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BACKGROUND: Cisplatin is integral to ovarian cancer treatment, yet resistance to this drug often results in adverse patient outcomes. The association of circular RNA (circRNA) with cisplatin resistance in ovarian cancer has been observed, but the mechanisms governing this relationship require further elucidation. METHODS: High-throughput sequencing was utilized to profile circRNA expression in cisplatin-resistant ovarian cancer cells. Gain-and-loss-of-function experiments assessed the impact on cisplatin sensitivity, both in vitro and in vivo. Fluorescence in situ hybridization was conducted to determine the cellular distribution of circRNAs, and RNA pulldown and immunoprecipitation experiments were performed to identify associated binding proteins. RESULTS: The study revealed that circ_ARHGEF28 is overexpressed in certain cisplatin-resistant ovarian cancer tissues and cell lines, and is associated with reduced progression-free survival in patients. It was observed that circ_ARHGEF28 contributes to cisplatin resistance in ovarian cancer models, both in vitro and in vivo. Importantly, circ_ARHGEF28 was found to interact directly with MST1/2, inhibiting the SARAH coiled-coil binding domains and consequently deactivating the Hippo pathway. CONCLUSION: This investigation identifies circ_ARHGEF28 as a novel circRNA that contributes to cisplatin resistance in ovarian cancer by suppressing the Hippo pathway. Therapeutic strategies targeting circ_ARHGEF28 may offer a potential avenue to mitigate cisplatin resistance in ovarian cancer treatment.
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Erros Inatos do Metabolismo dos Carboidratos , Duplicação Gênica , Transportador de Glucose Tipo 1 , Humanos , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/deficiência , Erros Inatos do Metabolismo dos Carboidratos/genética , Masculino , Mutação , Feminino , Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Transporte de Monossacarídeos/deficiênciaRESUMO
BACKGROUND: Hemophilia A (HA) is an X-linked recessive genetic disorder caused by pathogenic variations of the factor VIII -encoding gene, F8 gene. Due to the large size and diverse types of variations in the F8 gene, causative mutations in F8 cannot be simultaneously detected in one step by traditional molecular analysis, and genetic molecular diagnosis and prenatal screening of HA still face significant difficulties and challenges in clinical practice. Therefore, we aimed to develop and validate an efficient, accurate, and time-saving method for the genetic detection of HA. METHODS: A comprehensive analysis of hemophilia A (CAHEA) method based on long-range PCR and long-read sequencing (LRS) was used to detect F8 gene mutations in 14 clinical HA samples. The LRS results were compared with those of the conventional methods to evaluate the accuracy and sensitivity of the proposed approach. RESULTS: The CAHEA method successfully identified 14 F8 variants in all probands, including 3 small insertion deletions, 4 single nucleotide variants, and 7 intron 22 inversions in a "one-step" manner, of which 2 small deletions have not been reported previously. Moreover, this method provided an opportunity to analyze the mechanism of rearrangement and the pathogenicity of F8 variants. The LRS results were validated and found to be in 100% agreement with those obtained using the conventional method. CONCLUSION: Our proposed LRS-based F8 gene detection method is an accurate and reproducible genetic screening and diagnostic method with significant clinical value. It provides efficient, comprehensive, and accurate genetic screening and diagnostic services for individuals at high risk of HA as well as for premarital and prenatal populations.
