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There are limited data on the optimal choice of anticoagulation in multiple myeloma (MM) patients receiving immunomodulatory drugs (IMiDs). We conducted a propensity score-matched cohort study using the TriNetX database to compare the efficacy and safety of factor Xa inhibitors and warfarin in this patient population. Compared to warfarin, factor Xa inhibitors had a similar risk of deep vein thrombosis (hazard ratio [HR]: 1.11 [95% CI: 0.50-2.46]) or pulmonary embolism (HR: 1.08 [95% CI: 0.59-2.00]). There were no differences in the risk of gastrointestinal or intracranial bleeding. Factor Xa inhibitor-treated patients had lower all-cause mortality (HR: 0.56 [95% CI: 0.36-0.86]) compared with warfarin. These data suggest that factor Xa inhibitors had similar safety and efficacy compared with warfarin for MM patients on IMiDs.
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Anticoagulantes , Inhibidores del Factor Xa , Mieloma Múltiple , Warfarina , Humanos , Warfarina/uso terapéutico , Warfarina/efectos adversos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/complicaciones , Mieloma Múltiple/mortalidad , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Trombosis de la Vena/prevención & control , Trombosis de la Vena/etiología , Agentes Inmunomoduladores/uso terapéutico , Agentes Inmunomoduladores/efectos adversos , Anciano de 80 o más Años , Embolia Pulmonar/prevención & control , Embolia Pulmonar/etiologíaRESUMEN
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant (B.1.617.2) was the predominant variant behind the surges of COVID-19 in the United States, Europe, and India in the second half of 2021. The information available regarding the defining mutations and their effects on the structure, transmission, and vaccine efficacy of SARS-CoV-2 is constantly evolving. With waning vaccine immunity and relaxation of social distancing policies across the globe driving the increased spread of the Delta variant, there is a great need for a resource aggregating the most recent information for clinicians and researchers concerning the Delta variant. Accordingly, this narrative review comprehensively reviews the genetics, structure, epidemiology, clinical course, and vaccine efficacy of the Delta variant. Comparison with the omicron variant is also discussed. The Delta variant is defined by 15 mutations in the Spike protein, most of which increase affinity for the ACE-2 receptor or enhance immune escape. The Delta variant causes similar symptoms to prototypical COVID-19, but it is more likely to be severe, with a greater inflammatory phenotype and viral load. The reproduction number is estimated to be approximately twice the prototypical strains present during the early pandemic, and numerous breakthrough infections have been reported. Despite studies demonstrating breakthrough infection and reduced antibody neutralisation, full vaccination effectively reduces the likelihood of severe illness and hospitalisation.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiología , COVID-19/prevención & control , Eficacia de las Vacunas , Infección Irruptiva , InmunidadRESUMEN
INTRODUCTION: The management of childhood constipation is challenging. Pelvic floor dysfunction (PFD) is one of the most common causes of childhood constipation. Percutaneous tibial nerve stimulation (PTNS) with pelvic floor exercises (PFE) has achieved a satisfactory outcome in the elderly individuals and women with PFD. The efficacy of PTNS with PFE in childhood constipation has not been established. METHODS: A randomized, double-blind, controlled trial with 84 children who met the inclusion criteria was conducted. All participants were randomly assigned to PTNS with PFE or sham PTNS with PFE groups and received their individual intervention for 4 weeks with a 12-week follow-up evaluation. The spontaneous bowel movements (SBM) ≥3 per week were the main outcomes, and the risk ratio (RR) with 95% confidence interval (CI) were calculated. High-resolution anorectal manometry and surface electromyography were used for the assessment of pelvic floor function, and the adverse effects were assessed based on symptoms. RESULTS: At the end of the follow-up period, 26 patients (61.9%) in the PTNS with PFE group and 15 patients (35.7%) in the sham group had ≥3 SBM per week compared with baseline (net difference 26.2%, 95% CI 5.6%-46.8%; RR 2.750, 95% CI 1.384-5.466; P < 0.05). PFD remission occurred in 49 children, 33 (78.6%) in the PTNS with PFE group and 16 (38.1%) in the sham group (RR 2.063, 95% CI 1.360-3.128, P < 0.05). No adverse effects occurred. DISCUSSION: PTNS with PFE is a safe and effective method in the treatment of childhood constipation, particularly in children with PFD or dyssynergic defecation.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Estimulación Eléctrica Transcutánea del Nervio , Niño , Humanos , Femenino , Anciano , Diafragma Pélvico , Estreñimiento/terapia , Nervio Tibial/fisiología , Terapia por Ejercicio , Resultado del TratamientoRESUMEN
Autoimmune pancreatitis (AIP) is an uncommon fibro-inflammatory disorder precipitated by autoimmune/inflammatory reactions. Currently, there are two clinical subtypes of AIP (type 1 [AIP-1] and type 2 [AIP-2]) that correspond to two histologic descriptors (lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis, respectively). While our understanding of AIP-1 has evolved considerably over the years, little is known about AIP-2 due to its rarity, often leading to misdiagnosis, delayed treatment, and even unnecessary surgical resection. Compared to AIP-1, AIP-2 exhibits distinct clinical and histologic features. Because AIP-2 is a pancreas-restricted disease without a specific serum marker, the evaluation of histologic features (e.g., granulocytic epithelial lesions) is essential for an accurate diagnosis. Patients with AIP-2 respond well to glucocorticoids, with anti-tumor necrosis factor-alpha antibodies as a promising alternative therapy. The prognosis of AIP-2 is generally favorable and relapse is uncommon. Here, we provide an overview of our current knowledge on the clinical features, diagnosis, therapeutic regimens, prognosis, and putative mechanisms underlying AIP-2. Notably, the diagnostic differentiation between AIP-2, especially the mass-forming/focal type, and pancreatic cancer is important, but challenging. In this regard, endoscopic ultrasound-guided core biopsy has a key role, but novel diagnostic markers and modalities are clearly needed.
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As coronavirus variants are constantly occurring, we tried to understand more about the omicron and delta variants that have hit the world. We provided dynamic information on the case fatality rate (CFR) of the Omicron variant over time and to compare it with that of the Delta variant through meta-analysis. Twenty-four countries were selected by submission counts, submission dates, and confirmed cases. We defined the Delta or the Omicron epidemic period for individual countries as when each variant is over 90%. We further analyzed the Omicron period by dividing it into the initial plateau, increasing, and decreasing phases according to the number of newly confirmed daily cases. Finally, the meta-analysis examined the summary and between-study heterogeneity. The CFR of COVID-19 during the Omicron epidemic was lower than that during the Delta epidemic (odds ratio [OR]: 0.252, 95% confidence interval [CI] 0.205-0.309). The CFR of COVID-19 during the initial plateau phase of Omicron was higher than during other phases. (OR: 1.962, 95% CI 1.607-2.397). The CFR of COVID-19 during the increasing phase was lower than during the decreasing phases (OR: 0.412, 95% CI 0.342-0.498). The Omicron variant had lower CFR compared to the Delta variant, and the initial plateau phase had higher CFR compared to the noninitial phases. These results can help establish global health policies for COVID-19 in the future.
