National Medical Journal of China
Volume 101 · Issue 27 · 2021
Natl Med J China
Acromegaly is a rare disease, and multidisciplinary collaboration is essential for its diagnosis, treatment, and follow-up.In recent years, a series of novel findings have been echieved in clinical studies on acromegaly.Therefore, the China Pituitary Adenoma Specialist council has convened Chinese specialists in neurosurgery, endocrinology, radiology, and radiotherapy to release the Chinese Consensus for the Diagnosis and Treatment of Acromegaly (2021), which aims to promote the standardized and individualized management of acromegaly.Looking back to the past, the consensuses and guidelines have played vital roles in establishing the widely recognized biochemical remission criteria, promoting new drugs and novel therapeutic strategies which are of significance for standardized treatment, and emphasizing the need to focus on the systemic complications of acromegaly and the long-term quality of life. In this editorial, we briefly reviewed the expert consensuses and clinical guidelines on acromegaly at home and abroad, and discussed their important roles in promoting standardized disease management from three aspects including biochemical remission standards, medical treatment, and the diagnosis and treatment of systemic complications.
Led by the China Pituitary Adenoma Specialist Council, the Chinese Consensus for the Diagnosis and Treatment of Acromegaly (2021 Edition) is developed combined with the research progress of pituitary growth hormone (GH)-secreting adenoma both at home and abroad, evidence-based evidence of the diagnosis and treatment of acromegaly, and China′s national conditions. Based on the guideline for acromegaly (2013 Edition), the new version of consensus emphasizes the importance of multidisciplinary team (MDT) and individual therapy. The criteria for control of acromegaly is discussed. Pathological criteria for the diagnosis of pituitary GH-secreting adenoma is updated. New developments in surgery, drug and radiotherapy are introduced. Meanwhile, the diagnosis and treatment of acromegaly patients concurrent with other particular scenarios, including pregnancy and refractory pituitary GH-secreting adenoma is suggested. This article aims to describe the updated key points of the new version of the consensus, and thus facilitate the clinical implementation of standardized diagnosis and treatment for acromegaly patients.
The Consensus on the Diagnosis and Treatment of Acromegaly in China (2021 Edition) combines the research progress of pituitary growth hormone adenoma at home and abroad, evidence-based evidence on the diagnosis and treatment of acromegaly and China's national conditions, aiming to standardize the early screening, complication diagnosis and treatment and long-term follow-up of patients with acromegaly, and strengthen the multidisciplinary cooperative diagnosis and treatment model and the concept of individualized diagnosis and treatment.
To investigate abnormal directional functional connectivity of the nucleus accumbens (NAc) in chronic tinnitus patients using resting-state functional magnetic resonance imaging (fMRI), and to determine the relationship between the degree of this connectivity and tinnitus characteristics.
The resting-state fMRI data of 40 patients with bilateral chronic tinnitus (12 males and 28 females, aged from 26 to 63(50.6±11.6) years) and 40 healthy controls with normal hearing (16 males and 24 females, aged from 26 to 70(45.9±12.4)years) were retrospectively enrolled from the Department of Otolaryngology, Nanjing First Hospital from January 2017 to January 2020. The bilateral NAc were selected as seeds to detect the directional functional connectivity with the whole brain, then the effective connectivity values between the two groups were compared using Granger Causality Analysis (GCA), and the correlation between the effective connectivity and the characteristics of tinnitus was calculated.
Compared with healthy controls, the effective connectivity from the left NAc to left middle frontal gyrus in patients with bilateral chronic tinnitus was increased [(1.0±0.2)vs(0.6±0.3)], the effective connectivity from the right NAc to left inferior frontal gyrus was enhanced [(0.9±0.3)vs(0.6±0.4)], the effective connectivity from the right middle temporal gyrus to left NAc was enhanced [(1.0±0.2)vs(0.5±0.3)], the effective connectivity from the right middle frontal gyrus to right NAc was also enhanced[(1.0±0.2)vs(0.5±0.3)](allP<0.05). After adjusting for age, gender, education level, and gray matter volume, positive correlations was observed between the Tinnitus Handicap Questionnaire (THQ) scores and increased effective connectivity values from the left NAc to the left middle frontal gyrus (r=0.386, P=0.020). Additionally, enhanced effective connectivity values from the right middle frontal gyrus to the right NAc was also positively associated with tinnitus duration (r=0.390, P=0.019).