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Fator VIII , Hemofilia A , Hemofilia A/genética , Hemofilia A/diagnóstico , Humanos , Fator VIII/genética , Variação Genética , Mutação , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNARESUMO
BACKGROUND: Mild to moderate thalassemia trait (TT) and iron deficiency anemia (IDA) are the most common conditions of microcytic hypochromic anemia (MHA) and they exhibit highly similar clinical and laboratory features. It is sometimes difficult to make a differential diagnosis between TT and IDA in clinical practice. Therefore, a simple, effective, and reliable index is needed to discriminate between TT and IDA. METHODS: Data of 598 patients (320 for TT and 278 for IDA) were enrolled and randomly assigned to training set (278 of 598, 70%) and validation set (320 of 598, 30%). Stepwise discriminant analysis was used to define the best diagnostic formula for the discrimination between TT and IDA in training set. The accuracy and diagnostic performance of formula was tested and verified by receiver operating characteristic (ROC) analysis in validation set and its diagnostic performance was compared with other published indices. RESULTS: A novel formula, Thalassemia and IDA Discrimination Index (TIDI) = -13.932 + 0.434 × RBC + 0.033 × Hb + 0.025 ×MCHC + 53.593 × RET%, was developed to discriminate TT from IDA. TIDI showed a high discrimination performance in ROC analysis, with the Area Under the Curve (AUC) = 0.936, Youden' s index = 78.7%, sensitivity = 89.5%, specificity = 89.2%, respectively. Furthermore, the formula index also obtained a good classification performance in distinguishing 5 common genotypes of TT from IDA (AUC from 0.854-0.987). CONCLUSION: The new, simple algorithm can be used as an effective and robust tool for the differential diagnosis of mild to moderate TT and IDA in Guangxi region, China.
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Algoritmos , Anemia Ferropriva , Curva ROC , Talassemia , Humanos , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/sangue , Diagnóstico Diferencial , Masculino , Feminino , Talassemia/diagnóstico , Adulto , Análise Discriminante , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
Third-generation sequencing (TGS) has led to a brave new revolution in detecting genetic diseases over the last few years. TGS has been rapidly developed for genetic disease applications owing to its significant advantages such as long read length, rapid detection, and precise detection of complex and rare structural variants. This approach greatly improves the efficiency of disease diagnosis and complements the shortcomings of short-read sequencing. In this paper, we first briefly introduce the working mechanism of one of the most important representatives of TGS, single-molecule real-time (SMRT) sequencing by Pacific Bioscience (PacBio), followed by a review and comparison of the advantages and disadvantages of different sequencing technologies. Finally, we focused on the progress of SMRT sequencing applications in genetic disease detection. Future perspectives on the applications of TGS in other fields were also presented. With the continuous innovation of the SMRT technologies and the expansion of their fields of application, SMRT sequencing has broad clinical application prospects in genetic diseases detection, and is expected to become an important tool for the molecular diagnosis of other diseases.
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Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Análise de Sequência de DNARESUMO
Enlarged vestibular aqueduct is an autosomal genetic disease mainly caused by mutations in the SLC26A4 gene and includes non-syndromic and syndromic types. This study aimed to identify genetic defects in a Chinese patient with non-syndromic enlarged vestibular aqueduct (NSEVA) and to investigate the impact of variants on the severity of non-syndromic enlarged vestibular aqueduct. A male patient with NSEVA, aged approximately 6 years, was recruited for this study. The clinical characteristics and results of auxiliary examinations, including laboratory and imaging examinations, were collected, and 127 common hereditary deafness genes were detected by chip capture high-throughput sequencing. Protein structure predictions, the potential impact of mutations, and multiple sequence alignments were analyzed in silico. Compound heterozygote mutations c.1523_1528delinsAC (p.Thr508Asnfs*3) and c.422T>C (p.Phe141Ser) in the SLC26A4 gene were identified. The novel frameshift mutation c.1523_1528delinsAC produces a severely truncated pendrin protein, and c.422T>C has been suggested to be a disease-causing mutation. Therefore, this study demonstrates that the novel mutation c.1523_1528delinsAC in compound heterozygosity with c.422T>C in the SLC26A4 gene is likely to be the cause of NSEVA. Cochlear implants are the preferred treatment modality for patients with NSEVA and severe-to-profound sensorineural hearing loss Genetic counseling and prenatal diagnosis are essential for early diagnosis. These findings expand the mutational spectrum of SLC26A4 and improve our understanding of the molecular mechanisms underlying NSEVA.
