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1.
Arthroplast Today ; 27: 101360, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38690095

RESUMO

Background: In primary total knee arthroplasty (TKA), there is ongoing controversy about optimal fixation (cemented vs cementless). Cemented TKA remains the gold standard, with the largest body of long-term evidence available to support it. However, cementless TKA implants are gaining popularity due to potential biomechanical advantages and a growing body of literature supporting survivorship. Due to paucity of literature investigating fixation methods in robotic-assisted TKA (Ra-TKA), we aim to compare clinical outcomes of cementless Ra-TKA with those of cemented Ra-TKA. Methods: This is a retrospective cohort study of patients who underwent Ra-TKA by 19 surgeons comparing results of cases using cementless vs cemented fixation. We observed short-term complications, emergency room visits, and readmissions. We collected patient-reported outcomes measurement information system and knee injury and osteoarthritis outcome scores preoperatively and 12 weeks after surgery. Results: A total of 582 TKA cases were included: 335 cementless and 247 cemented. The patients in the cementless group were younger and had a higher body mass index. The cemented group had a higher rate of return to the operating room, with manipulation under anesthesia for stiffness being the most common indication in both groups. There were no statistically significant differences in 30-day readmissions, 90-day emergency room visits, or patient-reported outcomes. Conclusions: Our retrospective study demonstrated higher return to operating room in the cemented group vs the cementless group. We reported no differences in any other short-term outcomes between the cementless and cemented Ra-TKA. Our data support efficacy and safety of cementless Ra-TKA at 3-month follow-up.

2.
Front Oncol ; 14: 1362786, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38751813

RESUMO

Background: Fast adaptation of glycolytic and mitochondrial energy pathways to changes in the tumour microenvironment is a hallmark of cancer. Purely glycolytic ρ0 tumour cells do not form primary tumours unless they acquire healthy mitochondria from their micro-environment. Here we explored the effects of severely compromised respiration on the metastatic capability of 4T1 mouse breast cancer cells. Methods: 4T1 cell lines with different levels of respiratory capacity were generated; the Seahorse extracellular flux analyser was used to evaluate oxygen consumption rates, fluorescent confocal microscopy to assess the number of SYBR gold-stained mitochondrial DNA nucleoids, and the presence of the ATP5B protein in the cytoplasm and fluorescent in situ nuclear hybridization was used to establish ploidy. MinION nanopore RNA sequence analysis was used to compare mitochondrial DNA transcription between cell lines. Orthotopic injection was used to determine the ability of cells to metastasize to the lungs of female Balb/c mice. Results: OXPHOS-deficient ATP5B-KO3.1 cells did not generate primary tumours. Severely OXPHOS compromised ρ0D5 cells generated both primary tumours and lung metastases. Cells generated from lung metastasis of both OXPHOS-competent and OXPHOS-compromised cells formed primary tumours but no metastases when re-injected into mice. OXPHOS-compromised cells significantly increased their mtDNA content, but this did not result in increased OXPHOS capacity, which was not due to decreased mtDNA transcription. Gene set enrichment analysis suggests that certain cells derived from lung metastases downregulate their epithelial-to-mesenchymal related pathways. Conclusion: In summary, OXPHOS is required for tumorigenesis in this orthotopic mouse breast cancer model but even very low levels of OXPHOS are sufficient to generate both primary tumours and lung metastases.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38758048

RESUMO

Background: Surgical site infections (SSIs) are common healthcare-associated infections, and national guidelines recommend that antimicrobial prophylaxis (AP) be administered 60 min prior to incision. However, there are limited data regarding the "most optimal" time for administration within the 60-min window. Patients and Methods: This was a multicenter, retrospective study of adult (≥18-year-old) patients that underwent an abdominal hysterectomy, colorectal surgery, or craniotomy and received AP within 60 min of incision. Incidence of SSI was compared between patients who received AP 0-30 versus 31-60 min of incision. In addition, a predefined subgroup analysis evaluated incidence of SSI for 15-min intervals within the 60-min timeframe. Results: Of the 277 patients included in the primary analysis, 233 (84.1%) and 44 (15.9%) received AP 0-30 min and 31-60 min prior to incision, respectively. SSIs were documented in 6.0% (14/233) versus 4.5% (2/44) of patients in the primary analysis (p = 0.703). In the secondary analysis, 137 (49.5%), 95 (34.3%), 34 (12.3%), and 11 (4.0%) patients received AP 0-15, 16-30, 31-45, and 46-60 min prior to incision, respectively. There was no difference in incidence of SSIs among the 15-min intervals (4.4% vs. 8.4% vs. 2.9% vs. 9.1%, p = 0.487). Of the 16 patients in this study that incurred a SSI, 5 patients had positive cultures, of which 3 contained bacteria that proved to be resistant to the antibiotic used for AP. Conclusions: The results of our analysis support current national guidelines. Future investigation of different intervals (e.g., AP 15-45 min prior to incision) may be beneficial on the basis of pharmacokinetics of routinely prescribed AP.