The directional functional connectivity between the NAc and prefrontal cortex in patients with chronic tinnitus is enhanced.
To investigate the changes of natural killer(NK) cell function, and clarify the effect of granulocytic myeloid derived suppressor cells (G-MDSCs) on NK cell functionality in patients with treatment-naive chronic hepatitis C (CHC) who were cured by direct-acting antiviral agents (DAAs).
Thirteen treatment-naive CHC patients and 13 healthy controls were prospectively included in this study from March 2016 to January 2017. They were divided into case group and control group, respectively. The patients of case group,6 males and 7 females aged 21-65 years old with an average of (37±14),were treated with daclatasvir and asunaprevir combination (DCV/ASV) at the Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital. While 13 healthy individuals, 6 males and 7 females aged 21-57 (36±11) years old, were enrolled as healthy controls(control group). Flow cytometry was used to determine the immunological characteristics of peripheral blood NK cells subset, and detect the frequencies of gMDSCs in peripheral blood of people in two groups. It was specifically notes that CHC patients of case group would be detected before, during and after treatment. The correlations between gMDSCs and each NK cell subset function were also examined. The impact of gMDSCs on NK cell functionalities and the relevant regulatory mechanisms were explored using co-culture experiments of sorted NK cells and gMDSCsin vitro.
Compared with healthy controls, the decreased IFN-γ production[M(Q1,Q3)] [3.182 (2.757, 4.237) vs 6.675 (4.476, 8.280),1.434 (1.127, 2.434) vs 3.045 (1.680, 4.856), 2.611 (1.749, 3.498) vs 5.160 (4.232, 7.683)] and increased CD107a degranulation [9.314 (7.838, 13.543) vs 3.480 (2.938, 6.824), 2.544 (1.366, 4.768) vs 0.552 (0.408, 1.560), 10.339 (9.145, 12.534) vs 3.488 (3.117, 5.651)] (allP<0.05) were found on NK cell and its subsets. The frequencies of gMDSCs and plasma concentration of arginase-1 in CHC patients was significantly higher than that in healthy controls [7.050 (4.180, 12.538) vs 1.440 (0.444, 2.261), 114.278 (68.492, 163.724) vs 64.753 (50.809, 93.278)](allP<0.05). The production of IFN-γ was increased and the secretion of CD107a was decreased in NK cell and its subsets after DAAs treatment (P<0.05). The frequencies of gMDSCs and plasma arignase I levels were also decreased in CHC patients treated with DAAs (P<0.05).The results of the study indicated that the frequencies of G-MDSCs were inversely associated with the levels of IFN-γproduction of NK cells and CD56dim NK cells in CHC patients (r=0.668, -0.750, respectively, both P<0.05). In addition, the frequencies of gMDSCs were positively associated with the expression of CD107a in the CD56bright NK cell subset (r=0.711, P=0.021). In vitro, the inhibition of gMDSCs on the IFN-γ production of NK cells was demonstrated in the co-culture experiments of sorted NK cells and gMDSCs, and blocking arginase I can significantly increase the ability of NK cells to produce IFN-γ, restore NK cell IFN-γ production.
gMDSCs in peripheral blood of CHC patients has been shown to suppress NK cell IFN-γ production in an arginase I-dependent manner. Direct-acting antiviral-mediated clearance of HCV is associated with the normalization of NK cell function and gMDSCs frequency.
To investigate the value of serum mitochondrial ATP synthase C subunit level in the evaluation of cardiac functional status and prognosis in patients with sepsis.
A total of 165 sepsis patients admitted to the Emergency Intensive Care Unit (EICU) of the First Affiliated Hospital of Wenzhou Medical University from January 1, 2017 to December 31, 2018 were included, there were 103 males (62.4%) and 62 females (37.6%) with an age of (63±14) years. Human ATP synthase lipid binding protein (ATP5G1) ELISA kit was used to detect the level of serum ATP synthase C subunit within 24 h after admission to EICU, and compared with that in 45 healthy subjects. Clinical data of patients were collected and divided into groups according to different left ventricular ejection fraction (LVEF) and clinical outcomes. The differences in clinical indicators among each group were compared to evaluate the value of serum ATP synthase C subunit level in the evaluation of cardiac functional state and prognosis of patients with sepsis, and the independent risk factors for cardiac functional state and prognosis of patients with sepsis were analyzed.