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BACKGROUND Intracardiac leiomyomatosis (ICLM) is an extremely rare tumor which is benign but presents with aggressive behavior. To date, there is still no standard of care for ICLM therapy, and treatment for complicated ICLM has obtained even less attention. Radical surgery was usually recommended to remove the patients' tumors completely. Since initial complete surgical resection cannot be performed in all cases, bilateral salpingo-oophorectomy (BSO), via its effects of estrogen deprivation, may be a feasible primary step in the treatment of premenopausal women with unresectable ICLM. CASE REPORT We describe a case of a residual mass in the inferior vena cava and right atrium that shrank dramatically after BSO. The patient was a 41-year-old woman with initially unresectable ICLM. Total hysterectomy with BSO and excision of the retroperitoneal mass was performed, but the intracaval tumor above L5 was not removed. Pathology revealed a benign leiomyoma which was strongly positive for both estrogen receptor and progesterone receptor. Two weeks after the BSO, the patient's serum estradiol level had decreased to a postmenopausal level. At the same time, the proximal end of the intracaval tumor shrank dramatically from the level of the right atrium to the level of L3 only 2 weeks after the surgery. Therefore, this may provide a therapeutic window for a second reduction surgery. CONCLUSIONS BSO, via its estrogen deprivation effect, may provide a simple but effective initial treatment choice for premenopausal women who suffer from primary unresectable ICLM.
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Neoplasias Cardíacas , Leiomiomatose , Neoplasias Uterinas , Humanos , Feminino , Adulto , Leiomiomatose/cirurgia , Leiomiomatose/patologia , Receptores de Progesterona , Salpingo-Ooforectomia , Receptores de Estrogênio , Neoplasias Uterinas/cirurgia , Neoplasias Uterinas/patologia , Neoplasias Cardíacas/cirurgia , Neoplasias Cardíacas/patologia , Veia Cava Inferior/cirurgia , Veia Cava Inferior/patologia , Histerectomia , Estradiol , EstrogêniosRESUMO
AIM: The purpose of this study was to investigate the surgical techniques and clinical feasibility of nonuterine manipulator and enclosed colpotomy to avoid cancer cell spillages in laparoscopic radical trachelectomy (LRT) for patients with early-stage cervical cancer. METHODS: We performed the newly optimized surgical techniques of round ligament suspension and vaginal purse-string suture in LRT in 12 patients with early-stage cervical cancer from May 2019 to October 2020. Surgical information and postoperative results were recorded. RESULTS: All 12 patients successfully underwent LRT with round ligament suspension and vaginal purse-string suture, and no conversion to laparotomy was required. The median operation time was 268.5 min (range 200-320 min), including 5 min of round ligament suspension, and the median blood loss was 20 mL (range 5-50 mL). The median number of pelvic lymph nodes removed was 27 (range 19-35), and median amounts of paracervical tissue was 24 mm (range 21-26 mm) and vaginal tissue was 18 mm (range 16-26 mm). No intraoperative complication or serious postoperative complications were reported. CONCLUSION: Round ligament suspension and vaginal purse-string suture techniques are feasible and effective in LRT. They can replace uterine manipulator and unprotected colpotomy with satisfactory perioperative outcomes.
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Laparoscopia , Ligamentos Redondos , Traquelectomia , Neoplasias do Colo do Útero , Feminino , Humanos , Laparoscopia/métodos , Ligamentos Redondos/patologia , Técnicas de Sutura , Suturas , Traquelectomia/métodos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgiaRESUMO
STUDY OBJECTIVES: The purpose of this study was to evaluate the feasibility of "cuff-sleeve" sutures for reconstructing a functional neocervix in laparoscopic radical trachelectomy (RT). DESIGN: A retrospective analysis of a case series. SETTING: A teaching hospital. PATIENTS: Twenty-five patients who were diagnosed as early-stage cervical cancer from June 2017 to October 2020 in Sun Yat-sen Memorial Hospital. INTERVENTIONS: Laparoscopic RT with the "cuff-sleeve" suture method for cervicovaginal reconstruction. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients successfully underwent the laparoscopic RT with the "cuff-sleeve" suture method for cervicovaginal reconstruction, and no intraoperative complications occurred or conversion to laparotomy was needed. For all patients, approximately 80% of the cervical length was removed. Surgical radicality and negative surgical margins were also confirmed. During a median follow-up time of 29 months (range 8-48 months), no severe postoperative complications were observed. No cervical stenosis or secondary abnormal menstruation was reported. After the removal of the uterine stent 6 months after surgery, the neocervix length was approximately 14 mm (range 10-19 mm) and almost all the neocervixes were restored closely to the original anatomy. Four of 8 patients attempting actively to conceive were successful, and the cervical length of these pregnant patients was greater than or equal to 15 mm in all but one measurement at different gestational age. Three patients were ongoing pregnant, and the other had delivered successfully with a 16- mm cervix at term without cerclage. CONCLUSION: The "cuff-sleeve" suture method in cervicovaginal reconstruction is feasible in laparoscopic RT. This simplified suture technique can provide a functional neocervix to reduce cervical stenosis and incompetence.
