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1.
Int J Clin Oncol ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38679628

RESUMEN

BACKGROUND AND AIM: The incidence of cancer colon has increased dramatically. In addition, the database lacks a review to analyze the outcomes of surgeries for mid-transverse colon cancer with several recent controversial studies. We aimed to compare the outcomes of extended hemicolectomy versus transverse colectomy for mid-transverse colon cancer. METHOD: PubMed, Scopes, Web of Science and Cochrane Library were searched for eligible studies from inception to 1 December 2022 and a systematic review and meta-analysis were done to detect. RESULTS: According to eligibility criteria, 8 studies (2237 patients) were included in our study. The pooled results of the included studies showed no difference in the 5-year OS, 3-year DFS and 5-year DFS between the two types of surgery (5-year OS, RR = 1.15, 95% CI 0.94-1.39, P = 0.17), (3-year OS, RR = 0.96, 95% CI 0.88-1.06, P = 0.42) and (5-year DFS, RR = 1.21, 95% CI 0.91-1.62, P = 0.20). In addition to that, the recurrence rate and the incidence of complications were similar in the two groups (Recurrence rate, RR = 1.08, 95% CI 0.62-1.89, P = 0.79) and (Complications, RR = 1.07, 95% CI 0.74-1.54, P = 0.72). However, the number of LN harvest and the time of the operation were more in case of extended hemicolectomy. CONCLUSION: Despite harvesting less LN, transverse colectomy has similar oncological outcomes to extended hemicolectomy for mid-transverse colon cancer. In addition to that, there was no significant difference in the incidence of complications between the two surgeries.

2.
J Clin Med ; 13(6)2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38541860

RESUMEN

Background: The BIO REACT study is designed to investigate the incremental value of Extravascular UltraSound (EVUS) added to conventional angiography, compared to conventional angiography only for the identification of Flow-Limiting Dissections (FLD) and to evaluate the safety and efficacy of the REsponse Adapted Combination Therapy (REACT) for the treatment of femoropopliteal lesions. Methods: The primary endpoints were the specificity and sensitivity of EVUS added to angiography for the detection of FLD. Secondary endpoints were primary patency of the REACT therapy within 12 months, fCD-TLR, freedom from MAE, major target limb amputations (mTLA) and survival rates within 24 months. Results: A total of 150 patients were included. EVUS added to angiography had an overall sensitivity of 29% and specificity of 93% for the detection of FLD. There was no PSVR cut-off offering a clinically acceptable trade-off between meaningful sensitivity and specificity values for the detection of FLD. At 12 months, treatment with the REACT resulted in primary patency and fCD-TLR of 81.6% and 94.3%, respectively. In addition, freedom from MAE was 94.3% at 12 months. At 24 months, the survival rate was 94.0%. No mTLA was reported up to the 24-month follow-up. Conclusions: The addition of DUS to angiography showed limited value for detecting FLD in femoropopliteal artery disease.

3.
Cell Rep ; 43(4): 114005, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38551961

RESUMEN

The retina is exquisitely patterned, with neuronal somata positioned at regular intervals to completely sample the visual field. Here, we show that phosphatase and tensin homolog (Pten) controls starburst amacrine cell spacing by modulating vesicular trafficking of cell adhesion molecules and Wnt proteins. Single-cell transcriptomics and double-mutant analyses revealed that Pten and Down syndrome cell adhesion molecule Dscam) are co-expressed and function additively to pattern starburst amacrine cell mosaics. Mechanistically, Pten loss accelerates the endocytic trafficking of DSCAM, FAT3, and MEGF10 off the cell membrane and into endocytic vesicles in amacrine cells. Accordingly, the vesicular proteome, a molecular signature of the cell of origin, is enriched in exocytosis, vesicle-mediated transport, and receptor internalization proteins in Pten conditional knockout (PtencKO) retinas. Wnt signaling molecules are also enriched in PtencKO retinal vesicles, and the genetic or pharmacological disruption of Wnt signaling phenocopies amacrine cell patterning defects. Pten thus controls vesicular trafficking of cell adhesion and signaling molecules to establish retinal amacrine cell mosaics.


