Quantitative and Aesthetic Analysis of Changes in Eyebrow Position After Subbrow Blepharoplasty.

BACKGROUND: Narrowing of the distance between the eyes and eyebrows is commonly observed after subbrow blepharoplasty. The purpose of this study was to quantify the changes in brow-lid distance after subbrow blepharoplasty in Asian women. METHODS: We observed and standardized the pre- and postoperative photographs of 63 patients who underwent subbrow blepharoplasty from January 2020 to October 2022. We measured the distances from the medial and lateral eyebrow to the lower lid margin on the right side of the face and then analyzed the changes in postoperative brow-lid distance using the standard iris diameter for Asian women of 11.5 mm as a reference. RESULTS: Photographs of 63 patients were included in the study. All 63 patients were females. The average postoperative distance of the lateral eyebrow to the lower lid margin was 30.08 ± 2.74 mm, a significant decrease in comparison to the preoperative distance (31.84 ± 2.65 mm) (P < 0.001). The mean postoperative distance of the medial eyebrow to the lower lid margin was 25.84 ± 2.87 mm, compared with that of the preoperative distance (27.59 ± 2.94 mm), which was a significant decrease (P<0.001). All 63 patients (100%) had a decrease in the lateral eyebrow distance, while 59 (93.65%) had a decreased medial eyebrow distance. CONCLUSIONS: There was a statistically significant change in brow position, consistent with our observations. Subbrow blepharoplasty can cause a decrease in the distance between the eyebrows and eyes. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A new glutamine synthetase index to evaluate hepatic lobular restoration in advanced fibrosis during anti-HBV therapy.

Hepatic lobular architecture distortion is a deleterious turning point and a crucial histological feature of advanced liver fibrosis in chronic liver diseases. Regression of fibrosis has been documented in chronic hepatitis B (CHB) patients. However, whether lobular architecture could be restored following fibrosis regression after antiviral therapy is still unclear. Glutamine synthetase (GS) is generally expressed by perivenular hepatocytes around hepatic veins (HV). In this study, we defined abnormal lobular architecture (GSPT ) as GS expressing in the vicinity of portal tracts (PT), which denotes parenchymal extinction and lobular collapse. We defined normal lobular architecture (GSHV ) as GS positivity area not approximating PTs. Therefore, we propose a new GS-index, defined as the percentage of GSHV /(GSHV + GSPT ), to evaluate the extent of architectural disruption and restoration. We evaluated 43 CHB patients with advanced fibrosis (Ishak stage ≥4). Posttreatment liver biopsy was performed after 78 weeks of anti-HBV therapy. The median GS-index improved from 7% (interquartile range [IQR]: 0%-23%) at baseline to 36% (IQR: 20%-57%) at Week 78 (p < 0.001). Totals of 22 patients (51%) had significant GS-index improvement from 0% (IQR: 0%-13%) to 55% (IQR: 44%-81%), while the other half had almost no change between 17% (IQR: 0%-33%) to 20% (IQR: 12%-31%). When GS-index78w ≥ 50% was used to define hepatic lobular restoration, 37% of patients (16/43) achieved lobular restoration, with much improvement in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (median value of ∆/Baseline in ALT: restored vs. nonrestored was 79.1% vs. 48.8%, p = 0.018; median value of ∆/Baseline in AST: restored vs. nonrestored was 69.1% vs. 32.5%, p = 0.005). More importantly, lobular restoration correlated with fibrosis regression (median value of ∆/Baseline in Ishak stage: restored vs. nonrestored was 25.0% vs. 0%, p = 0.008). Therefore, in the era of antiviral therapy for CHB, restoration of hepatic lobular architecture is achievable in patients with advanced fibrosis. GS-index provides additional insight into fibrosis regression that goes beyond collagen degradation.

Persistent steatosis correlates with decreased fibrosis regression during anti-HBV treatment in patients with chronic HBV infection.

