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Messenger RNA (mRNA) is rapidly growing as a therapeutic modality for vaccination and the treatment of a wide range of diseases. As a result, there is an increased demand for mRNA-based analytical methods capable of assessing purity and stability, which are considered critical quality attributes (CQAs). In recent decades capillary electrophoresis (CE) has emerged alongside liquid chromatography (LC) as an important tool for the assessment of purity and stability of mRNA therapeutics. CE offers a variety of advantages over conventional LC or gel-based analytical methods, including reduced injection volume, increased resolution, and increased separation efficiency. In this study we compared CE-based analytical methods: the Agilent RNA 6000 Nano Kit, the Revvity RNA Reagent Kit, the Sciex RNA 9000 Purity and Integrity Kit, and the Agilent HS RNA Kit. These methods were evaluated on their vendor-recommended instruments: the Bioanalyzer, LabChip GXII, PA800 Plus, and Fragment Analyzer, respectively. We assessed the ability of these methods to measure mRNA integrity, purity, and stability. Furthermore, several parameters for each method were also assessed: selectivity, precision, resolution, analysis time, and ease of use. Based on our results, all four methods are suitable for use in the characterization of in vitro transcribed (IVT) mRNA, depending on the intended application. The Sciex RNA 9000 Purity and Integrity kit method achieved the highest selectivity and resolving power compared with the other methods, making it the most suitable for high-resolution, in-depth sample characterization. In comparison, the Agilent RNA 6000 Nano Kit, Revvity RNA Reagent Kit, and Agilent HS RNA Kit achieved lower selectivity and resolution, but their faster analysis times make them more suitable for high-throughput and screening applications.
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Electroforesis Capilar , Estabilidad del ARN , ARN Mensajero , Electroforesis Capilar/métodos , ARN Mensajero/genética , ARN Mensajero/análisis , Transcripción GenéticaRESUMEN
Introduction: The management of patients with COVID-19 infection has placed great pressure on the healthcare systems around the world. The aim of this study was to investigate the impact of the COVID-19 pandemic on the treatment outcomes of patients with rectal cancer by comparing them to those of patients with the same diagnosis in the pre-pandemic period. Methods: Retrospective data analysis of patients undergoing multimodal treatment for rectal cancer at the four university hospitals during the COVID-19 pandemic (2020-2021) and the 2-year pre-pandemic period (2018-2019). Results: A total of 693 patients (319 in the pre-pandemic period and 374 in the pandemic period) with rectal cancer were included in the study. The demographic and clinical characteristics of patients in both study periods were comparable, as was the spectrum of surgical procedures. Palliative surgery was more common in the pandemic period (18% vs 13%, p=0.084). The proportion of patients undergoing minimally invasive surgery was higher during the COVID-19 pandemic (p=0.025). There were no statistically significant differences between the study periods in the incidence/severity of post-operative complications, 30-day mortality and length of hospital stay. The number of positive resection margins was similar (5% vs 5%). Based on these results, COVID-19 had no effect on the postoperative morbidity and mortality in patients undergoing surgery for rectal cancer. Neoadjuvant treatment was more common in the pre-pandemic period (50% vs 45%). Long-course RT was predominantly offered in the pre-pandemic period, short-course RT during the pandemic. Significantly shorter "diagnosis-surgery" intervals were observed during the pandemic (23 days vs 33 days, p=0.0002). The "surgery-adjuvant therapy" interval was similar in both analysed study periods (p=0.219). Conclusion: Our study showed, that despite concerns about the COVID-19 pandemic, multimodal treatment of rectal cancer was associated with unchanged postoperative morbidity rates, increased frequency of short-course neoadjuvant RT administration and shorter "diagnosis-surgery" intervals.
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Heightened interest in messenger RNA (mRNA) therapeutics has accelerated the need for analytical methodologies that facilitate the production of supplies for clinical trials. Forced degradation studies are routinely conducted to provide an understanding of potential weak spots in the molecule that are exploited by stresses encountered during bulk purification, production, shipment, and storage. Consequently, temperature fluctuations and excursions are often experienced during these unit operations and may accelerate mRNA degradation. Here, we present a concise panel of chromatography-based stability-indicating assays for evaluating thermally stressed in vitro transcribed (IVT) mRNA as part of a forced degradation study. We found that addition of EDTA to the mRNAs prior to heat exposure reduced the extent of degradation, suggesting that transcripts may be fragmenting via a divalent metal-ion mediated pathway. Trace divalent metal contamination that can accelerate RNA instability is likely carried over from upstream steps. We demonstrate the application of these methods to evaluate the critical quality attributes (CQAs) of mRNAs as well as to detect intrinsic process- and product-related impurities.
