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1.
Pediatr Transplant ; 28(3): e14722, 2024 May.
Article in English | MEDLINE | ID: mdl-38553820

ABSTRACT

BACKGROUND: Immediate extubation is becoming more common in liver transplantation. However, limited data exist on how to identify pediatric patients with potential for successful immediate extubation and how this intervention may affect recovery. METHODS: This retrospective review evaluated patients who underwent liver transplantation from 2015 to 2021 at Children's Healthcare of Atlanta. Preoperative status and intraoperative management were evaluated and compared. Outcomes comprised thrombosis, surgical reexploration, retransplantation, as well as reintubation, high flow nasal cannula (HFNC) usage, postoperative infection, the length of stay (LOS), and mortality. RESULTS: A total of 173 patients were analyzed, with 121 patients (69.9%) extubated immediately. The extubation group had older age (median 4.0 vs 1.25 years, p = .048), lower PELD/MELD (28 vs. 34, p = .03), decreased transfusion (10.2 vs. 41.7 mL/kg, p < .001), shorter surgical time (332 vs. 392 min, p < .001), and primary abdominal closure (81% vs. 40.4%, p < .001). Immediate extubation was associated with decreased HFNC (0.21 vs. 0.71 days, p = .02), postoperative infection (9.9% vs. 26.9%, p = .007), mortality (0% vs. 5.8%, p = .036), and pediatric intensive care unit LOS (4.7 vs. 11.4 days, p < .001). The complication rate was lower in the extubation group (24.8% vs. 36.5%), but not statistically significant. CONCLUSIONS: Approximately 70% of patients were able to be successfully extubated immediately, with only 2.5% requiring reintubation. Those immediately extubated had decreased need for HFNC, lower infection rates, shorter LOS, and decreased mortality. Our results show that with proper patient selection and a multidisciplinary approach, immediate extubation allows for improved recovery without increased respiratory complications after pediatric liver transplantation.


Subject(s)
Liver Transplantation , Humans , Child , Airway Extubation/methods , Retrospective Studies , Cannula , Intensive Care Units, Pediatric , Postoperative Complications/epidemiology , Length of Stay
2.
Am J Transplant ; 23(2): 171-179, 2023 02.
Article in English | MEDLINE | ID: mdl-36695685

ABSTRACT

The American Society of Transplant Surgeons supports efforts to increase the number of organs that are critically needed for patients desperately awaiting transplantation. In the United States, transplantation using organs procured from donation after circulatory death (DCD) donors has continued to increase in number. Despite these increases, substantial variability in the utilization and practices of DCD transplantation still exists. To improve DCD organ utilization, it is important to create a set of best practices for DCD recovery. The following recommendations aim to provide guidance on contemporary issues surrounding DCD organ procurement in the United States. A work group was composed of members of the American Society of Transplant Surgeon Scientific Studies Committee and the Thoracic Organ Transplantation Committee. The following topics were identified by the group either as controversial or lacking standardization: prewithdrawal preparation, definition of donor warm ischemia time, DCD surgical technique, combined thoracic and abdominal procurements, and normothermic regional perfusion. The proposed recommendations were classified on the basis of the grade of available evidence and the strength of the recommendation. This information should be valuable for transplant programs as well as for organ procurement organizations and donor hospitals as they develop robust DCD donor procurement protocols.


Subject(s)
Cardiovascular System , Organ Transplantation , Tissue and Organ Procurement , Humans , United States , Tissue Donors , Perfusion/methods , Death , Organ Preservation/methods
3.
Am J Transplant ; 21(1): 314-321, 2021 01.
Article in English | MEDLINE | ID: mdl-32808730

