2017年 · 第56卷第11期

Multiple myeloma (MM) is a common hematological malignancy, ranking second in the prevalence of hematological tumors in many countries, and it is still incurable. MM often occurs in the elderly. With the progress of China's aging society, it can be predicted that this disease will become more and more common. In recent years, there have been many new advances in the field of MM, including the continuous change of disease diagnosis and differential diagnosis, the continuous introduction of new efficacy evaluation standards, and the introduction of new treatment plans. The "Guidelines for the Diagnosis and Treatment of Multiple Myeloma in China" formulated by the Hematology Branch of Chinese Medical Association and the Hematologist Branch of Chinese Medical Doctors Association have also been greatly updated, and the full text is published in this issue. It is believed that every update of MM diagnosis and treatment guidelines is of great significance to improve the diagnosis and treatment level of MM in China. We invited Professor Lu Jin of Peking University People's Hospital to write a monograph "Flowers are gradually charming, and clouds and sails are waiting to hang in the sea-Message to the Fourth Revision of the Guidelines for the Diagnosis and Treatment of Multiple Myeloma in China", and specially participated in the revision of various parts of this guide to interpret the efficacy standards, initial treatment, relapsed/refractory myeloma treatment and other parts of the MM guidelines. Renal damage is a common manifestation of functional impairment of myeloma-related organs. This issue also published the "Expert Consensus on Diagnosis and Treatment of Kidney Damage in Multiple Myeloma" completed by China's Expert Collaboration Group, and invited Professor Chen Nan of the Institute of Nephrology, Shanghai Jiaotong University School of Medicine to write a monograph "Attaching importance to the diagnosis and treatment of kidney damage in multiple myeloma". Welcome to Read.

multiple myeloma (MM) is the second most common hematological malignant tumor in many countries, and it tends to occur in the elderly. With the progress of China's aging society, it can be predicted that this disease will become more and more common. In recent years, the treatment of MM has made obvious progress, and the demand for standardized diagnosis and treatment of MM is increasingly strong. The revised guidelines for diagnosis and treatment of MM every two years partially meet this demand. At the same time, due to many new advances at home and abroad, including the constant change of disease diagnosis and differential diagnosis, the constant introduction of new efficacy evaluation standards, and the introduction of new treatment plans, we are also required to constantly update the progress in this field in the MM guidelines, so that Chinese doctors can have dialogue with their counterparts all over the world in the same "language".

Multiple myeloma (MM) is a malignant tumor disease of plasma cells. Abnormally proliferating tumor cells mainly infiltrate bone marrow and soft tissue, and produce a large number of abnormal monoclonal immunoglobulins, resulting in bone destruction, anemia, immune dysfunction and kidney injury. The disease can present a variety of manifestations when it involves the kidney, the most common manifestation is tubular nephropathy, in which a large number of light chains are excreted from the kidney, blocking and damaging the renal tubules. In addition, the light chain aggregates into amyloid fibers, and the deposition of renal tissue can lead to renal amyloidosis. The pathogenic light chain protein is mainly lambda light chain; If the denatured light chain or heavy chain protein does not form beta fold protein, deposition of renal tissue can lead to monoclonal immunoglobulinopathy and the like.

Guidelines for Diagnosis and Treatment of Multiple Myeloma in China (Revised in 2017)^[1]Treatment recommendations for asymptomatic myeloma and solitary plasmacytoma have not been changed from the 2015 revision. For the initial treatment of symptomatic myeloma, compared with the previous version, it remained basically stable, and some contents were slightly updated. Strategically, the overall structure of induction therapy, high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation or conventional chemotherapy consolidation therapy and maintenance therapy is still maintained. The recommended protocols for induction therapy and maintenance therapy have been updated.

With the widespread application of proteasome inhibitors and immunosuppressants in newly diagnosed multiple myeloma (MM), the remission time and survival time of MM patients are gradually prolonged, but MM patients will eventually relapse. And because proteasome inhibitors and immunosuppressants have been widely used in the first line, it is increasingly difficult to choose the treatment of relapsed/refractory MM. With the limited number of new drugs in China, it is crucial to evaluate the disease of relapsed patients before treatment. Choosing an appropriate treatment plan can further improve the efficacy of relapsed/refractory MM and benefit the survival of patients. Here's an interpretation of this part of the 2017 edition of the MM Guide.