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Estabilidad del ARN , ARN Mensajero , Ácido Edético/química , Transcripción Genética , CalorRESUMEN
BACKGROUND: Blunt trauma acting against the human body presents the fundamental cause of pulmonary fat embolism (PFE) and fat embolism syndrome. The aim of the present study was to investigate PFE in non-survivors after cardiopulmonary resuscitation (CPR). METHODS: This was a prospective cohort study conducted in University Hospital Ostrava, Czech Republic. Within a 4-year study period, all non-survivors after CPR because of out-of-hospital cardiac arrest were assessed for the study eligibility. The presence/seriousness of PFE was determined by microscopic examination of cryo-sections of lung tissue (staining with Oil Red O). RESULTS: In total, 106 persons after unsuccessful CPR were enrolled in the study. The most frequent cause of death in the study population (63.2% of cases) was cardiac disease (ischemic heart disease); PFE was not determined as the cause of death in any of our study cases. Sternal fractures were identified 66.9%, rib fractures (usually multiple) in 80.2% of study cases; the median number of rib fractures was 10.2 fractures per person. Serious intra-thoracic injuries were found in 34.9% of cases. Microscopic examination of lung cryo-sections revealed PFE in 40 (37.7%) study cases; PFE was most frequently evaluated as grade I or II. Occurrence of sternal and rib fractures was significantly higher in persons with PFE than between persons without PFE (p = 0.033 and p = <0.001). Number of rib fractures was also significantly higher in persons with PFE. The occurrence of serious intra-thoracic injuries was comparable in both our study groups (p = 0.089). CONCLUSIONS: PFE presents a common resuscitation injury which can be found in more than 30% of persons after CPR. Persons with resuscitation skeletal chest fractures have significantly higher risk of PFE development. During autopsy of persons after unsuccessful CPR, it is necessary to distinguish CPR-associated injuries including PFE from injuries that arise from other mechanisms.
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Reanimación Cardiopulmonar , Embolia Grasa , Embolia Pulmonar , Fracturas de las Costillas , Traumatismos Torácicos , Humanos , Fracturas de las Costillas/etiología , Reanimación Cardiopulmonar/efectos adversos , Estudios Prospectivos , Traumatismos Torácicos/etiología , Embolia Pulmonar/complicaciones , Embolia Grasa/complicacionesRESUMEN
Pulmonary fat embolism (PFE) is usually observed in patients with long bone fractures, patients with extensive subcutaneous fat contusions or skin burns. Chest compressions during cardiopulmonary resuscitation (CPR) present powerful repetitive violence against victim's chest. Skeletal chest fractures are the most frequent complication of CPR, and probably the most important cause of PFE autopsy finding in persons, which have been resuscitated before death. The aim of the present paper was to investigate the prevalence and seriousness of PFE in non-survivors after out-of-hospital cardiac arrest. During autopsy, PFE can be diagnosed in 30 - 42 % of persons after unsuccessful CPR; skeletal chest fractures are associated with significantly higher prevalence of PFE. After successful CPR, fat embolism may contribute significantly to acute respiratory distress syndrome, or multiorgan failure. The issue of CPR associated injuries has two medical aspects - clinical and forensic. From clinical point of view, the presence of CPR associated injuries must be acknowledged when offering healthcare to patients after successful CPR. During autopsy, CPR associated injuries should be diagnosed and evaluated as these injuries may contribute to death or may be potentially lethal.