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Laparoscopia , Traquelectomia , Neoplasias do Colo do Útero , Constrição Patológica/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Laparoscopia/métodos , Gravidez , Estudos Retrospectivos , Técnicas de Sutura , Suturas , Traquelectomia/métodos , Neoplasias do Colo do Útero/cirurgiaRESUMO
BACKGROUND: Intracardiac leiomyomatosis (ICLM) is a rare life-threatening form of intravenous leiomyomatosis (IVLM). The incomplete resection and recurrence are associated with high morbidity and mortality. The objective of this study is to identify that whether estrogen deprivation therapies, including bilateral salpingo-oophorectomy (BSO)-based surgery and gonadotrophin releasing hormone agonists (GnRHa) administration, could bring benefits to patients with primary unresectable ICLM. METHODS: PubMed/MEDLINE (Ovid) was searched (up to May 2021) for studies reporting individual patient data on demographics, clinicopathological features, treatment, and follow-up information. Exclusion criteria were patients who may have been included in two or more publications. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 114 patients from 70 papers were included. Several reports showed that the tumor in the right atrium and inferior vena cava shrank dramatically after BSO-based surgery, or GnRHa administrated preoperatively in premenopausal women. The rate of complete resection was 64.04% in patients with ICLM, which was 85.25% in no/slight adhesion and no pulmonary nodules group, while 22.22% in firm/extensive adhesion and/or pulmonary nodules group (p < 0.0001). Meanwhile, the recurrence rates in patients with complete resection and incomplete resection were 4.29% and 37.84% respectively (p < 0.0001). Furthermore, complete resection with BSO had the lowest recurrence rate of 3.13%, incomplete resection with BSO had a progression rate of 45.45%, while incomplete resection with ovarian preservation had the highest progression rate of 75.00%. CONCLUSIONS: The recurrence rate of ICLM was closely related to firm/extensive adhesion in IVC or above, and/or pulmonary nodules. BSO-based surgery might reduce the recurrence rate no matter ICLM could be completely resected or not. In addition, estrogen deprivation therapies could decrease tumor burden as a primary treatment, and further make a secondary complete resection feasible in premenopausal women with initially unresectable ICLM.
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Leiomiomatose , Estrogênios/uso terapêutico , Feminino , Humanos , Leiomiomatose/tratamento farmacológico , Leiomiomatose/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Veia Cava InferiorRESUMO
PURPOSE: The role of HHLA2, a new immune checkpoint ligand, is gradually being elucidated in various solid tumours. However, its role in ovarian cancer remains unclear; thus, its expression profile and clinical significance in ovarian cancer must be examined. METHODS: We performed immunohistochemistry to examine HHLA2 expression in 64 ovarian cancer tissues and 16 normal ovarian tissues. The relationships between HHLA2 expression and clinicopathological features, prognosis, and CD8+ tumour-infiltrating lymphocytes (TILs) in patients were analysed. Additionally, the Cancer Cell Line Encyclopedia database was used to analyse the correlation between HHLA2 expression and PD-L1 or B7x expression. Furthermore, the biological function of HHLA2 in ovarian cancer cells was initially explored. RESULTS: Only 17.2% of ovarian cancer patients showed HHLA2 expression, which was significantly associated with the differentiation of ovarian cancer cells (p = 0.027), and well-differentiated tumours expressed higher levels of HHLA2. The density of CD8+ TIL was associated with increased HHLA2 expression (p = 0.017), and the CD8+ TIL count was higher in the HHLA2-positive group than that in the HHLA2-negative group (p = 0.023). Moreover, multivariate analysis identified HHLA2 expression as an independent prognostic factor that predicted improved survival (p = 0.049; HR = 0.156; 95% CI = 0.025-0.992). Additionally, we also found that overexpressing HHLA2 inhibited the proliferation of ovarian cancer cells. CONCLUSION: HHLA2 is associated with tumour differentiation and high CD8+ TIL levels; and predicts improved survival in ovarian cancer. Along with previously reported findings that HHLA2 behaves as a co-stimulatory ligand, our study suggests that the loss of HHLA2 may contribute to the immunosuppressive microenvironment and progression of ovarian cancer.
