Honing the Hunt: A Comprehensive Review of Cell-free Tumor DNA to Predict Neoadjuvant Therapy Efficacy in Bladder Cancer.

OBJECTIVE: To provide an updated view on the role of cell-free DNA as a predictor of pathological response to neoadjuvant therapy in patients with muscle-invasive bladder cancer. METHODS: A systematic review was conducted from September 2023 to October 2023. Selected studies from the MEDLINE and clinical trial databases were critically analyzed regarding the clinical efficacy of cell-free DNA as a predictive instrument after neoadjuvant therapy in bladder cancer. The methodological quality assessment was based on the QUADAS-2 tool. RESULTS: In this systematic review, we analyzed 5 studies encompassing a cumulative patient cohort of 780 individuals diagnosed with muscle-invasive bladder cancer, with a median follow-up ranging from 6 to 23 months. Among these studies, 4 primarily focused on detecting and analyzing circulating tumor DNA in plasma, while 1 study uniquely utilized cell-free tumor DNA in urine samples. The diagnostic accuracy of cell-free DNA in plasma ranges from 79% to 100%, indicating a variable yet significant predictive capability. In contrast, the study utilizing urinary cell-free DNA demonstrated an accuracy of 81% in predicting treatment response post-neoadjuvant chemotherapy. CONCLUSION: Cell-free DNA is emerging as a valuable biomarker for predicting response to neoadjuvant chemotherapy in patients with muscle-invasive bladder tumors.

Robotic-assisted approaches to urachal carcinoma: A comprehensive systematic review of the safety and efficacy outcomes.

Introduction: Surgical intervention is the treatment of choice in patients with urachal carcinoma. Due to complications and to reduce hospital stay from open surgery, minimally invasive approaches are desirable. Nowadays, robotic-assisted surgery has become increasingly popular, and robot-assisted cystectomy can be performed in patients with urachal carcinoma with low complication rates. Methods: We performed a systematic review to search for studies that evaluated patients who underwent robotic-assisted surgery for urachal carcinoma. The outcomes of interest were the type of cystectomy performed, whether there was umbilicus resection, total operative time, console time, intraoperative complications, estimated blood loss, postoperative complications, time of hospitalisation, positive surgical margins and the presence of documented tumour recurrence. Results: In this study, we evaluated three cohorts comprising a total of 21 patients. The median follow-up period ranged from 8 to 40 months. Medium age was between 51 and 54 years, with a majority (63.1%) being male. One patient (5.2%) underwent a radical cystectomy, and 19 patients (94.7%) underwent to partial cystectomy. Umbilical resections were performed in all cases, and pelvic lymphadenectomy in 14 cases (73.6%). Recurrence occurred in three patients at a median of 17 months postoperation, two cases in the trocar insertion site. Additionally, there was one death, which was attributed to postoperative cardiovascular complications. Conclusion: Robotic-assisted partial cystectomy has a low incidence of adverse outcomes in patients with urachal carcinoma. Controlled studies, ideally randomised, are warranted to establish the comparative efficacy and safety of the robotic-assisted cystectomy approach relative to open surgery.

Gait analysis after total hip arthroplasty by direct minimally invasive anterolateral approach: A controlled study.