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Reanimación Cardiopulmonar , Embolia Grasa , Fracturas Óseas , Paro Cardíaco Extrahospitalario , Embolia Pulmonar , Humanos , Reanimación Cardiopulmonar/efectos adversos , Embolia Pulmonar/etiología , Paro Cardíaco Extrahospitalario/etiología , Embolia Grasa/etiologíaRESUMEN
BACKGROUND: Lung cancer poses a significant challenge with high mortality rates. Minimally invasive surgical approaches, including the uniportal thoracoscopic technique, offer potential benefits in terms of recovery and patient compliance. This study focuses on evaluating the radicality of mediastinal lymphadenectomy during uniportal thoracoscopic lung resection, specifically assessing the reachability of established lymphatic stations. METHODS: A comparative study was conducted at the University Hospital Ostrava from January 2015 to July 2022, focusing on the evaluation of radicality in mediastinal lymphadenectomy across three patient subgroups: uniportal thoracoscopic approach, multiportal thoracoscopic approach, and thoracotomy approach. The study implemented the routine identification and excision of 8 lymph node stations from the respective hemithorax to assess the radicality of lymph node harvesting. RESULTS: A total of 428 patients were enrolled and evaluated. No significant differences were observed in the number of lymph nodes removed between the subgroups. The mean number of lymph nodes removed was 6.50 in the left hemithorax and 6.49 in the right hemithorax. The 30-day postoperative morbidity rate for the entire patient population was 27.3%, with 17.5% experiencing minor complications and 6.5% experiencing major complications. Statistically significant differences were observed in major complications between the uniportal approach and the thoracotomy approach (3.5% vs 12.0%, p = 0.002). The overall mortality rate in the study population was 3%, with a statistically significant difference in mortality between the uniportal and multiportal approaches (1.0% vs 6.4%, p = 0.020). CONCLUSIONS: The uniportal approach demonstrated comparable accessibility and lymph node yield to multiportal and thoracotomy techniques. It is equivalent to established methods in terms of postoperative complications, with fewer major complications compared to thoracotomy. While our study indicates a potential for lower mortality following uniportal lung resection in comparison to multiportal lung resection, and demonstrates comparable outcomes to thoracotomy, it is important to approach these findings cautiously and refrain from drawing definitive conclusions.
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Neoplasias Pulmonares , Toracotomía , Humanos , Neumonectomía/efectos adversos , Neumonectomía/métodos , Cirugía Torácica Asistida por Video/métodos , Estudios Retrospectivos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Escisión del Ganglio Linfático/métodos , Pulmón/patologíaRESUMEN
Although pneumonia presents a relatively common diagnosis, it does not always present with classic clinical symptoms, nor does it follow a regular course without complications. The presented case describes a rare case of aspiration necrotizing pneumonia, which despite intensive therapy, progressed to lung gangrene and required a lung lobectomy. Another peculiarity is that the correct diagnosis was established only after the onset of abdominal pain, surprisingly by a trauma surgeon. This case emphasizes the necessity of a thorough general examination and draws attention to a rare, but conservatively intractable necrotizing pneumonia complicated by lung gangrene.
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Neumonía por Aspiración , Neumonía Necrotizante , Humanos , Preescolar , Gangrena , Dolor Abdominal , PulmónRESUMEN
The 3' poly(A) tail is an important component of messenger RNA (mRNA). The length of the poly(A) tail has direct impact on the stability and translation efficiency of the mRNA molecule and is therefore considered to be a critical quality attribute (CQA) of mRNA-based therapeutics and vaccines. Various analytical methods have been developed to monitor this CQA. Methods like ion-pair reversed-phase liquid chromatography (IPRP-LC) can be used to quantify the percentage of mRNA with poly(A) tail but fail to provide further information on the actual length of poly(A). High-resolution methods such as liquid chromatography coupled with mass spectrometry (LC-MS) or next generation sequencing (NGS) can separate poly(A) tail length by one nucleotide (n/n + 1 resolution) but are complicated to implement for release testing of manufactured mRNA. In this study, a workflow utilizing capillary gel electrophoresis (CGE) for characterizing the poly(A) tail length of mRNA was developed. The CGE method demonstrated resolution comparable with the LC-MS method. With UV detection and the addition of poly(A) length markers, this method can provide poly(A) tail length information and can also provide quantitation of each poly(A) length, making it a suitable release method to monitor the CQA of poly(A) tail length.
