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BACKGROUND: Long-term medical and quality of life (QOL) outcomes in voluntary liver donors remain under investigated. The objective of the current study was to report long-term medical outcomes and re-evaluate QOL in living liver donors. METHODS: This was a single-center retrospective cohort study of donors who underwent donor hepatectomy between 2012 and 2018. We investigated long-term outcomes in 7 domains. These include medical problems, surgical procedures, work-related issues, pregnancy outcomes, psychiatric interventions, willingness to donate again, and long-term mortality. QOL was evaluated using short-form 36. RESULTS: The median follow-up time was 61.4 months (53.3-83.7). Among 698 donors, 80 (11.5%) experienced medical problems, 4 (0.6%) had work-related issues, and 20 (2.9%) needed psychiatric assistance. Surgery was performed in 49 donors (7%), and females were more likely to have undergone incisional hernia repair (5.8% vs 1.9%, P = .006). There were 79 postdonation pregnancies including 41 normal vaginal deliveries (51.9%), 35 cesarean sections (44.3%), and 3 miscarriages (3.8%). Willingness to donate again was reported by 658 donors (94.3%). Donors whose recipients were alive were more likely to donate again (95.5% vs 90.5%, P = .01). There were 3 deaths (0.4%) in the long-term. The mean physical composite score at initial and follow-up evaluation was 86.7 ± 13.9 and 76.5 ± 20.9 (P = .001), and the mean mental composite score at initial and follow-up evaluation was 92.1 ± 13.5 and 80.7 ± 16 (P = .001). CONCLUSION: The overall long-term outlook in living liver donors is promising. QOL parameters might deteriorate over time and frequent re-evaluation might be considered.
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Hepatectomia , Transplante de Fígado , Doadores Vivos , Qualidade de Vida , Humanos , Feminino , Masculino , Estudos Retrospectivos , Adulto , Doadores Vivos/psicologia , Hepatectomia/psicologia , Transplante de Fígado/psicologia , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez , Seguimentos , Fatores de Tempo , Adulto Jovem , HerniorrafiaRESUMO
Haemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder caused by uncontrolled activation of the immune system, leading to phagocytosis of blood cells and cytokine storm. HLH can manifest in childhood due to a genetic mutation, but in adults HLH arises secondary to viral infections, autoimmune diseases or neoplastic processes. The most common viral infections associated with HLH are Epstein-Barr virus (EBV) and cytomegalovirus (CMV). EBV and CMV coinfection associated with HLH, however, is exceedingly rare. We present a case of HLH secondary to EBV and CMV coinfection in a young adult who presented with recurrent intermittent high-grade fevers and epistaxis. This case illustrates the importance of considering HLH in patients with idiopathic fevers and to consider all the potential aetiologies for HLH to ensure proper treatment.
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Coinfecção , Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Linfo-Histiocitose Hemofagocítica , Humanos , Linfo-Histiocitose Hemofagocítica/virologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etiologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Masculino , Herpesvirus Humano 4 , Antivirais/uso terapêutico , Citomegalovirus , AdultoRESUMO
Background and Objective: A thorough insight into the management of hand injuries can shape the approach of a surgeon in order to achieve optimal outcomes for the patients. The aim of this study was to share our experience in reconstruction of the hand and establishing an algorithm for classification and treatment of hand injuries. Methods: This is a descriptive cross sectional study and was conducted from January 2020 to August 2022 at Burns and Plastic Surgery center, Peshawar. Data was collected from medical records about the patient demographics, mechanism of injury and type of procedures done. Defect size was classified into small (<5cm), medium (5cm to 10 cm) and large (>10cm). The defect site and size was cross tabulated against the method of soft tissue reconstruction in order to make the algorithm for reconstruction of hand injuries. Data was analyzed using SPSS. Results: The study population included 41 (75.9%) male and 13 (24.1%) female patients, mean age 31.56±14.1. Machine injuries (33.3%) and electric burns (24.1%) were the most common cause of hand soft tissue defects. The most commonly performed flap was Posterior introsseous artery (PIA) flap, followed by First dorsal metacarpal artery (FDMA) flap. Flap necrosis was observed in three cases (5.6%). Conclusion: This treatment algorithm for coverage of soft tissue defects in hand injuries will help with the decision making process of hand reconstruction and has didactic value for novice surgeons. It will also form the foundation for further work on this aspect of hand injuries.