INTRODUCTION: Clinical and functional improvement after minimally invasive total hip arthroplasty (THA) has become increasingly controversial. The minimally invasive anterolateral approach (MIALA) allows rapid recovery resulting in a reduced need for rehabilitation. Alterations in muscle and static balance have previously been demonstrated. Results in the context of quantified gait analysis (QGA) and MIALA compared to an asymptomatic population remain unknown beyond one year postoperatively. Thus, the main objective of this controlled study was to compare the spatiotemporal parameters of gait, obtained using a QGA, beyond one year postoperatively in subjects operated on for THA by MIALA, with a group of asymptomatic subjects of the same age. The secondary objectives of the study were to compare the other QGA and EMG data acquired in operated subjects with asymptomatic subjects. HYPOTHESIS: We hypothesized that QGA and EMG parameters would not normalize beyond one year postoperatively. PATIENTS AND METHODS: Thirty-one subjects were recruited, including 16 patients (68 years old; IQR: 65-70) who underwent MIALA, at 15.5 months postoperatively (IQR: 13-17) and 15 asymptomatic subjects (62 years old; IQR: 61-71). Subjects underwent QGA and maximal isometric muscle force tests on the gluteus medius, gluteus maximus, Tensor Fascia Lata (TFL) and Sartorius muscles. Spatiotemporal gait parameters were the primary endpoint. The other QGA parameters: kinetics (characteristic values of vertical ground reaction forces, peak hip moments) and kinematics (hip joint amplitudes and pelvic mobility in the frontal and sagittal plane) constituted the secondary criteria. RESULTS: Five subjects were excluded for unrestored offset. Walking speed was lower in operated patients (1.03m/s versus 1.18m/s, p=0.005). Maximal isometric muscle force moments were lower in patients operated on for the gluteus maximus and medius as well as the TFL (p<0.005). The vertical ground reaction forces were lower for the operated patients for the loading phase (FzFCmax, p=0.001), the single stance phase (FzSPmin, p=5.05.10-2) and the swing phase (FzTOmax, p=0.0002). The moments were lower in the sagittal plane for the operated patients (0.6N.m for the operated versus 1.1N.m for the asymptomatic, p=0.02). The pelvic amplitudes in the sagittal plane were lower for operated patients (3.3° versus 7.2°, p=0.05). DISCUSSION: Our hypothesis appears to be validated. Gait deficits persisted beyond one year postoperatively after THA with MIALA. A decrease in walking speed, maximal isometric muscle force of the gluteus medius and gluteus maximus and TFL was observed, as well as a decrease in propulsive force and peak hip moment. Functionally, these results could signify muscle damage following surgery, requiring rehabilitation for improved muscle function. LEVEL OF PROOF: III: Non-randomized controlled trial.

Encuesta nacional de atención del paciente neurocrítico / National survey of neurocritical care patients / Pesquisa nacional de cuidados a pacientes neurocriticos

Antecedentes: los pacientes neurocríticos constituyen un subgrupo especial en la medicina intensiva. Estudios internacionales recientes han mostrado variabilidad en su monitorización y manejo terapéutico. Objetivo: conocer las características de la atención y manejo de los pacientes neurocríticos en Uruguay. Métodos: estudio prospectivo y descriptivo. Se realizó una encuesta telefónica basada en un cuestionario de estructuras y procesos en la asistencia del paciente neurocrítico. Fue diseñado por la comisión de neurocríticos de la SUMI. Se entrevistó a jefes o coordinadores de cada unidad de cuidado intensivo (UCI), de forma voluntaria y anónima. Resultados: se encuestaron 52 UCI (98% del país), 67% correspondieron al Interior y 65% al sector privado del país. 96% de las UCI reciben pacientes neurocríticos. Se cuenta con neurocirugía presencial en 46%. El estudio de neuroimagen más disponible es la tomografía computada (81%). Se realiza: monitorización de presión intracraneana en 65%, oximetría yugular en 27% y neuromonitorización no invasiva en 58%, siendo la ultrasonografía la más frecuente. Las estrategias más utilizadas para el tratamiento de la hipertensión intracraneana son: osmoterapia (salino hipertónico en 100%), propofol (85%), bloqueo muscular (78%) y descompresiva (75%). Reperfusión en ataque cerebrovascular: trombolisis (88%) y trombectomía mecánica (44%). Los fármacos antiepilépticos más utilizados son: midazolam (100%), levetiracetam y fenitoína (96%). Tratamiento del aneurisma cerebral: clipado quirúrgico (98%) y endovascular (66%). Protocolización en 96% y realización de ateneos clínicos en 61%. Conclusiones: se presenta el primer trabajo realizado en nuestro país sobre el tema. Se encontró variabilidad en la monitorización así como en la disponibilidad de neuroimagenología y especialidades neurointervencionistas. Este estudio proporciona una oportunidad para la investigación comparativa de efectividad.