Compared with the control group, the level of serum ATP synthase C subunit in the sepsis group was higher ((116±62) μg/L vs (77±34) μg/L, P<0.001). Compared with normal cardiac function group, the level of serum ATP synthase C subunit in septic cardiac dysfunction group was higher (P<0.001). Compared with the survival group, the level of serum ATP synthase C subunit in the death group was higher (P<0.05). The receiver operating curve (ROC) was drawn to analyze the value of ATP synthase C subunit, creatine kinase isoenzyme (CK-MB), B-type natriuretic peptide (BNP), troponin I (cTnI), left atrial end diastolic diameter, left ventricular end systolic diameter, left ventricular end diastolic volume, left ventricular end systolic volume in evaluating the cardiac function in patients with sepsis, and the area under the curve (AUC) was 0.928, 0.661, 0.837, 0.814, 0.703, 0.831, 0.794 and 0.765, respectively. The cut-off value, sensitivity and specificity of ATP synthase C subunit in it was 139.44 ng/L, 100% and 75.2%, respectively. ROC was drawn to analyze the prognostic value of age, urea nitrogen (BUN), ATP synthase C subunit, APACHEⅡ score and SAPSⅡ score in patients with sepsis, and the AUC was 0.719, 0.772, 0.656, 0.868 and 0.884, respectively. The cut-off value, sensitivity and specificity of ATP synthase C subunit in it was 131.24 ng/L, 61.9% and 68.7%, respectively. Logistic regression analysis showed that age, BUN, ATP synthase C subunit, cardiac dysfunction, APACHEⅡ score and SAPS Ⅱ score were independent risk factors for the prognosis of patients with sepsis.
The level of serum ATP synthase C subunit is closely related to cardiac dysfunction in patients with sepsis, and can effectively predict the prognosis of patients with sepsis.
To investigate the serratus anterior plane block combined with pectoral nerves block I can produce a non-inferior analgesic effect compared with thoracic paravertebral block for radical mastectomy.
From October 2020 to February 2021, Sixty-four patients of Beijing Tongren Hospital, Capital Medical University scheduled for radical mastectomy with general anesthesia,were divided into two groups (n = 32 each) using a random number table method: thoracic paravertebral block group (TPVB group) and serratus anterior plane block combined with pectoral nerves block I group (S&P group). All patients received patient controlled intravenous analgesia (PCIA) postoperatively. The numerical rating scale (NRS) at post anesthesia care unit (PACU), 4, 8, 12, 24, 48 h after operation were compared between the two groups. Sufentanil cumulative dosage of PCIA in 24 h and 48 h, first press time after operation, total press times, the dosage of propofol, remifentanil and vasoactive drugs during operation, intraoperative blood pressure and heart rate, the operation time of block and adverse effects were all compared. Non-inferiority could be claimed if the difference of sufentanil cumulative dosage in 24 h between S&P group and TPVB group is higher than the negative value (-3.8) of the non-inferiority effect.
There was no significant difference in postoperative NRS at PACU, 4, 8, 12, 24, 48 h after operation, first press time after operation, total press times, propofol and remifentanil dosage, sufentanil cumulative dosage of PCIA in 24 h and 48 h, and adverse effects (all P>0.05). The sufentanil cumulative dosage of PCIA in 24 h of S&P group and of TPVB group were (15.8±4.7) μg and (15.2±3.2) μg. The 95% confidence interval (CI) of the difference between S&P group and of TPVB group was -1.478 to 2.694, and the lower limit was greater than non-inferiority margin -3.8. The mean arterial pressure of TPVB patients after induction and at the beginning of the operation were (63±7) mmHg and (70±7) mmHg, which were significantly lower than the (77±5) mmHg and (79±8) mmHg at the same time in the combination group (bothP<0.05). The frequency of vasoactive drugs usage in TPVB group was 56.3%, which was statistically significant higher than the 18.8% in S&P group (P<0.01). Nerve block time in TPVB group was 10 (9, 11) min, which was significantly longer than 8 (6, 10) min in S&P group (P<0.01).