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COVID-19 , Epidemias , Humanos , SARS-CoV-2 , Política de SaludRESUMEN
BACKGROUND AND AIM: We aimed to capture the breadth of health outcomes that have been associated with the presence of Urinary Incontinence (UI) and systematically assess the quality, strength, and credibility of these associations through an umbrella review and integrated meta-analyses. METHODS: We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p-values, 95% prediction intervals, heterogeneity, small-study effects, and excess significance. We graded the evidence from convincing (Class I) to weak (Class IV). RESULTS AND DISCUSSION: From 3172 articles returned in search of the literature, 9 systematic reviews were included with a total of 41 outcomes. Overall, 37 out of the 41 outcomes reported nominally significant summary results (p < 0.05), with 22 associations surviving the application of a more stringent p-value (p < 10-6). UI was associated with worse scores than controls in female sexual function (Class II), while it was also associated with a higher prevalence of depression (odds ratio [OR] = 1.815; 95% confidence interval [CI]: 1.551-2.124), and anxiety (OR = 1.498; 95% CI: 1.273-1.762) (Class IV). UI was associated with poorer quality of life (QoL), higher rate of mortality (hazard ratio = 2.392; 95% CI: 2.053-2.787) an increase in falls, frailty, pressure ulcers, diabetes, arthritis, and fecal incontinence (Class IV). CONCLUSIONS: UI is associated with female sexual dysfunction, with highly suggestive evidence. However, the evidence of other adverse outcomes including depression, anxiety, poorer QoL, higher mortality, falls, pressure ulcers, diabetes, arthritis, fecal incontinence, and frailty is only weak. A multidimensional approach should be taken in managing UI in the clinical setting.
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Artritis , Diabetes Mellitus , Incontinencia Fecal , Fragilidad , Úlcera por Presión , Incontinencia Urinaria , Humanos , Femenino , Calidad de Vida , Incontinencia Urinaria/epidemiologíaRESUMEN
BACKGROUND: Lichen sclerosus (LS) is a common autoimmune dermatological condition that is often under-diagnosed in women and has been documented to affect quality of life and sexual function. AIM: To determine the prevalence of sexual dysfunction among women with vulvar lichen sclerosus. METHODS: The authors conducted a systematic review and meta-analysis of the existing research on LS and sexual function in database including PubMed using search terms: lichen sclerosus OR vulvar lichen sclerosus OR vulvar lichen sclerosus et atrophicus OR kraurosis vulvae) AND (sexual function OR sexual functions OR sexual disorder OR sexual disorders OR sexual activity OR sexual activities OR sexual dysfunction OR sexual dysfunctions OR dyspareunia OR vaginismus). OUTCOMES: Nearly 60% of women with lichen sclerosus suffer from sexual dysfunction. RESULTS: Two hundred and ten studies were initially identified. Twenty-six articles met inclusion criteria and 3 were excluded as they did not relate to sexual function, were regarding a surgical or medical intervention and sexual dysfunction and one was a review article. Therefore, 23 studies were included in the final analysis resulting in a cumulative 486 participants with LS with 208 patients experiencing any kind of sexual dysfunction. Meta-analysis presented prevalence of sexual dysfunction among LS patients as 59% (95% CI: 48 - 70%). Dyspareunia or generalized pain with intercourse was the most commonly reported type of dysfunction. CLINICAL IMPLICATIONS: Discussing sexual concerns with women with LS could empower them to seek treatment. STRENGTHS AND LIMITATIONS: Few articles met criteria for inclusion. CONCLUSION: A large proportion of women with LS experience sexual dysfunction. More research is needed, especially that which includes biopsy-proven LS and validated tools on sexual function. Pope R, Lee MH, Myers A, et al. Lichen Sclerosus and Sexual Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2022;19:1616-1624.