ABSTRACT

Kidney transplant program performance in the United States is commonly measured by posttransplant outcomes. Inclusion of pretransplant measures could provide a more comprehensive assessment of transplant program performance and necessary information for patient decision-making. In this study, we propose a new metric, the waitlisting rate, defined as the ratio of patients who are waitlisted in a center relative to the person-years referred for evaluation to a program. Furthermore, we standardize the waitlisting rate relative to the state average in Georgia, North Carolina, and South Carolina. The new metric was used as a proof-of-concept to assess transplant-program access compared to the existing transplant rate metric. The study cohorts were defined by linking 2017 United States Renal Data System (USRDS) data with transplant-program referral data from the Southeastern United States between January 1, 2012 and December 31, 2016. Waitlisting rate varied across the 9 Southeastern transplant programs, ranging from 10 to 22 events per 100 patient-years, whereas the program-specific waitlisting rate ratio ranged between 0.76 and 1.33. Program-specific waitlisting rate ratio was uncorrelated with the transplant rate ratio (r = -.15, 95% CI, -0.83 to 0.57). Findings warrant collection of national data on early transplant steps, such as referral, for a more comprehensive assessment of transplant program performance and pretransplant access.


Subject(s)
Kidney Failure, Chronic , Kidney Transplantation , Humans , Kidney Failure, Chronic/surgery , North Carolina , Referral and Consultation , United States , Waiting Lists
4.
Transpl Infect Dis ; 23(1): e13435, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32748558

ABSTRACT

Adenovirus infection is commonly associated with self-limited respiratory and gastrointestinal illnesses. However, infection in immunocompromised individuals, such as transplant recipients, can cause severe life-threatening illness including pneumonitis, hemorrhagic cystitis, nephritis, hepatitis, and enterocolitis. In orthotopic liver transplant recipients, adenovirus viremia can cause hepatitis leading to marked transaminitis, allograft loss, and death. Although hepatic abscesses mediated by adenovirus have been described in other immunosuppressed patient populations, it has very rarely been described in liver transplant recipients. Here, we report two adult cases of hepatic abscesses following liver transplantation secondary to adenovirus infection and describe the successful treatment of these patients. Adenovirus should be considered as an uncommon etiology of hepatic abscess and unexplained fevers in adults following liver transplantation.


Subject(s)
Adenoviridae Infections , Liver Abscess , Liver Transplantation , Adenoviridae , Adenoviridae Infections/complications , Adult , Fever , Humans , Liver Abscess/etiology , Transplant Recipients
5.
Clin Transplant ; 33(6): e13568, 2019 06.
Article in English | MEDLINE | ID: mdl-31006146

ABSTRACT

Belatacept, the CD28-B7 costimulation pathway inhibitor, has been approved as a calcineurin inhibitor (CNI) alternative in kidney transplantation. Although costimulation blockade (CoB) allows for CNI avoidance, it is associated with increased rates of early rejection, prompting a search for agents to pair with belatacept. Methotrexate (MTX) is an antimetabolite that has been found to be complimentary with abatacept, a lower affinity CD28-B7-specific analogue of belatacept, in the treatment of rheumatoid arthritis (RA). We examined whether this synergy would extend to prevention of kidney allograft rejection. Rhesus macaques underwent kidney transplantation treated with abatacept maintenance therapy with either a steroid taper, MTX, or both. The combination of abatacept maintenance with steroids prolonged graft survival compared to untreated historical controls and previous reports of abatacept monotherapy. The addition of MTX did not provide additional benefit. These data demonstrate that abatacept with adjuvant therapy may delay the onset of acute rejection, but fail to show synergy between abatacept and MTX beyond that of steroids. These findings indicate that MTX is unlikely to be a suitable adjuvant to CoB in kidney transplantation, but also suggest that with further modification, a CoB regimen used for advanced RA may suffice for RA patients requiring kidney transplantation.


Subject(s)
Abatacept/therapeutic use , Graft Rejection/drug therapy , Graft Survival/drug effects , Kidney Transplantation/adverse effects , Methotrexate/therapeutic use , T-Lymphocytes, Regulatory/immunology , Animals , Graft Rejection/etiology , Graft Survival/immunology , Humans , Immunoconjugates , Immunologic Memory/drug effects , Immunologic Memory/immunology , Immunosuppressive Agents/therapeutic use , Macaca mulatta , T-Lymphocytes, Regulatory/drug effects
6.
J Med Internet Res ; 21(4): e11864, 2019 04 22.
Article in English | MEDLINE | ID: mdl-31008707