Despite the increasing prevalence of steatosis in patients with chronic hepatitis B (CHB), whether the changes in steatosis impact fibrosis regression during antiviral therapy remain unclear. We aimed to identify the association between histological changes of steatosis and fibrosis in patients undergone antiviral treatment. Patients with paired liver biopsies before and after 78 weeks of antiviral therapy were enrolled in this study. Liver fibrosis was assessed by the Ishak score combined with Beijing Classification predominantly progressive, indeterminate, and predominately regressive score. Steatosis was evaluated by the nonalcoholic fatty liver disease activity score. Collagen in each site was quantitated by second harmonic generation/two photon excitation fluorescence technology. Serum proteomic changes after treatment were characterized by mass-based spectrometry. A total of 239 CHB patients were included and divided into four groups according to the changes in steatosis: 162 (67.8%) had no steatosis throughout, 24 (10.0%) developed new-onset steatosis, 21 (8.8%) had initial steatosis which disappeared, and 32 (13.4%) had persistent steatosis. The persistent steatosis group showed the lowest rate of fibrosis regression (14/32, 43.8%). Persistent steatosis correlated with decreased fibrosis regression significantly after adjusting for age, sex, fibrosis stage, and metabolic factors at baseline, as well as the viral response (adjusted odds ratio = 0.380, 95% confidence interval 0.145-0.996, p = 0.049). This decreased fibrosis regression was associated with accumulated collagen in the perisinusoidal area. Patients with persistent steatosis showed unique changes in glycolipid metabolism according to the serum proteomic atlas. Persistent steatosis correlated with decreased fibrosis regression during antiviral therapy in patients with CHB.

Cutis Laxa and the Value of Rhytidectomy: 4 Patients and Years of Follow-Up.

The modalities of the esthetic treatment of cutis laxa (CL) patients have rarely been discussed. Here, the authors present 4 CL rhytidectomy cases. The surgery method was designed based on the traditional full-incision face-lift technique combined with lamellar superficial musculoaponeurotic system flap elevation and plication. Temporal, buccal, mandibular, and cervical regions were targeted. The shortest follow-up was 30 months, and the longest was 72. The results were assessed by subjective satisfaction and third-party photo evaluation. The subjective satisfaction was graded into worse than preoperation, no improvement, slight improvement, moderate improvement, and obvious improvement. The satisfaction rate was the sum of moderate and obvious improvement. Eighteen uncorrelated professionals participated in the third-party photo evaluation, in which the preoperative and follow-up photos were presented, and frontal, temporal, mid-face (including jowl), and cervical (including mandibular line) regions were evaluated as improved or nonimproved. The outcome of the subjective satisfaction was graded as no improvement (2/12, 16.7%), slight improvement (3/12, 25%), moderate improvement (4/12, 33.3%), and obvious improvement (3/12, 25%). The satisfaction rate was 58.3%, most investigators denied the frontal and temporal region improvement, 60% observed mid-face improvement, and 80% noticed cervical improvement. Most patients and their parents had positive attitudes towards the treatment results; however, the full expectation was not achieved. The cervical region maintained the best improvement after our treatment and the mid-face ranked second. This surgery method conduces to the esthetic requirement of CL patients; however, skin laxity remains a challenge.

Factors Influencing the Lagophthalmos and Lid Lag After Simple Congenital Blepharoptosis Correction.

BACKGROUND: Lagophthalmos and lid lag is the most common complication after ptosis correction. Great efforts had been made to control it, but little was known about the factors influencing it. So we ran this research to explore the possible mechanisms underlying it. This would be beneficial to solving this problem. MATERIALS AND METHODS: In this cohort study, patients treated with the forked frontalis muscle aponeurosis suspension and levator aponeurosis-Muller's muscle complex resection were identified. Lagophthalmos height and lid lag was measured at the postoperative week 1 visits. The Spearman correlation test was run to test whether lagophthalmos was related to patients' age, levator function, and severity of ptosis. Then we measured the contents of collagen and elastin fibers of frontalis muscle fascia and levator aponeurosis from the patients and levator aponeurosis from cadaver heads histologically and compared the contents in these 3 groups. RESULTS: No correlation was found between patients' age, levator function, the severity of ptosis, and with lagophthalmos height. However, the contents of collagen and elastic fibers were both higher in the frontalis fascia than in the normal aponeurosis tissues. The difference in collagen fibers content between frontalis muscle fascia and patients' aponeurosis was statistically insignificant. CONCLUSIONS: The severe lagophthalmos and lid lag may be caused by the poor mechanical features of the frontalis muscle. A better source of motive force to elevate the eyelids and a novel sling material with proper elasticity and stiffness would be the solution to improve the lagophthalmos and lid lag after ptosis correction.

