BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Objective:To observe the path and anatomic distribution of cutaneous branch of second dorsal metacarpal artery(SDMA) from the back of hand to the web of the fingers, and to explore the feasibility and clinical effect on the transfer of free flap of SDMA.Methods:Between June 2018 and September 2018, with perfusion of red latex, 22 hand specimens were dissected to explore the course, vessel calibre and distribution of cutaneous branches of SDMA, and to discover the existence of an innervation of cutaneous nerve in Department of Hand Surgery of Tangshan Second Hospital. Later on, from February 2019 to July 2020, 2 thumb pulp defects of 2 patients were reconstructed with the free flaps of SDMA. One defect was in the left thumb and the other in the right, both were male and compression injuries. Size of thumb pulp and a skin defect was at 3.5 cm×2.0 cm in 1 patient, and 2.0 cm×2.5 cm in the other. There was no neurovascular injury, but 1 patient had a distal phalangeal fracture and a nail bed laceration. The sizes of the flaps were 3.8 cm×2.3 cm and 2.8 cm×2.5 cm. Functional exercises started from 3 weeks after surgery. Patients attended postoperation follow up regularly by outpatient visit, telephone or internet interviews. Follow-up observations included the appearance, texture, sensory recovery of the flaps and thumb functions.Results:Multiple perforating branches (4-9 branches) were found from SDMA, which distributed in the distal 1/3 of SDMA in the anatomic study. It was found that the outer diameter of SDMA was 0.76 mm±0.25 mm at the intersection of extensor tendon of index finger and that of the digital web artery was 0.71 mm±0.12 mm. The length of digital web artery was 11.00 mm±1.27 mm. The 2 surgically transferred flaps were all survived. One patient showed the function of thumb in excellent with two-point discrimination (TPD) at 7.0 mm, at 18 months of follow-up. The other patient showed good thumb movement, soft and elastic skin of the flap and with a 7.5 mm in TPD, at 15 months of follow-up. According to the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, the results of the 2 flaps were all excellent.Conclusion:The flap of SDMA has a constant cutaneous nerve and a long vascular pedicle with an ideal vessel size. It is suitable for free transfer and can be used to reconstruct soft tissue defects of thumb.

Objective:To explore the clinical efficacy and safety of single-layer with full thickness of duct-to-mucosa pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy.Methods:The clinical data of 45 patients who underwent laparoscopic pancreaticoduodenectomy with the procedures of single-layer with full thickness in Second Hospital of Hebei Medical University from Jan 2020 to Jan 2022 were retrospectively collected and compared with 45 matched patients with traditional two-layer pancreaticojejunostomy.Results:The laparoscopic pancreaticoduodenectomy procedures were successfully performed in all the 90 cases. The mean operation time (285.6±92.4 minutes) and the media pancreaticojejunostomy time 20(15, 35) minutes) of the single-layer with full thickness pancreaticojejunostomy group were shorter than those of the two-layer pancreaticojejunostomy group [the mean operation time: 317.0±85.5 minutes, the media pancreaticojejunostomy time: 46(30, 58) minutes] with significantly statistical differences (all P value<0.05). There were no significantly statistical differences on intraoperative blood loss, the postoperative complications or hospital stay between the two groups. Conclusions:Compared with traditional pancreaticojejunostomy, the single-layer with full thickness of duct-to-mucosa pancreaticojejunostomy is simple and safe, which has the advantage of easy manipulation and less time-consuming and can be recommended for laparoscopic procedures.

Objective:To investigate the safety and efficacy of self-made multifunctional endoscopic instrument accessory stent in endoscopic mucosal dissection (ESD).Methods:A total of 80 patients who received ESD in 924th Hospital of Joint Logistic Support Force of Chinese People′s Liberation Army from May 2019 to February 2021 were selected as research object. Random number table method was used to divide patients into control group and experimental group, 40 cases in each group. The experimental group used self-made endoscopic instrument accessory stent, and the control group did not use self-made endoscopic instrument accessory stent. The length of operation, the number of instruments taken by mistake, the number of instruments polluted during operation and the infection of postoperative 3-7 days under the same operation position, operating doctors and nurses were analyzed and compared between the two groups.Results:The incidence of instruments taken by mistake, the incidence of instruments polluted during operation and the infection rate of postoperative 3-7 days were 0.9% (8/856), 1.4% (12/856) and 2.5% (1/40) in the experimental group, which in the control group were 10.8% (96/887), 11.8% (105/887) and 15.0% (6/40) respectively, there were significant differences between the two groups ( χ2=75.92, 75.76, 3.91, all P<0.05). The length of operation in the experimental group was (51.56 ± 2.32) min, and that in the control group was (79.02 ± 2.83) min, the difference was statistically significant ( t=-8.72, P<0.05). Conclusions:When the patients underwent ESD surgery, the self-made multifunctional accessory stent was used to place the required instrument accessory. The length of operation was shorter, the incidence of instruments taken by mistake, the incidence of instruments polluted during operation and the infection rate of postoperative 3-7 days were reduced, the quality of minimally invasive endoscopic surgery was improved.