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This study aims to develop a nanodrug delivery system containing podophyllotoxin (PTOX), a known anticancer drug, loaded on graphene oxide (GO). The system's ability to inhibit α-amylase and α-glucosidase enzymes was also investigated. PTOX was isolated from Podophyllum hexandrum roots with a yield of 2.3%. GO, prepared by Hummer's method, was converted into GO-COOH and surface-mobilized using polyethylene glycol (PEG) (1:1) in an aqueous medium to obtain GO-PEG. PTOX was loaded on GO-PEG in a facile manner with a 25% loading ratio. All the samples were characterized using FT-IR spectroscopy, UV/visible spectroscopy, and scanning electron microscopy (SEM). In FT-IR spectral data, GO-PEG-PTOX exhibited a reduction in acidic functionalities and there was an appearance of the ester linkage of PTOX with GO. The UV/visible measurements suggested an increase of absorbance in 290-350 nm regions for GO-PEG, suggesting the successful drug loading on its surface (25%). GO-PEG-PTOX exhibited a rough, aggregated, and scattered type of pattern in SEM with distinct edges and binding of PTOX on its surface. GO-PEG-PTOX remained potent in inhibiting both α-amylase and α-glucosidase with IC50 values of 7 and 5 mg/mL, closer to the IC50 of pure PTOX (5 and 4.5 mg/mL), respectively. Owing to the 25% loading ratio and 50% release within 48 h, our results are much more promising. Additionally, the molecular docking studies confirmed four types of interactions between the active centers of enzymes and PTOX, thus supporting the experimental results. In conclusion, the PTOX-loaded GO nanocomposites are promising α-amylase- and α-glucosidase-inhibitory agents when applied in vitro and have been reported for the first time.
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PURPOSE: Radiofrequency ablation (RFA) is a curative treatment option for small lung metastases, which conventionally involves multiple freehand manipulations until the treating electrode is satisfactorily positioned. Stereotactic and robotic guidance has been gaining popularity for liver ablation, although has not been established in lung ablation. The purpose of this study is to determine the feasibility, safety, and accuracy of robotic RFA for pulmonary metastases, and compare procedures with a conventional freehand cohort. METHODS: A single center study with prospective robotic cohort, and retrospective freehand cohort. RFA was performed under general anesthesia using high frequency jet ventilation and CT guidance. Main outcomes were (i) feasibility/technical success (ii) safety using Common Terminology Criteria for Adverse Events (iii) targeting accuracy (iv) number of needle manipulations for satisfactory ablation. Robotic and freehand cohorts were compared using Mann-Whitney U tests for continuous variables, and Fisher's exact for categorical variables. RESULTS: Thirty-nine patients (mean age 65 ± 13 years, 20 men) underwent ablation of 44 pulmonary metastases at single specialist cancer center between July 2019 and August 2022. 20 consecutive participants underwent robotic ablation, and 20 consecutive patients underwent freehand ablation. All 20/20 (100%) robotic procedures were technically successful, and none were converted to freehand procedures. There were 6/20 (30%) adverse events in the robotic cohort, and 15/20 (75%) in the freehand cohort (P = 0.01). Robotic placement was highly accurate with 6 mm tip-to-target distance (range 0-14 mm) despite out-of-plane approaches, with fewer manipulations than freehand placement (median 0 vs. 4.5 manipulations, P < 0.001 and 7/22, 32% vs. 22/22, 100%, P < 0.001). CONCLUSIONS: Robotic radiofrequency ablation of pulmonary metastases with general anesthesia and high frequency jet ventilation is feasible and safe. Targeting accuracy is high, and fewer needle/electrode manipulations are required to achieve a satisfactory position for ablation than freehand placement, with early indications of reduced complications.