In the past decade or so, with the application of new drugs, especially after the combination of autologous hematopoietic stem cell transplantation, post-transplantation consolidation therapy, and long-term maintenance therapy, the remission rate and depth of remission in patients with multiple myeloma (MM) have been greatly improved. Complete remission (CR) can be achieved in more than 50% of patients^[1]。 But what is unsatisfactory is that despite this deep level of remission, most patients will eventually relapse^[2]Therefore, CR cannot ideally reflect deeper remission, and new efficacy criteria are needed to define deeper efficacy than CR. Recent research has focused on the application of flow cytometry and gene sequencing to detect minimal residual disease (MRD) in bone marrow, and imaging techniques reflecting cell invasiveness and proliferative activity have also been used to detect residual lesions. Many studies have confirmed that MRD can more sensitively and deeply reflect the depth of remission of disease, and is closely related to the prognosis of disease^[3]。 The International Myeloma Working Group (IMWG) combined these new tests to define new efficacy criteria, with the aim of evaluating according to unified efficacy criteria in different clinical trials.

Example 1The patient was a 46-year-old male. He was admitted to hospital on October 14, 2014 due to intermittent hemoptysis for more than 5 months. Five months ago, the patient had cough and sputum with blood in the sputum after catching a cold. After half a month of anti-infection and hemostatic treatment according to bronchitis in the local clinic (the specific medication is unknown), the blood in the sputum stopped without obvious discomfort. One month ago, the patient had cough and hemoptysis again after catching a cold. The whole mouth of blood, about 5 ml, contained blood clots. The chest CT examination at the local hospital showed that the soft tissue shadow in the middle and upper trachea obstructed part of the lumen. Bronchoscopy showed that the new organism in the middle of the trachea protruded from the lumen and obstructed most of the airway. The surface tissue of the new organism was obtained by biopsy, and the pathology showed that it was polyp, and no cancer cells were found. Admitted to our hospital for further diagnosis and treatment. Past physical fitness. Physical examination at admission: temperature 36.2 ℃, pulse 104 beats/min, breathing 23 beats/min, blood pressure 132/101 mmHg (1 mmHg =0.133 kPa). The auscultation of both lungs showed coarse breathing sounds, and no dry and wet rales were heard. The heart rate was 104 beats/min, the rhythm was uniform, and no pathological murmur was heard in the auscultation area of each valve. The abdomen was soft, without tenderness and rebound pain, and the liver and spleen were not palpable under the costs. Admission diagnosis: The nature of the mass in the airway is to be investigated. Perfect relevant examinations after admission, WBC 6.9×10⁹/L, Hb 154 g/L, PLT 222×10⁹/L, normal urine and fecal routine, normal liver and kidney function, normal hemagglutination test, HBsAg negative, anti-HBs positive, anti-Treponema pallidum antibody negative, anti-HIV negative, anti-HCV negative, tumor marker negative, C-reactive protein 1.2 mg/L, ESR 0.4 mm/1h, G test 134.6 pg/ml. Bronchoscopy showed a new organism about 4 cm below the glottis, occupying 2/3 of the lumen, with abundant blood vessels on the surface (Figure 1), obvious powder staining under the new biofluorescence microscope (Figure 2), new biological surface tissue was obtained by biopsy, and pathology showed chronic inflammation with fibrous tissue hyperplasia. On October 21, bronchoscopy was performed again. The new organism had a rough surface, and white necrosis was visible (Figure 3), the biopsy clamp removed the white necrotic tissue, and the pathology showed chronic inflammation of the mucosa, and more necrosis and exudates were seen. On October 23, chest enhanced CT showed soft tissue shadows in the upper and middle airways, with mild uneven enhancement (Figure 4)。 On October 27th, the third bronchoscopy showed that the tumor was smaller than before, and bleeding was visible on the surface. High-frequency electric cauterization with a ferrule was performed, and the tumor was cut along the tracheal wall (Figure 5), pathology suggests glomus tumor (Figure 6), keratin (CK) negative, epithelial membrane protein (EMA) negative, Vimentin (Vimentin) positive, CD₃₁Negative, CD₃₄Negative, smooth muscle actin (SMA) positive, CD₅₆negative, synaptophysin (Syn) negative, transcription mediator-1 (TIF-1) negative, CK7 negative, Ki-67 (<5%＋)。 Then he was transferred to the thoracic surgery department for "partial tracheectomy plus tracheal reconstruction", and he recovered well after operation. The histopathology showed glomus tumor, which was consistent with the results of bronchoscopic pathology. After 2 years of follow-up, no recurrence was observed.