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Nucleótidos , Vacunas , ARN Mensajero/genética , Flujo de Trabajo , Electroforesis Capilar/métodosRESUMEN
PURPOSE: Magnetic resonance imaging (MRI) is a fundamental diagnostic modality for the evaluation of primary rectal cancer, but MRI assessment of nodal involvement remains a confounding factor. METHOD: This prospective cohort study was conducted to investigate the accuracy of preoperative MRI in the assessment of nodal status by comparing histopathology reports to MRI findings on a node-by-node basis in 69 patients with rectal cancer. RESULTS: Primary surgery was performed in 40 (58.0%) patients; 29 (42.0%) study patients underwent neoadjuvant chemoradiotherapy (CRT). Histopathological examination revealed T1 tumour in 8 (11.6%) patients, T2 tumour in 30 (43.5%), and T3 tumour in 25 (36.2%). In total, 897 lymph nodes (LNs) have been harvested (13.1 ± 5.4 LNs per specimen). There were 77 MRI-suspicious LNs, 21 (27.3%) of which were histologically proven malignant. The sensitivity of MRI for assessing nodal involvement was 51.2% and specificity 93.4%. Of the 28 patients with MRI-suspicious LNs the diagnosis was correct in 42.8%. The MRI accuracy was 33.3% in "primary surgery" subgroup (n = 18, malignant LNs found in 6 patients). Diagnosis of MRI-negative LNs was correct in 90.2% of study patients; malignant nodes were found in 9.8% of patients initially classified as cN0. CONCLUSIONS: MRI prediction of nodal status in patients with rectal cancer has very low accuracy. Decisions regarding neoadjuvant CRT should not be based on MRI assessment of nodal status, but on the MRI evaluation of tumour depth invasion (T stage and relationship between the tumour and mesorectal fascia).
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Neoplasias del Recto , Humanos , Estudios Prospectivos , Estadificación de Neoplasias , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: Opioids and epidural analgesia are a mainstay of perioperative analgesia but their influence on cancer recurrence remains unclear. Based on retrospective data, we found that cancer recurrence following colorectal cancer surgery correlates with the number of circulating tumor cells (CTCs) in the early postoperative period. Also, morphine- but not piritramide-based postoperative analgesia increases the presence of CTCs and shortens cancer-specific survival. The influence of epidural analgesia on CTCs has not been studied yet. METHODS: We intend to enroll 120 patients in four centers in this prospective randomized controlled trial. The study protocol has been approved by Ethics Committees in all participating centers. Patients undergoing radical open colorectal cancer surgery are randomized into epidural, morphine, and piritramide groups for perioperative analgesia. The primary outcome is the difference in the number of CTCs in the peripheral blood before surgery, on the second postoperative day, and 2-4 weeks after surgery. The number of CTCs is measured using molecular biology methods. Perioperative care is standardized, and relevant data is recorded. A secondary outcome, if feasible, would be the expression and activity of various receptor subtypes in cancer tissue. We intend to perform a 5-year follow-up with regard to metastasis development. DISCUSSION: The mode of perioperative analgesia favorably affecting cancer recurrence would decrease morbidity/mortality. To identify such techniques, trials with long-term follow-up periods seem suboptimal. Given complex oncological therapeutic strategies, such trials likely disable the separation of perioperative analgesia effects from other factors. We believe that early postoperative CTCs presence/dynamics may serve as a sensitive marker of various perioperative interventions´ influences on cancer recurrence. Importantly, it is unbiased to the influence of long-term factors and minimally invasive. Analysis of opioid/cannabinoid receptor subtypes in cancer tissue would improve understanding of underlying mechanisms and promote personalization of treatment. We are not aware of any similar ongoing studies. TRIAL REGISTRATION NUMBER: NCT03700411, registration date: October 3, 2018. STUDY STATUS: recruiting.
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Analgesia Epidural , Neoplasias Colorrectales , Células Neoplásicas Circulantes , Humanos , Analgésicos Opioides/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Morfina , Neoplasias Colorrectales/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
Since mammographic screening programmes were initiated, the spectrum of breast cancer has changed in terms of impalpable tumours, thus causing the development of new localisation methods, including magnetic markers. We offer herein an up-to-date review focused on two magnetic markers (Magseed, MaMaLoc) currently used in breast cancer surgery for the localisation of breast tumours or pathological axillary nodes. Magnetic marker localisation presents a safe and reliable method for breast tumour marking. Four currently available prospective studies demonstrate that the Magseed system has a negative margin rate and a successful localisation rate, both of which are comparable to standard marking systems used in breast cancer surgery. The main benefits of magnetic markers are that they require no radiation safety measures, and they offer the possibility of longer deployment times, thus simplifying surgery scheduling. The most important drawbacks are cost of the system, depth limitation and need for frequent probe recalibration.
