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PURPOSE: Endoscopic biopsy is recommended for diagnosis of nasopharyngeal carcinoma (NPC). A proportion of lesions are hidden from endoscopic view but detected with magnetic resonance imaging (MRI). This systematic review and meta-analysis investigated the diagnostic performance of MRI for detection of NPC. METHODS: An electronic search of twelve databases and registries was performed. Studies were included if they compared the diagnostic accuracy of MRI to a reference standard (histopathology) in patients suspected of having NPC. The primary outcome was accuracy for detection of NPC. Random-effects models were used to pool outcomes for sensitivity, specificity, and positive and negative likelihood ratio (LR). Bias and applicability were assessed using the modified QUADAS-2 tool. RESULTS: Nine studies were included involving 1736 patients of whom 337 were diagnosed with NPC. MRI demonstrated a pooled sensitivity of 98.1% (95% CI 95.2-99.3%), specificity of 91.7% (95% CI 88.3-94.2%), negative LR of 0.02 (95% CI 0.01-0.05), and positive LR of 11.9 (95% CI 8.35-16.81) for detection of NPC. Most studies were performed in regions where NPC is endemic, and there was a risk of selection bias due to inclusion of retrospective studies and one case-control study. There was limited reporting of study randomization strategy. CONCLUSION: This study demonstrates that MRI has a high pooled sensitivity, specificity, and negative predictive value for detection of NPC. MRI may be useful for lesion detection prior to endoscopic biopsy and aid the decision to avoid biopsy in patients with a low post-test probability of disease.
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Imagen por Resonancia Magnética , Neoplasias Nasofaríngeas , Estudios de Casos y Controles , Humanos , Imagen por Resonancia Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Neoplasias Nasofaríngeas/diagnóstico por imagen , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Identification of reliable outcome predictors in coronavirus disease 2019 (COVID-19) is of paramount importance for improving patient's management. METHODS: A systematic review of literature was conducted until 24 April 2020. From 6843 articles, 49 studies were selected for a pooled assessment; cumulative statistics for age and sex were retrieved in 587 790 and 602 234 cases. Two endpoints were defined: (a) a composite outcome including death, severe presentation, hospitalization in the intensive care unit (ICU) and/or mechanical ventilation; and (b) in-hospital mortality. We extracted numeric data on patients' characteristics and cases with adverse outcomes and employed inverse variance random-effects models to derive pooled estimates. RESULTS: We identified 18 and 12 factors associated with the composite endpoint and death, respectively. Among those, a history of CVD (odds ratio (OR) = 3.15, 95% confidence intervals (CIs) 2.26-4.41), acute cardiac (OR = 10.58, 5.00-22.40) or kidney (OR = 5.13, 1.78-14.83) injury, increased procalcitonin (OR = 4.8, 2.034-11.31) or D-dimer (OR = 3.7, 1.74-7.89), and thrombocytopenia (OR = 6.23, 1.031-37.67) conveyed the highest odds for the adverse composite endpoint. Advanced age, male sex, cardiovascular comorbidities, acute cardiac or kidney injury, lymphocytopenia and D-dimer conferred an increased risk of in-hospital death. With respect to the treatment of the acute phase, therapy with steroids was associated with the adverse composite endpoint (OR = 3.61, 95% CI 1.934-6.73), but not with mortality. CONCLUSIONS: Advanced age, comorbidities, abnormal inflammatory and organ injury circulating biomarkers captured patients with an adverse clinical outcome. Clinical history and laboratory profile may then help identify patients with a higher risk of in-hospital mortality.