Background: neurocritical care patients constitute a special subgroup in intensive care medicine. Recent international studies have shown variability in their monitoring and therapeutic handling. Objective. to learn about the handling and care characteristics of neurocritical patients in Uruguay. Method: prospective, descriptive study. A telephone survey was conducted based on a structure and processes questionnaire on neurocritical patients' care. It was designed by the Neurocritical Patients Comittee of the Uruguayan Society of Intensive Medicine (SUMI). Chiefs or coordinators of each intensive care units were interviewed, their participation being voluntary an anonymous. Results: 52 ICU in the country were interviewed, 67% were located in the provinces and 65% belonged to the private sector. 96% of intensive care units received neurocritical care patients. Routine neurosurgery was available in 46% of cases. Computerized technology was the most widely available imaging study (81%). The following procedures were conducted: intracranial pressure monitoring in 65% of patients, jugular venous oximetry in 27%, non-invasive neuromonitoring in 58%, ultrasound being the most frequently used. The most commonly used strategies to treat intracranial hypertension are: osmotherapy (hypertonic saline in 100%), propofol (85%), muscular blockade (78%) and decompressive craniectomy (75%). Reperfusion in cerebrovascular attack, thrombolisis (88%) and mechanical thrombectomy (44%). The most widely used antiepileptic drugs are: midazolam (100%), levetiracetam y phenytoin (96%). Cerebral aneurysm was treated with surgical clipping (98%) and endovascular treatment (66%). Protocols were followed in 96% and case conferences were organized in 61%. Conclusions: the study presents the first research conducted on this topic in our country and it found variability in terms of monitorization and availability of neuro-imagining and neurointerventionist special strategies. The study represents an opportunity for effectiveness comparative research.

Introdução: os pacientes neurocríticos constituem um subgrupo especial na medicina intensiva. Estudos internacionais recentes têm mostrado variabilidade em seu monitoramento e manejo terapêutico. Objetivo: conhecer as características de atendimento e manejo de pacientes neurocríticos no Uruguai. Métodos: estudo prospectivo e descritivo. Fez-se uma pesquisa telefônica utilizando um questionário sobre estruturas e processos do cuidado de pacientes neurocríticos. Foi projetado pela comissão de neurocríticos de la Sociedad Uruguaya de Medicina Intensiva. Os chefes ou coordenadores de cada unidade de terapia intensiva (UTI) foram entrevistados de forma voluntária e anônima. Resultados: pesquisaram-se 52 UTIs (98% do país), 67% do Interior e 65% do setor privado do país. 96% das UTIs recebem pacientes neurocríticos. A neurocirurgia no local está disponível em 46%. O estudo de neuroimagem mais disponível é a tomografia computadorizada (81%). Realiza-se monitorização da pressão intracraniana em 65%, oximetria jugular em 27% e neuromonitorização não invasiva em 58%, sendo a ultrassonografia a mais frequente. As estratégias mais utilizadas para o tratamento da hipertensão intracraniana são: osmoterapia (soro fisiológico 100% hipertônico), propofol (85%), bloqueio muscular (78%) e descompressão (75%). Faz-se reperfusão no ataque cerebrovascular por trombólise (88%) e trombectomia mecânica (44%). As drogas antiepilépticas mais utilizadas são: midazolam (100%), levetiracetam e fenitoína (96%). Tratamento do aneurisma cerebral: clipagem cirúrgica (98%) e endovascular (66%). Protocolização em 96% e reuniões clínicas em 61%. Conclusões: este é o primeiro trabalho realizado em nosso país sobre o tema. Foi encontrada variabilidade no monitoramento, bem como na disponibilidade de especialidades de neuroimagem e neurointervenção. Este estudo oferece uma oportunidade para a pesquisa comparativa de eficácia.

Quantitative gait analysis after total hip arthroplasty through a minimally invasive direct anterior approach: A case control study.