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OBJECTIVE: This study aimed to evaluate our experience with the use of Magseed, the magnetic metallic marker, as a localization technique followed by Sentimag probe detection in patients with solitary intra-abdominal local metastases with subsequent resection of the lesions. METHODS: Five patients underwent resection after the lesion was marked with the Magseed magnetic marker. Prior to the surgery, a computed tomography scan of the chest and abdomen and/or positron emission tomography was performed to rule out the dissemination of the disease. The indication for surgery was evaluated in a meeting of a multidisciplinary team, and the placement of the magnetic marker under computed tomography control had been performed the day before the planned procedure. RESULTS: The present preliminary outcomes have revealed that Magseed might be a promising technique that is feasible and safe, particularly when the postsurgical anatomic conditions in the abdominal cavity are altered and the lesions are not visible or palpable. Surgical extirpation of lesions occurred without complications in each case. In all the cases, the resection was complete and curative, and one wound infection in all (20%), without any major complications, had occurred. The mean hospital stay was 6.6 days. CONCLUSION: Magseed utilization, as a localization technique, followed by Sentimag probe detection in intra-abdominal tumors has not been reported before. Improving the visualization and, consequently, the precise marking of the lesion with subsequent radical removal can prevent insufficient or excessive removal of healthy tissue, leading to a faster diagnosis and better overall clinical outcomes.
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Cavidad Abdominal , Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Rayos X , Cintigrafía , Fenómenos MagnéticosRESUMEN
OBJECTIVE: Peptic ulcer perforation presents the most serious complication of ulcer disease with mortality that varies significantly depending on the age and conditions. The coronavirus disease 2019 pandemic was effective worldwide in 2020 and continues to date. The aim of this study was to investigate the initial clinical parameters and short-term outcomes of patients with acute peptic ulcer perforation before and during the coronavirus disease 2019 pandemic. METHODS: A retrospective cohort study was conducted in the Department of Surgery, University Hospital Ostrava, Czech Republic. The patients undergoing surgical modality of a simple suture of peptic ulcer perforation with/without omentoplasty in the post-coronavirus disease 2019 (January 1, 2020 to December 31, 2021) and the pre-coronavirus disease 2019 (January 1, 2018 to December 31, 2019) had been incorporated in this study. RESULTS: This study included a total of 46 cases (26 in the pre-coronavirus disease 2019, 20 in the post-coronavirus disease 2019). The age, body mass index, Boey score, duration of symptoms, surgery time, and length of hospital stay were comparable in both study subgroups. During the coronavirus disease 2019 pandemic, patients were admitted with a statistically significantly lower degree of perioperative risk according to the American Society of Anesthesiologists classification (p=0.013). Notably, 30-day postoperative morbidity was significantly higher in pre-coronavirus disease 2019 (73.1 vs. 55.0%, p=0.038). The mortality rate in the laparoscopic group was 13.6%, in the laparotomy group 41.4%, and the mortality rate was higher in pre-coronavirus disease 2019 than in post-coronavirus disease 2019 (34.6 vs. 20.0%, p=0.166). CONCLUSION: In fact, the coronavirus disease 2019 pandemic had not significantly influenced therapeutic management and short-term outcomes of patients undergoing acute surgical repair of peptic ulcer perforation.
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COVID-19 , Laparoscopía , Úlcera Péptica Perforada , Humanos , Úlcera Péptica Perforada/diagnóstico , Úlcera Péptica Perforada/etiología , Úlcera Péptica Perforada/cirugía , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Pandemias , COVID-19/complicaciones , Laparoscopía/efectos adversos , Enfermedad AgudaRESUMEN
SUMMARY OBJECTIVE: Peptic ulcer perforation presents the most serious complication of ulcer disease with mortality that varies significantly depending on the age and conditions. The coronavirus disease 2019 pandemic was effective worldwide in 2020 and continues to date. The aim of this study was to investigate the initial clinical parameters and short-term outcomes of patients with acute peptic ulcer perforation before and during the coronavirus disease 2019 pandemic. METHODS: A retrospective cohort study was conducted in the Department of Surgery, University Hospital Ostrava, Czech Republic. The patients undergoing surgical modality of a simple suture of peptic ulcer perforation with/without omentoplasty in the post-coronavirus disease 2019 (January 1, 2020 to December 31, 2021) and the pre-coronavirus disease 2019 (January 1, 2018 to December 31, 2019) had been incorporated in this study. RESULTS: This study included a total of 46 cases (26 in the pre-coronavirus disease 2019, 20 in the post-coronavirus disease 2019). The age, body mass index, Boey score, duration of symptoms, surgery time, and length of hospital stay were comparable in both study subgroups. During the coronavirus disease 2019 pandemic, patients were admitted with a statistically significantly lower degree of perioperative risk according to the American Society of Anesthesiologists classification (p=0.013). Notably, 30-day postoperative morbidity was significantly higher in pre-coronavirus disease 2019 (73.1 vs. 55.0%, p=0.038). The mortality rate in the laparoscopic group was 13.6%, in the laparotomy group 41.4%, and the mortality rate was higher in pre-coronavirus disease 2019 than in post-coronavirus disease 2019 (34.6 vs. 20.0%, p=0.166). CONCLUSION: In fact, the coronavirus disease 2019 pandemic had not significantly influenced therapeutic management and short-term outcomes of patients undergoing acute surgical repair of peptic ulcer perforation.