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Lesión Renal Aguda/epidemiología , Enfermedades Cardiovasculares/epidemiología , Infecciones por Coronavirus/terapia , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Neumonía Viral/terapia , Polipéptido alfa Relacionado con Calcitonina/metabolismo , Fumar/epidemiología , Trombocitopenia/epidemiología , Enfermedad Aguda , Corticoesteroides/uso terapéutico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Betacoronavirus , Proteína C-Reactiva/metabolismo , COVID-19 , Trastornos Cerebrovasculares/epidemiología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/mortalidad , Diabetes Mellitus/epidemiología , Femenino , Ferritinas/metabolismo , Cardiopatías , Mortalidad Hospitalaria , Hospitalización , Humanos , Hipertensión/epidemiología , Unidades de Cuidados Intensivos , Interleucina-6/metabolismo , Hepatopatías/epidemiología , Linfopenia/epidemiología , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Obesidad/epidemiología , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/metabolismo , Neumonía Viral/mortalidad , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Respiración Artificial , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factores Sexuales , Adulto JovenRESUMEN
INTRODUCTION: In recent years, the preservation of residual hearing has become a major factor in patients undergoing cochlear implantation (CI). In studies attempting to pharmaceutically improve hearing preservation rates, glucocorticoids (GCs) applied perioperatively in many institutions have emerged as a promising treatment regimen. Although dexamethasone is most commonly used and has been applied successfully by various research groups, recently pharmacological properties have been reported to be relatively unsuitable for topical delivery to the inner ear. Consequently other glucocorticoids merit further evaluation. The aim of this study was therefore to evaluate the otoprotective effects of the topical application of a sustained-release triamcinolone acetonide (TAAC) hydrogel in CI with hearing preservation. METHODS: Normal-hearing pigmented guinea pigs were randomized into a group receiving a single dose of a 6% TAAC poloxamer 407 hydrogel, a group receiving a 30% TAAC hydrogel and a control group. All hydrogel applications were performed 1 day prior to CI. After a cochleostomy was drilled, a specifically designed silicone electrode was inserted into the scala tympani for 5 mm. Frequency-specific compound action potentials of the auditory nerve (0.5-32 kHz) were measured pre- and directly postoperatively as well as on days 3, 7, 14, 21, and 28. Finally, temporal bones were harvested for histological evaluation. RESULTS: Application of the TAAC hydrogels resulted in significantly reduced hearing threshold shifts in low, middle and high frequencies and improved spiral ganglion cell survival in the second turn of the cochlea. Outer hair cell numbers in the basal and second turn of the cochlea were slightly reduced after TAAC application. CONCLUSION: In summary, we were able to demonstrate functional benefits of a single preoperative application of a TAAC hydrogel in a guinea pig model for CI, which persisted until the end of the observational period, that is, 28 days after surgery.
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Implantación Coclear/efectos adversos , Implantes Cocleares , Pérdida Auditiva/prevención & control , Audición/efectos de los fármacos , Hidrogeles/administración & dosificación , Triamcinolona Acetonida/administración & dosificación , Potenciales de Acción/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Cóclea/efectos de los fármacos , Cóclea/cirugía , Preparaciones de Acción Retardada/administración & dosificación , Cobayas , Pérdida Auditiva/etiología , Pruebas Auditivas , Ganglio Espiral de la Cóclea/efectos de los fármacosRESUMEN
OBJECTIVE: The objective of our study was to assess whether HPV-positive TSCC had better survival and prognosis rates, when compared to HPV-negative TSCC. METHOD: A systematic review and meta-analysis was performed comparing HPV status in TSCC patients. TSCC was confirmed with histopathology and HPV status was confirmed with PCR, immunohistochemistry and/or in-situ-hybridisation. The primary endpoints were overall survival (OS) and disease free survival (DFS). RESULTS: Twenty-four studies were identified, involving 1921 TSCC cases, of which 56.2% (1079) were HPV positive. OS was significantly higher in patients with HPV-positive compared to HPV-negative TSCC in years 1-5 (OR 2.54, P < 0.01; OR 2.93 P < 0.01; OR 2.74 P < 0.01; OR 2.20 P < 0.01, and OR 2.14 P < 0.01 respectively). Similarly, DFS was also significantly higher in patients with HPV-positive compared to HPV-negative TSCC in years 1-3 (OR 2.86, P < 0.01; OR 2.60 P < 0.02; and OR 2.60 P < 0.01 respectively), which was attenuated in years 4 and 5 (OR 1.83, P = 0.10 and OR 1.50, P = 0.12). CONCLUSION: This is the largest meta-analysis with 1921 patients, comparing non-HPV induced TSCC and HPV induced TSCC, looking at outcome and survival. HPV-positive had better OS and DFS.