The serratus anterior block combined with pectoral nerves block I can produce a non-inferior analgesic effect compared with thoracic paravertebral block for radical mastectomy, and the intraoperative hemodynamics is more stable and the block time is shorter than that of thoracic paravertebral block for radical mastectomy.
To analyze the clinicopathological characteristics of T1 breast cancer, the risk of lymph node metastasis and related prognostic factors.
The National Cancer Institute Surveillance, Epidemiology and Results (SEER) database was utilized to search and screen out 73 421 female patients with T1 breast cancer from 2010 to 2015 for retrospective analysis. Logistic regression was used to assess the risk factors of lymph node metastasis. Kaplan-Meier survival analysis was used to analysis overall survival (OS) and breast cancer-specific survival (BCSS); Log-rank test and Cox risk model were used for prognostic analysis.
A total of 73 421 female patients were enrolled, including 61 955 (84.4%) N0 stage, 9 995 N1 stage (13.6%), 1 087 N2 stage (1.5%) and 384 N3 stage (0.5%). Patients with invasive cancer, histological grade 3, T1c stage, progesterone receptor (PR) positive and human epidermal growth factor receptor-2 (HER-2) positive were most likely to develop lymph node metastasis (all P<0.05). The median follow-up time was 55 months. The 5-year survival rate was 93.8%, and the 5-year BCSS rate was 98.2%. Cox regression analysis showed that T stage (HR=1.517, 95%CI: 1.382-1.666, P<0.01), N stage (HR=5.173, 95%CI: 4.424-6.049, P<0.01), estrogen receptor (ER) status (HR=0.774, 95%CI: 0.607-0.987, P=0.039), PR status (HR=0.745, 95%CI: 0.689-0.806, P<0.01) and subtype (HR=1.439, 95%CI: 1.078-1.478, P=0.011) were independent prognostic risk factors for the OS. Histological grade (HR=2.100, 95%CI: 1.766-2.483, P<0.01), T stage (HR=1.310, 95%CI: 1.193-1.439, P<0.01), N stage (HR=21.230, 95%CI: 17.980-25.060, P<0.01), PR status (HR=0.855, 95%CI: 0.791-0.925, P<0.01) were independent prognostic risk factors for the BCSS in T1 breast cancer.
The lymph node metastasis rate of T1 breast cancer is low and the overall prognosis is good. Pathological type, histological grade, tumor size and subtype maybe helpful in predicting the lymph node metastasis of T1 breast cancer.
To investigate the clinical characteristics, diagnosis, treatment and outcome of adnexal torsion at different gestational weeks during pregnancy.
A retrospective analysis was conducted of the clinical data of 24 pregnancy patients with adnexal torsion, aged 21-38 (30.6±4.4) years old, who were admitted and delivered in Peking University Third Hospital from 2015 to 2019. According to the gestational age, all patients were divided into two groups:<28 weeks group (11cases) and ≥28 weeks group (13 cases), to compare the intergroup differences in clinical characteristics, treatment and outcome, and the differences of clinical data and outcome between two groups were compared.
The proportion of patients with twin pregnancy and assisted reproductive technology in the<28 weeks group was significantly higher than that in the ≥28 weeks group (5/11 vs 1/13, 8/11 vs 1/13,P<0.05). No significant differences between the two groups were recorded in terms of the size of the adnexal mass, the cycles of torsion and the duration from onset to operation. Compared with the≥28 weeks group, the adnexal removal rate of the<28 weeks group was lower (3/11 vs 6/13), but the difference was not statistically significant. The proportion of blood flow signals of ultrasound before operation, cases undergoing laparoscopic surgery and cases whose pathological findings were physiological cysts in the<28 weeks group were significantly higher than that in the ≥28 weeks group (8/11 vs 4/13, 8/11 vs 0, 8/11vs 4/13;P<0.05). Concerning the pregnancy outcomes, there was no difference in the mode of delivery, the delivery gestational age and the body weight of newborns between the two groups.