Asunto(s)
Células Amacrinas , Adhesión Celular , Endocitosis , Fosfohidrolasa PTEN , Retina , Vía de Señalización Wnt , Animales , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Retina/metabolismo , Ratones , Células Amacrinas/metabolismo , Ratones Noqueados , Transporte de Proteínas , Proteínas Wnt/metabolismo , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/genética
4.
bioRxiv ; 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38293104

RESUMEN

Background: Traumatic injury is a leading cause of death for those under the age of 45, with 40% occurring due to hemorrhage. Severe tissue injury and hypoperfusion lead to marked changes in coagulation, thereby preventing formation of a stable blood clot and increasing hemorrhage associated mortality. Objectives: We aimed to quantify changes in clot formation and mechanics occurring after traumatic injury and the relationship to coagulation kinetics, and fibrinolysis. Methods: Plasma was isolated from injured patients upon arrival to the emergency department. Coagulation kinetics and mechanics of healthy donors and patient plasma were compared with rheological, turbidimetric and thrombin generation assays. ELISA's were performed to determine tissue plasminogen activator (tPA) and D-dimer concentration, as fibrinolytic markers. Results: Sixty-three patients were included in the study. The median injury severity score (ISS) was 17, median age was 37.5 years old, and mortality rate was 30%. Rheological, turbidimetric and thrombin generation assays indicated that trauma patients on average, and especially deceased patients, exhibited reduced clot stiffness, increased fibrinolysis and reduced thrombin generation compared to healthy donors. Fibrinogen concentration, clot stiffness, D-dimer and tPA all demonstrated significant direct correlation to increasing ISS. Machine learning algorithms identified and highlighted the importance of clinical factors on determining patient outcomes. Conclusions: Viscoelastic and biochemical assays indicate significant contributors and predictors of mortality for improved patient treatment and therapeutic target detection. ESSENTIALS: Traumatic injury may lead to alterations in a patient's ability to form stable blood clotsA study was performed to assess how trauma severity affects coagulation kineticsKey alterations were observed in trauma patients, who exhibit weaker and slower forming clotsPaired with machine learning methods, the results indicate key aspects contributing to mortality.

5.
Ir J Med Sci ; 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38294607

RESUMEN

Pelvic congestion syndrome (PCS) poses a significant health, diagnostic, and economic challenges. Transcatheter embolisation has emerged as a promising treatment for PCS. A systematic review was performed in order to assess the safety and efficacy of transcatheter embolisation in the treatment of PCS. A systematic search of electronic databases was performed using 'PubMed', 'Embase', 'Medline (OVID)', and 'Web of Science', for articles pertaining to efficacy of embolotherapy for the treatment of pelvic congestion syndrome. A total of 25 studies were included in this systematic review with a combined total of 2038 patients. All patients included were female with a mean average age of 37.65 (31-51). Of the 25 studies, 18/25 studies reported pre- and post-procedural pelvic pain outcomes using a visual analogue scale (VAS). All studies showed a reduction in VAS post-procedure. Transcatheter embolisation had a high technical success rate (94%) and an overall complication rate of 9.0%, of which 10.4% were major and 89.6% were minor. Fifteen out of 19 (78.9%) major complications required a subsequent intervention. Transcatheter embolisation using various techniques is effective and safe in treating PCS. A low quality of evidence limits the currently available literature; however, embolisation has shown to improve symptoms in the majority of patients with low complication rates and recurrence rates.