Objective:To compare and analyze the perioperative outcomes of jaundiced patients undergoing laparoscopic pancreaticoduodenectomy (LPD) using preoperative percutaneous transhepatic cholangial drainage (PTCD) versus endoscopic nasobiliary drainage (ENBD).Methods:The perioperative data of 173 patients who underwent LPD at the Second Hospital of Hebei Medical University from January 2016 to December 2020 and were treated preoperatively with either PTCD versus ENBD to alleviate jaundiced were retrospectively analyzed. There were 100 males and 73 females, with age of (60.4±10.8) years old. These patients were divided into the PTCD group ( n=126) and the ENBD group ( n=47). Clinical data including operation time, blood loss, transfusion volume, R 0 resection, and postoperative complications were compared. Results:There was no convension to open surgery. There were no significant differences in operation time, blood loss, transfusion volume, R 0 resection rate, pathological results and hospital stay between the two groups ( P>0.05). For the PTCD group, the pancreatic fistula rate was 10.3% (13/126) and the post-operative hemorrhage rate was 8.7% (11/126). They were both significantly lower than those of the ENBD group [25.5% (12/47) and 25.5% (12/47) respectively, P<0.05]. There were also significant differences in the postoperative complications according to the Clavien-Dindo classification system between the two groups ( P=0.008). Conclusion:Compared with ENBD, PTCD had the advantages of lower post-operative pancreatic fistula and post-operative hemorrhage rates, resulting in a better postoperative recovery.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To explore clinical results in reconstruction of finger C-shape soft tissue defect with the wrist crease free flap carrying cutaneous nerve.Methods:From June, 2017 to April, 2019, 7 fingers(7 patients) with C-shape defect were treated with the wrist crease free flap carrying cutaneous nerve. The size of defect ranged from 1.0 cm × 2.5 cm-2.2 cm × 4.0 cm; the flap sizes were 1.3 cm × 2.7 cm-2.5 cm × 4.5 cm. Five fingers had unilateral defect of proper palmar digital artery. Two fingers that had bilateral defect of proper palmar digital artery with poor blood circulation were re-established with blood supply by Flow-through flaps. Four fingers had unilateral defect of proper palmar digital nerves, and 3 had bilateral defect of proper palmar digital artery. Five of the fingers were repaired by the superficial branch of the radial nerve and 2 repaired by palmar cutaneous branch of median nerve. Regular outpatient follow-up was conducted after surgery for 8 to 15 (mean 11) months.Results:All the fingers and flaps survived with primary healing. Numbness existed in the areas of functional dominance of the cutaneous nerve. At the end of follow-up, the flaps showed good texture without significant bloated appearance with the recovery of protective sensation. The sensation of fingertip recovered to S 4 in 5 fingers and S 3+ in 2 fingers. Finger pulps were plump. All of the fingers moved freely. Linear scars were observed at donor sites and the wrists moved freely. Numbness feeling in the areas of cutaneous nerve disappeared at 6 to 8 weeks after surgery. According to the Functional Evaluation Criteria of the Finger Replantation published by the Hand Surgery Society of the Chinese Medical Association, the results were excellent in 6 fingers and good in 1 finger. Conclusion:The wrist crease free flap carrying cutaneous nerve is constant and can be dissected transversely to reconstruct and fit the C-shape defect of finger. It can re-establish the blood supply as well as to repair the proper palmar digital nerve defect at the same time.

Objective:To evaluate the deformity changes in the treatment of congenital clubfoot in infants by ultrasound, and to explore its clinical application value.Methods:Seventeen infants with congenital clubfoot treated in the Department of Pediatric Orthopaedics of the Third Affiliated Hospital of Zhengzhou University from March 2020 to June 2021 and 27 normal infants in the same period were selected. The distance between medial malleolus and scaphoids (MM-N distance) of all feet was measured by ultrasound. The distance from the tangent line of the lateral edge of calcaneus to the midpoint of the lateral edge of the chondroid bone (C-C distance), medial soft tissue thickness and tibial calcaneal angle were measured by ultrasound. The data before, after treatment and during follow-up were statistically analyzed.Results:A total of 88 feet of 44 infants were evaluated. The mean number of cast was 4.7±1.1, the follow-up time was (96.9±59.3)days. The MM-N distance, C-C distance and posterior tibial calcaneal angle in the clubfoot group were improved after treatment and at the last follow-up, and the differences were statistically significant (all P<0.01). During the treatment, 1 case had false correction, and 2 cases recurred in the last follow-up. Conclusions:Ultrasound can clearly display the medial, dorsal, lateral and posterior articular structures of normal and clubfoot, and can observe the deformity changes of clubfoot during the correction process, which can provide guidance for the clinical treatment of clubfoot.