The patients with adnexal torsion prior to 28 weeks(<28 weeks)of pregnancy were more likely to be conceived by assisted reproductive technologies, and the etiology was more likely to be ovarian physiological cysts. Both laparoscopy and laparotomy were safe and effective in the treatment of adnexal torsion with good outcome for mother and infant in the study.
To present the surgical technique of endoscope assisted arthroplasty for total hip replacement via minimum invasive direct anterior approach and analyze its early clinical outcome.
From November 2019 to May 2020, endoscopic total hip arthroplasty via direct anterior approach was performed on 30 patients (32 hips), including 12 males (13 hips) and 18 females (19hips), in the Department of Orthopedics of Fujian Provincial Hospital. The average age of patients was (63±14) years (ranged 32-87 years). The average body mass index (BMI) of the patients was (26.9±4.5) kg/m2. There were 12 cases whose BMI was higher than 28.0 kg/m2 and the maximum BMI was 35.2 kg/m2. The surgery was performed on supine position using a 5-6 cm proximal transverse incision and a distal selective percutaneous puncture incision to perform the acetabulum preparation and the prosthesis implantation with the novel designed split tool under the monitoring of endoscope; the lift-top tractor system was used to raise the femur in the transverse incision for femoral side preparation and prosthesis implantation. Relevant data such as the perioperative status, operation time, postoperative pain score assessed with visual analogue score (VAS), prosthesis position, joint function, lateral femoral cutaneous nerve function and patient satisfaction were recorded to analyze the short-term efficacy.
The average length of incision of the 30 cases(32 hips)was (5.9±0.4) cm. All patients in this study had I/A wound healing with no perioperative complications such as infection, poor wound healing and fractures of the proximal femur. The average operation time was (65±14) min, and the average amount of blood loss was (136±56) ml. The average acetabular abduction angle and acetabular antegrade inclinations was 41.4°±3.6° and 16.0°±5.3°, respectively. The resting-state VAS of pain at 6 h and 24 h after operation were all ≤2, and there was no significant difference between the VAS scores after exercise and the VAS scores at the resting state (both P>0.05). There was no statistically significant difference between the VAS scores at the same state at different times (both>0.05). The weight-bearing exercise was applied in all patients within 12 h after surgery. The length of postoperative hospital stays varied from 1 to 3 days((2.0±0.9) days). At the 6th-month follow-up, the Harris score of the hip was 94.7±3.0, which significantly improved when compared with that before the operation (35.5±8.1)(P<0.01). No sensory abnormalities were observed. The satisfaction score of the patients was 9.3±0.5 (full score set to 10).
The efficacy and safety of the endoscope assisted total hip arthroplasty for total hip replacement is acceptable. This procedure can help to reduce the compression of the muscles by the retractor in the conventional operation. It can be applied to obese and muscular patients.
This study reviewed the clinical data of patients who were hospitalized in the Department of Neurology of Henan Provincial People′s Hospital from January 2017 to October 2020. A total of 46 patients with positive serum anti-CV2 antibody were included. The average age of the patients was (54±15) years old, with a male to female ratio of 1.88∶1. Twenty-six patients were diagnosed with paraneoplastic neurological syndrome (PNS). The most malignant tumors were thymoma, small cell lung cancer, and prostate cancer. The most common PNS included myasthenia gravis, subacute cerebellar degeneration, and subacute/chronic sensorimotor neuropathies. Twenty non-PNS patients exhibited subacute/old cerebral infarction, Parkinson′s disease, Alzheimer′s disease, and so on. Among them, brain magnetic resonance imaging (MRI) of 10 cases showed different degrees of white matter demyelination, some of which were accompanied by brain atrophy. The current study found that the positive predictive value of anti-CV2 antibody for the diagnosis of PNS was 56.5%, which was relatively weak. As an accompanying antibody, it may be a coincidence, and it may also be related to the involvement of family members in the pathological process of the diseases.