ABSTRACT

BACKGROUND: Kidney and liver transplant recipients must manage a complex care regimen after kidney transplant. Although the use of Web-based patient portals is known to improve patient-provider communication and health outcomes in chronic disease populations by helping patients manage posttransplant care, disparities in access to and use of portals have been reported. Little is known about portal usage and disparities among kidney and liver transplant recipients. OBJECTIVE: The aim of this study was to examine patient racial/ethnic, socioeconomic, and clinical characteristics associated with portal usage among kidney and liver transplant recipients. METHODS: The study included all adult kidney and liver transplant recipients (n=710) at a large academic transplant center in the Southeastern United States between March 2014 and November 2016. Electronic medical record data were linked with Cerner portal usage data. Patient portal use was defined as any portal activity (vs no activity) recorded in the Cerner Web-based portal, including viewing of health records, lab results, medication lists, and the use of secure messaging. Multivariable log-binomial regression was used to determine the patient demographic, clinical, and socioeconomic characteristics associated with portal usage, stratified by organ. RESULTS: Among 710 transplant recipients (n=455 kidney, n=255 liver), 55.4% (252/455) of kidney recipients and 48.2% (123/255) of liver recipients used the patient portal. Black patients were less likely to use the portal versus white patients among both kidney (57% black vs 74% white) and liver (28% black vs 55% white) transplant recipients. In adjusted multivariable analyses, kidney transplant recipients were more likely to use the portal if they had higher education; among liver recipients, patients who were white versus black and had higher education were more likely to use the portal. CONCLUSIONS: Despite studies showing that patient portals have the potential to benefit transplant recipients as a tool for health management, racial and socioeconomic disparities should be considered before widespread implementation. Transplant centers should include portal training and support to all patients to encourage use, given its potential to improve outcomes.


Subject(s)
Healthcare Disparities/ethnology , Kidney Transplantation/methods , Liver Transplantation/methods , Patient Portals/standards , Cross-Sectional Studies , Ethnicity , Female , Humans , Internet , Male , Middle Aged , Racial Groups
7.
Curr Opin Organ Transplant ; 21(4): 393-8, 2016 08.
Article in English | MEDLINE | ID: mdl-27328037

ABSTRACT

PURPOSE OF REVIEW: Advances in surgical technique and immunosuppression have significantly improved outcomes after pancreas transplantation, and as a result pancreas transplants increasingly are being performed for indications other than type 1 diabetes mellitus. This review summarizes the current literature on pancreas transplantation in unconventional recipient populations. RECENT FINDINGS: An increasing body of work suggests that pancreas transplantation can be performed with good outcomes in patients with type 2 diabetes mellitus and those 50 years of age and older. Obesity appears detrimental to patient and pancreas graft survival, and bariatric surgery prior to transplantation may be of increasing interest and relevance. There are limited data yielding mixed outcomes on pancreas transplantation in patients with HIV or hepatitis C virus. However, rapidly improving antiviral therapies are prolonging survival in patients with HIV and chronic hepatitis C virus infections and may increase the number of candidates available for pancreas transplantation in these populations in the future. SUMMARY: Despite limited literature in these patient populations, pancreas transplantation may be a viable treatment option for endocrine pancreas failure in appropriately selected patients regardless of disease cause or age.


Subject(s)
Diabetes Mellitus, Type 2/therapy , Pancreas Transplantation , Humans , Patient Selection
8.
Tech Vasc Interv Radiol ; 26(4): 100922, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38123284

ABSTRACT

Liver transplantation is a technically demanding surgical procedure with known complications, and the optimal approach to addressing vascular and biliary complications requires a coordinated effort between surgical and interventional radiology teams. Vascular complications involving the hepatic artery, portal vein, or hepatic veins can be characterized by their mechanism, chronicity, and timing of presentation. These factors help determine whether the optimal therapeutic approach is surgical or endovascular. Very early presentation in the perioperative period favors surgical revision, while later presentation is best addressed endovascularly. Biliary complications can be categorized as leaks or strictures, and coordinated surgical, endoscopic, and percutaneous management is needed to address these types of complications. Through advances in technique and the management of complications, outcomes after liver transplantation continue to improve.