6.
ANZ J Surg ; 94(1-2): 181-186, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37772450

RESUMEN

BACKGROUND: The Australian population is ageing, with an increasing number of patients diagnosed with colorectal cancer in their eighth decade. This group represents a challenging cohort to deliver multidisciplinary care, with increased morbidity and mortality related to surgical and oncological therapies. This project aimed to compare surgical and oncological outcomes in octogenarian and non-octogenarian patients with colorectal cancer. METHODS: A matched case-control retrospective review of a prospectively maintained institutional database of colorectal cancer patients treated between 2005 and 2021 was conducted. Patient demographics, treatment details, peri-operative complications, and long-term survival were reported. The primary outcome, cancer-specific survival, was investigated using time-to-event analysis and interrogated with multivariate regression. RESULTS: There were 747 patients included in the study. There was no difference in five-year cancer-specific survival and recurrence-free survival between cohorts. Multivariate analysis for octogenarians confirmed a significant hazard signal associated with worsening cancer stage and a survival benefit associated with the administration of adjuvant therapy. However, we noted that stage-matched octogenarian patients received less adjuvant treatment compared to non-octogenarians. CONCLUSION: Octogenarians undergoing treatment for colorectal cancer have similar cancer-specific survival and recurrence-free survival to non-octogenarians. Our study demonstrates a survival benefit when adjuvant therapy is provided to octogenarians, despite only half of this cohort receiving therapy compared to their younger peers. Further research into adjuvant therapy with surgical resection for CRC in older Australians is required.


Asunto(s)
Adenocarcinoma , Pueblos de Australasia , Neoplasias Colorrectales , Anciano de 80 o más Años , Humanos , Anciano , Octogenarios , Australia/epidemiología , Neoplasias Colorrectales/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Estudios Retrospectivos , Quimioterapia Adyuvante , Resultado del Tratamiento
7.
Cureus ; 15(11): e48112, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37920422

RESUMEN

Hepatic artery thrombosis (HAT) is the most serious vascular complication after liver transplantation (LT). Moreover, in comparison to deceased donor liver transplantation (DDLT), hepatic artery (HA) anastomosis is more challenging in living donor liver transplantation (LDLT) with a lot of controversial topics about the use of microscopic surgery. We aimed to compare the use of microscopic and loupe surgery in HA anastomosis in adult and pediatric LDLT to decrease the incidence of vascular complications. We searched PubMed, Scopes, Web of Science, and Cochrane Library for eligible studies from inception to April 2023 and a systematic review and a meta-analysis were done. According to our eligibility criteria, 10 studies with a total of 1939 patients were included. In comparison to microscopic surgery, loupe anastomosis has a similar incidence of HAT (thrombosis, risk ratio (RR) = 0.96, 95% CI = 0.26-3.48, P = 0.95). In addition to that, no significant difference was detected between the two types in terms of stenosis, decreased blood flow and hospital stay (decreased blood flow, RR = 0.68, 95% CI = 0.01-86.65, P = 0.88), (stenosis, RR = 1.81, 95% CI = 0.19-17.21, P = 0.60), (hospital stay, mean deviation (MD) = 1.16, 95% CI = -3.79-6.11, P = 0.65). However, the anastomotic time was longer in the case of microscopic surgery (anastomotic time, MD = 24.09, 95% CI = 7.79-40.39, P = 0.004). With an equal incidence of complications and longer anastomotic time, there is no added benefit of the routine use of microscopic surgery in HA anastomosis in LDLT.

8.
Cureus ; 15(11): e48108, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37920423

RESUMEN

With an incidence exceeding 30%, biliary complications after pediatric liver transplantation remain a great challenge. In addition, the database includes numerous controversial papers about the safety of duct-to-duct anastomosis compared to Reux-en-Y hepaticojejunostomy for pediatric living donor liver transplantation (LDLT). We aim to compare the two techniques in pediatric LDLT by conducting a systematic review and meta-analysis. PUBMED, Web of Science, Scopus, and Cochrane Library were searched for eligible studies from 1989 to October 2022. According to our eligibility criteria, seven articles (561 pediatric LDLT) were included in our study. On one hand, DD anastomosis is associated with a higher rate of biliary stricture in comparison to RYHJ (OR: 2.47, 95% CI = 1.20-5.09, P = 0.01; I2 = 12%). On the other hand, the incidence of cholangitis was higher in RYHJ (OR: 0.10 95% CI = 0.01- 0.84, P = 0.03; I2 = 0%). However, there was no significant difference in the overall incidence of complications, leakage and mortality between the two groups (overall incidence of complication OR: 1.12, 95% CI = 0.34-3.68, P = 0.86; I2 = 62%), (Leakage OR: 2.22, 95% CI = 0.79-6.23, P = 0.13; I2 = 18%) and (Mortality OR: 2.53, 95% CI = 0.61-10.57, P = 0.30; I2 = 0%). In conclusion, with a lower incidence of cholangitis, an equal overall incidence of biliary complication, and the possibility of RY conversion in case of stricture, DD anastomosis offers a feasible, safe, and more physiological alternative to RYHJ for pediatric LDLT.