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Dispareunia , Liquen Escleroso y Atrófico , Disfunciones Sexuales Fisiológicas , Liquen Escleroso Vulvar , Humanos , Femenino , Liquen Escleroso y Atrófico/complicaciones , Liquen Escleroso y Atrófico/terapia , Liquen Escleroso Vulvar/complicaciones , Liquen Escleroso Vulvar/cirugía , Dispareunia/epidemiología , Dispareunia/etiología , Calidad de Vida , Disfunciones Sexuales Fisiológicas/epidemiología , Disfunciones Sexuales Fisiológicas/etiologíaRESUMEN
BACKGROUND AND AIM: According to the United Nations' Sustainable Development Goal (SDG) target 3.4, premature mortality from four non-communicable diseases (cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes mellitus, collectively referred to as NCD4) should achieve a minimum decline of 33% in 2030 relative to 2015. This remains a challenge for China. This study aimed to evaluate the current status and progress towards this target in Liaoning Province, one of the three provinces in northeast China. METHODS: We calculated the premature mortality rates (PMRs) per year and average annual percentage changes (AAPCs) from NCD4 using mortality data between 2004 and 2017. The trend was analyzed in the whole population, as well as in subpopulations of gender (male/female) and inhabiting area (urban/rural). PMRs from NCD4 for 2030 were projected by fitting a linear regression based on the current trend, which was identified by a Joinpoint model. FINDINGS: In the whole population, only chronic respiratory diseases showed a significant decline (AAPC: - 6.5%, p < 0.05), while only cancer showed a significant increase (AAPC: + 1.3%, p < 0.05); taken together, NCD4 showed a significant increase (AAPC: + 0.6%, p < 0.05). In the subpopulations, while males showed a significant increase in NCD4 (AAPC: + 1.5%, p < 0.05), cardiovascular diseases (AAPC: + 1.7%, p < 0.05), cancer (AAPC: + 1.8%, p < 0.05), and diabetes mellitus (AAPC: + 4.2%, p < 0.05), females showed a significant decline in NCD4 (AAPC: - 1.2%, p < 0.05), cardiovascular diseases (AAPC: - 1.8%, p < 0.05), diabetes mellitus (AAPC: - 2.1%, p < 0.05), but showed a mild increase in cancer (AAPC: + 0.5%, p > 0.05). A comparative analysis of the projected PMRs for 2030 with the 2015 levels revealed that only chronic respiratory diseases are expected to achieve the SDG target 3.4, apart from in the urban male subpopulation. CONCLUSION: Except for chronic respiratory diseases, NCD4 cannot be expected to achieve the SDG target 3.4 in the whole population of Liaoning Province. Under these circumstances, special attention should be paid to reducing the risks of cancer and providing preventative interventions for men.
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Enfermedades no Transmisibles , Desarrollo Sostenible , China/epidemiología , Femenino , Objetivos , Humanos , Masculino , Mortalidad Prematura , Enfermedades no Transmisibles/epidemiologíaRESUMEN
BACKGROUND: It is important for lymph node dissection around the inferior mesenteric artery (IMA) with preservation of the left colic artery (LCA) to be aware of the track and the length of the LCA. We aimed to investigate the branching pattern and trajectory of LCA and measure the distances from the root of the IMA to the origin of the LCA (D mm) and from the origin of LCA to intersection of LCA and IMV (d mm) during laparoscopic left-sided colorectal operations. METHODS: We analyzed 106 patients who underwent laparoscope-assisted left-side colorectal surgery during laparoscopic surgery. The branching patterns among the IMA, LCA, and sigmoidal trunk were evaluated; the trajectory of LCA was examined; the D mm and d mm were measured using a length of silk in the surgical operation. RESULTS: In 59.5% patients, the LCA arose independently from the sigmoidal trunk (type A); in 8.5% patients, the LCA and sigmoidal trunk arose from the IMA at the same point (type B); in 29.2% patients, the LCA and sigmoidal trunk had a common trunk (type C); the LCA did not exist in 2.8% (type D).The D mm and d mm for all cases ranged from 15.0 to 65.3 mm (median, 43.1 mm) and from 20.3 to 46.2 mm (median, 34.8 mm), respectively. 74.8% of the LCA went straight upper left and upward to proximal part of descending colon (type I), 25.2% went to the lower left at first, then turned to travel straight upward to proximal part of descending colon (type II). CONCLUSION: This study showed the anatomic variations of LCA during laparoscopic left-sided colorectal operation, which would help surgeons safely perform laparoscopic surgery in the left-side colon and rectum.