Subject(s)
Biliary Tract Diseases , Liver Transplantation , Humans , Liver Transplantation/adverse effects , Biliary Tract Diseases/therapy , Hepatic Artery , Portal Vein/diagnostic imaging , Portal Vein/surgery , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Postoperative Complications/therapy , Retrospective Studies
9.
Transplant Direct ; 9(8): e1500, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37456590

ABSTRACT

Liver allografts protect renal allografts from the same donor from some, but not all, preformed donor specific alloantibodies (DSA). However, the precise mechanisms of protection and the potential for more subtle alterations/injuries within the grafts resulting from DSA interactions require further study. Methods: We reevaluated allograft biopsies from simultaneous liver-kidney transplant recipients who had both allografts biopsied within 60 d of one another and within 30 d of DSA being positive in serum (positive: mean florescence intensity ≥5000). Routine histology, C4d staining, and specialized immunohistochemistry for Kupffer cells (KCs; CD163) and a C4d receptor immunoglobulin-like transcript-4 were carried out in 4 patients with 6 paired biopsies. Results: Overt antibody-mediated rejection was found in 3 of 4 renal and liver allografts. One patient had biopsy-confirmed renal and liver allograft antibody-mediated rejection despite serum clearance of DSA. All biopsies showed KC hypertrophy (minimal: 1; mild: 2; moderate: 1; severe: 2) and cytoplasmic C4d KC staining was easily detected in 2 biopsies from 2 patients; minimal and negative in 2 biopsies each. Implications of which are discussed. Control 1-y protocol liver allograft biopsies from DSA- recipients showed neither KC hypertrophy nor KC C4d staining (n = 6). Conclusions: Partial renal allograft protection by a liver allograft from the same donor may be partially mediated by phagocytosis/elimination of antibody and complement split products by KCs, as shown decades ago in controlled sensitized experimental animal experiments.

10.
Rev Paul Pediatr ; 40: e2021002, 2022.
Article in English, Portuguese | MEDLINE | ID: mdl-35019011

ABSTRACT

OBJECTIVE: To perform a systematic review of the health economic evidence on the care of children and adolescents with complex clinical conditions, comparing groups included and not included (control group) in palliative care at the end of life. DATA SOURCE: The seven databases searched were PubMed, Embase, Web of Science, Cochrane Library, Virtual Health Library-Latin American and Caribbean Health Sciences Literature (VHL-LILACS), EBSCOhost, and Paediatric Economic Database Evaluation, following recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement, from January 1979 to November 2020. The review included studies of patients under 18 years of age with complex clinical conditions that compared a palliative care group with a control group. The economic outcomes analyzed were length and place of stay at the end of life (home, hospice, ward, intensive care unit, emergency room), diagnostic and therapeutic procedures performed, and health-related costs. The exclusion criteria were: studies without a matched control group, conference/congress abstracts, letters to the editor, editorials, comments, qualitative studies, narrative reviews, studies with ten or fewer participants in each group, articles published in languages other than English, Portuguese, or Spanish. DATA SYNTHESIS: Out of the 518 articles identified, 4 met the inclusion criteria. We found evidence of direct economic benefits, such as reduced health costs, indirect savings, and protection of patients from undergoing invasive procedures, surgeries, and costly therapies, which cause greater suffering at the end of life. Therefore, participating in a palliative care program saved financial and technological resources, besides increasing the frequency of deaths at home and improving the quality of life. CONCLUSIONS: Public and private policies to promote palliative care represent better efficiency when allocating available health care resources.


Subject(s)
Palliative Care , Quality of Life , Adolescent , Child , Cost-Benefit Analysis , Death , Humans
11.
J Investig Med High Impact Case Rep ; 10: 23247096221129467, 2022.
Article in English | MEDLINE | ID: mdl-36214295

ABSTRACT

Mycoplasma and Ureaplasma infections have been described as a cause of hyperammonemia syndrome leading to devastating neurological injury in the post-transplant period, most commonly in lung transplant recipients. The occurrence of significant hyperammonemia caused by other urease-producing organisms remains unclear. We describe a case of disseminated cryptococcosis presenting with profound hyperammonemia in a 55-year-old orthotopic liver transplant recipient. Through a process of elimination, other potential causes for hyperammonemia were excluded revealing a probable association between hyperammonemia and disseminated cryptococcosis.