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Ablação por Cateter , Neoplasias Pulmonares , Ablação por Radiofrequência , Procedimentos Cirúrgicos Robóticos , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Estudos de Coortes , Estudos Prospectivos , Ablação por Cateter/métodos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Thymoma, a tumor of thymic lymphocytes or thymic epithelial cells (TECs), is a common spontaneous tumor in Wistar Han rats, especially in females with up to 18% incidence in controls. In addition to sex, there are rat strain differences in background incidence of thymomas such as Sprague Dawley versus Wistar Han rats. Human thymomas are very rare and without clear differences in incidence between males and females. Immunomodulatory and anti-inflammatory pharmaceutical drug classes, including Janus kinase inhibitors, increase the incidence of benign thymoma in two-year rat carcinogenicity studies. Potential non-genotoxic mechanisms that might contribute to the pathogenesis of thymoma development in one sex (female) Wistar Han rats include: (1) hormonal differences, (2) high proliferation rate of TECs, (3) delayed physiologic thymic involution, and/or (4) significant level of immunosuppression at high doses of a pharmaceutical drug. Factors to consider in the human cancer risk assessment of pharmaceutical-induced thymoma are: the genotoxicity of the test article, sex and strain of rats, exposure safety margins, and pathophysiologic differences and similarities of thymoma between rats and humans. Totality of weight of evidence approach and available data suggest thymomas observed in carcinogenicity studies of pharmaceutical drugs are not relevant for human risk at clinically relevant therapeutic doses.
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Anti-Inflamatórios , Agentes de Imunomodulação , Inibidores de Janus Quinases , Timoma , Neoplasias do Timo , Animais , Feminino , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Medição de Risco , Timoma/induzido quimicamente , Timoma/patologia , Neoplasias do Timo/induzido quimicamente , Neoplasias do Timo/patologia , Anti-Inflamatórios/efeitos adversos , Inibidores de Janus Quinases/efeitos adversos , Agentes de Imunomodulação/efeitos adversosRESUMO
This prospective single-center study enrolled 50 women with 51 contrast-enhanced mammography (CEM)-enhancing lesions that lacked a sonographic or mammographic correlate. Trial participants underwent CEM-guided biopsy. Biopsy was technically successful for 46 lesions and was not performed for five nonvisualized lesions (all nonmass enhancement), yielding a cancellation rate of 9.8%. Mean biopsy time was 16.6 minutes. All biopsies revealed concordant pathology (25 benign, 10 high-risk, 11 malignant). No non-visualized or benign lesion yielded malignancy at follow-up.
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Neoplasias da Mama , Mama , Feminino , Humanos , Biópsia , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Biópsia Guiada por Imagem , Mamografia , Estudos Prospectivos , UltrassonografiaRESUMO
To increase its operational stability and ongoing reusability, B. subtilis pectinase was immobilized on iron oxide nanocarrier. Through co-precipitation, magnetic iron oxide nanoparticles were synthesized. Scanning electron microscopy (SEM) and energy dispersive electron microscopy (EDEX) were used to analyze the nanoparticles. Pectinase was immobilized using glutaraldehyde as a crosslinking agent on iron oxide nanocarrier. In comparison to free pectinase, immobilized pectinase demonstrated higher enzymatic activity at a variety of temperatures and pH levels. Immobilization also boosted pectinase's catalytic stability. After 120 h of pre-incubation at 50 °C, immobilized pectinase maintained more than 90% of its initial activity due to the iron oxide nanocarrier, which improved the thermal stability of pectinase at various temperatures. Following 15 repetitions of enzymatic reactions, immobilized pectinase still exhibited 90% of its initial activity. According to the results, pectinase's catalytic capabilities were enhanced by its immobilization on iron oxide nanocarrier, making it economically suitable for industrial use.