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Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Carcinoma de Células Escamosas/virología , Humanos , Infecciones por Papillomavirus/virología , Pronóstico , Análisis de Supervivencia , Neoplasias Tonsilares/virologíaRESUMEN
The otoprotective effects of thermoreversible poloxamer 407 hydrogels containing dexamethasone or triamcinolone acetonide were evaluated in an animal model of noise-induced hearing loss. Seven days after noise exposure, hearing threshold shifts at 16 kHz were significantly reduced in the 6% dexamethasone group (p < 0.05). Even though no significant differences in hair cell counts were found, histological analysis revealed a significantly higher spiral ganglion cell density in the first turn of the cochlea in this group (p < 0.05). No otoprotective effects were observed after the application of the triamcinolone acetonide hydrogels. As the findings of this study indicate potential otoprotective effects of sustained topical dexamethasone delivery in the setting of noise-induced hearing loss, this strategy merits further evaluation.
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Preparaciones de Acción Retardada/uso terapéutico , Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Pérdida Auditiva Provocada por Ruido/tratamiento farmacológico , Hidrogeles/uso terapéutico , Triamcinolona Acetonida/uso terapéutico , Animales , Umbral Auditivo/efectos de los fármacos , Cóclea/efectos de los fármacos , Preparaciones de Acción Retardada/administración & dosificación , Dexametasona/administración & dosificación , Modelos Animales de Enfermedad , Femenino , Glucocorticoides/administración & dosificación , Cobayas , Audición/efectos de los fármacos , Hidrogeles/administración & dosificación , Masculino , Triamcinolona Acetonida/administración & dosificaciónRESUMEN
OBJECTIVES: Exact location of the inferior alveolar nerve (IAN) bundle is very important. The aim of this study is to evaluate the relationship between the mandibular third molar and the mandibular canal by cone-beam computed tomography. STUDY DESIGN: This was a cross-sectional study with convenience sampling. 94 mandibular CBCTs performed with CSANEX 3D machine (Soredex, Finland) and 3D system chosen. Vertical and horizontal relationship between the mandibular canal and the third molar depicted by 3D, panoramic reformat view of CBCT and cross-sectional view. Cross-sectional view was our gold standard and other view evaluated by it. RESULTS: There were significant differences between the vertical and horizontal relation of nerve and tooth in all views (p < 0.001). CONCLUSION: The results showed differences in the position of the inferior alveolar nerve with different views of CBCT, so CBCT images are not quite reliable and have possibility of error.