Hypercortisolism (Cushing's syndrome) is a general term for disorders caused by excessive cortisol secretion by the adrenal glands due to various etiologies. Excessive cortisol inhibits pituitary gonadotropin secretion, which often leads to ovulation disorders in female patients. Therefore, Cushing's syndrome complicated with pregnancy is very rare, and it is easy to be misdiagnosed and missed clinically. The following reports a case of successful pregnancy and delivery of a live fetus in a patient with Cushing's syndrome, and reviews the relevant literature to deepen the understanding of Cushing's syndrome complicated with pregnancy.

adrenal hypoplasia congenital (AHC) combined with hypogonadotropic hypogonadism (HH) is very rare, with an incidence of 1:140 000 to 1:1 200 000 live births^[1], Lin et al.^[1]Studies have shown that 58% of patients with HH originate fromDAX-1Genetic mutations. We recently treated two male patients with AHC for "delayed puberty", and genetic testing found thatDAX-1Genetic mutations. The report is as follows.

Top international academic journals in the field of hematology, June 2017LeukemiaA prospective clinical study of "Donor selection for allogeneic hematopoietic stem cell transplantation in the first remission stage of acute leukemia" completed by Professor Huang Xiaojun's team from the Institute of Hematology of Peking University (Wang Y, Wu DP, Liu QF, et al. Donor and recipient age, gender and ABO incompatibility regardless of donor source: validated criteria for donor selection for haematopoietic transplants. Leukemia, 2017.). Based on the prospective and multi-center clinical research practice of 1 199 cases of acute leukemia treated with haplotype transplantation in the first remission stage, the research group found that: (1) "older donor and recipient, female donor and male, and donor and recipient ABO blood group incompatibility" are the three risk factors for transplantation-related death, and have nothing to do with whether human leukemia antigen (HLA) is fully consistent; (2) The transplantation-related mortality rates of 0-1, 2 and 3 risk factors were 8%, 15% and 31%, respectively, and the 3-year disease-free survival rates were 78%, 74% and 58%; (3) The efficacy of all-consistent sibling donors with high risk score was worse than that of haplotype donors with low risk score. This study established a point system centered on age, sex and blood type compatibility of donors and recipients, challenging the classical rule that HLA full-contract siblings are always the first choice for hematopoietic stem cell donors. In this research paper, the donor selection rule proposed on the basis of a large number of clinical cases can effectively reduce the incidence of transplant complications and improve the survival rate of patients. This has important implications for improving the survival of a large number of patients.

Double-heart medicine is a discipline formed by the intersection and integration of cardiology and psychology. It mainly studies the correlation between psychological disorders and heart diseases, and the influence of controlling these psychological problems on the outcome of cardiovascular diseases. It emphasizes that while paying attention to patients' physical diseases, it pays attention to patients' mental and psychological states, respects patients' subjective feelings, and advocates health in the true sense-that is, the overall harmony and unity of body and mind. In 1995, Professor Hu Dayi put forward the concept of double-heart medicine. After years of difficult exploration and clinical practice, he formally put forward "double-heart medicine" in 2006, marking the official establishment of "double-heart medicine" as a discipline in China.

myelodysplastic syndrome (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells, characterized by abnormal myeloid cell differentiation and development. The clinical manifestations and pathogenesis of MDS are very heterogeneous, which makes its diagnosis and treatment complicated and difficult. The exact pathogenesis of MDS remains unclear, although numerous studies have been conducted in the past decades to explore the pathogenesis of MDS, and some genetic and epigenetic abnormalities have been found. In recent years, many studies suggest that there are many point mutations in MDS, mainly involved in splicing factors and epigenetic regulation^[1]。 These point mutations may suggest disease prognosis, correlate with clinical phenotype, and may also be introduced into the MDS prognostic scoring system in the future. However, since these point mutations can also occur in other myeloid malignancies, even in bone marrow without abnormal hematopoiesis, the diagnosis of MDS cannot be determined based on these point mutations^[2]。

Acute respiratory distress syndrome (ARDS) is a common critical disease in the Department of Critical Care Medicine. Although many advances have been made in treatment, its morbidity and mortality remain high^[1]。 There is a lack of sensitive clinical measures for early diagnosis of ARDS and monitoring the severity of the disease. endothelial cell-specific molecule-1 (ESM-1), also known as endocan, can attenuate the adhesion of leukocytes to endothelial cells, regulate the trans-endothelial migration of leukocytes, and participate in the process of pulmonary vascular endothelial injury. Pulmonary vascular endothelial injury occurs in the early stage of ARDS, which is the pathological basis of the occurrence and development of ARDS. Lower levels of ESM-1 can predict ARDS occurrence, while higher levels of ESM-1 in ARDS patients have worse prognosis. ESM-1 has important clinical significance in the process of lung endothelial injury in ARDS, and may become a new generation of biomarkers.