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SUMMARY OBJECTIVE: This study aimed to evaluate our experience with the use of Magseed, the magnetic metallic marker, as a localization technique followed by Sentimag probe detection in patients with solitary intra-abdominal local metastases with subsequent resection of the lesions. METHODS: Five patients underwent resection after the lesion was marked with the Magseed magnetic marker. Prior to the surgery, a computed tomography scan of the chest and abdomen and/or positron emission tomography was performed to rule out the dissemination of the disease. The indication for surgery was evaluated in a meeting of a multidisciplinary team, and the placement of the magnetic marker under computed tomography control had been performed the day before the planned procedure. RESULTS: The present preliminary outcomes have revealed that Magseed might be a promising technique that is feasible and safe, particularly when the postsurgical anatomic conditions in the abdominal cavity are altered and the lesions are not visible or palpable. Surgical extirpation of lesions occurred without complications in each case. In all the cases, the resection was complete and curative, and one wound infection in all (20%), without any major complications, had occurred. The mean hospital stay was 6.6 days. CONCLUSION: Magseed utilization, as a localization technique, followed by Sentimag probe detection in intra-abdominal tumors has not been reported before. Improving the visualization and, consequently, the precise marking of the lesion with subsequent radical removal can prevent insufficient or excessive removal of healthy tissue, leading to a faster diagnosis and better overall clinical outcomes.
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BACKGROUND AND AIMS: Fecal incontinence (FI) improvement following injection of autologous skeletal muscle-derived cells has been previously suggested. This study aimed to test the efficacy and safety of said cells through a multicenter, placebo-controlled study, to determine an appropriate cell dose, and to delineate the target patient population that can most benefit from cell therapy. METHODS: Patients experiencing FI for at least 6 months were randomized to receive a cell-free medium or low or high dose of cells. All patients received pelvic floor electrical stimulation before and after treatment. Incontinence episode frequency (IEF), FI quality of life, FI burden assessed on a visual analog scale, Wexner score, and parameters reflecting anorectal physiological function were all assessed for up to 12 months. RESULTS: Cell therapy improved IEF, FI quality of life, and FI burden, reaching a preset level of statistical significance in IEF change compared with the control treatment. Post hoc exploratory analyses indicated that patients with limited FI duration and high IEF at baseline are most responsive to cells. Effects prevailed or increased in the high cell count group from 6 to 12 months but plateaued or diminished in the low cell count and control groups. Most physiological parameters remained unaltered. No unexpected adverse events were observed. CONCLUSIONS: Injection of a high dose of autologous skeletal muscle-derived cells followed by electrical stimulation significantly improved FI, particularly in patients with limited FI duration and high IEF at baseline, and could become a valuable tool for treatment of FI, subject to confirmatory phase 3 trial(s). (ClinicalTrialRegister.eu; EudraCT Number: 2010-021463-32).