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Tomografía Computarizada de Haz Cónico/estadística & datos numéricos , Mandíbula/diagnóstico por imagen , Nervio Mandibular/diagnóstico por imagen , Tercer Molar/diagnóstico por imagen , Algoritmos , Anatomía Transversal/estadística & datos numéricos , Estudios Transversales , Humanos , Imagenología Tridimensional/estadística & datos numéricos , Mandíbula/inervación , Tercer Molar/inervación , Radiografía Panorámica/estadística & datos numéricos , Reproducibilidad de los Resultados , Ápice del Diente/diagnóstico por imagen , Raíz del Diente/diagnóstico por imagenRESUMEN
Anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy is an increasingly crucial in cancer treatment. To date, the Federal Drug Administration (FDA) has approved four PD-L1 immunohistochemistry (IHC) staining protocols, commercially available in the form of "kits", facilitating testing for PD-L1 expression. These kits comprise four PD-L1 antibodies on two separate IHC platforms, each utilizing distinct, non-interchangeable scoring systems. Several factors, including tumor heterogeneity and the size of the tissue specimens assessed, can lead to PD-L1 status misclassification, potentially hindering the initiation of therapy. Therefore, the development of more accurate predictive biomarkers to distinguish between responders and non-responders prior to anti-PD-1/PD-L1 therapy warrants further research. Achieving this goal necessitates refining sampling criteria, enhancing current methods of PD-L1 detection, and deepening our understanding of the impact of additional biomarkers. In this article, we review potential solutions to improve the predictive accuracy of PD-L1 assessment in order to more precisely anticipate patients' responses to anti-PD-1/PD-L1 therapy, monitor disease progression and predict clinical outcomes.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/metabolismo , Inmunohistoquímica , Antígeno B7-H1 , Biomarcadores de Tumor/metabolismo , InmunoterapiaRESUMEN
INTRODUCTION: Liver dysfunction can derive from severe sepsis and might be associated with poor prognosis. However, diagnosis of septic liver dysfunction is challenging due to a lack of appropriate tests. Measurement of maximal liver function capacity (LiMAx test) has been successfully evaluated as a new diagnostic test in liver resection and transplantation. The aim of this study was to evaluate the LiMAx test during sepsis in comparison to biochemical tests and the indocyanin green test (ICG-PDR). METHODS: We prospectively investigated 28 patients (8 female and 20 male, age range 35 to 80 years) suffering from sepsis on a surgical ICU. All patients received routine resuscitation from septic shock (surgery, fluids, catecholamines, antibiotic drugs). The first LiMAx test and ICG-PDR were carried out within the first 24 hours after onset of septic symptoms, followed by day 2, 5 and 10. Other biochemical parameters and scores determining the severity of illness were measured daily. Clinical outcome parameters were examined after 90 days or at the end of treatment. The population was divided into 2 groups (group A: non-survivors or ICU length of stay (ICU-LOS) >30 days versus group B: survivors and ICU-LOS <30 days) for analysis. RESULTS: Epidemiological baseline characteristics of both groups were similar. Group A patients had significant lower LiMAx and ICG-PDR values than patients in group B. Determination of ICG-PDR by finger probe failed in 14.3% of tests due to insufficient peripheral pulses. Respiratory, renal and hepatic dysfunction (LiMAx and ICG-PDR) were associated with prolonged ICU-LOS. Only LiMAx <100 µg/kg/h and respiratory dysfunction were associated with increased mortality. For LiMAx <100 µg/kg/h receiver operating characteristic-analysis revealed a 100% sensitivity and 77% specificity for death. CONCLUSIONS: Sepsis-related hepatic dysfunction can be diagnosed early and effectively by the LiMAx test. The extent of LiMAx impairment is predictive for patient morbidity and mortality. The sensitivity and specificity of the LiMAx test was superior to that of ICG-PDR regarding the prediction of mortality.
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Hepatopatías/diagnóstico , Hepatopatías/mortalidad , Sepsis/diagnóstico , Sepsis/mortalidad , APACHE , Adulto , Anciano , Anciano de 80 o más Años , Colorantes , Diagnóstico Precoz , Femenino , Humanos , Verde de Indocianina , Tiempo de Internación/estadística & datos numéricos , Pruebas de Función Hepática/métodos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Diálisis Renal/estadística & datos numéricos , Respiración Artificial/estadística & datos numéricos , Resucitación , Factores de RiesgoRESUMEN
Primary neuroendocrine tumor (NET) of bladder is rare. It has four subtypes, and large cell neuroendocrine carcinoma (LCNEC) is the rarest. LCNEC affects mostly men over 60. Most common symptom is gross hematuria. It has no specific treatment. Metastasis is common and once occurred, average survival would be less than three months. Herein we present diagnostic and therapeutic management of a 65-year-old female with LCNEC of bladder and concurrent high-grade urothelial carcinoma. Despite developing early liver metastasis, she achieved a one-year tumor-free survival.