9.
Trauma Case Rep ; 47: 100914, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37693744

RESUMEN

Penetrating injuries are recognized for the direct tissue damage, which is typically evident on physical examination. Secondary injuries resulting from kinetic energy transfer in the case of gunshot wounds (GSWs), often referred to as "blast injuries", may affect tissues distant to the ballistic trajectory and are often occult. We present a case of delayed cardiac tamponade resulting from secondary blast injury. The patient sustained a thoraco-abdominal GSW with entry adjacent to the cardiac box. An Advanced Trauma Life Support (ATLS)-guided assessment revealed intra-abdominal injuries necessitating operative intervention without evidence of cardiac injury. On post-operative day four, the patient developed chest pain, tachycardia, and shortness of breath. Imaging revealed a large pericardial effusion with cardiac tamponade. Emergent exploration revealed hemopericardium secondary to a bleeding epicardial hematoma without evidence of pericardial violation. Clinicians must maintain a high clinical suspicion for occult, indirect blast injuries which may be life-threatening.

10.
Urol Case Rep ; 50: 102464, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37560442

RESUMEN

Here we present a rare case of life-threatening spontaneous renal haemorrhage following elective vascular surgery. A 73-year-old gentleman presents to the ED with acute onset right sided flank pain, 24 hours post bilateral renal artery stent insertion for renal artery stenosis. Subsequent angiography demonstrated bilateral renal artery stent occlusion with near complete bilateral kidney infarction. The patient urgently underwent bilateral renal artery thrombectomy. Post-operatively the patient developed severe unilateral flank pain and became haemodynamically unstable. Subsequent imaging revealed a large right sided retroperitoneal haematoma with active arterial bleeding. The patient ultimately underwent a right sided trauma nephrectomy for haemorrhage control.

11.
Vascular ; : 17085381231194152, 2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37548646

RESUMEN

OBJECTIVES: The aim of this study was to evaluate the impact of sex on mid-term outcomes following stenting for aorto-iliac occlusive disease (AIOD). METHODS: The Covered versus Balloon Expandable Stent Trial (COBEST) compared the safety and efficacy of the covered stent (CS) with those of the bare metal stent (BMS) in the treatment of hemodynamically significant AIOD. It was identified that CS provided a significant benefit. The primary endpoint of our analysis was the rate of primary patency 5 years following stenting for AIOD (inclusive of both CS and BMS) in both sexes. RESULTS: Of the 168 lesions treated, 103 (61%) were present in men and 65 (39%) were present in women. Of the concomitant comorbidities, diabetes mellitus was significantly more common in women (17.5% vs 41.5%, p = .006). Although chronic limb threatening ischemia (CLTI) at the time of intervention was more common in women, the difference was not significant (16.5% vs 24.6%, p = .395). Sex was not associated with the primary patency rate (male; 0.70, 95% confidence interval [CI]: 0.23-2.19, p = .543). When considering both male sex and the utilization of BMS, no significant impact was found on the primary patency rate (hazard ratio [HR]: 3.43, 95% CI: 0.69-17.10, p = .133). All-cause mortality at 60 months was 22.6% in men compared to 19.4% in women (p = .695). CONCLUSIONS: No significant difference was identified in the primary patency rate between the sexes. Further investigation is warranted to ascertain whether sex-specific interventional guidelines are required in this regard.