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Incontinencia Fecal , Calidad de Vida , Humanos , Incontinencia Fecal/terapia , Músculo Esquelético , Resultado del TratamientoRESUMEN
AIMS: This study aimed to evaluate the effect of preoperative administration of oral nutritional supplements (ONS) on the self-sufficiency, physical status, and nutritional status of patients undergoing elective colorectal resections. METHODS: This prospective randomized clinical trial was conducted in a single institution. Patients scheduled to undergo colorectal cancer surgery were randomized to either ONS twice per day for 7 days before surgery or no ONS. RESULTS: We enrolled 120 patients in the study. The two study groups had comparable hospital stay times and comparable numbers of postoperative complications. Laboratory parameter (albumin and prealbumin) values declined in the postoperative period, but differences between study groups were not significant. The groups had comparable arm circumference measurements, muscle mass and fat proportions, and water weights. Patient self-sufficiency in the postoperative period was comparable between groups (P=0.313). Lower limb force declined after surgery, but differences between the groups were not significant (P=0.579). CONCLUSION: Preoperative administration of ONS to patients undergoing elective colorectal surgery did not reduce postoperative morbidity or enhance recovery. Moreover, patient self-sufficiency, physical status, and nutritional status were not influenced by preoperative ONS. Patients should be properly selected for malnourishment before providing nutritional support to manage costs efficiently. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03930888).
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Neoplasias Colorrectales , Apoyo Nutricional , Humanos , Estudios Prospectivos , Apoyo Nutricional/efectos adversos , Estado Nutricional , Tiempo de Internación , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Neoplasias Colorrectales/cirugía , Suplementos DietéticosRESUMEN
Over the past decade, therapeutic monoclonal antibodies (mAbs) have established their role as valuable agents in the treatment of various diseases ranging from cancers to infectious, cardiovascular and autoimmune diseases. Reactive groups of the amino acids within these proteins make them susceptible to many kinds of chemical modifications during manufacturing, storage and in vivo circulation. Among these reactions, the oxidation of methionine residues to their sulfoxide form is a commonly observed chemical modification in mAbs. When the oxidized methionine is in the complementarity-determining region (CDR), this modification can affect antigen binding and thus abrogate biological activity. For these reasons, it is essential to identify oxidation liabilities during the antibody discovery and development phases. Here, we present an in silico method, based on protein modeling and molecular dynamics simulations, to predict the oxidation-liable residues in the variable region of therapeutic antibodies. Previous studies have used the 2-shell water coordination number descriptor (WCN) to identify methionine residues susceptible to oxidation. Although the WCN descriptor successfully predicted oxidation liabilities when the residue was solvent exposed, the method was much less accurate for partially buried methionine residues. Consequently, we introduce a new descriptor, WCN-OH, that improves the accuracy of prediction of methionine oxidation susceptibility by extending the theoretical framework of the water coordination number to incorporate the effects of polar amino acids side chains in close proximity to the methionine of interest.
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Anticuerpos Monoclonales , Metionina , Metionina/química , Anticuerpos Monoclonales/química , Racemetionina , Oxidación-Reducción , Agua , AminoácidosRESUMEN
Perforation, per se, presents the most serious complication of peptic ulcer disease with a mortality rate that cannot be underestimated. Surgery is the only treatment option, which can be performed laparoscopically or via conventional laparotomy. The present study aimed to compare the short-term outcomes of laparoscopy and laparotomy techniques in the surgical treatment of peptic ulcer perforation. A retrospective study design was structured to compare the perioperative and short-term postoperative outcomes of 102 patients who had undergone laparoscopic and conventional repair of the perforated peptic ulcer over a six-year interval (January 1, 2016, to December 31, 2021). Of these, 44 (43.1%) had undergone laparoscopic repair while 58 (56.9%) had surgical repair via conventional laparotomy. The operative time and length of hospital stay were comparable in both subgroups (p=0.984 and p =0.585). Nevertheless, 30-day postoperative morbidity was significantly higher in the open surgery subgroup (75.9% vs. 59.1%, p= 0.032). The risk of relaparotomy was similar in both study subgroups; however, suture dehiscence as a reason for surgical revision was significantly more frequent in the laparoscopic subgroup (13.6% vs 3.4%). Of note, the mortality rate in the laparoscopic group of patients was 13.6%, and in the laparotomy group 41.4%. The laparoscopic approach to peptic ulcer perforation is the procedure of choice for low-risk patients. Conventional surgery seems to be associated with a significantly higher incidence of severe postoperative complications and mortality. However, the higher mortality in these patients is probably related to their worse initial clinical condition.
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Thoracic duct injuries are very rare due to its protected location. Duct is most often injured in polytraumas and during operations in his vicinity. Treatment is primarily conservative, based on a low-fat diet or parenteral nutrition and adequate chest drainage. If the conservative management fails, a surgical duct ligation via thoracotomy, or more conveniently thoracoscopic approach, is necessary. The presented case reports describe the surgical treatment of isolated injury of the thoracic duct via thoracoscopic approach.