Objective:To study the factors related to development of pancreatic fistula after laparoscopic distal pancreatectomy.Methods:The clinical data of all patients who underwent laparoscopic distal pancreatectomy at the Second Hospital of Hebei Medical University from January 2019 to December 2020 were retrospectively analyzed. Gender, age, intraoperative blood loss, treatment of pancreatic stump, body mass index (BMI), pancreatic texture, albumin and other indicators were analyzed between patients with and without pancreatic fistula. Logistic regression analysis was used to determine independent risk factors for pancreatic fistula.Results:Of 93 patients in this study, there were 33 males and 60 females, mean age (49.23±15.62), range 16 to 76 years. The incidence of postoperative pancreatic fistula was 34.4% (32/93). On univariate analysis, BMI (χ 2=4.515, P=0.034), pancreatic texture (χ 2=3.891, P=0.049), preoperative serum albumin ( t=2.644, P=0.010) and albumin difference ( t=-2.293, P=0.024) were significantly associated with postoperative pancreatic fistula. Multivariate logistic regression analysis showed that low preoperative albumin ( OR=0.551, P<0.001), large difference in albumin ( OR=1.542, P<0.001), BMI≥25 kg/m 2 ( OR=3.303, P=0.035) and soft pancreatic texture ( OR=3.065, P=0.049) were independent risk factors for pancreatic fistula. Conclusion:For patients with BMI≥25 kg/m 2 and patients with a soft pancreas, there was a higher chance to develop pancreatic fistula after operation.

Objective:To analyze the predictive value of enhanced MRI in the outcome of prolapsed and sequestrated lumbar disc herniation through a retrospective analysis.Methods:A retrospective analysis of the data of 64 patients with prolapsed and sequestrated lumbar disc herniation from January 2015 to December 2018, including 38 males and 26 females; age 35.72±12.44 years (range, 22-64 years) ; 43 cases of prolapsed type, 21 cases of sequestrated type. Conservative treatment was the first choice for all patients, in case of surgical indications during the treatment, percutaneous endoscopic lumbar discectomy or fenestration discectomy will be performed. Enhanced MRI was performed at the first and last inspections, the volume of the protrusion, the thickness of rim enhancement (Tr), and the extent of rim enhancement (Er) were measured and calculated at the same time. According to the ring around the protrusion, the size of the rim-enhancement area was divided into type I-III; then compared the relationship between the rim-enhancement signal differentiation and the resorption rate of protrusions, and the correlation between Tr, Er values and the resorption rate of protrusions during the initial inspection.Results:Among the 64 patients, 42 patients completed conservative treatment, and 22 received surgical treatment. According to the rim-enhancement signal differentiation, 23 cases were treated conservatively for type I, 3 cases were treated by surgery; 16 cases were treated for type II conservatively, 7 cases were treated by surgery; 3 cases were treated for type III conservatively, and 12 cases were treated by surgery. All patients were followed up for 12 to 34 months. Among 42 conservatively treated patients, The volume of the protrusion before treatment was 2 645.67±690.86 mm 3, and the volume of the protrusion after treatment was 842.76±573.35 mm 3. The volume of protrusions before and after treatment was statistical significance ( t=11.897, P<0.001), Tr was 1.38±0.83 mm, and Er was 73.08%±34.39%, the resorption rate of protrusions was 65.10%±24.50%, and 39 cases (92.86%, 39/42) reached the standard for protrusion resorption (resorption rate ≥30%); 23 cases of type I , the resorption rate was 76.54%±18.62%; 16 cases of type II had an resorption rate of 56.81%±21.44%; 3 cases of type III had an resorption rate of 21.58%±12.19%. The resorption rate of type III were compared by single factor analysis of variance, and the difference was statistically significant ( F=12.885, P<0.001); 32 cases of both type I and II (82.05%, 32/39) had significant resorption (resorption rate ≥50%), and no case of type Ⅲ had significant resorption, comparing with type I and II, the difference was statistically significant ( P=0.010); Tr was positively correlated with resorption rate ( r=0.569, P<0.001), Er was positively correlated with resorption rate ( r=0.677, P<0.001). Conclusion:Under close clinical observation, parts of the prolapsed or sequestrated lumbar disc herniations can be conservatively treated, and the herniated disc can be resorption in many people and the clinical symptoms were alleviated. Rim-enhancement signal differentiation by enhanced MR has a better predictive value for the outcome of the herniation, type I is more prone to resorption, preferred conservative treatment, type Ⅲ is not easy to resorption, preferred surgery treatment, and the higher thickness of rim enhancement, the greater extend the rim-enhancement, the more prone to resorption phenomenon.