Efficacy and Safety of Surgical Procedures for Congenital Moderate and Severe Blepharoptosis: A Network Meta-analysis.

BACKGROUND: There are various surgical approaches to treat congenital moderate and severe blepharoptosis (CMSBP), but their efficacy and safety remain unclear owing to a lack of high-level evidence. This network meta-analysis aimed to evaluate the efficacy and safety of 3 classical operations: and their modifications frontal muscle flap suspension (FMS), levator palpebrae muscle shortening (LMS), conjoint fascial sheath suspension (CFSS), and modified CFSS. METHODS: We searched the PubMed, MEDLINE, Cochrane Library, CNKI, and Wanfang databases until March 2022. A Bayesian network meta-analysis was conducted for the 5 most common treatments. Outcome indicators were the number of patients with good correction and adverse events. RESULTS: Twenty-one studies were included, with 2402 eyes in 1863 patients. Five surgical methods were evaluated: FMS, LMS, CFSS, and conjoint fascial sheath suspension combined with levator muscle shortening (CFSS+LMS), or with levator palpebrae muscle composite flap suspension (CFS+L). Meta-analysis indicated that CFSS is more effective than LMS and FMS, but inferior to CFSS+LMS and CFS+L. Efficacy rates of CFSS+LMS and CFS+L were comparable. Frontal muscle flap suspension was more effective than LMS. Safety data meta-analysis found CFSS safer than FMS and LMS but with more complications than CFSS+LMS and CFS+L. Complication rates were comparable between CFS+L and CFSS+LMS, and also for FMS and LMS. CONCLUSIONS: When correcting CMSBP, CFSS+LMS, and CFS+L may be better therapeutic strategies for effectiveness and safety. Conjoint fascial sheath suspension also yielded good surgical effects. Plastic surgeons should be cautious about LMS and FMS. LEVEL OF EVIDENCE: Level IV.

Trapezius Perforator Flaps Based on Superficial Cervical Artery and Dorsal Scapular Artery: An Anatomical Study and a Systematic Review of Their Clinical Application.

BACKGROUND: The flaps in the trapezius region are routinely elevated as musculocutaneous flaps. The anatomy of trapezius perforators and their clinical application are unclear. METHODS: The number and distribution of superficial cervical artery perforators (SCAPs) and dorsal scapular artery perforators (DSAPs) were studied on 8 cadavers. The clinical usage of SCAP and DSAP flaps was investigated through a systematic literature review. RESULTS: A total of 27 SCAPs and 28 DSAPs were found in the 16 hemibacks. The mean calibers of SCAP and DSAP were 0.9 ± 0.2 and 0.8 ± 0.2 mm, respectively. The vascular length to the takeoff of the source artery was 7.3 ± 2.0 cm (range, 4.7-9.7 cm) for SCAPs and was 8.1 ± 2.8 cm (range, 3.2-13.6 cm) for DSAPs. Contour and density heat maps showed that the SCAPs were clustered within approximately 3 to 5 cm above the horizontal line through the medial point of the scapular spine (x-axis) and 5 to 8 cm from the midline (y-axis, P = 0.001) and clustered DSAPs located in approximately 4 to 9 cm below the x-axis and 4 to 10 cm from the y-axis ( P = 0.002). Four SCAP and 19 DSAP flaps were found in literature. The mean sizes of SCAP flaps and DSAP flaps were 18.5 × 7.8 and 16.5 × 8.7 cm, respectively. CONCLUSIONS: Both SCAP and DSAP flaps can be elevated with a relatively long pedicle. The anatomical knowledge of the location of major clusters of perforators contributes to the application of these flaps.