4.
Spinal Cord Ser Cases ; 10(1): 22, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627367

RESUMO

INTRODUCTION: Powered robotic exoskeleton (PRE) physiotherapy programmes are a relatively novel frontier which allow patients with reduced mobility to engage in supported walking. Research is ongoing regarding their utility, risks, and benefits. This article describes the case of two fractures occurring in one patient using a PRE. CASE: We report the case of a 54 year old man who sustained bilateral tibial fractures while using a PRE, on a background of T10 AIS A SCI. The initial session was discontinued due to acute severe bilateral knee swelling after approximately 15 min. The patient attended their local hospital the following day, where radiographs demonstrated bilateral proximal tibial fractures. The patient was treated with manipulation under anaesthetic and long-leg casting for five weeks, at which point he was stepped down to hinged knee braces which were weaned gradually while he remained non-weight bearing for 12 weeks. The patient was investigated with DEXA scan and was diagnosed with osteoporosis. He was liaised with rheumatology services and bone protection was initiated. Fracture healing was achieved and weight-bearing precautions were discontinued, however this period of immobilisation led to significant spasticity. The patient was discharged from orthopaedic services, with ongoing rehabilitation and physiotherapy follow-up. CONCLUSION: PRE assisted physiotherapy programmes are a promising concept in terms of rehabilitation and independence, however they are not without risk and it is important that both providers and patients are aware of this. Furthermore, SCI patients are at increased risk for osteoporosis and should be monitored and considered for bone protection.


Assuntos
Exoesqueleto Energizado , Osteoporose , Traumatismos da Medula Espinal , Fraturas da Tíbia , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/reabilitação , Fraturas da Tíbia/complicações , Caminhada
5.
J Nutr Biochem ; 122: 109456, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37788725

RESUMO

Diets high in fruit and vegetables are perceived to be beneficial for intestinal homeostasis, in health as well as in the context of inflammatory bowel diseases (IBDs). Recent breakthroughs in the field of immunology have highlighted the importance of the ligand-activated transcription factor aryl hydrocarbon receptor (AhR) as a critical regulator of mucosal immunity, including the intestinal trafficking of CD4+ helper T cells, an immune cell subset implicated in a wide range of homeostatic and pathogenic processes. Specifically, the AhR has been shown to directly regulate the expression of the chemoattractant receptor G Protein-Coupled Receptor 15 (GPR15) on CD4+ T cells. GPR15 is an important gut homing marker whose expression on CD4+ T cells in the peripheral circulation is elevated in patients suffering from ulcerative colitis, raising the possibility that, in this setting, the beneficial effect of a diet rich in fruits and vegetables may be mediated through the modulation of GPR15 expression. To address this, we screened physiologically-relevant polyphenol and glucosinolate metabolites for their ability to affect both AhR activity and GPR15 expression. Our complementary approach and associated findings suggest that polyphenol and glucosinolate metabolites can regulate GPR15 expression on human CD4+ T cells in an AhR-dependent manner.


