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1.
Cureus ; 16(4): e58532, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38957833

RESUMO

Introduction Cancer exerts a substantial influence on the body's metabolism through varied mechanisms, instigating a metabolic reprogramming that maintains the unchecked growth and survival of cancer cells, consequently perturbing diverse metabolic parameters. The introduction of positron emission tomography-computed tomography (PET/CT), delivering detailed insights into both metabolic and morphological aspects, has brought about a revolutionary shift in modern cancer detection. Exploring the potential connection between PET-CT metabolic features and the metabolic parameters of liver enzymes in an individual can unveil novel avenues for cancer diagnosis and prognosis. Materials and methods This study conducted a retrospective analysis of patient records from our institution, covering the period from January 2021 to September 2023, focusing on individuals with various malignancies. The data included information on gender, age, clinical history, and liver serum parameters, which were compiled into tables. Additionally, inflammatory indicators such as ALT (alanine transaminase), ALP (alkaline phosphatase), total protein (TP), ALT/AST ratio, and SUVmax were collected and plotted. The study used Pearson correlation analysis to assess the relationship between each inflammatory variable and SUV (max) as determined by PET-CT. Results In breast cancer, there was a statistically significant positive correlation (R2=0.0651) between serum ALP levels and SUVmax as determined by regression analysis. Hodgkin lymphoma, on the other hand, showed a statistically significant negative correlation between the ALT-to-AST ratio (ALT/AST) and SUVmax (r = -0.45, R2 = 0.204). In non-Hodgkin lymphoma patients, total protein (TP) was negatively correlated with SUVmax (R2=-0.081, r= -0.28), while in lung cancer patients, there was a significant positive correlation with regression correlation coefficients (R2 = 0.026, 0.024, 0.024, and 0.018 for ALT/AST, TP, ALP, albumin, and ALT, respectively). Conclusion Aligning with these results, it can be a recent addition to acknowledge that both the tumor metabolic parameter (SUVmax) and the levels of liver serum enzymes exhibit a potential for predicting patient prognosis in various cancers.

2.
Am J Gastroenterol ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016385

RESUMO

BACKGROUND: The prevalence of Metabolic dysfunction associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute on chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied. METHODS: Patients with MAFLD-ACLF were recruited from the AARC registry. The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease (CLD) as MAFLD (or previous nomenclature such as NAFLD, NASH, or NASH-cirrhosis). Patients with coexisting other etiologies of CLD (such as alcohol, HBV, HCV, etc.) were excluded. Data was randomly split into derivation (n=258) and validation (n=111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered. RESULTS: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27%, and hypertension in 29%. The dominant precipitants included viral hepatitis (HAV and HEV, 32%), drug-induced injury (DILI, 29%) and sepsis (23%). MELD-Na and AARC scores upon admission averaged 32±6 and 10.4±1.9. At 90 days, 51% survived. Non-viral precipitant, diabetes, bilirubin, INR, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for non-viral precipitant) and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts. CONCLUSION: Almost half of MAFLD-ACLF patients die within 90 days. Diabetes and non-viral precipitants such as DILI and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for MAFLD-ACLF patients.

3.
Clin Transplant ; 38(7): e15373, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39023085

RESUMO

BACKGROUND: Alternate complement dysregulation postrenal transplantation can result in thrombotic microangiopathy (TMA). There is a scarcity of data regarding outcomes based on the timing of TMA post-transplant, coupled with a lack of follow-up biopsy findings post TMA diagnosis. This study aims to assess allograft and patient outcomes in individuals developing early TMA, defined within 4 months post-transplantation, and explore any differences in follow-up surveillance biopsies compared to a non-TMA group. DESIGN: This is a single center retrospective study between January 1, 2002 and October 10, 2019. Patients who developed TMA within 4 months post-transplantation were compared to a propensity matched non-TMA group. RESULTS: Thirty-one patients developed TMA within 4 months of renal transplantation. Index TMA biopsy featured noticeable glomerular, and vascular lesions along with acute tubular injury. Four-month surveillance biopsy showed significant glomerulitis, transplant glomerulopathy and chronic interstitial fibrosis as compared to non-TMA group. However, at 1 year, these differences were no longer significant. There was no significant difference in patient survival (TMA vs. non-TMA, p = 0.083); however, death censored graft survival was significantly lower in the TMA group (p < 0.001). TMA patients had a significantly lower estimated glomerular filtration rate at 4 months and at 1 year as compared to the non-TMA group. CONCLUSION: Early onset TMA post renal transplant leads to decreased renal function and lower graft survival. Early recognition and prompt treatment may help in reducing the adverse outcomes.


