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Septic shock is the most critical stage of sepsis, and the core of the treatment is improving tissue hypoperfusion.In addition to the improvement of large circulation by fluid resuscitation, the microcirculation also need to be improved, then proper vasoactive drugs should be applied to different types of shock to meet the needs of the body for perfusion.The condition of septic shock progresses rapidly, and the microcirculation in different pathophysiological stages is different, which increases the difficulty of rational use of vasoactive drugs.Monitoring and accurate evaluation of peripheral microcirculation may provide guidance for individualized treatment of septic shock.
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Minimal residual disease (MRD) has been used not only for relapse prediction, prognosis re-classification and directing pre-emptive therapy of patients with acute leukemia, but also in the field of therapy for patients with other hematological malignancies or solid tumors. A deep understanding of the intension and extension of MRD is important for exploring novel methods for accurate prediction of relapse and consummating the individualized intervention strategies for malignant tumors.
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Circulating tumor cells (CTC) are tumor cells that escape from the primary or metastatic tumor into the circulatory system, and closely related to cancer metastasis. Since the samples can be obtained through simple and minimally invasive blood sampling operations, CTCs have a great clinical potential. PCa is one of the most common malignant tumors in men. In recent years, many scholars have conducted studies as to whether CTC technology can be used for the diagnosis and treatment of PCa, as well as for more accurate prediction of the risk of progression. This article summarizes the advances in researches relating CTC technology and the diagnosis and treatment of PCa. CTC detection has been developed from simple counting to phenotypic classification, and even to its combination with the determination of the expressions of specific genes (such as AR, AR-V7, etc.) and single-cell sequencing. Some reports showed that CTC technology has a certain significance in the early diagnosis of PCa, but its main value is demonstrated in drug sensitivity and prognosis evaluation in the late stage of the malignancy. The standardized detection methods and reference values of CTCs in PCa will be important research orientations in the near future.
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Humans , Male , Cell Count , Neoplasms, Second Primary , Neoplastic Cells, Circulating , Prognosis , Prostatic Neoplasms/therapyABSTRACT
Ulcerative colitis (UC) is a chronic, progressive and heterogeneous inflammatory bowel disease. Strategies for management of UC are shifting from simple control of symptoms toward clinical/patient-reported outcome remission (resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (mucosal healing), with the final aim of blocking the progression of the disease and promising better long-term outcomes. The therapeutic target for UC is a comprehensive one that combines subjective and objective goals as well as short-term and long-term goals. In order to achieve these goals, it is necessary to assess the severity of the disease first and predict the risk of UC progression, and then provide early intervention and individualized treatment for high-risk patients. The treatment should be timely tailored by close monitoring. Although the clinical implementation of UC treat-to-target (T2T) approach remains challenging, T2T strategy is the key-point for improving the quality of disease management.
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The application of antiglaucoma drugs is the main treatment for glaucoma,but there are differences in the response of patients to antiglaucoma drugs.Different races have different reactivities to prostaglandins;the same patient may has different reactivity to different prostaglandins;with the prolonged use of prostaglandins,the status of some patients have changed from being unresponsive to being reactive.The reasons for individual difference of drug response are complex.Drug receptor and metabolism gene polymorphisms are deemed as the cause of individual difference.Studying the relationship between drug responses and gene differences can realize individual therapy.This review summarized the response to antiglaucoma drugs and influence factors leading to individual difference of drug response,which may provide help for clinical individualized and precise treatment.
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Mycophenolate mofetil (MMF) is a cornerstone immunosuppressant in clinical therapy, such as organ transplantation. Because of the huge interindividual difference in genetic polymorphisms and some other, fixed-dose MMF-treated strategy can neither attain the targeted effective and safe MPA blood concentration nor satisfy the needs of individualized therapy,especially in children.The article reviews the value of genetic polymorphism of UGT,IMPDH,ABCC2,SLCO in MMF therapy in children to highlight its role in the precision treatment.