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Colon/irrigación sanguínea , Cirugía Colorrectal/métodos , Laparoscopía/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Exosomes, extracellular vesicles with diameters ranging from 30 to 150 nm, are widely present in various body fluids. Recently, microRNAs (miRNAs) have been identified in exosomes, the biogenesis, release, and uptake of which may involve the endosomal sorting complex required for transport (ESCRT complex) and relevant proteins. After release, exosomes are taken up by neighboring or distant cells, and the miRNAs contained within modulate such processes as interfering with tumor immunity and the microenvironment, possibly facilitating tumor growth, invasion, metastasis, angiogenesis and drug resistance. Therefore, exosomal miRNAs have a significant function in regulating cancer progression. Here, we briefly review recent findings regarding tumor-derived exosomes, including RNA sorting and delivering mechanism. We then describe the intercommunication occurring between different cells via exosomal miRNAs in tumor microenvironmnt, with impacts on tumor proliferation, vascularization, metastasis and other biological characteristics. Finally, we highlight the potential role of these molecules as biomarkers in cancer diagnosis and prognosis and tumor resistance to therapeutics.
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Exosomas/metabolismo , MicroARNs/genética , Neoplasias/genética , Neoplasias/metabolismo , Biomarcadores , Fibroblastos Asociados al Cáncer/metabolismo , Matriz Extracelular , Humanos , MicroARNs/metabolismo , Neoplasias/inmunología , Neoplasias/patología , Pronóstico , Transporte de ARN , Transducción de SeñalRESUMEN
Exosomes are extracellular vesicles released by many cell types and have been attributed for their roles in many diseases including cancer. Exosomes secreted by tumor cells and stromal cells are critical mediators of intercellular communication in tumor microenvironments. Long noncoding RNAs (lncRNAs) are selectively sorted into exosomes and can regulate cancer onset and progression in a variety of ways. In this review, we summarize the characteristics of exosomal lncRNAs and their dysregulation in multiple types of cancer. We provide an overview of current research on exosomal lncRNAs in tumor microenvironments, especially the functions of exosomal lncRNAs in regulating tumor biology. A deeper understanding of the role of exosomal lncRNAs in the tumor microenvironment may help provide new diagnostic and prognostic markers for cancer.
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Exosomas/genética , Neoplasias/genética , ARN Largo no Codificante/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico , Microambiente TumoralRESUMEN
Colorectal cancer (CRC) is one of the most common malignancies in the world. Easier recurrence and metastasis is the main cause of mortality in CRC patients, and the markers applied for diagnosis and treatment of CRC is still urgently needed to early diagnose and evaluate therapeutic effect. Long noncoding RNA (lncRNA) is a class of noncoding RNA that the length is more than 200 nucleotides. With the development of sequencing technique about transcriptome, increasing lncRNAs are focused on their function and mechanism related to the nosogenesis and pathology of CRC. Recent studies report that lncRNAs acted as crucial role in CRC and could be as biomarker for CRC diagnosis and treatment. In this review, we display the regulation of lncRNA by interacting with DNA, RNA and protein and highlight the double role of lncRNAs as oncogene or anti-tumor gene involved in Wnt signaling pathway, p53 signaling pathway or others to be an regulator in CRC development. Lastly, we discuss some new finding of lncRNAs, especially lncRNA in exosome, which could be as potential markers for diagnosis and treatment of CRC in future.
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Neoplasias Colorrectales/diagnóstico , ARN Largo no Codificante/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Humanos , ARN Largo no Codificante/genética , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismoRESUMEN
BACKGROUND/AIMS: Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes and cancer progression. Whether lncRNAs play any functional role in colorectal carcinoma (CRC) remains largely unknown. The aim of this study was to investigate the role of lncRNA CPS1 intronic transcript 1 (CPS1-IT1) in CRC. METHODS: Expression of CPS1-IT1 was initially assessed in human CRC tissues and in a series of CRC cell lines. The correlations between CPS1-IT1 levels and survival outcomes were analyzed to elucidate the clinical significance of CPS1-IT1 in CRC. The underlying mechanisms of CPS1-IT1 in CRC were analyzed through in vitro and in vivo functional assays. RESULTS: Expression of CPS1-IT1 was significantly decreased in CRC tissues and cell lines, and patients with low CPS1-IT1 expression had poor survival outcomes. The results of in vitro assays revealed that CPS1-IT1 significantly reduced cell proliferation, migration and invasion capacities and accelerated cell apoptosis, thereby suppressing epithelial-mesenchymal transition (EMT). An in vivo animal model also demonstrated the tumor-suppressive role of CPS1-IT1. CONCLUSION: In this study, we found that CPS1-IT1 has a tumor-suppressive role in CRC. Our data suggest that CPS1-IT1 could be used as a new prognostic biomarker and therapeutic target for CRC.