Assuntos
Linfócitos T CD4-Positivos , Colite Ulcerativa , Humanos , Linfócitos T CD4-Positivos/metabolismo , Glucosinolatos/farmacologia , Receptores de Hidrocarboneto Arílico , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Peptídeos
6.
Urogynecology (Phila) ; 29(12): 953-958, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37195817

RESUMO

IMPORTANCE: Accurate diagnosis of urinary tract infection after pelvic organ prolapse (POP) surgery is essential to postoperative care. OBJECTIVE: Our aim was to determine the agreement between the urinalysis of a clean-catch versus a straight catheter urine specimen in women who underwent vaginal surgery for POP. STUDY DESIGN: This was a cross-sectional study evaluating patients after vaginal surgery for POP. A clean-catch and straight catheter urine specimen were collected at routine postoperative appointments. Routine urinalyses and urine cultures were performed for all patients. A urine culture yielding mixed urogenital flora (which includes Lactobacillus species), coagulase-negative staphylococci, and Streptococcus species was considered a contaminated result. The agreement between the characteristics of urinalysis obtained via the clean catch versus the straight catheter at 3 weeks postoperatively was evaluated using weighted κ statistic. RESULTS: Fifty-nine participants enrolled. The agreement between the characteristics of urinalysis obtained via the clean catch versus the straight catheter was poor (κ = 0.018). The urine culture was more likely to be contaminated from the clean-catch urine specimen than from the straight catheter urine specimen (53.7% vs 23.1%).The positive and negative predictive values of leukocyte esterase on clean catch were 22.6% and 100%, respectively. CONCLUSIONS: Diagnosing urinary tract infection based on contaminated urinalyses may lead to antibiotic overuse and misdiagnosis of postoperative complications. Our results can help educate health care partners and discourage the use of clean-catch urine specimens when assessing women who have recently undergone vaginal surgery.


Assuntos
Prolapso de Órgão Pélvico , Infecções Urinárias , Humanos , Feminino , Estudos Transversais , Urinálise/métodos , Infecções Urinárias/diagnóstico , Coleta de Urina/métodos , Prolapso de Órgão Pélvico/diagnóstico
7.
Nat Immunol ; 24(3): 516-530, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36732424

RESUMO

How lipidome changes support CD8+ effector T (Teff) cell differentiation is not well understood. Here we show that, although naive T cells are rich in polyunsaturated phosphoinositides (PIPn with 3-4 double bonds), Teff cells have unique PIPn marked by saturated fatty acyl chains (0-2 double bonds). PIPn are precursors for second messengers. Polyunsaturated phosphatidylinositol bisphosphate (PIP2) exclusively supported signaling immediately upon T cell antigen receptor activation. In late Teff cells, activity of phospholipase C-γ1, the enzyme that cleaves PIP2 into downstream mediators, waned, and saturated PIPn became essential for sustained signaling. Saturated PIP was more rapidly converted to PIP2 with subsequent recruitment of phospholipase C-γ1, and loss of saturated PIPn impaired Teff cell fitness and function, even in cells with abundant polyunsaturated PIPn. Glucose was the substrate for de novo PIPn synthesis, and was rapidly utilized for saturated PIP2 generation. Thus, separate PIPn pools with distinct acyl chain compositions and metabolic dependencies drive important signaling events to initiate and then sustain effector function during CD8+ T cell differentiation.


Assuntos
Fosfatos de Fosfatidilinositol , Fosfatidilinositóis , Fosfatidilinositóis/metabolismo , Transdução de Sinais , Fosfolipases Tipo C/metabolismo , Linfócitos T CD8-Positivos/metabolismo
8.
Cureus ; 14(11): e31161, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36483905

RESUMO

The natural history of Kienböck's disease (KD) is often indolent until it progresses to an advanced stage causing pain and stiffness. Lunate fragmentation and collapse can sometimes occur with trauma. However, concomitant fracture of the distal radius is a rare phenomenon, and this combination can limit treatment options. The aim of this case report is to outline our management algorithm in the operative fixation of a young mechanic with known ipsilateral KD who was involved in a road traffic accident and suffered a combined distal radius and lunate fracture. He was managed with an open reduction internal fixation using a volar plate and a temporary dorsal spanning internal fixator. At a later date, the internal fixator was removed and a scaphocapitate fusion was performed to offload the lunate in order to avoid a total wrist fusion.

