mid root fractures presents a formidable challenge for clinicians because of the difficulty of achieving a stable reunion of fracture fragments. Root fractures in permanent teeth are uncommon injuries among dental traumas accounting for 0.5-0.7% of the cases. The most common type of root fracture is in the middle third, followed by apical and coronal part. This case report discusses two different treatment modalities for intra- radicular stabilization of horizontal root fractures. [ABSTRACT FROM AUTHOR]

Situs inversus totalis is a rare condition with a predicted incidence of one in 10,000 among the general population, the aetiologic factors for which are still not completely understood. In a patient with situs inversus totalis, not just the diagnosis of any acute abdomen pathology is difficult due to distorted anatomy and transposition of thoraco-abdominal viscera but equally challenging is the anaesthetic management during the respective surgical procedure. We are reporting a patient who had situs inversus totalis and was operated for open cholecystectomy. The present case report lays an emphasis on the potential difficulties during anaesthetic management and its various implications. [ABSTRACT FROM AUTHOR]

Noonan syndrome is a genetically transmitted autosomal dominant disorder characterized by various anatomic anomalies and pathophysiologic derangements. Anesthetic management in such cases poses a multitude of challenges, especially related to the airway management and maintenance of cardiovascular stability. We report a case of a 9-year-old male child weighing 24 kg, who was diagnosed as a case of Noonan syndrome and had undergone ligation of patent ductus arteriosus during early childhood. The child was operated on for release of bilateral neck bands under general anesthesia. The case report pertains to the successful airway and anesthetic management in the background of difficult airway and existence of various cardiac lesions. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplant has been used in the treatment of multiple myeloma. Its use in the treatment of POEMS syndrome is still under investigation. We describe the clinical course and long term follow-up of a patient with POEMS syndrome unresponsive to standard chemotherapy. The patient had rapid and dramatic improvement in neuropathy and dermatologic features after autologous stem cell transplantation. A review of the literature is also presented. High-dose chemotherapy followed by stem cell transplantation is a potential treatment option for patients with POEMS syndrome. [ABSTRACT FROM AUTHOR]

The article presents a case series of 15 patients with fibrotic polyps who were treated with endoscopic mucosal resection followed by ablation and cold avulsion technique along with a video and table on the same. It mentions that a scarred submucosa limits depth and effectiveness of lifting solution used for resecting a polyp. It informs about supplementary ablative techniques such as use of argon plasma coagulation with submucosal injection or hot avulsion using electrocautery biopsy forceps.

Study Design: Retrospective review of a prospective database.Objective: The aim of this study was to define the role of sagittal orientation of the construct at the upper instrumented levels in the development of proximal junctional kyphosis (PJK) in adult spinal deformity (ASD) patients.Summary Of Background Data: PJK following ASD surgery remains challenging. The final alignment of the upper instrumented vertebral segments has been proposed as a risk factor for PJK, but has not been fully investigated.Methods: ASD patients with 2-year follow-up and long posterior fusion to the pelvis were analyzed. Radiographic measurements included pelvic incidence (PI), lumbar lordosis (LL), pelvic tilt (PT), sagittal vertical axis, and two upper-most instrumented vertebra (UIV) parameters: UIV slope (UIV vs. horizontal) and inclination of the proximal-end of the construct. UIV parameters were secondarily evaluated with regard to the compensatory impact of post-PJK increased PT (PREF). A comparison between PJK and non-PJK patients was performed, according to the UIV location (upper thoracic [UT] or thoracolumbar).Results: A total of 252 patients (mean age, 61.5 years, 83% females) were included. PJK incidence was 56% at 2-years. PJK patients had a greater change in LL and thoracic kyphosis than non-PJK patients. In the UT group, there was no difference in UIV slope for PJK versus non-PJK. However, PJK patients had a smaller inclination of the upper instrumented segments versus vertical (P < 0.001) and the PREF (P = 0.005). Similarly, in the LT group, PJK patients had a posterior inclination versus the vertical (P < 0.001) and the PREF (P = 0.041).Conclusion: Analysis revealed that a more posterior construct inclination was present in patients who developed PJK. These results support previous hypotheses suggesting that PJK may develop in response to excessive spinal realignment. Proper rod contouring, especially at the proximal end, may reduce the risk of PJK.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

Abstract: Background: Dendritic cell (DC) therapy is a promising technology for the treatment of HIV infected individuals. HIV-1 Gag- and Nef RNA-loaded DC have previously been shown to induce immune responses ex vivo following coculture with autologous lymphocytes. However, polyfunctionality and memory responses following coculture have not been evaluated. In addition, little is known regarding whether specific HIV-1 proteome components, such as highly conserved regions of the HIV-1, could enhance clinical responses following DC therapy. Methodology and principal findings: To determine the breadth of the immune responses to antigen loaded DC, we analyzed polyfunctional T cell response ex vivo to Gag RNA loaded DC. Blood samples were used to generate monocyte derived DC, which were then matured and cocultured with autologous lymphocytes. We found that cytokine-matured DC loaded with Gag RNA was able to induce Gag-specific IFN-γ and IL-2 responses after a 12-day coculture. We characterized these responses by polyfunctional intracellular cytokine staining and evaluation of T cell memory phenotypes. Central memory CD8+ T cells were induced ex vivo after DC coculture from each of 3 patients, and the effector memory pool was increased by DC coculture from 2 patients. We also observed a decrease in the terminal effector and intermediate CD8+ T cell pool and an increase in the naïve/other population. There was a reduction in terminal effector and intermediate CD4+ T cells, and a corresponding increase in naïve/other CD4+ T cells. Finally, we evaluated conserved regions of Gag as a novel DC therapy immunogen and found that a conserved element (CE) p24 Gag antigen elicited IFN-γ and IL-2 responses comparable to those induced by a full-length Gag antigen. Conclusions: We showed that RNA-loaded DC therapy induced a polyfunctional T cell response ex vivo, supporting the use of such DC-therapy for HIV infection. However, the central and effector memory phenotypes of T cells did not appear to be enhanced during coculture with Gag RNA-loaded DC. Furthermore, comparable antigen-specific responses were induced in HIV infected individuals using full-length Gag or only conserved elements of the Gag p24 protein. This indicates that immune responses can be focused onto the conserved elements of Gag in the absence of other Gag components. [Copyright &y& Elsevier]