12.
Am Surg ; 89(11): 5012-5016, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37449920

RESUMEN

Alkaline reflux esophagitis is a recognized complication of procedures that compromise the lower esophageal sphincter (LES), including gastrectomy. Incidence of reflux is dependent on the reconstructive procedure, with Roux-en-Y (RY) esophagojejunostomy commonly accepted as the optimal method. The authors report their experience of 5 patients who underwent remedial intervention for severe alkaline reflux esophagitis following gastric cancer surgery, over a 6-year period (2014-2020). Primary diagnoses encompassed 4 gastric adenocarcinomas and 1 gastric neuroendocrine tumor. Four patients previously underwent total gastrectomy and 1 subtotal gastrectomy with RY reconstruction. Onset of postoperative reflux symptoms ranged from 2 weeks to 3 years. Failing medical management, all patients underwent jejunojejunal anastomosis and Roux limb length revision with surgical jejunostomy. At follow-up, 4 out of 5 patients had some degree of symptom resolution and one with unresolved symptoms. The authors report our experience of managing this complication following gastrectomy with jejunojejunal anastomosis and Roux limb length revision.


Asunto(s)
Esofagitis Péptica , Neoplasias Gástricas , Humanos , Esofagitis Péptica/etiología , Esofagitis Péptica/cirugía , Gastrectomía/efectos adversos , Gastrectomía/métodos , Anastomosis en-Y de Roux/efectos adversos , Anastomosis Quirúrgica/efectos adversos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/complicaciones , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía
13.
ANZ J Surg ; 93(10): 2363-2369, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37012584

RESUMEN

BACKGROUND: Secondary aorto-enteric fistulae (SAEF) are a rare, complex and life-threatening complication following aortic repair. Traditional treatment strategy has been with open aortic repair (OAR), with emergence of endovascular repair (EVAR) as a potentially viable initial treatment option. Controversy exists over optimal immediate and long-term management. METHODS: This was a retrospective, observational, multi-institutional cohort study. Patients who had been treated for SAEF between 2003 and 2020 were identified using a standardized database. Baseline characteristics, presenting features, microbiological, operative, and post-operative variables were recorded. The primary outcomes were short and mid-term mortality. Descriptive statistics, binomial regression, Kaplan-Meier and Cox age-adjusted survival analyses were performed. RESULTS: Across 5 tertiary centres, a total of 47 patients treated for SAEF were included, 7 were female and the median (range) age at presentation was 74 years (48-93). In this cohort, 24 (51%) patients were treated with initially with OAR, 15 (32%) with EVAR-first and 8 (17%) non-operatively. The 30-day and 1-year mortality for all cases that underwent intervention was 21% and 46% respectively. Age-adjusted survival analysis revealed no statistically significant difference in mortality in the EVAR-first group compared to the OAR-first group, HR 0.99 (95% CI 0.94-1.03, P = 0.61). CONCLUSION: In this study there was no difference in all-cause mortality in patients who had OAR or EVAR as first line treatment for SAEF. In the acute setting, alongside broad-spectrum antimicrobial therapy, EVAR can be considered as an initial treatment for patients with SAEF, as a primary treatment or a bridge to definitive OAR.


Asunto(s)
Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Estudios de Cohortes , Resultado del Tratamiento , Aneurisma de la Aorta Abdominal/cirugía , Análisis de Supervivencia , Estudios Retrospectivos , Factores de Riesgo , Complicaciones Posoperatorias/etiología
14.
J Asthma ; 60(9): 1775-1786, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-36883949