9.
Cureus ; 14(10): e30880, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36465782

RESUMO

Background Clear, accurate written documentation plays an important role in the handover of medical information, helping to improve care efficiency and avoid medical errors. Both HSE and the Irish National Orthopaedic Models of Care guidelines include key documentation standards for admission notes. Standardised medical admission proforma can help improve documentation standards, but their usage across Irish orthopaedic units is limited to three centres. We evaluated whether an admission proforma improved the documentation standards of acute orthopaedic trauma admission notes within our regional trauma unit. Methods Cycle 1 consisted of a retrospective review of 50 consecutive acute orthopaedic trauma admissions. Exclusion criteria included planned admissions, age <16 years, spinal or pelvic trauma, and 'hip' fractures for whom an existing proforma was in use. Cycle 2 consisted of a prospective review of 50 consecutive acute trauma admissions using the new proforma. Each cycle was scored against a pre-determined checklist incorporating Irish Health Service Executive and Orthopaedic Models of Care documentation standards, with results collated and statistical analysis then performed using Fisher's exact test. Findings Significant improvements in admission note compliance with national documentation were observed. This encompassed multiple domains including clinical identification, e.g., consultant identification (78% to 100% p=0.0005), clinical history, time of injury (72% to 100% p=0.0001), medical history, smoking status (86% to 100% p=0.0001), and patient assessment, vital signs (28% to 70% p=0.0001). Conclusion Improvements in admission note compliance with national documentation standards followed the introduction of a standardised proforma. These findings may encourage the introduction of similar proforma in other units, with potential benefits in patient care.

10.
Urogynecology (Phila) ; 28(12): 848-854, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36409642

RESUMO

IMPORTANCE: An evaluation of Enhanced Recovery After Surgery (ERAS) effect on perioperative patient phone calls. OBJECTIVE: The aim of this study was to compare perioperative patient phone calls before and after implementation of ERAS. STUDY DESIGN: This is a retrospective chart review of women who underwent surgery by urogynecologists where ERAS was implemented. Patients who underwent surgery were identified before the implementation and compared with the same time period after implementation. Perioperative phone calls were reviewed and categorized by reason for call. Differences between the 2 groups were compared with a Student t test if normally distributed or with a Mann-Whitney U test if not. Categorical outcomes were reported with a percentage and compared with a χ2 test with an α level of 0.05. RESULTS: We reviewed 387 records. There was no difference in the percentage of patient calls before and after implementation of ERAS (preoperatively: 19.8% vs 25.1% [ P = 0.21], postoperatively: 64.1% vs 61.5% [ P = 0.61]). Questions about chronic home medications were the most common reasons for calling before surgery (pre-ERAS: 16 [42.1%]; post-ERAS: 12 [28.6%]). Questions related to medications, pain, and bowels were the top reasons people called postoperatively. These remained the top 3 in the post-ERAS time period; however, bowel-related questions switched with medications for the top reason. CONCLUSIONS: Despite patient education being an essential component of ERAS with written and verbal instructions provided, our study found no difference in preoperative or postoperative calls with the implementation. By focusing on common concerns, we may be able to improve the patients experience and reduce office phone calls.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Procedimentos de Cirurgia Plástica , Feminino , Humanos , Período Pós-Operatório , Estudos Retrospectivos , Telefone
11.
Urogynecology (Phila) ; 28(9): 590-595, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36256965

RESUMO

IMPORTANCE: This study was performed to understand opioid consumption after midurethral sling (MUS) procedures to provide surgeons with guidelines on appropriate prescription regimens. OBJECTIVE: This study aimed to evaluate postdischarge narcotic use (PDNU) after MUS surgery using a restrictive postdischarge opioid regimen. STUDY DESIGN: This prospective clinical practice study included women undergoing MUS surgery from December 2018 to October 2019. Patients were discharged with an electronic prescription for 5 tablets of an oral narcotic. Brief Pain Inventory (BPI) surveys were collected preoperatively. Patients answered questions regarding remaining number of opioid tablets, BPI scores, and patient satisfaction on day 1, week 1 (postoperative week [POW] 1), and 4-6 weeks (POW4-6) postoperatively. Electronic records were reviewed to determine narcotic refills. Primary outcome was PDNU measured in morphine milligram equivalents (MME). Secondary outcomes evaluated refill rate, BPI scores, and patient satisfaction. Standard statistical tests were applied. RESULTS: Fifty-six patients were included in the analysis. Total median (interquartile range) PDNU was 12.5 (0-37.5) MME at POW1 and 15.0 (0-37.5) MME at POW4-6, which is approximately equivalent to 2 oxycodone (5 mg) tablets. Eighteen patients (32.1%) took 0 narcotics postdischarge. Brief Pain Inventory scores showed that "worst pain" was highest on postoperative day 1 with a median (interquartile range) score of 6 (4-8). At the POW1 and POW4-6 mark, 94.3% and 92% of patients, respectively, were satisfied or extremely satisfied with their pain control. Seven patients (11.8%) required a refill. CONCLUSIONS: Most patients undergoing MUS surgery used no more than 2 oxycodone (5 mg) tablets during their 6-week postoperative course, with almost a third not requiring any narcotics. Low pain scores and high patient satisfaction rates were noted.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Slings Suburetrais , Humanos , Feminino , Analgésicos Opioides/uso terapêutico , Oxicodona/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Estudos Prospectivos , Assistência ao Convalescente , Alta do Paciente , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Entorpecentes
12.
Front Immunol ; 13: 946713, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36016938