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Neoplasias Colorrectales/patología , ARN Largo no Codificante/metabolismo , Animales , Apoptosis , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Transición Epitelial-Mesenquimal , Células HCT116 , Células HT29 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Interferencia de ARN , ARN Largo no Codificante/antagonistas & inhibidores , ARN Largo no Codificante/genética , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/uso terapéutico , Trasplante HeterólogoRESUMEN
Gastrointestinal (GI) tract perforation is one of the most severe acute abdomens. In clinical practice, abdominal x-ray plain film remains the first-line diagnostic modality for this entity. A proportion of the perforated patients, however, do not exhibit a classic x ray sign: free air at the subphrenic area. This insufficiency can bring difficulties to the diagnosis, delay appropriate treatments, and even cause lethal consequences. We describe herein a case of GI tract perforation, which was not detected by the abdominal x-ray plain film initially. Strikingly, the abdominal computed tomographic (CT)scan established the diagnosis and predicted the site and cause of the perforation, which were consistent with the intraoperative findings and pathological examination. In addition, CT scan was useful in monitoring the progression of the disease. Given the high performance of CT scan in the present case, we recommend it as a preferred diagnostic modality for patients who are suspected of GI perforation,especially when the abdominal x-ray plain film is inconclusive.
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Enfermedades del Íleon/diagnóstico por imagen , Perforación Intestinal/diagnóstico por imagen , Anciano , Humanos , Masculino , Radiografía Abdominal , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Early ampullary cancers present with good prognosis. Pancreaticoduodenectomy (PD) has been standard treatment for ampullary cancers, but it remains high rate of postoperative complications. So there raises a discussion on the role of local ampullectomy for early ampullary cancers (mainly focusing on pT1). METHODS: 89 patients with pT1 ampullary cancer who underwent surgical treatment between 1978 and 2010 were retrospectively studied. RESULTS: Rate of postoperative complications, especially post-operative pancreatic fistula (P = 0.009), after PD was higher than after local ampullectomy, . Multivariate analysis showed that tumor size (HR 2.204; P = 0.014), lymph node metastasis (HR 4.362; P < 0.001), lymph vascular invasion (HR 4.258; P < 0.001), and perineural invasion (HR 4.467; P < 0.001), gross morphology (HR 2.536; P = 0.004) and tumor grade (HR 4.213; P = 0.001) were independent risk factors for long-term survival, as well as risk factors for failure of ampullectomy in early ampullary cancer. For patients absent of these factors, local ampullectomy would achieve a good prognosis. CONCLUSIONS: Because of high rate of lymph node metastasis, PD should be preferably performed for radical resection. Local ampullectomy could be an alternative for patients in high operative risk; and would achieve a good outcome in patients whose tumors were well differentiated and showed polypoid gross morphology and size ≤1 cm.