Assuntos
Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Rim , Complicações Pós-Operatórias , Microangiopatias Trombóticas , Humanos , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/patologia , Transplante de Rim/efeitos adversos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Seguimentos , Prognóstico , Complicações Pós-Operatórias/etiologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Adulto , Taxa de Filtração Glomerular , Fatores de Risco , Testes de Função Renal , Taxa de Sobrevida , Falência Renal Crônica/cirurgia
4.
JCI Insight ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916963

RESUMO

Despite epidermal turnover, the skin is host to a complex array of microbes including viruses, such as the human papillomavirus (HPV), which must infect and manipulate skin keratinocyte stem cells (KSC) to survive. This crosstalk between the virome and KSC populations remains largely unknown. Here, we investigated the effect of HPV8 on KSCs using various mouse models. We observed that the HPV8 early region gene E6 specifically caused Lrig1+ hair follicle junctional zone KSC proliferation and expansion, which would facilitate viral transmission. Within Lrig1+ KSCs specifically, HPV8 E6 bound intracellular p300 to phosphorylate the STAT3 transcriptional regulatory node. This induces ΔNp63 expression, resulting in KSC expansion into the overlying epidermis. HPV8 was associated with 70% of human actinic keratoses (AK). Together these results define the "hit and run" mechanism for HPV8 in human actinic keratosis as an expansion of KSCs, which lacks melanosome protection and is thus susceptible to sun-light-induced malignant transformation.

5.
Polymers (Basel) ; 16(9)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38732749

RESUMO

Wounds are breaks in the continuity of the skin and underlying tissues, resulting from external causes such as cuts, blows, impacts, or surgical interventions. Countless individuals suffer minor to severe injuries, with unfortunate cases even leading to death. In today's scenario, several commercial products are available to facilitate the healing process of wounds, although chronic wounds still present more challenges than acute wounds. Nevertheless, the huge demand for wound-care products within the healthcare sector has given rise to a rapidly growing market, fostering continuous research and development endeavors for innovative wound-healing solutions. Today, there are many commercially available products including those based on natural biopolymers, stem cells, and microRNAs that promote healing from wounds. This article explores the recent breakthroughs in wound-healing products that harness the potential of natural biopolymers, stem cells, and microRNAs. A comprehensive exploration is undertaken, covering not only commercially available products but also those still in the research phase. Additionally, we provide a thorough examination of the opportunities, obstacles, and regulatory considerations influencing the potential commercialization of wound-healing products across the diverse markets of Europe, America, and Asia.

6.
Infect Immun ; 92(2): e0028923, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38174929

RESUMO

Brucella species are Gram-negative intracellular bacterial pathogens that cause the worldwide zoonotic disease brucellosis. Brucella can infect many mammals, including humans and domestic and wild animals. Brucella manipulates various host cellular processes to invade and multiply in professional and non-professional phagocytic cells. However, the host targets and their modulation by Brucella to facilitate the infection process remain obscure. Here, we report that the host ubiquitin-specific protease, USP8, negatively regulates the invasion of Brucella into macrophages through the plasma membrane receptor, CXCR4. Upon silencing or chemical inhibition of USP8, the membrane localization of the CXCR4 receptor was enriched, which augmented the invasion of Brucella into macrophages. Activation of USP8 through chemical inhibition of 14-3-3 protein affected the invasion of Brucella into macrophages. Brucella suppressed the expression of Usp8 at its early stage of infection in the infected macrophages. Furthermore, we found that only live Brucella could negatively regulate the expression of Usp8, suggesting the role of secreted effector protein of Brucella in modulating the gene expression. Subsequent studies revealed that the Brucella effector protein, TIR-domain containing protein from Brucella, TcpB, plays a significant role in downregulating the expression of Usp8 by targeting the cyclic-AMP response element-binding protein pathway. Treatment of mice with USP8 inhibitor resulted in enhanced survival of B. melitensis, whereas mice treated with CXCR4 or 14-3-3 antagonists showed a diminished bacterial load. Our experimental data demonstrate a novel role of Usp8 in the host defense against microbial intrusion. The present study provides insights into the microbial subversion of host defenses, and this information may ultimately help to develop novel therapeutic interventions for infectious diseases.