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Enzimas Imobilizadas , Nanopartículas de Magnetita , Enzimas Imobilizadas/metabolismo , Estabilidade Enzimática , Glutaral , Poligalacturonase/metabolismo , Concentração de Íons de Hidrogênio , Nanopartículas Magnéticas de Óxido de Ferro , Temperatura , CinéticaRESUMO
Due to functional and physicochemical properties, starch in its native state has limited range of applications. Simultaneously, information on effects of different sugars and their interactions with modified starch on gluten-free model dough is also limited. To better overcome these restrictions, the effects of sucrose, trehalose, maltose and xylose on rheology, water mobility and microstructure of gluten-free dough prepared with high hydrostatic pressure (HHP) treated maize (MS), potato (PS) and sweet potato starch (SS) were investigated. MS, PS and SS dough with trehalose exhibited a lower degree of dependence of G' on frequency sweep (z'), higher strength (K) and relative elastic part of maximum creep compliance (Je/Jmax), suggesting stable network structure formation. Total gas production (VT) of MS dough with maltose, PS dough with sucrose and SS dough with trehalose was increased from 588 to 1454 mL, 537 to 1498 mL and 637 to 1455 mL respectively. Higher weakly bound water (T22) was found in the dough with trehalose at 60 min of fermentation, suggesting more hydrogen bonds and stable network. Thus, trehalose might be a potential improver in HHP treated starch-based gluten-free products.
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Maltose , Trealose , Xilose , Sacarose , Água/química , Pressão Hidrostática , Amido/química , Reologia , Glutens/química , FarinhaRESUMO
Backgrounds/Aims: Locally advanced gallbladder cancer (GBC) is associated with survival limited to a few months. Extended resections (ER) are occasionally performed in this group and outcomes remain inconclusive. This study assessed outcomes after ER for locally advanced GBC. Methods: Patients who underwent ER for GBC between 2011 and 2020 were reviewed. ER was defined as a major hepatectomy alone (n = 9), a pancreaticoduodenectomy (PD) with or without minor hepatectomy (n = 3), a major hepatectomy with PD (HPD) (n = 3) or vascular resection and reconstruction (n = 4). We assessed 30-day morbidity, mortality, and 2-year overall survival (OS). Results: Among 19 patients, negative margins were achieved in 14 (73.6%). The 30-day mortality was 1/9 (11.1%) for a major hepatectomy, 0/3 (0%) for a minor HPD, 2/3 (66.7%) for a major HPD, and 1/4 (25.0%) for vascular resection. All short term survivors (< 6 months) (n=8) had preoperative jaundice and 6/8 (75.0%) underwent a major HPD or vascular resection. There were five (26.3%) long term survivors. The median OS in patients with and without preoperative jaundice was 4.1 months (0.7-11.1 months) and 13.7 months (12-30.4 months), respectively (p = 0.009) (2-year OS = 7% vs. 75%; p = 0.008). The median OS in patients who underwent a major hepatectomy alone or a minor HPD was 11.3 months (6.8-17.3 months) versus 1.4 months (0.3-4.1 months) (p = 0.02) in patients who underwent major HPD or vascular resection (2 year OS = 33% vs. not reached) (p = 0.010) respectively. Conclusions: In selected patients with GBC, when ER is limited to a major hepatectomy alone, or a minor HPD, acceptable survival can be achieved.
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BACKGROUND: The cynomolgus macaque has become the most used non-human primate species in nonclinical safety assessment during the past decades. METHODS: This review summarizes the biological data and organ system development milestones of the cynomolgus macaque available in the literature. RESULTS: The cynomolgus macaque is born precocious relative to humans in some organ systems (e.g., nervous, skeletal, respiratory, and gastrointestinal). Organ systems develop, refine, and expand at different rates after birth. In general, the respiratory, gastrointestinal, renal, and hematopoietic systems mature at approximately 3 years of age. The female reproductive, cardiovascular and hepatobiliary systems mature at approximately 4 years of age. The central nervous, skeletal, immune, male reproductive, and endocrine systems complete their development at approximately 5 to 9 years of age. CONCLUSIONS: The cynomolgus macaque has no meaningful developmental differences in critical organ systems between 2 and 3 years of age for use in nonclinical safety assessment.