Subject(s)
Cryptococcosis , Hyperammonemia , Liver Transplantation , Cryptococcosis/complications , Cryptococcosis/diagnosis , Humans , Hyperammonemia/etiology , Liver Transplantation/adverse effects , Middle Aged , Urease
12.
Eur J Pediatr Surg ; 31(5): 396-406, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33186999

ABSTRACT

INTRODUCTION: Postoperative diaphragmatic hernia (DH) is a rare but potentially life-threatening complication following pediatric liver transplantation (LT). In the current literature, a total of 49 such hernias have been reported in 17 case series. We present eight additional cases, three of which reoccurred after surgical correction, and review the current literature with a focus on recurrence. MATERIALS AND METHODS: The study sample included children (<18 years of age) who underwent LT between June 2013 and June 2020 at five large transplant centers and who subsequently presented with DH. During the study period, a total of 907 LT was performed. Eight DH were recognized, and risk factors were analyzed. RESULTS: For the eight children with DH, the mean age at LT was 28.0 (5-132) months. All patients with a DH received left lateral segment split grafts except one, who received a full left lobe. The mean weight at time of LT was 11.8 (6.6-34) kg. Two patients had a primary abdominal muscle closure, and six had a temporary silastic mesh closure. All eight children presented with a right posterolateral DH. The small bowel was herniated in the majority of cases. Symptoms reported included nausea, vomiting, and respiratory distress. Two patients were asymptomatic, and discovery was incidental. All patients underwent prompt primary surgical repair. Three DH hernias (37.5%) recurred despite successful surgical correction. CONCLUSION: DH following liver transplant with technical variant grafts may be underreported and is prone to recur despite surgical correction. A better understanding of the pathophysiology and more thorough reporting may help increase awareness. Early detection and prompt surgical management are the cornerstones of a successful outcome.


Subject(s)
Hernia, Diaphragmatic/etiology , Liver Transplantation/adverse effects , Postoperative Complications/etiology , Child , Child, Preschool , Hernia, Diaphragmatic/diagnosis , Hernia, Diaphragmatic/surgery , Humans , Infant , Postoperative Complications/diagnostic imaging , Postoperative Complications/surgery , Recurrence , Retrospective Studies
13.
Cell Motil Cytoskeleton ; 65(12): 964-78, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18937352

ABSTRACT

Mutations in genes encoding desmosomal proteins have been implicated in the pathogenesis of heart and skin diseases. This has led to the hypothesis that defective cell-cell adhesion is the underlying cause of injury in tissues that repeatedly bear high mechanical loads. In this study, we examined the effects of two different mutations in plakoglobin on cell migration, stiffness, and adhesion. One is a C-terminal mutation causing Naxos disease, a recessive syndrome of arrhythmogenic right ventricular cardiomyopathy (ARVC) and abnormal skin and hair. The other is an N-terminal mutation causing dominant inheritance of ARVC without cutaneous abnormalities. To assess the effects of plakoglobin mutations on a broad range of cell mechanical behavior, we characterized a model system consisting of stably transfected HEK cells which are particularly well suited for analyses of cell migration and adhesion. Both mutations increased the speed of wound healing which appeared to be related to increased cell motility rather than increased cell proliferation. However, the C-terminal mutation led to dramatically decreased cell-cell adhesion, whereas the N-terminal mutation caused a decrease in cell stiffness. These results indicate that different mutations in plakoglobin have markedly disparate effects on cell mechanical behavior, suggesting complex biomechanical roles for this protein.


Subject(s)
Arrhythmogenic Right Ventricular Dysplasia/genetics , Cell Movement/genetics , Mutation , Wound Healing/genetics , gamma Catenin/genetics , Cell Adhesion/genetics , Cell Line , Humans
14.
J Bras Nefrol ; 40(1): 66-72, 2018.
Article in English, Portuguese | MEDLINE | ID: mdl-29796576