Assuntos
Brucella melitensis , Brucella , Brucelose , Animais , Humanos , Camundongos , Proteases Específicas de Ubiquitina/metabolismo , Macrófagos/microbiologia , Brucelose/microbiologia , Proteínas de Bactérias/genética , Mamíferos , Endopeptidases/metabolismo , Ubiquitina Tiolesterase/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo
7.
Br J Dermatol ; 190(5): 729-739, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38288865

RESUMO

BACKGROUND: Mutant BRAF targeted therapies remain a standard of care for the treatment of metastatic malignant melanoma (MM); however, high initial response rates are tempered by the persistence of residual MM cells that eventually lead to disease recurrence and mortality. As MM recurrence during targeted therapy can present with the simultaneous occurrence of multiple tumour nodules at the original body sites, we hypothesized the presence of an intrinsically resistant MM cell subpopulation. OBJECTIVES: To identify an MM cell subpopulation that is intrinsically resistant to targeted therapy and possibly responsible for MM recurrence. METHODS: Using melanoma cell lines, we defined culture conditions for the reproducible three-dimensional growth of melanospheres to investigate putative cancer stem cell populations. We undertook RNA sequencing and bioinformatic analysis to characterize cell populations between adherent and nonadherent culture, and cells expressing or not expressing CD20. Furthermore, we defined an in vitro assay to evaluate the killing of melanoma cancer stem cells as a therapeutic test using combination therapies targeting driver mutation and CD20. RESULTS: We described the culture conditions that promote MM cells to form melanospheres with a reproducible colony-forming efficiency rate of 0.3-1.3%. RNA sequencing of melanosphere vs. conventional MM cell cultures (n = 6), irrespective of the BRAF mutation status, showed that melanosphere formation was associated with growth and differentiation transcriptional signatures resembling MM tumours. Importantly, melanosphere formation also led to the emergence of a CD20+ MM cell subpopulation, similar to that observed in primary human MM tumours. CD20+ MM cells were resistant to BRAF inhibitor therapy and, consistent with this finding, demonstrated a Forkhead box protein M1 transcriptomic profile (n = 6). Combining BRAF inhibitor and anti-CD20 antibody treatment led to the additional killing of previously resistant CD20+  BRAF mutant MM cells. CONCLUSIONS: In patients with MM that harbour a CD20+ subpopulation, combined therapy with BRAF inhibitor and anti-CD20 antibody could potentially kill residual MM cells and prevent disease recurrence.


Assuntos
Melanoma , Humanos , Melanoma/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases/farmacologia , Mutação , Linhagem Celular Tumoral
8.
Sci Rep ; 13(1): 22108, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38092779

RESUMO

Due to its advantages, the asymmetrical dual three-phase induction motor drive is a strong choice in high-power applications. However, the common-mode voltage produced by the voltage source inverters affects the winding insulation and damages the bearings. Common-mode voltage is also responsible for electromagnetic interference and leakage currents. This paper, therefore, analyses the common-mode voltage produced by the inverter supplying a dual three-phase induction motor drive and proposes a novel modified space vector decomposition-based Space Vector Pulse Width Modulation (SVPWM) technique for common mode reduction. The vector space decomposition-based space vector modulation technique offers excellent flexibility as it reduces the common-mode voltage (CMV) by exploiting the additional degree of freedom in a dual three-phase system. The common-mode voltage (CMV) can be reduced to one-sixth of the DC link voltage compared to the highest CMV, i.e. half of the DC-link voltage produced in conventional space vector modulation. The proposed method is also validated experimentally to demonstrate the effectiveness of the proposed scheme in terms of the amplitude of CMV, pulsations, and total harmonic distortion(THD) in current.