RESUMO

The fortification of flour with folic acid for the prevention of neural tube defects (NTD) is currently mandated in over eighty countries worldwide, hence compelling its consumption by the greater part of the world's population. Notwithstanding its beneficial impact on rates of NTD, pervasive folic acid supplementation has invariably led to additive daily intakes reaching well beyond their original target, resulting in the circulation of unmetabolized folic acid. Associated idiopathic side-effects ranging from allergies to cancer have been suggested, albeit inconclusively. Herein, we hypothesize that their inconsistent detection and elusive etiology are linked to the in vivo generation of the immunosuppressive folic acid metabolite 6-formylpterin, which interferes with the still emerging and varied functions of Major Histocompatibility Complex-related molecule 1 (MR1)-restricted T cells. Accordingly, we predict that fortification-related adverse health outcomes can be eliminated by substituting folic acid with the bioequivalent folate vitamer 5-methyltetrahydrofolate, which does not break down into 6-formylpterin.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Defeitos do Tubo Neural , Farinha , Ácido Fólico/efeitos adversos , Alimentos Fortificados/efeitos adversos , Antígenos de Histocompatibilidade Classe I , Humanos , Antígenos de Histocompatibilidade Menor , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/prevenção & controle
13.
JACC Case Rep ; 4(7): 406-410, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35693902

RESUMO

We describe the case of an 86-year-old man with an extensive cardiac history, including previous coronary artery bypass grafting, who experienced a delayed extracardiac hematoma, 350 mL in volume, after retrograde chronic total occlusion-percutaneous coronary intervention. The patient was successfully treated with resultant liquefaction of the hematoma. (Level of Difficulty: Advanced.).

14.
Female Pelvic Med Reconstr Surg ; 28(1): 27-32, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34978544

RESUMO

OBJECTIVE: The objective of this study is to investigate the impact of support person participation during the preoperative appointment. METHODS: This is a prospective cohort study involving patients scheduled to undergo pelvic reconstructive surgery. Eligible patients were enrolled at the preoperative appointment and compared by presence or absence of a support person. Questionnaires were completed before and after the preoperative appointment, 1-3 days before surgery, and at the postoperative appointment. Previsit questionnaires included the Generalized Anxiety Disorder-7, 6-item short form of the Spielberger State-Trait Anxiety Inventory (STAI-6), and Brief Health Literacy screen. Postvisit questionnaires included the STAI-6, satisfaction with decision scale for pelvic floor disorders, preoperative preparedness questionnaire, and knowledge questionnaire. At the postoperative appointment, participants completed the patient global impression of improvement and postoperative symptom and satisfaction questionnaire. Primary outcome was patient anxiety measured by the STAI-6. RESULTS: Seventy-six patients participated in the study: 37 were categorized in the support person cohort and 39 were categorized in the no support person cohort. The mean scores of the STAI-6 did not differ between the support person and no support person cohorts at all time points (previsit: 42.97 ± 13.23 vs 41.53 ± 17.11, P = 0.68; postvisit: 38.11 ± 12.76 vs 36.33 ± 11.72, P = 0.53, and 1-3 days before surgery: 42.61 ± 13.0 vs 41.05 ± 16.39, P = 0.65). Overall preparedness, satisfaction with decision scale for pelvic floor disorders, and knowledge questionnaire did not differ between cohorts at both time points. Perioperative phone calls were similar between cohorts. CONCLUSION: Our study suggests that the presence of a support person at preoperative counseling for pelvic floor surgery should be a personal preference and not a recommendation.