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Biologia , Masculino , Feminino , Animais , Macaca fascicularisRESUMO
PURPOSE: To determine the relationship of various systemic and ocular characteristics with perifoveal and macular vessel density in healthy African American eyes. DESIGN: A population-based cross-sectional study of prospectively recruited African Americans ≥40 years of age. Participants underwent 3×3 mm and 6×6 mm macula scans using spectral-domain optical coherence tomography angiography (OCTA), clinical examinations and clinical questionnaires. Participants with glaucoma, severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy and macular oedema were excluded. Custom MATLAB based software quantified vessel area density (VAD) and vessel skeleton density (VSD) in the superficial retinal layer of the macula. Multivariable regression analysis, controlling for inter-eye correlation, was performed to determine systemic and ocular determinants of macular vessel metrics using stepwise selection. Candidate variables included: age, gender, body mass index, history of smoking, history of diabetes, diabetes duration, history of stroke or brain haemorrhage, systolic blood pressure, diastolic blood pressure (DBP), pulse pressure, mean arterial pressure, central subfield thickness (CSFT), visual field mean deviation, intraocular pressure, axial length (AL), mean ocular perfusion pressure and signal strength (SS). RESULTS: A total of 2221 OCTA imaged eyes from 1472 participants were included in this study. Reduced perifoveal and macular VAD and VSD were independently associated with longer AL, reduced SS, reduced CSFT and older age. Male gender and lower DBP were also associated with reduced perifoveal and macular VSD. CONCLUSIONS: When interpreting OCTA images in a clinical setting, it is important to consider the effects ocular and systemic characteristics may have on the macular microcirculation.
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Retinopatia Diabética , Vasos Retinianos , Humanos , Masculino , Negro ou Afro-Americano , Estudos Transversais , Retinopatia Diabética/diagnóstico , Angiofluoresceinografia/métodos , Pressão Intraocular , Tomografia de Coerência Óptica/métodos , Feminino , AdultoRESUMO
Poly(ADP-ribose) polymerase inhibitors (PARPi) are approved as monotherapies in BRCA1/2-mutated (mBRCA1/2) metastatic breast and ovarian cancers, and in advanced pancreatic and metastatic castration-resistant prostate cancers. Differential safety profiles across PARPi necessitate improved mechanistic understanding of inhibitor differences, especially with expansion of PARPi indications and drug combinations. Here, we report in vitro evaluations of PARPi (-/+ PARP trapper temozolomide, TMZ) with reference to total clinical mean concentration average or maximum (tCavg, tCmax), to elucidate contributions of primary pharmacology and structural differences to clinical efficacy and safety. In biochemical assays, rucaparib and niraparib demonstrated off-target secondary pharmacology activities, and in selectivity assays, talazoparib, olaparib, and rucaparib inhibited a broader panel of PARP enzymes. In donor-derived human bone marrow mononuclear cells, only olaparib both increased early apoptosis and decreased the cell viability half inhibitory concentration (IC50) at ≤ tCavg, whereas other PARPi only did so in the presence of TMZ. In cancer cell lines with DNA damage repair mutations, all PARPi decreased cell viability in H1048 but not TK6 cells, and only talazoparib decreased cell growth in DU145 cells at ≤ tCavg concentrations. When combined with low dose TMZ, only talazoparib left-shifted the functional consequences of PARP trapping (S-phase arrest, apoptosis, S-phase double-stranded breaks) and reduced cell viability/growth in TK6 and DU145 cell lines at ≤ tCavg, whereas the other inhibitors required high-dose TMZ. Our study suggests structural differences across PARPi may contribute to differences in PARP selectivity and off-target activities, which along with distinct pharmacokinetic properties, may influence inhibitor-specific toxicities in patients.
