Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ²=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.
Female ; Humans ; Adult ; Medroxyprogesterone Acetate/adverse effects* ; Endometrial Hyperplasia/pathology* ; Dydrogesterone/adverse effects* ; Hyperplasia ; Prospective Studies

Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Objective To assess the value of free-hand transperineal multiparametric nagnetic resonance imaging/transrectal ultrasound (mpMRI/TRUS) fusion-guided targeted biopsy (TB) for the diagnosis of prostate cancer(PCa).Methods Patients with elevated PSA level and/or an abnormal DRE finding were recruited prospectively between January 2015 and September 2016.Patients were classified to various scores from 2 to 5 according to prebiopsy mpMRI PI-RADS.Based on free-hand transperineal mpMRI/TRUS fusion-guiding,a 2-cores TB for each cancer-suspicious lesion were carried out and followed 12-cores systematic biopsy (SB) protocol.Pathological findings of biopsy and radical prostatectomy (RP) specimens were analyzed.Results A total of 397 patients were enrolled in this study.The median age of the patients was (68.2 ± 7.4) years old,ranging 42-78 years.The median PSA level was (15.0 ±12.4)ng/ml,ranging 3.0-88.3 ng/ml.DRE showed abnormality in 28 patients(7.1％).The median prostate volume was (41.6 ± 16.4)cm3,ranging 24.6-89.8 cm3.The PCa detection rate of TB was significantly increased compared with SB (44.8 ％ vs.34.8％) (P =0.003),especially in clinically significant PCa (P ＜ 0.001) and intermediate/high-risk PCa (P =0.003),respectively.Of the all 588 mpMRI targeted lesions,277 lesions were positive.A total of 105 index tumors were identified in RP specimens,the locations of TB-proven cancer showed 96.6％ (85/88) in correspondence with the location of the index lesion in RP specimens.Conclusions Free-hand transperineal mpMRI/TRUS fusion-guided TB providing greater detection of intermediate-high risk PCa while limits over detection of low risk PCa.Moreover,TB can reliably predict the location of an index tumor.

Objective: To investigate the pathogen spectrum distribution and drug resistance of febrile neutropenic patients with hematological diseases in Shanghai. Methods: A retrospective study was conducted on the clinical isolates from the febrile neutropenic patients hospitalized in the departments of hematology in 12 general hospitals in Shanghai from January 2012 to December 2014. The drug susceptibility test was carried out by Kirby-Bauer method. WHONET 5.6 software was used to analyze pathogenic bacteria and drug susceptibility data. Results: A total of 1 260 clinical isolates were collected from the febrile neutropenic patients. Gram-positive bacteria accounted for 33.3% and Gram-negative bacteria accounted for 66.7%. Klebsiella pneumoniae (12.5%) , Stenotrophomonas maltophilia (9.5%) , Escherichia coli (9.1%) , Pseudomonas aeruginosa (8.7%) , Acinetobacter baumannii (6.6%) , Staphylococcus aureus (5.6%) and Enterococcus faecium (5.0%) were ranked in the first 7 of all pathogens. In the respiratory tract secretions specimens, non-fermented strains accounted for 56.2%. Stenotrophomonas maltophilia accounted for 15.2%. Enterobacteriaceae and coagulase-negative Staphylococci accounted for 42.3% (104/246) and 32.6% (85/246) respectively in blood samples. Enterobacteriaceae and Enterococcus bacteria accounted for 39.4% (76/193) and 28.5% (55/193) respectively in pus specimens. The detection rates of methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant coagulase negative Staphylococci (MRCNS) were 54.3% and 82.5%, respectively. Staphylococcus bacterial strain was not found to be resistant to linezolid, vancomycin and teicoplanin. The detection rate of Enterococcus vancomycin-resistant strains was 8.9%. Enterococcus was not detected resistance to oxazolidinone strains. Enterobacteriaceae bacteria were highly sensitive to carbapenems. The resistance rate of Pseudomonas aeruginosa to imipenem and meropenem was 34.1% and 15.8%, respectively. Stenotrophomonas maltophilia was more sensitive to minocycline hydrochloride, levofloxacin and sulfamethoxazole. The resistance rate of Acinetobacter baumannii only to cefoperazone-sulbactam was less than 10.0%. The antibiotic resistance rate of Klebsiella pneumoniae, Stenotrophomonas maltophilia, Pseudomonas aeruginosa and Acinetobacter baumanii to most of common antibiotics was lower than that of the CHINET surveillance. Conclusions The pathogenic strain distribution in common infection sites of febrile neutropenic patients was characterized. Bacterial resistance surveillance was better than the CHINET nationwide large sample surveillance in China.

OBJECTIVETo explore the feasibility and safety of laparoscopic radical coloproctectomy and hepatectomy for resectalble colorectal cancer with liver metastases (CRCLM), and evaluate the survival outcomes of short-middle term for these patients.