Guided Internal Fixation Technique for Transconjunctival Orbital Fat Transposition.

ABSTRACT: The predominant method for transconjunctival orbital fat transposition is by conducting 1 or several temporary externalized sutures. A new method that could internally and more securely fixate the fat to the periosteum remains desirable. This manuscript introduces a technique that utilizes a titanium ring to guide transconjunctival orbital fat fixation for lower blepharoplasty. With 8 to 10 mm transconjunctival incisions, the orbicularis retaining ligaments were released. An intraoperatively made ring guided the sutures that was made transcutaneously and anchored on the periosteum to exit the preseptal space through the transconjunctival incision. The orbital fat graft was then fixated internally by this suture. From October 2017 to November 2019, 51 patients were included in this study. The mean patient age was 35.7 years (ranged 28-42 years). The mean operative time for the surgical procedure was 52 minutes. No major complications were noticed in any patients. There was 1 case in which the eye bag relapses at fifth week postoperatively, but was corrected by the same approach. At the average follow-up period of 12.1 months, all patients presented significant improvement of the lower eyelid cosmesis. Forty-four patients rated the aesthetic outcomes as "Very Satisfied," the other 7 rated "Satisfied" in a self-assessment questionnaire.Global Aesthetic Improvement Scale echoed similar outcomes. This guided internal fixation technique is technically practical when properly executed. It offers a new method for facilitating orbital fat transposition in lower blepharoplasty.

Can Procerus Transection Alter the Radix Morphology and Influence the Nasal Length? A Study of Photogrammetric Assessments and Anthropometric Measurements on Asian Patients.

BACKGROUND: The procerus is the main muscle across the radix that needs to be operated during rhytidectomy, however, it is unclear whether transecting it can morphologically affect the nose. METHODS: A retrospective study of Asian patients who underwent procerus transection during rhytidectomy in our single institution was performed to assess whether the radix profile had any change postoperatively. The procerus was transected at a plane above the nasion. RESULTS: Ninety-four patients were included. All of them were female with an average age of 50.7 ± 5.2 years and a mean follow-up time of 7.8 ± 3.2 months. Twenty-seven (28.7%) had moderate horizontal wrinkles preoperatively, and sixty-seven (71.3%) had severe rhytides. Different degrees of wrinkle improvement were seen on 91 (96.8%) patients, and no improvement occurred to 3 (3.2%) patients after procerus transection. The anthropometric measurements on these patients did not find any significant difference between the preoperative and postoperative nasal heights, radix projections, nasal lengths, or nasofrontal angles (all p >0.05). CONCLUSIONS: Procerus transection primary contributes to wrinkle improvement. The morphological change of the radix following this operation is too subtle to be observed. This conclusion should be further verified on large samples as well as on other ethnic cohorts in a long-term follow-up. LEVEL OF EVIDENCE IV: This journal requires that authors 10 assign a level of evidence to each article. For a full 11 description of these Evidence-Based Medicine ratings, 12 please refer to the Table of Contents or the online 13 Instructions to Authors www.springer.com/00266 .

Persistent Low Level of Hepatitis B Virus Promotes Fibrosis Progression During Therapy.

BACKGROUND & AIMS: Progression of liver fibrosis still occurs in some patients with chronic hepatitis B virus (HBV) infection despite antiviral therapy. We aimed to identify risk factors for fibrosis progression in patients who received antiviral therapy. METHODS: We conducted a longitudinal study of patients with chronic HBV infection and liver biopsies collected before and after 78 weeks of anti-HBV therapy. Fibrosis progression was defined as Ishak stage increase ≥ 1 or as predominantly progressive classified by P-I-R system (Beijing Classification). Levels of HBV DNA and HBV RNA in blood samples were measured by real-time quantitative PCR. HBV RNA in liver tissue was detected by in situ hybridization. RESULTS: A total of 239 patients with chronic HBV infection with paired liver biopsies were included. Among the 163 patients with significant fibrosis at baseline (Ishak ≥ stage 3), fibrosis progressed in 22 patients (13%), was indeterminate in 24 patients (15%), and regressed in 117 patients (72%). Univariate and multivariate analyses revealed that independent risk factors for fibrosis progression were higher rate of detected HBV DNA at week 78 (odds ratio, 4.84; 95% CI, 1.30-17.98; P = .019) and alcohol intake (odds ratio, 23.84; 95% CI, 2.68-212.50; P = .004). HBV DNA was detected in blood samples from a significantly higher proportion of patients with fibrosis progression (50%) at week 78 than patients with fibrosis regression (19%) or indeterminate fibrosis (26%) (P = .015), despite low viremia (20-200 IU/mL) in all groups. The decrease of serum HBV RNA from baseline in the fibrosis regression group was larger than that in the fibrosis progression group. CONCLUSIONS: In a longitudinal study of patients with chronic HBV infection, we associated liver fibrosis progression at week 78 of treatment with higher rates of detected HBV DNA. We propose that a low level of residual HBV may still promote fibrosis progression, and that patients' levels of HBV DNA should be carefully monitored.