ABSTRACT

INTRODUCTION: Urinary tract infection (UTI) is the most common serious bacterial infection in young infants. Signs and symptoms are often nonspecific. OBJECTIVES: To describe clinical, demographic and laboratory features of UTI in infants ≤ 3 months old. METHODS: Cross-sectional study of infants ≤ 3 months old with UTI diagnosed in a pediatric emergency department, for the period 2010-2012. UTI was defined as ≥ 50,000 colony-forming units per milliliter of a single uropathogen isolated from bladder catheterization. Paired urinalysis and urine culture from group culture-positive and group culture-negative were used to determine the sensitivity and specificity of pyuria and nitrite tests in detecting UTI. RESULTS: Of 519 urine cultures collected, UTI was diagnosed in 65 cases (prevalence: 12.5%); with male predominance (77%). The most common etiologies were Escherichia coli (56.9%), Klebsiella pneumoniae (18.5%) and Enterococcus faecalis (7.7%). Frequent clinical manifestations were fever (77.8%), irritability (41.4%) and vomiting (25.4%). The median temperature was 38.7°C. The sensitivity of the nitrite test was 30.8% (95%CI:19.9-43.4%), specificity of 100% (95%CI:99.2-100%). Pyuria ≥ 10,000/mL had a sensitivity of 87.7% (95%CI:77.2-94.5%), specificity of 74.9% (95%CI:70.6 -78.8%). The median peripheral white blood cell count was 13,150/mm3; C-reactive protein levels were normal in 30.5% of cases. CONCLUSIONS: The male: female ratio for urinary tract infection was 3.3:1. Non-Escherichia coli etiologies should be considered in empirical treatment. Fever was the main symptom. Positive nitrite is highly suggestive of UTI but has low sensitivity; whereas pyuria ≥ 10,000/mL revealed good sensitivity, but low specificity. Peripheral white blood cell count and C-reactive protein concentration have limited usefulness to suggest UTI.


Subject(s)
Urinary Tract Infections/diagnosis , Urinary Tract Infections/urine , Cohort Studies , Cross-Sectional Studies , Female , Humans , Infant , Infant, Newborn , Male , Retrospective Studies
15.
J Am Coll Surg ; 235(4): 641-642, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35816727

Subject(s)
Benchmarking , Humans
16.
Rev. Paul. Pediatr. (Ed. Port., Online) ; 40: e2021002, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1356761

ABSTRACT

Abstract Objective: To perform a systematic review of the health economic evidence on the care of children and adolescents with complex clinical conditions, comparing groups included and not included (control group) in palliative care at the end of life. Data source: The seven databases searched were PubMed, Embase, Web of Science, Cochrane Library, Virtual Health Library-Latin American and Caribbean Health Sciences Literature (VHL-LILACS), EBSCOhost, and Paediatric Economic Database Evaluation, following recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement, from January 1979 to November 2020. The review included studies of patients under 18 years of age with complex clinical conditions that compared a palliative care group with a control group. The economic outcomes analyzed were length and place of stay at the end of life (home, hospice, ward, intensive care unit, emergency room), diagnostic and therapeutic procedures performed, and health-related costs. The exclusion criteria were: studies without a matched control group, conference/congress abstracts, letters to the editor, editorials, comments, qualitative studies, narrative reviews, studies with ten or fewer participants in each group, articles published in languages other than English, Portuguese, or Spanish. Data synthesis: Out of the 518 articles identified, 4 met the inclusion criteria. We found evidence of direct economic benefits, such as reduced health costs, indirect savings, and protection of patients from undergoing invasive procedures, surgeries, and costly therapies, which cause greater suffering at the end of life. Therefore, participating in a palliative care program saved financial and technological resources, besides increasing the frequency of deaths at home and improving the quality of life. Conclusions: Public and private policies to promote palliative care represent better efficiency when allocating available health care resources.