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The application of antiglaucoma drugs is the main treatment for glaucoma,but there are differences in the response of patients to antiglaucoma drugs. Different races have different reactivities to prostaglandins;the same patient may has different reactivity to different prostaglandins;with the prolonged use of prostaglandins,the status of some patients have changed from being unresponsive to being reactive. The reasons for individual difference of drug response are complex. Drug receptor and metabolism gene polymorphisms are deemed as the cause of individual difference. Studying the relationship between drug responses and gene differences can realize individual therapy. This review summarized the response to antiglaucoma drugs and influence factors leading to individual difference of drug response,which may provide help for clinical individualized and precise treatment.
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Oxcarbazepine (OXC) is a common antiepileptic drugs. In this study, one hundred and eighty four epilepsy patients with 196 observations of oxcarbazepine's active metabolite, 10,11-dihydro-10-monohydroxy carbazepine (MHD) were collected prospectively from routine clinical monitoring. Nonlinear mixed effect modeling was employed to develop a population pharmacokinetic model of oxcarbazepine in Chinese patients with epilepsy to investigate the impact of gender, age, weight, co-medications and genetic polymorphisms of UGT2B7 c.802T>C, ABCC2 c.1249G>A, ABCC 23972C>T on pharmacokinetic characteristics of OXC. The population estimate of apparent clearance (CL/F) and apparent volume of distribution (V/F) was 1.84 L·h−1 and 275 L, respectively. Gender and UGT2B7 c.802T>C affected the clearance rate of MHD significantly. The established model was:CL/F=1.84×0.848UGT2B7×1.17GENDER. Where the genotype of UGT2B7 c.802T>C was CC, UGT2B7=0, otherwise UGT2B7=1. When the patient was male, GENDER=1, otherwise GENDER=0. The final model was evaluated by normalized predictive distribution error (NPDE) and bootstrap method. The model was stable and reliable, which offers a powerful approach for rational use of OXC in epilepsy patients.
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The incidence and mortality of colorectal cancer (CRC) increased rapidly in recent decades and become enormous challenges in China.Lack of effective early warning of molecular markers and dynamic monitoring technology in term of early diagnosis,treatment evaluation,dynamic recurrence and metastasis monitoring are the clinical diagnosis and treatment bottlenecks of CRC.Traditional diagnosis and treatment of CRC rely on a single level of patient information with low accuracy.Based on the system of biology medical model,to carry out a joint diagnostic model,will overcome the traditional problems through a number of multi-level information integration of the joint diagnosis model,will significantly improve the sensitivity and specificity of diagnosis of CRC.The major challenge in patients with advanced and metastatic CRC is the instability of the tumor genome and the treatment-induced resistance during chemotherapy and targeted therapy.It is necessary to carry out continuous dynamic biopsy in order to accurately guide the development of treatment decisions.Compared with the pathological examination of traditional surgical specimen,liquid biopsy,such as circulating tumor cells,circulating tumor DNA detection technology,with noninvasive,real-time dynamic monitoring,could evaluate the efficacy of treatment,and guide the precise individual diagnosis and treatment.Today,the new strategy and new technology need to undergo clinical trials urgency,through technology optimization,reduction of costs and improvement of detection accuracy,would quickly extended to clinical applications in future.
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Patient-derived xenograft models (PDXs) of lung cancer are obtained by directly implanting lung cancer tissue fragments in-to immunocompromised mice. The implanted tumor fragments can be proliferated and passaged in these mice models. The PDXs maintain the tumor microenvironment, histological and pathological characteristics, and tumor biomarkers of the original tumor tis-sues. The PDX also offers an ideal mice model that mimics the human tumor microenvironment. These models have important roles in the pre-clinical evaluation of cancer, the assessment of anti-tumor drug responses, and the analysis of biomarkers. These models also present a new direction for the individualized therapy of lung cancer patients.