Prolonged interval of total bilirubin decline is an early independent predictive factor of chronic persistent drug-induced liver injury.

AIM: Chronic drug-induced liver injury (DILI) with persistent abnormal liver function tests (LFTs) >6 months after cessation of the insulting drugs could progress to cirrhosis. The aim of the present study was to identify the risk factors of chronic DILI for early recognition and better management. METHODS: History of drug intake and results of LFTs were retrospectively retrieved for patients with a discharge diagnosis of DILI for at least 1-year follow up. The risk factors independently associated with chronic DILI were analyzed by multiple logistic regression analyses. RESULTS: A total of 33 of the 140 DILI patients had persistent abnormal LFTs >6 months, which were considered as chronic DILI. It was found that the time intervals of alanine aminotransferase and total bilirubin decline from the peak to their half peak (T0.5ALT , T0.5TBIL ) were significantly longer in the chronic DILI group than that in the recovered group (P = 0.001 and P < 0.001). The risk factors associated with chronic DILI independently were T0.5TBIL (OR 1.315, 95% CI 1.038-1.668), longer period of insulting drug(s) intake (OR 1.018, 95% CI 1.003-1.033), mixed/cholestatic pattern (OR 97.159, 95% CI 1.866-5005.994). More importantly, receiver operating characteristic curve analysis showed that the prognostic value of T0.5TBIL for chronic DILI had a sensitivity of 60.0% at a specificity of 90.7% with the threshold of 16 days. CONCLUSIONS: The time intervals of total bilirubin decline from its peak to half of its peak (T0.5TBIL ) was an early independent predictive factor of chronic DILI, suggesting that T0.5TBIL might serve as an indicator for chronicity.

Vertical Midface Lifting: An Improved Technique for Asians.

BACKGROUND: Treatment of the aging midface is increasingly deemed a key part of facial and periorbital rejuvenation. Compared with Westerners, Asians tend to have a relatively prominent zygoma and mandibular angle, thicker dermis, and greater propensity for scar formation. OBJECTIVE: This study was performed to review our surgical method of vertical midface lifting in Asian patients and evaluate the clinical outcomes. METHODS AND MATERIALS: This retrospective observational study involved 116 Asian women who complained of an aged midface. All patients underwent midface rejuvenation surgery with one lower eyelid incision and 2 small frontal-temporal incisions. Clinical results were assessed objectively using photographs and subjectively by a patient satisfaction survey. RESULTS: All patients recovered well without major complications. High patient satisfaction (94%) was attained. The improvement scores as evaluated by the panel demonstrated a higher level of improvement for the malar eminence (8.3 ± 0.6), nasojugal groove (8.0 ± 0.8), and nasolabial fold (7.9 ± 0.7) than for the lower face (6.2 ± 1.0). CONCLUSION: Our vertical midface lift technique is safe and effective for older Asian patients with a midface aging appearance. LEVEL OF EVIDENCE: Therapeutic IV.

A New Surgical Technique Used for Correction of Congenital Blepharoptosis.