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Inibidores de Poli(ADP-Ribose) Polimerases , Humanos , Masculino , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , TemozolomidaRESUMO
PURPOSE: Textbook outcome (TO) is a composite measure of outcome and provides superior assessment of quality of care after surgery. TO after major living donor hepatectomy (MLDH) has not been assessed. The objective of this study was to determine the rate of TO and its associated factors, after MLDH. METHODS: This was a single center retrospective review of living liver donors who underwent MLDH between 2012 and 2021 (n = 1022). The rate of TO and its associated factors was determined. RESULTS: Among 1022 living donors (of whom 693 [67.8%] were males, median age 26 [range, 18-54] years), TO was achieved in 714 (69.9%) with no donor mortality. Majority of donors met the cutoffs for individual outcome measures: 908 (88.8%) for no major complications, 904 (88.5%) for ICU stay ≤ 2 days, 900 (88.1%) for hospital stay ≤ 10 days, 990 (96.9%) for no perioperative blood transfusion, 1004 (98.2%) for no 30-day re-admission, and 1014 (99.2%) for no post-hepatectomy liver failure. Early donation era (before streamlining of donor operative pathways) was associated with failure to achieve TO [OR 1.4, CI 1.1-1.9, P = 0.006]. TO was achieved in 506/755 (67%) donors in the early donation era versus 208/267 (77.9%) in the later period (P = 0.001). CONCLUSION: Despite zero mortality and low complication rate, TO was achieved in approximately 70% donors. TO was modifiable and improved with changes in donor operative pathway.
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Transplante de Fígado , Doadores Vivos , Masculino , Humanos , Adulto , Feminino , Hepatectomia/efeitos adversos , Coleta de Tecidos e Órgãos/efeitos adversos , Transplante de Fígado/efeitos adversos , Fígado , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND: Ureteroscopy (URS) is a safe and highly effective treatment option for treatment of ureteral calculi. With the advancement of technology, there is also expansion of its indications including use in early or emergency setting. This study aims to compare safety and efficacy of emergency ureteroscopy (EmURS) versus elective ureteroscopy (ElURS) for ureteral stones. METHODS: Patients with unilateral single radio-opaque ureteral stone who underwent semi-rigid URS from January 2008 till December 2019 were included. Patients with solitary kidney, uro-sepsis, pregnancy or pre-operative drainage with nephrostomy or JJ stent were excluded. EmURS was defined as URS being performed within 48 hours of presentation, while ElURS was defined as URS performed after failed medical expulsive therapy. Patient, stone and outcome related variables were compared in both groups. Stone free rate was defined as no evidence of stone on plain x-ray KUB after 1 week. RESULTS: We compared 132 patients in EmURS group against 264 in ElURS group. Age, gender, comorbidities, stone location, laterality and mean stone size were comparable in both groups. EmURS had a less median operative time (p=0.05). Stone free rate achieved was 90.2% in EmURS and 87.1% in ElURS, respectively (p=0.38). Double J stent was placed in 44.7% and 46.2% of EmURS and ElURS respectively (p=0.89). Ancillary procedures were performed in 9.8% of EmURS and 11.7% of ElURS (p=0.57). Overall complication rates were reported in 7.6% in EmURS and 11.7% in ElURS (p=0.22) and most were Clavien grade 1. CONCLUSIONS: Emergency URS for ureteral stones is a safe and effective one-stage definitive treatment option for patients with acute renal colic not responding to conservative management.