9.
Indian J Pathol Microbiol ; 66(4): 862-864, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38084550

RESUMO

Biliary obstruction secondary to malignancy is a common clinical problem. Rarely, biliary obstruction is due to leukemia, and obstructive jaundice in these patients usually presents late in the course of the disease. We present a rare case of a patient who presented with fever, jaundice, and pruritus with multiple nodular swellings in the left shoulder, left thigh, and lower back. Magnetic resonance cholangiopancreatography (MRCP) revealed periampullary mass lesion causing dilated common bile duct (CBD) and intrahepatic bile ducts; hence, endoscopic retrograde cholangiography with plastic stenting was done. Biopsy from the shoulder lesion revealed a mesenchymal tumor, and immunohistochemistry (IHC) confirmed the lesion as myeloid sarcoma. Myeloid sarcoma is an extramedullary tumor, a subtype of acute myeloid leukemia, and presentation as biliary lesions with multiple anatomical sites is very rare. The patient was started on chemotherapy after the normalization of bilirubin. The patient showed improvement of skin lesions and normalization of liver function test (LFT) after 3 weeks of chemotherapy.


Assuntos
Colestase , Icterícia Obstrutiva , Sarcoma Mieloide , Humanos , Icterícia Obstrutiva/diagnóstico , Icterícia Obstrutiva/etiologia , Sarcoma Mieloide/complicações , Sarcoma Mieloide/diagnóstico , Colestase/complicações , Colestase/patologia , Ductos Biliares Intra-Hepáticos/patologia , Ducto Colédoco/patologia
10.
Front Med (Lausanne) ; 10: 1282827, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928458

RESUMO

Introduction: JC polyomavirus (JCPyV) is a ubiquitous virus that can be latent in the brain and the kidney. It is the etiologic agent responsible for progressive multifocal leukoencephalopathy, a fatal, demyelinating disease of the central nervous system, and rarely causes polyomavirus nephropathy in immunocompromised kidney transplant recipients. Case description: We present the first case of JCPyV nephropathy in a simultaneous heart-kidney transplant patient, where viral-specific in situ hybridization staining of the kidney tissue was utilized to confirm the diagnosis. The patient was diagnosed 6 years after simultaneous heart-kidney transplantation and was treated with immunosuppression reduction and intravenous immunoglobulin. Discussion: JCPyV nephropathy should be considered in the differential diagnosis of kidney allograft injury, particularly, with suggestive light microscopy histologic features in the absence of BK polyomavirus viremia and/or viruria. In addition to obtaining JCPyV PCR in the blood, in situ hybridization staining may have a utility in confirming the diagnosis. To date, we lack effective JCPyV-specific therapies, and prompt initiation of immunosuppression reduction remains the mainstay of treatment.

11.
Nanoscale Adv ; 5(22): 6155-6161, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37941946

RESUMO

We design and fabricate hybrid organic inorganic perovskite photodetectors that utilize hole transport layer poly(3,4-ethylene dioxythiophene):poly (styrenesulfonate) PEDOT:PSS confined in alumina nanocylinders. This structural asymmetry in the device where the alumina nanopore template is partially filled with PEDOT:PSS provides features that improve certain device characteristics. The leakage component of the current in such devices is considerably suppressed, resulting in enhanced responsivity and detectivity. The funneling aspect of the photogenerated charge carrier transit ultimately leads to fast detectors as compared to conventional perovskite detectors.