INTRODUCTION: Total Hip Arthroplasty (THA) leads to excellent clinical and functional results. The Minimally Invasive Anterior Approach (MIAA) theoretically allows rapid recovery and a reduction in the need for rehabilitation, but alterations in muscle and static balance have previously been demonstrated. Kinetic, kinematic and muscular alterations have been shown to persist up to 1year postoperatively but data beyond 1year postoperatively is lacking. Thus, the objective of this study was to compare the data from Quantitative Gait Analysis (QGA) coupled with electromyography (EMG), of patients one year postoperatively with THA through MIAA, compared to an asymptomatic control group. HYPOTHESIS: We hypothesized that QGA and EMG parameters would not normalize beyond one year postoperatively. PATIENTS AND METHODS: Twenty-seven patients were recruited, including 15 subjects (64.6±6.6years) operated on by MIAA, who at 15.9±3.1months postoperatively, along with 12 asymptomatic control subjects (68.9±9.7years), who underwent QGA and maximal isometric muscle strength tests, coupled with EMG on the gluteus medius and maximus, Tensor Fascia Lata (TFL) and Sartorius muscles. The spatiotemporal parameters of walking (step length, walking speed, cadence, single leg support time), kinetics (vertical ground reaction forces, hip moments in the 3 planes) and kinematics (coxofemoral and pelvic amplitudes) were analyzed. RESULTS: The walking speed was lower on the non-operated side of the experimental subjects (0.96ms-1 compared to 1.13ms-1 for asymptomatic [p=0.018]), as was the step length on the operated side (0.53m compared to 0.60m for asymptomatic [p=0.042]). Maximal isometric muscle strength was lower in subjects operated on for the gluteus maximus and medius (p=0.004), compared to asymptomatic subjects. Moments were lower in the subjects operated on in extension (0.72Nm on the operated side, 0.75Nm on the non-operated side compared to 1.06Nm for asymptomatic [p=0.007 and p=0.024]) and lateral rotation (0.09Nm on the operated side, 0.05Nm on the non-operated side compared to 0.16Nm for asymptomatic subjects [p=0.009 and p=0.0005]). Hip adduction amplitudes were lower on the operated side compared to asymptomatic subjects (3.93° versus 9.14° for asymptomatic [p=0.005]). Pelvic amplitudes in the frontal plane were lower amongst operated subjects (0.44° against 1.97° for asymptomatic [p=0.041]). Pelvic amplitudes in the sagittal plane were higher in the operated subjects (15.74° on the operated side, 15.43° on the non-operated side compared to 9.65° for asymptomatic [p=0.041 and p=0.032]). DISCUSSION: Our initial hypothesis was validated, since walking deficits persisted beyond one year postoperatively after THA through MIAA. A decrease in maximal isometric muscle strength of the gluteus medius and gluteus maximus was observed, as well as an alteration of kinetic and kinematic parameters in the sagittal and frontal planes. The results were in agreement with the literature and reflected the establishment of compensatory mechanisms to overcome alterations in joint strength and range more than one year postoperatively. These results would allow rehabilitation programs to be more specific and would justify a study on the other approaches for THA. LEVEL OF EVIDENCE: III; non-randomized control trial.

Stabilometric assessments of two rehabilitation protocols on postural parameters after posterior total hip arthroplasty: A prospective randomized comparative study.

INTRODUCTION: After total hip arthroplasty (THA), patients continue to have muscular, functional and postural deficits. The literature seems to support the use of postoperative rehabilitation, especially self-directed programs. However, there is no set protocol for the management of postural disorders. Therefore, the purpose of this study was to compare postural parameters of a group of patients who underwent posterior THA followed by 2 different types of rehabilitation (stabilometric platform (SP) and home-based self-directed protocols) with a control group of operated patients who did not undergo rehabilitation and a control group of age-matched asymptomatic subjects. HYPOTHESIS: We hypothesized that rehabilitation would normalize the stabilometric parameters. PATIENTS AND METHODS: A total of 67 subjects were enrolled in this study (mean age 67.85±1.22years) and divided into 4 groups. Forty-one of these subjects had undergone a posterior THA were randomly assigned between D10 and D21 to one of the following 3 groups: no rehabilitation control group (THACG=14), supervised rehabilitation with a stabilometric platform group (RSPG=16), and a self-directed home-based rehabilitation group (SDHRG=11). The 4th group was a control group made up of 26 age-matched asymptomatic nonoperated subjects (CG55-80). These rehabilitation protocols lasted 3weeks. At the end of the 3weeks, the groups performed the same stabilometric single leg and double leg stance tests (considering lower limb dominance) on an SP. RESULTS: No significant differences were observed between groups in the bipedal stance, except between the CG55-80 and the THACG, where a higher energy expenditure was observed in the THACG during the static stance with eyes open (EO) and eyes closed (EC): increase in the path length (Plength) covered by the center of pressure (COP) (EO: p=01; EC: p=03) and the average velocity (Vavg) of the COP (EO: p=01; EC: p=03). These differences were not observed in the SDHRG and RSPG whether they were compared with one another or with both control groups. In the unipedal stance, subjects in the RSPG and SDHRG showed greater muscle activity in the anterior and posterior chains and hip abductors, and used less energy to maintain the stance than those in the CG55-80, regardless of lower limb dominance: decrease in the mediolateral range of COP displacement (Xrange) (hip abductor muscles) (p=02) and anteroposterior range of COP displacement (Yrange) (anterior and posterior chains) (p=3.49.10-3), 95% confidence ellipse area (Earea) of COP data (p=1.47.10-3), Plength (p=04) and Vavg (p=04). The RSPG had a smaller Earea than the SDHRG (p=04), demonstrating a better postural stability during the unipedal stance performed on the dominant operated leg. DISCUSSION: Our results were consistent with the literature on the benefits of rehabilitation after THA, thus confirming our hypothesis that rehabilitation normalized stabilometric parameters between D31-D45, depending on the subjects. These results provide new information regarding rehabilitation techniques to be implemented postoperatively after a THA. A home-based self-directed rehabilitation program is just as effective as an SP program in managing postural disorders. LEVEL OF EVIDENCE: II; randomized controlled trial with low statistical power.