RESUMEN

OBJECTIVE: To investigate effectiveness of two different educational methods to improve inhaler techniques in patients with prior diagnosis of asthma, hospitalized with a non-asthma-related diagnosis. METHODS: We undertook a real-world, opportunistic quality-improvement project. Inhaler technique in hospitalized patients with prior diagnosis of asthma was assessed in two cohorts over two 12-week cycles using a standardized device-specific proforma of seven-step inhaler technique, classed: "good" if 6/7 steps achieved; "fair" if 5/7 compliant; "poor" for others. Baseline data was collected in both cycles. Cycle one involved face-to-face education by a healthcare professional; cycle two involved additional use of an electronic device to show device-specific videos (asthma.org.uk). In both cycles, patients were reassessed within two days for improvements and the two methods compared for effectiveness. RESULTS: During cycle one 32/40 patients were reassessed within 48 h; eight lost to follow-up. During cycle two 38/40 patients were reassessed within 48 h; two lost to follow-up During cycle one, two and 12 had good/fair baseline technique respectively, and 26 poor. Most commonly missed steps were no expiry check/not rinsing mouth after steroid use. On reassessment 17% patients improved from poor to fair/good. During cycle two, initial technique assessment identified: 23 poor; 12 fair; five good. Post-videos, 35% of patients improved from poor to fair/good. Proportion of patients improving from poor to fair, or poor/fair to good increased in cycle two vs one (52.5% vs 33%). CONCLUSION: Visual instruction is associated with improved technique compared to verbal feedback. This is a user-friendly and cost-effective approach to patient education.


Asunto(s)
Asma , Humanos , Adulto , Asma/tratamiento farmacológico , Nebulizadores y Vaporizadores , Cooperación del Paciente , Escolaridad , Electrónica , Administración por Inhalación
16.
Ann Biomed Eng ; 51(1): 137-149, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36070049

RESUMEN

Computer Modeling and Simulation (CM&S) provides the opportunity to drastically reduce clinical trial patient burden and advance regulatory decision making. At the suggestion of the US Food and Drug Administration (FDA), MannKind Corporation and Nudge BG submitted an application to the FDA Model-Informed Drug Development (MIDD) pilot program to support a label change for the initial dose of Afrezza® (insulin human), a novel inhalable insulin with a rapid pharmacokinetic and pharmacodynamic profile. The MIDD pilot program demonstrates the FDA's commitment to advancing regulatory science through the adoption of evidence generated by CM&S. A simulation framework was developed based on empirical data. It was used to generate evidence to support the label change. Briefing packages and presentations were prepared for two meetings with the FDA, over a period of four months. The model was thoroughly characterized, determined to be low risk for the question of interest, and submitted along with additional clinical evidence for validation. The FDA found the simulation framework to be helpful in providing insights into the question of interest and provides reasonable glycemic outcome predictions. At the conclusion of the MIDD paired meetings, FDA personnel from the Center for Drug Evaluation and Research review team accepted the simulation and requested additional, traditional clinical evidence to support the proposed label change. In the post-meeting comments, the FDA invited MannKind to submit a proposal for a data package including the CM&S evidence in a Type C meeting for further discussion on the label change. This MIDD pilot experience suggests that CM&S is a credible method for evidence generation. Collaboration between sponsor organizations as well as all stakeholders in the FDA, including proponents of CM&S, can further support regulatory decision-making. The learnings from early participants will allow the program to reach its full potential and thereby ultimately benefit patients, sponsors, and FDA.


Asunto(s)
Ensayos Clínicos como Asunto , Simulación por Computador , Humanos , Insulinas , Estados Unidos , United States Food and Drug Administration
18.
Thromb Res ; 220: 131-140, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36347079

RESUMEN

INTRODUCTION: Trauma induced coagulopathy (TIC) is common after severe trauma, increasing transfusion requirements and mortality among patients. TIC has several phenotypes, with primary hyperfibrinolysis being among the most lethal. We aimed to investigate the contribution of hypercoagulation, hemodilution, and fibrinolytic activation to the hyperfibrinolytic phenotype of TIC, by examining fibrin formation in a plasma-based model of TIC. We hypothesized that instabilities arising from TIC will be due primarily to increased fibrinolytic activation rather than hemodilution or tissue factor (TF) induced hypercoagulation. METHODS: The influence of TF, hemodilution, fibrinogen consumption, tissue plasminogen activator (tPA), and the antifibrinolytic tranexamic acid (TXA) on plasma clot formation and structure were examined using rheometry, optical properties, and confocal microscopy. These were then compared to plasma samples from trauma patients at risk of developing TIC. RESULTS: Combining TF-induced clot formation, 15 % hemodilution, fibrinogen consumption, and tPA-induced fibrinolysis, the clot characteristics and hyperfibrinolysis were consistent with primary hyperfibrinolysis. TF primarily increased fibrin polymerization rates and reduced fiber length. Hemodilution decreased clot optical density but had no significant effect on mechanical clot stiffness. TPA addition induced primary clot lysis as observed mechanically and optically. TXA restored mechanical clot formation but did not restore clot structure to control levels. Patients at risk of TIC showed increased clot formation, and lysis like that of our simulated model. CONCLUSIONS: This simulated TIC plasma model demonstrated that fibrinolytic activation is a primary driver of instability during TIC and that clot mechanics can be restored, but clot structure remains altered with TXA treatment.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Hemostáticos , Trombofilia , Ácido Tranexámico , Humanos , Activador de Tejido Plasminógeno , Trastornos de la Coagulación Sanguínea/etiología , Hemodilución , Tromboplastina , Fibrinógeno , Fibrina
19.
J Diabetes Sci Technol ; : 19322968221110622, 2022 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-35833638