12.
J Oral Maxillofac Pathol ; 27(3): 469-475, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38033979

RESUMO

Background: Oral cancer still represents the leading cause of mortality in India. Due to the drawbacks of current treatment options, a safe, low-cost therapy is the need of the hour. Recently, novel plant extracts with anti-cancer properties have gained greater attention. One among them is Annona muricata and its leaf extract, which has been studied for its anti-cancer effect against various cancers. However, studies on oral cancer cells are very much limited and hence the study. Aims: To evaluate the cytotoxic, anti-proliferative, anti-metastatic and pro-apoptotic effect of aqueous leaf extract of Annona muricata (ALEAM) against SCC-15 cell lines through in vitro assays. Materials and Methods: In vitro assays such as MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], colony formation and wound healing assays were performed. Furthermore, to evaluate the underlying mechanism, gene and protein expression analysis of apoptotic/anti-apoptotic marker genes Bax, P53 and Bcl2, were done using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Student's t-test has been performed for analysis of experimental data. Results: The results showed that ALEAM exhibited significant cytotoxic activity in a dose-dependent manner as well as inhibited colony formation and cell migration. The pro-apoptotic properties were affirmed by a highly significant drop in Bcl-2 gene expression and a highly significant rise in P53 and Bax genes in the study group compared to the control (P < 0.05). Conclusion: The current study provides evidence that ALEAM has the potential to be developed as a novel anti-cancer drug for the treatment of SCC after further clinical studies.

13.
J Cancer Res Ther ; 19(5): 1450-1453, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37787328

RESUMO

Spindle cell carcinoma (SpCC) is a rare variant of oral squamous cell carcinoma (SCC) with unique clinicopathological characteristics, a high recurrence rate, and metastatic potential. It will be truly devastating when it occurs as a second wave in a cancer survivor. Despite the multidisciplinary approach in the management of oral SCC, the incidence of second malignancies or multiple carcinomas has been constantly reporting in the literature. Although radiotherapy has saved the lives of countless cancer patients, its several serious late effects are well-documented in the literature, making it a double-edged sword. Radiation epidemiology studies revealed an increased risk of developing radiogenic second cancers after 5 or more years. The purpose of this article is to document a case of SpCC arising in a patient after a span of 5 years who was previously diagnosed and treated with radiotherapy for well-differentiated SCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço
14.
J Biol Chem ; 299(11): 105309, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37778729

RESUMO

Toll-like receptors (TLRs) are essential components of innate immunity that serves as the first line of defense against the invaded microorganisms. However, successful infectious pathogens subvert TLR signaling to suppress the activation of innate and adaptive responses. Brucella species are infectious intracellular bacterial pathogens causing the worldwide zoonotic disease, brucellosis, that impacts economic growth of many countries. Brucella species are considered as stealthy bacterial pathogens as they efficiently evade or suppress host innate and adaptive immune responses for their chronic persistence. However, the bacterial effectors and their host targets for modulating the immune responses remain obscure. Brucella encodes various outer membrane proteins (Omps) that facilitate their invasion, intracellular replication, and immunomodulation. Outer membrane protein 25 (Omp25) of Brucella plays an important role in the immune modulation through suppression of proinflammatory cytokines. However, the mechanism and the signaling pathways that are targeted by Omp25 to attenuate the production of proinflammatory cytokines remain obscure. Here, we report that Omp25 and its variants, viz. Omp25b, Omp25c, and Omp25d, suppress production of proinflammatory cytokines that are mediated by various TLRs. Furthermore, we demonstrate that Omp25 and its variants promote enhanced ubiquitination and degradation of TLRs and their adaptor proteins to attenuate the expression of proinflammatory cytokines. Targeting multiple TLRs and adaptor proteins enables Omp25 to effectively suppress the expression of proinflammatory cytokines that are induced by diverse pathogen-associated molecular patterns. This can contribute to the defective adaptive immune response and the chronic persistence of Brucella in the host.