Predicting factors for long-term survival in patients with out-of-hospital cardiac arrest - A propensity score-matched analysis.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is one of the leading causes of death worldwide, with acute coronary syndromes accounting for most of the cases. While the benefit of early revascularization has been clearly demonstrated in patients with ST-segment-elevation myocardial infarction (STEMI), diagnostic pathways remain unclear in the absence of STEMI. We aimed to characterize OHCA patients presenting to 2 tertiary cardiology centers and identify predicting factors associated with survival. METHODS: We retrospectively analyzed 519 patients after OHCA from February 2003 to December 2017 at 2 centers in Munich, Germany. Patients undergoing immediate coronary angiography (CAG) were compared to those without. Multivariate regression analysis and inverse probability treatment weighting (IPTW) were performed to identify predictors for improved outcome in a matched population. RESULTS: Immediate CAG was performed in 385 (74.1%) patients after OHCA with presumed cardiac cause of arrest. As a result of multivariate analysis after propensity score matching, we found that immediate CAG, return of spontaneous circulation (ROSC) at admission, witnessed arrest and former smoking were associated with improved 30-days-survival [(OR, 0.46; 95% CI, 0.26-0.84), (OR, 0.21; 95% CI, 0.10-0.45), (OR, 0.50; 95% CI, 0.26-0.97), (OR, 0.43; 95% CI, 0.23-0.81)], and 1-year-survival [(OR, 0.39; 95% CI, 0.19-0.82), (OR, 0.29; 95% CI, 0.12-0.7), (OR, 0.43; 95% CI, 0.2-1.00), (OR, 0.3; 95% CI, 0.14-0.63)]. CONCLUSIONS: In our study, immediate CAG, ROSC at admission, witnessed arrest and former smoking were independent predictors of survival in cardiac arrest survivors. Improvement in prehospital management including bystander CPR and best practice post-resuscitation care with optimized triage of patients to an early invasive strategy may help ameliorate overall outcome of this critically-ill patient population.

Evaluation of the relationship between effervescent paracetamol and blood pressure: clinical trial.

BACKGROUND: Paracetamol's solubility is achieved by adding to the excipient sodium salts, either as bicarbonate, carbonate or citrate. As the relationship between salt and hypertension is well known, due to the sodium content it has raised a hypothesis that may interfere with the control of that risk factor. Therefore, the objective of this study is to evaluate the effect on blood pressure of effervescent paracetamol compared to non-effervescent, in hypertensive patients. METHODS/DESIGN: This is the protocol of a phase IV multicenter clinical trial, randomized, controlled, crossover, open, which will compare the effect of two different formulations of paracetamol (effervescent or non-effervescent) in the blood pressure of hypertensive patients, with a seven weeks follow up. 49 controlled hypertensive patients will be included (clinical BP lower than 150 and 95 mmHg, and lower than 135 mmHg and 85 mmHg in patients with diabetes or a history of cardiovascular event, and daytime ambulatory measurements lower than 140 and 90 mmHg) and mild to moderate pain (Visual Analog Scale between 1 and 4). The study was approved by the ethics committee of the Fundació Jordi Gol i Gurina and following standards of good clinical practice. The primary endpoint will be the variations in systolic BP in 24 h Ambulatory Blood Pressure Monitoring, considering significant differences 2 or more mmHg among those treated with non-effervescent and effervescent formulations. Intention-to-treat and per-protocol analysis will be held. DISCUSSION: Despite the broad recommendation not to use effervescent drugs in patients with hypertension, there are relatively little studies that show exactly this pressor effect due to sodium in salt that gives the effervescence of the product. This is the first clinical trial designed to study the effect of effervescence compared to the non-effervescent, in well-controlled hypertensive patients with mild to moderate pain, performed in routine clinical practice. TRIAL REGISTRATION: NCT 02514538.