Resumo Objetivo: Realizar revisão sistemática das evidências de economia da saúde no cuidado de crianças e adolescentes com condições clínicas complexas, comparando no fim de vida o grupo inserido em cuidados paliativos com o grupo não inserido (grupo controle). Fontes de dados: As sete bases de dados pesquisadas foram PubMed, Embase, Web of Science, Cochrane Library, Biblioteca Virtual da Saúde-Literatura Latino-Americana e do Caribe em Ciências da Saúde (BVS-LILACS), EBSCOhost e Paediatric Economic Database Evaluation, seguindo as recomendações do Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement, de janeiro/1979 a novembro/2020. A revisão incluiu estudos com pacientes com condições clínicas complexas, idade inferior a 18 anos, comparativos de um grupo inserido em cuidados paliativos com um grupo controle não inserido em cuidados paliativos. Os desfechos econômicos analisados foram tempo e local de permanência no fim de vida (casa, hospice, enfermaria, unidade de terapia intensiva, pronto-socorro), procedimentos diagnósticos e terapêuticos realizados e custos relacionados aos cuidados de saúde. Os critérios de exclusão foram: estudos sem grupo controle pareados, resumos de conferências/congressos, cartas ao editor, editoriais, comentários, estudos qualitativos, revisões narrativas, estudos com dez ou menos participantes, artigos publicados em outras línguas além de inglês, português e espanhol. Síntese dos dados: Do total de 518 artigos identificados, quatro preencheram os critérios de inclusão. Houve evidências de benefícios econômicos diretos de redução de custos monetários relacionados à saúde e também indiretos, de economia e proteção ao paciente de procedimentos invasivos, cirurgias e terapias onerosas, que geram maior sofrimento no fim de vida. Portanto, estar inserido em um programa de cuidados paliativos promoveu economia de recursos financeiros e tecnológicos, além de ter possibilitado maior frequência de óbitos no domicílio e maior qualidade de vida. Conclusões: Políticas públicas e privadas para promover cuidados paliativos representam melhor eficiência na alocação dos recursos disponíveis para cuidados em saúde.

17.
J Med Chem ; 48(10): 3630-8, 2005 May 19.
Article in English | MEDLINE | ID: mdl-15887970

ABSTRACT

Sansalvamide A, a cyclic depsipeptide isolated from a marine fungus of the genus Fusarium, is composed of four hydrophobic amino acids (Phe, two Leu, Val) and one hydroxy acid ((S)-2-hydroxy-4-methylpentanoic acid; O-Leu) with five stereogenic centers all having S-stereochemistry. We have recently synthesized the corresponding cyclic peptide (Gu, W.; Liu, S.; Silverman, R. B. Organic Lett. 2002, 4, 4171-4174) and found that it too has antitumor activity. N-Methylation can enhance potency and selectivity for peptides. Consequently, here we synthesize 12 different N-methylated sansalvamide A peptide analogues and show that for several different tumor cell lines three of these analogues are more potent than the natural product; in pancreatic cells, sansalvamide A shows little activity, but the N-methylsansalvamide peptides are potent cytotoxic agents.


Subject(s)
Antineoplastic Agents/chemical synthesis , Depsipeptides/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Depsipeptides/chemistry , Depsipeptides/pharmacology , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Structure-Activity Relationship , Time Factors
18.
Mol Endocrinol ; 17(3): 318-32, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12554780

ABSTRACT

FSH is controlled by a variety of positive and negative stimuli, and the unique FSHbeta-subunit is a major target for this regulation. Activin is a key modulator of FSHbeta transcription and hormone secretion. The signal transduction pathway leading to FSH expression was previously unknown. Here, we show that the transcription factors Smad3 and Smad4 mediate activin-stimulated activity of the rat FSHbeta promoter in a pituitary-derived cell line, LbetaT2. Cells were transiently transfected with the rat FSHbeta promoter fused to a luciferase reporter gene (-338rFSHbeta-Luc), and a minimal activin-responsive region was identified. Transfection of Smad3, but not the highly related Smad2, led to a ligand-independent stimulation of the FSHbeta promoter activity. As expected, activin caused an additional increase of luciferase expression, which was blocked by cotreatment with follistatin. Although Smad4 alone had no effect on FSHbeta transcription, it significantly augmented Smad3 and activin-mediated stimulation of the promoter. A palindromic consensus Smad-binding element in the proximal promoter was found to bind Smad4, and elimination of the region resulted in a loss of activin-mediated FSHbeta transcription. The activin signaling pathway is conserved in a number of cells, but FSHbeta expression is restricted to gonadotropes. A pituitary-specific transcription factor necessary for activin-dependent induction of the FSHbeta promoter has been identified that permits FSHbeta expression in nongonadotrope cells. Pitx2 is a member of Pitx subfamily of bicoid-related homeodomain factors that is required for pituitary development and is present in the adult pituitary. This factor was transfected into LbetaT2 cells, where it caused up-regulation of basal and activin-mediated FSHbeta promoter activity. Furthermore, cotransfection of Pitx2c with Smad3 in kidney-derived TSA cells resulted in activin-regulated FSHbeta response, suggesting its important role in tissue-restricted regulation of FSHbeta by activin. A Pitx2c binding site was identified within the proximal promoter, and elimination of this region also resulted in a loss of activin-regulated FSHbeta promoter activity. Taken together, these studies suggest that the regulation of FSHbeta is dependent on activin-mediated signaling factors in concert with pituitary-derived nuclear regulatory proteins.