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In certain instances, patients who underwent endoscopic laser excision (ELE) for biopsy-proven early glottic carcinoma do not show any evidence of carcinomatous cells on histopathologic analysis. Our study aims to determine the incidence of this phenomenon. A retrospective analysis of patients with biopsy-proven early glottic squamous cell carcinoma who underwent ELE was conducted. 121 patients with a mean age of 68.2 ± 10.7 were included in this study. Initial biopsy showed carcinoma in situ in 38 patients, (31.4%), T1a in 41 patients (33.9%), and T1b in 42 patients (34.7%). Following ELE, a pathologically negative excision was seen in 26 patients (21.5%). Disease recurrence occurred in 3 patients who had a pathologically negative excision (11.5%). Following repeat ELE, all patients remained disease free. A significant number of early glottic carcinoma present with small volume disease which may be eradicated with diagnostic biopsy alone.
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We investigated the transformation of four pharmaceuticals (Diclofenac, Naproxen, Ibuprofen and Carbamazepine) in a moving bed biofilm reactor subjected to different COD/N ratios in four experimental phases. The shift from medium to high range COD/N ratio (i.e., 5:1 to 100:1) intensified the competition between heterotrophs and nitrifying communities, leading to a transition from co-existence of heterotrophic and autotrophic conditions with high COD removal and nitrification rate in phase I to dominant heterotrophic conditions in phase II. At lower range COD/N ratios (i.e., 1:2 and 1:8) in phase III and IV, autotrophic conditions prevailed, resulting in increased nitrification rates and high abundance of amoA gene in the biofilm. Such shifts in the operating condition were accompanied by notable changes in the biofilm concentrations, composition and abundance of microbial populations as well as biodiversity in the biofilms, which collectively affected the degradation rates of the pharmaceuticals. We observed higher kinetic rates per unit of biofilm concentration under autotrophic conditions compared to heterotrophic conditions for all compounds except Naproxen, indicating the importance of nitrification in the transformation of such compounds. The results also revealed a positive relationship between biodiversity and biomass-normalized kinetic rates of most compounds.
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Biodiversidad , Naproxeno , Biotransformación , Biopelículas , Preparaciones FarmacéuticasRESUMEN
Background: Cisplatin is among the most effective antineoplastic agents and has revolutionized the treatment of many cancer diseases. However, one of its serious side effects is a progressive and irreversible hearing loss, occurring in both adults and children. For the development of otoprotective therapies that prevent this side effect, cisplatin-induced hearing loss animal models are indispensable. Due to the high toxicity of cisplatin, the establishment of such animal models is a difficult and time-consuming task. Here we introduce the detailed protocol of a sophisticated guinea pig model with a sufficient and permanent hearing loss induced by cisplatin. This manuscript is intended to provide guidance in the development of future cisplatin guinea pig models which may reduce the mortality rate of the animals and help to gain more reproducible results. Methods: Pigmented and unpigmented guineapigs were treated with an intravenous single application of 8 mg/kg cisplatin under general anesthesia. An extensive and long-term intensive care protocol consisting of scheduled application of fluids, antiemetics, analgesics, glucose and supportive feeding among others, was used to ensure wellbeing of the animals. Hearing tests were performed prior to and 5 days after cisplatin application. Animals were then euthanized. Results: The ABR audiometry 5 days after cisplatin application revealed a hearing threshold ranging from 70 dB to 90 dB in the frequencies from 1 kHz to 32 kHz respectively.All animals presented a good health condition despite the treatment with cisplatin. Discussion: The introduced care protocol in this manuscript is intended to serve as a guidance for the establishment of a stable guinea pig model for short- and long-term investigation regarding the inner ear and its protection in the frame work of cisplatin-induced damage.