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Adenocarcinoma/cirugía , Ampolla Hepatopancreática/cirugía , Neoplasias del Conducto Colédoco/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pancreaticoduodenectomía , Complicaciones Posoperatorias/epidemiología , Pronóstico , Estudios RetrospectivosRESUMEN
We are writing in response to the paper published in the World Journal of Gastroenterology by Zhou et al. The authors identified higher serum immunoglobulin (Ig) G4 levels and age over 55 years as independent risk factors for disease relapse. Despite notable strengths, it is crucial to address potential biases. Firstly, the cohort study included 189 patients with autoimmune pancreatitis (AIP) type 1 (with higher IgG4 seropositivity and higher relapse) and 24 with type 2 (with lower IgG4 seropositivity and lower relapse). Consequently, most, if not all, AIP type 2 patients were assigned to the normal group, possibly inflating the association of higher serum IgG4 levels with relapse and potentially exaggerating the association of older age with relapse. Secondly, the authors did not provide sufficient details regarding AIP diagnosis, such as the ratio of definitive vs probable cases and the proportion of biopsies. In cases where histological evidence is unavailable or indeterminate, AIP type 2 may be misdiagnosed as definitive type 1, and type 1 may also be misdiagnosed as probable type 2, particularly in cases with normal or mildly elevated serum IgG4 levels. Lastly, in this retrospective study, approximately one-third of the consecutive patients initially collected were excluded for various reasons. Accordingly, the impact of non-random exclusion on relapse outcomes should be carefully considered. In conclusion, the paper by Zhou et al offers plausible, though not entirely compelling, evidence suggesting a predictive role of elevated serum IgG4 levels and advanced age in AIP relapse. The foundation for future investigations lies in ensuring a reliable diagnosis and accurate disease subtyping, heavily dependent on obtaining histological specimens. In this regard, endoscopic ultrasound-guided fine-needle biopsy emerges as a pivotal component of the diagnostic process, contributing to mitigating biases in future explorations of the disease.
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Enfermedades Autoinmunes , Pancreatitis Autoinmune , Pancreatitis , Humanos , Persona de Mediana Edad , Pancreatitis Autoinmune/diagnóstico , Estudios Retrospectivos , Estudios de Cohortes , Enfermedad Crónica , Inmunoglobulina G , RecurrenciaRESUMEN
Background: Ubiquitination, a major post-translational modification, significantly impacts tumorigenesis, progression, and prognosis. This study aims to classify colon cancer at the molecular level and create a reliable signature using ubiquitination-related genes (URGs) to assess the immune microenvironment and prognosis. Methods: We employed non-negative matrix factorization to subtype colon cancer based on ubiquitination-related gene (URG) expression patterns. Quantitative scores for 28 immune cell infiltrates and the tumor microenvironment were computed using single-sample gene set enrichment analysis (ssGSEA) and the Estimate algorithm. Subtype feature genes were selected through Lasso logistic regression and SVM-RFE algorithm. The ubiquitination-related signature was constructed using univariate Cox, Lasso, and stepwise regression methods to categorize patients into high and low-risk groups. Validation included log-rank tests, receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and external dataset validation. Immune therapy response was compared using Tumor Immune Dysfunction and Exclusion (TIDE), Immunophenoscore (IPS), and submap analyses. Clinical variables and risk scores were integrated into an enhanced nomogram. The early diagnostic value of four URGs was confirmed via quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. The cell proliferation was assessed through colony formation, EdU staining, and xenograft tumorigenesis assays. Results: Prognostic ubiquitination-related genes (URGs) stratified patients into subtypes, revealing differences in survival, immune cell infiltration, and pathological staging. A signature of 6 URGs (ARHGAP4, MID2, SIAH2, TRIM45, UBE2D2, WDR72) was identified from 57 subtype-related genes. The high-risk group exhibited characteristics indicative of enhanced epithelial-mesenchymal transition, immune escape, immunosuppressive myeloid-derived suppressor cells, regulatory T cell infiltration, and lower immunogenicity. In contrast, the low-risk group demonstrated the opposite trend but showed a better response to CTLA4 checkpoint inhibitors. The predictive performance of the nomogram significantly improved with the integration of risk score, stage, and age. ARHGAP4 and SIAH2 exhibit promising early diagnostic capabilities. Additionally, WDR72 knockdown significantly inhibited CRC cell proliferation both in vitro and in vivo. Conclusion: Our developed ubiquitination-related signature and genes serve as promising biomarkers for colon cancer prognosis, immune microenvironment, and diagnosis.