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Objective To investigate clinicopathologic characteristics,individualized immunotherapy and prognosis of antibody-mediated rejection (AMR)after renal transplantation.Methods Clinical data of 32 patients,who were confirmed as AMR after renal transplantation by pathology and admitted in the Department of Urology and Renal Transplantation of the First Affiliated Hospital of Henan Traditional Medical College from January 2010 to December 2013,were retrospectively studied.The corresponding immunological intervention was adopted according to the clinicopathologic characteristics of different patients.The indicators including renal function,panel reactive antibody (PRA)and serum immunoglobulin (Ig)G,IgA and IgM level before and after treatment were determined,and adverse reactions were observed.Results Of all 32 patients, 18 developed acute antibody-mediated rejection (AAMR ) and 14 developed chronic antibody-mediated rejection (CAMR).Of 13 PRA-positive patients,8 (62%,8 /13)cases were with donor specific antibody and 5 (38%,5 /13)cases were with non-donor specific antibody.The primary pathological manifestations of early AAMR were changes of acute tubular necrosis (ATN ),peritubular capillary inflammation,glomerulitis, fibrinoid necrosis of small arteries,linear C4d deposition in peritubular capillaries (PTC)and immunoglobulin or C3 deposition in arterial wall.The pathological manifestations of CAMR were changes of glomerulopathy, splitting of PTC basement membrane,fibrous intimal thickening and diffuse C4d deposition in PTC.After treatment,the renal function of 20 (63%,20 /32)patients returned to normal,the renal function of 7 (22%, 7 /32)patients were stable,the serum creatinine (Scr)of 5 (16%,5 /32)patients increased slowly.Of such 5 patients,2 (2 /5 )patients continued hemodialysis,3 (3 /5 )patients did not need hemodialysis and no patient died.The indicators including blood urea nitrogen (BUN),Scr,PRA and serum IgG,IgA and IgM after treatment decreased significantly when compared with those before treatment (all in P <0.01).No serious adverse reaction was noted during the treatment.Conclusions AMR may manifest as AAMR or CAMR after renal transplantation.The gold standard for diagnosing AMR is pathologic biopsy of transplant kidney.To adopt effective individualized immunotherapy in time is the critical measure for treatment of AMR.
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OBJECTIVE: To develop software for individualized dosage regimen of valproic acid and carbamazepine according to population pharmacokinetics and Bayesian estimation method. METHODS: Based on the prior population pharmacokinetic (PPK) information, Microsoft Excel 2010 was employed as the input-output interface to run the PPK program, Nonlinear Mixed Effect Modeling (NONMEM), to estimate the PK parameters and design the regimen. RESULTS: The software fulfills the functions of patient information management, initial dosage design, dosage calculation by maximum a posterior Bayesian estimation (MAPB) and compliance assessment. CONCLUSION: The established software provides a powerful tool in the clinical settings to facilitate the individualized therapy for the epilepsy patients.
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OBJECTIVE: To review and summarize the progress in the genetic association studies between human leucocyte antigen (HLA) polymorphisms and drug-induced liver injury(DILI). METHODS: Based on the literature research, the results of the studies on the association between HLA alleles and DILI are presented and evaluated. RESULTS AND CONCLUSION: Several strong genetic associations between DILI and HLA alleles were observed in previous studies, such as HLA-B*5701 has a strong association with flucloxacillin induced liver injury (odds ratio=80.6). Due to the racial differences in HLA alleles frequency, the incidence of DILI by nevirapine, ticlopidine, ximelagatran varied largely in different ethnic populations. These studies can help us better understand the immunogenic pathogenesis in the underlying mechanism of DILI. The discovery of genetic biomarkers can be developed as a predictive test will improve drug safety and facilitate the individual therapy.
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Objective To discuss pharmaceutical care for patients with acute pancreatitis , investigate and expand the role of clinical pharmacists in the clinical treatment .Methods To prepare pharmaceutical care , medication guidance and interventions of life were offered to an acute pancreatitis patient .Results The patient′s medication compliance was enhanced and good for the clinical ther-apy.Conclusion Clinical pharmacists could play an important role in patient′s implementation of a comprehensive and effective pro-gram of individual administration .
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OBJECTIVE: To review the target concentration intervention (TCI) theory and provide reliable evidences for the optimization of drug treatment in clinical practice. METHODS: Relevant literatures were extensively and comprehensively reviewed. RESULTS: Since 1960s, therapeutic drug monitoring (TDM) had been applied in clinical practice to realize individualized drug administration. Due to some potential limitations of TDM such as neglecting inter-individual variability and failure to take drug effects into account, more and more scholars proposed a new theory which is called TCI as an alternative of TDM. The TCI approach takes advantage of known patient variables, pharmacokinetics and pharmacodynamics to interpret drug effect and concentration observations. It not only overcomes the defects of TDM, but also provides a complete strategy for individual administration. CONCLUSION: TCI is an extension of TDM, which has clinical significance for individualized therapy.