BACKGROUND: Blepharoptosis is defined as the drooping or lower displacement of the upper eyelids. Various kinds of surgical techniques and modifications have been introduced to improve the surgical outcomes, but the high recurrence rate and unsatisfying cosmetic results remain as a common problem. PURPOSE: To solve the problem mentioned above, we came up with our new surgical technique and conducted a retrospective review to verify its effectiveness. PATIENTS AND METHODS: A retrospective review was conducted among the patients diagnosed as genuine congenital blepharoptosis and receiving the surgical treatments where our unique technique was used between January 2016 and January 2019. The clinical records and preoperative and postoperative photographs were collected and evaluated. RESULTS: A total of 83 patients were included in our study, 78 (94%) of them acquired good surgical outcomes, while 4 (4.8%) of them got fair results, and 1 (1.2%) of them got a poor result. No long-term lagophthalmos, ectropion, entropion and fornix conjunctival prolapse were noted. CONCLUSIONS: Our surgical technique introduced here is effective in the management of genuine congenital blepharoptosis. LEVEL OF EVIDENCE III: For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Early steep decline of liver stiffness predicts histological reversal of fibrosis in chronic hepatitis B patients treated with entecavir.

It is unknown whether dynamic changes of liver stiffness measurement (LSM) can predict the reversibility of fibrosis. Therefore, we evaluated the utility of LSM changes in predicting histological changes of fibrosis in patients with chronic hepatitis B (CHB) on antiviral therapy. In a prospective cohort of CHB patients treated with entecavir, virological measurement and biochemical measurement along with LSM were measured at baseline and every 6 months. Liver biopsies were conducted at baseline and month 18 of treatment. Fibrosis regression was defined by the following two criteria: (a) Ishak score decrease ≥1 stage, (b) Ishak score decrease ≥1 stage or predominantly regressive by post-treatment PIR classification. The dynamic changes of LSM and its predictive value for histological reversibility were evaluated with piecewise linear mixed-effects model and ROC analysis. We found that at month 18 of antiviral therapy, liver fibrosis was reserved in 86 of 212 (40.6%) CHB patients by Ishak reversal criterion. Overall, a decline in LSM was associated with attenuation of Ishak score. The rate of LSM decline in the first 6 months was significantly faster in patients with fibrosis reversal (ΔLSM%Ishak  = -2.19%/month, P = 0.0025; ΔLSM%Ishak/PIR  = -2.56%/month, P = 0.0004). The predictive model based on baseline FIB-4 and Ishak score as well as baseline LSM, PLT, albumin and their changes during the first 6 months could predict histological reversal (AUROCIshak  = 0.74, 95% CI: 0.67-0.80; AUROCIshak/PIR  = 0.81, 95% CI: 0.74-0.87). We conclude that in CHB patients, changes in LSM during the first 6 months of entecavir therapy can predict histological reversibility of liver fibrosis at month 18 of antiviral therapy.

On-treatment changes of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein are associated with the regression of liver fibrosis in chronic hepatitis B patients on interferon α add-on therapy.

Wisteria floribunda agglutinin-positive Mac-2-binding protein (M2BP) has been identified as a predictor for the response of interferon α (IFN-α) in patients with viral hepatitis. However, whether serum glycosylation isomer of M2BP (M2BPGi) was associated with the regression of liver fibrosis in patients with chronic hepatitis B (CHB) during IFN-α add-on therapy is still unknown. CHB patients were treated with entecavir for 26 weeks followed by entecavir plus pegylated IFN-α for 52 weeks. Liver biopsies were taken at baseline and treatment week 78. The regression of fibrosis was identified according to Ishak standard or Ishak plus Progressive-Indeterminate-Regressive (P-I-R) standard. Serum M2BPGi and liver function tests were measured at baseline and every 26 weeks of treatment. A total of 72 CHB patients were included in the present study. Serum M2BPGi was correlated with fibrosis and necroinflammation both at baseline and week 78. If Ishak standard was used as the reference, only the percent change of M2BPGi at week 52 from week 26 (Δ%M2BPGi26w-52W ) was independently associated with fibrosis regression at treatment week 78, the area under the ROC curve (AUROC) of Δ%M2BPGi26w-52W for predicting fibrosis regression was 0.705. As for Ishak plus P-I-R standard, the AUROC of the predictive model for fibrosis regression (0.896*M2BPGi52W + 0.363*necroinflammation score0w + 2.051*Ishak score0w - 4.489) was 0.888. These data indicated that dynamic changes of serum M2BPGi were associated with fibrosis regression in CHB patients on IFN-α add-on therapy.