Assuntos
Proteínas da Membrana Bacteriana Externa , Brucella , Brucelose , Receptores Toll-Like , Humanos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismo , Brucella/genética , Citocinas/metabolismo , Imunidade Inata , Receptores Toll-Like/metabolismo
15.
Cureus ; 15(9): e44779, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809121

RESUMO

BACKGROUND:  The immune defense against tumor cells is mainly mediated by the natural killer (NK) cells. Cluster of differentiation 57 (CD57) is a 110-kd glycoprotein, typically expressed by the NK cells, attacks the cancer cells and inhibits tumor development. Proliferating cell nuclear antigen (PCNA) is a 36-kd auxiliary protein for DNA polymerase delta that correlates with cell proliferation and DNA synthesis. It is an essential component of DNA replication, DNA recombination, and DNA repair. The uncoordinated proliferation of PCNA protein characterizes the biological behavior of malignant lesions. AIM:  The aim of the present study is to compare and correlate the expression of CD57 and PCNA in different grades of oral squamous cell carcinoma (OSCC) by immunohistochemistry. MATERIALS AND METHODS:  This retrospective analysis comprises 30 samples of various grades of OSCCs and 10 samples of healthy mucosa. Sections of 4-5 µm thickness were done and stained with monoclonal anti-PCNA and anti-CD57 antibodies. The statistical package for social science (SPSS) version 16.0 software (IBM Corp., Armonk, NY) was used to analyze the data in this study. The expression of CD57 and PCNA was compared and correlated between the groups using analysis of variance (ANOVA) post hoc, Dunnet t-test, and Pearson's correlation coefficient test. For statistical significance, a p-value of 0.05 or less was used. RESULTS: A significant decrease in CD57 labeling index was seen from well-differentiated squamous cell carcinoma (16.63 ± 2.33) to poorly differentiated squamous cell carcinoma (5.53 ± 1.20) whereas the significant increase in PCNA labeling index was noted from well-differentiated squamous cell carcinoma (45.88 ± 2.20), followed by moderately differentiated and poorly differentiated squamous cell carcinoma (72.77 ± 4.35). CONCLUSION:  The combination of CD57 and PCNA biomarkers appears to be good indicators of the immune status of the patient and the aggressiveness of the lesion.

16.
Clin Transplant ; 37(12): e15125, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37705388

RESUMO

BACKGROUND: Urinary Tract Infections are the most common post-transplant infection and can have varied presentations. This study aimed to describe the outcomes of kidney transplant recipients with asymptomatic histologic pyelonephritis on allograft biopsy. Histologic Pyelonephritis was defined as neutrophil cast or neutrophilic tubulitis, interstitial infiltrates with predominant neutrophils, and no evidence of rejection or glomerulonephritis on biopsy. METHODS: The study included 123 kidney transplant recipients, of whom 95 underwent protocol biopsies, and 28 had biopsies for elevated creatinine within the first 2 years of a kidney transplant. RESULTS: The mean age of the cohort was 55.3 years, with 52% females and 78% deceased donor transplants. The risk factors for asymptomatic histologic pyelonephritis were recipient female sex (OR 1.89, 1.3-2.7, diabetes mellitus (OR 2.479, 1.687-3.645), and deceased donation (OR 1.69, 1.098-2.63). The incidence of asymptomatic pyelonephritis on protocol biopsy was 1.7%, with 52% having positive urine cultures and Escherichia coli being the most common bacteria. Subjects with asymptomatic pyelonephritis had inferior graft survival compared to the matched cohort HR 1.88 (1.06-3.35), p = .0281. In addition, of these 123 subjects, 68 (55%) subsequently developed pyelonephritis, and 34 subjects had pyelonephritis within 6 months after this episode. Subjects with recurrent infections exhibited lower survival HR 2.86 (1.36-6.02) and a trend toward higher rejection risk. CONCLUSION: Asymptomatic histologic pyelonephritis can occur in kidney transplant recipients and is associated with inferior graft survival.