RESUMEN

BACKGROUND: Technosphere Insulin (TI) is an ultra-rapid-acting inhaled insulin. This study assessed the mean peak two-hour postprandial glucose concentration with the initial TI dose (dose 1) calculated per the current label (United State Prescribing Information) compared with a ~2× higher dose (dose 2). Secondary objectives were to evaluate hypoglycemia within the two-hour postprandial period, evaluate change in forced expiratory volume in one second (FEV1) before and after the two-hour postprandial period, and monitor for other adverse events. METHODS: Twenty patients with diabetes, on basal-bolus insulin therapy, received an initial dose 1 of TI followed by the higher dose 2, one to three days later. Subjects received an identical meal for both visits, and TI doses were administered immediately prior to the meal. RESULTS: The higher dose 2 provided significant reductions in mean postprandial glucose excursion (PPGE) in the two-hour postprandial period starting from 45 minutes (P = .008) to 120 minutes (P < .0001). Mean peak glucose was reduced from 228.6 to 179.3 mg/dL (P < .001) at two hours. Two hypoglycemic events (one level 1, one level 2) were observed in a single subject during the two-hour postprandial period with dose 2. There were no significant changes in FEV1 after either dose of TI. CONCLUSIONS: The higher dose 2 reduced PPGE versus the current label recommended dose 1 within the two-hour postprandial timeframe without any new safety concerns. When confirmed with a larger study, this higher TI dosing recommendation may help patients and clinicians minimize immediate postprandial hyperglycemia when titrating TI for prandial glucose control.

20.
Front Cell Dev Biol ; 10: 887764, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35663397

RESUMEN

Vision commences in the retina with rod and cone photoreceptors that detect and convert light to electrical signals. The irreversible loss of photoreceptors due to neurodegenerative disease leads to visual impairment and blindness. Interventions now in development include transplanting photoreceptors, committed photoreceptor precursors, or retinal pigment epithelial (RPE) cells, with the latter protecting photoreceptors from dying. However, introducing exogenous human cells in a clinical setting faces both regulatory and supply chain hurdles. Recent work has shown that abnormalities in central cell metabolism pathways are an underlying feature of most neurodegenerative disorders, including those in the retina. Reversal of key metabolic alterations to drive retinal repair thus represents a novel strategy to treat vision loss based on cell regeneration. Here, we review the connection between photoreceptor degeneration and alterations in cell metabolism, along with new insights into how metabolic reprogramming drives both retinal development and repair following damage. The potential impact of metabolic reprogramming on retinal regeneration is also discussed, specifically in the context of how metabolic switches drive both retinal development and the activation of retinal glial cells known as Müller glia. Müller glia display latent regenerative properties in teleost fish, however, their capacity to regenerate new photoreceptors has been lost in mammals. Thus, re-activating the regenerative properties of Müller glia in mammals represents an exciting new area that integrates research into developmental cues, central metabolism, disease mechanisms, and glial cell biology. In addition, we discuss this work in relation to the latest insights gleaned from other tissues (brain, muscle) and regenerative species (zebrafish).

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