Clinical features of idiopathic portal hypertension in China: A retrospective study of 338 patients and literature review.

BACKGROUND AND AIM: Idiopathic portal hypertension (IPH) refers to a relatively rare condition characterized by intrahepatic portal hypertension in the absence of underlying disease such as liver cirrhosis. METHODS: We retrospectively reviewed 338 patients with IPH that were diagnosed at the pathological consultation center of our hospital. RESULTS: The ratio of male to female patients was 1:1. Mean age at onset was 35.1 ± 16.5 years; male patients on average were 12 years younger than female patients at onset. The median duration from onset to IPH diagnosis was 12 months. In 50 patients, medication use may have been an etiological factor. The most common clinical manifestations were splenomegaly (91.3%) and hypersplenism (68.9%); 57.0% patients presented varicosis, while 25.1% patients had a history of variceal bleeding. Nodular regenerative hyperplasia was found in 22.2% liver biopsies. Among patients for whom laboratory data were available, 65.0%, 50.3%, and 71.4% patients presented leukopenia, anemia, and thrombocytopenia due to hypersplenism. Liver function was mostly in the compensated stage. Female patients showed worse leukopenia and anemia, while male patients were more likely to have abnormal serum transaminase and bilirubin levels. Sixty-seven patients received surgical or interventional treatment. CONCLUSIONS: High-quality liver biopsy, detailed clinical information, and expert pathologist are necessary for diagnosis of IPH. IPH can occur concurrently with other liver disease such as hepatitis and drug-induced liver injury. Medication appears to be an important etiological factor for IPH in China. Management approach was largely focused on treatment of portal hypertension and its complications.

Transplantation of Adipose-Derived Stem Cells Before Flap Expansion and After Expanded Flap Elevation Result in Different Effects.

BACKGROUND: Studies of using mesenchymal stem cells to assist skin and soft tissue expansion have shown that stem cells can improve expansion efficiency through promoting tissue regeneration. However, the issue that whether the flap viability is also improved is unknown. METHODS: Sixteen pigs were equally divided into 2 groups. A pair of 150 mL expanders was symmetrically inserted into each pig's dorsum. Group 1 received adipose-derived stem cells (ADSCs) injection before expansion, and group 2 received ADSCs grafting after flap elevation. After 4 weeks' expansion, a random flap measuring 2 cm × 16 cm was elevated along the long axis of each expanded flap on the pigs' back. Flap viability was measured at postoperative day 7. Histological analysis and cell tracking were performed. The expression of vascular endothelial growth factor was determined. RESULTS: The flap viability of the ADSCs-grafted expanded flap (75.5 ± 6.6%) was similar to the control (69.4 ± 8.4%) in group 1 (transplantation before expansion). However, in group 2 (transplantation after flap elevation), the ADSCs-grafted expanded flap had a higher flap viability (92.6 ± 5.7%) compared with control (66.2 ± 7.4%). Moreover, the ADSCs-grafted expanded flap in group 1 showed increased skin thickness, collagen content, cells proliferation, vascularization, and vascular endothelial growth factor expression. Cell tracking showed that the positively stained cell differentiating into an endotheliocyte could be seen in group 2. CONCLUSIONS: Transplantation of ADSCs before tissue expansion does not improve flap viability but can promote tissue regeneration. Injection of ADSCs after flap elevation can increase the surviving rate of the expanded flap.

Advanced septa size quantitation determines the evaluation of histological fibrosis outcome in chronic hepatitis B patients.