This article reports a young female patient with immune thrombocytopenia (ITP) who developed progressive headache, nausea, papilledema and other symptoms of intracranial hypertension with significant reduction of platelets. Multiple CT examinations did not identify the cause, and it was confirmed by magnetic resonance imaging (MRI) and venous magnetic resonance angiography (MRV) that it was caused by cerebral venous sinus thrombosis (CVST). Dehydration with mannitol to reduce intracranial pressure did not improve symptoms, and eventually death resulted from failure of thrombolytic therapy. The clinical experience of this patient suggests that ITP is not only a hemorrhagic disease, but also a rare and serious thrombotic disease such as CVST, which can occur even when the platelet count is low.
Genetic or genetic background is related to some interstitial lung diseases. Genes and their abnormal expression products determine the clinical phenotype of the disease and are also an important basis for diagnosis. Patients may have a family genetic history and special clinical manifestations, with common characteristics and differences with other interstitial lung diseases in terms of clinical manifestations, imaging, pathology, diagnosis, evaluation, treatment and prognosis. In multidisciplinary comprehensive diagnosis and treatment, it is necessary to take into account the screening and follow-up of patients' family members. In this paper, the genetic hereditary interstitial lung diseases are classified and introduced by combining clinical, imaging, pathological and genetic abnormalities.
In patients with acromegaly who are not well controlled by octreotide or lanreotide, long-acting pasireotide can effectively reduce insulin-like growth factor 1 (IGF-1) to normal levels. In order to further clarify the long-term safety and efficacy of pasireotide, including the time required to achieve biochemical control, the time required to achieve the best treatment response, and the risk of diabetes, Akirov et al. conducted a multicenter retrospective study on patients with active acromegaly treated with pasireotide for more than 12 months. Nineteen patients treated with pasireotide were included in the study [10 men; Age (48.0 ± 12.9) years; Treatment time (50 ± 36) months]. Four patients discontinued treatment with pasireotide during follow-up. During treatment with long-acting pasireotide, 15 patients (79.0%) could maintain long-term tolerance and achieve biochemical control. The time from initiation of long-acting pasireotide to normalization of IGF-1 was (13.6 ± 16.9) months, with early biochemical remission (<12 months) in 11 (64.7%) and in 6 (35.3%) with delayed biochemical remission. Six (35.3%) patients had the lowest value of IGF-1 within 12 months of treatment initiation; Eleven patients had the lowest IGF-1 values after 12 months of treatment, including four patients with early IGF-1 normalization. Of the 7 patients with prediabetes, 5 developed new onset diabetes; Of the five patients with normal glucose metabolism at baseline, one developed new onset diabetes. In patients with prediabetes or diabetes before treatment with long-acting pasireotide, glycosylated hemoglobin increased by 0.56%±1.00%. The results of this study confirm the long-term safety and efficacy of long-acting pasireotide in the treatment of acromegaly, and suggest that the normalization of IGF-1 by pasireotide treatment may have a delayed effect.
Acromegaly is a rare chronic progressive endocrine disease with insidious onset. Due to its low incidence, there are no systematic reviews and meta-analyses reported on the global epidemiology of acromegaly. Crisafulli et al. report on the global epidemiology of acromegaly through a systematic literature review and meta-analysis. By searching the MEDLINE, EMBASE, and Cochrane Library databases for studies on the epidemiology of acromegaly as of January 31, 2020. This meta-analysis incorporated original observational studies written in English reporting the prevalence and/or incidence of acromegaly in well-defined geographical areas. Two evaluators independently extracted data and conducted quality assessments. A summary of the prevalence and incidence of acromegaly was concluded. A total of 32 studies were included in the systematic review, of which 22 were included in the study. By meta-analysis, the prevalence of acromegaly was 5.9 per 100,000 people (95%CI: 4.4 to 7.9), while the incidence rate was 0.38 per 100,000 person-years (95%CI:0.32~0.44)。 Considerable study heterogeneity was found for prevalence and incidence (I299.3% and 86.0%, respectively). Of these, 20 studies were rated as moderate for the quality of their research reports and 12 studies were rated as low for the quality of their research reports. While a significant amount of heterogeneity is due to the high accuracy of study estimates, the level of study related to data sources and geographic regions can explain approximately 50% of the total inter-study variability. Therefore, it is highly necessary to conduct large-scale, high-quality studies leading to precise epidemiological results of acromegaly to assist the public health system in decision-making.
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