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BACKGROUND: Diverticular disease of the colon occurs commonly in developed countries. Immunosuppressed patients are thought to be more at risk of developing acute diverticulitis, worse disease, and higher complications secondary to therapy. This study aimed to assess outcomes for immunosuppressed patients with acute diverticulitis. METHOD: A retrospective single-centre review was conducted of all patients presenting with acute diverticulitis at a major tertiary Australian hospital from 2006 to 2018. RESULT: A total of 751 patients, comprising of 46 immunosuppressed patients, were included. Immunosuppressed patients were found to be older (62.25 versus 55.96, p = 0.016), have more comorbidities (median Charlson Index 3 versus 1, P < 0.001), and undergo more operative management (13.3% versus 5.1%, P = 0.020). Immunosuppressed patients with paracolic/pelvic abscesses (Modified Hinchey 1b/2) were more likely to undergo surgery (56% versus 24%, P = 0.046), while in patients with uncomplicated diverticulitis, there was no difference in immunosuppressed patients undergoing surgery (6.1% versus 5.1% P = 0.815). Immunosuppressed patients were more likely to have Grade III-IV Clavien-Dindo complication (P < 0.001). CONCLUSION: Immunosuppressed patients with uncomplicated diverticulitis can be treated safely with non-operative management. Immunosuppressed patients were more likely to have operative management for Hinchey 1b/II and more likely to have grade III/IV complications.
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Diverticulitis del Colon , Diverticulitis , Humanos , Diverticulitis del Colon/complicaciones , Diverticulitis del Colon/cirugía , Estudios Retrospectivos , Australia/epidemiología , Recurrencia Local de Neoplasia , Diverticulitis/cirugía , Enfermedad AgudaRESUMEN
To shed some light on glycotargeting as a potential strategy for nasal drug delivery, a reliable preparation method for human nasal mucosa samples and a tool to investigate the carbohydrate building blocks of the glycocalyx of the respiratory epithelium are required. Applying a simple experimental setup in a 96-well plate format together with a panel of six fluorescein-labeled lectins with different carbohydrate specificities allowed for the detection and quantification of accessible carbohydrates in the mucosa. As confirmed by binding experiments at 4 °C, both quantitatively by fluorimetry and qualitatively by microscopy, the binding of wheat germ agglutinin exceeded that of the others by 150% on average, indicating a high content of N-acetyl-D-glucosamine and sialic acid. Providing energy by raising the temperature to 37 °C revealed uptake of the carbohydrate-bound lectin into the cell. Moreover, repeated washing steps during the assay gave a slight hint as to the influence of mucus renewal on bioadhesive drug delivery. All in all, the experimental setup reported here for the first time is not only a suitable approach to estimating the basics and potential of nasal lectin-mediated drug delivery but also meets the needs for answering a broad variety of scientific questions involving the use of ex vivo tissue samples.
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Introduction: Early laryngeal carcinomas may be treated by transoral laser microsurgery (TLM) or external beam radiotherapy. We review our experience of surgical treatment of laryngeal pre-malignant and malignant lesions over the past 15 years in a high-volume head neck unit. Methods: A review of a prospective patient database of patients with laryngeal SCC, who were treated with CO2 TLM between 2004 and 2019 was carried out. Results: 83 patients with a mean age of 67.7 (SD: 10.6) years underwent primary curative TLM for T1a/b SCC. 5-year overall survival was 93.2% (95%CI 86.9-100%), disease free survival was 86.0% (95%CI 78.1-94.6%), locoregional control was 91.2% (95%CI: 85.1-97.7%) and larynx preservation rate of 95.1% at 5 years. Conclusion: TLM is an excellent treatment modality for T1 early glottic SCC, with excellent locoregional control and disease-free survival. It is minimally invasive, outpatient-based, and cost-effective procedure preserving upper aerodigestive tract dysfunction for all activities of daily living.