Assuntos
Transplante de Rim , Pielonefrite , Infecções Urinárias , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Transplante de Rim/efeitos adversos , Pielonefrite/etiologia , Pielonefrite/patologia , Infecções Urinárias/etiologia , Transplante Homólogo , Bactérias , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Rim/patologia
17.
Chirality ; 35(11): 889-898, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37345319

RESUMO

A novel, simple, specific, rapid, enantioselective normal phase chiral high-performance liquid chromatographic method with amylose-based Chiral Pak IG-3(250 × 4.6 mM) 3.0 µM column was developed and validated for separation and quantification of isomers and enantiomer of Valbenazine. The mobile phase composed of n-Heptane, isopropyl alcohol, dichloromethane, ethanol, and diethylamine in the ratio of 70:10:15:5:0.1 (V/V/V/VV) with a gradient flow rate was applied. The injection volume was 10 µl, and detection was carried out using a photodiode array detector at 282 nM. The column compartment was set at 35°C. The resolution between the enantiomer and isomers was found to be more than 2.0. The method was linear over the concentration range of limit of quantitation to 250% for isomers and enantiomers. The method was found to be robust with column temperature. The proposed chiral method is applicable for the determination of isomers and enantiomer of Valibenazine and was successfully used in the quality control of bulk drug manufacturing and pharmaceuticals.

19.
Cureus ; 15(4): e37912, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37220470

RESUMO

Aim and objectives The infection of microbial agents in cirrhosis has increased due to poor immunity, which increases morbidities and mortalities worldwide. The present study aimed to assess the incidence, the type of infections, the pattern of resistance, and the course of hospitalization among cirrhotic patients in the Eastern coastal region. Methodology The study was a descriptive cross-sectional study, and the current study was undertaken for 24 months at the Department of Gastroenterology and Hepatobiliary Sciences, IMS, and SUM. Hospital, Bhubaneswar. Consecutive cirrhotic patients admitted with bacterial infection were prospectively evaluated, and the infection patterns were accessed. The data were collected in a well-structured proforma designed by our study team. Results Out of the total 200 cases, a fraction of 72.5% of males outnumbered the females; the mean age of presentation was 59 ± 12 years. A fraction of 59% of cases had the habit of consuming alcohol which amounted to the predominant etiological factor for cirrhosis, followed by non-alcoholic steatohepatitis (NASH). Urinary tract infection (UTI) and spontaneous bacterial peritonitis (SBP) were more common types of infections in the healthcare-associated (HCA) group; however, pneumonia and skin and soft tissue infections (SSTI) were predominant types of infections in community-acquired (CA) group. The model for end-stage liver disease (MELD) scores were not significantly different amongst the three groups with infections at the time of Diagnosis infection and at the time of hospitalization. However, the MELD scores were substantially higher at the time of infection diagnosis than the MELD scores at the time of admission amongst the three groups with infection. Conclusion The present study showed that infections in cirrhosis were relatively common. Due to increasing resistance patterns, the judicious usage of antibiotics in cirrhosis could be the need of the hour.

20.
Indian J Anaesth ; 67(3): 277-282, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37250523

RESUMO

Background and Aims: Prolapsed intervertebral disc (IVDP) is a major cause of low back pain. Platelet-rich plasma (PRP) has emerged as a viable option for these patients, with fewer adverse effects and long-term sustainability of pain relief. This double-blinded, randomised study aimed to evaluate the effect of autologous PRP on low back pain in patients with IVDP. Methods: A total of 42 patients with IVDP were randomised either to the autologous PRP (n = 21) group or control (epidural local anaesthetics with steroids; n = 21) group. Change in pain was assessed using the Numeric Rating Scale (NRS). Impact of treatment was assessed using the Global Perceived Effect (GPE) scale. All the patients were followed up for six months. Data was compared using Chi-square, independent sample t, and Mann-Whitney U tests. Results: The two groups were similar in their demographic and clinical profile. The baseline mean NRS ± standard deviation (SD) was 6.91 ± 0.94 in the PRP group and 7.38 ± 1.16 in the control group (P = 0.099). At six months, the mean NRS ± SD was 1.43 ± 0.75 in the PRP group compared to 5.43 ± 0.75 in the control group (P < 0.001). The GPE score was also found to be significantly higher in the PRP group, compared to the control group in the final assessment (P < 0.001). During the course of the study, the PRP group showed a consistent decline in NRS, whereas the control group showed an initial decline followed by consistent increase in NRS. Conclusion: PRP provided sustained relief from low back pain due to IVDP and can be recommended as a safe and promising alternative to epidural local anaesthetics and steroids.

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