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BACKGROUND The utility of cancer antigen 125 (CA-125), estrogen receptor (ER), and progesterone receptor (PR) in evaluation for ovarian metastasis of endometrial cancer has yet to be determined. The purpose of this study was to investigate the incidence and the possible risk factors of ovarian metastasis. MATERIAL AND METHODS A retrospective study was performed in endometrial cancer patients who accepted surgical intervention of hysterectomy and oophorectomy during 2002-2013 in Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China. Clinico-pathologic characteristics and the possible risk factors were investigated. RESULTS A total of 565 patients were identified, of which 5.7% had ovarian metastasis. Univariate analysis and multivariate analysis revealed that deeper myometrial invasion, tubal involvement, and parametrial involvement were independent risk factors. In subgroup analysis, univariate analysis showed that elevated CA-125 level and negative ER were associated with ovarian metastasis (P<0.05), however multivariate analysis revealed that only high CA-125 level was an independent risk factor (P<0.05). The incidence of ovarian metastasis in patients with high CA-125 level and who were ER-negative was 24%. For patients with normal CA-125 level and who were ER-positive, the incidence was 1.19%. The optimal cutoff value that provided the best sensitivity and specificity was 110.5 U/ml. CONCLUSIONS The incidence of ovarian metastasis in endometrial cancer is low. Ovarian preservation should be considered for women without abnormal CA-125 level and who have deeper myometrial invasion, tubal involvement, parametrial involvement, and who are ER-negative. These findings may facilitate clinical decision-making.
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Antígeno Ca-125/metabolismo , Neoplasias do Endométrio/patologia , Neoplasias Ovarianas/secundário , Receptores de Estrogênio/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Curva ROC , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND The aim of this study was to investigate the advantages and disadvantages of using laparoscopic slip knot with purse-string suture technique in the surgical management of unruptured heterotopic interstitial pregnancies compared with other surgical strategies. MATERIAL AND METHODS We retrospectively analyzed data on 13 patients with unruptured heterotopic interstitial pregnancies who underwent laparoscopy in our hospital between May 2012 and August 2018. The control group consisted of 10 patients who underwent cornual resection or cornuostomy with conventional sutures and knots. The study group consisted of 3 patients whose surgical plans involved use of the slip knot with purse-string suture technique followed by cornuostomy. We evaluated the surgical records and video to comparatively analyze their operation duration, intraoperative blood loss, and pregnancy outcomes. RESULTS The average volume of intraoperative blood loss was 76.67±25 ml in the study group and 215.00±110 ml in the control group. On average, the intraoperative blood loss volume in the study group was 138 ml less than in the control group and the difference was statistically significant (P<0.05). There was no statistically significant difference in the live birth rate and operation time between the 2 groups (P>0.05). The duration of hemostasis in the study group was 11 min shorter than in the control group, while the duration of cornual electrocoagulation in the study group was 18.5 s shorter. Both groups achieved thorough hemostasis without the help of vasopressin and avoided use of embryo-killing drugs such as methotrexate. Neither group required second surgery or developed postoperative complications such as uterus rupture or persistent ectopic pregnancy. CONCLUSIONS This strategy is safe and reliable for gestational sac clearance while simultaneously preventing any potential harm to the intrauterine embryo. It is particularly suitable for unruptured HIP patients who have a strong desire to preserve their intrauterine embryos.