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Primary malignant melanoma (PMM) of the urinary bladder is a rare disease. Symptoms include gross hematuria and irritative LUTS. The diagnosis is made with cystoscopy and TURBT. Treatment options include TURBT and adjuvant therapies. We present a 61-year-old female who was referred with persistent irritative LUTS without gross or microscopic hematuria. After undergoing cystoscopy, TURBT, and extensive workup, she was diagnosed with PMM of the urinary bladder. Due to her past medical history, recurrent PMM of the urinary bladder was the final diagnosis. She refused to receive further treatment or refer for follow-up.
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Currently, multiple myeloma is not yet considered a curable disease. Despite the recent advances in therapy, the average patient lifespan is still unsatisfactory. Recently, CDK9 inhibitors emerged as a suitable agent to overcome resistance and prolong survival in patients with poor diagnoses. Downregulation of c-MYC, XIAP, Mcl-1 and restoration of p53 tumor-suppressive functions seems to play a key role in achieving clinical response. The applicability of the first generation of CDK9 inhibitors was limited due to relatively high toxicity, but the introduction of novel, highly selective drugs, seems to reduce the effects of off-target inhibition. CDK9 inhibitors were able to induce dose-dependent cytotoxicity in Doxorubicin-resistant, Lenalidomide-resistant and Bortezomib-resistant cell lines. They seem to be effective in cell lines with unfavorable prognostic factors, such as p53 deletion, t(4; 14) and t(14; 16). In preclinical trials, the application of CDK9 inhibitors led to tumor cells apoptosis, tumor growth inhibition and tumor mass reduction. Synergistic effects between CDK9 inhibitors and either Venetoclax, Bortezomib, Lenalidomide or Erlotinib have been proven and are awaiting verification in clinical trials. Although conclusions should be drawn with due care, obtained reports suggest that including CDK9 inhibitors into the current drug regimen may turn out to be beneficial, especially in poor prognosis patients.
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Antineoplásicos/farmacología , Quinasa 9 Dependiente de la Ciclina/antagonistas & inhibidores , Mieloma Múltiple/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Animales , Apoptosis/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Terapia Molecular DirigidaRESUMEN
BACKGROUND: Perinueral invasion (PNI) is recognized as an independent adverse prognostic factor associated with shorter disease free and disease specific survival in a range of malignancies. However, not all histologically detected PNI demonstrate aggressive biologic behaviour. Herein, we systematically review the literature to identify neurotrophic biomarkers that may potentially be used to predict the biologic potential of PNI. METHOD: A systematic review was conducted based on PRISMA guidelines utilising the search terms 'PNI', 'DNA' and 'RNA' analysis in select malignancies following registry of the search strategy on PROSPERO. The biologic role of the molecular markers identified through the literature review was examined using publicly available databases, such as Gene Cards and Kyoto Encyclopedia of Genes and Genomes (KEGG) with a focused literature review of the identified pathways. RESULTS: The systematic search identified 256 studies, of which 78 studies were suitable for data extraction. A variety of methodologies including immunohistochemistry, immunoblotting, nucleic acid sequencing, Luciferase assays and CRISPR techniques have been undertaken to evaluate the biologic potential of PNI. The studies evaluated 136 unique molecules. Of these, only 15 molecules were investigated through multiple studies with concordant results or had robust functional analyses. Three pathways were identified as playing a role in PNI, namely; the epithelial-mesenchymal transition pathway, neurotrophic pathway and Notch pathway. DISCUSSION: Our understanding of the complex and reciprocal interaction between tumour and nerve cells that drives PNI is still evolving. The knowledge gaps can largely be attributed to publication bias, lack of availability of high-quality patient derived tissues and limitations of currently available technology. This review summarises the current knowledge regarding development and progression of PNI that can be harnessed for prognostication and treatment. This review also summarises the lacunae in our understanding of the pathogenesis of PNI thus identifying avenues for future studies.