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Litotripsia , Cólica Renal , Cálculos Ureterais , Feminino , Humanos , Litotripsia/métodos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Cálculos Ureterais/terapia , Ureteroscopia/efeitos adversos , Ureteroscopia/métodosRESUMO
OBJECTIVE: A commercially available CT-guided robot offers enhanced abilities in planning, targeting, and confirming accurate needle placement. In this short communication, we describe our first UK experience of robotic interventional oncology procedures. METHODS: We describe the device, discuss installation, operation, and report upon needle insertion success, accuracy (path deviation; PD and tip deviation; TD), number of adjustments, complications, and procedural success. RESULTS: Nine patients (seven males), median age 66 years (range 43-79) were consented for biopsy or ablation between March and April 2021. Needle placement in biopsy was more accurate than ablation (median 1 vs 11 mm PD and 1 vs 20 mm TD) and required fewer adjustments (median 0 vs 5). No complications arose, and all procedures were successful (diagnostic material obtained or complete ablation at follow-up). CONCLUSION: Short procedure times and very high levels of accuracy were readily achieved with biopsy procedures, although tumour ablation was less accurate which likely reflects higher procedural complexity. ADVANCES IN KNOWLEDGE: Achieving highly accurate robotic biopsy with is feasible within a very short time span. Further work is required to maximise the potential of robotic guidance in tumour ablation procedures, which is likely due to higher complexity giving a longer learning curve.
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Procedimentos Cirúrgicos Robóticos , Robótica , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Agulhas , Procedimentos Cirúrgicos Robóticos/métodos , Tomografia Computadorizada por Raios X/métodos , Reino UnidoRESUMO
The nonclinical safety package to support development and approval of drugs intended to be administered by topical application generally follows International Council for Harmonisation multidisciplinary 3 (ICH M3) and topic specific safety (ICH S) guidances. However, some aspects of topical drug development may require case-by-case determination of nonclinical safety strategies. The necessity to conduct a dermal rodent carcinogenicity study is one such example that is not considered an obligate component of a nonclinical safety data package for drug approval. While absence of systemic exposure, as stated in ICH M3, is a primary reason to forego a dermal carcinogenicity assessment, there may also be other factors for consideration in determining the need for a life-time carcinogencity study by dermal route to aid in the overall human cancer risk assessment. We therefore reviewed nonclinical carcinogencity data packages from drugs approved by the FDA or PMDA over a ~25 year time period to evaluate outcomes of oral versus topical carcinogencity studies and to understand their utility for informing the overall human risk assessment. We also discuss various other properties of topical small molecules that could impact the decisions to conduct a dermal life-time rodent carcinogenicity study. Collectively, the need to conduct 2-year dermal carcinogenicity studies in rodents should be determined case-by-case and consider scientific factors such existing systemic toxicity and carcinogenicity study data, anticipated drug exposures in skin, skin evaluation from the chronic minipig toxicity study, and genetic toxicity profile.
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Preparações Farmacêuticas , Roedores , Animais , Testes de Carcinogenicidade , Medição de Risco , Suínos , Porco MiniaturaRESUMO
OBJECTIVE: The aim of this article is to share our experience of thumb defects based on the defect irrespective of the etiology of the defect and to work towards standardizing the treatment for thumb defects. METHODOLOGY: This study was conducted at the Burns and plastic surgery center at Hayatabad Medical complex from 2018 to 2021. Thumb defects were divided into small (< 3 cm), medium (4-8cm) and large defects (> 9cm). Post-operatively, patients were evaluated for complications. The type of flaps were stratified for size and site of the soft tissue defects to generate a standardized algorithm for thumb soft tissue reconstruction. RESULTS: After scrutinizing the data, 35 patients qualified for the study, including 71.4% (25) males and 28.6% (10) females. The mean age was 31.17+15.8SD. Right thumb was affected in majority of the study population (57.1%). Majority of the study population was affected by machine injury and post-traumatic contractures, affecting 25.7% (n=9) and 22.9% (n=8) respectively. First web-space and injuries distal to IPJ of thumb were the most common areas affected, accounting for 28.6% (n=10) each. First dorsal metacarpal artery flap was the most common flap followed by retrograde posterior interosseous artery flap, observed in 11 (31.4%) and 6 (17.1%) cases. The most common complication observed in the study population was flap congestion (n=2, 5.7%) with a complete flap loss in 1 patient (2.9%) cases. Based on the cross tabulation of flaps against the size and location of defects, an algorithm was developed to help standardize reconstruction of thumb defects. CONCLUSION: Thumb reconstruction is critical in restoring hand function of the patient. The structured approach towards these defects make their assessment and reconstruction easy especially for novice surgeons. This algorithm can further be extended to include defects of the hand irrespective of etiology. Most of these defects can be covered with local easy to do flaps without the need for a microvascular reconstruction.