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Gravidez Heterotópica/cirurgia , Gravidez Intersticial/cirurgia , Técnicas de Sutura , Adulto , Perda Sanguínea Cirúrgica , Feminino , Humanos , Laparoscopia/métodos , Duração da Cirurgia , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Suturas/tendênciasRESUMO
The recent discovery of complete ammonia oxidation (comammox) process in a single organism challenged the division of labor between two functional groups in the classical two-step nitrification model. However, the distribution and activity of comammox bacteria in various environments remain largely unknown. This study presented a large-scale investigation of the geographical distribution, phylogenetic diversity, and activity of comammox Nitrospira in typical agricultural soils. Among the 23 samples harvested across China, comammox Nitrospira clade A was ubiquitously detected at 4.14 × 104-1.65 × 107amoA gene copies/g dry soil, with 90% belonging to the subclade A2. The abundance of comammox Nitrospira clade B was two orders of magnitude lower than clade A. In all samples, comammox Nitrospira were 1-2 orders of magnitude less abundant than canonical nitrifiers, and soils with slightly high pH and C/N tended to enrich more comammox Nitrospira. Unlike canonical nitrifiers, comammox Nitrospira had sustained amoA gene transcription regardless of external ammonia supply, indicating their competitive advantage over other nitrifiers under low-ammonia conditions. When fed with 1 mM ammonium for 15 days, comammox Nitrospira in tested soils were enriched 2.36 times higher than those enriched by the same amount of nitrite, indicating their preference to utilizing ammonia as the substrate. DNA-SIP further confirmed the in situ nitrification activity of comammox Nitrospira. This study provided new insights into the broad distribution and diversity of comammox Nitrospira in agricultural soils, which could potentially play an important role in the microbial nitrogen cycle in soils.
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Nitrificação , Solo , Amônia , Archaea , Bactérias , China , Oxirredução , Filogenia , Microbiologia do SoloRESUMO
BACKGROUND The aim of this study was to compare magnetic resonance imaging (MRI) and hysteroscopy (HS) for assessing cervical involvement in early-stage endometrial adenocarcinoma in order to establish a more reliable screening method to aid in clinical decision-making. MATERIAL AND METHODS A retrospective analysis was performed on the clinicopathological data from 88 patients with stage I or II endometrial adenocarcinoma who underwent MRI and HS prior to surgery in the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China. Chi-square and Fisher's exact tests were performed to compare the accuracy, sensitivity, specificity, and positive and negative predictive values in the diagnosis of cervical involvement by MRI and HS. The relationship between clinicopathological factors and the deviation of diagnosis by MRI and HS from that by pathology was also analyzed. RESULTS The accuracy of assessing cervical conditions was 93.2% by MRI and 55.7% by HS. Among these variables, the accuracy, specificity, and positive predictive values of MRI were significantly different from those of HS, while the sensitivity and negative predictive values of MRI and HS were not significantly different from each other. Age, tumor size, tumor differentiation, and depth of myometrial invasion were not associated with the differences in cervical assessment between MRI and HS. However, the tumor location may affect assessment by HS. CONCLUSIONS MRI is better than HS for cervical assessment. The negative predictive values of both MRI and HS are high and unsatisfactory.