[Evaluation of the p53 Arg72Pro polymorphism as a prognostic factor in severe head injury and the inclusion of this indicator in a predictive model]. / Evaluación del polimorfismo Arg72Pro de p53 como factor pronóstico del traumatismo craneoencefálico grave y su participación en la construcción de un modelo predictivo.

BACKGROUND AND OBJECTIVE: Physiologic variables have traditionally been studied as prognostic factors in severe head injury. Until recently it was not thought that genetic factors might play a role. The main objective of this study was to construct a logistic regression model including physiologic variables and the p53 Arg72Pro polymorphism, which can promote neuron death through apoptosis. MATERIAL AND METHODS: We included 90 patients admitted to the postoperative recovery unit with severe head injury. Patients with previous neurologic deficits were excluded. Clinical variables were recorded. The p53 Arg72Pro polymorphism was analyzed using polymerase chain reaction of DNA in blood. Neurologic outcome was assessed on the Glasgow Outcome Scale. A predictive logistic regression model was then constructed based on relevant candidate variables (sex, age, poor Glasgow score, the Acute Physiology and Chronic Health Evaluation II score, pupil size, pupil reactivity, subarachnoid hemorrhage, number of days in the recovery unit, number of days on mechanical ventilation, and the early development of hypotension) in addition to the p53 Arg72Pro polymorphism. RESULTS: The Arg/Arg polymorphism was an independent predictor of poor outcome (odds ratio, 3.55; 95% confidence interval [CI], 1.11-1132; P = .032). The selected model (including the variables age, gene polymorphism, pupil reactivity, and Glasgow score) had adequate discriminatory power (sensitivity 823%, 95% CI 72.8%-91.8%; specificity 78.6%, 95% CI 63.4%-93.8%), classifying 81.1% of the patients correctly. The p53 Arg72Pro polymorphism, along with pupil reactivity, age and Glasgow score, is useful in a predictive model of good or poor outcome on discharge after head injury.

Relationship between the Arg72Pro polymorphism of p53 and outcome for patients with traumatic brain injury.

OBJECTIVE: To determine the relationship between the Arg72Pro polymorphism of p53 and the outcome after traumatic brain injury (TBI) in humans. DESIGN AND SETTING: A prospective study was carried out in a ten-bed surgical intensive care unit (SICU) of a university hospital. PATIENTS: The study included 90 caucasian patients who had experienced a severe TBI within the previous 24 h. The exclusion criterion was a previous deficit in the central nervous system. MEASUREMENTS AND RESULTS: The main recorded outcomes were values on the Glasgow Outcome Scale (GOS) at discharge from the SICU (GOS-0) and 6 months later (GOS-6). A blood sample was taken from each patient and all samples were analyzed by an allele-specific polymerase chain reaction for detection of Arg72Pro polymorphism of p53. These polymorphisms were tested for their association with values of GOS-0 and GOS-6. A two-tailed value of p<0.05 was considered statistically significant. The frequency of the argine/argine (Arg/Arg) genotype was greater among the patients who had a bad outcome at GOS-0 (69 vs 31% in the bad-outcome group; p=0.029). A multiple logistic regression analysis showed that patients with the Arg/Arg variation had a 2.9-fold greater risk of having a bad outcome at discharge from the SICU (95% confidence interval, 1.05-8.31; p=0.039 ). There was no similar relationship with respect to GOS-6. CONCLUSION: The Arg/Arg genotype of the Arg72Pro polymorphism in p53 is associated with increased likelihood of a bad outcome at discharge from the SICU.