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Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Polegar/irrigação sanguínea , Polegar/lesões , Polegar/cirurgia , Lesões dos Tecidos Moles/cirurgia , Retalhos Cirúrgicos/irrigação sanguínea , Padrões de Referência , Resultado do Tratamento , Transplante de PeleRESUMO
PURPOSE: The aims of this study were to develop and apply a method to correct for the differences in partial volume effects of pre-therapy Technetium-99 m (99mTc)-MAA SPECT and post-therapy Yttrium-90 (90Y) bremsstrahlung SPECT imaging in selective internal radiation therapy, and to use this method to improve quantitative comparison of predicted and delivered 90Y absorbed doses. METHODS: The spatial resolution of 99mTc SPECT data was converted to that of 90Y SPECT data using a function calculated from 99mTc and 90Y point spread functions. This resolution conversion method (RCM) was first applied to 99mTc and 90Y SPECT phantom data to validate the method, and then to clinical data to assess the power of 99mTc SPECT imaging to predict the therapeutic absorbed dose. RESULTS: The maximum difference between absorbed doses to phantom spheres was 178%. This was reduced to 27% after the RCM was applied. The clinical data demonstrated differences within 38% for mean absorbed doses delivered to the normal liver, which were reduced to 20% after application of the RCM. Analysis of clinical data showed that therapeutic absorbed doses delivered to tumours greater than 100 cm3 were predicted to within 52%, although there were differences of up to 210% for smaller tumours, even after the RCM was applied. CONCLUSIONS: The RCM was successfully verified using phantom data. Analysis of the clinical data established that the 99mTc pre-therapy imaging was predictive of the 90Y absorbed dose to the normal liver to within 20%, but had poor predictability for tumours smaller than 100 cm3.
Assuntos
Embolização Terapêutica , Neoplasias Hepáticas , Humanos , Microesferas , Agregado de Albumina Marcado com Tecnécio Tc 99m , Tomografia Computadorizada de Emissão de Fóton Único , Radioisótopos de Ítrio/uso terapêuticoRESUMO
Outpatient parenteral administration of medications and blood transfusions using an outpatient parenteral antibiotic therapy (OPAT) unit has gradually become a standard of care. We report a continuous quality improvement project that was conducted on an OPAT unit of a tertiary care cancer hospital in Lahore, Pakistan. Prior to the initiation of the project, it was identified that 52% of the patient encounters in the OPAT unit were being delayed by a median of 63.5 minutes. A cause-and-effect analysis was performed, using a fishbone diagram, to identify the reasons for the delay in appointments. Based on the findings, several modifications were made to the processes of the OPAT unit including, but not limited to, a computerised physician order entry (CPOE) system module for prescribing, dispensing, reviewing and dispensing medications, changes in the nursing and staffing roster, and assignment of additional duties to the ward clerks. These changes resulted in improvement of waiting time to a median of 24.5 minutes and percentage delay in patient meetings decreased to 18%. Likewise, in 2019, 5,399 (27%) more patient meetings took place compared with 2018, which would have otherwise costed the hospital between 21.28 to 45.85 million Pakistani rupees. The use of continuous quality improvement techniques in the OPAT unit can result in substantial and appropriate changes in the process of patient flow, leading to measurable and significant reductions in the variability of care, and optimisation of service.