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Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/diagnóstico , Adenocarcinoma/patologia , Adulto , Idoso , China , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histeroscopia/métodos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Studies have shown that granzyme B expression was up-regulated during acute renal rejection, which provides hopes for a noninvasive and reliable diagnostic method. However, the diagnostic performance has not been assessed systematically so far. METHODS: Relevant materials were searched from electronic databases before February 1, 2012. Clinical studies that reported the diagnostic performance of detecting granzyme B mRNA using polymerase chain reaction techniques in acute renal rejection patients were included. The data of true-positive, true-negative, false-positive, and false-negative cases identified by granzyme B detection were extracted from each data set of the relevant materials. The publication year, sample origin, mRNA quantification method, and housekeeping gene were extracted as potential confounding variables. RESULTS: Fourteen studies with a total of 514 cases were included. The overall diagnostic performance of granzyme B was pooled sensitivity of 0.76 (95% confidence interval [CI], 0.69-0.81), pooled specificity of 0.87 (95% CI, 0.83-0.90), diagnostic odds ratio of 19.27 (95% CI, 1.20-195.00), and area under the summary receiver operating characteristic curve value of 0.8900±0.0270. The univariate analysis of potential variables showed no statistically significant variations. CONCLUSIONS: Despite interstudy variability, granzyme B mRNA demonstrated both sensitivity and specificity in the diagnosis of acute rejection and showed consistency under circumstances of methodologic changes. However, the clinical practice requires careful consideration and other supplementary tests.
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Rejeição de Enxerto/diagnóstico , Granzimas/genética , Doença Aguda , Granzimas/análise , Humanos , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/análiseRESUMO
BACKGROUND: Studies in the past have shown that perforin expression is up-regulated during acute renal rejection, which provided hopes for a non-invasive and reliable diagnostic method to identify acute rejection. However, a systematic assessment of the value of perforin as a diagnostic marker of acute renal rejection has not been performed. We conducted this meta-analysis to document the diagnostic performance of perforin mRNA detection and to identify potential variables that may affect the performance. METHODOLOGY/PRINCIPAL FINDINGS: Relevant materials that reported the diagnostic performance of perforin mRNA detection in acute renal rejection patients were extracted from electronic databases. After careful evaluation of the studies included in this analysis, the numbers of true positive, true negative, false positive and false negative cases of acute renal rejection identified by perforin mRNA detection were gathered from each data set. The publication year, sample origin, mRNA quantification method and housekeeping gene were also extracted as potential confounding variables. Fourteen studies with a total of 501 renal transplant subjects were included in this meta-analysis. The overall performance of perforin mRNA detection was: pooled sensitivity, 0.83 (95% confidence interval: 0.78 to 0.88); pooled specificity, 0.86 (95% confidence interval: 0.82 to 0.90); diagnostic odds ratio, 28.79 (95% confidence interval: 16.26 to 50.97); and area under the summary receiver operating characteristic curves value, 0.9107±0.0174. The univariate analysis of potential variables showed some changes in the diagnostic performance, but none of the differences reached statistical significance. CONCLUSIONS/SIGNIFICANCE: Despite inter-study variability, the test performance of perforin mRNA detected by polymerase chain reaction was consistent under circumstances of methodological changes and demonstrated both sensitivity and specificity in detecting acute renal rejection. These results suggest a great diagnostic potential for perforin mRNA detection as a reliable marker of acute rejection in renal allograft recipients.
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Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Transplante de Rim/imunologia , Perforina/genética , Reação em Cadeia da Polimerase/métodos , Regulação da Expressão Gênica , Humanos , Razão de Chances , Perforina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Curva ROC , Sensibilidade e EspecificidadeRESUMO
Because of the severe organ shortage, living donor liver transplantation (LDLT) offers a timely alternative to deceased donor liver transplantation (DDLT) for patients with hepatocellular carcinoma (HCC). However, the higher recurrence rate of HCC after LDLT and the indication criteria remain controversial. By conducting a quantitative meta-analysis, we sought to compare the survival outcomes and recurrence rates with LDLT and DDLT for patients with HCC. Comparative studies of LDLT and DDLT for HCC, which were identified by a comprehensive literature search, were included in this study. The evaluated outcomes included patient survival, recurrence-free survival (RFS), and recurrence rates at defined time points. Seven studies with a total of 1310 participants were included in this study. For LDLT and DDLT recipients, we found comparable patient survival rates [1 year, odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.62-1.73; 3 years, OR = 1.07, 95% CI = 0.77-1.48; and 5 years, OR = 0.64, 95% CI = 0.33-1.24] and RFS rates (1 year, OR = 0.86, 95% CI = 0.54-1.38; 3 years, OR = 1.04, 95% CI = 0.69-1.58; and 5 years, OR = 1.11, 95% CI = 0.70-1.77). Moreover, we found no significant differences in the 1-, 3-, or 5-year recurrence rates between LDLT and DDLT recipients (1 year, OR = 1.55, 95% CI = 0.36-6.58; 3 years, OR = 2.57, 95% CI = 0.53-12.41; and 5 years, OR = 1.21, 95% CI = 0.44-3.32). A subgroup analysis revealed similar outcomes for patients with HCC meeting the Milan criteria. These findings demonstrate that for HCC patients (especially those within the Milan criteria), LDLT represents an acceptable option that does not compromise patient survival or increase HCC recurrence in comparison with DDLT.