Subject(s)
Activins/physiology , Follicle Stimulating Hormone, beta Subunit/physiology , Transcriptional Activation/physiology , Xenopus Proteins , Animals , Base Sequence , Cell Line , Cells, Cultured , DNA-Binding Proteins/physiology , Electrophoretic Mobility Shift Assay , Follicle Stimulating Hormone, beta Subunit/biosynthesis , Follicle Stimulating Hormone, beta Subunit/genetics , Haplorhini , Homeodomain Proteins/physiology , Humans , Molecular Sequence Data , Pituitary Gland/physiology , Promoter Regions, Genetic/physiology , Rats , Signal Transduction/genetics , Signal Transduction/physiology , Smad3 Protein , Trans-Activators/physiology , Transcription, Genetic/physiology , Transfection
19.
Rev Paul Pediatr ; 33(3): 333-40, 2015.
Article in Portuguese | MEDLINE | ID: mdl-25765447

ABSTRACT

OBJECTIVE: To associate the nutritional status and the self-perception of nutritional status with the use of licit drugs among adolescents. METHODS: Cross-sectional study in which 210 adolescents answered a questionnaire on alcohol and tobacco experimentation and self-perceptions about their nutritional status. The correspondence between the adolescents' perception of their own nutritional status and actual nutritional status was analyzed, as well as associations between nutritional status, self-perception of nutritional status, gender, age, and presence of smokers at home with alcohol and tobacco use. The variables were analyzed separately in a bivariate analysis and, subsequently, a multivariate analysis determined the factors associated with drug use. RESULTS: The study included 210 adolescents with a median age of 148 months; 56.6% were females. Of the total sample, 6.6% have tried cigarettes, and 20% have tried alcohol; 32.3% had BMI Z-Score≥1, 12.85% had BMI Z-Score≥2, and 50.7% had a correct perception of his/her weight. After a multivariate analysis, only the self-perception about weight statistically influenced experimentation of tobacco, and patients who identified themselves as having very high weight were more likely to experiment tobacco (odds ratio (OR) 13.57; confidence interval (95% CI) 2.05-89.8; p=0.007); regarding alcohol use, adolescents who identified themselves as having high weight were 2.4 times more likely to experiment with alcohol than adolescents that identified themselves as having normal weight (95% CI 1.08-5.32, p=0.031). CONCLUSIONS: Adolescents with self-perception of excess weight may constitute a risk group for alcohol and tobacco use.


Subject(s)
Alcohol Drinking/epidemiology , Nutritional Status , Self Concept , Smoking/epidemiology , Adolescent , Child , Cross-Sectional Studies , Female , Humans , Male , Self Report
20.
Pediatr Infect Dis J ; 34(9): 1023-5, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26075812

ABSTRACT

Staphylococcus saprophyticus is a rarely reported agent of urinary tract infection (UTI) in the pediatric population. In our retrospective 3-year study, S. saprophyticus comprised 24.5% of 106 isolates of UTIs in female adolescents 12-15 years of age who attended an emergency department. Clinicians should be aware of the high prevalence of this etiology when empirically treating UTIs in female adolescents.


Subject(s)
Staphylococcal Infections/epidemiology , Staphylococcus saprophyticus/isolation & purification , Urinary Tract Infections/epidemiology , Urinary Tract Infections/microbiology , Adolescent , Child , Female , Humans , Prevalence , Retrospective Studies
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