Assuntos
Distúrbios do Assoalho Pélvico , Ansiedade/etiologia , Humanos , Consentimento Livre e Esclarecido , Estudos Prospectivos , Inquéritos e Questionários
15.
Int Urogynecol J ; 33(8): 2151-2157, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34748034

RESUMO

BACKGROUND: Vaginal epithelial abnormalities (VEA) are a common complication associated with pessary use. The objective of this study was to determine if there is a host pro-inflammatory response associated with pessary use and VEA. METHODS: Patients wearing pessaries for at least two weeks for the management of pelvic organ prolapse and/or urinary incontinence were screened for eligibility. Vaginal swabs were collected from women with VEA (cases) and without VEA (controls). Cases were matched to controls in a 1:3 ratio. Cytokine analysis of the collected samples was performed using multiplex analysis to determine the concentrations of interleukin (IL)6, interferon alpha 2 (IFNα2), tumor necrosis factor alpha (TNFα) and IL1ß. A cross-sectional analysis was performed, comparing vaginal cytokine concentrations in women with and without VEA. RESULTS: We enrolled 211 patients in this analysis: 50 cases and 161 controls. The median concentrations (pg/mL) of the four cytokines for cases and controls respectively were; IL6: 6.7 (IQR <2.9 [the lower limit of detection, LLD]-14.2) and < 2.9 (LLD) (IQR <2.9 [LLD]-5.5), IFNα2: 8.2 (IQR 6.1-13.9) and 7.9 (IQR 3.9-13.6), TNFα: 15.2 (IQR 6.1-30.4) and 4.68 (IQR <2.3 [LLD]-16.3), IL1ß 195.7 (IQR 54.5-388.6) and 38.5 (IQR 6.7-154.9). The differences in median cytokine levels were statistically higher in cases for IL6, TNFα, and IL1ß (all p < 0.001) compared to controls. Older age (OR: 1.062, 95% CI, 1.015-1.112), lower BMI (OR: 0.910, 95% CI, 0.839-0.986) and presence of VEA at last check (OR: 5.377, 95% CI, 2.049-14.108) were associated with higher odds of having VEA on multivariate analysis. CONCLUSION: Pro-inflammatory cytokines, specifically IL6, TNFα, and IL1ß, are elevated in pessary-wearing patients who have VEA. Additional prospective studies are needed to assess baseline vaginal inflammatory profiles before and after pessary placement to understand VEA formation in pessary patients.


Assuntos
Prolapso de Órgão Pélvico , Pessários , Estudos Transversais , Feminino , Humanos , Interleucina-6 , Prolapso de Órgão Pélvico/complicações , Pessários/efeitos adversos , Fator de Necrose Tumoral alfa
16.
Pharmaceutics ; 13(11)2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34834387

RESUMO

Lung cancer is a significant health problem worldwide. Unfortunately, current therapeutic strategies lack a sufficient level of specificity and can harm adjacent healthy cells. Consequently, to address the clinical need, novel approaches to improve treatment efficiency with minimal side effects are required. Nanotechnology can substantially contribute to the generation of differentiated products and improve patient outcomes. Evidence from previous research suggests that nanotechnology-based drug delivery systems could provide a promising platform for the targeted delivery of traditional chemotherapeutic drugs and novel small molecule therapeutic agents to treat lung cancer cells more effectively. This has also been found to improve the therapeutic index and reduce the required drug dose. Nanodrug delivery systems also provide precise control over drug release, resulting in reduced toxic side effects, controlled biodistribution, and accelerated effects or responses. This review highlights the most advanced and novel nanotechnology-based strategies, including targeted nanodrug delivery systems, stimuli-responsive nanoparticles, and bio-nanocarriers, which have recently been employed in preclinical and clinical investigations to overcome the current challenges in lung cancer treatments.