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Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Doadores Vivos , Doadores de Tecidos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/mortalidade , Masculino , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/mortalidade , Prevalência , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To investigate the efficacy and safety of an immunosuppressive regimen of steroid avoidance in combination with induction therapy and tacrolimus in liver transplant recipients. MATERIALS AND METHODS: Eighty-two adult liver transplant recipients were randomized into 2 groups: standard protocol group (n=41) in which steroids were withdrawn 3 months after the operation, and a 24-hour steroid avoidance group (n=41) in which steroids were eliminated within 24 hours. The incidence of acute rejections, infections (bacterial, fungal, and cytomegalovirus), and metabolic complications were analyzed between the groups. RESULTS: The incidence of early posttransplant diabetes mellitus and the average dosage of insulin consumption among diabetic recipients were significantly higher in recipients in the standard protocol group than in the 24-hour avoidance group (P < .05). In addition, the incidence of hypertension and infection during the follow-up were also higher in patients of the standard protocol group (P < .05). The incidence of hypertension in the early posttransplant period, hyperlipemia, and acute rejection during the follow-up were comparable between the groups (P > .05). CONCLUSIONS: Twenty-four hour steroid avoidance combined with induction therapy and tacrolimus maintenance is a safe and efficient immunosuppression strategy that can significantly reduce posttransplant infections and other complications owing to long-term use of steroids, without increasing the risk of acute rejection.
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Anticorpos Monoclonais/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Fígado/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico , Esteroides/uso terapêutico , Tacrolimo/uso terapêutico , Suspensão de Tratamento , Adulto , Idoso , Basiliximab , China , Diabetes Mellitus/epidemiologia , Quimioterapia Combinada , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Humanos , Hipertensão/epidemiologia , Incidência , Estimativa de Kaplan-Meier , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: The Cylex ImmuKnow cell function assay (CICFA) is being considered as a possible tool for identification of infection and rejection in transplant recipients. However, the predictive capability of CICFA is still unclear. METHODS: Herein, we performed a meta-analysis to assess the efficacy of CICFA in identifying risks of infection and rejection posttransplantation. After a careful review of eligible studies, sensitivity, specificity, and other measures of the accuracy of CICFA were pooled. Summary receiver operating characteristic curves were used to represent the overall test performance. RESULTS: Nine studies met the inclusion criteria. The pooled estimates for CICFA in identification of infection risk were poor, with a sensitivity of 0.58 (95% confidence interval [CI]: 0.52-0.64), a specificity of 0.69 (95% CI: 0.66-0.70), a positive likelihood ratio of 2.37 (95% CI: 1.90-2.94), a negative likelihood ratio of 0.39 (95% CI: 0.16-0.70), and a diagnostic odds ratio of 7.41 (95% CI: 3.36-16.34). The pooled estimates for CICFA in identifying risk of rejection were also fairly poor with a sensitivity of 0.43 (95% CI: 0.34-0.52), a specificity of 0.75 (95% CI: 0.72-0.78), a positive likelihood ratio of 1.30 (95% CI: 0.74-2.28), a negative likelihood ratio of 0.96 (95% CI: 0.85-1.07), and a diagnostic odds ratio of 1.19 (95% CI: 0.65-2.20). CONCLUSION: The current evidence suggests that CICFA is not able to identify individuals at risk of infection or rejection. Additional studies are still needed to clarify the usefulness of this test for identifying risks of infection and rejection in transplant recipients.