Hepatitis B (HBV)-related fibrosis can be reversed after effective antiviral therapy. However, detailed changes of collagen characteristics during fibrosis regression remain unclear. Paired biopsy samples obtained from chronic hepatitis B patients were imaged with second harmonic generation/two photon excitation fluorescence (SHG/TPEF)-based microscopy to identify and quantify collagen features in portal, septal, and fibrillar areas. According to the changes of Ishak stage and qFibrosis score, a total of 117 patients with paired liver biopsy appeared to have four different outcomes after 78-week antiviral therapy: fast reverse (9%), reverse (63%), stable (15%), or progress (13%) on fibrosis. Among 71 collagen features identified by SHG/TPEF analysis, the most prominent fibrosis reversion occurred in the "septal" area, followed by the "fibrillar" area, but not in the "portal" area (P < 0.001). Further analysis of 1060 individual septa identified four parameters that correlated with fibrosis reversion: average width, maximum width, number of fibers, and number of cross-link fibers (P < 0.001). Average septal width was independently associated with regressive septa (odds ratio (OR) = 5.22, 95% confidence interval (CI): 4.17-6.53; P < 0.001), with an AUROC of 0.96 (95% CI: 0.95-0.97). The threshold used to discriminate reversal of fibrosis was 30 µm. In conclusion, septal collagen was determined to be the most useful histological feature for evaluation of dynamic changes in liver fibrosis. Septal width was the most predictive indicator of prognosis in liver fibrosis.

Functional study on new FOXL2 mutations found in Chinese patients with blepharophimosis, ptosis, epicanthus inversus syndrome.

BACKGROUND: Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) is a rare inheritable disease that mainly affects eyelid development associated with (type I) or without (type II) ovarian dysfunction, resulting in premature ovarian failure (POF). Mutations in the gene forkhead box L2 (FOXL2) have been shown to be responsible for BPES. The aim of this study was to determine and functionally validate the FOXL2 mutation in a Chinese BPES family. METHODS: Twelve individuals including five BPES patients from a Chinese family were enrolled. Genomic DNA was extracted from peripheral blood of enrolled subjects. The coding region of the FOXL2 gene was amplified and mutations were determined by sequencing analyses. Functional analysis was carried out to study changes in expression and transcriptional activity of the mutant FOXL2 protein. RESULTS: A novel mutation in the FOXL2 gene (c.931C > T) was detected in all five BPES patients, which converts a histidine residue into a tyrosine (p.H311Y) in the FOXL2 protein. Functional analysis revealed that this point mutation reduces FOXL2 protein expression, concomitant with decreased transcriptional activity on the steroidogenic acute regulatory (StAR) gene promotor. CONCLUSIONS: Our results expand the mutational spectrum of the FOXL2 gene and provide additional insights to the research on the molecular pathogenesis of FOXL2 in BPES.

New classification of liver biopsy assessment for fibrosis in chronic hepatitis B patients before and after treatment.

Liver fibrosis is the net result of dynamic changes between fibrogenesis and fibrolysis. Evidence has shown that antiviral therapy can reverse liver fibrosis or even early cirrhosis caused by hepatitis B virus. However, current evaluation systems mainly focus on the severity of, but not the dynamic changes in, fibrosis. Here, we propose a new classification to evaluate the dynamic changes in the quality of fibrosis, namely: predominantly progressive (thick/broad/loose/pale septa with inflammation); predominately regressive (delicate/thin/dense/splitting septa); and indeterminate, which displayed an overall balance between progressive and regressive scarring. Then, we used this classification to evaluate 71 paired liver biopsies of chronic hepatitis B patients before and after entecavir-based therapy for 78 weeks. Progressive, indeterminate, and regressive were observed in 58%, 29%, and 13% of patients before treatment versus in 11%, 11%, and 78% after treatment. Of the 55 patients who showed predominantly regressive changes on posttreatment liver biopsy, 29 cases (53%) had fibrosis improvement of at least one Ishak stage, and, more interestingly, 25 cases (45%) had significant improvement in terms of Laennec substage, collagen percentage area, and liver stiffness despite remaining in the same Ishak stage. CONCLUSION: This new classification highlights the importance of assessing and identifying the dynamic changes in the quality of fibrosis, especially relevant in the era of antiviral therapy.(Hepatology 2017;65:1438-1450).