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10.3969/j.issn.1007-3969.2013.05.002
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Objective To compare clinical outcomes in cardiac transplant recipients treated with individualized dosing (ID) and fixed dosing (FD) of mycophenolate mofetil (MMF).Methods Fortyeight de novo cardiac transplant patients in ID group received MMF (2.0 g/day) in combination with calcineurin inhibitors and prednisone.The MMF dosages were adjusted individually based on clinical events and MPA trough levels (MPA-C0).The target range of C0 was maintained within 2.0-4.0rng/L.The FD group included 55 recipients retrospectively from the transplant database who were also treated with MMF (2.0 g/day).In this group,the MMF dose adjustment was performed empirically according to clinical events only.All of the follow-up data were collected up to 12 months post-transplantation.Results The follow-up rate was 95.8％ and the mean MPA-AUC0-12 was (54.37± 17.03) rng h-1 L-1 in the ID group.The mean MPA-C0 on the day 7 post-transplantation was significantly higher in the ID group than that at 12th month [(3.44 ± 0.58) mg/L vs.(2.79 ± 0.54)mg/L] (P＜0.05).The dose of MMF was significantly lower in the ID group at 4th week posttransplantation than in control group [(1.49± 0.48) g/day vs.(1.96 ± 0.39) g/d] (P＜0.05),while there was no significant difference at 12 th month post-transplantation [(1.61 ± 0.77) g/day vs.(1.68 ± 0.84) g/day] (P＞ 0.05).No significant difference was found in the incidence of acute rejection episode between two groups (8.7％ vs.9.1％,P＞0.05).57.6％ of overall side effects were observed within one month postoperatively,and the incidence of MPA-related side effects was significantly lower in the ID group than in the control group (47.8％ vs.67.3％,P＜0.05).Conclusion It was demonstrated that individualized use of MMF based on therapeutic drug monitoring may prevent MMF-related side effect and appears to be valuable to optimize the treatment of cardiac transplantation.
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The toxic effects of immunosuppressants are often dangerous factors which influence long-term survival of recipients.Individualized immunosuppressive therapy has been a hotspot and difficulty for comprehensive treatment of liver transplantation.Immunosuppressive therapy has been gradually developed to pursue long-term survival for receipients and graft,minimized side effects of immunosuppressants,optimized quality of life of patients,and reduce the economic burden of patients.Through consideration of patient's pathophysiological state,understanding the characteristics and side effects of various immunosuppressive,appropriate choose of the immune inhibitor,correct evaluation of immune state of recipients and graft,minimization of drug doses,individualized dosing regimen could be successfully carried out.
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Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors,and more than half of newly diagnosed patients with NSCLC are stage Ⅲ B or Ⅳ.Maintenance treatment has been intensively investigated in the field in order to improve time to recurrence and survival time.This paper reviewed recent advances in the maintenance treatment for NSCLC.
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Introduction: Sickle cell disease (SCD) has a wide range of clinical presentation. We evaluated hematological parameters, which are widely evaluable and assessable, as indices of clinical outcome in SCD. These parameters, although largely established as indices of clinical outcome in other SCD populations, have not been widely evaluated in African patients. Materials and Methods: One hundred and thirty six consecutive stable SCD patients who presented in the sickle cell clinic of a teaching hospital were studied retrospectively using a questionnaire. Hematological parameters of full blood count (FBC) for each patient were obtained using a cell counter. FBC parameters such as White blood cell count (WBC) were then statistically correlated with complications such as ankle ulcers, osteomylitis and others. A Chi-square text was used to compare frequencies and generate P values. Results: The presence of sickle cell complications was significantly associated with raised white blood cell count (WBC) above 11 × 10 9 /l (P0 = 0.03).The WBC of the patients increased with increasing numbers of complications ( P = 0.07). Mean packed cell volume (PCV) and WBC tended toward the reference range for age and sex (in apparently normal individuals) as the age at diagnosis of SCD increased. This trend was significant for PCV (P = 0.01). Conclusion: Our data provide additional support that widely evaluable and assessable hematological parameters such as PCV and WBC can be used as indices to predict SCD outcome in African patients. This is likely to impart positively on individualized therapy.