17.
J Agric Food Chem ; 69(31): 8625-8633, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34338516

RESUMO

The ligand-activated aryl hydrocarbon receptor (AhR) is an important molecular regulator of immune function, whose activity can be modulated by dietary glucosinolate- and tryptophan-derived metabolites. In contrast, the potential use of polyphenols as dietary regulators of AhR-dependent immunity remains unclear. In this perspective, we discuss how cellular metabolism may alter the net effect of polyphenols on AhR, thus potentially reconciling some of the conflicting observations reported in the literature. We further provide a methodological roadmap, across the fields of immunology, metabolomics, and gut microbial ecology, to explore the potential effects of polyphenol-rich diets on AhR-regulated immune function in humans.


Assuntos
Imunidade , Polifenóis , Receptores de Hidrocarboneto Arílico , Humanos , Ligantes , Polifenóis/farmacologia , Receptores de Hidrocarboneto Arílico/genética , Triptofano
18.
Proc Natl Acad Sci U S A ; 118(25)2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34161266

RESUMO

Fever can provide a survival advantage during infection. Metabolic processes are sensitive to environmental conditions, but the effect of fever on T cell metabolism is not well characterized. We show that in activated CD8+ T cells, exposure to febrile temperature (39 °C) augmented metabolic activity and T cell effector functions, despite having a limited effect on proliferation or activation marker expression. Transcriptional profiling revealed an up-regulation of mitochondrial pathways, which was consistent with increased mass and metabolism observed in T cells exposed to 39 °C. Through in vitro and in vivo models, we determined that mitochondrial translation is integral to the enhanced metabolic activity and function of CD8+ T cells exposed to febrile temperature. Transiently exposing donor lymphocytes to 39 °C prior to infusion in a myeloid leukemia mouse model conferred enhanced therapeutic efficacy, raising the possibility that exposure of T cells to febrile temperatures could have clinical potential.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Febre/imunologia , Mitocôndrias/metabolismo , Biossíntese de Proteínas , Animais , Antineoplásicos/metabolismo , Linfócitos T CD8-Positivos/ultraestrutura , Citocinas/biossíntese , Glucose/metabolismo , Leucemia Mieloide/imunologia , Leucemia Mieloide/patologia , Leucemia Mieloide/prevenção & controle , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mitocôndrias/ultraestrutura , Modelos Biológicos , Temperatura
19.
Clin Transplant ; 35(8): e14311, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33829561

RESUMO

Postoperative pain is a significant source of morbidity in patients undergoing living donor nephrectomy (LDN) and a deterrent for candidates. We implemented a standardized multimodal analgesic regimen, which consists of pharmacist-led pre-procedure pain management education, a combination transversus abdominis plane and rectus sheath block performed by the regional anesthesia team, scheduled acetaminophen and gabapentin, and as-needed opioids. This single-center retrospective study evaluated outcomes between patients undergoing LDN who received a multimodal analgesic regimen and a historical cohort. The multimodal cohort had a significantly shorter length of stay (LOS) (days, mean ± SD: 1.8 ± 0.7 vs. 2.6 ± 0.8; p < .001) and a greater proportion who were discharged on postoperative day (POD) 1 (38.6% vs. 1.5%; p < .001). The total morphine milligram equivalents (MME) that patients received during hospitalization were significantly less in the multimodal cohort on POD 0-2. The outpatient MME prescribed through POD 60 was also significantly less in the multimodal cohort (median [IQR]; 180 [150-188] vs. 225 [150-300]; p < .001). The mean patient-reported pain score (PRPS) was significantly lower in the multimodal cohort on POD 0-2. The maximum PRPS was significantly lower on POD 0 (mean ± SD: 7 ± 2 vs. 8 ± 1, respectively; p = .02). This study suggests that our multimodal regimen significantly reduces LOS, PRPS, and opioid requirements and has the potential to improve the donation experience.


Assuntos
Laparoscopia , Doadores Vivos , Analgésicos/uso terapêutico , Humanos , Nefrectomia , Estudos Retrospectivos
20.
Cancer Cell ; 39(4): 460-462, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33848476

RESUMO

Competition for glucose regulates the balance between cancer and immune responses. New findings published in Nature show that regulatory T cells (Treg) shape their metabolism to avoid glucose competition, thus maintaining their stability and sustaining tumor progression. This research suggests hijacking the "eating habits" of Treg could improve cancer therapy.


Assuntos
Neoplasias , Linfócitos T Reguladores , Glucose , Humanos , Imunidade
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