Multiple myeloma (MM) is a clonal plasma cell malignancy, mainly in elderly people and still incurable at present. In the ear of novel agents and sensitive laboratory exams, the diagnosis and treatment of MM have been significantly improved. Chinese MM guidelines for the diagnosis and treatment were updated every two years according to the progression of international and domestic research and clinical studies. In this version, we updated the response criteria and new combination regimens in newly diagnosed patients. Monoclonal gammopathy of renal significance (MGRS) was added as a new part of differential diagnosis, meanwhile, relapsed/refractory MM patients should be treated as long as possible.

Renal impairment (RI) is a common complication of multiple myeloma (MM), which is presented as chronic kidney disease (CKD) or acute kidney injury (AKI). The typical pathological feature is cast nephropathy. Presently international system staging (ISS) is used in evaluating MM. Although the classic Durie-Salmon staging system could be still used in clinical practice, it may miss out some patients with renal impairment. For evaluations of RI in MM patients with CKD, it′s recommended to assess the estimated glomerular filtration rate (eGFR) by creatinine based formula CKD-epidemiology collaboration (EPI) or modification of diet in renal disease(MDRD) and to stage the renal injuries according to 2013 Kidney Disease Improving Global Outcomes (KDIGO) CKD guidelines. For MM patients with AKI, KDIGO AKI guidelines is recommended for evaluation. Renal biopsy is not a routine procedure in all MM patients. It′s necessary for patients presenting with glomerular injuries such as albuminuria > 1 g/24 h to eliminate immunoglobulin associated amyloidosis (AL) and monoclonal immunoglobulin deposition disease (MIDD). The effective treatment of MM can reduce serum light chain concentration and improve renal function. The basis of the RI treatment in MM is bortizomib-based regimen, which does not require dosage adjustment in patients with dialysis or renal insufficiency. Thalidomide and lenalidomide are two major immunomodulators in MM treatment. Thalidomide can be used effectively in RI patients without dosage adjustment while lenalidomide should be used cautiously in patients with mild or moderate RI with dosage adjustment and serum toxicity surveillance. High-dose therapy (HDT) and autologous peripheral blood stem cell transplantation (APBSCT) can be therapeutical options for RI patients younger than 65 y, and they should be considered more prudently in patients with severe renal insufficiency (GFR<30 ml/min). For patients who are not suitable for the treatment mentioned above, they can be treated with conventional chemotherapy, including VAD (vincristine, adriamycin and dexamethasone), MP (mephalan and prednisolone) and high-dose dexamethasone regimen. Adequate hydration (at least 3 litres of fluid intake a day or 2 L·m^-2·d^-1) and correcting reversible causes of RI are key points for the supportive care. Renal replacement therapy (more often hemodialysis) should be started in patients with severe AKI and end stage renal disease (ESRD). High flux or high cut-off membrane are recommended because routine hemodialysis could not remove the serum free light chain (sFLC) effectively. Plasmapheresis (PE) is recommended for patients with hyperviscosity syndrome or cast nephropathy presented with AKI, which may help to increase the dialysis-independency.

Gastric diseases are very common in China, especially gastric cancer with a continuous high level of morbidity and mortality. As an important screening method of gastric diseases, magnetically-controlled-capsule-gastroscopy (MCCG) has already been widely used in medical institutions worldwide. Several clinical trials have already showed that MCCG has comparable accuracy in diagnosing gastric diseases compared with conventional gastroscopy. Furthermore, MCCG has the advantages of anesthesia free, no risks of cross infection, and excellent compliance. Thus MCCG could be a potential alternative technique of conventional gastroscopy. Based on the clinical practice of MCCG during recent years, Chinese doctors have gained a lot of experience. In order to standardize and popularize the application of MCCG, the expert consensus for the clinical application of MCCG was developed through several discussions and modifications among Chinese experts in the field of capsule endoscopy.

China has stepped into an aging society. Hypertension is an independent risk factor of cardio-cerebrovascular diseases and related to mortality and disability of the elderly. Compared to middle-aged and young patients with similar blood pressure elevation, the risks of cardiovascular and cerebrovascular events significantly increase in the elderly. Since the Chinese expert consensus on the diagnosis and treatment of hypertension in the elderly(2008, 2011 version) were published, many guidelines have been accordingly updated, which further improved the prevention and control strategy of hypertension. In this article, Chinese expert consensus on the diagnosis and treatment of hypertension in the elderly(2017) is revised as to facilitate the prevention and treatment of hypertension in Chinese elderly. The consensus is composed of eight parts, including definition, epidemiology, characteristics, evidence, treatment objectives and measurements of elderly hypertension. The purpose of the consensus is to provide guidance for management of elderly hypertensive patients.

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