METHODSTotally 36 cases of CRCLM which were evaluated to undergo laparoscopic coloproctectomy and hepatectomy preoperatively, were enrolled from January 2009 to January 2014, including 28 synchronous and 8 metachronous CLM respectively. Laparoscopic colorectal resection and hepatectomies were performed in 35 cases, including 24 male and 11 female patients, with a mean age of (64 ± 12) years and a median age of 67 years (ranging from 35 to 80 years). Management strategies were made by a board of multi-disciplinary team. Intra-operative ultrasonography was used to detect the metastases in all cases. Overall survival and disease free survival were calculated by Kaplan-Meier curve.

RESULTSRadical total colectomy, right hemicolectomy, left hemicolectomy, sigmoidectomy, and proctectomy and were performed in 1 case of familial adenomatous polyposis with transverse colon cancer, 5 cases of cecal or asending colon cancer, 1 case of descending colon cancer, 14 cases of sigmoid colon cancer, and 14 cases of rectal cancer respectively. Metastasectomy only, anatomic hepatectomy only, and metastasectomy plus anatomic hepatectomy were done in 21, 10 and 4 cases respectively. Totally 35 colorectal tumors and 62 liver lesions were removed. The mean blood loss of colorectal and liver surgery were (80 ± 32) and (212 ± 153) ml, the median blood loss was 70 ml and 150 ml respectively. Colorectal and hepatic specific complications were not observed in all cases except a case of biliary leakage following right hemihepatectomy. Relapses were observed in 15 cases during a mean follow-up of (26 ± 16) months (median follow-up of 22 months). Four cases died of late-stage cachexia. The 1- and 3-year cumulative overall survival rates were 92.9% and 79.4% respectively. The 1- and 3-year cumulative disease free survival rates were 61.1% and 49.4% respectively.

CONCLUSIONSLaparoscopic coloproctectomy and hepatectomy for resectable CRCLM in carefully selected cases is safe and feasible, which makes simultaneous surgery possible. The oncologic outcome of short-middle term is acceptable, and long-term survival is expected.

Adult ; Aged ; Biopsy ; Cecum ; Colectomy ; methods ; Colorectal Neoplasms ; surgery ; Disease-Free Survival ; Female ; Hepatectomy ; methods ; Humans ; Laparoscopy ; methods ; Liver Neoplasms ; secondary ; surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Survival Rate ; Treatment Outcome

Objective To prospective study the use of minimally invasive surgery (MIS) for colorectal cancer with liver metastases (CRCLM) and to analyze the safety and survival outcomes.Methods 31 patients with resectable CRCLM were enrolled into this study from January 2009 to August 2011.Synchronous or metachronous liver metastases were diagnosed in 26 and 5 patients,respectively.The treatment strategy was discussed and decided by a multi disciplinary team which consisted of experienced colorectal surgeons,hepatic surgeons,medical oncologists,radiologists,and pathologists.Treatment included the use of neoadjuvant chemotherapy,one or two-staged surgery,and suitability to use laparoscopic surg(e)ry.Results Coloproctectomy and partial hepatectomy were carried out in all these patients,and every patient received at least one laparoscopic procedure.The operations in cluded: laparoscopic coloproctectomy plus hepatectomy (n=10),laparoscopic coloproctectomy only (n 18) and laparoscopic partial hepatcctomy only (n=3).One-staged coloproctectomy and hepatectomy were performed in 19 patients who presented with synchronous CRCLM.Colorectal and hepatic specific complications,such as anastomotic leak,liver failure,biliary leak,abdominal infection and abdominal bleeding,were not detected in these pati(e)nts.Neoadjuvant chemotherapy was used in 12 patients.Adjuvant chemotherapy was given to every patient.At a mean follow-up of 23.3 months from the diagnosis of liver metastases,the overall survival and disease-free survival were 87.1％ and 71.0％,respectively.Conclusions MIS for resectable CRCLM in carefully selected patients was safe and feasible.A one staged laparoscopic coloproctectomy and partial hepatectomy was possible.The short-middle oncologic outcomes were acceptable,but the long-term survival was still not clear.

OBJECTIVESTo analyze the survival outcomes of the surgery for colorectal cancer with liver metastases (CRCLM), and study the mode of multi-disciplinary team (MDT) for CRCLM.

METHODSThe retrospective analysis was conducted for 38 patients with CRCLM received MDT management and surgical treatment from January 2009 to August 2011. The peri-operative and survival outcomes of MDT and surgery were evaluated.

RESULTSAll the cases met the present criteria of resetability for CRCLM, but only 4 cases (10.5%) met the previous one. Coloproctectomy and hepatectomy were performed in all cases, with 39 colorectal neoplasms and 155 liver lesions removed. One case died of postoperative septic shock. Colorectal and hepatic specific complications were absent in the others patients except one case of biliary leak which was treated with conservative management. Neoadjuvant chemotherapy was arranged in 13 cases. Adjuvant chemotherapy was administered for every patient. After a mean follow-up of (22 ± 10) months according to the finding time of liver metastases, recurrence and metastases were observed in 16 cases and 6 cases died of late-stage cachexia. The 1-, 2- and 3-overall survival rate were 94.4%, 85.3% and 75.8% respectively, and the 1-, 2- and 3-disease-free survival rate were 70.1%, 54.2% and 54.2% respectively.