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Productos Biológicos , Transición Epitelial-Mesenquimal , Supervivencia sin Enfermedad , Humanos , Invasividad Neoplásica/patología , Nervios Periféricos/patología , PronósticoRESUMEN
OBJECTIVES: To measure the unit-level variation in Acute Kidney Injury (AKI) incidence post-thoracic surgery over a contemporary 1-year period. Secondary aims include examining the associations with sex, age group, operation type, length of stay and mortality. DESIGN: A multicentre, observational, retrospective study in thoracic surgery. SETTING: 17 of 35 Society for Cardiothoracic Surgery of Great Britain and Ireland (SCTS) units participated. The student wing, known as SCTS STUDENTS, supported data collection. PARTICIPANTS: Overall, 15 229 patients were collected of which 15 154 were included for analysis after exclusions. All patients (age≥18 years) undergoing any thoracic surgery from 1 April 2016 to 31 March 2017 were included. For analysis, we excluded patients with preoperative end-stage renal failure and those with incomplete data. MAIN OUTCOME MEASURES: The primary outcome is the incidence of AKI within 7 days of the procedure or discharge date if earlier. Secondary outcomes include assessing associations with patient demographics (age, sex), type of procedure (open and minimally invasive), length of stay and mortality. RESULTS: Out of 15 154 patients AKI was diagnosed in 1090 patients (7.2%) within 7 days of surgery with AKI stage 1 (4.8%), stage 2 (1.7%) and stage 3 (0.7%). There was a statistically significant variation in AKI incidence between units from 3.1 to 16.1% (p<0.05). Significant differences between AKI and non-AKI were found in post-operative length of stay (7 vs 3 days, p<0.001), 30-day mortality (9 vs 1.6%, p<0.001), 90-day mortality (14.7 vs 4.4%, p<0.001) and 1-year mortality (23.1 vs 12.2 %, p<0.001). CONCLUSIONS: Following thoracic surgery, AKI incidence ranged from 3.1% to 16.1% between units (p<0.05) with associations between AKI and both length of stay and mortality. We propose AKI as a suitable comparative and absolute quality measure in thoracic surgery. Reducing rates of AKI may improve patient outcomes, length of stay and reduce costs.
Asunto(s)
Lesión Renal Aguda , Cirugía Torácica , Procedimientos Quirúrgicos Torácicos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Adolescente , Humanos , Incidencia , Estudios Retrospectivos , Factores de Riesgo , Procedimientos Quirúrgicos Torácicos/efectos adversosRESUMEN
AIM: To present an institution's experience and survival outcomes for patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) and perineural spread (PNS). METHOD: Retrospective study of patients with HNcSCC and PNS treated between January 2010 and August 2020 from the Sydney Head and Neck Cancer Institute database, Sydney, Australia; a high-volume, tertiary, academic head and neck centre. Patient demographics, primary site, involved cranial nerves, treatment modality, loco-regional failure and survival data were obtained. RESULTS: Forty-five patients were identified, of which 32 patients were male (71%). Mean age at diagnosis was 68.7 years (range 43-90). Median follow-up was 16.1 months (range 1-107). The trigeminal nerve was most frequently involved (n = 30, 66.6%) followed by facial nerve (n = 13, 28.9%). Most patients underwent surgery followed by radiotherapy (n = 33, 73%) and eight received definitive radiotherapy. The median overall survival (OS) was 4.5 years (95% CI 3.71-5.38), median disease-specific survival 5.1 years (95% CI 4.21-5.97) and median disease-free survival (DFS) was 1.7 years (95% CI 1.11-2.22). The estimated 5-year OS and DFS were 45% and 25%, respectively. Patients treated with surgery and adjuvant radiotherapy with a clear proximal nerve margin had favourable DFS (P = 0.035) and trended towards better OS (P = 0.134) compared with patients with an involved nerve margin. Patients treated surgically with involved proximal nerve margins had similar outcomes compared with patients with treated definitive radiotherapy (HR 0.80, 95% CI 0.29-2.22, P = 0.664). CONCLUSION: The likelihood of achieving a clear proximal nerve margin should be a strong consideration in the selection of appropriate patients for primary surgery.