CONCLUSIONSMDT mode for resectable CRCLM is recommendable. Surgical resection of CRCLM is feasible and safe, which seems to achieve favourable short-middle oncologic outcomes. And long-term survival is expected.

Adult ; Aged ; Chemotherapy, Adjuvant ; Colorectal Neoplasms ; mortality ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; mortality ; secondary ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Treatment Outcome

BACKGROUNDAttention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood, characterized by the core symptoms of hyperactivity, impulsivity and inattention and puts great burden on children themselves, their families and the society. Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH). It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles. The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting.

METHODSThis 6-week, multi-center, prospective, open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg, 36 mg or 54 mg) treatment. The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales, physician-rated CGI-I and parent-rated global efficacy assessment scale. Blood pressure, pulse rate measurement, adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures.

RESULTSA total of 1447 children with ADHD (mean age (9.52 ± 2.36) years) were enrolled in this trial. Totally 96.8% children received an OROS-MPH modal dose of 18 mg, 3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study. The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P < 0.001) improvement with OROS-MPH (mean: 6.95 ± 2.71) versus the score at baseline (10.45 ± 2.72). The change in the parent IOWA Conners O/D subscale, CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment. Fewer than half of 1447 patients (511(35.3%)) reported AEs, and the majority of the events reported were mild (68.2%). No serious adverse events were reported during the study.

CONCLUSIONThis open-label, naturalistic study provides further evidence of effectiveness and safety of OROS-MPH in school-aged children under routine practice.

Adolescent ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; Child ; Delayed-Action Preparations ; Female ; Humans ; Male ; Methylphenidate ; administration & dosage ; adverse effects ; therapeutic use ; Prospective Studies ; Treatment Outcome

OBJECTIVETo evaluate and compare the effect of naso-intestinal tube decompression and octreotide in conservative management of early post-operative inflammatory ileus (EPII).

METHODSFrom March 2005 to January 2009, forty-five patients diagnosed with EPII, who failed to improve with conventional conservative management including nasogastric tube decompression, were enrolled in this study. All patients were prospectively nonrandomized into naso-intestinal tube group (n = 23) or Octreotide group (n = 22). The outcomes were compared between nasogastric tube, naso-intestinal tube and Octreotide groups.

RESULTSAll the forty-five patients with EPII refractory to conservative management with nasogastric decompression were treated successfully with the naso-intestinal tube decompression or octreotide in 3-12 days. Compared with the Octreotide group, the first passage of flatus was earlier [(4.7 +/- 1.9) d vs (6.7 +/- 1.6) d] and abdominal circumference recovered faster [(90.4 +/- 2.0)% vs (95.1 +/- 1.3)%] in the naso-intestinal tube group (P < 0.05). But the volume of cumulative and daily gastrointestinal decompression were more in naso-intestinal tube group than those in Octreotide group [(4037 +/- 1155) ml vs (3316 +/- 1038) ml; (890 +/- 181) ml vs (492 +/- 83) ml; P < 0.05].

CONCLUSIONSPatients with EPII could be safely and effectively managed by naso-intestinal tube decompression or octreotide. It is possible for those patients to avoid second laparotomy. Naso-intestinal tube decompression and octreotide are associated with faster recovery and less fluid loss respectively.

Abdomen ; surgery ; Adult ; Aged ; Aged, 80 and over ; Decompression ; methods ; Female ; Humans ; Intestinal Obstruction ; etiology ; therapy ; Intubation, Gastrointestinal ; Male ; Middle Aged ; Octreotide ; therapeutic use ; Postoperative Complications ; therapy ; Prospective Studies ; Treatment Outcome ; Young Adult

Leigh syndrome is a genetically heterogeneous disease caused by defects in enzymes involved in aerobic energy metabolism and the Krebs', cycle. Mitonchondrial complex I deficiency is a main cause of Leigh syndrome. In this study, a Chinese child with Leigh syndrome caused by 13513G>A mutation was reported. The proband was the first child of his parents. The previously healthy boy presented with generalized epilepsy at 12 years of age. When he visited Peking University First Hospital at 13 years of age, he had subacute loss of vision in two eyes and temporal defect of visual field in the left eye. He walked with a spastic gait. His blood lactate and pyruvate levels were elevated. Muscle biopsy showed mild lipid accumulation in muscle fiber. An electrocardiogram showed incomplete right bundle branch block. Brain magnetic resonance imaging showed bilateral, symmetrical lesions in the basal ganglia, supporting the diagnosis of Leigh syndrome. 13513G>A mutation was identified by gene analysis in the patient, which led to mitochondrial respiratory chain complex I deficiency. Multivitamins and L-carnitine were administered. At present, the patient is 16 years old and has progressive deterioration with significant muscle weakness and body weight loss. He is absent from school. He has no obvious retardation in intelligence. 13513G>A mutation was first identified by gene analysis in Chinese population with Leigh syndrome. This may be helpful in genetic counseling.
Adolescent ; DNA, Mitochondrial ; genetics ; Electron Transport Complex I ; deficiency ; Humans ; Leigh Disease ; genetics ; Male ; Mutation